Body

Researchers from the HealthPartners Institute and University of Minnesota in Minneapolis conducted an observational analysis of interviews and characteristics of primary care clinics, comparing the strategies, facilitators and barriers to high performance in treating patients with diabetes. The purpose of the study was to learn what strategies and factors seem most important to leaders of primary care clinics to ensure high performance. The percentage of Minnesota diabetes patients who achieved optimal diabetes care measures increased from 12 to 45 percent between 2004 and 2017, while national measures of diabetes care outcomes did not improve significantly around the same time span.

The main difference among the strategies and factors was the degree to which top performing clinics used patient data to guide proactive and outreach methods to intensify treatment and monitor impact. The authors state that while confirmatory studies are needed, clinic leaders should consider the value of this paradigm shift in approach to care.

Intervention research focusing on patients with multiple, simultaneous chronic illnesses is a priority for health organizations such as the National Institutes of Health and Canadian Institutes of Health Research. This is important as physicians seek to better understand how one disease may influence the course of another coexisting one, and how to best care for patients who are battling multiple health issues. Researchers conducted a controlled trial in patients 18 to 80 years with three or more chronic conditions. They collected quantitative data and conducted in-depth interviews with patients, family members and health care providers, then measured the effectiveness of a four-month intervention based on changes in care delivery. For the study, health care professionals were trained to coach patients on adopting healthy lifestyle changes and managing their own health.

After four months, the intervention showed no effect on quantitative measures of self-management or self-efficacy. However, patients reported in qualitative interviews that the intervention improved their self-management and self-efficacy. The authors warn that complex interventions can be difficult to evaluate and important effects may be missed in evaluations that only include quantitative assessments.

Cooperation is generally a good thing -- working together to reach a goal.

But in the case of cancer, it can be detrimental. University of Cincinnati researchers have discovered that cooperation between two key genes drive cancer growth, spread and treatment resistance in one particularly aggressive type of breast cancer.

The good news is, though, with this knowledge, they can continue to aim their targeted treatments at these genes, singularly and together, to stop breast cancer in its tracks.

This study is published in the March 9 online edition of the journal Cell Reports.

"According to the American Cancer Society's estimate, over 280,000 new cases of invasive breast cancer will be diagnosed in women in 2021," explains Xiaoting Zhang, PhD, professor and Thomas Boat Endowed Chair in UC's Department of Cancer Biology, director of the Breast Cancer Research Program and member of the University of Cincinnati Cancer Center, who led this research. "Like many other cancers, breast cancer cells are fueled by mutations and overproduction of 'driver' genes, which lead the process of cancer development."

He says one of these genes, called HER2 (human epidermal growth factor receptor 2), accounts for about 20% of all human breast cancer cases, and while there are some therapies to target it, unwanted side effects and treatment resistance often occur in patients, causing relapse.

"There are about a dozen additional genes, including one called MED1, located within the same chromosomal region where HER2 and other genes are multiplied in breast cancer, but it's not known whether any of these genes are simply 'passenger' genes, and let HER2 to do the driving, or actually collaborate with the gene to play significant roles in the development, spread and treatment resistance of this type of breast cancer."

To investigate this, the team created an animal model with an overproduction of both genes, HER2 and MED1, in the mammary gland.

This helped researchers discover the key role MED1 played in helping HER2 promote breast tumor growth, spread and treatment resistance. They found that the genes could in fact work with each other to further speed up their production and activities, which in turn promotes rapid cell multiplication, movement and invasion to spread cancer and cause treatment resistance.

Zhang adds that previous research has shown that MED1 has a role in treatment resistance in another type of breast cancer, ER+ (estrogen receptor positive). This UC study established MED1 as a key driver in the development and treatment resistance of two major kinds of breast cancer.

"Our findings suggest that targeting MED1, alone and in combination with current therapies, could be an effective treatment strategy for nearly 90% of breast cancer patients in clinics and combat treatment resistance to two widely used breast cancer therapies," Zhang says.

Zhang and his team have already developed a treatment targeting MED1 specifically in tumors, using RNA nanotechnology similar to that used for the COVID-19 vaccines, and have observed positive outcomes. This technology is currently patent pending.

Creating foundations for future research, careers

Yongguang Yang, PhD, first author on this study and a research associate in Zhang's lab, says the work he's done on studying the roles of these genes in cancer and treatment resistance is eye-opening and takes a true "teamwork" approach.

"Working together as a team is very important in this process, as collaborations with the basic cancer biology researchers, clinical teams and physicians ensure our access to their unique insights and firsthand clinical experience, data and samples," he says. "These findings are exciting and relate very closely to how this cancer impacts people. This new animal model we created has a wide range of future applications and will allow us to continue to study basic molecular mechanisms of this type of breast cancer to find and test new therapies."

"It was very exciting to be able to not only conduct my graduate studies on something so innovative and impactful as identifying new ways that breast cancers function, but also to develop potential applications for the future of cancer treatment," adds co-author, Marissa Leonard, PhD, a recent doctoral graduate of the cancer and cell biology program at UC. "One or the other is often seen in research labs, but doing both is something I would consider a rare opportunity."

"The scientific experience, knowledge and writing skills I gained from Dr. Zhang's lab and our graduate program at UC have greatly broadened my horizons and allowed me to familiarize myself with a wide range of scientific concepts," says Leonard, who is now a medical writer. "These broad, laboratory-based skill sets bode well for many different career paths, too, whether that includes continued research, medical writing, regulatory science, patent law, teaching or others."

A mobile app designed to help women manage urinary incontinence was as effective as usual, in-person treatment of incontinence in primary care, according to new research from the Netherlands. The study included 262 women with frequent stress incontinence, overactive bladder or a mix of symptoms. Participants were randomly assigned to use a standalone mobile app called URinControl, which offered pelvic floor muscle and bladder training exercises. Those in a control group received standard care and were referred to their own primary care doctors who were broadly advised to follow the Dutch guidelines for primary care. After four months, women who used only the incontinence app and those who continued with standard care experienced similar results, with a decline in the severity of their symptoms, less frequent leakage and improved quality of life. Statistical analysis showed just over a one-half percentage point difference between the two groups' average decline in symptom severity. Therefore, the authors conclude that primary care physicians can offer care-as-usual and/or app-based treatment to women seeking help for urinary incontinence. Most importantly, the authors note, a mobile app will only be clinically relevant if it can demonstrate that it is either a less expensive option or offers an accessible and user-friendly alternative with significant long-term outcomes.

App-Based Treatment in Primary Care for Urinary Incontinence: A Pragmatic, Randomized Controlled Trial
Anne M. M. Loohuis, MD, et al
University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands
https://www.annfammed.org/content/19/2/102

App-based and self-management tools have the potential to help individuals take control of their common urinary issues. In a corresponding editorial, Joel Heidelbaugh, MD, a clinical professor of family medicine and urology at the University of Michigan, discusses the significance of Loohuis et al's mobile app study and Albarqouni et al's review of self-management interventions, and highlights their value to both patients and primary care physicians. For patients, new e-health programs could help individuals manage their symptoms and improve their quality of life without medication, or they may experience additional benefits when combined with medication. For primary care physicians, apps and self-management tools might be a cost-effective and empowering strategy compared to usual care.

Self-Directed Technology to Improve Urinary Symptoms
Joel J. Heidelbaugh, MD
University of Michigan Medical School, Ann Arbor, Michigan
https://www.annfammed.org/content/19/2/100

According to two national surveys by researchers at the University of Michigan Medical School, US teens and young adults are engaged in the ongoing COVID-19 pandemic with most being knowledgeable about the disease, concerned about its impacts on others, and practicing social distancing. On March 6, 2020, 70 percent reported knowledge of the pandemic, with 46 percent noting they got information from news sources. By March 20, 2020, nearly all respondents, 95 percent, reported impact. Worry about the pandemic increased from 25 to 51 percent. For some young people who weren't worried early on about the pandemic, staying at home and engaging in other preventive public health guidelines made them feel safer. Between the two surveys, pandemic preparation seemed to shift. Initially, respondents primarily reported doing nothing (36 percent), but by March 20th, 50 percent reported practicing social distancing. The authors recommend that, as public health planning evolves, it will be important to acknowledge young people's concern for others as a driver of their behavior and to create programs that are informed by their beliefs and perspectives.

Last fall, nearly half of older adults were on the fence about COVID-19 vaccination - or at least taking a wait-and-see attitude, according to a University of Michigan poll taken at the time.

But a new follow-up poll shows that 71% of people in their 50s, 60s and 70s are now ready to get vaccinated against COVID-19 when a dose becomes available to them, or had already gotten vaccinated by the time they were polled in late January. That's up from 58% in October.

Three groups of older adults with especially high risk of severe COVID-19 -- Blacks, Hispanics and people in fair or poor health - had even bigger jumps in vaccine receptiveness between October and late January.

The poll shows a 20-point jump in just four months in the percentage of Black respondents who said they would likely get vaccinated, and an 18-point jump for Hispanic older adults. The jump for white respondents in that time was 9 points.

People who said their health was fair or poor - likely including many with chronic conditions that can increase their risk of serious illness if they catch the coronavirus - had an 11-point jump in likelihood of getting vaccinated. However, they were still less likely to want to get vaccinated than those in better health.

By late January, 60% of Black respondents, 69% of Hispanic respondents, and 62% of those in fair or poor health said they were very likely or somewhat likely to get vaccinated, or had already gotten at least one dose. Among all white respondents regardless of health status, it was 72%.

The data come from the National Poll on Healthy Aging, based at U-M's Institute for Healthcare Policy and Innovation with support from AARP and Michigan Medicine, U-M's academic medical center. In November 2020, the poll published a full report based on data from a poll conducted in October. The new data come from a question asked in late January and are being issued as an update to the previous poll.

"This is incredibly encouraging, given the amount of hesitancy we saw in our poll from late fall," says Preeti Malani, M.D., the poll's director and a professor of infectious diseases at U-M. "But these new data still reveal gaps in attitudes about COVID-19 vaccination between racial and ethnic groups. We hope this new knowledge will help the various groups doing education and outreach tailor their approach so they can address questions, concerns and reasons for vaccine hesitancy."

In both outings, the poll asked older adults the question, "Assuming no cost to you, when a COVID vaccine is available, how likely are you to get it?" Respondents in January had the additional option to answer that they had already been vaccinated.

The percentage of all respondents who were most enthusiastic about vaccination - those who said they were 'very likely' to get the vaccine - jumped 20 percentage points, from 33% in October to 53% in January.

As states like Michigan open up vaccination eligibility to people over 50, the poll reveals that this group may need a bit more persuading than those 65 and up. The younger half of the poll group had an 11-point rise in likelihood of vaccination, compared with 14-point rise in the older group.

As in October, the new poll shows that individuals who have higher household incomes or more education were also more likely to report they would get a COVID vaccine.

The National Poll on Healthy Aging results are based on responses from a nationally representative sample of adults aged 50 to 80 who answered a wide range of questions online; the October poll included 1,553 respondents, and the January one included 2,022 respondents. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have them.

A full report of the findings and methodology of the October report is available at http://www.healthyagingpoll.org, along with past National Poll on Healthy Aging reports.

BOSTON - Almost immediately after the first mRNA-based COVID-19 vaccines were authorized for emergency use and were administered to individuals outside of clinical trials, reports of anaphylaxis--a life-threatening whole-body allergic reaction--raised widespread concerns among experts and the public. Now, real world data on vaccinations among employees at Mass General Brigham provide reassurances of the rarity of such serious reactions, and the ability to recover from them. The findings are published in the Journal of the American Medical Association.

"The COVID-19 mRNA vaccines are the first vaccines of their kind, and they have remarkable efficacy and safety across all populations. It is critical to have accurate information on allergic reactions to these vaccines, not only for our current situation, but also because this new vaccine platform is so important for future pandemic responses," says lead author Kimberly Blumenthal, MD, MSc, co-director of the Clinical Epidemiology Program within Massachusetts General Hospital's Division of Rheumatology, Allergy and Immunology.

With this in mind, Blumenthal and her colleagues decided to carefully document all allergic reactions, including anaphylaxis, once they began employee vaccinations at Mass General Brigham. The team analyzed employee surveys to estimate the incidence of allergic reactions after mRNA vaccines and used multiple surveillance methods to identify the true incidence of anaphylaxis.

Among 52,805 employees (including an estimated 4,000 with significant allergies to foods and medications) who were surveyed after they received their first dose of an mRNA COVID-19 vaccine, 2% experienced allergic reactions, and anaphylaxis occurred at a rate of 2.47 per 10,000 individuals. "To put this in perspective, this is largely comparable to anaphylactic reactions from common antibiotics," says Blumenthal.

The investigators noted that although the incidence of anaphylaxis was higher than that estimated by the Centers for Disease Control and Prevention--which put the rate at 0.025 to 0.11 per 10,000 vaccinations--it is still exceedingly low and should provide reassurances, especially for individuals with a history of food or drug allergies. "The only allergy exclusion for vaccination was a prior episode of anaphylaxis to an inactive ingredient in the vaccine, called polyethylene glycol, or a cross-reactive inactive ingredient called polysorbate," says co-senior author Paige Wickner, MD, MPH, medical director of the Department of Quality and Safety at Brigham and Women's Hospital. "Another important aspect of our study is that all of our anaphylaxis cases recovered--no one had anaphylactic shock or required a breathing tube, even temporarily."

Past studies on whether incarcerated people with mental illness are more likely to be placed in solitary confinement have yielded mixed results. A new study examined the issue in one state's prisons, taking into account factors related to incarcerated men and the facilities where they were imprisoned. It found that having a mental illness was associated with a significant increase in the likelihood of being placed in extended solitary confinement.

The study, by researchers at Florida State University (FSU), appears in Justice Quarterly, a publication of the Academy of Criminal Justice Sciences.

"Our findings provide new information on how mental illness shapes experiences for incarcerated men, and more broadly, on how the criminal justice system responds to people with mental illness," explains Sonja Siennick, professor of criminology and criminal justice at FSU, who led the study. "The bottom line is that incarcerated people with mental illness appear to garner differential responses from the prison system."

Solitary confinement--placing incarcerated people in isolation cells for 22 to 24 hours a day--is controversial. While some argue that it helps with safety, others suggest it is unethical and poses psychological risks, especially for prisoners with mental illness. This study focused on extended periods of solitary confinement that last for months.

Researchers studied 155,018 men who entered prisons in a large state on or after July 1, 2007, and were released on or before December 31, 2015. The men were assessed within 60 days of their arrival to determine if they met criteria for psychiatric diagnosis. More than 15,000 of the men were diagnosed with a mental health condition. These men were matched with a control group of the same size--men who had equivalent personal characteristics and were housed in similar facilities but who were not diagnosed with a mental health condition.

The study used propensity score matching, a technique that estimates the effect of an intervention, to assess whether the incarcerated men with mental illness were more likely to be placed in extended solitary confinement than the similar incarcerated men without mental illness. Researchers considered characteristics of both the individual prisoners and the facilities in which they were incarcerated. For the men, these included prior arrests and convictions, recidivism, victimization in prison, age, race/ethnicity, education, alcohol and drug use, family and romantic relationships, and other demographics. For the facilities, these included distance from the incarcerated man's home and information related to the inmate population (e.g., average age, race/ethnicity, percentage in solitary confinement, percentage receiving mental health care) as well as the correctional staff.

The study found that one percent of all of the men were placed in extended solitary confinement after 60 days. It also found that prisoners with mental illness were up to 170 percent more likely to be placed for extended periods of time in solitary, depending on their diagnosis. This increased risk is higher than identified by previous research. The higher risk was present for a variety of mental health disorders (including bipolar disorder, major depression, schizophrenia, psychotic antisocial personality disorder, and other personality disorders, but not disorders related to anxiety, impulse control, and post-traumatic stress), and only partially explained by prison misconduct, the authors note.

Incarcerated men placed in solitary confinement were separated from the general population for months; placed alone in a cell for 23 hours a day; and restricted from using the telephone, having visitors, and receiving other privileges. Reasons for placements included safety concerns, problems with institutional adjustment, and possessing or trafficking contraband such as weapons and drugs.

Among the study's limitations, according to the authors, are that differences in how men and women are housed in the facilities studied prevented a complete examination of women; however, the researchers note that the main results for women were substantively similar to those for men. In addition, because most prisoners in the state serve sentences of less than three years, the study's findings may not generalize to people who are incarcerated for longer periods.

Also, the study examined state prisons and not jails, so the association of mental illness with solitary confinement could differ between these settings. Finally, because a new edition of the Diagnostic and Statistical Manual of Mental Disorders was published midway through the study and included changes to criteria for mental illness, men admitted later in the study could have been diagnosed differently than men admitted earlier.

"Our results suggest that the association between mental illness and solitary confinement is not simply a matter of more violent behavior by this population," says Mayra Picon, a doctoral student in criminology and criminal justice at FSU, who coauthored the study. "Rather, incarcerated men with mental illness may have more difficulty adjusting to prison and its rules, resulting in more punitive responses by prison staff.

"Treatment, officer training, and related initiatives may help offset negative consequences for incarcerated people with mental illness, but first, we must develop a better understanding of the intersection of mental illness and corrections," she added.

Over the summer and fall, paper after paper revealed that mothers are one of the demographics hardest hit by the pandemic. From layoffs and leaving careers to do caretaking, to submission rate decreases and additional service projects, the data were clear, but the follow up less so. Many of the problems are not new and will remain after the pandemic. But a new paper, published this week in PLOS Biology, outlines methods to help solve them.

"In the spirit of the well-worn adage 'never let a good crisis go to waste,' we propose using these unprecedented times as a springboard for necessary, substantive and lasting change," write the 13 co-authors, led by researchers from Boston University and hailing from seven institutions, including Michigan Technological University, University of Connecticut, and University of Houston - Clear Lake. The team's goal: Solutions for retaining mothers in science during and after COVID-19, especially parents who are Black, Indigenous or people of color.

"The news was reporting these studies as if they were a surprise," said Robinson Fulweiler from Boston University, one of the lead authors alongside Sarah Davies, also of Boston University. Fulweiler adds, "There's already been a lot of data gathered about this issue. But there have been no solutions. Our level of frustration peaked. We decided we need to make a plan to fix things."

The paper offers specific solutions to different groups that can enact change:

Mentors: Know university parental leave policies, support and model a "healthy work-life teeter-totter" and keep mentees with child care duties engaged and involved in lab, department and multi-institution activities.

University administrators: Look up 500 Women Scientists, rethink tenure procedures and timelines, listen, provide course releases and avoid making "gender- or race-neutral policies because the effects of the pandemic are not neutral across race or gender."

Scientific societies: Consider how to keep parts of virtual conferences with lower costs, expand governing board diversity, expand networking opportunities and continue supporting early-career members, especially researchers who are Black, Indigenous, and people of color.

Publishers: Expand editorial boards and, during the pandemic, incentivize submissions through fee waivers for mothers with child care duties and keep extending deadlines for review and revisions.

Funding agencies: Streamline paperwork, ask for COVID disruption statements and look into supplemental and short-term bridge awards.

Mothers in the Pandemic

Amy Marcarelli, associate professor of biological sciences at Michigan Tech, helped lead the paper's section addressing professional societies. When the pandemic hit -- and Marcarelli had less than five days to shift all her classes and research to remote formats -- she was wrapping up a two-year strategic planning process with the Society for Freshwater Science that included a deep dive into effective and fair practices for diversity, equity and inclusion. She sees the work through her lens as an ecosystem ecologist.

"Some of my most recent work has been around cascading and indirect effects and how effects viewed on short time scales may have very different outcomes at long time scales," Marcarelli said. "What I've learned from that research is that you can't abstract a single characteristic of an organism and expect that to explain its ecological role. And [in academia] we try so often to treat ourselves as researchers -- and not as mothers and partners and daughters and leaders -- and that's to the detriment of all of us. It's to the detriment of us as individuals but it's also to the detriment of our academic system because if we don't treat people as whole people then we fail them."

Marcarelli emphasizes that she feels like she has been lucky during the pandemic; she secured tenure several years ago, her kid is older, Michigan K-12 schools reopened in September, and her mom, who was furloughed, helped with spring schooling and summer child care. While the extra service projects and retooling research, instruction and life were not easy, Marcarelli recognizes that not everyone's situation has been like hers.

The most pressing change Marcarelli sees is to rethink tenure extensions: "We have to figure out how to make motherhood and tenure compatible, not just extend tenure -- it's not a solution." She adds that the greatest challenge will be money. "These are inequities, but they are not inequities that everybody sees. And during a time of what is going to be an extended budget crisis in a lot of higher ed, that's going to be the hardest part. But it's the part that has to be solved because good intentions only get us so far."

Marcarelli says the conversation that sparked the PLOS Biology article started on Twitter, a lively back-and-forth on how to shift the dialogue to a solutions mindset.

"At the same time, several of us were working on big service activities around how to improve conditions for all different axes of diversity in our departments and universities, in our societies," she said. "We had invested a lot of thinking and real work that was going into small reports and small-scale documents that weren't going to be read widely."

The team's service work, lived experiences and hope informed the PLOS Biology paper as much as their research and collaboration.

"Part of the motivation for writing this article is that in some ways the pandemic provides a window into why this is important, why we need to do the hard work of dismantling these systems," Marcarelli said. "Quite frankly, it's an opportunity."

PHILADELPHIA (March 9, 20201) - The PhD degree prepares nurse scientists to advance knowledge through research that improves health, translates into policy, and enhances education. However, as the role of the nurse has changed, and health care has grown more complex, there is a need to re-envision how PhD programs can attract, retain, and create the nurse-scientists of the future and improve patient care.

To begin the dialog about the future of PhD education in research-intensive schools, the University of Pennsylvania School of Nursing (Penn Nursing) invited 41 educational, governmental, professional, and philanthropic institutions to a summit in 2019. During the summit, participants collaborated on re-envisioning how nursing PhD programs can successfully advance nursing science and situate research-focused nursing PhD graduates for success in academia and beyond. An upcoming issue of the Journal of Professional Nursing features manuscripts from that forum, which offer a broader, overall strategy for informing stakeholder groups that shape nursing PhD programs in research-intensive institutions.

"This synthesis of discussions, considerations, and challenges affecting research-focused doctoral programs of nursing serve as a basis and catalyst for further discussion and action to ensure PhD research-focused programs are preparing successful nurse scientists of the future," says Antonia M. Villarruel, PhD, RN, FAAN, Professor and Margaret Bond Simon Dean of Nursing.

"Re-envisioning of research doctorate programs is urgently needed to ensure the advancement of science and the development of new knowledge to situate our graduates for success - in academia and beyond," says Julie A. Fairman, PhD, RN, FAAN, Endowed Chair, Nightingale Professor in Honor of Nursing Veterans. Villarruel and Fairman were guest editors of the issue.

Advancing Nursing Science Through Re-envisioned PhD Programs

PhD programs, in general, remain fairly traditional in approach and scope, instigating few changes in programmatic offerings and moving existing curriculum online. The Penn Nursing summit in 2019 was held to address these issues.

The article "Invitational Summit: Re-envisioning Research-Focused PhD Programs of the Future" shares the questions used to survey the summit attendees before the program and the responses. The article outlines the challenges facing research-intensive nursing PhD programs, emerging innovations within programs, and suggested changes to re-envision the future education of nurse scientists.

Fairman and Villarruel co-authored the article with Kathleen McCauley, PhD, RN, FAAN, FAHA, Professor Emerita of Cardiovascular Nursing at Penn Nursing; and Nicholas A. Giordano, Assistant Professor, Emory University Nell Hodgson Woodruff School of Nursing.

Approaching Doctoral Nursing Education in Novel Ways

The rapid growth of science and the need to prepare the next generation of nurse scientists call for innovative approaches in educating and supporting them throughout their careers. Aside from curricular changes, a new PhD education model for nurses should include new approaches to mentoring, funding, and networking supports. Equally important are rigorous process and outcome measures for innovations to inform changes to doctoral programs.

The article "Innovations in PhD Education to Prepare Nurse Scientists for the Future" outlines those recommendations and includes the need to structure faculty development earlier in professorial careers, develop team models of advisement, and longitudinal follow-up of alumni graduates from PhD programs to examine the effectiveness of innovations.

Villarruel co-authored the article with Marion E. Broome, Duke University School of Nursing; and Hilaire J. Thompson, University of Washington School of Nursing.

Advancing Nursing Science Through PhD Programs

Nurses are well-positioned to be groundbreaking researchers, scientists, leaders, and innovators to improve the health and well-being of individuals, families, and communities. Thoughtful consideration is required about the preparation of PhD nurse scientists to ensure they are equipped with the knowledge and skill sets to meet the needs of society and to ensure the relevance and competitive status of nursing science.

The article "PhD Programs and the Advancement of Nursing Science" outlines three aspects of PhD education and nursing science. These include examining important elements to support nurse scientist development; identifying key gaps in science that the discipline needs to address in educating the next generation of nurse scientists; and preparing nurse scientists for the competitive funding environment.

Authors of the article include Therese S. Richmond, PhD, RN, FAAN, Andrea B. Laporte Professor of Nursing and Associate Dean for Research & Innovation at Penn Nursing; Paule V. Joseph, of the National Institute of Nursing Research; and Linda McCauley of the Emory University Nell Hodgson Woodruff School of Nursing.

Leveraging Insight from Funders and Sponsors

Re-envisioning PhD education at research-intensive institutions to produce the nurse scientists of the future is imperative for the discovery of solutions for current and complex health care challenges facing the country. Philanthropic funders and sponsors of PhD nursing education have important insights into how investments in PhD education have direct and positive impacts on health care and bring important perspectives to emerging roles for PhD-prepared nurses.

The article, "Emerging Roles for Research Intensive Ph.D.-Prepared Nurses as Leaders and Innovators: Views from Funders/Sponsors" reports on the ideas these funders shared, including the importance of increasing the focus on formal leadership preparation and training in innovation.

Co-authors of the article include Nancy A. Hodgson, PhD, RN, FAAN, Professor & Chair of the Department of Biobehavioral Health Sciences; MaryJoan Ladden, formerly of Robert Wood Johnson Foundation; Elizabeth Madigan, Sigma Theta Tau International Honor Society of Nursing; Ahrin Mishan, Rita and Alex Hillman Foundation; and Wanda Montalvo, Jonas Nursing & Veterans Healthcare.

Preparing Nurses for Nontraditional Career Paths

Advancing the health of patients and communities depends on preparing the next generation of nurse scientists to pursue career trajectories outside of traditional academic institutions. Redesigning nursing PhD curricula must include preparation for careers in many sectors of health care, professional organizations, government, or industry.

During the summit, executives from health systems and organizations shared their career trajectories, experiences, and perspectives for revamping PhD curriculum and offered educational experiences to broaden the scope of academic rigor to inspire and prepare future nurse scientists for nontraditional research positions in practice. Their thoughts regarding why research-intensive PhD programs must address the PhD study milestones to enable their graduates to be competitive in seeking positions in emerging roles outside of academic institutions and recommendations for achieving these milestones are included in the article "Emerging Roles for Research Intensive PhD Prepared Nurses: Beyond Faculty Positions."

Rosemary C. Polomano, PhD, RN, FAAN, Associate Dean for Practice Professor of Pain Practice, is the lead author of the article. Co-authors include Nicholas A. Giordano, Emory University Nell Hodgson Woodruff School of Nursing; Suzanne Miyamoto, American Academy of Nursing; Deborah Trautman, American Association of Colleges of Nursing; Sheila Kempf, Penn Medicine Princeton Health; and Paula Milone Nuzzo, Massachusetts General Hospital.

Pedagogical Innovations in PhD Nursing Education

Over the past decade there have been numerous innovations in PhD programs that have redesigned the curricula and delivery of research-focused doctoral nursing education. The article, "Opportunities and Challenges Presented by Recent Pedagogical Innovations in Doctoral Nursing Education," explores core issues resulting from key program changes such as expanding both 3-year and PhD programs and BSN to PhD programs. This paper makes the case for a national effort to evaluate the effects of these program modifications on the development of nurse scientists and, ultimately, the nursing discipline. Understanding the impact of pedagogical innovations will inform ongoing improvements essential to educate the next generation of nurse scientists to conduct high quality research in an increasingly multidisciplinary environment.

Authors of the article include Mary D. Naylor, PhD, RN, FAAN, Marian S. Ware Professor in Gerontology & Director of the NewCourtland Center for Transitions and Health; Peggy Compton, PhD, RN, FAAN, van Ameringen Chair in Psychiatric and Mental Health Nursing; Nicholas A. Giordano, Emory University Nell Hodgson Woodruff School of Nursing; Paule V. Joseph, National Institute of Nursing Research; Carol Ann Romano, Uniformed Services University of the Health Sciences; and Mariann R. Piano, Vanderbilt University School of Nursing.

PhD Programs of the Future

Over the last 20 years, the number of research-focused doctoral programs in nursing has nearly doubled--from 78 programs in 1999 to 145 programs in 2019. Yet, despite this significant increase in programs, the number of students pursuing the PhD (or equivalent programs) in nursing has declined over the past five years.

From recruiting strategies and subject areas to evaluation methods and funding, discussions at both the Penn Nursing summit and the AACN Doctoral Education Conference authors identified opportunities for improving research-focused doctoral programs for nurses. The article "From Vision to Action: Next Steps In Designing PhD Programs of the Future" synthesizes those discussions and outlines next steps in refining doctoral education in general and in research-focused programs in particular.

Villarruel is lead author with co-authors Fairman and Deborah Trautman, American Association of Colleges of Nursing.

COLUMBUS, Ohio - A new SARS-CoV-2 vaccine candidate, developed by giving a key protein's gene a ride into the body while encased in a measles vaccine, has been shown to produce a strong immune response and prevent SARS-CoV-2 infection and lung disease in multiple animal studies.

Scientists attribute the vaccine candidate's effectiveness to strategic production of the antigen to stimulate immunity: using a specific snippet of the coronavirus spike protein gene, and inserting it into a sweet spot in the measles vaccine genome to boost activation, or expression, of the gene that makes the protein.

Even with several vaccines already on the market, researchers say this candidate may have advantages worth exploring - especially related to the measles vaccine's established safety, durability and high-efficacy profile.

"The measles vaccine has been used in children since the 1960s, and has a long history of safety for children and adults," said Jianrong Li, senior author of the study and a professor of virology in The Ohio State University Department of Veterinary Biosciences.

"We also know the measles vaccine can produce long-term protection. The hope is that with the antigen inside, it can produce long-term protection against SARS-CoV-2. That would be a big advantage, because right now we don't know how long protection will last with any vaccine platforms."

The Ohio State Innovation Foundation has exclusively licensed the technology to Biological E. Limited (BE), a Hyderabad, India-based vaccine & pharmaceutical company.

The research is published online today (March 9, 2021) in the journal Proceedings of the National Academy of Sciences.

The coronavirus that causes COVID-19 uses the spike protein on its surface to bind to its target cells in the nose and lungs, where it makes copies of itself and releases them to infect other cells. Like all vaccines, this candidate initiates the production of antibodies that recognize the new protein as foreign, training the immune system to attack and neutralize the spike protein if SARS-CoV-2 ever enters the body.

Li created the COVID-19 vaccine using a live attenuated measles virus as a vehicle with colleagues Mijia Lu, a postdoctoral researcher in Li's laboratory and first author on the paper, and co-authors Stefan Niewiesk, Ohio State professor of veterinary biosciences, and Mark Peeples, professor of pediatrics at Ohio State and a researcher at Nationwide Children's Hospital in Columbus.

For this work, the researchers tested seven versions of the spike protein to find the most effective antigen. They landed on a stabilized "prefusion" version of the protein - the shape the protein is in before it infects a cell.

The scientists inserted the prefusion spike protein gene containing manufacturing instructions into a segment of the measles vaccine genome to generate high expression of the protein, reasoning that the more SARS-CoV-2 spike protein produced, the better the immune response.

The team tested the vaccine candidate in several animal models to gauge its effectiveness, and found that the vaccine induced high levels of neutralizing antibodies against SARS-CoV-2 in all of the animals.

Some may think most humans' immunity to measles, thanks to decades of widespread vaccination, would render its status as a coronavirus vaccine vehicle useless. To quell those concerns, researchers gave cotton rats a measles vaccine and showed that a second immunization with the measles-based SARS-CoV-2 vaccine candidate could induce a strong neutralizing antibody response to the coronavirus.

Genetically modified mice produced helper T cells - a type of white blood cell - in response to the vaccine, another important way the body fights infection, and severe disease in particular.

"The orientation of T helper cells induced by a vaccine is an important predictor of protection, and this vaccine mainly induces Th1 cells, which enhances the safety and efficacy of the vaccine," said co-author Amit Kapoor, associate professor of pediatrics at Ohio State and a researcher at Nationwide Children's Hospital.

Golden Syrian hamsters, which are susceptible to contracting COVID-19, received the vaccine and were then injected with the coronavirus. The vaccinated hamsters were protected from lung infection and other sickness symptoms indicated through weight loss.

"When we looked at the amount of neutralizing antibody induced in the hamster, it was actually higher than from people who had been infected with COVID, suggesting the vaccine may be better than SARS-CoV-2 infection in inducing protective immunity. That was our goal," Peeples said.

The researchers have confidence in the platform not only because the measles vaccine is safe, effective and affordable to produce, but because several experimental measles-based vaccines against other viruses are in development. A vaccine against chikungunya virus, spread by mosquitos, has been shown to be safe, well-tolerated and good at provoking an immune response in a Phase 2 clinical trial.

And even with a variety of COVID-19 vaccines now available in the United States and other countries, there is still a lot to learn about which are the safest and most effective for specific populations, such as children and pregnant women, and which vaccines are the most economical to produce.

"We can make vaccines much more quickly now than in the past. But if we had to do it the traditional way this time, we wouldn't have a vaccine protecting us in this short amount of time," Niewiesk said. "The mRNA vaccines in use now were made in record time. And they protect against disease and are safe. Although not quite as fast, we were able to make this vaccine much more quickly than the original measles vaccine.

"We don't yet know how long the mRNA vaccines will protect or how much they will cost. In the meantime, an alternative vaccine that should protect for a long time, is easy to manufacture and cheap seems like a good idea."

People living with a patient undergoing an intensive weight loss treatment also benefit from this therapy. This has been demonstrated by a team of researchers from the Hospital del Mar Medical Research Institute (IMIM-Hospital del Mar) along with doctors from Hospital del Mar and the CIBER on the Physiopathology of Obesity and Nutrition (CIBERObn), in collaboration with IDIAPJGol, the Pere Virgili Health Research Institute (IISPV), IDIBELL, IDIBAPS and the Sant Joan de Reus University Hospital. The study has been published in the journal International Journal of Obesity.

The study analysed data from 148 family members of patients included in the weight loss and lifestyle programme PREDIMED-Plus (PREVencióDIetaMEDiterranea Plus) over a two-year period. The researchers analysed whether these people also indirectly benefited from the programme, as they were not enrolled in the study and did not receive any direct treatment. PREDIMED-Plus is a multicentre study in which a group of patients follow an intensive weight reduction programme based on the Mediterranean diet and a plan promoting physical activity.

Weight loss despite not being included in the programme

The relatives (three out of four were the patient's partner and the rest were children, parents, siblings or had some other degree of kinship), lost an average of 1.25 kg of weight during the first year of the programme, compared to the relatives of the patients in the control group (those who did not follow the intensive treatment proposed by PREDIMED-Plus). This rose to almost 4 kg in the second year. These figures were better in cases where the family member ate with the patient and, above all, when it was the patient themselves who cooked.

The treatment, aimed at achieving weight loss in people with obesity and high cardiovascular risk by following the Mediterranean diet, "Achieved effects beyond just weight loss in the patient, and this extended to their family environment", explains Dr. Albert Goday, the principal investigator on the project, head of section in the Department of Endocrinology and Nutrition at Hospital del Mar, researcher in the Cardiovascular Risk and Nutrition Research Group at the IMIM-Hospital del Mar and a CIBERobn researcher. "The effect was contagious, in this context it was, fortunately, a beneficial 'contagion', resulting in weight loss and improved dietary habits." Dr. Goday points out that "among the many possible dietary approaches to weight loss, the one based on the Mediterranean diet is the most easilt shared within a family environment."

According to Dr. Olga Castañer, the final author of the study and a researcher in the Cardiovascular Risk and Nutrition Research Group at the IMIM-Hospital del Mar and CIBERobn, the good results can be explained "By an improved diet, since the same contagious effect was not observed in terms of physical activity among the patients and their relatives."

Family members also showed increased commitment to the Mediterranean diet, according to a questionnaire assessing adherence to the dietary patterns of this regimen. But the same was not true in terms of physical activity. As Dr Castañer points out, "In addition to weight loss, there was greater adherence to the Mediterranean diet, which has intrinsic health benefits, such as protection against cardiovascular and neurodegenerative risks."

The results of the study "Demonstrate the contagion effect, the halo effect, of a treatment programme in the relatives of participants involved in an intensive weight loss procedure, as well as increased adherence to the Mediterranean diet", stresses Dr. Albert Goday. "The beneficial effect of the programme on one member of the family unit can be extended to its other members, which is extremely significant in terms of reducing the burden of obesity on the public health system", he explains. The family members not only lost weight but also improved the quality of their diet.

Effect of the programme on patients

The study also analysed the results of the PREDIMED-Plus programme in 117 patients. Compared to participants in the control group, they lost 5.10 kg in the first year of intervention rising to 6.79 kg in the second year. They also significantly increased their physical activity levels, as well as their adherence to the Mediterranean diet.

A staple for many, chickpeas are a rich source of vitamins, minerals, and fiber and offer many health benefits, such as improving digestion and reducing the risk of ailments including heart disease and cancer. However, chickpeas possess a rather narrow genetic diversity and are susceptible to Ascochyta blight, a devastating disease that can cause a yield loss of up to 100 percent. In Australia alone, this disease costs an average of $4.8 million annually.

To help curtail the impact of Ascochyta blight, plant pathologists in Western Australia have turned to wild relatives of the chickpea: Cicer reticulatum and Cicer echinospermum and found that these plants have a natural resistance to the disease. This is the first report of Ascochyta blight resistance in a novel wild Cicer collection.

"Identifying such sources of resistance is a very exciting finding for the chickpea industry and can offer growers better genetic control of the disease," explained Lars Kamphuis, one of the scientists involved with the study. "These sources of resistance can be utilized in chickpea breeding programs around the world to improve their resistance to this pathogen."

Kamphuis and his colleagues used a germplasm collection that has also been a valuable source of resistance to other diseases and pests such as root lesion nematodes and pod-borer. Using the disease scores for Ascochyta blight and genotypic information of the germplasm, they were also able to identify Ascochyta blight-associated regions in the wild Cicer genome.

"Collaborators in Australia are evaluating this resource for sources of resistance to Phytophthora root rot, acid soil, and chilling tolerance," said Kamphuis. "This novel wild Cicer germplasm is thus being mined for novel sources of biotic and abiotic stress resistance and will help improve the genetic diversity within chickpea breeding programs."

Diphtheria - a relatively easily-preventable infection - is evolving to become resistant to a number of classes of antibiotics and in future could lead to vaccine escape, warn an international team of researchers from the UK and India.

The researchers, led by scientists at the University of Cambridge, say that the impact of COVID-19 on diphtheria vaccination schedules, coupled with a rise in the number of infections, risk the disease once more becoming a major global threat.

Diphtheria is a highly contagious infection that can affect the nose and throat, and sometimes the skin. If left untreated it can prove fatal. In the UK and other high-income countries, babies are vaccinated against infection. However, in low- and middle-income countries, the disease can still cause sporadic infections or outbreaks in unvaccinated and partially-vaccinated communities.

The number of diphtheria cases reported globally has being increasing gradually. In 2018, there were 16,651 reported cases, more than double the yearly average for 1996-2017 (8,105 cases).

Diphtheria is primarily caused by the bacterium Corynebacterium diphtheriae and is mainly spread by coughs and sneezes, or through close contact with someone who is infected. In most cases, the bacteria cause acute infections, driven by the diphtheria toxin - the key target of the vaccine. However, non-toxigenic C. diphtheria can also cause disease, often in the form of systemic infections.

In a study published today in Nature Communications, an international team of researchers from the UK and India used genomics to map infections, including a subset from India, where over half of the globally reported cases occurred in 2018.

By analysing the genomes of 61 bacteria isolated from patients and combining these with 441 publicly available genomes, the researchers were able to build a phylogenetic tree - a genetic 'family tree' - to see how the infections are related and understand how they spread. They also used this information to assess the presence of antimicrobial resistance (AMR) genes and assess toxin variation.

The researchers found clusters to genetically-similar bacteria isolated from multiple continents, most commonly Asia and Europe. This indicates that C. diphtheriae has been established in the human population for at least over a century, spreading across the globe as populations migrated.

The main disease-causing component of C. diphtheriae is the diphtheria toxin, which is encoded by the tox gene. It is this component that is targeted by vaccines. In total, the researchers found 18 different variants of the tox gene, of which several had the potential to change the structure of the toxin.

Professor Gordon Dougan from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) said: ""The diphtheria vaccine is designed to neutralise the toxin, so any genetic variants that change the toxin's structure could have an impact on how effective the vaccine is. While our data doesn't suggest the currently used vaccine will be ineffective, the fact that we are seeing an ever-increasing diversity of tox variants suggests that the vaccine, and treatments that target the toxin, need to be appraised on a regular basis."

Diphtheria infections can usually be treated with a number of classes of antibiotic. While C. diphtheriae resistant to antibiotics have been reported, the extent of such resistance remains largely unknown.

When the team looked for genes that might confer some degree of resistance to antimicrobials, they found that the average number of AMR genes per genome was increasing each decade. Genomes of bacteria isolated from infections from the most recent decade (2010-19) showed the highest average number of AMR genes per genome, almost four times as many on average than in the next highest decade, the 1990s.

Robert Will, a PhD student at CITIID and the study's first author, said: "The C. diphtheriae genome is complex and incredibly diverse. It's acquiring resistance to antibiotics that are not even clinically used in the treatment of diphtheria. There must be other factors at play, such as asymptomatic infection and exposure to a plethora of antibiotics meant for treating other diseases."

Erythromycin and penicillin are the traditionally recommended antibiotics of choice for treating confirmed cases of early-stage diphtheria, though there are several different classes of antibiotics available to treat the infection. The team identified variants resistant to six of these classes in isolates from the 2010s, higher than in any other decades.

Dr Pankaj Bhatnagar from the World Health Organization country office for India said: "AMR has rarely been considered as a major problem in the treatment of diphtheria, but in some parts of the world, the bacterial genomes are acquiring resistance to numerous classes of antibiotics. There are likely to be a number of reasons to this, including exposure of the bacteria to antibiotics in their environment or in asymptomatic patients being treated against other infections."

The researchers say that COVID-19 has had a negative impact on childhood vaccination schedules worldwide and comes at a time when reported case numbers are rising, with 2018 showing the highest incidence in 22 years.

Dr Ankur Mutreja from CITIID, who led the study, said: "It's more important than ever that we understand how diphtheria is evolving and spreading. Genome sequencing gives us a powerful tool for observing this in real time, allowing public health agencies to take action before it's too late.

"We mustn't take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form."

It is well-known that patients who undergo Fontan surgery slowly develop liver fibrosis for years post-operatively. In the past decade, these incidences have been steadily increasing and this is due partly to the need for an accurate diagnostic method. A research group led by Dr. Daisuke Tokuhara, Associate Professor of Pediatrics, Osaka City University Graduate School of Medicine and Dr. Yuki Cho have found that the conventional methods of ultrasound elastography and biomarkers via blood tests do not show the actual status of postoperative liver fibrosis. Their findings have been published in Hepatology Research.

With a sample size of 22 postoperative patients, their illumination into this matter was 3-prong.

Frist, the team observed dilation of the sinusoid during a long-term period post-Fontan surgery, with moderate fibrosis extending from the sinusoidal region to the portal vein region in about half of the patients, and a severe form developing in 30% of the patients. "After Fontan surgery, we believe as central venous pressure increases and the sinusoids dilate, fibrosis spreads from the sinusoidal region to the portal vein region", states Professor Tokuhara. Contrast this with hepatitis C and B, which are well-known causes of cirrhosis, where fibrosis is observed mainly in the portal region.

Then the team tested this unique regional development of fibrosis. Using a method of investigation that measures liver stiffness called ultrasound elastography, they found that the score did not significantly relate to liver fibrosis after Fontan surgery because the liver hardness tended to be related to portal pressure.

Next, they diagnosed liver fibrosis by looking for the elements that are naturally present as a result of the diseases progression. The research team investigated a variety of these fibrosis biomarkers from blood tests. Analysis of hyaluronic acid, type 4 collagen 7s, APRI, FIB-4 Index, and FibroTest did not render any association with the liver fibrosis score after Fontan surgery. The biomarker M2BPGi showed a significant inverse U-shaped association with postoperative liver fibrosis score, "but this cannot be used in a clinical practice", says Dr. Cho.

The team concluded that the complication with long-term care after Fontan surgery lies in a specific liver fibrosis that is difficult to assess using conventional methods. "Postoperative patients should receive regular medical care at specialized medical institutions for the presence of liver complications for at least 10 years after surgery, and until useful biomarkers and imaging techniques are established", advises Dr. Tokuhara. "We will use the liver tissue and serum obtained from this study to continue our search for the world`s first biomarker for liver fibrosis specific to post-Fontan surgery."