Can you get cipro over the counter

As part of our ongoing commitment to prioritizing healing and humanity as we stand against social injustice, Mathematica is http://robertrizzo.com/can-you-get-cipro-over-the-counter/ pleased to announce that President and CEO Paul Decker is joining more than 1,300 CEOs and business leaders can you get cipro over the counter as a member of CEO Action for Diversity and Inclusion™. This coalition represents the largest CEO-driven business commitment to advancing workplace diversity, equity, and inclusion, while working to ensure opportunity at the highest levels of corporate leadership.“During a time when the nation continues to be tested by unresolved issues of social justice, Mathematica has taken significant strides toward centering diversity, equity, and inclusion in our interactions with each other and in our approach to our work,” said Decker. €œToday, we’re taking another important step forward by joining CEO Action for can you get cipro over the counter Diversity and Inclusion, an organization that unites business leaders from around the world to advance DEI initiatives in our own workplaces and beyond.

I’m honored to represent Mathematica in this coalition fighting for meaningful change.”CEO Action represents approximately 13 million employees across more than 85 industries. As a member through its CEO, Mathematica has committed to dedicating time and resources to advancing diversity, equity, and inclusion both within Mathematica and as part of the CEO Action network. Decker has also taken the CEO Action pledge to “check my bias, speak up for others and show up for all.”A 100% employee-owned company, Mathematica works with private- and public-sector agencies, corporations, and foundations around the world, using data and evidence to improve can you get cipro over the counter the lives of people and communities.

About CEO Action for Diversity &. Inclusion™ CEO can you get cipro over the counter Action for Diversity &. Inclusion™ is the largest CEO-driven business commitment to advance diversity and inclusion within the workplace.

Bringing together more than 1,000 CEOs of America’s leading organizations, the commitment outlines actions that participating companies pledge to take to cultivate a workplace where diverse perspectives and experiences are welcomed and respected, employees feel comfortable and encouraged to discuss diversity and inclusion, and where best known—and successful—actions can be shared across organizations. Learn more at CEOAction.com and connect with can you get cipro over the counter them on Twitter. @CEOAction.

For more information, please contact:Jennifer de Vallancejdevallance@mathematica-mpr.com202-484-4692.

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In 1945, as World cipro nausea War II came to a More about close, scientists logged a record drop in carbon dioxide emissions. They reckoned that global CO2 emissions fell by some 790 million metric tons—a record that stood for more than 70 years. Then 2020 cipro nausea rolled around. Global emissions fell 1,550 million metric tons in the first half of 2020, according to a study published yesterday in Nature Communications, obliterating the 1945 record and underlining the depths of the economic damage wrought by the antibiotics cipro this year.

The study, conducted by a team of 43 scientists from across the world, confirms earlier research on the emissions impact of the cipro (Climatewire, May 20). It at once highlighted how much emissions have fallen as a result of the cipro and the difficult road facing the world as it cipro nausea seeks to meet the targets of the Paris climate agreement. The world essentially would need to replicate 2020’s emission reductions every year for the next decade to have any chance of limiting warming to 1.5 degrees Celsius by century’s end, according to the United Nations’ Intergovernmental Panel on Climate Change. €œConsidering how disruptive the cipro has been in all our lives, it seems like a small number,” said Steven Davis, a professor at the University of California, Irvine, who contributed to the study.

€œThe task of decarbonizing our planet will not mean just changes in personal behavior but changes in the energy structure.” In the immediate term, the study’s largest cipro nausea impact may be on emissions monitoring itself. Researchers compiled a lengthy list of real-time energy and emissions statistics from countries around the world. The authors described the effort as a major step forward for a field that has traditionally relied on previous years’ cipro nausea data to develop emissions estimates. €œThe cipro has really forced our hand to do better and find these data sources where they are,” Davis said, noting that researchers plan to continue the emissions monitoring efforts.

€œWhat is critical is we need to shorten the feedback cycle from the policymaker putting some policy in place to the scientific community telling the policymaker whether that has had an effect on emissions.” The data sources allowed researchers to pinpoint the locations of emission reductions as the cipro rolled across the world. The year began with deep reductions in emissions in China, where the shutdown of heavy industry and resulting drop cipro nausea in power demand led to big decreases in CO2. Emissions from the Chinese cement industry, about 22% of the country’s industrial emissions, fell by a combined 30% in January and February compared to 2019 levels. But cement emissions began to surge as the Chinese economy jolted back to life.

By April, cipro nausea Chinese cement emissions were up 3.8% over the same month last year. The rebound in Chinese economic activity, and cement in particular, helps explain the relatively modest 3.7% reduction, or 187 million tons, in overall Chinese emissions over the first half of 2020. By the spring, the cipro nausea cipro had the United States and Europe in its grasp. There, the emissions reduction story was largely about transportation.

American transportation emissions, the largest source of CO2 emissions in the U.S., were down 24% over the first seven months of 2020. Overall U.S cipro nausea. Emissions fell 13.8% compared to 2019 levels or by 338 million tons, the largest absolute drop in the world. Still, the study suggests the cipro has not altered the worldwide energy system in a fundamental way.

Emissions across the cipro nausea globe were rebounding quickly as large parts of the world began to shake off the cipro over the summer. The research team has continued to monitor emissions beyond the time period in the Nature Communications study. By August, they showed that world emissions had fallen 1,481 million tons since the start of the year, suggesting that some of the reductions from earlier in the year already have been offset. Reprinted from Climatewire with permission cipro nausea from E&E News.

E&E provides daily coverage of essential energy and environmental news at www.eenews.net.The human eye is a limited organ. The portion of the electromagnetic spectrum that we can see is about 0.0035 percent of the total cipro nausea light in the universe. Without any aid, a normal human eye with 20/20 vision can clearly view up to only about five kilometers (about three miles) in the distance and can distinguish an object as small as about 0.1 millimeter. Just as spyglasses and telescopes extended our range of sight across Earth and into the cosmos, light microscopes allow us to peer at scales hundreds of times smaller than we would otherwise be able to detect.

Such technology has bred innumerable discoveries in medicine, biology, geology and cipro nausea plant science. For 46 years, camera company Nikon has run its Small World contest, which prizes excellence in photography at the tiniest scales—achieved with the aid of the light microscope. Scientists make up a substantial proportion of contest entrants because their work naturally lends itself to stunning visualization. Below is this year’s first-place winner and our editors’ picks for cipro nausea the best images.

As entrant Jason Kirk of the Baylor College of Medicine says, the contest is a “unique opportunity to celebrate the convergence of art and science. Images like cipro nausea the ones showcased here are a [wonderful] bridge between the scientific community and the general public.” This year’s winning image of a juvenile zebra fish was captured as part of research by a team at the National Institutes of Health. They discovered that zebra fish have lymphatic vessels inside their skull—a feature previously thought to only occur in mammals. Such a discovery could expedite and revolutionize research related to neurological diseases such as Alzheimer’s.

The researchers stitched together more than 350 individual cipro nausea images to create this single one. Radula, or “tongue,” of a freshwater snail, stained and captured as a stack of images. The realm of tiny animals is replete with bizarre and sometimes alien forms, says the image’s creator, Igor Siwanowicz of Howard Hughes Medical Institute, who obtained the snail from his lab mate’s aquarium. €œIt's a snail's tongue, looking like a decadent rococo chandelier,” he adds cipro nausea.

The image won third place. Scale from the wing of a blue emperor butterfly (Papilio ulysses) cipro nausea. Photographer Yousef Al Habshi, says the challenge in creating this image was finding the correct focal balance between the camera and the scales to capture the light, avoiding overexposure or underexposure. Daphnia, a water microorganism.

To create this image, photographer Paweł Błachowicz used cipro nausea the reflected-light technique. Light bounces off the subject and is captured by the camera. This method is usually reserved for opaque objects, Błachowicz says, so he was surprised at this striking outcome. €œDaphnia is cipro nausea a transparent organism, and despite this, with the reflected-light technique, it looks astonishing,” he adds.

Crystals formed after heating an ethanol-and-water solution containing L-glutamine and beta-alanine. The proportions of both amino acids must be precisely balanced in order to form such striking crystal structures, says photographer Justin Zoll. He used a polarized-light cipro nausea filter to capture this image, which won 13th place. Lateral view of a leaf-roller weevil (Byctiscus betulae).

The hard exoskeleton is highly reflective and therefore challenging to capture, says photographer Özgür Kerem Bulur, who had to balance the light properly in order to cipro nausea capture these rainbow colors. This image won 14th place. Head of a tapeworm (Taenia pisiformis) from the gut of a rabbit. The angle of this cipro nausea photograph shows the “teeth” on the edge of the parasite’s head that help it embed itself in its host’s digestive tract.

€œI love the image's geometrical beauty, its sculptural qualities and its ambiguity,” says image creator David Maitland. €œIs it a fossil or something embedded in sandstone?. What is cipro nausea it?. € Credit.

Jason Kirk Baylor College of Medicine Microtubules (orange) inside a bovine cipro nausea pulmonary artery endothelial cell. The nucleus is shown in cyan. In his work, Jason Kirk of the Baylor College of Medicine uses such cells to benchmark the performance of his microscopy equipment. But the end result, which cipro nausea won seventh place, deserves acknowledgement for its artistic value.

Science in Images is a new category of articles featuring photographs and videos from all the disciplines of science. Click on the button below to see the full collection. Science in cipro nausea Images“Clow-dia,” I say once. Twice.

A third time cipro nausea. Defeated, I say the Americanized version of my name. €œClaw-dee-ah.” Finally, Siri recognizes it. Having to adapt our way of speaking to interact with speech-recognition technologies is a familiar experience for people whose first language is not English or who cipro nausea do not have conventionally American-sounding names.

I have now stopped using Siri, Apple's voice-based virtual assistant, because of it. The growth of this tech in the past decade—not just Siri but Alexa and Cortana and others—has unveiled a problem in it. Racial bias cipro nausea. One recent study, published in the Proceedings of the National Academy of Sciences USA, showed that speech-recognition programs are biased against Black speakers.

On average, the authors found, all five programs from leading technology companies, including Apple and Microsoft, showed significant race disparities. They were roughly twice as cipro nausea likely to incorrectly transcribe audio from Black speakers compared with white speakers. This effectively censors voices that are not part of the “standard” languages or accents used to create these technologies. €œI don't get to negotiate with these devices unless I adapt my language patterns,” says Halcyon Lawrence, an assistant professor of technical communication and information design cipro nausea at Towson University, who was not part of the study.

€œThat is problematic.” For Lawrence, who has a Trinidad and Tobagonian accent, or for me as a Puerto Rican, part of our identity comes from speaking a particular language, having an accent or using a set of speech forms such as African American Vernacular English (AAVE). Having to change such an integral part of an identity to be able to be recognized is inherently cruel. The inability to be understood impacts other marginalized communities, such as people with visual or movement disabilities who rely on voice cipro nausea recognition and speech-to-text tools, says Allison Koenecke, a computational graduate student and first author of the PNAS study. For someone with a disability who is dependent on these technologies, being misunderstood could have serious consequences.

There are probably many culprits for these disparities, but Koenecke points to the most likely. The data used for training, which are predominantly cipro nausea from white, native speakers of American English. By using databases that are narrow both in the words that are used and how they are said, training systems exclude accents and other ways of speaking that have unique linguistic features. Humans, presumably including cipro nausea those who create these technologies, have accent and language biases.

For example, research shows that the presence of an accent affects whether jurors find people guilty and whether patients find their doctors competent. Recognizing these biases would be an important way to avoid implementing them in technologies. But developing more inclusive technology takes time, effort and money, and often the decision to invest cipro nausea these are market-driven. (In response to several queries, only a Google spokesperson responded in time for publication, saying, in part, “We've been working on the challenge of accurately recognizing variations of speech for several years and will continue to do so.”) Safiya Noble, an associate professor of information studies at the University of California, Los Angeles, admits that it's a tricky challenge.

€œLanguage is contextual,” says Noble, who was not involved in the study. €œBut that doesn't mean that companies shouldn't strive to decrease bias and disparities.” To do this, cipro nausea they need the input of humanists and social scientists who understand how language actually works. From the tech side, feeding more diverse training data into the programs could close this gap, Koenecke says. Noble adds that tech companies should also test their products more widely and have more diverse workforces cipro nausea so people from different backgrounds and perspectives can directly influence the design of speech technologies.

Koenecke suggests that automated speech-recognition companies use the PNAS study as a preliminary benchmark and keep using it to assess their systems over time. In the meantime, many of us will continue to struggle between identity and being understood when interacting with Alexa, Cortana or Siri. But Lawrence chooses identity cipro nausea every time. €œI'm not switching,” she says.

€œI'm not doing it.”Hiral Tipirneni spent nearly a decade working in emergency medicine in Arizona. She started out 23 years ago at Banner Good Samaritan Hospital in downtown Phoenix, treating patients with cipro nausea broken bones, failing hearts and a lot of other problems. Then some health tragedies hit home. €œOur family suffered a great loss to cancer.

My mom cipro nausea and nephew,” she says. Tipirneni felt she should do something to combat the illness that took her loved ones. In 2010 she accepted a position as a scientific review officer for the Society of Research Administrators International, a global research management cipro nausea group overseeing cancer studies. But when Donald Trump was elected U.S.

President in 2016, “I was terrified of the threats of ‘repeal and replace’ of the Affordable Care Act,” she recalls. €œAfter years spent in the ER seeing thousands of families cipro nausea come through with no access to health care..., it was too much to stand by. That prompted me to throw my hat into the ring.” Following a failed bid for a seat in the House of Representatives during a 2018 special election, Tipirneni, a Democrat, is running for the state’s sixth congressional district in the November 3 election. The district includes part of Maricopa county and some Phoenix suburbs.

She is challenging Republican incumbent David Schweikert, a former businessman now serving his fourth consecutive term in cipro nausea that seat and his fifth overall in the House. Republicans have held this seat since 1995. But in cipro nausea the middle of a cipro that has killed more than 5,700 Arizonans—more than 3,400 of them in Maricopa County—Tipirneni is hoping her medical background will carry weight with voters. €œWe see decision after decision being made not based on data, not based on science, but rather on political expediency, partisanship—or based on the election calendar,” she says.

€œThat’s blasphemy for a scientist or physician.” Tipirneni is one of several candidates with a scientific background running for federal office this fall. The election will serve as cipro nausea the political climax to a year that saw raging wildfires fueled by climate change, devastating hurricanes and the buy antibiotics cipro, which has claimed the lives of more than 216,000 Americans—a death toll medical experts say has been driven high by politicians who have ignored public health guidelines. Given these catastrophic outcomes, Tipirneni and another physician-politician, Barbara Bollier, who is running for an open U.S. Senate seat in Kansas, hope voters will be swayed by candidates who tout respect for science when making policy decisions.

Both races are incredibly close, with recent polls showing Tipirneni and Bollier either ahead or behind their opponents by only a few percentage points cipro nausea. The stakes are high. If Democrats manage to flip a Senate seat in Kansas, along with achieving a few other wins, they will gain control of the Senate cipro nausea. And Tipirneni winning in Arizona could help them hold onto their majority in the House.

Both outcomes would put Democrats in charge of the two houses of Congress, ending the current split with Republicans. €œAfter a big military conflict, you often see a surge in military veterans running cipro nausea for office,” says Eitan Hersh, a political scientist at Tufts University. €œFollowing the 2016 election, more women ran than ever before [in the midterms.] And after buy antibiotics, it’s not surprising that some physicians would run for office, feeling like their voices need to be heard. If there’s a big surge in doctors running, some will get in.” Grand Battle in the Grand Canyon State In Arizona, Tipirneni has raised more than $1 million more in campaign funding than Schweikert.

Generally, a September poll by the Arizona cipro nausea Policy Lab found that science-based approaches to fighting buy antibiotics, including mask mandates, were popular among Arizonan voters in both parties. €œThere is really strong disapproval for how Donald Trump and how Republican governor Doug Ducey have handled buy antibiotics,” says Samara Klar, a political scientist at the University of Arizona. Ducey, for instance, pushed hard for the resumption of activities with few restrictions in the spring, only to see a surge in buy antibiotics cases that forced another shutdown. Klar adds that polls show that “at the same time, there’s been strong support for how local mayors have dealt with it.” This, she says, could hurt the Republicans’ chances cipro nausea in Arizona.

Schweikert did not respond to requests for comment from Scientific American. He has been a vocal supporter of the use of masks, cipro nausea however. In a July tweet, he encouraged his constituents to “continue wearing our face coverings when out in public, or when in close proximity to others.” He also advocated for increased access to federal resources to purchase items such as personal protective equipment (PPE). €œWe ...

Ask the U.S cipro nausea. Department of Health and Human Resources (HHS) and the Federal Emergency Management Agency (FEMA) for an immediate influx of federal resources to combat the cipro, through increased testing, contact tracing, personal protective equipment (PPE), staffing support, and emergency funding for local initiatives to respond to and mitigate further spread,” he and four other Arizonan congresspeople wrote in a letter in August. But despite Schweikert’s support for public health practices, his messages may be tainted by the president’s handling of the cipro. Recent polls show that Republicans cipro nausea have begun to drift away from Trump.

Biden currently leads Trump, 49 percent to 41 percent, in Arizona. On energy policy, Schweikert and Tipirneni’s cipro nausea messaging diverges. €œArizona should be leading the charge on a renewable energy economy,” Tipirneni says, adding that those energy sources are key to reducing the impacts of climate change. €œBut we have leaders like my opponent, who has stood at every opportunity to block those kinds of initiatives because he is someone who still takes money from fossil fuels and is driven by party leadership to invest in other forms of energy.” Schweikert’s platform promotes an “‘all of the above’ energy solution,” tapping into “traditional energy reserves” but also expanding renewable energy resources.

In his time in the House, however, he has taken dozens of antienvironmental positions, including voting against protecting Chaco Canyon from oil and gas drilling, banning offshore drilling in the cipro nausea Atlantic and Pacific Ocean, and implementing methane pollution safeguards. The Kansas Contest Democrats have not cornered the market on physician candidates. In Kansas, Roger Marshall, a Republican representative in the House and an ob-gyn, is running against Bollier, a Democratic former anesthesiologist, creating a rare doctor-doctor duel. But despite sharing a medical background, the two appear diametrically opposed on issues pertaining to cipro nausea science.

Barbara Bollier (left) and Roger Marshall (right). Credit. Barbara Bollier Flickr (Bollier). Eric Connolly U.S.

House Office of Photography (Marshall) Bollier had been a Republican until she switched parties in 2018, and has served in the state’s legislature for a decade. She acknowledges that climate change is caused by people and has committed to greatly expand wind energy in the state. In contrast, Marshall has rejected the scientific consensus on climate, stating, “I’m not sure that there is even climate change” in 2017. His campaign Web site makes no mention of the issue.

Bollier “is a scientist and data nerd at heart,” says her communications director Alexandra De Luca. €œBarbara follows science. She always listens to the experts. Roger Marshall does not.

If Roger Marshall followed science, he wouldn’t be holding events indoors, shaking hands with vulnerable Kansans.” Bollier’s campaign, De Luca says, held more than 40 virtual town halls on Zoom this summer. And Bollier only began in-person campaigning in late August—always outdoors and physically distanced. Marshall did push for additional antibiotics testing kits for Kansas in April, saying that more testing could keep workers at large meat processing plants on the job—processors in Kansas had already had big outbreaks of the cipro. But Marshall differed from much medical research in May, when he told the Wall Street Journal he was taking the antimalarial drug hydroxychloroquine as a preventive measure against buy antibiotics.

Though touted by President Trump as a possible cure, the data supporting the medication was always sparse, and emergency authorization for it was revoked by the U.S. Food and Drug Administration in June. In the May article, Marshall added that he “would encourage any person over the age of 65 or with an underlying medical condition to talk to their own physician about taking hydroxychloroquine.” In September, Marshall wrote a Facebook post suggesting that most buy antibiotics deaths were from other ailments. Facebook deleted the post.

His campaign did not respond to Scientific American’s requests for an interview. Marshall regularly plays up his medical credentials. He has given himself the nickname “Doc,” and his Twitter username is @RogerMarshallMD. He also has used his medical skills to help in the cipro, he says.

In late April, Marshall tweeted, “Today, I began treating buy antibiotics patients on a volunteer basis in Wyandotte County, KS. I began the process of onboarding several days ago, and have started in the clinic today.” Thus far, polls show the race between Bollier and Marshall “as surprisingly close for a Republican state,” with all of them falling within the margin of error, says Don Haider-Markel, a political scientist at the University of Kansas. Despite electing a Democratic governor in 2018, he says, the state still leans conservative, and to have a competitive Democrat in the running is “not typical, to say the least.” After the economy and jobs, Haider-Markel observes, Kansans care most about the handling of the cipro in this election cycle—ranking that issue ahead of education and civil unrest. In the final days of campaigning, Democrats are trying to focus attention on health care, he adds, but “it’s not clear that voters are prioritizing that more than last month.” Bollier is likely succeeding at picking up moderate Republican and independent voters, Haider-Markel says.

Trump’s election alienated many Republican women in the suburbs in eastern Kansas and around Wichita who have likely switched to supporting the Democratic candidate, he explains. €œI think Bollier’s messaging on evidence-based policy will resonate with them—but they were already going to be more attracted to her to begin with.” Patti Doll, a 67-year-old former social worker who lives in Wichita, has been following the Senate race closely. She is a Democrat and says the cipro has made her pay greater attention to candidates’ adherence to scientific guidelines. Marshall, she notes with dissatisfaction, is still campaigning without a mask in October.

€œIt’s his job to lead and show people that this is important,” she says. €œIf it was switched, and it was Bollier who was a Republican, and Marshall was a Democrat, I would vote across party lines in this situation. It doesn’t matter to me. Follow the science.”Every time I log onto Facebook, I brace myself.

My newsfeed—like everyone else’s I know—is filled with friends, relatives and acquaintances arguing about buy antibiotics, masks and Trump. Facebook has become a battleground among partisan “echo chambers.” But what is it about social media that makes people so polarized?. To find out, my colleagues and I ran a social media experiment in which we divided Democrats and Republicans into “echo chambers,” or small groups whose members affiliate with just one political party. Next, we picked the most polarizing issues we could think of.

Immigration, gun control and unemployment. We asked each participant what they thought of those issues, then let people talk to each other and revise their opinions. After several rounds of discussion and revision, we evaluated each group’s viewpoint. To our surprise, the echo chambers did not make people more polarized, but less.

After interacting in social networks with likeminded peers, each echo chamber—Republican and Democrat—had adopted a more moderate opinion. All groups independently moved toward opinions that were closer to the opinions on the “opposite” side of the political spectrum. As a scientist who studies networks, I’m used to being surprised by the results of my experiments. Technology has allowed us to access more information and data about people’s social networks, debunking many of our assumptions about human behavior.

But even my team at the Network Dynamics Group was surprised. Why did our social media experiment find the opposite of what happens all the time in the real world of social media?. The answer lies in something social media has amplified. €œinfluencers.” By now, most of us have a fairly specific understanding of what an “influencer” is.

The word conjures up a young, wealthy person whose lifestyle is sponsored by brands like Instagram, TikTok or YouTube. But the word has a very specific network science meaning. In social media, networks tend to be centralized. A small number of people, or perhaps just one person, at the “center” of the network is connected to lots of other people in the “periphery.” The multitudes in the periphery of the social network have only a modest number of connections, while the few—the so-called “influencers”—at the center of the network are connected to nearly everyone.

This puts these people into the powerful position of being able to exert a disproportionate level of “influence” over the group. By contrast, the networks used in our study were “egalitarian”—the opposite of centralized. In an egalitarian network, everyone has an equal number of contacts, and therefore influence, throughout the network. The key feature of an egalitarian network is that new ideas and opinions can emerge from anywhere in the community and spread to everyone.

But in centralized networks—like many social media sites—ideas are filtered through, or sometimes even blocked, by a powerful social influencer. As I show in my upcoming book Change. The Power in the Periphery to Make Big Things Happen, centralized and egalitarian networks have very different effects on partisan bias and the acceptance of new ideas. In a centralized echo chamber, if the influencer at the middle shows even a small amount of partisan bias, it can become amplified throughout the entire group.

But in egalitarian networks, ideas spread based on their quality, and not the person touting them. There is a lot of wisdom in network peripheries, in regular people with good ideas. When the social network enables those people to talk with each other, new thinking that challenge a group’s biases can take hold and spread. To see how egalitarian networks might affect other kinds of contentious issues, we conducted another experiment with smokers and nonsmokers discussing the risks of cigarette smoking.

The effects were the same as with the partisan study. Both groups moved toward a more accurate understanding of smoking risks. Moreover, when participants were interviewed after the study, they reported having developed higher opinions of the other. Both smokers and nonsmokers had come to view the other group as more reasonable and trustworthy about the risks of smoking.

But the exchange of ideas and eradication of bias only works when networks are egalitarian. The problem of partisan bias is exacerbated on social media because online networks are often organized around a few key influencers. This feature of social media is one of the main reasons why misinformation and fake news has become so pervasive. In centralized networks, biased influencers have a disproportionate impact on their community—enabling small rumors and suppositions to become amplified into widespread misconceptions and false beliefs.

Our country has been struggling with bias and polarization a long time. But the issue is about to get much more urgent. As the debate over buy antibiotics vaccination heats up, biased viewpoints will undoubtedly become entrenched in communities with powerful influencers at their center. If we want to eradicate, or at least lessen the impacts of the antibiotics, we should rethink how our online communities operate.

The solution to the problem of treatment hesitancy is not to eliminate echo chambers. Rather, it is to be intentional about the social networks in those echo chambers. The more equity in people’s social networks, the less biased and more informed groups will become—even when those groups start off with highly partisan opinions..

In 1945, as World War II came to can you get cipro over the counter a close, scientists logged a record drop buy generic cipro in carbon dioxide emissions. They reckoned that global CO2 emissions fell by some 790 million metric tons—a record that stood for more than 70 years. Then 2020 can you get cipro over the counter rolled around. Global emissions fell 1,550 million metric tons in the first half of 2020, according to a study published yesterday in Nature Communications, obliterating the 1945 record and underlining the depths of the economic damage wrought by the antibiotics cipro this year. The study, conducted by a team of 43 scientists from across the world, confirms earlier research on the emissions impact of the cipro (Climatewire, May 20).

It at can you get cipro over the counter once highlighted how much emissions have fallen as a result of the cipro and the difficult road facing the world as it seeks to meet the targets of the Paris climate agreement. The world essentially would need to replicate 2020’s emission reductions every year for the next decade to have any chance of limiting warming to 1.5 degrees Celsius by century’s end, according to the United Nations’ Intergovernmental Panel on Climate Change. €œConsidering how disruptive the cipro has been in all our lives, it seems like a small number,” said Steven Davis, a professor at the University of California, Irvine, who contributed to the study. €œThe task can you get cipro over the counter of decarbonizing our planet will not mean just changes in personal behavior but changes in the energy structure.” In the immediate term, the study’s largest impact may be on emissions monitoring itself. Researchers compiled a lengthy list of real-time energy and emissions statistics from countries around the world.

The authors described the effort as a major step forward for a field that has traditionally relied on previous years’ data to develop can you get cipro over the counter emissions estimates. €œThe cipro has really forced our hand to do better and find these data sources where they are,” Davis said, noting that researchers plan to continue the emissions monitoring efforts. €œWhat is critical is we need to shorten the feedback cycle from the policymaker putting some policy in place to the scientific community telling the policymaker whether that has had an effect on emissions.” The data sources allowed researchers to pinpoint the locations of emission reductions as the cipro rolled across the world. The year began with deep reductions can you get cipro over the counter in emissions in China, where the shutdown of heavy industry and resulting drop in power demand led to big decreases in CO2. Emissions from the Chinese cement industry, about 22% of the country’s industrial emissions, fell by a combined 30% in January and February compared to 2019 levels.

But cement emissions began to surge as the Chinese economy jolted back to life. By April, Chinese cement emissions were up 3.8% over the same month last year can you get cipro over the counter. The rebound in Chinese economic activity, and cement in particular, helps explain the relatively modest 3.7% reduction, or 187 million tons, in overall Chinese emissions over the first half of 2020. By the spring, the cipro can you get cipro over the counter had the United States and Europe in its grasp. There, the emissions reduction story was largely about transportation.

American transportation emissions, the largest source of CO2 emissions in the U.S., were down 24% over the first seven months of 2020. Overall U.S can you get cipro over the counter. Emissions fell 13.8% compared to 2019 levels or by 338 million tons, the largest absolute drop in the world. Still, the study suggests the cipro has not altered the worldwide energy system in a fundamental way. Emissions across can you get cipro over the counter the globe were rebounding quickly as large parts of the world began to shake off the cipro over the summer.

The research team has continued to monitor emissions beyond the time period in the Nature Communications study. By August, they showed that world emissions had fallen 1,481 million tons since the start of the year, suggesting that some of the reductions from earlier in the year already have been offset. Reprinted from can you get cipro over the counter Climatewire with permission from E&E News. E&E provides daily coverage of essential energy and environmental news at www.eenews.net.The human eye is a limited organ. The portion of the electromagnetic can you get cipro over the counter spectrum that we can see is about 0.0035 percent of the total light in the universe.

Without any aid, a normal human eye with 20/20 vision can clearly view up to only about five kilometers (about three miles) in the distance and can distinguish an object as small as about 0.1 millimeter. Just as spyglasses and telescopes extended our range of sight across Earth and into the cosmos, light microscopes allow us to peer at scales hundreds of times smaller than we would otherwise be able to detect. Such technology has bred innumerable discoveries in can you get cipro over the counter medicine, biology, geology and plant science. For 46 years, camera company Nikon has run its Small World contest, which prizes excellence in photography at the tiniest scales—achieved with the aid of the light microscope. Scientists make up a substantial proportion of contest entrants because their work naturally lends itself to stunning visualization.

Below is this year’s first-place winner and our editors’ can you get cipro over the counter picks for the best images. As entrant Jason Kirk of the Baylor College of Medicine says, the contest is a “unique opportunity to celebrate the convergence of art and science. Images like can you get cipro over the counter the ones showcased here are a [wonderful] bridge between the scientific community and the general public.” This year’s winning image of a juvenile zebra fish was captured as part of research by a team at the National Institutes of Health. They discovered that zebra fish have lymphatic vessels inside their skull—a feature previously thought to only occur in mammals. Such a discovery could expedite and revolutionize research related to neurological diseases such as Alzheimer’s.

The researchers stitched together more than 350 individual images to create this single one can you get cipro over the counter. Radula, or “tongue,” of a freshwater snail, stained and captured as a stack of images. The realm of tiny animals is replete with bizarre and sometimes alien forms, says the image’s creator, Igor Siwanowicz of Howard Hughes Medical Institute, who obtained the snail from his lab mate’s aquarium. €œIt's a snail's tongue, looking like a decadent rococo chandelier,” he adds can you get cipro over the counter. The image won third place.

Scale from the wing of a blue can you get cipro over the counter emperor butterfly (Papilio ulysses). Photographer Yousef Al Habshi, says the challenge in creating this image was finding the correct focal balance between the camera and the scales to capture the light, avoiding overexposure or underexposure. Daphnia, a water microorganism. To create this image, photographer Paweł Błachowicz used the reflected-light technique can you get cipro over the counter. Light bounces off the subject and is captured by the camera.

This method is usually reserved for opaque objects, Błachowicz says, so he was surprised at this striking outcome. €œDaphnia is a transparent organism, and despite this, with the reflected-light technique, it looks astonishing,” he adds can you get cipro over the counter. Crystals formed after heating an ethanol-and-water solution containing L-glutamine and beta-alanine. The proportions of both amino acids must be precisely balanced in order to form such striking crystal structures, says photographer Justin Zoll. He used a polarized-light filter to capture this image, which won 13th place can you get cipro over the counter.

Lateral view of a leaf-roller weevil (Byctiscus betulae). The hard exoskeleton is highly reflective and therefore challenging to capture, says photographer Özgür Kerem Bulur, who had to balance the can you get cipro over the counter light properly in order to capture these rainbow colors. This image won 14th place. Head of a tapeworm (Taenia pisiformis) from the gut of a rabbit. The angle of this photograph shows the “teeth” on the edge of the parasite’s head that help it embed itself in its host’s digestive tract can you get cipro over the counter.

€œI love the image's geometrical beauty, its sculptural qualities and its ambiguity,” says image creator David Maitland. €œIs it a fossil or something embedded in sandstone?. What is it? can you get cipro over the counter. € Credit. Jason Kirk Baylor College of Medicine Microtubules (orange) inside can you get cipro over the counter a bovine pulmonary artery endothelial cell.

The nucleus is shown in cyan. In his work, Jason Kirk of the Baylor College of Medicine uses such cells to benchmark the performance of his microscopy equipment. But the end result, which won can you get cipro over the counter seventh place, deserves acknowledgement for its artistic value. Science in Images is a new category of articles featuring photographs and videos from all the disciplines of science. Click on the button below to see the full collection.

Science in can you get cipro over the counter Images“Clow-dia,” I say once. Twice. A third can you get cipro over the counter time. Defeated, I say the Americanized version of my name. €œClaw-dee-ah.” Finally, Siri recognizes it.

Having to adapt our way of speaking to interact with speech-recognition can you get cipro over the counter technologies is a familiar experience for people whose first language is not English or who do not have conventionally American-sounding names. I have now stopped using Siri, Apple's voice-based virtual assistant, because of it. The growth of this tech in the past decade—not just Siri but Alexa and Cortana and others—has unveiled a problem in it. Racial bias can you get cipro over the counter. One recent study, published in the Proceedings of the National Academy of Sciences USA, showed that speech-recognition programs are biased against Black speakers.

On average, the authors found, all five programs from leading technology companies, including Apple and Microsoft, showed significant race disparities. They were roughly twice as likely to can you get cipro over the counter incorrectly transcribe audio from Black speakers compared with white speakers. This effectively censors voices that are not part of the “standard” languages or accents used to create these technologies. €œI don't get to negotiate with these devices unless I adapt my language patterns,” says Halcyon Lawrence, an assistant professor of technical communication and information design at Towson University, who was not can you get cipro over the counter part of the study. €œThat is problematic.” For Lawrence, who has a Trinidad and Tobagonian accent, or for me as a Puerto Rican, part of our identity comes from speaking a particular language, having an accent or using a set of speech forms such as African American Vernacular English (AAVE).

Having to change such an integral part of an identity to be able to be recognized is inherently cruel. The inability can you get cipro over the counter to be understood impacts other marginalized communities, such as people with visual or movement disabilities who rely on voice recognition and speech-to-text tools, says Allison Koenecke, a computational graduate student and first author of the PNAS study. For someone with a disability who is dependent on these technologies, being misunderstood could have serious consequences. There are probably many culprits for these disparities, but Koenecke points to the most likely. The data used for training, which are predominantly from white, can you get cipro over the counter native speakers of American English.

By using databases that are narrow both in the words that are used and how they are said, training systems exclude accents and other ways of speaking that have unique linguistic features. Humans, presumably including those who create these technologies, have can you get cipro over the counter accent and language biases. For example, research shows that the presence of an accent affects whether jurors find people guilty and whether patients find their doctors competent. Recognizing these biases would be an important way to avoid implementing them in technologies. But developing more inclusive technology takes time, effort and money, and often the decision to invest these are market-driven can you get cipro over the counter.

(In response to several queries, only a Google spokesperson responded in time for publication, saying, in part, “We've been working on the challenge of accurately recognizing variations of speech for several years and will continue to do so.”) Safiya Noble, an associate professor of information studies at the University of California, Los Angeles, admits that it's a tricky challenge. €œLanguage is contextual,” says Noble, who was not involved in the study. €œBut that doesn't mean that companies shouldn't strive to decrease bias and disparities.” To do this, they need the input of humanists can you get cipro over the counter and social scientists who understand how language actually works. From the tech side, feeding more diverse training data into the programs could close this gap, Koenecke says. Noble adds that tech companies should also test their products more widely and have more diverse workforces so people from different backgrounds and perspectives can directly influence the design of speech can you get cipro over the counter technologies.

Koenecke suggests that automated speech-recognition companies use the PNAS study as a preliminary benchmark and keep using it to assess their systems over time. In the meantime, many of us will continue to struggle between identity and being understood when interacting with Alexa, Cortana or Siri. But Lawrence can you get cipro over the counter chooses identity every time. €œI'm not switching,” she says. €œI'm not doing it.”Hiral Tipirneni spent nearly a decade working in emergency medicine in Arizona.

She started out 23 years ago at Banner Good Samaritan Hospital in downtown Phoenix, treating patients with broken bones, failing can you get cipro over the counter hearts and a lot of other problems. Then some health tragedies hit home. €œOur family suffered a great loss to cancer. My mom can you get cipro over the counter and nephew,” she says. Tipirneni felt she should do something to combat the illness that took her loved ones.

In 2010 she accepted a position as a scientific review officer can you get cipro over the counter for the Society of Research Administrators International, a global research management group overseeing cancer studies. But when Donald Trump was elected U.S. President in 2016, “I was terrified of the threats of ‘repeal and replace’ of the Affordable Care Act,” she recalls. €œAfter years spent in the ER seeing thousands of families come through with no access to health care..., it was too much to stand can you get cipro over the counter by. That prompted me to throw my hat into the ring.” Following a failed bid for a seat in the House of Representatives during a 2018 special election, Tipirneni, a Democrat, is running for the state’s sixth congressional district in the November 3 election.

The district includes part of Maricopa county and some Phoenix suburbs. She is challenging Republican incumbent David Schweikert, a former businessman now serving his fourth consecutive term in can you get cipro over the counter that seat and his fifth overall in the House. Republicans have held this Recommended Reading seat since 1995. But in can you get cipro over the counter the middle of a cipro that has killed more than 5,700 Arizonans—more than 3,400 of them in Maricopa County—Tipirneni is hoping her medical background will carry weight with voters. €œWe see decision after decision being made not based on data, not based on science, but rather on political expediency, partisanship—or based on the election calendar,” she says.

€œThat’s blasphemy for a scientist or physician.” Tipirneni is one of several candidates with a scientific background running for federal office this fall. The election will serve as the political climax to a year that saw raging wildfires fueled by climate change, devastating hurricanes and the buy antibiotics cipro, which has claimed the lives of more than 216,000 Americans—a death toll medical experts say has been driven high by politicians who have ignored public health guidelines can you get cipro over the counter. Given these catastrophic outcomes, Tipirneni and another physician-politician, Barbara Bollier, who is running for an open U.S. Senate seat in Kansas, hope voters will be swayed by candidates who tout respect for science when making policy decisions. Both races are incredibly close, with recent polls showing Tipirneni and Bollier either ahead or can you get cipro over the counter behind their opponents by only a few percentage points.

The stakes are high. If Democrats manage to flip a Senate seat in Kansas, along with achieving a few other wins, they will gain control of the can you get cipro over the counter Senate. And Tipirneni winning in Arizona could help them hold onto their majority in the House. Both outcomes would put Democrats in charge of the two houses of Congress, ending the current split with Republicans. €œAfter a big military conflict, you often see a surge in military veterans running for office,” can you get cipro over the counter says Eitan Hersh, a political scientist at Tufts University.

€œFollowing the 2016 election, more women ran than ever before [in the midterms.] And after buy antibiotics, it’s not surprising that some physicians would run for office, feeling like their voices need to be heard. If there’s a big surge in doctors running, some will get in.” Grand Battle in the Grand Canyon State In Arizona, Tipirneni has raised more than $1 million more in campaign funding than Schweikert. Generally, a September poll by the Arizona Policy Lab found that science-based approaches to fighting buy antibiotics, can you get cipro over the counter including mask mandates, were popular among Arizonan voters in both parties. €œThere is really strong disapproval for how Donald Trump and how Republican governor Doug Ducey have handled buy antibiotics,” says Samara Klar, a political scientist at the University of Arizona. Ducey, for instance, pushed hard for the resumption of activities with few restrictions in the spring, only to see a surge in buy antibiotics cases that forced another shutdown.

Klar adds that polls show that “at the same time, there’s been strong support for how local mayors have dealt with it.” This, she says, could hurt the Republicans’ chances can you get cipro over the counter in Arizona. Schweikert did not respond to requests for comment from Scientific American. He has been a vocal supporter of the can you get cipro over the counter use of masks, however. In a July tweet, he encouraged his constituents to “continue wearing our face coverings when out in public, or when in close proximity to others.” He also advocated for increased access to federal resources to purchase items such as personal protective equipment (PPE). €œWe ...

Ask the can you get cipro over the counter U.S. Department of Health and Human Resources (HHS) and the Federal Emergency Management Agency (FEMA) for an immediate influx of federal resources to combat the cipro, through increased testing, contact tracing, personal protective equipment (PPE), staffing support, and emergency funding for local initiatives to respond to and mitigate further spread,” he and four other Arizonan congresspeople wrote in a letter in August. But despite Schweikert’s support for public health practices, his messages may be tainted by the president’s handling of the cipro. Recent polls show that Republicans have begun to drift away from can you get cipro over the counter Trump. Biden currently leads Trump, 49 percent to 41 percent, in Arizona.

On energy policy, Schweikert can you get cipro over the counter and Tipirneni’s messaging diverges. €œArizona should be leading the charge on a renewable energy economy,” Tipirneni says, adding that those energy sources are key to reducing the impacts of climate change. €œBut we have leaders like my opponent, who has stood at every opportunity to block those kinds of initiatives because he is someone who still takes money from fossil fuels and is driven by party leadership to invest in other forms of energy.” Schweikert’s platform promotes an “‘all of the above’ energy solution,” tapping into “traditional energy reserves” but also expanding renewable energy resources. In his time in the House, however, he has taken dozens of antienvironmental positions, including voting against protecting Chaco Canyon from oil and gas drilling, banning offshore drilling in the Atlantic and Pacific Ocean, can you get cipro over the counter and implementing methane pollution safeguards. The Kansas Contest Democrats have not cornered the market on physician candidates.

In Kansas, Roger Marshall, a Republican representative in the House and an ob-gyn, is running against Bollier, a Democratic former anesthesiologist, creating a rare doctor-doctor duel. But despite sharing a medical can you get cipro over the counter background, the two appear diametrically opposed on issues pertaining to science. Barbara Bollier (left) and Roger Marshall (right). Credit. Barbara Bollier Flickr (Bollier).

Eric Connolly U.S. House Office of Photography (Marshall) Bollier had been a Republican until she switched parties in 2018, and has served in the state’s legislature for a decade. She acknowledges that climate change is caused by people and has committed to greatly expand wind energy in the state. In contrast, Marshall has rejected the scientific consensus on climate, stating, “I’m not sure that there is even climate change” in 2017. His campaign Web site makes no mention of the issue.

Bollier “is a scientist and data nerd at heart,” says her communications director Alexandra De Luca. €œBarbara follows science. She always listens to the experts. Roger Marshall does not. If Roger Marshall followed science, he wouldn’t be holding events indoors, shaking hands with vulnerable Kansans.” Bollier’s campaign, De Luca says, held more than 40 virtual town halls on Zoom this summer.

And Bollier only began in-person campaigning in late August—always outdoors and physically distanced. Marshall did push for additional antibiotics testing kits for Kansas in April, saying that more testing could keep workers at large meat processing plants on the job—processors in Kansas had already had big outbreaks of the cipro. But Marshall differed from much medical research in May, when he told the Wall Street Journal he was taking the antimalarial drug hydroxychloroquine as a preventive measure against buy antibiotics. Though touted by President Trump as a possible cure, the data supporting the medication was always sparse, and emergency authorization for it was revoked by the U.S. Food and Drug Administration in June.

In the May article, Marshall added that he “would encourage any person over the age of 65 or with an underlying medical condition to talk to their own physician about taking hydroxychloroquine.” In September, Marshall wrote a Facebook post suggesting that most buy antibiotics deaths were from other ailments. Facebook deleted the post. His campaign did not respond to Scientific American’s requests for an interview. Marshall regularly plays up his medical credentials. He has given himself the nickname “Doc,” and his Twitter username is @RogerMarshallMD.

He also has used his medical skills to help in the cipro, he says. In late April, Marshall tweeted, “Today, I began treating buy antibiotics patients on a volunteer basis in Wyandotte County, KS. I began the process of onboarding several days ago, and have started in the clinic today.” Thus far, polls show the race between Bollier and Marshall “as surprisingly close for a Republican state,” with all of them falling within the margin of error, says Don Haider-Markel, a political scientist at the University of Kansas. Despite electing a Democratic governor in 2018, he says, the state still leans conservative, and to have a competitive Democrat in the running is “not typical, to say the least.” After the economy and jobs, Haider-Markel observes, Kansans care most about the handling of the cipro in this election cycle—ranking that issue ahead of education and civil unrest. In the final days of campaigning, Democrats are trying to focus attention on health care, he adds, but “it’s not clear that voters are prioritizing that more than last month.” Bollier is likely succeeding at picking up moderate Republican and independent voters, Haider-Markel says.

Trump’s election alienated many Republican women in the suburbs in eastern Kansas and around Wichita who have likely switched to supporting the Democratic candidate, he explains. €œI think Bollier’s messaging on evidence-based policy will resonate with them—but they were already going to be more attracted to her to begin with.” Patti Doll, a 67-year-old former social worker who lives in Wichita, has been following the Senate race closely. She is a Democrat and says the cipro has made her pay greater attention to candidates’ adherence to scientific guidelines. Marshall, she notes with dissatisfaction, is still campaigning without a mask in October. €œIt’s his job to lead and show people that this is important,” she says.

€œIf it was switched, and it was Bollier who was a Republican, and Marshall was a Democrat, I would vote across party lines in this situation. It doesn’t matter to me. Follow the science.”Every time I log onto Facebook, I brace myself. My newsfeed—like everyone else’s I know—is filled with friends, relatives and acquaintances arguing about buy antibiotics, masks and Trump. Facebook has become a battleground among partisan “echo chambers.” But what is it about social media that makes people so polarized?.

To find out, my colleagues and I ran a social media experiment in which we divided Democrats and Republicans into “echo chambers,” or small groups whose members affiliate with just one political party. Next, we picked the most polarizing issues we could think of. Immigration, gun control and unemployment. We asked each participant what they thought of those issues, then let people talk to each other and revise their opinions. After several rounds of discussion and revision, we evaluated each group’s viewpoint.

To our surprise, the echo chambers did not make people more polarized, but less. After interacting in social networks with likeminded peers, each echo chamber—Republican and Democrat—had adopted a more moderate opinion. All groups independently moved toward opinions that were closer to the opinions on the “opposite” side of the political spectrum. As a scientist who studies networks, I’m used to being surprised by the results of my experiments. Technology has allowed us to access more information and data about people’s social networks, debunking many of our assumptions about human behavior.

But even my team at the Network Dynamics Group was surprised. Why did our social media experiment find the opposite of what happens all the time in the real world of social media?. The answer lies in something social media has amplified. €œinfluencers.” By now, most of us have a fairly specific understanding of what an “influencer” is. The word conjures up a young, wealthy person whose lifestyle is sponsored by brands like Instagram, TikTok or YouTube.

But the word has a very specific network science meaning. In social media, networks tend to be centralized. A small number of people, or perhaps just one person, at the “center” of the network is connected to lots of other people in the “periphery.” The multitudes in the periphery of the social network have only a modest number of connections, while the few—the so-called “influencers”—at the center of the network are connected to nearly everyone. This puts these people into the powerful position of being able to exert a disproportionate level of “influence” over the group. By contrast, the networks used in our study were “egalitarian”—the opposite of centralized.

In an egalitarian network, everyone has an equal number of contacts, and therefore influence, throughout the network. The key feature of an egalitarian network is that new ideas and opinions can emerge from anywhere in the community and spread to everyone. But in centralized networks—like many social media sites—ideas are filtered through, or sometimes even blocked, by a powerful social influencer. As I show in my upcoming book Change. The Power in the Periphery to Make Big Things Happen, centralized and egalitarian networks have very different effects on partisan bias and the acceptance of new ideas.

In a centralized echo chamber, if the influencer at the middle shows even a small amount of partisan bias, it can become amplified throughout the entire group. But in egalitarian networks, ideas spread based on their quality, and not the person touting them. There is a lot of wisdom in network peripheries, in regular people with good ideas. When the social network enables those people to talk with each other, new thinking that challenge a group’s biases can take hold and spread. To see how egalitarian networks might affect other kinds of contentious issues, we conducted another experiment with smokers and nonsmokers discussing the risks of cigarette smoking.

The effects were the same as with the partisan study. Both groups moved toward a more accurate understanding of smoking risks. Moreover, when participants were interviewed after the study, they reported having developed higher opinions of the other. Both smokers and nonsmokers had come to view the other group as more reasonable and trustworthy about the risks of smoking. But the exchange of ideas and eradication of bias only works when networks are egalitarian.

The problem of partisan bias is exacerbated on social media because online networks are often organized around a few key influencers. This feature of social media is one of the main reasons why misinformation and fake news has become so pervasive. In centralized networks, biased influencers have a disproportionate impact on their community—enabling small rumors and suppositions to become amplified into widespread misconceptions and false beliefs. Our country has been struggling with bias and polarization a long time. But the issue is about to get much more urgent.

As the debate over buy antibiotics vaccination heats up, biased viewpoints will undoubtedly become entrenched in communities with powerful influencers at their center. If we want to eradicate, or at least lessen the impacts of the antibiotics, we should rethink how our online communities operate. The solution to the problem of treatment hesitancy is not to eliminate echo chambers. Rather, it is to be intentional about the social networks in those echo chambers. The more equity in people’s social networks, the less biased and more informed groups will become—even when those groups start off with highly partisan opinions..

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

Can you drink alcohol while on cipro

The Biden administration said Friday it has no timeline on whether it will allow states to import drugs from can you drink alcohol while on cipro Canada, an effort that was approved under President Donald Trump as a key strategy to control costs. Six states have passed laws to start such programs, and Florida, Colorado and New Mexico are the furthest along in plans to get federal approval. The Biden administration said states still have can you drink alcohol while on cipro several hurdles to get through, including a review by the Food and Drug Administration, and such efforts may face pressures from the Canadian government, which has warned its drug industry not to do anything that could cause drug shortages in that country.

“Although two proposals have been submitted to FDA, no timeline exists for the agency to make a decision. Thus, the possible future injuries to Plaintiffs’ members are overly speculative and not imminent,” the Biden administration wrote in a court filing late Friday seeking to dismiss a lawsuit from the Pharmaceutical Research and Manufacturers of America, an industry trade group. Drugmakers are asking can you drink alcohol while on cipro the court to overturn the rule set by the Health and Human Services Department in October that for the first time approved allowing states to import drugs from Canada.

EMAIL SIGN-Up Subscribe to California Healthline's free Daily Edition. The Biden administration said the lawsuit was moot because it’s unclear when or if any states would get an importation plan approved. Drug importation has been hotly debated for decades, with many states and advocates believing it would help lower the prices Americans pay while the drug industry contends it would undercut the safety of the can you drink alcohol while on cipro U.S. Drug supply.

Critics note most brand-name drugs sold in the U.S. Are manufactured can you drink alcohol while on cipro abroad. Friday’s court filing had been eagerly anticipated, as it was the first time the Biden administration weighed in on the issue.

Promises to curb high drug prices have been a standard sound bite of political campaigns, and importation enjoys broad public support. Supporters of importation range the political can you drink alcohol while on cipro spectrum from progressive Sen. Bernie Sanders (I-Vt.) to Florida’s conservative Republican governor, Ron DeSantis.

They argue can you drink alcohol while on cipro Americans should not pay more for drugs than consumers in other countries. Rachel Sachs, a health law expert at Washington University in St. Louis, said the rhetoric in the court filing is probably “disheartening” to DeSantis and other supporters hoping states’ importation programs would be approved soon.

€œThey are laying out that there is no time limit on the FDA and there are many steps that states have to undergo before approval,” she said can you drink alcohol while on cipro. Supporters of drug importation say they still have hope, especially if the court agrees to the administration’s effort to throw out the suit. “While articulating possible hurdles that may prevent state drug importation programs from moving forward, can you drink alcohol while on cipro the Biden administration’s motion to dismiss PhRMA’s lawsuit keeps alive opportunities for more Americans to benefit from drug importation,” said Gabriel Levitt, president of Pharmacychecker.com, which verifies online foreign pharmacies for customers.

Importing drugs from Canada, where government controls keep prices lower, has been debated for decades in the U.S. A 2003 federal law gave the executive branch permission to do it, but only if certified as safe and cost-effective by the HHS secretary. Then-HHS Secretary can you drink alcohol while on cipro Alex Azar announced in September that he would become the first to do that, and the department issued its rule in October.

Florida, Colorado, Maine, New Hampshire, New Mexico and Vermont are pursuing efforts to import drugs. PhRMA filed its suit in November in the U.S. District Court can you drink alcohol while on cipro for the District of Columbia.

In the court filing late Friday, the Biden administration said the FDA could reject state importation plans for many reasons, including safety concerns and lack of significant savings for consumers. In an emailed statement, PhRMa can you drink alcohol while on cipro spokesperson Nicole Longo said. €œWe continue to believe the Trump Administration violated federal law when it finalized its rule permitting state-sponsored drug importation from Canada without proper certification and, in doing so, putting the health and safety of Americans in jeopardy.” Canada has opposed efforts to send its drugs to the United States, fearing it could exacerbate shortages there.

Last year, Canadian health regulators warned companies against exporting any drugs that could lead to shortages. During the presidential campaign, Joe Biden supported drug importation can you drink alcohol while on cipro. His HHS secretary, Xavier Becerra, voted for the 2003 Canadian drug importation law as a member of Congress.

In most circumstances, the can you drink alcohol while on cipro FDA says it’s illegal for individuals to import drugs for personal use. Yet, for nearly 20 years, storefronts in Florida have helped people buy drugs online from pharmacies in Canada and other nations at typically half the U.S. Price.

The FDA has periodically cracked down on the operators but has allowed the stores to stay open can you drink alcohol while on cipro. The Florida legislature in 2019 approved the state drug importation program, and the state submitted its proposal to the federal government last year. While DeSantis has boasted of the strategy at news conferences in the retiree-heavy community of The Villages, the state program would have little direct effect on most Floridians.

That’s because the state effort is geared to getting lower-cost drugs to state agencies for prison health programs and other needs and for Medicaid, the state-federal health program for can you drink alcohol while on cipro the poor. Medicaid enrollees already pay little or nothing for medications. Florida has identified about 150 drugs — can you drink alcohol while on cipro many of them expensive HIV/AIDS, diabetes and mental health medicines — that it plans to import.

Insulin, one of the most expensive widely used drugs, is not included in the program. DeSantis said the importation plan would save the state between $80 million and $150 million. The state has a $96 billion budget, can you drink alcohol while on cipro he said.

“It’s been under review enough,” DeSantis said Friday, hours before the Biden administration’s court filing. €œWe have followed can you drink alcohol while on cipro every regulation. We’ve met every requirement that we were asked to meet, and we want now to be able to get this final approval so that we can finally move forward.” Christina Pushaw, a spokesperson for DeSantis, said the governor was disappointed by the Biden court filing.

“Governor DeSantis calls on the Biden Administration to step out of the way of innovation and act immediately to approve Florida’s plan that provides safe and effective drugs to drive down prescription costs,” she said in an email to KHN. The governor appeared at LifeScience Logistics in Lakeland, Florida, where state regulators worked can you drink alcohol while on cipro with the company to construct an FDA-compliant warehouse to process pharmaceuticals from Canada. “We’re ready, willing and able, and I think that this could be really, really significant,” DeSantis said.

He said the warehouse could begin receiving drugs from Canada within 90 days if the state were to get approval from Washington. LifeScience Logistics officials said they are working with Methapharm Specialty Pharmaceuticals, which has offices can you drink alcohol while on cipro near Toronto and Fort Lauderdale, Florida, to act as its Canadian wholesaler. Quality checks would be done on the drugs in Canada and again in Florida, said Richard Beeny, CEO of LifeScience Logistics.

LifeScience has begun early talks on negotiating prices with drug manufacturers that would deliver medications can you drink alcohol while on cipro to Methapharm, which in turn would send drugs to the Lakeland warehouse. €œThere is broad interest in the program,” Beeny said about drug companies wanting to participate. €œBut the pending suit is a bit of a roadblock, so we have to wait and see how that pans out.” Unlike Florida’s plan, Colorado’s Canadian importation program would help individuals buy the medicines at their local pharmacy.

Colorado also would give health insurance plans the option to include imported can you drink alcohol while on cipro drugs in their benefit designs. Mara Baer, a health consultant who has worked with Colorado on its proposal, said the Biden decision leaves open the question of whether state importation plans might eventually be approved. €œHHS could have let the rule fall and they did not, which is important given the challenges facing Congress in moving major drug pricing reform in the short term,” she said.

This story was produced by KHN (Kaiser Health News), a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Phil Galewitz. pgalewitz@kff.org, @philgalewitz Related Topics Contact Us Submit a Story Tip.

The Biden administration said Friday it has can you get cipro over the counter no timeline on whether it will allow states to import drugs from Canada, an effort that was approved under President Donald Trump as a key strategy to control costs. Six states have passed laws to start such programs, and Florida, Colorado and New Mexico are the furthest along in plans to get federal approval. The Biden administration said states still have several hurdles to get through, including a review by the can you get cipro over the counter Food and Drug Administration, and such efforts may face pressures from the Canadian government, which has warned its drug industry not to do anything that could cause drug shortages in that country. “Although two proposals have been submitted to FDA, no timeline exists for the agency to make a decision.

Thus, the possible future injuries to Plaintiffs’ members are overly speculative and not imminent,” the Biden administration wrote in a court filing late Friday seeking to dismiss a lawsuit from the Pharmaceutical Research and Manufacturers of America, an industry trade group. Drugmakers are asking the court to overturn the rule set by the can you get cipro over the counter Health and Human Services Department in October that for the first time approved allowing states to import drugs from Canada. EMAIL SIGN-Up Subscribe to California Healthline's free Daily Edition. The Biden administration said the lawsuit was moot because it’s unclear when or if any states would get an importation plan approved. Drug importation has been hotly debated for decades, with can you get cipro over the counter many states and advocates believing it would help lower the prices Americans pay while the drug industry contends it would undercut the safety of the U.S.

Drug supply. Critics note most brand-name drugs sold in the U.S. Are manufactured can you get cipro over the counter abroad. Friday’s court filing had been eagerly anticipated, as it was the first time the Biden administration weighed in on the issue.

Promises to curb high drug prices have been a standard sound bite of political campaigns, and importation enjoys broad public support. Supporters of importation range the political spectrum can you get cipro over the counter from progressive Sen. Bernie Sanders (I-Vt.) to Florida’s conservative Republican governor, Ron DeSantis. They argue Americans should not pay more for drugs can you get cipro over the counter than consumers in other countries.

Rachel Sachs, a health law expert at Washington University in St. Louis, said the rhetoric in the court filing is probably “disheartening” to DeSantis and other supporters hoping states’ importation programs would be approved soon. €œThey are laying out that there is no time limit on the FDA and there are can you get cipro over the counter many steps that states have to undergo before approval,” she said. Supporters of drug importation say they still have hope, especially if the court agrees to the administration’s effort to throw out the suit.

“While articulating possible hurdles that may prevent state drug importation programs from moving forward, the Biden administration’s motion to dismiss PhRMA’s lawsuit keeps alive opportunities for more Americans to benefit from drug can you get cipro over the counter importation,” said Gabriel Levitt, president of Pharmacychecker.com, which verifies online foreign pharmacies for customers. Importing drugs from Canada, where government controls keep prices lower, has been debated for decades in the U.S. A 2003 federal law gave the executive branch permission to do it, but only if certified as safe and cost-effective by the HHS secretary. Then-HHS Secretary Alex Azar announced can you get cipro over the counter in September that he would become the first to do that, and the department issued its rule in October.

Florida, Colorado, Maine, New Hampshire, New Mexico and Vermont are pursuing efforts to import drugs. PhRMA filed its suit in November in the U.S. District Court can you get cipro over the counter for the District of Columbia. In the court filing late Friday, the Biden administration said the FDA could reject state importation plans for many reasons, including safety concerns and lack of significant savings for consumers.

In an emailed statement, PhRMa spokesperson Nicole Longo can you get cipro over the counter said. €œWe continue to believe the Trump Administration violated federal law when it finalized its rule permitting state-sponsored drug importation from Canada without proper certification and, in doing so, putting the health and safety of Americans in jeopardy.” Canada has opposed efforts to send its drugs to the United States, fearing it could exacerbate shortages there. Last year, Canadian health regulators warned companies against exporting any drugs that could lead to shortages. During the presidential campaign, Joe Biden supported can you get cipro over the counter drug importation.

His HHS secretary, Xavier Becerra, voted for the 2003 Canadian drug importation law as a member of Congress. In most circumstances, the FDA says it’s illegal for individuals to import drugs for personal use can you get cipro over the counter. Yet, for nearly 20 years, storefronts in Florida have helped people buy drugs online from pharmacies in Canada and other nations at typically half the U.S. Price.

The FDA has periodically cracked down on the operators but has allowed the can you get cipro over the counter stores to stay open. The Florida legislature in 2019 approved the state drug importation program, and the state submitted its proposal to the federal government last year. While DeSantis has boasted of the strategy at news conferences in the retiree-heavy community of The Villages, the state program would have little direct effect on most Floridians. That’s because the state effort is geared to getting lower-cost drugs to state agencies for prison health programs and other needs and for Medicaid, the state-federal health program for the can you get cipro over the counter poor.

Medicaid enrollees already pay little or nothing for medications. Florida has identified about 150 drugs — can you get cipro over the counter many of them expensive HIV/AIDS, diabetes and mental health medicines — that it plans to import. Insulin, one of the most expensive widely used drugs, is not included in the program. DeSantis said the importation plan would save the state between $80 million and $150 million.

The state has a $96 billion can you get cipro over the counter budget, he said. “It’s been under review enough,” DeSantis said Friday, hours before the Biden administration’s court filing. €œWe have can you get cipro over the counter followed every regulation. We’ve met every requirement that we were asked to meet, and we want now to be able to get this final approval so that we can finally move forward.” Christina Pushaw, a spokesperson for DeSantis, said the governor was disappointed by the Biden court filing.

“Governor DeSantis calls on the Biden Administration to step out of the way of innovation and act immediately to approve Florida’s plan that provides safe and effective drugs to drive down prescription costs,” she said in an email to KHN. The governor appeared at LifeScience Logistics in Lakeland, Florida, where state regulators worked with the company to construct can you get cipro over the counter an FDA-compliant warehouse to process pharmaceuticals from Canada. “We’re ready, willing and able, and I think that this could be really, really significant,” DeSantis said. He said the warehouse could begin receiving drugs from Canada within 90 days if the state were to get approval from Washington.

LifeScience Logistics officials said they are working with Methapharm Specialty Pharmaceuticals, which has can you get cipro over the counter offices near Toronto and Fort Lauderdale, Florida, to act as its Canadian wholesaler. Quality checks would be done on the drugs in Canada and again in Florida, said Richard Beeny, CEO of LifeScience Logistics. LifeScience has begun early talks on negotiating prices with drug manufacturers that would deliver medications to Methapharm, which in turn would send can you get cipro over the counter drugs to the Lakeland warehouse. €œThere is broad interest in the program,” Beeny said about drug companies wanting to participate.

€œBut the pending suit is a bit of a roadblock, so we have to wait and see how that pans out.” Unlike Florida’s plan, Colorado’s Canadian importation program would help individuals buy the medicines at their local pharmacy. Colorado also can you get cipro over the counter would give health insurance plans the option to include imported drugs in their benefit designs. Mara Baer, a health consultant who has worked with Colorado on its proposal, said the Biden decision leaves open the question of whether state importation plans might eventually be approved. €œHHS could have let the rule fall and they did not, which is important given the challenges facing Congress in moving can you get cipro over the counter major drug pricing reform in the short term,” she said.

This story was produced by KHN (Kaiser Health News), a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing can you get cipro over the counter information on health issues to the nation. Phil Galewitz.

pgalewitz@kff.org, @philgalewitz Related Topics Contact Us Submit a Story Tip.

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September 21, Where can i get viagra 2021Contact can cipro treat sinus . Office of CommunicationsPhone. 202-693-1999US Department of Labor to hold virtual meeting to solicit publicinput on OSHA whistleblower program WASHINGTON, DC - The can cipro treat sinus U.S. Department of Labor’s Occupational Safety and Health Administration will hold a virtual meeting Oct. 13, 2021, to solicit public comments and suggestions on key issues facing OSHA’s Whistleblower Protection Program.

This is the eighth in a series of meetings on how the can cipro treat sinus agency can improve the whistleblower program. Open to the public, the meeting will be held from 2 p.m. To 5 p.m. ET via telephone and virtually via Microsoft can cipro treat sinus Teams. The agency will provide Spanish language translation during the meeting.

Those interested in joining or participating in the meeting must register in English or Spanish can cipro treat sinus by Oct. 6, 2021. There is no fee to register. OSHA is can cipro treat sinus seeking comments on. How can OSHA deliver better whistleblower customer service?.

What kind of assistance can OSHA provide to help explain the agency’s whistleblower laws to employees and employers?. What can OSHA do to ensure that workers are protected from retaliation for raising concerns can cipro treat sinus related to the cipro?. Comments must be submitted electronically at http://www.regulations.gov, which is the Federal eRulemaking portal and should be identified with Docket No. OSHA-2018-0005. The deadline for submitting comments can cipro treat sinus is Oct.

6, 2021. Read the can cipro treat sinus Federal Register notice for details. Learn more about OSHA’s Whistleblower Protection Program. # # # U.S. Department of Labor news materials are accessible at can cipro treat sinus http://www.dol.gov.

The department’s Reasonable Accommodation Resource Center converts departmental information and documents into alternative formats, which include Braille and large print. For alternative format requests, please contact the department at (202) 693-7828 (voice) or (800) 877-8339 (federal relay).21 de Septiembre de 2021Comuniquese con la Oficina deComunicacionesTeléfono. 202-693-1999El Departamento de Trabajo de EE.UU can cipro treat sinus . Celebrará una reuniónvirtual para solicitar la opinión del público sobre el programa deprotección de denunciantes de OSHA WASHINGTON, DC - La Administración de Seguridad y Salud Ocupacional del Departamento de Trabajo de los Estados Unidos celebrará una reunión virtual el 13 de octubre de 2021 para solicitar comentarios y sugerencias del público sobre cuestiones clave a las que se enfrenta el Programa de Protección de Denunciantes de OSHA. Esta es la octava de una serie de can cipro treat sinus reuniones sobre cómo la agencia puede mejorar el programa de protección de denunciantes.

Abierta al público, la reunión se celebrará de 2 p.m. A 5 p.m. ET por teléfono y virtualmente a can cipro treat sinus través de Microsoft Teams. La agencia proporcionará traducción al español durante la reunión. Los interesados en unirse o participar en la reunión deben completar la inscripción en inglés o español antes del 6 de octubre de 2021.

La inscripción es gratuita can cipro treat sinus . OSHA solicita comentarios sobre. ¿Cómo puede OSHA ofrecer un mejor servicio de atención al cliente a los denunciantes?. ¿Qué tipo de asistencia puede proporcionar OSHA para ayudar can cipro treat sinus a explicar las leyes de denuncia de la agencia a los empleados y empleadores?. ¿Qué puede hacer OSHA para garantizar que los trabajadores estén protegidos contra las represalias por expresar preocupaciones relacionadas con la pandemia?.

Los comentarios deben ser presentados electrónicamente en http://www.regulations.gov, que es el portal federal de eRulemaking y deben can cipro treat sinus ser identificados con el Docket No. OSHA-2018-0005. La fecha límite para presentar comentarios es el 6 de octubre de 2021. Lea el aviso del Registro Federal para más detalles can cipro treat sinus . Obtenga más información sobre el Programa de Protección de Denunciantes de OSHA.

# # # U.S. Department of Labor news materials are accessible can cipro treat sinus at http://www.dol.gov. The department’s Reasonable Accommodation Resource Center converts departmental information and documents into alternative formats, which include Braille and large print. For alternative format requests, please contact the department at (202) 693-7828 (voice) or (800) 877-8339 (federal relay)..

September 21, can you get cipro over the counter 2021Contact. Office of CommunicationsPhone. 202-693-1999US Department of Labor to hold virtual meeting to solicit publicinput on OSHA whistleblower program can you get cipro over the counter WASHINGTON, DC - The U.S. Department of Labor’s Occupational Safety and Health Administration will hold a virtual meeting Oct. 13, 2021, to solicit public comments and suggestions on key issues facing OSHA’s Whistleblower Protection Program.

This is the eighth in a series of meetings on how the agency can improve can you get cipro over the counter the whistleblower program. Open to the public, the meeting will be held from 2 p.m. To 5 p.m. ET via telephone can you get cipro over the counter and virtually via Microsoft Teams. The agency will provide Spanish language translation during the meeting.

Those interested can you get cipro over the counter in joining or participating in the meeting must register in English or Spanish by Oct. 6, 2021. There is no fee to register. OSHA is can you get cipro over the counter seeking comments on. How can OSHA deliver better whistleblower customer service?.

What kind of assistance can OSHA provide to help explain the agency’s whistleblower laws to employees and employers?. What can OSHA do to ensure that workers are protected from retaliation for raising can you get cipro over the counter concerns related to the cipro?. Comments must be submitted electronically at http://www.regulations.gov, which is the Federal eRulemaking portal and should be identified with Docket No. OSHA-2018-0005. The deadline for submitting comments is Oct can you get cipro over the counter.

6, 2021. Read the Federal Register notice can you get cipro over the counter for details. Learn more about OSHA’s Whistleblower Protection Program. # # # U.S. Department of Labor news materials are accessible at can you get cipro over the counter http://www.dol.gov.

The department’s Reasonable Accommodation Resource Center converts departmental information and documents into alternative formats, which include Braille and large print. For alternative format requests, please contact the department at (202) 693-7828 (voice) or (800) 877-8339 (federal relay).21 de Septiembre de 2021Comuniquese con la Oficina deComunicacionesTeléfono. 202-693-1999El Departamento de Trabajo de EE.UU can you get cipro over the counter. Celebrará una reuniónvirtual para solicitar la opinión del público sobre el programa deprotección de denunciantes de OSHA WASHINGTON, DC - La Administración de Seguridad y Salud Ocupacional del Departamento de Trabajo de los Estados Unidos celebrará una reunión virtual el 13 de octubre de 2021 para solicitar comentarios y sugerencias del público sobre cuestiones clave a las que se enfrenta el Programa de Protección de Denunciantes de OSHA. Esta es la octava de una serie de reuniones sobre cómo la agencia puede mejorar el programa de can you get cipro over the counter protección de denunciantes.

Abierta al público, la reunión se celebrará de 2 p.m. A 5 p.m. ET por teléfono y virtualmente a través can you get cipro over the counter de Microsoft Teams. La agencia proporcionará traducción al español durante la reunión. Los interesados en unirse o participar en la reunión deben completar la inscripción en inglés o español antes del 6 de octubre de 2021.

La inscripción es gratuita can you get cipro over the counter. OSHA solicita comentarios sobre. ¿Cómo puede OSHA ofrecer un mejor servicio de atención al cliente a los denunciantes?. ¿Qué tipo de asistencia puede proporcionar OSHA para ayudar a explicar las leyes de denuncia de la agencia a los empleados can you get cipro over the counter y empleadores?. ¿Qué puede hacer OSHA para garantizar que los trabajadores estén protegidos contra las represalias por expresar preocupaciones relacionadas con la pandemia?.

Los comentarios deben ser presentados electrónicamente en http://www.regulations.gov, que es el portal federal de eRulemaking can you get cipro over the counter y deben ser identificados con el Docket No. OSHA-2018-0005. La fecha límite para presentar comentarios es el 6 de octubre de 2021. Lea el aviso del Registro Federal para can you get cipro over the counter más detalles. Obtenga más información sobre el Programa de Protección de Denunciantes de OSHA.

# # # U.S. Department of Labor news materials are accessible at can you get cipro over the counter http://www.dol.gov. The department’s Reasonable Accommodation Resource Center converts departmental information and documents into alternative formats, which include Braille and large print. For alternative format requests, please contact the department at (202) 693-7828 (voice) or (800) 877-8339 (federal relay)..

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AbstractIntroduction Buy cipro with prescription cipro denk 500 tablets. We report a very rare case of familial breast cancer and diffuse gastric cancer, with germline pathogenic variants in both BRCA1 and CDH1 genes. To the best of our knowledge, this is the first report cipro denk 500 tablets of such an association.Family description.

The proband is a woman diagnosed with breast cancer at the age of 52 years. She requested genetic counselling in 2012, at the age of 91 years, because of a history of breast cancer in her daughter, her sister, her niece and her paternal grandmother cipro denk 500 tablets and was therefore concerned about her relatives. Her sister and maternal aunt also had gastric cancer.

She was tested for several genes associated cipro denk 500 tablets with hereditary breast cancer.Results. A large deletion of BRCA1 from exons 1 to 7 and two CDH1 pathogenic cis variants were identified.Conclusion. This complex situation cipro denk 500 tablets is challenging for genetic counselling and management of at-risk individuals.cancer.

Breastcancer. Gastricclinical geneticsgenetic screening/counsellingmolecular geneticsIntroductionGLI-Kruppel family member 3 (GLI3) encodes for a zinc finger transcription factor which plays a key role in the sonic hedgehog (SHH) signalling pathway essential in both limb and craniofacial development.1 2 In hand development, SHH is expressed in the zone of polarising activity (ZPA) on the posterior side of cipro denk 500 tablets the handplate. The ZPA expresses SHH, creating a gradient of SHH from the posterior to the anterior side of the handplate.

In the presence of SHH, full length GLI3-protein is produced (GLI3A), whereas absence of SHH causes cleavage of GLI3 into its repressor form (GLI3R).3 4 Abnormal cipro denk 500 tablets expression of this SHH/GLI3R gradient can cause both preaxial and postaxial polydactyly.2Concordantly, pathogenic DNA variants in the GLI3 gene are known to cause multiple syndromes with craniofacial and limb involvement, such as. Acrocallosal syndrome5 (OMIM. 200990), Greig cephalopolysyndactyly cipro denk 500 tablets syndrome6 (OMIM.

175700) and Pallister-Hall syndrome7 (OMIM. 146510). Also, in non-syndromic polydactyly, such as preaxial polydactyly-type 4 (PPD4, OMIM.

174700),8 pathogenic variants in GLI3 have been described. Out of these diseases, Pallister-Hall syndrome is the most distinct entity, defined by the presence of central polydactyly and hypothalamic hamartoma.9 The other GLI3 syndromes are defined by the presence of preaxial and/or postaxial polydactyly of the hand and feet with or without syndactyly (Greig syndrome, PPD4). Also, various mild craniofacial features such as hypertelorism and macrocephaly can occur.

Pallister-Hall syndrome is caused by truncating variants in the middle third of the GLI3 gene.10–12 The truncation of GLI3 causes an overexpression of GLI3R, which is believed to be the key difference between Pallister-Hall and the GLI3-mediated polydactyly syndromes.9 11 Although multiple attempts have been made, the clinical and genetic distinction between the GLI3-mediated polydactyly syndromes is less evident. This has for example led to the introduction of subGreig and the formulation of an Oro-facial-digital overlap syndrome.10 Other authors, suggested that we should not regard these diseases as separate entities, but as a spectrum of GLI3-mediated polydactyly syndromes.13Although phenotype/genotype correlation of the different syndromes has been cumbersome, clinical and animal studies do provide evidence that distinct regions within the gene, could be related to the individual anomalies contributing to these syndromes. First, case studies show isolated preaxial polydactyly is caused by both truncating and non-truncating variants throughout the GLI3 gene, whereas in isolated postaxial polydactyly cases truncating variants at the C-terminal side of the gene are observed.12 14 These results suggest two different groups of variants for preaxial and postaxial polydactyly.

Second, recent animal studies suggest that posterior malformations in GLI3-mediated polydactyly syndromes are likely related to a dosage effect of GLI3R rather than due to the influence of an altered GLI3A expression.15Past attempts for phenotype/genotype correlation in GLI3-mediated polydactyly syndromes have directly related the diagnosed syndrome to the observed genotype.10–12 16 Focusing on individual hand phenotypes, such as preaxial and postaxial polydactyly and syndactyly might be more reliable because it prevents misclassification due to inconsistent use of syndrome definition. Subsequently, latent class analysis (LCA) provides the possibility to relate a group of observed variables to a set of latent, or unmeasured, parameters and thereby identifying different subgroups in the obtained dataset.17 As a result, LCA allows us to group different phenotypes within the GLI3-mediated polydactyly syndromes and relate the most important predictors of the grouped phenotypes to the observed GLI3 variants.The aim of our study was to further investigate the correlation of the individual phenotypes to the genotypes observed in GLI3-mediated polydactyly syndromes, using LCA. Cases were obtained by both literature review and the inclusion of local clinical cases.

Subsequently, we identified two subclasses of limb anomalies that relate to the underlying GLI3 variant. We provide evidence for two different phenotypic and genotypic groups with predominantly preaxial and postaxial hand and feet anomalies, and we specify those cases with a higher risk for corpus callosum anomalies.MethodsLiterature reviewThe Human Gene Mutation Database (HGMD Professional 2019) was reviewed to identify known pathogenic variants in GLI3 and corresponding phenotypes.18 All references were obtained and cases were included when they were diagnosed with either Greig or subGreig syndrome or PPD4.10–12 Pallister-Hall syndrome and acrocallosal syndrome were excluded because both are regarded distinct syndromes and rather defined by the presence of the non-hand anomalies, than the presence of preaxial or postaxial polydactyly.13 19 Isolated preaxial or postaxial polydactyly were excluded for two reasons. The phenotype/genotype correlations are better understood and both anomalies can occur sporadically which could introduce falsely assumed pathogenic GLI3 variants in the analysis.

Additionally, cases were excluded when case-specific phenotypic or genotypic information was not reported or if these two could not be related to each other. Families with a combined phenotypic description, not reducible to individual family members, were included as one case in the analysis.Clinical casesThe Sophia Children’s Hospital Database was reviewed for cases with a GLI3 variant. Within this population, the same inclusion criteria for the phenotype were valid.

Relatives of the index patients were also contacted for participation in this study, when they showed comparable hand, foot, or craniofacial malformations or when a GLI3 variant was identified. Phenotypes of the hand, foot and craniofacial anomalies of the patients treated in the Sophia Children's Hospital were collected using patient documentation. Family members were identified and if possible, clinically verified.

Alternatively, family members were contacted to verify their phenotypes. If no verification was possible, cases were excluded.PhenotypesThe phenotypes of both literature cases and local cases were extracted in a similar fashion. The most frequently reported limb and craniofacial phenotypes were dichotomised.

The dichotomised hand and foot phenotypes were preaxial polydactyly, postaxial polydactyly and syndactyly. Broad halluces or thumbs were commonly reported by authors and were dichotomised as a presentation of preaxial polydactyly. The extracted dichotomised craniofacial phenotypes were hypertelorism, macrocephaly and corpus callosum agenesis.

All other phenotypes were registered, but not dichotomised.Pathogenic GLI3 variantsAll GLI3 variants were extracted and checked using Alamut Visual V.2.14. If indicated, variants were renamed according to standard Human Genome Variation Society nomenclature.20 Variants were grouped in either missense, frameshift, nonsense or splice site variants. In the group of frameshift variants, a subgroup with possible splice site effect were identified for subgroup analysis when indicated.

Similarly, nonsense variants prone for nonsense mediated decay (NMD) and nonsense variants with experimentally confirmed NMD were identified.21 Deletions of multiple exons, CNVs and translocations were excluded for analysis. A full list of included mutations is available in the online supplementary materials.Supplemental materialThe location of the variant was compared with five known structural domains of the GLI3 gene. (1) repressor domain, (2) zinc finger domain, (3) cleavage site, (4) activator domain, which we defined as a concatenation of the separately identified transactivation zones, the CBP binding domain and the mediator binding domain (MBD) and (5) the MID1 interaction region domain.1 6 22–24 The boundaries of each of the domains were based on available literature (figure 1, exact locations available in the online supplementary materials).

The boundaries used by different authors did vary, therefore a consensus was made.In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1.

Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations." data-icon-position data-hide-link-title="0">Figure 1 In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1.

Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations.Supplemental materialLatent class analysisTo cluster phenotypes and relate those to the genotypes of the patients, an explorative analysis was done using LCA in R (R V.3.6.1 for Mac. Polytomous variable LCA, poLCA V.1.4.1.). We used our LCA to detect the number of phenotypic subgroups in the dataset and subsequently predict a class membership for each case in the dataset based on the posterior probabilities.In order to make a reliable prediction, only phenotypes that were sufficiently reported and/or ruled out were feasible for LCA, limiting the analysis to preaxial polydactyly, postaxial polydactyly and syndactyly of the hands and feet.

Only full cases were included. To determine the optimal number of classes, we fitted a series of models ranging from a one-class to a six-class model. The optimal number of classes was based on the conditional Akaike information criterion (cAIC), the non adjusted and the sample-size adjusted Bayesian information criterion (BIC and aBIC) and the obtained entropy.25 The explorative LCA produces both posterior probabilities per case for both classes and predicted class membership.

Using the predicted class membership, the phenotypic features per class were determined in a univariate analysis (χ2, SPSS V.25). Using the posterior probabilities on latent class (LC) membership, a scatter plot was created using the location of the variant on the x-axis and the probability of class membership on the y-axis for each of the types of variants (Tibco Spotfire V.7.14). Using these scatter plots, variants that give similar phenotypes were clustered.Genotype/phenotype correlationBecause an LC has no clinical value, the correlation between genotypes and phenotypes was investigated using the predictor phenotypes and the clustered phenotypes.

First, those phenotypes that contribute most to LC membership were identified. Second those phenotypes were directly related to the different types of variants (missense, nonsense, frameshift, splice site) and their clustered locations. Quantification of the relation was performed using a univariate analysis using a χ2 test.

Because of our selection criteria, meaning patients at least have two phenotypes, a multivariate using a logistic regression analysis was used to detect the most significant predictors in the overall phenotype (SPSS V.25). Finally, we explored the relation of the clustered genotypes to the presence of corpus callosum agenesis, a rare malformation in GLI3-mediated polydactyly syndromes which cannot be readily diagnosed without additional imaging.ResultsWe included 251 patients from the literature and 46 local patients,10–12 16 21 26–43 in total 297 patients from 155 different families with 127 different GLI3 variants, 32 of which were large deletions, CNVs or translocations. In six local cases, the exact variant could not be retrieved by status research.The distribution of the most frequently observed phenotypes and variants are presented in table 1.

Other recurring phenotypes included developmental delay (n=22), broad nasal root (n=23), frontal bossing or prominent forehead (n=16) and craniosynostosis (n=13), camptodactyly (n=8) and a broad first interdigital webspace of the foot (n=6).View this table:Table 1 Baseline phenotypes and genotypes of selected populationThe LCA model was fitted using the six defined hand/foot phenotypes. Model fit indices for the LCA are displayed in table 2. Based on the BIC, a two-class model has the best fit for our data.

The four-class model does show a gain in entropy, however with a higher BIC and loss of df. Therefore, based on the majority of performance statistics and the interpretability of the model, a two-class model was chosen. Table 3 displays the distribution of phenotypes and genotypes over the two classes.View this table:Table 2 Model fit indices for the one-class through six-class model evaluated in our LCAView this table:Table 3 Distribution of phenotypes and genotypes in the two latent classes (LC)Table 1 depicts the baseline phenotypes and genotypes in the obtained population.

Note incomplete data especially in the cranium phenotypes. In total 259 valid genotypes were present. In total, 289 cases had complete data for all hand and foot phenotypes (preaxial polydactyly, postaxial polydactyly and syndactyly) and thus were available for LCA.

Combined, for phenotype/genotype correlation 258 cases were available with complete genotypes and complete hand and foot phenotypes.Table 2 depicts the model fit indices for all models that have been fitted to our data.Table 3 depicts the distribution of phenotypes and genotypes over the two assigned LCs. Hand and foot phenotypes were used as input for the LCA, thus are all complete cases. Malformation of the cranium and genotypes do have missing cases.

Note that for the LCA, full case description was required, resulting in eight cases due to incomplete phenotypes. Out of these eight, one also had a genotype that thus needed to be excluded. Missingness of genotypic data was higher in LC2, mostly due to CNVs (table 1).In 54/60 cases, a missense variant produced a posterior phenotype.

Likewise, splice site variants show the same phenotype in 23/24 cases (table 3). For both frameshift and nonsense variants, this relation is not significant (52 anterior vs 54 posterior and 26 anterior vs 42 posterior, respectively). Therefore, only for nonsense and frameshift variants the location of the variant was plotted against the probability for LC2 membership in figure 1.

A full scatterplot of all variants is available in online supplementary figure 1.Figure 1 reveals a pattern for these nonsense and frameshift variants that reveals that variants at the C-terminal of the gene predict anterior phenotypes. When relating the domains of the GLI3 protein to the observed phenotype, we observe that the majority of patients with a nonsense or frameshift variant in the repressor domain, the zinc finger domain or the cleavage site had a high probability of an LC2/anterior phenotype. This group contains all variants that are either experimentally determined to be subject to NMD (triangle marker in figure 1) or predicted to be subject to NMD (diamond marker in figure 1).

Frameshift and nonsense variants in the activator domain result in high probability for an LC1/posterior phenotype. These variants will be further referred to as truncating variants in the activator domain.The univariate relation of the individual phenotypes to these two groups of variants are estimated and presented in table 4. In our multivariate analysis, postaxial polydactyly of the foot and hand are the strongest predictors (Beta.

2.548, p<0001 and Beta. 1.47, p=0.013, respectively) for patients to have a truncating variant in the activator domain. Moreover, the effect sizes of preaxial polydactyly of the hand and feet (Beta.

ˆ’0.797, p=0123 and −1.772, p=0.001) reveals that especially postaxial polydactyly of the foot is the dominant predictor for the genetic substrate of the observed anomalies.View this table:Table 4 Univariate and multivariate analysis of the phenotype/genotype correlationTable 4 shows exploration of the individual phenotypes on the genotype, both univariate and multivariate. The multivariate analysis corrects for the presence of multiple phenotypes in the underlying population.Although the craniofacial anomalies could not be included in the LCA, the relation between the observed anomalies and the identified genetic substrates can be studied. The prevalence of hypertelorism was equally distributed over the two groups of variants (47/135 vs 21/47 respectively, p<0.229).

However for corpus callosum agenesis and macrocephaly, there was a higher prevalence in patients with a truncating variant in the activator domain (3/75 vs 11/41, p<0.001. OR. 8.8, p<0.001) and 42/123 vs 24/48, p<0.05).

Noteworthy is the fact that 11/14 cases with corpus callosum agenesis in the dataset had a truncating variant in the activator domain.DiscussionIn this report, we present new insights into the correlation between the phenotype and the genotype in patients with GLI3-mediated polydactyly syndromes. We illustrate that there are two LCs of patients, best predicted by postaxial polydactyly of the hand and foot for LC1, and the preaxial polydactyly of the hand and foot and syndactyly of the foot for LC2. Patients with postaxial phenotypes have a higher risk of having a truncating variant in the activator domain of the GLI3 gene which is also related to a higher risk of corpus callosum agenesis.

These results suggest a functional difference between truncating variants on the N-terminal and the C-terminal side of the GLI3 cleavage site.Previous attempts of phenotype to genotype correlation have not yet provided the clinical confirmation of these assumed mechanisms in the pathophysiology of GLI3-mediated polydactyly syndromes. Johnston et al have successfully determined the Pallister-Hall region in which truncating variants produce a Pallister-Hall phenotype rather than Greig syndrome.11 However, in their latest population study, subtypes of both syndromes were included to explain the full spectrum of observed malformations. In 2015, Demurger et al reported the higher incidence of corpus callosum agenesis in the Greig syndrome population with truncating mutations in the activator domain.12 Al-Qattan in his review summarises the concept of a spectrum of anomalies dependent on haplo-insufficiency (through different mechanisms) and repressor overexpression.13 However, he bases this theory mainly on reviewed experimental data.

Our report is the first to provide an extensive clinical review of cases that substantiate the phenotypic difference between the two groups that could fit the suggested mechanisms. We agree with Al-Qattan et al that a variation of anomalies can be observed given any pathogenic variant in the GLI3 gene, but overall two dominant phenotypes are present. A population with predominantly preaxial anomalies and one with postaxial anomalies.

The presence of preaxial or postaxial polydactyly and syndactyly is not mutually exclusive for one of these two subclasses. Meaning that preaxial polydactyly can co-occur with postaxial polydactyly. However, truncating mutations in the activator domain produce a postaxial phenotype, as can be derived from the risk in table 4.

The higher risk of corpus callosum agenesis in this population shows that differentiating between a preaxial phenotype and a postaxial phenotype, instead of between the different GLI3-mediated polydactyly syndromes, might be more relevant regarding diagnostics for corpus callosum agenesis.We chose to use LCA as an exploratory tool only in our population for two reasons. First of all, LCA can be useful to identify subgroups, but there is no ‘true’ model or number of subgroups you can detect. The best fitting model can only be estimated based on the available measures and approximates the true subgroups that might be present.

Second, LC membership assignment is a statistical procedure based on the posterior probability, with concordant errors of the estimation, rather than a clinical value that can be measured or evaluated. Therefore, we decided to use our LCA only in an exploratory tool, and perform our statistics using the actual phenotypes that predict LC membership and the associated genotypes. Overall, this method worked well to differentiate the two subgroups present in our dataset.

However, outliers were observed. A qualitative analysis of these outliers is available in the online supplementary data.The genetic substrate for the two phenotypic clusters can be discussed based on multiple experiments. Overall, we hypothesise two genetic clusters.

One that is due to haploinsufficiency and one that is due to abnormal truncation of the activator. The hypothesised cluster of variants that produce haploinsufficiency is mainly based on the experimental data that confirms NMD in two variants and the NMD prediction of other nonsense variants in Alamut. For the frameshift variants, it is also likely that the cleavage of the zinc finger domain results in functional haploinsufficiency either because of a lack of signalling domains or similarly due to NMD.

Missense variants could cause haploinsufficiency through the suggested mechanism by Krauss et al who have illustrated that missense variants in the MID1 domain hamper the functional interaction with the MID1-α4-PP2A complex, leading to a subcellular location of GLI3.24 The observed missense variants in our study exceed the region to which Krauss et al have limited the MID-1 interaction domain. An alternative theory is suggested by Zhou et al who have shown that missense variants in the MBD can cause deficiency in the signalling of GLI3A, functionally implicating a relative overexpression of GLI3R.22 However, GLI3R overexpression would likely produce a posterior phenotype, as determined by Hill et al in their fixed homo and hemizygous GLI3R models.15 Therefore, our hypothesis is that all included missense variants have a similar pathogenesis which is more likely in concordance with the mechanism introduced by Krauss et al. To our knowledge, no splice site variants have been functionally described in literature.

However, it is noted that the 15 and last exon encompasses the entire activator domain, thus any splice site mutation is by definition located on the 5′ side of the activator. Based on the phenotype, we would suggest that these variants fail to produce a functional protein. We hypothesise that the truncating variants of the activator domain lead to overexpression of GLI3R in SHH rich areas.

In normal development, the presence of SHH prevents the processing of full length GLI34 into GLI3R, thus producing the full length activator. In patients with a truncating variant of the activator domain of GLI3, thus these variants likely have the largest effect in SHH rich areas, such as the ZPA located at the posterior side of the hand/footplate. Moreover, the lack of posterior anomalies in the GLI3∆699/- mouse model (hemizygous fixed repressor model) compared with the GLI3∆699/∆699 mouse model (homozygous fixed repressor model), suggesting a dosage effect of GLI3R to be responsible for posterior hand anomalies.15 These findings are supported by Lewandowski et al, who show that the majority of the target genes in GLI signalling are regulated by GLI3R rather than GLI3A.44 Together, these findings suggest a role for the location and type of variant in GLI3-mediated syndromes.Interestingly, the difference between Pallister-Hall syndrome and GLI3-mediated polydactyly syndromes has also been attributed to the GLI3R overexpression.

However, the difference in phenotype observed in the cases with a truncating variant in the activator domain and Pallister-Hall syndrome suggest different functional consequences. When studying figure 1, it is noted that the included truncating variants on the 3′ side of the cleavage site seldomly affect the CBP binding region, which could provide an explanation for the observed differences. This binding region is included in the Pallister-Hall region as defined by Johnston et al and is necessary for the downstream signalling with GLI1.10 11 23 45 Interestingly, recent reports show that pathogenic variants in GLI1 can produce phenotypes concordant with Ellis von Krefeld syndrome, which includes overlapping features with Pallister-Hall syndrome.46 The four truncating variants observed in this study that do affect the CBP but did not result in a Pallister-Hall phenotype are conflicting with this theory.

Krauss et al postulate an alternative hypothesis, they state that the MID1-α4-PP2A complex, which is essential for GLI3A signalling, could also be the reason for overlapping features of Opitz syndrome, caused by variants in MID1, and Pallister-Hall syndrome. Further analysis is required to fully appreciate the functional differences between truncating mutations that cause Pallister-Hall syndrome and those that result in GLI3-mediated polydactyly syndromes.For the clinical evaluation of patients with GLI3-mediated polydactyly syndromes, intracranial anomalies are likely the most important to predict based on the variant. Unfortunately, the presence of corpus callosum agenesis was not routinely investigated or reported thus this feature could not be used as an indicator phenotype for LC membership.

Interestingly when using only hand and foot phenotypes, we did notice a higher prevalence of corpus callosum agenesis in patients with posterior phenotypes. The suggested relation between truncating mutations in the activator domain causing these posterior phenotypes and corpus callosum agenesis was statistically confirmed (OR. 8.8, p<0.001).

Functionally this relation could be caused by the GLI3-MED12 interaction at the MBD. Pathogenic DNA variants in MED12 can cause Opitz-Kaveggia syndrome, a syndrome in which presentation includes corpus callosum agenesis, broad halluces and thumbs.47In conclusion, there are two distinct phenotypes within the GLI3-mediated polydactyly population. Patients with more posteriorly and more anteriorly oriented hand anomalies.

Furthermore, this difference is related to the observed variant in GLI3. We hypothesise that variants that cause haploinsufficiency produce anterior anomalies of the hand, whereas variants with abnormal truncation of the activator domain have more posterior anomalies. Furthermore, patients that have a variant that produces abnormal truncation of the activator domain, have a greater risk for corpus callosum agenesis.

Thus, we advocate to differentiate preaxial or postaxial oriented GLI3 phenotypes to explain the pathophysiology as well as to get a risk assessment for corpus callosum agenesis.Data availability statementData are available upon reasonable request.Ethics statementsPatient consent for publicationNot required.Ethics approvalThe research protocol was approved by the local ethics board of the Erasmus MC University Medical Center (MEC 2015-679)..

AbstractIntroduction. We report a very rare case of familial breast cancer and diffuse gastric cancer, with germline pathogenic variants in both BRCA1 and CDH1 genes. To the best of our knowledge, this is the first report of such an association.Family description. The proband is a woman diagnosed with breast cancer at the age of 52 years.

She requested genetic counselling in 2012, at the age of 91 years, because of a history of breast cancer in her daughter, her sister, her niece and her paternal grandmother and was therefore concerned about her relatives. Her sister and maternal aunt also had gastric cancer. She was tested for several genes associated with hereditary breast cancer.Results. A large deletion of BRCA1 from exons 1 to 7 and two CDH1 pathogenic cis variants were identified.Conclusion.

This complex situation is challenging for genetic counselling and management of at-risk individuals.cancer. Breastcancer. Gastricclinical geneticsgenetic screening/counsellingmolecular geneticsIntroductionGLI-Kruppel family member 3 (GLI3) encodes for a zinc finger transcription factor which plays a key role in the sonic hedgehog (SHH) signalling pathway essential in both limb and craniofacial development.1 2 In hand development, SHH is expressed in the zone of polarising activity (ZPA) on the posterior side of the handplate. The ZPA expresses SHH, creating a gradient of SHH from the posterior to the anterior side of the handplate.

In the presence of SHH, full length GLI3-protein is produced (GLI3A), whereas absence of SHH causes cleavage of GLI3 into its repressor form (GLI3R).3 4 Abnormal expression of this SHH/GLI3R gradient can cause both preaxial and postaxial polydactyly.2Concordantly, pathogenic DNA variants in the GLI3 gene are known to cause multiple syndromes with craniofacial and limb involvement, such as. Acrocallosal syndrome5 (OMIM. 200990), Greig cephalopolysyndactyly syndrome6 (OMIM. 175700) and Pallister-Hall syndrome7 (OMIM.

146510). Also, in non-syndromic polydactyly, such as preaxial polydactyly-type 4 (PPD4, OMIM. 174700),8 pathogenic variants in GLI3 have been described. Out of these diseases, Pallister-Hall syndrome is the most distinct entity, defined by the presence of central polydactyly and hypothalamic hamartoma.9 The other GLI3 syndromes are defined by the presence of preaxial and/or postaxial polydactyly of the hand and feet with or without syndactyly (Greig syndrome, PPD4).

Also, various mild craniofacial features such as hypertelorism and macrocephaly can occur. Pallister-Hall syndrome is caused by truncating variants in the middle third of the GLI3 gene.10–12 The truncation of GLI3 causes an overexpression of GLI3R, which is believed to be the key difference between Pallister-Hall and the GLI3-mediated polydactyly syndromes.9 11 Although multiple attempts have been made, the clinical and genetic distinction between the GLI3-mediated polydactyly syndromes is less evident. This has for example led to the introduction of subGreig and the formulation of an Oro-facial-digital overlap syndrome.10 Other authors, suggested that we should not regard these diseases as separate entities, but as a spectrum of GLI3-mediated polydactyly syndromes.13Although phenotype/genotype correlation of the different syndromes has been cumbersome, clinical and animal studies do provide evidence that distinct regions within the gene, could be related to the individual anomalies contributing to these syndromes. First, case studies show isolated preaxial polydactyly is caused by both truncating and non-truncating variants throughout the GLI3 gene, whereas in isolated postaxial polydactyly cases truncating variants at the C-terminal side of the gene are observed.12 14 These results suggest two different groups of variants for preaxial and postaxial polydactyly.

Second, recent animal studies suggest that posterior malformations in GLI3-mediated polydactyly syndromes are likely related to a dosage effect of GLI3R rather than due to the influence of an altered GLI3A expression.15Past attempts for phenotype/genotype correlation in GLI3-mediated polydactyly syndromes have directly related the diagnosed syndrome to the observed genotype.10–12 16 Focusing on individual hand phenotypes, such as preaxial and postaxial polydactyly and syndactyly might be more reliable because it prevents misclassification due to inconsistent use of syndrome definition. Subsequently, latent class analysis (LCA) provides the possibility to relate a group of observed variables to a set of latent, or unmeasured, parameters and thereby identifying different subgroups in the obtained dataset.17 As a result, LCA allows us to group different phenotypes within the GLI3-mediated polydactyly syndromes and relate the most important predictors of the grouped phenotypes to the observed GLI3 variants.The aim of our study was to further investigate the correlation of the individual phenotypes to the genotypes observed in GLI3-mediated polydactyly syndromes, using LCA. Cases were obtained by both literature review and the inclusion of local clinical cases. Subsequently, we identified two subclasses of limb anomalies that relate to the underlying GLI3 variant.

We provide evidence for two different phenotypic and genotypic groups with predominantly preaxial and postaxial hand and feet anomalies, and we specify those cases with a higher risk for corpus callosum anomalies.MethodsLiterature reviewThe Human Gene Mutation Database (HGMD Professional 2019) was reviewed to identify known pathogenic variants in GLI3 and corresponding phenotypes.18 All references were obtained and cases were included when they were diagnosed with either Greig or subGreig syndrome or PPD4.10–12 Pallister-Hall syndrome and acrocallosal syndrome were excluded because both are regarded distinct syndromes and rather defined by the presence of the non-hand anomalies, than the presence of preaxial or postaxial polydactyly.13 19 Isolated preaxial or postaxial polydactyly were excluded for two reasons. The phenotype/genotype correlations are better understood and both anomalies can occur sporadically which could introduce falsely assumed pathogenic GLI3 variants in the analysis. Additionally, cases were excluded when case-specific phenotypic or genotypic information was not reported or if these two could not be related to each other. Families with a combined phenotypic description, not reducible to individual family members, were included as one case in the analysis.Clinical casesThe Sophia Children’s Hospital Database was reviewed for cases with a GLI3 variant.

Within this population, the same inclusion criteria for the phenotype were valid. Relatives of the index patients were also contacted for participation in this study, when they showed comparable hand, foot, or craniofacial malformations or when a GLI3 variant was identified. Phenotypes of the hand, foot and craniofacial anomalies of the patients treated in the Sophia Children's Hospital were collected using patient documentation. Family members were identified and if possible, clinically verified.

Alternatively, family members were contacted to verify their phenotypes. If no verification was possible, cases were excluded.PhenotypesThe phenotypes of both literature cases and local cases were extracted in a similar fashion. The most frequently reported limb and craniofacial phenotypes were dichotomised. The dichotomised hand and foot phenotypes were preaxial polydactyly, postaxial polydactyly and syndactyly.

Broad halluces or thumbs were commonly reported by authors and were dichotomised as a presentation of preaxial polydactyly. The extracted dichotomised craniofacial phenotypes were hypertelorism, macrocephaly and corpus callosum agenesis. All other phenotypes were registered, but not dichotomised.Pathogenic GLI3 variantsAll GLI3 variants were extracted and checked using Alamut Visual V.2.14. If indicated, variants were renamed according to standard Human Genome Variation Society nomenclature.20 Variants were grouped in either missense, frameshift, nonsense or splice site variants.

In the group of frameshift variants, a subgroup with possible splice site effect were identified for subgroup analysis when indicated. Similarly, nonsense variants prone for nonsense mediated decay (NMD) and nonsense variants with experimentally confirmed NMD were identified.21 Deletions of multiple exons, CNVs and translocations were excluded for analysis. A full list of included mutations is available in the online supplementary materials.Supplemental materialThe location of the variant was compared with five known structural domains of the GLI3 gene. (1) repressor domain, (2) zinc finger domain, (3) cleavage site, (4) activator domain, which we defined as a concatenation of the separately identified transactivation zones, the CBP binding domain and the mediator binding domain (MBD) and (5) the MID1 interaction region domain.1 6 22–24 The boundaries of each of the domains were based on available literature (figure 1, exact locations available in the online supplementary materials).

The boundaries used by different authors did vary, therefore a consensus was made.In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed. The full figure, including all variant types, can be found in the online supplementary figure 1. Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant.

If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle. Again, the size indicates the number of observations." data-icon-position data-hide-link-title="0">Figure 1 In this figure the posterior probability of an anterior phenotype is plotted against the location of the variant, stratified for the type of mutation that was observed. For better overview, only variants with a location effect were displayed.

The full figure, including all variant types, can be found in the online supplementary figure 1. Each mutation is depicted as a dot, the size of the dot represents the number of observations for that variant. If multiple observations were made, the mean posterior odds and IQR are plotted. For the nonsense variants, variants that were predicted to produce nonsense mediated decay, are depicted using a triangle.

Again, the size indicates the number of observations.Supplemental materialLatent class analysisTo cluster phenotypes and relate those to the genotypes of the patients, an explorative analysis was done using LCA in R (R V.3.6.1 for Mac. Polytomous variable LCA, poLCA V.1.4.1.). We used our LCA to detect the number of phenotypic subgroups in the dataset and subsequently predict a class membership for each case in the dataset based on the posterior probabilities.In order to make a reliable prediction, only phenotypes that were sufficiently reported and/or ruled out were feasible for LCA, limiting the analysis to preaxial polydactyly, postaxial polydactyly and syndactyly of the hands and feet. Only full cases were included.

To determine the optimal number of classes, we fitted a series of models ranging from a one-class to a six-class model. The optimal number of classes was based on the conditional Akaike information criterion (cAIC), the non adjusted and the sample-size adjusted Bayesian information criterion (BIC and aBIC) and the obtained entropy.25 The explorative LCA produces both posterior probabilities per case for both classes and predicted class membership. Using the predicted class membership, the phenotypic features per class were determined in a univariate analysis (χ2, SPSS V.25). Using the posterior probabilities on latent class (LC) membership, a scatter plot was created using the location of the variant on the x-axis and the probability of class membership on the y-axis for each of the types of variants (Tibco Spotfire V.7.14).

Using these scatter plots, variants that give similar phenotypes were clustered.Genotype/phenotype correlationBecause an LC has no clinical value, the correlation between genotypes and phenotypes was investigated using the predictor phenotypes and the clustered phenotypes. First, those phenotypes that contribute most to LC membership were identified. Second those phenotypes were directly related to the different types of variants (missense, nonsense, frameshift, splice site) and their clustered locations. Quantification of the relation was performed using a univariate analysis using a χ2 test.

Because of our selection criteria, meaning patients at least have two phenotypes, a multivariate using a logistic regression analysis was used to detect the most significant predictors in the overall phenotype (SPSS V.25). Finally, we explored the relation of the clustered genotypes to the presence of corpus callosum agenesis, a rare malformation in GLI3-mediated polydactyly syndromes which cannot be readily diagnosed without additional imaging.ResultsWe included 251 patients from the literature and 46 local patients,10–12 16 21 26–43 in total 297 patients from 155 different families with 127 different GLI3 variants, 32 of which were large deletions, CNVs or translocations. In six local cases, the exact variant could not be retrieved by status research.The distribution of the most frequently observed phenotypes and variants are presented in table 1. Other recurring phenotypes included developmental delay (n=22), broad nasal root (n=23), frontal bossing or prominent forehead (n=16) and craniosynostosis (n=13), camptodactyly (n=8) and a broad first interdigital webspace of the foot (n=6).View this table:Table 1 Baseline phenotypes and genotypes of selected populationThe LCA model was fitted using the six defined hand/foot phenotypes.

Model fit indices for the LCA are displayed in table 2. Based on the BIC, a two-class model has the best fit for our data. The four-class model does show a gain in entropy, however with a higher BIC and loss of df. Therefore, based on the majority of performance statistics and the interpretability of the model, a two-class model was chosen.

Table 3 displays the distribution of phenotypes and genotypes over the two classes.View this table:Table 2 Model fit indices for the one-class through six-class model evaluated in our LCAView this table:Table 3 Distribution of phenotypes and genotypes in the two latent classes (LC)Table 1 depicts the baseline phenotypes and genotypes in the obtained population. Note incomplete data especially in the cranium phenotypes. In total 259 valid genotypes were present. In total, 289 cases had complete data for all hand and foot phenotypes (preaxial polydactyly, postaxial polydactyly and syndactyly) and thus were available for LCA.

Combined, for phenotype/genotype correlation 258 cases were available with complete genotypes and complete hand and foot phenotypes.Table 2 depicts the model fit indices for all models that have been fitted to our data.Table 3 depicts the distribution of phenotypes and genotypes over the two assigned LCs. Hand and foot phenotypes were used as input for the LCA, thus are all complete cases. Malformation of the cranium and genotypes do have missing cases. Note that for the LCA, full case description was required, resulting in eight cases due to incomplete phenotypes.

Out of these eight, one also had a genotype that thus needed to be excluded. Missingness of genotypic data was higher in LC2, mostly due to CNVs (table 1).In 54/60 cases, a missense variant produced a posterior phenotype. Likewise, splice site variants show the same phenotype in 23/24 cases (table 3). For both frameshift and nonsense variants, this relation is not significant (52 anterior vs 54 posterior and 26 anterior vs 42 posterior, respectively).

Therefore, only for nonsense and frameshift variants the location of the variant was plotted against the probability for LC2 membership in figure 1. A full scatterplot of all variants is available in online supplementary figure 1.Figure 1 reveals a pattern for these nonsense and frameshift variants that reveals that variants at the C-terminal of the gene predict anterior phenotypes. When relating the domains of the GLI3 protein to the observed phenotype, we observe that the majority of patients with a nonsense or frameshift variant in the repressor domain, the zinc finger domain or the cleavage site had a high probability of an LC2/anterior phenotype. This group contains all variants that are either experimentally determined to be subject to NMD (triangle marker in figure 1) or predicted to be subject to NMD (diamond marker in figure 1).

Frameshift and nonsense variants in the activator domain result in high probability for an LC1/posterior phenotype. These variants will be further referred to as truncating variants in the activator domain.The univariate relation of the individual phenotypes to these two groups of variants are estimated and presented in table 4. In our multivariate analysis, postaxial polydactyly of the foot and hand are the strongest predictors (Beta. 2.548, p<0001 and Beta.

1.47, p=0.013, respectively) for patients to have a truncating variant in the activator domain. Moreover, the effect sizes of preaxial polydactyly of the hand and feet (Beta. ˆ’0.797, p=0123 and −1.772, p=0.001) reveals that especially postaxial polydactyly of the foot is the dominant predictor for the genetic substrate of the observed anomalies.View this table:Table 4 Univariate and multivariate analysis of the phenotype/genotype correlationTable 4 shows exploration of the individual phenotypes on the genotype, both univariate and multivariate. The multivariate analysis corrects for the presence of multiple phenotypes in the underlying population.Although the craniofacial anomalies could not be included in the LCA, the relation between the observed anomalies and the identified genetic substrates can be studied.

The prevalence of hypertelorism was equally distributed over the two groups of variants (47/135 vs 21/47 respectively, p<0.229). However for corpus callosum agenesis and macrocephaly, there was a higher prevalence in patients with a truncating variant in the activator domain (3/75 vs 11/41, p<0.001. OR. 8.8, p<0.001) and 42/123 vs 24/48, p<0.05).

Noteworthy is the fact that 11/14 cases with corpus callosum agenesis in the dataset had a truncating variant in the activator domain.DiscussionIn this report, we present new insights into the correlation between the phenotype and the genotype in patients with GLI3-mediated polydactyly syndromes. We illustrate that there are two LCs of patients, best predicted by postaxial polydactyly of the hand and foot for LC1, and the preaxial polydactyly of the hand and foot and syndactyly of the foot for LC2. Patients with postaxial phenotypes have a higher risk of having a truncating variant in the activator domain of the GLI3 gene which is also related to a higher risk of corpus callosum agenesis. These results suggest a functional difference between truncating variants on the N-terminal and the C-terminal side of the GLI3 cleavage site.Previous attempts of phenotype to genotype correlation have not yet provided the clinical confirmation of these assumed mechanisms in the pathophysiology of GLI3-mediated polydactyly syndromes.

Johnston et al have successfully determined the Pallister-Hall region in which truncating variants produce a Pallister-Hall phenotype rather than Greig syndrome.11 However, in their latest population study, subtypes of both syndromes were included to explain the full spectrum of observed malformations. In 2015, Demurger et al reported the higher incidence of corpus callosum agenesis in the Greig syndrome population with truncating mutations in the activator domain.12 Al-Qattan in his review summarises the concept of a spectrum of anomalies dependent on haplo-insufficiency (through different mechanisms) and repressor overexpression.13 However, he bases this theory mainly on reviewed experimental data. Our report is the first to provide an extensive clinical review of cases that substantiate the phenotypic difference between the two groups that could fit the suggested mechanisms. We agree with Al-Qattan et al that a variation of anomalies can be observed given any pathogenic variant in the GLI3 gene, but overall two dominant phenotypes are present.

A population with predominantly preaxial anomalies and one with postaxial anomalies. The presence of preaxial or postaxial polydactyly and syndactyly is not mutually exclusive for one of these two subclasses. Meaning that preaxial polydactyly can co-occur with postaxial polydactyly. However, truncating mutations in the activator domain produce a postaxial phenotype, as can be derived from the risk in table 4.

The higher risk of corpus callosum agenesis in this population shows that differentiating between a preaxial phenotype and a postaxial phenotype, instead of between the different GLI3-mediated polydactyly syndromes, might be more relevant regarding diagnostics for corpus callosum agenesis.We chose to use LCA as an exploratory tool only in our population for two reasons. First of all, LCA can be useful to identify subgroups, but there is no ‘true’ model or number of subgroups you can detect. The best fitting model can only be estimated based on the available measures and approximates the true subgroups that might be present. Second, LC membership assignment is a statistical procedure based on the posterior probability, with concordant errors of the estimation, rather than a clinical value that can be measured or evaluated.

Therefore, we decided to use our LCA only in an exploratory tool, and perform our statistics using the actual phenotypes that predict LC membership and the associated genotypes. Overall, this method worked well to differentiate the two subgroups present in our dataset. However, outliers were observed. A qualitative analysis of these outliers is available in the online supplementary data.The genetic substrate for the two phenotypic clusters can be discussed based on multiple experiments.

Overall, we hypothesise two genetic clusters. One that is due to haploinsufficiency and one that is due to abnormal truncation of the activator. The hypothesised cluster of variants that produce haploinsufficiency is mainly based on the experimental data that confirms NMD in two variants and the NMD prediction of other nonsense variants in Alamut. For the frameshift variants, it is also likely that the cleavage of the zinc finger domain results in functional haploinsufficiency either because of a lack of signalling domains or similarly due to NMD.

Missense variants could cause haploinsufficiency through the suggested mechanism by Krauss et al who have illustrated that missense variants in the MID1 domain hamper the functional interaction with the MID1-α4-PP2A complex, leading to a subcellular location of GLI3.24 The observed missense variants in our study exceed the region to which Krauss et al have limited the MID-1 interaction domain. An alternative theory is suggested by Zhou et al who have shown that missense variants in the MBD can cause deficiency in the signalling of GLI3A, functionally implicating a relative overexpression of GLI3R.22 However, GLI3R overexpression would likely produce a posterior phenotype, as determined by Hill et al in their fixed homo and hemizygous GLI3R models.15 Therefore, our hypothesis is that all included missense variants have a similar pathogenesis which is more likely in concordance with the mechanism introduced by Krauss et al. To our knowledge, no splice site variants have been functionally described in literature. However, it is noted that the 15 and last exon encompasses the entire activator domain, thus any splice site mutation is by definition located on the 5′ side of the activator.

Based on the phenotype, we would suggest that these variants fail to produce a functional protein. We hypothesise that the truncating variants of the activator domain lead to overexpression of GLI3R in SHH rich areas. In normal development, the presence of SHH prevents the processing of full length GLI34 into GLI3R, thus producing the full length activator. In patients with a truncating variant of the activator domain of GLI3, thus these variants likely have the largest effect in SHH rich areas, such as the ZPA located at the posterior side of the hand/footplate.

Moreover, the lack of posterior anomalies in the GLI3∆699/- mouse model (hemizygous fixed repressor model) compared with the GLI3∆699/∆699 mouse model (homozygous fixed repressor model), suggesting a dosage effect of GLI3R to be responsible for posterior hand anomalies.15 These findings are supported by Lewandowski et al, who show that the majority of the target genes in GLI signalling are regulated by GLI3R rather than GLI3A.44 Together, these findings suggest a role for the location and type of variant in GLI3-mediated syndromes.Interestingly, the difference between Pallister-Hall syndrome and GLI3-mediated polydactyly syndromes has also been attributed to the GLI3R overexpression. However, the difference in phenotype observed in the cases with a truncating variant in the activator domain and Pallister-Hall syndrome suggest different functional consequences. When studying figure 1, it is noted that the included truncating variants on the 3′ side of the cleavage site seldomly affect the CBP binding region, which could provide an explanation for the observed differences. This binding region is included in the Pallister-Hall region as defined by Johnston et al and is necessary for the downstream signalling with GLI1.10 11 23 45 Interestingly, recent reports show that pathogenic variants in GLI1 can produce phenotypes concordant with Ellis von Krefeld syndrome, which includes overlapping features with Pallister-Hall syndrome.46 The four truncating variants observed in this study that do affect the CBP but did not result in a Pallister-Hall phenotype are conflicting with this theory.

Krauss et al postulate an alternative hypothesis, they state that the MID1-α4-PP2A complex, which is essential for GLI3A signalling, could also be the reason for overlapping features of Opitz syndrome, caused by variants in MID1, and Pallister-Hall syndrome. Further analysis is required to fully appreciate the functional differences between truncating mutations that cause Pallister-Hall syndrome and those that result in GLI3-mediated polydactyly syndromes.For the clinical evaluation of patients with GLI3-mediated polydactyly syndromes, intracranial anomalies are likely the most important to predict based on the variant. Unfortunately, the presence of corpus callosum agenesis was not routinely investigated or reported thus this feature could not be used as an indicator phenotype for LC membership. Interestingly when using only hand and foot phenotypes, we did notice a higher prevalence of corpus callosum agenesis in patients with posterior phenotypes.

The suggested relation between truncating mutations in the activator domain causing these posterior phenotypes and corpus callosum agenesis was statistically confirmed (OR. 8.8, p<0.001). Functionally this relation could be caused by the GLI3-MED12 interaction at the MBD. Pathogenic DNA variants in MED12 can cause Opitz-Kaveggia syndrome, a syndrome in which presentation includes corpus callosum agenesis, broad halluces and thumbs.47In conclusion, there are two distinct phenotypes within the GLI3-mediated polydactyly population.

Patients with more posteriorly and more anteriorly oriented hand anomalies. Furthermore, this difference is related to the observed variant in GLI3. We hypothesise that variants that cause haploinsufficiency produce anterior anomalies of the hand, whereas variants with abnormal truncation of the activator domain have more posterior anomalies. Furthermore, patients that have a variant that produces abnormal truncation of the activator domain, have a greater risk for corpus callosum agenesis.

Thus, we advocate to differentiate preaxial or postaxial oriented GLI3 phenotypes to explain the pathophysiology as well as to get a risk assessment for corpus callosum agenesis.Data availability statementData are available upon reasonable request.Ethics statementsPatient consent for publicationNot required.Ethics approvalThe research protocol was approved by the local ethics board of the Erasmus MC University Medical Center (MEC 2015-679)..

Can cipro raise blood sugar

US President Joe Biden has can cipro raise blood sugar replaced his disgraced science adviser, Eric Lander, with two scientists who will cipro pill price split Lander’s duties “until permanent leadership is nominated and confirmed”, according to the White House. Alondra Nelson, deputy director for science and society at the Office of Science and Technology Policy (OSTP), which Lander led, will become acting director of the agency. And Francis Collins, who led the US National Institutes of Health before retiring in December, will temporarily become Biden’s science adviser and co-chair the can cipro raise blood sugar President’s Council of Advisors on Science and Technology (PCAST). Lander resigned on 7 February, after the news outlet Politico revealed that, according to a White House investigation, he had violated the Biden administration’s Safe and Respectful Workplace Policy by mistreating staff members at the OSTP.

In his resignation letter, Lander acknowledged that things he had said to team members “crossed the line at times into can cipro raise blood sugar being disrespectful and demeaning”. Biden moved swiftly to name interim replacements for Lander, who had been leading some of the president’s priority science initiatives—in particular, the creation of the Advanced Research Projects Agency for Health (ARPA-H), a high-risk, high-reward biomedical innovations agency. And the revamping of his ‘Cancer Moonshot’ programme, which launched five years ago and has the new goal of decreasing cancer deaths by at least 50% in the next 25 years. The OSTP did not answer can cipro raise blood sugar Nature’s query about why Lander’s duties have been split between two people.

Since the agency was established in 1976, its director has also gone by the title of science adviser to the president. The OSTP director oversees a staff of roughly 150 people who are charged with coordinating scientific activities across the federal government and ensuring that the can cipro raise blood sugar president and the executive branch have access to the best available scientific information as they make decisions and craft federal policies. The role of presidential science adviser has varied by administration. Both Lander and John Holdren, science adviser under former president Barack Obama, also served as ‘assistant to the president’, a role that granted them can cipro raise blood sugar more direct access to the Oval Office.

Biden had also elevated Lander to his cabinet, a first for an OSTP director. Kenneth Bernard, an epidemiologist and biodefence researcher who has worked for the US government under several presidential administrations, says that Lander’s swift, interim replacements make sense. Although he doesn’t have inside knowledge, he speculates that Biden might have chosen Collins because of his can cipro raise blood sugar grounding in biomedical laboratory research and his extended experience heading a government agency. And Collins, Bernard suggests, might not have wanted to manage the OSTP, having just retired from the NIH.

He adds that Nelson is can cipro raise blood sugar well suited to running the OSTP, having been deputy director for the past year. The White House announcement said. €œThe selections are responsive to the dual importance of a strong OSTP that can drive science and technology solutions to our greatest challenges—and the very specific attention the President wants to give to the creation of a new ARPA-H research and discovery agency, the building of support for a Cancer Moonshot 2.0, the search for a new head of NIH, and the broad advisory work of PCAST.” Nelson is a prominent sociologist, whose selection by Biden as an OSTP deputy drew praise from the scientific community. She has studied the societal impact of can cipro raise blood sugar emerging technology and the effect of racism on science and medicine.

As OSTP deputy director for science and society, she co-leads a task force charged with bolstering scientific-integrity policies and protecting scientists from political interference across the federal government. Collins was director of the NIH under three US presidents, serving for longer than any other presidentially appointed head can cipro raise blood sugar of the biomedical agency. He built a reputation as a shrewd spokesperson for scientific research and steered the NIH through the early stages of the buy antibiotics cipro. Known for leading the Human Genome Project in the 1990s can cipro raise blood sugar and early 2000s, he had returned to his laboratory at the National Human Genome Research Institute to continue his research after retiring.

Neal Lane, a physicist at Rice University in Houston, Texas, who served as science adviser to former president Bill Clinton, says that splitting Lander’s duties is not a permanent solution. €œThe director of OSTP has always been, and should continue to be, the president’s science adviser,” he says. €œOSTP is the one agency in the federal government that has the expertise to provide advice on all aspects of US science and technology.” This article is reproduced with permission and can cipro raise blood sugar was first published on February 17 2022.The United States still owes the world details about how it plans to meet President Biden’s pledge to cut greenhouse gas emissions in half by the end of this decade. The White House promised last year that those would come in the form of a comprehensive “U.S.

National Climate Strategy.” That term was used more than 20 can cipro raise blood sugar times by the American government in a report submitted to the U.N. Climate body last year on how the United States would zero out emissions by 2050. That submission, known as “The Long-Term Strategy of the United States,” calls the National Climate Strategy, or NCS, a “companion” document that “focuses on the immediate policies and actions that will put America on track to reduce emissions by 50-52 percent below 2005 can cipro raise blood sugar levels in 2030.” Participants in the global climate talks assumed the NCS would be released at the U.N. Climate conference in Glasgow, Scotland, in November.

It still hasn’t been made public. Releasing the strategy would end the mystery around Biden’s ambitious promise to slash can cipro raise blood sugar emissions in half by 2030. Currently, no one knows exactly how the administration will achieve those cuts. And that may be why the strategy hasn’t been can cipro raise blood sugar released.

Because the administration isn’t sure either. A week before the conference opened, White House climate adviser Gina McCarthy and national economic adviser Brian Deese briefed environmental groups on the National Climate Strategy, leaving them with the impression that the strategy’s release was imminent. €œMy belief is, they were getting a little out over their can cipro raise blood sugar skis,” one participant said. At the time, the White House and Democratic leaders in Congress still hoped that the House and Senate would pass the “Build Back Better Act”—a sprawling climate and social spending bill that would go a long way toward meeting Biden’s promise to slash emissions in half by 2030.

House Speaker Nancy can cipro raise blood sugar Pelosi (D-Calif.) called passage of the act “imperative” to U.S. Credibility at the climate talks. But then “Build Back Better” faltered in the Senate after moderate Democrats balked can cipro raise blood sugar at its price tag and social spending provisions. Three months later, it remains mired in gridlock on Capitol Hill.

Meanwhile, the Biden administration faces the prospect this year of a Supreme Court decision that could severely restrict its ability to achieve its 2030 commitment through regulations that would limit power plant emissions. Amid all this uncertainty, the White can cipro raise blood sugar House has stopped talking about its 2030 road map—the National Climate Strategy. It didn’t respond to inquiries for this story. Advocates who are in touch with McCarthy and her staff say they’re focused on trying to resuscitate the climate provisions in “Build Back Better” rather than cobbling together a plan B for the 2030 emissions goal can cipro raise blood sugar.

And for now, they say, that’s fine. €œI’m not sure that sooner would be better than later if sooner means uncertainty about both of those elements,” said Alden Meyer, a senior associate with E3G, referring to Congress and the Supreme Court. €œThe utility of a product that lays out a strategy on can cipro raise blood sugar how we meet our emissions targets before we pass a much-needed legislative vehicle is marginal,” said Jamal Raad, executive director of Evergreen Action, a left-leaning climate group. The Paris Agreement’s rulebook doesn’t actually ask countries to provide a full accounting on how they plan to meet their nationally determined contributions, or NDCs.

The Biden can cipro raise blood sugar administration turned in its other U.N. Climate homework last year, including the 2050 decarbonization plan and a biennial report on emissions and carbon sinks that was overdue from the Trump administration. Still, international climate experts say more details would be welcome—from the United States can cipro raise blood sugar particularly, after it left the Paris deal under former President Trump. Meyer said international partners are “informally asking for reassurances whenever they have conversations with the U.S.” “But they understand very well that we have a separation-of-powers government, and they understand how narrow the control is, especially in the Senate,” he said.

€œI haven’t heard anyone pressing the U.S. To make a formal submission of can cipro raise blood sugar its climate strategy before it has some sense of what’s going to happen in Congress.” But he said that if Congress doesn’t act before the next round of U.N. Climate talks—in Egypt this November—the Biden administration will have to show its cards about how it plans to meet its emissions commitment—particularly if Democrats are poised to lose their majorities in Congress after the midterm election. €˜Sort of waiting’ McCarthy’s White House climate office is taking the lead in writing the National Climate Strategy, just as can cipro raise blood sugar it did the 2030 pledge that Biden unveiled at his Earth Day summit last year.

Climate envoy John Kerry’s staff took the lead in drafting the report on the U.S. Long-term decarbonization pathway and has given input on the National Climate Strategy. But the domestic climate office is responsible for nationally determined contributions, and the strategy can cipro raise blood sugar to meet it. McCarthy’s deputy, Ali Zaidi, is overseeing its development with policy adviser Greg Carlock.

Those briefed say the National Climate Strategy was already partially written before the talks in Glasgow, when can cipro raise blood sugar it was assumed that “Build Back Better” would be enacted. Observers don’t think the office is actively running scenarios now for how to meet the 50-to-52-percent pledge without legislation. The White House can cipro raise blood sugar has little incentive to do so. Putting out a road map that relies on uncertain congressional action could anger key lawmakers —like West Virginia Democratic Sen.

Joe Manchin, who has yet to sign off on a version of the “Build Back Better” climate provisions despite some suggestions that he might do so. A White House strategy previewing can cipro raise blood sugar an aggressive regime of EPA regulatory actions and limited fossil fuel development aimed at delivering the 2030 target could displease Manchin, a staunch champion of his state’s coal industry. Meanwhile, West Virginia’s other senator has made Biden’s Paris Agreement pledge her top oversight priority as ranking member of the Senate Energy and Natural Resources Committee. Sen.

Shelley Moore Capito (R-W.Va.), has written to EPA and the White House numerous times demanding details about how the 2030 climate goal was constructed. €œCongress has yet to receive any data generated or used to determine Biden’s greenhouse gas target,” she wrote in a November op-ed in The Hill newspaper. €œBy hiding its calculations, the Biden administration is avoiding tough questions about the policies that would be required to meet our climate pledge and how those policies would impact the lives of everyday Americans and small businesses.” Nate Hultman, the director of the Center for Global Sustainability at the University of Maryland, who joined Kerry’s staff last year and was lead author of the U.S. Long-Term Strategy, said both reports were based on the same modeling.

€œThe general trajectory that’s noted in the LTS is consistent with our NDC—50 to 52 [percent]—and does include some underlying policy drivers in that,” said Hultman, who returned to the University of Maryland earlier this year. €œSo it’s just that we weren’t as explicit in that, because we were sort of waiting for the [National Climate Strategy] to be able to do that deep dive into what’s happening in the near term.” ‘Push and pull’ The long-term road map points to Biden administration commitments that underly the 2050 decarbonization trajectory, like the pledge that U.S. Power-sector emissions would be zeroed out by 2035. The long-term strategy says that can be achieved through incentives, emission standards, investments in technology to “increase the flexibility of the electricity system” and other steps that it promises will be detailed in the National Climate Strategy.

Hultman was an architect of the original nationally determined contribution under former President Obama—a 26-to-28-percent carbon reduction by 2025. Hultman worked on it in 2014 during a previous stint at the White House under senior climate aide Rick Duke, whom Kerry tapped last week to be the U.S. Lead negotiator on climate change. During the Trump years, Hultman did modeling and reporting on the kind of commitment the United States could make when—and if—it returned to the Paris Agreement.

The United States would need to offer a new and tighter pledge for 2030 that would align with an emerging global focus on keeping warming to 1.5 degrees Celsius above preindustrial levels. Hultman co-authored two reports that were part of a broader wealth of peer-reviewed literature by outside groups like Rhodium Group, Princeton University and Energy Innovation that all indicated the United States could cut its greenhouse gas emissions about in half by 2030. These models all pointed to reduction opportunities from federal executive authority, state and local action, and legislation. Most assumed that Congress would act to make low-carbon technologies more competitive through incentives, if not through clean energy standards or other policy options that were cut from earlier versions of “Build Back Better.” The most recent version of the package would spend more than $550 billion supporting a low-carbon transition.

And that could make regulation more cost-effective, said Robbie Orvis, senior director of energy policy design at Energy Innovation. By helping renewable energy achieve higher levels of penetration in the power grid at a lower cost, federal agencies could introduce regulations that would focus on retiring unabated coal-fired power without burdening consumers. €œIt’s definitely like a push and pull,” said Orvis. €œThe more we can do in ‘Build Back Better’ with incentives, the easier it makes the standards side of things.” Without congressional action, he said, the Biden administration would need to fall back on “a mix” of stronger standards for sectors that have already come under carbon regulation while exploring new regulatory options.

The Biden administration introduced an initiative this week aimed at wringing emissions reductions out of the manufacturing sector by leveraging federal procurement. The sector accounts for roughly a quarter of U.S. Emissions but has yet to face direct carbon dioxide regulation under the Clean Air Act. But Orvis suggested that might be the kind of opportunity that would allow the United States to meet its 2030 commitment absent action by Congress.

€˜Zero chance’ But if Biden’s climate objectives face an uncertain future on Capitol Hill, they’re facing headwinds in the courts, too. Oral arguments begin in 10 days in West Virginia v. EPA, a case that has the potential to severely limit the scope not only of EPA’s regulations for power plant carbon emissions but of future greenhouse gas rulemakings for other stationary sources, like refineries and cement plants. The Supreme Court’s decision last year to take up the challenge to a defunct Obama-era rule that the Biden administration has said it will not reinstate was seen by many as an eagerness of the court’s conservative majority to clip EPA’s regulatory wings on climate change.

The court’s decision is expected in June—about the time global climate negotiators meet for a mid-year conference on implementing rules related to the Paris Agreement. McCarthy, who served as EPA administrator under Obama, said during a virtual event last week hosted by POLITICO that she was confident EPA’s future rules would stand up to legal challenge. €œAnd we’re not going to try to be creative,” she pledged. Obama’s EPA took an expansive view of its authorities under the Clean Air Act by looking for opportunities to reduce emissions across the power grid and encouraging fuel switching.

The rule took years to construct and was stayed by the Supreme Court. Many of the same officials who worked on it have returned to senior positions in Biden’s EPA. Nat Keohane, president of the Center for Climate and Energy Solutions, said there is no practical pathway to Biden’s 2030 climate pledge without congressional action. €œIf the idea is, well, we’ll just fall back on regulation to meet the 2030 goal, I think that has zero chance of support,” he said.

€œFrom just a hard-nosed sort of political, what’s-actually-possible-in-the-real-world point of view ... A strategy that tries to achieve the NDC without the kinds of investments in ‘Build Back Better’ is just not going to succeed.” Reprinted from E&E News with permission from POLITICO, LLC. Copyright 2022. E&E News provides essential news for energy and environment professionals.Last summer, at a time when the cipro had strained many people’s finances, inflation was rising and unemployment was still high, the sight of the richest man in the world joyriding in space hit a nerve.

On July 20 Amazon founder Jeff Bezos rode to the edge of space onboard a rocket built by his company Blue Origin. A few weeks earlier ProPublica had revealed that he did not pay any income taxes for two years, and in other years he paid a tax rate of just 0.98 percent. To many watching, it rang hollow when Bezos thanked Amazon’s workers, whose low-paid labor had enriched him enough to start his own rocket company, even though Amazon had quashed workers’ efforts to unionize several months before. The fact that another billionaire, Richard Branson, had also launched himself onboard his own company’s rocket just a week earlier did not help.

buy antibiotics changed many people’s willingness to shrug off the excesses of the rich. The cipro drew an impossible-to-ignore distinction between those who can literally escape our world and the rest of us stuck on the ground confronting the ills of Earth. Racism, climate change, global diseases. Even several members of Congress expressed their disapproval of Bezos.

€œSpace travel isn’t a tax-free holiday for the wealthy,” said Representative Earl Blumenauer of Oregon. Bezos and Branson putting the spotlight on themselves as passengers served to downplay the work that hundreds of scientists and engineers at Blue Origin and Virgin Galactic had put into designing, building and testing their spacecraft. It also masked the reality that advances in private spaceflight really could eventually pay off in greater access to space for all and more opportunities for scientific research that could benefit everyone. All their flights did was give the impression that space—historically seen as a brave pursuit for the good of all humankind—has just become another playground for the 0.0000001 percent..

US President Joe Biden has replaced his disgraced science cipro low cost adviser, can you get cipro over the counter Eric Lander, with two scientists who will split Lander’s duties “until permanent leadership is nominated and confirmed”, according to the White House. Alondra Nelson, deputy director for science and society at the Office of Science and Technology Policy (OSTP), which Lander led, will become acting director of the agency. And Francis Collins, who led the US National Institutes of Health before retiring in December, can you get cipro over the counter will temporarily become Biden’s science adviser and co-chair the President’s Council of Advisors on Science and Technology (PCAST). Lander resigned on 7 February, after the news outlet Politico revealed that, according to a White House investigation, he had violated the Biden administration’s Safe and Respectful Workplace Policy by mistreating staff members at the OSTP. In his resignation letter, Lander acknowledged that things he had said to team members “crossed the line at times can you get cipro over the counter into being disrespectful and demeaning”.

Biden moved swiftly to name interim replacements for Lander, who had been leading some of the president’s priority science initiatives—in particular, the creation of the Advanced Research Projects Agency for Health (ARPA-H), a high-risk, high-reward biomedical innovations agency. And the revamping of his ‘Cancer Moonshot’ programme, which launched five years ago and has the new goal of decreasing cancer deaths by at least 50% in the next 25 years. The OSTP did not answer Nature’s query about can you get cipro over the counter why Lander’s duties have been split between two people. Since the agency was established in 1976, its director has also gone by the title of science adviser to the president. The OSTP director oversees a staff of roughly 150 people who are charged with coordinating scientific activities across the federal government and ensuring that the president and the executive branch have can you get cipro over the counter access to the best available scientific information as they make decisions and craft federal policies.

The role of presidential science adviser has varied by administration. Both Lander and John Holdren, science adviser under former president Barack Obama, also served as ‘assistant to the president’, a role that can you get cipro over the counter granted them more direct access to the Oval Office. Biden had also elevated Lander to his cabinet, a first for an OSTP director. Kenneth Bernard, an epidemiologist and biodefence researcher who has worked for the US government under several presidential administrations, says that Lander’s swift, interim replacements make sense. Although he doesn’t have inside knowledge, he speculates that can you get cipro over the counter Biden might have chosen Collins because of his grounding in biomedical laboratory research and his extended experience heading a government agency.

And Collins, Bernard suggests, might not have wanted to manage the OSTP, having just retired from the NIH. He adds that Nelson is well suited to running the OSTP, having been deputy director for the past year can you get cipro over the counter. The White House announcement said. €œThe selections are responsive to the dual importance of a strong OSTP that can drive science and technology solutions to our greatest challenges—and the very specific attention the President wants to give to the creation of a new ARPA-H research and discovery agency, the building of support for a Cancer Moonshot 2.0, the search for a new head of NIH, and the broad advisory work of PCAST.” Nelson is a prominent sociologist, whose selection by Biden as an OSTP deputy drew praise from the scientific community. She has studied the societal impact of emerging technology and the effect can you get cipro over the counter of racism on science and medicine.

As OSTP deputy director for science and society, she co-leads a task force charged with bolstering scientific-integrity policies and protecting scientists from political interference across the federal government. Collins was director of the NIH under three US presidents, serving for can you get cipro over the counter longer than any other presidentially appointed head of the biomedical agency. He built a reputation as a shrewd spokesperson for scientific research and steered the NIH through the early stages of the buy antibiotics cipro. Known for leading the Human Genome Project in the can you get cipro over the counter 1990s and early 2000s, he had returned to his laboratory at the National Human Genome Research Institute to continue his research after retiring. Neal Lane, a physicist at Rice University in Houston, Texas, who served as science adviser to former president Bill Clinton, says that splitting Lander’s duties is not a permanent solution.

€œThe director of OSTP has always been, and should continue to be, the president’s science adviser,” he says. €œOSTP is the one agency in the federal government that has the expertise to provide advice on all aspects of US science and technology.” This article is reproduced with permission and was first published on February 17 2022.The United States still owes the world details about how it plans to meet President Biden’s pledge to cut greenhouse gas emissions in half by the end of this can you get cipro over the counter decade. The White House promised last year that those would come in the form of a comprehensive “U.S. National Climate Strategy.” That term was used more than 20 times by the American government in a report submitted can you get cipro over the counter to the U.N. Climate body last year on how the United States would zero out emissions by 2050.

That submission, known as “The Long-Term Strategy of the United States,” can you get cipro over the counter calls the National Climate Strategy, or NCS, a “companion” document that “focuses on the immediate policies and actions that will put America on track to reduce emissions by 50-52 percent below 2005 levels in 2030.” Participants in the global climate talks assumed the NCS would be released at the U.N. Climate conference in Glasgow, Scotland, in November. It still hasn’t been made public. Releasing the strategy would end the mystery around Biden’s ambitious can you get cipro over the counter promise to slash emissions in half by 2030. Currently, no one knows exactly how the administration will achieve those cuts.

And that may can you get cipro over the counter be why the strategy hasn’t been released. Because the administration isn’t sure either. A week before the conference opened, White House climate adviser Gina McCarthy and national economic adviser Brian Deese briefed environmental groups on the National Climate Strategy, leaving them with the impression that the strategy’s release was imminent. €œMy belief is, can you get cipro over the counter they were getting a little out over their skis,” one participant said. At the time, the White House and Democratic leaders in Congress still hoped that the House and Senate would pass the “Build Back Better Act”—a sprawling climate and social spending bill that would go a long way toward meeting Biden’s promise to slash emissions in half by 2030.

House Speaker Nancy Pelosi (D-Calif.) called passage of the act “imperative” can you get cipro over the counter to U.S. Credibility at the climate talks. But then “Build Back Better” faltered in the Senate after moderate Democrats balked at its price tag and social can you get cipro over the counter spending provisions. Three months later, it remains mired in gridlock on Capitol Hill. Meanwhile, the Biden administration faces the prospect this year of a Supreme Court decision that could severely restrict its ability to achieve its 2030 commitment through regulations that would limit power plant emissions.

Amid all this uncertainty, the White House has can you get cipro over the counter stopped talking about its 2030 road map—the National Climate Strategy. It didn’t respond to inquiries for this story. Advocates who are can you get cipro over the counter in touch with McCarthy and her staff say they’re focused on trying to resuscitate the climate provisions in “Build Back Better” rather than cobbling together a plan B for the 2030 emissions goal. And for now, they say, that’s fine. €œI’m not sure that sooner would be better than later if sooner means uncertainty about both of those elements,” said Alden Meyer, a senior associate with E3G, referring to Congress and the Supreme Court.

€œThe utility of a product that lays out a strategy on how we meet our emissions targets before we pass a much-needed can you get cipro over the counter legislative vehicle is marginal,” said Jamal Raad, executive director of Evergreen Action, a left-leaning climate group. The Paris Agreement’s rulebook doesn’t actually ask countries to provide a full accounting on how they plan to meet their nationally determined contributions, or NDCs. The Biden administration turned in its other can you get cipro over the counter U.N. Climate homework last year, including the 2050 decarbonization plan and a biennial report on emissions and carbon sinks that was overdue from the Trump administration. Still, international climate experts say more details would be can you get cipro over the counter welcome—from the United States particularly, after it left the Paris deal under former President Trump.

Meyer said international partners are “informally asking for reassurances whenever they have conversations with the U.S.” “But they understand very well that we have a separation-of-powers government, and they understand how narrow the control is, especially in the Senate,” he said. €œI haven’t heard anyone pressing the U.S. To make a formal submission of its climate strategy before it has some sense of what’s going to happen in can you get cipro over the counter Congress.” But he said that if Congress doesn’t act before the next round of U.N. Climate talks—in Egypt this November—the Biden administration will have to show its cards about how it plans to meet its emissions commitment—particularly if Democrats are poised to lose their majorities in Congress after the midterm election. €˜Sort of waiting’ McCarthy’s White House climate office is taking the lead in writing can you get cipro over the counter the National Climate Strategy, just as it did the 2030 pledge that Biden unveiled at his Earth Day summit last year.

Climate envoy John Kerry’s staff took the lead in drafting the report on the U.S. Long-term decarbonization pathway and has given input on the National Climate Strategy. But the domestic climate office is responsible for nationally determined contributions, and the strategy to can you get cipro over the counter meet it. McCarthy’s deputy, Ali Zaidi, is overseeing its development with policy adviser Greg Carlock. Those briefed say the National Climate Strategy was already partially written before the talks in Glasgow, when it was assumed that “Build can you get cipro over the counter Back Better” would be enacted.

Observers don’t think the office is actively running scenarios now for how to meet the 50-to-52-percent pledge without legislation. The White House has little can you get cipro over the counter incentive to do so. Putting out a road map that relies on uncertain congressional action could anger key lawmakers —like West Virginia Democratic Sen. Joe Manchin, who has yet to sign off on a version of the “Build Back Better” climate provisions despite some suggestions that he might do so. A White House strategy previewing can you get cipro over the counter an aggressive regime of EPA regulatory actions and limited fossil fuel development aimed at delivering the 2030 target could displease Manchin, a staunch champion of his state’s coal industry.

Meanwhile, West Virginia’s other senator has made Biden’s Paris Agreement pledge her top oversight priority as ranking member of the Senate Energy and Natural Resources Committee. Sen. Shelley Moore Capito (R-W.Va.), has written to EPA and the White House numerous times demanding details about how the 2030 climate goal was constructed. €œCongress has yet to receive any data generated or used to determine Biden’s greenhouse gas target,” she wrote in a November op-ed in The Hill newspaper. €œBy hiding its calculations, the Biden administration is avoiding tough questions about the policies that would be required to meet our climate pledge and how those policies would impact the lives of everyday Americans and small businesses.” Nate Hultman, the director of the Center for Global Sustainability at the University of Maryland, who joined Kerry’s staff last year and was lead author of the U.S.

Long-Term Strategy, said both reports were based on the same modeling. €œThe general trajectory that’s noted in the LTS is consistent with our NDC—50 to 52 [percent]—and does include some underlying policy drivers in that,” said Hultman, who returned to the University of Maryland earlier this year. €œSo it’s just that we weren’t as explicit in that, because we were sort of waiting for the [National Climate Strategy] to be able to do that deep dive into what’s happening in the near term.” ‘Push and pull’ The long-term road map points to Biden administration commitments that underly the 2050 decarbonization trajectory, like the pledge that U.S. Power-sector emissions would be zeroed out by 2035. The long-term strategy says that can be achieved through incentives, emission standards, investments in technology to “increase the flexibility of the electricity system” and other steps that it promises will be detailed in the National Climate Strategy.

Hultman was an architect of the original nationally determined contribution under former President Obama—a 26-to-28-percent carbon reduction by 2025. Hultman worked on it in 2014 during a previous stint at the White House under senior climate aide Rick Duke, whom Kerry tapped last week to be the U.S. Lead negotiator on climate change. During the Trump years, Hultman did modeling and reporting on the kind of commitment the United States could make when—and if—it returned to the Paris Agreement. The United States would need to offer a new and tighter pledge for 2030 that would align with an emerging global focus on keeping warming to 1.5 degrees Celsius above preindustrial levels.

Hultman co-authored two reports that were part of a broader wealth of peer-reviewed literature by outside groups like Rhodium Group, Princeton University and Energy Innovation that all indicated the United States could cut its greenhouse gas emissions about in half by 2030. These models all pointed to reduction opportunities from federal executive authority, state and local action, and legislation. Most assumed that Congress would act to make low-carbon technologies more competitive through incentives, if not through clean energy standards or other policy options that were cut from earlier versions of “Build Back Better.” The most recent version of the package would spend more than $550 billion supporting a low-carbon transition. And that could make regulation more cost-effective, said Robbie Orvis, senior director of energy policy design at Energy Innovation. By helping renewable energy achieve higher levels of penetration in the power grid at a lower cost, federal agencies could introduce regulations that would focus on retiring unabated coal-fired power without burdening consumers.

€œIt’s definitely like a push and pull,” said Orvis. €œThe more we can do in ‘Build Back Better’ with incentives, the easier it makes the standards side of things.” Without congressional action, he said, the Biden administration would need to fall back on “a mix” of stronger standards for sectors that have already come under carbon regulation while exploring new regulatory options. The Biden administration introduced an initiative this week aimed at wringing emissions reductions out of the manufacturing sector by leveraging federal procurement. The sector accounts for roughly a quarter of U.S. Emissions but has yet to face direct carbon dioxide regulation under the Clean Air Act.

But Orvis suggested that might be the kind of opportunity that would allow the United States to meet its 2030 commitment absent action by Congress. €˜Zero chance’ But if Biden’s climate objectives face an uncertain future on Capitol Hill, they’re facing headwinds in the courts, too. Oral arguments begin in 10 days in West Virginia v. EPA, a case that has the potential to severely limit the scope not only of EPA’s regulations for power plant carbon emissions but of future greenhouse gas rulemakings for other stationary sources, like refineries and cement plants. The Supreme Court’s decision last year to take up the challenge to a defunct Obama-era rule that the Biden administration has said it will not reinstate was seen by many as an eagerness of the court’s conservative majority to clip EPA’s regulatory wings on climate change.

The court’s decision is expected in June—about the time global climate negotiators meet for a mid-year conference on implementing rules related to the Paris Agreement. McCarthy, who served as EPA administrator under Obama, said during a virtual event last week hosted by POLITICO that she was confident EPA’s future rules would stand up to legal challenge. €œAnd we’re not going to try to be creative,” she pledged. Obama’s EPA took an expansive view of its authorities under the Clean Air Act by looking for opportunities to reduce emissions across the power grid and encouraging fuel switching. The rule took years to construct and was stayed by the Supreme Court.

Many of the same officials who worked on it have returned to senior positions in Biden’s EPA. Nat Keohane, president of the Center for Climate and Energy Solutions, said there is no practical pathway to Biden’s 2030 climate pledge without congressional action. €œIf the idea is, well, we’ll just fall back on regulation to meet the 2030 goal, I think that has zero chance of support,” he said. €œFrom just a hard-nosed sort of political, what’s-actually-possible-in-the-real-world point of view ... A strategy that tries to achieve the NDC without the kinds of investments in ‘Build Back Better’ is just not going to succeed.” Reprinted from E&E News with permission from POLITICO, LLC.

Copyright 2022. E&E News provides essential news for energy and environment professionals.Last summer, at a time when the cipro had strained many people’s finances, inflation was rising and unemployment was still high, the sight of the richest man in the world joyriding in space hit a nerve. On July 20 Amazon founder Jeff Bezos rode to the edge of space onboard a rocket built by his company Blue Origin. A few weeks earlier ProPublica had revealed that he did not pay any income taxes for two years, and in other years he paid a tax rate of just 0.98 percent. To many watching, it rang hollow when Bezos thanked Amazon’s workers, whose low-paid labor had enriched him enough to start his own rocket company, even though Amazon had quashed workers’ efforts to unionize several months before.

The fact that another billionaire, Richard Branson, had also launched himself onboard his own company’s rocket just a week earlier did not help. buy antibiotics changed many people’s willingness to shrug off the excesses of the rich. The cipro drew an impossible-to-ignore distinction between those who can literally escape our world and the rest of us stuck on the ground confronting the ills of Earth. Racism, climate change, global diseases. Even several members of Congress expressed their disapproval of Bezos.

€œSpace travel isn’t a tax-free holiday for the wealthy,” said Representative Earl Blumenauer of Oregon. Bezos and Branson putting the spotlight on themselves as passengers served to downplay the work that hundreds of scientists and engineers at Blue Origin and Virgin Galactic had put into designing, building and testing their spacecraft. It also masked the reality that advances in private spaceflight really could eventually pay off in greater access to space for all and more opportunities for scientific research that could benefit everyone. All their flights did was give the impression that space—historically seen as a brave pursuit for the good of all humankind—has just become another playground for the 0.0000001 percent..