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Abstract Background The Diabetes Prevention Program (DPP) is a nationally disseminated lifestyle intervention shown to prevent type 2 diabetes (diabetes). However, enrollment in the program remains variable. We sought to identify patient characteristics associated with enrollment in a virtual DPP program among women Veterans to inform ongoing diabetes prevention efforts. Methods We conducted a retrospective analysis of 2021–2024 Department of Veterans Affairs (VA) data collected through the VA Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER) 2.0 Program, an effectiveness-implementation trial to expand access to preventative health services for women Veterans. We included women meeting DPP eligibility criteria (BMI ≥ 25 kg/m2 [or ≥ 23 if Asian] with ≥ 1 risk factor for diabetes [e.g., prediabetes]) who received care at six VA sites implementing virtual DPP. We used logistic regression to examine the association between DPP enrollment and prior use of VA preventive services for weight management or diabetes prevention including the VA MOVE! clinic, Whole Health visits, nutrition visits, weight loss medications, and/or metformin. We adjusted for sociodemographic factors, comorbidities, number of DPP recruitment contacts, and site. Results A total of 1473 women Veterans received DPP outreach. On average, their age was 53 years (range 20–96), BMI 34 kg/m2, HbA1c 5.9%, 0.7% were Asian, 44% Black, 2% Hispanic, and 44% White. In our adjusted models, prior use of VA preventative services was not significantly associated with DPP enrollment. Younger women (OR:0.97, p = 0.002) and those who received more recruitment contacts (OR:2.63, p

Abstract Background Qualitative methods are a critical tool for enhancing implementation planning and tailoring, yet rapid turn-around of qualitative insights can be challenging in large implementation trials. The Department of Veterans Affairs-funded EMPOWER 2.0 Quality Enhancement Research Initiative (QUERI) is conducting a hybrid type 3 effectiveness-implementation trial comparing the impact of Replicating Effective Programs (REP) and Evidence-Based Quality Improvement (EBQI) as strategies for implementing three evidence-based practices (EBPs) for women Veterans. We describe the development of the Rapid Implementation Feedback (RIF) report, a pragmatic, team-based approach for the rapid synthesis of qualitative data to aid implementation planning and tailoring, as well as findings from a process evaluation of adopting the RIF report within the EMPOWER 2.0 QUERI. Methods Trained qualitative staff conducted 125 semi-structured pre-implementation interviews with frontline staff, providers, and leadership across 16 VA sites between October 2021 and October 2022. High-priority topic domains informed by the updated Consolidated Framework for Implementation Research were selected in dialogue between EMPOWER 2.0 implementation and evaluation teams, and relevant key points were summarized for each interview to produce a structured RIF report, with emergent findings about each site highlighted in weekly written and verbal communications. Process evaluation was conducted to assess EMPOWER 2.0 team experiences with the RIF report across pre-implementation data collection and synthesis and implementation planning and tailoring. Results Weekly RIF updates supported continuous EMPOWER 2.0 team communication around key findings, particularly questions and concerns raised by participating sites related to the three EBPs. Introducing the RIF report into team processes enhanced: team communication; quality and rigor of qualitative data; sensemaking around emergent challenges; understanding of site readiness; and tailoring of REP and EBQI implementation strategies. RIF report findings have facilitated rapid tailoring of implementation planning and rollout, supporting increased responsiveness to sites’ needs and concerns. Conclusions The RIF report provides a structured strategy for distillation of time-sensitive findings, continuous team communication amid a complex multi-site implementation effort, and effective tailoring of implementation rollout in real-time. Use of the RIF report may also support trust-building by enhancing responsiveness to sites during pre- and early implementation. Trial registration Enhancing Mental and Physical Health of Women Veterans (NCT05050266); https://clinicaltrials.gov/study/NCT05050266?term=EMPOWER%202.0&rank=1 Date of registration: 09/09/2021.

Introduction: Only 53% of American adults receive influenza vaccination, and disparities in vaccination exist among particular racial and ethnic groups. This study determines how race, ethnicity, sex, and rurality are associated with influenza vaccination adherence in a national Veteran Health Affairs Administration cohort. Methods: The authors examined differences in documented influenza vaccinations for the 2019–2020 influenza season among Veteran Health Affairs Administration patients in a retrospective cohort study using Veteran Health Affairs Administration administrative electronic health record data. The author used logistic regression to model receipt of influenza vaccination in association with race, ethnicity, sex, and rurality while controlling for clinical diagnoses, demographics, and ambulatory care utilization. The authors also stratified the models by sex and rurality. Results: Among 5,943,918 veterans, 48.6% received influenza vaccination. Unadjusted comparisons showed that those who were vaccinated were more likely to be White, to be of male sex, and to be older. Similar proportions of unvaccinated and unvaccinated veterans were from rural settings. In adjusted models, Black race was most strongly associated with decreased vaccination (AOR=0.69; 95% CI=0.69, 0.70), and American Indian/Alaskan Native race also had reduced odds of vaccination (AOR=0.94; 95% CI=0.92, 0.95) compared with White race. Female veterans had increased odds of vaccination (AOR=1.20; 95% CI=1.19, 1.20) compared with men. Rurality (AOR=0.97; 95% CI=0.96, 0.97) was associated with a small decreased odds of vaccination compared with urban. In stratified models, Black veterans were less likely to receive influenza vaccination regardless of sex and rurality than White veterans. American Indian/Alaska Native female veterans had equal odds of vaccination as White female veterans, whereas American Indian/Alaska Native male veterans had reduced odds of vaccination compared with White male veterans. Conclusions: During the 2019–2020 influenza season, Black and American Indian/Alaskan Native veterans had lower odds of vaccination. Despite the Veteran Health Affairs Administration's universal approach to healthcare, racial disparities still exist in preventive care.

Endocytosis and endolysosomal trafficking are essential for almost all aspects of physiological functions of eukaryotic cells. As our understanding on these membrane trafficking events are mostly from studies in yeast and cultured mammalian cells, one challenge is to systematically evaluate the findings from these cell-based studies in multicellular organisms under physiological settings. One potentially valuable in vivo system to address this challenge is the vitellogenic oocyte in Drosophila, which undergoes extensive endocytosis by Yolkless (Yl), a low-density lipoprotein receptor (LDLR), to uptake extracellular lipoproteins into oocytes and package them into a specialized lysosome, the yolk granule, for storage and usage during later development. However, by now there is still a lack of sufficient understanding on the molecular and cellular processes that control yolk granule biogenesis. Here, by creating genome-tagging lines for Yl receptor and analyzing its distribution in vitellogenic oocytes, we observed a close association of different endosomal structures with distinct phosphoinositides and actin cytoskeleton dynamics. We further showed that Rab5 and Rab11, but surprisingly not Rab4 and Rab7, are essential for yolk granules biogenesis. Instead, we uncovered evidence for a potential role of Rab7 in actin regulation and observed a notable overlap of Rab4 and Rab7, two Rab GTPases that have long been proposed to have distinct spatial distribution and functional roles during endolysosomal trafficking. Through a small-scale RNA interference (RNAi) screen on a set of reported Rab5 effectors, we showed that yolk granule biogenesis largely follows the canonical endolysosomal trafficking and maturation processes. Further, the data suggest that the RAVE/V-ATPase complexes function upstream of or in parallel with Rab7, and are involved in earlier stages of endosomal trafficking events. Together, our study provides s novel insights into endolysosomal pathways and establishes vitellogenic oocyte in Drosophila as an excellent in vivo model for dissecting the highly complex membrane trafficking events in metazoan.

Abstract Background Women Veterans are the fastest-growing segment of Veterans Health Administration (VA) users. The VA has invested heavily in delivering care for women Veterans that is effective, comprehensive, and gender-tailored. However, gender disparities persist in cardiovascular (CV) and diabetes risk factor control, and the rate of perinatal depression among women Veterans is higher than that among civilian women. Challenges such as distance, rurality, negative perception of VA, discrimination (e.g., toward sexual and/or gender minority individuals), and harassment on VA grounds can further impede women’s regular use of VA care. Enhancing Mental and Physical Health of Women through Engagement and Retention (EMPOWER) 2.0 builds on work to date by expanding access to evidence-based, telehealth preventive and mental health services for women Veterans with high-priority health conditions in rural and urban-isolation areas. Methods EMPOWER 2.0 will evaluate two implementation strategies, Replicating Effective Practices (REP) and Evidence-Based Quality Improvement (EBQI), in supporting the implementation and sustainment of three evidence-based interventions (Virtual Diabetes Prevention Program; Telephone Lifestyle Coaching Program; and Reach Out, Stay Strong Essentials) focused on preventive and mental health care for women Veterans. We will conduct a mixed-methods implementation evaluation using a cluster-randomized hybrid type 3 effectiveness-implementation trial design to compare the effectiveness of REP and EBQI on improved access to and rates of engagement in telehealth preventive lifestyle and mental health services. Other outcomes of interest include (a) VA performance metrics for telehealth care delivery and related clinical outcomes; (b) progression along the Stages of Implementation Completion; (c) adaptation, sensemaking, and experiences of implementation among multilevel stakeholders; and (d) cost and return on investment. We will also generate implementation playbooks for program partners to support scale-up and spread of these and future evidence-based women’s health programs and policies. Discussion EMPOWER 2.0 provides a model for mixed-methods hybrid type 3 effectiveness-implementation trial design incorporating evaluation of performance metrics, implementation progress, stakeholder experience, and cost and return on investment, with the ultimate goal of improving access to evidence-based preventive and mental telehealth services for women Veterans with high-priority health conditions. Trial registration ClinicalTrials.gov, NCT05050266 . Registered on 20 September 2021.

Introduction: Race-, ethnicity-, and rurality-related disparities in COVID-19 vaccine uptake have been documented in the U.S. We determined whether these disparities existed among patients at the Department of Veterans Affairs, the largest healthcare system in the U.S. Methods: Using Department of Veterans Affairs Corporate Data Warehouse data, we included 5,871,438 patients (9.4% women) with at least 1 primary care visit in 2019 in a retrospective cohort study. Each patient was assigned a single race and ethnicity, which were mutually exclusive, self-reported categories. Rurality was based on the 2019 home address at the ZIP code level. Our primary outcome was time to first COVID-19 vaccination between December 15, 2020 and June 15, 2021. Additional covariates included age (in years), sex, geographic region (North Atlantic, Midwest, Southeast, Pacific, continental), smoking status (current, former, never), Charlson Comorbidity Index (based on ≥1 inpatient or 1 outpatient International Classification of Diseases codes), service connection (any/none, using standardized Department of Veterans Affairs cut offs for disability compensation), and influenza vaccination in 2019–2020 (yes/no). Results: Compared with unvaccinated patients, those vaccinated (n=3,238,532; 55.2%) were older (mean age in years vaccinated=66.3 [SD=14.4] vs unvaccinated=57.7 [18.0], p

BackgroundDigital cognitive behavioral therapy (CBT) interventions can effectively prevent and treat depression and anxiety, but engagement with these programs is often low. Although extensive research has evaluated program use as a proxy for engagement, the extent to which users acquire knowledge and enact skills from these programs has been largely overlooked. ObjectiveThis study aimed to investigate how skill enactment and knowledge acquisition have been measured, evaluate postintervention changes in skill enactment and knowledge acquisition, examine whether mental health outcomes are associated with skill enactment or knowledge acquisition, and evaluate predictors of skill enactment and knowledge acquisition. MethodsPubMed, PsycINFO, and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) published between January 2000 and July 2022. We included RCTs comparing digital CBT with any comparison group in adolescents or adults (aged ≥12 years) for anxiety or depression. Eligible studies reported quantitative measures of skill enactment or knowledge acquisition. The methodological quality of the studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for RCTs. Narrative synthesis was used to address the review questions. ResultsIn total, 43 papers were included, of which 29 (67%) reported a skill enactment measure and 15 (35%) reported a knowledge acquisition measure. Skill enactment was typically operationalized as the frequency of enacting skills using the completion of in-program activities (ie, formal skill enactment; 13/29, 45%) and intervention-specific (9/29, 31%) or standardized (8/29, 28%) questionnaires. Knowledge measures included tests of CBT knowledge (6/15, 40%) or mental health literacy (5/15, 33%) and self-report questionnaires (6/15, 40%). In total, 17 studies evaluated postintervention changes in skill enactment or knowledge acquisition, and findings were mostly significant for skill enactment (6/8, 75% of the studies), CBT knowledge (6/6, 100%), and mental health literacy (4/5, 80%). Of the 12 studies that evaluated the association between skill enactment and postintervention mental health outcomes, most reported ≥1 significant positive finding on standardized questionnaires (4/4, 100%), formal skill enactment indicators (5/7, 71%), or intervention-specific questionnaires (1/1, 100%). None of the 4 studies that evaluated the association between knowledge acquisition and primary mental health outcomes reported significant results. A total of 13 studies investigated predictors of skill enactment; only type of guidance and improvements in psychological variables were associated with increased skill enactment in ≥2 analyses. Predictors of knowledge acquisition were evaluated in 2 studies. ConclusionsDigital CBT for depression and anxiety can improve skill enactment and knowledge acquisition. However, only skill enactment appears to be associated with mental health outcomes, which may depend on the type of measure examined. Additional research is needed to understand what types and levels of skill enactment and knowledge acquisition are most relevant for outcomes and identify predictors of these constructs. Trial RegistrationPROSPERO CRD42021275270; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=275270

Perturbation of huntingtin (HTT)’s physiological function is one postulated pathogenic factor in Huntington’s disease (HD). However, little is known how HTT is regulated in vivo. In a proteomic study, we isolated a novel ~40kDa protein as a strong binding partner of Drosophila HTT and demonstrated it was the functional ortholog of HAP40, an HTT associated protein shown recently to modulate HTT’s conformation but with unclear physiological and pathologic roles. We showed that in both flies and human cells, HAP40 maintained conserved physical and functional interactions with HTT. Additionally, loss of HAP40 resulted in similar phenotypes as HTT knockout. More strikingly, HAP40 strongly affected HTT’s stability, as depletion of HAP40 significantly reduced the levels of endogenous HTT protein while HAP40 overexpression markedly extended its half-life. Conversely, in the absence of HTT, the majority of HAP40 protein were degraded, likely through the proteasome. Further, the affinity between HTT and HAP40 was not significantly affected by polyglutamine expansion in HTT, and contrary to an early report, there were no abnormal accumulations of endogenous HAP40 protein in HD cells from mouse HD models or human patients. Lastly, when tested in Drosophila models of HD, HAP40 partially modulated the neurodegeneration induced by full-length mutant HTT while showed no apparent effect on the toxicity of mutant HTT exon 1 fragment. Together, our study uncovers a conserved mechanism governing the stability and in vivo functions of HTT and demonstrates that HAP40 is a central and positive regulator of endogenous HTT. Further, our results support that mutant HTT is toxic regardless of the presence of its partner HAP40, and implicate HAP40 as a potential modulator of HD pathogenesis through its multiplex effect on HTT’s function, stability and the potency of mutant HTT’s toxicity. Author summary Abnormal polyglutamine expansion in huntingtin (HTT) protein causes neurodegenerative Huntington’s disease (HD). Given the complex and still unclear pathogenic mechanisms underlying HD, there is great interest in targeting HTT as a therapeutic strategy against HD. Accordingly, it is important to understand how HTT is normally regulated. In a proteomic study in Drosophila, we isolated a novel protein as a strong binding partner of fly HTT homolog and demonstrated that it was the functional counterpart of mammalian HAP40, a protein known to modulate HTT’s conformation but with unclear physiological and pathologic roles. We found that the physical and functional interactions of HTT with HAP40 were conserved from flies to human cells, and HAP40 was essential for HTT’s normal functions and protein stability, while in the absence of HTT, HAP40 was quickly cleared through the proteasome. Further, polyglutamine expansion in HTT protein did not affect its affinity for HAP40 or cause abnormal accumulation of HAP40 in HD cells. Lastly, we observed that HAP40 could modulate HD-associated neurodegeneration in fly models that expressed full-length mutant HTT. Together, our study demonstrates that HAP40 is a highly conserved and essential regulator of HTT and a potential candidate for achieving specific HTT-lowering in HD cells.

Abstract The modified Friedreich Ataxia Rating Scale (mFARS) is a disease specific, exam‐based neurological rating scale commonly used as a outcome measure in clinical trials. While extensive clinimetric testing indicates it’s validity in measuring disease progression, formal test–retest reliability was lacking. To fill this gap, we acquired results from screening and baseline visits of several large clinical trials and calculated intraclass correlation coefficients, coefficients of variance, standard error, and the minimally detectable changes. This study demonstrated excellent test–retest reliability of the mFARS, and it’s upright stability subscore.

Abstract The transcription factor, p53, is critical for many important cellular functions involved in genome integrity, including cell cycle control, DNA damage response, and apoptosis. Disruption of p53 results in a wide range of disorders including cancer, metabolic diseases, and neurodegenerative diseases. Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by protein aggregates that contribute to disease pathology. Although p53 is known to aggregate, its propensity to aggregate in AD has never been assessed. Moreover, AD neuropathology includes lethal cell cycle re-entry, excessive DNA damage, and abnormal cell death which are all controlled by p53. Here, we show p53 forms oligomers and fibrils in human AD brain, but not control brain. p53 oligomers can also be detected in htau and P301L mouse models. Additionally, we demonstrate that p53 interacts with tau, specifically tau oligomers, in AD brain and can be recapitulated by in vitro exogenous tau oligomer treatment in C57BL/6 primary neurons. p53 oligomers also colocalize, potentially seeding, endogenous p53 in primary neurons. Lastly, we demonstrate that in the presence of DNA damage, phosphorylated p53 is mislocalized outside the nucleus and p53-mediated DNA damage responders are significantly decreased in AD brain. Control brain shows a healthy DNA damage response, indicating a loss of nuclear p53 function in AD may be due to p53 aggregation and/or interactions with tau oligomers. Given the critical role of p53 in cellular physiology, the disruption of this crucial transcription factor may set an irreversible course towards neurodegeneration in AD and potentially other tauopathies, warranting further investigation.

Introduction: Presence of a firearm is associated with increased risk of violence and suicide. United States military veterans are at disproportionate risk of suicide. Routine healthcare provider screening of firearm access may prompt counseling on safe storage and handling of firearms. The objective of this study was to determine the frequency with which Veterans Health Administration (VHA) healthcare providers document firearm access in electronic health record (EHR) clinical notes, and whether this varied by patient characteristics. Methods: The study sample is a post-9–11 cohort of veterans in their first year of VHA care, with at least one outpatient care visit between 2012–2017 (N = 762,953). Demographic data, veteran military service characteristics, and clinical comorbidities were obtained from VHA EHR. We extracted clinical notes for outpatient visits to primary, urgent, or emergency clinics (total 105,316,004). Natural language processing and machine learning (ML) approaches were used to identify documentation of firearm access. A taxonomy of firearm terms was identified and manually annotated with text anchored by these terms, and then trained the ML algorithm. The random-forest algorithm achieved 81.9% accuracy in identifying documentation of firearm access. Results: The proportion of patients with EHR-documented access to one or more firearms during their first year of care in the VHA was relatively low and varied by patient characteristics. Men had significantly higher documentation of firearms than women (9.8% vs 7.1%; P < .001) and veterans >50 years old had the lowest (6.5%). Among veterans with any firearm term present, only 24.4% were classified as positive for access to a firearm (24.7% of men and 20.9% of women). Conclusion: Natural language processing can identify documentation of access to firearms in clinical notes with acceptable accuracy, but there is a need for investigation into facilitators and barriers for providers and veterans to improve a systemwide process of firearm access screening. Screening, regardless of race/ethnicity, gender, and age, provides additional opportunities to protect veterans from self-harm and violence.

Abstract Background Ethnography has been proposed as a valuable method for understanding how implementation occurs within dynamic healthcare contexts, yet this method can be time-intensive and challenging to operationalize in pragmatic implementation. The current study describes an ethnographically-informed method of guided discussions developed for use by a multi-project national implementation program. Methods The EMPOWER QUERI is conducting three projects to implement innovative care models in VA women’s health for high-priority health concerns – prediabetes, cardiovascular risk, and mental health – utilizing the Replicating Effective Programs (REP) implementation strategy enhanced with stakeholder engagement and complexity science. Drawing on tenets of ethnographic research, we developed a lightly-structured method of guided “periodic reflections” to aid in documenting implementation phenomena over time. Reflections are completed as 30–60 min telephone discussions with implementation team members at monthly or bi-monthly intervals, led by a member of the implementation core. Discussion notes are coded to reflect key domains of interest and emergent themes, and can be analyzed singly or in triangulation with other qualitative and quantitative assessments to inform evaluation and implementation activities. Results Thirty structured reflections were completed across the three projects during a 15-month period spanning pre-implementation, implementation, and sustainment activities. Reflections provide detailed, near-real-time information on projects’ dynamic implementation context, including characteristics of implementation settings and changes in the local or national environment, adaptations to the intervention and implementation plan, and implementation team sensemaking and learning. Reflections also provide an opportunity for implementation teams to engage in recurring reflection and problem-solving. Conclusions To implement new, complex interventions into dynamic organizations, we must better understand the implementation process as it unfolds in real time. Ethnography is well suited to this task, but few approaches exist to aid in integrating ethnographic insights into implementation research. Periodic reflections show potential as a straightforward and low-burden method for documenting events across the life cycle of an implementation effort. They offer an effective means for capturing information on context, unfolding process and sensemaking, unexpected events, and diverse viewpoints, illustrating their value for use as part of an ethnographically-minded implementation approach. Trial registration The two implementation research studies described in this article have been registered as required: Facilitating Cardiovascular Risk Screening and Risk Reduction in Women Veterans (NCT02991534); and Implementation of Tailored Collaborative Care for Women Veterans (NCT02950961).

Abstract Background We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson’s disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target. Methods We treated seven-month-old mice overexpressing mutated α-synuclein (A53T mice) with tau oligomer-specific monoclonal antibody (TOMA) and a control antibody and assessed both behavioral and pathological phenotypes. Results We found that A53T mice treated with TOMA were protected from cognitive and motor deficits two weeks after a single injection. Levels of toxic tau oligomers were specifically decreased in the brains of TOMA-treated mice. Tau oligomer depletion also protected against dopamine and synaptic protein loss. Conclusion These results indicate that targeting tau oligomers is beneficial for a mouse model of synucleinopathy and may be a viable therapeutic strategy for treating diseases in which tau and α-synuclein have a synergistic toxicity.

Abstract Background Parkinson’s disease (PD) is often accompanied by clinically identified depression. Providing effective pharmacotherapies that concomitantly treat both motor and psychological symptoms can pose a challenge to physicians. For this reason, alternatives to standard anti-depressant treatments, such as repetitive transcranial magnetic stimulation (rTMS), have been evaluated within the Parkinson’s population. Methods A literature search was conducted on the PubMed database for all studies that evaluated rTMS as a treatment in patients with both depression and PD. A meta-analysis was performed on all studies that reported mean pre- and post-rTMS depression inventory scores. Widely used depression inventories included both self-report and clinician-administered measures. Effect size for individual study groups and across all studies was calculated. Results Six of 7 studies meeting inclusion criteria reported significantly improved depression scores, large effect sizes, and significant p-values. Total weighted average effect size was calculated at 1.32 across all study groups that applied rTMS. Conclusions Across all but one study, rTMS appears to effectively reduce depression scores among self-reported and clinician administered inventories. The total weight average effect size showed that, when considering study sample sizes and degree of findings, this form of neurostimulation can relieve PD patients of their depressive symptoms. Further, rTMS is a promising alternative to traditional anti-depressant therapies when treating refractory depression in patients with PD.

Abstract Background The Enhancing Mental and Physical health of Women through Engagement and Retention or EMPOWER program represents a partnership with the US Department of Veterans Health Administration (VA) Health Service Research and Development investigators and the VA Office of Women’s Health, National Center for Disease Prevention and Health Promotion, Primary Care-Mental Health Integration Program Office, Women’s Mental Health Services, and the Office of Patient Centered Care and Cultural Transformation. EMPOWER includes three projects designed to improve women Veterans’ engagement and retention in evidence-based care for high-priority health conditions, i.e., prediabetes, cardiovascular, and mental health. Methods/Design The three proposed projects will be conducted in VA primary care clinics that serve women Veterans including general primary care and women’s health clinics. The first project is a 1-year quality improvement project targeting diabetes prevention. Two multi-site research implementation studies will focus on cardiovascular risk prevention and collaborative care to address women Veterans’ mental health treatment needs respectively. All projects will use the evidence-based Replicating Effective Programs (REP) implementation strategy, enhanced with multi-stakeholder engagement and complexity theory. Mixed methods implementation evaluations will focus on investigating primary implementation outcomes of adoption, acceptability, feasibility, and reach. Program-wide organizational-, provider-, and patient-level measures and tools will be utilized to enhance synergy, productivity, and impact. Both implementation research studies will use a non-randomized stepped wedge design. Discussion EMPOWER represents a coherent program of women’s health implementation research and quality improvement that utilizes cross-project implementation strategies and evaluation methodology. The EMPOWER Quality Enhancement Research Initiative (QUERI) will constitute a major milestone for realizing women Veterans’ engagement and empowerment in the VA system. EMPOWER QUERI will be conducted in close partnership with key VA operations partners, such as the VA Office of Women’s Health, to disseminate and spread the programs nationally. Trial registration The two implementation research studies described in this protocol have been registered as required: Facilitating Cardiovascular Risk Screening and Risk Reduction in Women Veterans: Trial registration NCT02991534 , registered 9 December 2016. Implementation of Tailored Collaborative Care for Women Veterans: Trial registration NCT02950961 , registered 21 October 2016.

Background: Friedreich's ataxia (FRDA) is a characterized by progressive loss of coordination and balance leading to loss of ambulation (LoA) in nearly all affected individuals. While transition to becoming fully wheelchair bound is a critical milestone in the disease course, it presents a particularly challenging prediction, mostly due to variability in inter- and intra-subject severity and progression. For these reasons, LoA or potential surrogates have been impractical as outcomes in clinical trials. Methods: We studied progressive features leading to LoA in participants enrolled into the Friedreich's Ataxia Clinical Outcome Measures Study (FA-COMS), a natural history study with currently 4606 yearly follow up visits in 1021 patients. Loss of specific functions related to walking and standing of the neurological Friedreich Ataxia Rating Scale (FARS) exams were evaluated using time to event methods. To account for different severities, patients were stratified by age of disease onset. Findings: Early onset FRDA patients (

The spin frustrated magnetism of the 2-D molecular magnet material Cu9Cl2(cpa)6 (cpa = anion of 2-carboxypentonic acid), abbreviated as CPA, has been the subject of experimental and theoretical studies that suggest this Heisenberg lattice may be among the most frustrated of materials, along with other Kagome, garnet and pyrochlore systems. The CPA framework is a triangles-in-triangles, or a triangulated-Kagome-lattice (TKL) for which M(T,H) phase diagrams rich in topologically induced spin-liquid states should result from deliberate chemical manipulations. While the spin frustrated topology of CPA makes it of interest for the fundamental physics of quantum spin liquids (QSLs), we report here that the low temperature magnetothermodynamic properties also make it of interest for the study of the magnetocaloric effect (MCE). Highly frustrated materials that do not have clearly distinctive first- or second-order phase transitions can have MCEs due to the persistent entropy of low-lying eigenstates with large degrees of degeneracy. We present field-dependent data up to H = 1T that allow estimates for the MCE of CPA to be calculated from magnetization and demonstrate that a H-T phase boundary exists for temperatures above T = 2K in applied fields below H = 1T. When taken in combination with the phase boundary discovered in the heat capacity data below T = 2K, as well as synthetic results that demonstrate CPA can be taken as a broad materials class, the presence of this second phase boundary suggest chemical variations should present tremendous opportunity to design additional materials. The synthetic challenge will be to produce high quality crystals with consistent, well-understood chemical compositions.

Although it is clear that the accident signatures from each affected unit at the Fukushima Daiichi Nuclear Power Station [Daiichi] differ, much is not known about the end-state of core materials within these units. Some of this uncertainty can be attributed to a lack of information related to cooling system operation and cooling water injection. There is also uncertainty in our understanding of phenomena affecting: a) in-vessel core damage progression during severe accidents in boiling water reactors (BWRs), and b) accident progression after vessel failure (ex-vessel progression) for BWRs and Pressurized Water Reactors (PWRs). These uncertainties arise due to limited full scale prototypic data. Similar to what occurred after the accident at Three Mile Island Unit 2, these Daiichi units offer the international community a means to reduce such uncertainties by obtaining prototypic data from multiple full-scale BWR severe accidents. Information obtained from Daiichi is required to inform Decontamination and Decommissioning activities, improving the ability of the Tokyo Electric Power Company (TEPCO) to characterize potential hazards and to ensure the safety of workers involved with cleanup activities. This paper reports initial results from the US Forensics Effort to utilize examination information obtained by TEPCO to enhance the safety of existing and future nuclear power plant designs. In this paper, three examples are presented in which examination information, such as visual images, dose surveys, sample evaluations, and muon tomography examinations, along with data from plant instrumentation, are used to obtain significant safety insights in the areas of component performance, fission product release and transport, debris end-state location, and combustible gas generation and transport. In addition to reducing uncertainties related to severe accident modeling progression, these insights confirm actions, such as the importance of water addition and containment venting, that are emphasized in updated guidance for severe accident prevention, mitigation, and emergency planning.

Abstract Background Stepped wedge designs have gained recognition as a method for rigorously assessing implementation of evidence-based quality improvement interventions (QIIs) across multiple healthcare sites. In theory, this design uses random assignment of sites to successive QII implementation start dates based on a timeline determined by evaluators. However, in practice, QII timing is often controlled more by site readiness. We propose an alternate version of the stepped wedge design that does not assume the randomized timing of implementation while retaining the method’s analytic advantages and applying to a broader set of evaluations. To test the feasibility of a nonrandomized stepped wedge design, we developed simulated data on patient care experiences and on QII implementation that had the structures and features of the expected data from a planned QII. We then applied the design in anticipation of performing an actual QII evaluation. Methods We used simulated data on 108,000 patients to model nonrandomized stepped wedge results from QII implementation across nine primary care sites over 12 quarters. The outcome we simulated was change in a single self-administered question on access to care used by Veterans Health Administration (VA), based in the United States, as part of its quarterly patient ratings of quality of care. Our main predictors were QII exposure and time. Based on study hypotheses, we assigned values of 4 to 11 % for improvement in access when sites were first exposed to implementation and 1 to 3 % improvement in each ensuing time period thereafter when sites continued with implementation. We included site-level (practice size) and respondent-level (gender, race/ethnicity) characteristics that might account for nonrandomized timing in site implementation of the QII. We analyzed the resulting data as a repeated cross-sectional model using HLM 7 with a three-level hierarchical data structure and an ordinal outcome. Levels in the data structure included patient ratings, timing of adoption of the QII, and primary care site. Results We were able to demonstrate a statistically significant improvement in adoption of the QII, as postulated in our simulation. The linear time trend while sites were in the control state was not significant, also as expected in the real life scenario of the example QII. Conclusions We concluded that the nonrandomized stepped wedge design was feasible within the parameters of our planned QII with its data structure and content. Our statistical approach may be applicable to similar evaluations.

Impaired colon motility is one of the leading problems associated with inflammatory bowel disease (IBD). An expanding body of evidence supports the role of microbiome in normal gut function and in progression of IBD. The objective of this work is to determine whether diseased full thickness colon specimens, including the neuromuscular region (critical for colon motility function), contain specific oral and gut pathogens. In addition, we compared the differences in colon microbiome between Caucasians (CA) and African Americans (AA). Thirty-nine human full thickness colon (diseased colon and adjacent healthy colon) specimens were collected from Crohn's Colitis (CC) or Ulcerative Colitis (UC) patients while they underwent elective colon surgeries. We isolated and analyzed bacterial ribosomal RNA (rRNA) from colon specimens by amplicon sequencing of the 16S rRNA gene region. The microbiome proportions were quantified into Operational Taxonomic Units (OTUs) by analysis with Quantitative Insights Into Microbial ecology (QIIME) platform. Two hundred twenty-eight different bacterial species were identified by QIIME analysis. However, we could only decipher the species name of fifty-three bacteria. Our results show that proportion of non-detrimental bacteria in CC or UC colon samples were altered compared to adjacent healthy colon specimens. We further show, for the first time in full thickness colon specimens, that microbiome of CC and UC diseased specimens is dominated by putative oral pathogens belonging to the Phyla Firmicutes (Streptococcus, Staphylococcus, Peptostreptococcus), and Fusobacteria (Fusobacterium). In addition, we have identified patterns of differences in microbiome levels between CA and AA specimens with potential implications for health disparities research. Overall, our results suggest a significant association between oral and gut microbes in the modulation of colon motility in colitis patients.

Magnetic field-dependent heat capacity measurements on the tunable molecular magnet Cu9Cl2(cpa)6, a metal organic framework (MOF) based on copper(II) ions and carboxypentonic acid, suggest that this molecular magnetic material could serve as a candidate for quantum spin liquid (QSL) studies. The 2-D framework has been described as a ‘triangles-in-triangles’ (TIT) Kagomé or triangulated-Kagomé-lattice (TKL), and previous magnetic experiments and theoretical studies have suggested this Kagomé Heisenberg antiferromagnet (KHAF) is highly frustrated. Here we report heat capacity data down to 50mK that confirms this frustration. Above 5K the material exhibits field-independent heat capacity that largely fits C = αT3+βT behavior with parameters that vary with the temperature window of analysis. Below 5K, the zero-field heat capacity exhibits no obvious phase transition down to 0.050K and levels off at a nonzero value. Upon the application of magnetic field, a peak in the heat capacity (Cmax) emerges from below 0.050K. The temperature at which (Cmag/T)max occurs, Tmax, scales linearly with applied field. As Tmax increases, the magnitude of (Cmag/T)max decreases and the peak broadens, eventually subsumed into the αT3 behavior above 3T. Below Cmax, the heat capacity decreases to zero at finite temperatures in large fields. These data corroborate magnetic data and confirm that this frustrated TKL material does not exhibit a phase transition in low-to-zero field down to 0.050 K. Further, the temperature Tmax nominally extrapolates to 0K in zero-field, yielding a T-H phase diagram similar to Herbertsmithite; one that suggests CPA could be a possible candidate to develop additional chemical variants for QSL studies.

Chemical modifications of the magnetic metal organic framework (MOF) Cu9X2(cpa)6·42H2O (X = F, Cl, Br; cpa = anion of 2-carboxypentonicacid) have been investigated as a means of modifying, in a tunable manner, the magnetism of this 2-D material best described as a triangles-in-triangles (TIT) or triangulated-Kagomé-latttice (TKL). Since numerous theoretical studies have already attempted to describe the enigmatic ground state of this Heisenberg lattice, tunable chemical modifications should provide an excellent opportunity to expand this class of materials for studies concerning fundamental physics of frustrated spins, and applications such as adiabatic demagnetization refrigeration (ADR) that depend on the magnetocaloric effect (MCE). The chemical modification investigated is the intercalation of d- and f-orbital ions into the voids of the framework (channels of nearly 20 Å diameter). Magnetic measurements in the temperature range 1.8 – 300 K confirm signature features of TKL magnetism in intercalated samples persist, specifically: i) large negative Weiss constant (θCW); ii) absence of a phase transition down to 1.8 K; iii) minimum in χMT; iv) low temperature χMT values increasingly divergent at low fields indicating net ferromagnetic correlations; and, v) increasing field dependence of magnetization at low temperatures suggestive of intermediate plateaus, or ferrimagnetism, not saturation.

IntroductionGreater specification of implementation strategies is a challenge for implementation science, but there is little guidance for delineating the use of multiple strategies involved in complex interventions. The Cardiovascular (CV) Toolkit project entails implementation of a toolkit designed to reduce CV risk by increasing women’s engagement in appropriate services. The CV Toolkit project follows an enhanced version of Replicating Effective Programs (REP), an evidence-based implementation strategy, to implement the CV Toolkit across four phases: pre-conditions, pre-implementation, implementation, and maintenance and evolution. Our current objective is to describe a method for mapping implementation strategies used in real time as part of the CV Toolkit project. This method supports description of the timing and content of bundled strategies and provides a structured process for developing a plan for implementation evaluation.MethodsWe conducted a process of strategy mapping to apply Proctor and colleagues’ rubric for specification of implementation strategies, constructing a matrix in which we identified each implementation strategy, its conceptual group, and the corresponding REP phase(s) in which it occurs. For each strategy, we also specified the actors involved, actions undertaken, action targets, dose of the implementation strategy, and anticipated outcome addressed. We iteratively refined the matrix with the implementation team, including use of simulation to provide initial validation.ResultsMapping revealed patterns in the timing of implementation strategies within REP phases. Most implementation strategies involving the development of stakeholder interrelationships and training and educating stakeholders were introduced during the pre-conditions or pre-implementation phases. Strategies introduced in the maintenance and evolution phase emphasized communication, re-examination, and audit and feedback. In addition to its value for producing valid and reliable process evaluation data, mapping implementation strategies has informed development of a pragmatic blueprint for implementation and longitudinal analyses and evaluation activities.DiscussionWe update recent recommendations on specification of implementation strategies by considering the implications for multi-strategy frameworks and propose an approach for mapping the use of implementation strategies within complex, multi-level interventions, in support of rigorous evaluation. Developing pragmatic tools to aid in operationalizing the conduct of implementation and evaluation activities is essential to enacting sound implementation research.