Des jeunes, acteurs de leur avenir

How to get minipress online

#ffffff. Color. #121212. Box-sizing. Border-box.

Calc(100% - 40px). Border-top. 5px solid #121212. Border-bottom. 2px solid #121212.

Padding. 5px 0 10px 0. } @media only screen and (min-width. 600px) { #styln-briefing-block { margin. 40px auto.

} } #styln-briefing-block a { color. #121212. } #styln-briefing-block ul { margin-left. 15px. } #styln-briefing-block a.briefing-block-link { color.

#121212. Border-bottom. 1px solid #cccccc. Font-size. 0.9375rem.

Line-height. 1.375rem. } #styln-briefing-block a.briefing-block-link:hover { border-bottom. None. } #styln-briefing-block .briefing-block-bullet::before { content.

-2px. Position. Relative. } #styln-briefing-block .briefing-block-bullet:not(:last-child) { margin-bottom. 0.75em.

} #styln-briefing-block .briefing-block-header-section { margin-bottom. 16px. } #styln-briefing-block .briefing-block-header { font-weight. 700. Font-size.

1.125rem. Line-height. 1.375rem. Display. Inline-block.

Margin-bottom. 5px. } @media only screen and (min-width. 600px) { #styln-briefing-block .briefing-block-header { font-size. 1.25rem.

Line-height. 1.5625rem. } } #styln-briefing-block .briefing-block-header a { text-decoration. None. Color.

#333. } #styln-briefing-block .briefing-block-header a::after { content. '›'. Position. Relative.

Font-weight. 500. Margin-left. 5px. } #styln-briefing-block .briefing-block-footer { font-size.

14px. Margin-top. 1.25em. /* padding-top. 1.25em.

Border-top. 1px solid #e2e2e2. */ } #styln-briefing-block .briefing-block-briefinglinks a { font-weight. Bold. Margin-right.

6px. } #styln-briefing-block .briefing-block-footer a { border-bottom. 1px solid #ccc. } #styln-briefing-block .briefing-block-footer a:hover { border-bottom. 1px solid transparent.

} #styln-briefing-block .briefing-block-header { border-bottom. None. } #styln-briefing-block .briefing-block-lb-items { display. Grid. Grid-template-columns.

Auto 1fr. Grid-column-gap. 20px. Grid-row-gap. 15px.

Line-height. 1.2. } #styln-briefing-block .briefing-block-update-time a { color. #999. Font-size.

12px. } #styln-briefing-block .briefing-block-update-time.active a { color. #D0021B. } #styln-briefing-block .briefing-block-footer-meta { display. None.

Justify-content. Space-between. Align-items. Center. } #styln-briefing-block .briefing-block-ts { color.

} @media only screen and (min-width. 600px) { #styln-briefing-block a.briefing-block-link { font-size. 1.0625rem. Line-height. 1.5rem.

} #styln-briefing-block .briefing-block-bullet::before { content. '•'. Margin-right. 10px. Color.

Top. -2px. Position. Relative. } #styln-briefing-block .briefing-block-update-time a { font-size.

13px. } } @media only screen and (min-width. 1024px) { #styln-briefing-block { width. 100%. } } Latest Updates.

The Coronavirus Outbreak 5m ago With a rule change and some unusual help from a private jet, Nick Saban coached the Crimson Tide to victory. 2h ago Scientists raise doubts about Britain’s plan to deliberately infect volunteers. 2h ago Afghans seeking medical care in Pakistan are killed in a stampede. See more updates More live coverage. Markets A New York Times database has tracked clusters of at least 50 coronavirus cases in a dozen rural jails in Montana, Idaho, Utah and New Mexico during the pandemic.

Among them. The Purgatory Correctional Center in Hurricane, Utah, with 166 infections. The jail in Twin Falls, Idaho, with 279. And, in New Mexico, the Cibola County Correctional Center, which has reported 357 cases.In Cascade County, infections at the jail make up about a quarter of all known virus cases in the county. Health authorities say that the jail’s outbreak, which began in mid-August, was not believed to be the main cause of the community’s recent surge, but that it had led to some cases.

In the past two months, Mr. Krogue said, the jail released 29 people who were considered actively infected.Infections at the jail make up about a quarter of Cascade County’s known virus cases.Credit...Tailyr Irvine for The New York TimesGreat Falls, home to about 58,000 residents, is in the less mountainous part of Montana, with the Missouri River flowing through and a large oil refinery on its banks. The Cascade County Detention Center sits along a highway at the edge of town. Drive five miles in any direction and you are surrounded by wide-open plains.Montana requires that masks be worn inside businesses and indoor public spaces, and many people in Great Falls wear them when walking around downtown’s Central Avenue, where shops and cafes are still recovering from shutting down in the spring. Others go without masks, citing the open space and lack of crowds.Bob Kelly, the mayor, said people had not been overly worried about how the jail outbreak might affect the rest of town when it started.“I think that by the very definition of a jail, hopefully, the disease will be incarcerated, as well as the patients,” he said.

€œIs there concern?. Sure, there’s concern. But is there overreaction?. No.”The mayor of Great Falls said that residents had considered the jail’s outbreak a distant concern at first.Credit...Tailyr Irvine for The New York TimesSome residents’ nonchalance about the risks of the virus, said Mr. Krogue, the jail’s medical director, can be traced to a spring and early summer when almost no one in Cascade County knew anyone who had been sickened.“We benefited from that early on,” he said.

€œBut in some ways, I think it did us a disservice, too, because it also created a certain level of complacency.”That has quickly shifted now, he said, as cases have spiked.The number of active cases known to county officials on any given day has risen sharply to about 600, according to Trisha Gardner, Cascade County’s health officer. The county has seen 1,261 cases and six deaths during the pandemic, a Times database shows. Some of the cases have been tied to the jail outbreak, she said, and others have been connected to bars and restaurants. Even figuring out what has led to some cases has been complex, she said, as residents have been reluctant to cooperate with contact tracers.“Our hospitals are at capacity, our public health system is at capacity,” she said. €œIt’s not sustainable at this rate.”When the outbreak at the jail began, social distancing was impossible, the authorities said.

Three inmates shared cells designed for two. At night, men slept on thin blue pads in every available space. On the floor in the day room, in shower stalls, in stairwells, in hallways outside of cells.Inmates did not receive masks until August, and jail officials said many have refused to wear them.In interviews with more than a dozen inmates and their family members, inmates described the jail during the outbreak as chaotic and unsanitary. They said their pleas for help often went unanswered by nurses and guards.Newly arriving inmates were not always quarantined from one another before their test results were known because of a lack of space, inmates and jail officials said.Owen Hawley, 30, said every inmate in his living area of 38 men had tested positive for the virus. He said he had been unable to eat for three days, had intensive body aches and suffered from a headache so powerful it felt as if it was “behind my eyes.”“After the fourth day of like, not eating and stuff, I just shut off, you know?.

€ he said.A jail area set aside for quarantining new inmates.Credit...Tailyr Irvine for The New York TimesAt one point, Mr. Hawley said, he and other prisoners protested the way the virus was being handled by refusing to leave their living areas and by blocking new inmates from entering. Everyone was ultimately tested, Mr. Hawley said, and each prisoner was given a disposable mask.Sierra Jasmine Wells, 25, another inmate, said women in her dormitory had grown ill, one after the next.“Everyone around me was getting sick and it was tough on me,” she said. €œBy then, I had already accepted the fact that I was going to get sick.”When she became infected, she said, she was given cough syrup and Tylenol.“I kind of was just left alone to deal with it,” she said.Jesse Slaughter, the county sheriff who oversees the jail, said that the jail’s medical staff was doing everything it could, and that he had been seeking health care assistance from other counties.

Officials defended their handling of the outbreak, noting that all inmates received standard medications including Tylenol twice a day and were taken to area hospitals when they needed added care. Seven inmates, as well as some staff members, were hospitalized. No one from the jail has died from the virus, officials said.Sheriff Jesse Slaughter, who oversees the jail, said he had been seeking health care assistance from other counties.Credit...Tailyr Irvine for The New York TimesMr. Krogue said that since the start of the outbreak he had been working up to 16 hours each day and sleeping in his basement, away from his wife and children. He remains healthy but says he fears bringing the virus home.

The virus has slowed some in the jail, and officials have moved some inmates to other facilities, but other prisons and jails in the state are now seeing outbreaks.“You can start to see what some of these other places experienced much earlier on, and we just didn’t have that experience, but it’s certainly happening now,” Mr. Krogue said. €œIt’s just real in a way that it wasn’t.”Lucy Tompkins reported from Great Falls, Maura Turcotte from Chicago and Libby Seline from Lincoln, Neb. Reporting was contributed by Izzy Colón from Columbia, Mo., Brendon Derr from Phoenix, Rebecca Griesbach from Tuscaloosa, Ala., Danya Issawi and Timothy Williams from New York, Ann Hinga Klein from Des Moines, K.B. Mensah from Silver Spring, Md., and Mitch Smith from Chicago.Start Preamble Federal Transit Administration (FTA), DOT.

Notice of funding opportunity. The Coronavirus Disease 2019 (COVID-19) 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 COVID-19. 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 COVID-19 public health emergency. Demonstration grants under this NOFO are authorized under FTA's Public Transportation Innovation Program (49 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 disinfection. (2) exposure mitigation measures. (3) innovative mobility such as contactless payments.

And (4) measures that strengthen public confidence in transit services. The total funding available for awards under this NOFO is $10,000,000. FTA may supplement this amount if additional funding 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 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 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 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 Information C.

Eligibility Information D. Application and Submission Information E. Application Review Information F. Federal Award Administration Information G. Federal Awarding Agency Contact Information A.

Program Description The Public Transportation COVID-19 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 COVID-19 public health emergency. Eligible projects will propose to develop and deploy innovative solutions in four major areas. (1) Vehicle, facility, equipment and infrastructure cleaning and disinfection. (2) exposure mitigation measures.

(3) innovative mobility such as contactless payments. And (4) measures that strengthen public confidence in transit. As required by 49 U.S.C. 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 Transportation Innovation Program (49 U.S.C. 5312) to finance the Public Transportation COVID-19 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 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 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 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. 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 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 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 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 surplus. Replacement or depreciation cash fund or reserve.

New capital. 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, equipment and infrastructure cleaning and disinfection. 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. 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 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 forms. 1. The SF-424 Mandatory Form (downloadable from GRANTS.GOV) and 2.

The supplemental form for the FY 2020 COVID-19 Demonstration Program (downloadable from GRANTS.GOV), which is available on FTA's website at (placeholder for FTA COVID-19 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 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 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 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” 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 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 information, including. I. Applicant Name ii. Dun and 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 type) vi. A detailed description of the need for the project vii. A detailed description 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 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 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 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 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 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 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 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 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 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. 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 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 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 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 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.

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.

Generic minipress online for sale

Minipress
Nemasole
Duration of action
5mg 30 tablet $60.00
$
Does medicare pay
No
Online
Best price for brand
RX pharmacy
RX pharmacy
Prescription
5mg 60 tablet $115.00
$

Jim Robinson has one word for anyone generic minipress online for sale living near a wildfire. Leave. Jim Robinson (pictured with Karen Fiscus) wants others to know about his experiences with the most recent wine country fire. (Courtesy Jim Robinson.)He wishes he had done that sooner.

Like so many others, he underestimated the intensity and speed of a fire that ended up trapping him and his girlfriend, Karen Fiscus. For them, it was the LNU Lightning Complex fire that devastated wine country beginning in mid-August.The costs of waiting have been much too high. He and Fiscus had to hide in a drainage pipe as fire surrounded them twice before emergency responders were able to reach them.Today, Robinson is still recovering from second- and third-degree burns on 27% of his body following seven weeks in the UC Davis Burn Center. He also is grieving, as his girlfriend died from her injuries.

His Napa hog farm is now an eerie moonscape and his animals are gone.Still, he wants to talk about what happened, and offer advice to those in wildfire zones.“In the past, we’ve been able to wait out the fires,” Robinson said. €œIt kind of goes with living where I live. But this fire was different. Way different.

It had its own atmosphere.”UC Davis surgeon Tina Palmieri is a nationally recognized expert on treating and improving outcomes for burn patients.Two bright spots for Robinson as he recovers have been his family and the Burn Center, where a specially trained team treated his injuries and helped him accept his survival. The weeks he spent there were, he said, “One of the best experiences I ever had. The doctors and nurses were phenomenal.”The Burn Center treats adults in Northern California and Western Nevada who need intensive burn care. Tina Palmieri, a burn surgeon and director of the center, said the number of wildfire-injured patients her team treats has steadily increased over the past few years.“Wildfire-related burns can be particularly challenging because they are often severe, and because transportation to a hospital for care can be delayed by the fire itself,” Palmieri said.Palmieri echoes Robinson’s guidance about leaving quickly once a fire breaks out in your area.

She also suggests covering up from head to toe, despite the heat of a fire, and bringing a flashlight. Both helped Robinson. His clothes offered some protection for his skin and the flashlight guided emergency responders to him.As wildfires in Northern California increase so do the number of patients in UC Davis’ Burn Center with wildfire-related injuries.If you do get burned, Palmieri said, rinse the burn injury with cool water for up to 20 minutes if you can, as this may decrease the extent of the injury. However, keep the rest of your skin covered and dry.

And, as soon as possible, get emergency care.Robinson said that while protecting your property may be your first instinct in a fire, you should ignore that instinct.“Give yourself enough time to get your belongings together and just go,” he said. €œYou can start over, but you can’t bring a life back.” A Center of Excellence, the Firefighters Burn Institute Regional Burn Center at UC Davis Medical Center unites the exceptional surgical, critical care and rehabilitation resources of UC Davis Health to care for the unique needs of adult burn patients. The team also treats pediatric burn patients through a partnership with Shriners Hospitals for Children – Northern California. In addition to a comprehensive clinical program, the burn center conducts research aimed at improving patient outcomes, leads community outreach to support burn survivors, and provides education to reduce burn injuries.

More information is on the Burn Center website.The Burn Center also hosts a support group for all burn survivors in the region. For information about joining, email Lauren Spink at lhspink@ucdavis.edu.Related stories and resourcesThe Burn Center team braces for wildfire seasonDon’t forget to include these health items in your emergency ‘go bag’Staying safe during a wildfire information from the U.S. Centers for Disease Control and Prevention CAL FIRE incident mapNurse Carla Martin, executive director for Patient Care Services at UC Davis Medical Center, saw first-hand the preparedness, the anxiety and the stress in receiving and treating the first known community-transmitted COVID-19 patient in the U.S.In her harrowing and inspirational account of those tense hours and days, Carla shares her unique perspective on how UC Davis Health leaders and care providers navigated totally uncharted waters.Hear the full story, in Carla’s own words.In celebration of Florence Nightingale's 200th birthday, 2020 is the Year of the Nurse. Beginning on National Nurses Week (May 6-12) and continuing throughout the year, a special blog will feature the stories, memories and motivations of UC Davis Health nurses.Hear their words, and get to know why and how they invest such heart, passion, expertise and commitment in their life-changing work..

Jim Robinson has one how to get minipress online word for anyone living near a wildfire. Leave. Jim Robinson (pictured with Karen Fiscus) wants others to know about his experiences with the most recent wine country fire. (Courtesy Jim Robinson.)He wishes he had done that sooner. Like so many others, he underestimated the intensity and speed of a fire that ended up trapping him and his girlfriend, Karen Fiscus.

For them, it was the LNU Lightning Complex fire that devastated wine country beginning in mid-August.The costs of waiting have been much too high. He and Fiscus had to hide in a drainage pipe as fire surrounded them twice before emergency responders were able to reach them.Today, Robinson is still recovering from second- and third-degree burns on 27% of his body following seven weeks in the UC Davis Burn Center. He also is grieving, as his girlfriend died from her injuries. His Napa hog farm is now an eerie moonscape and his animals are gone.Still, he wants to talk about what happened, and offer advice to those in wildfire zones.“In the past, we’ve been able to wait out the fires,” Robinson said. €œIt kind of goes with living where I live.

But this fire was different. Way different. It had its own atmosphere.”UC Davis surgeon Tina Palmieri is a nationally recognized expert on treating and improving outcomes for burn patients.Two bright spots for Robinson as he recovers have been his family and the Burn Center, where a specially trained team treated his injuries and helped him accept his survival. The weeks he spent there were, he said, “One of the best experiences I ever had. The doctors and nurses were phenomenal.”The Burn Center treats adults in Northern California and Western Nevada who need intensive burn care.

Tina Palmieri, a burn surgeon and director of the center, said the number of wildfire-injured patients her team treats has steadily increased over the past few years.“Wildfire-related burns can be particularly challenging because they are often severe, and because transportation to a hospital for care can be delayed by the fire itself,” Palmieri said.Palmieri echoes Robinson’s guidance about leaving quickly once a fire breaks out in your area. She also suggests covering up from head to toe, despite the heat of a fire, and bringing a flashlight. Both helped Robinson. His clothes offered some protection for his skin and the flashlight guided emergency responders to him.As wildfires in Northern California increase so do the number of patients in UC Davis’ Burn Center with wildfire-related injuries.If you do get burned, Palmieri said, rinse the burn injury with cool water for up to 20 minutes if you can, as this may decrease the extent of the injury. However, keep the rest of your skin covered and dry.

And, as soon as possible, get emergency care.Robinson said that while protecting your property may be your first instinct in a fire, you should ignore that instinct.“Give yourself enough time to get your belongings together and just go,” he said. €œYou can start over, but you can’t bring a life back.” A Center of Excellence, the Firefighters Burn Institute Regional Burn Center at UC Davis Medical Center unites the exceptional surgical, critical care and rehabilitation resources of UC Davis Health to care for the unique needs of adult burn patients. The team also treats pediatric burn patients through a partnership with Shriners Hospitals for Children – Northern California. In addition to a comprehensive clinical program, the burn center conducts research aimed at improving patient outcomes, leads community outreach to support burn survivors, and provides education to reduce burn injuries. More information is on the Burn Center website.The Burn Center also hosts a support group for all burn survivors in the region.

For information about joining, email Lauren Spink at lhspink@ucdavis.edu.Related stories and resourcesThe Burn Center team braces for wildfire seasonDon’t forget to include these health items in your emergency ‘go bag’Staying safe during a wildfire information from the U.S. Centers for Disease Control and Prevention CAL FIRE incident mapNurse Carla Martin, executive director for Patient Care Services at UC Davis Medical Center, saw first-hand the preparedness, the anxiety and the stress in receiving and treating the first known community-transmitted COVID-19 patient in the U.S.In her harrowing and inspirational account of those tense hours and days, Carla shares her unique perspective on how UC Davis Health leaders and care providers navigated totally uncharted waters.Hear the full story, in Carla’s own words.In celebration of Florence Nightingale's 200th birthday, 2020 is the Year of the Nurse. Beginning on National Nurses Week (May 6-12) and continuing throughout the year, a special blog will feature the stories, memories and motivations of UC Davis Health nurses.Hear their words, and get to know why and how they invest such heart, passion, expertise and commitment in their life-changing work..

Where can I keep Minipress?

Keep out of the reach of children in a container that small children cannot open.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.

Blum minipress parts

First-of-its-kind study, based on a mouse model, finds living in a polluted environment could be comparable to eating a high-fat diet, leading to a pre-diabetic state CLEVELAND—Air pollution is blum minipress parts the world’s leading environmental risk factor, and causes more than nine million deaths per year. New research published in the Journal of Clinical Investigation shows air pollution may play a role in the development of cardiometabolic diseases, such as diabetes. Importantly, the blum minipress parts effects were reversible with cessation of exposure. Researchers found that air pollution was a “risk factor for a risk factor” that contributed to the common soil of other fatal problems like heart attack and stroke.

Similar to how an unhealthy diet and lack of exercise can lead to disease, exposure to air pollution could be added to this risk factor list as well. “In this study, we created an environment that mimicked a polluted day in New Delhi or Beijing,” said Sanjay Rajagopalan, MD, first author on the study, Chief of Cardiovascular Medicine at University Hospitals Harrington Heart and Vascular Institute, and Director of the Case Western Reserve blum minipress parts University Cardiovascular Research Institute. €œWe concentrated fine particles of air pollution, called PM2.5 (particulate matter component <. 2.5 microns) blum minipress parts.

Concentrated particles like this develop from human impact on the environment, such as automobile exhaust, power generation and other fossil fuels.” These particles have been strongly connected to risk factors for disease. For example, cardiovascular effects of air pollution can lead to heart attack and stroke. The research team has shown exposure to air pollution can increase the likelihood of the same risk factors that lead to heart disease, blum minipress parts such as insulin resistance and type 2 diabetes. In the mouse model study, three groups were observed.

A control group receiving clean filtered air, a group exposed to polluted air for 24 weeks, and a group fed a high-fat diet. Interestingly, the researchers found that being exposed to air pollution was comparable to eating blum minipress parts a high-fat diet. Both the air pollution and high-fat diet groups showed insulin resistance and abnormal metabolism – just like one would see in a pre-diabetic state. These changes were blum minipress parts associated with changes in the epigenome, a layer of control that can masterfully turn on and turn off thousands of genes, representing a critical buffer in response to environmental factors.

This study is the first-of-its-kind to compare genome-wide epigenetic changes in response to air pollution, compare and contrast these changes with that of eating an unhealthy diet, and examine the impact of air pollution cessation on these changes.“The good news is that these effects were reversible, at least in our experiments” added Dr. Rajagopalan. €œOnce the air pollution was removed from the environment, the mice appeared healthier and the pre-diabetic state seemed blum minipress parts to reverse.” Dr. Rajagopalan explains that if you live in a densely polluted environment, taking actions such as wearing an N95 mask, using portable indoor air cleaners, utilizing air conditioning, closing car windows while commuting, and changing car air filters frequently could all be helpful in staying healthy and limiting air pollution exposure.Next steps in this research involve meeting with a panel of experts, as well as the National Institutes of Health, to discuss conducting clinical trials that compare heart health and the level of air pollution in the environment.

For example, if someone has a heart attack, should they be wearing an N95 mask or using a portable air filter at home during recovery?. Dr blum minipress parts. Rajagopalan and his team believe that it is important to address the environment as a population health risk factor and continue to diligently research these issues. The authors also note that these findings should encourage policymakers to enact measures aimed at reducing air pollution.Shyam Biswal, PhD, Professor in the Department of Environmental Health and Engineering at Johns Hopkins University School blum minipress parts of Public Health, is the joint senior author on the study.

Drs. Rajagopalan and Biswal are co-PIs on the NIH grant that supported this work.###Rajagopalan, S., Biswal, S., et al. €œMetabolic effects of air pollution exposure and reversibility.” blum minipress parts Journal of Clinical Investigation. DOI.

10.1172/JCI137315. This work was supported by the National Institute of Environmental Health Sciences TaRGET II Consortium grant U01ES026721, as well as grants R01ES015146 and R01ES019616.About one in five women experience some form of depression during pregnancy, with poorly understood effects on the fetus. Prenatal depression is linked to behavioural and developmental issues in children as well as an increased risk for depression as young adults. But how prenatal depression leads to these changes remains unclear.

UCalgary researcher Dr. Catherine Lebel, PhD, is helping understand what may be happening in the developing brains of these children. The research team has shown that young children whose mothers experienced more numerous symptoms of depression in pregnancy have weakened connectivity in brain pathways involved in emotion. These structural changes can be related to increased hyperactivity and aggression in boys.

The research is based on diffusion magnetic resonance imaging, an imaging technique that probes the strength of structural connections between brain regions. The findings are published in The Journal of Neuroscience. Catherine Lebel, senior author and investigator. Riley Brandt, University of Calgary “The results help us understand how depression can have multigenerational impacts, and speaks to the importance of helping mothers who may be experiencing depression during pregnancy,” says Lebel, an associate professor at the Cumming School of Medicine, and researcher in the Alberta Children’s Hospital Research Institute.

She holds the Canada Research Chair in Paediatric Neuroimaging. Lebel and her team studied 54 Calgary mothers and their children. They were enrolled from the ongoing, prospective study called the Alberta Pregnancy Outcomes and Nutrition study. Mothers answered a survey about their depression symptoms at several points during their pregnancy.

Their children were followed after birth and undertook an MRI scan at the Alberta Children’s Hospital at around age four. As well, the children’s behaviour was assessed within six months of their MRI scan. The team found a significant reduction in structural brain connectivity between the amygdala, a structure essential for emotional processing, and the frontal cortex. Weakened connectivity between the amygdala and frontal cortex is associated with disruptive behaviours and vulnerability to depression.

The first author on the study, Dr. Rebecca Hay, MD, stresses the importance of recognition of depression and intervention in prenatal health. €œThese results suggest complex associations between the prenatal environment and children’s brain development, and may help us to understand why children of depressed mothers are more vulnerable to depression themselves,” says Hay, a resident physician in paediatrics and recent Cumming School of Medicine graduate. The main clinical takeaway from this is to emphasize the importance of recognizing, treating prenatal depression and supporting mothers, both for better maternal outcomes and to help future child development.

Rebecca Hay, the study's first author. Courtesy Rebecca Hay Current study looks at stress during pandemic Lebel and her research team are currently trying to understand how stress and mental health are affecting pregnant women during the COVID-19 pandemic. She is examining how factors such as social supports might mitigate stress, and how this may influence pregnancy and birth outcomes. If you are interested, you can get involved here in the Pregnancy During the COVID-19 Pandemic study at the University of Calgary.

So far, approximately 7,500 women from across Canada are enrolled and supplying information through questionnaires. €œIt is critical to appropriately recognize and treat prenatal maternal mental health problems, both for the mothers and to improve child outcomes,” says Lebel. €œNow more than ever, with increased stress, anxiety and depression during the COVID-19 pandemic, we should do more to support mothers to positively impact the health of their children.” Lebel is an associate professor in the Department of Radiology at the Cumming School of Medicine, adjunct associate professor in the Werklund School of Education and a member of The Mathison Centre for Mental Health Research &. Education, Owerko Centre at ACHRI, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute.

The study was funded by the Canadian Institute of Health Research, Alberta Innovates - Health Solutions, the Alberta Children's Hospital Foundation, the National Institute of Environmental Health Sciences, the Mach-Gaensslen Foundation, and an Eyes High University of Calgary Postdoctoral Scholar. Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six research strategies guiding the University of Calgary toward its Eyes High goals. The strategy provides a unifying direction for brain and mental health research at the university..

First-of-its-kind study, based on a mouse model, finds living in a how to get minipress online polluted environment could be comparable to eating a high-fat diet, leading to a pre-diabetic state CLEVELAND—Air pollution is the world’s leading environmental risk factor, and causes more than nine million deaths per year. New research published in the Journal of Clinical Investigation shows air pollution may play a role in the development of cardiometabolic diseases, such as diabetes. Importantly, the effects were reversible how to get minipress online with cessation of exposure.

Researchers found that air pollution was a “risk factor for a risk factor” that contributed to the common soil of other fatal problems like heart attack and stroke. Similar to how an unhealthy diet and lack of exercise can lead to disease, exposure to air pollution could be added to this risk factor list as well. “In this study, we created an environment that mimicked a polluted day in New Delhi or Beijing,” said Sanjay Rajagopalan, MD, first how to get minipress online author on the study, Chief of Cardiovascular Medicine at University Hospitals Harrington Heart and Vascular Institute, and Director of the Case Western Reserve University Cardiovascular Research Institute.

€œWe concentrated fine particles of air pollution, called PM2.5 (particulate matter component <. 2.5 microns) how to get minipress online. Concentrated particles like this develop from human impact on the environment, such as automobile exhaust, power generation and other fossil fuels.” These particles have been strongly connected to risk factors for disease.

For example, cardiovascular effects of air pollution can lead to heart attack and stroke. The research team has shown exposure to air how to get minipress online pollution can increase the likelihood of the same risk factors that lead to heart disease, such as insulin resistance and type 2 diabetes. In the mouse model study, three groups were observed.

A control group receiving clean filtered air, a group exposed to polluted air for 24 weeks, and a group fed a high-fat diet. Interestingly, the researchers found that being exposed how to get minipress online to air pollution was comparable to eating a high-fat diet. Both the air pollution and high-fat diet groups showed insulin resistance and abnormal metabolism – just like one would see in a pre-diabetic state.

These changes were associated with changes in the epigenome, a layer of control that can masterfully turn on and turn off thousands of genes, representing a critical buffer in response to environmental how to get minipress online factors. This study is the first-of-its-kind to compare genome-wide epigenetic changes in response to air pollution, compare and contrast these changes with that of eating an unhealthy diet, and examine the impact of air pollution cessation on these changes.“The good news is that these effects were reversible, at least in our experiments” added Dr. Rajagopalan.

€œOnce the air pollution was removed from the environment, the how to get minipress online mice appeared healthier and the pre-diabetic state seemed to reverse.” Dr. Rajagopalan explains that if you live in a densely polluted environment, taking actions such as wearing an N95 mask, using portable indoor air cleaners, utilizing air conditioning, closing car windows while commuting, and changing car air filters frequently could all be helpful in staying healthy and limiting air pollution exposure.Next steps in this research involve meeting with a panel of experts, as well as the National Institutes of Health, to discuss conducting clinical trials that compare heart health and the level of air pollution in the environment. For example, if someone has a heart attack, should they be wearing an N95 mask or using a portable air filter at home during recovery?.

Dr how to get minipress online. Rajagopalan and his team believe that it is important to address the environment as a population health risk factor and continue to diligently research these issues. The authors how to get minipress online also note that these findings should encourage policymakers to enact measures aimed at reducing air pollution.Shyam Biswal, PhD, Professor in the Department of Environmental Health and Engineering at Johns Hopkins University School of Public Health, is the joint senior author on the study.

Drs. Rajagopalan and Biswal are co-PIs on the NIH grant that supported this work.###Rajagopalan, S., Biswal, S., et al. €œMetabolic effects of air pollution exposure and how to get minipress online reversibility.” Journal of Clinical Investigation.

DOI. 10.1172/JCI137315. This work was supported by the National Institute of Environmental Health Sciences TaRGET II Consortium grant U01ES026721, as well as grants R01ES015146 and R01ES019616.About one in five women experience some form of depression during pregnancy, with poorly understood effects on the fetus.

Prenatal depression is linked to behavioural and developmental issues in children as well as an increased risk for depression as young adults. But how prenatal depression leads to these changes remains unclear. UCalgary researcher Dr.

Catherine Lebel, PhD, is helping understand what may be happening in the developing brains of these children. The research team has shown that young children whose mothers experienced more numerous symptoms of depression in pregnancy have weakened connectivity in brain pathways involved in emotion. These structural changes can be related to increased hyperactivity and aggression in boys.

The research is based on diffusion magnetic resonance imaging, an imaging technique that probes the strength of structural connections between brain regions. The findings are published in The Journal of Neuroscience. Catherine Lebel, senior author and investigator.

Riley Brandt, University of Calgary “The results help us understand how depression can have multigenerational impacts, and speaks to the importance of helping mothers who may be experiencing depression during pregnancy,” says Lebel, an associate professor at the Cumming School of Medicine, and researcher in the Alberta Children’s Hospital Research Institute. She holds the Canada Research Chair in Paediatric Neuroimaging. Lebel and her team studied 54 Calgary mothers and their children.

They were enrolled from the ongoing, prospective study called the Alberta Pregnancy Outcomes and Nutrition study. Mothers answered a survey about their depression symptoms at several points during their pregnancy. Their children were followed after birth and undertook an MRI scan at the Alberta Children’s Hospital at around age four.

As well, the children’s behaviour was assessed within six months of their MRI scan. The team found a significant reduction in structural brain connectivity between the amygdala, a structure essential for emotional processing, and the frontal cortex. Weakened connectivity between the amygdala and frontal cortex is associated with disruptive behaviours and vulnerability to depression.

The first author on the study, Dr. Rebecca Hay, MD, stresses the importance of recognition of depression and intervention in prenatal health. €œThese results suggest complex associations between the prenatal environment and children’s brain development, and may help us to understand why children of depressed mothers are more vulnerable to depression themselves,” says Hay, a resident physician in paediatrics and recent Cumming School of Medicine graduate.

The main clinical takeaway from this is to emphasize the importance of recognizing, treating prenatal depression and supporting mothers, both for better maternal outcomes and to help future child development. Rebecca Hay, the study's first author. Courtesy Rebecca Hay Current study looks at stress during pandemic Lebel and her research team are currently trying to understand how stress and mental health are affecting pregnant women during the COVID-19 pandemic.

She is examining how factors such as social supports might mitigate stress, and how this may influence pregnancy and birth outcomes. If you are interested, you can get involved here in the Pregnancy During the COVID-19 Pandemic study at the University of Calgary. So far, approximately 7,500 women from across Canada are enrolled and supplying information through questionnaires.

€œIt is critical to appropriately recognize and treat prenatal maternal mental health problems, both for the mothers and to improve child outcomes,” says Lebel. €œNow more than ever, with increased stress, anxiety and depression during the COVID-19 pandemic, we should do more to support mothers to positively impact the health of their children.” Lebel is an associate professor in the Department of Radiology at the Cumming School of Medicine, adjunct associate professor in the Werklund School of Education and a member of The Mathison Centre for Mental Health Research &. Education, Owerko Centre at ACHRI, Hotchkiss Brain Institute and Alberta Children's Hospital Research Institute.

The study was funded by the Canadian Institute of Health Research, Alberta Innovates - Health Solutions, the Alberta Children's Hospital Foundation, the National Institute of Environmental Health Sciences, the Mach-Gaensslen Foundation, and an Eyes High University of Calgary Postdoctoral Scholar. Led by the Hotchkiss Brain Institute, Brain and Mental Health is one of six research strategies guiding the University of Calgary toward its Eyes High goals. The strategy provides a unifying direction for brain and mental health research at the university..

How do you get minipress

People in Aboriginal communities across NSW will have access to expanded suicide how do you get minipress prevention support thanks to an investment of $7.7 million from the NSW Government.Minister for Mental Health Bronnie Taylor said the funding would enable 12 community organisations to deliver culturally appropriate suicide prevention activities. €œIn Aboriginal communities, there is a growing body of evidence around the healing power of culture when it comes to mental health issues and suicide prevention,” Mrs Taylor said. €œThis funding how do you get minipress will support community-led and culturally appropriate initiatives to tackle these important issues.“These new programs will involve Elders and focus on building identity and connection, as well as helping Aboriginal people access mental health services.” The funding has been allocated to 12 Aboriginal Community Controlled Health Organisations (ACCHOs) which can use the funds flexibly for a combination of grassroots community activities and clinical services.

Suicide is the fourth leading cause of death for Indigenous Australians living in NSW, compared to 17th for non-Indigenous Australians. Minister for Aboriginal Affairs Don Harwin praised how do you get minipress the initiative and echoed the importance of targeted efforts to address the issue within Aboriginal communities. €œToo many Aboriginal families in NSW are sadly impacted by suicide,” Mr Harwin said.

€œI’m heartened that as part of the NSW Government’s Towards Zero Suicides strategy, this important investment will enable Aboriginal Community Controlled Health Organisations to deliver services to support the mental health and social and emotional wellbeing of our Aboriginal people and communities across how do you get minipress the State.” Tharawal Aboriginal Medical Services in Campbelltown is one of the ACCHOs to receive funding and CEO Darryl Wright said he wants to see the next generation flourish. €œThis funding will go towards reducing the intergenerational grief and trauma that still impacts our youth today. For every family that how do you get minipress we can help heal and nourish, our community will grow stronger and our futures glow brighter," Mr Wright said.

Building on Resilience in Aboriginal Communities is part of Towards Zero Suicides, a NSW Premier’s Priority and NSW Government investment of $87 million over three years in new and exisiting suicide prevention initiatives. If you, or someone you know, is thinking about suicide or experiencing a personal crisis or distress, please seek help immediately by calling 000 or one of these services. Lifeline 13 11 14Suicide Call Back Service 1300 659 467NSW Mental Health Line 1800 011 511 ​​​15 full-time equivalent specialist counsellors will be deployed across rural NSW to help prevent suicide, with the first two counsellors how do you get minipress starting in the Eurobodalla and Snowy Mountains regions.NSW Mental Health Minister Bronnie Taylor said the relatively high rates of suicide in rural areas are devastating families and communities, and the $6.75 million investment will add another layer of help.“Many factors can contribute to suicide, from domestic violence, to relationship issues or unemployment, to stress and hardship,” Mrs Taylor said.

€œThese specialist mental health counsellors are there on the ground to support people thinking of suicide or impacted by suicide, and I encourage communities across the state to lean on them for support.”Director Mental Health Drug and Alcohol for Southern NSW Local Health District Damien Eggleton said he wants more people to ask for help when they need it. €œOur rural communities have proven beyond a doubt they’re resilient and fearless when faced with adversity, whether that be geographic isolation, searing drought or the impact of the how do you get minipress current pandemic – but they don’t need to go it alone,” Mr Eggleton said. €œThe support provided by these counsellors will complement the peer work and drought support provided by our Farm Gate Counsellors and Drought Counsellors.”Rural counsellor Samara Byrne said she wants young people to know there are people you can turn to when feeling overwhelmed with life or feeling like a burden on others.

€œWe are here for you and here to listen if you how do you get minipress are feeling distressed, anxious or a burden to loved ones. The service is easily accessible through the Mental Health Line. Just ask for the Rural Counsellor.”“Having moved from Sydney in 2016 to our beautiful farm how do you get minipress in SNSW, I am so pleased to be able to do what I am most passionate about, supporting people’s wellbeing in Rural Australia and building on the natural local community resilience”.Minister Taylor urges people in the bush to get help by contacting these rural counsellors.

€œSupport is available, all you need to do is pick up the phone and make an appointment by calling the NSW Mental Health Line on 1800 011 511.”The 15 rural counselling positions are part of the Towards Zero Suicides. A $87 million investment over three years how do you get minipress in new suicide prevention initiatives. A NSW Premier’s Priority, this is a whole-of-government commitment to transforming the way we identify and support anyone impacted by suicide.If you, or someone you know, is thinking about suicide or experiencing a personal crisis or distress, please seek help immediately in a life-threatening situation by calling 000 or seek support though one of these services:Lifeline 13 11 14Suicide Call Back Service 1300 659 467NSW Mental Health Line 1800 011 511​Regional and rural patients now have access to 24-hour critical care under a $21.7 million telestroke service being rolled out across NSW.Patients at Port Macquarie and Coffs Harbour hospitals are the first to benefit from the NSW Telestroke Service, based at Sydney’s Prince of Wales Hospital.

Health Minister Brad Hazzard said the revolutionary service will expand how do you get minipress to up to 23 sites over the next three years. €œThe NSW Telestroke Service will remove geographical barriers and improve outcomes for thousands of regional and rural stroke patients every year, giving them a much greater chance of surviving and leading a normal life,” Mr Hazzard said. €œPeople in regional and rural areas have a far greater risk of hospitalisation from stroke and this vital service will provide them with immediate, life-saving diagnosis and treatment from the state’s leading clinicians.” In 2018-19, 13,651 people were hospitalised for a stroke in NSW.

Of those, 32 per cent were from regional, how do you get minipress rural or remote areas. A successful pilot project in the Hunter New England, Central Coast and Mid North Coast local health districts since 2017 has already helped 1200 patients. The Stroke Foundation’s Chief Executive Officer how do you get minipress Sharon McGowan welcomed the launch of the statewide service, jointly funded by the State and Federal governments.

€œWhen a stroke strikes, it kills up to 1.9 million brain cells per minute. This service will have an enormous impact by providing time-critical, best-practice treatment that saves lives and reduces lifelong how do you get minipress disability,” Ms McGowan said. Prince of Wales Hospital’s Director of Clinical Neuroscience Professor Ken Butcher said.

€œThe service links how do you get minipress expert stroke clinicians with local emergency physicians to quickly determine the best possible treatment plan for a patient.” ​A strict permit system is in place for all flights arriving in NSW from Victoria and passengers undergo comprehensive police and health checks upon arrival. Health Minister Brad Hazzard said all flights are met by NSW Health staff and police officers to ensure anyone entering NSW complies with the current health orders. “There are only limited reasons anyone from how do you get minipress Victoria should be entering NSW and people have been turned back despite being allowed on the plane in Melbourne,” Mr Hazzard said.

€œVictorian residents are not permitted into NSW at all unless they are needed for specific purposes and even then have to apply for and get a permit. €œWe are constantly reviewing the situation in Victoria and will adjust the health orders as necessary to protect the people of NSW.” Anyone who flies into NSW from Victoria must either be a NSW resident or have a relevant permit that allows entry into NSW – that can include:defence officialsdoctors and nursescritical workers in energy, mining and constructionchild protection workersdisability workers.All travellers are provided with a pack of two masks and hand sanitiser by the airlines. Upon arrival into NSW all how do you get minipress passengers from Victoria are.

given masks if they left them on the planetemperature checkedasked relevant questions about their health. And their permit how do you get minipress is checked to ensure it complies with the strict permit system.Anyone without a valid permit is referred to NSW Police and taken to the Special Health Accommodation to complete 14 days of quarantine. Strict instructions and rules are in place for those going into ‘Home Isolation’ including.

Recommended they be collected in a private car by family or friendsnot to use public transport to get hometo only sit in the back seat of a car with the windows open and air conditioning not on recirculationtold to wear their face masks and observe hand hygiene recommendations, andcalled to how do you get minipress make sure they arrive home.NSW Health is provided the contact details of everyone who enters NSW from Victoria. NSW Police is conducting regular compliance checks for people told to go into ‘Home Isolation’ as well as responding to reports from the community in relation to suspected breaches. Over the weekend, how do you get minipress NSW Police visited almost 600 homes to check that those that were meant to be self-isolating were doing so.

In addition to that, over the same period NSW Police received 374 calls to Crime Stoppers reporting suspected breaches of the health orders, the majority of which were for people suspected of not following self-isolation rules. ​.

People in Aboriginal communities across NSW will have access to expanded suicide prevention support thanks to an investment of $7.7 million from the NSW Government.Minister for Mental Health Bronnie Taylor said the funding would enable 12 community organisations to how to get minipress online deliver culturally appropriate suicide prevention activities. €œIn Aboriginal communities, there is a growing body of evidence around the healing power of culture when it comes to mental health issues and suicide prevention,” Mrs Taylor said. €œThis funding will support community-led and culturally appropriate initiatives to tackle these important issues.“These new programs will involve Elders and focus on building identity and connection, as well as helping Aboriginal people access mental health services.” The funding how to get minipress online has been allocated to 12 Aboriginal Community Controlled Health Organisations (ACCHOs) which can use the funds flexibly for a combination of grassroots community activities and clinical services. Suicide is the fourth leading cause of death for Indigenous Australians living in NSW, compared to 17th for non-Indigenous Australians. Minister for Aboriginal Affairs Don Harwin praised the initiative and echoed the importance of targeted efforts to address the how to get minipress online issue within Aboriginal communities.

€œToo many Aboriginal families in NSW are sadly impacted by suicide,” Mr Harwin said. €œI’m heartened that how to get minipress online as part of the NSW Government’s Towards Zero Suicides strategy, this important investment will enable Aboriginal Community Controlled Health Organisations to deliver services to support the mental health and social and emotional wellbeing of our Aboriginal people and communities across the State.” Tharawal Aboriginal Medical Services in Campbelltown is one of the ACCHOs to receive funding and CEO Darryl Wright said he wants to see the next generation flourish. €œThis funding will go towards reducing the intergenerational grief and trauma that still impacts our youth today. For every family that how to get minipress online we can help heal and nourish, our community will grow stronger and our futures glow brighter," Mr Wright said. Building on Resilience in Aboriginal Communities is part of Towards Zero Suicides, a NSW Premier’s Priority and NSW Government investment of $87 million over three years in new and exisiting suicide prevention initiatives.

If you, or someone you know, is thinking about suicide or experiencing a personal crisis or distress, please seek help immediately by calling 000 or one of these services. Lifeline 13 11 14Suicide Call Back Service 1300 659 467NSW Mental Health Line 1800 011 511 ​​​15 full-time equivalent specialist counsellors will be deployed across rural NSW to help prevent suicide, with the first two counsellors starting in the Eurobodalla and Snowy Mountains regions.NSW Mental Health Minister Bronnie Taylor said the relatively high rates of suicide in rural areas are devastating families and communities, and the how to get minipress online $6.75 million investment will add another layer of help.“Many factors can contribute to suicide, from domestic violence, to relationship issues or unemployment, to stress and hardship,” Mrs Taylor said. €œThese specialist mental health counsellors are there on the ground to support people thinking of suicide or impacted by suicide, and I encourage communities across the state to lean on them for support.”Director Mental Health Drug and Alcohol for Southern NSW Local Health District Damien Eggleton said he wants more people to ask for help when they need it. €œOur rural communities have proven beyond a doubt they’re resilient and fearless when faced with adversity, whether that be geographic isolation, searing drought or the impact of the current how to get minipress online pandemic – but they don’t need to go it alone,” Mr Eggleton said. €œThe support provided by these counsellors will complement the peer work and drought support provided by our Farm Gate Counsellors and Drought Counsellors.”Rural counsellor Samara Byrne said she wants young people to know there are people you can turn to when feeling overwhelmed with life or feeling like a burden on others.

€œWe are here for you and here to listen how to get minipress online if you are feeling distressed, anxious or a burden to loved ones. The service is easily accessible through the Mental Health Line. Just ask for the Rural Counsellor.”“Having moved from Sydney in 2016 to our beautiful farm in SNSW, I am so pleased to be able to do what I am how to get minipress online most passionate about, supporting people’s wellbeing in Rural Australia and building on the natural local community resilience”.Minister Taylor urges people in the bush to get help by contacting these rural counsellors. €œSupport is available, all you need to do is pick up the phone and make an appointment by calling the NSW Mental Health Line on 1800 011 511.”The 15 rural counselling positions are part of the Towards Zero Suicides. A $87 million investment over three years in new how to get minipress online suicide prevention initiatives.

A NSW Premier’s Priority, this is a whole-of-government commitment to transforming the way we identify and support anyone impacted by suicide.If you, or someone you know, is thinking about suicide or experiencing a personal crisis or distress, please seek help immediately in a life-threatening situation by calling 000 or seek support though one of these services:Lifeline 13 11 14Suicide Call Back Service 1300 659 467NSW Mental Health Line 1800 011 511​Regional and rural patients now have access to 24-hour critical care under a $21.7 million telestroke service being rolled out across NSW.Patients at Port Macquarie and Coffs Harbour hospitals are the first to benefit from the NSW Telestroke Service, based at Sydney’s Prince of Wales Hospital. Health Minister Brad Hazzard said the revolutionary service will expand to up to how to get minipress online 23 sites over the next three years. €œThe NSW Telestroke Service will remove geographical barriers and improve outcomes for thousands of regional and rural stroke patients every year, giving them a much greater chance of surviving and leading a normal life,” Mr Hazzard said. €œPeople in regional and rural areas have a far greater risk of hospitalisation from stroke and this vital service will provide them with immediate, life-saving diagnosis and treatment from the state’s leading clinicians.” In 2018-19, 13,651 people were hospitalised for a stroke in NSW. Of those, 32 per cent were from regional, rural or remote areas how to get minipress online.

A successful pilot project in the Hunter New England, Central Coast and Mid North Coast local health districts since 2017 has already helped 1200 patients. The Stroke Foundation’s Chief Executive Officer Sharon McGowan welcomed the launch of the statewide service, jointly funded by the how to get minipress online State and Federal governments. €œWhen a stroke strikes, it kills up to 1.9 million brain cells per minute. This service will have an enormous impact by providing how to get minipress online time-critical, best-practice treatment that saves lives and reduces lifelong disability,” Ms McGowan said. Prince of Wales Hospital’s Director of Clinical Neuroscience Professor Ken Butcher said.

€œThe service links expert stroke how to get minipress online clinicians with local emergency physicians to quickly determine the best possible treatment plan for a patient.” ​A strict permit system is in place for all flights arriving in NSW from Victoria and passengers undergo comprehensive police and health checks upon arrival. Health Minister Brad Hazzard said all flights are met by NSW Health staff and police officers to ensure anyone entering NSW complies with the current health orders. “There are only limited reasons anyone from Victoria should be entering NSW and people have been turned back despite being allowed on the plane in Melbourne,” Mr Hazzard said how to get minipress online. €œVictorian residents are not permitted into NSW at all unless they are needed for specific purposes and even then have to apply for and get a permit. €œWe are constantly reviewing the situation in Victoria and will adjust the health orders as necessary to protect the people of NSW.” Anyone who flies into NSW from Victoria must either be a NSW resident or have a relevant permit that allows entry into NSW – that can include:defence officialsdoctors and nursescritical workers in energy, mining and constructionchild protection workersdisability workers.All travellers are provided with a pack of two masks and hand sanitiser by the airlines.

Upon arrival into how to get minipress online NSW all passengers from Victoria are. given masks if they left them on the planetemperature checkedasked relevant questions about their health. And their permit is checked to ensure it complies with the strict permit system.Anyone without a how to get minipress online valid permit is referred to NSW Police and taken to the Special Health Accommodation to complete 14 days of quarantine. Strict instructions and rules are in place for those going into ‘Home Isolation’ including. Recommended they be collected in a private car by family or friendsnot to use public transport to get hometo only sit in the back seat of a car with the windows how to get minipress online open and air conditioning not on recirculationtold to wear their face masks and observe hand hygiene recommendations, andcalled to make sure they arrive home.NSW Health is provided the contact details of everyone who enters NSW from Victoria.

NSW Police is conducting regular compliance checks for people told to go into ‘Home Isolation’ as well as responding to reports from the community in relation to suspected breaches. Over the weekend, NSW Police how to get minipress online visited almost 600 homes to check that those that were meant to be self-isolating were doing so. In addition to that, over the same period NSW Police received 374 calls to Crime Stoppers reporting suspected breaches of the health orders, the majority of which were for people suspected of not following self-isolation rules. ​.

Buy minipress online without prescription

No Supplementary Data.No buy minipress online without prescription Article MediaNo MetricsDocument Type. Research ArticleAffiliations:1. Department of Rehabilitation, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe 2.

3 buy minipress online without prescription. UCSF Pulmonary Rehabilitation and Sleep Disorders Center 4. Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, CA, USA, , Email.

[email protected]Publication date:01 July buy minipress online without prescription 2020More about this publication?. The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on lung health world-wide.

Department of Rehabilitation, University of Zimbabwe College of Health Sciences, Harare, how to get minipress online Zimbabwe 2. 3. UCSF Pulmonary Rehabilitation and Sleep Disorders Center 4.

Division of Pulmonary and Critical Care Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California how to get minipress online San Francisco, San Francisco, CA, USA, , Email. [email protected]Publication date:01 July 2020More about this publication?. The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research.

The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of how to get minipress online information on lung health world-wide. To share scientific research of immediate concern as rapidly as possible, The Union is fast-tracking the publication of certain articles from the IJTLD and publishing them on The Union website, prior to their publication in the Journal. Read fast-track articles.Certain IJTLD articles are also selected for translation into French, Spanish, Chinese or Russian.

Blum minipress m51n1053 manual

Covid-19 has created a crisis throughout the blum minipress m51n1053 manual world. This crisis has produced blum minipress m51n1053 manual a test of leadership. With no good options to combat a novel pathogen, countries were forced to make hard choices blum minipress m51n1053 manual about how to respond. Here in blum minipress m51n1053 manual the United States, our leaders have failed that test. They have taken a crisis and turned it into a tragedy.The magnitude of this failure is blum minipress m51n1053 manual astonishing.

According to the Johns Hopkins Center for Systems Science and Engineering,1 the United States leads the world in Covid-19 cases and in deaths due to the disease, far exceeding the numbers in much larger countries, such as China. The death rate in this country is more than double that of Canada, exceeds that of Japan, a country with a vulnerable blum minipress m51n1053 manual and elderly population, by a factor of almost 50, and even dwarfs the rates in lower-middle-income countries, such as Vietnam, by a factor of almost 2000. Covid-19 is an overwhelming challenge, and blum minipress m51n1053 manual many factors contribute to its severity. But the one we can control is blum minipress m51n1053 manual how we behave. And in the United blum minipress m51n1053 manual States we have consistently behaved poorly.We know that we could have done better.

China, faced with the first outbreak, chose strict quarantine and isolation after an initial delay. These measures were severe but effective, essentially eliminating transmission at the point where the outbreak began and reducing the death rate to a reported 3 per million, as compared blum minipress m51n1053 manual with more than 500 per million in the United States. Countries that had far more exchange with China, such as Singapore and South Korea, began intensive testing early, along with aggressive contact tracing and appropriate isolation, blum minipress m51n1053 manual and have had relatively small outbreaks. And New Zealand has used these same measures, together with its geographic advantages, blum minipress m51n1053 manual to come close to eliminating the disease, something that has allowed that country to limit the time of closure and to largely reopen society to a prepandemic level. In general, not only blum minipress m51n1053 manual have many democracies done better than the United States, but they have also outperformed us by orders of magnitude.Why has the United States handled this pandemic so badly?.

We have failed at almost every step. We had ample warning, but when the disease first arrived, we were incapable of blum minipress m51n1053 manual testing effectively and couldn’t provide even the most basic personal protective equipment to health care workers and the general public. And we continue to be way behind the blum minipress m51n1053 manual curve in testing. While the absolute numbers of tests have increased substantially, the more useful metric is the number of tests performed per infected person, a rate that puts us far down blum minipress m51n1053 manual the international list, below such places as Kazakhstan, Zimbabwe, and Ethiopia, countries that cannot boast the biomedical infrastructure or the manufacturing capacity that we have.2 Moreover, a lack of emphasis on developing capacity has meant that U.S. Test results are often long delayed, rendering the results useless for disease control.Although we tend blum minipress m51n1053 manual to focus on technology, most of the interventions that have large effects are not complicated.

The United States instituted quarantine and isolation measures late and inconsistently, often without any effort to enforce them, after the disease had spread substantially in many communities. Our rules on social distancing have in many places been blum minipress m51n1053 manual lackadaisical at best, with loosening of restrictions long before adequate disease control had been achieved. And in much of the country, people simply don’t wear masks, largely because our leaders have stated outright that masks are political tools rather than effective infection blum minipress m51n1053 manual control measures. The government has appropriately invested heavily in vaccine development, but its rhetoric has politicized the development process and led to growing public distrust.The United States blum minipress m51n1053 manual came into this crisis with enormous advantages. Along with tremendous manufacturing capacity, we have a blum minipress m51n1053 manual biomedical research system that is the envy of the world.

We have enormous expertise in public health, health policy, and basic biology and have consistently been able to turn that expertise into new therapies and preventive measures. And much of that national expertise resides in government institutions blum minipress m51n1053 manual. Yet our leaders have largely chosen to ignore and even denigrate experts.The response of our blum minipress m51n1053 manual nation’s leaders has been consistently inadequate. The federal blum minipress m51n1053 manual government has largely abandoned disease control to the states. Governors have varied in their responses, not so much blum minipress m51n1053 manual by party as by competence.

But whatever their competence, governors do not have the tools that Washington controls. Instead of using those tools, the federal government blum minipress m51n1053 manual has undermined them. The Centers for Disease Control and Prevention, which was the world’s blum minipress m51n1053 manual leading disease response organization, has been eviscerated and has suffered dramatic testing and policy failures. The National Institutes of Health have played a key role in vaccine blum minipress m51n1053 manual development but have been excluded from much crucial government decision making. And the Food and Drug Administration has been shamefully blum minipress m51n1053 manual politicized,3 appearing to respond to pressure from the administration rather than scientific evidence.

Our current leaders have undercut trust in science and in government,4 causing damage that will certainly outlast them. Instead of relying on expertise, the administration has turned to uninformed “opinion leaders” and charlatans who obscure the truth and facilitate the promulgation of outright lies.Let’s be clear about blum minipress m51n1053 manual the cost of not taking even simple measures. An outbreak that blum minipress m51n1053 manual has disproportionately affected communities of color has exacerbated the tensions associated with inequality. Many of our children are missing school at blum minipress m51n1053 manual critical times in their social and intellectual development. The hard work of health blum minipress m51n1053 manual care professionals, who have put their lives on the line, has not been used wisely.

Our current leadership takes pride in the economy, but while most of the world has opened up to some extent, the United States still suffers from disease rates that have prevented many businesses from reopening, with a resultant loss of hundreds of billions of dollars and millions of jobs. And more than 200,000 Americans have blum minipress m51n1053 manual died. Some deaths from Covid-19 blum minipress m51n1053 manual were unavoidable. But, although it is impossible blum minipress m51n1053 manual to project the precise number of additional American lives lost because of weak and inappropriate government policies, it is at least in the tens of thousands in a pandemic that has already killed more Americans than any conflict since World War II.Anyone else who recklessly squandered lives and money in this way would be suffering legal consequences. Our leaders have largely claimed immunity for blum minipress m51n1053 manual their actions.

But this election gives us the power to render judgment. Reasonable people will certainly disagree about the many blum minipress m51n1053 manual political positions taken by candidates. But truth is blum minipress m51n1053 manual neither liberal nor conservative. When it comes to the response to the largest public health crisis of our blum minipress m51n1053 manual time, our current political leaders have demonstrated that they are dangerously incompetent. We should not abet them and enable the deaths of thousands more Americans by allowing blum minipress m51n1053 manual them to keep their jobs.Patients Figure 1.

Figure 1. Enrollment and blum minipress m51n1053 manual Randomization. Of the 1114 patients who were assessed blum minipress m51n1053 manual for eligibility, 1062 underwent randomization. 541 were assigned to the remdesivir group and 521 to the placebo group (intention-to-treat population) (Figure blum minipress m51n1053 manual 1). 159 (15.0%) were categorized as having mild-to-moderate disease, and 903 (85.0%) were in blum minipress m51n1053 manual the severe disease stratum.

Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Fifty-two patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious blum minipress m51n1053 manual adverse event other than death and 10 withdrew consent. Of those assigned to receive placebo, 517 patients (99.2%) received blum minipress m51n1053 manual placebo as assigned. Seventy patients discontinued placebo before day 10 because of an blum minipress m51n1053 manual adverse event or a serious adverse event other than death and 14 withdrew consent. A total of 517 patients in the remdesivir group and 508 in the placebo group completed the trial through day 29, blum minipress m51n1053 manual recovered, or died.

Fourteen patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. A total of 54 of the patients who were in the mild-to-moderate stratum at randomization were subsequently blum minipress m51n1053 manual determined to meet the criteria for severe disease, resulting in 105 patients in the mild-to-moderate disease stratum and 957 in the severe stratum. The as-treated population included 1048 patients who received the assigned blum minipress m51n1053 manual treatment (532 in the remdesivir group, including one patient who had been randomly assigned to placebo and received remdesivir, and 516 in the placebo group). Table 1 blum minipress m51n1053 manual. Table 1 blum minipress m51n1053 manual.

Demographic and Clinical Characteristics of the Patients at Baseline. The mean age of the patients was 58.9 blum minipress m51n1053 manual years, and 64.4% were male (Table 1). On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at sites blum minipress m51n1053 manual in North America, 15.3% in Europe, and 4.9% in Asia (Table S1 in the Supplementary Appendix). Overall, 53.3% blum minipress m51n1053 manual of the patients were White, 21.3% were Black, 12.7% were Asian, and 12.7% were designated as other or not reported. 250 (23.5%) were Hispanic or Latino blum minipress m51n1053 manual.

Most patients had either one (25.9%) or two or more (54.5%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (50.2%), obesity (44.8%), and type 2 diabetes mellitus (30.3%). The median number of days between symptom onset and randomization was 9 (interquartile blum minipress m51n1053 manual range, 6 to 12) (Table S2). A total of 957 patients (90.1%) had severe blum minipress m51n1053 manual disease at enrollment. 285 patients (26.8%) met category 7 criteria on the blum minipress m51n1053 manual ordinal scale, 193 (18.2%) category 6, 435 (41.0%) category 5, and 138 (13.0%) category 4. Eleven patients (1.0%) had missing ordinal scale data blum minipress m51n1053 manual at enrollment.

All these patients discontinued the study before treatment. During the study, 373 patients (35.6% of the 1048 patients in the as-treated population) blum minipress m51n1053 manual received hydroxychloroquine and 241 (23.0%) received a glucocorticoid (Table S3). Primary Outcome blum minipress m51n1053 manual Figure 2. Figure 2 blum minipress m51n1053 manual. Kaplan–Meier Estimates of Cumulative blum minipress m51n1053 manual Recoveries.

Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score blum minipress m51n1053 manual of 4 on the ordinal scale (not receiving oxygen. Panel B), in those with a baseline score of 5 (receiving oxygen. Panel C), in blum minipress m51n1053 manual those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with a baseline score of 7 (receiving mechanical blum minipress m51n1053 manual ventilation or extracorporeal membrane oxygenation [ECMO]. Panel E).Table blum minipress m51n1053 manual 2.

Table 2 blum minipress m51n1053 manual. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3 blum minipress m51n1053 manual. Figure 3 blum minipress m51n1053 manual. Time to Recovery According to Subgroup blum minipress m51n1053 manual.

The widths of the confidence intervals have not been adjusted for multiplicity and blum minipress m51n1053 manual therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients.Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 10 days, as compared with 15 days. Rate ratio blum minipress m51n1053 manual for recovery, 1.29. 95% confidence interval [CI], blum minipress m51n1053 manual 1.12 to 1.49. P<0.001) (Figure blum minipress m51n1053 manual 2 and Table 2).

In the severe disease stratum (957 patients) the median time to recovery blum minipress m51n1053 manual was 11 days, as compared with 18 days (rate ratio for recovery, 1.31. 95% CI, 1.12 to 1.52) (Table S4). The rate ratio for recovery was largest among patients with a blum minipress m51n1053 manual baseline ordinal score of 5 (rate ratio for recovery, 1.45. 95% CI, 1.18 blum minipress m51n1053 manual to 1.79). Among patients with a blum minipress m51n1053 manual baseline score of 4 and those with a baseline score of 6, the rate ratio estimates for recovery were 1.29 (95% CI, 0.91 to 1.83) and 1.09 (95% CI, 0.76 to 1.57), respectively.

For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal score of 7), the rate ratio for recovery was 0.98 (95% blum minipress m51n1053 manual CI, 0.70 to 1.36). Information on interactions of treatment with baseline ordinal score as a continuous variable is provided in Table S11. An analysis adjusting for baseline ordinal score as a covariate was conducted to evaluate the overall blum minipress m51n1053 manual effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a similar treatment-effect estimate (rate ratio for recovery, 1.26 blum minipress m51n1053 manual. 95% CI, blum minipress m51n1053 manual 1.09 to 1.46).

Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.37 (95% CI, 1.14 to 1.64), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.20 (95% CI, 0.94 to 1.52) (Figure blum minipress m51n1053 manual 3). The benefit of remdesivir was larger when given earlier in the illness, though the benefit persisted in most analyses of duration of symptoms (Table S6). Sensitivity analyses in which data were censored at earliest reported use of glucocorticoids or hydroxychloroquine still blum minipress m51n1053 manual showed efficacy of remdesivir (9.0 days to recovery with remdesivir vs. 14.0 days to recovery with blum minipress m51n1053 manual placebo. Rate ratio, 1.28 blum minipress m51n1053 manual.

95% CI, 1.09 to blum minipress m51n1053 manual 1.50, and 10.0 vs. 16.0 days to recovery. Rate ratio, 1.32 blum minipress m51n1053 manual. 95% CI, 1.11 blum minipress m51n1053 manual to 1.58, respectively) (Table S8). Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by blum minipress m51n1053 manual a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.5.

95% CI, 1.2 to 1.9, adjusted for disease blum minipress m51n1053 manual severity) (Table 2 and Fig. S7). Mortality Kaplan–Meier estimates of mortality by day 15 were 6.7% blum minipress m51n1053 manual in the remdesivir group and 11.9% in the placebo group (hazard ratio, 0.55. 95% CI, 0.36 to blum minipress m51n1053 manual 0.83). The estimates by day 29 were 11.4% and 15.2% in two groups, blum minipress m51n1053 manual respectively (hazard ratio, 0.73.

95% CI, blum minipress m51n1053 manual 0.52 to 1.03). The between-group differences in mortality varied considerably according to baseline severity (Table 2), with the largest difference seen among patients with a baseline ordinal score of 5 (hazard ratio, 0.30. 95% CI, 0.14 to 0.64) blum minipress m51n1053 manual. Information on interactions of treatment with baseline ordinal blum minipress m51n1053 manual score with respect to mortality is provided in Table S11. Additional Secondary blum minipress m51n1053 manual Outcomes Table 3.

Table 3 blum minipress m51n1053 manual. Additional Secondary Outcomes. Patients in the remdesivir group had a shorter time to improvement of one or of two categories on the ordinal scale from baseline than patients in blum minipress m51n1053 manual the placebo group (one-category improvement. Median, 7 vs blum minipress m51n1053 manual. 9 days blum minipress m51n1053 manual.

Rate ratio for recovery, 1.23 blum minipress m51n1053 manual. 95% CI, 1.08 to 1.41. Two-category improvement blum minipress m51n1053 manual. Median, 11 blum minipress m51n1053 manual vs. 14 days blum minipress m51n1053 manual.

Rate ratio, blum minipress m51n1053 manual 1.29. 95% CI, 1.12 to 1.48) (Table 3). Patients in the remdesivir group had a shorter time to discharge or to a National Early Warning Score of 2 or lower than those in blum minipress m51n1053 manual the placebo group (median, 8 days vs. 12 days blum minipress m51n1053 manual. Hazard ratio, blum minipress m51n1053 manual 1.27.

95% CI, blum minipress m51n1053 manual 1.10 to 1.46). The initial length of hospital stay was shorter in the remdesivir group than in the placebo group (median, 12 days vs. 17 days) blum minipress m51n1053 manual. 5% of blum minipress m51n1053 manual patients in the remdesivir group were readmitted to the hospital, as compared with 3% in the placebo group. Among the blum minipress m51n1053 manual 913 patients receiving oxygen at enrollment, those in the remdesivir group continued to receive oxygen for fewer days than patients in the placebo group (median, 13 days vs.

21 days), and the incidence of new oxygen use among patients who were not receiving oxygen at enrollment blum minipress m51n1053 manual was lower in the remdesivir group than in the placebo group (incidence, 36% [95% CI, 26 to 47] vs. 44% [95% CI, 33 to 57]). For the 193 patients receiving noninvasive ventilation or high-flow oxygen at enrollment, the median duration of use of these interventions was 6 days in both the remdesivir blum minipress m51n1053 manual and placebo groups. Among the 573 patients who were not receiving noninvasive ventilation, high-flow oxygen, invasive ventilation, or ECMO at baseline, the incidence of new noninvasive ventilation or high-flow oxygen use was lower in the remdesivir blum minipress m51n1053 manual group than in the placebo group (17% [95% CI, 13 to 22] vs. 24% [95% CI, blum minipress m51n1053 manual 19 to 30]).

Among the 285 patients who were receiving mechanical ventilation or ECMO at enrollment, patients in the remdesivir group received these interventions for fewer subsequent blum minipress m51n1053 manual days than those in the placebo group (median, 17 days vs. 20 days), and the incidence of new mechanical ventilation or ECMO use among the 766 patients who were not receiving these interventions at enrollment was lower in the remdesivir group than in the placebo group (13% [95% CI, 10 to 17] vs. 23% [95% blum minipress m51n1053 manual CI, 19 to 27]) (Table 3). Safety Outcomes In the as-treated population, serious adverse events occurred in 131 of 532 patients (24.6%) blum minipress m51n1053 manual in the remdesivir group and in 163 of 516 patients (31.6%) in the placebo group (Table S17). There were blum minipress m51n1053 manual 47 serious respiratory failure adverse events in the remdesivir group (8.8% of patients), including acute respiratory failure and the need for endotracheal intubation, and 80 in the placebo group (15.5% of patients) (Table S19).

No deaths were blum minipress m51n1053 manual considered by the investigators to be related to treatment assignment. Grade 3 or 4 adverse events occurred on or before day 29 in 273 patients (51.3%) in the remdesivir group and in 295 (57.2%) in the placebo blum minipress m51n1053 manual group (Table S18). 41 events were judged by the investigators to be related to remdesivir and 47 events to placebo (Table S17). The most common nonserious adverse events blum minipress m51n1053 manual occurring in at least 5% of all patients included decreased glomerular filtration rate, decreased hemoglobin level, decreased lymphocyte count, respiratory failure, anemia, pyrexia, hyperglycemia, increased blood creatinine level, and increased blood glucose level (Table S20). The incidence of these adverse events was generally similar blum minipress m51n1053 manual in the remdesivir and placebo groups.

Crossover After the data and safety monitoring board recommended that the preliminary primary analysis report be provided to the sponsor, data on a total of 51 patients (4.8% blum minipress m51n1053 manual of the total study enrollment) — 16 (3.0%) in the remdesivir group and 35 (6.7%) in the placebo group — were unblinded. 26 (74.3%) of blum minipress m51n1053 manual those in the placebo group whose data were unblinded were given remdesivir. Sensitivity analyses evaluating the unblinding (patients whose treatment assignments were unblinded had their data censored at the time of unblinding) and crossover (patients in the placebo group treated with remdesivir had their data censored at the initiation of remdesivir treatment) produced results similar to those of the primary analysis (Table S9).Trial Design and Oversight The RECOVERY trial is an investigator-initiated platform trial to evaluate the effects of potential treatments in patients hospitalized with Covid-19. The trial is being conducted blum minipress m51n1053 manual at 176 hospitals in the United Kingdom. (Details are provided in blum minipress m51n1053 manual the Supplementary Appendix, available with the full text of this article at NEJM.org.) The investigators were assisted by the National Institute for Health Research Clinical Research Network, and the trial is coordinated by the Nuffield Department of Population Health at the University of Oxford, the trial sponsor.

Although patients are no longer being enrolled in the hydroxychloroquine, dexamethasone, and lopinavir–ritonavir groups, the trial continues to study the effects of azithromycin, tocilizumab, convalescent plasma, and REGN-COV2 (a combination of two monoclonal antibodies blum minipress m51n1053 manual directed against the SARS-CoV-2 spike protein). Other treatments blum minipress m51n1053 manual may be studied in the future. The hydroxychloroquine that was used in this phase of the trial was supplied by the U.K. National Health Service blum minipress m51n1053 manual (NHS). Hospitalized patients were eligible for the trial if they had clinically-suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, blum minipress m51n1053 manual put patients at substantial risk if they were to participate in the trial.

Initially, recruitment was limited to patients blum minipress m51n1053 manual who were at least 18 years of age, but the age limit was removed as of May 9, 2020. Written informed consent was obtained from all the patients or from a legal representative if they were too unwell or unable blum minipress m51n1053 manual to provide consent. The trial was conducted in accordance with Good Clinical Practice guidelines of the International Conference on Harmonisation and was approved by the U.K. Medicines and Healthcare Products blum minipress m51n1053 manual Regulatory Agency (MHRA) and the Cambridge East Research Ethics Committee. The protocol with its statistical analysis plan are available at NEJM.org, with additional information blum minipress m51n1053 manual in the Supplementary Appendix and on the trial website at www.recoverytrial.net.

The initial version of the manuscript was drafted by the first and last authors, developed by the writing blum minipress m51n1053 manual committee, and approved by all members of the trial steering committee. The funders had no role in the analysis of blum minipress m51n1053 manual the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication. The first and last members of the writing committee vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan. Randomization and Treatment We collected baseline data using a Web-based case-report form that included demographic data, level of respiratory support, major coexisting illnesses, the suitability of the trial treatment for a particular patient, and treatment availability blum minipress m51n1053 manual at the trial site. Using a Web-based unstratified randomization method with the concealment of trial group, we assigned patients to receive either the usual standard of care or the usual standard of care plus hydroxychloroquine or blum minipress m51n1053 manual one of the other available treatments that were being evaluated.

The number of patients blum minipress m51n1053 manual who were assigned to receive usual care was twice the number who were assigned to any of the active treatments for which the patient was eligible (e.g., 2:1 ratio in favor of usual care if the patient was eligible for only one active treatment group, 2:1:1 if the patient was eligible for two active treatments, etc.). For some patients, hydroxychloroquine was unavailable at the hospital at the time of enrollment or was considered by the managing physician to be either definitely indicated or definitely blum minipress m51n1053 manual contraindicated. Patients with a known prolonged corrected QT interval on electrocardiography were ineligible to receive hydroxychloroquine. (Coadministration with medications that prolong the QT interval was not an absolute contraindication, but attending clinicians were advised to check the QT interval by performing electrocardiography.) These patients were excluded from entry in blum minipress m51n1053 manual the randomized comparison between hydroxychloroquine and usual care. In the hydroxychloroquine group, patients received hydroxychloroquine sulfate (in the form of a 200-mg tablet containing a 155-mg base equivalent) in a loading dose of four tablets (total dose, 800 mg) at baseline and at 6 hours, which was followed by two tablets (total dose, 400 blum minipress m51n1053 manual mg) starting at 12 hours after the initial dose and then every 12 hours for the next 9 days or until discharge, whichever occurred earlier (see the Supplementary Appendix).15 The assigned treatment was prescribed by the attending clinician.

The patients and local trial staff members were aware of the assigned blum minipress m51n1053 manual trial groups. Procedures A single online follow-up form was to be completed by the local trial staff members when each trial blum minipress m51n1053 manual patient was discharged, at 28 days after randomization, or at the time of death, whichever occurred first. Information was recorded regarding the adherence to the assigned treatment, receipt of other treatments for Covid-19, duration of admission, receipt of respiratory support (with duration and type), receipt of renal dialysis or hemofiltration, and vital status (including cause of death). Starting on blum minipress m51n1053 manual May 12, 2020, extra information was recorded on the occurrence of new major cardiac arrhythmia. In addition, we obtained routine health care and registry data that included information on blum minipress m51n1053 manual vital status (with date and cause of death) and discharge from the hospital.

Outcome Measures The primary outcome was all-cause mortality blum minipress m51n1053 manual within 28 days after randomization. Further analyses were specified blum minipress m51n1053 manual at 6 months. Secondary outcomes were the time until discharge from the hospital and a composite of the initiation of invasive mechanical ventilation including extracorporeal membrane oxygenation or death among patients who were not receiving invasive mechanical ventilation at the time of randomization. Decisions to initiate invasive mechanical ventilation were made by the attending clinicians, who were informed by blum minipress m51n1053 manual guidance from NHS England and the National Institute for Health and Care Excellence. Subsidiary clinical outcomes included cause-specific mortality (which was recorded in all patients) and major cardiac arrhythmia (which was blum minipress m51n1053 manual recorded in a subgroup of patients).

All information presented in this report is blum minipress m51n1053 manual based on a data cutoff of September 21, 2020. Information regarding the primary outcome is complete for all blum minipress m51n1053 manual the trial patients. Statistical Analysis For the primary outcome of 28-day mortality, we used the log-rank observed-minus-expected statistic and its variance both to test the null hypothesis of equal survival curves and to calculate the one-step estimate of the average mortality rate ratio in the comparison between the hydroxychloroquine group and the usual-care group. Kaplan–Meier survival curves were blum minipress m51n1053 manual constructed to show cumulative mortality over the 28-day period. The same methods were used to analyze the time until hospital discharge, with censoring of data on day 29 for patients who had died in blum minipress m51n1053 manual the hospital.

We used the Kaplan–Meier estimates to calculate the median time until blum minipress m51n1053 manual hospital discharge. For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among patients who had not been receiving invasive mechanical ventilation at randomization), the precise date of the initiation of blum minipress m51n1053 manual invasive mechanical ventilation was not available, so the risk ratio was estimated instead. Estimates of the between-group difference in absolute risk were also calculated. All the analyses were performed according to the intention-to-treat principle blum minipress m51n1053 manual. Prespecified analyses of the primary outcome were performed in six subgroups, blum minipress m51n1053 manual as defined by characteristics at randomization.

Age, sex, race, level of respiratory support, days since symptom onset, and predicted 28-day risk blum minipress m51n1053 manual of death. (Details are provided in the Supplementary Appendix.) Estimates of rate and risk ratios are shown with 95% blum minipress m51n1053 manual confidence intervals without adjustment for multiple testing. The P value for the assessment of the primary outcome is two-sided. The full database is held by the trial team, which collected blum minipress m51n1053 manual the data from the trial sites and performed the analyses, at the Nuffield Department of Population Health at the University of Oxford. The independent blum minipress m51n1053 manual data monitoring committee was asked to review unblinded analyses of the trial data and any other information that was considered to be relevant at intervals of approximately 2 weeks.

The committee was then charged with determining whether the randomized comparisons in the trial provided evidence with respect to mortality that was blum minipress m51n1053 manual strong enough (with a range of uncertainty around the results that was narrow enough) to affect national and global treatment strategies. In such a circumstance, the committee would inform the members of the trial steering committee, who would blum minipress m51n1053 manual make the results available to the public and amend the trial accordingly. Unless that happened, the steering committee, investigators, and all others involved in the trial would remain unaware of the interim results until 28 days after the last patient had been randomly assigned to a particular treatment group. On June 4, 2020, in response to a request from the MHRA, the independent data monitoring committee conducted a review of the blum minipress m51n1053 manual data and recommended that the chief investigators review the unblinded data for the hydroxychloroquine group. The chief investigators blum minipress m51n1053 manual and steering committee members concluded that the data showed no beneficial effect of hydroxychloroquine in patients hospitalized with Covid-19.

Therefore, the enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, and the preliminary result for the primary outcome blum minipress m51n1053 manual was made public. Investigators were advised that any patients who were receiving hydroxychloroquine as part of the trial should discontinue the blum minipress m51n1053 manual treatment.Trial Objectives, Participants, and Oversight We assessed the safety and immunogenicity of three dose levels of BNT162b1 and BNT162b2. Healthy adults 18 to 55 years of age or 65 to 85 years of age were eligible for inclusion. Key exclusion criteria were known infection with human immunodeficiency virus, hepatitis C virus, or hepatitis blum minipress m51n1053 manual B virus. An immunocompromised condition blum minipress m51n1053 manual.

A history of blum minipress m51n1053 manual autoimmune disease. A previous clinical or microbiologic diagnosis blum minipress m51n1053 manual of Covid-19. The receipt of medications intended to prevent Covid-19. Any previous blum minipress m51n1053 manual coronavirus vaccination. Positive test for blum minipress m51n1053 manual SARS-CoV-2 IgM or IgG at the screening visit.

And positive nasal-swab results blum minipress m51n1053 manual on a SARS-CoV-2 nucleic acid amplification test within 24 hours before the receipt of trial vaccine or placebo. BioNTech was the regulatory blum minipress m51n1053 manual sponsor of the trial. Pfizer was responsible for the trial blum minipress m51n1053 manual design. For the collection, analysis, and interpretation of the data. And for the writing of blum minipress m51n1053 manual the report.

The corresponding author had full access to all the data in the trial and had final responsibility for the decision to submit the manuscript for publication blum minipress m51n1053 manual. All the trial blum minipress m51n1053 manual data were available to all the authors. Trial Procedures Using an interactive Web-based response technology system, we randomly assigned blum minipress m51n1053 manual trial participants to groups defined according to the vaccine candidate, dose level, and age range. Groups of participants 18 to 55 years of age and 65 to 85 years of age were to receive doses of 10 μg, 20 μg, or 30 μg of BNT162b1 or BNT162b2 (or placebo) on a two-dose schedule. One group of participants 18 to 55 years blum minipress m51n1053 manual of age was assigned to receive 100-μg doses of BNT162b1 or placebo.

All the participants were assigned to receive two 0.5-ml injections of active vaccine (BNT162b1 or BNT162b2) or placebo into the deltoid, administered 21 days apart blum minipress m51n1053 manual. The first five participants in each new dose level or age group (with a randomization ratio of 4:1 for active vaccine:placebo) were observed for 4 blum minipress m51n1053 manual hours after the injection to identify immediate adverse events. All the other blum minipress m51n1053 manual participants were observed for 30 minutes. Blood samples were obtained for safety and immunogenicity assessments. Safety The primary end points in phase 1 of this trial were solicited local reactions (i.e., specific local reactions as prompted by and recorded in an electronic diary), systemic events, and use of antipyretic or pain medication within 7 days after the receipt of blum minipress m51n1053 manual vaccine or placebo, as prompted by and recorded in an electronic diary.

Unsolicited adverse events and serious adverse events (i.e., those reported by the participants, without electronic-diary prompts), assessed from blum minipress m51n1053 manual the receipt of the first dose through 1 month and 6 months, respectively, after the receipt of the second dose. Clinical laboratory abnormalities, assessed 1 blum minipress m51n1053 manual day and 7 days after the receipt of vaccine or placebo. And grading shifts in laboratory assessments between baseline and 1 day and 7 blum minipress m51n1053 manual days after the first dose and between 2 days and 7 days after the second dose. Protocol-specified safety stopping rules were in effect for all the participants in the phase 1 portion of the trial. The full protocol, including the statistical blum minipress m51n1053 manual analysis plan, is available with the full text of this article at NEJM.org.

An internal review committee and an external data and safety monitoring committee reviewed all safety data blum minipress m51n1053 manual. Immunogenicity Immunogenicity assessments (SARS-CoV-2 serum neutralization assay and receptor-binding domain [RBD]–binding or S1-binding IgG direct Luminex immunoassays) were conducted before the administration of vaccine or placebo, at 7 days and 21 days after the first dose, and at 7 blum minipress m51n1053 manual days (i.e., day 28) and 14 days (i.e., day 35) after the second dose. The neutralization assay, which also generated previously described virus-neutralization data from trials of the BNT162 candidates,2,5 used a previously described strain of SARS-CoV-2 (USA_WA1/2020) that had been blum minipress m51n1053 manual generated by reverse genetics and engineered by the insertion of an mNeonGreen gene into open reading frame 7 of the viral genome.11,12 The 50% neutralization titers and 90% neutralization titers were reported as the interpolated reciprocal of the dilutions yielding 50% and 90% reductions, respectively, in fluorescent viral foci. Any serologic values below the lower limit of quantitation were set to 0.5 times the lower limit of quantitation. Available serologic results were blum minipress m51n1053 manual included in the analysis.

Immunogenicity data from a blum minipress m51n1053 manual human convalescent serum panel were included as a benchmark. A total of 38 serum samples were obtained from donors 18 to 83 years of age (median age, 42.5 years) who had recovered from SARS-CoV-2 infection or blum minipress m51n1053 manual Covid-19. Samples were obtained at least 14 days after a polymerase blum minipress m51n1053 manual chain reaction–confirmed diagnosis and after symptom resolution. Neutralizing geometric mean titers (GMTs) in subgroups of the donors were as follows. 90, among blum minipress m51n1053 manual 35 donors with symptomatic infections.

156, among 3 blum minipress m51n1053 manual donors with asymptomatic infection. And 618, in 1 blum minipress m51n1053 manual donor who was hospitalized. Each serum blum minipress m51n1053 manual sample in the panel was from a different donor. Thus, most of the serum samples were obtained from persons with moderate Covid-19 who had not been hospitalized. The serum samples were obtained from Sanguine Biosciences, the MT Group, and Pfizer Occupational Health blum minipress m51n1053 manual and Wellness.

Statistical Analysis blum minipress m51n1053 manual We report descriptive results of safety and immunogenicity analyses, and the sample size was not based on statistical hypothesis testing. Results of the safety analyses are presented as counts, percentages, and associated Clopper–Pearson 95% confidence intervals for local reactions, systemic events, and any adverse events after the blum minipress m51n1053 manual administration of vaccine or placebo, according to terms in the Medical Dictionary for Regulatory Activities, version 23.0, for each vaccine group. Summary statistics blum minipress m51n1053 manual are provided for abnormal laboratory values and grading shifts. Given the small number of participants in each group, the trial was not powered for formal statistical comparisons between dose levels or between age groups. Immunogenicity analyses of SARS-CoV-2 serum neutralizing blum minipress m51n1053 manual titers, S1-binding IgG and RBD-binding IgG concentrations, GMTs, and geometric mean concentrations (GMCs) were computed along with associated 95% confidence intervals.

The GMTs blum minipress m51n1053 manual and GMCs were calculated as the mean of the assay results after the logarithmic transformation was made. We then exponentiated the mean to express results on the original blum minipress m51n1053 manual scale. Two-sided 95% confidence intervals were obtained by performing logarithmic transformations of titers or concentrations, calculating the 95% confidence interval with reference to Student’s t-distribution, and then exponentiating the limits of the confidence intervals.Supported by a philanthropic donation from Stein Erik blum minipress m51n1053 manual Hagen and Canica. By a grant from the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). By a blum minipress m51n1053 manual Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Covid-19 Biobank grant (to Dr.

Valenti). By grants from the Italian Ministry of Health (RF-2016-02364358, to Dr. Valenti) and Ministero dell’Istruzione, dell’Università e della Ricerca project “Dipartimenti di Eccellenza 2018–2022” (D15D18000410001 to the Department of Medical Sciences, University of Turin. By a grant from the Spanish Ministry of Science and Innovation JdC fellowship (IJC2018-035131-I, to Dr. Acosta-Herrera).

And by the GCAT Cession Research Project PI-2020-01. HLA typing was performed and supported by the Stefan-Morsch-Stiftung. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Dr. Ellinghaus and Ms.

Degenhardt and Drs. Valenti, Franke, and Karlsen contributed equally to this article.The members of the writing committee (David Ellinghaus, Ph.D., Frauke Degenhardt, M.Sc., Luis Bujanda, M.D., Ph.D., Maria Buti, M.D., Ph.D., Agustín Albillos, M.D., Ph.D., Pietro Invernizzi, M.D., Ph.D., Javier Fernández, M.D., Ph.D., Daniele Prati, M.D., Guido Baselli, Ph.D., Rosanna Asselta, Ph.D., Marit M. Grimsrud, M.D., Chiara Milani, Ph.D., Fátima Aziz, B.S., Jan Kässens, Ph.D., Sandra May, Ph.D., Mareike Wendorff, M.Sc., Lars Wienbrandt, Ph.D., Florian Uellendahl-Werth, M.Sc., Tenghao Zheng, M.D., Ph.D., Xiaoli Yi, Raúl de Pablo, M.D., Ph.D., Adolfo G. Chercoles, B.S., Adriana Palom, M.S., B.S., Alba-Estela Garcia-Fernandez, B.S., Francisco Rodriguez-Frias, M.S., Ph.D., Alberto Zanella, M.D., Alessandra Bandera, M.D., Ph.D., Alessandro Protti, M.D., Alessio Aghemo, M.D., Ph.D., Ana Lleo, M.D., Ph.D., Andrea Biondi, M.D., Andrea Caballero-Garralda, M.S., Ph.D., Andrea Gori, M.D., Anja Tanck, Anna Carreras Nolla, B.S., Anna Latiano, Ph.D., Anna Ludovica Fracanzani, M.D., Anna Peschuck, Antonio Julià, Ph.D., Antonio Pesenti, M.D., Antonio Voza, M.D., David Jiménez, M.D., Ph.D., Beatriz Mateos, M.D., Ph.D., Beatriz Nafria Jimenez, B.S., Carmen Quereda, M.D., Ph.D., Cinzia Paccapelo, M.Sc., Christoph Gassner, Ph.D., Claudio Angelini, M.D., Cristina Cea, B.S., Aurora Solier, M.D., David Pestaña, M.D., Ph.D., Eduardo Muñiz-Diaz, M.D., Ph.D., Elena Sandoval, M.D., Elvezia M. Paraboschi, Ph.D., Enrique Navas, M.D., Ph.D., Félix García Sánchez, Ph.D., Ferruccio Ceriotti, M.D., Filippo Martinelli-Boneschi, M.D., Ph.D., Flora Peyvandi, M.D., Ph.D., Francesco Blasi, M.D., Ph.D., Luis Téllez, M.D., Ph.D., Albert Blanco-Grau, B.S., M.S., Georg Hemmrich-Stanisak, Ph.D., Giacomo Grasselli, M.D., Giorgio Costantino, M.D., Giulia Cardamone, Ph.D., Giuseppe Foti, M.D., Serena Aneli, Ph.D., Hayato Kurihara, M.D., Hesham ElAbd, M.Sc., Ilaria My, M.D., Iván Galván-Femenia, M.Sc., Javier Martín, M.D., Ph.D., Jeanette Erdmann, Ph.D., Jose Ferrusquía-Acosta, M.D., Koldo Garcia-Etxebarria, Ph.D., Laura Izquierdo-Sanchez, B.S., Laura R.

Bettini, M.D., Lauro Sumoy, Ph.D., Leonardo Terranova, Ph.D., Leticia Moreira, M.D., Ph.D., Luigi Santoro, M.S., Luigia Scudeller, M.D., Francisco Mesonero, M.D., Luisa Roade, M.D., Malte C. Rühlemann, Ph.D., Marco Schaefer, Ph.D., Maria Carrabba, M.D., Ph.D., Mar Riveiro-Barciela, M.D., Ph.D., Maria E. Figuera Basso, Maria G. Valsecchi, Ph.D., María Hernandez-Tejero, M.D., Marialbert Acosta-Herrera, Ph.D., Mariella D’Angiò, M.D., Marina Baldini, M.D., Marina Cazzaniga, M.D., Martin Schulzky, M.A., Maurizio Cecconi, M.D., Ph.D., Michael Wittig, M.Sc., Michele Ciccarelli, M.D., Miguel Rodríguez-Gandía, M.D., Monica Bocciolone, M.D., Monica Miozzo, Ph.D., Nicola Montano, M.D., Ph.D., Nicole Braun, Nicoletta Sacchi, Ph.D., Nilda Martínez, M.D., Onur Özer, M.Sc., Orazio Palmieri, Ph.D., Paola Faverio, M.D., Paoletta Preatoni, M.D., Paolo Bonfanti, M.D., Paolo Omodei, M.D., Paolo Tentorio, M.S., Pedro Castro, M.D., Ph.D., Pedro M. Rodrigues, Ph.D., Aaron Blandino Ortiz, M.D., Rafael de Cid, Ph.D., Ricard Ferrer, M.D., Roberta Gualtierotti, M.D., Rosa Nieto, M.D., Siegfried Goerg, M.D., Salvatore Badalamenti, M.D., Ph.D., Sara Marsal, Ph.D., Giuseppe Matullo, Ph.D., Serena Pelusi, M.D., Simonas Juzenas, Ph.D., Stefano Aliberti, M.D., Valter Monzani, M.D., Victor Moreno, Ph.D., Tanja Wesse, Tobias L.

Lenz, Ph.D., Tomas Pumarola, M.D., Ph.D., Valeria Rimoldi, Ph.D., Silvano Bosari, M.D., Wolfgang Albrecht, Wolfgang Peter, Ph.D., Manuel Romero-Gómez, M.D., Ph.D., Mauro D’Amato, Ph.D., Stefano Duga, Ph.D., Jesus M. Banales, Ph.D., Johannes R Hov, M.D., Ph.D., Trine Folseraas, M.D., Ph.D., Luca Valenti, M.D., Andre Franke, Ph.D., and Prof. Tom H. Karlsen, M.D., Ph.D.) assume responsibility for the overall content and integrity of this article.This article was published on June 17, 2020, at NEJM.org.We thank all the patients who consented to participate in this study, and we express our condolences to the families of patients who died from Covid-19. We also thank the entire clinical staff during the outbreak situation at the different centers who were able to work on this scientific study in parallel with their clinical duties.

All the members of the Humanitas Covid-19 Task Force for contributions to the recruitment of patients (see the Supplementary Notes section in Supplementary Appendix 1). Sören Brunak and Karina Banasik for discussions on the ABO association. Goncalo Abecasis and his team for providing the Michigan imputation server. Fabrizio Bossa and Francesca Tavano for contributions to control-sample acquisition. Maria Reig for help in the case-sample acquisition.

The staff of the Basque Biobank in Spain for assistance in the acquisition of samples. The staff of GCAT|Genomes for Life, a cohort study of the Genomes of Catalonia, Institute for Health Science Research Germans Trias i Pujol, for data contribution. Alexander Eck, Jenspeter Horst, and Jens Scholz for supporting the HLA typing in the project. And the members of the ethics commissions, review boards, and consortia who fast-track reviewed our applications and enabled this rapid genetic discovery study..

Covid-19 has created a how to get minipress online crisis throughout the world. This crisis has how to get minipress online produced a test of leadership. With no good options to how to get minipress online combat a novel pathogen, countries were forced to make hard choices about how to respond.

Here in the United States, our leaders how to get minipress online have failed that test. They have taken a crisis and turned it into how to get minipress online a tragedy.The magnitude of this failure is astonishing. According to the Johns Hopkins Center for Systems Science and Engineering,1 the United States leads the world in Covid-19 cases and in deaths due to the disease, far exceeding the numbers in much larger countries, such as China.

The death rate in this country is more than double that of Canada, exceeds that of Japan, a country with a vulnerable and elderly how to get minipress online population, by a factor of almost 50, and even dwarfs the rates in lower-middle-income countries, such as Vietnam, by a factor of almost 2000. Covid-19 is how to get minipress online an overwhelming challenge, and many factors contribute to its severity. But the one we can control how to get minipress online is how we behave.

And in how to get minipress online the United States we have consistently behaved poorly.We know that we could have done better. China, faced with the first outbreak, chose strict quarantine and isolation after an initial delay. These measures were severe but effective, essentially eliminating transmission at the point where the outbreak began and reducing the death rate to a reported 3 per million, as how to get minipress online compared with more than 500 per million in the United States.

Countries that had far more exchange with how to get minipress online China, such as Singapore and South Korea, began intensive testing early, along with aggressive contact tracing and appropriate isolation, and have had relatively small outbreaks. And New Zealand has used these same measures, together with its geographic advantages, to come close to eliminating the disease, something that has allowed that country to limit how to get minipress online the time of closure and to largely reopen society to a prepandemic level. In general, not only have many democracies done better than the how to get minipress online United States, but they have also outperformed us by orders of magnitude.Why has the United States handled this pandemic so badly?.

We have failed at almost every step. We had ample warning, but when the disease first arrived, we were incapable of testing effectively and couldn’t provide even the most basic personal how to get minipress online protective equipment to health care workers and the general public. And we continue to be way behind the how to get minipress online curve in testing.

While the absolute numbers of tests have increased substantially, the more useful metric is the number of tests performed per infected person, a rate how to get minipress online that puts us far down the international list, below such places as Kazakhstan, Zimbabwe, and Ethiopia, countries that cannot boast the biomedical infrastructure or the manufacturing capacity that we have.2 Moreover, a lack of emphasis on developing capacity has meant that U.S. Test results how to get minipress online are often long delayed, rendering the results useless for disease control.Although we tend to focus on technology, most of the interventions that have large effects are not complicated. The United States instituted quarantine and isolation measures late and inconsistently, often without any effort to enforce them, after the disease had spread substantially in many communities.

Our rules how to get minipress online on social distancing have in many places been lackadaisical at best, with loosening of restrictions long before adequate disease control had been achieved. And in how to get minipress online much of the country, people simply don’t wear masks, largely because our leaders have stated outright that masks are political tools rather than effective infection control measures. The government has appropriately invested heavily in vaccine how to get minipress online development, but its rhetoric has politicized the development process and led to growing public distrust.The United States came into this crisis with enormous advantages.

Along with tremendous how to get minipress online manufacturing capacity, we have a biomedical research system that is the envy of the world. We have enormous expertise in public health, health policy, and basic biology and have consistently been able to turn that expertise into new therapies and preventive measures. And much of how to get minipress online that national expertise resides in government institutions.

Yet our leaders have largely chosen to ignore and even denigrate experts.The response of our nation’s leaders has been consistently inadequate how to get minipress online. The federal how to get minipress online government has largely abandoned disease control to the states. Governors have varied in their responses, not so much by party as by competence how to get minipress online.

But whatever their competence, governors do not have the tools that Washington controls. Instead of using how to get minipress online those tools, the federal government has undermined them. The Centers for Disease Control and Prevention, which was the how to get minipress online world’s leading disease response organization, has been eviscerated and has suffered dramatic testing and policy failures.

The National how to get minipress online Institutes of Health have played a key role in vaccine development but have been excluded from much crucial government decision making. And the Food and Drug Administration has been shamefully politicized,3 appearing to respond to pressure from the how to get minipress online administration rather than scientific evidence. Our current leaders have undercut trust in science and in government,4 causing damage that will certainly outlast them.

Instead of relying on expertise, the administration has turned to uninformed “opinion leaders” and charlatans who obscure the truth and facilitate the how to get minipress online promulgation of outright lies.Let’s be clear about the cost of not taking even simple measures. An outbreak that has disproportionately affected communities of color has exacerbated the tensions associated with inequality how to get minipress online. Many of how to get minipress online our children are missing school at critical times in their social and intellectual development.

The hard work of health care professionals, who have put how to get minipress online their lives on the line, has not been used wisely. Our current leadership takes pride in the economy, but while most of the world has opened up to some extent, the United States still suffers from disease rates that have prevented many businesses from reopening, with a resultant loss of hundreds of billions of dollars and millions of jobs. And more than 200,000 Americans how to get minipress online have died.

Some deaths from Covid-19 were how to get minipress online unavoidable. But, although it is impossible to project the precise number of additional American lives lost because of weak and inappropriate government policies, it is at least in the tens of thousands in a pandemic that has how to get minipress online already killed more Americans than any conflict since World War II.Anyone else who recklessly squandered lives and money in this way would be suffering legal consequences. Our leaders have largely claimed immunity for their actions how to get minipress online.

But this election gives us the power to render judgment. Reasonable people how to get minipress online will certainly disagree about the many political positions taken by candidates. But truth how to get minipress online is neither liberal nor conservative.

When it comes to the response to how to get minipress online the largest public health crisis of our time, our current political leaders have demonstrated that they are dangerously incompetent. We should not abet them and enable the deaths of thousands how to get minipress online more Americans by allowing them to keep their jobs.Patients Figure 1. Figure 1.

Enrollment and how to get minipress online Randomization. Of the 1114 patients who were assessed for eligibility, 1062 underwent randomization how to get minipress online. 541 were assigned to how to get minipress online the remdesivir group and 521 to the placebo group (intention-to-treat population) (Figure 1).

159 (15.0%) were categorized as having mild-to-moderate disease, and how to get minipress online 903 (85.0%) were in the severe disease stratum. Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Fifty-two patients how to get minipress online had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death and 10 withdrew consent.

Of those how to get minipress online assigned to receive placebo, 517 patients (99.2%) received placebo as assigned. Seventy patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death how to get minipress online and 14 withdrew consent. A total of 517 patients in the remdesivir group and how to get minipress online 508 in the placebo group completed the trial through day 29, recovered, or died.

Fourteen patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. A total of 54 of the patients who were in how to get minipress online the mild-to-moderate stratum at randomization were subsequently determined to meet the criteria for severe disease, resulting in 105 patients in the mild-to-moderate disease stratum and 957 in the severe stratum. The as-treated how to get minipress online population included 1048 patients who received the assigned treatment (532 in the remdesivir group, including one patient who had been randomly assigned to placebo and received remdesivir, and 516 in the placebo group).

Table 1 how to get minipress online. Table 1 how to get minipress online. Demographic and Clinical Characteristics of the Patients at Baseline.

The mean age of the patients was 58.9 years, and 64.4% were male how to get minipress online (Table 1). On the basis how to get minipress online of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1 in the Supplementary Appendix). Overall, 53.3% of how to get minipress online the patients were White, 21.3% were Black, 12.7% were Asian, and 12.7% were designated as other or not reported.

250 (23.5%) how to get minipress online were Hispanic or Latino. Most patients had either one (25.9%) or two or more (54.5%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (50.2%), obesity (44.8%), and type 2 diabetes mellitus (30.3%). The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12) (Table how to get minipress online S2).

A total of 957 patients (90.1%) had severe disease at enrollment how to get minipress online. 285 patients how to get minipress online (26.8%) met category 7 criteria on the ordinal scale, 193 (18.2%) category 6, 435 (41.0%) category 5, and 138 (13.0%) category 4. Eleven patients (1.0%) had missing how to get minipress online ordinal scale data at enrollment.

All these patients discontinued the study before treatment. During the study, 373 patients (35.6% of the 1048 patients how to get minipress online in the as-treated population) received hydroxychloroquine and 241 (23.0%) received a glucocorticoid (Table S3). Primary Outcome how to get minipress online Figure 2.

Figure 2 how to get minipress online. Kaplan–Meier Estimates how to get minipress online of Cumulative Recoveries. Cumulative recovery estimates are shown in the overall population (Panel A), in patients with how to get minipress online a baseline score of 4 on the ordinal scale (not receiving oxygen.

Panel B), in those with a baseline score of 5 (receiving oxygen. Panel C), in those with a baseline score of 6 (receiving how to get minipress online high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with a baseline score of 7 (receiving mechanical ventilation how to get minipress online or extracorporeal membrane oxygenation [ECMO].

Panel E).Table 2 how to get minipress online. Table 2 how to get minipress online. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population.

Figure 3 how to get minipress online. Figure 3 how to get minipress online. Time to Recovery According to how to get minipress online Subgroup.

The widths of the confidence how to get minipress online intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients.Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 10 days, as compared with 15 days. Rate ratio how to get minipress online for recovery, 1.29.

95% confidence interval [CI], 1.12 to 1.49 how to get minipress online. P<0.001) (Figure how to get minipress online 2 and Table 2). In the severe disease stratum (957 patients) the median time to recovery was 11 days, as compared how to get minipress online with 18 days (rate ratio for recovery, 1.31.

95% CI, 1.12 to 1.52) (Table S4). The rate ratio for recovery was largest among patients with a baseline ordinal score of 5 (rate ratio for recovery, 1.45 how to get minipress online. 95% CI, 1.18 how to get minipress online to 1.79).

Among patients with a baseline score of 4 and those with a baseline score of 6, the rate ratio estimates for recovery were 1.29 (95% CI, 0.91 to 1.83) and 1.09 (95% CI, 0.76 to 1.57), respectively how to get minipress online. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal score of 7), the rate ratio for recovery was how to get minipress online 0.98 (95% CI, 0.70 to 1.36). Information on interactions of treatment with baseline ordinal score as a continuous variable is provided in Table S11.

An analysis adjusting for baseline ordinal score as a covariate was conducted to evaluate the overall how to get minipress online effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced how to get minipress online a similar treatment-effect estimate (rate ratio for recovery, 1.26. 95% CI, how to get minipress online 1.09 to 1.46).

Patients who underwent randomization during the first 10 days after how to get minipress online the onset of symptoms had a rate ratio for recovery of 1.37 (95% CI, 1.14 to 1.64), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.20 (95% CI, 0.94 to 1.52) (Figure 3). The benefit of remdesivir was larger when given earlier in the illness, though the benefit persisted in most analyses of duration of symptoms (Table S6). Sensitivity analyses in which data were censored at earliest reported use how to get minipress online of glucocorticoids or hydroxychloroquine still showed efficacy of remdesivir (9.0 days to recovery with remdesivir vs.

14.0 days to how to get minipress online recovery with placebo. Rate ratio, 1.28 how to get minipress online. 95% CI, how to get minipress online 1.09 to 1.50, and 10.0 vs.

16.0 days to recovery. Rate ratio, how to get minipress online 1.32. 95% CI, 1.11 to 1.58, respectively) (Table S8) how to get minipress online.

Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in how to get minipress online the placebo group (odds ratio for improvement, 1.5. 95% CI, 1.2 to 1.9, adjusted for disease severity) (Table how to get minipress online 2 and Fig. S7).

Mortality Kaplan–Meier estimates of mortality by day 15 were 6.7% in the remdesivir how to get minipress online group and 11.9% in the placebo group (hazard ratio, 0.55. 95% CI, 0.36 to how to get minipress online 0.83). The estimates by how to get minipress online day 29 were 11.4% and 15.2% in two groups, respectively (hazard ratio, 0.73.

95% CI, 0.52 to how to get minipress online 1.03). The between-group differences in mortality varied considerably according to baseline severity (Table 2), with the largest difference seen among patients with a baseline ordinal score of 5 (hazard ratio, 0.30. 95% CI, how to get minipress online 0.14 to 0.64).

Information on how to get minipress online interactions of treatment with baseline ordinal score with respect to mortality is provided in Table S11. Additional Secondary Outcomes how to get minipress online Table 3. Table 3 how to get minipress online.

Additional Secondary Outcomes. Patients in the remdesivir group had a shorter time to improvement of one or of how to get minipress online two categories on the ordinal scale from baseline than patients in the placebo group (one-category improvement. Median, 7 vs how to get minipress online.

9 days how to get minipress online. Rate ratio how to get minipress online for recovery, 1.23. 95% CI, 1.08 to 1.41.

Two-category improvement how to get minipress online. Median, 11 how to get minipress online vs. 14 days how to get minipress online.

Rate ratio, how to get minipress online 1.29. 95% CI, 1.12 to 1.48) (Table 3). Patients in the remdesivir group had a shorter time to discharge or to a how to get minipress online National Early Warning Score of 2 or lower than those in the placebo group (median, 8 days vs.

12 days how to get minipress online. Hazard ratio, 1.27 how to get minipress online. 95% CI, how to get minipress online 1.10 to 1.46).

The initial length of hospital stay was shorter in the remdesivir group than in the placebo group (median, 12 days vs. 17 days) how to get minipress online. 5% of patients in how to get minipress online the remdesivir group were readmitted to the hospital, as compared with 3% in the placebo group.

Among the 913 patients how to get minipress online receiving oxygen at enrollment, those in the remdesivir group continued to receive oxygen for fewer days than patients in the placebo group (median, 13 days vs. 21 days), and the incidence of new oxygen use among patients who were not receiving oxygen at enrollment was lower how to get minipress online in the remdesivir group than in the placebo group (incidence, 36% [95% CI, 26 to 47] vs. 44% [95% CI, 33 to 57]).

For the 193 patients receiving noninvasive ventilation or high-flow oxygen at enrollment, the median duration of use of how to get minipress online these interventions was 6 days in both the remdesivir and placebo groups. Among the 573 patients who were not receiving noninvasive ventilation, high-flow oxygen, invasive ventilation, or ECMO at baseline, the incidence of new noninvasive ventilation or high-flow oxygen use was lower in the remdesivir group than in the placebo group (17% how to get minipress online [95% CI, 13 to 22] vs. 24% [95% CI, 19 how to get minipress online to 30]).

Among the 285 patients how to get minipress online who were receiving mechanical ventilation or ECMO at enrollment, patients in the remdesivir group received these interventions for fewer subsequent days than those in the placebo group (median, 17 days vs. 20 days), and the incidence of new mechanical ventilation or ECMO use among the 766 patients who were not receiving these interventions at enrollment was lower in the remdesivir group than in the placebo group (13% [95% CI, 10 to 17] vs. 23% [95% CI, 19 to 27]) (Table how to get minipress online 3).

Safety Outcomes In the as-treated population, serious adverse events occurred in 131 of 532 patients how to get minipress online (24.6%) in the remdesivir group and in 163 of 516 patients (31.6%) in the placebo group (Table S17). There were 47 serious respiratory failure adverse events in the remdesivir group (8.8% of patients), including acute respiratory failure and the need for endotracheal intubation, and 80 in the placebo how to get minipress online group (15.5% of patients) (Table S19). No deaths were considered by how to get minipress online the investigators to be related to treatment assignment.

Grade 3 or 4 adverse events occurred how to get minipress online on or before day 29 in 273 patients (51.3%) in the remdesivir group and in 295 (57.2%) in the placebo group (Table S18). 41 events were judged by the investigators to be related to remdesivir and 47 events to placebo (Table S17). The most common nonserious adverse events occurring in at least 5% of all patients included decreased glomerular filtration rate, decreased hemoglobin level, decreased lymphocyte count, respiratory failure, anemia, pyrexia, hyperglycemia, increased blood creatinine level, and increased blood glucose level (Table how to get minipress online S20).

The incidence how to get minipress online of these adverse events was generally similar in the remdesivir and placebo groups. Crossover After the data and safety monitoring board recommended that the preliminary primary analysis report be provided to the sponsor, data on a total of 51 patients how to get minipress online (4.8% of the total study enrollment) — 16 (3.0%) in the remdesivir group and 35 (6.7%) in the placebo group — were unblinded. 26 (74.3%) how to get minipress online of those in the placebo group whose data were unblinded were given remdesivir.

Sensitivity analyses evaluating the unblinding (patients whose treatment assignments were unblinded had their data censored at the time of unblinding) and crossover (patients in the placebo group treated with remdesivir had their data censored at the initiation of remdesivir treatment) produced results similar to those of the primary analysis (Table S9).Trial Design and Oversight The RECOVERY trial is an investigator-initiated platform trial to evaluate the effects of potential treatments in patients hospitalized with Covid-19. The trial is being conducted at 176 how to get minipress online hospitals in the United Kingdom. (Details are provided in the Supplementary Appendix, available with the full text of this article at NEJM.org.) The investigators were assisted by the National Institute for Health Research Clinical Research Network, and the trial is coordinated by the how to get minipress online Nuffield Department of Population Health at the University of Oxford, the trial sponsor.

Although patients are no longer being enrolled in the hydroxychloroquine, dexamethasone, and lopinavir–ritonavir groups, the trial continues to study the effects of how to get minipress online azithromycin, tocilizumab, convalescent plasma, and REGN-COV2 (a combination of two monoclonal antibodies directed against the SARS-CoV-2 spike protein). Other treatments may be how to get minipress online studied in the future. The hydroxychloroquine that was used in this phase of the trial was supplied by the U.K.

National Health Service how to get minipress online (NHS). Hospitalized patients were eligible for the trial if they had clinically-suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might, in the opinion of the attending clinician, put patients at substantial risk if they were to how to get minipress online participate in the trial. Initially, recruitment was limited to patients who were at least 18 years of age, but the age how to get minipress online limit was removed as of May 9, 2020.

Written informed consent was obtained how to get minipress online from all the patients or from a legal representative if they were too unwell or unable to provide consent. The trial was conducted in accordance with Good Clinical Practice guidelines of the International Conference on Harmonisation and was approved by the U.K. Medicines and Healthcare Products Regulatory Agency (MHRA) how to get minipress online and the Cambridge East Research Ethics Committee.

The protocol with its statistical analysis how to get minipress online plan are available at NEJM.org, with additional information in the Supplementary Appendix and on the trial website at www.recoverytrial.net. The initial version of the manuscript was drafted by the first and last authors, developed by the writing committee, how to get minipress online and approved by all members of the trial steering committee. The funders had no role in the analysis of the data, in how to get minipress online the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication.

The first and last members of the writing committee vouch for the completeness and accuracy of the data and for the fidelity of the trial to the protocol and statistical analysis plan. Randomization and Treatment We collected baseline data using a Web-based case-report form that included demographic data, level of respiratory support, major coexisting illnesses, the suitability of the trial treatment for a particular patient, and treatment availability at the trial how to get minipress online site. Using a Web-based unstratified randomization method with the concealment of trial group, we assigned patients to receive either the usual standard of care or the usual standard of care plus hydroxychloroquine or one of the other available treatments how to get minipress online that were being evaluated.

The number of patients who were assigned to receive how to get minipress online usual care was twice the number who were assigned to any of the active treatments for which the patient was eligible (e.g., 2:1 ratio in favor of usual care if the patient was eligible for only one active treatment group, 2:1:1 if the patient was eligible for two active treatments, etc.). For some patients, hydroxychloroquine how to get minipress online was unavailable at the hospital at the time of enrollment or was considered by the managing physician to be either definitely indicated or definitely contraindicated. Patients with a known prolonged corrected QT interval on electrocardiography were ineligible to receive hydroxychloroquine.

(Coadministration with medications that prolong the QT interval was not an absolute contraindication, but attending clinicians were advised to check the QT interval by performing electrocardiography.) These patients were excluded from entry in the randomized comparison between hydroxychloroquine and usual care how to get minipress online. In the hydroxychloroquine group, patients received hydroxychloroquine sulfate (in the form of a 200-mg tablet containing a 155-mg base equivalent) in a loading dose of four tablets (total dose, 800 mg) at baseline and at 6 hours, which was followed by two tablets (total dose, 400 mg) starting at 12 hours after the initial dose and then how to get minipress online every 12 hours for the next 9 days or until discharge, whichever occurred earlier (see the Supplementary Appendix).15 The assigned treatment was prescribed by the attending clinician. The patients and local trial staff members were aware of the how to get minipress online assigned trial groups.

Procedures A single online follow-up form was to be completed by the local trial staff members when each trial patient was discharged, at 28 days after randomization, or at the time how to get minipress online of death, whichever occurred first. Information was recorded regarding the adherence to the assigned treatment, receipt of other treatments for Covid-19, duration of admission, receipt of respiratory support (with duration and type), receipt of renal dialysis or hemofiltration, and vital status (including cause of death). Starting on May 12, 2020, extra how to get minipress online information was recorded on the occurrence of new major cardiac arrhythmia.

In addition, we obtained routine health care and registry data that included information on vital status (with date and cause of death) and how to get minipress online discharge from the hospital. Outcome Measures The primary outcome was all-cause mortality within how to get minipress online 28 days after randomization. Further analyses were specified at 6 how to get minipress online months.

Secondary outcomes were the time until discharge from the hospital and a composite of the initiation of invasive mechanical ventilation including extracorporeal membrane oxygenation or death among patients who were not receiving invasive mechanical ventilation at the time of randomization. Decisions to initiate invasive mechanical ventilation were made by the attending clinicians, who were informed by guidance from NHS how to get minipress online England and the National Institute for Health and Care Excellence. Subsidiary clinical outcomes included cause-specific mortality (which was recorded in all patients) and major cardiac arrhythmia (which was recorded in a subgroup of how to get minipress online patients).

All information presented in this report is based on a data cutoff of September 21, 2020 how to get minipress online. Information regarding the primary outcome is complete for how to get minipress online all the trial patients. Statistical Analysis For the primary outcome of 28-day mortality, we used the log-rank observed-minus-expected statistic and its variance both to test the null hypothesis of equal survival curves and to calculate the one-step estimate of the average mortality rate ratio in the comparison between the hydroxychloroquine group and the usual-care group.

Kaplan–Meier survival curves were constructed to show cumulative mortality over the 28-day period how to get minipress online. The same methods were used to analyze the time until hospital discharge, with censoring how to get minipress online of data on day 29 for patients who had died in the hospital. We used the Kaplan–Meier estimates to calculate the median how to get minipress online time until hospital discharge.

For the prespecified composite secondary outcome of invasive mechanical ventilation or death within 28 days (among patients who had not been receiving invasive mechanical ventilation how to get minipress online at randomization), the precise date of the initiation of invasive mechanical ventilation was not available, so the risk ratio was estimated instead. Estimates of the between-group difference in absolute risk were also calculated. All the analyses how to get minipress online were performed according to the intention-to-treat principle.

Prespecified analyses of the how to get minipress online primary outcome were performed in six subgroups, as defined by characteristics at randomization. Age, sex, race, level of respiratory support, days since symptom onset, and predicted 28-day risk of death how to get minipress online. (Details are provided in the Supplementary Appendix.) Estimates of rate and risk ratios are shown with 95% confidence intervals without how to get minipress online adjustment for multiple testing.

The P value for the assessment of the primary outcome is two-sided. The full database how to get minipress online is held by the trial team, which collected the data from the trial sites and performed the analyses, at the Nuffield Department of Population Health at the University of Oxford. The independent data monitoring committee was asked to review unblinded analyses of the trial data and any other information how to get minipress online that was considered to be relevant at intervals of approximately 2 weeks.

The committee how to get minipress online was then charged with determining whether the randomized comparisons in the trial provided evidence with respect to mortality that was strong enough (with a range of uncertainty around the results that was narrow enough) to affect national and global treatment strategies. In such a circumstance, the committee would inform the members of the trial steering committee, who how to get minipress online would make the results available to the public and amend the trial accordingly. Unless that happened, the steering committee, investigators, and all others involved in the trial would remain unaware of the interim results until 28 days after the last patient had been randomly assigned to a particular treatment group.

On June 4, 2020, in response to a request from the MHRA, the independent data monitoring committee conducted a review of the data and recommended that the chief investigators review the how to get minipress online unblinded data for the hydroxychloroquine group. The chief investigators and steering committee members concluded that the data showed no beneficial effect how to get minipress online of hydroxychloroquine in patients hospitalized with Covid-19. Therefore, the enrollment of patients in the hydroxychloroquine group was closed on June 5, 2020, and the preliminary result for the primary outcome was made how to get minipress online public.

Investigators were advised that any patients who were receiving hydroxychloroquine as part of the trial should discontinue the treatment.Trial Objectives, Participants, and Oversight We assessed the safety and immunogenicity of how to get minipress online three dose levels of BNT162b1 and BNT162b2. Healthy adults 18 to 55 years of age or 65 to 85 years of age were eligible for inclusion. Key exclusion criteria were known infection with human immunodeficiency virus, how to get minipress online hepatitis C virus, or hepatitis B virus.

An immunocompromised how to get minipress online condition. A history of autoimmune disease how to get minipress online. A previous clinical or microbiologic how to get minipress online diagnosis of Covid-19.

The receipt of medications intended to prevent Covid-19. Any previous coronavirus how to get minipress online vaccination. Positive test for SARS-CoV-2 IgM or IgG at how to get minipress online the screening visit.

And positive nasal-swab results on a SARS-CoV-2 nucleic acid how to get minipress online amplification test within 24 hours before the receipt of trial vaccine or placebo. BioNTech was how to get minipress online the regulatory sponsor of the trial. Pfizer was responsible for how to get minipress online the trial design.

For the collection, analysis, and interpretation of the data. And for the writing of the report how to get minipress online. The corresponding author had full access to all the data in the trial and had final responsibility for the decision to submit how to get minipress online the manuscript for publication.

All the how to get minipress online trial data were available to all the authors. Trial Procedures Using an interactive Web-based response technology system, we randomly assigned trial participants to groups defined according to the vaccine candidate, dose level, and age how to get minipress online range. Groups of participants 18 to 55 years of age and 65 to 85 years of age were to receive doses of 10 μg, 20 μg, or 30 μg of BNT162b1 or BNT162b2 (or placebo) on a two-dose schedule.

One group of participants 18 to 55 years of age was assigned to receive 100-μg doses how to get minipress online of BNT162b1 or placebo. All the participants were assigned to receive two 0.5-ml injections of active vaccine (BNT162b1 or BNT162b2) or placebo how to get minipress online into the deltoid, administered 21 days apart. The first five participants in each new dose level or age group (with a randomization ratio of 4:1 for active vaccine:placebo) were observed for 4 hours after the injection to identify immediate how to get minipress online adverse events.

All the other how to get minipress online participants were observed for 30 minutes. Blood samples were obtained for safety and immunogenicity assessments. Safety The primary end points in phase 1 of this trial were solicited local reactions (i.e., specific local reactions as prompted how to get minipress online by and recorded in an electronic diary), systemic events, and use of antipyretic or pain medication within 7 days after the receipt of vaccine or placebo, as prompted by and recorded in an electronic diary.

Unsolicited adverse events and serious adverse events (i.e., those reported by the participants, without electronic-diary prompts), assessed from how to get minipress online the receipt of the first dose through 1 month and 6 months, respectively, after the receipt of the second dose. Clinical laboratory abnormalities, assessed 1 day and 7 how to get minipress online days after the receipt of vaccine or placebo. And grading shifts in laboratory assessments between baseline and 1 day and 7 days after the first how to get minipress online dose and between 2 days and 7 days after the second dose.

Protocol-specified safety stopping rules were in effect for all the participants in the phase 1 portion of the trial. The full protocol, including the statistical analysis plan, how to get minipress online is available with the full text of this article at NEJM.org. An internal review committee and an how to get minipress online external data and safety monitoring committee reviewed all safety data.

Immunogenicity Immunogenicity assessments (SARS-CoV-2 serum neutralization assay and receptor-binding domain [RBD]–binding or S1-binding IgG direct Luminex immunoassays) were conducted before the administration of vaccine or placebo, at 7 days and 21 days after the how to get minipress online first dose, and at 7 days (i.e., day 28) and 14 days (i.e., day 35) after the second dose. The neutralization how to get minipress online assay, which also generated previously described virus-neutralization data from trials of the BNT162 candidates,2,5 used a previously described strain of SARS-CoV-2 (USA_WA1/2020) that had been generated by reverse genetics and engineered by the insertion of an mNeonGreen gene into open reading frame 7 of the viral genome.11,12 The 50% neutralization titers and 90% neutralization titers were reported as the interpolated reciprocal of the dilutions yielding 50% and 90% reductions, respectively, in fluorescent viral foci. Any serologic values below the lower limit of quantitation were set to 0.5 times the lower limit of quantitation.

Available serologic results how to get minipress online were included in the analysis. Immunogenicity data from how to get minipress online a human convalescent serum panel were included as a benchmark. A total of 38 serum samples were obtained from donors 18 to 83 years of age (median age, 42.5 years) who had recovered from how to get minipress online SARS-CoV-2 infection or Covid-19.

Samples were how to get minipress online obtained at least 14 days after a polymerase chain reaction–confirmed diagnosis and after symptom resolution. Neutralizing geometric mean titers (GMTs) in subgroups of the donors were as follows. 90, among how to get minipress online 35 donors with symptomatic infections.

156, among 3 donors with how to get minipress online asymptomatic infection. And 618, in 1 donor how to get minipress online who was hospitalized. Each serum how to get minipress online sample in the panel was from a different donor.

Thus, most of the serum samples were obtained from persons with moderate Covid-19 who had not been hospitalized. The serum samples were obtained from Sanguine Biosciences, the MT how to get minipress online Group, and Pfizer Occupational Health and Wellness. Statistical Analysis how to get minipress online We report descriptive results of safety and immunogenicity analyses, and the sample size was not based on statistical hypothesis testing.

Results of the safety analyses are presented as counts, percentages, and associated Clopper–Pearson 95% confidence intervals for local reactions, systemic events, and any adverse events after the administration of vaccine or placebo, according to terms in the Medical Dictionary for Regulatory Activities, version how to get minipress online 23.0, for each vaccine group. Summary statistics are how to get minipress online provided for abnormal laboratory values and grading shifts. Given the small number of participants in each group, the trial was not powered for formal statistical comparisons between dose levels or between age groups.

Immunogenicity analyses of SARS-CoV-2 serum neutralizing titers, S1-binding IgG and RBD-binding IgG how to get minipress online concentrations, GMTs, and geometric mean concentrations (GMCs) were computed along with associated 95% confidence intervals. The GMTs and GMCs were calculated as the mean of the assay results after the logarithmic transformation was how to get minipress online made. We then exponentiated the mean to express results on how to get minipress online the original scale.

Two-sided 95% confidence intervals were obtained by performing logarithmic transformations of titers or concentrations, calculating the 95% confidence interval how to get minipress online with reference to Student’s t-distribution, and then exponentiating the limits of the confidence intervals.Supported by a philanthropic donation from Stein Erik Hagen and Canica. By a grant from the Deutsche Forschungsgemeinschaft Cluster of Excellence “Precision Medicine in Chronic Inflammation” (EXC2167). By a Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico Covid-19 Biobank how to get minipress online grant (to Dr.

Valenti). By grants from the Italian Ministry of Health (RF-2016-02364358, to Dr. Valenti) and Ministero dell’Istruzione, dell’Università e della Ricerca project “Dipartimenti di Eccellenza 2018–2022” (D15D18000410001 to the Department of Medical Sciences, University of Turin.

By a grant from the Spanish Ministry of Science and Innovation JdC fellowship (IJC2018-035131-I, to Dr. Acosta-Herrera). And by the GCAT Cession Research Project PI-2020-01.

HLA typing was performed and supported by the Stefan-Morsch-Stiftung. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org. Dr.

Ellinghaus and Ms. Degenhardt and Drs. Valenti, Franke, and Karlsen contributed equally to this article.The members of the writing committee (David Ellinghaus, Ph.D., Frauke Degenhardt, M.Sc., Luis Bujanda, M.D., Ph.D., Maria Buti, M.D., Ph.D., Agustín Albillos, M.D., Ph.D., Pietro Invernizzi, M.D., Ph.D., Javier Fernández, M.D., Ph.D., Daniele Prati, M.D., Guido Baselli, Ph.D., Rosanna Asselta, Ph.D., Marit M.

Grimsrud, M.D., Chiara Milani, Ph.D., Fátima Aziz, B.S., Jan Kässens, Ph.D., Sandra May, Ph.D., Mareike Wendorff, M.Sc., Lars Wienbrandt, Ph.D., Florian Uellendahl-Werth, M.Sc., Tenghao Zheng, M.D., Ph.D., Xiaoli Yi, Raúl de Pablo, M.D., Ph.D., Adolfo G. Chercoles, B.S., Adriana Palom, M.S., B.S., Alba-Estela Garcia-Fernandez, B.S., Francisco Rodriguez-Frias, M.S., Ph.D., Alberto Zanella, M.D., Alessandra Bandera, M.D., Ph.D., Alessandro Protti, M.D., Alessio Aghemo, M.D., Ph.D., Ana Lleo, M.D., Ph.D., Andrea Biondi, M.D., Andrea Caballero-Garralda, M.S., Ph.D., Andrea Gori, M.D., Anja Tanck, Anna Carreras Nolla, B.S., Anna Latiano, Ph.D., Anna Ludovica Fracanzani, M.D., Anna Peschuck, Antonio Julià, Ph.D., Antonio Pesenti, M.D., Antonio Voza, M.D., David Jiménez, M.D., Ph.D., Beatriz Mateos, M.D., Ph.D., Beatriz Nafria Jimenez, B.S., Carmen Quereda, M.D., Ph.D., Cinzia Paccapelo, M.Sc., Christoph Gassner, Ph.D., Claudio Angelini, M.D., Cristina Cea, B.S., Aurora Solier, M.D., David Pestaña, M.D., Ph.D., Eduardo Muñiz-Diaz, M.D., Ph.D., Elena Sandoval, M.D., Elvezia M. Paraboschi, Ph.D., Enrique Navas, M.D., Ph.D., Félix García Sánchez, Ph.D., Ferruccio Ceriotti, M.D., Filippo Martinelli-Boneschi, M.D., Ph.D., Flora Peyvandi, M.D., Ph.D., Francesco Blasi, M.D., Ph.D., Luis Téllez, M.D., Ph.D., Albert Blanco-Grau, B.S., M.S., Georg Hemmrich-Stanisak, Ph.D., Giacomo Grasselli, M.D., Giorgio Costantino, M.D., Giulia Cardamone, Ph.D., Giuseppe Foti, M.D., Serena Aneli, Ph.D., Hayato Kurihara, M.D., Hesham ElAbd, M.Sc., Ilaria My, M.D., Iván Galván-Femenia, M.Sc., Javier Martín, M.D., Ph.D., Jeanette Erdmann, Ph.D., Jose Ferrusquía-Acosta, M.D., Koldo Garcia-Etxebarria, Ph.D., Laura Izquierdo-Sanchez, B.S., Laura R.

Bettini, M.D., Lauro Sumoy, Ph.D., Leonardo Terranova, Ph.D., Leticia Moreira, M.D., Ph.D., Luigi Santoro, M.S., Luigia Scudeller, M.D., Francisco Mesonero, M.D., Luisa Roade, M.D., Malte C. Rühlemann, Ph.D., Marco Schaefer, Ph.D., Maria Carrabba, M.D., Ph.D., Mar Riveiro-Barciela, M.D., Ph.D., Maria E. Figuera Basso, Maria G.

Valsecchi, Ph.D., María Hernandez-Tejero, M.D., Marialbert Acosta-Herrera, Ph.D., Mariella D’Angiò, M.D., Marina Baldini, M.D., Marina Cazzaniga, M.D., Martin Schulzky, M.A., Maurizio Cecconi, M.D., Ph.D., Michael Wittig, M.Sc., Michele Ciccarelli, M.D., Miguel Rodríguez-Gandía, M.D., Monica Bocciolone, M.D., Monica Miozzo, Ph.D., Nicola Montano, M.D., Ph.D., Nicole Braun, Nicoletta Sacchi, Ph.D., Nilda Martínez, M.D., Onur Özer, M.Sc., Orazio Palmieri, Ph.D., Paola Faverio, M.D., Paoletta Preatoni, M.D., Paolo Bonfanti, M.D., Paolo Omodei, M.D., Paolo Tentorio, M.S., Pedro Castro, M.D., Ph.D., Pedro M. Rodrigues, Ph.D., Aaron Blandino Ortiz, M.D., Rafael de Cid, Ph.D., Ricard Ferrer, M.D., Roberta Gualtierotti, M.D., Rosa Nieto, M.D., Siegfried Goerg, M.D., Salvatore Badalamenti, M.D., Ph.D., Sara Marsal, Ph.D., Giuseppe Matullo, Ph.D., Serena Pelusi, M.D., Simonas Juzenas, Ph.D., Stefano Aliberti, M.D., Valter Monzani, M.D., Victor Moreno, Ph.D., Tanja Wesse, Tobias L. Lenz, Ph.D., Tomas Pumarola, M.D., Ph.D., Valeria Rimoldi, Ph.D., Silvano Bosari, M.D., Wolfgang Albrecht, Wolfgang Peter, Ph.D., Manuel Romero-Gómez, M.D., Ph.D., Mauro D’Amato, Ph.D., Stefano Duga, Ph.D., Jesus M.

Banales, Ph.D., Johannes R Hov, M.D., Ph.D., Trine Folseraas, M.D., Ph.D., Luca Valenti, M.D., Andre Franke, Ph.D., and Prof. Tom H. Karlsen, M.D., Ph.D.) assume responsibility for the overall content and integrity of this article.This article was published on June 17, 2020, at NEJM.org.We thank all the patients who consented to participate in this study, and we express our condolences to the families of patients who died from Covid-19.

We also thank the entire clinical staff during the outbreak situation at the different centers who were able to work on this scientific study in parallel with their clinical duties. All the members of the Humanitas Covid-19 Task Force for contributions to the recruitment of patients (see the Supplementary Notes section in Supplementary Appendix 1). Sören Brunak and Karina Banasik for discussions on the ABO association.

Goncalo Abecasis and his team for providing the Michigan imputation server. Fabrizio Bossa and Francesca Tavano for contributions to control-sample acquisition. Maria Reig for help in the case-sample acquisition.

The staff of the Basque Biobank in Spain for assistance in the acquisition of samples. The staff of GCAT|Genomes for Life, a cohort study of the Genomes of Catalonia, Institute for Health Science Research Germans Trias i Pujol, for data contribution. Alexander Eck, Jenspeter Horst, and Jens Scholz for supporting the HLA typing in the project.

And the members of the ethics commissions, review boards, and consortia who fast-track reviewed our applications and enabled this rapid genetic discovery study..