Multidisciplinary Team Of Scientists Research Articles

Development of systematic care pathways to tackle multimorbidity in elderly patients with atrial fibrillation: results of a Delphi process among the Horizon 2020 EHRA-PATHS investigators

Abstract Background Atrial fibrillation (AF) is the result of underlying diseases and many underlying comorbidities impact clinical outcomes. Elderly AF patients (≥65 years) have on average five comorbidities. Comorbidity management requires a systematic approach and interdisciplinary care pathways, which are lacking in most care settings. The EHRA-PATHS H2020 project No. 945260, coordinated by EHRA and ESC, aims to tackle this problem. Purpose Searching consensus on the development of care pathways to systematically address multimorbidity in elderly patients with AF. Methods The EHRA-PATHS project comprises a consortium of 14 partners from 11 different European countries. Each partner comprised at least one other specialty besides cardiology, forming a multidisciplinary scientific team. Several steps were executed to develop care pathways for each comorbidity or risk factor, while guarding the overall feasibility of patient evaluation. (i) An extensive literature study identified the most common and relevant AF-related comorbidities. (ii) Groups of consortium partners created uniformly structured templates for each comorbidity care pathway through online meetings and discussions. (iii) A Two-Round Delphi study was performed to obtain consortium consensus on the final pathways, with experts reviewing the care pathway templates (for which they felt qualified). Templates with insufficient agreement (i.e. <80%) during Round 1 were adapted and presented during Round 2 for re-evaluation. The second Delphi Round was also used to rank/prioritize all the comorbidities for their impact on the clinical outcome of AF patients, and a grouping in those with mandatory vs. optional evaluation in AF patients. Results The literature study led to the initial identification of 22 different AF-related comorbidities, which was adjusted to 23 comorbidities after Delphi Round 1. The Delphi survey was sent to 37 experts from the consortium (Round 1: n=28 and Round 2: n=27 responses). After Round 1, 13 comorbidity templates had an agreement ≥80% and 9 comorbidities did not (Figure 1A). Based on these results, 12 comorbidities were included in Delphi Round 2 (since physical (in)activity and polypharmacy were added due to major adjustments, and osteoporosis was considered a separate comorbidity). After Round 2, 8 of these 12 comorbidity templates received an agreement ≥80% (Figure 1B). The final 4 comorbidity templates were finalized after further expert discussion. In the group of ‘mandatory’ comorbidities, hypertension, heart failure and overweight were seen as the most important ones. Sleep apnoea, low medication adherence and mild cognitive impairment, dementia, frailty were the top optional comorbidities. Conclusion A structured process of expert meetings and two Delphi Rounds led to the development and ranking of 23 care pathways to evaluate and manage comorbidities in AF patients. All pathways will now be combined and implemented into a decision support software system.Figure 1

Cholesterol Metabolism in Cancer and Cell Death.

Significance: Cholesterol is a type of lipid that plays a crucial role in building and maintaining cell membranes, producing certain hormones, and aiding in digestion. The two main types of cholesterol are low-density lipoprotein and high-density lipoprotein, and maintaining a healthy balance between them is essential for cellular function and organism health. Recent Advances: Cholesterol metabolism is a complex and dynamic process that involves biosynthesis, uptake, efflux, transport, and esterification. Disruptions in cholesterol metabolism are implicated in all stages of cancer, contributing to drug resistance, immune evasion, and autophagy dysfunction. These disruptions have also been linked to various types of regulated cell death, such as apoptosis, anoikis, lysosome-dependent cell death, pyroptosis, NETosis, necroptosis, entosis, ferroptosis, alkaliptosis, immunogenic cell death, and paraptosis. Critical Issues: Understanding the complex interplay between cholesterol metabolism and cell death and their impact on cancer development and progression is still a significant challenge. In addition, there is currently a lack of reliable biomarkers that can accurately reflect cholesterol metabolism dysregulation in cancer. Future Directions: To develop more specific and effective cholesterol metabolism-targeted therapies, a better understanding of the mechanisms by which cholesterol metabolism dysregulation contributes to cell death and cancer progression is needed. In addition, improving the accuracy and reliability of biomarkers will be crucial for monitoring and diagnosing cholesterol-related cancer subtypes and evaluating the effectiveness of cholesterol metabolism-targeted therapies. These efforts will require ongoing research and collaboration among multidisciplinary teams of scientists and clinicians. Antioxid. Redox Signal. 39, 102-140.

Digital Health Games for Older Adults: Development, Implementation, and Programmatic Implications of Health Game Use in Senior Centers

AbstractBy 2030, an estimated 21.6% of the U.S. population will exceed 65 years old. Within this demographic, ongoing broad efforts are needed to address modifiable factors related to common chronic conditions of aging. Digital, or “serious,” health games offer one innovative approach to reach and engage older adults, with documented positive impacts on physical, mental/cognitive, and social health. Informed by healthy aging theory and community‐engaged, user‐centered design methods, our multidisciplinary team has developed a prototype multicomponent educational exergame designed to educate about and promote healthy lifestyle behaviors (i.e., healthy eating, physical activity), stimulate cognitive functioning, engage movement, and promote social connection. Additionally, we included functional near infrared spectroscopy (fNIRS) in our pilot work to measure real time brain activation during gameplay. Our objectives are to: 1) describe the formative development and testing process of an example multi‐component educational exergame, including multidisciplinary team science collaboration, application of aging theory, and use of community‐engaged and user‐centered approaches; and 2) present a pilot study examining implementation and multiple aspects of an innovative educational exergame, including usability, acceptability, preliminary impact, and cognitive function measurement using brain imaging technology (fNIRS) to measure changes in cognitive load during gameplay. The results provide initial support for acceptability, usability, and positive perceived impact, as well as the preliminary encouraging pre to post improvements in behavioral intention, content knowledge, and relative neural efficiency. This paper also explores the potential of implementing serious health games in senior centers as part of their regular programming.

Blunt Force Skeletal Trauma Research Methods

A key component of the forensic anthropological examination is skeletal trauma analysis, which accounts for the majority of forensic anthropologists’ expert testimonies. However, a major gap in the current knowledge surrounding skeletal trauma has been identified, specifically the data necessary to conduct comprehensive bone trauma analysis with established error rates are lacking. Current methods and standards of skeletal blunt force trauma analysis rarely meet Daubert guidelines that require: (1) validated studies, (2) peer review, (3) known or potential error rate, and (4) general acceptance, nor do they provide data or analyses that are comprehensible to the medicolegal community and the general public. Therefore, a multidisciplinary approach with a biomechanical emphasis is critical to improve the validity of skeletal trauma analysis and interpretation through precise, accurate, and repeatable analytical methods. The objectives of this review are to: (1) provide an overview of current approaches to blunt force skeletal trauma research across disciplines while highlighting the applications, strengths, and limitations of these methods, and (2) address gaps in discipline-specific methodologies to emphasize the importance of multidisciplinary scientific teams for improvement of skeletal trauma research. This review highlights the need for large-scale controlled experimental bone trauma studies utilizing human specimens and the various methodologies available for further skeletal trauma research.

Addressing diversity and inclusion challenges in global neuro-psychiatric and behavioral genomics research.

Advancements in neuro-psychiatric and behavioral genomics offer significant opportunities for better understanding the human brain, behavior and associated disorders. Such advancements may help us prevent, manage and/or cure complex conditions. The serious challenge confronted by these disciplines however is diversity. Both fields lack diversity in terms of genomic reference datasets needed for discovery research, engagement of diverse communities in translational research and in terms of diverse and multidisciplinary scientific teams. This is a challenge because diversity is needed on all levels in order to increase representation and inclusion of all populations across the globe as we move research activities forward. The lack of diversity can translate to an inability to use scientific innovations from these fields for the benefit of all people everywhere and signifies a missed opportunity to address pervasive global health inequities. In this commentary we identify three persistent barriers to reaching diversity targets while focusing on discovery and translational science. Additionally, we propose four suggestions on how to advance efforts and rapidly move towards achieving diversity and inclusion in neuro-psychiatric and behavioral genomics. Without systematically addressing the diversity gap within these fields, the benefits of the science may not be relevant and accessible to all people.

The role of exercise in the treatment of depression: biological underpinnings and clinical outcomes.

Globally, depression is a leading cause of disability and has remained so for decades. Antidepressant medications have suboptimal outcomes and are too frequently associated with side effects, highlighting the need for alternative treatment options. Although primarily known for its robust physical health benefits, exercise is increasingly recognized for its mental health and antidepressant benefits. Empirical evidence indicates that exercise is effective in treating individuals with depression; however, the mechanisms by which exercise exerts anti-depressant effects are not fully understood. Acute bouts of exercise have been shown to transiently modulate circulating levels of serotonin and norepinephrine, brain-derived neurotrophic factor, and a variety of immuno-inflammatory mechanisms in clinical cohorts with depression. However, exercise training has not been demonstrated to consistently modulate such mechanisms, and evidence linking these putative mechanisms and reductions in depression is lacking. The complexity of the biological underpinnings of depression coupled with the intricate molecular cascade induced by exercise are significant obstacles in the attempt to disentangle exercise's effects on depression. Notwithstanding our limited understanding of these effects, clinical evidence uniformly argues for the use of exercise to treat depression. Regrettably, exercise remains underutilized despite being an accessible, low-cost alternative/adjunctive intervention that can simultaneously reduce depression and improve overall health. To address the gaps in our understanding of the clinical and molecular effects of exercise on depression, we propose a model that leverages systems biology and multidisciplinary team science with a large-scale public health investment. Until the science matches the scale of complexity and burden posed by depression, our ability to advance knowledge and treatment will continue to be plagued by fragmented, irreproducible mechanistic findings and no guidelines for standards of care.

Utility of HIV support groups in advancing implementation research in resource-limited settings: experiences from an urban-setting HIV support group in Zimbabwe

Support groups for people living with the Human Immunodeficiency Virus (HIV) have continued to evolve since their emergence over two decades ago. In addition to providing HIV education and fostering psychosocial support, recent efforts have shifted the focus to socio-economic activities and retention in care. The sense of urgency to adopt new treatment and prevention strategies in sub-Saharan Africa necessitates greater engagement of established HIV care programs, especially among researchers seeking to conduct implementation research, promote prevention strategies and optimize treatment as prevention. To maximize the utility of support groups in doing so, efforts to create an organized, collaborative framework should be considered. This paper aims to describe the process of refocusing an adult HIV peer-support group and illustrate how a structured program was strengthened to sustain implementation research in resource-limited settings, while promoting patient recruitment and retention. A multidisciplinary team of scientists supporting an HIV peer-support group spearheaded the implementation process that authored the successes, challenges and lessons documented over eight years. Psychosocial support, nutrition care and support, adherence education and income generating projects were the main interventions employed. The initiative resulted in seven peer-reviewed publications, submission of 23 scientific abstracts, scientific dissemination at 12 international conferences. Eleven research studies and 16 income generating projects were successfully conducted over eight years. More than 900 patients participated in peer-support group activities every month and 400 were engaged in income generating activities. This multidisciplinary structured program was valuable in the retention and recruitment of patients for implementation research and benefits extended to psychosocial support, microeconomic projects, and improved nutrition. The support group contributed to strengthening implementation research through providing a platform for identification of research priorities, patient recruitment and retention in studies and dissemination of research findings.

Secondary Use of Electronic Medical Record Data from Primary Health Care is Feasible: Report from RADAR Project

Objectives It is difficult to obtain longitudinal 'real world' data from ambulatory medical care in Germany in a systematic way. Our vision is a large German research data repository featuring representative, anonymized patient and outpatient health care data, longitudinal, continuously updated and across different providers, offering a perspective of linking secondary care data or additional data obtained from research cohorts, for example patient reported data or biodata, and will be accessible for other researchers. Here we report specific methods and results from the RADAR project.Methods Survey of legislation, design of technical processes and organisational solutions, with a feasibility study to evaluate technical and content functionality, acceptability and performance fitness for health services research questions.Results In 2016, a multi-disciplinary scientific team initiated the development of a privacy protection and IT security concept for data exported from the electronic medical records (EMR) of physicians' practices in line with the European General Data Protection Regulation. Technical and organisational requirements for lawful research infrastructure were developed and executed for use in a specific case, namely ̒oral anticoagulation'. In 7 Lower Saxonian general practices, 100 patients were selected by their physician and their data - reduced to 40 essential data fields - extracted from EMR via a mandatory software interface after informed consent. Still in the practice, the data were split into identifying or medical data. These were encrypted and transferred either to a trusted third party (TTP) or to a data repository, respectively. 75 patients who met our inclusion criteria (minimum of one year of oral anticoagulation treatment) received a quality-of-life questionnaire via the TTP. Of the 66 returns, 63 responses were then linked to the EMR data in the repository.Conclusion Results from RADAR project proved the technical and organisational feasibility of lawful, pseudonymised data acquisition and the linkage of questionnaires to EMR data. The protecting concepts privacy by design and data minimization (Art. 25 GDPR with Recital 78) were implemented. Without informed consent, secondary use of routine data from ambulatory care which are sufficiently anonymized but still meaningful is all but impossible under current German law.

Co-production of knowledge reveals loss of Indigenous hunting opportunities in the face of accelerating Arctic climate change

Profound sea ice loss is rapidly transforming coupled social-ecological Arctic marine systems. However, explicit impacts to harvesting of traditional resources for coastal Indigenous communities remain largely unquantified, particularly where the primary research questions are posed by the Indigenous community as a result of emerging approaches such as knowledge co-production. Here, we directly link reduced sea ice coverage to decreasing harvesting opportunities for ugruk (bearded seal, Erignathus barbatus) as a component of a partnership among a multidisciplinary team of scientists, Indigenous Elder Advisory Council, and sovereign Indigenous tribe in northwest Alaska, USA. We collaboratively established research questions, coordinated data collection, and interpreted results to understand the causes and consequences of changing ugruk harvests for the community of Qikiqtaġruk (Kotzebue). The duration of spring ugruk hunts by the Qikiqtaġruŋmiut declined significantly during 2003–2019 due to a shift (∼3 weeks earlier) in the timing of regional sea ice breakup. Harvests now cease ∼26 d earlier than in the past decade. Using historical sea ice records, we further demonstrate that ice coverage in May now resembles conditions that were common in July during the mid-20th century. Overall, we show that climate change is constraining hunting opportunities for this traditional marine resource, although Qikiqtaġruŋmiut hunters have so far been able to offset a shortened season with changes in effort. Notwithstanding recent hunting success in unprecedentedly sparse ice conditions, accessibility to traditional resources remains a prominent concern for many Arctic communities. Management and policy decisions related to Arctic marine mammal resources, such as ugruk, are therefore also interwoven with food security, well-being, and culture of Indigenous communities. Hence, research that originates with Indigenous sovereignty over the entire research process, such as demonstrated here, has the potential to also lead to more inclusive, sustainable, and equitable outcomes in the face of rapid and accelerating Arctic change.

Sample Identifiers and Metadata to Support Data Management and Reuse in Multidisciplinary Ecosystem Sciences

Physical samples are foundational entities for research across biological, Earth, and environmental sciences. Data generated from sample-based analyses are not only the basis of individual studies, but can also be integrated with other data to answer new and broader-scale questions. Ecosystem studies increasingly rely on multidisciplinary team-science to study climate and environmental changes. While there are widely adopted conventions within certain domains to describe sample data, these have gaps when applied in a multidisciplinary context. In this study, we reviewed existing practices for identifying, characterizing, and linking related environmental samples. We then tested practicalities of assigning persistent identifiers to samples, with standardized metadata, in a pilot field test involving eight United States Department of Energy projects. Participants collected a variety of sample types, with analyses conducted across multiple facilities. We address terminology gaps for multidisciplinary research and make recommendations for assigning identifiers and metadata that supports sample tracking, integration, and reuse. Our goal is to provide a practical approach to sample management, geared towards ecosystem scientists who contribute and reuse sample data.

Effects of psychosocial interventions among people cared for in emergency departments after a suicide attempt: a systematic review protocol

BackgroundThe care of the emergency department (ED) for a person after a suicide attempt can act as a protector against future suicidal behavior. For this reason, it is essential that the ED ensure an assistance that involves effective interventions in preventing suicidal behaviors. Among suicidal behaviors, it is known that suicide attempt is one of the most lethal risk factors for consummated suicide. In addition, the risk for further attempts is greater in the period from the immediate post-discharge up to 12 months after the last attempt. This makes the ED a key link in the suicide prevention chain. The purpose of this review is to investigate the effects of psychosocial interventions on suicide prevention, when applied in the ED after a suicide attempt.MethodsThis systematic review protocol was built and registered with the collaboration of a multidisciplinary scientific team. The review will include randomized clinical studies, quasi-experimental trials, and comparative observational studies, all conducted with people (11 years old or more) who have received a psychosocial suicide prevention intervention initiated in the ED after a suicide attempt. The research will be conducted across databases such as Cochrane Library, PubMed, EMBASE, PsycINFO, and DARE. The repetition of a suicide attempt and death by suicide as primary outcomes will be analyzed. The eligibility of the studies and data extraction will be carried out by matched and blind researchers. The risk of bias will be addressed using appropriate instruments. The analyses and synthesis of the results will be both qualitative and quantitative.DiscussionFrom a public health point of view, suicide is in itself a public health problem and requires appropriate interventions at different levels of care in order to be prevented. Taking into account that a high percentage of people who died by suicide sought the ED for suicide attempt in the year before their death, the ED is a clinical context with a privileged potential to implement these interventions. Presently, several clinical studies seek to validate interventions to be adopted regarding the prevention of suicidal behavior. Current evidence indicates that different interventions must be strategically combined to reduce suicide attempts and their mortality.Systematic review registrationPROSPERO registration number CRD42019131040

Adding Rigor to Biomarker Evaluations-EDRN Experience.

The cancer early-detection biomarker field was, compared with the therapeutic arena, in its infancy when the Early Detection Research Network (EDRN) was initiated in 2000. The EDRN has played a crucial role in changing the culture and the ways people conduct biomarker studies. The EDRN proposed biomarker developmental guidelines and biomarker pivotal trial study design standards, created biomarker reference sets and functioned as an unbiased broker for the field, implemented the most rigorous blinding policy in the biomarker field, developed an array of statistical and computational tools for early-detection biomarker evaluations, and developed a multidisciplinary team-science approach. We reviewed these contributions made by the EDRN and their impacts on maturing the field. Future challenges and opportunities in cancer early-detection biomarker translational research are discussed, particularly in strengthening biomarker discovery pipeline and conducting more efficient biomarker validation studies.See all articles in this CEBP Focus section, "NCI Early Detection Research Network: Making Cancer Detection Possible."

Abstract IA-20: Team science: Lessons from a few decades on the pancreatic cancer research team

Abstract With the exception of a few examples of solitary genius embodied by Alfred Russell Wallace and Gregor Mendel, biomedical research has arguably always been a team sport. However, the genomic era has been associated with the increasing realization that large, multi-disciplinary scientific teams are required to push forward ambitious research programs combining computational and experimental work. At the same time, institutional promotions and tenure committees are increasingly recognizing participation and success in “team science” as worthy criteria for academic advancement. Opportunities for multi-institutional and multi-disciplinary collaboration are especially abundant in pancreatic cancer research, as our field is known for its particularly strong sense of community and for its collegial and collaborative spirit. Motivations for pursuing collaborative team science vary widely, and include the need to assemble the necessary workforce required to complete an ambitious body of work, transcend individual research disciplines, provide optimal educational opportunities for trainees, defuse unproductive competition, avoid being “scooped”, and simply to build fulfilling lifelong relationships with scientific colleagues. There are also many strategies by which investigators can effectively pursue team science, not all of which involve multiple authorship. In this short talk, I will review these motivations and strategies, drawing on lessons learned during several decades on the pancreatic cancer research team. Citation Format: Steven D. Leach. Team science: Lessons from a few decades on the pancreatic cancer research team [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr IA-20.

4457 Adopting a Team Science Communication Module for Community-Partnered Teams

OBJECTIVES/GOALS: There is increased recognition that patients and community members are critical to creating impactful research. To this end the UCLA CTSI Community Engagement & Research Program modified an established multidisciplinary team science communication module to train academic-community research teams. METHODS/STUDY POPULATION: Community partners who have had previous experience in participatory research provided input such as limiting the emphases of individual academic introductions to group icebreakers (to level the playing field), reduced academic jargon to lay language, reducing the amount of text to key principles, and changed academic team scenarios for the team activity to represent community-academic teams. Academic partners articulated institutional barriers to integrating community into institutional systems. Iterative testing and modifications occurred through pilots with eleven teams (49 individuals). RESULTS/ANTICIPATED RESULTS: Embedding community partners in team science training involved creating a level playing field with less emphasis on academic credentials, using lay language in the didactic sessions and ensuring accessibility in all aspects of the training. An example of modifications: communication scenarios were read out loud by participants, which community partners felt were not inclusive of potential varying literacy levels and all partners may not feel comfortable reading aloud in a group setting. The vignettes were replaced with short videos of the scenarios with audio recordings. Several modifications were made the training’s team activity of the training module. DISCUSSION/SIGNIFICANCE OF IMPACT: Traditional academic team science training required significant modifications for an academic/community-partnered team to allow for optimal collaboration, inclusion, and strategically reduce the power dynamics that can naturally occur. Long-term followup to assess their effectiveness is needed.

The Human Body as a Super Network: Digital Methods to Analyze the Propagation of Aging.

Biological aging is a complex process involving multiple biological processes. These can be understood theoretically though considering them as individual networks—e.g., epigenetic networks, cell-cell networks (such as astroglial networks), and population genetics. Mathematical modeling allows the combination of such networks so that they may be studied in unison, to better understand how the so-called “seven pillars of aging” combine and to generate hypothesis for treating aging as a condition at relatively early biological ages. In this review, we consider how recent progression in mathematical modeling can be utilized to investigate aging, particularly in, but not exclusive to, the context of degenerative neuronal disease. We also consider how the latest techniques for generating biomarker models for disease prediction, such as longitudinal analysis and parenclitic analysis can be applied to as both biomarker platforms for aging, as well as to better understand the inescapable condition. This review is written by a highly diverse and multi-disciplinary team of scientists from across the globe and calls for greater collaboration between diverse fields of research.

Abstract IA02: New structural insights into KRAS biology

Abstract Oncogenic mutations of RAS proteins are responsible for approximately 30% of all human cancers. Among the three RAS isoforms—HRAS, KRAS, and NRAS—KRAS is the most commonly mutated gene (in 86% of RAS-driven cancers) and the mutations are often present in pancreatic, colorectal, and lung cancers. Despite decades of research, no RAS inhibitors have reached the clinic. The NCI RAS Initiative at Frederick National Laboratory for Cancer Research (FNLCR) comprises multidisciplinary teams of scientists that are exploring innovative approaches for designing inhibitors against RAS-driven cancers. Structural biology efforts within the RAS Initiative are focused on solving structures of protein-small-molecule complexes and unraveling new structural insights into KRAS biology. RAS proteins act as binary molecular switches that cycle between active GTP-bound and inactive GDP-bound states. The conversion from inactive to the active form is stimulated by guanine nucleotide exchange factors (GEFs). Conversion back to the inactive form is mediated by GTPase-activating proteins (GAPs). In the active state, RAS proteins interact with a variety of effector proteins, such as RAF kinase, PI3K, and RalGDS, leading to activation of downstream signaling pathways. Oncogenic RAS mutations are predominantly found at amino acid positions G12, G13, and Q61 and impair intrinsic and GAP-mediated GTPase function. In this meeting, I will present our structural work on wild-type and oncogenic mutants of KRAS in the active state, and their complexes with various regulators. We recently solved structures of the most common oncogenic mutants of KRAS in the active state (bound to GMPPNP, a nonhydrolyzable analog of GTP). Structures of KRAS mutants in state 1 conformation show novel pockets that are likely to be amenable to in silico drug discovery approaches. We also solved structures of wild-type and mutant KRAS in complex with two major RasGAP proteins, RASA1/p120GAP and neurofibromin. Structures of RAS-GAP complexes provide insights into impaired GAP-mediated GTP hydrolysis process in the oncogenic mutants of KRAS. SPRED1, which causes Legius syndrome, functions as a negative regulator of the RAS-MAPK pathway and interacts with neurofibromin. Recent studies have shown that the EVH1 domain of SPRED1 binds to the GTPase activating protein-related domain of neurofibromin without interfering with its catalytic activity. Our structural work on a ternary complex consisting of KRAS, neurofibromin, and SPRED1 provides novel insights into the regulation of the RAS-MAPK pathway by neurofibromin and SPRED1. Structural studies on wild-type and oncogenic mutants of KRAS in the active state, and in complex with various regulators, have provided new insights into the KRAS biology as well as new blueprints for structure-based drug discovery approaches. Citation Format: Dhirendra K. Simanshu. New structural insights into KRAS biology [abstract]. In: Proceedings of the AACR Special Conference on Targeting RAS-Driven Cancers; 2018 Dec 9-12; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(5_Suppl):Abstract nr IA02.

Impact of Cognitive Impairment Across Specialties: Summary of a Report From the U13 Conference Series.

Although declines in cognitive capacity are assumed to be a characteristic of aging, increasing evidence shows that it is age-related disease, rather than age itself, that causes cognitive impairment. Even so, older age is a primary risk factor for cognitive decline, and with individuals living longer as a result of medical advances, cognitive impairment and dementia are increasing in prevalence. On March 26 to 27, 2018, the American Geriatrics Society convened a conference in Bethesda, MD, to explore cognitive impairment across the subspecialties. Bringing together representatives from several subspecialties, this was the third of three conferences, supported by a U13 grant from the National Institute on Aging, to aid recipients of Grants for Early Medical/Surgical Specialists' Transition to Aging Research (GEMSSTAR) in integrating geriatrics into their subspecialties. Scientific sessions focused on the impact of cognitive impairment, sensory contributors, comorbidities, links between delirium and dementia, and issues of informed consent in cognitively impaired populations. Discussions highlighted the complexity not only of cognitive health itself, but also of the bidirectional relationship between cognitive health and the health of other organ systems. Thus, conference participants noted the importance of multidisciplinary team science in future aging research. This article summarizes the full conference report, "The Impact of Cognitive Impairment Across Specialties," and notes areas where GEMSSTAR scholars can contribute to progress as they embark on their careers in aging research. J Am Geriatr Soc 67:2011-2017, 2019.

Transforming prenatal care: Multidisciplinary team science improves a broad range of maternal-child outcomes.

Every 8 seconds a baby is born in the United States. Maternal and newborn care are the nation's most expensive clinical services, and despite spending more per capita on health services, the United States experiences worse perinatal outcomes than most other developed countries, and even worse than many developing countries when it comes to maternal and infant mortality, preterm birth, and other comorbid conditions. We established a transdisciplinary clinical research team nearly 2 decades ago to improve maternal and child health through an innovative approach to maternal care delivery: group prenatal care. Our team has included psychologists (social, health, clinical, community), physicians (obstetrics, maternal fetal medicine, pediatrics), nurse-midwives, epidemiologists, biostatisticians, sociologists, social workers, and others. Though we come from different disciplines, we share a commitment to women's health, to using empirical evidence to design the best interventions, to social justice and health equity, and to transdisciplinary team science. In authentic collaboration, we have drawn on the best of each discipline to meet the triple aim (enhanced quality, improved outcomes, lower costs) for maternal care and to develop a deeper understanding of risk and protective factors for pregnant women and their families. This article describes how we leveraged and integrated our diverse perspectives to achieve these goals, including the theoretical and clinical foundations underlying the development and evaluation of the group prenatal care approach, research methodology employed, impact on the field, and lessons learned. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

The New Orleans Alcohol Use in HIV Study: Launching a Translational Investigation of the Interaction of Alcohol Use with Biological and Socioenvironmental Risk Factors for Multimorbidity in People Living with HIV.

Alcohol use disorders (AUDs) are highly prevalent in people living with HIV (PLWH) and are associated with increased HIV risk behaviors, suboptimal treatment adherence, potential interaction with medication pharmacodynamics, and greater risk for disease progression. Preclinical studies show that chronic binge alcohol administration accelerates disease progression and aggravates pathogenesis in the simian immunodeficiency virus (SIV)-infected rhesus macaque model despite viral suppression by antiretroviral therapy. To translate preclinical findings in the rhesus macaque model of chronic binge alcohol administration and SIV infection and to address areas of uncertainty surrounding the biological mechanisms and socioenvironmental modifiers that contribute to the relationship between alcohol use and HIV-associated comorbidities, precocious aging, and disease progression, we designed a translational multiproject, longitudinal, cohort study, and the New Orleans Alcohol Use in HIV (NOAH) Study. The NOAH Study is led by a multidisciplinary team of scientists, with a research focus on the interaction of AUD and HIV. The overarching hypothesis is that alcohol use will lead to adverse health outcomes in PLWH. In this report, we describe the study design and baseline descriptive characteristics of our cohort. Three-hundred and sixty-five participants completed the baseline testing. The cohort is predominantly male (69%) and African American (83.5%). The majority of participants report incomes below 200% of the federal poverty level. CD4 counts<200cells/μl were found in 12.8% and viral loads<50copies/ml were found in 73.6%. These HIV status variables did not differ based upon alcohol use. The NOAH Study facilitates bidirectional translational investigation of alcohol's impact on PLWH. Translation of preclinical findings to PLWH permits confirmation of basic biological mechanisms in humans and also allows incorporation of sociobehavioral factors that may affect biology but are challenging to replicate in preclinical models.

Adding the Team into T1 Translational Research: A Case Study of Multidisciplinary Team Science in the Evaluation of Biomarkers of Prostate Cancer Risk and Prognosis.

Given translational research challenges, multidisciplinary team science is promoted to increase the likelihood of moving from discovery to health effect. We present a case study documenting the utility of multidisciplinary team science in prostate cancer tissue biomarker validation. We used primary data generated by a team consisting of a pathologist, cancer biologists, a biostatistician, and epidemiologists. We examined their contributions by phase of biomarker evaluation to identify when, through the practice of team science, threats to internal validity were recognized and solved. Next, we quantified the extent of bias avoided in evaluating the association of Ki67 (immunohistochemistry), stromal cell telomere length (fluorescence in situ hybridization), and microRNA (miRNA) (miR-21, miR-141, miR-221; quantitative RT-PCR) with prostate cancer risk or recurrence in nested case-control studies. Threats to validity were tissue storage time (Ki67, miRNA) and laboratory equipment maintenance (telomeres). Solutions were all in the data analysis phase and involved using tissue storage-time specific cutpoints and/or batch-specific cutpoints. Bias in the regression coefficient for quantiles of each biomarker ranged from 24% to 423%, and the coefficient for the test for trend ranged from 15% to 910%. The interpretation of the associations changed as follows: Ki67, null to positive; stromal cell telomere length, null to positive; miR-21 and miR-141 remained null; miR-221, weak to moderate inverse. In this case study, we documented the inferential benefits of multidisciplinary team science when the team's collaboration and coordination led to the identification of threats to validity and the implementation of appropriate solutions.