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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Current evidence underscores a need to transform how we do clinical research, shifting from academic-driven priorities to co-led community partnership focused programs, accessible and relevant career pathway programs that expand opportunities for career development, and design of trainings and practices to develop cultural competence among research teams. Failures of equitable research translation contribute to health disparities. Drivers of this failed translation include lack of diversity in both researchers and participants, lack of alignment between research institutions and the communities they serve, and lack of attention to structural sources of inequity and drivers of mistrust for science and research. The Duke University Research Equity and Diversity Initiative (READI) is a program designed to better align clinical research programs with community health priorities through community engagement. Organized around three specific aims, READI-supported programs targeting increased workforce diversity, workforce training in community engagement and cultural competence, inclusive research engagement principles, and development of trustworthy partnerships.
Edited by
David Mabey, London School of Hygiene and Tropical Medicine,Martin W. Weber, World Health Organization,Moffat Nyirenda, London School of Hygiene and Tropical Medicine,Dorothy Yeboah-Manu, Noguchi Memorial Institute for Medical Research, University of Ghana,Jackson Orem, Uganda Cancer Institute, Kampala,Laura Benjamin, University College London,Michael Marks, London School of Hygiene and Tropical Medicine,Nicholas A. Feasey, Liverpool School of Tropical Medicine
Valid comparisons of hypertension prevalence over time and between populations are difficult owing to differing definitions of hypertension and population age structures. However, studies suggest that raised blood pressure (BP) is increasingly common in most African countries and a major contributor to mortality and morbidity (Cappuccio & Miller 2016). In contrast, early studies found a very low prevalence. Donnison (1929), for example, found no cases of hypertension among 1800 admissions to a rural Kenyan hospital. Rural populations once exhibited less hypertension compared to urban dwellers. However, rural mean BPs and rates of hypertension are now nearing those found in urban areas. For instance, a study of almost 30,000 Malawians found little difference between rural and urban hypertensive prevalence (Price et al. 2018).
The health benefits of the long-chain omega-3 polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been known for over 50 years and underpin the UK population recommendation to consume >450 mg EPA + DHA per day. These recommendations, last revised in 2004, are based mainly on epidemiological evidence. Much research has been conducted in the interim. Most randomised controlled trials (RCT) use doses of EPA + DHA of 840 mg/d or more. For anti-inflammatory, triacylglycerol-lowering and anti-hypertensive effects, >1.5 g EPA + DHA per day is needed. Cognitive benefits are also likely to require these higher intakes. Farmed salmon now contains considerably less EPA + DHA relative to farmed fish of 20 years ago, meaning one portion per week will no longer provide the equivalent of 450 mg EPA + DHA per day. Oily fish alone can only provide a fraction of the EPA + DHA required to meet global needs. Furthermore, there is low global oily fish consumption, with typical intakes of <200 mg EPA + DHA per day, and limited intakes in vegans and vegetarians. Therefore, there is an urgent need for affordable, acceptable, alternative EPA + DHA sources, including vegan/vegetarian friendly options, such as bio-enriched poultry, red meat and milk products; fortified foods; enriched oilseeds (for example, genetically modified Camelina sativa); algae and algal oils; and approaches which enhance endogenous EPA/DHA synthesis. In this narrative review, we suggest that current EPA + DHA intake recommendations are too low, consider EPA/DHA from a holistic health-sustainability perspective and identify research, policy and knowledge mobilisation areas which need attention.
Reliable population estimates are one of the most elementary needs for the management of wildlife, particularly for introduced ungulates on oceanic islands. We aimed to produce accurate and precise density estimates of Philippine deer (Rusa marianna) and wild pigs (Sus scrofa) on Guam using motion-triggered cameras combined with distance sampling to estimate densities from observations of unmarked animals while accounting for imperfect detection. We used an automated digital data processing pipeline for species recognition and to estimate the distance to detected species. Our density estimates were slightly lower than published estimates, consistent with management to reduce populations. We estimated the number of camera traps needed to obtain a 0.1 coefficient of variation was substantial, requiring > ten-fold increase in camera traps, while estimates with precision of 0.2 or 0.3 were more achievable, requiring doubling to quadrupling the number of camera traps. We provide best practices for establishing and conducting distance sampling with camera trap surveys for density estimation based on lessons learned during this study. Future studies should consider distance sampling with camera traps to efficiently survey and monitor unmarked animals, particularly medium-sized ungulates, in tropical, oceanic island ecosystems.
This pilot study is the first formal exploration of the concept of “Organizational Professionalism” (OP) among health system leaders in high-performing healthcare organizations. Semi-structured key informant interviews with 23 leaders from 8 healthcare organizations that were recipients of the Malcolm Baldrige National Quality Award (MBNQA) or Baldrige-based state quality award programs explored conceptualization, operationalization, and measurement of OP. Further exploration and understanding of OP in healthcare organizations has the potential to establish and sustain professional and ethical organizational cultures that bolster trust through the sound implementation of laws, policies, and procedures to support the delivery of high-quality patient care.
Machine learning (ML) has developed classifiers differentiating patient groups despite concerns regarding diagnostic reliability. An alternative strategy, used here, is to develop a functional classifier (hyperplane) (e.g. distinguishing the neural responses to received reward v. received punishment in typically developing (TD) adolescents) and then determine the functional integrity of the response (reward response distance from the hyperplane) in adolescents with externalizing and internalizing conditions and its associations with symptom clusters.
Methods
Two hundred and ninety nine adolescents (mean age = 15.07 ± 2.30 years, 117 females) were divided into three groups: a training sample of TD adolescents where the Support Vector Machine (SVM) algorithm was applied (N = 65; 32 females), and two test groups– an independent sample of TD adolescents (N = 39; 14 females) and adolescents with a psychiatric diagnosis (major depressive disorder (MDD), generalized anxiety disorder (GAD), attention deficit hyperactivity disorder (ADHD) & conduct disorder (CD); N = 195, 71 females).
Results
SVM ML analysis identified a hyperplane with accuracy = 80.77%, sensitivity = 78.38% and specificity = 88.99% that implicated feature neural regions associated with reward v. punishment (e.g. nucleus accumbens v. anterior insula cortices). Adolescents with externalizing diagnoses were significantly less likely to show a normative and significantly more likely to show a deficient reward response than the TD samples. Deficient reward response was associated with elevated CD, MDD, and ADHD symptoms.
Conclusions
Distinguishing the response to reward relative to punishment in TD adolescents via ML indicated notable disruptions in this response in patients with CD and ADHD and associations between reward responsiveness and CD, MDD, and ADHD symptom severity.
Childhood bullying is a public health priority. We evaluated the effectiveness and costs of KiVa, a whole-school anti-bullying program that targets the peer context.
Methods
A two-arm pragmatic multicenter cluster randomized controlled trial with embedded economic evaluation. Schools were randomized to KiVa-intervention or usual practice (UP), stratified on school size and Free School Meals eligibility. KiVa was delivered by trained teachers across one school year. Follow-up was at 12 months post randomization. Primary outcome: student-reported bullying-victimization; secondary outcomes: self-reported bullying-perpetration, participant roles in bullying, empathy and teacher-reported Strengths and Difficulties Questionnaire. Outcomes were analyzed using multilevel linear and logistic regression models.
Findings
Between 8/11/2019–12/02/2021, 118 primary schools were recruited in four trial sites, 11 111 students in primary analysis (KiVa-intervention: n = 5944; 49.6% female; UP: n = 5167, 49.0% female). At baseline, 21.6% of students reported being bullied in the UP group and 20.3% in the KiVa-intervention group, reducing to 20.7% in the UP group and 17.7% in the KiVa-intervention group at follow-up (odds ratio 0.87; 95% confidence interval 0.78 to 0.97, p value = 0.009). Students in the KiVa group had significantly higher empathy and reduced peer problems. We found no differences in bullying perpetration, school wellbeing, emotional or behavioral problems. A priori subgroup analyses revealed no differences in effectiveness by socioeconomic gradient, or by gender. KiVa costs £20.78 more per pupil than usual practice in the first year, and £1.65 more per pupil in subsequent years.
Interpretation
The KiVa anti-bullying program is effective at reducing bullying victimization with small-moderate effects of public health importance.
Funding
The study was funded by the UK National Institute for Health and Care Research (NIHR) Public Health Research program (17-92-11). Intervention costs were funded by the Rayne Foundation, GwE North Wales Regional School Improvement Service, Children's Services, Devon County Council and HSBC Global Services (UK) Ltd.
Our systematic review aims to synthesise the evidence on interventions targeting improvement in patient adherence to psychological treatments for common mental disorders. A search was conducted on six electronic databases using search terms under the following concepts: common mental disorders, adherence, psychological treatments and controlled trial study design. Due to the heterogeneity in intervention content and outcomes evaluated in the included studies, a narrative synthesis was conducted. Risk of bias was assessed using the Cochrane Risk of Bias Version 2 tool for randomised controlled trials and the Cochrane ROBINS-I tool for non-randomised controlled trials. The search yielded 23 distinct studies with a total sample size of 2,779 participants. All studies were conducted in high-income or upper-middle-income countries. Interventions to improve patient adherence to psychological treatments included reminders and between-session engagement (e.g., text messages), motivational interviewing, therapy orientation (e.g., expectation-setting) and overcoming structural barriers (e.g., case management). Interventions from 18 out of 23 studies were successful in improving at least one primary adherence outcome of interest (e.g., session attendance). Some studies also reported an improvement in secondary outcomes – six studies reported an improvement in at least one clinical outcome (e.g., depression), and three studies reported improvements in at least one measure of well-being or disability (e.g., days spent in in-patient treatment). By incorporating these interventions into psychological treatment services, therapists can better engage with and support their patients, potentially leading to improved mental health outcomes and overall well-being.
Severe mental illness (SMI), which includes schizophrenia, schizoaffective disorder and bipolar disorder, has profound health impacts, even in the elderly.
Aims
To evaluate relative risk of hospital admission and length of hospital stay for physical illness in elders with SMI.
Method
To construct a population-based retrospective cohort observed from April 2007 to March 2016, data from a case registry with full but de-identified electronic health records were retrieved for patients of the South London and Maudsley NHS Foundation Trust, the single secondary mental healthcare service provider in south-east London. We compared participants with SMI aged >60 years old with the general population of the same age and residing in the same areas through data linkage by age-, sex- and fiscal-year-standardised admission ratios (SARs) for primary diagnoses at hospital discharge. Furthermore, we compared the duration of hospital stay with an age-, sex- and cause-of-admission-matched random group by linear regression for major causes of admission.
Results
In total, records for 4175 older people with SMI were obtained, relating to 10 342 admission episodes, showing an overall SAR for all physical illnesses of 5.15 (95% CI: 5.05, 5.25). Among the top causes of admission, SARs ranged from 3.87 for circulatory system disorders (ICD-10 codes: I00–I99) to 6.99 for genitourinary system or urinary conditions (N00–N39). Specifically, the diagnostic group of ‘symptoms, signs and findings, not elsewhere classified’ (R00–R99) had an elevated SAR of 6.56 (95% CI: 6.22, 6.90). Elders with SMI also had significantly longer hospital stays than their counterparts in the general population, especially for digestive system illnesses (K00–K93), after adjusting for confounding.
Conclusions
Poorer overall physical health and specific patterns were identified in elders with SMI.
Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.
Methods
Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange.
Results
The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39).
Conclusions
Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed.
Military Servicemembers and Veterans are at elevated risk for suicide, but rarely self-identify to their leaders or clinicians regarding their experience of suicidal thoughts. We developed an algorithm to identify posts containing suicide-related content on a military-specific social media platform.
Methods
Publicly-shared social media posts (n = 8449) from a military-specific social media platform were reviewed and labeled by our team for the presence/absence of suicidal thoughts and behaviors and used to train several machine learning models to identify such posts.
Results
The best performing model was a deep learning (RoBERTa) model that incorporated post text and metadata and detected the presence of suicidal posts with relatively high sensitivity (0.85), specificity (0.96), precision (0.64), F1 score (0.73), and an area under the precision-recall curve of 0.84. Compared to non-suicidal posts, suicidal posts were more likely to contain explicit mentions of suicide, descriptions of risk factors (e.g. depression, PTSD) and help-seeking, and first-person singular pronouns.
Conclusions
Our results demonstrate the feasibility and potential promise of using social media posts to identify at-risk Servicemembers and Veterans. Future work will use this approach to deliver targeted interventions to social media users at risk for suicide.
Pediatric medical devices lag behind adult devices due to economic barriers, smaller patient populations, changing anatomy and physiology of patients, regulatory hurdles, and especially difficulties in executing clinical trials. We investigated the requirements, challenges, associated timeline, and costs of conducting a multi-site pivotal clinical trial for a Class II pediatric physiologic monitoring device.
Methods:
This case study focused on the negotiation of clinical trial agreements (CTAs), budgets, and Institutional Review Board (IRB) processing times for a pediatric device trial. We identified key factors contributing to delays in clinical trial execution and potential best practices to expedite the process while maintaining safety, ethics, and efficacy.
Results:
The total time from site contact to first patient enrollment averaged 14 months. CTA and budget negotiations were the most time-consuming processes, averaging nearly 10 and 9 months, respectively. Reliance and local IRB processing also contributed significantly to the timeline, overall adding an average of 6.5 months across institutions. Nearly half of all costs were devoted to regulatory oversight. The COVID-19 pandemic caused significant slowdowns and delays at multiple institutions during study enrollment. Despite these pandemic-induced delays, it is important to note that the issues and themes highlighted remain relevant and have post-pandemic applicability.
Conclusions:
Our case study results underscore the importance of establishing efficient and standardized processing of CTAs, budget negotiations, and use of reliance IRBs to expedite clinical trial execution for pediatric devices. The findings also highlight the need for a national clinical trials network to streamline the clinical trial process.
This Special Issue celebrates the 50th anniversary of Review of International Studies. Since 1975, the Review has published over 200 issues and over 1300 articles. The journal has played a key role in shaping the discipline of International Relations (IR), leading, or critically intervening in, key debates. To celebrate 50 years of Review of International Studies, we have curated a Special Issue examining the challenges facing global politics for the next 50 years. IR has regularly turned its attention backwards towards its historical origins. Instead, we look to the future. In this Introduction, we start by outlining four traditions of future-oriented thinking: positivist, realist prediction; planning, forecasting, and scenario-building; utopian dreams of an ideal political future; and prefigurative thinking in activist politics. From these traditions, we learn that thinking about the future is always thinking about the present. We then outline four themes in the Special Issue articles: How do we think about the future at all? How do we think about imperial pasts and the ongoing questions of colonization and racialization in the present? How will technological change mediate and generates geopolitical change? How are socioecological crises, and in particular climate change, increasingly shaping how we think about the future of global politics? Overall, these provide us with a diverse, stimulating, and thought-provoking set of essays about the future of global politics, as both discipline and set of empirical problems.
We explore some of the risks related to Artificial Intelligence (AI) from an actuarial perspective based on research from a transregional industry focus group. We aim to define the key gaps and challenges faced when implementing and utilising modern modelling techniques within traditional actuarial tasks from a risk perspective and in the context of professional standards and regulations. We explore best practice guidelines to attempt to define an ideal approach and propose potential next steps to help reach the ideal approach. We aim to focus on the considerations, initially from a traditional actuarial perspective and then, if relevant, consider some implications for non-traditional actuarial work, by way of examples. The examples are not intended to be exhaustive. The group considered potential issues and challenges of using AI, related to the following key themes:
Ethical
○ Bias, fairness, and discrimination
○ Individualisation of risk assessment
○ Public interest
Professional
○ Interpretability and explainability
○ Transparency, reproducibility, and replicability
○ Validation and governance
Lack of relevant skills available
Wider themes
This paper aims to provide observations that could help inform industry and professional guidelines or discussion or to support industry practitioners. It is not intended to replace current regulation, actuarial standards, or guidelines. The paper is aimed at an actuarial and insurance technical audience, specifically those who are utilising or developing AI, and actuarial industry bodies.
We present new stable oxygen and carbon isotope composite records (δ18O, δ13C) of speleothems from Sandkraal Cave 1 (SK1) on the South African south coast for the time interval between 104 and 18 ka (with a hiatus between 48 and 41 ka). Statistical comparisons using kernel-based correlation analyses and semblance analyses based on continuous wavelet transforms inform the relationships of the new speleothem records to other proxies and their changes through time. Between 105 and ~70 ka, changes of speleothem δ18O values at SK1 are likely related to rainfall seasonality. Variations of δ13C values are associated with changes of vegetation density, prior carbonate precipitation (PCP), CO2 degassing in the cave, and possibly variations of the abundance of C3 and C4 grasses in the vegetation. The relationships of δ18O with other proxies shift between ~70 and 48 ka (Marine Isotope Stages 4–3) so that both stable isotope records now reflect CO2 degassing, evaporation, and PCP. Similar relationships also continue after the hiatus for the deposition phase between 42 and 18 ka. Our findings support modeling results suggesting drier conditions in the study area when the Southern Hemisphere westerlies are shifted north and the paleo–Agulhas Plain is exposed.
Packed red blood cell transfusions occur frequently after congenital heart surgery to augment haemodynamics, with limited understanding of efficacy. The goal of this study was to analyse the hemodynamic response to packed red blood cell transfusions in a single cohort, as “proof-of-concept” utilising high-frequency data capture of real-time telemetry monitoring.
Methods:
Retrospective review of patients after the arterial switch operation receiving packed red blood cell transfusions from 15 July 2020 to 15 July 2021. Hemodynamic parameters were collected from a high-frequency data capture system (SickbayTM) continuously recording vital signs from bedside monitors and analysed in 5-minute intervals up to 6 hours before, 4 hours during, and 6 hours after packed red blood cell transfusions—up to 57,600 vital signs per packed red blood cell transfusions. Variables related to oxygen balance included blood gas co-oximetry, lactate levels, near-infrared spectroscopy, and ventilator settings. Analgesic, sedative, and vasoactive infusions were also collected.
Results:
Six patients, at 8.5[IQR:5-22] days old and weighing 3.1[IQR:2.8-3.2]kg, received transfusions following the arterial switch operation. There were 10 packed red blood cell transfusions administered with a median dose of 10[IQR:10-15]mL/kg over 169[IQR:110-190]min; at median post-operative hour 36[IQR:10-40]. Significant increases in systolic and mean arterial blood pressures by 5-12.5% at 3 hours after packed red blood cell transfusions were observed, while renal near-infrared spectroscopy increased by 6.2% post-transfusion. No significant changes in ventilation, vasoactive support, or laboratory values related to oxygen balance were observed.
Conclusions:
Packed red blood cell transfusions given after the arterial switch operation increased arterial blood pressure by 5-12.5% for 3 hours and renal near-infrared spectroscopy by 6.2%. High-frequency data capture systems can be leveraged to provide novel insights into the hemodynamic response to commonly used therapies such as packed red blood cell transfusions after paediatric cardiac surgery.