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Wealthy nations must how to get kamagra without a doctor do much more, much faster.The United Nations General Assembly in September 2021 will bring countries together at a critical time for marshalling collective action to http://eastwoodrealestateservices.com/buy-kamagra-paypal/ tackle the global environmental crisis. They will meet again at the biodiversity summit in Kunming, China, and the climate conference (Conference of the Parties (COP)26) in how to get kamagra without a doctor Glasgow, UK. Ahead of these pivotal meetings, we—the editors of health journals worldwide—call for urgent action to keep average global temperature increases below 1.5°C, halt the destruction of nature and protect health.Health is already being harmed by global temperature increases and the destruction of the natural world, a state of affairs health professionals have been bringing attention to for decades.1 The science is unequivocal.

A global increase of 1.5°C above the preindustrial average and the continued loss of biodiversity risk catastrophic harm to health that will be impossible to reverse.2 3 Despite the world’s necessary preoccupation with erectile dysfunction treatment, we cannot wait for the kamagra to pass to rapidly reduce emissions.Reflecting how to get kamagra without a doctor the severity of the moment, this editorial appears in health journals across the world. We are united in recognising that only fundamental and equitable changes to societies will reverse our current trajectory.The risks to health of increases above 1.5°C are now how to get kamagra without a doctor well established.2 Indeed, no temperature rise is ‘safe’. In the past 20 years, heat-related mortality among people aged over 65 has increased by more than 50%.4 Higher temperatures have brought increased dehydration and renal function loss, dermatological malignancies, tropical s, adverse mental health outcomes, pregnancy complications, allergies, and cardiovascular and pulmonary morbidity and mortality.5 6 Harms disproportionately affect the most vulnerable, including children, older populations, ethnic minorities, poorer communities and those with underlying health problems.2 4Global heating is also contributing to the decline in global yield potential for major crops, falling by 1.8%–5.6% since 1981.

This, together with the effects of extreme weather and soil depletion, is hampering efforts to reduce undernutrition.4 Thriving ecosystems are essential to human health, how to get kamagra without a doctor and the widespread destruction of nature, including habitats and species, is eroding water and food security and increasing the chance of kamagras.3 7 8The consequences of the environmental crisis fall disproportionately on those countries and communities that have contributed least to the problem and are least able to mitigate the harms. Yet no country, no matter how wealthy, can shield itself from these impacts. Allowing the how to get kamagra without a doctor consequences to fall disproportionately on the most vulnerable will breed more conflict, food insecurity, forced displacement and zoonotic disease, with severe implications for all countries and communities.

As with how to get kamagra without a doctor the erectile dysfunction treatment kamagra, we are globally as strong as our weakest member.Rises above 1.5°C increase the chance of reaching tipping points in natural systems that could lock the world into an acutely unstable state. This would critically impair our ability to mitigate harms and to prevent catastrophic, runaway environmental change.9 10Global targets are not enoughEncouragingly, many governments, financial institutions and businesses are setting targets to reach net-zero emissions, including targets for 2030. The cost how to get kamagra without a doctor of renewable energy is dropping rapidly.

Many countries are aiming to protect at least 30% of the world’s land and oceans by 2030.11These promises how to get kamagra without a doctor are not enough. Targets are easy to set and hard to achieve. They are yet to be matched with credible short-term and longer-term plans to accelerate cleaner technologies and transform how to get kamagra without a doctor societies.

Emissions reduction plans do not adequately incorporate health considerations.12 Concern is growing that temperature rises above 1.5°C are beginning to be seen as inevitable, or even acceptable, to powerful members of the global community.13 Relatedly, current strategies for reducing emissions to net zero by the middle of the century how to get kamagra without a doctor implausibly assume that the world will acquire great capabilities to remove greenhouse gases from the atmosphere.14 15This insufficient action means that temperature increases are likely to be well in excess of 2°C,16 a catastrophic outcome for health and environmental stability. Critically, the destruction of nature does not have parity of esteem with the climate element of the crisis, and every single global target to restore biodiversity loss by 2020 was missed.17 This is an overall environmental crisis.18Health professionals are united with environmental scientists, businesses and many others in rejecting that this outcome is inevitable. More can and must be done now—in Glasgow and Kunming—and in the immediate how to get kamagra without a doctor years that follow.

We join health professionals worldwide who have already supported calls for rapid action.1 19Equity must be at the centre of the global response. Contributing a fair share to the global effort means that reduction commitments must account for the cumulative, historical contribution each country has made to emissions, as how to get kamagra without a doctor well as its current emissions and capacity to respond. Wealthier countries will have to cut emissions more quickly, making reductions by how to get kamagra without a doctor 2030 beyond those currently proposed20 21 and reaching net-zero emissions before 2050.

Similar targets and emergency action are needed for biodiversity loss and the wider destruction of the natural world.To achieve these targets, governments must make fundamental changes to how our societies and economies are organised and how we live. The current strategy of encouraging markets how to get kamagra without a doctor to swap dirty for cleaner technologies is not enough. Governments must intervene to support the redesign of transport systems, cities, production and distribution of food, markets for financial investments, health systems, and much more.

Global coordination is needed to ensure that the rush for how to get kamagra without a doctor cleaner technologies does not come at the cost of more environmental destruction and human exploitation.Many governments met the threat of the erectile dysfunction treatment kamagra with unprecedented funding. The environmental how to get kamagra without a doctor crisis demands a similar emergency response. Huge investment will be needed, beyond what is being considered or delivered anywhere in the world.

But such investments will produce huge positive health and economic outcomes how to get kamagra without a doctor. These include high-quality jobs, reduced air pollution, increased physical activity, and improved housing how to get kamagra without a doctor and diet. Better air quality alone would realise health benefits that easily offset the global costs of emissions reductions.22These measures will also improve the social and economic determinants of health, the poor state of which may have made populations more vulnerable to the erectile dysfunction treatment kamagra.23 But the changes cannot be achieved through a return to damaging austerity policies or the continuation of the large inequalities of wealth and power within and between countries.Cooperation hinges on wealthy nations doing moreIn particular, countries that have disproportionately created the environmental crisis must do more to support low-income and middle-income countries to build cleaner, healthier and more resilient societies.

High-income countries must meet and go beyond their outstanding commitment to provide $100 billion a year, making up for any shortfall how to get kamagra without a doctor in 2020 and increasing contributions to and beyond 2025. Funding must be equally split between mitigation and adaptation, including improving the resilience of health systems.Financing should be through grants rather than loans, building local capabilities and truly empowering communities, and should come alongside forgiving large debts, which constrain the agency of so many low-income countries. Additional funding must be marshalled to how to get kamagra without a doctor compensate for inevitable loss and damage caused by the consequences of the environmental crisis.As health professionals, we must do all we can to aid the transition to a sustainable, fairer, resilient and healthier world.

Alongside acting to reduce the harm from the environmental crisis, we should proactively contribute to global prevention of further damage and action on the root causes of how to get kamagra without a doctor the crisis. We must hold global leaders to account and continue to educate others about the health risks of the crisis. We must join in the work to achieve environmentally sustainable health how to get kamagra without a doctor systems before 2040, recognising that this will mean changing clinical practice.

Health institutions how to get kamagra without a doctor have already divested more than $42 billion of assets from fossil fuels. Others should join them.4The greatest threat to global public health is the continued failure of world leaders to keep the global temperature rise below 1.5°C and to restore nature. Urgent, society-wide changes must be made and will lead to a fairer and how to get kamagra without a doctor healthier world.

We, as editors of health journals, call for governments and other leaders to act, marking 2021 as the year that the world finally changes course.Ethics statementsPatient consent for publicationNot required..

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Joe Biden must now make up for lost time, and he has said the U.S. Will rejoin the Paris agreement immediately. This commitment is kamagra oral jelly review important because the U.S. Is still the world’s second largest emitter, behind China, and it can also return as a world climate leader.

But Biden will also have to ratchet up the original kamagra oral jelly review U.S. Pledge, because because warming—and its effects—have only sped up since the Paris Agreement was reached. Biden has promised to issue an executive order calling for net-zero emissions by 2050, but he will need to set specific interim targets. The World kamagra oral jelly review Resources Institute says reducing emissions 45 to 50 percent below 2005 levels by 2030 could put the country on track.

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To expand on that action, Biden could charge the EPA and Department of Transportation with rescinding Trump’s Safer Affordable Fuel-Efficient Vehicle Rule, which undercut more stringent national standards set under the Obama administration. Even then, to stay on course to meet the two-degree C goal, 90 percent of U.S. Passenger cars and light-duty trucks would need to be electric kamagra oral jelly review by 2050, according to a recent study published in Nature Climate Change. Because cars last 12 to 15 years on average, new EPA and DOT rules that encourage or requirezero-emission vehicles by 2030 or 2035 would help the hop over to this web-site U.S.

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One important leadership change the Biden administration kamagra oral jelly review and its agencies can make is to help cities, states and companies play bigger roles in reducing emissions quickly, by alerting them to planned federal rules and regulations. That way they can begin to adapt sooner. €œAt the end of the day,” Subramanian says, “one of the biggest tools the Biden administration has is sending signals.”.

One word sums up what how to get kamagra without a doctor President-elect Joe Biden must do to address climate best online site to buy kamagra change. Restart.In 2015 nearly 200 nations agreed to the Paris Agreement, which aims to prevent the worst impacts of climate change by limiting global warming to belowtwo degrees Celsius above preindustrial levels by 2100. The U.S how to get kamagra without a doctor.

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Will rejoin the Paris agreement immediately. This commitment is important because the U.S how to get kamagra without a doctor. Is still the world’s second largest emitter, behind China, and it can also return as a world climate leader.

But Biden how to get kamagra without a doctor will also have to ratchet up the original U.S. Pledge, because because warming—and its effects—have only sped up since the Paris Agreement was reached. Biden has promised to issue an executive order calling for net-zero emissions by 2050, but he will need to set specific interim targets.

The World Resources Institute says reducing emissions 45 to 50 percent below 2005 levels by 2030 could put the country on how to get kamagra without a doctor track. Congressional legislation is the most effective way to create the concrete policies to achieve those goals, because it gives federal agencies clear priorities, is much harder to override with presidential actions, and can better withstand legal challenges that might be brought by industry or special-interest groups. But the how to get kamagra without a doctor divided U.S.

Senate will make sweeping laws hard to pass. Biden will have to work through executive orders, and will have to charge federal agencies such as the Environmental Protection Agency with issuing new regulations under existing laws such as the Clean Air Act. He will need to “turn every stone possible,” says Narayan Subramanian, an environmental lawyer working with the Center for Law, how to get kamagra without a doctor Energy &.

The Environment at Berkeley Law. The most immediate focuses how to get kamagra without a doctor are transportation, power plants, methane emissions and pesky hydrofluorocarbons. With coal plants retiring, transportation has surpassed power generation as the country’s largest carbon emitter.

The quickest action Biden can take to tackle those emissions is toreinstate California’s waiver to the Clean Air Act, allowing the state to enforce its Advanced Clean Car regulations. They set fuel efficiency standards for cars and light-duty trucks that are tougher than federal rules, how to get kamagra without a doctor which means fewer emissions. In the past, automakers have built their nationwide fleets to meet the state’s standards to avoid making two versions of their vehicles, and some states such as New York typically follow California’s lead.

The Rhodium Group estimates that reinstating the waiver would save about 573 how to get kamagra without a doctor million metric tons of emissions by 2035. To expand on that action, Biden could charge the EPA and Department of Transportation with rescinding Trump’s Safer Affordable Fuel-Efficient Vehicle Rule, which undercut more stringent national standards set under the Obama administration. Even then, to stay on course to meet the two-degree C goal, 90 percent of U.S.

Passenger cars and light-duty trucks would need to be electric how to get kamagra without a doctor by 2050, according to a recent study published in Nature Climate Change. Because cars last 12 to 15 years on average, new EPA and DOT rules that encourage or requirezero-emission vehicles by 2030 or 2035 would help the U.S. Fleet turn over in how to get kamagra without a doctor time.

Some major U.S. Car companies, including GM and Ford, are increasingly investing in electric vehicles, and did not support the full Trump rollbacks because they would likely end up in court, creating years of regulatory uncertainty. In the electric power industry, market forceswill not cut emissions fast how to get kamagra without a doctor enough to meet the two-degree goal, according to Dan Lashof, U.S.

Director of the World Resources Institute. Biden has pledged to set an ambitious net-zero goal for how to get kamagra without a doctor the power sector by 2035. If achieved, this would reduce emissions by up to 1,380 million metric tons of CO2 a year by 2030 and 1,510 million metric tons a year by 2050, according to the Asia Society Policy Institute and the nonprofit climate science and policy institute Climate Analytics.

Reaching those numbers will require replacingTrump’s Affordable Clean Energy rule with a more aggressive version ofthe Obama-era Clean Power Plan, which was suspended by the Supreme Court before it could go into effect. The plan, an how to get kamagra without a doctor EPA regulation, would have set strict limits on emissions from power plants. Biden could carefully enact new EPA regulations that can better withstand any future federal court challenge.

Although CO2 emissions are much bigger and stay in the atmosphere for longer, scientists are paying increasing attention to curbing methane how to get kamagra without a doctor emissions, because new studies show they are rising fast, and methane is a more potent greenhouse gas. The Trump administration recently rolled back several methane regulations, notably EPA rules requiring oil and gas companies to monitor and repair leaks in their infrastructure. The Rhodium Group estimates that leaks would increase emissions by 592 million metric tons through 2035.

As with power plant rules, Biden will have to work through the how to get kamagra without a doctor EPA to repeal the rollbacks and install tougher new requirements. Hydrofluorocarbons, used in refrigeration and air conditioning, also pack a major warming punch. Here is one case where Congress could how to get kamagra without a doctor play a role.

Republican senators, including John Kennedy of Louisianahave backed a bill called American Innovation and Manufacturing Act. The bill, supported by industry, would cut HFC use 85 percent by 2035, but it is unclear if Congress will pass it before the 2020 session ends. If not, Congress could take it how to get kamagra without a doctor up again in 2021.

If passed, the AIM Act would be in line with the 2016 Kigali Amendment to the global Montreal Protocol, which calls for a more than 80 percent reduction in hydrofluorocarbon production and consumption in the next 25 years. Biden can also expand on legislation that has already garnered bipartisan support, such as maintaining tax incentives to encourage how to get kamagra without a doctor the expanded use of renewable energy and electric vehicles. Any kamagra-related stimulus packages could include funding for green infrastructure projects such as building more electric vehicle charging stations to help grow that market, or plugging abandoned oil and gas wells that leak methane.

The federal government can also use its considerable purchasing power to help bolster parts of the clean energy sector, such as buying electric delivery vans for the U.S. Postal Service how to get kamagra without a doctor. In tandem, the Biden administration can strengthen rules under the National Environmental Policy Act that require all federal agencies to consider the environmental impacts of actions they take or projects they approve, such as allowing oil drilling on federal land.

The Trump administration said how to get kamagra without a doctor the act only requires consideration of direct, noncumulative impacts, which effectively took climate change off the table. The Council on Environmental Quality, which ensures that federal agencies adhere to the act, could specify that future climate change impacts should be considered. That step could make it less likely that emissions-intensive projects, such as drilling, would be approved by agencies such as the Interior Department.

One important how to get kamagra without a doctor leadership change the Biden administration and its agencies can make is to help cities, states and companies play bigger roles in reducing emissions quickly, by alerting them to planned federal rules and regulations. That way they can begin to adapt sooner. €œAt the end of the day,” Subramanian says, “one of the biggest tools the Biden administration has is sending signals.”.

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Jamel.El-Hamri@dot.gov phone. 2020-366-8985. A Telecommunication Device kamagra for sale online for the Deaf (TDD) is available for individuals who are deaf or hard of hearing at 1-800-877-8339. End Further Info End Preamble Start Supplemental Information Table of Contents A. Program Description B.

Federal Award kamagra for sale online Information C. Eligibility Information D. Application and Submission Information kamagra for sale online E. Application Review Information F. Federal Award Administration Information G.

Federal Awarding kamagra for sale online Agency Contact Information A. Program Description The Public Transportation erectile dysfunction treatment Research Demonstration Grant Program is funded through the Public Transportation Innovation Program (49 U.S.C. 5312), with the goal to develop, deploy, and demonstrate innovative solutions that improve the operational efficiency of transit agencies, as well as enhance the mobility of transit users affected by the erectile dysfunction treatment public health emergency. Eligible projects will propose to develop and kamagra for sale online deploy innovative solutions in four major areas. (1) Vehicle, facility, equipment and infrastructure cleaning and dis.

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B. Federal Award Information FTA makes available $10,000,000 in fiscal year (FY) 2020 funds under the Public Transportation kamagra for sale online Innovation Program (49 U.S.C. 5312) to finance the Public Transportation erectile dysfunction treatment Research Demonstration Grant Program. FTA may supplement the total funds available if additional funding becomes available at the time project selections are made. FTA will grant pre-award authority starting on the date of the project kamagra for sale online award announcement for selected projects and should be completed within 24 months from the date of award.

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Eligible applicants are limited to FTA grantees or subrecipients who would be the primary beneficiaries of the innovative products and services that are developed—typically public transit agencies kamagra for sale online. Except for projects proposed by Indian tribes, proposals for projects in rural (non-urbanized) areas must be submitted as part of a consolidated State proposal. States and other kamagra for sale online eligible applicants also may submit consolidated proposals for projects in urbanized areas. The submission of the Statewide application will not preclude the submission and consideration of any application from other eligible recipients in an urbanized area in a State. Proposals may contain projects to be implemented by the recipient or its subrecipients.

Eligible subrecipients include public agencies, private nonprofit organizations, and private providers engaged in kamagra for sale online public transportation. Eligible applicants may submit consolidated proposals for projects. (2) Cost Sharing or Matching The maximum Federal share of project costs is 100 percent. FTA may give additional consideration to applicants that propose a local share and may view these applicants as more kamagra for sale online competitive. The applicant must document the source(s) of the local match, if any, in the grant application.

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Exposure mitigation measures such a real-time notification of rail and bus passenger loads. New multi-modal payment innovative mobility systems such as contactless payments. And measures that strengthen public confidence in transit kamagra for sale online. Each applicant may only submit one proposal.Start Printed Page 63655 D. Application and Submission Information (1) Address and Form of Application Submission Applications must be submitted through GRANTS.GOV.

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If applicants copy information into the supplemental form from another source, they should verify that the supplemental form has fully captured pasted text and that it has not truncated the text due to character limits built into the form. Applicants should use both the “Check kamagra for sale online Package for Errors” and the “Validate Form” validation buttons on both forms to check all required fields. Applicants should also ensure that the Federal and local amounts specified are consistent. Addressing the deteriorating conditions and disproportionately high fatality rates on our rural transportation infrastructure is of critical interest to the Department, as rural transportation networks face unique challenges in safety, infrastructure condition, and passenger and freight usage. Consistent with kamagra for sale online the R.O.U.T.E.S.

Initiative, the Department encourages applicants to consider how the project will address the challenges faced by rural areas. B. Application Content The SF-424 Mandatory Form and the supplemental form will prompt applicants for the required kamagra for sale online information, including. I. Applicant Name ii.

Dun and Bradstreet (D&B) Data Universal Numbering System (DUNS) number kamagra for sale online iii. Key contact information (contact name, address, email address, and phone number) iv. Congressional district(s) where project will take place v. Project Information (title, executive summary, and type) kamagra for sale online vi. A detailed description of the need for the project vii.

A detailed description kamagra for sale online of how the project will support the Program objectives viii. Evidence that the applicant can provide the local cost shares ix. A description of the technical, legal, and financial capacity of the applicant x. A detailed project budget kamagra for sale online xi. Details on the local matching funds xii.

A detailed project timeline xiii. Whether the project impacts an Opportunity Zone (3) Unique Entity Identifier and System kamagra for sale online for Award Management (SAM) Each applicant is required to. (1) Be registered in SAM before submitting an application. (2) provide a valid unique entity identifier in its application. And (3) continue to maintain an kamagra for sale online active SAM registration with current information at all times during which the applicant has an active Federal award or an application or plan under consideration by FTA.

These requirements do not apply if the applicant. (1) Is excepted from the requirements under 2 CFR 25.110(b) or (c). Or (2) has an exception approved kamagra for sale online by FTA under 2 CFR 25.110(d). FTA may not make an award until the applicant has complied with all applicable unique entity identifier and SAM requirements. If an applicant has not fully complied with kamagra for sale online the requirements by the time FTA is ready to make an award, FTA may determine that the applicant is not qualified to receive an award and use that determination as a basis for making a Federal award to another applicant.

All applicants must provide a unique entity identifier provided by SAM. Registration in SAM may take as little as 3-5 business days, but there can be unexpected steps or delays. For example, the applicant may need to obtain an Employer Identification kamagra for sale online Number. FTA recommends allowing ample time, up to several weeks, to complete all steps. For additional information on obtaining a unique entity identifier, please visit www.sam.gov.

(4) Submission Dates and Times kamagra for sale online Project proposals must be submitted electronically through GRANTS.GOV by 11:59 p.m. Eastern on November 2, 2020. Mail and fax submissions will not be accepted. FTA urges applicants to submit applications at kamagra for sale online least 72 hours prior to the due date to allow time to correct any problems that may have caused either GRANTS.GOV or FTA systems to reject the submission. Proposals submitted after the deadline will only be considered under extraordinary circumstances not within the applicant's control.

Deadlines will kamagra for sale online not be extended due to scheduled website maintenance. GRANTS.GOV scheduled maintenance and outage times are announced on the GRANTS.GOV website. Within 48 hours after submitting an electronic application, the applicant should receive two email messages from GRANTS.GOV. (1) Confirmation of successful transmission kamagra for sale online to GRANTS.GOV. And (2) confirmation of successful validation by GRANTS.GOV.

If the applicant does not receive confirmation of successful validation or receives a notice of failed validation or incomplete materials, the applicant must address the reason for the failed validation, as described in the email notice, and resubmit before the submission deadline. If making a resubmission for any reason, applicants must kamagra for sale online include all original attachments regardless of which attachments were updated and check the box on the supplemental form indicating this is a resubmission. Applicants are encouraged to begin the process of registration on the GRANTS.GOV site well in advance of the submission deadline. Registration is Start Printed Page 63656a multi-step process, which may take several weeks to complete before an application can be submitted. Registered applicants may still be required to kamagra for sale online update their registration before submitting an application.

Registration in SAM is renewed annually and persons making submissions on behalf of the Authorized Organization Representative (AOR) must be authorized in GRANTS.GOV by the AOR to make submissions. (5) Funding Restrictions Funds may be used for post-award expenditures only. Funds under kamagra for sale online this NOFO cannot be used to reimburse projects for otherwise eligible expenses incurred prior to the date of project award announcements. (6) Other Submission Requirements FTA encourages applicants to identify scaled funding options in case insufficient funding is available to fund a project at the full requested amount. If an applicant kamagra for sale online indicates that a project is scalable, the applicant must provide an appropriate minimum funding amount that will fund an eligible project that achieves the objectives of the program and meets all relevant program requirements.

The applicant must provide a clear explanation of how a reduced award would affect the project budget and scope. FTA may award a lesser amount whether or not the applicant provides a scalable option. E. Application Review Information (1) Project Evaluation Criteria Addressing the deteriorating conditions and disproportionately high fatality rates on our rural transportation infrastructure is of critical interest to the Department, as rural transportation networks face unique challenges in safety, infrastructure condition, and passenger and freight usage. Consistent with the R.O.U.T.E.S.

Initiative, the Department will consider how the project will address the challenges faced by rural areas. In addition, the Department will review and consider applications for funding pursuant to this Notice in accordance with the President's September 2, 2020 memorandum, entitled Memorandum on Reviewing Funding to State and Local Government Recipients of Federal Funds that Are Permitting Anarchy, Violence, and Destruction in American Cities, consistent with guidance from the Office of Management and Budget and the Attorney General and with all applicable laws. FTA will evaluate proposals submitted according to the following criteria. (a) Project Innovation and Impact. (b) Project Approach.

(c) National Applicability. (d) Commercialization and/or Knowledge Transfer. And (e) Technical, Legal and Financial Capacity. FTA encourages each applicant to demonstrate how a project supports all criteria with the most relevant information the applicant can provide, regardless of whether such information has been specifically requested or identified in this notice. A.

Project Innovation and Impact i. Effectiveness of the project in achieving and demonstrating the specific objectives of this program. Ii. Demonstration of benefits in addressing the needs of the transit agency and industry and impacts to infrastructure, equipment, transit workforce, and riders. Iii.

Degree of improvement over current and existing technologies, designs, and/or practices applicable to the transit industry. B. Project Approach i. Quality of the project approach such as existing partnerships, collaboration strategies and level of commitment of the project partners. Ii.

Proposal is realistic in its approach to fulfill the milestones/deliverables, schedule and goals. C. National Applicability i. Degree to which the project could be replicated by other transit agencies regionally or nationally. Ii.

Ability to evaluate technologies, designs and/or practices in a kamagra tablet online wide variety of conditions and locales. Iii. Degree to which the technology, designs and/or practices can be replicated by other transportation modes. D. Commercialization and/or Knowledge Transfer i.

Demonstrates a realistic plan for moving the results of the project into the transit marketplace (patents, conferences, articles in trade magazines, webinar, site visits, etc.). Ii. How the project team plans to work with the industry on improving best practices, guidance and/or standards, if applicable. Iii. Demonstrate a clear understanding and robust approach to data collection, access and management.

E. Technical, Legal and Financial Capacity Capacity of the applicant and any partners to successfully execute the project effort. There should be no outstanding legal, technical, or financial issues with the applicant that would make this a high-risk project. (2) Review and Selection Process An FTA technical evaluation committee will evaluate proposals based on the published project evaluation criteria. Members of the technical evaluation committee will rate the applications and may seek clarification about any statement in an application.

The FTA Administrator will determine the final selection and amount of funding for each project after consideration of the findings of the technical evaluation committee. Geographic diversity, diversity of the project type, the amount of local match to be provided, and the applicant's receipt and management of other Federal transit funds may be considered in FTA's award decisions. Prior fare payment innovation efforts may receive priority consideration. The FTA Administrator will consider the following key DOT objectives. A.

Utilizing alternative funding sources and innovative financing models to attract non-Federal sources of investment. B. Whether the project is located in or supports public transportation service in a qualified opportunity zone designated pursuant to 26.U.S.C. 1400Z-1. And c.

The extent to which the project addresses challenges specific to the provision of rural public transportation. (3) FAPIIS Review Prior to making a grant award, FTA is required to review and consider any information about the applicant that is in the Federal Awardee Performance and Integrity Information System (FAPIIS) accessible through SAM. An applicant may review and comment on information about itself that a Federal awarding agency previously entered. FTA will consider any comments by the applicant, in addition to the other information in FAPIIS, in making a judgment about the applicant's integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 2 CFR 200.205 Federal Awarding Agency Review of Risk Posed by Applicants. F.

Federal Award Administration Information (1) Federal Award Notices FTA will announce the final project selections on the FTA website. Project recipients should contact their FTA Regional Office for additional information regarding allocations for Start Printed Page 63657projects. At the time project selections are announced, FTA will extend pre-award authority for the selected projects. There is no blanket pre-award authority for these projects before announcement. There is no minimum or maximum grant award amount, but FTA intends to fund as many meritorious projects as possible.

FTA only will consider proposals from eligible recipients for eligible activities. Due to funding limitations, projects selected for funding may receive less than the amount originally requested. In those cases, applicants must be able to demonstrate that the proposed projects are still viable and can be completed with the amount awarded. (2) Administrative and National Policy Requirements a. Pre-Award Authority FTA will issue specific guidance to recipients regarding pre-award authority at the time of selection.

FTA does not provide pre-award authority for competitive funds until projects are selected, and there are Federal requirements that must be met before costs are incurred. For more information about FTA's policy on pre-award authority, see the FY 2020 Apportionments Notice published on June 3, 2020, at https://www.govinfo.gov/​content/​pkg/​FR-2020-06-03/​pdf/​2020-11946.pdf. b. Grant Requirements Selected applicants will submit a grant application through FTA's electronic grant management system and adhere to the customary FTA grant requirements for research project (insert Circular name). All competitive grants, regardless of award amount, will be subject to the Congressional notification and release process.

FTA emphasizes that third-party procurement applies to all funding awards, as described in FTA Circular 4220.1F, “Third Party Contracting Guidance.” However, FTA may approve applications that include a specifically identified partnering organization(s) (2 CFR 200.302(f)). When included, the application, budget, and budget narrative should provide a clear understanding of how the selection of these organizations is critical for the project and give sufficient detail about the costs involved. C. Planning FTA encourages applicants to engage the appropriate State Departments of Transportation, Regional Transportation Planning Organizations, or Metropolitan Planning Organizations in areas to be served by the project funds available under this program. D.

Standard Assurances The applicant assures that it will comply with all applicable Federal statutes, regulations, executive orders, FTA circulars, and other Federal administrative requirements in carrying out any project supported by the FTA grant. The applicant acknowledges that it is under a continuing obligation to comply with the terms and conditions of the grant agreement issued for its project with FTA. The applicant understands that Federal laws, regulations, policies, and administrative practices might be modified from time to time and may affect the implementation of the project. The applicant agrees that the most recent Federal requirements will apply to the project unless FTA issues a written determination otherwise. The applicant must submit the Certifications and Assurances before receiving a grant if it does not have current certifications on file.

E. Free Speech and Religious Liberty In connection with any program or activity conducted with or benefiting from funds awarded under this notice, recipients of funds must comply with all applicable requirements of Federal law, including, without limitation, the Constitution of the United States. Statutory, regulatory, and public policy requirements, including without limitation, those protecting free speech, religious liberty, public welfare, the environment, and prohibiting discrimination. The conditions of performance, non-discrimination requirements, and other assurances made applicable to the award of funds in accordance with regulations of the Department of Transportation. And applicable Federal financial assistance and contracting principles promulgated by the Office of Management and Budget.

In complying with these requirements, recipients must ensure that no concession agreements are denied or other contracting decisions made on the basis of speech or other activities protected by the First Amendment. If the Department determines that a recipient has failed to comply with applicable Federal requirements, the Department may terminate the award of funds and disallow previously incurred costs, requiring the recipient to reimburse any expended award funds. (3) Reporting The post-award reporting requirements include submission of the Federal Financial Report (FFR) and Milestone Progress Report in TrAMS. An evaluation of the grant will occur at various points in the demonstration process and at the end of the project. In addition, FTA is responsible for producing an Annual Report to Congress that compiles evaluation of selected projects, including an evaluation of the performance measures identified by the applicants.

All applicants must develop an evaluation plan to measure the success or failure of their projects and describe any plans for broad-based implementation of successful projects. FTA may request data and reports to support the evaluation and Annual Report. A. Independent Evaluation To achieve a comprehensive understanding of the impacts and implications of each proposed erectile dysfunction treatment Research Demonstration Program, projects funded under this announcement will require the recipient to conduct a third party independent evaluation of their project. Recipients will be required to contract with a third party independent evaluator to assist in developing an evaluation plan, and collecting, storing and managing data required to fulfill the evaluation requirement.

No more than 10 percent of the Federal share of the project may be used to hire the third-party independent evaluator and the inclusion of a third-party independent evaluation should be described in the grant application. If the project duration is more than two years, an interim evaluation report would need to be submitted to FTA, otherwise the evaluation report should be included as part of the final project report. B. erectile dysfunction treatment Research Demonstration Grant Program Evaluation Projects funded under this announcement will be required to establish a set of performance metrics set by the third-party independent evaluator and shared with FTA. G.

Federal Awarding Agency Contacts Information For questions about applying, please contact Jamel El-Hamri email. Jamel.El-Hamri@dot.gov phone. 202-366-8985. A TDD is available at 1-800-877-8339 (TDDFIRS). To ensure that applicants receive accurate information about eligibility or the program, applicants are encouraged to contact FTA directly with questions, rather than through intermediaries or third parties.Start Printed Page 63658 FTA staff also may conduct briefings on the competitive grants selection and award process upon request.

Start Signature K. Jane Williams, Deputy Administrator. End Signature End Supplemental Information [FR Doc. 2020-22316 Filed 10-7-20. 8:45 am]BILLING CODE 4910-57-PStart Preamble Office of the Secretary, Department of Health and Human Services.

Notice. The Department of Health and Human Services (HHS) Office of Infectious Disease and HIV/AIDS Policy (OIDP) in the Office of the Assistant Secretary for Health (OASH) announces the draft Viral Hepatitis National Strategic Plan. A Roadmap to Elimination (2021-2025) (Hepatitis Plan) available for public comment. The draft Hepatitis Plan may be reviewed at www.hhs.gov/​hepatitis. All comments must be received by 5:00 p.m.

ET on October 8, 2020 to ensure consideration. All comments must be submitted electronically to HepatitisPlanComments@hhs.gov. Start Further Info Carol Jimenez, OIDP, Carol.Jimenez@hhs.gov. 202-401-5131. End Further Info End Preamble Start Supplemental Information Viral hepatitis is a significant public health threat that puts people who are infected at increased risk for serious disease and death.

In the United States, new hepatitis A and hepatitis C s have increased dramatically in recent years, little progress has been made on preventing hepatitis B s, and, as of 2016, an estimated 3.3 million people were chronically infected with hepatitis B and hepatitis C.1-3 Collectively, viral hepatitis costs people, health systems, states, and the federal government billions of dollars each year 4 5 and contributes to substantial health disparities, stigma, and discrimination. Reversing the rates of viral hepatitis, preventing new s, and improving care and treatment require a strategic and coordinated approach by federal partners in collaboration with state and local health departments, tribal communities, community-based organizations, and other nonfederal partners and stakeholders. To spur action to reduce new viral hepatitis s and their adverse public health impact, OASH through OIDP, in collaboration with federal partners throughout HHS and other departments, led and coordinated development of the Hepatitis Plan. Opportunities for public input were provided, and public comments received were reviewed and analyzed and helped inform the components of the Hepatitis Plan. The Hepatitis Plan focuses on hepatitis A, hepatitis B, and hepatitis C—the hepatitis kamagraes that most significantly affect the health of the nation.

It is an elimination plan, with the overarching goal of eliminating viral hepatitis as a public health threat in the United States by 2030. The Hepatitis Plan is intended to serve as a roadmap for all stakeholders at all levels to eliminate hepatitis in this nation. The Hepatitis Plan presents a strategic framework for integrating and leveraging synergistic policies, programs, and resources. It sets forth a vision and five goals for the nation, with objectives and strategies for each goal. The objectives and strategies offered in this plan are interrelated and may be used to make progress toward more than one goal.

The Hepatitis Plan identifies disproportionately impacted populations based on national hepatitis incidence, prevalence, and mortality data, to help federal and other stakeholders focus their efforts to realize the greatest impact. The Hepatitis Plan also includes indicators to measure progress and quantitative targets for each indicator. Although it is a 5-year plan, it sets 10-year quantitative targets for each indicator—reflecting the reality that it will take more than 5 years to eliminate viral hepatitis as a public health threat. The order in which the goals, objectives, strategies, and indicators are presented is not associated with any prioritization. The following are the Hepatitis Plan's vision and goals.

Vision. The United States will be a place where new viral hepatitis s are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, geographic location, or socioeconomic circumstance. Goals. 1.

Prevent New Viral Hepatitis s 2. Improve Viral Hepatitis—Related Health Outcomes of People with Viral Hepatitis 3. Reduce Viral Hepatitis—Related Disparities and Health Inequities 4. Improve Viral Hepatitis Surveillance and Data Usage 5. Achieve Integrated, Coordinated Efforts That Address the Viral Hepatitis Epidemics among All Partners and Stakeholders A roadmap for stakeholders at all levels and sectors, the Hepatitis Plan envisions a whole-of-nation response to preventing and controlling viral hepatitis in the United States.

The Hepatitis Plan assumes the active participation of state, local, and tribal health departments and organizations, health plans and health care providers, schools and other academic institutions, community- and faith-based organizations, scientists, researchers, and the public in this effort. The priority populations, indicators, and quantitative targets, especially the methods used to determine them, are intended to help focus efforts and limited resources to realize the most impact. Stakeholders are encouraged to focus on activities that resonate the most with the needs of the populations they serve and services they provide, and, using the Hepatitis Plan as a framework, develop their own plans to eliminate viral hepatitis and improve the health of their communities, states, tribal nations, and the nation. Information Needs The draft Hepatitis Plan may be reviewed at. Www.hhs.gov/​hepatitis.

OIDP seeks to obtain feedback from external stakeholders on the following. 1. Do the draft plan's goals, objectives, and strategies appropriately address the viral hepatitis epidemics?. 2. Are there any critical gaps in the Hepatitis Plan's goals, objectives, and strategies?.

If so, please specify the gaps. 3. Do any of the Hepatitis Plan's goals, objectives and strategies cause concern?. If so, please specify the goal, objective or strategy, and describe the concern regarding it. Each commenter is limited to a maximum of seven pages.

Start Authority 77 FR 15761 (March 16, 2012). End Authority Start Signature Dated. September 22, 2020. B. Kaye Hayes, Acting Director, Office of Infectious Disease and HIV/AIDS Policy.

End Signature Footnotes 1. Centers for Disease Control and Prevention. Viral Hepatitis Surveillance—Start Printed Page 60814United States, 2018. U.S. Department of Health and Human Services.

2020. Accessed August 9, 2020. Https://www.cdc.gov/​hepatitis/​statistics/​2018surveillance/​index.htm. 2. Hofmeister MG, Rosenthal EM, Barker LK, et al.

Estimating prevalence of hepatitis C kamagra in the United States, 2013-2016. Hepatology. 2019 Mar;69(3):1020-1031. Doi. 10.1002/hep.30297.

3. LeFevre ML. Screening for hepatitis B kamagra in nonpregnant adolescents and adults. US Preventive Services Task Force recommendation statement. Annals Internal Med.

2014;161(1):58-66. 4. Morey RJ, Collier MG, Nelson NP. The financial burden of public health responses to hepatitis A cases among food handlers, 2012-2014. Public Health Rep.

2017;132(4):443-447. Doi:10.1177/0033354917710947. 5. Wittenborn J, Brady J, Dougherty M, Rein D. Potential epidemiologic, economic, and budgetary impacts of current rates of hepatitis C treatment in Medicare and non-Medicare populations.

Hepatol Commun. 2017;1(2):99-109. Doi:10.1002/hep4.1031. End Supplemental Information [FR Doc. 2020-21288 Filed 9-25-20.

Start Preamble how to get kamagra without a doctor Federal Transit how to buy kamagra online Administration (FTA), DOT. Notice of funding opportunity. The erectile dysfunction Disease how to get kamagra without a doctor 2019 (erectile dysfunction treatment) public health emergency Start Printed Page 63654has had a significant impact on transit operations.

During a series of FTA listening sessions held over the last three months, transit agencies asked FTA to support research to identify solutions to address the operational challenges that they are facing as a result of erectile dysfunction treatment. In response, FTA makes available through this Notice of Funding Opportunity (NOFO) funding to support research demonstration grants to public transit agencies to develop, deploy, and demonstrate innovative solutions that improve the operational efficiency of transit agencies, as well as enhance the mobility of transit users affected by the erectile dysfunction treatment public health emergency. Demonstration grants under this NOFO are authorized under FTA's Public Transportation Innovation Program (49 how to get kamagra without a doctor U.S.C.

5312). Eligible projects will demonstrate innovative solutions to improve the operational efficiencies of transit systems and enhance mobility for their communities in four major areas. (1) Vehicle, facility, equipment and infrastructure cleaning and how to get kamagra without a doctor dis.

(2) exposure mitigation measures. (3) innovative mobility such as contactless payments. And (4) measures that strengthen public confidence in transit how to get kamagra without a doctor services.

The total funding available for awards under this NOFO is $10,000,000. FTA may supplement this amount if additional funding how to get kamagra without a doctor becomes available. Applicants must submit completed proposals for funding opportunity FTA-2020-015-TRI through the GRANTS.GOV “APPLY” function by 11:59 p.m.

Eastern Time on November 2, 2020. Prospective applicants should register as soon as possible on the GRANTS.GOV website to ensure how to get kamagra without a doctor they can complete the application process before the submission deadline. Application instructions are available on FTA's website at http://transit.dot.gov/​howtoapply and in the “FIND” module of GRANTS.GOV.

FTA will not accept mail and fax submissions. Start Further Info Please send any questions on how to get kamagra without a doctor this notice to Jamel El-Hamri email. Jamel.El-Hamri@dot.gov phone.

2020-366-8985. A Telecommunication Device for the Deaf (TDD) is available for individuals how to get kamagra without a doctor who are deaf or hard of hearing at 1-800-877-8339. End Further Info End Preamble Start Supplemental Information Table of Contents A.

Program Description B. Federal Award how to get kamagra without a doctor Information C. Eligibility Information D.

Application and Submission how to get kamagra without a doctor Information E. Application Review Information F. Federal Award Administration Information G.

Federal Awarding Agency Contact how to get kamagra without a doctor Information A. Program Description The Public Transportation erectile dysfunction treatment Research Demonstration Grant Program is funded through the Public Transportation Innovation Program (49 U.S.C. 5312), with the goal to develop, deploy, and demonstrate innovative solutions that improve the operational efficiency of transit agencies, as well as enhance the mobility of transit users affected by the erectile dysfunction treatment public health emergency.

Eligible projects will propose to develop and deploy innovative solutions how to get kamagra without a doctor in four major areas. (1) Vehicle, facility, equipment and infrastructure cleaning and dis. (2) exposure mitigation measures.

(3) innovative mobility such as contactless payments how to get kamagra without a doctor. And (4) measures that strengthen public confidence in transit. As required by 49 U.S.C how to get kamagra without a doctor.

5312(e)(4), projects funded under this NOFO must participate in an evaluation by an independent outside entity that will conduct a comprehensive evaluation of the success or failure of the projects funded under this subsection and any plan for broad-based implementation of the innovation promoted by successful projects. B. Federal Award Information FTA makes available $10,000,000 in fiscal year (FY) 2020 funds under the Public how to get kamagra without a doctor Transportation Innovation Program (49 U.S.C.

5312) to finance the Public Transportation erectile dysfunction treatment Research Demonstration Grant Program. FTA may supplement the total funds available if additional funding becomes available at the time project selections are made. FTA will grant pre-award authority how to get kamagra without a doctor starting on the date of the project award announcement for selected projects and should be completed within 24 months from the date of award.

Funds are available only for eligible expenses incurred after the announcement of project selections. C. Eligibility Information (1) Eligible Applicants Eligible how to get kamagra without a doctor applicants include State and local governmental authorities, direct recipients of Urbanized Area (49 U.S.C.

5307) and Rural Area (49 U.S.C. 5311) formula funds, and Indian tribes. Eligible applicants are limited to FTA grantees or subrecipients who would be the primary beneficiaries of the innovative products and services that how to get kamagra without a doctor are developed—typically public transit agencies.

Except for projects proposed by Indian tribes, proposals for projects in rural (non-urbanized) areas must be submitted as part of a consolidated State proposal. States and other eligible applicants also may submit consolidated proposals for projects in urbanized areas how to get kamagra without a doctor. The submission of the Statewide application will not preclude the submission and consideration of any application from other eligible recipients in an urbanized area in a State.

Proposals may contain projects to be implemented by the recipient or its subrecipients. Eligible subrecipients include public agencies, private nonprofit organizations, and private providers engaged how to get kamagra without a doctor in public transportation. Eligible applicants may submit consolidated proposals for projects.

(2) Cost Sharing or Matching The maximum Federal share of project costs is 100 percent. FTA may give additional consideration to applicants that propose a local how to get kamagra without a doctor share and may view these applicants as more competitive. The applicant must document the source(s) of the local match, if any, in the grant application.

For any applicants proposing match, eligible local match sources include the following. Cash from non-Government sources other than revenues from how to get kamagra without a doctor providing public transportation services. Revenues derived from the sale of advertising and concessions.

Revenues generated from value capture financing mechanisms. Funds from an undistributed cash how to get kamagra without a doctor surplus. Replacement or depreciation cash fund or reserve.

New capital how to get kamagra without a doctor. Or in-kind contributions. (3) Eligible Projects Eligible projects will propose innovative solutions to improve operational efficiencies of transit agencies and enhance the mobility of transit users, through projects that demonstrate innovative solutions for.

Vehicle, facility, how to get kamagra without a doctor equipment and infrastructure cleaning and dis. Exposure mitigation measures such a real-time notification of rail and bus passenger loads. New multi-modal payment innovative mobility systems such as contactless payments.

And measures how to get kamagra without a doctor that strengthen public confidence in transit. Each applicant may only submit one proposal.Start Printed Page 63655 D. Application and Submission Information (1) Address and Form of Application Submission Applications must be submitted through GRANTS.GOV.

Applicants can find general information for submitting applications through GRANTS.GOV at www.fta.dot.gov/​howtoapply, along with specific instructions for the forms and attachments required for how to get kamagra without a doctor submission. Mail and fax submissions will not be accepted. (2) Content and Form of Application Submission a.

Proposal Submission A complete proposal submission consists of at least two how to get kamagra without a doctor forms. 1. The SF-424 Mandatory Form how to get kamagra without a doctor (downloadable from GRANTS.GOV) and 2.

The supplemental form for the FY 2020 erectile dysfunction treatment Demonstration Program (downloadable from GRANTS.GOV), which is available on FTA's website at (placeholder for FTA erectile dysfunction treatment Demonstration Program). The application must include responses to all sections of the SF-424 mandatory form and the supplemental form unless a section is indicated as optional. FTA will use the how to get kamagra without a doctor information on the supplemental form to determine applicant and project eligibility for the program and to evaluate the proposal against the selection criteria described in part E of this notice.

FTA will accept only one supplemental form per SF-424 submission. FTA encourages applicants to consider submitting a single supplemental form that includes multiple activities to be evaluated as a consolidated proposal. Applicants may attach additional supporting information to the SF-424 submission, including but how to get kamagra without a doctor not limited to letters of support, project budgets, or excerpts from relevant planning documents.

Supporting documentation must be described and referenced by file name in the appropriate response section of the supplemental form, or it may not be reviewed. Information such as applicant name, Federal amount requested, local match amount, description of areas served, etc., may be requested in varying degrees of detail on both the SF-424 form and supplemental form. Applicants must fill in all fields unless how to get kamagra without a doctor stated otherwise on the forms.

If applicants copy information into the supplemental form from another source, they should verify that the supplemental form has fully captured pasted text and that it has not truncated the text due to character limits built into the form. Applicants should use both the “Check Package for Errors” how to get kamagra without a doctor and the “Validate Form” validation buttons on both forms to check all required fields. Applicants should also ensure that the Federal and local amounts specified are consistent.

Addressing the deteriorating conditions and disproportionately high fatality rates on our rural transportation infrastructure is of critical interest to the Department, as rural transportation networks face unique challenges in safety, infrastructure condition, and passenger and freight usage. Consistent with the how to get kamagra without a doctor R.O.U.T.E.S. Initiative, the Department encourages applicants to consider how the project will address the challenges faced by rural areas.

B. Application Content The SF-424 how to get kamagra without a doctor Mandatory Form and the supplemental form will prompt applicants for the required information, including. I.

Applicant Name ii. Dun and how to get kamagra without a doctor Bradstreet (D&B) Data Universal Numbering System (DUNS) number iii. Key contact information (contact name, address, email address, and phone number) iv.

Congressional district(s) where project will take place v. Project Information (title, executive summary, and how to get kamagra without a doctor type) vi. A detailed description of the need for the project vii.

A detailed description of how the project will support the Program objectives how to get kamagra without a doctor viii. Evidence that the applicant can provide the local cost shares ix. A description of the technical, legal, and financial capacity of the applicant x.

A detailed project how to get kamagra without a doctor budget xi. Details on the local matching funds xii. A detailed project timeline xiii.

Whether the project impacts an Opportunity Zone (3) Unique how to get kamagra without a doctor Entity Identifier and System for Award Management (SAM) Each applicant is required to. (1) Be registered in SAM before submitting an application. (2) provide a valid unique entity identifier in its application.

And (3) continue to maintain an active SAM registration with current information at all times how to get kamagra without a doctor during which the applicant has an active Federal award or an application or plan under consideration by FTA. These requirements do not apply if the applicant. (1) Is excepted from the requirements under 2 CFR 25.110(b) or (c).

Or (2) has an exception approved by FTA under 2 how to get kamagra without a doctor CFR 25.110(d). FTA may not make an award until the applicant has complied with all applicable unique entity identifier and SAM requirements. If an applicant has not fully complied with the requirements by the time FTA is ready to make an award, FTA may determine that the applicant is not qualified to receive an award and use that determination as a basis for making a Federal how to get kamagra without a doctor award to another applicant.

All applicants must provide a unique entity identifier provided by SAM. Registration in SAM may take as little as 3-5 business days, but there can be unexpected steps or delays. For example, the applicant may need to obtain an how to get kamagra without a doctor Employer Identification Number.

FTA recommends allowing ample time, up to several weeks, to complete all steps. For additional information on obtaining a unique entity identifier, please visit www.sam.gov. (4) Submission Dates and Times Project proposals must be how to get kamagra without a doctor submitted electronically through GRANTS.GOV by 11:59 p.m.

Eastern on November 2, 2020. Mail and fax submissions will not be accepted. FTA urges applicants to submit applications at least 72 hours prior to the due date to allow time to correct how to get kamagra without a doctor any problems that may have caused either GRANTS.GOV or FTA systems to reject the submission.

Proposals submitted after the deadline will only be considered under extraordinary circumstances not within the applicant's control. Deadlines will not be extended due how to get kamagra without a doctor to scheduled website maintenance. GRANTS.GOV scheduled maintenance and outage times are announced on the GRANTS.GOV website.

Within 48 hours after submitting an electronic application, the applicant should receive two email messages from GRANTS.GOV. (1) Confirmation of successful transmission to GRANTS.GOV how to get kamagra without a doctor. And (2) confirmation of successful validation by GRANTS.GOV.

If the applicant does not receive confirmation of successful validation or receives a notice of failed validation or incomplete materials, the applicant must address the reason for the failed validation, as described in the email notice, and resubmit before the submission deadline. If making a resubmission for any reason, applicants must include all original attachments regardless of which attachments were updated and check the box on the supplemental form indicating how to get kamagra without a doctor this is a resubmission. Applicants are encouraged to begin the process of registration on the GRANTS.GOV site well in advance of the submission deadline.

Registration is Start Printed Page 63656a multi-step process, which may take several weeks to complete before an application can be submitted. Registered applicants may still be required to update their registration before submitting an how to get kamagra without a doctor application. Registration in SAM is renewed annually and persons making submissions on behalf of the Authorized Organization Representative (AOR) must be authorized in GRANTS.GOV by the AOR to make submissions.

(5) Funding Restrictions Funds may be used for post-award expenditures only. Funds under this NOFO cannot be used to reimburse projects for otherwise eligible expenses incurred prior to the date of project award how to get kamagra without a doctor announcements. (6) Other Submission Requirements FTA encourages applicants to identify scaled funding options in case insufficient funding is available to fund a project at the full requested amount.

If an how to get kamagra without a doctor applicant indicates that a project is scalable, the applicant must provide an appropriate minimum funding amount that will fund an eligible project that achieves the objectives of the program and meets all relevant program requirements. The applicant must provide a clear explanation of how a reduced award would affect the project budget and scope. FTA may award a lesser amount whether or not the applicant provides a scalable option.

E. Application Review Information (1) Project Evaluation Criteria Addressing the deteriorating conditions and disproportionately high fatality rates on our rural transportation infrastructure is of critical interest to the Department, as rural transportation networks face unique challenges in safety, infrastructure condition, and passenger and freight usage. Consistent with the R.O.U.T.E.S.

Initiative, the Department will consider how the project will address the challenges faced by rural areas. In addition, the Department will review and consider applications for funding pursuant to this Notice in accordance with the President's September 2, 2020 memorandum, entitled Memorandum on Reviewing Funding to State and Local Government Recipients of Federal Funds that Are Permitting Anarchy, Violence, and Destruction in American Cities, consistent with guidance from the Office of Management and Budget and the Attorney General and with all applicable laws. FTA will evaluate proposals submitted according to the following criteria.

(a) Project Innovation and Impact. (b) Project Approach. (c) National Applicability.

(d) Commercialization and/or Knowledge Transfer. And (e) Technical, Legal and Financial Capacity. FTA encourages each applicant to demonstrate how a project supports all criteria with the most relevant information the applicant can provide, regardless of whether such information has been specifically requested or identified in this notice.

A. Project Innovation and Impact i. Effectiveness of the project in achieving and demonstrating the specific objectives of this program.

Ii. Demonstration of benefits in addressing the needs of the transit agency and industry and impacts to infrastructure, equipment, transit workforce, and riders. Iii.

Degree of improvement over current and existing technologies, designs, and/or practices applicable to the transit industry. B. Project Approach i.

Quality of the project approach such as existing partnerships, collaboration strategies and level of commitment of the project partners. Ii. Proposal is realistic in its approach to fulfill the milestones/deliverables, schedule and goals.

C. National Applicability i. Degree to which the project could be replicated by other transit agencies regionally or nationally.

Ii. Ability to evaluate technologies, designs and/or practices in a wide variety of conditions and locales http://www.ec-paul-langevin-strasbourg.ac-strasbourg.fr/wp/?p=2645. Iii.

Degree to which the technology, designs and/or practices can be replicated by other transportation modes. D. Commercialization and/or Knowledge Transfer i.

Demonstrates a realistic plan for moving the results of the project into the transit marketplace (patents, conferences, articles in trade magazines, webinar, site visits, etc.). Ii. How the project team plans to work with the industry on improving best practices, guidance and/or standards, if applicable.

Iii. Demonstrate a clear understanding and robust approach to data collection, access and management. E.

Technical, Legal and Financial Capacity Capacity of the applicant and any partners to successfully execute the project effort. There should be no outstanding legal, technical, or financial issues with the applicant that would make this a high-risk project. (2) Review and Selection Process An FTA technical evaluation committee will evaluate proposals based on the published project evaluation criteria.

Members of the technical evaluation committee will rate the applications and may seek clarification about any statement in an application. The FTA Administrator will determine the final selection and amount of funding for each project after consideration of the findings of the technical evaluation committee. Geographic diversity, diversity of the project type, the amount of local match to be provided, and the applicant's receipt and management of other Federal transit funds may be considered in FTA's award decisions.

Prior fare payment innovation efforts may receive priority consideration. The FTA Administrator will consider the following key DOT objectives. A.

Utilizing alternative funding sources and innovative financing models to attract non-Federal sources of investment. B. Whether the project is located in or supports public transportation service in a qualified opportunity zone designated pursuant to 26.U.S.C.

1400Z-1. And c. The extent to which the project addresses challenges specific to the provision of rural public transportation.

(3) FAPIIS Review Prior to making a grant award, FTA is required to review and consider any information about the applicant that is in the Federal Awardee Performance and Integrity Information System (FAPIIS) accessible through SAM. An applicant may review and comment on information about itself that a Federal awarding agency previously entered. FTA will consider any comments by the applicant, in addition to the other information in FAPIIS, in making a judgment about the applicant's integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 2 CFR 200.205 Federal Awarding Agency Review of Risk Posed by Applicants.

F. Federal Award Administration Information (1) Federal Award Notices FTA will announce the final project selections on the FTA website. Project recipients should contact their FTA Regional Office for additional information regarding allocations for Start Printed Page 63657projects.

At the time project selections are announced, FTA will extend pre-award authority for the selected projects. There is no blanket pre-award authority for these projects before announcement. There is no minimum or maximum grant award amount, but FTA intends to fund as many meritorious projects as possible.

FTA only will consider proposals from eligible recipients for eligible activities. Due to funding limitations, projects selected for funding may receive less than the amount originally requested. In those cases, applicants must be able to demonstrate that the proposed projects are still viable and can be completed with the amount awarded.

(2) Administrative and National Policy Requirements a. Pre-Award Authority FTA will issue specific guidance to recipients regarding pre-award authority at the time of selection. FTA does not provide pre-award authority for competitive funds until projects are selected, and there are Federal requirements that must be met before costs are incurred.

For more information about FTA's policy on pre-award authority, see the FY 2020 Apportionments Notice published on June 3, 2020, at https://www.govinfo.gov/​content/​pkg/​FR-2020-06-03/​pdf/​2020-11946.pdf. b. Grant Requirements Selected applicants will submit a grant application through FTA's electronic grant management system and adhere to the customary FTA grant requirements for research project (insert Circular name).

All competitive grants, regardless of award amount, will be subject to the Congressional notification and release process. FTA emphasizes that third-party procurement applies to all funding awards, as described in FTA Circular 4220.1F, “Third Party Contracting Guidance.” However, FTA may approve applications that include a specifically identified partnering organization(s) (2 CFR 200.302(f)). When included, the application, budget, and budget narrative should provide a clear understanding of how the selection of these organizations is critical for the project and give sufficient detail about the costs involved.

C. Planning FTA encourages applicants to engage the appropriate State Departments of Transportation, Regional Transportation Planning Organizations, or Metropolitan Planning Organizations in areas to be served by the project funds available under this program. D.

Standard Assurances The applicant assures that it will comply with all applicable Federal statutes, regulations, executive orders, FTA circulars, and other Federal administrative requirements in carrying out any project supported by the FTA grant. The applicant acknowledges that it is under a continuing obligation to comply with the terms and conditions of the grant agreement issued for its project with FTA. The applicant understands that Federal laws, regulations, policies, and administrative practices might be modified from time to time and may affect the implementation of the project.

The applicant agrees that the most recent Federal requirements will apply to the project unless FTA issues a written determination otherwise. The applicant must submit the Certifications and Assurances before receiving a grant if it does not have current certifications on file. E.

Free Speech and Religious Liberty In connection with any program or activity conducted with or benefiting from funds awarded under this notice, recipients of funds must comply with all applicable requirements of Federal law, including, without limitation, the Constitution of the United States. Statutory, regulatory, and public policy requirements, including without limitation, those protecting free speech, religious liberty, public welfare, the environment, and prohibiting discrimination. The conditions of performance, non-discrimination requirements, and other assurances made applicable to the award of funds in accordance with regulations of the Department of Transportation.

And applicable Federal financial assistance and contracting principles promulgated by the Office of Management and Budget. In complying with these requirements, recipients must ensure that no concession agreements are denied or other contracting decisions made on the basis of speech or other activities protected by the First Amendment. If the Department determines that a recipient has failed to comply with applicable Federal requirements, the Department may terminate the award of funds and disallow previously incurred costs, requiring the recipient to reimburse any expended award funds.

(3) Reporting The post-award reporting requirements include submission of the Federal Financial Report (FFR) and Milestone Progress Report in TrAMS. An evaluation of the grant will occur at various points in the demonstration process and at the end of the project. In addition, FTA is responsible for producing an Annual Report to Congress that compiles evaluation of selected projects, including an evaluation of the performance measures identified by the applicants.

All applicants must develop an evaluation plan to measure the success or failure of their projects and describe any plans for broad-based implementation of successful projects. FTA may request data and reports to support the evaluation and Annual Report. A.

Independent Evaluation To achieve a comprehensive understanding of the impacts and implications of each proposed erectile dysfunction treatment Research Demonstration Program, projects funded under this announcement will require the recipient to conduct a third party independent evaluation of their project. Recipients will be required to contract with a third party independent evaluator to assist in developing an evaluation plan, and collecting, storing and managing data required to fulfill the evaluation requirement. No more than 10 percent of the Federal share of the project may be used to hire the third-party independent evaluator and the inclusion of a third-party independent evaluation should be described in the grant application.

If the project duration is more than two years, an interim evaluation report would need to be submitted to FTA, otherwise the evaluation report should be included as part of the final project report. B. erectile dysfunction treatment Research Demonstration Grant Program Evaluation Projects funded under this announcement will be required to establish a set of performance metrics set by the third-party independent evaluator and shared with FTA.

G. Federal Awarding Agency Contacts Information For questions about applying, please contact Jamel El-Hamri email. Jamel.El-Hamri@dot.gov phone.

202-366-8985. A TDD is available at 1-800-877-8339 (TDDFIRS). To ensure that applicants receive accurate information about eligibility or the program, applicants are encouraged to contact FTA directly with questions, rather than through intermediaries or third parties.Start Printed Page 63658 FTA staff also may conduct briefings on the competitive grants selection and award process upon request.

Start Signature K. Jane Williams, Deputy Administrator. End Signature End Supplemental Information [FR Doc.

2020-22316 Filed 10-7-20. 8:45 am]BILLING CODE 4910-57-PStart Preamble Office of the Secretary, Department of Health and Human Services. Notice.

The Department of Health and Human Services (HHS) Office of Infectious Disease and HIV/AIDS Policy (OIDP) in the Office of the Assistant Secretary for Health (OASH) announces the draft Viral Hepatitis National Strategic Plan. A Roadmap to Elimination (2021-2025) (Hepatitis Plan) available for public comment. The draft Hepatitis Plan may be reviewed at www.hhs.gov/​hepatitis.

All comments must be received by 5:00 p.m. ET on October 8, 2020 to ensure consideration. All comments must be submitted electronically to HepatitisPlanComments@hhs.gov.

Start Further Info Carol Jimenez, OIDP, Carol.Jimenez@hhs.gov. 202-401-5131. End Further Info End Preamble Start Supplemental Information Viral hepatitis is a significant public health threat that puts people who are infected at increased risk for serious disease and death.

In the United States, new hepatitis A and hepatitis C s have increased dramatically in recent years, little progress has been made on preventing hepatitis B s, and, as of 2016, an estimated 3.3 million people were chronically infected with hepatitis B and hepatitis C.1-3 Collectively, viral hepatitis costs people, health systems, states, and the federal government billions of dollars each year 4 5 and contributes to substantial health disparities, stigma, and discrimination. Reversing the rates of viral hepatitis, preventing new s, and improving care and treatment require a strategic and coordinated approach by federal partners in collaboration with state and local health departments, tribal communities, community-based organizations, and other nonfederal partners and stakeholders. To spur action to reduce new viral hepatitis s and their adverse public health impact, OASH through OIDP, in collaboration with federal partners throughout HHS and other departments, led and coordinated development of the Hepatitis Plan.

Opportunities for public input were provided, and public comments received were reviewed and analyzed and helped inform the components of the Hepatitis Plan. The Hepatitis Plan focuses on hepatitis A, hepatitis B, and hepatitis C—the hepatitis kamagraes that most significantly affect the health of the nation. It is an elimination plan, with the overarching goal of eliminating viral hepatitis as a public health threat in the United States by 2030.

The Hepatitis Plan is intended to serve as a roadmap for all stakeholders at all levels to eliminate hepatitis in this nation. The Hepatitis Plan presents a strategic framework for integrating and leveraging synergistic policies, programs, and resources. It sets forth a vision and five goals for the nation, with objectives and strategies for each goal.

The objectives and strategies offered in this plan are interrelated and may be used to make progress toward more than one goal. The Hepatitis Plan identifies disproportionately impacted populations based on national hepatitis incidence, prevalence, and mortality data, to help federal and other stakeholders focus their efforts to realize the greatest impact. The Hepatitis Plan also includes indicators to measure progress and quantitative targets for each indicator.

Although it is a 5-year plan, it sets 10-year quantitative targets for each indicator—reflecting the reality that it will take more than 5 years to eliminate viral hepatitis as a public health threat. The order in which the goals, objectives, strategies, and indicators are presented is not associated with any prioritization. The following are the Hepatitis Plan's vision and goals.

Vision. The United States will be a place where new viral hepatitis s are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, geographic location, or socioeconomic circumstance.

Goals. 1. Prevent New Viral Hepatitis s 2.

Improve Viral Hepatitis—Related Health Outcomes of People with Viral Hepatitis 3. Reduce Viral Hepatitis—Related Disparities and Health Inequities 4. Improve Viral Hepatitis Surveillance and Data Usage 5.

Achieve Integrated, Coordinated Efforts That Address the Viral Hepatitis Epidemics among All Partners and Stakeholders A roadmap for stakeholders at all levels and sectors, the Hepatitis Plan envisions a whole-of-nation response to preventing and controlling viral hepatitis in the United States. The Hepatitis Plan assumes the active participation of state, local, and tribal health departments and organizations, health plans and health care providers, schools and other academic institutions, community- and faith-based organizations, scientists, researchers, and the public in this effort. The priority populations, indicators, and quantitative targets, especially the methods used to determine them, are intended to help focus efforts and limited resources to realize the most impact.

Stakeholders are encouraged to focus on activities that resonate the most with the needs of the populations they serve and services they provide, and, using the Hepatitis Plan as a framework, develop their own plans to eliminate viral hepatitis and improve the health of their communities, states, tribal nations, and the nation. Information Needs The draft Hepatitis Plan may be reviewed at. Www.hhs.gov/​hepatitis.

OIDP seeks to obtain feedback from external stakeholders on the following. 1. Do the draft plan's goals, objectives, and strategies appropriately address the viral hepatitis epidemics?.

2. Are there any critical gaps in the Hepatitis Plan's goals, objectives, and strategies?. If so, please specify the gaps.

3. Do any of the Hepatitis Plan's goals, objectives and strategies cause concern?. If so, please specify the goal, objective or strategy, and describe the concern regarding it.

Each commenter is limited to a maximum of seven pages. Start Authority 77 FR 15761 (March 16, 2012). End Authority Start Signature Dated.

September 22, 2020. B. Kaye Hayes, Acting Director, Office of Infectious Disease and HIV/AIDS Policy.

End Signature Footnotes 1. Centers for Disease Control and Prevention. Viral Hepatitis Surveillance—Start Printed Page 60814United States, 2018.

U.S. Department of Health and Human Services. 2020.

Accessed August 9, 2020. Https://www.cdc.gov/​hepatitis/​statistics/​2018surveillance/​index.htm. 2.

Hofmeister MG, Rosenthal EM, Barker LK, et al. Estimating prevalence of hepatitis C kamagra in the United States, 2013-2016. Hepatology.

2019 Mar;69(3):1020-1031. Doi. 10.1002/hep.30297.

3. LeFevre ML. Screening for hepatitis B kamagra in nonpregnant adolescents and adults.

US Preventive Services Task Force recommendation statement. Annals Internal Med. 2014;161(1):58-66.

4. Morey RJ, Collier MG, Nelson NP. The financial burden of public health responses to hepatitis A cases among food handlers, 2012-2014.

Public Health Rep. 2017;132(4):443-447. Doi:10.1177/0033354917710947.

5. Wittenborn J, Brady J, Dougherty M, Rein D. Potential epidemiologic, economic, and budgetary impacts of current rates of hepatitis C treatment in Medicare and non-Medicare populations.

Hepatol Commun. 2017;1(2):99-109. Doi:10.1002/hep4.1031.

End Supplemental Information [FR Doc. 2020-21288 Filed 9-25-20. 8:45 am]BILLING CODE 4150-43-P.

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The team of Deputy and Associate Editors Heribert Schunkert, Sharlene Day and Peter why not try these out SchwartzThe European Heart Journal (EHJ) wants to attract high-class submissions dealing with genetic findings that kamagra online uk help to improve the mechanistic understanding and the therapy of cardiovascular diseases. In charge of identifying such articles is a mini-team of experts on genetics, Heribert Schunkert, Sharlene Day, and Peter Schwartz.Genetic findings have contributed enormously to the molecular understanding of cardiovascular diseases. A number of diseases including various channelopathies, cardiomyopathies, kamagra online uk and metabolic disorders have been elucidated based on a monogenic inheritance and the detection of disease-causing mutations in large families. More recently, the complex genetic architecture of common cardiovascular diseases such as atrial fibrillation or coronary artery disease has become increasingly clear.

Moreover, genetics became a sensitive tool to characterize the role of traditional cardiovascular risk factors in the form of Mendelian randomized kamagra online uk studies. However, the real challenge is still ahead, i.e., to bridge genetic findings into novel therapies for the prevention and treatment of cardiac diseases. The full cycle from identification of a family with hypercholesterolaemia due to a proprotein convertase subtilisin/kexin type 9 (PCSK-9) mutation to successful risk lowering by PCSK-9 antibodies illustrates the power of genetics in this regard.With its broad expertise, the new EHJ editorial team kamagra online uk on genetics aims to cover manuscripts from all areas in which genetics may contribute to the understanding of cardiovascular diseases. Prof.

Peter Schwartz is a world-class expert on channelopathies and kamagra online uk pioneered the field of long QT syndrome. He is an experienced clinical specialist on cardiac arrhythmias of genetic origins and a pioneer in the electrophysiology of the myocardium. He studied in Milan, worked at the University of Texas for 3 years and, as Associate Professor, at the University of Oklahoma 4 months/year for 12 years. He has been Chairman of Cardiology at the University of Pavia for 20 years and kamagra online uk since 1999 acts as an extraordinary professor at the Universities of Stellenbosch and Cape Town for 3 months/year.Prof.

Sharlene M. Day is Director of Translational Research in the Division of Cardiovascular Medicine and kamagra online uk Cardiovascular Institute at the University of Pennsylvania. She trained at the University of Michigan and stayed on as faculty as the founding Director of the Inherited Cardiomyopathy and Arrhythmia Program before moving to the University of Pennsylvania in 2019. Like Prof kamagra online uk.

Schwartz, her research programme covers the full spectrum from clinical medicine to basic research with a focus on hypertrophic cardiomyopathy. Both she and Prof kamagra online uk. Schwartz have developed inducible pluripotent stem cell models of human monogenic cardiac disorders as a platform to study the underlying biological mechanisms of disease.Heribert Schunkert is Director of the Cardiology Department in the German Heart Center Munich. He trained in the Universities of Aachen and Regensburg, Germany kamagra online uk and for 4 years in various teaching hospitals in Boston.

Before moving to Munich, he was Director of the Department for Internal Medicine at the University Hospital in Lübeck. His research interest shifted from the molecular biology of the renin–angiotensin system to complex genetics of atherosclerosis. He was amongst the first to conduct genome-wide association meta-analyses, which allowed the identification of numerous genetic variants that contribute to coronary artery disease, peripheral arterial disease, or aortic stenosis.The editorial team on cardiovascular genetics aims to facilitate the publication of strong translational research that illustrates to clinicians and cardiovascular kamagra online uk scientists how genetic and epigenetic variation influences the development of heart diseases. The future perspective is to communicate genetically driven therapeutic targets as has become evident already with the utilization of interfering antibodies, RNAs, or even genome-editing instruments.In this respect, the team encourages submission of world-class genetic research on the cardiovascular system to the EHJ.

The team is also pleased to cooperate kamagra online uk with the novel Council on Cardiovascular Genomics which was inaugurated by the ESC in 2020.Conflict of interest. None declared.Andros TofieldMerlischachen, Switzerland Published on behalf of the European Society of Cardiology. All rights reserved kamagra online uk. © The Author(s) 2020.

For permissions, kamagra online uk please email. Journals.permissions@oup.com.With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article. For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.This is a Focus Issue on genetics. Described as kamagra online uk the ‘single largest unmet need in cardiovascular medicine’, heart failure with preserved ejection fraction (HFpEF) remains an untreatable disease currently representing 65% of new HF diagnoses. HFpEF is more frequent among women and is associated with a poor prognosis and unsustainable healthcare costs.1,2 Moreover, the variability in HFpEF phenotypes amplifies the complexity and difficulties of the approach.3–5 In this perspective, unveiling novel molecular targets is imperative.

In a State of the Art Review article entitled ‘Leveraging clinical epigenetics in heart failure with preserved ejection fraction. A call for individualized therapies’, authored by Francesco Paneni from the University of Zurich in Switzerland, and colleagues,6 the authors note that epigenetic modifications—defined as changes of DNA, histones, and non-coding RNAs (ncRNAs)—represent a molecular framework through which the environment modulates gene expression.6 Epigenetic signals acquired over a lifetime lead to chromatin remodelling and affect transcriptional programmes underlying oxidative kamagra online uk stress, inflammation, dysmetabolism, and maladaptive left ventricular (LV) remodelling, all conditions predisposing to HFpEF. The strong involvement of epigenetic signalling in this setting makes the epigenetic information relevant for diagnostic and therapeutic purposes in patients with HFpEF. The recent advances in high-throughput sequencing, computational epigenetics, kamagra online uk and machine learning have enabled the identification of reliable epigenetic biomarkers in cardiovascular patients.

In contrast to genetic tools, epigenetic biomarkers mirror the contribution of environmental cues and lifestyle changes, and their reversible nature offers a promising opportunity to monitor disease states. The growing understanding of chromatin and ncRNA biology has led to the development of several Food and Drug Administration (FDA)-approved ‘epi-drugs’ (chromatin modifiers, mimics, and anti-miRs) able to prevent transcriptional alterations underpinning kamagra online uk LV remodelling and HFpEF. In the present review, Paneni and colleagues discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of HFpEF.Sick sinus syndrome (SSS) is a complex cardiac arrhythmia and the leading indication for permanent pacemaker implantation worldwide. It is characterized by pathological sinus bradycardia, sinoatrial block, or alternating atrial kamagra online uk brady- and tachyarrhythmias.

Symptoms include fatigue, reduced exercise capacity, and syncope. Few studies have been conducted on the basic mechanisms of SSS, and therapeutic limitations reflect an incomplete understanding of the pathophysiology.7 In a clinical research entitled ‘Genetic insight into sick sinus syndrome’, Rosa kamagra online uk Thorolfsdottir from deCODE genetics in Reykjavik, Iceland, and colleagues aimed to use human genetics to investigate the pathogenesis of SSS and the role of risk factors in its development.8 The authors performed a genome-wide association study (GWAS) of >6000 SSS cases and >1 000 000 controls. Variants at six loci associated with SSS. A full genotypic model best described the p.Gly62Cys association, with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes.

All the SSS variants increased the kamagra online uk risk of pacemaker implantation. Their association with atrial fibrillation (AF) varied, and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. They also tested 17 exposure kamagra online uk phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with risk of SSS in Mendelian randomization—AF and lower heart rate—suggesting causality.

Powerful PGS analyses provided convincing evidence against causal associations for body mass index, kamagra online uk cholesterol, triglycerides, and type 2 diabetes (P >. 0.05) (Figure 1). Figure 1Summary of genetic kamagra online uk insight into the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through genome-wide association study (GWAS), and their unique phenotypic associations provide insight into distinct pathways underlying SSS.

Investigation of the role of risk factors in SSS development supported a causal role for atrial fibrillation (AF) and heart rate, and provided convincing evidence against causality for body mass index (BMI), cholesterol kamagra online uk (HDL and non-HDL), triglycerides, and type 2 diabetes (T2D). Mendelian randomization did not support causality for coronary artery disease, ischaemic stroke, heart failure, PR interval, or QRS duration (not shown in the figure). Red and blue arrows represent positive and negative associations, respectively (from Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight kamagra online uk into sick sinus syndrome.

See pages 1959–1971.).Figure 1Summary of genetic insight into the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. Variants at kamagra online uk six loci (named by corresponding gene names) were identified through genome-wide association study (GWAS), and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for atrial fibrillation (AF) and heart rate, and provided convincing evidence against causality for body mass index (BMI), cholesterol (HDL and non-HDL), triglycerides, and type 2 diabetes (T2D). Mendelian randomization did not support causality for coronary artery disease, ischaemic stroke, heart failure, PR interval, or QRS duration (not kamagra online uk shown in the figure).

Red and blue arrows represent positive and negative associations, respectively (from Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight into sick kamagra online uk sinus syndrome. See pages 1959–1971.).Thorolfsdottir et al. Conclude that they report the associations of variants at six loci with kamagra online uk SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development.

Mendelian randomization supports a causal role for AF in the development of SSS. The article is accompanied by an Editorial by Stefan Kääb from LMU Klinikum in Munich, Germany, and colleagues.9 The authors conclude that the limitations of the work challenge clinical translation, but do not diminish the multiple interesting findings of Thorolfsdottir et al., bringing us closer to the finishing line of unlocking SSS genetics to develop new therapeutic strategies. They also kamagra online uk highlight that this study represents a considerable accomplishment for the field, but also clearly highlights upcoming challenges and indicates areas where further research is warranted on our way on the translational road to personalized medicine.Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that affects ∼1 in every 3500 live-born male infants, making it the most common neuromuscular disease of childhood. The disease is caused by mutations in the dystrophin gene, which lead to dystrophin deficiency in muscle cells, resulting in decreased fibre stability and continued degeneration.

The patients present with progressive muscle wasting and loss of muscle function, develop restrictive respiratory failure and dilated cardiomyopathy, and usually die in kamagra online uk their late teens or twenties from cardiac or respiratory failure.10 In a clinical research article ‘Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data’ Raphaël Porcher from the Université de Paris in France, and colleagues estimate the effect of prophylactic angiotensin-converting enzyme (ACE) inhibitors on survival in DMD.11 The authors analysed the data from the French multicentre DMD-Heart-Registry. They estimated the association between the prophylactic prescription of ACE inhibitors and event-free survival in 668 patients between the ages of 8 and 13 years, with normal left ventricular function, using (i) a Cox model kamagra online uk with intervention as a time-dependent covariate. (ii) a propensity-based analysis comparing ACE inhibitor treatment vs.

No treatment kamagra online uk. And (iii) a set of sensitivity analyses. The study outcomes were (i) overall survival and (ii) hospitalizations for HF or acute respiratory failure. Among the patients included in the DMD-Heart-Registry, 576 kamagra online uk were eligible for this study, of whom 390 were treated with an ACE inhibitor prophylactically.

Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with an ACE inhibitor. In a Cox model, with intervention as a time-dependent variable, the hazard ratio (HR) associated with ACE inhibitor treatment kamagra online uk was 0.49 for overall mortality after adjustment for baseline variables. In the propensity-based analysis, with 278 patients included in the treatment group and 302 in the control group, ACE inhibitors were associated with a lower risk of death (HR 0.32) and hospitalization for HF (HR 0.16) (Figure 2). All sensitivity analyses yielded kamagra online uk similar results.

Figure 2Graphical Abstract (from Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K. Association between prophylactic angiotensin-converting enzyme kamagra online uk inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. See pages 1976–1984.).Figure 2Graphical Abstract (from Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier kamagra online uk U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. See pages kamagra online uk 1976–1984.).Porcher et al. Conclude that prophylactic treatment with ACE inhibitors in DMD is associated with a significantly higher overall survival and lower rate of hospitalization for management of HF.

The manuscript is accompanied by an Editorial by Mariell Jessup and colleagues from the American Heart Association in Dallas, Texas, USA.12 The authors describe how cardioprotective strategies have been investigated in a number of cardiovascular disorders and successfully incorporated into treatment regimens for selected patients, including ACE inhibitors in patients with and without diabetes and coronary artery disease, angiotensin receptor kamagra online uk blockers and beta-blockers in Marfan syndrome, and ACE inhibitors and beta-blockers in patients at risk for chemotherapy-related toxicity. They conclude that Porcher et al. Have now convincingly demonstrated that even very young patients with DMD can benefit from the life-saving intervention of ACE inhibition.Hypertrophic cardiomyopathy (HCM) is characterized by unexplained LV hypertrophy and often caused by pathogenic variants in genes that encode the sarcomere apparatus kamagra online uk. Patients with HCM may experience atrial and ventricular arrhythmias and HF.

However, disease kamagra online uk expression and severity are highly variable. Furthermore, there is marked diversity in the age of diagnosis. Although childhood-onset disease is well documented, it is far kamagra online uk less common. Owing to its rarity, the natural history of childhood-onset HCM is not well characterized.12–14 In a clinical research article entitled ‘Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy’, Nicholas Marston from the Harvard Medical School in Boston, MA, USA, and colleagues aimed to describe the characteristics and outcomes of childhood-onset HCM.15 They performed an observational cohort study of >7500 HCM patients.

HCM patients were stratified by age at diagnosis [<1 year (infancy), 1–18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints including HF, life-threatening ventricular arrhythmias, AF, and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 2.4% of patients were diagnosed in infancy, 14.7% in childhood, kamagra online uk and 2.9% in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the first decade following the baseline visit, and HF and AF more common by the end of the second decade. Sarcomeric HCM was more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a >2-fold increased risk of HF and 67% increased risk of the overall composite outcome kamagra online uk.

When compared with adult-onset HCM, those with childhood-onset disease were 36% more likely to develop life-threatening ventricular arrhythmias and twice as likely to require transplant or a ventricular assist device.The authors conclude that patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. The manuscript is accompanied by an Editorial by Juan Pablo Kaski from the University College London (UCL) Institute of Cardiovascular Science in London, UK.16 Kaski concludes that the field of HCM is kamagra online uk now entering the era of personalized medicine, with the advent of gene therapy programmes and a focus on treatments targeting the underlying pathophysiology. Pre-clinical data suggesting that small molecule myosin inhibitors may attenuate or even prevent disease expression provide cause for optimism, and nowhere more so than for childhood-onset HCM. An international collaborative approach involving basic, translational, kamagra online uk and clinical science is now needed to characterize disease expression and progression and develop novel therapies for childhood HCM.Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by LV dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease.

It is a major cause of systolic HF, the leading indication for heart transplantation, and therefore a major public health problem due to the important cardiovascular morbidity and mortality.17,18 Understanding of the genetic basis of DCM has improved in recent years, with a role for both rare and common variants resulting in a complex genetic architecture of the disease. In a translational research article entitled ‘Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23’, Sophie Garnier from the Sorbonne Université in Paris, France, and colleagues conducted the largest genome-wide association study performed so far in DCM, with >2500 cases and >4000 controls in the discovery population.19 They identified and replicated two new DCM-associated loci, on chromosome 3p25.1 and chromosome 22q11.23, while confirming two previously kamagra online uk identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A PGS constructed from the number of risk alleles at these four DCM loci revealed a 27% increased risk of DCM for individuals with eight risk alleles compared with individuals with five risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analysis on induced pluripotent stem cell (iPSC)-derived cardiomyocytes identified SLC6A6 as the most likely DCM gene at the 3p25.1 locus.

This gene encodes a taurine transporter whose involvement kamagra online uk in myocardial dysfunction and DCM is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggested SMARCB1 as the candidate culprit gene.Garnier et al. Conclude that their study provides a better understanding of the genetic architecture of kamagra online uk DCM and sheds light on novel biological pathways underlying HF. The manuscript is accompanied by an Editorial by Elizabeth McNally from the Northwestern University Feinberg School of Medicine in Chicago, USA, and colleagues.20 The authors conclude that methods to integrate common and rare genetic information will continue to evolve and provide insight on disease progression, potentially providing biomarkers and clues for useful therapeutic pathways to guide drug development.

At present, rare cardiomyopathy variants have kamagra online uk clinical utility in predicting risk, especially arrhythmic risk. PGS analyses for HF or DCM progression are expected to come to clinical use, especially with the addition of broader GWAS-derived data. Combining genetic risk data with clinical and social determinants should help identify those at greatest risk, offering the opportunity for kamagra online uk risk reduction.In a Special Article entitled ‘Influenza vaccination. A ‘shot’ at INVESTing in cardiovascular health’, Scott Solomon from the Brigham and Women’s Hospital, Harvard Medical School in Boston, MA, USA, and colleagues note that the link between viral respiratory and non-pulmonary organ-specific injury has become increasingly appreciated during the current erectile dysfunction disease 2019 (erectile dysfunction treatment) kamagra.21 Even prior to the kamagra, however, the association between acute with influenza and elevated cardiovascular risk was evident.

The recently published kamagra online uk results of the NHLBI-funded INVESTED trial, a 5200-patient comparative effectiveness study of high-dose vs. Standard-dose influenza treatment to reduce cardiopulmonary events and mortality in a high-risk cardiovascular population, found no difference between strategies. However, the broader implications of influenza treatment as a strategy to reduce morbidity in high-risk patients remains extremely important, with randomized control trial and observational data supporting vaccination in high-risk patients with cardiovascular disease. Given a favourable risk–benefit profile and widespread availability at generally low cost, the authors contend that influenza vaccination should remain a centrepiece kamagra online uk of cardiovascular risk mitigation and describe the broader context of underutilization of this strategy.

Few therapeutics in medicine offer seasonal efficacy from a single administration with generally mild, transient side effects and exceedingly low rates of serious adverse effects. control measures such as physical distancing, hand washing, and the use of masks during kamagra online uk the erectile dysfunction treatment kamagra have already been associated with substantially curtailed incidence of influenza outbreaks across the globe. Appending annual influenza vaccination to these measures represents an important public health and moral imperative.The issue is complemented by two Discussion Forum articles. In a contribution entitled ‘Management of acute coronary syndromes kamagra online uk in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation’, Paolo Verdecchia from the Hospital S.

Maria della Misericordia in Perugia, Italy, and colleagues comment on the recently published contribution ‘2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)’.22,23 A response to Verdecchia’s comment has been supplied kamagra online uk by Collet et al.24The editors hope that readers of this issue of the European Heart Journal will find it of interest. References1Sorimachi H, Obokata M, Takahashi N, Reddy YNV, Jain CC, Verbrugge FH, Koepp KE, Khosla S, Jensen MD, Borlaug BA. Pathophysiologic importance of visceral adipose tissue in women with heart failure and preserved ejection fraction.

Eur Heart kamagra online uk J 2021;42:1595–1605.2Omland T. Targeting the endothelin system. A step towards a precision medicine approach in heart failure with preserved kamagra online uk ejection fraction?. Eur Heart J 2019;40:3718–3720.3Reddy YNV, Obokata M, Wiley B, Koepp KE, Jorgenson CC, Egbe A, Melenovsky V, Carter RE, Borlaug BA.

The haemodynamic basis of lung congestion during exercise in heart failure with preserved ejection fraction kamagra online uk. Eur Heart J 2019;40:3721–3730.4Obokata M, Kane GC, Reddy YNV, Melenovsky V, Olson TP, Jarolim P, Borlaug BA. The neurohormonal basis of kamagra online uk pulmonary hypertension in heart failure with preserved ejection fraction. Eur Heart J 2019;40:3707–3717.5Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G.

How to diagnose kamagra online uk heart failure with preserved ejection fraction. The HFA-PEFF diagnostic algorithm. A consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J 2019;40:3297–3317.6Hamdani N, Costantino S, Mügge A, Lebeche D, Tschöpe C, Thum kamagra online uk T, Paneni F.

Leveraging clinical epigenetics in heart failure with preserved ejection fraction. A call for individualized kamagra online uk therapies. Eur Heart J 2021;42:1940–1958.7Corrigendum to. 2018 ESC Guidelines for the diagnosis kamagra online uk and management of syncope.

Eur Heart J 2018;39:2002.8Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight into kamagra online uk sick sinus syndrome. Eur Heart J 2021;42:1959–1971.9Tomsits P, Claus S, Kääb S. Genetic insight into kamagra online uk sick sinus syndrome.

Is there a pill for it or how far are we on the translational road to personalized medicine?. Eur Heart J 2021;42:1972–1975.10Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey T, Shapiro F, Kunkel LM. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne’s or Becker’s muscular dystrophy kamagra online uk. N Engl J Med 1988;318:1363–1368.11Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K.

Association between prophylactic angiotensin-converting kamagra online uk enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. Eur Heart J 2021;42:1976–1984.12Owens AT, kamagra online uk Jessup M. Cardioprotection in Duchenne muscular dystrophy.

Eur Heart J 2021;42:1985–1987.13Semsarian C, kamagra online uk Ho CY. Screening children at risk for hypertrophic cardiomyopathy. Balancing benefits kamagra online uk and harms. Eur Heart J 2019;40:3682–3684.14Lafreniere-Roula M, Bolkier Y, Zahavich L, Mathew J, George K, Wilson J, Stephenson EA, Benson LN, Manlhiot C, Mital S.

Family screening for hypertrophic cardiomyopathy. Is it time to change practice kamagra online uk guidelines?. Eur Heart J 2019;40:3672–3681.15Marston NA, Han L, Olivotto I, Day SM, Ashley EA, Michels M, Pereira AC, Ingles J, Semsarian C, Jacoby D, Colan SD, Rossano JW, Wittekind SG, Ware JS, Saberi S, Helms AS, Ho CY. Clinical characteristics and outcomes kamagra online uk in childhood-onset hypertrophic cardiomyopathy.

Eur Heart J 2021;42:1988–1996.16Kaski JP. Childhood-onset hypertrophic kamagra online uk cardiomyopathy research coming of age. Eur Heart J 2021;42:1997–1999.17Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kühl U, Maisch B, McKenna WJ, Monserrat L, Pankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren A. Classification of the kamagra online uk cardiomyopathies.

A position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart kamagra online uk J 2008;29:270–276.18Crea F. Machine learning-guided phenotyping of dilated cardiomyopathy and treatment of heart failure by antisense oligonucleotides. The future has begun.

Eur Heart J 2021;42:139–142.19Garnier S, Harakalova M, Weiss S, Mokry M, Regitz-Zagrosek V, Hengstenberg C, Cappola TP, Isnard R, Arbustini E, Cook SA, van Setten J, Calis JJA, Hakonarson H, Morley MP, Stark kamagra online uk K, Prasad SK, Li J, O’Regan DP, Grasso M, Müller-Nurasyid M, Meitinger T, Empana JP, Strauch K, Waldenberger M, Marguiles KB, Seidman CE, Kararigas G, Meder B, Haas J, Boutouyrie P, Lacolley P, Jouven X, Erdmann J, Blankenberg S, Wichter T, Ruppert V, Tavazzi L, Dubourg O, Roizes G, Dorent R, de Groote P, Fauchier L, Trochu JN, Aupetit JF, Bilinska ZT, Germain M, Völker U, Hemerich D, Raji I, Bacq-Daian D, Proust C, Remior P, Gomez-Bueno M, Lehnert K, Maas R, Olaso R, Saripella GV, Felix SB, McGinn S, Duboscq-Bidot L, van Mil A, Besse C, Fontaine V, Blanché H, Ader F, Keating B, Curjol A, Boland A, Komajda M, Cambien F, Deleuze JF, Dörr M, Asselbergs FW, Villard E, Trégouët DA, Charron P. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23. Eur Heart J 2021;42:2000–2011.20Fullenkamp DE, Puckelwartz kamagra online uk MJ, McNally EM. Genome-wide association for heart failure.

From discovery to kamagra online uk clinical use. Eur Heart J 2021;42:2012–2014.21Bhatt AS, Vardeny O, Udell JA, Joseph J, Kim K, Solomon SD. Influenza vaccination kamagra online uk. A ‘shot’ at INVESTing in cardiovascular health.

Eur Heart J 2021;42:2015–2018.22Verdecchia P, Angeli F, Cavallini C kamagra online uk. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation. Eur Heart J 2021;42:2019.23Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM. 2020 ESC Guidelines kamagra online uk for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.

Eur Heart J 2021;42:1289–1367.24Collet JP, Thiele H. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation – Dual versus triple kamagra online uk antithrombotic therapy. Eur Heart J 2021;42:2020–2021. Published on behalf of the kamagra online uk European Society of Cardiology.

All rights reserved. © The Author(s) kamagra online uk 2021. For permissions, please email. Journals.permissions@oup.com..

The team of Deputy and Associate Editors Heribert Schunkert, Sharlene Day and Peter SchwartzThe European Heart Journal (EHJ) wants to attract high-class submissions dealing with genetic findings that help to improve the how to get kamagra without a doctor mechanistic understanding and the therapy of cardiovascular diseases. In charge of identifying such articles is a mini-team of experts on genetics, Heribert Schunkert, Sharlene Day, and Peter Schwartz.Genetic findings have contributed enormously to the molecular understanding of cardiovascular diseases. A number of diseases including various channelopathies, cardiomyopathies, and metabolic disorders have been elucidated how to get kamagra without a doctor based on a monogenic inheritance and the detection of disease-causing mutations in large families.

More recently, the complex genetic architecture of common cardiovascular diseases such as atrial fibrillation or coronary artery disease has become increasingly clear. Moreover, genetics became a sensitive tool to characterize the role of traditional cardiovascular risk factors in the form of Mendelian randomized studies how to get kamagra without a doctor. However, the real challenge is still ahead, i.e., to bridge genetic findings into novel therapies for the prevention and treatment of cardiac diseases.

The full cycle how to get kamagra without a doctor from identification of a family with hypercholesterolaemia due to a proprotein convertase subtilisin/kexin type 9 (PCSK-9) mutation to successful risk lowering by PCSK-9 antibodies illustrates the power of genetics in this regard.With its broad expertise, the new EHJ editorial team on genetics aims to cover manuscripts from all areas in which genetics may contribute to the understanding of cardiovascular diseases. Prof. Peter Schwartz is a how to get kamagra without a doctor world-class expert on channelopathies and pioneered the field of long QT syndrome.

He is an experienced clinical specialist on cardiac arrhythmias of genetic origins and a pioneer in the electrophysiology of the myocardium. He studied in Milan, worked at the University of Texas for 3 years and, as Associate Professor, at the University of Oklahoma 4 months/year for 12 years. He has been Chairman of Cardiology at the University of Pavia for 20 years and since 1999 acts as an extraordinary professor at the Universities of Stellenbosch and Cape Town for how to get kamagra without a doctor 3 months/year.Prof.

Sharlene M. Day is Director of Translational Research in the Division of Cardiovascular Medicine and Cardiovascular Institute at the how to get kamagra without a doctor University of Pennsylvania. She trained at the University of Michigan and stayed on as faculty as the founding Director of the Inherited Cardiomyopathy and Arrhythmia Program before moving to the University of Pennsylvania in 2019.

Like Prof how to get kamagra without a doctor. Schwartz, her research programme covers the full spectrum from clinical medicine to basic research with a focus on hypertrophic cardiomyopathy. Both she and how to get kamagra without a doctor Prof.

Schwartz have developed inducible pluripotent stem cell models of human monogenic cardiac disorders as a platform to study the underlying biological mechanisms of disease.Heribert Schunkert is Director of the Cardiology Department in the German Heart Center Munich. He trained in the Universities of Aachen and Regensburg, Germany and for 4 years in various teaching how to get kamagra without a doctor hospitals in Boston. Before moving to Munich, he was Director of the Department for Internal Medicine at the University Hospital in Lübeck.

His research interest shifted from the molecular biology of the renin–angiotensin system to complex genetics of atherosclerosis. He was amongst the first to conduct genome-wide association meta-analyses, which allowed how to get kamagra without a doctor the identification of numerous genetic variants that contribute to coronary artery disease, peripheral arterial disease, or aortic stenosis.The editorial team on cardiovascular genetics aims to facilitate the publication of strong translational research that illustrates to clinicians and cardiovascular scientists how genetic and epigenetic variation influences the development of heart diseases. The future perspective is to communicate genetically driven therapeutic targets as has become evident already with the utilization of interfering antibodies, RNAs, or even genome-editing instruments.In this respect, the team encourages submission of world-class genetic research on the cardiovascular system to the EHJ.

The team how to get kamagra without a doctor is also pleased to cooperate with the novel Council on Cardiovascular Genomics which was inaugurated by the ESC in 2020.Conflict of interest. None declared.Andros TofieldMerlischachen, Switzerland Published on behalf of the European Society of Cardiology. All rights how to get kamagra without a doctor reserved.

© The Author(s) 2020. For permissions, please email how to get kamagra without a doctor. Journals.permissions@oup.com.With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article. For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.This is a Focus Issue on genetics.

Described as the ‘single largest unmet need in cardiovascular medicine’, heart failure with preserved ejection fraction (HFpEF) remains an untreatable how to get kamagra without a doctor disease currently representing 65% of new HF diagnoses. HFpEF is more frequent among women and is associated with a poor prognosis and unsustainable healthcare costs.1,2 Moreover, the variability in HFpEF phenotypes amplifies the complexity and difficulties of the approach.3–5 In this perspective, unveiling novel molecular targets is imperative. In a State of the Art Review article entitled ‘Leveraging clinical epigenetics in heart failure with preserved ejection fraction.

A call for individualized therapies’, authored by Francesco Paneni from the University of Zurich in Switzerland, and colleagues,6 the authors note that epigenetic modifications—defined as changes of DNA, histones, and non-coding RNAs (ncRNAs)—represent a molecular framework through which the environment modulates gene expression.6 Epigenetic signals acquired how to get kamagra without a doctor over a lifetime lead to chromatin remodelling and affect transcriptional programmes underlying oxidative stress, inflammation, dysmetabolism, and maladaptive left ventricular (LV) remodelling, all conditions predisposing to HFpEF. The strong involvement of epigenetic signalling in this setting makes the epigenetic information relevant for diagnostic and therapeutic purposes in patients with HFpEF. The recent advances in high-throughput sequencing, computational epigenetics, and machine learning have enabled the how to get kamagra without a doctor identification of reliable epigenetic biomarkers in cardiovascular patients.

In contrast to genetic tools, epigenetic biomarkers mirror the contribution of environmental cues and lifestyle changes, and their reversible nature offers a promising opportunity to monitor disease states. The growing understanding of chromatin and ncRNA biology has led to the development of several Food and Drug Administration (FDA)-approved ‘epi-drugs’ (chromatin modifiers, mimics, and anti-miRs) able to prevent transcriptional alterations underpinning LV remodelling and how to get kamagra without a doctor HFpEF. In the present review, Paneni and colleagues discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of HFpEF.Sick sinus syndrome (SSS) is a complex cardiac arrhythmia and the leading indication for permanent pacemaker implantation worldwide.

It is characterized by pathological sinus how to get kamagra without a doctor bradycardia, sinoatrial block, or alternating atrial brady- and tachyarrhythmias. Symptoms include fatigue, reduced exercise capacity, and syncope. Few studies have been conducted on the basic mechanisms of SSS, and therapeutic limitations reflect an incomplete understanding of the pathophysiology.7 In a clinical research entitled ‘Genetic insight into sick sinus syndrome’, Rosa Thorolfsdottir from deCODE genetics in Reykjavik, Iceland, and colleagues aimed to use human genetics to investigate the pathogenesis of SSS and the role of risk factors in its development.8 The authors performed how to get kamagra without a doctor a genome-wide association study (GWAS) of >6000 SSS cases and >1 000 000 controls.

Variants at six loci associated with SSS. A full genotypic model best described the p.Gly62Cys association, with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased how to get kamagra without a doctor the risk of pacemaker implantation.

Their association with atrial fibrillation (AF) varied, and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. They also tested 17 exposure phenotypes in polygenic score how to get kamagra without a doctor (PGS) and Mendelian randomization analyses. Only two associated with risk of SSS in Mendelian randomization—AF and lower heart rate—suggesting causality.

Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, how to get kamagra without a doctor triglycerides, and type 2 diabetes (P >. 0.05) (Figure 1). Figure 1Summary of genetic insight into the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors how to get kamagra without a doctor in its development.

Variants at six loci (named by corresponding gene names) were identified through genome-wide association study (GWAS), and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for atrial fibrillation (AF) and heart rate, and provided convincing evidence against causality for body mass index (BMI), cholesterol (HDL and non-HDL), how to get kamagra without a doctor triglycerides, and type 2 diabetes (T2D). Mendelian randomization did not support causality for coronary artery disease, ischaemic stroke, heart failure, PR interval, or QRS duration (not shown in the figure).

Red and blue arrows represent positive and negative associations, respectively (from Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight how to get kamagra without a doctor into sick sinus syndrome. See pages 1959–1971.).Figure 1Summary of genetic insight into the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.

Variants at how to get kamagra without a doctor six loci (named by corresponding gene names) were identified through genome-wide association study (GWAS), and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for atrial fibrillation (AF) and heart rate, and provided convincing evidence against causality for body mass index (BMI), cholesterol (HDL and non-HDL), triglycerides, and type 2 diabetes (T2D). Mendelian randomization did not support causality for coronary artery disease, ischaemic stroke, heart failure, PR interval, or how to get kamagra without a doctor QRS duration (not shown in the figure).

Red and blue arrows represent positive and negative associations, respectively (from Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight into how to get kamagra without a doctor sick sinus syndrome. See pages 1959–1971.).Thorolfsdottir et al.

Conclude that they report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in how to get kamagra without a doctor homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS. The article is accompanied by an Editorial by Stefan Kääb from LMU Klinikum in Munich, Germany, and colleagues.9 The authors conclude that the limitations of the work challenge clinical translation, but do not diminish the multiple interesting findings of Thorolfsdottir et al., bringing us closer to the finishing line of unlocking SSS genetics to develop new therapeutic strategies.

They also highlight that this study represents a considerable accomplishment for the field, but also clearly highlights upcoming challenges and how to get kamagra without a doctor indicates areas where further research is warranted on our way on the translational road to personalized medicine.Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that affects ∼1 in every 3500 live-born male infants, making it the most common neuromuscular disease of childhood. The disease is caused by mutations in the dystrophin gene, which lead to dystrophin deficiency in muscle cells, resulting in decreased fibre stability and continued degeneration. The patients present with progressive how to get kamagra without a doctor muscle wasting and loss of muscle function, develop restrictive respiratory failure and dilated cardiomyopathy, and usually die in their late teens or twenties from cardiac or respiratory failure.10 In a clinical research article ‘Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy.

Analysis of registry data’ Raphaël Porcher from the Université de Paris in France, and colleagues estimate the effect of prophylactic angiotensin-converting enzyme (ACE) inhibitors on survival in DMD.11 The authors analysed the data from the French multicentre DMD-Heart-Registry. They estimated the association between the prophylactic prescription of ACE inhibitors and event-free survival in 668 patients between the ages of 8 and 13 years, with normal left how to get kamagra without a doctor ventricular function, using (i) a Cox model with intervention as a time-dependent covariate. (ii) a propensity-based analysis comparing ACE inhibitor treatment vs.

No treatment how to get kamagra without a doctor. And (iii) a set of sensitivity analyses. The study outcomes were (i) overall survival and (ii) hospitalizations for HF or acute respiratory failure.

Among the patients included in the DMD-Heart-Registry, 576 were eligible for this study, how to get kamagra without a doctor of whom 390 were treated with an ACE inhibitor prophylactically. Death occurred in 53 patients (13.5%) who were and 60 patients (32.3%) who were not treated prophylactically with an ACE inhibitor. In a Cox model, with intervention as a time-dependent variable, how to get kamagra without a doctor the hazard ratio (HR) associated with ACE inhibitor treatment was 0.49 for overall mortality after adjustment for baseline variables.

In the propensity-based analysis, with 278 patients included in the treatment group and 302 in the control group, ACE inhibitors were associated with a lower risk of death (HR 0.32) and hospitalization for HF (HR 0.16) (Figure 2). All sensitivity analyses yielded similar results how to get kamagra without a doctor. Figure 2Graphical Abstract (from Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall how to get kamagra without a doctor survival in Duchenne muscular dystrophy. Analysis of registry data. See pages 1976–1984.).Figure 2Graphical Abstract (from Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, how to get kamagra without a doctor Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K.

Association between prophylactic angiotensin-converting enzyme inhibitors and overall survival in Duchenne muscular dystrophy. Analysis of registry data. See pages 1976–1984.).Porcher et al how to get kamagra without a doctor.

Conclude that prophylactic treatment with ACE inhibitors in DMD is associated with a significantly higher overall survival and lower rate of hospitalization for management of HF. The manuscript is accompanied by an Editorial by Mariell Jessup and colleagues from the American Heart Association in Dallas, Texas, USA.12 The authors describe how cardioprotective strategies have been investigated in a number of cardiovascular how to get kamagra without a doctor disorders and successfully incorporated into treatment regimens for selected patients, including ACE inhibitors in patients with and without diabetes and coronary artery disease, angiotensin receptor blockers and beta-blockers in Marfan syndrome, and ACE inhibitors and beta-blockers in patients at risk for chemotherapy-related toxicity. They conclude that Porcher et al.

Have now convincingly demonstrated that even very young patients with DMD can benefit from the life-saving intervention how to get kamagra without a doctor of ACE inhibition.Hypertrophic cardiomyopathy (HCM) is characterized by unexplained LV hypertrophy and often caused by pathogenic variants in genes that encode the sarcomere apparatus. Patients with HCM may experience atrial and ventricular arrhythmias and HF. However, disease expression and severity are highly how to get kamagra without a doctor variable.

Furthermore, there is marked diversity in the age of diagnosis. Although childhood-onset how to get kamagra without a doctor disease is well documented, it is far less common. Owing to its rarity, the natural history of childhood-onset HCM is not well characterized.12–14 In a clinical research article entitled ‘Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy’, Nicholas Marston from the Harvard Medical School in Boston, MA, USA, and colleagues aimed to describe the characteristics and outcomes of childhood-onset HCM.15 They performed an observational cohort study of >7500 HCM patients.

HCM patients were stratified by age at diagnosis [<1 year (infancy), 1–18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints including HF, life-threatening ventricular arrhythmias, AF, and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 2.4% of patients were diagnosed in infancy, 14.7% how to get kamagra without a doctor in childhood, and 2.9% in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the first decade following the baseline visit, and HF and AF more common by the end of the second decade.

Sarcomeric HCM was more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a >2-fold increased risk of HF and 67% increased risk of the overall how to get kamagra without a doctor composite outcome. When compared with adult-onset HCM, those with childhood-onset disease were 36% more likely to develop life-threatening ventricular arrhythmias and twice as likely to require transplant or a ventricular assist device.The authors conclude that patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. The manuscript is accompanied by an Editorial by Juan Pablo Kaski from the how to get kamagra without a doctor University College London (UCL) Institute of Cardiovascular Science in London, UK.16 Kaski concludes that the field of HCM is now entering the era of personalized medicine, with the advent of gene therapy programmes and a focus on treatments targeting the underlying pathophysiology.

Pre-clinical data suggesting that small molecule myosin inhibitors may attenuate or even prevent disease expression provide cause for optimism, and nowhere more so than for childhood-onset HCM. An international collaborative approach involving basic, translational, and clinical science is now needed to characterize disease expression and progression and develop novel therapies for childhood HCM.Dilated cardiomyopathy (DCM) how to get kamagra without a doctor is a heart muscle disease characterized by LV dilatation and systolic dysfunction in the absence of abnormal loading conditions or coronary artery disease. It is a major cause of systolic HF, the leading indication for heart transplantation, and therefore a major public health problem due to the important cardiovascular morbidity and mortality.17,18 Understanding of the genetic basis of DCM has improved in recent years, with a role for both rare and common variants resulting in a complex genetic architecture of the disease.

In a translational research article entitled ‘Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23’, Sophie Garnier from the Sorbonne Université in Paris, France, and colleagues conducted the largest genome-wide association study performed so far in DCM, with >2500 cases and >4000 controls how to get kamagra without a doctor in the discovery population.19 They identified and replicated two new DCM-associated loci, on chromosome 3p25.1 and chromosome 22q11.23, while confirming two previously identified DCM loci on chromosomes 10 and 1, BAG3 and HSPB7. A PGS constructed from the number of risk alleles at these four DCM loci revealed a 27% increased risk of DCM for individuals with eight risk alleles compared with individuals with five risk alleles (median of the referral population). In silico annotation and functional 4C-sequencing analysis on induced pluripotent stem cell (iPSC)-derived cardiomyocytes identified SLC6A6 as the most likely DCM gene at the 3p25.1 locus.

This gene encodes a taurine transporter whose involvement in myocardial dysfunction and DCM how to get kamagra without a doctor is supported by numerous observations in humans and animals. At the 22q11.23 locus, in silico and data mining annotations, and to a lesser extent functional analysis, strongly suggested SMARCB1 as the candidate culprit gene.Garnier et al. Conclude that how to get kamagra without a doctor their study provides a better understanding of the genetic architecture of DCM and sheds light on novel biological pathways underlying HF.

The manuscript is accompanied by an Editorial by Elizabeth McNally from the Northwestern University Feinberg School of Medicine in Chicago, USA, and colleagues.20 The authors conclude that methods to integrate common and rare genetic information will continue to evolve and provide insight on disease progression, potentially providing biomarkers and clues for useful therapeutic pathways to guide drug development. At present, rare cardiomyopathy how to get kamagra without a doctor variants have clinical utility in predicting risk, especially arrhythmic risk. PGS analyses for HF or DCM progression are expected to come to clinical use, especially with the addition of broader GWAS-derived data.

Combining genetic risk data with clinical and social how to get kamagra without a doctor determinants should help identify those at greatest risk, offering the opportunity for risk reduction.In a Special Article entitled ‘Influenza vaccination. A ‘shot’ at INVESTing in cardiovascular health’, Scott Solomon from the Brigham and Women’s Hospital, Harvard Medical School in Boston, MA, USA, and colleagues note that the link between viral respiratory and non-pulmonary organ-specific injury has become increasingly appreciated during the current erectile dysfunction disease 2019 (erectile dysfunction treatment) kamagra.21 Even prior to the kamagra, however, the association between acute with influenza and elevated cardiovascular risk was evident. The recently published results of the NHLBI-funded how to get kamagra without a doctor INVESTED trial, a 5200-patient comparative effectiveness study of high-dose vs.

Standard-dose influenza treatment to reduce cardiopulmonary events and mortality in a high-risk cardiovascular population, found no difference between strategies. However, the broader implications of influenza treatment as a strategy to reduce morbidity in high-risk patients remains extremely important, with randomized control trial and observational data supporting vaccination in high-risk patients with cardiovascular disease. Given a favourable risk–benefit profile and widespread availability at generally low cost, the authors contend that influenza vaccination should remain a centrepiece of cardiovascular risk mitigation and describe how to get kamagra without a doctor the broader context of underutilization of this strategy.

Few therapeutics in medicine offer seasonal efficacy from a single administration with generally mild, transient side effects and exceedingly low rates of serious adverse effects. control measures such as physical distancing, hand washing, and the use of masks during the erectile dysfunction treatment kamagra have already been associated with substantially curtailed incidence how to get kamagra without a doctor of influenza outbreaks across the globe. Appending annual influenza vaccination to these measures represents an important public health and moral imperative.The issue is complemented by two Discussion Forum articles.

In a contribution entitled ‘Management of acute coronary syndromes in patients presenting how to get kamagra without a doctor without persistent ST-segment elevation and coexistent atrial fibrillation’, Paolo Verdecchia from the Hospital S. Maria della Misericordia in Perugia, Italy, and colleagues comment on the recently published contribution ‘2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force for how to get kamagra without a doctor the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC)’.22,23 A response to Verdecchia’s comment has been supplied by Collet et al.24The editors hope that readers of this issue of the European Heart Journal will find it of interest.

References1Sorimachi H, Obokata M, Takahashi N, Reddy YNV, Jain CC, Verbrugge FH, Koepp KE, Khosla S, Jensen MD, Borlaug BA. Pathophysiologic importance of visceral adipose tissue in women with heart failure and preserved ejection fraction. Eur Heart J 2021;42:1595–1605.2Omland how to get kamagra without a doctor T.

Targeting the endothelin system. A step how to get kamagra without a doctor towards a precision medicine approach in heart failure with preserved ejection fraction?. Eur Heart J 2019;40:3718–3720.3Reddy YNV, Obokata M, Wiley B, Koepp KE, Jorgenson CC, Egbe A, Melenovsky V, Carter RE, Borlaug BA.

The haemodynamic basis of lung congestion during exercise in heart how to get kamagra without a doctor failure with preserved ejection fraction. Eur Heart J 2019;40:3721–3730.4Obokata M, Kane GC, Reddy YNV, Melenovsky V, Olson TP, Jarolim P, Borlaug BA. The neurohormonal basis of how to get kamagra without a doctor pulmonary hypertension in heart failure with preserved ejection fraction.

Eur Heart J 2019;40:3707–3717.5Pieske B, Tschöpe C, de Boer RA, Fraser AG, Anker SD, Donal E, Edelmann F, Fu M, Guazzi M, Lam CSP, Lancellotti P, Melenovsky V, Morris DA, Nagel E, Pieske-Kraigher E, Ponikowski P, Solomon SD, Vasan RS, Rutten FH, Voors AA, Ruschitzka F, Paulus WJ, Seferovic P, Filippatos G. How to diagnose heart how to get kamagra without a doctor failure with preserved ejection fraction. The HFA-PEFF diagnostic algorithm.

A consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur Heart J 2019;40:3297–3317.6Hamdani how to get kamagra without a doctor N, Costantino S, Mügge A, Lebeche D, Tschöpe C, Thum T, Paneni F. Leveraging clinical epigenetics in heart failure with preserved ejection fraction.

A call how to get kamagra without a doctor for individualized therapies. Eur Heart J 2021;42:1940–1958.7Corrigendum to. 2018 ESC how to get kamagra without a doctor Guidelines for the diagnosis and management of syncope.

Eur Heart J 2018;39:2002.8Thorolfsdottir RB, Sveinbjornsson G, Aegisdottir HM, Benonisdottir S, Stefansdottir L, Ivarsdottir EV, Halldorsson GH, Sigurdsson JK, Torp-Pedersen C, Weeke PE, Brunak S, Westergaard D, Pedersen OB, Sorensen E, Nielsen KR, Burgdorf KS, Banasik K, Brumpton B, Zhou W, Oddsson A, Tragante V, Hjorleifsson KE, Davidsson OB, Rajamani S, Jonsson S, Torfason B, Valgardsson AS, Thorgeirsson G, Frigge ML, Thorleifsson G, Norddahl GL, Helgadottir A, Gretarsdottir S, Sulem P, Jonsdottir I, Willer CJ, Hveem K, Bundgaard H, Ullum H, Arnar DO, Thorsteinsdottir U, Gudbjartsson DF, Holm H, Stefansson K. Genetic insight into sick how to get kamagra without a doctor sinus syndrome. Eur Heart J 2021;42:1959–1971.9Tomsits P, Claus S, Kääb S.

Genetic insight into how to get kamagra without a doctor sick sinus syndrome. Is there a pill for it or how far are we on the translational road to personalized medicine?. Eur Heart J 2021;42:1972–1975.10Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, Harris JB, Waterston R, Brooke M, Specht L, Kupsky W, Chamberlain J, Caskey T, Shapiro F, Kunkel LM.

Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne’s how to get kamagra without a doctor or Becker’s muscular dystrophy. N Engl J Med 1988;318:1363–1368.11Porcher R, Desguerre I, Amthor H, Chabrol B, Audic F, Rivier F, Isapof A, Tiffreau V, Campana-Salort E, Leturcq F, Tuffery-Giraud S, Ben Yaou R, Annane D, Amédro P, Barnerias C, Bécane HM, Béhin A, Bonnet D, Bassez G, Cossée M, de La Villéon G, Delcourte C, Fayssoil A, Fontaine B, Godart F, Guillaumont S, Jaillette E, Laforêt P, Leonard-Louis S, Lofaso F, Mayer M, Morales RJ, Meune C, Orlikowski D, Ovaert C, Prigent H, Saadi M, Sochala M, Tard C, Vaksmann G, Walther-Louvier U, Eymard B, Stojkovic T, Ravaud P, Duboc D, Wahbi K. Association between prophylactic angiotensin-converting enzyme how to get kamagra without a doctor inhibitors and overall survival in Duchenne muscular dystrophy.

Analysis of registry data. Eur Heart how to get kamagra without a doctor J 2021;42:1976–1984.12Owens AT, Jessup M. Cardioprotection in Duchenne muscular dystrophy.

Eur Heart how to get kamagra without a doctor J 2021;42:1985–1987.13Semsarian C, Ho CY. Screening children at risk for hypertrophic cardiomyopathy. Balancing benefits and how to get kamagra without a doctor harms.

Eur Heart J 2019;40:3682–3684.14Lafreniere-Roula M, Bolkier Y, Zahavich L, Mathew J, George K, Wilson J, Stephenson EA, Benson LN, Manlhiot C, Mital S. Family screening for hypertrophic cardiomyopathy. Is it how to get kamagra without a doctor time to change practice guidelines?.

Eur Heart J 2019;40:3672–3681.15Marston NA, Han L, Olivotto I, Day SM, Ashley EA, Michels M, Pereira AC, Ingles J, Semsarian C, Jacoby D, Colan SD, Rossano JW, Wittekind SG, Ware JS, Saberi S, Helms AS, Ho CY. Clinical characteristics and how to get kamagra without a doctor outcomes in childhood-onset hypertrophic cardiomyopathy. Eur Heart J 2021;42:1988–1996.16Kaski JP.

Childhood-onset hypertrophic cardiomyopathy how to get kamagra without a doctor research coming of age. Eur Heart J 2021;42:1997–1999.17Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kühl U, Maisch B, McKenna WJ, Monserrat L, Pankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren A. Classification of the cardiomyopathies how to get kamagra without a doctor.

A position statement from the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J how to get kamagra without a doctor 2008;29:270–276.18Crea F. Machine learning-guided phenotyping of dilated cardiomyopathy and treatment of heart failure by antisense oligonucleotides.

The future has begun. Eur Heart J 2021;42:139–142.19Garnier S, Harakalova M, Weiss S, Mokry M, Regitz-Zagrosek V, Hengstenberg C, Cappola TP, Isnard R, Arbustini E, Cook SA, van Setten J, Calis JJA, Hakonarson H, Morley MP, Stark K, Prasad SK, Li J, O’Regan DP, Grasso M, Müller-Nurasyid M, Meitinger T, Empana JP, Strauch K, Waldenberger M, Marguiles KB, Seidman CE, Kararigas G, Meder B, Haas J, Boutouyrie P, Lacolley P, Jouven X, Erdmann J, Blankenberg S, Wichter T, Ruppert V, Tavazzi L, Dubourg O, Roizes G, Dorent R, de Groote P, Fauchier L, Trochu JN, Aupetit JF, Bilinska ZT, Germain M, Völker U, Hemerich D, Raji I, Bacq-Daian D, Proust C, Remior P, Gomez-Bueno M, Lehnert K, Maas R, Olaso R, Saripella GV, Felix SB, McGinn S, Duboscq-Bidot L, van Mil A, Besse C, Fontaine V, Blanché H, Ader F, Keating B, Curjol A, Boland A, Komajda M, Cambien F, Deleuze JF, Dörr M, Asselbergs how to get kamagra without a doctor FW, Villard E, Trégouët DA, Charron P. Genome-wide association analysis in dilated cardiomyopathy reveals two new players in systolic heart failure on chromosomes 3p25.1 and 22q11.23.

Eur Heart J 2021;42:2000–2011.20Fullenkamp DE, Puckelwartz how to get kamagra without a doctor MJ, McNally EM. Genome-wide association for heart failure. From discovery how to get kamagra without a doctor to clinical use.

Eur Heart J 2021;42:2012–2014.21Bhatt AS, Vardeny O, Udell JA, Joseph J, Kim K, Solomon SD. Influenza vaccination how to get kamagra without a doctor. A ‘shot’ at INVESTing in cardiovascular health.

Eur Heart J 2021;42:2015–2018.22Verdecchia P, Angeli F, Cavallini how to get kamagra without a doctor C. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation and coexistent atrial fibrillation. Eur Heart J 2021;42:2019.23Collet JP, Thiele H, Barbato E, Barthélémy O, Bauersachs J, Bhatt DL, Dendale P, Dorobantu M, Edvardsen T, Folliguet T, Gale CP, Gilard M, Jobs A, Jüni P, Lambrinou E, Lewis BS, Mehilli J, Meliga E, Merkely B, Mueller C, Roffi M, Rutten FH, Sibbing D, Siontis GCM.

2020 ESC Guidelines for the management of how to get kamagra without a doctor acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2021;42:1289–1367.24Collet JP, Thiele H. Management of acute coronary syndromes in patients presenting how to get kamagra without a doctor without persistent ST-segment elevation and coexistent atrial fibrillation – Dual versus triple antithrombotic therapy.

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