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Introduction: Real-world data are limited on treatment sequencing and outcomes after first-line (1L) immune checkpoint inhibitor (CPI)-based combination treatment of advanced renal cell carcinoma (aRCC)., Patients and Methods: In this real-world, UK-based, retrospective study (CARINA; NCT04957160), data were obtained from hospital and electronic prescribing records. Patients were aged ≥ 18 years at aRCC diagnosis and had received 1L CPI-CPI or tyrosine kinase inhibitor (TKI)-CPI combination therapy before second-line (2L) therapy including cabozantinib. We describe treatment outcomes including 1L and 2L durations of treatment (DoT) and overall survival (OS)., Results: Data from April 2015 to June 2022 were collected on 281 patients from nine UK centres. Median 1L DoT was 2.3 months for CPI-CPI therapy (n = 171) and 5.0 months for TKI-CPI therapy (n = 58). After 1L CPI-CPI or TKI-CPI therapy, median 2L DoT was 5.8 versus 4.2 months, respectively, for cabozantinib (n = 163), and 3.8 versus 2.4 months for other therapies (n = 118); median 2L OS was 15.2 and 15.3 months, respectively, for cabozantinib, and 14.6 and 24.2 months for other therapies., Conclusion: DoT for 2L treatment was numerically better for cabozantinib than for other therapies, and after 1L CPI-CPI therapy than after 1L TKI-CPI therapy. Median OS was similar for 2L cabozantinib and other 2L therapies, and median OS for 2L cabozantinib was similar after both 1L therapy types. These results demonstrate the antitumour effect of 2L therapies, including cabozantinib, after 1L CPI-based combination treatment, regardless of whether 1L CPI-CPI or TKI-CPI therapy is used., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical research trials rely on informed consent forms (ICFs) to explain all aspects of the study to potential participants. Despite efforts to ensure the readability of ICFs, concerns about their complexity and participant understanding persist. There is a noted gap between Institutional Review Board (IRB) standards and the actual readability levels of ICFs, which often exceed the recommended 8th-grade reading level. This study evaluates the readability of over five thousand ICFs from ClinicalTrials.gov in the USA to assess their literacy levels., Methods: We analyzed 5,239 US-based ICFs from ClinicalTrials.gov using readability metrics such as the Flesch Reading Ease, Flesch-Kincaid Grade Level, Gunning Fog Index, and the percentage of difficult words. We examined trends in readability levels across studies initiated from 2005 to 2024., Results: Most ICFs exceeded the recommended 8th-grade reading level, with an average Flesch-Kincaid Grade Level of 10.99. While 91% of the ICFs were written above the 8th-grade level, there was an observable improvement in readability, with fewer studies exceeding a 10th-grade reading level in recent years., Conclusions: The study reveals a discrepancy between the recommended readability levels and actual ICFs, highlighting a need for simplification. Despite a trend toward improvement in more recent years, ongoing efforts are necessary to ensure ICFs are comprehensible to participants of varied educational backgrounds, reinforcing the ethical integrity of the consent process., Competing Interests: None., (© The Author(s) 2024.)

People with cancer experience higher rates of psychological dysfunction than the general population, with extreme inequity among indigenous people. Psychedelic-assisted therapy (PAT) is a reemerging area with promising evidence as a treatment for mental health difficulties. The current study aimed to investigate the perceptions of PAT in indigenous (Māori) and non-indigenous cancer patients in Aotearoa, New Zealand. Eighty-five cancer patients (Māori n  = 32, non-Māori n  = 53) completed a brief anonymous survey assessing demographics, psychological factors, and awareness and perceptions of PAT. Participants were recruited online (via social media and cancer support e-mail lists) and in person at Auckland City Hospital. Maori had significantly poorer psychological well-being than non-Māori. All participants had low awareness of this novel treatment and held largely neutral attitudes. Regression analyses revealed that predictors of more favorable attitudes toward PAT included greater awareness of psychedelics, advanced cancer stage, younger age, poorer holistic well-being, greater demoralization, and prioritizing treatment effectiveness over possible risks and uncertainty. The current study provides a foundational step in exploring perceptions toward PAT in indigenous and non-indigenous groups. These results have the potential to shape future research trials investigating PAT and further highlight the importance of indigenous involvement in the psychedelic research space.

Background: For almost 60 years, Indian psychiatry literature has called for all medical students to learn psychiatry so that millions of mentally unwell people across India might receive appropriate treatment. Yet for almost 60 years, medical students have disengaged from psychiatry education, resulting in limited learning. The literature has repeatedly cited the solution as one that involves longer exposure on posting and more exam questions, with little impact. This research sought to understand why medical students disengage from psychiatry education so that meaningful change might occur., Methods: The research utilized constructivist grounded theory, initially in one medical college in Mumbai, followed by a quantitative survey to test the findings with a wider group of interns across 10 states of India. An iterative process of data gathering and analysis was undertaken using the constant comparison method and theoretical integration., Results: Findings identified that 98% of interns believe all MBBS (doctors) should "know" psychiatry, with "know" meaning practical skills-how to assess and treat people with mental illness. The majority of students attend psychiatry to learn those skills, but on finding faculty too overworked to teach, they disengage, saying : "there's nothing in it for me ." The findings indicate that more exam questions would not increase engagement., Conclusion: Medical students want to learn skills to help those in mental distress. Faculty do not have time and, arguably, the training to teach them. To address the nation's mental health needs, the government needs to prioritize teaching of psychiatry skills by releasing and enabling psychiatry faculty, alongside the certification of psychiatry skills., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Author(s).)

Background: The Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms are designed to help obstetric practices address perinatal depression. The PRogram in Support of Moms includes the statewide Massachusetts Child Psychiatry Access Program for Moms program, plus proactive implementation support., Objective: The goal of this study was to understand the impact of these programs on perinatal generalized anxiety disorder and posttraumatic stress disorder symptoms among individuals screening positive for depression., Study Design: We conducted a secondary analysis of 2017-2022 data from a cluster randomized controlled trial of Massachusetts Child Psychiatry Access Program for Moms vs PRogram In Support of Moms. We included participants completing a generalized anxiety disorder or posttraumatic stress disorder screen at baseline (n=254) with antenatal Edinburgh Postnatal Depression Scale scores ≥10. We assessed changes in generalized anxiety disorder and posttraumatic stress disorder symptoms from pregnancy (4-25 weeks of gestational age or 32-40 weeks of gestational age), 4-12 weeks postpartum, and 11-13 months postpartum. We conducted a difference-in-difference analysis to compare symptom change from pregnancy to postpartum. We used adjusted linear mixed models with repeated measures to examine the impact of the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms on changes in the Generalized Anxiety Disorder 7 and the Posttraumatic Stress Disorder Checklist., Results: Mean Generalized Anxiety Disorder 7 scores decreased by 3.6 (Massachusetts Child Psychiatry Access Program for Moms) and 6.3 (PRogram In Support of Moms) points from pregnancy to 4-12 weeks postpartum. Mean Posttraumatic Stress Disorder Checklist scores decreased by 6.2 and 10.0 points, respectively, at 4-12 weeks postpartum among individuals scree ning positive on the Generalized Anxiety Disorder 7 (n=83) or Posttraumatic Stress Disorder Checklist (n=58) in pregnancy. Generalized Anxiety Disorder 7 and Posttraumatic Stress Disorder Checklist scores decreased among both groups at 11-13 months postpartum. These changes were clinically meaningful. PRogram In Support of Moms conferred a statistically significant greater decrease (2.7 points) on the Generalized Anxiety Disorder 7 than the Massachusetts Child Psychiatry Access Program for Moms at 4-12 weeks postpartum. No differences were found between the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms in Posttraumatic Stress Disorder Checklist or Generalized Anxiety Disorder 7 change at 11-13 months, although both were associated with a reduction in generalized anxiety disorder and posttraumatic stress disorder symptoms at 4-12 weeks and 11-13 months postpartum., Conclusion: Both the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms could help to improve symptoms for individuals experiencing co-occurring symptoms of depression, generalized anxiety disorder, or posttraumatic stress disorder. PRogram In Support of Moms may confer additional benefits in the early postpartum period, although this difference was not clinically significant., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions. The evidence-based and consensus recommendations contained in the NCCN Guidelines are intended to guide clinicians in selecting the most appropriate treatments for their patients with this clinically heterogeneous disease.

Objectives: Depression is common during pregnancy and the year following childbirth (the perinatal period). This study assessed the association of depressive symptoms and contraception decisions in perinatal individuals., Study Design: We conducted a secondary analysis using data from the PRogram in Support of Moms (PRISM) study, a cluster randomized controlled trial of active interventions which aimed to address perinatal depression. This analysis included 191 individuals aged 18-45 who screened positive for depression on the Edinburgh Postnatal Depression Scale (EPDS, score ≥10) during pregnancy or up to 3 months postpartum. We assessed contraception intent and method choice at 1-3 months postpartum. At 5-7 months postpartum, we assessed contraceptive method used and EPDS depression scores. We used logistic regressions to examine the relationship between depression and contraceptive use/method., Results: At 1-3 months postpartum, the majority of participants (76.4%) expressed an intention to use contraception. Of those, over half (53.4%) indicated a preference for higher effectiveness contraception methods. Participants with persistent depression symptoms (positive EPDS) at 5-7 months were significantly less likely to report using higher effectiveness contraceptive methods (aOR = 0.28, 95% CI = 0.11-0.70) compared to those without. Among participants with persistent depressive symptoms, 21.1% reported using a contraception method of lower effectiveness than had originally intended., Conclusion: Perinatal individuals with persistent depressive symptoms at 5-7 months postpartum reported greater use of less-effective contraception methods than originally planned., Implications: We found associations between perinatal depression and use of less effective contraception use. Provider discussions regarding contraception planning is important, particularly in those with perinatal depression symptoms., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Both atrial fibrillation (AF) and amyloidosis increase stroke risk. We evaluated the best anticoagulation strategy in AF patients with coexistent amyloidosis., Methods: Consecutive AF patients with concomitant amyloidosis were divided into two groups based on the postablation stroke-prophylaxis approach; group 1: left atrial appendage occlusion (LAAO) in eligible patients and group 2: oral anticoagulation (OAC). Group 1 patients were further divided into Gr. 1A: LAAO + half-does NOAC (HD-NOAC) for 6 months followed by aspirin 81 mg/day and Gr. 1B: LAAO + HD-NOAC. In group 1 patients, with complete occlusion at the 45-day transesophageal echocardiogram, patients were switched to aspirin, 81 mg/day at 6 months. In case of leak, or dense "smoke" in the left atrium (LA) or enlarged LA, they were placed on long-term half-dose (HD) NOAC. Group 2 patients remained on full-dose NOAC during the whole study period., Results: A total of 92 patients were included in the analysis; group 1: 56 and group 2: 36. After the 45-day TEE, 31 patients from group 1 remained on baby-aspirin and 25 on HD NOAC. At 1-year follow-up, four stroke, one TIA and six device-thrombus were reported in group 1A, compared to none in patients in group 1B (5/31 vs. 0/25, p = .03). No bleeding events were reported in group 1, whereas group 2 had five bleeding events (one subdural hematoma, one retinal hemorrhage, and four GI bleedings). Additionally, one stroke was reported in group 2 that happened during brief discontinuation of OAC., Conclusion: In patients with coexistent AF and amyloidosis, half-dose NOAC following LAAO was observed to be the safest stroke-prophylaxis strategy., (© 2024 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Neutron radiography is a technique uniquely suited to applications in nuclear diagnostics, non-destructive testing, and subcritical experiments. The spatial resolution of neutron radiographs is degraded by optical blur in the imaging system and the neutron source size, where the ideal source is point-like to optimize the point-spread function. A potential neutron source for radiography is the dense plasma focus (DPF), a coaxial Z-pinch that produces thermonuclear and beam-target neutrons. To assess if the source size is suitable for radiography, a neutron imaging system was used to measure the source size of the 4 MA Sodium DPF at the Nevada National Security Site operating with deuterium-tritium gas-fill. The source size was measured using the edge-spread function of tungsten objects, each having a rolled (convex) edge. The spot size was found to be 7-12 mm full-width at half-max (FWHM) assuming a Gaussian source, though comparison is presented for Lorentzian and Bennett distributions. The average FWHM was found to be 8.6 ± 1.2 mm vertically and 10.8 ± 1.2 mm horizontally with respect to the image plane, averaging over varied edges and alignments. The results were sensitive to source alignment and edge metrology, which introduced notable uncertainties. These results are consistent with separate experimental measurements as well as magnetohydrodynamics simulations of this DPF, which suggest that neutron production can originate from pinches ∼5-7 mm off-axis. These results suggest that the DPF should be used for radiography at low magnification (M < 1) where spot size does not dominate spatial blur., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: When performed well on appropriate patients, total knee arthroplasty (TKA) can dramatically improve quality of life. Patient-reported outcome measures (PROMs) are increasingly used to measure outcome following TKA. Accurate prediction of improvement in PROMs after TKA potentially plays an important role in judging the surgical quality of the health-care institutions as well as informing preoperative shared decision-making. Starting in 2027, the U.S. Centers for Medicare & Medicaid Services (CMS) will begin mandating PROM reporting to assess the quality of TKAs., Methods: Using data from a national cohort of patients undergoing primary unilateral TKA, we developed an original model that closely followed a CMS-proposed measure to predict success, defined as achieving substantial clinical benefit, specifically at least a 20-point improvement on the Knee injury and Osteoarthritis Outcome Score, Joint Arthroplasty (KOOS, JR) at 1 year, and an enhanced model with just 1 additional predictor: the baseline KOOS, JR. We evaluated each model's performance using the area under the receiver operator characteristic curve (AUC) and the ratio of observed to expected (model-predicted) outcomes (O:E ratio)., Results: We studied 5,958 patients with a mean age of 67 years; 63% were women, 93% were White, and 87% were overweight or obese. Adding the baseline KOOS, JR improved the AUC from 0.58 to 0.73. Ninety-four percent of those in the top decile of predicted probability of success under the enhanced model achieved success, compared with 34% in its bottom decile. Analogous numbers for the original model were less discriminating: 77% compared with 57%. Only the enhanced model predicted success accurately across the spectrum of baseline scores. The findings were virtually identical when we replicated these analyses on only patients ≥65 years of age., Conclusions: Adding a baseline knee-specific PROM score to a quality measurement model in a nationally representative cohort dramatically improved its predictive power, eliminating ceiling and floor effects and mispredictions for readily identifiable patient subgroups. The enhanced model neither favors nor discourages care for those with greater knee dysfunction and requires no new data collection., Level of Evidence: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This research was supported by grant P50HS018910 from the Agency for Healthcare Research and Quality (AHRQ). Dr. Ash also received grant 5UL1 TR001453-07 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H855 )., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: High-voltage pulses can cause hemolysis., Objectives: The authors evaluated the occurrence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF)., Methods: A consecutive series of patients with AF undergoing PFA were included in this analysis. The initial patients who did not receive postablation hydration immediately after the procedure were classified as group 1 (n = 28), and the rest of the study patients who received planned fluid infusion (0.9% sodium chloride ≥2 L) after the procedure were categorized as group 2 (n = 75)., Results: Of the 28 patients in group 1, 21 (75%) experienced hemoglobinuria during the 24 hours after catheter ablation. The mean postablation serum creatinine (S-Cr) was significantly higher than the baseline value in those 21 patients (1.46 ± 0.28 mg/dL vs 0.86 ± 0.24 mg/dL, P < 0.001). Of those 21 patients, 4 (19%) had S-Cr. >2.5 mg/dL (mean: 2.95 ± 0.21 mg/dL). The mean number of PF applications was significantly higher in those 4 patients than in the other 17 patients experiencing hemoglobinuria (94.63 ± 3.20 vs 46.75 ± 9.10, P < 0.001). In group 2 patients, no significant changes in S-Cr were noted. The group 2 patients received significantly higher amounts of fluid infusion after catheter ablation than did those in group 1 (2,082.50 ± 258.08 mL vs 494.01 ± 71.65 mL, P < 0.001). In multivariable analysis, both hydration (R 2  = 0.63, P < 0.01) and number of PFA applications (R 2  = 0.33, P < 0.01) were independent predictors of postprocedure acute kidney injury., Conclusions: On the basis of our findings, both the number of PFA applications and postablation hydration were independent predictors of renal insult that could be prevented using planned fluid infusion immediately after the procedure., Competing Interests: Funding Support and Author Disclosures Dr. Chierchia has received compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Boston Scientific, and Acutus Medical. Dr. Burkhardt is a consultant for Biosense Webster and Stereotaxis. Dr. Di Biase is a consultant for Biosense Webster, Boston Scientific, Stereotaxis, and St. Jude Medical and has received speaker honoraria from Medtronic, Atricure, EPiEP, and Biotronik. Dr. de Asmundis has received research grants on behalf of the center from Biotronik, Medtronic, Abbott, LivaNova, Boston Scientific, AtriCure, Philips, and Acutus and compensation for teaching purposes and proctoring from Medtronic, Abbott, Biotronik, Livanova, Boston Scientific, Atricure, Acutus Medical, and Daiichi Sankyo. Dr. Dello Russo is a consultant for Abbott Medical. Dr, Natale is a consultant for Abbott, Biosense Webster, Biotronik, Boston Scientific, and iRhythm. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Predictive biomarkers for immune checkpoint blockade in the second-line treatment of metastatic renal cell carcinoma (mRCC) are lacking., Materials and Methods: Patients with histologically confirmed RCC who started nivolumab after at least 4 months of tyrosine kinase inhibitors (TKIs) were recruited for this study. Serial tissue and blood samples were collected for immune biomarker evaluation. The primary endpoint was to determine the association of specific T-cell subsets with clinical outcomes tested using Wilcoxon rank sum for clinical benefit rate (CBR) and log-rank test for progression-free survival (PFS)., Results: Twenty patients were included in this trial with a median age of 64 years and followed-up for a median of 12 months. The median PFS for patients who received TKI was 13.8 months, while for those subsequently treated with nivolumab following TKI therapy, the median PFS was 2.6 months. CBR of nivolumab was 20% with two partial responses. Functionally active programmed cell death protein 1+ CD4+ T cells were enriched in non-responders ( q  = 0.003) and associated with worse PFS on nivolumab ( P  = 0.04). Responders showed a significant reduction in the effector CD4+T-cell (T EF ) fraction compared to non-responders at 3 months on nivolumab (0.40 versus 0.80, P  = 0.0005). CD127+CD4+ T cells were enriched in patients who developed immune-related adverse effects ( q  = 0.003). Using in-house validated multiplex immunohistochemistry for six markers, we measured tumour-associated immune cell densities in tissue samples . Responders to nivolumab showed a significantly higher mean of immune cell densities in tissue samples compared to non-responders (346 versus 87 cells/mm 2 , P  = 0.04)., Conclusions: In this small study, analysis of tissue-based and peripheral blood immune cell subsets predicted clinical outcomes of nivolumab. Further studies are warranted with larger populations to validate these observations., (© 2024 The Authors.)

Introduction: American Indian and Alaska Native (AIAN) communities continue to flourish and innovate in the face of the COVID-19 pandemic. Storytelling is an important tradition for AIAN communities that can function as an intervention modality. To support the needs of AIAN children and caregivers, we (a collaborative workgroup of Indigenous health researchers) developed a culturally grounded storybook that provides pandemic-related public health guidance and mental health coping strategies woven with Inter-Tribal values and teachings., Methods: A collaborative workgroup, representing diverse tribal affiliations, met via four virtual meetings in early 2021 to discuss evolving COVID-19 pandemic public health guidance, community experiences and responses to emerging challenges, and how to ground the story in shared AIAN cultural strengths. We developed and distributed a brief survey for caregivers to evaluate the resulting book., Results: The workgroup iteratively reviewed versions of the storyline until reaching a consensus on the final text. An AI artist from the workgroup created illustrations to accompany the text. The resulting book, titled Our Smallest Warriors, Our Strongest Medicine: Honoring Our Teachings during COVID-19 contains 46 pages of text and full-color illustrations. An online toolkit including coloring pages, traditional language activities, and caregiver resources accompanies the book. We printed and distributed 50,024 physical copies of the book and a free online version remains available. An online survey completed by N  = 34 caregivers who read the book with their child(ren) showed strong satisfaction with the book and interest in future books., Discussion: The development of this storybook provides insights for creative dissemination of future public health initiatives, especially those geared toward AIAN communities. The positive reception and widespread interest in the storybook illustrate how braiding AIAN cultural teachings with public health guidance can be an effective way to disseminate health information. This storybook highlights the importance of storytelling as an immersive learning experience through which caregivers and children connect to family, community, culture, and public health guidance. Culturally grounded public health interventions can be effective and powerful in uplifting AIAN cultural values and promoting health and well-being for present and future generations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Maudrie, Grubin, Conrad, Velasquez Baez, Saniguq Ullrich, Allison-Burbank, Martin, Austin, Joyner, Ronyak, Masten, Ingalls, Haroz and O’Keefe.)

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disorder characterized by progressive muscular weakness due to the selective loss of motor neurons. Mutations in the gene Fused in Sarcoma (FUS) were identified as one cause of ALS. Here, we report that mutations in FUS lead to upregulation of synaptic proteins, increasing synaptic activity and abnormal release of vesicles at the synaptic cleft. Consequently, FUS-ALS neurons showed greater vulnerability to glutamate excitotoxicity, which raised neuronal swellings (varicose neurites) and led to neuronal death. Fragile X mental retardation protein (FMRP) is an RNA-binding protein known to regulate synaptic protein translation, and its expression is reduced in the FUS-ALS lines. Collectively, our data suggest that a reduction of FMRP levels alters the synaptic protein dynamics, leading to synaptic dysfunction and glutamate excitotoxicity. Here, we present a mechanistic hypothesis linking dysregulation of peripheral translation with synaptic vulnerability in the pathogenesis of FUS-ALS., Competing Interests: Declaration of interests C.E.S. is the Chief Scientific and Clinical Advisor of AviadoBio., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: American Indian and Alaska Native (AIAN) populations are frequently associated with the highest rates of tuberculosis (TB) disease of any racial/ethnic group in the USA. We systematically investigated variation in patterns and potential drivers of TB epidemiology among geographically distinct AIAN subgroups., Methods: Using data reported to the National Tuberculosis Surveillance System during 2010-2020, we applied a geographic method of data disaggregation to compare annual TB incidence and the frequency of TB patient characteristics among AIAN persons in Alaska with AIAN persons in other states. We used US Census data to compare the prevalence of substandard housing conditions in AIAN communities in these two geographic areas., Results: The average annual age-adjusted TB incidence among AIAN persons in Alaska was 21 times higher than among AIAN persons in other states. Compared to AIAN TB patients in other states, AIAN TB patients in Alaska were associated with significantly higher frequencies of multiple epidemiologic TB risk factors (e.g., attribution of TB disease to recent transmission, previous diagnosis of TB disease) and significantly lower frequencies of multiple clinical risk factors for TB disease (e.g., diagnosis with diabetes mellitus, end-stage renal disease). Occupied housing units in AIAN communities in Alaska were associated with significantly higher frequencies of multiple measures of substandard housing conditions compared to AIAN communities in other states., Conclusions: Observed differences in patient characteristics and substandard housing conditions are consistent with contrasting syndromes of TB epidemiology in geographically distinct AIAN subgroups and suggest ways that associated public health interventions could be tailored to improve efficacy., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Within the UK, there is a goal that research is embedded into everyday healthcare practice. Currently education provided to students at pre-registration level is theoretical, with little focus on clinical research delivery., Aims: The paper's aim is to report on the development and evaluation of a pre-registration clinical research resource for nursing and midwifery students with direct application to clinical settings and patient care outcomes., Methods: An initial survey assessed whether the learning resource was useful for nursing pre-registration students. Based on the findings, alongside expert stakeholder input, adaptations were made to the learning resources and a second survey re-evaluated the learning resources. Survey findings were analysed using descriptive statistics. Free text responses were thematically grouped., Results: Ninety-seven pre-registration nursing students responded. Most students agreed that they had enjoyed using the resources, had improved understanding of clinical research, anticipated being actively involved in research and would consider a future clinical research role., Conclusions: The learning resources can help overcome barriers to research engagement by nurses and midwives. The results demonstrate that research can be incorporated into clinical, educational and academic roles, highlighting their worth in supporting the clinical research workforce., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Perinatal depression is a common and undertreated condition, with potential deleterious effects on maternal, obstetric, infant, and child outcomes. We aimed to compare the effectiveness of two systems-level interventions in the obstetric setting-the Massachusetts Child Psychiatry Access Program (MCPAP) for Moms and the PRogram In Support of Moms (PRISM)-in improving depression symptoms and participation in mental health treatment among women with perinatal depression., Methods: In this cluster-randomised, active-controlled trial, obstetric practices across Massachusetts (USA) were allocated (1:1) via covariate adaptive randomisation to either continue participating in the MCPAP for Moms intervention, a state-wide, population-based programme, or to participate in the PRISM intervention, which involved MCPAP for Moms plus a proactive, multifaceted, obstetric practice-level intervention with intensive implementation support. English-speaking women (aged ≥18 years) who screened positive for depression (Edinburgh Postnatal Depression Scale [EPDS] score ≥10) were recruited from the practices. Patients were followed up at 4-25 weeks of gestation, 32-40 weeks of gestation, 0-3 months postpartum, 5-7 months postpartum, and 11-13 months postpartum via telephone interview. Participants were masked to the intervention; investigators were not masked. The primary outcome was change in depression symptoms (EPDS score) between baseline assessment and 11-13 months postpartum. Analysis was done by intention to treat, fitting generalised linear mixed models adjusting for age, insurance status, education, and race, and accounting for clustering of patients within practices. This trial is registered with ClinicalTrials.gov, NCT02760004., Findings: Between July 29, 2015, and Sept 20, 2021, ten obstetric practices were recruited and retained; five (50%) practices were randomly allocated to MCPAP for Moms and five (50%) to PRISM. 1265 participants were assessed for eligibility and 312 (24·7%) were recruited, of whom 162 (51·9%) were enrolled in MCPAP for Moms practices and 150 (48·1%) in PRISM practices. Comparing baseline to 11-13 months postpartum, EPDS scores decreased by 4·2 (SD 5·2; p<0·0001) among participants in MCPAP for Moms practices and by 4·3 (SD 4.5; p<0·0001) among those in PRISM practices (estimated difference between groups 0·1 [95% CI -1·2 to 1·4]; p=0·87)., Interpretation: Both the MCPAP for Moms and PRISM interventions were equally effective in improving depression symptoms. This finding is important because the 4-point decrease in EPDS score is clinically significant, and MCPAP for Moms has a lower intensity and greater population-based reach than does PRISM., Funding: US Centers for Disease Control and Prevention., Competing Interests: Declaration of interests NB has received salary and funding support from Massachusetts Department of Mental Health via MCPAP for Moms; is the Medical Director of Research and Evaluation for MCPAP for Moms and the Executive Director of the Lifeline for Families Center at University of Massachusetts Chan Medical School (Worcester, MA, USA); has served on the Medscape Steering Committee on Clinical Advances in Postpartum Depression; has received honoraria from Global Learning Collaborative, Medscape, and Mathematica; and has served as a consultant for The Kinetix Group, VentureWell, and JBS International. TAMS is a consultant for MCPAP for Moms as the Obstetric Engagement Liaison; is the Obstetrics Director of the University of Massachusetts Chan Medical School Lifeline for Moms Program; has served on the American College of Obstetricians and Gynecologists obstetric clinical practice guidelines committee and co-chaired the perinatal mental health expert work group, the Council on Patient Safety in Women's Health and the subsequent Alliance on Innovation in Maternal Health perinatal mental health patient safety bundle work groups, and the Institute of Healthcare Innovation perinatal mental health patient safety bundle change package working group; and has received honoraria from Miller Medical Communications. LB, PS, JF, JYK, CLR, MZ, JA, and SP declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Transformative learning occurs when a person, group, or larger social unit encounters ideas that are at odds with their prevailing perspective. This discrepant perspective can lead to an examination of previously held beliefs, values, and assumptions. The Consortium for Advanced Research Training in Africa (CARTA) has since 2011 been training and supporting faculty from different African universities, to become more reflective and productive researchers, research leaders, educators, and change agents who will drive institutional changes in their institutions. As part of a mid-term evaluation of CARTA, an open-ended question was posed to the CARTA fellows asking them to describe any changes they had experienced in their professional lives as a result of the CARTA Programme. The 135 responses were inductively coded and analysed using qualitative thematic analysis. These themes were subsequently mapped onto Hoggan's typology of transformative learning outcomes. CARTA fellows reported shifts in their sense of self; worldviews; beliefs about the definition of knowledge, how it is constructed and evaluated; and changes in behaviour/practices and capacities. This paper argues that the changes described by the CARTA fellows reflect transformative learning that is embedded in CARTA's Theory of Change. The reported transformation was enabled by a curriculum intentionally designed to facilitate critical reflection, further exploration, and questioning, both formally and informally during the fellows' PhD journey with the support of CARTA facilitators. Documenting and disseminating these lessons provide a guide for future practice, and educators wishing to revitalise their PhD training may find it useful to review the CARTA PhD curriculum.

Background: Few studies have investigated the effects of teacher training and continued support on teachers' delivery of evidence-based HIV prevention programs. We examined these factors in a national implementation study of an evidence-based HIV risk reduction intervention for adolescents in the sixth grade in the Bahamas., Methods: Data were collected from 126 grade 6 teachers and 3,118 students in 58 government elementary schools in the Bahamas in 2019-2021. This is a Hybrid Type III implementation study guided by the Exploration, Preparation, Implementation, Sustainment (EPIS) model. Teachers attended 2-day training workshops. Trained school coordinators and peer mentors provided biweekly monitoring and mentorship. We used mixed-effects models to assess the effects of teacher training and continued support on implementation fidelity., Results: Teachers who received training in-person or both in-person and online taught the most core activities (27.0 and 27.2 of 35), versus only online training (21.9) and no training (14.9) ( F = 15.27, p < .001). Teachers with an "excellent" or "very good" school coordinator taught more core activities than those with a "satisfactory" coordinator or no coordinator (29.2 vs. 27.8 vs. 19.3 vs. 14.8, F = 29.20, p < .001). Teachers with a "very good" mentor taught more core activities and sessions than those with a "satisfactory" mentor or no mentor (30.4 vs. 25.0 vs. 23.1; F = 7.20; p < .01). Teacher training, implementation monitoring, peer mentoring, teachers' self-efficacy, and school-level support were associated with implementation fidelity, which in turn was associated with improved student outcomes (HIV/AIDS knowledge, preventive reproductive health skills, self-efficacy, and intention to use protection)., Conclusion: Teachers receiving in-person training and those having higher-rated school coordinator and mentor support taught a larger number of HIV prevention core activities. Effective teacher training, implementation monitoring, and peer mentoring are critical for improving implementation fidelity and student outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To observe nurse administration of carbapenem antibiotics, in the context of medication safety measures, in intensive care units., Research Methodology/design: A quantitative study was conducted using observation principles., Setting: Three adult private and public Intensive Care Units in the health district of a capital city in KwaZulu-Natal, South Africa., Main Outcome Measures: Nurse practices were observed for double-checking of the medication order, medication vial, and method of preparation and administration. Infusion bags were inspected for nurse labelling of medication and patient details. Patient medication treatment charts were inspected for nurse signature., Results: Carbapenem infusion administrations (n = 223) to twenty patients were observed. Adherence to the scheduled time occurred in 34.9% administrations, 5.4% doses were not given, and an incorrect dose given on 1.4% administrations. One hundred and forty-four (64.6%) infusion bags were inspected during the administrations: there was no medication label affixed to 21.5% bags, and only 8.3% of bags were labelled with essential details; the patient's name, drug, dose, date, time, signature of the nurse mixing and administering the dose, and signature of the secondary nurse., Conclusion: There was a lack of compliance with accepted medication risk mitigation measures. Sub-optimal double-checking resulted in the incorrect dose given, missed dose, and non-adherence to scheduled administration time. This has implications for the optimal administration of antimicrobial medications, raising concerns about the efficacy of treatment for critically ill patients., Implications for Clinical Practice: Parenteral administration errors pose a challenge in acute care areas. Risk mitigation measures include double-checking of medications. If antimicrobial treatment is not administered at the prescribed dosing intervals, this may have implications for the efficacy of time-dependent broad-spectrum antibiotics such as carbapenems. Medication administration errors involving antimicrobial medications should therefore be considered as high-risk errors, with the potential to contribute towards antimicrobial resistance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: There is an emerging need for plant-based, vegan options for patients requiring nutritional support., Methods: Twenty-four adults at risk of malnutrition (age: 59 years (SD 18); Sex: 18 female, 6 male; BMI: 19.0 kg/m 2 (SD 3.3); multiple diagnoses) requiring plant-based nutritional support participated in a multi-center, prospective study of a (vegan suitable) multi-nutrient, ready-to-drink, oral nutritional supplement (ONS) [1.5 kcal/mL; 300 kcal, 12 g protein/200 mL bottle, mean prescription 275 mL/day (SD 115)] alongside dietary advice for 28 days. Compliance, anthropometry, malnutrition risk, dietary intake, appetite, acceptability, gastrointestinal (GI) tolerance, nutritional goal(s), and safety were assessed., Results: Patients required a plant-based ONS due to personal preference/variety (33%), religious/cultural reasons (28%), veganism/reduce animal-derived consumption (17%), environmental/sustainability reasons (17%), and health reasons (5%). Compliance was 94% (SD 16). High risk of malnutrition ('MUST' score ≥ 2) reduced from 20 to 16 patients ( p  = 0.046). Body weight (+0.6 kg (SD 1.2), p  = 0.02), BMI (+0.2 kg/m 2 (SD 0.5), p  = 0.03), total mean energy (+387 kcal/day (SD 416), p  < 0.0001) and protein intake (+14 g/day (SD 39), p  = 0.03), and the number of micronutrients meeting the UK reference nutrient intake (RNI) (7 vs. 14, p  = 0.008) significantly increased. Appetite (Simplified Nutritional Appetite Questionnaire (SNAQ) score; p  = 0.13) was maintained. Most GI symptoms were stable throughout the study ( p  > 0.06) with no serious adverse events related., Discussion: This study highlights that plant-based nutrition support using a vegan-suitable plant-based ONS is highly complied with, improving the nutritional outcomes of patients at risk of malnutrition., Competing Interests: MD, CG, RC, GPH and RJS were employed by Nutricia Ltd. The authors declare that this study received funding from Nutricia Ltd. The funder had the following involvement in the study: study design, data analysis, preparation of the manuscript and decision to publish. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Delsoglio, Griffen, Syed, Cookson, Saliba, Vowles, Davies, Willey, Thomas, Millen, Odeh, Longstaff, Westran, Allan, Offer, Howell, Sanders, Gaffigan, Garrett, Foster, Salt, Carter, Moore, Bergin, Roper, Alvarez, Voss, Connolly, MacDonald, Thrower, Sills, Baxter, Manning, Gray, Voas, Richardson, Hurren, Murphy, Blake, McArdle, Walsh, Booth, Albrich, Ashley-Maguire, Allison, Brook, Capener, Hubbard and Stratton.)

Objective: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers., Design: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles., Results: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states ( phase I ), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations ( phase II ). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence., Conclusion: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact., Competing Interests: Competing interests: Board membership: TRL, RES, LG, FM, CS, RS, H-MC, ED, AK, HS, GAM, SI. Consultancy: LG, UL, GPY, FM, JM, SG, ED, AK, HS, SI. Expert testimony: FM. Grants or contract research: RSB, TRL, RES, FM, RS, FM, ED, ML, GAM, LC. Lectures/Other education events: LG, FM, H-MC, ED, AK. Patents: GPY, RSB, BC, AK, GAM. Receipt of equipment or supplies: LG, RES, ED, ML, GAM. Stock/Stock options: GPY, UL, JM, SG, ED, AK, GAM. Other professional relationships: GPY, SG., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tivozanib is a licensed as first-line treatment for metastatic renal cell carcinoma (mRCC)., Objective: To evaluate the outcomes from tivozanib in a real-world mRCC population., Patients and Methods: Patients with mRCC commencing first-line tivozanib between March 2017 and May 2019 were identified across four specialist cancer centres in the UK. Data relating to response, overall survival (OS), progression-free survival (PFS) and adverse events (AEs) were collected retrospectively with censoring on 31 December 2020., Results: A total of 113 patients were identified: median age was 69 years; 78% had ECOG PS 0-1; 82% had clear cell histology; 66% had previous nephrectomy; International Metastatic RCC Database Consortium (IMDC) score was 22% favourable (F), 52% intermediate (I) and 26% poor (P). Twenty-six per cent were switched from another tyrosine kinase inhibitor (TKI) to tivozanib due to toxicity. Median follow-up was 26.6 months with 18% remaining on treatment at data censoring. Median PFS was 8.75 months. Median PFS by IMDC risk group was: F = 23.0 months; I = 10.0 months; P = 3.0 months, p value < 0.0001. Median OS was 25.0 months (F = not reached (NR) with 72% alive at data cut-off; I = 26.0 months; P = 7.0 months, p value < 0.0001). Seventy-seven per cent had an AE of any grade, and 13% had a grade ≥ 3 AE. Eighteen per cent of patients discontinued treatment due to toxicity. No patients who discontinued a prior TKI due to AEs stopped tivozanib due to AEs., Conclusions: These data suggest comparable activity of tivozanib with the pivotal trial data and other TKIs in a real-world population. Its tolerability positions tivozanib as an attractive first-line option for those unsuitable for combination therapies or unable to tolerate other TKIs., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

YES. In patients with known cardiovascular disease (CVD), ezetimibe with a statin decreases major adverse cardiovascular events (MACE) but has no effect on all-cause and cardiovascular mortality, compared to a statin alone (strength of recommendation [SOR], A; meta-analysis of randomized controlled trials [RCTs] including 1 large RCT). In adults with atherosclerotic CVD (ASCVD), the combination of ezetimibe and a moderate-intensity statin (rosuvastatin 10 mg) was noninferior at decreasing cardiovascular death, major cardiovascular events, and nonfatal stroke, but was more tolerable, compared to a high-intensity statin (rosuvastatin 20 mg) alone (SOR, B; 1 RCT).

Cytokine release syndrome (CRS), also known as cytokine storm, is one of the most consequential adverse effects of chimeric antigen receptor therapies that have shown otherwise promising results in cancer treatment. When emerging, CRS could be identified by the analysis of specific cytokine and chemokine profiles that tend to exhibit similarities across patients. In this paper, we exploit these similarities using machine learning algorithms and set out to pioneer a meta-review informed method for the identification of CRS based on specific cytokine peak concentrations and evidence from previous clinical studies. To this end we also address a widespread challenge of the applicability of machine learning in general: reduced training data availability. We do so by augmenting available (but often insufficient) patient cytokine concentrations with statistical knowledge extracted from domain literature. We argue that such methods could support clinicians in analyzing suspect cytokine profiles by matching them against the said CRS knowledge from past clinical studies, with the ultimate aim of swift CRS diagnosis. We evaluate our proposed methods under several design choices, achieving performance of more than 90% in terms of CRS identification accuracy, and showing that many of our choices outperform a purely data-driven alternative. During evaluation with real-world CRS clinical data, we emphasize the potential of our proposed method of producing interpretable results, in addition to being effective in identifying the onset of cytokine storm., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Oskar Wysocki, Donal Landers, Andre Freitas reports financial support was provided by AstraZeneca PLC. Magdalena Wysocka, Holly Butterworth, Fiona Thistlethwaite reports financial support was provided by UK Research and Innovation. Alex Bogatu reports financial support was provided by Horizon 2020 European Innovation Council Fast Track to Innovation. Elaine Kilgour reports financial support was provided by Cancer Research UK. Manon Pillai, Jennifer Allison reports administrative support was provided by The Christie NHS Foundation Trust. Fiona Thistlethwaite reports a relationship with Zenzium Ltd that includes: funding grants., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To determine the effectiveness of a mobile application (app) in improving the quality of bowel preparation for colonoscopy., Method: An endoscopist-blinded randomised controlled trial enrolled patients who were undergoing a colonoscopy on the same day of bowel preparation. The intervention used a Vietnamese mobile app that provides instructions on bowel preparation while patients in the comparison group received conventional instructions. Outcomes included the Boston Bowel Preparation Scale (BBPS) to assess the quality of bowel preparation and the polyp detection rate (PDR) and adenoma detection rate (ADR)., Results: The study recruited 515 patients (256 in the intervention group). The median age was 42 years, 50.9% were females, 69.1% high school graduates and higher, and 45.2% from urban area. Patients in the intervention group had higher adherence to instructions (60.9% vs 52.4%, p=0.05) and longer length of taking laxatives (mean difference 0.17 hours, 95% CI 0.06 to 0.27). The intervention did not reduce the risk of poor bowel cleansing (total BBPS<6) in both overall (7.4% vs 7.7%; risk ratio 0.96, 95% CI 0.53 to 1.76) and subgroup analysis. PDR and ADR were similar between the two groups., Conclusions: The mobile app providing instructions on proper bowel preparation improved the practice during bowel preparation but did not improve the quality of bowel cleansing or PDR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of 24 cycles. A standard dose ibrutinib was initiated from cycle 2 onward and continued daily until progression. For patients who were already on ibrutinib at the time of study entry, the same was continued while nivolumab was initiated. A total of 24 patients with RT with a median age of 64.5 years (range, 47-88) were enrolled. Ten patients (42%) had received prior treatment for RT and 13 patients (54%) had received a prior BTKi. A total of 10 patients (42%) responded with a median duration of response of 15 months. The median overall survival was 13 months. Four of 24 (17%) patients had checkpoint inhibition-related immunological toxicities. In the CLL cohort, 10 patients were enrolled, of whom 3 patients converted from partial to complete remission; 1 patient had a grade 2 immunological toxicity. Combined nivolumab and ibrutinib is an active regimen for patients with DLBCL RT with an overall response rate of 42%. Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option. This trial is registered at www.clinicaltrials.gov as #NCT02420912., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Interventions to teach protective behaviors may be differentially effective within an adolescent population. Identifying the characteristics of youth who are less likely to respond to an intervention can guide program modifications to improve its effectiveness. Using comprehensive longitudinal data on adolescent risk behaviors, perceptions, sensation-seeking, peer and family influence, and neighborhood risk factors from 2564 grade 10-12 students in The Bahamas, this study employs machine learning approaches (support vector machines, logistic regression, decision tree, and random forest) to identify important predictors of non-responsiveness for precision prevention. We used 80% of the data to train the models and the rest for model testing. Among different machine learning algorithms, the random forest model using longitudinal data and the Boruta feature selection approach predicted intervention non-responsiveness best, achieving sensitivity of 85.4%, specificity of 78.4% and AUROC of 0.93 on the training data, and sensitivity of 84.3%, specificity of 67.1%, and AUROC of 0.85 on the test data. Key predictors include self-efficacy, perceived response cost, parent monitoring, vulnerability, response efficacy, HIV/AIDS knowledge, communication about condom use, and severity of HIV/STI. Machine learning can yield powerful predictive models to identify adolescents who are unlikely to respond to an intervention. Such models can guide the development of alternative strategies that may be more effective with intervention non-responders., (© 2022. The Author(s).)

Purpose: Esophageal mucosal admittance (MA) is a promising diagnostic method for gastroesophageal reflux disease (GERD). We conducted a study to describe the esophageal MA in patients with reflux symptoms and determine its diagnostic accuracy., Patients and Methods: We recruited 92 patients with ambulatory pH-impedance monitoring, upper gastrointestinal endoscopy, and MA measured by the tissue conductance meter. MA was measured during endoscopy at 5cm (distal esophagus) and 15cm above the Z line (middle esophagus), repeated at least five times at each position, and median MA was obtained. Afterwards, two biopsies were taken 5cm above the Z line for histopathological evaluation using the Esohisto criteria. Patients were classified as GERD or non-GERD according to the 2018 Lyon consensus., Results: The mean age was 43.2 years, and 42 patients were males. The most common symptoms were regurgitation (75.0%), belching (65.2%), and heartburn (46.7%). Twenty-three (32.3%) were diagnosed with GERD using the Lyon consensus, and 24 (26.1%) had esophagitis on histopathology. The median MA at the distal and middle esophagus was moderately correlated. The median MA at both positions was higher in the GERD group but only statistically significant in the middle esophagus. MA was not associated with pH-impedance parameters and esophagitis on histopathology. The diagnostic model developed using the logistic regression did not have good accuracy., Conclusion: MA was not different between GERD and non-GERD patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Dao et al.)

Background: In an arts integrated interdisciplinary study set to investigate ways to improve social accountability (SA) in medical education, our research team has established a renewed understanding of compassion in the current SA movement., Aim: This paper explores the co-evolution of compassion and SA., Methods: The study used an arts integrated approach to investigate people's perceptions of SA in four medical schools across Australia, Canada, and the USA. Each school engaged approximately 25 participants who partook in workshops and in-depth interviews., Results: We began with a study of SA and the topic of compassion emerged out of our qualitative data and biweekly meetings within the research team. Content analysis of the data and pedagogical discussion brought us to realize the importance of compassion in the practice of SA., Conclusions: The cultivation of compassion needs to play a significant role in a socially accountable medical educational system. Medical schools as educational institutions may operate themselves with compassion as a driving force in engaging partnership with students and communities. Social accountability without compassion is not SA; compassion humanizes institutional policy by engaging sympathy and care.

Recent studies have demonstrated the importance of temporal regulation of pathogen defense by the circadian clock. However, our understanding of the molecular basis underlying this role of the circadian clock is still in its infancy. We report here the mechanism by which the Arabidopsis master clock protein CCA1 regulates an output target gene GRP7 for its circadian expression and function in pathogen defense. Our data firmly establish that CCA1 physically associates with the GRP7 promoter via the predicted CCA1-binding motif, evening element (EE). A site-directed mutagenesis study showed that while individual EE motifs differentially contribute to robust circadian expression of GRP7, abolishing all four EE motifs in the proximal GRP7 promoter disrupts rhythmicity of GRP7 expression and results in misalignment of defense signaling mediated by GRP7 and altered pathogen responses. This study provides a mechanistic link of the circadian regulation of an output gene to its biological function in pathogen defense, underscoring the importance of temporal control of plant innate immunity., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Inpatient falls are one of the most frequent concerns to patient safety within the acute hospital environment, equating to 1700 falls per year in an 800-bed general hospital. They are predicted to cost approximately £2600 per patient, however, this estimate does not capture the costs and impact that inpatient falls have on the wider health and social care system. It also does not take into the account loss of confidence and delays in functional recovery.This report shares the learning from a quality improvement (QI) initiative that took place in a District General Hospital (DGH) in the UK. The initiative started in February 2020, was paused November 2020 due to wave 2 of the pandemic and restarted in March 2021. Improvement was achieved in January 2021.Data for falls within the Trust identified that falls were within common cause variation. A system change was needed to achieve an improvement.A QI project was commenced with the aim to achieve a 5% reduction in falls per 1000 bed days in a care of the elderly ward.Two primary drivers were identified: recognising patients at high risk of falls and preventing them from falling. Change ideas to address these primary drivers were tested using Plan Do Study Act (PDSA) cycles. Changes tested included: the development of an assessment tool to identify patients at high risk of falls, use of a wristband to identify patients at high risk of a fall, and increased observation.Change ideas achieved some success with the process measures but did not achieve an improvement with the outcome measures. A Trust wide change idea relating to the falls prevention service did lead to a sustained improvement in falls reduction.The barriers to the improvement included changing Trust priorities during the pandemic, and limited opportunities to fully engage the ward-based team with systems thinking and changing mental models., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Bathycoelia distincta (Pentatomidae) is the dominant pest in South African macadamia orchards, where adults are responsible for causing severe yield losses. Similar to other hemipterans, B. distincta release volatile compounds from scent glands that can deter natural enemies and act as an alarm signal among conspecifics. The overall aim of this study was to characterise the alarm pheromone of B. distincta. We: (i) analysed the scent gland contents of individual adult B. distincta by gas chromatography-mass spectrometry (GC-MS), (ii) quantified volatiles released from live stink bugs after stress, and (iii) evaluated the electrophysiological and behavioural activity of alarm pheromone compounds with dose-response experiments. A blend of fourteen compounds was identified in the scent gland extracts of adult stink bugs. Of these, six compounds were detected in the effluvia of live stressed stink bugs [(E)-2-hexenal, (E)-2-decenal, tridecane, dodecane, (E)-4-oxohex-2-enal and (E)-2-decenyl acetate]. No qualitative or quantitative differences were observed between sexes. Tridecane was the most abundant compound, comprising ∼50% of total secretions. Only (E)-2-hexenal, (E)-2-decenal, and (E)-4-oxohex-2-enal elicited an antennal response in both sexes. Finally, exposure to a mixture of (E)-2-hexenal, (E)-2-decenal, and (E)-4-oxohex-2-enal resulted in an increase in the speed and distance travelled by walking bugs and a decrease in time spent resting compared to unexposed bugs. Our results show that the blend of (E)-2-hexenal, (E)-2-decenal, and (E)-4-oxohex-2-enal can induce an alarm response in B. distincta., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Absent contractility is a rare esophageal motility disorder defined by high-resolution manometry which remains poorly understood in pathogenesis and management. We investigated the clinical symptoms, upper gastrointestinal endoscopy findings, and lower esophageal sphincter (LES) characteristics in adult patients diagnosed with absent contractility on high resolution manometry and factors associated with erosive esophagitis that were found on endoscopy in these patients. A cross-sectional study was conducted in patients with absent contractility who were examined at the Institute of Gastroenterology and Hepatology, Vietnam between March 2018 and December 2020. Clinical symptoms, endoscopic findings, and LES metrics were collected and compared between individuals with and without erosive esophagitis. Logistic regression analysis was used to examine a variety of factors associated with erosive esophagitis. Among 7519 patients who underwent high resolution manometry, 204 (2.7%) were diagnosed with absent contractility. The mean age of the study sample was 45.9 years, 65.7% were women, and none had systemic sclerosis. The most common symptoms were regurgitation, belching, epigastric pain, and bloating. On endoscopy, 50% had erosive esophagitis, mostly Los Angeles grade A (42.9%). On manometry, 44.6% of the patients had LES hypotension and 68.1% had low integrated relaxation pressure in 4 seconds (IRP4s). Male sex (adjusted odds ratio = 2.01, 95% confidence interval: 1.04-3.89) and an IRP4s < 5 mm Hg (adjusted odds ratio = 2.21, 95% confidence interval: 1.12-4.37) were significantly associated with erosive esophagitis. Absent contractility was present in many patients without known systemic diseases. Erosive esophagitis was common and associated with male sex and low IRP4s., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Purpose: The purpose of this study was to learn about the Abenaki Indigenous communities' access to services, specifically, their beliefs and knowledge about different types of mental health and substance abuse services and supports within their communities., Methods: This was an exploratory qualitative study using a focus group approach. Two focus groups were conducted in spring 2020 with community members and tribal leaders from different Abenaki Bands in Franklin, Chittenden, and Addison Counties and the Northeast Kingdom in Vermont. Participants were recruited via a mix of convenience and snowball sampling approaches., Results: A total of 15 Abenaki community members participated in 2 separate focus groups, including 5 current and former Chiefs who served or were currently serving as the primary leadership of this state-recognized tribe. Members of the Abenaki community communicated that the loss and erasure of their culture combined with lack of trust of community support agencies impacted the ways in which the Abenaki community conceptualizes health and wellness for themselves and thus impacts parenting and youth substance use as well as opioid use and prescription drug misuse for participants in this study., Conclusion: Abenaki Indigenous experience many obstacles to effective prevention and intervention services. Recruitment of American Indian and Alaska Native (AI/AN) individuals, specifically Abenaki, into the health and mental health workforce can support health equity efforts for this population. Finally, better efforts to foster and support AI/AN culture, specifically Abenaki culture, can support substance use and suicide prevention with this vulnerable community., Competing Interests: We have no conflicts of interest to disclose., (© Maria Mercedes Avila et al., 2022; Published by Mary Ann Liebert, Inc.)

Background: A new classification criterion for diagnosing ineffective esophageal motility (IEM) was proposed at the 2018 Stanford symposium, but limited data exists about the utility of this criterion., Methods: We conducted a cross-sectional study among 3826 patients treated at the Institute of Gastroenterology and Hepatology, Hanoi, Vietnam, between March 2018 and May 2020. Patients were classified as having normal motility, mild IEM, severe IEM, or absent contractility based on the Chicago classification version 3.0 and the new IEM criterion (severe IEM was defined as having >70% ineffective swallows). We examined the association between these 4 motility subgroups and the presence of erosive esophagitis and Barrett's esophagus, using multivariate logistic regression analysis., Results: The mean age of the study sample was 44.7 years and 66.3% were women. The prevalence of symptoms, hiatal hernia, and Helicobacter pylori -positive patients was similar in the 4 study groups. The 4-second integrated relaxation pressures and lower esophageal sphincter resting pressures were lower in patients with severe IEM and absent contractility. Severe IEM and absent contractility, but not mild IEM, were significantly associated with Los Angeles (LA) grade B-D esophagitis (relative risk ratio [RRR] for severe IEM 1.81, 95% confidence interval [CI] 1.17-2.80; and RRR for absent contractility 2.37, 95%CI 1.12-5.04). None of the hypomotility subgroups were associated with LA grade A esophagitis and Barrett's esophagus., Conclusions: Patients with severe IEM have a high prevalence of severe erosive esophagitis. These findings suggest the need for a more meaningful classification criterion for IEM., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with synaptic dysfunction identified as an early pathological hallmark. Although TDP-43 pathology and overt neurodegeneration are largely absent from the cerebellum, the pathological hallmarks of RNA foci and dipeptide repeat protein (DPR) inclusions are most abundant. Here, we present a systematic literature search in the databases of PubMed, Scopus, Embase, Web of Science and Science Direct up until March 5, 2021, which yielded 19,515 publications. Following the exclusion criteria, 72 articles were included having referred to C9orf72, synapses and the cerebellum. Meta-analyses were conducted on studies which reported experimental and control groups with means and standard deviations extracted from figures using the online tool PlotDigitizer. This revealed dendritic defects (P = 0.03), reduced C9orf72 in human patients (P = 0.005) and DPR-related neuronal loss (P = 0.0006) but no neuromuscular junction abnormalities (P = 0.29) or cerebellar neuronal loss (P = 0.23). Our results suggest that dendritic arborisation defects, synaptic gene dysregulation and altered synaptic neurotransmission may drive cerebellar synaptic dysfunction in C9-ALS/FTD. In this review, we discuss how the chronological appearance of the different pathological hallmarks alters synaptic integrity which may have profound implications for disease progression. We conclude that a reduction in C9orf72 protein levels combined with the accumulation of RNA foci and DPRs act synergistically to drive C9 synaptopathy in the cerebellum of C9-ALS/FTD patients., (© 2021. Crown.)

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP-NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP-NENs who developed BMs., Methods: A retrospective single-centre analysis of consecutive patients with EP-NENs (August 2004-February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan-Meier)., Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15-77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP-NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease ( p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5-139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery ( n = 3); radiotherapy ( n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2-31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0-8.3]., Conclusion: BMs in patients with EP-NENs are rare and of increased risk in G3 vs. G1 + G2 EP-NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes.

Purpose: Social accountability (SA) is the responsibility of faculties of medicine (FoMs) to address the health priorities of the communities they serve. Community engagement (CE) is a vital, but often ambiguous, component of SA. Practical guidance on how to engage community partners (CPs) is key for meaningful CE. We conducted a systematic scoping review of CE involving FoMs to map out how FoMs engage their communities, to provide practical recommendations for FoMs to take part in CE, and to highlight gaps in the literature., Materials and Methods: We searched electronic databases for articles describing projects or programs involving FoMs and CPs. Descriptive information was analyzed thematically., Results: Thirty-eight of 1406 articles were included, revealing three themes: (1) Partners (Who to Engage)-deciding who to engage establishes the basis for responsibility and creates space for communities to engage FoMs; (2) Partnerships (How to Engage)-fostering creative and authentic collaboration, enabling meaningful community contributions; and (3) Projects and Programs (With What to Engage)-identifying opportunities for communities to have a voice in many spaces within FoMs. Under these themes emerged 32 practical recommendations., Conclusion: Practical guidance facilitates meaningful commitments to communities. The literature is rich with examples of community-FoM partnerships. We provide recommendations for CE that are clear, evidence-based, and responsive.

Vestibular evoked myogenic potentials (VEMPs) are routinely used to test otolith function, but which specific vestibular afferent neurons and central circuits are activated by auditory frequency VEMP stimuli remains unclear. To examine this question, we analyzed the sensitivity of individual vestibular afferents in adult Sprague-Dawley rats to tone bursts delivered at 9 frequencies (125-4000 Hz) and 3 intensity levels (60, 70, 80 dB SL re: acoustic brainstem response (ABR) threshold). Afferent neuron tone sensitivity was quantified by the cumulative probability of evoking a spike (CPE). Based on a threshold CPE of 0.1, acoustic stimuli in the present study evoked responses in 78.2 % (390/499) of otolith afferent neurons vs. 48.4 % (431/891) of canal afferent neurons. Organ-specific vestibular inputs to the central nervous system in response to tone bursts differ based on intensity and frequency content of the stimulus. At frequencies below 500 Hz, tone bursts primarily activated both otolith afferents, even at the highest intensity tested (80 dB SL re ABR threshold). At 1500 Hz, however, tone bursts activated the canal and otolith afferents at the moderate and high intensities tested (70, 80 dB SL), but activated only otolith afferents at the low intensity tested (60 dB SL). Within an end organ, diversity of sensitivity between individual afferent neurons correlated with spontaneous discharge rate and regularity. Examination of inner ear fluid mechanics in silico suggests that the frequency response and preferential activation of the otolith organs likely arise from inner ear fluid motion trapped near the oval and round windows. These results provide insight into understanding the mechanisms of sound activation of the vestibular system and developing novel discriminative VEMP testing protocols and interpretative guidelines in humans., (© 2022. The Author(s) under exclusive licence to Association for Research in Otolaryngology.)

Background: India is at the epicentre of global child undernutrition. Strategies to identify at-risk populations are needed in the context of limited resources., Methods: Data from children under the age of five surveyed in the 2015-2016 National Family Health Survey were used. Child undernutrition was assessed using anthropometric measurements. Predictor variables were identified from the extant literature and included if they could be measured at the time of delivery. Survey-weighted logistic regression was applied to model the outcome. Internal validation of the model was performed using 200 bootstrapped samples representing half of the total data sets., Results: In 2016, 54.4% (95% CI = 54.0%-54.8%) of Indian children were undernourished, according to a composite index of anthropometric failure. The predictive model for overall undernutrition included maternal (height, education, reproductive history, number of antenatal visits), child (sex, birthweight), and household characteristics (district of residence, caste, rural residence, toilet availability, presence of a separate kitchen). The model demonstrated reasonable discrimination ability (optimism-adjusted c = 0.67). The group of children classified in the lowest decile for risk of undernutrition had a prevalence of 25.9%, while the group classified in the highest decile had a prevalence of 77.4%., Conclusions: It is possible to stratify newborns at the time of delivery based on their risk for undernutrition in the first five years of life. The model developed by this study represents a first step in adopting a risk-score based approach for the most vulnerable population to receive services in a timely manner., Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest Form (available upon request from the corresponding author), and declare no conflicts of interest., (Copyright © 2022 by the Journal of Global Health. All rights reserved.)

Purpose: Perinatal depression affects upwards of one in seven women and is associated with significant negative maternal and child consequences. Despite this, it remains under-detected and under-treated. We sought to identify clinician practices, self-efficacy, and remaining barriers to comprehensively addressing perinatal depression care. Materials and Methods: Surveys were administered to obstetric clinicians in Massachusetts that queried frequency of depression screening and Likert questions about subsequent depression management. Results: Approximately 79.0% of clinicians approached completed the survey. Whereas most clinicians (93.5%) screened for perinatal depression at 6 weeks postpartum, fewer clinicians (66.1%) screened during pregnancy. Most reported they were comfortable providing support to their patients (98.4%), but fewer endorsed being able to treat them on their own (43.0%). Most noted an ability to treat with antidepressants (77.9%); however, fewer endorsed adequate access to nonmedication treatment (45.5%). Conclusions: The majority of surveyed clinicians screen for depression consistent with guidelines. However, efforts are focused on the postpartum period, despite literature citing two-thirds of patients experiencing onset before or during pregnancy. Respondents indicated an ability to treat with medication management, while noting greater challenge with referral. These findings describe the challenges of interdisciplinary coordination as a barrier to comprehensive perinatal mental health care. Clinical Trial Registration Number: NCT02760004.

The somatic embryogenesis receptor kinase (SERK) gene family has been intensively studied in several plant species. Here we confirmed the existence of five SERK genes in grapevine (Chinese wild grapevine Vitis quinquangularis ) and named them VqSERK1 , VqSERK2 , VqSERK3 , VqSERK4 , and VqSERK5 . Analysis of the predicted structures of these SERK proteins revealed they include a signal peptide domain, a leucine zipper domain, a Ser-Pro-Pro domain, a single transmembrane domain, different leucine-rich repeats, and an intracellular kinase activity domain. The SERK genes of grapevine showed different gene expression patterns when treated with powdery mildew ( Erysiphe necator ) and hormones (salicylic acid, jasmonic acid, abscisic acid, and ethylene). Subcellular localization assays confirmed that VqSERK family proteins localized to the cell membrane. Moreover, we cloned the SERK3/BAK1 gene from the Chinese wild grapevine V. quinquangularis clone 'Shang-24'. Heterologous VqSERK3/BAK1 expression in the Arabidopsis bak1-4 mutant lines restored control of cell death, increased resistance to powdery mildew, and strengthened stomatal immunity. Our work may provide the foundation for further studies of SERK genes for pathogen resistance and hormone treatment in grapevine.

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool.

Background: India launched the National Rural Health Mission (NRHM) in 2005 to strengthen its primary healthcare system in high-focus and northeast-focus states. One of the NRHM objectives was to reduce child undernutrition in India., Methods and Findings: We used data from 1992, 1998, 2005, and 2015 National Family Health Survey (NFHS) of India to evaluate trends in child undernutrition prevalence before and after NRHM and across different categories of focus states. Stunting, Wasting, and Comprehensive Index of Anthropometric Failure (CIAF) were assessed using the World Health Organization (WHO) growth curves to assess chronic, acute, and overall undernutrition. The study included 187,452 children aged 3 years or under. Survey-weighted and confounder-adjusted average annualized reduction rates (AARRs) and predicted probability ratios were used to assess trends and socioeconomic disparities for child undernutrition, respectively. Nationwide, the prevalence of all types of undernutrition decreased from 1992 to 2015. However, the trends varied before and after NRHM implementation and differentially by focus states. After NRHM, acute undernutrition declined more rapidly among high-focus states (AARR 1.0%) but increased in normal-focus states (AARR -1.9% per year; p-value for the difference <0.001). In contrast, the prevalence of chronic undernutrition declined more rapidly (AARR 1.6%) in the normal-focus states in comparison to high-focus states (0.3%; p-value for the difference = 0.01). Income and caste-based disparities in acute undernutrition decreased but did not disappear after the implementation of the NRHM. However, similar disparities in prevalence of chronic undernutrition appear to be exacerbated after the implementation of the NRHM. Major limitations of this study include the observational and cross-sectional design, which preclude our ability to draw causal inferences., Conclusions: Our results suggests that NRHM implementation might be associated with improvement in wasting (acute) rather than stunting (chronic) forms of undernutrition. Strategies to combat undernutrition equitably, especially in high-focus states, are needed., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: One of the authors (ZAB) is on the editorial board of PLOS Medicine and was a Guest Editor for the Global Child and Adolescent Health Special Issue.

The quality and success of postgraduate education largely rely on effective supervision. Since its inception in 2008, the Consortium for Advanced Research Training in Africa (CARTA) has been at the forefront of providing training to both students and supervisors in the field of public and population health. However, there are few studies on supervisors' perceptions on effective doctoral supervision. We used a mostly descriptive study design to report CARTA-affiliated doctoral supervisors' reflections and perceptions on doctoral supervision, challenges and opportunities. A total of 77 out of 160 CARTA supervisors' workshop participants responded to the evaluation. The respondents were affiliated with 10 institutions across Africa. The respondents remarked that effective supervision is a two-way process, involving both supervisor and supervisee's commitment. Some reported that the requirements for effective supervision included the calibre of the PhD students, structure of the PhD programme, access to research infrastructure and resources, supervision training, multidisciplinary exposure and support. Male supervisors have significantly higher number of self-reported PhD graduates and published articles on Scopus but no difference from the females in h-index. We note both student and systemic challenges that training institutions may pursue to improve doctoral supervision in Africa.

Introduction: Considering the critical role that American Indian and Alaska Native (Native) men play in family and child health, there is an urgent need to collaborate with Native communities in developing interventions and policies to improve Native men's health status. This study aims to address a significant gap in research by designing and implementing a culturally grounded health promotion program to increase economic stability, promote positive parenting, and build healthy relationships among Native fathers. The Azhe'é Bidziil ("Strong Fathers") study protocol, developed in response to community advisory board feedback, illustrates a community-engaged approach to developing and implementing a fatherhood program in two Diné (Navajo) communities., Methods/analysis: Azhe'é Bidziil was adapted from three evidence-based interventions developed in collaboration with Native communities. Intervention lessons were iteratively reviewed by a tribal working group to ensure that the content is culturally appropriate and relevant. A pre-post study will assess feasibility, acceptability, and satisfaction with the Azhe'é Bidziil intervention, as well as short-term impacts on positive parenting, economic stability, and healthy relationship outcomes. The intervention is composed of 12 weekly group sessions conducted with fathers ( n = 750) that focus on developing knowledge and skills for positive father involvement, economic stability, and healthy relationships. Lesson content includes: honoring our roles as fathers, building healthy relationships, understanding the impact of historical trauma, goal-setting, and budgeting basics. Each of the 12 group lessons, consisting of 8-12 participants per group, last approximately 2 h. Eligible fathers or father figures are age ≥18 years, live within 50 miles of the participating Diné communities, and must be caregivers of at least one child ≤ 24 years. The outcomes for this study are acceptability, feasibility, and satisfaction with the intervention, as well as father involvement, quality of (co-) parenting communication, healthy relationships, fathers' engagement and communication with their children, protective factors (e.g., cultural connectedness and educational/career aspirations), and economic empowerment and stability. Participants will complete an outcome assessment at pre- and post-intervention (12 weeks later)., Discussion: This study protocol presents one of the few evaluations of a fatherhood intervention to increase economic stability, promote positive parenting, and build healthy relationships among Native fathers in rural tribal communities. Such a study is sorely needed to address the health disparities perpetuated by social and Indigenous determinants of health that Native men experience today. If proven efficacious, this pre- post-study will inform a large scale randomized controlled trial to evaluate intervention impact, and if proven efficacious may be disseminated widely in tribal nations. Study findings may also deepen our understanding of peer mentoring, Native men's health status, involvement with their children, co-parenting relationships, family relationships, cultural connectedness, and economic status. The data collected may also inform strategies to ensure acceptability, feasibility, and satisfaction of an intervention designed specifically for Native fathers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Richards, Begay, Chambers, Patel, Mayhew, Allison-Burbank, Gishie, Tsingine, Badoni, Staley, Harvey, Tsosie, Begay, Mitchell and Tingey.)