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Background and purposePosterior circulation strokes, accounting for 20% of acute ischemic strokes, significantly contribute to morbidity and mortality. Fibrinolysis by rtPA improves outcomes in stroke but the risk of intracranial hemorrhage limits benefit. Arterial recanalization of basilar artery occlusion by thrombolysis or endovascular thrombectomy improves outcomes in posterior circulation strokes. This study investigates a VWF-targeting RNA aptamer as a safer and more effective alternative to rtPA in a canine model.Materials and methodsAutologous clots were placed into the basilar artery to induce stroke in 24 beagles. To compare reperfusion, 0.9 mg/kg rtPA, 0.5 mg/kg BB-031, or vehicle were administered 60 min after the initiation of occlusion. Digital subtraction angiography, laser speckle imaging and magnetic resonance imaging were used to assess recanalization, reperfusion and infarct volume, respectively.ResultsTreatment with BB-031 resulted in recanalization of the posterior circulation on digital subtraction angiography with no evidence of microembolism assessed at sacrifice. 66.5% of animals treated with BB-031 resulted in reperfusion with a TICI score of ≥1 whereas vehicle remained at TICI score 0 as did all but one rtPA animal at sacrifice. Improved perfusion was seen in the basilar artery and surrounding blood vessels visualized through the cranial window with laser speckle imaging to ~47% of its original baseline in BB-031 group compared to rtPA at 37% and vehicle at 22%. Finally, BB-031-treatment resulted in an approximate 32% mean infarct volume, significantly smaller on magnetic resonance imaging compared to 56% in vehicle treated and 48% with rtPA treatment.ConclusionTargeted inhibition of VWF by BB-031 increased recanalization and reperfusion, and reduced infarct volume in a canine model of BAO stroke. It represents a promising target based on preliminary results for treating acute ischemic stroke.

Abstract Identifying women at high risk of osteoporotic fracture from aromatase inhibitor (AI) therapy for breast cancer is largely based on known risk factors for healthy postmenopausal women, which might not accurately reflect the risk in breast cancer patients post-AI therapy. To determine whether a polygenic score associated with fracture in healthy women is also significant in women treated with AIs for breast cancer, we used data from a prospective observational cohort of 2152 women diagnosed with hormonal receptor positive breast cancer treated with AIs as the initial endocrine therapy and examined a polygenic score of heel quantitative ultrasound speed of sound (gSOS) in relation to incident osteoporotic fracture after AI therapy during a median 6.1 years of follow up after AI initiation. In multivariable models, patients with the second and third highest tertiles (T) versus the lowest tertile of gSOS had significantly lower risk of fracture (T2: adjusted HR = 0.61, 95% CI: 0.46-0.80; T3: adjusted HR = 0.53, 95% CI: 0.40-0.70). The lower risk of fracture in patients with the highest tertile of gSOS remained significant after further adjustment for BMD at the hip (T3: adjusted HR = 0.62, 95% CI: 0.42-0.91). In conclusion, our analysis showed gSOS as a novel genetic predictor for fracture risk independent of BMD among breast cancer patients treated with AIs. Future studies are warranted to evaluate the performance of incorporating gSOS in prediction models for the risk of AI-related fracture in breast cancer patients.

Abstract Telomeres, the ends of eukaryotic chromosomes, protect genome integrity and enable cell proliferation. Maintaining optimal telomere length in the germline and throughout life limits the risk of cancer and enables healthy aging. Telomeres in the house mouse, Mus musculus, are about five times longer than human telomeres, limiting the use of this common laboratory animal for studying the contribution of telomere biology to aging and cancer. We identified a key amino acid variation in the helicase RTEL1, naturally occurring in the short-telomere mouse species M. spretus. Introducing this variation into M. musculus is sufficient to reduce the telomere length set point in the germline and generate mice with human-length telomeres. While these mice are fertile and appear healthy, the regenerative capacity of their colonic epithelium is compromised. The engineered Telomouse reported here demonstrates a dominant role of RTEL1 in telomere length regulation and provides a unique model for aging and cancer.

Background: People living with non-communicable diseases (NCDs) such as hypertension and diabetes are at high risk for mental health and psychosocial problems. These problems, in turn, can lead to social isolation, lower quality of life, greater health needs, and poorer health outcomes. The prevalence of NCDs is rising in humanitarian settings, where residents are already at an increased risk of mental health problems due to trauma and stressful living conditions. Yet there has been limited focus on understanding experiences and intersections between these often-co-occurring health conditions in humanitarian settings. Improving this understanding holds promise for supporting integrated care and better patient health outcomes. Objective: To describe mental health problems of displaced Myanmar adults with current poor medication adherence for hypertension and/or type 2 diabetes mellitus and identify factors associated with poor mental health among this population. Methods: Cross-sectional analysis of 224 adults with poor medication adherence (

In low- and middle-income countries (LMICs), children and families face a multitude of risk factors for mental health and well-being. These risks are even further exacerbated in humanitarian emergencies. However, access to effective mental health services in such settings is severely limited, leading to a large mental health treatment gap. Middle childhood (5–12 years) is a crucial period for human development during which symptoms of emotional distress often emerge, with one in three mental disorders developing prior to age 14. However, there is little evidence of effective psychological interventions for children in this developmental stage, and suitable for implementation within LMICs and humanitarian emergencies. We conducted this evidence review to inform the development of a new intervention package based on existing best practice for this age group, drawing insights from both global and LMIC resources. Our review synthesizes the findings of 52 intervention studies from LMICs and humanitarian settings; 53 existing systematic reviews and meta-analyses covering both LMICs and high-income countries, and 15 technical guidelines. Overall, there is limited high-quality evidence from which to draw recommendations for this age group; however, some promising intervention approaches were identified for children experiencing externalizing and internalizing symptoms, traumatic stress and a combination of difficulties. Several effective interventions utilize cognitive-behavioral techniques for children, in either group or individual format, and incorporate caregiver skills training into treatment, although the findings are mixed. Most evaluated interventions use specialists as delivery agents and are lengthy, which poses challenges for scale-up in settings where financial and human resources are scarce. These findings will inform the development of new psychological interventions for children in this age group with emotional and behavioral difficulties.

Abstract Background This study evaluated the effectiveness of Baby Friendly Spaces (BFS), a psychosocial support program for Rohingya refugee mothers of malnourished young children in Bangladesh. Because BFS was already being implemented, we examined the benefit of enhancing implementation supports. Methods In matched pairs, 10 sites were randomized to provide BFS treatment as usual (BFS-TAU) or to receive enhanced implementation support (BFS-IE). 600 mothers were enrolled and reported on maternal distress, functional impairment, subjective well-being and coping at baseline and 8-week follow-up. Data were analyzed using multilevel linear regression models to account for clustering; sensitivity analyses adjusted for the small number of clusters. Results Significant within-group improvements in BFSIE were observed for distres (−.48, p = .014), functional impairment (−.30, p = .002) and subjective well-being (.92, p = .011); improvements in BFS-TAU were smaller and not statistically significant. Between-group comparisons favored BFS-IE for distress (β = −.30, p = .058) and well-being (β = .58, p = .038). Sensitivity adjustments produced p-values above .05 for all between-group comparisons. Discussion Feasible adjustments to implementation can improve program delivery to increase impact on maternal distress and well-being. Although results should be interpreted with caution, study design limitations are common in pragmatic, field-based research.

BackgroundThere is emerging evidence that cancer and its treatments may accelerate the normal aging process, increasing the magnitude and rate of decline in functional capacity. This accelerated aging process is hypothesized to hasten the occurrence of common adverse age-related outcomes in cancer survivors, including loss of muscle mass and decrease in physical function. However, there is no data describing age-related loss of muscle mass and its relation to physical function in the long-term in cancer survivors.MethodsThis study protocol describes the use of a novel method of muscle mass measurement, D3-creatine dilution method (D3Cr), in a large sample (n~6000) of community dwelling postmenopausal women from the Women's Health Initiative (WHI). D3Cr will be used to obtain a direct measure of muscle mass remotely. Participants will be drawn from two sub-cohorts embedded within the WHI that have recently completed an in-home visit. Cancer survivors will be drawn from the Life and Longevity After Cancer (LILAC) cohort, and cancer-free controls will be drawn from the WHI Long Life Study 2. The overall objective of this study is to examine the antecedents and consequences of low muscle mass in cancer survivors. The study aims are to: 1) create age-standardized muscle mass percentile curves and z-scores to characterize the distribution of D3- muscle mass in cancer survivors and non-cancer controls, 2) compare muscle mass, physical function, and functional decline in cancer survivors and non- cancer controls, and 3) use machine learning approaches to generate multivariate risk-prediction algorithms to detect low muscle mass.DiscussionThe D3Cr method will transform our ability to measure muscle mass in large-scale epidemiologic research. This study is an opportunity to advance our understanding of a key source of morbidity among older and long-term female cancer survivors. This project will fill knowledge gaps, including the antecedents and consequences of low muscle mass, and use innovative methods to overcome common sources of bias in cancer research. The results of this study will be used to develop interventions to mitigate the harmful effects of low muscle mass in older adults and promote healthy survivorship in cancer survivors in the old (>65) and oldest-old (>85) age groups.

Objectives In the first year of the COVID-19 pandemic, health systems implemented programmes to manage outpatients with COVID-19. The goal was to expedite patients’ referral to acute care and prevent overcrowding of medical centres. We sought to evaluate the impact of such a programme, the COVID-19 Home Care Team (CHCT) programme.Design Retrospective cohort.Setting Kaiser Permanente Northern California.Participants Adult members before COVID-19 vaccine availability (1 February 2020–31 January 2021) with positive SARS-CoV-2 tests.Intervention Virtual programme to track and treat patients with ‘CHCT programme’.Outcomes The outcomes were (1) COVID-19-related emergency department visit, (2) COVID-19-related hospitalisation and (3) inpatient mortality or 30-day hospice referral.Measures We estimated the average effect comparing patients who were and were not treated by CHCT. We estimated propensity scores using an ensemble super learner (random forest, XGBoost, generalised additive model and multivariate adaptive regression splines) and augmented inverse probability weighting.Results There were 98 585 patients with COVID-19. The majority were followed by CHCT (n=80 067, 81.2%). Patients followed by CHCT were older (mean age 43.9 vs 41.6 years, p

AbstractUniversity students experience various factors that impact their well-being in higher education learning. Self-determination theory (SDT) shares the underlying philosophy of eudaimonia and well-being. This study examined the relationship between satisfaction of the basic psychological needs for autonomy, competence, and relatedness in predicting greater well-being among first-year university students in a private university in Selangor, Malaysia. The sample derived from 173 first-year university students studying in Selangor, Malaysia. Participants completed measures of the Basic Psychological Needs Satisfaction Scale and Subjective Vitality Scale. The findings of this study indicated that autonomy, competence, and relatedness significantly predicted students’ well-being. Moreover, the roles of basic psychological needs appeared to be important factors in predicting well-being among university students. Results of this study further highlighted that when students feel autonomous, sense of school connectedness, and sense of scholastic competence, they are able to flourish under a positive learning environment and cultivate eudaimonic well-being.

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1–1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water.

Objectives To examine the cost-effectiveness of Multi-specialty INterprofessional Team (MINT) Memory Clinic care in comparison to the provision of usual care.Design Using a Markov-based state transition model, we performed a cost-utility (costs and quality-adjusted life years, QALY) analysis of MINT Memory Clinic care and usual care not involving MINT Memory Clinics.Setting A primary care-based Memory Clinic in Ontario, Canada.Participants The analysis included data from a sample of 229 patients assessed in the MINT Memory Clinic between January 2019 and January 2021.Primary outcome measures Effectiveness as measured in QALY, costs (in Canadian dollars) and the incremental cost-effectiveness ratio calculated as the incremental cost per QALY gained between MINT Memory Clinics versus usual care.Results MINT Memory Clinics were found to be less expensive ($C51 496 (95% Crl $C4806 to $C119 367) while slightly improving quality of life (+0.43 (95 Crl 0.01 to 1.24) QALY) compared with usual care. The probabilistic analysis showed that MINT Memory Clinics were the superior treatment compared with usual care 98% of the time. Variation in age was found to have the greatest impact on cost-effectiveness as patients may benefit from the MINT Memory Clinics more if they receive care beginning at a younger age.Conclusion Multispecialty interprofessional memory clinic care is less costly and more effective compared with usual care and early access to care significantly reduces care costs over time. The results of this economic evaluation can inform decision-making and improvements to health system design, resource allocation and care experience for persons living with dementia. Specifically, widespread scaling of MINT Memory Clinics into existing primary care systems may assist with improving quality and access to memory care services while decreasing the growing economic and social burden of dementia.

BackgroundChild maltreatment is a global public health crisis with negative consequences for physical and mental health. Children in low- and middle-income countries (LMIC)-particularly those affected by poverty, armed conflict, and forced migration-may be at increased risk of maltreatment due to heightened parental distress and disruptions to social support networks. Parenting interventions have been shown to reduce the risk of child maltreatment as well as improve a range of caregiver and child outcomes, yet large-scale implementation remains limited in low-resource displacement settings. This study will examine the impact of an entertainment-education narrative film intervention on reducing physical and emotional abuse and increasing positive parenting among migrant and displaced families from Myanmar living in Thailand.MethodThe study is a pragmatic, superiority cluster randomized controlled trial with approximately 40 communities randomized to the intervention or treatment as usual arms in a 1:1 ratio. Participating families in the intervention arm will be invited to attend a community screening of the film intervention and a post-screening discussion, as well as receive a poster depicting key messages from the film. Primary outcomes are changes in physical abuse, emotional abuse, and positive parenting behaviour. Secondary outcomes include caregiver knowledge of positive parenting, caregiver attitudes towards harsh punishment, caregiver psychological distress, and family functioning. Outcomes will be assessed at 3 time points: baseline, 4 weeks post-intervention, and 4-month follow up. A mixed methods process evaluation will be embedded within the trial to assess intervention delivery, acceptability, perceived impacts, and potential mechanisms of change.DiscussionTo our knowledge, this study will be the first randomized controlled trial evaluation of a film-based intervention to reduce child maltreatment among migrant and displaced families in a LMIC. An integrated knowledge translation approach will inform uptake of study findings and application to potential scale up pending evaluation results.Trial registrationThe study was prospectively registered with the Thai Clinical Trials Registry on 22 February 2023 (TCTR20230222005).

Background: Forced displacement is associated with elevated risk for poor psychosocial wellbeing, yet there remains a lack of clarity around the effectiveness of commonly implemented psychosocial support interventions focused on preventing disorder and promoting wellbeing. This study aimed to synthesize the literature on evaluations of psychosocial support interventions for populations affected by forced displacement. Methods: We searched for peer reviewed and gray literature in seven databases (PubMed, Embase, Global Health, CINAHL, SocIndex, PsychInfo, PILOTS), fifteen organizational websites, and via solicitation through multiple networks. Various study designs were included, with the criteria that they report an evaluation of a psychosocial intervention delivered to populations affected by forced displacement, and included quantitative or qualitative data on psychosocial outcomes. Records were screened independently by two reviewers at both title/abstract and full-text review; data was double-extracted and study quality assessed, with discrepancies resolved by consensus. Meta-analyses for seven outcomes were conducted on a subset of 33 studies. Results: We identified 162 reports. Over half (55%) used a single-group study design, with fewer using non-random (19%) or randomized (21%) comparisons. Study designs incorporating comparison conditions were less likely to report positive findings than single-group studies. In the meta-analyses, a moderately strong overall effect was found for psychosocial wellbeing (ES: -0.534, 95% CI: [-0.870, -0.197], p=.005); small effects on both internalizing (ES: -0.152, 95% CI: [-0.310, 0.005], p= .057) and externalizing (ES: -0.249, 95% CI: [-0.515, 0.016], p=.064) problems were promising but not conclusive. Subgroup analysis suggested differential impacts on internalizing problems for adults (improvement; ES: -0.289, 95% CI: [-0.435, -0.143], p=.001) and children (worsening; ES: 0.129, 95% CI: [.054, 0.204], p=.002). Other subgroup analyses showed little meaningful variation by context, population, or intervention characteristics. Conclusion: Pragmatic, field-driven program evaluations are dominated by single-group designs with significant risk of bias. Findings from controlled studies are promising but highlight a need for more rigorous research to support causal inference, align outcomes with theories of change, improve measurement of more positive or wellbeing-focused outcomes, examine subgroup differences, and report potentially negative impacts.

Abstract Background Globally, policy-makers face challenges to using evidence in health decision-making, particularly lack of interaction between research and policy. Knowledge-brokering mechanisms can fill research–policy gaps and facilitate evidence-informed policy-making. In Myanmar, the need to promote evidence-informed policy is significant, and thus a mechanism was set up for this purpose. This paper discusses lessons learned from the development of the Knowledge Broker Group–Myanmar (KBG-M), supported by the Johns Hopkins Bloomberg School of Public Health’s Applied Mental Health Research Group (JHU) and Community Partners International (CPI). Methods Sixteen stakeholders were interviewed to explore challenges in formulating evidence-informed policy. Two workshops were held: the first to further understand the needs of policy-makers and discuss knowledge-brokering approaches, and the second to co-create the KBG-M structure and process. The KBG-M was then envisioned as an independent body, with former officials of the Ministry of Health and Sports (MoHS) and representatives from the nongovernmental sector actively engaging in the health sector, with an official collaboration with the MoHS. Results A development task force that served as an advisory committee was established. Then, steps were taken to establish the KBG-M and obtain official recognition from the MoHS. Finally, when the technical agreement with the MoHS was nearly complete, the process stopped because of the military coup on 1 February 2021, and is now on hold indefinitely. Conclusions Learning from this process may be helpful for future or current knowledge-brokering efforts, particularly in fragile, conflict-affected settings. Experienced and committed advisory committee members enhanced stakeholder relationships. Responsive coordination mechanisms allowed for adjustments to a changing bureaucratic landscape. Coordination with similar initiatives avoided overlap and identified areas needing technical support. Recommendations to continue the work of the KBG-M itself or similar platforms include the following: increase resilience to contextual changes by ensuring diverse partnerships, maintain advisory committee members experienced and influential in the policy-making process, ensure strong organizational and funding support for effective functioning and sustainability, have budget and timeline flexibility to allow sufficient time and resources for establishment, organize ongoing needs assessments to identify areas needing technical support and to develop responsive corrective approaches, and conduct information sharing and collaboration between stakeholders to ensure alignment.

Background: Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown. Methods: Cohort study of 2896 women aged 60–79 years recruited after attending mammography screening between 10/2012 and 2/2015. BAC status (presence versus absence) and quantity (calcium mass mg) was determined using digital mammograms. Pre-specified endpoints were incident coronary heart disease (CHD), ischemic stroke, heart failure and its subtypes and all CVD. Results: After 7.4 (SD = 1.7) years of follow-up, 51 CHD, 30 ischemic stroke and 46 heart failure events were ascertained. At a limit of detection of 1.6 ng/L, 98.3 of the cohort had measurable hsTnI concentration. HsTnI in the 4–10 ng/L range were independently associated of CHD (adjusted hazard ratio[aHR] = 2.78; 95% CI, 1.48–5.22; p = 0.002) and all CVD (aHR = 2.06; 95% CI, 1.37–3.09; p = 0.0005) and hsTnI over 10 ng/L was independently associated with CHD (aHR = 4.75; 95% CI, 1.83–12.3; p = 0.001), ischemic stroke (aHR = 3.81; 95% CI, 1.22–11.9; p = 0.02), heart failure (aHR = 3.29; 95% CI, 1.33–8.13; p = 0.01) and all CVD (aHR = 4.78; 95% CI, 2.66–8.59; p

Stony Coral Tissue Loss Disease (SCTLD) has affected Caribbean coral reef colonies since it was first detected in Florida in 2014. Its rapid spread and virulent nature are a major concern to coastal nations in the Caribbean Sea. Belize and Honduras have approached their management and strategies in somewhat different ways, but with the same goal of evaluating and controlling the spread and reducing mortality rates of their coral colonies. They both used amoxicillin trihydrate powder with Coral Ointment Base2B which proved effective in halting the spread of the disease and lowered mortality rates in treated corals. In addition to treatment, both countries have continued to monitor the extent of the disease, entering the data into the collaborative disease tracker platform on AGRRA.org. Between October 2020 and November 2021, a total of 14,495 corals from 29 species were assessed at sites in Belize and Honduras that were affected by SCTLD. The overall prevalence (all coral species) of SCTLD at these sites was 14%. Three species (Meandrina meandrites, Dendrogyra clyindrus and Dichocoenia stokesi) were in the top affected species in both countries, with 42%, 38% and 32% SCTLD prevalence, respectively. The sharing of information allowed Belize and Honduras to be relatively prepared for the onset of SCTLD in their waters through a series of monitoring and intervention actions. Although the treatment has proved to be somewhat effective, it is time and labor intensive. Reducing other well-known anthropogenic including sewage and dredging, is key to supporting coral reef health and resiliency.

Abstract Background Semi-competing risks arise when interest lies in the time-to-event for some non-terminal event, the observation of which is subject to some terminal event. One approach to assessing the impact of covariates on semi-competing risks data is through the illness-death model with shared frailty, where hazard regression models are used to model the effect of covariates on the endpoints. The shared frailty term, which can be viewed as an individual-specific random effect, acknowledges dependence between the events that is not accounted for by covariates. Although methods exist for fitting such a model to right-censored semi-competing risks data, there is currently a gap in the literature for fitting such models when a flexible baseline hazard specification is desired and the data are left-truncated, for example when time is on the age scale. We provide a modeling framework and openly available code for implementation. Methods We specified the model and the likelihood function that accounts for left-truncated data, and provided an approach to estimation and inference via maximum likelihood. Our model was fully parametric, specifying baseline hazards via Weibull or B-splines. Using simulated data we examined the operating characteristics of the implementation in terms of bias and coverage. We applied our methods to a dataset of 33,117 Kaiser Permanente Northern California members aged 65 or older examining the relationship between educational level (categorized as: high school or less; trade school, some college or college graduate; post-graduate) and incident dementia and death. Results A simulation study showed that our implementation provided regression parameter estimates with negligible bias and good coverage. In our data application, we found higher levels of education are associated with a lower risk of incident dementia, after adjusting for sex and race/ethnicity. Conclusions As illustrated by our analysis of Kaiser data, our proposed modeling framework allows the analyst to assess the impact of covariates on semi-competing risks data, such as incident dementia and death, while accounting for dependence between the outcomes when data are left-truncated, as is common in studies of aging and dementia.

BackgroundIn response to the COVID-19 pandemic, the Global Mental Health research group at Johns Hopkins School of Public Health worked with three local partner organizations in Myanmar to develop a psychosocial support (PSS) program that could be delivered by community-based focal points in internally displaced persons camps. This PSS program was designed to be delivered in communities with limited access to regional mental health services due to pandemic travel restrictions. The content of the PSS program was based on materials from an ongoing Common Elements Treatment Approach (CETA) mental health program; CETA counselors based in the three partner organizations were available to provide telephone-based CETA counseling. In April 2020, the partners organizations recruited and trained PSS focal points in 25 IDP camps to establish a multi-tiered system of MHPSS supports.ImplementationThe PSS program including psychoeducation handouts focused on stress and coping during COVID-19 and skills for cognitive restructuring (i.e., changing unhelpful thoughts) in simplified terms, audio recordings of the content of these handouts and referral opportunities for telephone-based services by CETA counselors located outside of the camps. PSS focal points distributed the handouts, had the recordings played via radio and loudspeaker, and were available to answer questions and provide access to a PSS program phones to connect with the CETA counselors. After 6 months of implementation, program monitoring logs were reviewed and a cross-sectional evaluation was conducted to assess the PSS program's reach, understanding, and perceived utility.EvaluationForty-one focal points implemented the PSS program in 25 IDP camps in Kachin and northern Shan States. From May to September 2020, the focal points distributed handouts to 5,725 households and reported 679 visits by IDPs, including facilitating 332 calls to a CETA counselor. Data from the program evaluation (n = 793 participants) found high levels of handout readership and perceived utility of the information, and good comprehension of the content and application of skills.DiscussionFindings suggest that provision of a multi-tiered MHPSS program, with PSS focal points providing direct information and linkages to further mental health services via telephone, was feasible despite the constraints of the pandemic. Utilizing camp-based focal points was acceptable and successful in delivering basic psychosocial supports to a broad population while serving as points of contact for individuals who wanted and needed telephone-based counseling services.

Little is known about effective strategies to reduce rates of suicide among refugees and other displaced populations. This review aims to synthesise and assess the evidence base for suicide prevention and response programmes in refugee settings. We conducted a systematic review from peer-reviewed literature databases (five databases) and grey literature sources of literature published prior to November 27, 2017. We identified eight records (six peer-reviewed articles and two grey literature reports) that met our inclusion criteria. None of the eight records provided conclusive evidence of effectiveness. Five records had an unclear level of evidence and three records were potentially promising or promising. Most of the studies reviewed utilised multiple synergistic strategies. The most rigorous study showed the effectiveness of Brief Intervention and Contact and Safety planning. There is limited evidence of the effectiveness of other suicide prevention strategies for these groups. Future studies should attempt to better understand the impact of suicide prevention strategies, and explicitly unpack the individual and synergistic effects of multiple-strategies on suicide-related outcomes. Evidence from this review supports the use of Brief Intervention and Contact type interventions, but more research is needed to replicate findings particularly among populations in displacement. Key implications for practice Despite lack of evidence for displaced populations, multitiered and public health approaches to suicide seem most promising. Simple scalable interventions based on brief caring contacts are feasible and effective. Strong evaluations of suicide prevention efforts are needed to better inform practice.

Abstract Background TdP is a form of polymorphic ventricular tachycardia which develops in the setting of a prolonged QT interval. There are limited data describing risk factors, treatment, and outcomes of this potentially fatal arrhythmia. Objective Our goals were as follows: (1) to validate cases presenting with Torsade de Pointes (TdP), (2) to identify modifiable risk factors, and (3) to describe the management strategies used for TdP and its prognosis in a real‐world healthcare setting. Methods Case–control study (with 2:1 matching on age, sex, and race/ethnicity) nested within the Genetic Epidemiology Research on Aging (GERA) cohort. Follow‐up of the cohort for case ascertainment was between January 01, 2005 and December 31, 2018. Results A total of 56 cases of TdP were confirmed (incidence rate = 3.6 per 100,000 persons/years). The average (SD) age of the TdP cases was 74 (13) years, 55 percent were female, and 16 percent were non‐white. The independent predictors of TdP were potassium concentration 480 ms (OR = 4.4) and prior history of coronary artery disease (OR = 2.6). Exposure to furosemide and amiodarone was significantly greater in cases than in controls. The most common treatment for TdP was IV magnesium (78.6%) and IV potassium repletion (73.2%). The in‐hospital and 1‐year mortality rates for TdP cases were 10.7% and 25.0% percent, respectively. Conclusions These findings may inform quantitative multivariate risk indices for the prediction of TdP and could guide practitioners on which patients may qualify for continuous ECG monitoring and/or electrolyte replacement therapy.

Abstract Background Dental problems are the most prevalent chronic disease worldwide, with up to half of all kindergarten children having tooth decay. However, there is a lack of evidence of whether unaddressed dental needs (UDNs) are associated with children’s developmental health, a concept reflecting holistic child development - encompassing physical, emotional, and cognitive development. The objective of the current study was to evaluate the relationship between UDNs and developmental health among kindergarten children using the Early Development Instrument (EDI). Methods We examined associations between teacher reported UDNs and developmental vulnerability on the EDI. Children were included in the study if they were enrolled in kindergarten in publicly-funded schools in Canada between 2010 and 2015, had been in the classroom for at least one month, and had no more than 25% of missing items on the questionnaire. Results Among 576,264 children who met inclusion criteria (95.4% of eligible children), 2465 (0.4%) were identified as having UDNs by their teachers. Children with UDNs had 4.58 to 8.27 times higher odds of being vulnerable on any of the five developmental domains (physical health and well-being, social competence, emotional maturity, language and cognitive development, communication skills and general knowledge), compared to children without UDNs. Conclusion In this study, teacher-reported UDNs were associated with developmental vulnerability in kindergarten children. Teacher reported unmet dental needs in kindergarten children may be a proxy for poor developmental health at school entry, and thus a marker for supporting both children’s oral health and early developmental needs.

Abstract Background Integrating evidence-based mental health services into primary care has been identified as one strategy for overcoming the treatment gap in low and middle-income countries, yet their uptake into standard practice remains poor. The purpose of this study was to understand stakeholder perspectives regarding barriers and facilitators to integration of mental health services into primary care settings in Northern Iraq. Methods Using a convergent mixed methods study design, quantitative and qualitative questionnaires assessed respondent perceptions of implementation factors under the domains of Autonomy, Acceptability, Appropriateness, Feasibility, Penetration/Accessibility, Sustainability, and Organizational Climate. We interviewed four types of stakeholders: clients, providers of mental health services, non-mental health (MH) staff working at the centers, and center directors. Interviews were conducted with clients at the completion of services, and with all other stakeholder groups in the latter half of the first year of program implementation, by Kurdish-speaking interviewer pairs. Qualitative and quantitative data were analyzed separately and merged using qualitative data transformation to quantify frequency of theme and integrate with quantitative findings through woven narrative. Results 123 clients, 26 providers, 40 non-MH staff, and 12 directors provided data. Positive perceptions of the program’s acceptability, appropriateness, feasibility, and positive impacts were reported across all stakeholder levels. Providers reported that the program length (8–12 sessions) was a challenge. Clients described logistical challenges (e.g.: transportation, childcare, home duties); support from family and friends appeared to be critical. Lack of private space, insufficient staffing, and need for greater government support were also important issues. Conclusions This mixed methods study is unique in its inclusion of non-MH staff and director perspectives on integration of mental health services in primary care clinics. Their inclusion proved vital since they included critical human resource barriers to feasibility. Providers reported generally positive integration experiences but that some colleagues (clinic staff not involved in mental health services) were unsupportive. Most non-MH staff were supportive, but some did report negative impacts on their working environment. Future studies of integration of mental health services into other service platforms should include the perspectives of stakeholders not involved in provision of mental health services.

Enhancer of Zeste Homolog 2 (EZH2) inhibitors (EZH2i) are approved to treat certain cancer types. Previous studies have suggested the potential to combine EZH2i with immune checkpoint blockade targeting coinhibitory receptors like PD-(L)1 and CTLA-4, but whether it can also enhance the activity of agents targeting costimulatory receptors is not known. Here, we explore the combination between EZH2i and an agonist antibody targeting the T cell costimulatory receptor 4-1BB (α4-1BB). Our data show that EZH2i compromise the efficacy of α4-1BB in both CT26 colon carcinoma and in an in vivo protein immunization model. We link this to reduced effector survival and increased BIM expression in CD8+ T cells upon EZH2i treatment. These data support the requirement of EZH2 function in 4-1BB-mediated CD8+ T cell expansion and effector programming and emphasize the consideration that must be given when combining such antitumoral therapies.

Background Long QT has been associated with ventricular dysrhythmias, cardiovascular disease (CVD) mortality, and sudden cardiac death. However, no studies to date have investigated the dynamics of within‐person QT change over time in relation to risk of incident CVD and all‐cause mortality in a real‐world setting. Methods and Results A cohort study among members of an integrated health care delivery system in Northern California including 61 455 people (mean age, 62 years; 60% women, 42% non‐White) with 3 or more ECGs (baseline in 2005–2009; mean±SD follow‐up time, 7.6±2.6 years). In fully adjusted models, tertile 3 versus tertile 1 of average QT corrected (using the Fridericia correction) was associated with cardiac arrest (hazard ratio [HR], 1.66), heart failure (HR, 1.62), ventricular dysrhythmias (HR, 1.56), all CVD (HR, 1.31), ischemic heart disease (HR, 1.28), total stroke (HR, 1.18), and all‐cause mortality (HR, 1.24). Tertile 3 versus tertile 2 of the QT corrected linear slope was associated with cardiac arrest (HR, 1.22), ventricular dysrhythmias (HR, 1.12), and all‐cause mortality (HR, 1.09). Tertile 3 versus tertile 1 of the QT corrected root mean squared error was associated with ventricular dysrhythmias (HR, 1.34), heart failure (HR, 1.28), all‐cause mortality (HR, 1.20), all CVD (HR, 1.14), total stroke (HR, 1.08), and ischemic heart disease (HR, 1.07). Conclusions Our results demonstrate improved predictive ability for CVD outcomes using longitudinal information from serial ECGs. Long‐term average QT corrected was more strongly associated with CVD outcomes than the linear slope or the root mean squared error. This new evidence is clinically relevant because ECGs are frequently used, noninvasive, and inexpensive.

Objective: While the molecular events controlling insulin secretion from β-cells have been documented in detail, the exact mechanisms governing glucagon release by α-cells are understood only partially. This is a critical knowledge gap, as the normal suppression of glucagon secretion by elevated glucose levels fails in type 2 diabetes (T2D) patients, contributing to hyperglycemia through stimulation of hepatic glucose production. A critical role of glycolytic flux in regulating glucagon secretion was supported by recent studies in which manipulation of the activity and expression of the glycolytic enzyme glucokinase altered the setpoint for glucose-suppression of glucagon secretion (GSGS). Given this precedent, we hypothesized that genetic activation of glucokinase specifically in α-cells would enhance GSGS and mitigate T2D hyperglucagonemia. Methods: We derived an inducible, α-cell-specific glucokinase activating mutant mouse model (GckLoxPGck∗/LoxPGck∗; Gcg-CreERT2; henceforth referred to as “α-mutGCK”) in which the wild-type glucokinase gene (GCK) is conditionally replaced with a glucokinase mutant allele containing the ins454A activating mutation (Gck∗), a mutation that increases the affinity of glucokinase for glucose by almost 7-fold. The effects of α-cell GCK activation on glucose homeostasis, hormone secretion, islet morphology, and islet numbers were assessed using both in vivo and ex vivo assays. Additionally, the effect of α-cell GCK activation on GSGS was investigated under diabetogenic conditions of high-fat diet (HFD) feeding that dysregulate glucagon secretion. Results: Our study shows that α-mutGCK mice have enhanced GSGS in vivo and ex vivo, independent of alterations in insulin levels and secretion, islet hormone content, islet morphology, or islet number. α-mutGCK mice maintained on HFD displayed improvements in glucagonemia compared to controls, which developed the expected obesity, glucose intolerance, elevated fasting blood glucose, hyperinsulinemia, and hyperglucagonemia. Conclusions: Using our novel α-cell specific activation of GCK mouse model, we have provided additional support to demonstrate that the glycolytic enzyme glucokinase is a key determinant in glucose sensing within α-cells to regulate glucagon secretion. Our results contribute to our fundamental understanding of α-cell biology by providing greater insight into the regulation of glucagon secretion through α-cell intrinsic mechanisms via glucokinase. Furthermore, our HFD results underscore the potential of glucokinase as a druggable target which, given the ongoing development of allosteric glucokinase activators (GKAs) for T2D treatment, could help mitigate hyperglucagonemia and potentially improve blood glucose homeostasis.

Medulloblastoma is one of the most prevalent malignant brain tumors in children and has very poor prognosis. In this study, the authors show, using a mouse model of medulloblastoma, that Gfi1 promotes tumor growth by recruiting Lsd1, that this interaction inhibits genes involved in neuronal differentiation, and that Lsd1 may be a therapeutic target in Gfi1-activated tumors.

Background: Studies on the Omicron variant infection have generally been restricted to descriptions of its initial clinical and epidemiological characteristics. We investigated the timeline-related progression and clinical outcome in hospitalized individuals with the Omicron variant. Methods: We conducted a retrospective, single-centered study including 226 laboratory-confirmed cases with the Omicron variant between 6 April and 11 May 2022 in Shanghai, China. The final date of follow-up was 30 May 2022. Results: Among 226 enrolled patients, the median age was 52 years, and 118 (52.2%) were female. The duration from onset of symptoms to hospitalization was 3 days (interquartile range (IQR): 2–4 days) for symptomatic patients. Cough occurred in 168 patients (74.3%). The median interval to negative reverse-transcriptase PCR tests of nasopharynx swab was 10 days ((IQR): 8–13 days). No radiographic progressions were found in 196 patients on the 7th day after onset of symptoms. The median duration of fever in all participants was 5 days (IQR: 4–6 days). The median PCR conversion time of Paxlovid-treated patients was 8 days (IQR: 7–10 days) compared with that of a traditional Chinese herb medicine lianhuaqingwen (10 days, IQR: 8–13 days) (p = 0.00056). Booster vaccination can significantly decrease the severity of Omicron infection when compared with unvaccinated patients (p = 0.009). In multivariate logistic analysis, erythrocyte sedimentation rate (ESR) (OR = 1.05) was independently related to the severity of the infection. Conclusions: The majority of clinical symptoms of Omicron infection were not severe. Early and aggressive administration of Paxlovid can significantly reduce the PCR conversion time. Booster vaccination should also be highly recommended in the population over 14 years old.

The recent school gate protests about the inclusion of LGBT identities in the curriculum suggest that sexual identity remains an issue of moral panic in UK schools. Given this current climate, and the legacy of Section 28, schools have rarely been easy workplaces for LGBT teachers. For LGBT teachers, significant energy and vigilance is required then to navigate the heteronormative and cis-normative staffroom and classroom. There is evidence that LGBT teachers try to remain as invisible as possible in their schools so as to not draw attention to themselves (Lee, 2019a). Some avoid promotion to school leadership roles fearing that the status will necessitate greater personal scrutiny by school stakeholders. Based on key attributes including, reading people, compassion, and commitment to the inclusion of others, making connections managing uncertainty, courage, and risk-taking, this perspective piece argues that some of the strategies LGBT teachers deploy to manage the intersection of personal and professional identities in school equip them with an array of particular skills that are conducive to excellent school leadership.

Background The survival benefit associated with cumulative adherence to multiple clinical and lifestyle‐related guideline recommendations for secondary prevention after acute myocardial infarction (AMI) is not well established. Methods and Results We examined adults with AMI (mean age 68 years; 64% men) surviving at least 30 (N=25 778) or 90 (N=24 200) days after discharge in a large integrated healthcare system in Northern California from 2008 to 2014. The association between all‐cause death and adherence to 6 or 7 secondary prevention guideline recommendations including medical treatment (prescriptions for β‐blockers, renin‐angiotensin‐aldosterone system inhibitors, lipid medications, and antiplatelet medications), risk factor control (blood pressure

Abstract Background In Kachin State, Myanmar, collapse of a ceasefire in 2011 has resulted in widespread exposure to conflict and ongoing internal displacement. Such exposures are known risk factors for mental health and psychosocial (MHPS) problems, yet mental health services for children and youth are typically scarce in such circumstances. Following evaluation of a mental health treatment for adult trauma survivors on the Thailand-Myanmar border, our study team received requests to support the development of a similar intervention for displaced children in Kachin State. To inform this work, we conducted a brief qualitative needs assessment to explore priority MHPS problems among this population. Methods Data were collected in internally displaced persons camps in Kachin State during July and August, 2016. Free list interviews with a convenience sample of 28 adolescents and 12 adults produced a list of problems affecting children and adolescents in this area. Four problems were further explored in key informant interviews with a convenience sample of 26 adolescents and 4 adults. Data analysis was conducted by the local interview team. Results Priority problems included: behavior problems, substance use, effects of war, and feeling sad/depressed/hopeless. Descriptions emphasized the interconnectedness between the problems. Overall, most problems were related to specific events that suggest that the symptoms themselves are responses to unusual situations; however, the problems were also linked to current psychosocial stressors such as poverty, poor nutrition, and discrimination. Effects of war were described primarily as a constellation of social and economic problems rather than a list of mental health symptoms, although descriptions of these problems did include post-traumatic stress symptoms. Conclusions Findings fit well within explanatory models of distress that include both direct trauma exposure and exacerbation of daily stressors. Results of this study have been used to inform intervention adaptation and evaluation, but also contribute to the literature on the needs of young people in situations of protracted conflict.

Abstract Background Very young adolescents (VYA) in humanitarian settings are largely neglected in terms of sexual and reproductive health (SRH). This study describes the characteristics of VYA aged 10-14 years in two humanitarian settings, focusing on transitions into puberty and access to SRH information. Methods Data were collected through a cross-sectional survey with Somali VYA residing in the Kobe refugee camp in Ethiopia (N = 406) and VYA from Myanmar residing in the Mae Sot and Phop Phra migrant communities in Thailand (N = 399). The average age was 12 years (about half were girls) in both communities. Participants were recruited using multi-stage cluster-based sampling with probability proportional to size in each site. Descriptive statistics were used to describe the sociodemographic, family, peer, and schooling characteristics and to explore transitions into puberty and access to SRH information. Results Most VYA in both sites reported living with both parents; nine in ten reported feeling that their parents/guardians care about them, and over half said that their parents/guardians monitor how and with whom they spend their free time. High proportions in both sites were currently enrolled in school (91.4% Somali, 87.0% from Myanmar). Few VYA, particularly those aged 10-12, reported starting puberty, although one in four Somali indicated not knowing whether they did so. Most girls from Myanmar who had started menstruating reported access to menstrual hygiene supplies (water, sanitation, cloths/pads). No Somali girls reported access to all these supplies. While over half of respondents in both sites reported learning about body changes, less than 20% had learnt about pregnancy and the majority (87.4% Somali, 78.6% from Myanmar) indicated a need for more information about body changes. Parents/guardians were the most common source of SRH information in both sites, however VYA indicated that they would like more information from friends, siblings, teachers and health workers. Conclusions This study highlights gaps in SRH information necessary for healthy transitions through puberty and supplies for menstrual hygiene in two humanitarian settings. VYA in these settings expressed closeness to their parents/guardians and the majority were in school. Introducing early SRH interventions that involve parents and educational centers may thus yield promising results, providing VYA with the necessary skills for understanding and dealing with their pubertal and sexual development.

Abstract Background The very young adolescent (VYA) population age 10–14 years is often neglected in the field of sexual and reproductive health (SRH) research due to the combined sensitivity of the topic and the young age group, resulting in little data about the SRH needs and concerns of VYA. In 2013, the Women’s Refugee Commission (WRC), Johns Hopkins University (JHU), Adolescent and Reproductive Health Network (ARHN) and Karen Youth Organization (KYO) implemented qualitative participatory research to explore the SRH needs and risks of VYA. The study was conducted in Mae Sot town and Mae La refugee camp, both in Thailand, with migrant populations and refugees, respectively. Methods A total of 22 focus group discussions (FGD) were conducted with 176 participants. FGD were implemented with girls and boys aged 10–16, and adults in both settings. The FGD with 10–14 year olds included community mapping and photo elicitation interviews. These activities gathered information about their own perspectives, experiences and values regarding SRH, as well as SRH risks. The FGD with 15–16 year olds and adults focused on their perspectives regarding the SRH needs and risks of VYA. Results Fourteen (64%) of FGD were conducted in Mae Sot town, and 8 (36%) were conducted in Mae La refugee camp. Schools, youth centers and religious institutions were identified as key locations for obtaining SRH information. Schools are most promising, but access to schools is unequal between boys and girls. Parents can provide support and education to adolescents if they are supported to do so and if trust and comfort can be built between adolescents and parents around SRH. Conclusions To a large degree, the same themes emerged from both locations, in terms of the awareness of body changes and puberty, the centrality of peer influences, and the value of education. These findings call for rigorous study of youth-directed programs and policies that meaningfully involve key influential adults identified by vulnerable young adolescents and utilize the specific places young adolescents, themselves, voice as being critical settings for obtaining information on SRH issues.

Abstract Background Between 2013 and 2014, a series of qualitative and quantitative research efforts were undertaken in three conflict affected communities (Syrian refugees in the Bekaa Valley, Lebanon, Somali refugees in Kobe Refugee camp Ethiopia, and migrant communities from Myanmar settled in Tak Province, Thailand) that sought to understand the lived experiences of very young adolescents during emergencies. A research consortium that included the Women’s Refugee Commission, Johns Hopkins University, American University in Beirut, International Medical Corps in Ethiopia, Save the Children in Lebanon and the Adolescent Reproductive Health Network in Thailand convened around these activities. Methods The core research initiative, “Sexual and Reproductive Health Needs and Risks of Very Young Adolescents in Humanitarian Contexts” involved three phases of research: 1) A program needs assessment completed with key informants working on adolescent sexual and reproductive health in each context 2) qualitative research, that incorporated participatory approaches, with adolescents 10–16 years of age, and adults in the community in all three settings, and 3) A household survey with 10–14 year-olds in Ethiopia and Thailand. An additional phase of research was added in Lebanon and Ethiopia, to further explore the issue of child marriage which was a prominent experience identified within the core research initiative on very young adolescents. Results This research supplement, exploring the experiences during early adolescence, highlighted the crucial role of education, prominent experiences of insecurity, existing knowledge on body change and fertility, peer and family relationships among this age group, as well as concerns around child marriage (Lebanon and Ethiopia), child labor (Thailand), and gender roles. Conclusion Given the findings presented within this supplement, there are broad implications for work with very young adolescents by humanitarian actors in the settings where research was undertaken, and potentially, more broadly. Programs that promote health and well-being during early adolescence are critically needed in settings of conflict and displacement, and coordination among the diverse range of actors involved in such programming will be essential. Additionally, SRH programs for adolescents (10–14 years of age) in emergencies should include, at minimum, sensitive care for survivors of sexual violence, menstrual hygiene management, life skills, and fertility education. Humanitarian programs can better engage with parents, teachers, and community leaders as partners in the development and implementation of programs. Finally, fundamental rights to protection and education for all adolescents must be upheld.

This article shows how external data sources can be utilised in autoethnographic research. Beginning with an account of a critical incident that examines the incompatibility of private and professional identities, I show how, through the collection of data sources, I capture the impact of homophobic and heteronormative discursive practices on health, wellbeing and identity. In the critical incident, I explore how I prospered as a teacher at a British village school for almost 10 years by censoring my sexuality and carefully managing the intersection between my private and professional identities. However, when a malicious and homophobic neighbour and parent of children at the school exposed my sexuality to the Headteacher, I learned the extent to which the rural school community privileged and protected the heteronormative discourse. A poststructuralist theoretical framework underpins this article. My experience of being a subject is understood as the outcome of discursive practices. Sexual identity, teacher identity and autoethnographer identity are understood to be fluid, and constantly produced and reproduced in response to social, cultural and political influences. The article describes how email correspondence, medical records and notes from a course of cognitive behaviour therapy were deployed to augment my personal recollection and give a depth and richness to the narrative. As the critical incident became a police matter, examination takes place of how I sought to obtain and utilise data from the police national computer in the research. Attempts to collect data from the police and Crown Prosecution Service were problematic and provided an unexpected development in the research and offered additional insight into the nature of the British rural community and its police force.

BackgroundBreast arterial calcification (BAC) may be a predictor of cardiovascular events and is highly prevalent in persons with end-stage kidney disease. However, few studies to date have examined the association between mild-to-moderate kidney function and proteinuria with BAC.MethodsWe prospectively enrolled women with no prior cardiovascular disease aged 60 to 79 years undergoing mammography screening at Kaiser Permanente Northern California between 10/24/2012 and 2/13/2015. Urine albumin-to-creatinine ratio (uACR), along with specific laboratory, demographic, and medical data, were measured at the baseline visit. Baseline estimated glomerular filtration rate (eGFR), medication history, and other comorbidities were identified from self-report and/or electronic medical records. BAC presence and gradation (mass) was measured by digital quantification of full-field mammograms.ResultsAmong 3,507 participants, 24.5% were aged ≥70 years, 63.5% were white, 7.5% had eGFR 0 mg) was 27.9%. Neither uACR ≥30 mg/g nor uACR ≥300 were significantly associated with BAC in crude or multivariable analyses. Reduced eGFR was associated with BAC in univariate analyses (odds ratio 1.53, 95% CI: 1.18-2.00), but the association was no longer significant after adjustment for potential confounders. Results were similar in various sensitivity analyses that used different BAC thresholds or analytic approaches.ConclusionsAmong women without cardiovascular disease undergoing mammography screening, reduced eGFR and albuminuria were not significantly associated with BAC.

Background: For older adults, the capacity to self-manage medications may be limited by several factors. However, currently available tools do not permit a comprehensive assessment of such limitations. The Domain Specific Limitation in Medication Management Capacity (DSL-MMC) was developed to address this need. This study aimed to establish the face and content validity of the DSL-MMC. Methods: The DSL-MMC tool consisted of 4 domains and 12 sub-domains with 42 items including: 1. physical abilities (vision, dexterity, hearing); 2. cognition (comprehension, memory, executive functioning); 3. medication regimen complexity (dosing regimen, non-oral administration, polypharmacy); and 4. access/caregiver (prescription refill, new prescription, caregiver). Pharmacists assessed each item for relevance, importance, readability, understandability, and representation. Items with content validity index (CVI) scores of

This paper aims to explore how social work students can support lesbian, gay, bisexual, transgender, queer or questioning (LGBTQ+) young people in schools. Drawing on the reflective practice portfolio documents of four students who worked with LGBTQ+ young people in a school as part of a social workers in school (SWIS) student placement project, the article uses thematic analysis to identify how the students were able to support young people identifying as LGBTQ+. The article subscribes to a poststructuralist theoretical framework which sees gender and sexual identities as multiple, fragmented and constructed in relation to others and within the systems of knowledge and power that exist in schools. The article demonstrates the benefit to schools of having social work students on practice placement. The students' own reflections critically contemplate the way in which they were able to spend more prolonged periods of time with young people than the teachers could, both with individuals and LGBTQ+ groups. The students' reflective portfolios show the value of the school placements to their own development of knowledge and skills

Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for a variety of hematologic malignancies and disorders. Unfortunately, acute graft-versus-host disease (GVHD) is a frequent complication of HCT. While substantial research has identified clinical, genetic and proteomic risk factors for acute GVHD, few studies have sought to develop risk prediction tools that quantify absolute risk. Such tools would be useful for: optimizing donor selection; guiding GVHD prophylaxis, post-transplant treatment and monitoring strategies; and, recruitment of patients into clinical trials. Using data on 9,651 patients who underwent first allogeneic HLA-identical sibling or unrelated donor HCT between 01/1999-12/2011 for treatment of a hematologic malignancy, we developed and evaluated a suite of risk prediction tools for: (i) acute GVHD within 100 days post-transplant and (ii) a composite endpoint of acute GVHD or death within 100 days post-transplant. We considered two sets of inputs: (i) clinical factors that are typically readily-available, included as main effects; and, (ii) main effects combined with a selection of a priori specified two-way interactions. To build the prediction tools we used the super learner, a recently developed ensemble learning statistical framework that combines results from multiple other algorithms/methods to construct a single, optimal prediction tool. Across the final super learner prediction tools, the area-under-the curve (AUC) ranged from 0.613-0.640. Improving the performance of risk prediction tools will likely require extension beyond clinical factors to include biological variables such as genetic and proteomic biomarkers, although the measurement of these factors may currently not be practical in standard clinical settings.

This research study investigated the application of the American College Personnel Association/National Association of Student Personnel Administrators (ACPA/NASPA) competencies in the development of a graduate preparation course at a large, multi-campus research university in the UK. Expert practitioner feedback was used to adapt the competency framework and construct a tool for use in a British higher education setting. One hundred and five Student Affairs professionals participated in the resulting mixed methods study. Findings from this study have implications for applying the ACPA/NASPA professional competencies in the development of postgraduate professional preparation courses outside of the continental US.

This article examines how lesbian, gay and bisexual teachers in rural schools negotiate their sexual identities within the workplace. Although there has been progress towards LGBT (lesbian, gay, bisexual and transgender) inclusion for teachers in urban and suburban schools, this article shows that their rural counterparts often experience their school communities differently. A questionnaire gathered data from school teachers in the United Kingdom identifying as LGBT. Whilst a small number of transgender, gender queer and non-binary teachers completed the questionnaire, it is important to note that these teachers taught only in urban environments. In rural schools, respondents identified only as lesbian, gay or bisexual (LGB). Therefore, LGB is used when referring to the rural respondents in this study and LGBT is used when referring generally to the lesbian, gay, bisexual and transgender community. The experiences of teachers working in rural schools were compared with those working in urban or suburban school settings. Results showed that LGB teachers in rural communities lack the opportunity to speak their identity into existence at school, and often find their personal and professional identities incompatible, leading to low self-worth, depression and anxiety. The article shows that in rural school communities, traditional and conservative rural norms and values are compelling and are often protected at the expense of creating safe and inclusive workplaces for LGB teachers.

This article is an autoethnographic examination of my experiences as a pet owner during a particularly challenging time in my life. Beginning with a summary of a critical incident, it shows the way in which fears for the safety of my pet cat, Lily, and my relationship with her impacted my health, wellbeing and identity. Depicting self-knowledge as partial, local and culturally located, I deconstruct the relationship I had with Lily in relation to the particular set of circumstances in which it was situated. I was seen by my doctor and prescribed a course of cognitive behaviour therapy (CBT) during this period, and so, my account draws on my medical records, CBT notes and my CBT thought diary in an attempt to understand how and why my anxiety was manifested in my concern for Lily. The article calls for cognitive behaviour therapists to carefully evaluate external stressors before fears are dismissed irrational and reformulated as alternative thoughts. This article also demonstrates that familiesare diverse, and there are many ways of ‘doing family’. For many heterosexual and same-sex couples, pets give stability to a partnership and elevate it to family status, if only within the privacy of the home. Human−animal attachments can be comparable to human−human attachments, and where attachments to pets are as strong as those toward humans, fear of harm can be devastating.

Photonic integrated circuits provide a compact and stable platform for quantum photonics. Here we demonstrate a silicon photonics quantum key distribution (QKD) encoder in the first high-speed polarization-based QKD field tests. The systems reach composable secret key rates of 1.039 Mbps in a local test (on a 103.6-m fiber with a total emulated loss of 9.2 dB) and 157 kbps in an intercity metropolitan test (on a 43-km fiber with 16.4 dB loss). Our results represent the highest secret key generation rate for polarization-based QKD experiments at a standard telecom wavelength and demonstrate photonic integrated circuits as a promising, scalable resource for future formation of metropolitan quantum-secure communications networks.

Existing studies of mental health interventions in low-resource settings have employed highly structured interventions delivered by non-professionals that typically do not vary by client. Given high comorbidity among mental health problems and implementation challenges with scaling up multiple structured evidence-based treatments (EBTs), a transdiagnostic treatment could provide an additional option for approaching community-based treatment of mental health problems. Our objective was to test such an approach specifically designed for flexible treatments of varying and comorbid disorders among trauma survivors in a low-resource setting.We conducted a single-blinded, wait-list randomized controlled trial of a newly developed transdiagnostic psychotherapy, Common Elements Treatment Approach (CETA), for low-resource settings, compared with wait-list control (WLC). CETA was delivered by lay workers to Burmese survivors of imprisonment, torture, and related traumas, with flexibility based on client presentation. Eligible participants reported trauma exposure and met severity criteria for depression and/or posttraumatic stress (PTS). Participants were randomly assigned to CETA (n = 182) or WLC (n = 165). Outcomes were assessed by interviewers blinded to participant allocation using locally adapted standard measures of depression and PTS (primary outcomes) and functional impairment, anxiety symptoms, aggression, and alcohol use (secondary outcomes). Primary analysis was intent-to-treat (n = 347), including 73 participants lost to follow-up. CETA participants experienced significantly greater reductions of baseline symptoms across all outcomes with the exception of alcohol use (alcohol use analysis was confined to problem drinkers). The difference in mean change from pre-intervention to post-intervention between intervention and control groups was -0.49 (95% CI: -0.59, -0.40) for depression, -0.43 (95% CI: -0.51, -0.35) for PTS, -0.42 (95% CI: -0.58, -0.27) for functional impairment, -0.48 (95% CI: -0.61, -0.34) for anxiety, -0.24 (95% CI: -0.34, -0.15) for aggression, and -0.03 (95% CI: -0.44, 0.50) for alcohol use. This corresponds to a 77% reduction in mean baseline depression score among CETA participants compared to a 40% reduction among controls, with respective values for the other outcomes of 76% and 41% for anxiety, 75% and 37% for PTS, 67% and 22% for functional impairment, and 71% and 32% for aggression. Effect sizes (Cohen's d) were large for depression (d = 1.16) and PTS (d = 1.19); moderate for impaired function (d = 0.63), anxiety (d = 0.79), and aggression (d = 0.58); and none for alcohol use. There were no adverse events. Limitations of the study include the lack of long-term follow-up, non-blinding of service providers and participants, and no placebo or active comparison intervention.CETA provided by lay counselors was highly effective across disorders among trauma survivors compared to WLCs. These results support the further development and testing of transdiagnostic approaches as possible treatment options alongside existing EBTs.ClinicalTrials.gov NCT01459068 Please see later in the article for the Editors' Summary.

This study represents the first description of whale sharks, Rhincodon typus, occurring at a provisioning site in Oslob, Cebu, Philippines. Frequent observations of sharks are often difficult, even at tourism sites, giving rise to provisioning activities to attract them. The present study provides repeated longitudinal data at a site where daily provisioning activities took place, and whale sharks were present every day. A total of 158 individual whale sharks were photographically identified between Mar 2012 and Dec 2013, with 129 males (82%), 19 females (12%) and 10 (6%) of undetermined sex. Mean estimated total length was 5.5 m (±1.3 m S.D.). Twenty individuals were measured with laser photogrammetry to validate researchers’ estimated sizes, yielding a good correlation (r2 = 0.83). Fifty-four (34%) individuals were observed being hand-fed by local fishermen (provisioned), through in-water behavioural observations. Maximum likelihood methods were used to model mean residency time of 44.9 days (±20.6 days S.E.) for provisioned R. typus contrasting with 22.4 days (±8.9 days S.E.) for non-provisioned individuals. Propeller scars were observed in 47% of the animals. A mean of 12.7 (±4.3 S.D.) R. typus were present in the survey area daily, with a maximum of 26 individuals (Aug 10 2013) and a minimum of 2 (Dec 6 2012). Twelve (8%) individuals were seen on at least 50% of survey days (n = 621), with a maximum residency of 572 days for one individual (P-396). Twenty four individuals were photographically identified across regional hotsposts, highlighting the species’ migratory nature and distribution. Extended residency and differences in lagged identification rates suggest behavioural modification on provisioned individuals, underlying the necessity for proper management of this tourism activity.

The specification and differentiation of pancreatic endocrine cell populations (α-, β-, δ, PP- and ε-cells) is orchestrated by a combination of transcriptional regulators. In the pancreas, Aristaless-related homeobox gene (Arx) is expressed first in the endocrine progenitors and then restricted to glucagon-producing α-cells. While the functional requirement of Arx in early α-cell specification has been investigated, its role in maintaining α-cell identity has yet to be explored. To study this later role of Arx, we have generated mice in which the Arx gene has been ablated specifically in glucagon-producing α-cells. Lineage-tracing studies and immunostaining analysis for endocrine hormones demonstrate that ablation of Arx in neonatal α-cells results in an α-to-β-like conversion through an intermediate bihormonal state. Furthermore, these Arx-deficient converted cells express β-cell markers including Pdx1, MafA, and Glut2. Surprisingly, short-term ablation of Arx in adult mice does not result in a similar α-to-β-like conversion. Taken together, these findings reveal a potential temporal requirement for Arx in maintaining α-cell identity.

ARX/Arx is a homeodomain-containing transcription factor necessary for the specification and early maintenance of pancreatic endocrine α-cells. Many transcription factors important to pancreas development, including ARX/Arx, are also crucial for proper brain development. Although null mutations of ARX in human patients result in the severe neurologic syndrome XLAG (X-linked lissencephaly associated with abnormal genitalia), the most common mutation is the expansion of the first polyalanine tract of ARX, which results primarily in the clinical syndrome ISSX (infantile spasms). Mouse models of XLAG, ISSX and other human ARX mutations demonstrate a direct genotype-phenotype correlation in ARX-related neurologic disorders. Furthermore, mouse models utilizing a polyalanine tract expansion mutation have illustrated critical developmental differences between null mutations and expansion mutations in the brain, revealing context-specific defects. Although Arx is known to be required for the specification and early maintenance of pancreatic glucagon-producing α-cells, the consequences of the Arx polyalanine expansion on pancreas development remain unknown. Here we report that mice with an expansion mutation in the first polyalanine tract of Arx exhibit impaired α-cell specification and maintenance, with gradual α-cell loss due to apoptosis. This is in contrast to the re-specification of α-cells into β- and δ-cells that occurs in mice null for Arx. Overall, our analysis of an Arx polyalanine expansion mutation on pancreatic development suggests that impaired α-cell function might also occur in ISSX patients.