Culture

Scientists from Far Eastern Federal University (FEFU) together with leading international experts suggest reconsidering the existing treatment protocol for severe spasticity, one of the main complications after spinal cord injury with partial spinal cord disruption. Spasticity aggravates a patient's state and dramatically reduces the prospects of rehabilitation. The new treatment protocol has been run at FEFU Medical Center. A related article was published in the Progress in Brain Research journal.

A team from FEFU developed a protocol helping to learn the eligibility of disabled patients with spinal cord trauma and severe spasticity for the implantation of a spinal cord stimulator or an Intrathecal Baclofen infusion pump. For the first time, these alternative methodologies were compared in two experimental groups.

The team suggest subjecting patients to 3-5 days long preliminary experimental spinal cord stimulation before approving them for surgery. If no response to the impulses of current is registered, a patient needs to be tested for their reaction to Baclofen. This important step helps both the patient and their doctor make an informed decision about the type of surgery.

According to the team, 12 months after the surgery the state of the patients in both groups improved considerably related to the control group. Moreover, patients with implanted Baclofen infusion pumps showed improved motor functions. However, the team still believes spinal cord stimulation (SCS) to be a prospective therapeutic method and suggests reconsidering existing international practices of treating patients with severe spinal cord trauma.

"Over 800 thousand people suffer from concomitant spine injuries with spinal cord transection every year. Only one out of three patients survives this severe condition. The survivors are often 20 to 25 years old. Sadly, they usually stay disabled for the rest of their lives. 80% of the patients develop spastic syndrome that dramatically reduces the prospects of rehabilitation and causes severe complications. Intrathecal Baclofen Therapy (IBT) is the most popular type of treatment for these patients. A pump implanted into a patient's body delivers Baclofen directly to the spinal cord thus reducing the muscle tone. However, this method is associated with many risks and complications, and more importantly, it makes a patient forever dependent on Baclofen treatment and deprives them of any hope of improvement," explained Igor Bryukhovetskiy, the Head of the Laboratory of Molecular and Cellular Neurobiology, Department of Fundamental Medicine of the School of Biomedicine at FEFU.

SCS, or electrical neuromodulation of the spinal cord with a small implanted stimulator, is the next step to approach the issues of verticalization and motor rehabilitation of patients after severe spinal trauma. This type of surgery gives paralyzed patients the biggest chances for maximum future rehabilitation.

After the surgery, a stimulator begins to send signals to electrodes implanted in the spinal cord which helps activate the neuronal circuits below the injured area. The circuits regain their ability to receive commands from the brain and to activate the neurons that move the leg muscles.

"Statistically, complete spinal cord neurotmesis or disruption happens quite rarely, while partial allows for a certain degree of recovery. In the first and second years of treatment, the main methods are systematic neuroprotection and regenerative therapy, specifically, with the use of biomedical cell products. These methods can help considerably improve a patient's neurological functions. However, the therapy of spastic syndrome requires a completely different approach. To solve this issue, we suggest implanting a spinal cord stimulation system that can reduce spasticity by means of suppressing pathological impulses in the spinal cord with electric current," says Artur Biktimirov, a co-author of the work, a neurosurgeon at FEFU Medical Center, and an analyst at the FEFU National Technological Initiative Center.

According to him, patients with complete spinal cord neurotmesis have very limited rehabilitation potential. However, SCS opens new prospects for motor neurorehabilitation even at the stages when other methods fail.

The study is based on the results of the treatment of 66 patients of FEFU Medical Center. The patients were 18 to 62 years of age (36 on average), suffered from spinal cord trauma and severe spasticity, and were paralyzed below the injury level. Based on the outcome of preliminary testing, the first group of 18 patients underwent the implanting of SCS devices, while the second group (15 patients) received Baclofen pumps. The rest of the patients preferred conservative treatment to surgery and consent to form a control group.

The neuromodulation method is being developed by the FEFU School of Biomedicine, and the FEFU National Technological Initiative Center for Neurotechnology, VR, and AR in collaboration with leading Russian and international experts.

Regulators have expressed concerns that audit firms' emphasis on non-audit services (NAS) such as consulting could distract from an audit, and quality does suffer in certain cases, according to new research from the University of Notre Dame.

"The distraction effect of non-audit services on audit quality" is forthcoming in the Journal of Accounting and Economics from Erik Beardsley and Andrew Imdieke, assistant professors of accountancy at Notre Dame's Mendoza College of Business, along with Thomas Omer at the University of Nebraska-Lincoln.

Prior research has examined individual clients and whether they hire their auditor for other services. This study is the first to directly examine the "distraction" effect when the audit office places an overall emphasis on non-audit services, not just to a specific client.

"We find that even clients who do not purchase significant consulting services receive lower audit quality from offices that provide high consulting services to other clients," Beardsley explained. "This points to a broader concern of having a business model that includes both audit and consulting services. Too great a focus on consulting relative to auditing can harm audit quality, even if a particular client does not purchase consulting themselves."

The team examined financial statement restatement rates for clients of audit offices from 2005 to 2015. Each firm they examined had data from a varying number of years, for a total of 29,502 observations in the dataset.

When financial statements are restated because o a material error, this means the audit team missed the error in the initial issuance, indicating lower audit quality. The team considered the extent of focus on NAS/consulting at the audit office level using an aggregated measure of total non-audit fees paid by audit clients.

"We provide evidence on what level of non-audit services leads to a reduction in audit quality," Imdieke said. "Our results suggest a reduction occurs when an audit office receives approximately one quarter of its fees from audit clients in the form of non-audit fees. This provides a benchmark for regulators and practitioners concerned about the point at which an office's percentage of fees could negatively affect audit quality."

The level is significant for regulators including the Public Company Accounting Oversight Board and the SEC, which are concerned about the effects of too much emphasis on non-audit services.

"Our study provides evidence that their concerns are warranted," Beardsley said, "and should be important to consider for audit firms, audit committees and regulators as they consider the impact of these types of services on audit quality."

Humans, followed by ferrets and to a lesser extent cats, civets and dogs are the most susceptible animals to SARS-CoV-2 infection, according to an analysis of ten different species carried out by researchers at the Centre for Genomic Regulation (CRG), based in Barcelona.

The findings, published in PLOS Computational Biology, found that ducks, rats, mice, pigs and chickens had lower or no susceptibility to infection compared to humans.

"Knowing which animals are susceptible to SARS-CoV-2 helps us prevent building up animal reservoirs from which the coronavirus can re-emerge at a later date," says Luis Serrano, ICREA Research Professor, Director of the CRG and senior author of the study. "Our findings offer a clue for why minks - which are closely related to the ferret - are being infected by the disease, which is probably made worse by their packed living conditions and close contact with human workers."

"Though we also find a potential susceptibility to infection by cats, they don't co-exist with humans in the same conditions as other animals, which may explain why so far there are no known cases of people being infected by their pets," adds Dr. Serrano.

Ten species were studied in this paper. Five species - humans, cats, ferrets, civets, and dogs - have had documented cases of infection by SARS-CoV-2. There are no reports of infection in the other five species - mice, rats, pigs, chickens and ducks.

The researchers used computer modelling to test how the coronavirus uses its spike proteins, which protrude from the surface of the virus, to infiltrate the cells of different animals. The main point of entry on a cell's surface is the ACE2 receptor, which binds with the spike protein through a lock-and-key mechanism. There are many different variants of ACE2 within human populations and across different species.

Variants of the ACE2 receptor in humans followed by ferrets, cats, dogs and civets have the highest binding affinities to the viral spike protein, while mice, rats, chicken and ducks have poor binding energy.

However, binding affinity is not enough on its own to gage a cell's susceptibility to infection. The researchers also tested the different species' 'codon adaptation index' - which is how efficient the coronavirus is at commandeering a cell's machinery once it has entered. The more efficient the process, the better the coronavirus can create the proteins it needs to replicate.

Humans, chickens and ducks have the highest codon adaptation index, while the other species are worse adapted.

Considering both binding affinity and the codon adaptation index, the researchers conclude that humans, followed by ferrets, cats, civets and dogs are the most susceptible animals to infection by coronavirus.

They also found that different human variants of ACE2 showed differences in stability and binding to the spike protein, a sensitivity that may underlie why some people suffer from severe COVID-19 symptoms.

"We have identified mutations on the S-protein that dramatically reduces the capacity of SARS-CoV-2 to enter into the cell, protecting the host from catching Covid-19," says Javier Delgado, researcher at the CRG and first author of the study. "We are now engineering mini-proteins from the human ACE2 protein to 'distract' the attention of the virus from entering cells and block an infection. Should new mutations of the viral spike protein arise, we could engineer new variants to block them."

Understanding SARS-CoV-2 infectivity across different species can better inform public health measures, helping reduce human contact with other susceptible animals and avoiding the potential prolongment of the COVID-19 pandemic.

A population-based study revealed reasons behind elevated suicide risk, attempted suicides, and other self-harm, which require special health care, among adolescents and young adults with autism spectrum disorders. Comorbid disorders, especially non-affective psychoses and affective and anxiety disorders, explained the risk.

A new study conducted at the University of Turku showed that the autistic children and youth did not have an elevated risk for accidental death. The higher risk for the premature mortality was associated with natural causes. In those cases, the risk was relatively highest among females and among subjects with intellectual disability.

- This observation is in the line with earlier studies. The result is probably connected to the fact that autistic females have a higher risk for intellectual disability and, for example, to epilepsy than males, says Postdoctoral Researcher Elina Jokiranta-Olkoniemi from the Department of Child Psychiatry of the University of Turku, Finland.

The results were the same when other factors, such as the mother's socio-economic status or the psychiatric disorders among the family members, were taken into consideration.

Core symptoms of autism make it more difficult to receive help for other psychiatric symptoms

The risk of self-harm in autistic adolescents and young adults is approximately double compared to their peers. Based to the results, it is important that public health care is able to identify their psychiatric symptoms as early as possible and offer efficient care.

- The challenge is that the core symptoms of autism, in other words, the difficulties of social intercourse and communication, can make it more difficult to search for help and thus it is difficult to identify the psychiatric disorders and provide efficient care, Jokiranta-Olkoniemi says.

New York, NY--December 10, 2020--Cost information, when paired with information about clinical treatment options, greatly enhances the value of shared decision making, reported a FAIR Health brief released today. This was among the lessons learned from a FAIR Health initiative presenting patient decision aids for shared decision making in palliative care scenarios, as described in the brief Cost Information Enhances Shared Decision Making: Lessons from FAIR Health's Shared Decision-Making Initiative.

Shared decision making means the discussion between patients/caregivers and healthcare providers regarding various treatment options, guided by evidence-based strategies and patient decision aids. Shared decision making shows promise for reducing unnecessary healthcare spending and costs, and for improving decision making without adverse effects on clinical outcomes. But in the past, the utility of shared decision-making tools, or decision aids, has been limited by the absence of cost data to complement the clinical information.

As part of a pilot generously funded by The New York Community Trust, FAIR Health launched a new shared decision-making feature with cost information in March 2020. The feature combines cost data from FAIR Health with decision aids for three palliative care scenarios:

Kidney dialysis for patients with kidney failure (whether to continue or stop);

Nutrition options when swallowing is difficult; and

Breathing assistance (whether to continue or stop).

Following the successful implementation of this initiative, FAIR Health compiled its findings from the program in a brief so that a range of stakeholders--clinicians, payors, policy makers and the like--can use these learnings in future shared decision-making initiatives. Among the lessons learned were:

Conversations surrounding cost in palliative care are part of decision making;

Shared decision-making tools are useful and valuable for providers and patients alike;

There is an appetite for additional shared decision-making tools for other medical conditions;

Provider acceptance of these tools is a critical pathway for promoting shared decision making;

There is a need to improve awareness of shared decision making and patient decision aids among providers; and

Palliative care conversations require special sensitivity.

As noted, the program findings confirm the utility of cost information in shared decision making. Notably, conversations about clinical treatment options and costs present an opportunity to empower healthcare consumers and patients to make critical healthcare decisions with their clinicians that not only affect their health but their finances.

FAIR Health collaborated with organizations and professionals, such as Dr. Glyn Elwyn, BA, MD, MSc, PhD, professor at the Geisel School of Medicine at Dartmouth College, and Dr. Diane Meier, Director of the Center to Advance Palliative Care, to create, evaluate and promote awareness of this resource.

The findings from this initiative are being used to inform FAIR Health's currently active project, generously funded by the Fan Fox and Leslie R. Samuels Foundation, to create a companion educational site for healthcare providers. This new initiative contemplates the development and dissemination of a provider-facing, online educational portal that will promote the use of the shared decision-making tools to New York City-based providers serving older adults with serious illnesses. FAIR Health will launch the new portal in March 2021.

FAIR Health President Robin Gelburd said, "Based on the insights FAIR Health collected, we observed that providers and consumers alike deemed the shared decision-making tools useful and valuable to their conversations in palliative care scenarios. We hope to expand our efforts in shared decision making to other preference-sensitive conditions through future collaborations."

Diane E. Meier, MD, Director of the Center to Advance Palliative Care, Icahn School of Medicine at Mount Sinai, stated: "Having witnessed the need for clear and accurate information when making critical health decisions during chronic and serious illness, I am heartened by FAIR Health's effort to promote shared decision making for patients and caregivers when they most need clarity and guidance."

Owners of a dog with diabetes are more likely to develop type 2 diabetes than owners of a dog without diabetes. No shared risk of diabetes could be detected for cat owners and their cats. These novel findings, from a register-based study conducted at Uppsala University in collaboration with three other universities, have now been published in The BMJ.

Previous studies have reported a possible association between adiposity in dog owners and their dogs. But could there also be a shared risk of diabetes for pet owners and their dogs and cats? Researchers at Uppsala University, the Swedish University of Agricultural Sciences, Karolinska Institutet and the University of Liverpool have now together investigated this matter in a large cohort study.

Combining a Swedish veterinary insurance register with Swedish population and health registers, the researchers could extract information on pet owners residing in Sweden. More than 175,000 dog owners and nearly 90,000 cat owners and their dogs and cats were included in the study.

The dog and cat owners were all middle-aged or older at the start of the study, and were followed up to six years. The researchers then analysed the incidence of type 2 diabetes in the pet owners and of canine and feline diabetes in the dogs and cats.

The main finding was that compared with owning a dog without diabetes, owning a dog with diabetes was associated with a 38% increased risk of type 2 diabetes. No such shared risk of diabetes could be detected in cat owners and their cats. The elevated risk for dog owners could not be explained by the age, sex, or socioeconomic circumstances of the owners, or by the age, sex, or breed of the dogs.

"Our results indicate that a dog with diabetes in the household might signal an increased risk of the dog owner developing type 2 diabetes as well. We have not had access to information about household lifestyle behaviours, but we think the association might be due to shared physical activity patterns and possibly also shared dietary habits as well as shared risk of adiposity. If shared exercise habits are indeed a key factor, it might further help explain why we don't see any shared diabetes risk in cat owners and their cats," says Beatrice Kennedy, a postdoctoral research fellow in medical epidemiology at Uppsala University, one of the senior authors of the study.

Canine diabetes generally requires lifelong insulin therapy. Diabetes is more commonly diagnosed in older dogs, and in females that have not been spayed (castrated) during their prolonged dioestrus phase. Diabetes in female dogs has also been linked to overweight, and occurs more often in some Swedish hunting dog breeds. The frequency of spaying and relative popularity of different breeds vary across countries, and the shared diabetes risk observed in this study may therefore not be applicable to other parts of the world with different dog ownership practices.

"Humans and dogs have lived together for at least 15,000 years, and continue to share their everyday lives for better or worse. In this unique study, we show that there might be common lifestyle and environmental factors that influence the risk of diabetes in the household, both in the dogs and in their owners," comments Tove Fall, Professor of Molecular Epidemiology at Uppsala University, the other senior author of the study.

SEATTLE (10 December 2020) - As the world watches how UK residents respond to COVID-19 vaccinations, three leading experts on the virus are urging Americans and the US government to be vigilant against anti-vaccination advocates and their "rumors, misinformation, and conspiracy theories in a fractured media universe."

The experts - Dr. Ali Mokdad of the Institute for Health Metrics and Evaluation, Dr. Peter Hotez of the Baylor College of Medicine and the Texas Children's Center for Vaccine Development in Houston, and Dr. Walter Orenstein of Emory University - are calling for a national communications strategy to counter such misleading information. This strategy, they contend, demands "an unprecedented level of communication between federal agencies and the American people."

The commentary, "We have to get it right: Ensuring success," was published today in EClinicalMedicine, an online publication of the international medical journal The Lancet.

"We must recognize the pervasive aspects of anti-vaccine messaging across the internet, including social media and e-commerce platforms," the three experts write. "Anti-vaccination rumors, misinformation, and conspiracy theories swirl in a fractured media universe; their origins are diverse and include dedicated anti-vaccine organizations and political extremist groups."

In addition, they note that "a growing body of scientific literature" demonstrates that COVID-19 disproportionally affects minorities in the US, and that a "plan tailored to meet the challenges of ensuring vaccine access for these communities is imperative."

Other arguments in the commentary include:

The need to monitor the capacity of health care systems to deliver vaccines to everyone by surveying local health departments to assess their vaccine-delivery readiness.

Safety and efficacy of each vaccine must be "paramount." Possible side effects or adverse reactions to vaccinations need to be tracked and monitored.

Orenstein remarked that vaccines represent the best way people can protect themselves against the deadly virus.

"Vaccines do not save lives. Vaccinations save lives," he said. "A vaccine dose that remains in the vial is zero percent effective, no matter the results of the clinical trials."

Mokdad commented that states and the US government must work effectively together on assessing the implementation of the vaccine.

"It is imperative and essential to monitor the uptake of the vaccine," he said. "We have a collective obligation to understand who is taking it, who is not, and address these gaps."

Hotez reiterated one of the commentary's key points: countering opposition to the vaccine.

"We are facing an aggressive anti-vaccine disinformation campaign," he said. "The concept of medical freedom is, quite simply, as fake as it is dangerous."

HOUSTON - (Dec. 10, 2020) - Rice University researchers have discovered a more efficient way for social media companies to keep misinformation from spreading online using probabilistic filters trained with artificial intelligence.

The new approach to scanning social media is outlined in a study presented today at the online-only 2020 Conference on Neural Information Processing Systems (NeurIPS 2020) by Rice computer scientist Anshumali Shrivastava and statistics graduate student Zhenwei Dai. Their method applies machine learning in a smarter way to improve the performance of Bloom filters, a widely used technique devised a half-century ago.

Using test databases of fake news stories and computer viruses, Shrivastava and Dai showed their Adaptive Learned Bloom Filter (Ada-BF) required 50% less memory to achieve the same level of performance as learned Bloom filters.

To explain their filtering approach, Shrivastava and Dai cited some data from Twitter. The social media giant recently revealed that its users added about 500 million tweets a day, and tweets typically appeared online one second after a user hit send.

"Around the time of the election they were getting about 10,000 tweets a second, and with a one-second latency that's about six tweets per millisecond," Shrivastava said. "If you want to apply a filter that reads every tweet and flags the ones with information that's known to be fake, your flagging mechanism cannot be slower than six milliseconds or you will fall behind and never catch up."

If flagged tweets are sent for an additional, manual review, it's also vitally important to have a low false-positive rate. In other words, you need to minimize how many genuine tweets are flagged by mistake.

"If your false-positive rate is as low as 0.1%, even then you are mistakenly flagging 10 tweets per second, or more than 800,000 per day, for manual review," he said. "This is precisely why most of the traditional AI-only approaches are prohibitive for controlling the misinformation."

Shrivastava said Twitter doesn't disclose its methods for filtering tweets, but they are believed to employ a Bloom filter, a low-memory technique invented in 1970 for checking to see if a specific data element, like a piece of computer code, is part of a known set of elements, like a database of known computer viruses. A Bloom filter is guaranteed to find all code that matches the database, but it records some false positives too.

"Let's say you've identified a piece of misinformation, and you want make sure it is not spread in tweets," Shrivastava said. "A Bloom filter allows to you check tweets very quickly, in a millionth of a second or less. If it says a tweet is clean, that it does not match anything in your database of misinformation, that's 100% guaranteed. So there is no chance of OK'ing a tweet with known misinformation. But the Bloom filter will flag harmless tweets a fraction of the time."

Within the past three years, researchers have offered various schemes for using machine learning to augment Bloom filters and improve their efficiency. Language recognition software can be trained to recognize and approve most tweets, reducing the volume that need to be processed with the Bloom filter. Use of machine learning classifiers can lower how much computational overhead is needed to filter data, allowing companies to process more information in less time with the same resources.

"When people use machine learning models today, they waste a lot of useful information that's coming from the machine learning model," Dai said.

The typical approach is to set a tolerance threshold and send everything that falls below that threshold to the Bloom filter. If the confidence threshold is 85%, that means information that the classifier deems safe with an 80% confidence level is receiving the same level of scrutiny as information it is only 10% sure about.

"Even though we cannot completely rely on the machine-learning classifier, it is still giving us valuable information that can reduce the amount of Bloom filter resources," Dai said. "What we've done is apply those resources probabilistically. We give more resources when the classifier is only 10% confident versus slightly less when it is 20% confident and so on. We take the whole spectrum of the classifier and resolve it with the whole spectrum of resources that can be allocated from the Bloom filter."

Shrivastava said Ada-BF's reduced need for memory translates directly to added capacity for real-time filtering systems.

"We need half of the space," he said. "So essentially, we can handle twice as much information with the same resource."

Despite the success of immunotherapy in the treatment of cancers such as lung or melanoma, it is still not effective in breast cancers for being 'cold', with low infiltration of immune cells. Tumours use strategies to evade immune surveillance by reducing the infiltration of cells that could attack them or by attracting immunosuppressive cells. These strategies can contribute to the poor prognosis observed in breast cancer of young women and make them unresponsive to immunotherapy. For this reason, the identification of a therapy that could convert immunologically 'cold' tumours -in which immunotherapy is not effective- into 'warm' tumours would represent an important step to increase the efficiency of immunological therapies for breast cancer, since these are based on the reactivation of immune cells to attack tumour cells.

In an article published today in the journal Nature Communications, the Transformation and Metastasis Group led by Eva Gonzalez-Suarez, first from the Bellvitge Institute for Biomedical Research (IDIBELL) and currently at the Spanish National Cancer Research Center (CNIO), proposes RANK signalling pathway as a key candidate to modulate the immune response in breast tumours. Furthermore, in collaboration with Christos Sotiriou, from the Jules Bordet Institute in Belgium, RANK pathway's immunomodulatory activity has been confirmed in a clinical trial with premenopausal patients with luminal breast cancer, one of the most resistant types to immunotherapy.

The study reports that the inhibition of RANK protein promotes the recruitment of immune cells within the tumor in mouse models and in patients with breast cancer. In addition, tumors appear to be more sensitive to immunotherapy after inhibiting RANK pathway in tumor cells. These results suggest that this protein is playing an essential role in the communication between tumor and immune cells. Furthermore, they point to RANK pathway as a possible escape route of cancer cells against immunotherapy.

The clinical trial led by Christos Sotiriou with cancer patients with premenopausal breast early stage showed that patients tolerate the administration of a monoclonal antibody that inhibits RANK, achieved good results enhancing infiltration of immune cells in tumours and identified biomarkers that could help select patients who would benefit from therapy.

The strength of this work lies in the fact that two independent studies, a clinical trial and preclinical research, conclude that inhibition of RANK signalling enhances antitumor immune response.

González-Suárez indicates that "the monoclonal antibody being tested in this study is used routinely for the treatment of bone diseases such as osteoporosis and bone metastases, but not for cancer treatment. Our results support the use of this antibody in combination with immunotherapy against breast cancer," and adds: "This strategy could turn immunologically cold breast cancers into tumours sensitive to the immune system activity."

Tumour immune surveillance

The immune system, which recognizes foreign microorganisms, viruses and bacteria, and provides a response to destroy these disease-causing agents, plays a similar role in protecting the body against malignancies. Cancer cells express abnormal proteins that can be recognized by immune cells because they act as tags that allow the immune system to find and destroy those cells.

The presence of immune cells within the tumour, the so-called immune infiltration, is associated with a good prognosis. However, tumours have mechanisms that allow them to escape the immune responses that often prevent the development of malignant tumours, which means that immunotherapy is not yet fully effective in the treatment of various types of cancer. Studies like the one now published by IDIBELL and CNIO contribute to improving this promising strategy for cancer treatments.

The study has been funded by the Ministry of Science and Innovation, the National Institute of Health Carlos III, the European Research Agency, the European Regional Development Fund, the La Marató de TV3 Foundation, the National Fund for Scientific Research of Belgium, Televie, the US National Institutes of Health, and Amgen.

Ann Arbor, December 10, 2020 - Quantifying the mitigating impact of social distancing on the spread of COVID-19 is critical for evaluating the efficacy of social restrictions and informing future health policy decisions. While most studies have used government stay-at-home dates in their models, new research finds that individuals actually changed their behavior in reaction to the presence of COVID-19 in their state a median 12 days before a government lockdown. This underestimates the impact social distancing has in controlling the spread of the virus. The research, appearing in the American Journal of Preventive Medicine, published by Elsevier, examines sociodemographic variables as well and finds that individual behavior across certain groups may partially account for the disproportionate impact of COVID-19 on vulnerable communities in the United States.

"To many, social distancing and government stay-at-home orders are interlinked," explained corresponding author Moustafa Abdalla, PhD, Harvard Medical School, Boston, MA, USA. "Historically, however, public health behavior has varied dramatically from government mandates, especially along sociodemographic lines. By using government dates as proxies for individual behavior, we miss the variation in adoption of social distancing practices - which, as we discovered, can partially account for the higher burden of disease observed in vulnerable communities. We shouldn't be too quick to simplify individual or population behavior with government dates."

The investigators used cell phone data from 1,124 counties across 42 states to quantify the time between when COVID-19 infections became prevalent in a state (defined as 10 confirmed cases) and when individuals began to change their behavior, compared with the date of a government stay-at-home order. A systematic review of the literature was used to assess the underestimation of the impact of social distancing on COVID-19 infections when measured by government stay-at-home dates instead of mobility data. A machine-learning model of sociodemographic variables was used to explain the variation in county-level delays in social distancing.

Across all 42 states with stay-at-home orders, individuals began to spend more time at home before the government lockdowns and continued to stay at home after lockdowns were lifted. Individuals began to socially distance a median of five days after COVID-19 became locally prevalent. Overall, people began to socially distance 12 days before state orders to do so. Researchers noted that studies using only government data found a 10.2 percent decrease related to social distancing in the number of daily cases compared with an 18.6 percent reduction using mobility data; government data captured only 55 percent of the true impact of social distancing orders.

The COVID-19 pandemic has highlighted and exacerbated many of the health disparities that exist in America. The investigators looked at 43 sociodemographic variables and found that 23 were significantly associated with a delay in individual social distancing behavior. Counties with less education, larger minority populations, and more non-English speakers were most strongly associated with a delay in social distancing. Investigators hypothesize that the higher case burden and mortality observed among these vulnerable communities may be partly explained by these findings. Reasons underlying the hesitancy to social distance might be related to a distrust of science, lower medical literacy, or the lack of non-English language educational resources, but further research is needed.

The investigators observe that their research demonstrates that decisions to impose or lift social restrictions may be partly based on previous models of social distancing efficacy that have not properly accounted for testing capacity or social mobility predating government interventions. "Future investigation on the effects of social distancing should not solely rely on policy time points, but instead should take into account predated awareness and action," commented Dr. Abdalla.

A planet in an unlikely orbit around a double star 336 light-years away may offer a clue to a mystery much closer to home: a hypothesized, distant body in our solar system dubbed "Planet Nine."

This is the first time that astronomers have been able to measure the motion of a massive Jupiter-like planet that is orbiting very far away from its host stars and visible debris disk. This disk is similar to our Kuiper Belt of small, icy bodies beyond Neptune. In our own solar system, the suspected Planet Nine would also lie far outside of the Kuiper Belt on a similarly strange orbit. Though the search for a Planet Nine continues, this exoplanet discovery is evidence that such oddball orbits are possible.

"This system draws a potentially unique comparison with our solar system," explained the paper's lead author, Meiji Nguyen of the University of California, Berkeley. "It's very widely separated from its host stars on an eccentric and highly misaligned orbit, just like the prediction for Planet Nine. This begs the question of how these planets formed and evolved to end up in their current configuration."

The system where this gas giant resides is only 15 million years old. This suggests that our Planet Nine -- if it does exist -- could have formed very early on in the evolution of our 4.6-billion-year-old solar system.

An Extreme Orbit

The 11-Jupiter-mass exoplanet called HD 106906 b was discovered in 2013 with the Magellan Telescopes at the Las Campanas Observatory in the Atacama Desert of Chile. However, astronomers did not know anything about the planet's orbit. This required something only the Hubble Space Telescope could do: collect very accurate measurements of the vagabond's motion over 14 years with extraordinary precision. The team used data from the Hubble archive that provided evidence for this motion.

The exoplanet resides extremely far from its host pair of bright, young stars -- more than 730 times the distance of Earth from the Sun, or nearly 68 billion miles. This wide separation made it enormously challenging to determine the 15,000-year-long orbit in such a relatively short time span of Hubble observations. The planet is creeping very slowly along its orbit, given the weak gravitational pull of its very distant parent stars.

The Hubble team was surprised to find that the remote world has an extreme orbit that is very misaligned, elongated and external to the debris disk that surrounds the exoplanet's twin host stars. The debris disk itself is very unusual-looking, perhaps due to the gravitational tug of the wayward planet.

How Did It Get There?

So how did the exoplanet arrive at such a distant and strangely inclined orbit? The prevailing theory is that it formed much closer to its stars, about three times the distance that Earth is from the Sun. But drag within the system's gas disk caused the planet's orbit to decay, forcing it to migrate inward toward its stellar pair. The gravitational effects from the whirling twin stars then kicked it out onto an eccentric orbit that almost threw it out of the system and into the void of interstellar space. Then a passing star from outside the system stabilized the exoplanet's orbit and prevented it from leaving its home system.

Using precise distance and motion measurements from the European Space Agency's Gaia survey satellite, candidate passing stars were identified in 2019 by team members Robert De Rosa of the European Southern Observatory in Santiago, Chile, and Paul Kalas of the University of California.

A Messy Disk

In a study published in 2015, Kalas led a team that found circumstantial evidence for the runaway planet's behavior: the system's debris disk is strongly asymmetric, rather than being a circular "pizza pie" distribution of material. One side of the disk is truncated relative to the opposite side, and it is also disturbed vertically rather than being restricted to a narrow plane as seen on the opposite side of the stars.

"The idea is that every time the planet comes to its closest approach to the binary star, it stirs up the material in the disk," explains De Rosa. "So every time the planet comes through, it truncates the disk and pushes it up on one side. This scenario has been tested with simulations of this system with the planet on a similar orbit -- this was before we knew what the orbit of the planet was."

"It's like arriving at the scene of a car crash, and you're trying to reconstruct what happened," explained Kalas. "Is it passing stars that perturbed the planet, then the planet perturbed the disk? Is it the binary in the middle that first perturbed the planet, and then it perturbed the disk? Or did passing stars disturb both the planet and disk at the same time? This is astronomy detective work, gathering the evidence we need to come up with some plausible storylines about what happened here."

A Planet Nine Proxy?

This scenario for HD 106906 b's bizarre orbit is similar in some ways to what may have caused the hypothetical Planet Nine to end up in the outer reaches of our own solar system, well beyond the orbit of the other planets and beyond the Kuiper Belt. Planet Nine could have formed in the inner solar system and been kicked out by interactions with Jupiter. However, Jupiter -- the proverbial 800-pound gorilla in our solar system -- would very likely have flung Planet Nine far beyond Pluto. Passing stars may have stabilized the orbit of the kicked-out planet by pushing the orbit path away from Jupiter and the other planets in the inner solar system.

"It's as if we have a time machine for our own planetary system going back 4.6 billion years to see what may have happened when our young solar system was dynamically active and everything was being jostled around and rearranged," said Kalas.

To date, astronomers only have circumstantial evidence for Planet Nine. They've found a cluster of small celestial bodies beyond Neptune that move in unusual orbits compared with the rest of the solar system. This configuration, some astronomers say, suggests these objects were shepherded together by the gravitational pull of a huge, unseen planet. An alternative theory is that there is not one giant perturbing planet, but instead the imbalance is due to the combined gravitational influence of multiple, much smaller objects. Another theory is that Planet Nine does not exist at all and the clustering of smaller bodies may be just a statistical anomaly.

A Target for the Webb Telescope

Scientists using NASA's upcoming James Webb Space Telescope plan to get data on HD 106906 b to understand the planet in detail. "One question you could ask is: Does the planet have its own debris system around it? Does it capture material every time it goes close to the host stars? And you'd be able to measure that with the thermal infrared data from Webb," said De Rosa. "Also, in terms of helping to understand the orbit, I think Webb would be useful for helping to confirm our result."

Because Webb is sensitive to smaller, Saturn-mass planets, it may be able to detect other exoplanets that have been ejected from this and other inner planetary systems. "With Webb, we can start to look for planets that are both a little bit older and a little bit fainter," explained Nguyen. The unique sensitivity and imaging capabilities of Webb will open up new possibilities for detecting and studying these unconventional planets and systems.

The environment is polluted by microplastics worldwide. The tiny particles enter food chains, and thereby the digestive systems of animals and humans; moreover, they can be inhaled. Instead of being excreted, small microplastics can be incorporated into the body tissue. A research team at the University of Bayreuth has now discovered that microplastic particles find their way into living cells more easily if they were exposed to natural aquatic environments, i.e. fresh water and seawater. Biomolecules occurring in the water are deposited on the microplastic surfaces, which promote the internalization of the particles into cells. The researchers present their results in "Science Advances".

The interdisciplinary research team led by Prof. Dr. Christian Laforsch (Animal Ecology) and Prof. Dr. Holger Kress (Biological Physics) focused on microplastic particles with a diameter of around three micrometres for the new study. Particles of this size are often found in the environment. To simulate their exposure in the environment, some microplastic particles were placed in fresh water from an artificial pond, while other microplastic particles were placed in salt water from a marine aquarium. Biomolecules were deposited on the surfaces of these particles within two weeks exposure time.

"Spectroscopic examinations indicate that these biomolecules are carbohydrates, amino acids, nucleic acids, and proteins. We are talking about an 'eco-corona' that forms on the microplastic particles in a natural environment," explains Anja Ramsperger M.Sc., first author of the new study and PhD student at the Department of Animal Ecology I and in the Biological Physics group.

The research team has now examined the microplastic particles coated with biomolecules to see how they interact with living cells. For this purpose, cells from an established mouse cell line were used. In order to distinguish whether the particles are actually internalized or only adhere to the exterior of the cells, important components of the cell interior, the actin filaments, were stained. On the resulting microscopic images, the internalized particles could be recognised as "dark holes". "The fluorescent labeling of the actin filaments enabled us to see exactly which particles were internalized by the cells. Based on spectroscopic methods, we verified that these particles were indeed microplastics - or more precisely: polystyrene particles - and not accidental impurities," says Prof. Dr. Holger Kress, Professor of Biological Physics at the University of Bayreuth. The control group in this experiment consisted of microplastic particles that had been incubated in ultra pure water and were therefore not coated with an eco-corona. It turned out that these untreated microplastic particles were only occasionally internalized by the cells.

"Our study supports the assumption that microplastics which were exposed to the natural environment - and are therefore coated with biomolecules - not only pass through the digestive tract when ingested with food, but may also be incorporated into tissue. The coating of biomolecules may act as a kind of Trojan horse that allows plastics to be internalized into living cells. The precise damage that the particles can cause here has not yet been sufficiently investigated. It is also still largely unclear which of the properties of microplastics are actually responsible for any negative effects. These questions represent a central topic for the 'Microplastics' Collaborative Research Centre in Bayreuth. Finding precise answers to these questions is important in order to be able to develop new materials and solutions in this area in the future," says Prof. Dr. Christian Laforsch, spokesperson of the DFG-funded "Microplastics" Collaborative Research Centre at the University of Bayreuth, and Chair of Animal Ecology I.

"The interdisciplinary network in the 'Microplastics' Collaborative Research Centre enables us to examine the complex questions that this topic poses with the necessary diversity of research approaches and perspectives. The need for an interdisciplinary approach is evident in the study now published. Scientists from various scientific disciplines at the University of Bayreuth have contributed to it - from animal ecology, to polymer chemistry, to biological physics," says Laforsch.

A new and less invasive treatment developed by Cancer Research UK researchers is safer than standard major surgery for early-stage rectal cancer, giving patients a better quality of life with fewer life-altering side effects, results from a pilot study show.

Results from the TREC trial show that a combination of local keyhole surgery and radiotherapy, rather than major surgery that removes the whole rectum, prevents debilitating side effects, such as diarrhoea, or the need for a permanent colostomy bag.

Patients reported a better quality of life with the new treatment, with less impact on their family and social life, and felt more positive about their body image and the way their bowels work.

The findings are published in The Lancet Gastroenterology & Hepatology today (Thursday)*, and a clinical trial is now open to eligible patients who wish to receive this new treatment**.

Every year, 11,500 people in the UK are diagnosed with a tumour located in the rectum,*** the last part of the intestine which connects to the anus. Standard treatment is a major operation to remove the whole rectum, even if the cancer is early stage. About 25% of these major surgeries are done on small, early-stage tumours, and while it is effective, the operation can lead to long-term side-effects that seriously impacts quality of life for survivors.

43% of rectal cancers are caught at an early stage (stage 1 and 2) and doctors need better, less invasive treatments for these tumours.

Mr Simon Bach and his team at the University of Birmingham, along with collaborators at the University of Leeds, have developed a new treatment approach called 'organ preservation' for early-stage rectal cancer that uses radiotherapy followed by local keyhole surgery 8-10 weeks later to remove only the part of the rectum affected by cancer.

Mr Simon Bach, lead researcher, says: "We took a lot of inspiration from progress against breast cancer. In the early 90s, most people with breast cancer would have a mastectomy, where the whole breast is removed, as the first part of their treatment. But now, due to awareness campaigns, the breast screening programme and new treatments, mastectomy is much rarer. We wanted to test a similar approach for our rectal cancer patients."

To test whether organ preservation treatment could be a suitable alternative to major surgery for early-stage rectal cancer, 123 patients were enrolled in the TREC trial****.

Doctors gave the new treatment to 61 patients for whom the major surgery would have been considered unsafe.

In addition, 55 patients were randomised to two treatment approaches; 28 received major surgery and 27 received the new organ preserving treatment. 70% (19/27) of these were treated successfully, meaning their tumour was removed while preserving the rest of their rectum and their cancer did not return during the 3- to 5-year follow-up period. People who received the new treatment also reported fewer side-effects***** than people who had major surgery.

The analysis of patient-reported quality of life for 3 years after treatment, by Cancer Research UK clinical trial fellow Dr Alexandra Gilbert, found that people who received the new treatment fared better. They reported less diarrhoea, less embarrassment about their bowel functions, felt more satisfied with their body image, and felt like their treatment interfered less with their family life and social life compared with those who received major surgery.

Similar results were also seen in the 61 patients for whom the standard surgery would have been considered unsafe, showing that the new treatment could be a safe and effective option.

Co-author Dr Alexandra Gilbert, from the University of Leeds and Leeds Teaching Hospitals NHS Trust, said: "When talking about cancer treatment, the focus is rarely on how severe the effects can be for patients. But we studied this in detail and found that our organ preservation approach made a significant difference to people's quality of life. One of the most striking benefits was avoiding the need for a stoma bag, which we know is really important to our patients."

Mr Simon Bach and his team are now running an international, larger-scale version of their study, called STAR TREC******, across the UK, Netherlands and Denmark. The trial will help decide whether the new treatment should become the new standard treatment for early rectal cancer. This follow-up trial is currently open for recruitment, and importantly, patients may decide if they prefer to receive organ preservation.

The researchers are encouraging people who have been diagnosed with an early-stage rectal tumour to discuss their options with their surgeon should they wish to consider joining the ongoing trial.

Michelle Mitchell, chief executive of Cancer Research UK, said: "When people with cancer finish their cancer therapy, it's not the end of the ordeal. The physical and emotional strain from the effects of treatment can last for years afterwards, or even a lifetime.

"Patients are at the heart of what we do, and that's why results from trials like TREC are such good news. If we can find less intensive treatments with fewer side-effects, patients feel stronger and more confident, and they are in a better place to socialise, enjoy time with their friends and family, and live life to the fullest."

Martin Ledwick, Cancer Research UK's head information nurse, said: "This new treatment could be life-changing for people diagnosed with early-stage cancer. Diagnosing bowel cancer earlier means treatments are far more likely to work, so we encourage eligible people to consider taking part in bowel cancer screening when they receive their testing kit, and for anyone who notices any changes to their body to tell their GP about it."

Researchers at the University of Maryland, Baltimore County (UMBC) have developed a method of generating high-quality chest X-ray images that can be used to diagnose COVID-19 more accurately than current methods. The research team, led by Sumeet Menon, a Ph.D. student in computer science at UMBC, will publish its findings in the proceedings of the IEEE Big Data 2020 Conference to be held virtually in December.

"The availability of data is one of the most important aspects of machine learning and our research has taken an incremental theoretical step towards generating data using the MTT-GAN," explains Menon.

The need for rapid and accurate COVID-19 testing is high, including testing that can determine if COVID-19 is impacting a patient's respiratory system. Many clinicians use x-ray technology to classify images of possible cases of COVID-19, but the limited data available makes it more challenging to classify those images accurately.

Menon and his collaborators developed their tool as an extension of generative adversarial networks (GANs)--machine learning frameworks that can quickly generate new data based on statistics from a training set. The team's more advanced method uses what they call Mean Teacher + Transfer Generative Adversarial Networks (MTT-GAN). The MTT-GANs, explains Menon, are superior to GANs because the images they generate are much more similar to authentic images generated by x-ray machines.

The MTT-GAN classification system has the potential to help improve the accuracy of COVID-19 classifiers, making it an important diagnostic tool physicians who are still working to understand the range of ways this complex disease presents in patients. "This paper mainly focuses on generating more COVID-19 x-rays using the MTT-GAN, which could be widely used to train machine learning models and could have many applications, including classification of CT-scans and segmentation."

Astronomers are still searching for a hypothetical "Planet Nine" in the distant reaches of our solar system, but an exoplanet 336 light years from Earth is looking more and more like the Planet Nine of its star system .

Planet Nine, potentially 10 times the size of Earth and orbiting far beyond Neptune in a highly eccentric orbit about the sun, was proposed in 2012 to explain perturbations in the orbits of dwarf planets just beyond Neptune's orbit, so-called detached Kuiper Belt objects. It has yet to be found, if it exists.

A similarly weird extrasolar planet was discovered far from the star HD 106906 in 2013, the only such wide-separation planet known. While much heavier than the predicted mass of Planet Nine -- perhaps 11 times the mass of Jupiter, or 3,500 times the mass of Earth -- it, too, was sitting in a very unexpected location, far above the dust plane of the planetary system and tilted at an angle of about 21 degrees.

The big question, until now, has been whether the planet, called HD 106906 b, is in an orbit perpetually bound to the binary star -- which is a mere 15 million years old compared to the 4.5 billion-year age of our sun -- or whether it's on its way out of the planetary system, never to return.

In a paper appearing Dec. 10 in the Astronomical Journal, astronomers finally answer that question. By precisely tracking the planet's position over 14 years, they determined that it is likely bound to the star in a 15,000-year, highly eccentric orbit, making it a distant cousin of Planet Nine.

If it is in a highly eccentric orbit around the binary, "This raises the question of how did these planets get out there to such large separations," said Meiji Nguyen, a recent UC Berkeley graduate and first author of the paper. "Were they scattered from the inner solar system? Or, did they form out there?"

According to senior author Paul Kalas, University of California, Berkeley, adjunct professor of astronomy, the resemblance to the orbit of the proposed Planet Nine shows that such distant planets can really exist, and that they may form within the first tens of millions of years of a star's life. And based on the team's other recent discoveries about HD 106906, the planet seems to favor a scenario where passing stars also play a role.

"Something happens very early that starts kicking planets and comets outward, and then you have passing stars that stabilize their orbits," he said. "We are slowly accumulating the evidence needed to understand the diversity of extrasolar planets and how that relates to the puzzling aspects of our own solar system."

A young, dusty star with a weird planet

HD 106906 is a binary star system located in the direction of the constellation Crux. Astronomers have studied it extensively for the past 15 years because of its prominent disk of dust, which could be birthing planets. Our solar system may have looked like HD 106906 about 4.5 billion years ago as the planets formed in the swirling disk of debris left over from the formation of the sun.

Surprisingly, images of the star taken in 2013 by the Magellan Telescopes in Chile revealed a planet glowing from its own internal heat and sitting at an unusually large distance from the binary: 737 times farther from the binary than Earth is from the sun (737 astronomical units, or AU). That's 25 times farther from the star than Neptune is from the sun.

Kalas, who searches for planets and dust disks around young stars, co-led a team that used the Gemini Planet Imager on the Gemini South Telescope to obtain the first images of the star's debris disk. In 2015, these observations provided evidence that led theorists to propose that the planet formed close to the binary star and was kicked out because of gravitational interactions with the binary. The evidence: The stars' outer dust disk and inner comet belt are lopsided, suggesting that something -- the planet -- perturbed their symmetry.

"The idea is that every time the planet comes to its closest approach to the binary star, it stirs up the material in the disk," said team member Robert De Rosa of the European Southern Observatory in Santiago, Chile, who is a former UC Berkeley postdoctoral fellow. "So, every time the planet comes through, it truncates the disk and pushes it up on one side. This scenario has been tested with simulations of this system with the planet on a similar orbit -- this was before we knew what the orbit of the planet was."

The problem, as pointed out by those simulating such planet interactions, is that a planet would normally be kicked out of the system entirely, becoming a rogue planet. Some other interaction, perhaps with a passing star, would be necessary to stabilize the orbit of an eccentric planet like HD 106906 b.

A similar scenario has been proposed for the formation of Planet Nine: that its interaction with our giant planets early in our solar system's history kicked it out of the inner solar system, after which passing stars in our local cluster stabilized its orbit.

Kalas went looking for such a fly-by star for HD 106906 b, and last year he and De Rosa, then at Stanford University, reported finding several nearby stars that would have zipped by the planetary system 3 million years earlier, perhaps providing the nudge needed to stabilize the planet's orbit.

Now, with precise measurements of the planet's orbit between 2004 and 2018, Nguyen, de Rosa and Kalas present evidence that the planet is most likely in a stable, but very elliptical, orbit around its binary star.

"Though it's only been 14 years of observations, we were still able to, surprisingly, get a constraint on the orbit for the first time, confirming our suspicion that it was very misaligned and also that the planet is on an approximately 15,000-year orbit." Nguyen said. "The fact that our results are consistent with predictions is, I think, a strong piece of evidence that this planet is, indeed, bound. In the future, a radial velocity measurement is needed to confirm our findings."

The science team's orbital measurements came from comparing astrometric data from the European Space Agency's Gaia observatory, which accurately maps the positions of billions of stars, and images from the Hubble Space Telescope. Because Hubble must obscure the glare from the binary star to see the dimmer debris disk, astronomers were unable to determine the exact position of the star relative to HD 106906 b. Gaia data allowed the team to determine the binary's position more precisely, and thus chart the movement of the planet relative to the binary between 2004 and 2018, less than one-thousandth of its orbital period.

"We can harness the extremely precise astrometry from Gaia to infer where the primary star should be in our Hubble images, and then measuring the position of the companion is rather trivial," Nguyen said.

In addition to confirming the planet's 15,000-year orbit, the team found that the orbit is actually tilted much more severely to the plane of the disk: between 36 and 44 degrees. At its closest approach to the binary, its elliptical orbit would take it no closer than about 500 AU from the stars, implying that it has no effect on inner planets also suspected to be part of the system. That is also the case with Planet Nine, which has no observed effect on any of the sun's eight planets.

"What I really think makes HD 106906 unique is that it is the only exoplanet that we know that is directly imaged, surrounded by a debris disk, misaligned relative to its system and is widely separated," Nguyen said. "This is what makes it the sole candidate we have found thus far whose orbit is analogous to the hypothetical Planet Nine."