Culture

Kanazawa, Japan - Bone infections caused by implants are difficult to treat and usually require a prolonged course of antibiotic treatment. In a new study, researchers from Kanazawa University discovered that implant-related bone infections can be effectively treated with a combinational treatment consisting of antibiotics and antibiotic-laden stem cells.

Bone fractures often require implants for stabilization and effective healing of the broken bone. However, implants can cause serious bone infections, such as osteomyelitis, that can only be managed with a prolonged antibiotic treatment. This in turn bears the risk of contributing to the development of antibiotic-resistant bacteria. While major efforts are currently underway to develop new antibiotics that cover these antibiotic-resistant bacteria, a different path has been to study the antibiotic effects of stem cells. One type is the so-called mesenchymal stem cells that naturally reside in the bone marrow and adipose tissue, among others, and that have been shown to possess antimicrobial properties.

"Adipose-derived stem cells, or ADSCs, have the distinct advantage of being abundant in subcutaneous adipose tissues and can thus be easily harvested," says the corresponding author of the study Tamon Kabata. "The goal of our study was to investigate the therapeutic effects of ADSCs in combination with the antibiotic ciprofloxacin in an animal model of implant-related bone infection."

To achieve their goal, the researchers first focused on the effects of ciprofloxacin on ADSCs and found an efficient, time-dependent loading of ADSCs with the antibiotic in the first 24 hours with no adverse effects of ciprofloxacin on the function or viability of the stem cells. The researchers then tested the antimicrobial activity of the antibiotic-loaded ADSCs in vitro (in a tube) and found that they effectively decreased the growth of the bacterium S. aureus, which is also the main microbe causing bone implant-related infections.

But could this novel approach also mitigate implant-related infection in a living organism? The researchers tested this on rats, who received bone implants using screws coated with S. aureus bacteria. The rats developed osteomyelitis 7 days after surgery. Then, the researchers administered one of the following to the animals: ADSCs loaded with ciprofloxacin, ADSCs alone, ciprofloxacin alone, or no treatment at all. Because osteomyelitis can lead to soft tissue swelling and abscess formation at the site of the infection, the researchers quantified the extent of the disease in the animals and found that only ADSCs loaded with ciprofloxacin presented as an effective treatment. Using the imaging modality micro-computed tomography to visualize the affected bones, the researchers further found that ADSC-loaded ciprofloxacin decreased the appearance of osteolysis, or bone degradation, which is not only important for bone health, but also for the stability of the implant.

"These are striking results that show how ADSCs can efficiently be loaded with antibiotics to exert a strong antimicrobial effect. Our findings suggest a potential novel therapy for implant-associated osteomyelitis, for which conventional treatment with only antibiotics is usually insufficient," says Kabata.

As the level of understanding about climate change has increased, the term "climate security" has been increasingly used in the rapidly growing literature on this subject. Although Japan has officially acknowledged the importance of tackling climate change, discussion of climate security has been almost nonexistent among Japanese governmental officials, politicians, and academics. Our aim was to trace discourses related to climate security in Japan to determine why so little exists in Japan and whether or not such discourse could suggest new areas for consideration to more comprehensively respond to the climate change problem.

Because of different interpretations and uses of the term "climate security" in the existing literature, we first categorized existing approaches to climate security into four types and used this categorization to examine Japan's discourse from these perspectives (Table 1). Two of the approaches, namely "long-term irreversible planetary changes" and "short-term abrupt risks to individuals", had been considered in Japan previously but without specific reference to the term climate security. The other two, "cause of conflict and violence" and "impacts to military and defense organizations", however, had not been used and need to be included in discussions of climate change in Japan.

Some of the topics not discussed in Japan include indirect economic losses of Japanese industries via supply chains, loss of Japan's exclusive economic zone due to sea-level rise, and the potential inflow of refugees resulting from extreme weather patterns outside of Japan.

Breast cancer is one of the most common cancers among women in the U.S. It's also the most costly cancer to treat. Now, Jefferson researchers have shown that although the use of an effective and less expensive treatment is on the rise, some patients, specifically Black women and those without private insurance are offered the beneficial therapy less often. The findings pave the way for reducing healthcare costs and increasing patient satisfaction.

"We have identified patient populations at risk of not receiving a beneficial and more cost-effective therapy," says Dr. Alliric Willis, a surgical oncologist and associate professor of surgery at Sidney Kimmel Medical College (SKMC) - Jefferson Health, who led the study along with his research team from SKMC and the College of Population Health at Thomas Jefferson University.

"This research really illustrates that not all patients are being treated equally," says Dr. Willis, who published the results online September 12, 2020 in the International Journal of Radiation Oncology Biology Physics, also known as the Red Journal.

Standard breast-conserving cancer treatment involves surgery followed by radiation therapy, which helps to lower the risk of cancer recurring in the treated breast. Traditionally, patients receive 25 to 30 daily radiation treatments over five to six weeks. In recent years, however, doctors have begun using an alternative radiation treatment plan known as hypofractionated whole breast radiation (HR).

HR uses a higher radiation dose per treatment than the traditional regimen. The higher dose means patients require about half as many treatment sessions -15 to 16 treatments over three to four weeks - to achieve the same total dose. Compared with traditional radiation therapy, the approach is just as effective at reducing the risk of the cancer returning, more cost-effective and offers patients fewer side effects and better breast restoration outcomes following treatment.

"Despite the fact that both patients and practitioners say they prefer hypofractionated radiation because of its efficacy and better cosmetic outcomes, HR use in the U.S., while increasing, has lagged for particular groups," Dr. Willis says.

To better understand who is at risk of missing out on the valuable therapy, Dr. Willis and colleagues turned to the National Cancer Database. The researchers examined data from nearly 260,000 early-stage breast cancer patients over 40 years old who were diagnosed between 2012 and 2016. All patients studied had received radiation treatment following breast conserving surgery. The researchers looked at demographics, tumor attributes and treatment facility characteristics between patients who received either HR or traditional radiation.

The investigation revealed that HR use increased over the four-year study period, from about a quarter of eligible patients in 2012 to more than two-thirds in 2016. Despite the upward trend, the analysis uncovered marked disparities among those who received HR therapy. Patients who identified as white were most likely to receive HR, whereas HR use was lowest for African Americans, for example.

"When we took all other factors into account, African American women were 15% less likely to be treated with HR than white women," Dr. Willis says. "This demonstrates that even though treatment guidelines do not take race into account, race is a factor in breast cancer treatment."

Socioeconomic status also affected those who received HR therapy. Patients with private insurance were more likely to receive HR than uninsured patients or those on Medicaid, according to the study. In addition, patients who lived in zip codes with the highest income levels were 25% more likely to undergo HR than patients from zip codes in the lowest income category.

Where patients sought care made a difference in their treatment, too. Treatment facilities associated with academic medical centers were twice as likely to use HR as community cancer or integrated network cancer facilities.

"This tells us that there is a need to actively communicate information to healthcare providers about the spectrum of treatment options across all treatment facility types," Dr. Willis says.

Dr. Willis hopes that this research will shine light on treatment inconsistencies and motivate physicians to expand their treatment repertoire.

"Patients should have access to all treatment options no matter their race, socioeconomic background or where they seek care," he says. "Hopefully, our research will help to address gaps in provider education and extend this favorable treatment to all patients."

In many patients with Crohn's disease abdominal fat migrates to the wall of the inflamed small intestines. What prompts the fat tissue to "creep" through the abdomen and wrap around the intestines of many patients with this inflammatory bowel disease (IBD) has been an enduring mystery.

Now, investigators have identified a critical clue. In a study published in the journal CELL this week, researchers from Cedars-Sinai show that the peculiar creeping activity of the fat appears to initially be protective but then ends up doing more harm than good.

"Creeping fat is often a landmark for surgeons performing resections on an IBD patient's bowels because they know when they see it, that's likely where the lesions are located," said Suzanne Devkota, PhD, principal investigator and lead author of the study. "But we don't know whether the presence of the fat is making the disease worse or trying to protect the intestines from something."

Devkota and a team of investigators performed in-depth molecular examinations of small intestine and fat tissue samples from 11 Crohn's patients who had undergone surgery. Adipose tissue - commonly known as fat -- is more than an energy storehouse. It is a dynamic endocrine tissue full of immune cells that appear to be triggered in certain cases of inflammatory bowel disease.

"We found that the adipose tissue is actually responding to bacteria that have migrated out of the patient's damaged intestines and directly into the fat. We believe the 'creeping' migration of the fat around the intestines is intended to try and plug leaks in the diseased organ to prevent the gut bacteria from getting into the bloodstream," Devkota said.

But the response that begins as protective apparently has no "off" switch. If the bacteria remains in the fat it will continue to migrate to a possible source of the gut bug. But the presence of the fat may be contributing to the development of severe intestinal scarring, or fibrosis, which occurs in 40% of Crohn's patients. Surgical removal of parts of the small bowel is the only option for many of them and it comes with life-changing consequences. Patients with ulcerative colitis, the other most common IBD, do not develop creeping fat.

The data led researchers to a specific microbe responsible for prompting the fat to travel to the small intestine and protectively encase the organ, imperiling its function.

"We identified a pathogen found in the digestive system, Clostridium innocuum, as the microbial invader that triggers the fat to creep over to the small bowel. Also, the structure of this particular infectious agent makes it well-suited for a lipid-rich environment," said David Underhill, PhD, co-investigator on the study and chair of Biomedical Sciences and the Janis and William Wetsman Family Chair in Inflammatory Bowel Disease at Cedars-Sinai.

This research could point the way to new therapeutics, Cedars-Sinai experts say.

"Improving the lives of our IBD patients is the goal of our research. We've identified a specific infectious agent that can trigger a process that makes Crohn's worse. This is a critical step toward the development of therapies that target C. innocuum, allowing us to prevent or minimize the damaging effect of creeping fat," said Stephan R. Targan, MD, director of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai.

A study from the University of Pittsburgh School of Medicine and Cedars-Sinai addresses a mystery first raised in March: Why do some people with COVID-19 develop severe inflammation? The research shows how the molecular structure and sequence of the SARS-CoV-2 spike protein-part of the virus that causes COVID-19-could be behind the inflammatory syndrome cropping up in infected patients.

The study, published this week in the Proceedings of the National Academy of Sciences, uses computational modeling to zero in on a part of the SARS-CoV-2 spike protein that may act as a "superantigen," kicking the immune system into overdrive as in toxic shock syndrome-a rare, life-threatening complication of bacterial infections.

Symptoms of a newly identified condition in pediatric COVID-19 patients, known as Multisystem Inflammatory Syndrome in Children (MIS-C), include persistent fever and severe inflammation that can affect a host of bodily systems. While rare, the syndrome can be serious or even fatal.

The first reports of this condition coming out of Europe caught the attention of study co-senior author Moshe Arditi, M.D., director of the Pediatric Infectious Diseases and Immunology Division at Cedars-Sinai and an expert on another pediatric inflammatory disease-Kawasaki disease.

Arditi contacted his long-time collaborator, Ivet Bahar, Ph.D., distinguished professor and John K. Vries Chair of computational and systems biology at Pitt School of Medicine, and the two started searching for features of the SARS-CoV-2 virus that might be responsible for MIS-C.

Bahar and her team created a computer model of the interaction between the SARS-CoV-2 viral spike protein and the receptors on human T cells, the foot soldiers of the immune system. Under normal circumstances, T cells help the body fight off infection, but when these cells are activated in abnormally large quantities, as is the case with superantigens, they produce massive amounts of inflammatory cytokines-small proteins involved in immune system signaling--in what's known as a "cytokine storm."

Using this computer model, the team was able to see that a specific region on the spike protein with superantigenic features interacts with T cells. Then, they compared this region to a bacterial protein that causes toxic shock syndrome and found striking similarities in both sequence and structure. Importantly, the proposed SARS-CoV-2 superantigen showed a high affinity for binding T cell receptors-the first step toward touching off a runaway immune response.

"Everything came one after another, each time a huge surprise. The pieces of the puzzle ended up fitting extremely well," said Bahar, co-senior author on the study.

By finding protein-level similarities between SARS-CoV-2 and the bacterial structure that causes toxic shock syndrome, the researchers said they may have opened up new avenues for treating not only MIS-C patients, but also adults with COVID-19 infection experiencing cytokine storm.

The researchers also collaborated with scientists studying adult COVID-19 patients in Germany and found that those who experienced severe symptoms had a T cell response similar to what is seen in people exposed to superantigens and very different from the T cell response in patients who had only mild symptoms.

"Our research finally begins to unravel the potential mechanisms involved and raises the possibility that therapeutic options for toxic shock syndrome, such as intravenous immunoglobulin and steroids, may be effective for managing and treating MIS-C in children and hyperinflammation in adult coronavirus patients," said Arditi, professor of pediatrics and biomedical sciences at Cedars-Sinai.

Arditi's and Bahar's labs are now using the ideas generated by this study to search for and test antibodies specific to the SARS-CoV-2 superantigen, with the goal of developing therapies that specifically address MIS-C and cytokine storm in COVID-19 patients.

Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection. New research appearing in the journal Nature Immunology describes how different cells in the immune system work together, communicate, and - in the case of cells called neutrophils - bring about their own death to help fight off infections. The findings could have important implications for the development of vaccines and anti-viral therapies.

"The immune system consists of several different types of cells, all acting in coordination," said Minsoo Kim, Ph.D., a professor of Microbiology and Immunology at the University of Rochester Medical Center (URMC) and senior author of the study. "These findings show that cells called neutrophils play an important altruistic role that benefits other immune cells by providing key resources for their survival and, in the process, enhancing the body's immune response against a virus."

Neutrophils are a key component of the innate immune system, the part of the body's defenses that is always switched on and alert for bacterial and viral invaders. The vast majority of white cells circulating in blood are neutrophils and, as a result, these cells are the first on the scene to respond to an infection.

However, neutrophils are not fully equipped to eliminate a viral threat by themselves. Instead, when the respiratory tract is infected with a virus like influenza or COVID-19, a large number of neutrophils rush to the infection site and release chemical signals. This triggers the production of specialized T cells, which are part of the body's adaptive immune system, which is activated to produce a more direct response to specific infections. Once mobilized in sufficient quantities, a process that typically takes several days, these T cells target and ultimately destroy the infected cells.

The new study, which was conducted in mice infected with the flu virus, shows that in addition to jump-starting the adaptive immune response, neutrophils have one more important mission that requires that they sacrifice themselves. As T cells arrive at the infection site, the neutrophils initiate a process called apoptosis, or controlled death, which releases large quantities of a molecule called epidermal growth factor (EGF). EGF provides T cells with the extra boost in energy necessary to finish the job.

"This study represents an important paradigm shift and shows that the adaptive immune system doesn't generate a successful response without instruction and help from the innate immune system," said Kim. "The findings reveal, for the first time, how different immune cells work together, and even sacrifice themselves, to accomplish the same goal of protecting the host from the viral infection."

Kim and his colleagues point out that this new understanding of how the immune system functions opens the door to potential new methods to intervene and optimize the collaboration between different immune cells during viral infection. These efforts could ultimately lead to more effective vaccines and anti-viral therapies for respiratory infections like the flu and coronavirus.

Is it time to reframe the assisted dying debate?

Several articles published by The BMJ today explore the debate around assisted dying, in which, subject to safeguards, terminally ill people who are near to death, suffering, and of sound mind, could ask for drugs that they would take to end their lives.

The views expressed are the authors' own and do not reflect the position of any organisation that they are associated with.

Lucy Thomas is a consultant in public health who also works closely with patients with life-limiting illnesses and their families. This experience has led her to question why assisted dying is framed as a medical solution to a medical problem and to propose radically de-medicalising the debate.

She points to studies showing that physical symptoms are not predictive, or only weakly predictive, of the desire to hasten death, whereas depression, hopelessness, and perception of being a burden are the strongest predictors.

She argues that responding to a patient's expressed desire to end life in a fundamentally different way depending on whether or not they have a serious illness or disability institutionalises discriminatory attitudes about the relative value of different lives.

She states that "with medical criteria for what constitutes an acceptable reason for ending life, and with doctors as the arbiters and administrators, medically-assisted dying extends medical authority rather than enhancing patient autonomy, with deeply damaging unintended consequences".

So what happens if we challenge this profoundly medicalised perspective, she asks?

She believes that moving outside the medical frame "brings the fundamental ethical and practical dilemmas into focus, facilitating serious discussion about how society should respond to those with mental capacity and a consistent desire to end life prematurely."

Discussions should include philosophical issues such as what constitutes a rational decision to end one's life, as well as more practical questions such as how could we judge whether an individual's desire to end life is a response to circumstances that should be challenged rather than accepted, how could we predict that someone's desire to end life could never be reversed and, if society were to legalise assistance to end life, who would be best placed to provide it?

As with any issue as complex as this, there are no easy answers or simple solutions, concludes Thomas. "Acknowledging this profound complexity may be the first step towards a more constructive debate."

In a second article, Paul Cosford, Emeritus Medical Director at Public Health England explains how incurable lung cancer has prompted him to consider again his personal views on assisted dying.

"I never wanted to be a supporter of changing the law in favour of assisted dying," he writes. "I have always thought that the law is too blunt an instrument to deal well with the complexities of such difficult moral and ethical issues."

He points to the dangers - that assisted dying becomes an expectation, not just an option in certain clearly defined circumstances, and that the lives of people who are seriously ill, who live with disability, or are just different from the norm might be devalued.

These are genuine concerns, he says, but he is convinced that it is time to look at this again. "We need to set aside entrenched positions on each side of the debate and look openly at the problems faced by people at the end of their lives," he writes.

"We need to understand why rational, law abiding people sometimes feel compelled to travel to Switzerland for such care, often not telling their families why they are going. And we need to understand why their loved ones are sometimes prosecuted afterwards for helping them."

"Surely this tells us that our current arrangements are inhumane," he concludes. "I, among others, would be happy to help with such a review."

More open-minded and constructive conversations about end-of-life choice is also something that general practitioner Dr Zoe Norris calls for in a linked opinion article.

She acknowledges that doctors have expertise to offer on this important topic, but says "we must ensure the full breadth of opinion is represented, and we should not allow our contributions to the debate to drown out others' especially not those of our patients."

Regardless of our own personal views, "we cannot ignore the voices of those who have witnessed first-hand the horrific things that can happen when we deny people choice and control over their death," she writes. "I believe as doctors it is our duty to listen to them."

"The BMJ supports the legalisation of assisted dying," says Dr Fiona Godlee, Editor in chief. "The great majority of the British public are in favour and there is now good evidence that it works well in other parts of the world, as a continuation of care for patients who request it and are in sound mind.

"We believe that this should be a decision for Society and Parliament, and that medical organisations should adopt at least a neutral position to allow an open and informed public debate."

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."