Culture

COLUMBIA, Mo. - Kerry Karaffa is the first MU Counseling Center psychologist to be embedded specifically within the University of Missouri College of Veterinary Medicine, where he provides tailored counseling services for professional students training to become veterinarians. He is also aware that veterinarians are at increased risk for mental health concerns and suicidality compared to the general public due to the stressful demands of the job.

To help universities better serve students dealing with high levels of stress and anxiety, Karaffa conducted a research study in which he developed and distributed a survey to other counselors specifically embedded in veterinary medical programs at universities throughout the country. He hoped to better understand the benefits they provide to their students and create a blueprint for practicing counselors and college administrators considering embedded counseling services in specific programs or colleges on campus. He concluded that embedded counseling services offer a convenient way to increase accessibility to mental health services for students with demanding schedules and made several suggestions for developing and sustaining these services.

"The benefit of being embedded specifically within the MU College of Veterinary Medicine is that I have a greater understanding of the challenges veterinary medical students have, and I am better prepared to tailor services to meet the needs of the students I work with," Karaffa said. "Veterinary medical students may work very long hours in their courses and clinical training, so the fact that my office is located just down the hall from them means they don't have to go all the way across campus to the Counseling Center if their schedule doesn't allow that flexibility."

Karaffa added that as more universities start to consider embedding counselors in specific programs or colleges on campus, several factors should be considered. These include logistical factors such as office space and information technology resources, ethical and practice challenges, as well as the need to hire licensed, well-qualified counselors. In addition, providing the embedded counselors with mentorship and professional development support can ensure a smoother transition.

"While this particular study focuses on counselors embedded within colleges of veterinary medicine, I also want to help counseling center directors and university administrators who are truly just trying their best to serve their students in a variety of ways," Karaffa said. "Medical schools and law schools are other areas where graduate and professional students are often under a lot of stress, so those could be areas where embedded counseling services could offer tremendous benefits to students going forward."

In addition to improving mental health on college campuses, Karaffa believes improving accessibility to counseling services will benefit students even after they graduate from school and enter their various professions in society.

"People who are psychologically healthy tend to be happier with their jobs and do better work," Karaffa said. "They also tend to have happier relationships, so early intervention and prevention work is always better than waiting until a small problem turns into a big one."

Older people in Japan have an "attitude of gratitude" which keeps them feeling hopeful despite the challenges of aging, a new study says.

Feeling thankful and grateful for the care and support they have had during their life helps pensioners in the country to be more optimistic, even when they experienced difficulties and were anxious about getting older, an expert found.

Dr Iza Kavedžija, from the University of Exeter, observed people in their 80s and 90s in the course of long-term ethnographic fieldwork in a merchant neighbourhood in the city of Osaka. Her research is published in the journal Anthropology and Aging.

Dr Kavedžija found many members of the older community cultivated a "quiet hope", even though they had concerns for the future, such as getting dementia like their parents or becoming a burden to their children. They said they believed things would work out "somehow" (nantonaku). They accepted the uncertainty ahead, but remained actively engaged in their wider community. This gave them a sense of security, and offered them some confidence for the future.

Dr Kavedžija said: "As people move through life, through their later years, many experience a sense of loss. But this time for them also offers opportunities to reflect more on life, with a heightened realisation of their interconnections with others. If one habitually invokes the involvement of others and their role in one's life, one is reminded how much other people have helped them, in countless small and more substantive ways. The same events seem different when one focuses on how others have helped."

"An attitude of gratitude was embedded in older peoples' recollections of the past, but also allowed them to think about the present in a hopeful way. A world in which one has received much good will from others is a different place than one in which one has experienced loss, even if the facts of life are the same."

"Gratitude in Japan can be seen to a large extent as a recognition of how much one relies on others as one moves through life. Gratitude highlights feelings of interdependence in the social world."

Many people said they wouldn't be the person they were without others who played a significant part in their life. A phrase they liked to use was arigatai, "I am grateful," and sometimes kansha, "gratitude". This gratitude might exist for having been able to lead a full life, for having had a good husband who supported the family, for having understanding in-laws, or simply for an opportunity to work.

Dr Kavedžija said: "While people in Japan might hesitate to say they are happy, gratitude is mentioned frequently. Through appreciation, dependence on others is not seen as simply a burden or a potential source of embarrassment, but also as moving and deeply meaningful. Meaningful relationships and encounters with others comprise a valuable foundation for what Japanese people call ikigai, or that which makes life worth living."

Two out of five individuals delayed or missed medical care in the early phase of the pandemic--from March through mid-July 2020--according to a new survey from researchers at the Johns Hopkins Bloomberg School of Public Health.

The survey of 1,337 U.S. adults found that 544, or 41 percent, delayed or missed medical care during the survey period. Among the 1,055 individuals who reported needing medical care, 29 percent (307 respondents), indicated fear of transmission of COVID-19 as the main reason. Seven percent (75 respondents) reported financial concerns as the main reason for delaying or missing care.

The findings were published online in JAMA Network Open on January 21.

"Understanding the reasons individuals forgo care is important in order to design policy and clinical interventions to limit the extent of forgone care," says lead author Kelly Anderson, a doctoral student in the Department of Health Policy and Management at the Bloomberg School. "This is particularly relevant as COVID-19 cases are surging again."

During the initial phase of the COVID-19 pandemic, the U.S. health care system experienced major disruptions including the closures of medical practices, cancellation of elective procedures, and the shift of many health services to telehealth. As a result of the disruptions, many individuals missed or postponed medical care which can lead to increased health complications, cost, and delayed diagnosis.

The survey, part of Johns Hopkins COVID-19 Civic Life and Public Health Survey, was fielded from July 7 to July 22, 2020. The sample was drawn from NORC's Amerispeak Panel, a nationally representative online sample of U.S. households. Respondents were asked whether they missed several types of care, including doses of prescription medications, scheduled preventive care visits, scheduled outpatient medical or mental health visits, elective surgical procedures, or care for new severe physical or mental health issues.

Among the 1,337 survey respondents, 29 percent (387 respondents) reported missing a preventive care visit, 26 percent (343 respondents) reported missing an outpatient general medical appointment, 8 percent (108 respondents) reported missing one or more doses of a prescription medication, 8 percent (105 respondents) reported missing an outpatient mental health appointment, 6 percent (77 respondents) reported missing an elective surgery, and 3 percent (38 respondents) reported not receiving health care for a new severe mental or physical health issue.

Among the 1,055 individuals who reported needing medical care from March to mid-July 2020, more than half, 52 percent (554 respondents) reported missing care. Among those, 58 percent who had a scheduled preventive care appointment missed the appointment and 60 percent (77 respondents) with a scheduled elective surgical procedure forwent the procedure. Approximately half, 51 percent (38 respondents), of respondents with a new severe mental health or physical health issue that started after the start of the pandemic, reported not seeking care for a new health issue.

The survey also found disruptions to prescription medication. Among 725 respondents who reported taking a prescription medication, three times as many Hispanic respondents reported missing prescription medications compared to non-Hispanic, white respondents--30 percent (33 of 109 respondents) compared to 10 percent (50 of 482 respondents). Twenty-two percent of respondents from 18 to 34 reported missing prescription medication (45 of 204 respondents) compared to 6 percent of adults over 65 (10 of 160 respondents) and 16 percent of aged 35-49 (29 of 182 respondents). Twenty-seven percent of respondents in households with incomes less than $35,000 dollars a year reported missing prescription medications compared to 6 percent of respondents in households with higher incomes of at least $75,000 (66 of 244 respondents and 16 of 255 respondents). Thirty-six percent of individuals insured through Medicaid reported a higher frequency of missed prescription medications (41 of 114 respondents), as compared to 10 percent of individuals with commercial insurance (52 of 517 respondents).

Finally, among those who reported needing medical care, respondents who were unemployed reported higher frequencies of any forgone medical care (65 percent versus 50 percent, 121 of 186 respondents and 251 of 503 respondents, respectively), missed doses of medications (39 percent versus 13 percent, 46 of 117 respondents and 46 of 367 respondents, respectively), and missed scheduled appointments (70 percent versus 56 percent, 111 of 159 respondents and 225 of 405 respondents, respectively) as compared to individuals who were employed.

"These COVID-19-related interruptions in needed medical care will likely have longer term consequences beyond the pandemic--including exacerbating health disparities," says Colleen Barry, MPP, PhD, Fred and Julie Soper Professor, chair of the Department of Health Policy and Management at the Bloomberg School, and senior author on the study. "Our study indicates that many people are forgoing medical care for economic reasons, and this suggests that economic stimulus policies such as extension of unemployment benefits could also have important health benefits."

Researchers from the University Hospitals in Zurich and Basel, ETH Zurich, University of Zurich and the pharmaceutical company Roche have set out to improve cancer diagnostics by developing a platform of state-of-the-art molecular biology methods. The "Tumor Profiler" project aims to derive the comprehensive molecular profile of tumours in cancer patients, which has the potential to predict the efficacy of a host of new cancer medications. It will therefore make it possible to offer treating physicians personalised and improved therapy recommendations.

Three years ago, the researchers began a large-scale clinical study involving 240 patients suffering from metastatic skin cancer (melanoma), metastatic ovarian cancer, or acute myeloid leukaemia. The thorough investigation of these patients' tumours provides the researchers with a comprehensive understanding of the cellular composition and biology of each tumour. The researchers recently published details of their study design in an article in the journal Cancer Cell.

Investigating at the single-cell level

What's new about the "Tumor profiler" study is that it harnesses a suite of advanced tumour-testing methods to gain new insights by exploring how these can be combined in a clinically meaningful way. The study ventures far beyond the current use of molecular biology methods practised in leading hospitals. "We've brought together all the cutting-edge technology available at ETH Zurich and the project partners. Working with physicians from Zurich and Basel, we've developed an advancement in oncology, one that serves the patients," says Mitch Levesque, professor at the University Hospital Zurich and one of the article's corresponding authors.

The scope of testing includes the cancer cells' DNA, RNA and proteins. Single-cell level data provides the researchers an understanding of each tumour's cellular diversity, which includes not only cancer cells, but also immune cells. "We examine the entire tumour and its microenvironment," says Andreas Wicki, senior physician at the University Hospital Zurich. Part of the analysis also includes functional tests, in which biopsies of the tumour are treated with drugs in the laboratory to see if the drugs work. Information from medical imaging and other patient data is also taken into account.

Informing treatment decisions

"We end up with vast amounts of data for each patient, which we prepare and analyse using data science methods," says Gunnar Rätsch, professor at ETH Zurich and another corresponding author of the publication. The Tumor Profiler findings are then made available to the treating physicians, who discuss them at the interdisciplinary tumour board sessions. Since in science, detailed molecular tests are referred to with terms with the suffix -omics (genomics, transcriptomics, proteomics), this approach which encompasses very many "omics areas" is called a multi-omics approach.

"We want the Tumor Profiler study to show that the widespread use of advanced profiling methods in oncology is not only possible but offers specific clinical benefits," says Viola Heinzelmann, Head of Gynecological Oncology at the University Hospital Basel, and a senior author of the study. This is why the study also focuses on whether and how molecular analyses may have influenced a physicians' treatment decisions.

In the long-term, the Tumor Profiler approach aims to expand treatment options for patients in terms of personalised medicine. This involves addressing the question of whether certain patients would benefit from medications that do not belong to the standard range of oncological treatments but are approved for other types of cancer.

Data collection for the Tumor Profiler study will end in two months' time, after which the research team will analyze the data and present the results.

LA JOLLA, CA--A big question on people's minds these days: how long does immunity to SARS-CoV-2 last following infection?

Now a research team from La Jolla Institute for Immunology (LJI), The University of Liverpool and the University of Southampton has uncovered an interesting clue. Their new study suggests that people with severe COVID-19 cases may be left with more of the protective "memory" T cells needed to fight reinfection.

"The data from this study suggest people with severe COVID-19 cases may have stronger long-term immunity," says study co-leader LJI Professor Pandurangan Vijayanand, M.D., Ph.D.

The research, published Jan. 21 in Science Immunology, is the first to describe the T cells that fight SARS-CoV-2 in "high resolution" detail.

"This study highlights the enormous variability in how human beings react to a viral challenge," adds co-leader Christian H Ottensmeier, M.D., Ph.D., FRCP, a professor at the University of Liverpool and adjunct professor at LJI.

Since early in the COVID-19 pandemic, scientists at LJI have investigated which antibodies and T cells are important for fighting SARS-CoV-2. As experts in genomics, Vijayanand and Ottensmeier have used sequencing tools to uncover which T cell subsets may control disease severity. In October, the team published the first detailed look at how CD4+ T cells respond to the virus.

For the new study, the researchers used a technique called single-cell transcriptomics analysis to study the expression of individual genes of more than 80,000 CD8+ T cells isolated from both COVID-19 patients and non-exposed donors. CD8+ T cells are the cells responsible for destroying virus-infected host cells. "Memory" CD8+ T cells are also important for protecting the body from reinfection against many viruses.

The team studied CD8+ T cells from 39 COVID-19 patients and 10 subjects who had never been exposed to the virus (their blood samples were given before the pandemic). Of the COVID-19 patients, 17 patients had a milder case that did not require hospitalization, 13 had been hospitalized, and nine had needed additional ICU support.

To the researchers' surprise, they saw weaker CD8+ T cell responses in patients with milder COVID-19 cases. The researchers saw the strongest CD8+ T cell responses in the severely ill patients who required hospitalization or ICU support.

"There is an inverse link between how poorly T cells work and how bad the infection is," says Ottensmeier. "I think that was quite unexpected."

One could expect to see a stronger CD8+ T cell response in the mild cases, since these are the cases where the immune system was equipped to fight off a severe infection--but the study showed the opposite. In fact, CD8+ T cells in the milder cases showed the molecular signs of a phenomenon called T cell "exhaustion." In cases of T cell exhaustion, cells receive so much immune system stimulation during a viral attack that they are less effective in doing their jobs.

While more research is needed, Vijayanand and Ottensmeier think it is worth studying whether T cell exhaustion in the mild COVID-19 cases may hinder a person's ability to build long-term immunity.

"People who have severe disease are likely to end up with a good number of memory cells," says Vijayanand. "People with milder disease have memory cells, but they seem exhausted and dysfunctional--so they might not be effective for long enough."

The new study provides a valuable window into CD8+ T cell responses, but it is limited because it relies on the CD8+ T cells found in blood samples. As a next step, the researchers hope to shed light on how T cells in tissues hit hardest by SARS-CoV-2, such as the lungs, react to the virus. This step will be important because the memory T cells that provide long-term immunity need to live in the tissues.

"This study is very much a first step in understanding the spectrum of immune responses against infectious agents," says Ottensmeier. Going forward, the researchers hope to use single-cell sequencing techniques to look at CD8+ T cells in cancer patients with COVID-19 infection.

"This research highlights the power of these new tools to understand human immunology," says Vijayanand.

It is no secret that over the last few decades, humans have changed nature at an ever-increasing rate. A growing collection of research covers the many ways this is impacting our quality of life, from air quality to nutrition and income. To better understand how which areas are most at risk, scientists have combed through volumes of literature to present global trends in the relationship between human wellbeing and environmental degradation.

Their work, which included Fabrice DeClerck from the Alliance of Bioversity International and CIAT, was summarized in "Global trends in nature's contributions to people", which was recently published in Proceedings of the National Academy of Sciences.

This systematic review builds on the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) Global Assessment Report, which in 2019 provided the most comprehensive assessment yet of nature's decline and biodiversity loss, when it emphasized that 1 million plant and animal species face extinction.

The PNAS review evaluates how biodiversity loss affects human wellbeing. It differentiates between nature's potential contributions, realized contributions, environmental conditions, and impact on quality of life. Material and non-material indicators, including greenhouse gas concentration, pest control and cultural knowledge were used to assess whether trends were worsening, about the same, or improving since 1970. Unsurprisingly, many were shown to be in sharp decline. Particularly in the context of agriculture, the review underscores that we face interrelated risks such as declining crop yields, declining pollinator populations, and reduced soil productivity.

Even increases in areas such as volume of crop commodity production hold a warning, as trends on human health from food diverge depending on variables such as region and socioeconomic context.

This paper represents one step in documenting the importance of nature's contributions to people, which the scientists hope can improve our ability to manage earth systems effectively, equitably, and sustainably.

"Nature contributes to our health and well-being in many ways, and our actions put these benefits at risk," said author Kate Brauman of the University of Minnesota.

WASHINGTON, January 21, 2021 -- Despite cancer being a leading cause of death worldwide, treatment options for many types of cancers remain limited. This is partly due to the in vitro tools used to model cancers, which cannot adequately predict the behavior of a cancer or its sensitivity to drugs.

Further, animal models, like mice, biologically differ from humans in ways that play a critical role in immunotherapy, and results from animal studies do not always translate well to human disease.

These shortcomings point to a clear need for a better, patient-specific model to improve the understanding of cancer cells and their impacts.

Researchers from the University of Wisconsin and the University of California, San Francisco suggest bioengineered microscale organotypic models (BMOMs) can address this need. They discuss the advantages and capabilities of this technique, as well as its challenges, in the journal APL Bioengineering, from AIP Publishing.

Due to their very small size, BMOMs require only a tiny patient-derived biopsy sample to monitor biological processes. This reduces any concern about the translatability of findings, since all the associated models are developed directly from human material. In addition, BMOMs can be integrated with microscopes and miniaturized sensors to watch the response of the cell culture to test treatments in high resolution and real time.

"BMOMs attempt to merge the best of in vivo and in vitro models," said David Beebe, one of the authors. "These models place human cells in a more realistic environment context, where they are more likely to respond to treatment in a way more reflective of the patient response.

"The 3D and multicellular attributes of BMOMs capture more of the myriad and complex cell-cell and cell-matrix interactions that regulate treatment response."

Though promising, these devices have several limitations. They are difficult to fabricate in large quantities, and they require specialized training to use. Beyond these hurdles, BMOMs are also restricted in their capacity to consider human behavioral responses and fall short in modeling the interactions that occur between multiple organs in complex diseases.

With additional research and clinical trials, the authors are optimistic about the applications of BMOMs. Their use with primary cells taken directly from patient tissue can help with patient-specific cancer treatments and drug testing.

WASHINGTON, January 21, 2021 -- Cancer is a major, worldwide challenge, and its impact is projected to escalate due to aging and growth of the population. Researchers recognize that new approaches to diagnose and treat deadly cancers, including identifying new drugs to treat cancer, will be essential to curbing the growing impact of the disease.

While decades of investment in research have resulted in substantial improvements in surviving cancer, a key challenge remains in identifying new drugs that improve outcomes for cancer patients, particularly for cancers when tumors have spread throughout the body.

In APL Bioengineering, by AIP Publishing, researchers suggest a major hurdle to identifying new drugs is the paucity of models -- organisms mimicking human cancers in a lab setting -- for cancer research that accurately represent patient tumors. They provide a perspective on strategies for developing models to inform cancer treatment using models from individual patients and where the field needs to go in terms of research in animal systems and in culture systems.

"In addition to having better models for cancer research, we are trying to evolve patient-derived models to the point where we can have speedy and reliable drug testing on patient specimens to help personalize cancer care," said author Alana Welm. "This is the concept of functional precision oncology."

In functional precision oncology, tumor samples from individual patients are tested for susceptibility to various drugs in the context of a patient-derived xenograft or culture system in order to guide patient therapy during the course of their disease.

The researchers suggest an even more powerful approach to accelerating the pace of cancer research would be to couple patient-derived model development with the plethora of clinical trials being run every day.

If clinical data and models were collated and shared along with drug response information, machine learning could facilitate analysis of this big data to discover complex patterns of drug response or resistance across individuals, which could then be further tested in the patient-derived models.

The researchers envision that patients' tumors may be bioinformatically profiled to identify a complex set of features that can be used to predict response to various therapies and informed by functional drug response data collected from previous studies. The researchers believe this would facilitate selection of more effective drugs earlier in treatment, while preventing administration of toxic drugs that offer no benefit.

These types of data could even be integrated with germline DNA sequence variants that predict aberrant drug metabolism and toxicity for an even more personalized approach to reduce mortality from cancer while simultaneously reducing toxicity as much as possible.

EUGENE, Ore. -- Jan. 21, 2021 -- Developing economies suffer from a paradox: they don't receive investment flows from developed economies because they lack stability and high-quality financial and lawmaking institutions, but they can't develop those institutions without foreign funds.

A study co-authored by Brandon Julio, a professor in the Department of Finance at the University of Oregon's Lundquist College of Business, found that bilateral investment treaties, commonly known as BITs, can help developing economies overcome this paradox, but only as long as those countries can demonstrate a commitment to property and contract rights.

Julio published the research, "A BIT Goes a Long Way: Bilateral Investment Treaties and Cross-border Mergers," in a paper that published online Dec. 11 ahead of print in the Journal of Financial Economics with co-authors Vineet Bhagwat of the George Washington University School of Business and Jonathan Brogaard of the Eccles School of Business at the University of Utah.

"Controlling for year-fixed effects, country-pair fixed effects, and other determinants of cross-border merger and acquisition activity, we find that the probability of a cross-border merger taking place in a country's economy more than doubles, increasing from 1.6 percent before the treaty to 4.5 percent after the treaty is signed," the researchers stated.

The researchers argue that even in an era of globalization with global capital flows continuing to gain velocity, developing economies should not overlook the value of bilateral investment treaties to overcome what is known as the Lucas paradox.

The paradox was named for Nobel Laureate Robert Lucas, a University of Chicago economist who articulated it in his seminal 1990 paper in the journal American Economic Review. It demonstrated that funds do not flow to poorer countries despite the fact that returns to capital are higher in the developing world.

By looking at mergers and acquisitions, Julio and his co-authors set out to assess whether bilateral investment treaties help spur investment in developing economies.

Using data from Securities Data Co.'s database on mergers and acquisitions, the researchers analyzed merger data for all countries between 1980 and 2014. They then correlated that data with 1,057 BITs from 139 countries.

The analysis found that both the number and size, in terms of dollars, of cross-border deals increased after a treaty was signed. BITs also made mergers more likely between asset-rich companies or those in asset-intensive industries, like mining or airlines because they decrease the risk of government expropriation of property.

"The basic idea is to provide clear and enforceable rules to protect foreign investment and reduce country or political risks, which should encourage investment," the researchers noted.

But BITs are no panacea, according to Julio, Bhagwat and Brogaard.

If a country has a bad reputation for upholding property rights, or seems politically unstable, corporations will not attempt to do business there even if a BIT is in place. Similarly, if a country is already deemed low risk, then a BIT makes a deal no more likely. Countries with median-level political risk benefit the most from these agreements, the researchers said.

"While the results do not completely resolve the Lucas paradox, and most cross-border capital remains within the borders of developed countries, the proportion of cross-border deals flowing from the developed to the developing world has increased significantly as more and more countries sign BITs," they concluded.

As bilateral investment treaties are difficult and time consuming to negotiate and are often struck between nations with more mature economies, the findings from the research encourages leaders of developing nations to look to BITs as a faster way to attract foreign investments from companies in Europe, America and Japan.

So long as a country can demonstrate a commitment to property and contract rights, these agreements can be effective and can support both local economies and equities markets, the researchers concluded.

A new study from researchers at MIT uncovers the kinds of infrastructure improvements that would make the biggest difference in increasing the number of electric cars on the road, a key step toward reducing greenhouse gas emissions from transportation.

The researchers found that installing charging stations on residential streets, rather than just in central locations such as shopping malls, could have an outsized benefit. They also found that adding on high-speed charging stations along highways and making supplementary vehicles more easily available to people who need to travel beyond the single-charge range of their electric vehicles could greatly increase the vehicle electrification potential.

The findings are reported today in the journal Nature Energy, in a paper by MIT associate professor of energy studies Jessika Trancik, graduate student Wei Wei, postdoc Sankaran Ramakrishnan, and former doctoral student Zachary Needell SM '15, PhD '18.

The researchers developed a new methodology to identify charging solutions that would conveniently fit into people's daily activities. They used data collected from GPS tracking devices in cars, as well as survey results about people's daily driving habits and needs, including detailed data from the Seattle area and more general data from the U.S. as a whole. Greatly increasing the penetration of electric cars into the personal vehicle fleet is a central feature of climate mitigation policies at local, state, and federal levels, Trancik says. A goal of this study was "to better understand how to make these plans for rapid vehicle electrification a reality," she adds.

In deciding how to prioritize different kinds of improvements in vehicle charging infrastructure, she says, "the approach that we took methodologically was to emphasize building a better understanding of people's detailed energy consuming behavior, throughout the day and year."

To do that, "we examine how different people are moving from location to location throughout the day, and where they are stopping," she says. "And from there we're able to look at when and where they would be able to charge without interrupting their daily travel activities."

The team looked at both regular daily activities and the variations that occur over the course of a year. "The longitudinal view is important for capturing the different kinds of trips that a driver makes over time, so that we can determine the kinds of charging infrastructure needed to support vehicle electrification," Wei says.

While the vast majority of people's daily driving needs can be met by the range provided by existing lower-cost electric cars, as Trancik and her colleagues have reported, there are typically a few times when people need to drive much farther. Or, they may need to make more short trips than usual in a day, with little time to stop and recharge. These "high-energy days," as the researchers call them, when drivers are consuming more than the usual amount of energy for their transportation needs, may only happen a handful of times per year, but they can be the deciding factor in people's decision making about whether to go electric.

Even though battery technology is steadily improving and extending the maximum range of electric cars, that alone will not be enough to meet all drivers' needs and achieve rapid emissions reductions. So, addressing the range issue through infrastructure is essential, Trancik says. The highest-capacity batteries tend to be the most expensive, and are not affordable to many, she points out, so getting infrastructure right is also important from an equity perspective.

Being strategic in placing infrastructure where it can be most convenient and effective -- and making drivers aware of it so they can easily envision where and when they will charge -- could make a huge difference, Trancik says.

"There are various ways to incentivize the expansion of such charging infrastructures," she says. "There's a role for policymakers at the federal level, for example, for incentives to encourage private sector competition in this space, and demonstration sites for testing out, through public-private partnerships, the rapid expansion of the charging infrastructure." State and local governments can also play an important part in driving innovation by businesses, she says, and a number of them have already signaled their support for vehicle electrification.

Providing easy access to alternative transportation for those high-energy days could also play a role, the study found. Vehicle companies may even find it advantageous to provide or partner with convenient rental services to help drive their electric car sales.

In their analysis of driving habits in Seattle, for example, the team found that the impact of either adding highway fast-charging stations or increasing availability of supplementary long-range vehicles for up to four days a year meant that the number of homes that could meet their driving needs with a lower cost electric vehicle increased from 10 percent to 40 percent. This number rose to above 90 percent of households when fast-charging stations, workplace charging, overnight public charging, and up to 10 days of access to supplementary vehicles were all available. Importantly, charging options at residential locations (on or off-street) is key across all of these scenarios.

The study's findings highlight the importance of making overnight charging capabilities available to more people. While those who have their own garages or off-street parking can often already easily charge their cars at home, many people do not have that option and use public parking. "It's really important to provide access -- reliable, predictable access -- to charging for people, wherever they park for longer periods of time near home, often overnight," Trancik says.

That includes locations such as hotels as well as residential neighborhoods, she says. "I think it's so critical to emphasize these high-impact approaches, such as figuring out ways to do that on public streets, rather than haphazardly putting a charger at the grocery store or at the mall or any other public location." Not that those aren't also useful, she says, but public planning should be aiming to expand accessibility to a greater part of the population. Being strategic about infrastructure expansion will continue to be important even as fast chargers fall in cost and new designs begin to allow for more rapid charging, she adds.

The study should help to provide some guidance to policymakers at all levels who are looking for ways to facilitate the reduction of greenhouse gas emissions, since the transportation sector accounts for about a third of those emissions overall. "If you have limited funds, which you typically always do, then it's just really important to prioritize," Trancik says, noting that this study could indicate the areas that could provide the greatest return for those investments. The high-impact charging solutions they identify can be mixed and matched across different cities, towns, and regions, the researchers note in their paper.

The researchers' approach to analyzing high-resolution, real-world driving patterns is "valuable, enabling several opportunities for further research," says Lynette Cheah, an associate professor of engineering systems and design at Singapore University of Technology and Design, who was not associated with this work. "Real-world driving data can not only guide infrastructure and policy planning, but also optimal EV charging management and vehicle purchasing and usage decisions. ... This can provide greater confidence to drivers about the feasibility and operational implications of switching to EVs."

Abnormally hyperactive areas in the brain may help better predict the onset of Alzheimer's disease, according to findings of a research team led by Université de Montreal psychology professor Sylvie Belleville, scientific Director of the Institut universitaire de gériatrie de Montréal research centre.

Hyperactivation could be an early biomarker of Alzheimer's disease, the researchers say in their study published today in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, co-authored by Belleville and Nick Corriveau-Lecavalier, a doctoral student she supervises.

Worried about their memory

In their research, the team found hyperactivation in certain brain areas in people not yet diagnosed with Alzheimer's but who were worried about their memory and who exhibited risk factors for the disease.

The study marks an important milestone in this research area, as the hyperactivation of regions susceptible to the Alzheimer's as shown by functional magnetic resonance imaging (fMRI) was observed in people with no clinical symptoms and before the onset of cognitive impairments detected with standardized tests.

"This study indicates that abnormal activation in these areas may be observed many years before diagnosis," said Belleville.

This finding is crucial to the advancement of knowledge about the disease., she continued.

"Alzheimer's disease is progressive and may emerge in the brain 20 to 30 years before diagnosis. It is therefore very important to pinpoint biomarkers - that is, physical and detectable signs of the disease - and to better understand the initial effects on the brain. Hyperactivation could therefore represent one of the first signs of Alzheimer's disease."

An inverse U-shape

The team observed that, as the disease progresses, neuronal activation follows an inverse U-shape trajectory. Indeed, activation in certain areas of the brain in the early stages of Alzheimer's may significantly increase before the neuronal loss that is caused by the disease leads to a clear decrease in activation.

"This form may characterize the underlying pathological process and help doctors determine the stage of the disease," explained Corriveau-Lecavalier, the study's first author. "When combined with other indicators such as blood work and cognitive tests, this type of neuroimaging investigation could help with possible earlier detection."

For their study, the team used data from the Consortium for the Early Identification of Alzheimer's Disease to study brain activation in groups of individuals at a high risk of developing Alzheimer's disease who had performed a memory task while being scanned with fMRI. One group consisted of 28 individuals who were concerned about their memory but who did not show cognitive impairments on traditional clinical tests. The other group included 26 individuals with mild cognitive impairments.

The researchers found that the individuals in the first group, or those with memory complaints but who did not show objective cognitive impairments, had abnormally high levels of activation in multiple key regions of the brain affected by Alzheimer's disease. Individuals with mild cognitive impairments, who are considered to be at a more advanced stage of the disease, tended to show decreased activation in these brain regions.

A new study of Type 2 diabetes (T2D) in Japanese populations has uncovered a previously uncharacterized genetic variant that puts male carriers at greater risk for the disease, as well as the mechanism by which it does so. The impact of the variant was most pronounced in sedentary men; those with the variant had a 65% greater rate of T2D than sedentary men without it.

Researchers from the University of Southern California, along with colleagues in Japan, led by Professor Noriyuki Fuku of Juntendo University, found higher rates of harmful belly fat and T2D among Japanese men with a specific mitochondrial gene variant. This variant, in the site of the mitochondrial peptide MOTS-c, is found only in East Asian populations and was shown, in human and mice data, to prevent the normal production of MOTS-c, and to diminish the beneficial action the exercise-mimicking peptide usually performs in preventing weight gain and normalizing metabolism. Furthermore, carriers of the deleterious variant were secreting high levels of a bio-inactive form of the peptide in an attempt to compensate for its deficiency.

The findings, published Jan 19 in the journal Aging, also suggest that moderate to vigorous levels of daily physical activity can offset the increased risk posed by the variant allele. Researchers say this underscores the power of gene-environment interactions and highlights the role exercise can play in preventing the disease.

"Our study suggests that individuals with this particular variant can modify their genetic risk by adopting an exercise regime," said co-lead author Su-Jeong Kim, a research assistant professor at the USC Leonard Davis School. "A deeper understanding of the effects of this genetic variation will provide a basis for developing physical activity strategies to maximize the benefits of exercise in T2D."

The study also provides a possible explanation as to why T2D is more common in East Asian populations. It is estimated that 7-10% of East Asians carry this variant and the research team believes their results are generalizable to other East Asians, including Koreans and Northern Chinese. According to the International Diabetes Federation, close to 40% of the world's T2D cases come from the region that includes China, Korea and Japan.

"This is particularly noteworthy because, although East Asian populations have lower mean body mass index (BMI) than Caucasian populations, they have a higher susceptibility to T2D," said co-senior author Pinchas Cohen, professor of gerontology, medicine and biological sciences and dean of the USC Leonard Davis School. "These results provide us with both a better understanding of how mitochondrial genetic variants can contribute to diseases and insights for developing precision-medicine-based therapies for treating them including replacing the defective peptide with drugs that mimic its actions."

These findings were male-specific. The variant did not affect females in either the human or mouse data. Researchers speculate this is due to an interaction between mitochondrial peptides and hormones but say the mechanism is currently unclear.

More on MOTS-C

MOTS-c is one of several more recently identified hormones that are encoded in the DNA of mitochondria, the "powerhouses" of cells that convert food into energy; most other hormones are encoded in DNA in the nucleus. Cohen and Changhan David Lee, an assistant professor at the USC Leonard Davis School, first described MOTS-c in 2015, along with its role in
restoring insulin sensitivity and counteracting diet-induced and age-dependent insulin resistance - effects commonly associated with exercising. In a separate paper published January 20, in Nature Communication, the same authors demonstrated that MOTS-c has "exercise mimetic" activities.

The current paper in Aging found that a variant at the coding region of MOTS-c was responsible for changing the amino acid of the MOTS-c peptide. Individuals carrying the C allele, rather than the more prevalent A allele, produced a form of MOTS-c called K14Q MOTS-c that lacked health-promoting features of the more common form.

The study found that the C allele MOTS-c variant was less effective as a metabolic regulator in cell and animal models and is associated with suppressed insulin sensitizing effects and higher body fat. In male mice, MOTS-c administration significantly reduced weight gain from a high-fat diet. In contrast, K14Q MOTS-c failed to protect against high-fat-diet-induced weight gain. In addition, mice administrated with MOTS-c performed better on glucose tolerance tests than K14Q injected mice.

"We showed that K14Q MOTS-c has a reduced effect on insulin sensitivity and weight gain compared to the more common form of MOTS-c in mice and speculate that this variant increases the prevalence of T2D in sedentary men because the C allele carriers produce the less effective form of MOTS-c," said Kim.

Comparing Cohorts

The researchers next studied the effect of the C allele variant on T2D in three cohorts of individuals of Japanese descent: the Japan Multi-Institutional Collaborative Cohort Study (J-MICC), which includes 4,963 men and 6,889 women; Japanese-American subjects in the Multiethnic Cohort (MEC) study, which includes 1,810 men and 1,577 women of Japanese descent living in the US; and the Tohoku Medical Megabank project (TMM), which includes 4,471 males and 7,817 females.

Meta-analysis of the three cohorts showed that males with the C-allele had higher rates of T2D. Regardless of exercise status, the C-allele increased the risk of T2D by more than one third.

The J-MICC study contained measures of daily activities. The researchers performed a comparison and found that among the least active men, those with the C allele had a 65% greater rate of T2D than men with the A allele. This higher rate of disease was not seen in C-allele men who engaged in more than 40 minutes of daily moderate to vigorous physical activity.

These results strongly suggest that a combination of sedentary lifestyle and the C allele variant contributes to elevated T2D risk, according to the researchers, who posit that the variant may have evolved to best fit living conditions characterized by highly active lifestyles and limited caloric intake. In the past this might have presented an advantage, but in the twenty-first century, it is a metabolic liability, they say.

"As MOTS-c analogues are currently in clinical development for the treatment of T2D complications, the recognition that activity levels can affect T2D risk in carriers of this SNP may inform future clinical trials," said Cohen. "This novel discovery suggests that additional ethnic-specific mitochondrial variants may be involved in metabolic disease risk. It also provides a blueprint for additional investigations into the mechanisms behind how mitochondria regulate disease and the search for potential mitochondria-based therapeutics."

Black women have higher recurrence and mortality rates than non-Hispanic white women for certain types of breast cancer, according to a University of Illinois Chicago researcher's study published recently in JAMA Oncology.

Dr. Kent Hoskins, associate professor in the UIC College of Medicine's division of hematology/oncology, and co-leader of the Breast Cancer Research group in the University of Illinois Cancer Center, published the study, "Association of race/ethnicity and the 21-gene Recurrence Score with breast cancer-specific mortality among US women" in the Jan. 21 online issue.

Hoskins and the research team sought to discover if breast cancer-specific mortality among women with estrogen receptor-positive, axillary node-negative breast cancer differs by race within risk categories defined by the Oncotype Recurrence Score, or RS, which is a genomic test that analyzes the activity of a group of genes that can affect how a cancer is likely to behave and respond to treatment. They also wanted to find out if the prognostic accuracy of the RS differs by race.

"Using data from the national SEER registry that included more than 70,000 patients across the U.S., we found there was a much higher mortality rate for African American women with the most common subtype of breast cancer event when they are diagnosed at an early stage," Hoskins said.

Women with hormone-dependent breast cancer typically have a favorable prognosis, but Hoskins found that even after adjusting for age at diagnosis, tumor stage and treatment, there is still a significant mortality gap between Black and non-Hispanic white women with axillary node-negative, hormone-dependent tumors that have a comparable RS.

The research also found that Black women are more likely to have a high-risk RS, indicating that Black women disproportionately develop biologically aggressive tumors. According to Hoskins, the underlying cause of this is unknown, but this is an active area of research among UI Cancer Center investigators. The Oncotype test also had lower prognostic accuracy in Black women, indicating that genomic tumor tests used to identify candidates for chemotherapy may require re-calibration in populations with greater racial and ethnic diversity, according to Hoskins' research.

The paper's findings are based on a retrospective, population-based cohort study database that contained data on women 18 years and older who were diagnosed with first primary stages I-III, estrogen receptor-positive breast cancer between 2004-2015.

"This study highlights a widespread problem that may contribute to health disparities," Hoskins said. "Research to develop and validate new medical tests frequently have inadequate representation of individuals from racial/ethnic minority groups. Because of this, new tests may be less accurate in individuals who belong to minority groups."

Because the RS is used by oncologists to make informed treatment decisions on the need for chemotherapy, Hoskins' study points out that the Oncotype RS model needs to be recalibrated to reflect racial differences.

The same lack of adequate representation of individuals from racial/ethnic minority groups plagues clinical trials of new cancer treatments, according to Hoskins.

"Our study is just one more example of how exclusion of minority patients from research can lead to inequities in health outcomes," he said.

While the study concluded that there is a disparity in mortality among Black women with early-stage breast cancer, further research is needed to understand the role of tumor biology and of structural violence in this disparity. Structural violence refers to systematic ways in which social structures harm or otherwise disadvantage individuals. Hoskins said the next step is to look at population health data and molecular data to determine the mechanisms driving the differences.

"We really think there is an intersection between social determinants of health and tumor biology and that is what we are trying to understand with follow-up studies," Hoskins said.

In addition to Hoskins, the research team included Dr. Oana Danciu and Dr. Gregory Calip, who are both UI Cancer Center members, and Dr. Naomi Ko of Boston University.

Simon Fraser University researchers have found evidence that large ambush-predatory worms--some as long as two metres--roamed the ocean floor near Taiwan over 20 million years ago. The finding, published today in the journal Scientific Reports, is the result of reconstructing an unusual trace fossil that they identified as a burrow of these ancient worms.

According to the study's lead author, SFU Earth Sciences PhD student, Yu-Yen Pan, the trace fossil was found in a rocky area near coastal Taiwan. Trace fossils are part of a research field known as ichnology. "I was fascinated by this monster burrow at first glance," she says. "Compared to other trace fossils which are usually only a few tens of centimetres long, this one was huge; two-metres long and two-to-three centimetres in diameter. The distinctive, feather-like structures around the upper burrow were also unique and no previously studied trace fossil has shown similar features."

Pan and SFU Earth Sciences professor Shahin Dashtgard are part of an international team that named the homes of these ancient giant worms Pennichnus formosae. Pan initiated the work while completing her M.Sc. degree under the supervision of Professor Ludvig Löwemark, from the Department of Geosciences at National Taiwan University, Taiwan.

After investigating 319 specimens preserved in early Miocene strata (22 million - 20 million years ago) in northeast Taiwan, the morphological model of this trace fossil was constructed.

"Shahin encouraged us to reach out to marine biologists, marine photographers and aquarium keepers to compare the burrows to biological analogs, which enabled us to reach the conclusion that this trace fossil was produced by giant, ambush-predatory worms," says Pan.

The modern-day Bobbit worm, which is also large and predatory, is sometimes called the 'sand striker,' sensing prey with its antennae, then grabbing them with its powerful jaws, and retreating into its burrow. When it burrows, its body occupies the whole burrow which explains the two-metre-long burrow observed in Pennichnus.

Further analysis revealed a high concentration of iron around the upper burrow, leading researchers to believe the worm secreted mucus to reinforce and rebuild its burrow wall after each feeding.

Modern Bobbit worm burrow openings are similar to that of Pennichnus, suggesting that the sediment collapsed into the burrow upon retreating or pulling still live prey below the seafloor.

Marine predatory worms have existed since the early Palaeozoic (> 400 million years ago), but their soft tissue bodies decay leaving little trace of their existence behind. Pennichnus formosae is believed to be the first known trace fossil produced by a sub-surface ambush predator, allowing researchers a rare opportunity to learn more about this ancient sand striker's behaviour.

A new collaborative study from researchers at the Geisel School of Medicine at Dartmouth and the University of Washington (UW) and published in the Proceedings of the National Academy of Sciences (PNAS), reveals unexpected insights into how skin exposure to ultraviolet (UV) light can worsen clinical symptoms in autoimmune diseases such as lupus.

Lupus, an autoimmune disease that can cause inflammation of the joints, skin, kidneys, blood cells, brain, heart and lungs, is caused when the immune system attacks its own tissue.

Previous research has established that in up to 80 percent of lupus patients, sunlight exposure can trigger both local skin inflammation and systemic flares, including kidney disease. But little has been understood about the underlying mechanisms that drive this process.

To define how UV light triggers kidney inflammation, the research team investigated the role of neutrophils--a type of white blood cell abundantly found in the body that acts as a first responder to any kind of inflammation and has been linked to skin and kidney tissue injury in lupus patients.

In the study, the researchers looked for markers of inflammation and injury in the skin, the blood, and the kidney at different time points following UV light exposure in mice. They were able to demonstrate that neutrophils not only infiltrated the UV light-exposed skin, but also dispersed throughout the circulatory system and migrated to the kidney.

"Interestingly, one subset of these neutrophils, the ones that we think are more damaging, first went to the skin that was exposed to the UV light and then turned around and went to the kidney," says Sladjana Skopelja-Gardner, PhD, an assistant professor of medicine at Geisel who worked with Keith Elkon, MD, at UW on the study. "That's a bit unusual--we normally think of neutrophils as short-lived cells that sort of zoom to where the inflammation is and then die off there."

The investigators found that a single exposure of skin to UV light stimulates inflammatory and injury processes in the kidney, including transient proteinuria, even in normal, healthy mice.

"To be clear, normal, healthy mice don't get the clinical type of kidney disease that you see in lupus patients," explains Skopelja-Gardner. "They get what we call subclinical injury, meaning there is an inflammatory and injury process happening in the kidney that is not visible by pathology or looking at the tissue itself. The mice recover and are fine afterwards.

"However," she adds, "this subclinical injury may lead to pathologic consequences in the vulnerable setting of pre-existing inflammation in lupus patients, and lead to kidney disease flare after exposure to sunlight."

Importantly, the inflammatory and injury markers they detected in the mouse kidneys following UV light exposure were very similar to the renal injury markers that are associated with more severe kidney damage in lupus patients. In addition, the exposure to UV light also triggered an immune response that is often expressed in most lupus patients--the type 1 interferon response--in both the skin and kidney.

"Overall, I think what our research demonstrates is that skin exposure to UV light can be the source of inflammatory pathways that are relevant to lupus, and that neutrophils play an important role as a pathogenic mediator in this process, contributing to kidney damage," says Skopelja-Gardner.