Culture

MINNEAPOLIS - Even for people with a gene mutation tied to Parkinson's disease, coffee consumption may be associated with a lower risk of actually developing the disease, according to a new study published in the September 30, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology.

"These results are promising and encourage future research exploring caffeine and caffeine-related therapies to lessen the chance that people with this gene develop Parkinson's," said study author Grace Crotty, M.D., of Massachusetts General Hospital in Boston and a member of the American Academy of Neurology. "It's also possible that caffeine levels in the blood could be used as a biomarker to help identify which people with this gene will develop the disease, assuming caffeine levels remain relatively stable."

Earlier studies have shown that coffee consumption may protect against the development of Parkinson's disease in people who have no genetic risk factors for the disease. This study looked at people with a genetic mutation that increases the risk of Parkinson's. The mutation is in a gene called LRRK2 for leucine-rich repeat kinase 2. But having the abnormal gene does not guarantee that people will develop the disease, so researchers are hoping to identify other genetic or environmental factors that affect whether people develop the disease.

The study compared 188 people who had Parkinson's disease to 180 people who did not have the disease; both groups had people with the LRRK2 gene mutation and those without it. Researchers looked at the amount of caffeine in the blood, as well as other chemicals that are produced as caffeine is metabolized in the body, and how it varied among the groups. A total of 212 of the participants also completed questionnaires about how much caffeine they consumed each day.

Among people carrying the LRRK2 gene mutation, those who had Parkinson's had a 76% lower concentration of caffeine in their blood than those who did not have Parkinson's. People with Parkinson's with a normal copy of the gene had a 31% lower concentration of caffeine in their blood than non-carriers without Parkinson's.

Carriers of the gene mutation who had Parkinson's also had lower consumption of caffeine in their diet. The gene carriers with Parkinson's consumed 41% less caffeine per day than the people who did not have Parkinson's, both with and without the gene mutation.

"We don't know yet whether people who are predisposed to Parkinson's may tend to avoid drinking coffee or if some mutation carriers drink a lot of coffee and benefit from its neuroprotective effects," Crotty said.

Crotty noted that the study looked at people at one point in time, so it does not help researchers understand any effect caffeine has over time on the risk for Parkinson's or how it may affect the disease's progression. It also does not prove that caffeine consumption directly causes a lower risk of Parkinson's; it only shows an association.

MINNEAPOLIS - Stroke patients who get professional rehabilitation training in their homes through live video consultations may recover their motor skills better than those who do their rehab in person with a therapist at an outpatient rehabilitation facility, according to a study published in the September 30, 2020, online issue of Neurology®, the medical journal of the American Academy of Neurology. Remote rehabilitation may also promote greater brain connectivity, the study said.

"During the pandemic, when travel and human contact might not be possible, it's important to find out if it's safe and effective for stroke patients to recover at home, using video consultations for their therapy," said study author Chuancheng Ren, Ph.D., of Fudan University in Shanghai, China. "Our findings are exciting because they suggest remote rehabilitation programs may be more effective than in-person rehabilitation in two ways: on the physical level, with greater increases in physical mobility, and on the brain level, with increased functional brain activity."

The study involved 52 people with stroke with paralysis on one side of their bodies who had their strokes an average of two weeks before the study. Half were randomly assigned to a home-based telerehabilitation group, half to a conventional outpatient group. All the participants did at least 12 weeks of rehab. For both groups, each session included 60 minutes of occupational and physical therapy, plus 20 minutes of neuromuscular stimulation. All the participants were assessed for both motor function and brain changes at the start of the study, immediately after completion of the rehabilitative sessions and again three months later.

Researchers used a test that measures the recovery of motor skills in the arms and legs after stroke. In this test where an increase of at least 10 points is needed to show meaningful improvement, the group rehabilitating remotely scored an average of 11 points higher than they did at the beginning of the study, while the group receiving conventional in-person rehabilitation scored on average 5.3 points higher.

To measure changes in the brain, researchers used resting-state functional imaging. The remote training group increased their resting state brain connectivity compared to the conventional therapy group.

"We believe the convenience of rehabbing at home may have helped study participants stick to their rehabilitation programs, and that in turn may have helped them recover motor skills better than their conventionally treated peers," Ren said. "Also, the home environment may have given people more opportunities to participate in, and learn from real-life family activities."

A limitation of the study is that there was no control group receiving no rehabilitation training, which would have allowed researchers to estimate the amount of recovery that might occur naturally.

Rutgers researchers, together with colleagues at Columbia University, have reported an increased mortality risk in adults with depression who initiated augmentation with newer antipsychotic medications compared to a control group that initiated augmentation with a second antidepressant.

The study was published in the journal PLOS ONE.

Although antidepressants are the first-line pharmacological treatment for depression, many people do not respond to the first course of treatment. Subsequent treatment options include switching to another antidepressant followed by various augmentation strategies, including augmentation with a second antidepressant and augmentation with newer antipsychotics, such as aripiprazole, quetiapine and olanzapine.

"Antipsychotics have well-recognized and often serious adverse effects, including a more than 50 percent increased mortality risk in older adults with dementia," said lead author Tobias Gerhard, an associate professor at Rutgers Ernest Mario School of Pharmacy. "It had been previously unknown whether this mortality risk applies to non-elderly adults using newer antipsychotics as augmentation treatment for depression. The clinical trials that led to the approval of various newer antipsychotics for depression were just too small and too short to be informative for this question."

The researchers looked at data of 39,582 Medicaid beneficiaries ages 25 to 64 from 2001 to 2010, linked to the National Death Index. After a period of treatment with a single antidepressant, study patients initiated either augmentation with a newer antipsychotic or with a second antidepressant. The researchers found a 45 percent relative increase in mortality risk for those initiating a newer antipsychotic, which for the study cohort translated to one additional death for every 265 people taking the antipsychotic for one year.

"Our results require replication, ideally with a publicly financed pragmatic randomized controlled trial. However, in the meantime, our study suggests that physicians should consider prescribing antipsychotics to adults with depression carefully, as the potential health risks are substantial and the benefits are quite modest and controversially debated," said Gerhard. "Of particular relevance for our results is a finding from our previous work. It is well-known that most antidepressants take about four to six weeks to be fully effective. However, contrary to the drug label and treatment guidelines many patients in the United States initiate antipsychotic treatment for depression without having completed an adequate prior trial with a single antidepressant. Our results emphasize the importance of considering newer antipsychotics only after non-response to less risky, evidence-based treatment options has been established."

Stunning Arnhem Land rock art images including three rare depictions of bilbies and a dugong have been described by researchers in a new paper in Australian Archaeology today (Oct 1).

Led by Professor Paul Taçon, Australian Research Council Laureate Fellow and Griffith University Chair in Rock Art Research, the team documented 572 previously unknown images ranging in age from 6000 to 9400 years from 87 sites from 2008 to 2018.

Named Maliwawa Figures, they are found in northwest Arnhem Land and recorded at sites from Awunbarna (Mount Borradaile area) to the Namunidjbuk clan estate of the Wellington Range.

The Maliwawa images include large (over 50cm high, sometimes life-size) naturalistic humans and macropods with animals more often depicted than human figures. Painted in various shades of red with stroke-infill or outline forms with a few red strokes as infill, they are shown with little material culture other than various forms of headdresses.

Professor Taçon said the rock art provided a window into the past and showed us what people were doing at this time. "They're a missing link between the well-known early-style Dynamic Figures, about 12,000 years of age, and X-ray figures made in the past 4000 years."

"Maliwawas are depicted as solitary figures and as part of group scenes showing various activities and some may have a ceremonial context. Human figures are frequently depicted with animals, especially macropods, and these animal-human relationships appear to be central to the artists' message," he said.

He also said the Maliwawa Figures and scenes were not just simple depictions of everyday life.

"The artists are clearly communicating aspects of their cultural beliefs, with an emphasis on important animals and interactions between humans and other humans or animals.

"Indeed, animals are much more common than in the Dynamic Figure style rock art in terms of percentage of subject matter, as 89% of Dynamic Figures are human, whereas only about 42% of Maliwawa Figures are human."

Professor Taçon said in some images animals almost appeared to be participating in or watching some human activity.

"This occurrence, and the frequency and variability of headdresses, suggests a ritual context for some of the production of Maliwawa rock art.

Co-author Dr Sally K. May from Griffith University's Place, Evolution and Rock Art Heritage Unit said the discovery of what appear to be depictions of 'bilbies' at an Awunbarna site was surprising.

"Bilbies are associated with arid and semi-arid environments far to the south and Arnhem Land has not been within their range in historic times,'' she said.

"Two of these animals are back-to-back and almost identical in size. The third bilby-like depiction appears to have been made at a different time, and perhaps by a different artist, as it is larger, has a longer snout, has more line infill, and is in a lighter shade of red.

"There is also the possibility that the depictions are of Agile Wallabies, Northern Nailtail Wallabies or Short-eared Rock-wallabies, all widespread across Kakadu-Arnhem Land today, but all of these species have much shorter ears and snouts than extant bilbies and the creatures depicted at Awunbarna."

The researchers also recorded the oldest know depiction of a dugong.

"The solitary dugong painting also seems out of place,'' Dr May said.

"Today it is located about 15 kilometres south of the Arafura Sea but 6000-9400 years ago the coast would have been further north. It indicates a Maliwawa artist visited the coast but the lack of other saltwater fauna may suggest this was not a frequent occurrence."

At some sites there are two large macropods shown back-to-back with a small space between them. There are also some back-to-back human figures and the back-to-back 'bilbies'.

"The Maliwawa back-to-back figures are the oldest known for western Arnhem Land and it appears this painting convention began with the Maliwawa style. It continues to the present with bark paintings and paintings on paper,'' Professor Taçon said.

"But was the Maliwawa rock art sporadic and made during a short time period or did it continue over a long period of time?

He said they could not rule out the possibility that Maliwawa rock paintings were produced by a small number of artists. It is even possible only a couple artists made most of the paintings, with one responsible for the more outline forms with minimal infill and another creating much of the fuller stroke-line infill examples.

"At the same time, much art produced after the Maliwawa style demonstrates a remarkable consistency in the manner of depiction and a significant increase in the standardisation of some subject matter such as X-ray fish.

"So, perhaps what we are observing is increasing standardisation in the manner of depiction after the period in which Dynamic Figures were made. This has implications for rock art research everywhere in which a style or manner of depiction is suggested to have been made over hundreds of years or millennia."

A new study led by researchers from Brigham and Women's Hospital and the University of Minnesota, Minneapolis sheds light on why female primary care physicians receive lower wages than their male counterparts. The study found that female PCPs generated 11 percent less revenue due to conducting 11 percent fewer visits in a year (doctors are largely paid by the visit). But while previous studies based on surveys have suggested that this wage gap is due, in part, to female physicians working fewer hours than male physicians, the new study finds just the opposite: Female physicians spent more time with their patients per visit, per day, and per year. Results are published in The New England Journal of Medicine.

"When talking about the gender wage gap, researchers have long assumed that women are working fewer hours, or that they're working part time," said first author Ishani Ganguli, MD, MPH, a health policy researcher and assistant professor of Medicine at Harvard Medical School and the Brigham’s Division of General Internal Medicine and Primary Care. "Yet when we compared just the time doctors spent face to face with patients alone, women physicians, in fact, spent more time than their male counterparts despite making 87 cents to the dollar for that work."

The research team gathered nationwide data on the gender pay gap between female and male physicians, observing visit revenue, visit counts, days worked, and visit time for 24.4 million primary care office visits across the United States during 2017. The team used electronic health records, including detailed time data, provided by athenahealth, a technology company that provides electronic health records software, that allowed them to compare female and male physician visits within the same practices. The team controlled for age of physician, degree level, specialty, and number of sessions worked per week as well as for characteristics of the patients and visits they were studying. By doing so, the study was able to capture a more nuanced portrait of female and male physicians' daily practices than previous studies.

The researchers found that female PCPs generated 11 percent less revenue and conducted 11 percent fewer visits over just 2.6 fewer clinical days per year. However, female PCPs spent 1200 more minutes with patients per year, or 2.4 more minutes per visit on average, than their male counterparts.

"Our findings provide more evidence that our current system of paying doctors based on the volume of services they provide is a flawed measure of work effort," said senior author Hannah Neprash, PhD, a health economist at the University of Minnesota's School of Public Health. "Female physicians report the highest rates of burnout and our findings may help explain why. If longer visits contribute to feelings of time pressure and a chaotic work environment - for lower pay - it's understandable that job satisfaction might be lower."

The researchers were unable to explore whether this increase in time spent per patient improved patient outcomes and/or patient care. Additional limitations include the authors did not have information on physicians with non-binary gender identities and the study focused on using athenahealth as the sole data source.

"All doctors, especially in primary care, want more time with their patients," said Ganguli. "What we're seeing is that female doctors seem to spend more time but at a personal cost."

Sexist attitudes influence how politicians accused of sexual misconduct are viewed, even more than partisanship, according to a Dartmouth study. The findings are published in Research & Politics.

"Our study shows that partisanship clearly plays a major role in affecting people's favorability about a politician who is accused of #MeToo allegations," explained lead author, Mia Costa, an assistant professor of government at Dartmouth. "Gender attitudes about women however, is really what influences whether and how people react to sexual misconduct scandals, above and beyond partisanship, even though both are obviously important," she said.

The purpose of the study was to understand how partisanship and sexist attitudes affect how voters view political candidates who are accused of sexual allegations. Dartmouth undergraduate students came up with the idea for the study last fall, as part of the course, Experiments in Politics. They wanted to investigate how #MeToo political scandals affect voters' sentiments.

To evaluate how voters react to sexual misconduct allegations, over 2,800 respondents were surveyed online in October 2019. The participants were given a series of pretest and posttest questions to evaluate how favorably they viewed a fictional, male Senator and how likely they would be to vote to reelect him. Respondents were provided a brief biography about the politican and were asked to provide their favorability and reelection ratings. They were then shown a news article that reflected one of three experimental conditions: allegations that the Senator had sexually assaulted women, allegations that he had often made sexist jokes, or a control condition that the Senator had recently visited a county fair. After reading the news article, they were asked how favorably they feel towards the Senator, whether they would vote for his reelection, and what type of punitive consequences he should face, if any, such as whether he should apologize or resign. The Senator's political party affiliation was randomly assigned.

The findings showed that overall, favorability and electoral support decreased after respondents read about the allegations of either sexual assault or sexist jokes, even when they had the same party affiliation as that of the Senator. Reactions were stronger to allegations of sexual assault than sexist jokes.

The results also demonstrated several instances of "partisan motivated reasoning." Partisan motivated reasoning happens when people process information with the aim of protecting their pre-existing, partisan interests. In an era of heightened polarization, "motivated reasoners" prioritize their party identification above all else. Respondents appeared to be more sympathetic to the Senator when they had the same party affiliation. For example, after respondents with the same party as the Senator read about sexual assault allegations, favorability decreased by 31.9 percent as compared to the control while those with the opposite party affiliation decreased their favorability by 38.6 percent. Respondents appeared to be less critical of the allegations of sexist jokes as well if the Senator was from the same party. Favorability decreased by 20.4 percent for those of the same party as compared to 28.5 percent for those of the opposite party, illustrating the degree to which partisanship plays a role. In addition, those who had the same party affiliation as the Senator were less likely to indicate that the he should be penalized (e.g. lose his seat) for sexual assault allegations or making sexist jokes.

The sexual assault allegations and sexist jokes by the Senator had zero effect, however, on favorability and electoral support for respondents who ranked highest on the sexism scale. This means that the most sexist respondents indicated that they would have been just as likely to vote for the Senator had they had not heard about the allegations or sexist jokes. The higher the respondents were on the sexism scale, the less likely they thought that the Senator should be penalized.

The impact of sexual assault allegations and sexist jokes on changes in favorability and electoral support was much larger for women than men. For women, electoral support decreased by 34 percent for assault allegations as compared to 23 percent for men.

When the results were broken out by party affiliation, the data demonstrated that Republicans decrease their favorability and electoral support much less than Democrats do, illustrating a partisan divide on how the #MeToo movement is perceived.

Regarding age, changes in favorability and electoral support was highest among millenials (age 18-24), who decreased favorability by 53 percent and decreased electoral support by 42 percent for the Senator accused of sexual assault, as compared to older age groups, who only decreased by an average of 30 percent and 26 percent, respectively.

"In the last few weeks of the 2016 campaign, the Access Hollywood tapes put issues of sexual assault on the top of the agenda for voters. In 2020, we may very well see such issues resurface and our study helps to understand what consequence, if any, that would have for the outcome of the election," added Costa.

Subtle differences in cognition may help identify individuals at risk for becoming dependent years later upon others to complete daily activities, such as managing medications or finances and other essential activities.

Writing in the September 29, 2020 online issue of the Journal of Alzheimer's Disease, researchers at University of California San Diego School of Medicine, with colleagues elsewhere, linked poorer cognitive performance in a single testing with subsequent greater risk for impaired daily life activities nearly a decade later.

The study involved a diverse but understudied cohort of Latinos living in the United States. Outcomes were most severe for individuals 70 years and older, but gender and ethnic background, such as Mexican or Puerto Rican, were not significant differentiators. The authors said the findings in sum highlight the need for early preventive care across Latinos and Latinas of various backgrounds.

Family members often provide unpaid care for individuals with impairments in daily activities; Latinos are no exception. Among the more than 16 million unpaid caregivers of persons with dementia, Latinos spend an average of 10 more hours per week in caregiving duties than their non-Latino, white counterparts, according to the Alzheimer's Association.

"Identifying risk factors for impairments in activities of daily living among Latinos is a crucial first step in protecting independence in aging, reducing caregiver burden, minimizing dementia disparities and decreasing public health costs associated with dementia," said senior author Hector M. Gonzalez, PhD, associated professor in the Department of Neurosciences at UC San Diego School of Medicine and a member of the Shiley-Marcos Alzheimer's Disease Research Center.

Study authors examined data from more than 6,000 participants enrolled in the Hispanic Community Health Study/Study of Latinos, the most comprehensive study of Hispanic/Latino health and disease in the U.S. and the Study of Latinos-Investigation of Neurocognitive Aging, an ongoing study supported by the National Institute on Aging (NIH). Participants resided in one of four U.S. metropolitan areas: Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA and represented diverse Latino backgrounds, including Central Americans, Cubans, Dominicans, Mexicans, Puerto Ricans and South Americans.

Participants underwent a variety of cognitive tests at a single testing point. Approximately seven years later, researchers assessed their level of dependence in activities of daily living (IADL), based on a self-report questionnaire. Specifically, researchers looked at cognitively engaging activities considered important to everyday living, such as managing finances. These types of mentally engaging activities tend to decline earlier in the dementia disease process than basic activities, like personal grooming.

"The majority of participants did not show impairments in IADLs, which is to be expected in a relatively healthy community-dwelling sample of 50-plus year-olds," said first author Ariana M. Stickel, PhD, a postdoctoral scholar in the Department of Neurosciences at UC San Diego School of Medicine.

"Despite this, we found that individuals with poorer cognitive performance at the initial visit were more at-risk for later impairments in IADLs, which points to the importance of maintaining cognitive health in middle-age and older adulthood."

In addition to predicting risk, performance on learning and memory tasks helped predict severity of future IADL impairment, indicating these measures may be most closely linked to independence in daily functions.

"Declines in learning and memory are common in dementia, particularly Alzheimer's disease," Gonzalez said. "We may be uncovering the earliest stages in which the disease manifests behavioral impairments."

"We plan to investigate multiple biological, genetic and psychosocial pathways in which cognition and IADLs might be connected, using the NIA's Health Disparities Framework, and the Research Framework for Cognitive Aging and Alzheimer's disease for Diverse Latinos," Gonzalez he said. "The more comprehensive our investigations of Latino cognitive aging, the better we can inform interventions that aim to maintain independence in daily activities."

"Imagine what an extra year of independence would mean, especially for Latino families who disproportionately face economic hardships relative to whites," added Stickel. "Being able to hold onto one's independence later in life sends positive ripple effects to the individual, the family and the general public."

A new study suggests some hackers aren't just in it for the money but instead are motivated by their disappointment in a company's attempts to fake social responsibility.

"There is emerging evidence that the hacking community is not homogenous, and at least some hackers appear to be motivated by what they dislike, as opposed to solely financial gain," said John D'Arcy, a co-author and professor of management information systems (MIS) at the University of Delaware. "Recent hacks against the World Health Organization, due to its actions (or supposed inactions) related to the COVID-19 pandemic, are a case in point."

D'Arcy and his coauthors, interested in exploring whether a firm's corporate social performance (CSP) impacts their likelihood of being breached, studied a unique dataset that included information on data breach incidents, external assessments of firms' CSP and other factors. The results, published on Sept. 18 in the Information Systems Research paper "Too Good to Be True: Firm Social Performance and the Risk of Data Breach," were intriguing.

The key to these results, D'Arcy explained, lies in understanding the difference between two different types of corporate social responsibility efforts: those that are more minor and peripheral (like recycling programs or charitable donations) versus those that involve social responsibility being embedded throughout the firm's core business and processes (like diversity initiatives and producing eco-friendly products).

Companies only participating in peripheral efforts and not more deeply embedded ones are sometimes called "greenwashing," attempting to give the appearance of social responsibility without infusing such practices throughout their entire organization. According to D'Arcy's research, firms that do this are more likely to face problems from hackers.

"An example of a firm that has been accused of greenwashing is Walmart," D'Arcy said. "This is because Walmart has touted its investments in charitable causes and environmental programs, but at the same time has been criticized for providing low wages and neglecting investments in employees' physical and psychological working environment."

The study found that hackers of all kinds -- from internal disgruntled employees to external hacktivist groups -- can "sniff out" these actions that only give the appearance of social responsibility. To an even further extent, when companies not only are trying to improve their image but also are using these actions to mask poor overall CSP, they are especially likely to be breached.

"Consequently, these firms are more likely to be victimized by a malicious data breach for these reasons," D'Arcy said. "Firms may be placing a proverbial target on their back, in an information security sense, by engaging in greenwashing efforts."

Conversely, the study found that when firms that engage in more embedded and meaningful forms of corporate responsibility, they are more likely to see solely positive outcomes. In this case, that means fewer hacks and data breaches.

"These same internal and external hackers are likely to see such embedded CSP efforts as genuine attempts at social responsibility (in other words, the company is 'walking its talk' when it comes to social responsibility) and thus they will be less likely to target these firms for a computer attack that results in a breach," D'Arcy said.

What lessons should companies take from this research? D'Arcy warned that companies should be cautious about promoting peripheral CSP efforts if they have otherwise poor records on corporate social issues.

"What was once accepted as meaningful CSP activity may no longer appease certain stakeholders," he said. "And in this era of increased information transparency and greater expectations of the firm's role in society, engaging in only peripheral actions may result in stakeholder backlash. Firms need to be cautious about promoting their CSP activities unless they can defend their actions as embedded in core practices and as authentically motivated."

In a study published in the scientific journal Nature, researchers at the RIKEN Center for Brain Science (CBS) in Japan report that a part of the mouse brain called the SuM is specialized for detecting new experiences. Within the SuM, responses to experiences related to unknown individuals--called social novelty--were segregated from those related to unfamiliar places--called context novelty--before being sent to distinct parts of the brain's main memory-formation center. This discovery can help us understand normal memory, as well as conditions in which recognizing and reacting to new information is impaired.

Meeting someone for the first time or entering an unfamiliar apartment is a much different experience than meeting an acquaintance or walking into your own home. Normal social interactions, daily functions, and even survival can depend on being able to make the distinction between the unknown and the familiar. Almost all animals seem to be born with this ability, and like other innate behaviors, the team at RIKEN CBS hypothesized that a region of the brain called the hypothalamus might be involved.

To test this hypothesis, they exposed mice to two types of novelty: contextual or social. The novel context was an unfamiliar cage with a few landmark objects and the social novelty was an unfamiliar juvenile mouse. They found that overall brain activity in a part of the hypothalamus called the SuM was much higher in these novel situations than when mice were placed in familiar cages or near familiar mice. "The hypothalamus is a very highly conserved region of the brain across evolution, mostly thought to be involved in innate behaviors like feeding, mating, parenting, and fighting," says Team Leader Thomas McHugh. "Our data suggest that it could also serve as a link between these survival-type behaviors and higher cognitive function."

Surprisingly, although the SuM signaled novelty overall, the majority of individual brain cells in the SuM only responded to one or the other type of novel situation. This is the first time that anyone has found a social/contextual split within a novelty circuit in the brain. In order to see how far the separation went, the team needed to create a new transgenic mouse line that would allow them to see exactly where these SuM neurons project and what they do.

A series of experiments showed that the neurons in the SuM connect with two parts of the hippocampus, the part of the brain known for being involved in memory formation and storage. Neurons that were selective for contextual novelty connected to the DG part of the hippocampus, while those that signaled social novelty were connected to the CA2 region.

Scientists often use novelty tests to assess memory. Mice explore new places and approach unfamiliar mice, making these behaviors both signs of novelty, and by inference, a lack of memory.

McHugh and his team used optogenetic light stimulation to show that output from the SuM directly affected social and contextual memory. For example, exciting the SuM-to-CA2 connection with blue light caused mice to behave as if they had a selective deficit in social memory; they frequently approached familiar mice as if they had never seen them before, but did not explore familiar rooms more than control mice. Likewise, they saw the reverse behavioral pattern when the SuM-to-DG connection was excited.

Accurately detecting contextual and social novelty allows us to adapt our behavior appropriately to changes in daily life. "Understanding how we recognize and react to novel information is fundamental to understanding memory," says McHugh. "Not only does novelty strengthen memory, both in mice and humans, impairment in recognizing and reacting to new information often accompanies psychiatric conditions. This research can thus provide a biological target to examine in such cases."

In a clinical trial testing whether a daily regimen of hydroxychloroquine could protect those most likely to be exposed to COVID-19, researchers from the Perelman School of Medicine at the University of Pennsylvania found there was no difference in infection rates among health care workers who took the drug versus those taking a placebo. While the researchers observed a lack of effect associated with hydroxychloroquine, infection levels were low among the participants, which the researchers believe points to the effectiveness of other prevention measures in the health system: social distancing, use of personal protective equipment, and proper hand hygiene. The study was published today in JAMA Internal Medicine.

"This work represents the first randomized trial of hydroxychloroquine's prophylactic effect for those not yet exposed to COVID-19," said the study's lead author, Benjamin Abella, MD, MPhil, a professor of Emergency Medicine and the director of Penn Medicine's Center for Resuscitation Science. "And while hydroxychloroquine is an effective drug for the treatment of diseases like lupus and malaria, we saw no differences that would lead us to recommend prescribing it as a preventive medication for COVID-19 in front line workers."

Due to the novel nature of COVID-19, the science and medical communities have had to rapidly assess treatment and prevention measures. One drug that has been considered as a potential preventive solution was hydroxychloroquine, based on laboratory studies that it could prevent SARS-CoV-2, the virus that causes COVID-19, from entering cells in tissue culture.

As such, Abella, along with the study's senior author Ravi Amaravadi, MD, an associate professor of Medicine in Hematology-Oncology and the program co-Leader of Cancer Therapeutics at the Abramson Cancer Center, and their co-authors set out to rigorously test whether taking a substantial dose of hydroxychloroquine - 600 milligrams daily for two months- would have an effect on infection rates. They conducted this study among hospital workers that regularly came into contact with COVID-19 patients.

The researchers were able to analyze a pool of 125 physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists that they recruited for the study. This population worked in several different areas of the two University hospitals, including the emergency departments and COVID-19 units. Roughly half of the participants in the study took hydroxychloroquine while the other half took a matching placebo (a cellulose pill). The study was double-blinded, meaning neither the researchers, nor the participants knew which drug they were assigned.

Extensive testing was used to rigorously prove who did or did not contract the virus. Each person received swab and antibody testing for COVID-19 at the start of their participation in the study, halfway through, and at the end--an eight-week span during the study period that began April 9 and ended July 14, 2020. Participants also had electrocardiogram (ECG) tests because of concerns about hydroxychloroquine causing heart rhythm problems in severe cases of COVID-19.

"To really test the potential of HCQ as a prevention drug, we felt it was key to recruit health care workers with many hours of direct physical exposure to COVID-19 patients, then randomize them in a double-blind manner between hydroxychloroquine or a matching placebo, and treat them for a long period of time," said Amaravadi. "Through that whole time, we monitored participants closely for their safety."

At the end of the study, 6.3 percent of those who took the hydroxychloroquine had tested positive for COVID-19 while 6.6 percent of those who took the placebos were positive. None required hospitalization. Additionally, there was no difference detected in the heart rhythms between those in either arm of the study, which showed that while the drug had no preventive effect, it was also not detrimental, outside of some temporary side effects like diarrhea for some.

"The differences we saw were negligible," Amaravadi said. "And those who did get the virus, whether they were taking hydroxychloroquine or not, were all asymptomatic or had very mild forms of COVID-19."

While the study was originally slated to recruit 200 health care workers, an analysis along the way showed that a continuation of enrollment would not yield different results. An independent data safety and monitoring board reviewed the findings and concurred.

These results will have an impact on the dozens of planned and ongoing clinical trials around the world that are testing hydroxychloroquine as a prevention for COVID-19 infection in health care workers. While a much larger study could potentially find a different result, the results of the Penn study suggest other forms of prevention, including vaccines, may be worth more attention.

What The Study Did: This single-center study of 77 patients describes the outcomes of patients with symptomatic severe aortic stenosis during the COVID-19 pandemic.

Authors: Stamatios Lerakis, M.D., Ph.D., of the Icahn School of Medicine at Mount Sinai in New York is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.19801)

Editor's Note: The article includes conflict of interest disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Physicists at Aalto University and VTT Technical Research Centre of Finland have developed a new detector for measuring energy quanta at unprecedented resolution. This discovery could help bring quantum computing out of the laboratory and into real-world applications. The results have been published today in Nature.

The type of detector the team works on is called a bolometer, which measures the energy of incoming radiation by measuring how much it heats up the detector. Professor Mikko Möttönen's Quantum Computing and Devices group at Aalto has been developing their expertise in bolometers for quantum computing over the past decade, and have now developed a device that can match current state-of-the-art detectors used in quantum computers.

'It is amazing how we have been able to improve the specs of our bolometer year after year, and now we embark on an exciting journey into the world of quantum devices,' says Möttönen.

Measuring the energy of qubits is at the heart of how quantum computers operate. Most quantum computers currently measure a qubit's energy state by measuring the voltage induced by the qubit. However, there are three problems with voltage measurements: firstly, measuring the voltage requires extensive amplification circuitry, which may limit the scalability of the quantum computer; secondly, this circuitry consumes a lot of power; and thirdly, the voltage measurements carry quantum noise which introduces errors in the qubit readout. Quantum computer researchers hope that by using bolometers to measure qubit energy, they can overcome all of these complications, and now Professor Möttönen's team have developed one that is fast enough and sensitive enough for the job.

'Bolometers are now entering the field of quantum technology and perhaps their first application could be in reading out the quantum information from qubits. The bolometer speed and accuracy seems now right for it,' says Professor Möttönen.

The team had previously produced a bolometer made of a gold-palladium alloy with unparalleled low noise levels in its measurements, but it was still too slow to measure qubits in quantum computers. The breakthrough in this new work was achieved by swapping from making the bolometer out of gold-palladium alloys to making them out of graphene. To do this, they collaborated with Professor Pertti Hakonen's NANO group - also at Aalto University - who have expertise in fabricating graphene-based devices. Graphene has a very low heat capacity, which means that it is possible to detect very small changes in its energy quickly. It is this speed in detecting the energy differences that makes it perfect for a bolometer with applications in measuring qubits and other experimental quantum systems. By swapping to graphene, the researchers have produced a bolometer that can make measurements in well below a microsecond, as fast as the technology currently used to measure qubits.

'Changing to graphene increased the detector speed by 100 times, while the noise level remained the same. After these initial results, there is still a lot of optimisation we can do to make the device even better,' says Professor Hakonen.

Now that the new bolometers can compete when it comes to speed, the hope is to utilise the other advantages bolometers have in quantum technology. While the bolometers reported in the current work performs on par with the current state-of-the-art voltage measurements, future bolometers have the potential to outperform them. Current technology is limited by Heisenberg's uncertainty principle: voltage measurements will always have quantum noise, but bolometers do not. This higher theoretical accuracy, combined with the lower energy demands and smaller size - the graphene flake could fit comfortably inside a single bacterium - means that bolometers are an exciting new device concept for quantum computing.

The next steps for their research is to resolve the smallest energy packets ever observed using bolometers in real-time and to use the bolometer to measure the quantum properties of microwave photons, which not only have exciting applications in quantum technologies such as computing and communications, but also in fundamental understanding of quantum physics.

Many of the scientists involved in the researchers also work at IQM, a spin-out of Aalto University developing technology for quantum computers. “IQM is constantly looking for new ways to enhance its quantum-computer technology and this new bolometer certainly fits the bill,” explains Dr Kuan Yen Tan, Co-Founder of IQM who was also involved in the research.

The immune system is equipped with numerous cell types that effectively fight the various pathogens, humans can encounter during their lives. T cells, for example, have a receptor through which they can specifically recognize and bind antigens. However, in recent decades, cell types with similar protective properties have been discovered that do not possess a specific antigen receptor.

Only a few years ago, scientists identified a group of lymphocytes, so-called "innate lymphoid cells" (ILCs), which are now among the most important players in the body's immune defense and make a significant contribution to the fight against pathogens. Unlike T cells, ILCs do not patrol the bloodstream but are predominantly tissue-resident cells. ILCs reside in various tissues where they interact with many immune and non-immune cell types and contribute to immune surveillance, activation of inflammatory responses, tissue homeostasis and repair and barrier functions. They are found in the bone marrow, secondary lymphoid organs such as lymph nodes and, most prominently, in non-lymphoid tissues with mucosal barriers such as the lung or the small intestine.

The ambivalent role of ILC2 in immune defense

The size of the ILC population and the subset composition varies between organs and can undergo dynamic changes during immune challenge. Type II ILCs (ILC2s) are the dominant subtype in the lung and have been shown to play a major role in immune defense against parasitic worm infection or in wound healing. On the other hand, ILC2s also contribute to the pathology of allergic respiratory inflammation such as asthma.

As in other tissues, ILC2s in the lung expand and differentiate during the first weeks of life after which a fraction persists as tissue-resident cells during adulthood. However, ILC2s can be generated and recruited from other tissues also during adult life in normal physiology and inflammatory conditions. It was unclear whether these ILC2s have specialized functions or whether they were recruited to replenish the local pool of resident cells.

Single-cell atlas of lung innate lymphoid cells

To shed light on these unknown mechanisms, scientists at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, headed by Dominic Grün, and colleagues from the Würzburg Institute of Systems Immunology led by Georg Gasteiger teamed up with researchers from New York and Marseille to generate a comprehensive single-cell atlas of mouse ILC populations in the bone marrow, neonatal and adult lung during normal physiological condition and during worm infection.

They discovered a pool of local progenitors which receives influx from the bone marrow and has the potential to generate the full spectrum of mature ILC2s observed in the lung during worm infection.

Cell plasticity in response to changing tissues

"Our work sheds light on how the local population of ILC2s in the lung is maintained. We found that progenitors recruited to the lung from other tissues via the bloodstream adjust to the lung environment by modulating their gene expression and differentiate into mature ILC2s that are almost indistinguishable from their counterparts derived from lung-resident progenitors. This is an exciting example for the plasticity of immune cell states in response to changing tissue environments", says Dominic Grün, Max Planck group leader and member of the CIBSS - Centre for Integrative Biological Signalling Studies, Cluster of Excellence at the University of Freiburg.

The study published in the scientific journal "Immunity" describes a "continuum" of ILC2 differentiation stages connecting the progenitors with the mature populations, including previously unknown ILC2 subtypes.

"We were able to reveal the complexity of the functions of ILC2s in an unprecedented manner and at the same time draw conclusions about their origin and development," explains Patrice Zeis, first author of the study. To detect the heterogeneity and development of lung ILC2s in a comparable systemic way, the scientists combined single-cell RNA sequencing with machine learning approaches. Thus, they successfully created "molecular fingerprints" for thousands of innate immune cells in the murine lung, and derived novel insights on the cell's identity, functions and the developmental relationships between the cells in the model organism.

Our proposed concepts of tissue differentiation and adaption of ILC2s may help to understand how local differentiation of ILCs can contribute to inflammatory diseases and might be applicable to other immune cell types", explains Patrice Zeis.

The causes of cerebral palsy have long been debated and often are attributed to in utero infections, premature birth, or brain injury to the baby near or during delivery, usually from a lack of oxygen. But many young children diagnosed with cerebral palsy have not experienced such events.

Now, scientists have identified mutations in single genes that can be responsible for at least some cases of cerebral palsy, according to a new study led by researchers at Washington University School of Medicine in St. Louis, the University of Arizona College of Medicine in Phoenix, and Yale University. The study indicates that many of the mutations occur randomly and are not inherited from a child's parents. The research is part of the International Cerebral Palsy Genomics Consortium, a global effort to understand genetic causes of cerebral palsy. The new knowledge could help improve the diagnosis of cerebral palsy and lead to future therapies.

The study appears Sept. 28 in the journal Nature Genetics.

The scientists were able to show that introducing mutations of the same genes into fruit flies caused the insects to have movement difficulties that resemble those common in people with cerebral palsy, a common neurodevelopmental disorder. Cerebral palsy can affect gait, balance and posture. It does not worsen over time but varies widely in severity, with some patients able to walk unaided, while others may use walkers or wheelchairs. According to the Centers for Disease Control and Prevention, it affects about two to four children per 1,000 globally.

"This international collaboration allowed us to conduct the largest genetic analysis of cerebral palsy patients and their parents to date," said Sheng Chih (Peter) Jin, PhD, an assistant professor of genetics at Washington University. "What is exciting about uncovering new genetic causes of cerebral palsy is the potential for the future development of therapies for these patients."

Researchers have suspected that genetics could contribute to an elevated risk of developing cerebral palsy, but until now, individual gene mutations that can cause the disorder had rarely been identified. To better understand genetic contributions to cerebral palsy, the scientists sequenced the entire protein-coding portion of the genomes from 250 participants -- cerebral palsy patients and both parents -- seeking mutations that could play causal roles in cerebral palsy.

In particular, the analysis identified two genes -- FBXO31 and RHOB -- that when mutated are each alone sufficient to cause cerebral palsy. Many of the additional genes carrying mutations were only present in the child with cerebral palsy -- meaning they arose randomly -- while others were inherited from both parents. In general, the researchers found that many of the genes implicated in cerebral palsy have important roles in the wiring of brain circuitry during early stages of development.

"When these mutations were introduced into fruit flies, they recapitulated what we see in human patients," said senior author Michael Kruer, MD, of the University of Arizona College of Medicine in Phoenix. "In a nutshell, the flies couldn't walk. The movement of the flies was greatly diminished, and this was examined in several different ways. We were able to validate that these genes -- nearly two dozen of them were tested in the flies -- play an important role in neuromotor function and in the biology of cerebral palsy."

The researchers also noted that some of the genes newly implicated in cerebral palsy have in past research been associated with autism, intellectual disability and epilepsy.

"For some individuals with cerebral palsy, they only have difficulty with movement and have no other disabilities whatsoever," Kruer said. "But we also see huge overlap among neurodevelopmental disorders. For example, more than half of cerebral palsy patients have some type of learning or intellectual disability. About 40% have epilepsy, and 6% to 8% have autism. So, what we see in the genetics of our new study is reflected in what we have seen in our patients for many years."

In about 12% of the cerebral palsy patients in the study, the causal genetic mutations were acquired by chance, not inherited from either parent. In about 2% of the patients in the study, the mutations were inherited from both parents, neither of whom had cerebral palsy. The remaining 86% of cases could have environmental causes, or contributions from other genetic variations that will require a larger study to reveal, or a combination of genetic mutations and environmental interactions that the researchers are still working to understand.

"We hope this study can help give peace of mind to parents who may have been told over the years that there must have been some kind of problem during the pregnancy or delivery to cause their child to have cerebral palsy," Kruer said. "Our study has implications for genetic counseling for parents who have a child with cerebral palsy, in helping determine the chances of a second child being similarly affected."

Added Jin: "We are continuing to study cerebral palsy patients and their parents, and as our sample size increases, we may begin to be able to measure the contributions from less common recessive and dominant mutations passed down from one or both parents. This study provides clues to where we can begin to design treatments. Our genetic understanding of cerebral palsy is still in its earliest phase -- we've just scratched the surface with this study. We look forward to continuing this research to better understand what causes cerebral palsy so we can find ways to prevent or treat it."

Since first appearing in late 2019, the novel virus, SARS-CoV-2, has had a range of impacts on those it infects. Some people become severely ill with COVID-19, the disease caused by the virus, and require hospitalization, whereas others have mild symptoms or are even asymptomatic.

There are several factors that influence a person's susceptibility to having a severe reaction, such as their age and the existence of other medical conditions. But one's genetics also plays a role, and, over the last few months, research by the COVID-19 Host Genetics Initiative has shown that genetic variants in one region on chromosome 3 impose a larger risk that their carriers will develop a severe form of the disease.

Now, a new study, published in Nature, has revealed that this genetic region is almost identical to that of a 50,000-year old Neanderthal from southern Europe. Further analysis has shown that, through interbreeding, the variants came over to the ancestors of modern humans about 60,000 years ago.

"It is striking that the genetic heritage from Neanderthals has such tragic consequences during the current pandemic," said Professor Svante Pääbo, who leads the Human Evolutionary Genomics Unit at the Okinawa Institute of Science and Technology Graduate University (OIST).

Is severe COVID-19 written in our genes?

Chromosomes are tiny structures that are found in the nucleus of cells and carry an organism's genetic material. They come in pairs with one chromosome in each pair inherited from each parent. Humans have 23 of these pairs. Thus, 46 chromosomes carry the entirety of our DNA - millions upon millions of base pairs. And although the vast majority are the same between people, mutations do occur, and variations persist, at the DNA level.

The research by the COVID-19 Host Genetics Initiative looked at over 3,000 people including both people who were hospitalized with severe COVID-19 and people who were infected by the virus but weren't hospitalized. It identified a region on chromosome 3 that influences whether a person infected with the virus will become severely ill and needs to be hospitalized.

The identified genetic region is very long, spanning 49.4 thousand base pairs, and the variants that impose a higher risk to severe COVID-19 are strongly linked - if a person has one of the variants then they're very likely to have all thirteen of them. Variants like these have previously been found to come from Neanderthals or Denisovans so Professor Pääbo, in collaboration with Professor Hugo Zeberg, first author of the paper and a researcher at the Max Planck Institute for Evolutionary Anthropology and Karolinska Institutet, decided to investigate whether this was the case.

They found that a Neanderthal from southern Europe carried an almost identical genetic region whereas two Neanderthals from southern Siberia and a Denisovan did not.

Next, they questioned whether the variants had come over from Neanderthals or had been inherited by both Neanderthals and present-day people through a common ancestor.

If the variants had come from interbreeding between the two groups of people, then this would have occurred as recently as 50,000 years ago. Whereas, if the variants had come from the last common ancestor, they would have been around in modern humans for about 550,000 years. But random genetic mutations, and recombination between chromosomes, would have also occurred during this time and because the variants between the Neanderthal from southern Europe and present-day people are so similar over such a long stretch of DNA, the researchers showed that it was much more likely that they came from interbreeding.

Professor Pääbo and Professor Zeberg concluded that Neanderthals related to the one from southern Europe contributed this DNA region to present-day people around 60,000 years ago when the two groups met.

Neanderthal variants pose up to three times the risk

Professor Zeberg explained that those who carry these Neanderthal variants have up to three times the risk of requiring mechanical ventilation. "Obviously, factors such as your age and other diseases you may have also affect how severely you are affected by the virus. But among genetic factors, this is the strongest one."

The researchers also found that there are major differences in how common these variants are in different parts of the world. In South Asia about 50% of the population carry them. However, in East Asia they're almost absent.

It is not yet known why the Neanderthal gene region is associated with increased risk of becoming severely ill. "This is something that we and others are now investigating as quickly as possible," said Professor Pääbo.