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Study protocol of a hybrid type 1 effectiveness-implementation multisite trial: Dialectical behavior therapy skills Group for Veterans at high-risk for suicide attempt
No full textBackground: Veterans of the United States Armed Forces are at disproportionately high risk for suicide death, requiring indicated strategies to mitigate that risk. Dialectical Behavior Therapy (DBT) is effective for reducing suicide attempts in individuals with emotional dysregulation and repeat suicidal behaviors or self-directed violence, but is a comprehensive, multi-component, resource-intensive treatment. A more resource-efficient component of DBT, the DBT Skills Group as an adjunctive treatment, with therapist consultation team (DBT-SG), has been shown to be as efficacious as comprehensive DBT in non-veteran samples, but its effectiveness and factors affecting its implementation have not been studied in the Veterans Health Administration (VHA). This research aims to assess the effectiveness of DBT-SG among high-risk veterans with recent and repeated suicide attempts and emotion dysregulation while systematically evaluating implementation barriers and facilitators.
Methods: This hybrid type 1 effectiveness-implementation study will evaluate DBT-SG effectiveness among veterans at high-risk for suicide attempt with emotion dysregulation using a randomized controlled trial of 18 months duration. Study conditions are 24-session DBT-SG plus full-spectrum VHA mental health treatment-as-usual (TAU), or VHA TAU. Outcomes are assessed at 3-, 6-, 12-, and 18-months post-randomization. Before, during, and after the effectiveness trial, implementation determinants of DBT-SG as an adjunctive treatment in VHA will be assessed using a mixed methods evaluation grounded in the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework.
Conclusions: This study will provide evidence for DBT-SG effectiveness for veterans at high risk for suicide and information about barriers and facilitators to support more widespread facilitation of implementing adjunctive DBT-SG in VHA if it is found effective.
Clinical trials registration: NCT05000749.No embarg
Sequential decreases in basolateral amygdala response to threat predict failure to recover from PTSD
Get PDFAmygdala hyperreactivity early-post trauma has been a demonstrable neurobiological correlate of future posttraumautic stress disorder (PTSD). The basolateral amygdala (BLA) particularly is vital for fear memory and threat processing, but BLA functional dynamics following a traumatic event are unexplored. BLA reactivity to threat may be a trait that can predict PTSD and persist over time. Alternatively, BLA responsivity to threat cues may change over time and be related to PTSD severity. As part of a larger, multisite study, AURORA, participants 18-75 years old were enrolled in an emergency department (ED) within 72 h of a traumatic event (N = 304, 199 female). At 2-weeks and 6-months post-trauma, PTSD symptoms, BLA responses to threat (fearful>neutral faces), and functional connectivity (FC) during fMRI were assessed. Generalizability of findings was assessed in an external replication sample of ED patients (n = 33). Two weeks post-trauma right BLA reactivity positively predicted later PTSD severity. However, left BLA reactivity to threat at 6 months post-trauma was negatively associated with PTSD severity at that timepoint (ΔPseudo-R = 0.04, IRR = 0.38, p < 0.001). In addition, a decrease in BLA reactivity from 2-weeks to 6-months predicted greater PTSD severity at 6 months (ΔPseudo-R = 0.03, IRR = 0.58, p < 0.001). This replicated in the external sample. A reduction in left BLA FC with the dorsal attention network predicted increased PTSD severity over time. These findings support a shift in BLA function within the first 6 months post-trauma that predicts PTSD pathology and stand in contrast to prior conceptualizations of amygdala hyperreactivity as a trait-like PTSD risk factor.No embarg
The ethics of proximity: Enrolling patients in emergency department hallway beds for suicide research
No full textBackground: Suicide is the 10th leading cause of death in the United States. Prior research suggests that 10% of people who died by suicide received some form of emergency department (ED) treatment in the 2 months preceding death. The risk of attempted suicide is high during transition back to the community after discharge from the ED, so this is an important opportunity to develop effective empirically validated prevention methods. However, the physical layout and crowded nature of most contemporary EDs, resulting in high rates of "hallway bed" assignments, presents some ethical challenges to conducting the requisite behavioral health research in ED settings.
Methods and results: In this report, we illustrate the clinical/research ethics controversy through the example of a specific ED-based suicide prevention research protocol, in which the proposed hallway bed recruitment was initially rejected by the institutional review board (IRB) based on concerns about privacy, data confidentiality, and related considerations. Through a consultation process that involved the IRB representatives, the research team (including ethicists), and ED personnel, along with the collection of data to evaluate the risk of compromised confidentiality in hallway bed settings, a viable and ethically grounded approach was reached.
Conclusions: This example illustrates the ethical considerations when enrolling patients who occupy a hallway bed into research and the value of a collaborative/problem solving focused dialogue between investigators, ethicists, and IRB personnel.No embarg
Impact of NLRP3 Effectors: IL-1β, IL-18, and GSDMD in Alzheimer's Disease
Get PDFAlzheimer’s disease (AD) is a neurodegenerative disease featuring memory dysfunction and amyloid beta (Ab) pathology. The brain’s resident antigen presenting cells, microglia, phagocytose Ab plaques. However, in AD, microglia are unable to clear Ab plaques. Accumulated levels of aggregated Ab trigger the innate immune system to initiate a nod-like receptor protein 3 (NLRP3) inflammasome- mediated proteolytic cascade that produces interleukin-1b (IL-1b) and -18 (IL-18), secreted through gasdermin D (GSDMD) pores formed by 30 kD N terminal fragments. To investigate the overall role of these NLRP3 effectors in AD, we bred various NLRP3 effector knockouts with APP/PS1 mice. Unexpectedly, our main findings show that Gsdmd-/-/APP/PS1 mice showed worsened AD phenotypes, such as a severe deficit in spatial memory formation compared to controls. Furthermore, despite a shift toward the anti-amyloidogenic pathway in these mice, there was substantial production of pathogenic Ab1-42. We found that when stimulated with pyroptotic and apoptotic stimuli, microglia produce multiple GSDMD fragments. When stimulated with etoposide, an apoptotic stimulus, immortalized microglia produce a non-pyroptotic, 11kDa GSDMD product. This nuclear-localized fragment has been shown to induce major histocompatibility complex (MHC) class II. In Gsdmd-/-/APP/PS1 hippocampi, NanoString analysis identified a statistically significant decrease in MHC II gene, H2-Eb1, expression compared to APP/PS1 mice. These results were confirmed with RT-qPCR analysis. Overall, Gsdmd-/- /APP/PS1 mice show both worsened AD phenotype and pathology. Further studies are warranted to not only elucidate the function and impact of this non-pyroptotic GSDMD fragment in AD but also further characterize our NLRP3 effector knockout APP/PS1 mice.Interdisciplinary Graduate Program6 months2025-07-2
Guidance for Researchers and Developers of Suicide Prevention Technology Tools
Get PDFThis tip sheet includes guidance for researchers working in digital health and technology tools for suicide prevention, as well as software developers and companies working in digital health for suicide prevention. These are not rules to follow, and instead are offered to center patient autonomy, choice, and transparency when offering digital tools. Suicide prevention refers to screening, assessment, risk management, and interventions.
Tools could include digital screening or assessment surveys or apps that are designed to practice coping skills or develop safety plans. Persons with a range of lived experiences—from acute to chron¬ic suicidal despair—should be meaningfully included in the design and development of these tools, to ensure the content is ground in real world perspectives. This guidance supports how to introduce technology tools to patients, but such tools should have perspectives of people with lived experience throughout their development.P50MH129701No embarg
Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response
No full textHIV-1 Env glycoprotein (Env) immunogenicity is limited in part by structural instability and extensive glycan shielding and is likely the greatest obstacle to an HIV-1 vaccine. Stabilized Env trimers can elicit serum neutralizing antibodies, but the response is short-lived. Here we use Newcastle Disease Virus-like particle (NDV-VLP) platform to present stabilized versions of HIV-1 Env at high valency and in the context of varied conformational stability, adjuvants, dose, and antigen persistence. Influenza virus hemagglutinin, or SARS-CoV2 Spike-bearing VLPs rapidly induce neutralizing antibodies, in contrast, they were not induced by those bearing Env. A replicating adenovirus type 4 expressing Env rapidly induces autologous neutralizing antibodies. However, durable neutralizing antibodies are induced only when multiple features of a replicating virus infection are combined, with the largest impact from dose and escalating dose. In summary, we show here immunogenicity of HIV-1 Env could be improved by reproducing features of virus infection.No embarg
Assessing Rural Veterans' Experiences with a Tele-Nephrology Program in the Veterans Health Administration (VHA)
No full textIntroduction: Rural living Veterans with chronic kidney disease (CKD) and refractory hypertension (rHTN) have a higher mortality rate and are hospitalized more frequently than Veterans living in urban or suburban areas. They also face particularly unique challenges in accessing nephrology specialty care. Previous studies suggest virtual nephrology care can be used to increase access to care for Veterans. The purpose of this study was to examine Veteran's perceptions and experiences with a VA virtual nephrology program.
Methods: We conducted semi-structured interviews with forty-four Veterans at five rural VA medical centers who were receiving virtual nephrology care ("tele-nephrology").
Results: Four major themes arose that represent the Veterans' perceptions and experiences with VA virtual nephrology care: 1) Tele-nephrology provides timely access to care for Veterans living in rural areas; 2) Clinical partnerships between primary care and tele-nephrology are key to Veterans' health; 3) Veterans' technology fears were assuaged with virtual nephrology care; 4) Improvements to care include more direct access to virtual nephrologists.
Conclusion: This evaluation represents an important step forward in how the VA can enhance virtual nephrology care to better meet the needs of rural Veterans receiving care at facilities without VA specialty providers. Prior to the Choice and MISSION Acts, Veterans were often required to drive long distances to the closest VA specialty provider. However, since the COVID-19 pandemic, the VA has been shifting care from community to VA via virtual care. Further research should examine Veterans' experiences with both different modalities of nephrology care as well as experiences from demographically and geographically diverse Veterans.No embarg
Afterhours diagnostic radiology in the USA: radiologists' views on imaging volumes, compensation, work-from-home, and compensatory time-off
No full textPurpose
To understand the afterhours radiology workforce and views towards imaging volumes, compensation, overnight challenges, and work-from-home.
Methods
Survey questions focusing on the afterhours radiology workforce were created. The survey was administered by the American College of Radiology (ACR) and the data analysis performed by the ACR in partnership with an independent market research agency. The confidence level was set at 95%, with an error rate of +/- 2.2%.
Results
A total of 1109 out of 1844 (60.1%) survey participants responded to the afterhours survey. A majority of respondents (56%) had worked an afterhours shift while a minority had worked a late-evening (18%) or overnight shift (13%). Irrespective of practice type, the majority of radiologists thought afterhours volumes were not manageable, and afterhours compensation was not equitable. Less than half of those who worked overnight shifts believed they were given adequate compensatory time-off for recovery. The majority of respondents supported work-from-home for afterhours shifts.
Conclusions
As the largest survey to date on after-hours radiology, these findings should be carefully considered by practices aiming to successfully recruit and retain radiologists in this critical niche.No embarg
The Physical Activity Policy Research and Evaluation Network: Evaluation Using CDC's Science Impact Framework
Get PDFThe Division of Nutrition, Physical Activity and Obesity (DNPAO) at the Centers for Disease Control and Prevention (CDC) funded the Physical Activity Policy Research and Evaluation Network (PAPREN) from 2019-2024 to address critical knowledge and translation gaps related to physical activity policy research, with an emphasis on supporting and advancing research and practice on the Guide to Community Preventive Services Task Force's recommendations to advance physical activity related to community design and parks and green spaces. During the 2019-2024 period, PAPREN grew to include over 1,000 members from sectors such as public health, social and behavioral sciences, transportation, planning, and parks and recreation. PAPREN also included academics, practitioners, and government employees. Using an adapted version of CDC's Science Impact Framework (SIF), we evaluated PAPREN's influence on five domains: creating awareness, catalyzing action, disseminating science, effecting change and shaping the future using network tracking activities and a member survey (n=95). Results indicated that PAPREN is having an impact in creating awareness through its communications and presentations infrastructure, catalyzing action through projects and other initiatives led by its topic-focused Work Groups, disseminating science by helping members stay informed about the field and disseminating resources and shaping the future by informing members' work and shaping the next generation of researchers. An area for growth relates to affecting change by fostering more opportunities for networking and promoting professional development. PAPREN can serve as a model for other collaborative, multi-sectoral networks designed to increase applied research and to use research findings to inform practice.No embarg
Inferring binding specificities of human transcription factors with the wisdom of crowds [preprint]
Get PDFThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.DNA motif discovery and, particularly, computational modeling of transcription factor binding motifs, has been a mecca of algorithmic bioinformatics for several decades. Here, we report the results of the largest open community challenge in Inferring BInding Specificities (IBIS), where participants all over the world were invited to construct binding specificity models from multi-assay experimental data for poorly studied human transcription factors. The submissions were rigorously tested against a rich held-out dataset. Benchmarking demonstrated a consistent advantage of properly designed deep learning models over traditional positional weight matrices and other machine learning methods. Yet, the positional weight matrices displayed a surprisingly strong performance out of the box, being only slightly behind the best deep learning models. A post-challenge assessment of a selection of other deep learning methods further solidified this finding. IBIS highlights the power of benchmarking in finding adequate DNA motif representations, emphasizes the pros and cons of various machine learning methods applied to DNA motif modeling, and establishes a rich dataset, benchmarking protocols, and computational framework for a fair cross-platform evaluation of future models of transcription factor binding motifs in DNA sequences.No embarg