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More than buy generic levitra uk 60 oil and gas companies committed to a new framework today to report methane emissions as the United Nations reported that atmospheric levels of the greenhouse gas reached a record high. The plan from the Climate &. Clean Air Coalition’s Oil and Gas Methane Partnership (OGMP) tasks companies with reporting methane emissions from both their core operations as well as joint buy generic levitra uk ventures.

As a part of the voluntary framework, companies will share their own methane reduction targets with OGMP, an initiative managed by the U.N. Environment Programme. The plan revamps an existing OGMP framework and calls on companies to outline buy generic levitra uk how they will realize their objectives to cut methane emissions.

The 62 companies that have joined OGMP represent an estimated 30% of global oil and gas production, according to the partnership. The group said it seeks to deliver a 45% reduction in the oil and gas industry’s methane emissions by 2025. Individual targets buy generic levitra uk from the companies—which include European firms like Equinor ASA, Total SE and Royal Dutch Shell PLC—will be reviewed periodically, in line with a “common objective to continuously reduce greenhouse gas emissions.” Methane is the chief component of natural gas.

Mark Brownstein, a senior vice president of energy at the Environmental Defense Fund, said while the framework is voluntary, it’s still an “important contribution to advancing the cause” of lowering oil and gas methane emissions. EDF has buy generic levitra uk worked with the Climate &. Clean Air Coalition since 2014, Brownstein said, and helped take OGMP and the methane reporting framework to its latest form.

€œFor the first time, companies are committing to regularly measure their methane emissions using strict science-based standards, as opposed to engineering estimates,” Brownstein said. According to the separate report today buy generic levitra uk from the World Meteorological Organization—a U.N. Agency—methane reached a new high in 2019 and has increased 161% above preindustrial levels “due to increased emissions from anthropogenic sources,” including the fossil fuel industry.

Roughly 60% of methane emitted into the atmosphere comes from man-made sources, like the development of fossil fuels, landfills, biomass burning and agriculture, the WMO report said. According to Brownstein, methane emission estimates based on engineering calculations by industry often understate the true amount of emissions buy generic levitra uk coming from oil and gas operations. He called the oil and gas framework “a step forward” because it moves to reporting data based on field measurements and ongoing monitoring.

The suite of monitoring technologies available to companies spans from the use of drones to satellites. Still, although buy generic levitra uk the partnership “applies to all segments of the oil and gas sector where material quantities of methane can be emitted,” it does not pertain to chunks like oil refining and chemical manufacturing, as well as “gas end use.” It also does not currently include U.S. Oil and gas majors, which have historically lagged behind their European counterparts when it comes to climate targets (Climatewire, Sept.

11). Manfredi Caltagirone, a program officer with the U.N. Environment Programme, said although U.S.

Companies aren’t participating at the moment, the partnership is talking with multiple firms and noted that “many OGMP member companies have assets in the U.S.” Brownstein echoed Caltagirone and said that “irrespective of whether U.S. Companies or other national oil companies join, the process of bringing transparency around your emissions begins with this new program.” The OGMP framework is meant to complement efforts like EDF’s MethaneSAT project, an initiative to measure emissions by satellite, he said. These kinds of voluntary initiatives also have to be coupled with regulations, he said, like those under development in the European Union.

€œVoluntary programs are a complement to government action, but they are not a substitute for it,” Brownstein said. He cautioned that “the degree to which this voluntary strategy results in real and substantial emissions reductions has everything to do with whether and how the companies that are committing to this program actually follow through on what they are committing to.” A spokesperson for Shell declined to comment for the story and spokespersons for Equinor and Total did not respond to inquiries. Reprinted from Climatewire with permission from E&E News.

E&E provides daily coverage of essential energy and environmental news at www.eenews.net.Sridhar Ravi was outdoors with his colleagues on a summer day in Germany when a group of bumblebees grabbed his attention.As the bees made their way from flower to flower, they skillfully flew between obstacles, dodging branches and shrubs. These actions seemed to require a complex awareness of one's physical body in relation to one’s environment that had only been proven to exist in animals with large brains. To examine this, a team of researchers at Australia’s University of New South Wales, Canberra, led by Ravi, set up a hive of bumblebees inside their laboratory.

The bees could come and go via a tunnel, which could be partially blocked with an adjustable barrier. Ravi and his team made the gap progressively smaller over time, and observed how the bees’ reactions changed. The study, published in the Proceedings of the National Academy of Sciences, found the bumblebees measured the gap by flying side-to-side to scan it.

When the gap became narrower than their wingspan, the bees took a longer time to scan the opening. And then they did something remarkable. They turned their bodies to fly through sideways.

Some of the bees’ bodies did bump the sides of the narrowed opening—but every one of the 400 recorded flights through the gap was a success. €œOver thousands of years nature has coded insects with some amazing attributes,” Ravi says. €œOur challenge now is to see how we can take this and apply similar coding to future robotic systems, enhancing their performance in the natural world.”Stephan Lewandowsky was deep in denial.

About six years ago the cognitive scientist had thrown himself into a study of why some people refuse to accept the overwhelming evidence that the planet is warming and humans are responsible. As he delved into this climate change denialism, Lewandowsky, then at the University of Western Australia, discovered that many of the naysayers also believed in outlandish plots, such as the idea that the Apollo moon landing was a hoax created by the American government. €œA lot of the discourse these people were engaging in on the Internet was totally conspiratorial,” he recalls.

Lewandowsky’s findings, published in 2013 in Psychological Science, brought these conspiracy theorists out of the woodwork. Offended by his claims, they criticized his integrity online and demanded that he be fired. (He was not, although he has since moved to the University of Bristol in England.) But as Lewandowsky waded through one irate post after another, he discovered that his critics—in response to his assertions about their conspiratorial tendencies—were actually spreading new conspiracy theories about him.

These people accused him and his colleagues of faking survey responses and of conducting the research without ethical approval. When his personal Web site crashed, one blogger accused him of intentionally blocking critics from seeing it. None of it was true.

The irony was amusing at first, but the ranting even included a death threat, and calls and e-mails to his university became so vicious that the administrative staff who fielded them asked their managers for help. That was when Lewandowsky changed his assessment. €œI quickly realized that there was nothing funny about these guys at all,” he says.

The dangerous consequences of the conspiratorial perspective—the idea that people or groups are colluding in hidden ways to produce a particular outcome—have become painfully clear. The gunman who shot and killed 11 people and injured six others in a Pittsburgh synagogue in October 2018 justified his attack by claiming that Jewish people were stealthily supporting illegal immigrants. In 2016 a conspiracy theory positing that high-ranking Democratic Party officials were involved in a child sex ring involving several Washington, D.C., area restaurants incited one believer to fire an assault weapon inside a pizzeria.

Luckily no one was hurt. The mindset is surprisingly common, although thankfully it does not often lead to gunfire. More than a quarter of the American population believes there are conspiracies “behind many things in the world,” according to a 2017 analysis of government survey data by University of Oxford and University of Liverpool researchers.

The prevalence of conspiracy mongering may not be new, but today the theories are becoming more visible, says Viren Swami, a social psychologist at Anglia Ruskin University in England, who studies the phenomenon. For instance, when more than a dozen bombs were sent to prominent Democrats and Trump critics, as well as CNN, in October 2018, a number of high-profile conservatives quickly suggested that the explosives were really a “false flag,” a fake attack orchestrated by Democrats to mobilize their supporters during the U.S. Midterm elections.

One obvious reason for the current raised profile of this kind of thinking is that the U.S. President is a vocal conspiracy theorist. Donald Trump has suggested, among other things, that the father of Senator Ted Cruz of Texas helped to assassinate President John F.

Kennedy and that Democrats funded the same migrant caravan traveling from Honduras to the U.S. That worried the Pittsburgh synagogue shooter. But there are other factors at play, too.

New research suggests that events happening worldwide are nurturing underlying emotions that make people more willing to believe in conspiracies. Experiments have revealed that feelings of anxiety make people think more conspiratorially. Such feelings, along with a sense of disenfranchisement, currently grip many Americans, according to surveys.

In such situations, a conspiracy theory can provide comfort by identifying a convenient scapegoat and thereby making the world seem more straightforward and controllable. €œPeople can assume that if these bad guys weren’t there, then everything would be fine,” Lewandowsky says. €œWhereas if you don’t believe in a conspiracy theory, then you just have to say terrible things happen randomly.” Discerning fact from fiction can be difficult, however, and some seemingly wild conspiracy ideas turn out to be true.

The once scoffed at notion that Russian nationals meddled in the 2016 presidential election is now supported by a slew of guilty pleas, evidence-based indictments and U.S. Intelligence agency conclusions. So how is one to know what to believe?.

There, too, psychologists have been at work and have uncovered strategies that can help people distinguish plausible theories from those that are almost certainly fake—strategies that seem to become more important by the day. The anxiety connection In May 2018 the American Psychiatric Association released the results of a national survey suggesting that 39 percent of Americans feel more anxious than they did a year ago, primarily about health, safety, finances, politics and relationships. Another 2017 report found that 63 percent of Americans are extremely worried about the future of the nation and that 59 percent consider this the lowest point in U.S.

History that they can remember. These feelings span the political spectrum. A 2018 Pew Research Center survey found that the majority of both Democrats and Republicans feel that “their side” in politics has been losing in recent years on issues they find important.

Such existential crises can promote conspiratorial thinking. In a 2015 study in the Netherlands, researchers split college students into three groups. People in one group were primed to feel powerless.

The scientists asked them to recall and write about a time in their lives when they felt they were not in control of the situation they were in. Those in a second group were cued in the opposite direction. They were asked to write about a time when they felt totally in control.

And still others, in a third group, were asked something neutral. To describe what they had for dinner last night. Then the researchers asked all the groups how they felt about the construction of a new subway line in Amsterdam that had been plagued by problems.

Conspiracy theorists believe plots are behind many situations. Some hold that the Apollo moon landing was faked (left), others that the White House forced Supreme Court Justice Anthony Kennedy to retire (right). Credit.

Getty Images (left). Brendan Smialowski Getty Images (right) Others claim that Trump slogans on a mail bomber's van were put there to frame Republicans (left). The gunman who killed 11 synagogue members in 2018 claimed a Jewish group was undermining America (right).

Credit. Alamy (left). Jeff Swensen Getty Images (right) Students who had been primed to feel in control were less likely than students in the other two groups to support conspiracy theories regarding the subway line, such as the belief that the city council was stealing from the subway’s budget and that it was intentionally jeopardizing residents’ safety.

Other studies have uncovered similar effects. Swami and his colleagues, for instance, reported in 2016 that individuals who feel stressed are more likely than others to believe in conspiracy theories, and a 2017 study found that promoting anxiety in people also makes them more conspiracy-minded. Feeling alienated or unwanted also seems to make conspiratorial thinking more attractive.

In 2017 Princeton University psychologists set up an experiment with trios of people. The researchers asked all participants to write two paragraphs describing themselves and then told them that their descriptions would be shared with the other two in their group, who would use that information to decide if they would work with the person in the future. After telling some subjects that they had been accepted by their group and others that they had been rejected, the researchers evaluated the subjects’ thoughts on various conspiracy-related scenarios.

The “rejected” participants, feeling alienated, were more likely than the others to think the scenarios involved a coordinated conspiracy. It is not just personal crises that encourage individuals to form conspiratorial suspicions. Collective social setbacks do so as well.

In a 2018 study, researchers at the University of Minnesota and Lehigh University surveyed more than 3,000 Americans. They found that participants who felt that American values are eroding were more likely than others to agree with conspiratorial statements, such as that “many major events have behind them the actions of a small group of influential people.” Joseph Uscinski, a political scientist at the University of Miami, and his colleagues have shown that people who dislike the current political party in power think more conspiratorially than those who support the controlling party. Recently in the U.S., a number of unproved conjectures have come from political liberals as conservatives have ascended to control the government.

These include the charge that the White House coerced Anthony Kennedy to retire from the U.S. Supreme Court and the allegation that Russian president Vladimir Putin is blackmailing Trump with a video of him watching prostitutes urinate on a Moscow hotel bed. When feelings of personal alienation or anxiety are combined with a sense that society is in jeopardy, people experience a kind of conspiratorial double whammy.

In a study conducted in 2009, near the start of the U.S.’s Great Recession, Daniel Sullivan, a psychologist now at the University of Arizona, and his colleagues told one group that parts of their lives were largely out of their control because they could be exposed to a natural disaster or some other catastrophe and told another group that things were under their control. Then participants were asked to read essays that argued that the government was handling the economic crisis either well or poorly. Those cued about uncontrolled life situations and told their government was doing a bad job were the most likely to think that negative events in their lives would be instigated by enemies rather than random chance, which is a conspiratorial hallmark.

While humans seek solace in conspiracy theories, however, they rarely find it. €œThey’re appealing but not necessarily satisfying,” says Daniel Jolley, a psychologist at Staffordshire University in England. For one thing, conspiratorial thinking can incite individuals to behave in a way that increases their sense of powerlessness, making them feel even worse.

A 2014 study co-authored by Jolley found that people who are presented with conspiracy theories about climate change—scientists are just chasing grant money, for instance—are less likely to plan to vote, whereas a 2017 study reported that believing in work-related conspiracies—such as the idea that managers make decisions to protect their own interests—causes individuals to feel less committed to their job. €œIt can snowball and become a pretty vicious, nasty cycle of inaction and negative behavior,” says Karen Douglas, a psychologist at the University of Kent in England and a co-author of the paper on work-related conspiracies. The negative and alienated beliefs can also promote dangerous behaviors in some, as with the Pittsburgh shootings and the pizzeria attack.

But the theories need not involve weapons to inflict harm. People who believe treatment conspiracy theories, for example, say they are less inclined to vaccinate their kids, which creates pockets of infectious disease that put entire communities at risk. Telling fact from fiction It may be possible to quell conspiracy ideation, at least to some degree.

One long-standing question has been whether or not it is a good idea to counter conspiracy theories with logic and evidence. Some older research has pointed to a “backfire effect”—the idea that refuting misinformation can just make individuals dig their heels in deeper. €œIf you think there are powerful forces trying to conspire and cover [things] up, when you’re given what you see as a cover story, it only shows you how right you are,” Uscinski says.

But more recent research suggests that this putative effect is, in fact, rare. A 2016 study reported that when researchers refuted a conspiracy theory by pointing out its logical inconsistencies, it became less enchanting to people. And in a paper published online in 2018 in Political Behavior, researchers recruited more than 10,000 people and presented them with corrections to various claims made by political figures.

The authors concluded that “evidence of factual backfire is far more tenuous than prior research suggests.” In a recent review, the researchers who first described the backfire effect said that it may arise most often when people are being challenged over ideas that define their worldview or sense of self. Finding ways to counter conspiracy theories without challenging a person’s identity may therefore be an effective strategy. Encouraging analytic thinking may also help.

In a 2014 study published in Cognition, Swami and his colleagues recruited 112 people for an experiment. First, they had everyone fill out a questionnaire that evaluated how strongly they believed in various conspiracy theories. A few weeks later the subjects came back in, and the researchers split them into two groups.

One group completed a task that included unscrambling words in sentences containing words such as “analyze” and “rational,” which primed them to think more analytically. The second group completed a neutral task. Then the researchers readministered the conspiracy theory test to the two groups.

Although the groups had been no different in terms of conspiratorial thinking at the beginning of the experiment, the subjects who had been incited to think analytically became less conspiratorial. Thus, by giving people “the tools and the skills to analyze data and to look at data critically and objectively,” we might be able to suppress conspiratorial thinking, Swami says. Analytic thinking can also help discern implausible theories from ones that, crazy as they sound, are supported by evidence.

Karen Murphy, an educational psychologist at Pennsylvania State University, suggests that individuals who want to improve their analytic thinking skills should ask three key questions when interpreting conspiracy claims. One. What is your evidence?.

Two. What is your source for that evidence?. Three.

What is the reasoning that links your evidence back to the claim?. Sources of evidence need to be accurate, credible and relevant. For instance, “you shouldn’t take advice from your mom about whether the yellow color under your fingernails is a bad sign,” Murphy says—that kind of information should come from someone who has expertise on the topic, such as a physician.

In addition, false conspiracy theories have several hallmarks, Lewandowsky says. Three of them are particularly noticeable. First, the theories include contradictions.

For example, some deniers of climate change argue that there is no scientific consensus on the issue while framing themselves as heroes pushing back against established consensus. Both cannot be true. A second telltale sign is when a contention is based on shaky assumptions.

Trump, for instance, claimed that millions of illegal immigrants cast ballots in the 2016 presidential election and were the reason he lost the popular vote. Beyond the complete lack of evidence for such voting, his assumption was that multitudes of such votes—if they existed—would have been for his Democratic opponent. Yet past polls of unauthorized Hispanic immigrants suggest that many of them would have voted for a Republican candidate over a Democratic one.

A third sign that a claim is a far-fetched theory, rather than an actual conspiracy, is that those who support it interpret evidence against their theory as evidence for it. When the van of the alleged mail bomber Cesar Sayoc was found in Florida plastered with Trump stickers, for instance, some individuals said this helped to prove that Democrats were really behind the bombs. €œIf anyone thinks this is what a real conservative’s van looks like, you are being willfully ignorant.

Cesar Sayoc is clearly just a fall guy for this obvious false flag,” one person posted on Twitter. Conspiracy theories are a human reaction to confusing times. €œWe’re all just trying to understand the world and what’s happening in it,” says Rob Brotherton, a psychologist at Barnard College and author of Suspicious Minds.

Why We Believe in Conspiracy Theories (Bloomsbury Sigma, 2015). But real harm can come from such thinking, especially when believers engage in violence as a show of support. By looking out for suspicious signatures and asking thoughtful questions about the stories we encounter, it is still possible to separate truth from lies.

It may not always be an easy task, but it is a crucial one for all of us..

Levitra how long does it last in your system

NCHS Data look at this site Brief levitra how long does it last in your system No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for chronic conditions such as cardiovascular disease (1) and levitra how long does it last in your system diabetes (2).

Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition. Menopause is “the levitra how long does it last in your system permanent cessation of menstruation that occurs after the loss of ovarian activity” (3). This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status.

The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of women are premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal levitra how long does it last in your system. Keywords.

Insufficient sleep, menopause, National Health Interview Survey Perimenopausal levitra how long does it last in your system women were more likely than premenopausal and postmenopausal women to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1). Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period.

Figure 1 levitra how long does it last in your system. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic trend by menopausal status (p levitra how long does it last in your system <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago levitra how long does it last in your system or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for Figure levitra how long does it last in your system 1pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who had trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in levitra how long does it last in your system the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week.

Figure 2 levitra how long does it last in your system. Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by levitra how long does it last in your system menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal levitra how long does it last in your system if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data levitra how long does it last in your system table for Figure 2pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the past week (26.7%) levitra how long does it last in your system (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week.

Figure 3 levitra how long does it last in your system. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear levitra how long does it last in your system trend by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual levitra how long does it last in your system cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for levitra how long does it last in your system Figure 3pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up levitra how long does it last in your system feeling well rested 4 days or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week.

Figure 4 levitra how long does it last in your system. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 4pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories.

Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5). Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion. DefinitionsMenopausal status.

A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?. €.

2) “Do you still have periods or menstrual cycles?. €. 3) “When did you have your last period or menstrual cycle?.

€. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries.

Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less. Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?.

€Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?. €Trouble falling asleep.

Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?.

€ Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis. NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone.

Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS. For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States.

The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS. Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option.

Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics. The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report.

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Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF.

Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon. 2016.Santoro N.

Perimenopause. From research to practice. J Women’s Health (Larchmt) 25(4):332–9.

2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended amount of sleep for a healthy adult. A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society.

J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

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SUDAAN (Release 11.0.0) [computer software]. 2012. Suggested citationVahratian A.

Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286. Hyattsville, MD.

National Center for Health Statistics. 2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J.

Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J.

Blumberg, Ph.D., Associate Director for Science.

NCHS Data buy generic levitra uk Brief No http://www.augenaerzte-georgstr.de/buy-viagra-online-usa/. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for chronic buy generic levitra uk conditions such as cardiovascular disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition. Menopause is “the permanent cessation of menstruation that occurs after the loss of ovarian activity” (3) buy generic levitra uk.

This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of women are premenopausal, 3.7% are perimenopausal, and buy generic levitra uk 22.1% are postmenopausal. Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than 7 hours, on average, buy generic levitra uk in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1).

Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period. Figure 1 buy generic levitra uk. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic trend buy generic levitra uk by menopausal status (p <.

0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual buy generic levitra uk cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for buy generic levitra uk Figure 1pdf icon.SOURCE.

NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble falling asleep four times or buy generic levitra uk more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week. Figure 2 buy generic levitra uk.

Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image buy generic levitra uk icon1Significant linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were buy generic levitra uk perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less.

Women were premenopausal if they still had a menstrual cycle. Access data table buy generic levitra uk for Figure 2pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the past week buy generic levitra uk (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women.

Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week. Figure 3 buy generic levitra uk. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, buy generic levitra uk 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal buy generic levitra uk if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for buy generic levitra uk Figure 3pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015.

The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well buy generic levitra uk rested 4 days or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week. Figure 4 buy generic levitra uk. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status.

United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES. Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle.

Access data table for Figure 4pdf icon.SOURCE. NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5). Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion.

DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?. €. 2) “Do you still have periods or menstrual cycles?.

€. 3) “When did you have your last period or menstrual cycle?. €. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries.

Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less. Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

€Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?. € Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis.

NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS. For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States.

The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS. Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics.

The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report. ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No. 141.

Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF. Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon.

2016.Santoro N. Perimenopause. From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al.

Recommended amount of sleep for a healthy adult. A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software]. 2012.

Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286. Hyattsville, MD. National Center for Health Statistics.

2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J. Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J.

Blumberg, Ph.D., Associate Director for Science.

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Authors Danielle Chelminsky, Debra Lipson, and Laura Kimmey discuss their research on the need for improved integrated plans across buy generic levitra uk Medicare and Medicaid to increase member retention. Emerging Evidence buy generic levitra uk on the Impact of erectile dysfunction treatment in Long-Term Care. Mathematica’s Patricia Rowan, Debra Lipson, Michael buy generic levitra uk Levere, and Noelle Denny-Brown review their research on the impact of erectile dysfunction treatment in nursing homes, including the effects of the levitra on the long-term care workforce. They will also examine strategies employed by facilities and government agencies in other states to support and strengthen the long-term care workforce during the early phase of the outbreak.Check out an agenda of all our activities at the 2021 Annual Research Meeting.

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€œI am excited for this opportunity for Mathematica and NewWave to help the Maryland T-MSIS team configure and use Imersis to improve Medicaid data quality for Maryland.” “We view T-MSIS as one of the most important projects which aims to improve data quality and realize better health outcomes through customer service and buy generic levitra uk program integrity - a vision the Department shares with CMS,” said David Wertheimer, Enterprise Architect with the Maryland Department of Health. €œBoth Mathematica and NewWave have demonstrated unparalleled expertise and leadership in T-MSIS and data quality reporting, and we are thrilled to partner with them on this project.”To learn more about Imersis, please visit www.mathematica.org/toolkits/imersis.ContactSarah RodriguezEmail. Sarah.rodriguez@newwave.io Todd Kohlhepp Email buy generic levitra uk. Tkohlhepp@mathematica-mpr.comThe levitra is not coming to an end soon — given that only a small proportion of the buy generic levitra uk world population has been vaccinated against erectile dysfunction treatment, a well-known epidemiologist told CNBC.Dr.

Larry Brilliant, an epidemiologist who was part of the World Health Organization's team that helped eradicate smallpox, said the delta variant is "maybe the most contagious levitra" ever.In recent months, the U.S., India and China, as well as other countries in Europe, Africa and Asia have been grappling with a highly transmissible delta variant of the levitra.WHO declared erectile dysfunction treatment a global levitra last March — after the disease, which first emerged in China in late 2019, spread throughout the world.The buy generic levitra uk good news is that treatments — particularly those using messenger RNA technology and the one by Johnson &. Johnson — are holding up against the delta variant, Brilliant told CNBC's "Squawk Box Asia" on Friday.Unless we vaccinate everyone in 200 plus countries, there will still be new variants.Larry BrilliantEpidemiologistStill, only 15% of the world population has been vaccinated and more than 100 countries have inoculated less than 5% of their people, noted Brilliant."I think we're closer to the beginning than we are to the end [of the levitra], and that's not because the variant that we're looking at right now is going to last that long," said Brilliant, who is now the founder and CEO of a levitra response consultancy, Pandefense Advisory."Unless we vaccinate everyone in 200 plus countries, there will still be new variants," he said, predicting that the erectile dysfunction will eventually become a "forever levitra" like influenza.Probability of 'super variant'Brilliant said his models on the erectile dysfunction treatment outbreak in San Francisco and New York predict an "inverted V-shape epidemic curve." That implies that s increase very quickly, but would also decline rapidly, he explained.If the prediction turns out be true, it means that the delta variant spreads so quickly that "it basically runs out of candidates" to infect, explained Brilliant. There appears to be a similar pattern buy generic levitra uk in the U.K. And India, where the spread of the delta variant has receded from recent highs.But I do caution people that this is the delta variant and we have not run buy generic levitra uk out of Greek letters so there may be more to come.Larry BrilliantEpidemiologistDaily reported cases in the U.K.

€” on a seven-day moving average basis — fell from a peak of around 47,700 cases on July 21 to around 26,000 cases on Thursday, according to statistics compiled by online database Our World in Data.In India, the seven-day moving average of daily reported cases has stayed below 50,000 since late June — far below the peak of more than 390,000 a day in May, the data showed."That may mean that this is a six-month phenomenon in a country, rather than a two-year phenomenon. But I do caution people that buy generic levitra uk this is the delta variant and we have not run out of Greek letters so there may be more to come," he said.The epidemiologist said there is a low probability that a "super variant" may emerge and treatments don't work against it. While it's buy generic levitra uk hard to predict these things, he added, it's a non-zero probability, which means it cannot be ruled out."It's such a catastrophic event should it occur, we have to do everything possible to prevent it," said Brilliant. "And that means get everyone vaccinated — not just in your neighborhood, not just in your family, not just in your country but all over the world."erectile dysfunction treatment boostersSome countries with relatively high vaccination buy generic levitra uk rates such as the U.S.

And Israel are planning booster shots for their population. Others, such as Haiti, only recently secured their first buy generic levitra uk batch of treatment doses.WHO has called on wealthy countries to hold off on erectile dysfunction treatment boosters to give low-income countries a chance to vaccinate their people.CNBC Health &. Science But in addition to boosting vaccination in countries with a low inoculation rate, Brilliant said one group of people needs a booster shot "right away" — those who are 65 years and buy generic levitra uk above, and were fully vaccinated more than six months ago but have a weakened immune system."It is this category of people that we've seen create multiple mutations when the levitra goes through their body," said the epidemiologist."So those people, I would say, should be given a third dose, a booster right away — as quickly as moving the treatments to those countries that haven't had a very high chance to buy them or have access to them. I consider those two things about equal," he added.— CNBC's Rich Mendez contributed to this report..

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NIH research could lead to new treatment strategies for stomach cancer Glucocorticoids and androgens promote a healthy stomach pit by inhibiting inflammation, generic levitra free shipping left, while their absence promotes inflammation and SPEM seen in a diseased pit, right. SPEM glands are also much larger than healthy stomach glands. (Photo courtesy of Jonathan Busada, Ph.D./NIEHS) Scientists at the National Institutes of Health determined that stomach generic levitra free shipping inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach.

The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition. The study was published in Gastroenterology.Researchers at NIH’s National Institute of Environmental Health Sciences (NIEHS) made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several generic levitra free shipping functions, one of them being suppressing inflammation.

With no glucocorticoids, the female mice soon developed stomach inflammation. The males did generic levitra free shipping not. However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females."The fact that androgens are regulating inflammation is a novel idea," said co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of the Molecular Endocrinology Group.

"Along with glucocorticoids, androgens offer a new way to control immune function in humans."While this study provides insight into how inflammation is being regulated in males, Cidlowski said additional research is underway to understand the process in females. The scientist handling this phase of research is co-corresponding author Jonathan Busada, Ph.D., assistant professor at West Virginia University School of Medicine in generic levitra free shipping Morgantown. When Busada started the project several years ago, he was a postdoctoral fellow working in Cidlowski’s group.Whether inflammation is inside the stomach or elsewhere in the body, Busada said rates of chronic inflammatory and autoimmune diseases vary depending on sex.

He said eight out of 10 individuals with autoimmune disease are women, and his long-term goal is to figure out how glucocorticoids and androgens affect stomach cancer, which is induced by chronic inflammation.The current research focused on stomach glands called pits, which are embedded generic levitra free shipping in the lining of the stomach.Busada said the study showed that glucocorticoids and androgens act like brake pedals on the immune system and are essential for regulating stomach inflammation. In his analogy, glucocorticoids are the primary brakes and androgens are the emergency brakes."Females only have one layer of protection, so if you remove glucocorticoids, they develop stomach inflammation and a pre-cancerous condition in the stomach called spasmolytic polypeptide-expressing metaplasia (SPEM)," Busada said. "Males have redundancy built in, so if something cuts the glucocorticoid brake line, it is okay, because the androgens can pick up the slack."The research also offered a possible mechanism — or biological process — behind this phenomenon.

In healthy stomach glands, the presence of glucocorticoids and generic levitra free shipping androgens inhibit special immune cells called type 2 innate lymphoid cells (ILC2s). But in diseased stomach glands, the hormones are missing. As a result, ILC2s may act like a fire alarm, directing other immune cells called macrophages to promote inflammation and damage gastric glands leading to SPEM and ultimately cancer."ILC2s are the only immune cells that contain androgen receptors and could be a potential therapeutic target," Cidlowski said.This press release describes a basic research finding.

Basic research increases our understanding generic levitra free shipping of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research generic levitra free shipping.

To learn more about basic research, visit Basic Research – Digital Media Kit.Grant Numbers:ZIAES090057Fi2GM123974P20GM103434P20GM121322U54GM104942P30GM103488 Reference. Busada JT, Peterson KN, Khadka S, Xu, X, Oakley RH, Cook DN, Cidlowski JA. 2021.

Glucocorticoids and androgens protect from gastric metaplasia by suppressing group 2 innate lymphoid cell activation. Gastroenterology. Doi.

10.1053/j.gastro.2021.04.075 [Online 7 May 2021].CORVALLIS, Ore. €“ A team of Oregon State University scientists has discovered a new class of anti-cancer compounds that effectively kill liver and breast cancer cells. The findings, recently published in the journal Apoptosis, describe the discovery and characterization of compounds, designated as Select Modulators of AhR-regulated Transcription (SMAhRTs).

Edmond Francis O’Donnell III and a team of OSU researchers conducted the research in the laboratory of Siva Kolluri, a professor of cancer research at Oregon State. They also identified the aryl hydrocarbon receptor (AhR) as a new molecular target for development of cancer therapeutics. €œOur research identified a therapeutic lead that acts through a new molecular target for treatment of certain cancers,” Kolluri said.

O’Donnell added. €œThis is an exciting development which lays a foundation for a new class of anti-cancer therapeutics acting through the AhR.” The researchers employed two molecular screening techniques to discover potential SMAhRTs and identified a molecule – known as CGS-15943 – that activates AhR signaling and kills liver and breast cancer cells. Specifically, they studied cells from human hepatocellular carcinoma, a common type of liver cancer, and cells from triple negative breast cancer, which account for about 15% of breast cancers with the worst prognosis.

€œWe focused on these two types of cancers because they are difficult to treat and have limited treatment options,” said Kolluri, a professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences. €œWe were encouraged by the results because they are unrelated cancers and targeting the AhR was effective in inducing death of both of these distinct cancers.” The researchers also identified the AhR-mediated pathways that contribute to the anti-cancer actions of CGS-15943. Developing cancer treatments requires a detailed understanding of how they act to induce anti-cancer effects.

The researchers determined that CGS-15943 increases the expression of a protein called Fas Ligand through the AhR and causes cancer cell death. These results provide exciting new leads for drug development, but human therapies based on these results may not be available to patients for 10 years, the researchers said. An editorial commemorating the 25th anniversary issue of the journal Apoptosis highlighted this discovery and the detailed investigation of cancer cell death promoted by CGS-15943.

In addition to Kolluri and O’Donnell, who recently completed medical school and is an orthopaedic surgery resident at UC Davis Medical Center, other authors of the paper are. Hyo Sang Jang and Nancy Kerkvliet, both from Oregon State. And Daniel Liefwalker, who formerly worked in Kolluri’s lab and is now at Oregon Health and Science University.

Kolluri is also part of Oregon State’s Linus Pauling Institute and The Pacific Northwest Center for Translational Environmental Health Research. Funding for the research came from the American Cancer Society, National Institute of Environmental Health Sciences, the U.S. Army Medical Research and Material Command, the Department of Defense Breast Cancer Research Program, Oregon State University and the National Cancer Institute.MDEL Bulletin, June 24 2021, from the Medical Devices Compliance Program On this page Fees for Medical Device Establishment Licences (MDELs) We issue Medical Device Establishment Licences (MDELs) to.

class I manufacturers importers or distributors of all device classes for human use in Canada The MDEL fee is a flat fee, regardless of when we receive your initial application. The same fee applies to applications for. a new MDEL the reinstatement of a suspended MDEL the annual licence review (ALR) of an MDEL If you submit any of these applications, you must pay the MDEL fee when you receive an invoice.

See Part 3, Division 2 of the Fees in Respect of Drugs and Medical Devices Order. Normally, we collect the MDEL fee before we review an application. However, to help meet the demand for medical devices during the erectile dysfunction treatment levitra, we have been reviewing and processing MDEL applications before collecting the fees.

As a result, some MDEL holders still haven't paid the fees for their 2020 initial MDEL application, despite multiple reminders. Authority to withhold services in case of non-payment As stated in the Food and Drug Act, Health Canada has the authority to withhold services, approvals, rights and/or privileges, if the fee for an MDEL application is not paid. Non-payment of fees 30.64.

The Minister may withdraw or withhold a service, the use of a facility, a regulatory process or approval or a product, right or privilege under this Act from any person who fails to pay the fee fixed for it under subsection 30.61(1). For more information, please refer to. Cancellation of existing MDELs We will cancel MDELs for existing MDEL holders with outstanding fees for.

initial applications or annual licence review applications If your establishment licence is cancelled, you are no longer authorized to conduct licensable activities (such as manufacturing, distributing or importing medical devices). You must stop licensable activities as soon as you receive your cancellation notice. Resuming activities after MDEL cancellation To resume licensable activities, you must re-apply for a new establishment licence and pay the MDEL fee.

See section 45 of the Medical Device Regulations. To find out how to re-apply for a MDEL, please refer to our Guidance on medical device establishment licensing (GUI-0016). In line with the Compliance and Enforcement Policy (POL-0001), Health Canada monitors activities for compliance.

If your MDEL has been cancelled, you may be subject to compliance and enforcement actions if you conduct non-compliant activities. If you have questions about a MDEL or the application process, please contact the Medical Device Establishment Licensing Unit at hc.mdel.questions.leim.sc@canada.ca. If you have questions about invoicing and fees for an MDEL application, please contact the Cost Recovery Invoicing Unit at hc.criu-ufrc.sc@canada.ca.

Related linksResponse to the Expert Panel Report on “Priority strategies to optimize testing and quarantine at Canada’s borders” The Industry Advisory Roundtable on erectile dysfunction treatment Testing, Screening, Tracing and Data Management is pleased to release its third report. This report reiterates the importance of balancing public health measures to reduce the importation of erectile dysfunction treatment with the need to ensure the free flow of people and goods across the Canadian border and support economic recovery. On this page Executive summary Soon after erectile dysfunction treatment was declared a global levitra in March 2020, international borders around the world closed in an effort to limit the spread of the levitra.

To ensure the health and safety of individuals, the movement of people and goods was restricted. Yet, it was important to maintain access to essential goods and services and sustain trade-based economic sectors. Canada responded in step with other countries.

The government implemented public health measures such as mandatory testing and quarantine when crossing international borders. Restrictions are necessary to curb the spread of the levitra. Yet, in a complex environment such as international borders, it’s crucial to implement and clearly communicate public health measures effectively and clearly.

Border measures such as testing regimes and other public health measures must be based on the most recent science-based public health evidence. Such measures must also leverage advances in testing options, consider vaccination rates and balance the needs of industries operating across borders. Furthermore, plans must be easy to implement consistently across several entry modes.

They should also be communicated broadly and include a roadmap for easing or increasing border restrictions based on objective criteria and benchmarks. As we enter the second year of the levitra, the Roundtable is offering insights and recommendations to adjust current border measures. We have based our recommendations on evidence collected from international scans and observations from industries that move goods and people across borders.

The Roundtable recognizes the effort required to implement plans for easing border restrictions, given rapidly evolving public health circumstances and emerging variants of concern. Prompt action is needed to design and implement a border measures plan that reduces the risk of the levitra spreading while proactively moving towards economic recovery. Current border environment In March 2020, the ability of people to move across the Canadian border was restricted.

Since then, several measures were taken to reduce the importation of erectile dysfunction treatment and limit the spread of the levitra. As circumstances changed over the following weeks and months, border measures became more restrictive. In early 2021, more stringent public health measures were introduced for non-essential travellers at air and land borders.

This was done to reduce the importation rate of erectile dysfunction treatment and its variants of concern. Measures included the following. mandatory pre-departure erectile dysfunction treatment molecular test contact/quarantine plan using the ArriveCAN application on-arrival and post-arrival testing for travellers arriving by air, mandatory 3-day quarantine in government-authorized hotels followed by quarantine or isolation at an approved location such as the traveller’s home The Government of Canada and the aviation industry also worked together on a plan to suspend Canadian air carrier flights to and from Mexico and Caribbean countries from January 31 to April 30, 2021.

Then on February 3, 2021, all incoming international commercial passenger flights to Canada were restricted to the 4 largest airports. Montreal, Toronto, Calgary and Vancouver. In order to prevent importation of variants of concern, the Government of Canada took additional measures that included suspension of flights from certain countries.

Canada suspended all commercial and passenger flights from the United Kingdom between December 20, 2020 and January 6, 2021. Additionally, on April 22, 2021, all commercial and private passenger flights from India and Pakistan were suspended in response to a high number of cases detected among individuals travelling on flights originating from the two countries. These measures are in place until at least June 21, 2021.

Internal data from the Public Health Agency of Canada indicates the following positivity rates for the seven days up to and including May 27, 2021, for air and land travel combined. the 7-day average positivity rate for testing on arrival was 0.2% the 7-day average positivity rate for second tests was 0.3% As well, all positive tests undergo genomic sequencing to identify variants of concern. Cross-border travel volumes decreased significantly from December 2019 to December 2020.

Statistics Canada data show that the. number of travellers to Canada was down 93% total number of international travellers to and from Canada declined from 96.8 million in 2019 to 25.9 million in 2020 Air travel has experienced the most dramatic shifts, as travellers arriving by air are mostly non-exempt from border measures. In comparison, travellers exempt from border measures make up the vast majority of land border traffic.

Essential travel continued largely unimpeded, as governments recognized the importance of preserving vital supply chains to ensure that food, fuel and life-saving medicines continue to reach people. A shifting landscape As of May 28, 2021, variants of concern account for an estimated 70% of reported cases in recent weeks. Any border measures must account for this new reality.

At the same time, individuals and organizations within and outside of Canada are increasingly looking for. a concrete roadmap to the economic reopening of the country clear guidelines for restarting cross-border travel Plans and guidelines should clearly spell out the public health criteria for adjusting border measures. They should also outline when and how restrictions should be eased in the short and longer term.

Guidelines must take into consideration the risk of importing new variants of concern in the move towards a safe restart of the trade and tourism industries that operate internationally. As scientists learn more about how the levitra spreads, as travellers are tested regularly and as vaccination efforts increase, it will be easier to manage the risk of importing erectile dysfunction treatment and its variants. Nevertheless, while the international border is open, there’s always the risk of importation.

For a safe reopening, we need a risk framework that takes into account public health measures and socio-economic factors. To bring the risk to an acceptable level, detection and surveillance options should be part of any robust border testing strategy. Evidence concerning restrictive border measures, including lengthy quarantines, shows that the effectiveness of these measures declines over time.

Non-compliance increases when measures are too tough and/or not communicated well. This can counter efforts to reduce the spread of the levitra and break the chains of transmission. As more and more people in Canada and abroad are vaccinated, it will be necessary to update Canada’s strategy to allow the movement of vaccinated travellers, based on emerging scientific evidence and while respecting public health measures.

Complex border measures may present significant implementation challenges, which can lead to disparities in how the various rules, regulations and guidelines are applied at ports of entry. This may have a negative impact on people crossing the Canadian border and those industries engaged in cross-border and transnational business. Small and medium companies may be especially impacted.

Although essential workers have largely been exempt from border measures, the Roundtable is aware of the challenges they face when rules are applied inconsistently. For example, several Canadian companies have reported incidences where some engineers, technicians and other specialists have faced challenges crossing the Canada-US border and meeting their contractual obligations to provide skilled services. Some business executives and professional services providers with cross-border responsibilities are constrained in their ability to manage their operations effectively.

As well, disruptions to the cross-border travel of these workers could expose businesses to legal recourse from clients for failure to meet commitments. Many countries, including Canada, are aggressively rolling out vaccination regimes and partially permitting the movement of people (with restrictions). Canada is now the top country in the G7, G20 and OECD for vaccination rates of first doses.

As the campaign shifts to second doses, Canada must continue to reach vulnerable populations to ensure treatment equity and broad-based coverage to facilitate re-opening the economy and growth. Canada’s biggest trading partner also shares its largest border. Efforts should be made to align public health and economic recovery goals between Canada and the United States.

Prioritizing the Canada-US border would be consistent with the commitments made by both countries in the Roadmap for a Renewed U.S.-Canada Partnership. This roadmap recommends a coordinated and science-based approach to ease border restrictions in the future. Countries around the world are also exploring cooperative arrangements with other countries and looking at piloting innovative technology and information-sharing platforms designed to facilitate safe travel, such as treatment certification.

Implementing significant changes requires wide support and cooperation, as highlighted in the Industry Strategy Council’s Restart, recover, and reimagine prosperity for all Canadians report. The report proposes a three-phase action plan – restart, recover, and reimagine – focused on investment and growth, and embodies values and principles of action and shared responsibility to mobilize all sectors to propel Canada forward. The phases are anchored in five recommendations to safely restore confidence and commerce, stabilize the hardest-hit sectors, reignite growth by doubling down on a future-oriented investment plan, develop an ambitious industrial strategy, and establish renewed public-private sector partnerships and investments anchored in a sound and rigorous fiscal framework.

At the same time, we must recognize we live in times of uncertainty and contend with a rapidly shifting landscape. Plans should be flexible in order to balance public health concerns with the desire to ease restrictions. We must work with public health experts to establish and clearly communicate criteria and benchmarks to help travellers and businesses understand how and when border restrictions will be eased or increased in the coming months.

Provinces and territories have outlined their reopening plans, with an important strength being the use of benchmarks to move between several steps of restrictions. Communicating a clear path with well-defined criteria will provide a much-needed level of predictability for reopening to industry and travellers alike. Recommendations The Industry Roundtable recommends an approach to border measures that include both short- and longer-term recommendations.

Short-term recommendations Provide clear definitions of cross-border essential travellers and apply these in a consistent manner at all ports of entry. Recognize that companies are well positioned to identify essential travellers within their organization, enabling them to leverage existing domestic testing regimes for employees to demonstrate that public health requirements are met. Accepting employer-issued proof of testing would shift the onus away from the border and alleviate traveller flow pressures.

Explicitly state the conditions for testing travellers and the criteria for shortening or removing quarantine measures. Connect the pace of vaccination rollout with public health measures and the gradual lifting of travel restrictions, and include clear procedures for vaccinated, partially vaccinated and unvaccinated travellers. This may need to adjust as new variants of concern emerge.

Enable industry to take an active role in meeting vaccination targets in Canada by supporting priority vaccination of cross-border essential workers. Aggressive vaccination targets for these workers would help companies contribute to the safe reopening of the economy in a timely manner. Apply measures consistently at air and land borders, whenever possible.

Provide clear, straightforward messaging for every person and company involved in the cross-border movement of people and goods. Clear communication leads to effective, consistent implementation of any border measure and subsequent updates. Longer-term recommendations Take into account evolving scientific evidence and adopt emerging findings.

For example, evidence suggests that rapid antigen testing can be effective as a screening tool and adds another layer of defence when used as part of surveillance testing. Ensure that processes, information systems and infrastructure needed to implement modified border measures are in place and can manage increased travel volumes effectively. Re-position Canada as a competitive participant in the tourism and global trade sectors through enabling border measures that facilitate the movement of people and goods across international borders.

In collaboration with the private sector, the government should develop an enhanced framework to better prepare for and respond to future levitras..

NIH research could lead to new treatment strategies for stomach cancer Glucocorticoids and androgens promote a healthy stomach pit by inhibiting inflammation, check my reference left, while buy generic levitra uk their absence promotes inflammation and SPEM seen in a diseased pit, right. SPEM glands are also much larger than healthy stomach glands. (Photo courtesy of Jonathan Busada, Ph.D./NIEHS) Scientists at the National buy generic levitra uk Institutes of Health determined that stomach inflammation is regulated differently in male and female mice after finding that androgens, or male sex hormones, play a critical role in preventing inflammation in the stomach. The finding suggests that physicians could consider treating male patients with stomach inflammation differently than female patients with the same condition.

The study was published in Gastroenterology.Researchers at NIH’s National Institute of Environmental Health Sciences (NIEHS) made the discovery after removing adrenal glands from mice of both sexes. Adrenal glands produce glucocorticoids, hormones that have several buy generic levitra uk functions, one of them being suppressing inflammation. With no glucocorticoids, the female mice soon developed stomach inflammation. The males buy generic levitra uk did not.

However, after removing androgens from the males, they exhibited the same stomach inflammation seen in the females."The fact that androgens are regulating inflammation is a novel idea," said co-corresponding author John Cidlowski, Ph.D., deputy chief of the NIEHS Laboratory of Signal Transduction and head of the Molecular Endocrinology Group. "Along with glucocorticoids, androgens offer a new way to control immune function in humans."While this study provides insight into how inflammation is being regulated in males, Cidlowski said additional research is underway to understand the process in females. The scientist handling this phase of research is co-corresponding author Jonathan Busada, Ph.D., assistant professor at West buy generic levitra uk Virginia University School of Medicine in Morgantown. When Busada started the project several years ago, he was a postdoctoral fellow working in Cidlowski’s group.Whether inflammation is inside the stomach or elsewhere in the body, Busada said rates of chronic inflammatory and autoimmune diseases vary depending on sex.

He said eight out of 10 individuals with autoimmune disease are women, and his long-term goal is to figure out how glucocorticoids and androgens affect stomach cancer, which is induced by chronic inflammation.The current research focused on stomach glands called pits, which are embedded in the lining of the stomach.Busada said the study showed that glucocorticoids and androgens act like brake pedals on the immune buy generic levitra uk system and are essential for regulating stomach inflammation. In his analogy, glucocorticoids are the primary brakes and androgens are the emergency brakes."Females only have one layer of protection, so if you remove glucocorticoids, they develop stomach inflammation and a pre-cancerous condition in the stomach called spasmolytic polypeptide-expressing metaplasia (SPEM)," Busada said. "Males have redundancy built in, so if something cuts the glucocorticoid brake line, it is okay, because the androgens can pick up the slack."The research also offered a possible mechanism — or biological process — behind this phenomenon. In healthy stomach glands, the presence of glucocorticoids and buy generic levitra uk androgens inhibit special immune cells called type 2 innate lymphoid cells (ILC2s).

But in diseased stomach glands, the hormones are missing. As a result, ILC2s may act like a fire alarm, directing other immune cells called macrophages to promote inflammation and damage gastric glands leading to SPEM and ultimately cancer."ILC2s are the only immune cells that contain androgen receptors and could be a potential therapeutic target," Cidlowski said.This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, buy generic levitra uk diagnose, and treat disease. Science is an unpredictable and incremental process — each research advance builds on past discoveries, often in unexpected ways.

Most clinical advances buy generic levitra uk would not be possible without the knowledge of fundamental basic research. To learn more about basic research, visit Basic Research – Digital Media Kit.Grant Numbers:ZIAES090057Fi2GM123974P20GM103434P20GM121322U54GM104942P30GM103488 Reference. Busada JT, Peterson KN, Khadka S, Xu, X, Oakley RH, Cook DN, Cidlowski JA. 2021.

Glucocorticoids and androgens protect from gastric metaplasia by suppressing group 2 innate lymphoid cell activation. Gastroenterology. Doi. 10.1053/j.gastro.2021.04.075 [Online 7 May 2021].CORVALLIS, Ore.

€“ A team of Oregon State University scientists has discovered a new class of anti-cancer compounds that effectively kill liver and breast cancer cells. The findings, recently published in the journal Apoptosis, describe the discovery and characterization of compounds, designated as Select Modulators of AhR-regulated Transcription (SMAhRTs). Edmond Francis O’Donnell III and a team of OSU researchers conducted the research in the laboratory of Siva Kolluri, a professor of cancer research at Oregon State. They also identified the aryl hydrocarbon receptor (AhR) as a new molecular target for development of cancer therapeutics.

€œOur research identified a therapeutic lead that acts through a new molecular target for treatment of certain cancers,” Kolluri said. O’Donnell added. €œThis is an exciting development which lays a foundation for a new class of anti-cancer therapeutics acting through the AhR.” The researchers employed two molecular screening techniques to discover potential SMAhRTs and identified a molecule – known as CGS-15943 – that activates AhR signaling and kills liver and breast cancer cells. Specifically, they studied cells from human hepatocellular carcinoma, a common type of liver cancer, and cells from triple negative breast cancer, which account for about 15% of breast cancers with the worst prognosis.

€œWe focused on these two types of cancers because they are difficult to treat and have limited treatment options,” said Kolluri, a professor in the Department of Environmental and Molecular Toxicology in the College of Agricultural Sciences. €œWe were encouraged by the results because they are unrelated cancers and targeting the AhR was effective in inducing death of both of these distinct cancers.” The researchers also identified the AhR-mediated pathways that contribute to the anti-cancer actions of CGS-15943. Developing cancer treatments requires a detailed understanding of how they act to induce anti-cancer effects. The researchers determined that CGS-15943 increases the expression of a protein called Fas Ligand through the AhR and causes cancer cell death.

These results provide exciting new leads for drug development, but human therapies based on these results may not be available to patients for 10 years, the researchers said. An editorial commemorating the 25th anniversary issue of the journal Apoptosis highlighted this discovery and the detailed investigation of cancer cell death promoted by CGS-15943. In addition to Kolluri and O’Donnell, who recently completed medical school and is an orthopaedic surgery resident at UC Davis Medical Center, other authors of the paper are. Hyo Sang Jang and Nancy Kerkvliet, both from Oregon State.

And Daniel Liefwalker, who formerly worked in Kolluri’s lab and is now at Oregon Health and Science University. Kolluri is also part of Oregon State’s Linus Pauling Institute and The Pacific Northwest Center for Translational Environmental Health Research. Funding for the research came from the American Cancer Society, National Institute of Environmental Health Sciences, the U.S. Army Medical Research and Material Command, the Department of Defense Breast Cancer Research Program, Oregon State University and the National Cancer Institute.MDEL Bulletin, June 24 2021, from the Medical Devices Compliance Program On this page Fees for Medical Device Establishment Licences (MDELs) We issue Medical Device Establishment Licences (MDELs) to.

class I manufacturers importers or distributors of all device classes for human use in Canada The MDEL fee is a flat fee, regardless of when we receive your initial application. The same fee applies to applications for. a new MDEL the reinstatement of a suspended MDEL the annual licence review (ALR) of an MDEL If you submit any of these applications, you must pay the MDEL fee when you receive an invoice. See Part 3, Division 2 of the Fees in Respect of Drugs and Medical Devices Order.

Normally, we collect the MDEL fee before we review an application. However, to help meet the demand for medical devices during the erectile dysfunction treatment levitra, we have been reviewing and processing MDEL applications before collecting the fees. As a result, some MDEL holders still haven't paid the fees for their 2020 initial MDEL application, despite multiple reminders. Authority to withhold services in case of non-payment As stated in the Food and Drug Act, Health Canada has the authority to withhold services, approvals, rights and/or privileges, if the fee for an MDEL application is not paid.

Non-payment of fees 30.64. The Minister may withdraw or withhold a service, the use of a facility, a regulatory process or approval or a product, right or privilege under this Act from any person who fails to pay the fee fixed for it under subsection 30.61(1). For more information, please refer to. Cancellation of existing MDELs We will cancel MDELs for existing MDEL holders with outstanding fees for.

initial applications or annual licence review applications If your establishment licence is cancelled, you are no longer authorized to conduct licensable activities (such as manufacturing, distributing or importing medical devices). You must stop licensable activities as soon as you receive your cancellation notice. Resuming activities after MDEL cancellation To resume licensable activities, you must re-apply for a new establishment licence and pay the MDEL fee. See section 45 of the Medical Device Regulations.

To find out how to re-apply for a MDEL, please refer to our Guidance on medical device establishment licensing (GUI-0016). In line with the Compliance and Enforcement Policy (POL-0001), Health Canada monitors activities for compliance. If your MDEL has been cancelled, you may be subject to compliance and enforcement actions if you conduct non-compliant activities. If you have questions about a MDEL or the application process, please contact the Medical Device Establishment Licensing Unit at hc.mdel.questions.leim.sc@canada.ca.

If you have questions about invoicing and fees for an MDEL application, please contact the Cost Recovery Invoicing Unit at hc.criu-ufrc.sc@canada.ca. Related linksResponse to the Expert Panel Report on “Priority strategies to optimize testing and quarantine at Canada’s borders” The Industry Advisory Roundtable on erectile dysfunction treatment Testing, Screening, Tracing and Data Management is pleased to release its third report. This report reiterates the importance of balancing public health measures to reduce the importation of erectile dysfunction treatment with the need to ensure the free flow of people and goods across the Canadian border and support economic recovery. On this page Executive summary Soon after erectile dysfunction treatment was declared a global levitra in March 2020, international borders around the world closed in an effort to limit the spread of the levitra.

To ensure the health and safety of individuals, the movement of people and goods was restricted. Yet, it was important to maintain access to essential goods and services and sustain trade-based economic sectors. Canada responded in step with other countries. The government implemented public health measures such as mandatory testing and quarantine when crossing international borders.

Restrictions are necessary to curb the spread of the levitra. Yet, in a complex environment such as international borders, it’s crucial to implement and clearly communicate public health measures effectively and clearly. Border measures such as testing regimes and other public health measures must be based on the most recent science-based public health evidence. Such measures must also leverage advances in testing options, consider vaccination rates and balance the needs of industries operating across borders.

Furthermore, plans must be easy to implement consistently across several entry modes. They should also be communicated broadly and include a roadmap for easing or increasing border restrictions based on objective criteria and benchmarks. As we enter the second year of the levitra, the Roundtable is offering insights and recommendations to adjust current border measures. We have based our recommendations on evidence collected from international scans and observations from industries that move goods and people across borders.

The Roundtable recognizes the effort required to implement plans for easing border restrictions, given rapidly evolving public health circumstances and emerging variants of concern. Prompt action is needed to design and implement a border measures plan that reduces the risk of the levitra spreading while proactively moving towards economic recovery. Current border environment In March 2020, the ability of people to move across the Canadian border was restricted. Since then, several measures were taken to reduce the importation of erectile dysfunction treatment and limit the spread of the levitra.

As circumstances changed over the following weeks and months, border measures became more restrictive. In early 2021, more stringent public health measures were introduced for non-essential travellers at air and land borders. This was done to reduce the importation rate of erectile dysfunction treatment and its variants of concern. Measures included the following.

mandatory pre-departure erectile dysfunction treatment molecular test contact/quarantine plan using the ArriveCAN application on-arrival and post-arrival testing for travellers arriving by air, mandatory 3-day quarantine in government-authorized hotels followed by quarantine or isolation at an approved location such as the traveller’s home The Government of Canada and the aviation industry also worked together on a plan to suspend Canadian air carrier flights to and from Mexico and Caribbean countries from January 31 to April 30, 2021. Then on February 3, 2021, all incoming international commercial passenger flights to Canada were restricted to the 4 largest airports. Montreal, Toronto, Calgary and Vancouver. In order to prevent importation of variants of concern, the Government of Canada took additional measures that included suspension of flights from certain countries.

Canada suspended all commercial and passenger flights from the United Kingdom between December 20, 2020 and January 6, 2021. Additionally, on April 22, 2021, all commercial and private passenger flights from India and Pakistan were suspended in response to a high number of cases detected among individuals travelling on flights originating from the two countries. These measures are in place until at least June 21, 2021. Internal data from the Public Health Agency of Canada indicates the following positivity rates for the seven days up to and including May 27, 2021, for air and land travel combined.

the 7-day average positivity rate for testing on arrival was 0.2% the 7-day average positivity rate for second tests was 0.3% As well, all positive tests undergo genomic sequencing to identify variants of concern. Cross-border travel volumes decreased significantly from December 2019 to December 2020. Statistics Canada data show that the. number of travellers to Canada was down 93% total number of international travellers to and from Canada declined from 96.8 million in 2019 to 25.9 million in 2020 Air travel has experienced the most dramatic shifts, as travellers arriving by air are mostly non-exempt from border measures.

In comparison, travellers exempt from border measures make up the vast majority of land border traffic. Essential travel continued largely unimpeded, as governments recognized the importance of preserving vital supply chains to ensure that food, fuel and life-saving medicines continue to reach people. A shifting landscape As of May 28, 2021, variants of concern account for an estimated 70% of reported cases in recent weeks. Any border measures must account for this new reality.

At the same time, individuals and organizations within and outside of Canada are increasingly looking for. a concrete roadmap to the economic reopening of the country clear guidelines for restarting cross-border travel Plans and guidelines should clearly spell out the public health criteria for adjusting border measures. They should also outline when and how restrictions should be eased in the short and longer term. Guidelines must take into consideration the risk of importing new variants of concern in the move towards a safe restart of the trade and tourism industries that operate internationally.

As scientists learn more about how the levitra spreads, as travellers are tested regularly and as vaccination efforts increase, it will be easier to manage the risk of importing erectile dysfunction treatment and its variants. Nevertheless, while the international border is open, there’s always the risk of importation. For a safe reopening, we need a risk framework that takes into account public health measures and socio-economic factors. To bring the risk to an acceptable level, detection and surveillance options should be part of any robust border testing strategy.

Evidence concerning restrictive border measures, including lengthy quarantines, shows that the effectiveness of these measures declines over time. Non-compliance increases when measures are too tough and/or not communicated well. This can counter efforts to reduce the spread of the levitra and break the chains of transmission. As more and more people in Canada and abroad are vaccinated, it will be necessary to update Canada’s strategy to allow the movement of vaccinated travellers, based on emerging scientific evidence and while respecting public health measures.

Complex border measures may present significant implementation challenges, which can lead to disparities in how the various rules, regulations and guidelines are applied at ports of entry. This may have a negative impact on people crossing the Canadian border and those industries engaged in cross-border and transnational business. Small and medium companies may be especially impacted. Although essential workers have largely been exempt from border measures, the Roundtable is aware of the challenges they face when rules are applied inconsistently.

For example, several Canadian companies have reported incidences where some engineers, technicians and other specialists have faced challenges crossing the Canada-US border and meeting their contractual obligations to provide skilled services. Some business executives and professional services providers with cross-border responsibilities are constrained in their ability to manage their operations effectively. As well, disruptions to the cross-border travel of these workers could expose businesses to legal recourse from clients for failure to meet commitments. Many countries, including Canada, are aggressively rolling out vaccination regimes and partially permitting the movement of people (with restrictions).

Canada is now the top country in the G7, G20 and OECD for vaccination rates of first doses. As the campaign shifts to second doses, Canada must continue to reach vulnerable populations to ensure treatment equity and broad-based coverage to facilitate re-opening the economy and growth. Canada’s biggest trading partner also shares its largest border. Efforts should be made to align public health and economic recovery goals between Canada and the United States.

Prioritizing the Canada-US border would be consistent with the commitments made by both countries in the Roadmap for a Renewed U.S.-Canada Partnership. This roadmap recommends a coordinated and science-based approach to ease border restrictions in the future. Countries around the world are also exploring cooperative arrangements with other countries and looking at piloting innovative technology and information-sharing platforms designed to facilitate safe travel, such as treatment certification. Implementing significant changes requires wide support and cooperation, as highlighted in the Industry Strategy Council’s Restart, recover, and reimagine prosperity for all Canadians report.

The report proposes a three-phase action plan – restart, recover, and reimagine – focused on investment and growth, and embodies values and principles of action and shared responsibility to mobilize all sectors to propel Canada forward. The phases are anchored in five recommendations to safely restore confidence and commerce, stabilize the hardest-hit sectors, reignite growth by doubling down on a future-oriented investment plan, develop an ambitious industrial strategy, and establish renewed public-private sector partnerships and investments anchored in a sound and rigorous fiscal framework. At the same time, we must recognize we live in times of uncertainty and contend with a rapidly shifting landscape. Plans should be flexible in order to balance public health concerns with the desire to ease restrictions.

We must work with public health experts to establish and clearly communicate criteria and benchmarks to help travellers and businesses understand how and when border restrictions will be eased or increased in the coming months. Provinces and territories have outlined their reopening plans, with an important strength being the use of benchmarks to move between several steps of restrictions. Communicating a clear path with well-defined criteria will provide a much-needed level of predictability for reopening to industry and travellers alike. Recommendations The Industry Roundtable recommends an approach to border measures that include both short- and longer-term recommendations.

Short-term recommendations Provide clear definitions of cross-border essential travellers and apply these in a consistent manner at all ports of entry. Recognize that companies are well positioned to identify essential travellers within their organization, enabling them to leverage existing domestic testing regimes for employees to demonstrate that public health requirements are met. Accepting employer-issued proof of testing would shift the onus away from the border and alleviate traveller flow pressures. Explicitly state the conditions for testing travellers and the criteria for shortening or removing quarantine measures.

Connect the pace of vaccination rollout with public health measures and the gradual lifting of travel restrictions, and include clear procedures for vaccinated, partially vaccinated and unvaccinated travellers. This may need to adjust as new variants of concern emerge. Enable industry to take an active role in meeting vaccination targets in Canada by supporting priority vaccination of cross-border essential workers. Aggressive vaccination targets for these workers would help companies contribute to the safe reopening of the economy in a timely manner.

Apply measures consistently at air and land borders, whenever possible. Provide clear, straightforward messaging for every person and company involved in the cross-border movement of people and goods. Clear communication leads to effective, consistent implementation of any border measure and subsequent updates. Longer-term recommendations Take into account evolving scientific evidence and adopt emerging findings.

For example, evidence suggests that rapid antigen testing can be effective as a screening tool and adds another layer of defence when used as part of surveillance testing. Ensure that processes, information systems and infrastructure needed to implement modified border measures are in place and can manage increased travel volumes effectively. Re-position Canada as a competitive participant in the tourism and global trade sectors through enabling border measures that facilitate the movement of people and goods across international borders. In collaboration with the private sector, the government should develop an enhanced framework to better prepare for and respond to future levitras..

Does levitra help you last longer

A broadly http://www.frogpondbandb.com/2016/10/08/hello-world/ neutralising antibody to prevent HIV transmissionTwo does levitra help you last longer HIV prevention trials (HVTN 704/HPTN 085. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse does levitra help you last longer events related to VRC01 were uncommon. In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of levitraes circulating in the trial regions).

However, VRC01 did not prevent with other HIV isolates and overall does levitra help you last longer HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al. Two randomized trials of neutralizing antibodies to prevent does levitra help you last longer HIV-1 acquisition. N Engl J Med.

2021;384:1003–1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel of 34 cytokines/chemokines in blood and semen of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their does levitra help you last longer partners and 22 who did not. Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in seminal fluid, but not in blood, differed significantly between transmitters and non-transmitters, with transmitters showing higher does levitra help you last longer seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferon‐gamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network and sexual HIV transmission in men who have sex with does levitra help you last longer men. Clin Infect Dis. 2020;71:2655–2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete does levitra help you last longer datasetsWorldwide, over 250 million people are estimated to live with chronic hepatitis B (CHB), although only ~11% is diagnosed and a minority receives antiviral therapy. An estimate of the global proportion eligible for treatment was not previously available.

A systematic review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine aminotransferase, hepatitis B levitra DNA >2000 or >20 000 IU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per does levitra help you last longer WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis. However, the estimate does levitra help you last longer should be interpreted with caution due to incomplete data acquisition and reporting in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al.

Estimating the proportion of people with chronic hepatitis B levitra eligible for hepatitis B antiviral treatment worldwide does levitra help you last longer. A systematic review and meta-analysis. Lancet Gastroenterol does levitra help you last longer Hepatol, 2021. 6:106–119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236 127 women with HIV.

HIV markedly increased the risk of cervical does levitra help you last longer cancer (pooled relative risk 6.07. 95% CI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV globally, although does levitra help you last longer the population-attributable fraction for HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in the African region. Cervical cancer is preventable and treatable.

Efforts are needed to expand access does levitra help you last longer to HPV vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al. Estimates of does levitra help you last longer the global burden of cervical cancer associated with HIV. Lancet Glob Health.

2020. 9:e161–69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma levitra Most cervical high-risk human papilloma levitra (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al. Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women.

J Infect Dis 2020. Online ahead of printPublished in STI—the editor’s choice. One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal).

Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7–15) between tests. Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556–561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI). The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women.

A recent meta-analysis of over 37 000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15–24 year-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited. The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia.

Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017. Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16–35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Counselling messages related to HIV risk were implemented consistently across the three groups throughout the trial.6The trial was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from participants or their parents/guardians and human experimentation guidelines of the United States Department of Health and Human Services and those of the authors' institution(s) were followed.Contraceptive exposureAt enrolment, women were randomly assigned (1:1:1) to DMPA-IM, copper IUD or LNG implant.6 Participants received an injection of 150 mg/mL DMPA-IM (Depo Provera. Pfizer, Puurs, Belgium) at enrolment and every 3 months until the final visit at 18 months after enrolment, a copper IUD (Optima TCu380A. Injeflex, Sao Paolo, Brazil) or a LNG implant (Jadelle.

Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1 month after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up. Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits.

Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion. Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex levitra type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders. Study site and age were retained in the final model.

Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit. Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1).

Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit. Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device. LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1).

Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up. Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods.

During the first 6 months, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups. Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25–35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C). Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively).

Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95% CI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95% CI (0.81 to 1.04)). Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95% CI (0.72 to 0.95)).

Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2). Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95% CI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95% CI (0.93 to 1.49)).

Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95% CI (0.52 to 0.87)). Results from as randomised and continuous use analyses did not differ. And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm.

Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group. The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B).

Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms. Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment." data-icon-position data-hide-link-title="0">Figure 3 Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D). Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain.

Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance. These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis.

Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes. Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10–12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge. More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment.

Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups. Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant.

However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini. While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

Routine access to more reliable diagnostics, like NAAT and novel point-of-care diagnostic tests, will be key to managing asymptomatic STIs and reducing STI prevalence and related morbidities in these settings.17This secondary analysis of the ECHO trial has strengths and limitations. Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method. It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively.

Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic. Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..

A broadly neutralising antibody to prevent HIV click here now transmissionTwo HIV prevention trials (HVTN 704/HPTN 085 buy generic levitra uk. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse events related to VRC01 were buy generic levitra uk uncommon. In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of levitraes circulating in the trial regions).

However, VRC01 did not buy generic levitra uk prevent with other HIV isolates and overall HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al. Two randomized trials of neutralizing buy generic levitra uk antibodies to prevent HIV-1 acquisition. N Engl J Med.

2021;384:1003–1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel of 34 cytokines/chemokines in blood and semen of buy generic levitra uk men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their partners and 22 who did not. Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in buy generic levitra uk seminal fluid, but not in blood, differed significantly between transmitters and non-transmitters, with transmitters showing higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferon‐gamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network and sexual HIV transmission in men who have sex with men buy generic levitra uk. Clin Infect Dis. 2020;71:2655–2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 million people are estimated to live with chronic buy generic levitra uk hepatitis B (CHB), although only ~11% is diagnosed and a minority receives antiviral therapy. An estimate of the global proportion eligible for treatment was not previously available.

A systematic review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence buy generic levitra uk of cirrhosis, abnormal alanine aminotransferase, hepatitis B levitra DNA >2000 or >20 000 IU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis. However, the estimate should be interpreted with caution due to incomplete data acquisition and buy generic levitra uk reporting in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al.

Estimating the proportion of buy generic levitra uk people with chronic hepatitis B levitra eligible for hepatitis B antiviral treatment worldwide. A systematic review and meta-analysis. Lancet Gastroenterol buy generic levitra uk Hepatol, 2021. 6:106–119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236 127 women with HIV.

HIV markedly increased the risk of cervical buy generic levitra uk cancer (pooled relative risk 6.07. 95% CI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV buy generic levitra uk globally, although the population-attributable fraction for HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in the African region. Cervical cancer is preventable and treatable.

Efforts are needed to buy generic levitra uk expand access to HPV vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global buy generic levitra uk burden of cervical cancer associated with HIV. Lancet Glob Health.

2020. 9:e161–69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma levitra Most cervical high-risk human papilloma levitra (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al. Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women.

J Infect Dis 2020. Online ahead of printPublished in STI—the editor’s choice. One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal).

Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7–15) between tests. Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556–561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI). The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women.

A recent meta-analysis of over 37 000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15–24 year-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited. The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia.

Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017. Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16–35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Counselling messages related to HIV risk were implemented consistently across the three groups throughout the trial.6The trial was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from participants or their parents/guardians and human experimentation guidelines of the United States Department of Health and Human Services and those of the authors' institution(s) were followed.Contraceptive exposureAt enrolment, women were randomly assigned (1:1:1) to DMPA-IM, copper IUD or LNG implant.6 Participants received an injection of 150 mg/mL DMPA-IM (Depo Provera. Pfizer, Puurs, Belgium) at enrolment and every 3 months until the final visit at 18 months after enrolment, a copper IUD (Optima TCu380A. Injeflex, Sao Paolo, Brazil) or a LNG implant (Jadelle.

Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1 month after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up. Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits.

Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion. Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex levitra type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders. Study site and age were retained in the final model.

Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit. Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1).

Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit. Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device. LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1).

Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up. Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods.

During the first 6 months, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups. Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25–35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C). Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively).

Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95% CI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95% CI (0.81 to 1.04)). Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95% CI (0.72 to 0.95)).

Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2). Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95% CI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95% CI (0.93 to 1.49)).

Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95% CI (0.52 to 0.87)). Results from as randomised and continuous use analyses did not differ. And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm.

Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group. The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B).

Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms. Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment." data-icon-position data-hide-link-title="0">Figure 3 Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D). Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain.

Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance. These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis.

Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes. Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10–12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge. More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment.

Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups. Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant.

However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini. While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

Routine access to more reliable diagnostics, like NAAT and novel point-of-care diagnostic tests, will be key to managing asymptomatic STIs and reducing STI prevalence and related morbidities in these settings.17This secondary analysis of the ECHO trial has strengths and limitations. Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method. It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively.

Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic. Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..

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Pixabay“Triclosan’s increasingly broad use where can i buy levitra in consumer products presents a risk of liver toxicity for humans,” said Robert H. Tukey, PhD, professor in the Department of Pharmacology at UC San Diego School of Medicine. €œOur study shows that common factors that we encounter in every-day life — the ubiquitous presence of triclosan, together with the prevalence of high consumption of dietary fat —constitute a good recipe for the development of fatty liver disease in mice.”Tukey led the study with Mei-Fei Yueh, PhD, a project scientist in his lab, and Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at UC San Diego School of Medicine.In a 2014 mouse study, the team found triclosan exposure promoted liver tumor formation by interfering with a protein responsible for clearing away foreign chemicals in where can i buy levitra the body. In the latest study, the researchers fed a high-fat diet to mice with type 1 diabetes. As previous studies have shown, the high-fat diet led to non-alcoholic fatty liver disease (NAFLD).

In humans, NAFLD is where can i buy levitra an increasingly common condition that can lead to liver cirrhosis and cancer. Diabetes and obesity are risk factors for NAFLD. Some of the mice where can i buy levitra were also fed triclosan, resulting in blood concentrations comparable to those found in human studies. Compared to mice only fed a high-fat diet, triclosan accelerated the development of fatty liver and fibrosis. According to the study, here’s what’s likely happening.

Eating a high-fat diet normally tells cells to produce more fibroblast growth factor 21, which helps protects liver cells from where can i buy levitra damage. Tukey and team discovered that triclosan messes with two molecules, ATF4 and PPARgamma, which cells need to make the protective growth factor. Not only where can i buy levitra that, the antimicrobial also disrupted a variety of genes involved in metabolism. In addition, the mice exposed to triclosan had less diversity in their gut microbiomes — fewer types of bacteria living in the intestines, and a makeup similar to that seen in patients with NAFLD. Less gut microbiome diversity is generally associated with poorer health.So far, these findings have only been observed in mice who ingested triclosan.

But since these same molecular systems also operate in humans, the where can i buy levitra new information will help researchers better understand risk factors for NAFLD, and give them a new place to start in designing potential interventions to prevent and mitigate the condition. €œThis underlying mechanism now gives us a basis on which to develop potential therapies for toxicant-associated NAFLD,” said Tukey, who is also director of the National Institute of Environmental Health Sciences Superfund Program at UC San Diego.In 2016, the U.S. Food and where can i buy levitra Drug Administration (FDA) ruled that over-the-counter wash products can no longer contain triclosan, given that it has not been proven to be safe or more effective than washing with plain soap and water. However, the antimicrobial is still found in some household and medical-grade products, as well as aquatic ecosystems, including sources of drinking water.An estimated 100 million adults and children in the U.S. May have NAFLD.

The precise cause of NAFLD is unknown, but diet and genetics play substantial roles where can i buy levitra. Up to 50 percent of people with obesity are believed to have NAFLD. The condition typically isn’t where can i buy levitra detected until it’s well advanced. There are no FDA-approved treatments for NAFLD, though several medications are being developed. Eating a healthy diet, exercising and losing weight can help patients with NAFLD improve.Additional co-authors of the study include.

Feng He, Chen Chen, Catherine Vu, Anupriya Tripathi, Rob Knight, and Shujuan Chen, all at UC San Diego.Funding for this research came, in part, from the National where can i buy levitra Institutes of Health (grants ES010337, R21-AI135677, GM126074, CA211794, CA198103, DK120714), Eli Lilly and UC San Diego Center for Microbiome Innovation. Disclosure. Michael Karin is a founder, inventor and an Advisory Board Member of Elgia Therapeutics and has equity in the company..

News ReleaseMonday, December 21, 2020RADx-rad program will fund buy generic levitra uk non-traditional and repurposed technologies http://www.ec-rodolphe-reuss-ii-strasbourg.site.ac-strasbourg.fr/wp/?p=3527 to combat the current levitra and address future viral disease outbreaks. The National Institutes of Health has awarded over $107 million to support new, non-traditional approaches and reimagined uses of existing tools to address gaps in erectile dysfunction treatment testing and surveillance. The program also will develop platforms that can be deployed in future outbreaks of buy generic levitra uk erectile dysfunction treatment and other infectious diseases. A part of the Rapid Acceleration of Diagnostics (RADx) initiative, the awards from the RADx Radical (RADx-rad) program will support 49 research projects and grant supplements at 43 institutions across the United States. It will focus on non-traditional viral screening approaches, such as biological or physiological markers, new analytical platforms with novel chemistries or engineering, rapid detection strategies, point-of-care devices, and home-based testing technologies.

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Development of buy generic levitra uk novel, safe and effective biosensing and detection technologies to spot signatures of erectile dysfunction treatment from human skin or mouth. Development of an innovative platform that integrates biosensing with touchscreen or other digital devices to achieve automatic, early detection and tracing of erectile dysfunction in real-time. Development of buy generic levitra uk a novel test to independently assess smell and taste function in individuals who are at high risk for contracting erectile dysfunction treatment. Development of wastewater technologies and data collection methods for detecting and estimating erectile dysfunction community levels, which can offer advanced knowledge of community spread and allow for targeted public health protection measures. Implementation of devices with integrated artificial intelligent systems for the detection, diagnosis, prediction, prognosis and monitoring of erectile dysfunction treatment in clinical, community and everyday settings.

Characterization of the spectrum of SARS CoV-2 associated illness, including the multisystem inflammatory syndrome buy generic levitra uk in children (MIS-C). Development of biomarkers and biosignatures for an algorithm utilizing artificial intelligence to predict the long-term risk of disease severity after a child is exposed to erectile dysfunction.Additionally, two intramural projects were supported by this initiative. A $1 million award to the National Institute buy generic levitra uk of Environmental Health Sciences for developing barcoded screening of erectile dysfunction. And a $200,000 award to the National Library of Medicine (NLM) for a Nationwide Early-Warning System and Data Platform to aid policy decisions for public health management of viral diseases with erectile dysfunction treatment as a use case. RADx-rad grants and supplements are supported by 11 NIH institutes and centers, including the National Center for Advancing Translational Sciences, the National Institute of Dental and Craniofacial Research, the National Heart, Lung, and Blood Institute, the National Institute on Drug Abuse, the National Institute on Alcohol Abuse and Alcoholism, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute on Deafness and Other Communication Disorders, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Minority Health and Health Disparities, the National Institute of Nursing Research, and NLM.

About the Rapid Acceleration of buy generic levitra uk Diagnostics (RADxSM) initiative. The RADx initiative was launched on April 29, 2020, to speed innovation in the development, commercialization and implementation of technologies for erectile dysfunction treatment testing. The initiative has buy generic levitra uk four programs. RADx Tech, RADx Advanced Technology Platforms, RADx Underserved Populations and RADx Radical. It leverages the existing NIH Point-of-Care Technology Research Network.

The RADx initiative partners with federal agencies, including the Office of the Assistant Secretary of Health, Department of Defense, the Biomedical Advanced buy generic levitra uk Research and Development Authority, and U.S. Food and Drug Administration. Learn more about the RADx buy generic levitra uk initiative and its programs. Https://www.nih.gov/radx.About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services.

NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases buy generic levitra uk. For more information about NIH and its programs, visit www.nih.gov. NIH…Turning Discovery Into Health®###​University of California San Diego School of Medicine researchers found evidence that triclosan — an antimicrobial found in many soaps and other household items — worsens fatty liver buy generic levitra uk disease in mice fed a high-fat diet.The study, published November 23, 2020 in Proceedings of the National Academy of Sciences, also details the molecular mechanisms by which triclosan disrupts metabolism and the gut microbiome, while also stripping away liver cells’ natural protections. Triclosan, an antimicrobial found in many soaps and other household items, worsens fatty liver disease in mice fed a high-fat diet. Credit.

Pixabay“Triclosan’s increasingly buy generic levitra uk broad use in consumer products presents a risk of liver toxicity for humans,” said Robert H. Tukey, PhD, professor in the Department of Pharmacology at UC San Diego School of Medicine. €œOur study shows that common factors that we encounter in every-day life — the ubiquitous presence of triclosan, together with the prevalence of high consumption of dietary fat —constitute a good recipe for the development of fatty liver disease in mice.”Tukey led the study with Mei-Fei Yueh, PhD, a project scientist in his lab, and Michael Karin, PhD, Distinguished buy generic levitra uk Professor of Pharmacology and Pathology at UC San Diego School of Medicine.In a 2014 mouse study, the team found triclosan exposure promoted liver tumor formation by interfering with a protein responsible for clearing away foreign chemicals in the body. In the latest study, the researchers fed a high-fat diet to mice with type 1 diabetes. As previous studies have shown, the high-fat diet led to non-alcoholic fatty liver disease (NAFLD).

In humans, NAFLD is an increasingly common condition that can lead to liver cirrhosis buy generic levitra uk and cancer. Diabetes and obesity are risk factors for NAFLD. Some of the mice were also fed triclosan, resulting in blood concentrations comparable to those found buy generic levitra uk in human studies. Compared to mice only fed a high-fat diet, triclosan accelerated the development of fatty liver and fibrosis. According to the study, here’s what’s likely happening.

Eating a high-fat diet normally tells cells to produce more fibroblast growth factor 21, which buy generic levitra uk helps protects liver cells from damage. Tukey and team discovered that triclosan messes with two molecules, ATF4 and PPARgamma, which cells need to make the protective growth factor. Not only buy generic levitra uk that, the antimicrobial also disrupted a variety of genes involved in metabolism. In addition, the mice exposed to triclosan had less diversity in their gut microbiomes — fewer types of bacteria living in the intestines, and a makeup similar to that seen in patients with NAFLD. Less gut microbiome diversity is generally associated with poorer health.So far, these findings have only been observed in mice who ingested triclosan.

But since these same buy generic levitra uk molecular systems also operate in humans, the new information will help researchers better understand risk factors for NAFLD, and give them a new place to start in designing potential interventions to prevent and mitigate the condition. €œThis underlying mechanism now gives us a basis on which to develop potential therapies for toxicant-associated NAFLD,” said Tukey, who is also director of the National Institute of Environmental Health Sciences Superfund Program at UC San Diego.In 2016, the U.S. Food and buy generic levitra uk Drug Administration (FDA) ruled that over-the-counter wash products can no longer contain triclosan, given that it has not been proven to be safe or more effective than washing with plain soap and water. However, the antimicrobial is still found in some household and medical-grade products, as well as aquatic ecosystems, including sources of drinking water.An estimated 100 million adults and children in the U.S. May have NAFLD.

The precise cause of NAFLD is unknown, but diet and genetics buy generic levitra uk play substantial roles. Up to 50 percent of people with obesity are believed to have NAFLD. The condition typically isn’t detected buy generic levitra uk until it’s well advanced. There are no FDA-approved treatments for NAFLD, though several medications are being developed. Eating a healthy diet, exercising and losing weight can help patients with NAFLD improve.Additional co-authors of the study include.

Feng He, Chen Chen, Catherine Vu, Anupriya Tripathi, Rob Knight, and Shujuan Chen, all at UC San Diego.Funding for this research came, in part, from the National Institutes of Health (grants ES010337, R21-AI135677, buy generic levitra uk GM126074, CA211794, CA198103, DK120714), Eli Lilly and UC San Diego Center for Microbiome Innovation. Disclosure. Michael Karin is a founder, inventor and an Advisory Board Member of Elgia Therapeutics and has equity in the company..