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More than 2/3 of Indiana nursing home staff would take COVID-19 vaccine

video: In a study led by Regenstrief Institute, Indiana University and the State of Indiana, conducted shortly before COVID-19 vaccines became available in the U.S., more than two-thirds of nursing home and assisted living staff in Indiana indicated willingness to receive a vaccine immediately or in the future.

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Regenstrief Institute

INDIANAPOLIS -- In a study conducted shortly before COVID-19 vaccines became available in the U.S., more than two-thirds of nursing home and assisted living staff in Indiana indicated willingness to receive a vaccine immediately or in the future. The study was led by researchers from Regenstrief Institute, Indiana University and the State of Indiana. Vaccine uptake by front-line staff is important because it will help protect against serious illness and death for the high-risk people who receive care in these facilities.

"The vaccines offer the opportunity to return to a more normal life within the nursing facility, but that cannot be achieved without staff being willing to take the vaccine," said study leader Kathleen Unroe, M.D., MHA, a Regenstrief research scientist, IU School of Medicine associate professor of medicine and a geriatrician. "The rates of willingness found in this survey are a positive sign, and more staff may be amenable to the vaccines if they receive more education and outreach."

Nursing home and assisted living facility staff were included in the first phase of vaccine distribution, so the Indiana State Department of Health sent an anonymous survey to staff in facilities across the state to gain an understanding of willingness to participate. More than 8,000 responded. 45 percent indicated they would be willing to take a vaccine as soon as it was available, and an additional 24 percent said they would take it at some point in the future.

Staff members were surveyed on their reasons for not wanting to receive a vaccine. The most common responses were:

Concern over side effects (70%)

Health concerns (34%)

Questions about effectiveness (20%)

Religious reasons (12%)

"We found significant differences in willingness to take a vaccine among staff sub-groups, for example older employees were more interested in getting it as soon as possible, whereas direct care clinical staff who deal directly with patients were less likely to report willingness to receive the vaccine in the first wave,"said Justin Blackburn, PhD, associate professor at Indiana University Richard M. Fairbanks School of Public Health at IUPUI. "This information can help public health and facility leaders identify which groups may need education and outreach about the vaccines so that these efforts can successfully protect residents." Dr. Blackburn is also a program faculty with the Indiana University National Library of Medicine Public Health Informatics T15 program hosted by Regenstrief Institute and Fairbanks School of Public Health.

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Regenstrief Institute

Globalization of cancer clinical trials linked to lower enrollment of Black patients

For the drug approval process in the United States, investigators have been expanding clinical trials to sites outside the country. However, a new study indicates that this trend may be widening racial disparities in patient enrollment in cancer clinical trials. The study is published by Wiley early online in CANCER, a peer-reviewed journal of the American Cancer Society.

Without adequate representation in clinical trials, it is difficult to assess whether a medication will be safe and effective for all populations. Unfortunately, Black individuals have historically been poorly represented in clinical trials of anticancer medications, and their inclusion has been decreasing in recent years. Globalization of cancer clinical trial enrollment may play a role in this trend: to reduce costs and expedite patient enrollment, trials have increasingly enlisted clinical sites outside the United States.

To investigate the issue, a team led by Matthew Galsky, MD and Serena Tharakan, BS, of the Icahn School of Medicine at Mount Sinai in New York City, analyzed demographic information from 21 cancer clinical trials leading to U.S. Food and Drug Administration approvals between 2015 and 2018.

The team found that clinical trials conducted primarily outside the United States were significantly less likely to enroll Black participants than U.S. clinical trials--on average, global trials enrolled less than half the proportion of Black patients than trials conducted primarily within the country. Of the 21 clinical trials supporting 18 FDA drug approvals where race and location data were available, 64 percent of patients were enrolled outside the United States, with Black patients accounting for only an average of 3.2 percent of enrollment.

"There have been a number of studies investigating factors such as access to healthcare, physician biases, and socioeconomic status that may lead to underrepresentation of Black patients," said Tharakan. "However, to our knowledge, our findings are the first to quantitatively demonstrate that the globalization of cancer clinical trials may also be a key driver of racial disparities in the U.S. drug approval process."

The study's investigators hope that their results may help to inform policies focused on addressing racial disparities in cancer research and care.

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Wiley

Drug to treat hypoactive sexual desire disorder in women of 'very limited use'

An independent analysis of the medical trials which formed the final basis of approval by the US Food and Drug Administration (FDA) strongly suggests the drug bremelanotide has very limited effectiveness as a treatment for hypoactive sexual desire disorder (HSDD) in women, and that trial participants preferred a placebo.

The analysis, published today in the peer-reviewed Journal of Sex Research, also highlights issues with the validity of HSDD as a diagnosis. The condition was removed from the American Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013.

Professor Glen Spielmans, of Metropolitan State University, USA, examined data from bremelanotide's FDA New Drug Application, the clinicaltrials.gov protocol entries for the two 24-week Phase III trials, and the journal article (Kingsberg et al., published in Obstetrics and Gynecology) that reported both trials. He also conducted a meta-analysis of efficacy and dropout data appearing in the FDA application and compared these outcomes to those reported in the journal paper.

Spielmans, a Professor in Psychology, found that 42.1% of trial participants given bremelanotide did not complete the study compared to 20.48% of participants given the placebo, with dropout rates due to adverse events much higher for those on bremelanotide. Among participants who reached the end of the trials' acute phase, 87.22% on the placebo wanted to continue treatment in the open-label phase that followed, compared to 69.97% on bremelanotide.

However, the Kingsberg article did not report that adverse event-induced discontinuation was substantially higher for bremelanotide or that participants preferred taking placebo, measured by the combination of both completing a clinical trial and choosing to participate in the follow-up open-label study.

A number of other problems with the article were found including incomplete data reporting, changed efficacy outcomes and conflicts of interest, with four of the authors working for either the company that conducted the trials (Palatin Technologies) or the company which was licensed to market bremelanotide in North America (AMAG Pharmaceuticals) before the license was transferred back to Palatin.

Professor Spielmans said: "My findings strongly suggest that bremelanotide has very limited treatment efficacy, that the protocol-specified outcomes of bremelanotide are mostly unreported in the main journal article reporting the clinical trial outcomes, and that trial participants would rather take a placebo than bremelanotide."

However, focusing solely on problems with the clinical trials runs the risk of unintentionally reifying the validity of HSDD, he warned. "The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence - including the pressure on women to satisfy the sexual desires of their male partners - in the experience of sexuality all render HSDD as a problematic entity," Professor Spielmans added.

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Taylor & Francis Group

Breast cancer: Mathematics for precision medicine

The precise choice of treatment for breast cancer depends upon the status of the hormone receptors (for oestrogen and progesterone). Their conventional determination by means of immunohistochemistry (IHC) is associated with a certain error rate, which can be reduced by adding genomic data. Even conventional statistics can bring about a notable improvement but now it is possible to use decision theory to optimally combine diagnostic findings, particularly where they are contradictory. This is the finding of a recent study conducted by MedUni Vienna under the leadership of Wolfgang Schreiner from the Center for Medical Statistics, Informatics and Intelligent Systems (CeMSIIS). The methodology has applications way beyond breast cancer and can be deployed in all circumstances where it is necessary to draw conclusions from many findings at the same time, even if the findings are contradictory.

Schreiner explains: "Driverless cars use multiple sensors to check whether they can travel freely. It can be that one of the sensors detects an obstruction and requests emergency braking, while another sensor fails to detect any danger in the same situation. What do you do then? There are two potentially bad decisions and each of them is risky in a different way: if the car does not brake, even though this is necessary, there could potentially be a serious accident. However, if the car brakes unnecessarily, there is a risk of a rear-impact collision by the following vehicle with potentially less serious damage." One faces a similar situation in choosing the treatment for breast cancer patients, which must be adapted to the status of the hormone receptors, on which it is dependent.

It can happen that the IHC test produces a 'positive' result, while a second method of measurement, such as gene expression, produces a 'negative' result for the same patient. Once again, there are two potentially bad decisions. Heinz Kölbl from MedUni Vienna's Division of General Gynecology and Gynecologic Oncology explains: "If you only offer hormone treatment, because you mistakenly think that the patient is 'positive', although in reality she is 'negative', she will miss out on life-saving chemotherapy. That would be the greatest harm. If, on the other hand, a 'false negative' patient is given aggressive chemotherapy instead of more conservative hormone treatment, she will suffer unnecessary side-effects."

So how do experts think one should respond in the face of contradictory measurement results? "This is precisely where decision theory comes into its own," stresses Schreiner. Unlike conventional statistics, decision theory does not merely consider a single number, namely the probability of an event (e.g., 'receptor positive'), but also the probability of other possibilities ('possibly receptor positive' or 'definitely not receptor positive' = 'receptor negative'). This comprehensive view improves the quality of the result compared to 'conventional' statistics, especially where several sources of findings are simultaneously relevant. In a Big Data re-use study, decision theory has now been applied to hormone receptor diagnostics for the first time: to do this, the team from CeMSIIS worked with Heinz Kölbl, Christian Singer and Cacsire Castillo-Tong from MedUni Vienna's Division of General Gynecology and Gynecologic Oncology. The IHC receptor status and the entire gene expression profile were determined and jointly analysed for 3,753 breast cancer patients.

Decision theory works and warns

In the original studies, treatments were selected according to IHC receptor status. Even conventional statistics showed that genomic data appeared to contradict the IHC results (gold standard) in some cases. It is precisely at this point that decision theory was used instead of conventional statistics, since, in many cases, it can generate an accurate overall result from contradictory individual results. Schreiner explains: "Decision theory also has the advantage that it 'realises' when it is uncertain: it then generates a clear result of 'undecidable'. This in itself is important information, a warning as it were." This occurred in the case of 153 patients, indicating that potentially suboptimal treatment decisions were taken based on the IHC data alone. In fact, this (small) patient group had significantly poorer survival than the remaining, much larger, group with confirmed IHC status and hence "correctly" selected treatments.

The effectiveness of decision theory was therefore demonstrated on a simple, but extremely clinically relevant, example for precision medicine: "Modern medicine is increasingly using many information sources, not least from the areas of laboratory, intensive care medicine and genomics. Evidence from different sources has to be combined to reach conclusions, hitherto often in SOPs (Standard Operating Procedures) with conventional Yes/No decisions or even intuitively. It is here that decision theory offers a vast array of potential improvements."

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Medical University of Vienna

Retreat to win -- How to sustain an online campaign and survive trolling and abuse

Trolling and extreme levels of abuse can kill an online campaign but momentum can be maintained, and the energy and morale of exhausted activists effectively restored, by tactical retreat and taking time out, new research into the landmark 'No More Page 3' campaign in the United Kingdom shows.

Dr. Sarah Glozer of the University of Bath School of Management and Dr. Lauren McCarthy of the Royal Holloway University of London School of Business and Management studied the 'No More Page 3' campaign, which from 2012 lobbied The Sun mass-circulation newspaper to stop publishing a photo of a topless woman on page 3, a daily feature launched in 1970. Page 3, the No More Page 3 campaign argued, was a symbol of institutionalised sexism. The Sun removed the Page 3 feature in 2015.

Glozer and McCarthy found the campaigners were subjected to extreme levels of abuse and hate-speech online, leading to considerable stress and exhaustion, but had developed effective measures to mitigate against these risks to their ultimately successful campaign. Key amongst those was simply retreating.

"It seems counter-intuitive - to urge campaigners to step back from the front line, take time out, perhaps retreat to silence, when campaigning seems to be so much about keeping the fight going. But our study shows it paid dividends, both for the individual's welfare and the effectiveness of the campaign itself," Glozer said.

Glozer said the No More Page 3 campaigners adopted different forms of sensory retreat - some went silent on social media or observed campaign efforts rather than participating actively. Some withdrew temporarily and deleted their accounts. Glozer said that these tactics, in most cases, ensured that most of the campaigners would return rejuvenated to the front line.

"This retreat tactic, which could have been an hour, a day or weeks at a time, allowed the campaigners to recover their emotional energy and heal - we heard the word 'healing' a lot," Glozer said.

Importantly, the campaign group's core activists, rather than demanding more and more from each other, were understanding and supportive of the need for retreat.

"They reported finding solace and taking strength in acting together. They understood the need for retreat and saw this not as a sign of weakness or flagging commitment to the cause", a lesson Glozer said could be helpful to corporates or governmental organisations wrestling with 'burn-out' cases.

McCarthy added that campaigner exhaustion was especially common when causes were directly related to individuals' identity.

"Women drew on their experiences of teenage shame about their bodies, or sexual harassment, as a kind of fuel for their campaigning. But at the same time, these experiences and continued abuse online, can lead to burnout. It's a Catch 22 situation," she said.

A key tactic in dealing with the 24/7 onslaught of social media abuse was a relay system. An exhausted campaigner wrestling with a hostile social media feed or forum would 'pass the baton' to another campaigner via a system of online messaging or 'tagging' across platforms, ensuring that campaign's momentum was unaffected.

Glozer noted that the No More Page 3 campaigners sought out their most vehement opponents to try to convince them of their argument and win their support; a brave tactic in the world of 'toxic Twitter'.

"While social media can cosset the user, surrounding us with like-minded people in a filter bubble or echo chamber, the NMP3 campaigners chose to actively enter the Lion's Den. We were struck by their tactics and how resilient they were, impressed by their rationality in the face of rude, abusive and downright abhorrent behaviour. But that takes an emotional toll," she said.

This experience in the virtual world also adversely affected the campaigners' expectations of public behaviour in the physical world.

"They became terrified they would face the same level of vitriol on the streets. Their online experience exaggerated their fears - in fact, this proved not to be the case when people were unable to hide behind their online identities," Glozer said.

Glozer said the research pointed to the need for digital platforms to do more to address the trolling and hate-speech that are still tolerated and excused in some social media channels.

"Women continue to experience inequality offline, and such tensions are only amplified online. Feminist environs provide safe spaces, and social media can help to mobilise - and has proven its value in campaigning - but there is more platforms can do to police hate-speech," she said.

McCarthy added that whilst looking to business to do more was appropriate, it was clear that campaigning organisations were taking action on their own.

"During the pandemic we saw the rise of mutual-aid groups organising on social media, far in advance of any governmental or corporate help. Similarly, campaigning groups are utilising the tools they have at their fingertips to protect and sustain their members. As we emerge from this pandemic, which has rolled the clock back on so many hard-won gains for women's equality, and only exasperated incidences of trolling and 'networked misogyny', more action is needed to fight inequality in both online and offline worlds," she said.

Video: https://www.youtube.com/watch?v=TAm0gW5v90E&ab_channel=UniversityofBathSchoolofManagement

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University of Bath

Paw hygiene no reason to ban assistance dogs from hospitals

image: Assistance dog user Iris and her dog Sandy in the recovery room after surgery. After a severe epileptic seizure, Iris was not doing well and Sandy was brought to the hospital in the hopes she could help improve Iris' condition, which was indeed the case. Sandy even accompanied Iris to the OR, where Iris had to undergo a major surgery. One year earlier, bringing Sandy along was not negotiable in this particular hospital. Photo: private photo of Iris and Sandy.

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Private photo of Iris and Sandy - may be re-used.

Over 10,000 people in Europe use an assistance dog; think of guide dogs for people with a visual impairment, hearing dogs for people with a hearing impairment, medical response service dogs and psychiatric service dogs.

According to a UN-agreement and the Dutch law, these dogs are welcome in stores, hospitals and other public places. However, in practice, many assistance dog users and their dogs are regularly refused entry. In the Netherlands, four out of five assistance dog users indicate that they regularly experience problems with this.

Often, hygiene reasons are given as the main argument for refusing entry to assistance dogs. Research by Utrecht University now shows that the paws of assistance dogs are cleaner than the shoe soles of their users, and thus, paw hygiene is no reason to ban assistance dogs from hospitals.

To investigate this, Jasmijn Vos, Joris Wijnker and Paul Overgaauw of Utrecht University's Faculty of Veterinary Medicine took samples from the paws of 25 assistance dogs and the shoe soles of their users. For comparison, they also investigated an equally large group of pet dogs and their owners. Vos and her colleagues examined the samples for poop bacteria (Enterobacteriaceae), which are very common outdoors, and for an important diarrhoeal bacteria (Clostridium difficile).

"The dogs' paws turned out to be cleaner than the soles of their shoes," says Jasmijn Vos, Masters student at Utrecht University. "This makes the hygiene argument that is often used to ban assistance dogs from public locations invalid." Moreover, the diarrhoeal bacteria did not occur on the dogs' paws whatsoever, and only once on a shoe sole.

81% of assistance dogs are refused

Dutch assistance dog users were also surveyed about their experiences. 81% are still regularly refused entry to public places with their dog, even though this is prohibited by law. This is mainly down to lack of knowledge on the part of the person refusing entry: lack of knowledge on what an assistance dog is, how it can be recognised, and about the rules of law.

The study also shows that assistance dog users constitute only a small fraction of the total number of patients in Dutch hospitals. Should they decide to bring their assistance dog to the hospital, or elsewhere, this should be made possible; assistance dogs are usually well trained and are no more of a hygiene hazard than people!

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Utrecht University

For teens, outdoor recreation during the pandemic linked to improved well-being

A study from North Carolina State University found outdoor play and nature-based activities helped buffer some of the negative mental health impacts of the COVID-19 pandemic for adolescents.

Researchers said the findings, published in the International Journal of Environmental Research and Public Health, point to outdoor play and nature-based activities as a tool to help teenagers cope with major stressors like the COVID-19 pandemic, as well as future natural disasters and other global stressors. Researchers also underscore the mental health implications of restricting outdoor recreation opportunities for adolescents, and the need to increase access to the outdoors.

"Families should be encouraged that building patterns in outdoor recreation can give kids tools to weather the storms to come," said Kathryn Stevenson, a study co-author and assistant professor of parks, recreation and tourism management at NC State. "Things happen in life, and getting kids outside regularly is an easy way to build some mental resilience."

In the survey, conducted from April 30 to June 15, 2020, researchers asked 624 adolescents between the ages of 10 to 18 years to report their participation in outdoor recreation both before the pandemic and after social distancing measures were in effect across the United States. They also asked adolescents about their subjective well-being, a measure of happiness, and mental health.

The findings revealed the pandemic had an impact on the well-being of many teens in the survey, with nearly 52 percent of adolescents reporting declines in subjective well-being. They also saw declines in teens' ability to get outside, with 64 percent of adolescents reporting their outdoor activity participation fell during the early months of the pandemic. Despite these declines in outdoor activity participation, nearly 77 percent of teens surveyed believed that spending time outside helped them deal with stress associated with the COVID-19 pandemic.

"We know that a lot of outdoor activities that kids engage in happen during school, in youth sports leagues or clubs, and those things got put on hold during the pandemic," said the study's lead author Brent Jackson, a graduate student in the Fisheries, Wildlife and Conservation Biology Program at NC State. "Based on our study, they were getting outside less - we think not being in school and having those activities really contributed to that."

When they broke down recreation by type, they saw participation in outdoor play activities such as sports, biking, going for walks, runs or skating declined by 41.6 percent, nature-based activities such as camping, hiking, fishing, hunting, and paddling dropped by 39.7 percent, and outdoor family activities declined by 28.6 percent. In those early months of the pandemic, about 60 percent of teens said they were able to get outside once a week or less.

"We saw declines in all three types of outdoor recreation participation," Jackson said. "Nature-based activities had the lowest participation before and during the pandemic, which may point to the need for more access to natural spaces in general."

Results showed that well-being and outdoor recreation trends were linked, and the negative trends they saw during the pandemic for well-being and participation in outdoor recreation were seen regardless of teens' race, gender, age, income community type or geographic region. Kids who did not get outside as much saw declines in well-being, but those who got outside both before and during the pandemic were able to maintain higher levels of well-being.

"This tells us that outdoor recreation can promote well-being for kids when it happens, and can potentially take away from well-being when it doesn't," Stevenson said.

Teens who had high rates of outdoor play before the pandemic were more resistant to negative changes in social well-being. Those who got outside frequently before the pandemic were more likely to experience a lesser decline in well-being, regardless of participation during the pandemic. And, for teens who were able to play outside or get involved in nature-based activities during the pandemic, their well-being was on par with pre-pandemic levels.

"Kids who were able to continue participating in outdoor play and nature-based activities had subjective well-being levels that were similar to what they were before the pandemic, but kids who weren't able to participate saw much greater declines," Jackson said.

The study's findings also point to strategies to help kids navigate future global stressor events, as well as the importance of ensuring access to outdoor recreation. They help define the risks associated with policies that reduce kids' ability get outside.

"Going outside and participating in activities that provide exposure to nature, physical activity and safe social interaction during the pandemic were really powerful in terms of improving kids' resilience," Jackson said.

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North Carolina State University

New CAR T-Cell therapy extends remission in heavily relapsed multiple myeloma patients

image:  A new type of CAR T-cell therapy more than triples the expected length of remission for multiple myeloma patients who have relapsed several times, according to an international clinical trial with UT Southwestern as the lead enrolling site.

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UT Southwestern Medical Center

DALLAS - March 8, 2021 - A new type of CAR T-cell therapy more than triples the expected length of remission for multiple myeloma patients who have relapsed several times, according to an international clinical trial with UT Southwestern as the lead enrolling site.

Results of the trial, published recently in the New England Journal of Medicine, were significantly better than those seen with other therapies available to heavily relapsed and refractory myeloma patients who had already received the three main classes of treatment. Nearly three-quarters of the patients had at least a partial response to the therapy. About a third achieved a complete remission, with the disappearance of all traces of cancer.

Median time without the disease worsening was 8.8 months with this new treatment, but Larry D. Anderson Jr., M.D., Ph.D., associate professor of internal medicine and co-first author of the journal article, points out that patients who received the trial's maximum dose of engineered T-cells experienced longer remissions, bringing the average to more than 12 months. Previously, similar patients treated with currently available therapies following multiple relapses have only had an average of three to four months of remission before their disease returned.

"We have patients that are over two years out from their single infusion of CAR T-cells and still in remission despite having no other treatment options when they were enrolled in this trial," says Anderson, a member of the Harold C. Simmons Comprehensive Cancer Center who cares exclusively for patients with plasma cell disorders, mostly myeloma patients. "The results mark a true breakthrough with unprecedented depth and duration of remissions from what we hope will be the first cellular therapy option to become available for myeloma patients. Even though we don't yet know if some of these patients may be cured, and many relapse within one to two years, it can at least buy many patients time until other treatment options become available. Most patients also have good quality of life with relatively low risk of severe CAR T-cell-related side effects."

Multiple myeloma, the second most common blood cancer, is a cancer of plasma cells, a white blood cell important in the immune system. The disease's attack on bone marrow puts patients at risk of life-threatening infections. It is diagnosed in more than 32,000 people a year, and African Americans are twice as likely as the general population to be diagnosed with this disease.

Three main classes of treatment are available now for multiple myeloma: drugs called proteasome inhibitors, drugs to modulate the immune system, and antibody treatments. Among more than a dozen new therapies for myeloma approved by the Food and Drug Administration over the past decade, most offer only a few months of remission for patients with multiple relapses. Until now, most treatments induce responses in only a third of patients, and complete remissions are rare.

The phase 2 trial involved 128 patients, ages 18 and older, who previously had been given regimens from the three main classes of treatment. The patients received a median of six previous antimyeloma regimens; 120 formerly had undergone stem cell transplantation.

The clinical trial included nine sites in the U.S., one in Canada, and 10 sites in five European countries. Several patients traveled from as far away as Michigan and Minnesota to UT Southwestern's Dallas campus to be part of the trial.

Study participants had their T-cells engineered to target a molecule called B-cell maturation antigen, or BCMA, which is only found in plasma cells and myeloma cells. This new T-cell therapy for myeloma patients is called idecabtagene vicleucel, or ide-cel. It is also known as bb2121.

The infusions of the engineered cells started a two-week hospitalization period during which doctors watched for possible side effects such as anemia; neutropenia, a drop in a type of white blood cells; and thrombocytopenia, a drop in blood platelets. Although low blood counts were common, they were manageable, and other severe side effects were uncommon.

"One of the nice things we saw in this study was that the rates of severe CAR T-cell-related toxicities - called neurotoxicity and cytokine release syndrome - were very low in multiple myeloma compared to what we have seen with lymphoma CAR T-cell infusions," Anderson says. "The majority of people had some side effects, but most were low level and manageable, and I would say this therapy is often much better tolerated than a stem cell transplant, which most of these patients had already gone through."

Pioneered in the late 1980s, CAR T-cell therapy is a promising and still emerging treatment for blood cancers. CAR, which stands for chimeric antigen receptor, takes part of its name from the chimera, the mythical animal with the tail of a serpent and head of a lion. In modern medicine's version of the chimera, the head is an antibody, and the tail is a T-cell receptor. CAR T-cell therapy involves harvesting a patient's own T-cells by withdrawing blood, reengineering them in a lab to have this cancer-fighting chimera, and then growing hundreds of millions of them to put back into the patient by infusion.

CAR T-cell therapy is currently approved for use only in lymphoma and leukemia. Several different CAR T-cell treatments for myeloma are in clinical trials, but this CAR T-cell treatment is the first to complete and publish data from an FDA registration trial. Based on these results, the pharmaceutical companies Bristol Myers Squibb and bluebird bio are seeking FDA approval of ide-cel as a standard therapy for relapsed myeloma with a decision expected by the end of March.

The trial was funded by bluebird bio and Celgene, a Bristol Myers Squibb company. Anderson is a consultant who serves on an advisory board for Celgene and has other consulting activities disclosed in the manuscript.

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UT Southwestern Medical Center

UCLA-led study reveals 'hidden costs' of being Black in the US

image: Vickie Mays, professor of psychology in the UCLA College and of health policy and management at the UCLA Fielding School of Public Health.

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Reed Hutchinson/UCLA

A woman grips her purse tightly as you approach. A store manager follows you because you look "suspicious." You enter a high-end restaurant, and the staff assume you're applying for a job. You're called on in work meetings only when they're talking about diversity.

The indignities and humiliations Black men -- even those who have "made it" -- regularly endure have long been seen as part and parcel of life in the United States among the Black community, a sort of "Black tax" that takes a heavy toll on physical and mental health.

Now, a new UCLA-led study reveals these "hidden costs" of being Black in America. Researchers who analyzed a national sample of the views of Black men and white men found that Black men of all income levels reported experiencing higher levels of discrimination than their white counterparts.

"Black men face constant experiences of discrimination and disappointment when they try to contribute. They are treated like criminals in a society where they often are not allowed to achieve their full potential," said the study's co-senior author, Vickie Mays, a professor of psychology in the UCLA College and of health policy and management at UCLA's Fielding School of Public Health.

"Successful Black men," she said, "hope their hard work will pay off and instead are tormented to find their education and income often do not protect them from racial discrimination. The 'return on achievement' is reduced for Blacks in the U.S. It's a disturbing wake-up call."

The study, "Money protects white but not African American men against discrimination," is published today in the peer-reviewed open-access International Journal of Environmental Research and Public Health.

To measure perceived discrimination, the researchers analyzed data from the National Survey of American Life that assessed the mental health of 1,271 Black and 372 non-Hispanic white adults who live in the same areas across the U.S. Survey questions inquired about chronic, daily experiences over the past year. For example, respondents were asked how often in their day-to-day lives any of the following had occurred: "being followed around in stores," "people acting as if they think you are dishonest," "receiving poorer service than other people at restaurants" and "being called names or insulted." Scaled response options ranged from 1 ("never") to 6 ("almost every day").

The results indicate that many Black men face discriminatory indignities on a nearly daily basis, year after year -- and the experience is exhausting, said Mays, who directs the National Institutes of Health-funded UCLA BRITE Center for Science, Research and Policy and is a special advisor to UCLA's chancellor on Black life. "It takes a toll on your physical and mental health. You get depleted."

The daily discrimination measured by the survey did not include other frequently cited injustices, such as being pulled over and questioned by police officers without cause and facing discrimination in housing, education, jobs and health care, said Mays. She noted that while the study's results were distressing, they were not particularly surprising.

"We've known this," she said, "but now it's documented. This is evidence."

Higher incomes and achievement offer Black men little relief

While the study found that for white men, increases in household income were inversely associated with perceived discrimination, this did not hold true for Black men, who continued to report high levels of discrimination regardless of any boost in income level.

The findings may explain why Black men, even as they attain greater financial and educational success on average, don't gain much protection against negative physical and mental health outcomes the way white men generally do, said co-senior author Susan Cochran, a professor of epidemiology at the Fielding School of Public Health.

"In the United States, many people believe that higher levels of income and education provide relief against being treated differently, badly or unfairly," Cochran said. "The results of our study show that is truer for white men, but it's clearly not the case for many Black men. Structural barriers limit the benefits of Black men's economic achievements, and perceived discrimination increases the risk of adverse physical and mental health outcomes."

For Black men, increases in income at all financial levels actually lead to more perceived discrimination, perhaps because they come into increased contact with whites, according to lead author Shervin Assari, who conducted the analysis as a researcher with the BRITE Center for Science, Research and Policy and is currently an associate professor of urban public health and family medicine at Charles R. Drew University of Medicine and Science.

"It was upsetting to write this study," Assari said. "Successful Blacks expect better treatment and think they deserve it but often do not get it."

Discrimination, the authors say, is embedded in the fabric of U.S. institutions and harms Black men in their daily lives. For Mays, the damage this does to equal opportunity brings to mind the 1951 Langston Hughes poem "Harlem," in which the poet asks, "What happens to a dream deferred? / Does it dry up / like a raisin in the sun?"

"Change has to come faster," Mays said. "Change has to be permanent. We are tired of hearing 'wait your turn.' Black men's dreams have been deferred for far too long."

Credit: 
University of California - Los Angeles

New research shows marijuana THC stays in breast milk for six weeks

Aurora, Colo. (March 8, 2021) - In a new study published in JAMA Pediatrics, researchers at Children's Hospital Colorado (Children's Colorado) have found that tetrahydrocannabinol (THC), the psychoactive component of marijuana, stays in breast milk for up to six weeks, further supporting the recommendations of the American Academy of Pediatrics, the American College of Obstetricians and Gynecologists and the Academy of Breastfeeding Medicine to abstain from marijuana use during pregnancy and while a mother is breastfeeding. This is the first study examining THC in breastmilk and plasma among women with known marijuana use in pregnancy since a 1982 study in the New England Journal of Medicine.

"With the increasing utilization of marijuana in society as a whole, we are seeing more mothers who use marijuana during pregnancy," said Erica Wymore, MD, MPH, primary investigator, neonatologist at Children's Colorado and assistant professor of pediatrics at the University of Colorado School of Medicine on the Anschutz Medical Campus. "However, given the lack of scientific data regarding how long THC persists in breast milk, it was challenging to provide mothers with a definitive answer regarding the safety of using marijuana while breastfeeding and simply 'pumping and dumping' until THC was no longer detectable in their milk. With this study, we aimed to better understand this question by determining the amount and duration of THC excretion in breast milk among women with known prenatal marijuana use."

The researchers studied women with prenatal marijuana use who delivered their infants at Children's Colorado and UCHealth's University of Colorado Hospital between November 1, 2016, and June 30, 2019. Specifically, researchers recruited women who:

Had a history of marijuana use during pregnancy/a positive urine test for THC when admitted
for delivery

Were over the age of 18

Had an intention to breastfeed

Were willing to abstain from marijuana use for six weeks after delivery

Were willing to provide milk, blood and urine samples during those six weeks

Of the 394 women who were screened, 25 enrolled. Seven of these women were ultimately able to abstain from marijuana use for the duration of the study. Reasons listed for the others' inability to abstain included stress, sleep and pain relief.

The study found that, while the concentrations of THC varied from woman to woman (likely depending on their level of use, BMI and metabolism), THC was excreted in the breast milk of these seven women for up to six weeks. In fact, all of the women still had detectable levels of THC in their breastmilk at the end of the study.

"This study provided invaluable insight into the length of time it takes a woman to metabolize the THC in her body after birth, but it also helped us understand why mothers use marijuana in the first place," said Maya Bunik, MD, MPH, senior investigator, medical director of the Child Health Clinic and the Breastfeeding Management Clinic at Children's Colorado and professor of pediatrics at the CU School of Medicine. "To limit the unknown THC effects on fetal brain development and promote safe breastfeeding, it is critical to emphasize marijuana abstention both early in pregnancy and postpartum. To help encourage successful abstention, we need to look at - and improve - the system of supports we offer new moms."

Longitudinal studies from the 1980s have shown that children born to mothers who used marijuana during pregnancy experienced long-term issues with cognitive and executive functioning, including impulsivity, as well as deficits in learning, sustained attention and visual problem-solving skills.

"This study was not about the impact marijuana has on babies, but we are concerned," said Wymore. "Especially when we consider that today's marijuana is five to six times higher in potency than what was available prior to recent marijuana legalization in many states."

Credit: 
Children's Hospital Colorado

Study of coronavirus variants predicts virus evolving to escape current vaccines

A new study of the U.K. and South Africa variants of SARS-CoV-2 predicts that current vaccines and certain monoclonal antibodies may be less effective at neutralizing these variants and that the new variants raise the specter that reinfections could be more likely.

The study was published in Nature on March 8, 2021. A preprint of the study was first posted to BioRxiv on January 26, 2021.

David Ho (Credit: Columbia University Irving Medical Center)

The study's predictions are now being borne out with the first reported results of the Novavax vaccine, says the study's lead author David Ho, MD. The company reported on Jan. 28 that the vaccine was nearly 90% effective in the company's U.K. trial, but only 49.4% effective in its South Africa trial, where most cases of COVID-19 are caused by the B.1.351 variant.

"Our study and the new clinical trial data show that the virus is traveling in a direction that is causing it to escape from our current vaccines and therapies that are directed against the viral spike," says Ho, the director of the Aaron Diamond AIDS Research Center and the Clyde'56 and Helen Wu Professor of Medicine at Columbia University Vagelos College of Physicians and Surgeons.

"If the rampant spread of the virus continues and more critical mutations accumulate, then we may be condemned to chasing after the evolving SARS-CoV-2 continually, as we have long done for influenza virus," Ho says. "Such considerations require that we stop virus transmission as quickly as is feasible, by redoubling our mitigation measures and by expediting vaccine rollout."

 

After vaccination, the immune system responds and makes antibodies that can neutralize the virus.

Ho and his team found that antibodies in blood samples taken from people inoculated with the Moderna or Pfizer vaccine were less effective at neutralizing the two variants, B.1.1.7, which emerged last September in England, and B.1.351, which emerged from South Africa in late 2020. Against the U.K. variant, neutralization dropped by roughly 2-fold, but against the South Africa variant, neutralization dropped by 6.5- to 8.5-fold.

"The approximately 2-fold loss of neutralizing activity against the U.K. variant is unlikely to have an adverse impact due to the large 'cushion' of residual neutralizing antibody activity," Ho says, "and we see that reflected in the Novavax results where the vaccine was 85.6% effective against the U.K. variant."

Data from Ho's study about the loss in neutralizing activity against the South Africa variant are more worrisome.

"The drop in neutralizing activity against the South Africa variant is appreciable, and we're now seeing, based on the Novavax results, that this is causing a reduction in protective efficacy," Ho says. 

The new study did not examine the more recent variant found in Brazil (B.1.1.28) but given the similar spike mutations between the Brazil and South Africa variants, Ho says the Brazil variant should behave similarly to the South Africa variant. 

 

 "We have to stop the virus from replicating and that means rolling out vaccine faster and sticking to our mitigation measures like masking and physical distancing. Stopping the spread of the virus will stop the development of further mutations," Ho says.  

The study also found that certain monoclonal antibodies used now to treat COVID patients may not work against the South Africa variant. And based on results with plasma from COVID patients who were infected earlier in the pandemic, the B.1.351 variant from South Africa has the potential to cause reinfection.

New study contains comprehensive analysis of variants

The new study conducted an extensive analysis of mutations in the two SARS-CoV-2 variants compared to other recent studies, which have reported similar findings. 

The new study examined all mutations in the spike protein of the two variants. (Vaccines and monoclonal antibody treatments work by recognizing the SARS-CoV-2 spike protein.)

The researchers created SARS-CoV-2 pseudoviruses (viruses that produce the coronavirus spike protein but cannot cause infection) with the eight mutations found in the U.K. variant and the nine mutations found in the South African variant.

They then measured the sensitivity of these pseudoviruses to monoclonal antibodies developed to treat COVID patients, convalescent serum from patients who were infected earlier in the pandemic, and serum from patients who have been vaccinated with the Moderna or Pfizer vaccine.

Implications for monoclonal antibody treatments

The study measured the neutralizing activity of 18 different monoclonal antibodies--including the antibodies in two products authorized for use in the United States. 

Against the U.K. variant, most antibodies were still potent, although the neutralizing activity of two antibodies in development was modestly impaired. 

Against the South Africa variant, however, the neutralizing activity of four antibodies was completely or markedly abolished. Those antibodies include bamlanivimab (LY-CoV555, approved for use in the United States) that was completely inactive against the South Africa variant, and casirivimab, one of the two antibodies in an approved antibody cocktail (REGN-COV) that was 58-fold less effective at neutralizing the South Africa variant compared to the original virus. The second antibody in the cocktail, imdevimab, retained its neutralizing ability, as did the complete cocktail.  

"Decisions of the use of these treatments will depend heavily on the local prevalence of the South Africa and Brazil variants," Ho says, "highlighting the importance of viral genomic surveillance and proactive development of next-generation antibody therapeutics." 

Reinfection implications

Serum from most patients who had recovered from COVID earlier in the pandemic had 11-fold less neutralizing activity against the South Africa variant and 4-fold less neutralizing activity against the U.K. variant.

"The concern here is that reinfection might be more likely if one is confronted with these variants, particularly the South Africa one," Ho says.

Credit: 
Columbia University Irving Medical Center

Study finds two servings of fish per week can help prevent recurrent heart disease

Hamilton, ON (March 8, 2021) - An analysis of several large studies involving participants from more than 60 countries, spearheaded by researchers from McMaster University, has found that eating oily fish regularly can help prevent cardiovascular disease (CVD) in high-risk individuals, such as those who already have heart disease or stroke.

The critical ingredient is omega-3 fatty acids, which researchers found was associated with a lower risk of major CVD events such as heart attacks and strokes by about a sixth in high-risk people who ate two servings of fish rich in omega-3 each week.

"There is a significant protective benefit of fish consumption in people with cardiovascular disease," said lead co-author Andrew Mente, associate professor of research methods, evidence, and impact at McMaster and a principal investigator at the Population Health Research Institute.

No benefit was observed with consumption of fish in those without heart disease or stroke.

"This study has important implications for guidelines on fish intake globally. It indicates that increasing fish consumption and particularly oily fish in vascular patients may produce a modest cardiovascular benefit."

Mente said people at low risk for cardiovascular disease can still enjoy modest protection from CVD by eating fish rich in omega-3, but the health benefits were less pronounced than those high-risk individuals.

The study was published in JAMA Internal Medicine on March 8.

The findings were based on data from nearly 192,000 people in four studies, including about 52,000 with CVD, and is the only study conducted on all five continents. Previous studies focused mainly on North America, Europe, China and Japan, with little information from other regions.

"This is by far the most diverse study of fish intake and health outcomes in the world and the only one with sufficient numbers with representation from high, middle and low income countries from all inhabited continents of the world," said study co-lead Dr. Salim Yusuf, professor of medicine at the Michael G. DeGroote School of Medicine and executive director of the PHRI.

This analysis is based in data from several studies conducted by the PHRI over the last 25 years. These studies were funded by the Canadian Institutes for Health Research, several different pharmaceutical companies, charities, the Population Health Research Institute and the Hamilton Health Sciences Research Institute.

Credit: 
McMaster University

New technique brings the study of molecular configuration into the microscopic domain

image: This work was featured on the cover of Analytical Chemistry. The image shows merged vibrational circular dichroism and infrared absorbance images of surgical breast tissue, taken at the same wavelength.

Image: 
Courtesy Analytical Chemistry

Researchers have developed a spectroscopic microscope to enable optical measurements of molecular conformations and orientations in biological samples. The novel measurement technique allows researchers to image biological samples at the microscopic level more quickly and accurately.

The new instrument is based on the discrete frequency infrared spectroscopic imaging technique developed by researchers at the Beckman Institute for Advanced Science and Technology at the University of Illinois Urbana-Champaign.

"This project is about bringing the study of molecular chirality into the microscopic domain," said Rohit Bhargava, a professor of bioengineering, and the director of the Cancer Center at Illinois.

Molecular chirality refers to the spatial orientation of atoms in molecules or multimolecule assemblies. In biological systems, one molecule may elicit a cellular response, while its mirror image could be inactive or even toxic. While vibrational circular dichroism can be employed to help determine a molecule's chemical structure and orientation, VCD measurements are time-intensive and could not previously be used to image complex biological systems or solid tissues samples.

The paper "Concurrent Vibrational Circular Dichroism Measurements with Infrared Spectroscopic Imaging" was published in Analytical Chemistry and featured on the cover.

The novel infrared microscope makes imaging of biomolecule chirality possible by accelerating both the acquisition time and improving the signal-to-noise ratio of traditional VCD techniques. "When you send light down a microscope from a spectrometer, you're essentially throwing away a lot of it," Bhargava said. "For VCD measurements, you also have to send it through a photoelastic modulator, which changes the polarization of light to left- or right-handed. At that point, you don't have a lot of light left, which means you have to average your signal for a long time to see just one pixel within an image."

The Chemical Imaging and Structures Laboratory, led by Bhargava, achieved rapid and concurrent infrared and VCD measurements by building on the framework of their high performance discrete frequency infrared imaging microscope. Instead of employing a traditional thermal light source, the instrument is built around a quantum cascade laser.

"The laser source motivated the whole design," said Yamuna Phal, a graduate student researcher in electrical and computer engineering. "The QCL source has higher power, which means we can acquire faster measurements. Previously, you could only perform VCD on liquid samples, but we can image solid tissues as well. This was never attempted before because it takes so long to acquire VCD signals in the first place."

Kevin Yeh, a postdoctoral research associate, who co-led the development of the microscope, asserted that other applications could arise from the microscope built for this project. "We initially envisioned the discrete frequency infrared microscope as a platform on which other techniques could be built," Yeh said. "We've solved one of these extensions, which is VCD, but we could envision many others."

Although the applications of this technique could span the biological sciences, the work itself is a testament to the strength of interdisciplinary science. "This project was possible only by bringing together thinking from different fields," Bhargava said. "It's a chemistry problem solved by a physics-based design, implemented by an electrical engineering student. It's in our DNA at Beckman to take that kind of approach to solving problems."

Credit: 
Beckman Institute for Advanced Science and Technology

How fast is the universe expanding? Galaxies provide one answer.

image: NGC 1453, a giant elliptical galaxy in the constellation Eridanus, was one of 63 galaxies used to calculate the expansion rate of the local universe. Last year, the MASSIVE survey team determined that the galaxy is located 166 million light years from Earth and has a black hole at its center with a mass nearly 3 billion times that of the sun.

Image: 
Photo courtesy of the Carnegie-Irvine Galaxy Survey

Determining how rapidly the universe is expanding is key to understanding our cosmic fate, but with more precise data has come a conundrum: Estimates based on measurements within our local universe don't agree with extrapolations from the era shortly after the Big Bang 13.8 billion years ago.

A new estimate of the local expansion rate -- the Hubble constant, or H0 (H-naught) -- reinforces that discrepancy.

Using a relatively new and potentially more precise technique for measuring cosmic distances, which employs the average stellar brightness within giant elliptical galaxies as a rung on the distance ladder, astronomers calculate a rate -- 73.3 kilometers per second per megaparsec, give or take 2.5 km/sec/Mpc -- that lies in the middle of three other good estimates, including the gold standard estimate from Type Ia supernovae. This means that for every megaparsec -- 3.3 million light years, or 3 billion trillion kilometers -- from Earth, the universe is expanding an extra 73.3 ±2.5 kilometers per second. The average from the three other techniques is 73.5 ±1.4 km/sec/Mpc.

Perplexingly, estimates of the local expansion rate based on measured fluctuations in the cosmic microwave background and, independently, fluctuations in the density of normal matter in the early universe (baryon acoustic oscillations), give a very different answer: 67.4 ±0.5 km/sec/Mpc.

Astronomers are understandably concerned about this mismatch, because the expansion rate is a critical parameter in understanding the physics and evolution of the universe and is key to understanding dark energy -- which accelerates the rate of expansion of the universe and thus causes the Hubble constant to change more rapidly than expected with increasing distance from Earth. Dark energy comprises about two-thirds of the mass and energy in the universe, but is still a mystery.

For the new estimate, astronomers measured fluctuations in the surface brightness of 63 giant elliptical galaxies to determine the distance and plotted distance against velocity for each to obtain H0. The surface brightness fluctuation (SBF) technique is independent of other techniques and has the potential to provide more precise distance estimates than other methods within about 100 Mpc of Earth, or 330 million light years. The 63 galaxies in the sample are at distances ranging from 15 to 99 Mpc, looking back in time a mere fraction of the age of the universe.

"For measuring distances to galaxies out to 100 megaparsecs, this is a fantastic method," said cosmologist Chung-Pei Ma, the Judy Chandler Webb Professor in the Physical Sciences at the University of California, Berkeley, and professor of astronomy and physics. "This is the first paper that assembles a large, homogeneous set of data, on 63 galaxies, for the goal of studying H-naught using the SBF method."

Ma leads the MASSIVE survey of local galaxies, which provided data for 43 of the galaxies -- two-thirds of those employed in the new analysis.

The data on these 63 galaxies was assembled and analyzed by John Blakeslee, an astronomer with the National Science Foundation's NOIRLab. He is first author of a paper now accepted for publication in The Astrophysical Journal that he co-authored with colleague Joseph Jensen of Utah Valley University in Orem. Blakeslee, who heads the science staff that support NSF's optical and infrared observatories, is a pioneer in using SBF to measure distances to galaxies, and Jensen was one of the first to apply the method at infrared wavelengths. The two worked closely with Ma on the analysis.

"The whole story of astronomy is, in a sense, the effort to understand the absolute scale of the universe, which then tells us about the physics," Blakeslee said, harkening back to James Cook's voyage to Tahiti in 1769 to measure a transit of Venus so that scientists could calculate the true size of the solar system. "The SBF method is more broadly applicable to the general population of evolved galaxies in the local universe, and certainly if we get enough galaxies with the James Webb Space Telescope, this method has the potential to give the best local measurement of the Hubble constant."

The James Webb Space Telescope, 100 times more powerful than the Hubble Space Telescope, is scheduled for launch in October.

Giant elliptical galaxies

The Hubble constant has been a bone of contention for decades, ever since Edwin Hubble first measured the local expansion rate and came up with an answer seven times too big, implying that the universe was actually younger than its oldest stars. The problem, then and now, lies in pinning down the location of objects in space that give few clues about how far away they are.

Astronomers over the years have laddered up to greater distances, starting with calculating the distance to objects close enough that they seem to move slightly, because of parallax, as the Earth orbits the sun. Variable stars called Cepheids get you farther, because their brightness is linked to their period of variability, and Type Ia supernovae get you even farther, because they are extremely powerful explosions that, at their peak, shine as bright as a whole galaxy. For both Cepheids and Type Ia supernovae, it's possible to figure out the absolute brightness from the way they change over time, and then the distance can be calculated from their apparent brightness as seen from Earth.

The best current estimate of H0 comes from distances determined by Type Ia supernova explosions in distant galaxies, though newer methods -- time delays caused by gravitational lensing of distant quasars and the brightness of water masers orbiting black holes -- all give around the same number.

The technique using surface brightness fluctuations is one of the newest and relies on the fact that giant elliptical galaxies are old and have a consistent population of old stars -- mostly red giant stars -- that can be modeled to give an average infrared brightness across their surface. The researchers obtained high-resolution infrared images of each galaxy with the Wide Field Camera 3 on the Hubble Space Telescope and determined how much each pixel in the image differed from the "average" -- the smoother the fluctuations over the entire image, the farther the galaxy, once corrections are made for blemishes like bright star-forming regions, which the authors exclude from the analysis.

Neither Blakeslee nor Ma was surprised that the expansion rate came out close to that of the other local measurements. But they are equally confounded by the glaring conflict with estimates from the early universe -- a conflict that many astronomers say means that our current cosmological theories are wrong, or at least incomplete.

The extrapolations from the early universe are based on the simplest cosmological theory -- called lambda cold dark matter, or ΛCDM -- which employs just a few parameters to describe the evolution of the universe. Does the new estimate drive a stake into the heart of ΛCDM?

"I think it pushes that stake in a bit more," Blakeslee said. "But it (ΛCDM) is still alive. Some people think, regarding all these local measurements, (that) the observers are wrong. But it is getting harder and harder to make that claim -- it would require there to be systematic errors in the same direction for several different methods: supernovae, SBF, gravitational lensing, water masers. So, as we get more independent measurements, that stake goes a little deeper."

Ma wonders whether the uncertainties astronomers ascribe to their measurements, which reflect both systematic errors and statistical errors, are too optimistic, and that perhaps the two ranges of estimates can still be reconciled.

"The jury is out," she said. "I think it really is in the error bars. But assuming everyone's error bars are not underestimated, the tension is getting uncomfortable."

In fact, one of the giants of the field, astronomer Wendy Freedman, recently published a study pegging the Hubble constant at 69.8 ±1.9 km/sec/Mpc, roiling the waters even further. The latest result from Adam Riess, an astronomer who shared the 2011 Nobel Prize in Physics for discovering dark energy, reports 73.2 ±1.3 km/sec/Mpc. Riess was a Miller Postdoctoral Fellow at UC Berkeley when he performed this research, and he shared the prize with UC Berkeley and Berkeley Lab physicist Saul Perlmutter.

MASSIVE galaxies

The new value of H0 is a byproduct of two other surveys of nearby galaxies -- in particular, Ma's MASSIVE survey, which uses space and ground-based telescopes to exhaustively study the 100 most massive galaxies within about 100 Mpc of Earth. A major goal is to weigh the supermassive black holes at the centers of each one.

To do that, precise distances are needed, and the SBF method is the best to date, she said. The MASSIVE survey team used this method last year to determine the distance to a giant elliptical galaxy, NGC 1453, in the southern sky constellation of Eridanus. Combining that distance, 166 million light years, with extensive spectroscopic data from the Gemini and McDonald telescopes -- which allowed Ma's graduate students Chris Liepold and Matthew Quenneville to measure the velocities of the stars near the center of the galaxy -- they concluded that NGC 1453 has a central black hole with a mass nearly 3 billion times that of the sun.

To determine H0, Blakeslee calculated SBF distances to 43 of the galaxies in the MASSIVE survey, based on 45 to 90 minutes of HST observing time for each galaxy. The other 20 came from another survey that employed HST to image large galaxies, specifically ones in which Type Ia supernovae have been detected.

Most of the 63 galaxies are between 8 and 12 billion years old, which means that they contain a large population of old red stars, which are key to the SBF method and can also be used to improve the precision of distance calculations. In the paper, Blakeslee employed both Cepheid variable stars and a technique that uses the brightest red giant stars in a galaxy -- referred to as the tip of the red giant branch, or TRGB technique -- to ladder up to galaxies at large distances. They produced consistent results. The TRGB technique takes account of the fact that the brightest red giants in galaxies have about the same absolute brightness.

"The goal is to make this SBF method completely independent of the Cepheid-calibrated Type Ia supernova method by using the James Webb Space Telescope to get a red giant branch calibration for SBFs," he said.

"The James Webb telescope has the potential to really decrease the error bars for SBF," Ma added. But for now, the two discordant measures of the Hubble constant will have to learn to live with one another.

"I was not setting out to measure H0; it was a great product of our survey," she said. "But I am a cosmologist and am watching this with great interest."

Credit: 
University of California - Berkeley

Greater tobacco use linked to higher levels of inflammation in HIV-positive people

image: Krishna Poudel is an associate professor in the UMass Amherst School of Public Health and Health Sciences and co-director of the of the UMass Amherst Institute for Global Health.

Image: 
UMass Amherst

Inflammation in the body has been linked to the intensity of tobacco smoking among people with HIV, according to a team of University of Massachusetts Amherst researchers.

Krishna Poudel, associate professor of community health education in the School of Public Health and Health Sciences, and colleagues reported positive linear relationships between intensity, duration and pack-years of smoking and inflammation in HIV-positive people. They believe it to be the first, more thorough examination of specific smoking-related variables with the levels of inflammation in this group, while also taking into account highly active antiretroviral therapy (HAART) and other important factors.

The study's findings suggest that people living with HIV would benefit not just from quitting smoking but from smoking less, says Poudel, co-director of the UMass Amherst Institute for Global Health. Poudel is lead author of the paper published in the March issue of the journal AIDS and Behavior.

"While it is important to support and encourage people living with HIV to ultimately quit smoking, it is also important to suggest they reduce the frequency of smoking until they can fully quit. That would also help their health status by reducing inflammation," says Poudel, noting that a high level of inflammation is linked to a greater risk of disease and death in people living with HIV.

Significantly, HIV-positive people who are receiving HAART have a greater risk of death from tobacco than from HIV-related factors.

In 2010, Poudel and co-author Kalpana Poudel-Tandukar, a UMass Amherst assistant professor of nursing, established the study cohort known as Positive Living with HIV (POLH). The public health researchers collaborated with five non-governmental organizations (NGOs) to recruit 322 HIV-positive people living in Nepal's Kathmandu Valley. Their goal was to gather behavioral, health and biologic information from participants to learn ways to improve the health and well-being of HIV-positive people, especially those in low- and middle-income countries.

The smoking and inflammation paper, whose UMass Amherst co-authors also include epidemiologist Elizabeth Bertone-Johnson and biostatistician Penelope Pekow, is the 18th publication in a peer-reviewed journal related to the POLH cohort study.

For the latest investigation, the researchers interviewed 284 study participants, gathering details about their smoking and medical history and other relevant information, such as whether they were receiving HAART. They asked about how many cigarettes were smoked per day (intensity) and for how many years (duration). Lifetime smoking exposure was gauged in pack-years, which is determined by multiplying the number of packs smoked daily by the number of years the person has smoked.

The team then measured serum C-reactive protein (CRP), a pro-inflammatory biomarker, and several strong predictors of inflammation in the participants. They adjusted for these variables while examining the relationships between smoking and inflammation, using both linear and logistic regression statistical analyses.

"We adjusted for zinc levels and hepatitis C. We adjusted for HAART status and CD4 cell counts. We adjusted for depression and the history of injected drug use," Poudel says. "We adjusted a total of 16 HIV-related symptoms, as well."

In each of the dose-response categories, researchers found a positive relationship between smoking and inflammation, although Poudel points out that the study's cross-sectional design cannot determine causality.

"A significantly higher proportion of the participants with high intensity of smoking (number of cigarettes smoked per day) had high levels of CRP concentrations compared to those with low intensity of smoking status," the paper states.

The researchers found similar results for smoking duration and pack-years of smoking; that is, participants who had smoked for longer periods and those who had greater pack-years were more likely to have high levels of CRP than those who had smoked for shorter periods and had fewer pack-years.

The important next step is to develop effective smoking reduction and cessation programs for HIV-positive people, whose tobacco use rate is two to three times higher than that of the general population. This is especially important in low- and middle-income countries, where such education and support are rarely available, Poudel says.

"Many HIV-positive people in low- and middle-income countries are willing to quit smoking and need support," Poudel says. "Our findings highlight an urgent need for providing smoking cessation support to HIV-positive people. While supporting HIV-positive people for quitting smoking is a critical public health priority, HIV care providers should encourage their patients at least to reduce the frequency of smoking, as this would be a positive step toward ultimately quitting smoking."

Credit: 
University of Massachusetts Amherst