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Thirteen new cases of erectile dysfunction treatment were diagnosed in the 24 hours to 8pm last can you get kamagra over the counter night, bringing the total number of cases in NSW to 3,830. Confirmed cases (including interstate residents in NSW health care facilities)3,830Deaths (in NSW from confirm​​ed cases)54Total tests carried out2,112,997There were 30,282 tests reported in the 24-hour reporting period, compared with 30,173 can you get kamagra over the counter in the previous 24 hours.Of the thirteen new cases to 8pm last night. One is a returned traveller who is in hotel quarantineSix are linked to the Sydney CBD clusterFour are locally acquired with their source still under investigationTwo are close contacts of previously reported cases who have not been linked to known clusters. One of the new cases is a student of St Gertrude’s Catholic Primary School can you get kamagra over the counter in Smithfield. Additionally, a staff member from Ryde Secondary College was confirmed to have erectile dysfunction treatment late last night.

This case can you get kamagra over the counter will be included in tomorrow’s numbers. Both St Gertrude’s Catholic Primary School and Ryde Secondary College are closed today for on-site learning and are being cleaned. All staff and students of both schools have been asked to self-isolate can you get kamagra over the counter while close contacts are identified and contacted.Two new cases are household contacts of previously reported cases who have not been linked to a known cluster.Wyndham College Quakers Hill, Schofields Public School and Riverstone High School have been cleaned and are re-opening today. Close contacts are in self-isolation.Further investigations have found that anyone who attended City Tattersalls Club Fitness Centre​ on Monday 24 August from 8am-2pm is a close contact and must get tested immediately and isolate for 14 days and remain isolated, even if the test result is negative.One of today’s cases attended Anytime Fitness gym in Marrickville on Monday 24 August from 7pm to 8pm. Anyone at the gym at this time is considered a close contact and is required to immediately get tested for erectile dysfunction treatment and self-isolate for 14 days until 8 September.People who have attended the following venues are considered casual contacts and advised to monitor for symptoms, and immediately isolate and get tested for erectile dysfunction treatment should symptoms develop can you get kamagra over the counter.

The Matterhorn, Turramurra - Saturday 22 August 6pm-8pm (NSW Health has identified and contacted close contacts)Parish of Holy Name, Wahroonga - Sunday 23 August 9.30am-10.15amLiquorland, Marrickville, 269-271 Marrickville Rd - Sunday 23 August 5.15pm-5.30pm​Eat Fuh, Marrickville - Sunday 23 August 5.20pm-5.40pmMetro Petroleum - Hurlstone Park - Monday 24 August 10.20am-10.30am Following diagnosis of erectile dysfunction treatment in a person who lives in Victoria, two NSW residents are in isolation for 14 days from the date of last contact with this case. Murrumbidgee LHD can you get kamagra over the counter contacted these two people and are continuing to monitor them while they remain in isolation. NSW Health is treating 69 erectile dysfunction treatment cases, including six in intensive care and four who are ventilated. 83 per cent of cases being treated by NSW Health can you get kamagra over the counter are in non-acute, out-of-hospital care.Data reported in this week’s erectile dysfunction treatment Weekly Surveillance in NSW report shows that almost half of the cases who acquired their in Sydney had a test more than three days after their symptoms began. This causes more transmission of the kamagra because of the delay in isolation of people with the .

It is can you get kamagra over the counter critically important people get tested the day their symptoms present and self-isolate immediately.erectile dysfunction treatment continues to circulate in the community and we must all be vigilant. It is vital that high rates of testing continue in order to find the source of the cases still under investigation and to identify and stop further spread of the kamagra. Locations linked to known cases, advice on testing and can you get kamagra over the counter isolation, and areas identified for increased testing can be found at NSW Government - Latest new and updates.Anyone identified as a close contact and directed to undertake 14 days self-isolation must stay in isolation for the full 14 days, even if they test negative during this time. Early testing may not detect an , and release from self-isolation based on a negative test could allow an infectious person to infect others in the community. People who are infected will generally develop can you get kamagra over the counter symptoms within 14 days of exposure.

If you have any cold or flu-like symptoms at all, assume it’s erectile dysfunction treatment until proven otherwise – isolate and get tested right away. Don’t delay.To help stop the spread of erectile dysfunction treatment can you get kamagra over the counter. If you are unwell, stay in, get tested and isolate.Wash your hands regularly. Take hand sanitiser with you when you go out.Keep your distance can you get kamagra over the counter. Leave 1.5 metres between yourself and others.

Wear a mask in situations can you get kamagra over the counter where you cannot physically distance. Confirmed cases to dateOverseas2,066Interstate acquired89Locally acquired – contact of a confirmed case and/or in a known cluster1,282Locally acquired – contact not identified393Under investigation​0 Counts reported for a particular day may vary over time with ongoing enhanced surveillance activities.Returned travellers in hotel quarantine to dateSymptomatic travellers tested4,740Found positive122As​ymptomatic travellers screened at a day 217,437Found positive87Asymptomatic travellers screened at a day 1030,523Found positive119​.

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See info here 1 2 1 2 3 1 2 Income $884 (up from $875 in 2020) $1300 (up from $1,284 in 2020) $1,482 $2,004 $2,526 $2,146 $2,903 Resources $15,900 (up from $15,750 in 2020) $23,400 (up from $23,100 in 2020) NO LIMIT** NO LIMIT 2020 levels are in GIS 19 MA/12 – cheap kamagra jelly 2020 Medicaid Levels and Other Updates and attachments here * MAGI and ESSENTIAL plan levels are based on Federal Poverty Levels, which kamagra reviews forum are not released until later in 2021. 2020 levels are used until then. NEED TO KNOW PAST MEDICAID INCOME AND RESOURCE LEVELS?. WHAT kamagra reviews forum IS THE HOUSEHOLD SIZE?. See rules here.

HOW TO READ THE HRA Medicaid Levels chart - Boxes 1 and 2 are NON-MAGI Income and Resource levels -- Age 65+, Blind or Disabled and other adults who need to use "spend-down" because they are over the MAGI income levels. Box 10 on page 3 are the MAGI income levels -- The Affordable Care Act changed the rules for Medicaid income eligibility for kamagra reviews forum many BUT NOT ALL New Yorkers. People in the "MAGI" category - those NOT on Medicare -- have expanded eligibility up to 138% of the Federal Poverty Line, so may now qualify for Medicaid even if they were not eligible before, or may now be eligible for Medicaid without a "spend-down." They have NO resource limit. Box 3 on page 1 is Spousal Impoverishment levels for Managed Long Term Care &. Nursing Homes and Box 8 has the Transfer Penalty rates for nursing home eligibility Box 4 has Medicaid Buy-In for Working People with Disabilities Under Age 65 (still 2017 levels til April 2018) Box 6 are Medicare Savings Program kamagra reviews forum levels (will be updated in April 2018) MAGI INCOME LEVEL of 138% FPL applies to most adults who are not disabled and who do not have Medicare, AND can also apply to adults with Medicare if they have a dependent child/relative under age 18 or under 19 if in school.

42 C.F.R. § 435.4. Certain populations have an even higher income limit - 224% kamagra reviews forum FPL for pregnant women and babies <. Age 1, 154% FPL for children age 1 - 19. CAUTION.

What is counted as income kamagra reviews forum may not be what you think. For the NON-MAGI Disabled/Aged 65+/Blind, income will still be determined by the same rules as before, explained in this outline and these charts on income disregards. However, for the MAGI population - which is virtually everyone under age 65 who is not on Medicare - their income will now be determined under new rules, based on federal income tax concepts - called "Modifed Adjusted Gross Income" (MAGI). There are kamagra reviews forum good changes and bad changes. GOOD.

Veteran's benefits, Workers compensation, and gifts from family or others no longer count as income. BAD kamagra reviews forum. There is no more "spousal" or parental refusal for this population (but there still is for the Disabled/Aged/Blind.) and some other rules. For all of the rules see. ALSO SEE 2018 Manual on Lump Sums and Impact on Public Benefits - with resource rules HOW TO DETERMINE SIZE OF HOUSEHOLD TO IDENTIFY WHICH INCOME LIMIT APPLIES The income limits increase with the "household size." In other words, the income limit for a family of 5 may be higher than the kamagra reviews forum income limit for a single person.

HOWEVER, Medicaid rules about how to calculate the household size are not intuitive or even logical. There are different rules depending on the "category" of the person seeking Medicaid. Here are the 2 basic categories and kamagra reviews forum the rules for calculating their household size. People who are Disabled, Aged 65+ or Blind - "DAB" or "SSI-Related" Category -- NON-MAGI - See this chart for their household size. These same rules apply to the Medicare Savings Program, with some exceptions explained in this article.

Everyone else -- MAGI - All children and adults under age 65, including people with disabilities who are not yet on Medicare -- this kamagra reviews forum is the new "MAGI" population. Their household size will be determined using federal income tax rules, which are very complicated. New rule is explained in State's directive 13 ADM-03 - Medicaid Eligibility Changes under the Affordable Care Act (ACA) of 2010 (PDF) pp. 8-10 of the PDF, This kamagra reviews forum PowerPoint by NYLAG on MAGI Budgeting attempts to explain the new MAGI budgeting, including how to determine the Household Size. See slides 28-49.

Also seeLegal Aid Society and Empire Justice Center materials OLD RULE used until end of 2013 -- Count the person(s) applying for Medicaid who live together, plus any of their legally responsible relatives who do not receive SNA, ADC, or SSI and reside with an applicant/recipient. Spouses or legally responsible for one kamagra reviews forum another, and parents are legally responsible for their children under age 21 (though if the child is disabled, use the rule in the 1st "DAB" category. Under this rule, a child may be excluded from the household if that child's income causes other family members to lose Medicaid eligibility. See 18 NYCRR 360-4.2, MRG p. 573, NYS GIS kamagra reviews forum 2000 MA-007 CAUTION.

Different people in the same household may be in different "categories" and hence have different household sizes AND Medicaid income and resource limits. If a man is age 67 and has Medicare and his wife is age 62 and not disabled or blind, the husband's household size for Medicaid is determined under Category 1/ Non-MAGI above and his wife's is under Category 2/MAGI. The following programs were available prior to 2014, but are now discontinued because kamagra reviews forum they are folded into MAGI Medicaid. Prenatal Care Assistance Program (PCAP) was Medicaid for pregnant women and children under age 19, with higher income limits for pregnant woman and infants under one year (200% FPL for pregnant women receiving perinatal coverage only not full Medicaid) than for children ages 1-18 (133% FPL). Medicaid for adults between ages 21-65 who are not disabled and without children under 21 in the household.

It was sometimes kamagra reviews forum known as "S/CC" category for Singles and Childless Couples. This category had lower income limits than DAB/ADC-related, but had no asset limits. It did not allow "spend down" of excess income. This category has now been kamagra reviews forum subsumed under the new MAGI adult http://brew17.com/?page_id=2 group whose limit is now raised to 138% FPL. Family Health Plus - this was an expansion of Medicaid to families with income up to 150% FPL and for childless adults up to 100% FPL.

This has now been folded into the new MAGI adult group whose limit is 138% FPL. For applicants between 138%-150% FPL, they will be eligible for a new program where Medicaid will subsidize their purchase of Qualified Health Plans kamagra reviews forum on the Exchange. PAST INCOME &. RESOURCE LEVELS -- Past Medicaid income and resource levels in NYS are shown on these oldNYC HRA charts for 2001 through 2019, in chronological order. These include Medicaid levels for MAGI and non-MAGI populations, Child Health Plus, MBI-WPD, Medicare Savings Programs and kamagra reviews forum other public health programs in NYS.

This article was authored by the Evelyn Frank Legal Resources Program of New York Legal Assistance Group.A huge barrier to people returning to the community from nursing homes is the high cost of housing. One way New York State is trying to address that barrier is with the Special Housing Disregard that allows certain members of Managed Long Term Care or FIDA plans to keep more of their income to pay for rent or other shelter costs, rather than having to "spend down" their "excess income" or spend-down on the cost of Medicaid home care. The special income standard for housing expenses helps pay for housing expenses kamagra reviews forum to help certain nursing home or adult home residents to safely transition back to the community with MLTC. Originally it was just for former nursing home residents but in 2014 it was expanded to include people who lived in adult homes. GIS 14/MA-017 Since you are allowed to keep more of your income, you may no longer need to use a pooled trust.

KNOW YOUR RIGHTS - FACT SHEET kamagra reviews forum on THREE ways to Reduce Spend-down, including this Special Income Standard. September 2018 NEWS -- Those already enrolled in MLTC plans before they are admitted to a nursing home or adult home may obtain this budgeting upon discharge, if they meet the other criteria below. "How nursing home administrators, adult home operators and MLTC plans should identify individuals who are eligible for the special income standard" and explains their duties to identify eligible individuals, and the MLTC plan must notify the local DSS that the individual may qualify. "Nursing home administrators, nursing home discharge planning staff, adult home operators and MLTC health plans are encouraged to identify individuals who may qualify for the special income standard, kamagra reviews forum if they can be safely discharged back to the community from a nursing home and enroll in, or remain enrolled in, an MLTC plan. Once an individual has been accepted into an MLTC plan, the MLTC plan must notify the individual's local district of social services that the transition has occurred and that the individual may qualify for the special income standard.

The special income standard will be effective upon enrollment into the MLTC plan, or, for nursing home residents already enrolled in an MLTC plan, the month of discharge to the community. Questions regarding the special income standard may be directed kamagra reviews forum to DOH at 518-474-8887. Who is eligible for this special income standard?. must be age 18+, must have been in a nursing home or an adult home for 30 days or more, must have had Medicaid pay toward the nursing home care, and must enroll in or REMAIN ENROLLED IN a Managed Long Term Care (MLTC) plan or FIDA plan upon leaving the nursing home or adult home must have a housing expense if married, spouse may not receive a "spousal impoverishment" allowance once the individual is enrolled in MLTC. How kamagra reviews forum much is the allowance?.

The rates vary by region and change yearly. Region Counties Deduction (2021) Central Broome, Cayuga, Chenango, Cortland, Herkimer, Jefferson, Lewis, Madison, Oneida, Onondaga, Oswego, St. Lawrence, Tioga, Tompkins $450 Long Island Nassau, Suffolk $1,393 NYC Bronx, Kings, Manhattan, Queens, Richmond $1,535 (up from 1,451 in 2020) Northeastern Albany, Clinton, Columbia, Delaware, Essex, Franklin, Fulton, Greene, Hamilton, Montgomery, Otsego, Rensselaer, Saratoga, Schenectady, Schoharie, Warren, Washington $524 North Metropolitan Dutchess, Orange, Putnam, Rockland, Sullivan, Ulster, Westchester $1,075 Rochester Chemung, Livingston, Monroe, Ontario, Schuyler, Seneca, Steuben, Wayne, Yates $469 Western Allegany, Cattaraugus, Chautauqua, Erie, Genesee, Niagara, Orleans, Wyoming $413 Past rates published as follows, available on DOH website 2021 rates published in Attachment I to GIS 20 MA/13 -- 2021 Medicaid Levels and Other Updates 2020 rates published in Attachment I to GIS 19 MA/12 – 2020 Medicaid Levels and Other Updates 2019 rates published in Attachment 1 to GIS 18/MA015 - 2019 Medicaid Levels and Other Updates 2018 rates published in GIS 17 MA/020 - 2018 Medicaid kamagra reviews forum Levels and Other Updates. The guidance on how the standardized amount of the disregard is calculated is found in NYS DOH 12- ADM-05. 2017 rate -- GIS 16 MA/018 - 2016 Medicaid Only Income and Resource Levels and Spousal Impoverishment Standards Attachment 12016 rate -- GIS 15-MA/0212015 rate -- Were not posted by DOH but were updated in WMS.

2015 kamagra reviews forum Central $382 Long Island $1,147 NYC $1,001 Northeastern $440 N. Metropolitan $791 Rochester $388 Western $336 2014 rate -- GIS-14-MA/017 HOW DOES IT WORK?. Here is a sample budget for a single person in NYC with Social Security income of $2,386/month paying a Medigap premium of $261/mo. Gross monthly income $2,575.50 DEDUCT Health insurance premiums (Medicare Part B) - 135.50 (Medigap) - 261.00 DEDUCT Unearned income disregard - 20 DEDUCT Shelter deduction (NYC—2019) - 1,300 DEDUCT Income limit kamagra reviews forum for single (2019) - 859 Excess income or Spend-down $0 WITH NO SPEND-DOWN, May NOT NEED POOLED TRUST!. HOW TO OBTAIN THE HOUSING DISREGARD.

When you are ready to leave the nursing home or adult home, or soon after you leave, you or your MLTC plan must request that your local Medicaid program change your Medicaid budget to give you the Housing Disregard. See September 2018 NYS DOH Medicaid Update that requires MLTC plan to help kamagra reviews forum you ask for it. The procedures in NYC are explained in this Troubleshooting guide. In NYC, submit the application with the MAP-751W (check off "Budgeting Changes" and "Special Housing Standard"). (The MAP-751W is also posted in languages other than English in this link.

(Updated 3-15-2021.)) NYC Medicaid program prefers that your MLTC plan file the request, using Form MAP-3057E - Special income housing Expenses NH-MLTC.pdf and Form MAP-3047B - MLTC/NHED Cover Sheet Form MAP-259f (revised 7-31-18)(page 7 of PDF)(DIscharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard. GOVERNMENT DIRECTIVES (beginning with oldest). NYS DOH 12- ADM-05 - Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility who Enroll into the Managed Long Term Care (MLTC) Program Attachment II - OHIP-0057 - Notice of Intent to Change Medicaid Coverage, (Recipient Discharged from a Skilled Nursing Facility and Enrolled in a Managed Long Term Care Plan) Attachment III - Attachment III – OHIP-0058 - Notice of Intent to Change Medicaid Coverage, (Recipient Disenrolled from a Managed Long Term Care Plan, No Special Income Standard) MLTC Policy 13.02. MLTC Housing Disregard NYC HRA Medicaid Alert Special Income Standard for housing expenses NH-MLTC 2-9-2013.pdf 2018-07-28 HRA MICSA ALERT Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility and who Enroll into the MLTC Program - update on previous policy. References Form MAP-259f (revised 7-31-18)(page 7 of PDF)(Discharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard.

GIS 18 MA/012 - Special Income Standard for Housing Expenses for Certain Managed Long-Term Care Enrollees Who are Discharged from a Nursing Home issued Sept. 28, 2018 - this finally implements the most recent Special Terms &. Conditions of the CMS 1115 Waiver that governs the MLTC program, dated Jan. 19, 2017. The section on this income standard is at pages 26-27.

In these revised ST&C, this special income standard applies to people who were in a NH or adult home paid by Medicaid and "who enroll into or remain enrolled in the MLTC program in order to receive community based long term services and supports" and to those in a NH who were required to enroll into MLTC because of "...the mandatory Nursing Facility transition, and subsequently able to be discharged to the community from the nursing facility, with the services of MLTC program in place." September 2018 DOH Medicaid Update - explains this benefit to medical providers (nursing homes, MLTC plans, home care agencies, adult home operators, and requires them to identify potential individuals who could benefit and help them apply - described here..

19 in school) 138% FPL*** can you get kamagra over the counter Children <. 5 and pregnant women have HIGHER LIMITS than shown ESSENTIAL PLAN* For MAGI-eligible people over MAGI income limit up to 200% FPL No long term care. See info here 1 2 1 2 3 1 2 Income $884 (up from $875 in 2020) $1300 (up from $1,284 in 2020) $1,482 $2,004 $2,526 $2,146 $2,903 Resources $15,900 (up from $15,750 in 2020) $23,400 (up from $23,100 in 2020) NO LIMIT** NO LIMIT 2020 levels are in GIS 19 MA/12 – 2020 Medicaid Levels and Other Updates and attachments here * MAGI and ESSENTIAL plan levels are based on Federal Poverty Levels, which are not released until later in 2021. 2020 levels can you get kamagra over the counter are used until then.

NEED TO KNOW PAST MEDICAID INCOME AND RESOURCE LEVELS?. WHAT IS THE HOUSEHOLD SIZE?. See can you get kamagra over the counter rules here. HOW TO READ THE HRA Medicaid Levels chart - Boxes 1 and 2 are NON-MAGI Income and Resource levels -- Age 65+, Blind or Disabled and other adults who need to use "spend-down" because they are over the MAGI income levels.

Box 10 on page 3 are the MAGI income levels -- The Affordable Care Act changed the rules for Medicaid income eligibility for many BUT NOT ALL New Yorkers. People in the "MAGI" category - those NOT on Medicare -- have expanded eligibility up to 138% of the Federal Poverty Line, so may now qualify for Medicaid even if they were not eligible before, or may now be eligible for Medicaid without a can you get kamagra over the counter "spend-down." They have NO resource limit. Box 3 on page 1 is Spousal Impoverishment levels for Managed Long Term Care &. Nursing Homes and Box 8 has the Transfer Penalty rates for nursing home eligibility Box 4 has Medicaid Buy-In for Working People with Disabilities Under Age 65 (still 2017 levels til April 2018) Box 6 are Medicare Savings Program levels (will be updated in April 2018) MAGI INCOME LEVEL of 138% FPL applies to most adults who are not disabled and who do not have Medicare, AND can also apply to adults with Medicare if they have a dependent child/relative under age 18 or under 19 if in school.

42 C.F.R can you get kamagra over the counter. § 435.4. Certain populations have an even higher income limit - 224% FPL for pregnant women and babies <. Age 1, can you get kamagra over the counter 154% FPL for children age 1 - 19.

CAUTION. What is counted as income may not be what you think. For the NON-MAGI Disabled/Aged 65+/Blind, income will still be determined by the can you get kamagra over the counter same rules as before, explained in this outline and these charts on income disregards. However, for the MAGI population - which is virtually everyone under age 65 who is not on Medicare - their income will now be determined under new rules, based on federal income tax concepts - called "Modifed Adjusted Gross Income" (MAGI).

There are good changes and bad changes. GOOD can you get kamagra over the counter. Veteran's benefits, Workers compensation, and gifts from family or others no longer count as income. BAD.

There is no more "spousal" or parental can you get kamagra over the counter refusal for this population (but there still is for the Disabled/Aged/Blind.) and some other rules. For all of the rules see. ALSO SEE 2018 Manual on Lump Sums and Impact on Public Benefits - with resource rules HOW TO DETERMINE SIZE OF HOUSEHOLD TO IDENTIFY WHICH INCOME LIMIT APPLIES The income limits increase with the "household size." In other words, the income limit for a family of 5 may be higher than the income limit for a single person. HOWEVER, Medicaid rules about how to calculate the household size are not intuitive or even logical can you get kamagra over the counter.

There are different rules depending on the "category" of the person seeking Medicaid. Here are the 2 basic categories and the rules for calculating their household size. People who are Disabled, Aged 65+ can you get kamagra over the counter or Blind - "DAB" or "SSI-Related" Category -- NON-MAGI - See this chart for their household size. These same rules apply to the Medicare Savings Program, with some exceptions explained in this article.

Everyone else -- MAGI - All children and adults under age 65, including people with disabilities who are not yet on Medicare -- this is the new "MAGI" population. Their household size can you get kamagra over the counter will be determined using federal income tax rules, which are very complicated. New rule is explained in State's directive 13 ADM-03 - Medicaid Eligibility Changes under the Affordable Care Act (ACA) of 2010 (PDF) pp. 8-10 of the PDF, This PowerPoint by NYLAG on MAGI Budgeting attempts to explain the new MAGI budgeting, including how to determine the Household Size.

See slides 28-49 can you get kamagra over the counter. Also seeLegal Aid Society and Empire Justice Center materials OLD RULE used until end of 2013 -- Count the person(s) applying for Medicaid who live together, plus any of their legally responsible relatives who do not receive SNA, ADC, or SSI and reside with an applicant/recipient. Spouses or legally responsible for one another, and parents are legally responsible for their children under age 21 (though if the child is disabled, use the rule in the 1st "DAB" category. Under this rule, a child may be excluded from the household if that child's income causes can you get kamagra over the counter other family members to lose Medicaid eligibility.

See 18 NYCRR 360-4.2, MRG p. 573, NYS GIS 2000 MA-007 CAUTION. Different people in the same household may be in different "categories" and hence can you get kamagra over the counter have different household sizes AND Medicaid income and resource limits. If a man is age 67 and has Medicare and his wife is age 62 and not disabled or blind, the husband's household size for Medicaid is determined under Category 1/ Non-MAGI above and his wife's is under Category 2/MAGI.

The following programs were available prior to 2014, but are now discontinued because they are folded into MAGI Medicaid. Prenatal Care Assistance Program (PCAP) was can you get kamagra over the counter Medicaid for pregnant women and children under age 19, with higher income limits for pregnant woman and infants under one year (200% FPL for pregnant women receiving perinatal coverage only not full Medicaid) than for children ages 1-18 (133% FPL). Medicaid for adults between ages 21-65 who are not disabled and without children under 21 in the household. It was sometimes known as "S/CC" category for Singles and Childless Couples.

This category had lower income limits than DAB/ADC-related, but can you get kamagra over the counter had no asset limits. It did not allow "spend down" of excess income. This category has now been subsumed under the new MAGI adult group whose limit is now raised to 138% FPL. Family Health Plus - this was an expansion of Medicaid to families with income up to 150% FPL and for childless adults can you get kamagra over the counter up to 100% FPL.

This has now been folded into the new MAGI adult group whose limit is 138% FPL. For applicants between 138%-150% FPL, they will be eligible for a new program where Medicaid will subsidize their purchase of Qualified Health Plans on the Exchange. PAST INCOME can you get kamagra over the counter &. RESOURCE LEVELS -- Past Medicaid income and resource levels in NYS are shown on these oldNYC HRA charts for 2001 through 2019, in chronological order.

These include Medicaid levels for MAGI and non-MAGI populations, Child Health Plus, MBI-WPD, Medicare Savings Programs and other public health programs in NYS. This article was authored by can you get kamagra over the counter the Evelyn Frank Legal Resources Program of New York Legal Assistance Group.A huge barrier to people returning to the community from nursing homes is the high cost of housing. One way New York State is trying to address that barrier is with the Special Housing Disregard that allows certain members of Managed Long Term Care or FIDA plans to keep more of their income to pay for rent or other shelter costs, rather than having to "spend down" their "excess income" or spend-down on the cost of Medicaid home care. The special income standard for housing expenses helps pay for housing expenses to help certain nursing home or adult home residents to safely transition back to the community with MLTC.

Originally it was just for can you get kamagra over the counter former nursing home residents but in 2014 it was expanded to include people who lived in adult homes. GIS 14/MA-017 Since you are allowed to keep more of your income, you may no longer need to use a pooled trust. KNOW YOUR RIGHTS - FACT SHEET on THREE ways to Reduce Spend-down, including this Special Income Standard. September 2018 NEWS -- Those already enrolled in MLTC plans before they are admitted to a nursing home or adult can you get kamagra over the counter home may obtain this budgeting upon discharge, if they meet the other criteria below.

"How nursing home administrators, adult home operators and MLTC plans should identify individuals who are eligible for the special income standard" and explains their duties to identify eligible individuals, and the MLTC plan must notify the local DSS that the individual may qualify. "Nursing home administrators, nursing home discharge planning staff, adult home operators and MLTC health plans are encouraged to identify individuals who may qualify for the special income standard, if they can be safely discharged back to the community from a nursing home and enroll in, or remain enrolled in, an MLTC plan. Once an individual has been accepted into an MLTC plan, the MLTC plan must notify the individual's local district of social services that the transition has occurred can you get kamagra over the counter and that the individual may qualify for the special income standard. The special income standard will be effective upon enrollment into the MLTC plan, or, for nursing home residents already enrolled in an MLTC plan, the month of discharge to the community.

Questions regarding the special income standard may be directed to DOH at 518-474-8887. Who is eligible for this special can you get kamagra over the counter income standard?. must be age 18+, must have been in a nursing home or an adult home for 30 days or more, must have had Medicaid pay toward the nursing home care, and must enroll in or REMAIN ENROLLED IN a Managed Long Term Care (MLTC) plan or FIDA plan upon leaving the nursing home or adult home must have a housing expense if married, spouse may not receive a "spousal impoverishment" allowance once the individual is enrolled in MLTC. How much is the allowance?.

The rates can you get kamagra over the counter vary by region and change yearly. Region Counties Deduction (2021) Central Broome, Cayuga, Chenango, Cortland, Herkimer, Jefferson, Lewis, Madison, Oneida, Onondaga, Oswego, St. Lawrence, Tioga, Tompkins $450 Long Island Nassau, Suffolk $1,393 NYC Bronx, Kings, Manhattan, Queens, Richmond $1,535 (up from 1,451 in 2020) Northeastern Albany, Clinton, Columbia, Delaware, Essex, Franklin, Fulton, Greene, Hamilton, Montgomery, Otsego, Rensselaer, Saratoga, Schenectady, Schoharie, Warren, Washington $524 North Metropolitan Dutchess, Orange, Putnam, Rockland, Sullivan, Ulster, Westchester $1,075 Rochester Chemung, Livingston, Monroe, Ontario, Schuyler, Seneca, Steuben, Wayne, Yates $469 Western Allegany, Cattaraugus, Chautauqua, Erie, Genesee, Niagara, Orleans, Wyoming $413 Past rates published as follows, available on DOH website 2021 rates published in Attachment I to GIS 20 MA/13 -- 2021 Medicaid Levels and Other Updates 2020 rates published in Attachment I to GIS 19 MA/12 – 2020 Medicaid Levels and Other Updates 2019 rates published in Attachment 1 to GIS 18/MA015 - 2019 Medicaid Levels and Other Updates 2018 rates published in GIS 17 MA/020 - 2018 Medicaid Levels and Other Updates. The guidance on how the standardized amount of the disregard can you get kamagra over the counter is calculated is found in NYS DOH 12- ADM-05.

2017 rate -- GIS 16 MA/018 - 2016 Medicaid Only Income and Resource Levels and Spousal Impoverishment Standards Attachment 12016 rate -- GIS 15-MA/0212015 rate -- Were not posted by DOH but were updated in WMS. 2015 Central $382 Long Island $1,147 NYC $1,001 Northeastern $440 N. Metropolitan $791 Rochester $388 Western $336 2014 rate -- GIS-14-MA/017 HOW DOES IT WORK?. Here is a sample budget for a single person in NYC with Social Security income of $2,386/month paying a Medigap premium of $261/mo.

Gross monthly income $2,575.50 DEDUCT Health insurance premiums (Medicare Part B) - 135.50 (Medigap) - 261.00 DEDUCT Unearned income disregard - 20 DEDUCT Shelter deduction (NYC—2019) - 1,300 DEDUCT Income limit for single (2019) - 859 Excess income or Spend-down $0 WITH NO SPEND-DOWN, May NOT NEED POOLED TRUST!. HOW TO OBTAIN THE HOUSING DISREGARD. When you are ready to leave the nursing home or adult home, or soon after you leave, you or your MLTC plan must request that your local Medicaid program change your Medicaid budget to give you the Housing Disregard. See September 2018 NYS DOH Medicaid Update that requires MLTC plan to help you ask for it.

The procedures in NYC are explained in this Troubleshooting guide. In NYC, submit the application with the MAP-751W (check off "Budgeting Changes" and "Special Housing Standard"). (The MAP-751W is also posted in languages other than English in this link. (Updated 3-15-2021.)) NYC Medicaid program prefers that your MLTC plan file the request, using Form MAP-3057E - Special income housing Expenses NH-MLTC.pdf and Form MAP-3047B - MLTC/NHED Cover Sheet Form MAP-259f (revised 7-31-18)(page 7 of PDF)(DIscharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard.

GOVERNMENT DIRECTIVES (beginning with oldest). NYS DOH 12- ADM-05 - Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility who Enroll into the Managed Long Term Care (MLTC) Program Attachment II - OHIP-0057 - Notice of Intent to Change Medicaid Coverage, (Recipient Discharged from a Skilled Nursing Facility and Enrolled in a Managed Long Term Care Plan) Attachment III - Attachment III – OHIP-0058 - Notice of Intent to Change Medicaid Coverage, (Recipient Disenrolled from a Managed Long Term Care Plan, No Special Income Standard) MLTC Policy 13.02. MLTC Housing Disregard NYC HRA Medicaid Alert Special Income Standard for housing expenses NH-MLTC 2-9-2013.pdf 2018-07-28 HRA MICSA ALERT Special Income Standard for Housing Expenses for Individuals Discharged from a Nursing Facility and who Enroll into the MLTC Program - update on previous policy. References Form MAP-259f (revised 7-31-18)(page 7 of PDF)(Discharge Notice) - NH must file with HRA upon discharge, certifying resident was informed of availability of this disregard.

GIS 18 MA/012 - Special Income Standard for Housing Expenses for Certain Managed Long-Term Care Enrollees Who are Discharged from a Nursing Home issued Sept. 28, 2018 - this finally implements the most recent Special Terms &. Conditions of the CMS 1115 Waiver that governs the MLTC program, dated Jan. 19, 2017.

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Do not take Kamagra with any of the following:

  • cisapride
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  • nitrates like amyl nitrite, isosorbide dinitrate, isosorbide mononitrate, nitroglycerin
  • nitroprusside
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Kamagra may also interact with the following:

  • certain drugs for high blood pressure
  • certain drugs for the treatment of HIV or AIDS
  • certain drugs used for fungal or yeast s, like fluconazole, itraconazole, ketoconazole, and voriconazole
  • cimetidine
  • erythromycin
  • rifampin

This list may not describe all possible interactions. Give your health care providers a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

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Credit kamagra 100mg oral jelly price viagra kamagra online. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of viagra kamagra online permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb.

Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged viagra kamagra online arteries. During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence viagra kamagra online of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition.

In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate viagra kamagra online to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls. Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. €œThe cause of the link between the two viagra kamagra online conditions remains unclear,” she says.

However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with viagra kamagra online excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition. The other viagra kamagra online authors on this paper were Ginette A.

Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit. The New England Journal of Medicine Share Fast Facts This study clears up how big an effect the mutational burden has viagra kamagra online on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumor’s DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors.

- Click to Tweet viagra kamagra online The “mutational burden,” or the number of mutations present in a tumor’s DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer Center researchers shows. The finding, published in the Dec. 21 New England Journal viagra kamagra online of Medicine, could be used to guide future clinical trials for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells.

As a result, the drugs buy kamagra jelly online cause the immune system to fight cancer in the same way that it would fight an . These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma viagra kamagra online and lung cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma. The mutational burden of certain tumor types has previously been proposed viagra kamagra online as an explanation for why certain cancers respond better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow.

Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on outcomes viagra kamagra online to immune checkpoint inhibitors across many different cancer types was unclear. To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of thousands of tumor samples from patients viagra kamagra online with different tumor types.

Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation. The higher a cancer type’s mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences in how well cancers responded to immune checkpoint inhibitors could viagra kamagra online be explained by the mutational burden of that cancer. €œThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive.

It’s one viagra kamagra online of those things that doesn’t sound right when you hear it,” says Hopkins. €œBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.” Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have a moderate number of mutations yet responds extremely well to checkpoint viagra kamagra online inhibitors. However, he explains, this cancer type is often caused by a kamagra, which seems to encourage a strong immune response despite the cancer’s lower mutational burden.

In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help viagra kamagra online guide clinical trials to test checkpoint inhibitors on cancer types for which these drugs haven’t yet been tried. Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of viagra kamagra online immunotherapy drugs.

€œThe end goal is precision medicine—moving beyond what’s true for big groups of patients to see whether we can use this information to help any given patient,” he says. Yarchoan receives funding viagra kamagra online from the Norman &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

Credit. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of permanent alopecia in this population. The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb.

Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries. During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over. The prevalence of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition.

In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids. The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls. Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. €œThe cause of the link between the two conditions remains unclear,” she says.

However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition. The other authors on this paper were Ginette A.

Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit. The New England Journal of Medicine Share Fast Facts This study clears up how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumor’s DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors.

- Click to Tweet The “mutational burden,” or the number of mutations present in a tumor’s DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer Center researchers shows. The finding, published in the Dec. 21 New England Journal of Medicine, could be used to guide future clinical trials for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells.

As a result, the drugs cause the immune system to fight cancer in the same way that it would fight an . These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma and lung cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma. The mutational burden of certain tumor types has previously been proposed as an explanation for why certain cancers respond better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow.

Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types was unclear. To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of thousands of tumor samples from patients with different tumor types.

Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation. The higher a cancer type’s mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences in how well cancers responded to immune checkpoint inhibitors could be explained by the mutational burden of that cancer. €œThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive.

It’s one of those things that doesn’t sound right when you hear it,” says Hopkins. €œBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.” Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have a moderate number of mutations yet responds extremely well to checkpoint inhibitors. However, he explains, this cancer type is often caused by a kamagra, which seems to encourage a strong immune response despite the cancer’s lower mutational burden.

In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help guide clinical trials to test checkpoint inhibitors on cancer types for which these drugs haven’t yet been tried. Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of immunotherapy drugs.

€œThe end goal is precision medicine—moving beyond what’s true for big groups of patients to see whether we can use this information to help any given patient,” he says. Yarchoan receives funding from the Norman &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

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IntroductionGastric cancer (GC) ranks as the fifth most commonly diagnosed and the third deadliest cancer worldwide, with a 5-year overall survival rate of less than 25%.1–3 The two main histotypes, intestinal and diffuse, are recognised by distinct morphological, molecular, aetiological, clinical and epidemiological features.4–6While most GCs are sporadic, 10% show familial kamagra gel oral clustering. Among these, only 1%–3% are thought to be hereditary, falling into one of the following syndromes. Hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), and familial intestinal gastric cancer (FIGC).7–9 Germline mutations and deletions within the E-cadherin gene (CDH1) are the main cause of HDGC and affect 14%–40% of families.10–12 Additionally, while α-E-catenin gene (CTNNA1) mutations have been proven to cause HDGC, germline variants in homologous recombination DNA repair genes, such as PALB2, await confirmation as potential causes of disease in mutation-negative HDGC families.13–15 Concerning GAPPS, APC promoter 1B point mutations are the underlying cause of this syndrome in several families.16 Unlike HDGC and GAPPS, FIGC remains genetically unexplained, despite the recent report of PALB2 germline mutations in three individuals with intestinal tumours but lacking family history of GC.14 17FIGC is characterised by an autosomal dominant inheritance pattern of intestinal gastric cancer (IGC), without gastric polyposis, and is defined according to GC incidence, as agreed by the International Gastric Cancer Linkage Consortium.9 Therefore, in high incidence countries, the diagnostic criteria is analogous to the Amsterdam criteria for hereditary non-polyposis colorectal cancer (HNPCC). At least three relatives should have IGC and one kamagra gel oral of them should be a first-degree relative of the other two. At least two successive generations should be affected.

And in one of the relatives, GC should be diagnosed before the age of 50. In countries kamagra gel oral with low incidence, the following criteria are used. At least two first-degree relatives (FDR) or second-degree relatives (SDR) affected by IGC, one diagnosed before the age of 50. Or three or more relatives with IGC at any age.9 Because no novel data exist supporting familial aggregation of IGC, no specific tumour spectrum has been defined, and no data support a particular age of onset. Hence, the kamagra gel oral above criteria have never been revisited or validated.

Therefore, these families are often neglected and rarely followed in oncogenetic consultations.GC also develops in the context of other inherited cancer predisposition syndromes.18 In particular, GC has been identified in the tumour spectrum of Lynch syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, familial adenomatous polyposis, juvenile polyposis, and hereditary breast and ovarian cancer, among others.19–22 Therefore, genes causing hereditary cancer susceptibility syndromes, even if only slightly associated with GC susceptibility, would be good candidates to test as potential FIGC causal genes.Herein, we used a next-generation sequencing approach to interrogate a panel of genes implicated in upper gastrointestinal tract cancer, or in cancer susceptibility syndromes, across 50 probands with familial aggregation of IGC from Tuscany, a region from Italy with high incidence of GC.23 The access to a highly homogeneous FIGC cohort, the largest ever studied, and its comparison with an HDGC series and a cohort of sporadic intestinal gastric cancer (SIGC) allowed us to define three objectives and to extend the current knowledge on FIGC predisposition. (1) characterise the age of cancer onset and disease spectrum of our FIGC cohort. (2) search for evidence for a Mendelian and monogenic kamagra gel oral pattern of inheritance. And (3) search for evidence of alternative oligogenic/polygenic modes of inheritance.Herein, we gathered evidence that FIGC is likely a genetically determined, GC-predisposing disease, different at the clinical, germline and somatic levels from SIGC and HDGC. We further proposed the first testing criteria for FIGC families.MethodsPatient selectionFifty FIGC and 17 HDGC-CDH1 mutation-negative probands were admitted at the Division of General Surgery and Surgical Oncology, University of Siena, Italy.

The selection of FIGC families kamagra gel oral was based on the following criteria. (1) proband presenting with GC of intestinal histology. (2) familial aggregation of GC. (3) family kamagra gel oral history of cancer, other than gastric. (4) negative genetic test for germline CDH1 coding sequence mutations (exclusion of HDGC).

And (5) negative genetic test for germline for the promoter 1B of APC (exclusion of GAPPS). The 17 HDGC probands were negative for CDH1 germline coding kamagra gel oral mutations and selected as a control group. Forty-seven patients with SIGC were collected in Portugal.Multigene panel sequencing, variant calling and filteringDNA from normal gastric mucosa (germline) and tumour tissue from 50 FIGC and 17 HDGC-CDH1 mutation-negative probands were sequenced using three Illumina MiSeq custom panels. TruSeq Custom Amplicon Assay 1, TruSeq Custom Amplicon Assay 2 and Nextera custom panel (online supplementary table 1). The selection of genes deposited in each panel was based kamagra gel oral on their implication in upper gastrointestinal tract cancers or in cancer susceptibility syndromes identified through literature review (online supplementary table 2).

FASTQ files were aligned to the RefSeq Human Genome GRCh38 using bwa-mem, and variants were called using Samtools.24 25 Called variants were defined as germline or somatic by normal-tumour pair comparison and annotated with Ensembl and Catalogue Of Somatic Mutations In Cancer (COSMIC (FATHMM- Functional Analysis through Hidden Markov Models).26 27 High-quality (HQ) germline or somatic variants were defined as presenting ≥20 reads per allele and genotype quality ≥90 and call quality ≥100. Next, all single nucleotide polymorphism database (dbSNP) identifiers available for FIGC germline variants (regardless of quality criteria) were screened in four European populations from 1000 Genomes. (1) 107 normal individuals from Tuscany (Italy, TSI) kamagra gel oral. (2) 91 normal individuals from Great Britain (GBR). (3) 99 normal individuals from Finland (FIN).

And (4) 107 normal individuals from Spain (IBS).28 Germline variants without dbSNP identifiers available in the 1000 Genomes were screened using Ensembl VEP for kamagra gel oral truncating consequences. Detected truncating variants presented on average less than four reads, that is, were of low quality and discarded. FIGC germline, rare HQ exclusive variants were selected if they (1) displayed genotypes in FIGCs distinct from GBR, FIN and IBS populations and below 1% in the TSI population. (2) presented kamagra gel oral ≥20 reads per allele, genotype quality ≥90 and call quality ≥100. (3) displayed genotypes distinct from HDGCs and SIGCs.

And (4) presented allele frequency in ExAC and gnomAD populations below 1%.29Supplemental materialSupplemental materialValidation of FIGC germline, rare HQ exclusive variants by Sanger sequencingTwelve out of 32 FIGC germline, rare HQ exclusive variants were validated by PCR-Sanger sequencing. Briefly, 20–50 ng kamagra gel oral of DNA from normal and matched tumour was amplified using Multiplex PCR Kit (Qiagen) and custom primers flanking each variant. PCR products were purified with ExoSAP-IT Express (Applied Biosystems) and sequenced on an ABI3100 Genetic Analyzer using BigDye Terminator V.3.1 Cycle Sequencing Kit (Applied Biosystems).Intronic germline variants were analysed using the splice site prediction software NetGene2 V.2.4.30Somatic second-hit analysisLoss of heterozygosity (LOH) and somatic second mutations were determined by calculating the variant allele frequency (VAF) and screening genes with FIGC germline, rare HQ exclusive variants, respectively. In particular, VAF was calculated by dividing the number of reads for the variant allele by the total number of reads both for the normal and for the corresponding tumour samples. LOH was defined when more than 20% increase of VAF over normal was observed.Germline and somatic landscape analysis of 50 FIGC casesFIGC germline and somatic landscapes were analysed kamagra gel oral on a per-variant and per-gene basis, considering the number of FIGC germline, rare HQ exclusive variants detected per proband (0, 1 or >1).

The similarities/differences for the germline and somatic variant and gene landscapes per FIGC class were analysed using unsupervised hierarchical clustering using R package ggplot2 for heatmap and dendrogram construction.31 For somatic variant/gene landscape analysis, FIGC classes were also divided according to microsatellite instable status and compared using analysis of variance statistics with R. The number of microsatellite instable (MSI) and microsatellite stable (MSS) tumours per FIGC class was compared using Pearson’s χ2 test.Comparison of germline and somatic landscapes for FIGC, SIGC and HDGCVCF files obtained from whole genome sequencing (Complete Genomics platform) of 47 SIGCs and VCF files of 17 HDGCs were analysed to detect germline and somatic variants, using the same germline/somatic variant definition and sequencing quality criteria previously described for FIGC cases. Of note, due to the differential resolution between whole genome sequencing and targeted sequencing, only variants detected in the 47 kamagra gel oral SIGCs in the same regions targeted by the custom panels were selected for downstream analysis.Germline and somatic landscapes of FIGC, SIGC and HDGC cases were performed on a per-gene basis. Each gene was classified as presenting 0 or ≥1 germline/somatic variants. Germline and somatic joint landscape was defined by counting the number of germline and somatic variants for each gene, which was classified as displaying no germline or somatic variants.

‰¥1 germline kamagra gel oral and 0 somatic variants. 0 germline and ≥1 somatic variants. Or ≥1 germline and ≥1 somatic variants. Results were kamagra gel oral plotted in a heatmap and a dendrogram, and principal component analysis was performed using R. The frequency of genes with germline/somatic variants in FIGCs, SIGCs and HDGCs was calculated, and genes with a frequency difference ≥50% were represented in a bar plot and in a heatmap using R.ResultsAge of onset and disease spectrum in FIGCOf the 50 FIGC probands (table 1), 18 were female and 32 were male.

The mean age at diagnosis was 71.8±8.0 years. From the 50 families depicted in table 1, kamagra gel oral 5 (10%) had >1 FDR with GC (mean age. 68.8±7.5 years). 14 (28%) had concomitantly FDR and SDR or FDR and third-degree relatives with GC (mean age. 68.7±8.4 years) kamagra gel oral.

29 (58%) had a single FDR with GC (mean age. 73.6±7.2 years). And 2 kamagra gel oral (4%) had only SDR affected with GC (mean. 74±15.6 years).View this table:Table 1 Clinical characteristics of FIGC probands and their family historyWhen considering the disease spectrum in these FIGC families, 19 different phenotypes have been observed affecting 208 family members (figure 1, table 1). The most prevalent phenotype was GC, detected in 138 of 208 (66.3%) family members.

50 probands with IGC and 88 additional patients with unknown kamagra gel oral GC histology. The second and third most prevalent phenotypes were colorectal/colon and breast cancer observed in nine patients from seven families. Of note, eight patients from six families were affected with gastric ulcer, a non-cancerous lesion, which is the third most common disease phenotype in this cohort. Besides these phenotypes, positive history of lung kamagra gel oral cancer was observed in six families. Leukaemia in five families.

Laryngotracheal and hepatobiliary cancer in four families. Osteosarcoma in kamagra gel oral three families. Prostate, liver, melanoma, gynaecological, bladder and brain cancers were detected in two families each. And thyroid, kidney and oral cancer in one family. Moreover, 11 families had relatives affected by an unidentified type of cancer that often coexisted with other cancer types such as colon, leukaemia, breast, liver and prostate.Disease spectrum of FIGC kamagra gel oral families.

The disease spectrum of FIGC encompassed 19 different phenotypes affecting 208 family members. The most prevalent phenotype was gastric cancer, detected in 138 of 208, followed by colorectal/colon and breast cancers in 9 of 208. FIGC, familial intestinal gastric kamagra gel oral cancer." data-icon-position data-hide-link-title="0">Figure 1 Disease spectrum of FIGC families. The disease spectrum of FIGC encompassed 19 different phenotypes affecting 208 family members. The most prevalent phenotype was gastric cancer, detected in 138 of 208, followed by colorectal/colon and breast cancers in 9 of 208.

FIGC, familial intestinal gastric cancer.Germline and somatic variant discovery across kamagra gel oral FIGC probandsMultigene panel sequencing analysis of normal-tumour DNA of 50 FIGC probands revealed a total of 10 062 variants (≥1 read covering the alternative allele). Of these, 4998 (49.7%) were detected in normal DNA and defined as germline variants. The remaining 5064 (50.3%) were called as somatic variants due to exclusive presence in tumour DNA. We started by exploring germline kamagra gel oral variants, focusing on rare variants in single genes (monogenic hypothesis) or variants co-occurring in several genes, regardless of their population frequency (oligogenic/polygenic hypothesis).Monogenic hypothesis. FIGC-associated rare germline variants and somatic second-hitsTo identify rare germline FIGC-predisposing variants, we performed a systematic analysis of all germline variants, focusing on their frequency across normal populations and GC cohorts, and sequencing quality.We identified 4998 germline variants in the 50 patients with FIGC (figure 2A).

From the 4998 FIGC germline variants, the genotype frequency of 1038 (20.8%) was available for four 1000 Genomes European populations.28 From the 79.2% of variants absent from 1000 Genomes, only 1.3% (n=53) presented truncating effects, however supported on average by less than four reads, that is, of very low quality and hence confidently discarded. From the 1038 variants present in 1000 Genomes, 121 (11.7%) kamagra gel oral presented genotypes absent from the four populations screened. Of these 121 variants, only 60 presented the abovementioned sequencing quality criteria. From these, 43 variants were exclusively detected in FIGC comparing with HDGC-CDH1 mutation-negative and SIGC cohorts. With regard to the 17 discarded variants, all were found in at least one HDGC proband and none kamagra gel oral in SIGC.90 and a call quality >100).

From these, 43 variants presented the RefSeq genotype in the HDGC-CDH1 mutation-negative and sporadic GC cohorts. A final set of 32 germline, rare and high-quality FIGC-exclusive variants were selected by screening the allele frequency of these variants in all ExAC and gnomAD populations available. (B) Germline variant burden of FIGC families with 0, 1 or >1 rare germline kamagra gel oral variants. P value was determined by ANOVA statistics. (C) Heatmap and dendrogram of 710 HQ FIGC germline variants of FIGC family classes (Z-score normalised expression level.

White, no detected kamagra gel oral variants. Purple, detected variants. (D) Heatmap and dendrogram of 64 genes with the 710 germline variants of FIGC family classes (Z-score normalised expression levels. White, genes with kamagra gel oral no detected variants. Light salmon, genes with a single variant.

Pink, gene carrying 2–5 distinct variants. Purple, gene with 6–10 distinct kamagra gel oral variants. Dark purple, gene with 11–15 distinct variants. ANOVA, analysis of variance. FIGC, familial intestinal gastric kamagra gel oral cancer.

GC, gastric cancer. HDGC, hereditary diffuse gastric cancer. HQ, high-quality." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1029038981" data-figure-caption="Co-occurrence of rare germline variants does not define a specific germline landscape kamagra gel oral. (A) Discovery of FIGC rare germline predisposition variants. A total of 4998 germline variants were detected in normal stomach using multigene panel sequencing.

From these, 1038 were identified by the kamagra gel oral 1000 Genomes Project, and 121 were absent from four distinct normal European populations. Of these 121 variants, only 60 were classified as variants of high quality (with at least 20 reads for each allele, a genotype quality >90 and a call quality >100). From these, 43 variants presented the RefSeq genotype in the HDGC-CDH1 mutation-negative and sporadic GC cohorts. A final kamagra gel oral set of 32 germline, rare and high-quality FIGC-exclusive variants were selected by screening the allele frequency of these variants in all ExAC and gnomAD populations available. (B) Germline variant burden of FIGC families with 0, 1 or >1 rare germline variants.

P value was determined by ANOVA statistics. (C) Heatmap and dendrogram of 710 HQ FIGC germline variants of FIGC family classes (Z-score normalised kamagra gel oral expression level. White, no detected variants. Purple, detected variants. (D) Heatmap kamagra gel oral and dendrogram of 64 genes with the 710 germline variants of FIGC family classes (Z-score normalised expression levels.

White, genes with no detected variants. Light salmon, genes with a single variant. Pink, gene kamagra gel oral carrying 2–5 distinct variants. Purple, gene with 6–10 distinct variants. Dark purple, gene with 11–15 distinct variants.

ANOVA, analysis of variance kamagra gel oral. FIGC, familial intestinal gastric cancer. GC, gastric cancer. HDGC, hereditary kamagra gel oral diffuse gastric cancer. HQ, high-quality." data-icon-position data-hide-link-title="0">Figure 2 Co-occurrence of rare germline variants does not define a specific germline landscape.

(A) Discovery of FIGC rare germline predisposition variants. A total of 4998 germline variants were detected in normal kamagra gel oral stomach using multigene panel sequencing. From these, 1038 were identified by the 1000 Genomes Project, and 121 were absent from four distinct normal European populations. Of these 121 variants, only 60 were classified as variants of high quality (with at least 20 reads for each allele, a genotype quality >90 and a call quality >100). From these, 43 variants presented the RefSeq genotype in the HDGC-CDH1 mutation-negative kamagra gel oral and sporadic GC cohorts.

A final set of 32 germline, rare and high-quality FIGC-exclusive variants were selected by screening the allele frequency of these variants in all ExAC and gnomAD populations available. (B) Germline variant burden of FIGC families with 0, 1 or >1 rare germline variants. P value was determined by ANOVA kamagra gel oral statistics. (C) Heatmap and dendrogram of 710 HQ FIGC germline variants of FIGC family classes (Z-score normalised expression level. White, no detected variants.

Purple, detected kamagra gel oral variants. (D) Heatmap and dendrogram of 64 genes with the 710 germline variants of FIGC family classes (Z-score normalised expression levels. White, genes with no detected variants. Light salmon, kamagra gel oral genes with a single variant. Pink, gene carrying 2–5 distinct variants.

Purple, gene with 6–10 distinct variants. Dark purple, kamagra gel oral gene with 11–15 distinct variants. ANOVA, analysis of variance. FIGC, familial intestinal gastric cancer. GC, gastric cancer kamagra gel oral.

HDGC, hereditary diffuse gastric cancer. HQ, high-quality.From the 43 germline, rare and HQ FIGC-exclusive variants, 31 (72.1%) displayed very low allele frequency in all ExAC and gnomAD populations (figure 2A, online supplementary table 3), and were present in 21 of 50 (42%) FIGC probands (7 missense, 7 3’untranslated (UTR), 2 5’UTR, 12 intronic and 3 synonymous in 18 genes. Online supplementary kamagra gel oral table 4). Fifteen probands carried a single variant and six exhibited co-occurrence of two or more variants (online supplementary table 5). After excluding variants classified as benign and predicted as intronic, synonymous or not impacting splicing, 12 variants were validated by Sanger sequencing (table 2).Supplemental materialSupplemental materialSupplemental materialView this table:Table 2 FIGC rare germline variants validated by Sanger sequencingA missense variant in PMS1 (c.224C>T), predicted as pathogenic, deleterious and probably damaging by FATHMM, SIFT and PolyPhen, respectively (table 2, online supplementary table 3), was found in family P1 (table 1, online supplementary table 4).

The probands, who developed an MSS IGC at 59 years, had an FDR with GC at 80 and two other FDR and kamagra gel oral SDR with unidentified cancers at 50 and 75 years, respectively. The only supporting evidence for the role of this variant in FIGC was its COSMIC record as somatic in one GC sample (COSM6198026) (online supplementary table 3).The proband of family P27 presented three germline variants of uncertain significance, two in SMAD4 (c.424+5G>A. C.454+38G>C) and one in PRSS1 (c.201-99G>C) (online supplementary table 4). Variants c.424+5G>A in SMAD4 and c.201–99G>C in kamagra gel oral PRSS1 were the only intronic variants predicted to disrupt RNA splicing (table 2, online supplementary tables 3 and 5,). In particular, SMAD4 variant c.424+5G>A decreases the confidence of a donor splice site, which may lead to intron 3 retention, a premature termination codon and generation of a 142 amino acid truncated protein.

On the other hand, PRSS1 variant c.201-99G>C creates a new, high-confidence acceptor splice site within intron 2, which may lead to a truncated 69 amino acid protein. Proband P27 developed an MSS IGC kamagra gel oral at age 64 and had family history of GC, gastric ulcer, laryngotracheal, gynaecological and hepatobiliary cancers (table 1, online supplementary table 4). The presence of these phenotypes seems to exclude juvenile polyposis and hereditary pancreatitis as underlying syndromes of this family, but could support a potential role for SMAD4 together with PRSS1 in FIGC.We then screened the primary tumours of P1 and P27 FIGC probands for somatic second-hit inactivating mechanisms (LOH, somatic mutation) in germline-affected genes. None of the two FIGC probands showed evidence of deleterious somatic variants nor LOH of the wild-type allele of the germline targeted genes (data not shown).Although interesting, these findings are insufficient to support the monogenic hypothesis for FIGC and a potentially causal role for the abovementioned affected genes.Oligogenic/polygenic hypothesis. Co-occurrence of rare germline variants determines somatic landscapes of FIGC tumoursWe kamagra gel oral then proceeded with the oligogenic/polygenic hypothesis, which takes into consideration the co-occurrence of germline variants, regardless of their population frequency, as a risk factor for this disease, which would determine the subsequent somatic events necessary for malignant transformation.We categorised the 50 FIGC probands according to the presence of rare germline variants.

Families with no variants (n=30). Families with a single variant (n=14). And families with multiple kamagra gel oral variants (n=6). To understand the germline and somatic variant burden for each of these three FIGC classes, we applied the previously described quality criteria obtaining 710 HQ germline variants and 344 HQ somatic variants. The average number of HQ germline variants was identical across the three classes of FIGC families (75.7, 77.4 and 74.5 for families without (0), with one (1) or more than one (>1) rare germline variants, respectively.

Figure 2B) kamagra gel oral. Germline landscape unsupervised hierarchical clustering revealed no associations between variants or variant-bearing genes and a particular FIGC family class (figure 2C,D).Concerning the somatic variant burden, no significant differences were observed across the three FIGC classes (15.0, 13.8 and 11.2 for families with 0, 1 or >1 rare germline variants, respectively. Figure 3A). Again, no clustering kamagra gel oral of specific variants/genes and particular FIGC classes was observed (figure 3B,C).1 rare germline variants. P value was determined by ANOVA statistics.

(B) Heatmap and dendrogram of 344 FIGC somatic variants of FIGC family classes (Z-score normalised expression level. White, no kamagra gel oral detected variants. Orange, detected variants. (C) Heatmap and dendrogram of 46 genes with the 344 somatic variants of FIGC family classes (Z-score normalised expression levels. White, gene with no detected variants kamagra gel oral.

Yellow, gene with a single variant. Orange, gene carrying 2–5 distinct variants. Light brown, gene with 6–10 distinct variants kamagra gel oral. Brown, gene with 11–15 distinct variants. (D) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants subdivided according to MSI status.

P value kamagra gel oral was determined by ANOVA statistics. ANOVA, analysis of variance. FIGC, familial intestinal gastric cancer. HQ, high-quality kamagra gel oral. MSI, microsatellite instable.

MSS, microsatellite stable." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1029038981" data-figure-caption="Rare germline variants are not major determinants of FIGC somatic events. (A) Somatic variant burden of FIGC kamagra gel oral families with 0, 1 or >1 rare germline variants. P value was determined by ANOVA statistics. (B) Heatmap and dendrogram of 344 FIGC somatic variants of FIGC family classes (Z-score normalised expression level. White, no detected variants kamagra gel oral.

Orange, detected variants. (C) Heatmap and dendrogram of 46 genes with the 344 somatic variants of FIGC family classes (Z-score normalised expression levels. White, gene kamagra gel oral with no detected variants. Yellow, gene with a single variant. Orange, gene carrying 2–5 distinct variants.

Light brown, gene kamagra gel oral with 6–10 distinct variants. Brown, gene with 11–15 distinct variants. (D) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants subdivided according to MSI status. P value was kamagra gel oral determined by ANOVA statistics. ANOVA, analysis of variance.

FIGC, familial intestinal gastric cancer. HQ, high-quality kamagra gel oral. MSI, microsatellite instable. MSS, microsatellite stable." data-icon-position data-hide-link-title="0">Figure 3 Rare germline variants are not major determinants of FIGC somatic events. (A) Somatic variant kamagra gel oral burden of FIGC families with 0, 1 or >1 rare germline variants.

P value was determined by ANOVA statistics. (B) Heatmap and dendrogram of 344 FIGC somatic variants of FIGC family classes (Z-score normalised expression level. White, no kamagra gel oral detected variants. Orange, detected variants. (C) Heatmap and dendrogram of 46 genes with the 344 somatic variants of FIGC family classes (Z-score normalised expression levels.

White, gene kamagra gel oral with no detected variants. Yellow, gene with a single variant. Orange, gene carrying 2–5 distinct variants. Light brown, kamagra gel oral gene with 6–10 distinct variants. Brown, gene with 11–15 distinct variants.

(D) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants subdivided according to MSI status. P value was determined kamagra gel oral by ANOVA statistics. ANOVA, analysis of variance. FIGC, familial intestinal gastric cancer. HQ, high-quality kamagra gel oral.

MSI, microsatellite instable. MSS, microsatellite stable.We verified that 38% of the FIGC tumours in our series displayed the MSI phenotype, and further investigated whether MSI could influence the somatic variant burden and landscape in families with 0, 1 or >1 rare germline variants. After subdividing each FIGC class according to its MSI status, no significant differences were observed both in terms of somatic variant burden and landscape between kamagra gel oral categories (figure 3B–D). Nevertheless, we observed that among FIGC families with multiple rare germline variants (>1), MSI tumours showed an average number of HQ somatic variants twofold higher than that of MSS tumours (17 vs 10 HQ somatic variants per case, respectively. Figure 3D, online supplementary figure 1A).

This observation prompted us to explore the influence kamagra gel oral of rare germline variants, independently of their number, on tumour instability and consequent somatic variant burden. Despite the lack of statistical significance, we observed an enrichment of MSI tumours in FIGC families carrying rare germline variants comparing with MSI tumours from families lacking rare germline variants (online supplementary figure 1B). Concerning the average of somatic variants, whereas MSI and MSS tumours from FIGC lacking rare germline variants displayed a similar average number, there was a non-significant trend for higher average number of HQ somatic variants in MSI tumours versus MSS tumours from FIGC families with rare germline variants (≥1. Online supplementary figure 1C).Supplemental materialAlthough our data did not support the hypothesis that co-occurrence of rare germline variants is a major determinant of FIGC-related somatic landscapes, these pinpointed a potential correlation between the coexistence of rare and common germline variants, high average number of somatic variants and MSI phenotype in FIGC.FIGC is genetically distinct from SIGC and from HDGC-CDH1 mutation-negativeSince the late age of onset in FIGC probands and their relatives makes it hard to distinguish bona fide FIGCs from SIGCs, we compared the age of onset of FIGC probands with the kamagra gel oral age of onset of a series of SIGC cases. We found that FIGC probands developed GC approximately 10 years earlier than patients with SIGC (p=4.5E-03.

Figure 4E).FIGC is a genetic entity distinct from SIGC. (A) Principal kamagra gel oral component analysis of genes with germline variants. (B) Principal component analysis of genes with somatic variants. (C) Frequency of genes with germline or somatic variants enriched in FIGC cases in comparison with SIGC cases. Purple for genes with germline events and orange kamagra gel oral for genes with somatic events.

(D) Heatmap and dendrogram of a panel of genes with the highest frequency of germline and/or somatic variants in FIGC (n=50) versus SIGC (n=47). (E) Age at diagnosis of FIGC (n=50) and SIGC cases (n=47). (F) Average number of somatic variants detected in FIGC (n=50) and SIGC cases kamagra gel oral (n=47). White, gene with no variants. Purple, gene with germline variants.

Orange, gene kamagra gel oral with somatic variants. Red, gene with germline and somatic variants. P values calculated with Wilcoxon signed-rank test. FIGC, familial kamagra gel oral intestinal gastric cancer. SIGC, sporadic intestinal gastric cancer, PC1, principal component 1.

PC2, principal component 2." data-icon-position data-hide-link-title="0">Figure 4 FIGC is a genetic entity distinct from SIGC. (A) Principal kamagra gel oral component analysis of genes with germline variants. (B) Principal component analysis of genes with somatic variants. (C) Frequency of genes with germline or somatic variants enriched in FIGC cases in comparison with SIGC cases. Purple for genes with germline events kamagra gel oral and orange for genes with somatic events.

(D) Heatmap and dendrogram of a panel of genes with the highest frequency of germline and/or somatic variants in FIGC (n=50) versus SIGC (n=47). (E) Age at diagnosis of FIGC (n=50) and SIGC cases (n=47). (F) Average number of somatic variants detected kamagra gel oral in FIGC (n=50) and SIGC cases (n=47). White, gene with no variants. Purple, gene with germline variants.

Orange, gene with somatic kamagra gel oral variants. Red, gene with germline and somatic variants. P values calculated with Wilcoxon signed-rank test. FIGC, familial intestinal gastric kamagra gel oral cancer. SIGC, sporadic intestinal gastric cancer, PC1, principal component 1.

PC2, principal component 2.We next explored whether these FIGC and SIGC were also distinct at the germline and/or somatic levels. Principal component analysis revealed that certain genes were differentially associated with kamagra gel oral FIGCs and SIGCs (figure 4A,B). Specifically, common germline variants in TP53 were present in more than 50% of FIGC probands, while only 11% of SIGC cases presented these germline variants (figure 4A,C). At the somatic level, the frequency of BRCA2, ATM, FOXF1, FHIT, SDHB, MSH6, CTNNA1 and PXN could distinguish FIGC from SIGC tumours, with more than 50% of FIGC displaying common variants in these genes, as compared with very low frequencies in SIGC (figure 4B,C).By combining all germline and somatic landscapes of 50 FIGCs and 47 SIGCs focusing only on the abovementioned genes, and using unsupervised hierarchical clustering, two main clusters were evidenced separating most FIGCs from SIGCs (figure 4D). Whereas FIGCs carried both germline and somatic variants in TP53, BRCA2, ATM, FOXF1, FHIT, SDHB, MSH6, CTNNA1 and PXN genes, SIGCs lacked TP53 and FHIT germline and somatic variants and mainly presented BRCA2, ATM, FOXF1, SDHB, MSH6, CTNNA1 and PXN somatic variants.Further supporting that FIGC represents a different entity likely evolving for longer than SIGCs is the fact that FIGC tumours presented statistically significantly more somatic common variants than SIGC tumours (p=4.2E-06), even if arising from patients 10 years younger on average (figure 4E,F).To further understand whether FIGC is a genetic entity also distinct from HDGC-CDH1 mutation-negative, we compared the germline and somatic landscapes of 7 FIGCs and 17 HDGCs sequenced with the same Next Generation Sequencing (NGS) panel kamagra gel oral.

We verified that indeed FIGC and HDGC also display considerable differences between germline and somatic landscapes (online supplementary figure 2)(). However, the low number of FIGC cases possible to analyse, which was due to sequencing panel differences, hampers more formal conclusions.Overall, our results suggest that FIGC, rather than a monogenic disease, is likely a polygenic disease with distinctive germline and somatic landscapes from SIGC and HDGC-CDH1-negative.DiscussionFIGC presents an autosomal dominant inheritance pattern of IGC, without gastric polyposis, and has been clinically defined by analogy to the Amsterdam criteria for HNPCC.9 However, lack of novel data supporting familial aggregation of IGC at a given age of onset as well as the non-existence of tumour spectrum descriptions have impeded the redefinition of FIGC testing criteria, useful for identification and management of these families.The primary strength of this study is the use of a large homogeneous cohort of probands with IGC, familial aggregation of GC, detailed personal/family history, age of disease onset and disease spectrum.

At least can you get kamagra over the counter two http://smilingprince.com/bebe-room-in-progress/ successive generations should be affected. And in one of the relatives, GC should be diagnosed before the age of 50. In countries with low incidence, the following criteria are used. At least two can you get kamagra over the counter first-degree relatives (FDR) or second-degree relatives (SDR) affected by IGC, one diagnosed before the age of 50.

Or three or more relatives with IGC at any age.9 Because no novel data exist supporting familial aggregation of IGC, no specific tumour spectrum has been defined, and no data support a particular age of onset. Hence, the above criteria have never been revisited or validated. Therefore, these families are often neglected and rarely followed in oncogenetic consultations.GC also develops in the context of other inherited cancer predisposition syndromes.18 In particular, GC has been identified in the tumour spectrum can you get kamagra over the counter of Lynch syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, familial adenomatous polyposis, juvenile polyposis, and hereditary breast and ovarian cancer, among others.19–22 Therefore, genes causing hereditary cancer susceptibility syndromes, even if only slightly associated with GC susceptibility, would be good candidates to test as potential FIGC causal genes.Herein, we used a next-generation sequencing approach to interrogate a panel of genes implicated in upper gastrointestinal tract cancer, or in cancer susceptibility syndromes, across 50 probands with familial aggregation of IGC from Tuscany, a region from Italy with high incidence of GC.23 The access to a highly homogeneous FIGC cohort, the largest ever studied, and its comparison with an HDGC series and a cohort of sporadic intestinal gastric cancer (SIGC) allowed us to define three objectives and to extend the current knowledge on FIGC predisposition. (1) characterise the age of cancer onset and disease spectrum of our FIGC cohort.

(2) search for evidence for a Mendelian and monogenic pattern of inheritance. And (3) search for evidence of can you get kamagra over the counter alternative oligogenic/polygenic modes of inheritance.Herein, we gathered evidence that FIGC is likely a genetically determined, GC-predisposing disease, different at the clinical, germline and somatic levels from SIGC and HDGC. We further proposed the first testing criteria for FIGC families.MethodsPatient selectionFifty FIGC and 17 HDGC-CDH1 mutation-negative probands were admitted at the Division of General Surgery and Surgical Oncology, University of Siena, Italy. The selection of FIGC families was based on the following criteria.

(1) proband presenting with can you get kamagra over the counter GC of intestinal histology. (2) familial aggregation of GC. (3) family history of cancer, other than gastric. (4) negative genetic test for germline CDH1 coding sequence mutations (exclusion of can you get kamagra over the counter HDGC).

And (5) negative genetic test for germline for the promoter 1B of APC (exclusion of GAPPS). The 17 HDGC probands were negative for CDH1 germline coding mutations and selected as a control group. Forty-seven patients with SIGC were collected in can you get kamagra over the counter Portugal.Multigene panel sequencing, variant calling and filteringDNA from normal gastric mucosa (germline) and tumour tissue from 50 FIGC and 17 HDGC-CDH1 mutation-negative probands were sequenced using three Illumina MiSeq custom panels. TruSeq Custom Amplicon Assay 1, TruSeq Custom Amplicon Assay 2 and Nextera custom panel (online supplementary table 1).

The selection of genes deposited in each panel was based on their implication in upper gastrointestinal tract cancers or in cancer susceptibility syndromes identified through literature review (online supplementary table 2). FASTQ files were aligned to the RefSeq Human Genome GRCh38 using bwa-mem, and variants were called using Samtools.24 25 Called variants were defined as germline or somatic by normal-tumour pair comparison and annotated with Ensembl and Catalogue Of Somatic Mutations can you get kamagra over the counter In Cancer (COSMIC (FATHMM- Functional Analysis through Hidden Markov Models).26 27 High-quality (HQ) germline or somatic variants were defined as presenting ≥20 reads per allele and genotype quality ≥90 and call quality ≥100. Next, all single nucleotide polymorphism database (dbSNP) identifiers available for FIGC germline variants (regardless of quality criteria) were screened in four European populations from 1000 Genomes. (1) 107 normal individuals from Tuscany (Italy, TSI).

(2) 91 normal individuals from can you get kamagra over the counter Great Britain (GBR). (3) 99 normal individuals from Finland (FIN). And (4) 107 normal individuals from Spain (IBS).28 Germline variants without dbSNP identifiers available in the 1000 Genomes were screened using Ensembl VEP for truncating consequences. Detected truncating variants presented on average less than four reads, that is, were of low quality can you get kamagra over the counter and discarded.

FIGC germline, rare HQ exclusive variants were selected if they (1) displayed genotypes in FIGCs distinct from GBR, FIN and IBS populations and below 1% in the TSI population. (2) presented ≥20 reads per allele, genotype quality ≥90 and call quality ≥100. (3) displayed genotypes distinct from HDGCs and SIGCs can you get kamagra over the counter. And (4) presented allele frequency in ExAC and gnomAD populations below 1%.29Supplemental materialSupplemental materialValidation of FIGC germline, rare HQ exclusive variants by Sanger sequencingTwelve out of 32 FIGC germline, rare HQ exclusive variants were validated by PCR-Sanger sequencing.

Briefly, 20–50 ng of DNA from normal and matched tumour was amplified using Multiplex PCR Kit (Qiagen) and custom primers flanking each variant. PCR products were purified with ExoSAP-IT Express (Applied Biosystems) and sequenced on an ABI3100 Genetic Analyzer can you get kamagra over the counter using BigDye Terminator V.3.1 Cycle Sequencing Kit (Applied Biosystems).Intronic germline variants were analysed using the splice site prediction software NetGene2 V.2.4.30Somatic second-hit analysisLoss of heterozygosity (LOH) and somatic second mutations were determined by calculating the variant allele frequency (VAF) and screening genes with FIGC germline, rare HQ exclusive variants, respectively. In particular, VAF was calculated by dividing the number of reads for the variant allele by the total number of reads both for the normal and for the corresponding tumour samples. LOH was defined when more than 20% increase of VAF over normal was observed.Germline and somatic landscape analysis of 50 FIGC casesFIGC germline and somatic landscapes were analysed on a per-variant and per-gene basis, considering the number of FIGC germline, rare HQ exclusive variants detected per proband (0, 1 or >1).

The similarities/differences for the germline and somatic variant and gene landscapes per FIGC class were analysed using unsupervised hierarchical clustering using R package ggplot2 for heatmap and dendrogram construction.31 For can you get kamagra over the counter somatic variant/gene landscape analysis, FIGC classes were also divided according to microsatellite instable status and compared using analysis of variance statistics with R. The number of microsatellite instable (MSI) and microsatellite stable (MSS) tumours per FIGC class was compared using Pearson’s χ2 test.Comparison of germline and somatic landscapes for FIGC, SIGC and HDGCVCF files obtained from whole genome sequencing (Complete Genomics platform) of 47 SIGCs and VCF files of 17 HDGCs were analysed to detect germline and somatic variants, using the same germline/somatic variant definition and sequencing quality criteria previously described for FIGC cases. Of note, due to the differential resolution between whole genome sequencing and targeted sequencing, only variants detected in the 47 SIGCs in the same regions targeted by the custom panels were selected for downstream analysis.Germline and somatic landscapes of FIGC, SIGC and HDGC cases were performed on a per-gene basis. Each gene was can you get kamagra over the counter classified as presenting 0 or ≥1 germline/somatic variants.

Germline and somatic joint landscape was defined by counting the number of germline and somatic variants for each gene, which was classified as displaying no germline or somatic variants. ‰¥1 germline and 0 somatic variants. 0 germline and ≥1 somatic can you get kamagra over the counter variants. Or ≥1 germline and ≥1 somatic variants.

Results were plotted in a heatmap and a dendrogram, and principal component analysis was performed using R. The frequency of genes with germline/somatic variants in FIGCs, SIGCs and HDGCs was calculated, and genes with a frequency difference ≥50% were represented in a bar plot and in a heatmap using can you get kamagra over the counter R.ResultsAge of onset and disease spectrum in FIGCOf the 50 FIGC probands (table 1), 18 were female and 32 were male. The mean age at diagnosis was 71.8±8.0 years. From the 50 families depicted in table 1, 5 (10%) had >1 FDR with GC (mean age.

68.8±7.5 years) can you get kamagra over the counter. 14 (28%) had concomitantly FDR and SDR or FDR and third-degree relatives with GC (mean age. 68.7±8.4 years). 29 (58%) had a single can you get kamagra over the counter FDR with GC (mean age.

73.6±7.2 years). And 2 (4%) had only SDR affected with GC (mean. 74±15.6 years).View this table:Table 1 Clinical characteristics of FIGC probands and their family historyWhen considering the disease spectrum in these FIGC families, 19 different can you get kamagra over the counter phenotypes have been observed affecting 208 family members (figure 1, table 1). The most prevalent phenotype was GC, detected in 138 of 208 (66.3%) family members.

50 probands with IGC and 88 additional patients with unknown GC histology. The second and third most can you get kamagra over the counter prevalent phenotypes were colorectal/colon and breast cancer observed in nine patients from seven families. Of note, eight patients from six families were affected with gastric ulcer, a non-cancerous lesion, which is the third most common disease phenotype in this cohort. Besides these phenotypes, positive history of lung cancer was observed in six families.

Leukaemia in can you get kamagra over the counter five families. Laryngotracheal and hepatobiliary cancer in four families. Osteosarcoma in three families. Prostate, liver, melanoma, gynaecological, bladder and brain cancers were detected in can you get kamagra over the counter two families each.

And thyroid, kidney and oral cancer in one family. Moreover, 11 families had relatives affected by an unidentified type of cancer that often coexisted with other cancer types such as colon, leukaemia, breast, liver and prostate.Disease spectrum of FIGC families. The disease spectrum of FIGC encompassed 19 different phenotypes affecting can you get kamagra over the counter 208 family members. The most prevalent phenotype was gastric cancer, detected in 138 of 208, followed by colorectal/colon and breast cancers in 9 of 208.

FIGC, familial intestinal gastric cancer." data-icon-position data-hide-link-title="0">Figure 1 Disease spectrum of FIGC families. The disease can you get kamagra over the counter spectrum of FIGC encompassed 19 different phenotypes affecting 208 family members. The most prevalent phenotype was gastric cancer, detected in 138 of 208, followed by colorectal/colon and breast cancers in 9 of 208. FIGC, familial intestinal gastric cancer.Germline and somatic variant discovery across FIGC probandsMultigene panel sequencing analysis of normal-tumour DNA of 50 FIGC probands revealed a total of 10 062 variants (≥1 read covering the alternative allele).

Of these, 4998 can you get kamagra over the counter (49.7%) were detected in normal DNA and defined as germline variants. The remaining 5064 (50.3%) were called as somatic variants due to exclusive presence in tumour DNA. We started by exploring germline variants, focusing on rare variants in single genes (monogenic hypothesis) or variants co-occurring in several genes, regardless of their population frequency (oligogenic/polygenic hypothesis).Monogenic hypothesis. FIGC-associated rare germline variants and somatic second-hitsTo identify rare germline FIGC-predisposing variants, we performed a systematic analysis of all germline variants, focusing on their can you get kamagra over the counter frequency across normal populations and GC cohorts, and sequencing quality.We identified 4998 germline variants in the 50 patients with FIGC (figure 2A).

From the 4998 FIGC germline variants, the genotype frequency of 1038 (20.8%) was available for four 1000 Genomes European populations.28 From the 79.2% of variants absent from 1000 Genomes, only 1.3% (n=53) presented truncating effects, however supported on average by less than four reads, that is, of very low quality and hence confidently discarded. From the 1038 variants present in 1000 Genomes, 121 (11.7%) presented genotypes absent from the four populations screened. Of these 121 variants, only 60 presented the abovementioned sequencing quality can you get kamagra over the counter criteria. From these, 43 variants were exclusively detected in FIGC comparing with HDGC-CDH1 mutation-negative and SIGC cohorts.

With regard to the 17 discarded variants, all were found in at least one HDGC proband and none in SIGC.90 and a call quality >100). From these, 43 variants presented the RefSeq genotype in the HDGC-CDH1 mutation-negative and can you get kamagra over the counter sporadic GC cohorts. A final set of 32 germline, rare and high-quality FIGC-exclusive variants were selected by screening the allele frequency of these variants in all ExAC and gnomAD populations available. (B) Germline variant burden of FIGC families with 0, 1 or >1 rare germline variants.

P value was determined by ANOVA can you get kamagra over the counter statistics. (C) Heatmap and dendrogram of 710 HQ FIGC germline variants of FIGC family classes (Z-score normalised expression level. White, no detected variants. Purple, detected can you get kamagra over the counter variants.

(D) Heatmap and dendrogram of 64 genes with the 710 germline variants of FIGC family classes (Z-score normalised expression levels. White, genes with no detected variants. Light salmon, genes with a single variant can you get kamagra over the counter. Pink, gene carrying 2–5 distinct variants.

Purple, gene with 6–10 distinct variants. Dark purple, gene with 11–15 can you get kamagra over the counter distinct variants. ANOVA, analysis of variance. FIGC, familial intestinal gastric cancer.

GC, gastric can you get kamagra over the counter cancer. HDGC, hereditary diffuse gastric cancer. HQ, high-quality." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1029038981" data-figure-caption="Co-occurrence of rare germline variants does not define a specific germline landscape. (A) Discovery can you get kamagra over the counter of FIGC rare germline predisposition variants.

A total of 4998 germline variants were detected in normal stomach using multigene panel sequencing. From these, 1038 were identified by the 1000 Genomes Project, and 121 were absent from four distinct normal European populations. Of these 121 variants, only 60 can you get kamagra over the counter were classified as variants of high quality (with at least 20 reads for each allele, a genotype quality >90 and a call quality >100). From these, 43 variants presented the RefSeq genotype in the HDGC-CDH1 mutation-negative and sporadic GC cohorts.

A final set of 32 germline, rare and high-quality FIGC-exclusive variants were selected by screening the allele frequency of these variants in all ExAC and gnomAD populations available. (B) Germline variant burden of can you get kamagra over the counter FIGC families with 0, 1 or >1 rare germline variants. P value was determined by ANOVA statistics. (C) Heatmap and dendrogram of 710 HQ FIGC germline variants of FIGC family classes (Z-score normalised expression level.

White, no detected can you get kamagra over the counter variants. Purple, detected variants. (D) Heatmap and dendrogram of 64 genes with the 710 germline variants of FIGC family classes (Z-score normalised expression levels. White, genes with can you get kamagra over the counter no detected variants.

Light salmon, genes with a single variant. Pink, gene carrying 2–5 distinct variants. Purple, gene with can you get kamagra over the counter 6–10 distinct variants. Dark purple, gene with 11–15 distinct variants.

ANOVA, analysis of variance. FIGC, familial can you get kamagra over the counter intestinal gastric cancer. GC, gastric cancer. HDGC, hereditary diffuse gastric cancer.

HQ, high-quality." data-icon-position data-hide-link-title="0">Figure 2 Co-occurrence of rare germline variants does not define a specific germline can you get kamagra over the counter landscape. (A) Discovery of FIGC rare germline predisposition variants. A total of 4998 germline variants were detected in normal stomach using multigene panel sequencing. From these, can you get kamagra over the counter 1038 were identified by the 1000 Genomes Project, and 121 were absent from four distinct normal European populations.

Of these 121 variants, only 60 were classified as variants of high quality (with at least 20 reads for each allele, a genotype quality >90 and a call quality >100). From these, 43 variants presented the RefSeq genotype in the HDGC-CDH1 mutation-negative and sporadic GC cohorts. A final set of 32 germline, rare and high-quality can you get kamagra over the counter FIGC-exclusive variants were selected by screening the allele frequency of these variants in all ExAC and gnomAD populations available. (B) Germline variant burden of FIGC families with 0, 1 or >1 rare germline variants.

P value was determined by ANOVA statistics. (C) Heatmap and dendrogram of 710 can you get kamagra over the counter HQ FIGC germline variants of FIGC family classes (Z-score normalised expression level. White, no detected variants. Purple, detected variants.

(D) Heatmap and dendrogram of 64 genes can you get kamagra over the counter with the 710 germline variants of FIGC family classes (Z-score normalised expression levels. White, genes with no detected http://inzola.com/ variants. Light salmon, genes with a single variant. Pink, gene carrying can you get kamagra over the counter 2–5 distinct variants.

Purple, gene with 6–10 distinct variants. Dark purple, gene with 11–15 distinct variants. ANOVA, analysis of variance can you get kamagra over the counter. FIGC, familial intestinal gastric cancer.

GC, gastric cancer. HDGC, hereditary diffuse gastric can you get kamagra over the counter cancer. HQ, high-quality.From the 43 germline, rare and HQ FIGC-exclusive variants, 31 (72.1%) displayed very low allele frequency in all ExAC and gnomAD populations (figure 2A, online supplementary table 3), and were present in 21 of 50 (42%) FIGC probands (7 missense, 7 3’untranslated (UTR), 2 5’UTR, 12 intronic and 3 synonymous in 18 genes. Online supplementary table 4).

Fifteen probands can you get kamagra over the counter carried a single variant and six exhibited co-occurrence of two or more variants (online supplementary table 5). After excluding variants classified as benign and predicted as intronic, synonymous or not impacting splicing, 12 variants were validated by Sanger sequencing (table 2).Supplemental materialSupplemental materialSupplemental materialView this table:Table 2 FIGC rare germline variants validated by Sanger sequencingA missense variant in PMS1 (c.224C>T), predicted as pathogenic, deleterious and probably damaging by FATHMM, SIFT and PolyPhen, respectively (table 2, online supplementary table 3), was found in family P1 (table 1, online supplementary table 4). The probands, who developed an MSS IGC at 59 years, had an FDR with GC at 80 and two other FDR and SDR with unidentified cancers at 50 and 75 years, respectively. The only can you get kamagra over the counter supporting evidence for the role of this variant in FIGC was its COSMIC record as somatic in one GC sample (COSM6198026) (online supplementary table 3).The proband of family P27 presented three germline variants of uncertain significance, two in SMAD4 (c.424+5G>A.

C.454+38G>C) and one in PRSS1 (c.201-99G>C) (online supplementary table 4). Variants c.424+5G>A in SMAD4 and c.201–99G>C in PRSS1 were the only intronic variants predicted to disrupt RNA splicing (table 2, online supplementary tables 3 and 5,). In particular, SMAD4 variant c.424+5G>A decreases the confidence of a donor splice site, which may lead to intron 3 retention, a premature termination codon and can you get kamagra over the counter generation of a 142 amino acid truncated protein. On the other hand, PRSS1 variant c.201-99G>C creates a new, high-confidence acceptor splice site within intron 2, which may lead to a truncated 69 amino acid protein.

Proband P27 developed an MSS IGC at age 64 and had family history of GC, gastric ulcer, laryngotracheal, gynaecological and hepatobiliary cancers (table 1, online supplementary table 4). The presence of these phenotypes seems to exclude juvenile polyposis and hereditary pancreatitis as underlying syndromes of this family, but could support a potential role for SMAD4 together with PRSS1 in FIGC.We then screened the primary tumours of P1 and P27 FIGC probands for somatic can you get kamagra over the counter second-hit inactivating mechanisms (LOH, somatic mutation) in germline-affected genes. None of the two FIGC probands showed evidence of deleterious somatic variants nor LOH of the wild-type allele of the germline targeted genes (data not shown).Although interesting, these findings are insufficient to support the monogenic hypothesis for FIGC and a potentially causal role for the abovementioned affected genes.Oligogenic/polygenic hypothesis. Co-occurrence of rare germline variants determines somatic landscapes of FIGC tumoursWe then proceeded with the oligogenic/polygenic hypothesis, which takes into consideration the co-occurrence of germline variants, regardless of their population frequency, as a risk factor for this disease, which would determine the subsequent somatic events necessary for malignant transformation.We categorised the 50 FIGC probands according to the presence of rare germline variants.

Families with can you get kamagra over the counter no variants (n=30). Families with a single variant (n=14). And families with multiple variants (n=6). To understand the germline and somatic variant burden for each of these three FIGC classes, we applied the previously described can you get kamagra over the counter quality criteria obtaining 710 HQ germline variants and 344 HQ somatic variants.

The average number of HQ germline variants was identical across the three classes of FIGC families (75.7, 77.4 and 74.5 for families without (0), with one (1) or more than one (>1) rare germline variants, respectively. Figure 2B). Germline landscape unsupervised hierarchical clustering revealed no associations between variants or variant-bearing genes and a particular FIGC family class (figure 2C,D).Concerning the somatic variant can you get kamagra over the counter burden, no significant differences were observed across the three FIGC classes (15.0, 13.8 and 11.2 for families with 0, 1 or >1 rare germline variants, respectively. Figure 3A).

Again, no clustering of specific variants/genes and particular FIGC classes was observed (figure 3B,C).1 rare germline variants. P value can you get kamagra over the counter was determined by ANOVA statistics. (B) Heatmap and dendrogram of 344 FIGC somatic variants of FIGC family classes (Z-score normalised expression level. White, no detected variants.

Orange, detected can you get kamagra over the counter variants. (C) Heatmap and dendrogram of 46 genes with the 344 somatic variants of FIGC family classes (Z-score normalised expression levels. White, gene with no detected variants. Yellow, gene with can you get kamagra over the counter a single variant.

Orange, gene carrying 2–5 distinct variants. Light brown, gene with 6–10 distinct variants. Brown, gene with 11–15 distinct variants can you get kamagra over the counter. (D) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants subdivided according to MSI status.

P value was determined by ANOVA statistics. ANOVA, analysis of variance can you get kamagra over the counter. FIGC, familial intestinal gastric cancer. HQ, high-quality.

MSI, microsatellite can you get kamagra over the counter instable. MSS, microsatellite stable." class="highwire-fragment fragment-images colorbox-load" rel="gallery-fragment-images-1029038981" data-figure-caption="Rare germline variants are not major determinants of FIGC somatic events. (A) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants. P value was determined by ANOVA statistics can you get kamagra over the counter.

(B) Heatmap and dendrogram of 344 FIGC somatic variants of FIGC family classes (Z-score normalised expression level. White, no detected variants. Orange, detected can you get kamagra over the counter variants. (C) Heatmap and dendrogram of 46 genes with the 344 somatic variants of FIGC family classes (Z-score normalised expression levels.

White, gene with no detected variants. Yellow, gene with can you get kamagra over the counter a single variant. Orange, gene carrying 2–5 distinct variants. Light brown, gene with 6–10 distinct variants.

Brown, gene can you get kamagra over the counter with 11–15 distinct variants. (D) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants subdivided according to MSI status. P value was determined by ANOVA statistics. ANOVA, analysis of can you get kamagra over the counter variance.

FIGC, familial intestinal gastric cancer. HQ, high-quality. MSI, microsatellite instable can you get kamagra over the counter. MSS, microsatellite stable." data-icon-position data-hide-link-title="0">Figure 3 Rare germline variants are not major determinants of FIGC somatic events.

(A) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants. P value was determined by can you get kamagra over the counter ANOVA statistics. (B) Heatmap and dendrogram of 344 FIGC somatic variants of FIGC family classes (Z-score normalised expression level. White, no detected variants.

Orange, detected can you get kamagra over the counter variants. (C) Heatmap and dendrogram of 46 genes with the 344 somatic variants of FIGC family classes (Z-score normalised expression levels. White, gene with no detected variants. Yellow, gene can you get kamagra over the counter with a single variant.

Orange, gene carrying 2–5 distinct variants. Light brown, gene with 6–10 distinct variants. Brown, gene with 11–15 distinct can you get kamagra over the counter variants. (D) Somatic variant burden of FIGC families with 0, 1 or >1 rare germline variants subdivided according to MSI status.

P value was determined by ANOVA statistics. ANOVA, analysis can you get kamagra over the counter of variance. FIGC, familial intestinal gastric cancer. HQ, high-quality.

MSI, microsatellite can you get kamagra over the counter instable. MSS, microsatellite stable.We verified that 38% of the FIGC tumours in our series displayed the MSI phenotype, and further investigated whether MSI could influence the somatic variant burden and landscape in families with 0, 1 or >1 rare germline variants. After subdividing each FIGC class according to its MSI status, no significant differences were observed both in terms of somatic variant burden and landscape between categories (figure 3B–D). Nevertheless, we observed that can you get kamagra over the counter among FIGC families with multiple rare germline variants (>1), MSI tumours showed an average number of HQ somatic variants twofold higher than that of MSS tumours (17 vs 10 HQ somatic variants per case, respectively.

Figure 3D, online supplementary figure 1A). This observation prompted us to explore the influence of rare germline variants, independently of their number, on tumour instability and consequent somatic variant burden. Despite the lack of statistical significance, we observed an enrichment of MSI tumours in FIGC can you get kamagra over the counter families carrying rare germline variants comparing with MSI tumours from families lacking rare germline variants (online supplementary figure 1B). Concerning the average of somatic variants, whereas MSI and MSS tumours from FIGC lacking rare germline variants displayed a similar average number, there was a non-significant trend for higher average number of HQ somatic variants in MSI tumours versus MSS tumours from FIGC families with rare germline variants (≥1.

Online supplementary figure 1C).Supplemental materialAlthough our data did not support the hypothesis that co-occurrence of rare germline variants is a major determinant of FIGC-related somatic landscapes, these pinpointed a potential correlation between the coexistence of rare and common germline variants, high average number of somatic variants and MSI phenotype in FIGC.FIGC is genetically distinct from SIGC and from HDGC-CDH1 mutation-negativeSince the late age of onset in FIGC probands and their relatives makes it hard to distinguish bona fide FIGCs from SIGCs, we compared the age of onset of FIGC probands with the age of onset of a series of SIGC cases. We found that FIGC probands developed GC approximately 10 years can you get kamagra over the counter earlier than patients with SIGC (p=4.5E-03. Figure 4E).FIGC is a genetic entity distinct from SIGC. (A) Principal component analysis of genes with germline variants.

(B) Principal component analysis can you get kamagra over the counter of genes with somatic variants. (C) Frequency of genes with germline or somatic variants enriched in FIGC cases in comparison with SIGC cases. Purple for genes with germline events and orange for genes with somatic events. (D) Heatmap and dendrogram of a panel of can you get kamagra over the counter genes with the highest frequency of germline and/or somatic variants in FIGC (n=50) versus SIGC (n=47).

(E) Age at diagnosis of FIGC (n=50) and SIGC cases (n=47). (F) Average number of somatic variants detected in FIGC (n=50) and SIGC cases (n=47). White, gene can you get kamagra over the counter with no variants. Purple, gene with germline variants.

Orange, gene with somatic variants. Red, gene with germline can you get kamagra over the counter and somatic variants. P values calculated with Wilcoxon signed-rank test. FIGC, familial intestinal gastric cancer.

SIGC, sporadic intestinal can you get kamagra over the counter gastric cancer, PC1, principal component 1. PC2, principal component 2." data-icon-position data-hide-link-title="0">Figure 4 FIGC is a genetic entity distinct from SIGC. (A) Principal component analysis of genes with germline variants. (B) Principal can you get kamagra over the counter component analysis of genes with somatic variants.

(C) Frequency of genes with germline or somatic variants enriched in FIGC cases in comparison with SIGC cases. Purple for genes with germline events and orange for genes with somatic events. (D) Heatmap and dendrogram of a panel of can you get kamagra over the counter genes with the highest frequency of germline and/or somatic variants in FIGC (n=50) versus SIGC (n=47). (E) Age at diagnosis of FIGC (n=50) and SIGC cases (n=47).

(F) Average number of somatic variants detected in FIGC (n=50) and SIGC cases (n=47). White, gene can you get kamagra over the counter with no variants. Purple, gene with germline variants. Orange, gene with somatic variants.

Red, gene with germline and can you get kamagra over the counter somatic variants. P values calculated with Wilcoxon signed-rank test. FIGC, familial intestinal gastric cancer. SIGC, sporadic intestinal gastric cancer, PC1, principal component can you get kamagra over the counter 1.

PC2, principal component 2.We next explored whether these FIGC and SIGC were also distinct at the germline and/or somatic levels. Principal component analysis revealed that certain genes were differentially associated with FIGCs and SIGCs (figure 4A,B). Specifically, common germline variants in TP53 were present in more than 50% of FIGC probands, while can you get kamagra over the counter only 11% of SIGC cases presented these germline variants (figure 4A,C). At the somatic level, the frequency of BRCA2, ATM, FOXF1, FHIT, SDHB, MSH6, CTNNA1 and PXN could distinguish FIGC from SIGC tumours, with more than 50% of FIGC displaying common variants in these genes, as compared with very low frequencies in SIGC (figure 4B,C).By combining all germline and somatic landscapes of 50 FIGCs and 47 SIGCs focusing only on the abovementioned genes, and using unsupervised hierarchical clustering, two main clusters were evidenced separating most FIGCs from SIGCs (figure 4D).

Whereas FIGCs carried both germline and somatic variants in TP53, BRCA2, ATM, FOXF1, FHIT, SDHB, MSH6, CTNNA1 and PXN genes, SIGCs lacked TP53 and FHIT germline and somatic variants and mainly presented BRCA2, ATM, FOXF1, SDHB, MSH6, CTNNA1 and PXN somatic variants.Further supporting that FIGC represents a different entity likely evolving for longer than SIGCs is the fact that FIGC tumours presented statistically significantly more somatic common variants than SIGC tumours (p=4.2E-06), even if arising from patients 10 years younger on average (figure 4E,F).To further understand whether FIGC is a genetic entity also distinct from HDGC-CDH1 mutation-negative, we compared the germline and somatic landscapes of 7 FIGCs and 17 HDGCs sequenced with the same Next Generation Sequencing (NGS) panel. We verified that indeed FIGC and HDGC also display considerable differences between germline and somatic landscapes can you get kamagra over the counter (online supplementary figure 2)(). However, the low number of FIGC cases possible to analyse, which was due to sequencing panel differences, hampers more formal conclusions.Overall, our results suggest that FIGC, rather than a monogenic disease, is likely a polygenic disease with distinctive germline and somatic landscapes from SIGC and HDGC-CDH1-negative.DiscussionFIGC presents an autosomal dominant inheritance pattern of IGC, without gastric polyposis, and has been clinically defined by analogy to the Amsterdam criteria for HNPCC.9 However, lack of novel data supporting familial aggregation of IGC at a given age of onset as well as the non-existence of tumour spectrum descriptions have impeded the redefinition of FIGC testing criteria, useful for identification and management of these families.The primary strength of this study is the use of a large homogeneous cohort of probands with IGC, familial aggregation of GC, detailed personal/family history, age of disease onset and disease spectrum. This series does not present clinical criteria compatible with any other gastrointestinal cancer-associated syndrome, is clearly enriched in GC and mainly of intestinal type, which suggests this is the first data-driven testing criteria for FIGC families.

We propose that any family presenting two GC cases, one confirmed of intestinal histology, independently can you get kamagra over the counter of age, and with or without colorectal cancer, breast cancer or gastric ulcers in other family members, could be considered FIGC.Besides potential testing criteria, our study also reported the first large-scale sequencing analysis of the germline and somatic landscapes of FIGC and respective comparisons with comparable landscapes of SIGC and HDGC-CDH1 mutation-negative. We used these data to explore the unknown inherited nature of FIGC. Among the FIGC-exclusive germline rare variants found, the missense PMS1 c.224C>T variant was the only one predicted as pathogenic in family P1.

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Transhumanists can’t wait kamagra cialis biz opinioni to become super-intelligent, immortal cyborgs, or disembodied digital souls dwelling in cyberspace. They say, Bring it on!. When these enthusiasts downplay practical as well as ethical objections, we take their hype with a grain a salt.

But critics of techno-enhancement, who superficially might kamagra cialis biz opinioni seem more credible, indulge in hype too, to alarm us. Perhaps some “critics” are sneakily trying to promote techno-enhancement with reverse psychology. Wouldn’t it be awful to quadruple your IQ, they ask us, or to be happy all the time, or to live hundreds of years?.

Crazy-like-a-fox Elon Musk, I suspect, rants about the threat of super-intelligent machines in order kamagra cialis biz opinioni to market his own investments in artificial intelligence. Sincere or not, wishful worrying leaves the public with a grossly distorted picture of science’s potential. Let me give you a few historical examples.

Cosmetic Psychopharmacology In the late 1980s, the pharmaceutical giant Eli Lilly introduced the antidepressant Prozac, a so-called selective serotonin kamagra cialis biz opinioni reuptake inhibitor, or SSRI, which supposedly elevates mood by altering levels of the neurotransmitter serotonin. In his 1993 bestseller Listening to Prozac, psychiatrist Peter Kramer claimed that Prozac could do more than simply relieve depression. It could make us “better than well.” Kramer proposed that Prozac might bring about an era of “cosmetic psychopharmacology,” in which drugs help the healthy and ill alike.

Kramer feared that if we don’t suffer any kamagra cialis biz opinioni more, if we’re always happy, we might not be fully human. Many readers, I’m guessing, couldn’t care less about Kramer’s windy philosophical ruminations. They thought, Give me Prozac, I want to be better than well!.

Prozac became a blockbuster for Lilly, one of the best-selling drugs of all kamagra cialis biz opinioni time. But Kramer’s “better than well” scenario rests on a bogus premise. As I pointed out in Scientific American in 1996, Prozac is not more effective than older antidepressants, which overall are scarcely more effective than placebos.

In fact, as I have reported recently (see here and here), there is growing evidence that antidepressants and other kamagra cialis biz opinioni psychiatric drugs, over the long run and in the aggregate, make us sicker. €œCosmetic psychopharmacology” now seems like a bad joke. Designer Babies Genetic engineering has spawned countless wishful worries.

Beginning in the late 1980s, kamagra cialis biz opinioni geneticists linked specific genes to a host of specific disorders and traits, from schizophrenia and aggression to high intelligence and homosexuality. Many pundits simply assumed that genetic engineering would soon enable us to shed bad traits and add good ones. The Human Genome Project, launched in 1990, would surely usher in the era of “designer babies,” whether or not we wanted it.

In his 1998 kamagra cialis biz opinioni book Remaking Eden. How Genetic Engineering and Cloning Will Transform the American Family, biologist Lee Silver cautioned that if only the wealthy can afford genetic enhancement, humanity might split into two separate species, the GenRich and the Naturals. (The 1997 film Gattaca also dramatized this possibility.) Each alleged advance in biotechnology revives such concerns.

In 2017, reports that scientists had identified genes associated with intelligence led The Guardian to fret over the possibility of “super-smart designer babies.” Last June The New York Times reported that the debate over genetic enhancement “has taken on new urgency in recent years” as a result of kamagra cialis biz opinioni CRISPR, a novel gene-editing method. But like every other gene-manipulation method, CRISPR works better in principle than in practice. A recent study found that CRISPR caused “serious side effects in the cells of human embryos,” according to The New York Times.

As of last year, according to Scientific American, the FDA had approved nine gene therapies, which for the most part target rare physiological disorders, such as adenosine deaminase deficiency and lipoprotein lipase deficiency kamagra cialis biz opinioni. Gene therapy for mental illnesses such as bipolar disorder and schizophrenia remains entirely hypothetical, as does genetic enhancement of intelligence and other cognitive traits. In a 1993 Scientific American article, “Eugenics Revisited,” I pointed out that scientists had not provided definitive evidence linking any cognitive traits or disorders to specific genes.

That situation kamagra cialis biz opinioni still holds. Please keep this in mind the next time you hear an “expert” warn that, given advances in CRISPR, “superintelligent humans are coming.” Brain Chips Then there are brain chips, implanted electronic devices that can receive signals from and transmit them to neural tissue. Brain chips could, in principle, give us enormous power over our brains, hence minds, hence behavior.

In 1969 Jose Delgado, a pioneer of the field, predicted in kamagra cialis biz opinioni his book Physical Control of the Mind. Toward a Psychocivilized Society that implanted “stimoceivers” would help us eliminate war, crime and other social problems. He and others also warned that tyrants might use brain chips to monitor and control our thoughts.

In 2003 the U.S kamagra cialis biz opinioni. Council on Bioethics, a group convened by President George Bush, brooded over brain chips’ possible effects on STEM education. €œIf computer chips in my brain were to ‘download’ a textbook of physics,” the authors wrote in their 2003 report Beyond Therapy, “would that make me a knower of physics?.

€ Talk kamagra cialis biz opinioni about a wishful worry!. As someone who has labored for the last eight months to learn quantum mechanics, I would love to download Feynman’s lectures directly into my head. Unfortunately, transferring this sort of complex information from a computer into a brain via implanted chips would require decoding the brain’s software, or neural code.

The neural kamagra cialis biz opinioni code is arguably science’s hardest problem. It is one of those mysteries that appears more intractable as more effort is expended on it. So don’t count on instantly mastering quantum mechanics—or helicopter flight or martial arts, like Neo in The Matrix—by means of a brain implant any time soon.

The one kamagra cialis biz opinioni undeniably successful neural prosthesis is the artificial cochlea, which restores hearing by feeding signals from a microphone into the auditory nerve. Brain implants for other applications—notably the treatment of depression—have failed to live up to their hype. There are lots of other wishful worries.

If we become immortal, overpopulation will be out of control! kamagra cialis biz opinioni. If we digitize our psyches and upload them into cyberspace, we’ll lose our sense of individuality, like The Borg in Star Trek!. Some of the silliest wishful worries are related to artificial intelligence and sex.

If sex-bots become sentient, we might have to grant kamagra cialis biz opinioni them rights, including the right not to have sex!. I’m not saying we always need to resolve could questions about a technology before we jump to should questions, because by then it might be too late to curb the technology. But let’s base should conversations on realistic assessments of current research.

Science, which is already kamagra cialis biz opinioni struggling with a replication crisis and other problems, cannot afford any further damage to its credibility. David Brock, who coined the phrase “wishful worries,” points out that they distract us from serious problems, which he calls “actual agonies.” These include “the rapid collapse of multiple, interconnected ecological systems on which human civilization depends. The unprecedented growth of wealth inequality through the engine of global capitalism….

The rise of fascistic movements weaving together nativism, racism, misogyny, homophobia, and climate denialism in service of klepto-plutarchy… Perhaps it’s no wonder that many of us would rather think kamagra cialis biz opinioni about the ethics of sex robots.” I get the need for distraction. Quantum mechanics and Star Trek. Deep Space Nine have become my go-to escapes from the world’s woes.

But if you’re actually concerned about our future, don’t waste your kamagra cialis biz opinioni time worrying that humanity is going to become “superintelligent” or “better than well.” We should be so unlucky. Further Reading. Has the Drug-Based Approach to Mental Illness Failed?.

Perhaps some “critics” are sneakily trying Buy kamagra oral jelly online uk to can you get kamagra over the counter promote techno-enhancement with reverse psychology. Wouldn’t it be awful to quadruple your IQ, they ask us, or to be happy all the time, or to live hundreds of years?. Crazy-like-a-fox Elon Musk, I suspect, rants about the threat of super-intelligent machines in order to market his own investments in artificial intelligence. Sincere or not, wishful worrying leaves the public with a grossly distorted picture of science’s can you get kamagra over the counter potential. Let me give you a few historical examples.

Cosmetic Psychopharmacology In the late 1980s, the pharmaceutical giant Eli Lilly introduced the antidepressant Prozac, a so-called selective serotonin reuptake inhibitor, or SSRI, which supposedly elevates mood by altering levels of the neurotransmitter serotonin. In his 1993 bestseller Listening to Prozac, psychiatrist Peter Kramer claimed that Prozac can you get kamagra over the counter could do more than simply relieve depression. It could make us “better than well.” Kramer proposed that Prozac might bring about an era of “cosmetic psychopharmacology,” in which drugs help the healthy and ill alike. Kramer feared that if we don’t suffer any more, if we’re always happy, we might not be fully human. Many readers, I’m guessing, couldn’t care can you get kamagra over the counter less about Kramer’s windy philosophical ruminations.

They thought, Give me Prozac, I want to be better than well!. Prozac became a blockbuster for Lilly, one of the best-selling drugs of all time. But Kramer’s “better than well” scenario can you get kamagra over the counter rests on a bogus premise. As I pointed out in Scientific American in 1996, Prozac is not more effective than older antidepressants, which overall are scarcely more effective than placebos. In fact, as I have reported recently (see here and here), there is growing evidence that antidepressants and other psychiatric drugs, over the long run and in the aggregate, make us sicker.

€œCosmetic psychopharmacology” now seems like a bad joke can you get kamagra over the counter. Designer Babies Genetic engineering has spawned countless wishful worries. Beginning in the late 1980s, geneticists linked specific genes to a host of specific disorders and traits, from schizophrenia and aggression to high intelligence and homosexuality. Many pundits simply assumed that genetic engineering would soon enable can you get kamagra over the counter us to shed bad traits and add good ones. The Human Genome Project, launched in 1990, would surely usher in the era of “designer babies,” whether or not we wanted it.

In his 1998 book Remaking Eden. How Genetic Engineering and Cloning Will Transform the American Family, biologist Lee Silver cautioned that if only the wealthy can you get kamagra over the counter can afford genetic enhancement, humanity might split into two separate species, the GenRich and the Naturals. (The 1997 film Gattaca also dramatized this possibility.) Each alleged advance in biotechnology revives such concerns. In 2017, reports that scientists had identified genes associated with intelligence led The Guardian to fret over the possibility of “super-smart designer babies.” Last June The New York Times reported that the debate over genetic enhancement “has taken on new urgency in recent years” as a result of CRISPR, a novel gene-editing method. But like every other gene-manipulation method, CRISPR can you get kamagra over the counter works better in principle than in practice.

A recent study found that CRISPR caused “serious side effects in the cells of human embryos,” according to The New York Times. As of last year, according to Scientific American, the FDA had approved nine gene therapies, which for the most part target rare physiological disorders, such as adenosine deaminase deficiency and lipoprotein lipase deficiency. Gene therapy for mental illnesses such as bipolar disorder and schizophrenia remains entirely hypothetical, can you get kamagra over the counter as does genetic enhancement of intelligence and other cognitive traits. In a 1993 Scientific American article, “Eugenics Revisited,” I pointed out that scientists had not provided definitive evidence linking any cognitive traits or disorders to specific genes. That situation still holds.

Please keep this in mind the next time you hear an “expert” warn that, given advances in can you get kamagra over the counter CRISPR, “superintelligent humans are coming.” Brain Chips Then there are brain chips, implanted electronic devices that can receive signals from and transmit them to neural tissue. Brain chips could, in principle, give us enormous power over our brains, hence minds, hence behavior. In 1969 Jose Delgado, a pioneer of the field, predicted in his book Physical Control of the Mind. Toward a Psychocivilized Society that implanted “stimoceivers” can you get kamagra over the counter would help us eliminate war, crime and other social problems. He and others also warned that tyrants might use brain chips to monitor and control our thoughts.

In 2003 the U.S. Council on Bioethics, a group convened by President George can you get kamagra over the counter Bush, brooded over brain chips’ possible effects on STEM education. €œIf computer chips in my brain were to ‘download’ a textbook of physics,” the authors wrote in their 2003 report Beyond Therapy, “would that make me a knower of physics?. € Talk about a wishful worry!. As someone who has labored for the last eight months to learn quantum mechanics, I would love to download Feynman’s lectures directly into can you get kamagra over the counter my head.

Unfortunately, transferring this sort of complex information from a computer into a brain via implanted chips would require decoding the brain’s software, or neural code. The neural code is arguably science’s hardest problem. It is one of those mysteries that appears more can you get kamagra over the counter intractable as more effort is expended on it. So don’t count on instantly mastering quantum mechanics—or helicopter flight or martial arts, like Neo in The Matrix—by means of a brain implant any time soon. The one undeniably successful neural prosthesis is the artificial cochlea, which restores hearing by feeding signals from a microphone into the auditory nerve.

Brain implants for other applications—notably the treatment of can you get kamagra over the counter depression—have failed to live up to their hype. There are lots of other wishful worries. If we become immortal, overpopulation will be out of control!. If we digitize our psyches and upload them can you get kamagra over the counter into cyberspace, we’ll lose our sense of individuality, like The Borg in Star Trek!. Some of the silliest wishful worries are related to artificial intelligence and sex.

If sex-bots become sentient, we might have to grant them rights, including the right not to have sex!. I’m not saying we always need to resolve could questions about a technology before we jump to should questions, because by then it might be too late to can you get kamagra over the counter curb the technology. But let’s base should conversations on realistic assessments of current research. Science, which is already struggling with a replication crisis and other problems, cannot afford any further damage to its credibility. David Brock, who coined the phrase “wishful worries,” points out that they distract us from serious problems, which he calls “actual agonies.” These include “the rapid collapse of multiple, interconnected ecological systems on can you get kamagra over the counter which human civilization depends.

The unprecedented growth of wealth inequality through the engine of global capitalism…. The rise of fascistic movements weaving together nativism, racism, misogyny, homophobia, and climate denialism in service of klepto-plutarchy… Perhaps it’s no wonder that many of us would rather think about the ethics of sex robots.” I get the need for distraction. Quantum mechanics can you get kamagra over the counter and Star Trek. Deep Space Nine have become my go-to escapes from the world’s woes. But if you’re actually concerned about our future, don’t waste your time worrying that humanity is going to become “superintelligent” or “better than well.” We should be so unlucky.

Further Reading. Has the Drug-Based Approach to Mental Illness Failed?. Can Psychiatry Heal Itself?. Meta-Post. Posts on Brain Implants Will Artificial Intelligence Ever Live Up to Its Hype?.

Do We Need Brain Implants to Keep Up with Robots?. See also my books Mind-Body Problems and Pay Attention.

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New York's largest healthcare provider, http://lifetech-hc.com/2018/06/19/hallo-welt/ Northwell Health, has added real-time bed visibility to its 19 facilities through a partnership with TeleTracking Technologies, a care coordination support company.The extended agreement centralizes Northwell's operations into one location through TeleTracking's kamagra cost per pill command center. It will give the health system the capability to see all available beds across its network.TeleTracking's data has the capacity to expedite bed turnover, improve the patient discharge process, automate workflows and enhance communications, according to the announcement.WHAT'S THE IMPACTEarly on in the kamagra, New York City was an epicenter for erectile dysfunction treatment and at one point it had roughly 5% of the world's confirmed cases.As a major provider in the area, Northwell Health was charged with managing kamagra cost per pill a significant number of those patients. The number of erectile dysfunction treatment hospitalizations throughout the health system went from 49 on March 16 to a peak of 3,425 on April 7, according to Northwell. The health system took creative measures in adding to its patient capacity by taking what was once a 4,000 acute-care bed system to creating nearly 2,000 more beds in lobbies, kamagra cost per pill auditoriums, conference rooms, operating rooms, catheterization labs, endoscopy suites and other procedure rooms."We worked tirelessly prior to the kamagra to help the system map long-term patient flow objectives, including aligning clinical and executive stakeholders," said Chris Johnson, the President of TeleTracking.

"When erectile dysfunction treatment struck, TeleTracking quickly mobilized to help manage patient logistics across the system by adding and tracking surge beds in areas like PACUs, catheterization labs, cafeterias, and other kamagra cost per pill spaces across acute care locations."With erectile dysfunction treatment cases rising across the country, Northwell will use the technology in its resurgence plans.THE LARGER TRENDAs a resurgence of erectile dysfunction treatment spreads across the country, the total number of cases in the U.S. Has surpassed 10 million, according to the Centers for Disease Control and Prevention.The single-day case number has been steadily rising and on November 12, the country broke a new record for a one-day total of 194,000 new cases, according to the CDC.Hospitalization rates have also increased, and there are currently more than 67,000 people hospitalized with erectile dysfunction treatment, according to the erectile dysfunction treatment Tracking Project. The soaring hospitalization rates have filled many hospitals intensive care units and are creating fears that there could be a shortage of kamagra cost per pill beds.As hospitals become more overwhelmed with erectile dysfunction treatment cases, they continue to ask the government for more erectile dysfunction treatment relief funding.Twitter. @HackettMalloryEmail the writer.

Mhackett@himss.orgA report released from KLAS this week ranked NextGen Healthcare, Cerner and Epic highly on measures of usability of shared patient data from outside sources.The report specifically focused on acute kamagra cost per pill and ambulatory electronic health record vendor adoption and usability of national interoperability networks Carequality and CommonWell Health Alliance. "Based on the expectations healthcare organizations reported in early 2019, KLAS had expected to see progress from a larger number of kamagra cost per pill vendors. However, little has changed for customers of Allscripts, athenahealth, CPSI, eClinicalWorks, Greenway Health, or MEDITECH," wrote report authors. HIMSS20 Digital Learn on-demand, earn credit, find products and solutions kamagra cost per pill.

Get Started >>. WHY IT MATTERSAs KLAS researchers noted in a parallel report also released this week, the CommonWell-Carequality connection has mostly been used by acute and ambulatory care health systems since it was established in 2018.Of the main acute and ambulatory EHR vendors, KLAS reported, NextGen, Epic and Cerner provide strong usability experiences, specifically with regard to flow kamagra cost per pill of outside data, reconciliation of problem, allergy, medication, and immunization (PAMI) data, lab data workflow and progress notes workflow.NextGen had the strongest showing, especially when it came to duplicate medication data – which continues to frustrate provider organizations."NextGen Healthcare is the only vendor whose customers report significant improvement in this area. The NextGen EMR is able to filter out duplicate medications, even kamagra cost per pill for inexact matches (e.g., Tylenol vs. Acetaminophen).

While other solutions may be capable of flagging duplicate information and removing some of it, customers say the process is often still very manual," wrote the report authors.Although Epic and Cerner scored high for end-user experience and integration, customers say the next step is for vendors to reduce duplication of PAMI.Overall, usability rates were lowest for CPSI and GreenWay Health.Nearly all of athenahealth and Epic's customers have adopted the CommonWell connection, noted the kamagra cost per pill report, with Cerner and NextGen showing leaps in the numbers of live customers in the past 18 months. "Additionally, through the CommonWell-Carequality connection, Cerner customers can share with Epic exchange partners, opening up access to a large volume of data," wrote the researchers.MEDHOST is the last major acute care EHR vendor to not be connected to either CommonWell or Carequality.And although Allscripts was a founding member of CommonWell in 2013, kamagra cost per pill it did not connect its first customer until this year.THE LARGER TRENDIn December 2018, KLAS reported that some health IT organizations were continuing to drag their feet on participating in new interoperability frameworks. At the time, all of the most prevalent EHR vendors except Allscripts and MEDHOST were connected to CommonWell-Carequality – "putting the ability to exchange patient records within the reach of most acute care or clinic-based provider organizations, regardless of size or financial situation."Now, nearly two years later, MEDHOST continues to be unconnected, with Allscripts only establishing a connection in the second half of 2020.Meanwhile, other barriers to interoperability continue to be addressed. In October, Carequality parent, the Sequoia Project, announced that kamagra cost per pill it's forming a new data usability workgroup focused on developing three implementation guides to data usability requirements for provider-to-provider, provider-to-public health agency and healthcare entity-to-consumer information exchange.ON THE RECORD"The national interoperability networks of Carequality and CommonWell Health Alliance have become some of the primary means by which patient records are shared between healthcare organizations in the U.S.," said KLAS researchers.

However, the number of organizations connected to these plug-and-play networks and the usability of the shared data vary significantly depending on the EMR in use." Kat Jercich is senior editor of Healthcare IT News.Twitter. @kjercichEmail. Kjercich@himss.orgHealthcare IT News is a HIMSS Media publication.Researchers at Mount Sinai in New York see promise in new machine learning models they've developed that can assess – within key windows of time – the risk of certain adverse clinical events in some erectile dysfunction treatment patients.WHY IT MATTERSResearch published earlier this month in the Journal of Medical Internet Research describes how the algorithms are enabling better insights into potential risks for a diverse group of erectile dysfunction treatment patients.Researchers at Mount Sinai's Icahn School of Medicine and Hasso Plattner Institute for Digital Health gathered electronic health record data from more than 4,000 adult patients admitted to five Mount Sinai Health System hospitals from this spring, during the kamagra's first wave. HIMSS20 Digital Learn on-demand, earn credit, find products and solutions.

Get Started >>. Clinicians from the Mount Sinai erectile dysfunction treatment Informatics Center analyzed characteristics of erectile dysfunction treatment patients – looking at past medical history, comorbidities, vitals and labs – to help predict the risk of mortality, or critical events such as the need for intubation, within clinically relevant time windows.By predicting risks for time windows of three, five, seven and 10 days from admission, Mount Sinai researchers say the models offer valuable insights to forecast short and medium-term care decisions for erectile dysfunction treatment patients over the course of their hospitalizations.For instance, they note that at the one-week mark – the time period that offered the most accurate prediction of critical events while returning the fewest false positives – conditions such acute kidney injury, fast breathing, high blood sugar and elevated lactate dehydrogenase (indicating tissue damage or disease) were the strongest drivers in predicting critical illness.Older age, blood level imbalance, and C-reactive protein levels indicating inflammation, were the strongest drivers in predicting mortality.THE LARGER TRENDSome experts have made the case that artificial intelligence had a somewhat disappointing showing in the early days of the kamagra's spread. And it's true that bias in certain algorithms might have an adverse effect on some healthcare disparities.But AI and machine learning have a big role to play in diagnosis and decision support as the erectile dysfunction treatment emergency reaches its newest peak. So far, an array of promising models, many pushed out to clinicians via EHR updates, have emerged to help detect the disease and assess risk on a population level.Mount Sinai, in particular, has been innovating its research into erectile dysfunction treatment over the eight months since it was inundated with patients during the kamagra's early peak.

It's created an AI model to diagnose erectile dysfunction treatment in patients with otherwise normal lung scans, for instance. And has also pioneered the use of Apple Watch to study erectile dysfunction treatment stress and burnout among healthcare workers.ON THE RECORD"From the initial outburst of erectile dysfunction treatment in New York City, we saw that erectile dysfunction treatment presentation and disease course are heterogeneous, and we have built machine learning models using patient data to predict outcomes," said Benjamin Glicksberg, assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, in a statement."Now in the early stages of a second wave, we are much better prepared than before," he said. "We are currently assessing how these models can aid clinical practitioners in managing care of their patients in practice."Added Dr. Girish Nadkarni, assistant professor of medicine in the nephrology department at the Icahn School.

"More importantly, we have created a method that identifies important health markers that drive likelihood estimates for acute care prognosis and can be used by health institutions across the world to improve care decisions, at both the physician and hospital level, and more effectively manage patients with erectile dysfunction treatment." Twitter. @MikeMiliardHITNEmail the writer. Mike.miliard@himssmedia.comHealthcare IT News is a HIMSS publication.With the next wave of the erectile dysfunction treatment kamagra beginning to crash down in hospitals around the country, it's more important than ever for health systems to be well attuned to their supply chain needs.One of the biggest challenges of the first wave this past spring, of course, was the shortage of personal protective equipment, ventilators and sometimes critical medications. Supply chain vulnerabilities were acute – and that's not counting the ongoing cyberattacks targeted at health system supply lines.Some of these challenges have been ironed out over the past eight months.

But as the erectile dysfunction treatment crisis surges again, CIOs and other IT professionals say robust supply chains are more important than ever.As Hal Wolf, CEO of HIMSS (parent company of Healthcare IT News) said this past week, a revolution in supply chain management is long overdue."We have really under-focused on supply chain," said Wolf, who noted the critical need to track the source of medications and equipment. Understand the quality of materials (being able to discern, for instance, that a shipment of N95 masks is really what it says it is). And ensuring supply chains are not interrupted – all while having visibility into price, inventory control and more.Hospital leaders around the country told Healthcare IT News that the current segmentation of systems has led to shortages right when facilities needed resources most. Models such as CISOM, developed to improve quality and safety through the integration of supply chain and clinical data in healthcare organizations, can address such inefficiencies.

But what are some ways that technology might play a role in making supply chain management a more seamless experience?. Chief information officers and other healthcare leaders who oversee the supply chains weighed in with their own experiences."At LifeBridge Health, we have approached the kamagra with a threefold supply strategy. Conserve. Source.

And, where needed, manufacture," said Tressa Springmann, CIO at LifeBridge Health in Baltimore. "Clearly, as we are now seeing cases rise again, a keen ability to pivot more quickly has surfaced, and a few additional tools would put us into an even better position both now and into the future."First, more complete analytics. Analytics that tie [predictions of] patient volume and acuity with supply demand would be helpful," she said. "Second, real-time artificial intelligence that makes visible the entire life cycle – end-to-end if you will – of the global supply chain.

This visibility would enable a more effective response to market disruption, risk reduction and position us more effectively for enhanced business continuity.""At LifeBridge Health, we have approached the kamagra with a three-fold supply strategy. Conserve. Source have a peek here. And, where needed, manufacture."Tressa Springmann, CIO, LifeBridge Health"The healthcare industry would tremendously benefit from supply chain IT systems being much more seamlessly integrated with electronic medical records and their respective materials data sets integrated side-by-side with clinical data," said Aaron Miri, chief information officer at Dell Medical School and UT Health in Austin, Texas."The current state of this system's bifurcation led us down some rabbit holes during the PPE crunch, during the erectile dysfunction treatment kamagra, and therefore causes data analytics teams to have to jump over hurdles that shouldn't be this difficult," said Miri."Further, it's holding back advancement in value-based care bundles and new VBC products that could be put to market, as looking at a patient's complete health often includes materials and respective pricing of materials used during surgery, recovery and ongoing therapy," he said.Some health system leaders pointed to technologies such as artificial intelligence and machine learning as ways to help augment inventory control."We at Stanford Children's Health would like to see our supply chain tool provide real-time visibility and predictive analysis, such as available inventory, preferential pricing, lead times from different suppliers and demand trending," said Garima Srivastava, executive director of enterprise business systems."We would also want a system that can be scaled to incorporate new robotic process automation, artificial intelligence and radio frequency identification-based management," Srivastava added.

"These are important for us to move towards the digital transformation and automate lots of manual work, which our supply chain department currently does. It will speed up some processes and will reduce manual errors."Using RFID in particular, Srivastava pointed out, "we will be able to track high-cost items and can manage our inventory better." "We would like to see our supply chain tool provide real time visibility and predictive analysis, such as available inventory, preferential pricing, lead times from different suppliers and demand trending."Garima Srivastava, executive director of enterprise business systems, Stanford Children's Health"We would love to see predictive forecasting and scenario planning, powered by machine learning and AI capabilities, integrated into our demand planning and supply modeling tools," agreed B.J. Moore, CIO at Providence in Renton, Washington. "Think about the ability to predict consumption of PPE items based on real-time erectile dysfunction treatment modeling, patient admissions, and/or case data, and not on historical consumption alone," he mused.St.

Jude Children's Research Hospital CIO Keith Perry also prioritized location awareness. He said he'd like "to have the ability to track an item throughout the supply chain, including (and most important) the 'last mile,' until it physically arrives at the final delivery destination."Unlocking or exposing supply-chain data as appropriate for the person who is ordering equipment" would help with efficiency at St. Jude, Perry continued. "That person is the ultimate customer of any supply-chain process.""Unlocking or exposing supply-chain data as appropriate for the person who is ordering equipment" would help with efficiency at St.

Jude"Keith Perry, CIO, St. Jude Children's Research HospitalBill Donato, vice president of supply chain at the Hospital for Special Surgery in New York City, noted the importance of visibility. "One of the critical tools to manage the current and future healthcare supply chain is our ability to monitor in 'real time' the status of our critical suppliers' products from their manufacturing plants through their distribution networks," he said. "Additional transparency of our suppliers' sales and operating plans would allow us to anticipate and more effectively manage disruptions to our supply chain."Leaders pointed out that the changes implemented in response to erectile dysfunction treatment would have lasting positive effects.

"The most pressing need currently which has been highlighted by the supply chain challenges presented by the kamagra is the need for an affordable, efficient and comprehensive, enterprise-wide inventory management system," said Larry Fogarty, vice president of supply chain management at Memphis-based Methodist Le Bonheur Healthcare. "This would create coordinated visibility into the availability, stocking profiles and near-expired product monitoring for supply areas across the organization. It would also go a long way in anticipating supply chain exposures, rather than simply reacting to them – a must in the post kamagra world," Fogarty continued."Finally, a coordinated system-wide inventory-management system would facilitate timely, inter-facility transfers to best allocate products where and when needed," Fogarty said."As the erectile dysfunction treatment kamagra continues to disrupt the supply chain, globally and at our five-hospital health system, I would love to see a warehouse-management-support system that could better manage, move and track inventory."Brian Murray, assistant vice president for supply chain procurement at NorthShore University HealthSystem, said, "Business intelligence software that automatically produces executive-level reporting and can help better forecast our need for gowns, gloves, N95s, isolation masks, thermometers and other PPE would be great."We are currently opening an offsite warehouse for our system and need a software program that will help us respond to and support erectile dysfunction treatment needs," he said."We are actively exploring robotic process automation to further streamline our operations and meet the needs of our community."Suzzanne Thomson Quintero, chief supply chain officer at Orlando HealthTanya Townsend, CIO for LCMC Health in New Orleans, said that her system is already taking steps to improve resource management."We are embarking on a new enterprise resource planning implementation which will include new Supply Chain functionality. I look forward to having more complete visibility to trace products and how that impacts patient care," said Townsend."I'm also excited about a more automated end-to-end process for managing inventory and procuring products," Townsend continued.Similarly, Suzzanne Thomson Quintero, chief supply chain officer at Orlando Health, said the system has taken advantage of existing capabilities.

"Orlando Health is fortunate to have its own 90,000 sq. Foot distribution center. This distribution hub uses a warehouse management system to forecast product needs for our 15 hospitals," Quintero explained. "We recently enhanced the system to provide meaningful reporting to our hospital operators.

In addition, we are introducing artificial intelligence into our purchasing operations to help purchase the right product, at the right price, from the right vendor," she said. "Also, we are actively exploring robotic process automation to further streamline our operations and meet the needs of our community.""Advanced inventory-demand planning, modeling and reporting would be a critical functionality to have in our tool kit to drive value in the supply chain, both long-term and during these unprecedented times," said Bill Moir, vice president of supply chain operations at Advocate Aurora Health in Wisconsin and Illinois."AAH is committed to enhancing our supply chain to ensure it is a strategic differentiator for our organization," said Moir. "Investments in our infrastructure, like enterprise resource planning, will ensure a strong standardized foundation that we can continue to build upon and innovate from for years to come." Kat Jercich is senior editor of Healthcare IT News.Twitter. @kjercichEmail.

Kjercich@himss.orgHealthcare IT News is a HIMSS Media publication.Boston Children’s Hospital was facing several problems that it had hoped it could solve with some new clinical tools.THE PROBLEMThe top problem was that its communications channels were not integrated into the larger healthcare ecosystem. Finding who was responsible for a given patient or a given role was in one system while finding out the phone number for that person or a role was in another system (or on cheat-sheets tacked up in workrooms or other places not available to everyone).The inability to efficiently find the right person at the right moment led 411-bed Boston Children’s to look for a better and more integrated solution.On another front, from a nursing perspective, the integrated health record at Boston Children’s allows for a comprehensive view of patient care. However, this view was limited to desktop workstations and portable workstations on wheels.“If there was an issue with the mobile workstation, it presented a potential risk for accessing the patient EHR and utilizing our built-in, point-of-care safeguards, such as bar code medication administration,” said Lynnetta Akins, RN-BC, director of clinical education and informatics. €œBoston Children’s wanted a mobile solution to incorporate a comprehensive view to deliver patient care while leveraging point-of-care functionality.”The same issue applied to nursing and communication.

Knowing who to contact and what number was a challenge, she added."Now, instead of knowing who the charge nurse is or what that role’s phone number is, I can look into the directory, search for the role, know who claimed the role at that moment, and securely text or call that person."Lynnetta Akins, Boston Children’s Hospital“Nursing would have to look in several places to communicate to the whole care team, decreasing the time nurses were spending at the bedside,” she said.PROPOSALBoston Children’s Hospital worked together with its EHR vendor Cerner to facilitate and coordinate care team communications. The hospital implemented CareAware Connect (CAC) and Connect Nursing, using Cerner’s newest cloud-deployment model.“The proposal from CAC and Connect Nursing was to effectively integrate and mobilize our care team to allow for more efficient and integrated secure communications,” said Dr. Jonathan Bickel, senior director of BCH clinical health record, business intelligence, health information management and the Boston Children’s Medical Library and Archives at Boston Children’s Hospital.“The CAC platform provided the interoperability solution to quickly communicate across our continuity of care,” he said.The nursing application allowed for greater mobility and streamlined workflow efficiencies for the clinical workforce while continuing to support safe care for patients, he added.MARKETPLACEThere are many vendors with electronic health records systems on the health IT market today, including Allscripts, athenahealth, Cerner, DrChrono, eClinicalWorks, Epic, Greenway Health, HCS, Meditech and NextGen Healthcare.MEETING THE CHALLENGECAC solves the challenges by allowing team members to claim roles that allow for efficient communication with the right person, Akins explained.“Now, instead of knowing who the charge nurse is or what that role’s phone number is, I can look into the directory, search for the role, know who claimed the role at that moment, and securely text or call that person,” she said. €œPutting the CAC devices in nurses’ hands allows for greater mobility while quickly communicating among the care team.”"Enabling Bluetooth for people who use personal protective equipment has been an ideal side benefit, because you can use the device without having to touch anything."Dr.

Jonathan Bickel, Boston Children’s HospitalWith Connect Nursing, staff was able to empower nurses with increased accessibility for clinical workflow, she added.“The mobility and flexibility to deliver patient care with tools in the palm of their hands,” she noted. €œOur nurses were able to dedicate more time spent at the patient bedside to providing safe and high-quality care. Connect Nursing brought greater mobility and flexibility to the bar code medication administration process, inclusive of positive patient identification.”For the pediatric population, staff had the flexibility for scanning to change the event sequence to support pediatrics medication preparation.“The Connect Nursing platform supports point-of-care alerts functionality,” she said. €œNurses have stated that having a mobile workflow that doesn’t require the use of a workstation on wheels to support safe and highly reliable medication administration has been a real win for safety, workflow and satisfaction.”RESULTS“The results speak for themselves,” Bickel said.

€œWith our prior secure texting platform, we had hundreds of users sending a few thousand texts a month. With our integrated CAC platform, we have about 300,000 messages sent a month across 3,580 providers. We are seeing 200,000 calls a month. This far exceeded our expectations, and highlights how much communication is needed to care for our complex pediatric population.”Additionally, Connect Nursing brought greater mobility and flexibility to the bar code medication administration process, Akins said.“Two of the largest patient care areas – emergency department and post-surgical unit – are using it for most of their medication administration events,” she reported.

€œNurses in those patient care areas say a mobile workflow that doesn’t require the use of a workstation on wheels supports safe and highly reliable medication administration.”In the fight against erectile dysfunction treatment, there are more capabilities for Boston Children’s staff to potentially use.“With Bluetooth, we can start to think about performing contact tracing using devices to record interactions with other personnel and their devices on a given floor,” Bickel observed. €œEnabling Bluetooth for people who use personal protective equipment has been an ideal side benefit, because you can use the device without having to touch anything. This implemented platform has been serendipitous and quite useful.”ADVICE FOR OTHERS“When considering a vendor, one needs to consider how tightly integrated the vendor’s collaboration is with your care team,” Bickel advised. €œDo you have a single source of truth of who, at any moment, is part of a given care team?.

Can that platform take the care team information and utilize this to facilitate communication?. Does the texting platform support all the functionality needed?. €Twitter. @SiwickiHealthITEmail the writer.

Bsiwicki@himss.orgHealthcare IT News is a HIMSS Media publication..

New York's largest healthcare provider, Northwell Health, has added real-time bed visibility to its http://www.jamiegianna.com/2020/01/10/life-as-a-new-cio-quick-wins/ 19 can you get kamagra over the counter facilities through a partnership with TeleTracking Technologies, a care coordination support company.The extended agreement centralizes Northwell's operations into one location through TeleTracking's command center. It will give the health system the capability to see all available beds across its network.TeleTracking's data has the capacity to expedite bed turnover, improve the patient discharge process, automate workflows and enhance communications, according to the announcement.WHAT'S THE IMPACTEarly on in the kamagra, New York City was can you get kamagra over the counter an epicenter for erectile dysfunction treatment and at one point it had roughly 5% of the world's confirmed cases.As a major provider in the area, Northwell Health was charged with managing a significant number of those patients. The number of erectile dysfunction treatment hospitalizations throughout the health system went from 49 on March 16 to a peak of 3,425 on April 7, according to Northwell.

The health system took can you get kamagra over the counter creative measures in adding to its patient capacity by taking what was once a 4,000 acute-care bed system to creating nearly 2,000 more beds in lobbies, auditoriums, conference rooms, operating rooms, catheterization labs, endoscopy suites and other procedure rooms."We worked tirelessly prior to the kamagra to help the system map long-term patient flow objectives, including aligning clinical and executive stakeholders," said Chris Johnson, the President of TeleTracking. "When erectile dysfunction treatment struck, TeleTracking quickly mobilized to help manage patient logistics across the system by adding and tracking surge beds can you get kamagra over the counter in areas like PACUs, catheterization labs, cafeterias, and other spaces across acute care locations."With erectile dysfunction treatment cases rising across the country, Northwell will use the technology in its resurgence plans.THE LARGER TRENDAs a resurgence of erectile dysfunction treatment spreads across the country, the total number of cases in the U.S. Has surpassed 10 million, according to the Centers for Disease Control and Prevention.The single-day case number has been steadily rising and on November 12, the country broke a new record for a one-day total of 194,000 new cases, according to the CDC.Hospitalization rates have also increased, and there are currently more than 67,000 people hospitalized with erectile dysfunction treatment, according to the erectile dysfunction treatment Tracking Project.

The soaring hospitalization rates have filled many hospitals intensive care units and are creating fears that there could can you get kamagra over the counter be a shortage of beds.As hospitals become more overwhelmed with erectile dysfunction treatment cases, they continue to ask the government for more erectile dysfunction treatment relief funding.Twitter. @HackettMalloryEmail the writer. Mhackett@himss.orgA report released from KLAS this week ranked NextGen Healthcare, Cerner and Epic highly on measures of usability of shared can you get kamagra over the counter patient data from outside sources.The report specifically focused on acute and ambulatory electronic health record vendor adoption and usability of national interoperability networks Carequality and CommonWell Health Alliance.

"Based on the expectations healthcare organizations reported in early 2019, KLAS had expected to see progress from a larger number can you get kamagra over the counter of vendors. However, little has changed for customers of Allscripts, athenahealth, CPSI, eClinicalWorks, Greenway Health, or MEDITECH," wrote report authors. HIMSS20 Digital can you get kamagra over the counter Learn on-demand, earn credit, find products and solutions.

Get Started >>. WHY IT MATTERSAs KLAS researchers noted in a parallel report also released this week, the CommonWell-Carequality connection has mostly been used by acute and ambulatory care health systems since it was established in 2018.Of the main acute and ambulatory EHR vendors, KLAS reported, NextGen, Epic and Cerner provide strong usability experiences, specifically with regard to flow can you get kamagra over the counter of outside data, reconciliation of problem, allergy, medication, and immunization (PAMI) data, lab data workflow and progress notes workflow.NextGen had the strongest showing, especially when it came to duplicate medication data – which continues to frustrate provider organizations."NextGen Healthcare is the only vendor whose customers report significant improvement in this area. The NextGen EMR is able to filter out duplicate medications, even for inexact matches (e.g., can you get kamagra over the counter Tylenol vs.

Acetaminophen). While other solutions may be capable of flagging duplicate information and removing some of it, customers say the process is often still very manual," wrote the report authors.Although Epic and Cerner scored high for end-user experience and integration, customers say the next step is for vendors to reduce duplication of PAMI.Overall, usability rates were lowest for CPSI and GreenWay Health.Nearly all of athenahealth and Epic's customers have adopted the CommonWell can you get kamagra over the counter connection, noted the report, with Cerner and NextGen showing leaps in the numbers of live customers in the past 18 months. "Additionally, through the CommonWell-Carequality connection, Cerner customers can share with Epic exchange partners, opening up access to a large volume of data," wrote the researchers.MEDHOST is the last major acute care EHR vendor to not be connected to either CommonWell or Carequality.And although Allscripts was a founding member of CommonWell in 2013, it did not connect its can you get kamagra over the counter first customer until this year.THE LARGER TRENDIn December 2018, KLAS reported that some health IT organizations were continuing to drag their feet on participating in new interoperability frameworks.

At the time, all of the most prevalent EHR vendors except Allscripts and MEDHOST were connected to CommonWell-Carequality – "putting the ability to exchange patient records within the reach of most acute care or clinic-based provider organizations, regardless of size or financial situation."Now, nearly two years later, MEDHOST continues to be unconnected, with Allscripts only establishing a connection in the second half of 2020.Meanwhile, other barriers to interoperability continue to be addressed. In October, Carequality parent, the Sequoia Project, announced that it's forming a new data usability workgroup can you get kamagra over the counter focused on developing three implementation guides to data usability requirements for provider-to-provider, provider-to-public health agency and healthcare entity-to-consumer information exchange.ON THE RECORD"The national interoperability networks of Carequality and CommonWell Health Alliance have become some of the primary means by which patient records are shared between healthcare organizations in the U.S.," said KLAS researchers. However, the number of organizations connected to these plug-and-play networks and the usability of the shared data vary significantly depending on the EMR in use." Kat Jercich is senior editor of Healthcare IT News.Twitter.

@kjercichEmail. Kjercich@himss.orgHealthcare IT News is a HIMSS Media publication.Researchers at Mount Sinai in New York see promise in new machine learning models they've developed that can assess – within key windows of time – the risk of certain adverse clinical events in some erectile dysfunction treatment patients.WHY IT MATTERSResearch published earlier this month in the Journal of Medical Internet Research describes how the algorithms are enabling better insights into potential risks for a diverse group of erectile dysfunction treatment patients.Researchers at Mount Sinai's Icahn School of Medicine and Hasso Plattner Institute for Digital Health gathered electronic health record data from more than 4,000 adult patients admitted to five Mount Sinai Health System hospitals from this spring, during the kamagra's first wave. HIMSS20 Digital Learn on-demand, earn credit, find products and solutions.

Get Started >>. Clinicians from the Mount Sinai erectile dysfunction treatment Informatics Center analyzed characteristics of erectile dysfunction treatment patients – looking at past medical history, comorbidities, vitals and labs – to help predict the risk of mortality, or critical events such as the need for intubation, within clinically relevant time windows.By predicting risks for time windows of three, five, seven and 10 days from admission, Mount Sinai researchers say the models offer valuable insights to forecast short and medium-term care decisions for erectile dysfunction treatment patients over the course of their hospitalizations.For instance, they note that at the one-week mark – the time period that offered the most accurate prediction of critical events while returning the fewest false positives – conditions such acute kidney injury, fast breathing, high blood sugar and elevated lactate dehydrogenase (indicating tissue damage or disease) were the strongest drivers in predicting critical illness.Older age, blood level imbalance, and C-reactive protein levels indicating inflammation, were the strongest drivers in predicting mortality.THE LARGER TRENDSome experts have made the case that artificial intelligence had a somewhat disappointing showing in the early days of the kamagra's spread. And it's true that bias in certain algorithms might have an adverse effect on some healthcare disparities.But AI and machine learning have a big role to play in diagnosis and decision support as the erectile dysfunction treatment emergency reaches its newest peak.

So far, an array of promising models, many pushed out to clinicians via EHR updates, have emerged to help detect the disease and assess risk on a population level.Mount Sinai, in particular, has been innovating its research into erectile dysfunction treatment over the eight months since it was inundated with patients during the kamagra's early peak. It's created an AI model to diagnose erectile dysfunction treatment in patients with otherwise normal lung scans, for instance. And has also pioneered the use of Apple Watch to study erectile dysfunction treatment stress and burnout among healthcare workers.ON THE RECORD"From the initial outburst of erectile dysfunction treatment in New York City, we saw that erectile dysfunction treatment presentation and disease course are heterogeneous, and we have built machine learning models using patient data to predict outcomes," said Benjamin Glicksberg, assistant professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai, in a statement."Now in the early stages of a second wave, we are much better prepared than before," he said.

"We are currently assessing how these models can aid clinical practitioners in managing care of their patients in practice."Added Dr. Girish Nadkarni, assistant professor of medicine in the nephrology department at the Icahn School. "More importantly, we have created a method that identifies important health markers that drive likelihood estimates for acute care prognosis and can be used by health institutions across the world to improve care decisions, at both the physician and hospital level, and more effectively manage patients with erectile dysfunction treatment." Twitter.

@MikeMiliardHITNEmail the writer. Mike.miliard@himssmedia.comHealthcare IT News is a HIMSS publication.With the next wave of the erectile dysfunction treatment kamagra beginning to crash down in hospitals around the country, it's more important than ever for health systems to be well attuned to their supply chain needs.One of the biggest challenges of the first wave this past spring, of course, was the shortage of personal protective equipment, ventilators and sometimes critical medications. Supply chain vulnerabilities were acute – and that's not counting the ongoing cyberattacks targeted at health system supply lines.Some of these challenges have been ironed out over the past eight months.

But as the erectile dysfunction treatment crisis surges again, CIOs and other IT professionals say robust supply chains are more important than ever.As Hal Wolf, CEO of HIMSS (parent company of Healthcare IT News) said this past week, a revolution in supply chain management is long overdue."We have really under-focused on supply chain," said Wolf, who noted the critical need to track the source of medications and equipment. Understand the quality of materials (being able to discern, for instance, that a shipment of N95 masks is really what it says it is). And ensuring supply chains are not interrupted – all while having visibility into price, inventory control and more.Hospital leaders around the country told Healthcare IT News that the current segmentation of systems has led to shortages right when facilities needed resources most.

Models such as CISOM, developed to improve quality and safety through the integration of supply chain and clinical data in healthcare organizations, can address such inefficiencies. But what are some ways that technology might play a role in making supply chain management a more seamless experience?. Chief information officers and other healthcare leaders who oversee the supply chains weighed in with their own experiences."At LifeBridge Health, we have approached the kamagra with a threefold supply strategy.

Conserve. Source. And, where needed, manufacture," said Tressa Springmann, CIO at LifeBridge Health in Baltimore.

"Clearly, as we are now seeing cases rise again, a keen ability to pivot more quickly has surfaced, and a few additional tools would put us into an even better position both now and into the future."First, more complete analytics. Analytics that tie [predictions of] patient volume and acuity with supply demand would be helpful," she said. "Second, real-time artificial intelligence that makes visible the entire life cycle – end-to-end if you will – of the global supply chain.

This visibility would enable a more effective response to market disruption, risk reduction and position us more effectively for enhanced business continuity.""At LifeBridge Health, we have approached the kamagra with a three-fold supply strategy. Conserve. Source http://www.sc-zwickl.zwettl.at/?facebookpost=timeline-photos-3.

And, where needed, manufacture."Tressa Springmann, CIO, LifeBridge Health"The healthcare industry would tremendously benefit from supply chain IT systems being much more seamlessly integrated with electronic medical records and their respective materials data sets integrated side-by-side with clinical data," said Aaron Miri, chief information officer at Dell Medical School and UT Health in Austin, Texas."The current state of this system's bifurcation led us down some rabbit holes during the PPE crunch, during the erectile dysfunction treatment kamagra, and therefore causes data analytics teams to have to jump over hurdles that shouldn't be this difficult," said Miri."Further, it's holding back advancement in value-based care bundles and new VBC products that could be put to market, as looking at a patient's complete health often includes materials and respective pricing of materials used during surgery, recovery and ongoing therapy," he said.Some health system leaders pointed to technologies such as artificial intelligence and machine learning as ways to help augment inventory control."We at Stanford Children's Health would like to see our supply chain tool provide real-time visibility and predictive analysis, such as available inventory, preferential pricing, lead times from different suppliers and demand trending," said Garima Srivastava, executive director of enterprise business systems."We would also want a system that can be scaled to incorporate new robotic process automation, artificial intelligence and radio frequency identification-based management," Srivastava added. "These are important for us to move towards the digital transformation and automate lots of manual work, which our supply chain department currently does. It will speed up some processes and will reduce manual errors."Using RFID in particular, Srivastava pointed out, "we will be able to track high-cost items and can manage our inventory better." "We would like to see our supply chain tool provide real time visibility and predictive analysis, such as available inventory, preferential pricing, lead times from different suppliers and demand trending."Garima Srivastava, executive director of enterprise business systems, Stanford Children's Health"We would love to see predictive forecasting and scenario planning, powered by machine learning and AI capabilities, integrated into our demand planning and supply modeling tools," agreed B.J.

Moore, CIO at Providence in Renton, Washington. "Think about the ability to predict consumption of PPE items based on real-time erectile dysfunction treatment modeling, patient admissions, and/or case data, and not on historical consumption alone," he mused.St. Jude Children's Research Hospital CIO Keith Perry also prioritized location awareness.

He said he'd like "to have the ability to track an item throughout the supply chain, including (and most important) the 'last mile,' until it physically arrives at the final delivery destination."Unlocking or exposing supply-chain data as appropriate for the person who is ordering equipment" would help with efficiency at St. Jude, Perry continued. "That person is the ultimate customer of any supply-chain process.""Unlocking or exposing supply-chain data as appropriate for the person who is ordering equipment" would help with efficiency at St.

Jude"Keith Perry, CIO, St. Jude Children's Research HospitalBill Donato, vice president of supply chain at the Hospital for Special Surgery in New York City, noted the importance of visibility. "One of the critical tools to manage the current and future healthcare supply chain is our ability to monitor in 'real time' the status of our critical suppliers' products from their manufacturing plants through their distribution networks," he said.

"Additional transparency of our suppliers' sales and operating plans would allow us to anticipate and more effectively manage disruptions to our supply chain."Leaders pointed out that the changes implemented in response to erectile dysfunction treatment would have lasting positive effects. "The most pressing need currently which has been highlighted by the supply chain challenges presented by the kamagra is the need for an affordable, efficient and comprehensive, enterprise-wide inventory management system," said Larry Fogarty, vice president of supply chain management at Memphis-based Methodist Le Bonheur Healthcare. "This would create coordinated visibility into the availability, stocking profiles and near-expired product monitoring for supply areas across the organization.

It would also go a long way in anticipating supply chain exposures, rather than simply reacting to them – a must in the post kamagra world," Fogarty continued."Finally, a coordinated system-wide inventory-management system would facilitate timely, inter-facility transfers to best allocate products where and when needed," Fogarty said."As the erectile dysfunction treatment kamagra continues to disrupt the supply chain, globally and at our five-hospital health system, I would love to see a warehouse-management-support system that could better manage, move and track inventory."Brian Murray, assistant vice president for supply chain procurement at NorthShore University HealthSystem, said, "Business intelligence software that automatically produces executive-level reporting and can help better forecast our need for gowns, gloves, N95s, isolation masks, thermometers and other PPE would be great."We are currently opening an offsite warehouse for our system and need a software program that will help us respond to and support erectile dysfunction treatment needs," he said."We are actively exploring robotic process automation to further streamline our operations and meet the needs of our community."Suzzanne Thomson Quintero, chief supply chain officer at Orlando HealthTanya Townsend, CIO for LCMC Health in New Orleans, said that her system is already taking steps to improve resource management."We are embarking on a new enterprise resource planning implementation which will include new Supply Chain functionality. I look forward to having more complete visibility to trace products and how that impacts patient care," said Townsend."I'm also excited about a more automated end-to-end process for managing inventory and procuring products," Townsend continued.Similarly, Suzzanne Thomson Quintero, chief supply chain officer at Orlando Health, said the system has taken advantage of existing capabilities. "Orlando Health is fortunate to have its own 90,000 sq.

Foot distribution center. This distribution hub uses a warehouse management system to forecast product needs for our 15 hospitals," Quintero explained. "We recently enhanced the system to provide meaningful reporting to our hospital operators.

In addition, we are introducing artificial intelligence into our purchasing operations to help purchase the right product, at the right price, from the right vendor," she said. "Also, we are actively exploring robotic process automation to further streamline our operations and meet the needs of our community.""Advanced inventory-demand planning, modeling and reporting would be a critical functionality to have in our tool kit to drive value in the supply chain, both long-term and during these unprecedented times," said Bill Moir, vice president of supply chain operations at Advocate Aurora Health in Wisconsin and Illinois."AAH is committed to enhancing our supply chain to ensure it is a strategic differentiator for our organization," said Moir. "Investments in our infrastructure, like enterprise resource planning, will ensure a strong standardized foundation that we can continue to build upon and innovate from for years to come." Kat Jercich is senior editor of Healthcare IT News.Twitter.

@kjercichEmail. Kjercich@himss.orgHealthcare IT News is a HIMSS Media publication.Boston Children’s Hospital was facing several problems that it had hoped it could solve with some new clinical tools.THE PROBLEMThe top problem was that its communications channels were not integrated into the larger healthcare ecosystem. Finding who was responsible for a given patient or a given role was in one system while finding out the phone number for that person or a role was in another system (or on cheat-sheets tacked up in workrooms or other places not available to everyone).The inability to efficiently find the right person at the right moment led 411-bed Boston Children’s to look for a better and more integrated solution.On another front, from a nursing perspective, the integrated health record at Boston Children’s allows for a comprehensive view of patient care.

However, this view was limited to desktop workstations and portable workstations on wheels.“If there was an issue with the mobile workstation, it presented a potential risk for accessing the patient EHR and utilizing our built-in, point-of-care safeguards, such as bar code medication administration,” said Lynnetta Akins, RN-BC, director of clinical education and informatics. €œBoston Children’s wanted a mobile solution to incorporate a comprehensive view to deliver patient care while leveraging point-of-care functionality.”The same issue applied to nursing and communication. Knowing who to contact and what number was a challenge, she added."Now, instead of knowing who the charge nurse is or what that role’s phone number is, I can look into the directory, search for the role, know who claimed the role at that moment, and securely text or call that person."Lynnetta Akins, Boston Children’s Hospital“Nursing would have to look in several places to communicate to the whole care team, decreasing the time nurses were spending at the bedside,” she said.PROPOSALBoston Children’s Hospital worked together with its EHR vendor Cerner to facilitate and coordinate care team communications.

The hospital implemented CareAware Connect (CAC) and Connect Nursing, using Cerner’s newest cloud-deployment model.“The proposal from CAC and Connect Nursing was to effectively integrate and mobilize our care team to allow for more efficient and integrated secure communications,” said Dr. Jonathan Bickel, senior director of BCH clinical health record, business intelligence, health information management and the Boston Children’s Medical Library and Archives at Boston Children’s Hospital.“The CAC platform provided the interoperability solution to quickly communicate across our continuity of care,” he said.The nursing application allowed for greater mobility and streamlined workflow efficiencies for the clinical workforce while continuing to support safe care for patients, he added.MARKETPLACEThere are many vendors with electronic health records systems on the health IT market today, including Allscripts, athenahealth, Cerner, DrChrono, eClinicalWorks, Epic, Greenway Health, HCS, Meditech and NextGen Healthcare.MEETING THE CHALLENGECAC solves the challenges by allowing team members to claim roles that allow for efficient communication with the right person, Akins explained.“Now, instead of knowing who the charge nurse is or what that role’s phone number is, I can look into the directory, search for the role, know who claimed the role at that moment, and securely text or call that person,” she said. €œPutting the CAC devices in nurses’ hands allows for greater mobility while quickly communicating among the care team.”"Enabling Bluetooth for people who use personal protective equipment has been an ideal side benefit, because you can use the device without having to touch anything."Dr.

Jonathan Bickel, Boston Children’s HospitalWith Connect Nursing, staff was able to empower nurses with increased accessibility for clinical workflow, she added.“The mobility and flexibility to deliver patient care with tools in the palm of their hands,” she noted. €œOur nurses were able to dedicate more time spent at the patient bedside to providing safe and high-quality care. Connect Nursing brought greater mobility and flexibility to the bar code medication administration process, inclusive of positive patient identification.”For the pediatric population, staff had the flexibility for scanning to change the event sequence to support pediatrics medication preparation.“The Connect Nursing platform supports point-of-care alerts functionality,” she said.

€œNurses have stated that having a mobile workflow that doesn’t require the use of a workstation on wheels to support safe and highly reliable medication administration has been a real win for safety, workflow and satisfaction.”RESULTS“The results speak for themselves,” Bickel said. €œWith our prior secure texting platform, we had hundreds of users sending a few thousand texts a month. With our integrated CAC platform, we have about 300,000 messages sent a month across 3,580 providers.

We are seeing 200,000 calls a month. This far exceeded our expectations, and highlights how much communication is needed to care for our complex pediatric population.”Additionally, Connect Nursing brought greater mobility and flexibility to the bar code medication administration process, Akins said.“Two of the largest patient care areas – emergency department and post-surgical unit – are using it for most of their medication administration events,” she reported. €œNurses in those patient care areas say a mobile workflow that doesn’t require the use of a workstation on wheels supports safe and highly reliable medication administration.”In the fight against erectile dysfunction treatment, there are more capabilities for Boston Children’s staff to potentially use.“With Bluetooth, we can start to think about performing contact tracing using devices to record interactions with other personnel and their devices on a given floor,” Bickel observed.

€œEnabling Bluetooth for people who use personal protective equipment has been an ideal side benefit, because you can use the device without having to touch anything. This implemented platform has been serendipitous and quite useful.”ADVICE FOR OTHERS“When considering a vendor, one needs to consider how tightly integrated the vendor’s collaboration is with your care team,” Bickel advised. €œDo you have a single source of truth of who, at any moment, is part of a given care team?.

Can that platform take the care team information and utilize this to facilitate communication?. Does the texting platform support all the functionality needed?. €Twitter.

@SiwickiHealthITEmail the writer. Bsiwicki@himss.orgHealthcare IT News is a HIMSS Media publication..

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