Prolonged grief disorder symptomology in three African countries: A network analysis and comparison.

Background: Bereavement is a globally prevalent life stressor, but in some instances, it may be followed by a persistent condition of grief and distress, codified within the 11th edition of the International Classification of Diseases (ICD-11) as prolonged grief disorder (PGD). Network analysis provides a valuable framework for understanding psychological disorders at a nuanced symptom-based level. Aim: This study novelly explores the network structure of ICD-11 PGD symptomology in a non-Western sample and assesses the replication of this across three African country sub-samples in these data. Methodology: Network models were estimated using the "Inventory of Complicated Grief-Revised" in a sample of trauma-exposed individuals who experienced bereavement throughout life (N = 1,554) from three African countries (Ghana, n = 290; Kenya, n = 619; Nigeria, n = 645). These networks were statistically evaluated using the network comparison test. Results: It was found that "Feelings of Loss" and "Difficulty moving on" were the most central symptoms in the combined sample network. These findings were largely consistent for the Ghana and Nigeria sub-samples, however, network structure differences were noted in the Kenya sub-sample. Conclusion: The identified PGD network highlights particular indicators and associations across three African samples. Implications for the assessment and treatment of PGD in these cultural contexts warrant consideration.

Understanding the impact of numerical solvers on inference for differential equation models.

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers that seem sufficiently accurate for the forward problem, i.e. for obtaining an accurate simulation, might not be sufficiently accurate for the inverse problem, i.e. for inferring the model parameters from data. We show that for both fixed step and adaptive step ODE solvers, solving the forward problem with insufficient accuracy can distort likelihood surfaces, which might become jagged, causing inference algorithms to get stuck in local 'phantom' optima. We demonstrate that biases in inference arising from numerical approximation of ODEs are potentially most severe in systems involving low noise and rapid nonlinear dynamics. We reanalyse an ODE change point model previously fit to the COVID-19 outbreak in Germany and show the effect of the step size on simulation and inference results. We then fit a more complicated rainfall run-off model to hydrological data and illustrate the importance of tuning solver tolerances to avoid distorted likelihood surfaces. Our results indicate that, when performing inference for ODE model parameters, adaptive step size solver tolerances must be set cautiously and likelihood surfaces should be inspected for characteristic signs of numerical issues.

Flexible emotional regulation typology: associations with PTSD symptomology and trait resilience.

BACKGROUND: Multiple factors influence posttraumatic stress disorder (PTSD) risk in trauma exposed individuals. An established association exists between trait resilience and decreased PTSD distress and between emotion regulation (ER) ability/flexibility and trait resilience. Typologies in ER ability/flexibility, associated with trait resilience and PTSD experience, could explain the difference in risk. This study aimed to explore the relationship between ER ability, ER flexibility, context sensitivity, resilience, and PTSD. METHODS: Data from N = 563 trauma exposed UK residents was used in a latent profile analysis (LPA) and membership in the resultant profiles was explored in a logistic regression of sociodemographics, resilience, and PTSD symptomology. RESULTS: Analysis showed 2 latent profiles (High Flexibility, Low Flexibility) typified by emotion regulation ability and context sensitivity. Members of the Low Flexibility profile were more likely to be younger, male, endorsing less trait resilience, and experiencing negative cognition/mood and hyperarousal PTSD symptomology. CONCLUSIONS: Difficulties in ER ability and flexibility could be improved with targeted learning in a therapeutic or home setting, potentially increasing trait resilience after trauma exposure and reducing PTSD distress.

Prevalence and concordance of International Classification of Diseases-11th Revision and Diagnostic and Statistical Manual-Fifth Edition posttraumatic stress diagnostics among Northern Irish military veterans.

BACKGROUND: There are two primary competing diagnostic criteria for posttraumatic stress disorder (PTSD); the International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual (DSM). These systems differ in terms of the number and nature of PTSD symptoms, the implied latent structure of the disorder, and associated posttraumatic diagnostic classifications. OBJECTIVE: To investigate the prevalence and concordance of ICD-11th Revision (ICD-11) and DSM-Fifth Edition (DSM-5) PTSD, complex-PTSD (C-PTSD), and dissociative subtype of PTSD (D-PTSD) criteria in a sample of Northern Irish military veterans. METHODOLOGY: Data were collected from a community sample of military veterans living in Northern Ireland (NI). Prevalence rates of ICD-11 PTSD and C-PTSD and DSM-5 PTSD and D-PTSD were estimated using validated self-report measures for each system. Concordance of caseness determined by diagnostic criteria was compared using Cohen's kappa. RESULTS: The DSM-5 algorithm criteria produced significantly higher prevalence estimates of PTSD (39.26%) relative to the ICD-11 algorithm criteria (32.09%). Both C-PTSD and D-PTSD were identified for subgroups within the sample (24.66% and 27.96%, respectively). There was moderate agreement between the diagnostic systems regarding PTSD caseness, and between C-PTSD and D-PTSD caseness. CONCLUSIONS: These findings have implications regarding the measurement of PTSD and associated diagnostic groupings for the wider literature, suggesting that the choice of diagnostic screening framework may influence classification. Both C-PTSD and D-PTSD may be relevant diagnostic considerations for the NI military veteran group. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Simulating clinical trials for model-informed precision dosing: using warfarin treatment as a use case.

Treatment response variability across patients is a common phenomenon in clinical practice. For many drugs this inter-individual variability does not require much (if any) individualisation of dosing strategies. However, for some drugs, including chemotherapies and some monoclonal antibody treatments, individualisation of dosages are needed to avoid harmful adverse events. Model-informed precision dosing (MIPD) is an emerging approach to guide the individualisation of dosing regimens of otherwise difficult-to-administer drugs. Several MIPD approaches have been suggested to predict dosing strategies, including regression, reinforcement learning (RL) and pharmacokinetic and pharmacodynamic (PKPD) modelling. A unified framework to study the strengths and limitations of these approaches is missing. We develop a framework to simulate clinical MIPD trials, providing a cost and time efficient way to test different MIPD approaches. Central for our framework is a clinical trial model that emulates the complexities in clinical practice that challenge successful treatment individualisation. We demonstrate this framework using warfarin treatment as a use case and investigate three popular MIPD methods: 1. Neural network regression; 2. Deep RL; and 3. PKPD modelling. We find that the PKPD model individualises warfarin dosing regimens with the highest success rate and the highest efficiency: 75.1% of the individuals display INRs inside the therapeutic range at the end of the simulated trial; and the median time in the therapeutic range (TTR) is 74%. In comparison, the regression model and the deep RL model have success rates of 47.0% and 65.8%, and median TTRs of 45% and 68%. We also find that the MIPD models can attain different degrees of individualisation: the Regression model individualises dosing regimens up to variability explained by covariates; the Deep RL model and the PKPD model individualise dosing regimens accounting also for additional variation using monitoring data. However, the Deep RL model focusses on control of the treatment response, while the PKPD model uses the data also to further the individualisation of predictions.

Evaluation of a pregnancy loss education intervention for undergraduate nursing students in Northern Ireland: A pre- and post-test study.

BACKGROUND: Research highlights the importance of compassionate communication, adequate delivery of information, and professional support to help alleviate parental distress following pregnancy loss. However, many healthcare professionals do not feel sufficiently trained to deal with pregnancy loss in practice. We aimed to address this deficiency with an evidence-informed educational intervention to increase knowledge, skills, self-awareness, and confidence regarding pregnancy loss among UK nursing students. METHODS: Educational resources, which included an 82-minute podcast and 40-minute online lecture were developed. The podcast focused on the lived experiences of three women who had experienced miscarriage, stillbirth, and termination of pregnancy for medical reasons. The pre-recorded lecture included definitions of types of pregnancy loss, discussion of the importance of communication, and information on the clinical management of pregnancy loss. Students were presented with both the lecture and podcast as a self-directed element of existing curricula. A pre-test/post-test cross-sectional survey design was used to investigate the impact of the educational intervention. The Perinatal Bereavement Care Confidence Scale (PBCCS) was completed by 244 first year BSc Nursing students before and up to a week after receiving the intervention. Quantitative data were analysed using a Paired Samples Wilcoxon test. Responses to open-ended questions, which allowed students to give feedback on the intervention content and delivery were analysed using Qualitative Content Analysis. RESULTS: 96% (n = 235) of the sample reported having no prior experience or training in the management and support of those experiencing pregnancy loss. At pre-test, 88% (n = 215) of students rated themselves as not confident in dealing with pregnancy loss in a professional capacity. Post-test, we found statistically significant effects for perceived competency on all learning outcomes (p < .001). Qualitative analysis of n = 745 individual text responses to open-ended questions indicated four categories related to the perceived value of using real-life stories for learning, demystifying a taboo subject, and providing tools for practice. Respondents suggested the inclusion of more information on memory-making, support networks, and mental health following pregnancy loss. CONCLUSIONS: The educational intervention increased student nurses' perceived knowledge, confidence, and skills in caring for families experiencing pregnancy loss. This offers potential for increased quality of care for those experiencing pregnancy loss in healthcare settings, increased patient satisfaction, and improved mental health-related outcomes.

ICD-11 complex post-traumatic stress disorder and psychiatric comorbidity among UK Armed Forces veterans in Northern Ireland: a latent class analysis.

Background: There is evidence to suggest that the experience of complex post-traumatic stress disorder (C-PTSD) may be commonly associated with elevated risk for several mental ill-health comorbidities.Objective: The current study seeks to contribute to the growing literature on C-PTSD comorbidity by examining the relationship between C-PTSD and other mental health disorders in a UK Armed Forces veteran sample.Method: This study used data from the Northern Ireland Veterans' Health and Wellbeing Study (NIVHWS). The effective sample consisted of 638 veterans (90.0% male). Tetrachoric correlations examined the relationship between C-PTSD caseness and other mental health outcomes. Latent class analysis was then conducted, determining the optimal number and nature of classes in the sample in relation to C-PTSD, depression, anxiety, and suicidality.Results: C-PTSD caseness (i.e. probable diagnosis) was found to be significantly associated with positive caseness of depression, anxiety, and suicidality. Overall, four latent classes emerged, with each of these classes characterized by varying degrees of comorbidity: a 'Resilient/Low Comorbidity' class, a 'Lifetime Suicidal' class, a 'PTSD Polymorbid' class, and a 'C-PTSD Polymorbid' class.Conclusions These findings support and extend previous results indicating the highly comorbid nature of C-PTSD. C-PTSD may be considered a highly polymorbid condition, increasing the risk for multiple mental health pathologies concurrently.

The results showed that probable complex PTSD was associated with depression, anxiety, and suicidality in this military veteran sample.Latent class analysis revealed that probable complex PTSD was associated with multiple conditions concurrently, suggesting that complex PTSD is not only highly comorbid but polymorbid.The findings highlight the importance of screening for multiple pathologies, particularly in cases of probable complex PTSD.

Phosphogypsum impacts on soil chemical properties and vegetation tissue following reclamation.

Phosphogypsum (PG) is a by-product of phosphorus fertilizer that is typically stacked near production sites. Phosphogypsum contains trace elements and naturally occurring radioactive materials which may be hazardous to the surrounding environment. Phosphogypsum stack reclamation typically involves placing a soil cap and seeding grass to create a barrier for reducing environmental impacts; using woody species is uncommon. This study used three soil treatments with grass and woody species to determine whether mixing PG with soil affects soil chemical properties, and metal and radionuclide concentrations in tissue. None of the elements in soil was above Canadian guidelines for industrial land use. Aluminum, beryllium, chromium, copper, iron, magnesium, manganese, nickel, and vanadium were significantly higher in both study and reference sites than in pure PG; cadmium, calcium, fluoride, and strontium were significantly higher in pure PG. There was a poor correlation between soil and plant concentrations for most elements indicating trace elements were not in a bioavailable form. Trace elemental concentrations in plant tissue generally differed significantly with vegetation type but not within similar species. Trace elements and isotopes in PG were not high enough to affect plant growth. Among the isotopes, 222Ra emissions differed significantly with vegetation covers; activity of 226Ra in pure PG was above Canadian guidelines, but lower in vegetation tissue. This study suggests 15 cm soil mixed with PG can be used for PG stack revegetation when fast-growing Salix and Populus species are used in reclamation.

Filter inference: A scalable nonlinear mixed effects inference approach for snapshot time series data.

Variability is an intrinsic property of biological systems and is often at the heart of their complex behaviour. Examples range from cell-to-cell variability in cell signalling pathways to variability in the response to treatment across patients. A popular approach to model and understand this variability is nonlinear mixed effects (NLME) modelling. However, estimating the parameters of NLME models from measurements quickly becomes computationally expensive as the number of measured individuals grows, making NLME inference intractable for datasets with thousands of measured individuals. This shortcoming is particularly limiting for snapshot datasets, common e.g. in cell biology, where high-throughput measurement techniques provide large numbers of single cell measurements. We introduce a novel approach for the estimation of NLME model parameters from snapshot measurements, which we call filter inference. Filter inference uses measurements of simulated individuals to define an approximate likelihood for the model parameters, avoiding the computational limitations of traditional NLME inference approaches and making efficient inferences from snapshot measurements possible. Filter inference also scales well with the number of model parameters, using state-of-the-art gradient-based MCMC algorithms such as the No-U-Turn Sampler (NUTS). We demonstrate the properties of filter inference using examples from early cancer growth modelling and from epidermal growth factor signalling pathway modelling.

Technical development and validation of a clinically applicable microenvironment classifier as a biomarker of tumour hypoxia for soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS) are rare, heterogeneous tumours and biomarkers are needed to inform management. We previously derived a prognostic tumour microenvironment classifier (24-gene hypoxia signature). Here, we developed/validated an assay for clinical application. METHODS: Technical performance of targeted assays (Taqman low-density array, nanoString) was compared in 28 prospectively collected formalin-fixed, paraffin-embedded (FFPE) biopsies. The nanoString assay was biologically validated by comparing to HIF-1α/CAIX immunohistochemistry (IHC) in clinical samples. The Manchester (n = 165) and VORTEX Phase III trial (n = 203) cohorts were used for clinical validation. The primary outcome was overall survival (OS). RESULTS: Both assays demonstrated excellent reproducibility. The nanoString assay detected upregulation of the 24-gene signature under hypoxia in vitro, and 16/24 hypoxia genes were upregulated in tumours with high CAIX expression in vivo. Patients with hypoxia-high tumours had worse OS in the Manchester (HR 3.05, 95% CI 1.54-5.19, P = 0.0005) and VORTEX (HR 2.13, 95% CI 1.19-3.77, P = 0.009) cohorts. In the combined cohort, it was independently prognostic for OS (HR 2.24, 95% CI 1.42-3.53, P = 0.00096) and associated with worse local recurrence-free survival (HR 2.17, 95% CI 1.01-4.68, P = 0.04). CONCLUSIONS: This study comprehensively validates a microenvironment classifier befitting FFPE STS biopsies. Future uses include: (1) selecting high-risk patients for perioperative chemotherapy; and (2) biomarker-driven trials of hypoxia-targeted therapies.

Involving men and boys in family planning: A systematic review of the effective components and characteristics of complex interventions in low- and middle-income countries.

Background: Involving men and boys as both users and supporters of Family Planning (FP) is now considered essential for optimising maternal and child health outcomes. Evidence on how to engage men and boys to meet FP needs is therefore important. Objectives: The main objective of this review was to assess the strength of evidence in the area and uncover the effective components and critical process- and system-level characteristics of successful interventions. Search Methods: We searched nine electronic databases, seven grey literature databases, organisational websites, and the reference lists of systematic reviews relating to FP. To identify process evaluations and qualitative papers associated with the included experimental studies, we used Connected Papers and hand searches of reference lists. Selection Criteria: Experimental and quasi-experimental studies of behavioural and service-level interventions involving males aged 10 years or over in low- and middle-income countries to increase uptake of FP methods were included in this review. Data Collection and Analysis: Methodology was a causal chain analysis involving the development and testing of a logic model of intervention components based on stakeholder consultation and prior research. Qualitative and quantitative data relating to the evaluation studies and interventions were extracted based on the principles of 'effectiveness-plus' reviews. Quantitative analysis was undertaken using r with robust variance estimation (RVE), meta-analysis and meta-regression. Qualitative analysis involved 'best fit' framework synthesis. Results: We identified 8885 potentially relevant records and included 127 in the review. Fifty-nine (46%) of these were randomised trials, the remainder were quasi-experimental studies with a comparison group. Fifty-four percent of the included studies were assessed as having a high risk of bias. A meta-analysis of 72 studies (k = 265) showed that the included group of interventions had statistically significantly higher odds of improving contraceptive use when compared to comparison groups (odds ratio = 1.38, confidence interval = 1.21 to 1.57, prediction interval = 0.36 to 5.31, p < 0.0001), but there were substantial variations in the effect sizes of the studies (Q = 40,647, df = 264, p < 0.0001; I 2 = 98%) and 73% was within cluster/study. Multi-variate meta-regression revealed several significant intervention delivery characteristics that moderate contraceptive use. These included community-based educational FP interventions, interventions delivered to women as well as men and interventions delivered by trained facilitators, professionals, or peers in community, home and community, or school settings. None of the eight identified intervention components or 33 combinations of components were significant moderators of effects on contraceptive use. Qualitative analysis highlighted some of the barriers and facilitators of effective models of FP that should be considered in future practice and research. Authors' Conclusions: FP interventions that involve men and boys alongside women and girls are effective in improving uptake and use of contraceptives. The evidence suggests that policy should continue to promote the involvement of men and boys in FP in ways that also promote gender equality. Recommendations for research include the need for evaluations during conflict and disease outbreaks, and evaluation of gender transformative interventions which engage men and boys as contraceptive users and supporters in helping to achieve desired family size, fertility promotion, safe conception, as well as promoting equitable family planning decision-making for women and girls.

A Bayesian nonparametric method for detecting rapid changes in disease transmission.

Whether an outbreak of infectious disease is likely to grow or dissipate is determined through the time-varying reproduction number, Rt. Real-time or retrospective identification of changes in Rt following the imposition or relaxation of interventions can thus contribute important evidence about disease transmission dynamics which can inform policymaking. Here, we present a method for estimating shifts in Rt within a renewal model framework. Our method, which we call EpiCluster, is a Bayesian nonparametric model based on the Pitman-Yor process. We assume that Rt is piecewise-constant, and the incidence data and priors determine when or whether Rt should change and how many times it should do so throughout the series. We also introduce a prior which induces sparsity over the number of changepoints. Being Bayesian, our approach yields a measure of uncertainty in Rt and its changepoints. EpiCluster is fast, straightforward to use, and we demonstrate that it provides automated detection of rapid changes in transmission, either in real-time or retrospectively, for synthetic data series where the Rt profile is known. We illustrate the practical utility of our method by fitting it to case data of outbreaks of COVID-19 in Australia and Hong Kong, where it finds changepoints coinciding with the imposition of non-pharmaceutical interventions. Bayesian nonparametric methods, such as ours, allow the volume and complexity of the data to dictate the number of parameters required to approximate the process and should find wide application in epidemiology. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

A path to post-trauma resilience: a mediation model of the flexibility sequence.

Background: Psychological resilience has grown in popularity as a topic of study in psychotraumatology research; however, this concept remains poorly understood and there are several competing theories of resilience. Objective: This study sought to assess the support for one proposed theory of resilience: the flexibility sequence. Method: This study use secondary data analysis of panel survey data (N = 563). Participants were aged 18 years or over and based in the UK. A series of sequential mediation models was used to test the flexibility sequence theory as a proposed pathway of resilience on mental health outcomes (post-traumatic stress disorder, anxiety, and depression) among a trauma-exposed sample from the UK. Results: The 'feedback' component of the proposed flexibility sequence components was associated with reduced symptom severity with all outcomes, whereas 'context sensitivity' and 'repertoire' were significantly associated only with depression as an outcome. When indirect mediation pathways were modelled via the flexibility sequence, statistically significant effects were observed for all outcomes under investigation. Conclusions: These findings support the theorized flexibility sequence pathway of resilience, suggesting that the combination of these skills/processes performs more favourably as a framework of resilience than any in isolation. Further research into more elaborate associations and feedback loops associated with this pathway is warranted.

Antecedentes: La resiliencia psicológica ha ganado popularidad como tema de estudio en la investigación en psicotraumatología, sin embargo este concepto sigue siendo poco comprendido. Hay varias teorías de resiliencia que compiten entre sí, sin embargo este estudio buscó evaluar el apoyo para una teoría propuesta: la Secuencia de Flexibilidad.Metodología: Este estudio utilizó análisis de datos secundarios de datos de encuestas de panel (N=563, los participantes tenían más de 18 años y residían en el Reino Unido). Se utilizaron una serie de modelos secuenciales para probar la teoría de Secuencia de Flexibilidad como una vía propuesta de Resiliencia en los resultados de salud mental (TEPT, Ansiedad y Depresión) entre una muestra del Reino Unido expuesta a traumas.Resultados: Se encontró que el componente de Retroalimentación de los componentes de la Secuencia de Flexibilidad propuesta se asoció con una reducción de la gravedad de los síntomas en todos los resultados y la Sensibilidad al Contexto y Repertorio se asociaron significativamente solo con Depresión como resultado. Cuando las vías de mediación indirecta se modelaron a través de la Secuencia de Flexibilidad, se observaron efectos estadísticamente significativos para todos los resultados bajo investigación.Discusión: Estos hallazgos respaldan el camino de Resiliencia teorizado de Secuencia de Flexibilidad, lo que sugiere que la combinación de estas habilidades/procesos funciona más favorablemente como una estructura de resiliencia que cualquiera de forma aislada. Se justifica una mayor investigación sobre asociaciones más elaboradas y circuitos de retroalimentación asociados con esta vía.

Addressing sexual and reproductive health and rights with men in prisons: co-production and feasibility testing of a relationship, sexuality and future fatherhood education programme.

PURPOSE: Young incarcerated male offenders are at risk of poorer sexual health, adolescent parenthood and lack opportunities for formative relationship and sexuality education (RSE) as well as positive male role models. The purpose of this paper is to report the process of co-production and feasibility testing of a novel, gender-transformative RSE programme with young male offenders to encourage positive healthy relationships, gender equality, and future positive fatherhood. DESIGN/METHODOLOGY/APPROACH: Using a rights-based participatory approach, the authors co-produced an RSE programme with young offenders and service providers at two UK prison sites using a sequential research design of: needs analysis, co-production and a feasibility pilot. Core components of the programme are grounded in evidence-based RSE, gender-transformative and behaviour change theory. FINDINGS: A needs analysis highlighted the men's interest in RSE along with the appeal of film drama and peer-group-based activities. In the co-production stage, scripts were developed with the young men to generate tailored film dramas and associated activities. This co-production led to "If I Were a Dad", an eight-week programme comprising short films and activities addressing masculinities, relationships, sexual health and future fatherhood. A feasibility pilot of the programme demonstrated acceptability and feasibility of delivery in two prison sites. The programme warrants further implementation and evaluation studies. ORIGINALITY/VALUE: The contribution of this paper is the generation of an evidence-based, user-informed, gender-transformative programme designed to promote SRHR of young male offenders to foster positive sexual and reproductive health and well-being in their own lives and that of their partners and (future) children.

Exploring complex-PTSD comorbidity in trauma-exposed Northern Ireland veterans.

Background: Complex posttraumatic stress disorder (CPTSD) describes the results of complex, prolonged, and/or inescapable trauma, and is typified by avoidance, re-experiencing, sense of threat, affect dysregulation, negative self-concept, and interpersonal disturbances. Additionally, CPTSD is highly comorbid with other common psychopathologies. Objectives: A study was conducted in a trauma-exposed UK Armed Forces Veteran population resident in Northern Ireland (N = 638, NI) to determine the prevalence of CPTSD and comorbid associations. Methods: Data from the Northern Ireland Veterans Health and Wellbeing Study (NIVHWS), including self-report data describing traumatic stress, depression, anxiety, and suicidality, were used in a latent class analysis to identify distinct profiles of symptomology in the sample, and in a multinomial logistic regression to identify comorbidities associated with class membership. Results: Three distinct classes emerged: a low endorsement 'baseline' class (36%), a 'Moderate Symptomatic' class (27%), and a high endorsement 'Probable CPTSD' class (37%). Both the Moderate Symptomatic and CPTSD classes were predicted by cumulative trauma exposure. Depression was highly comorbid (OR = 23.06 in CPTSD), as was anxiety (OR = 22.05 in CPTSD) and suicidal ideation (OR = 4.32 in CPTSD), with suicidal attempt associated with the CPTSD class (OR = 2.51). Conclusions: Cases of probable CPTSD were more prevalent than cases of probable posttraumatic stress disorder (PTSD) without Difficulties in Self-Organisation (DSO) symptoms in a UK Armed Forces veteran sample, were associated with repeated/cumulative trauma, and were highly comorbid across a range of psychopathologies. Findings validate previous literature on CPTSD and indicate considerable distress and thus need for support in UK Armed Forces veterans resident in NI.

Antecedentes:El trastorno de estrés postraumático complejo (TEPT-C) describe los resultados de un trauma complejo, prolongado y/o inevitable; y se caracteriza por la presencia de evitación, re-experimentación, sensación de amenaza, desregulación afectiva, un autoconcepto negativo y alteraciones en las relaciones interpersonales. Adicionalmente, el TEPT-C es altamente comórbido con otras psicopatologías frecuentes.Objetivos: Se realizó un estudio en una población de veteranos de las Fuerzas Armadas del Reino Unido expuestos a trauma residentes en Irlanda del Norte (N=638, NI) para determinar la prevalencia del TEPT-C y las asociaciones comórbidas.Métodos: Los datos del Estudio de Salud y Bienestar en Veteranos de Irlanda del Norte (NIVHWS, por sus siglas en inglés), incluidos datos de auto-reportes describiendo la presencia de estrés traumático, depresión, ansiedad y suicidalidad, fueron utilizados en un análisis de clases latentes para identificar distintos perfiles de sintomatología en la muestra y en una regresión logística multinomial para identificar las comorbilidades asociadas con la pertenencia a cada clase.Resultados: Surgieron tres clases distintas: una clase de "línea base" de bajo respaldo (36%), una clase de "sintomático moderado" (27%) y una clase de "TEPT-C probable" de alto respaldo (37%). La exposición acumulativa a trauma predijo tanto las clases de sintomático moderado como la del TEPT-C probable. La depresión fue altamente comórbida (OR=23.06 en TEPT-C), así como la ansiedad (OR=22.05 en TEPT-C) y la ideación suicida (OR=4.32 en TEPT-C), con intento de suicidio asociado a la clase de TEPT-C (OR=2.51).Conclusiones: Los casos de TEPT-C probable fueron más prevalentes que los casos de trastorno de estrés postraumático (TEPT) sin síntomas de alteraciones en la autoorganización (AAO) en una muestra de veteranos de las Fuerzas Armadas del Reino Unido. Asimismo, los casos de TEPT-C probable se asociaron a la exposición a trauma repetido/acumulativo y fueron altamente comórbidos con una variedad de psicopatologías. Los hallazgos validan la literatura previa concerniente al TEPT-C e indican una angustia considerable y, por lo tanto, demuestran la necesidad de soporte en los veteranos de las Fuerzas Armadas del Reino Unido residentes en Irlanda del Norte.

A Voltammetric Perspective of Multi-Electron and Proton Transfer in Protein Redox Chemistry: Insights From Computational Analysis of Escherichia coli HypD Fourier Transformed Alternating Current Voltammetry.

This paper explores the impact of pH on the mechanism of reversible disulfide bond (CysS-SCys) reductive breaking and oxidative formation in Escherichia coli hydrogenase maturation factor HypD, a protein which forms a highly stable adsorbed film on a graphite electrode. To achieve this, low frequency (8.96 Hz) Fourier transformed alternating current voltammetric (FTACV) experimental data was used in combination with modelling approaches based on Butler-Volmer theory with a dual polynomial capacitance model, utilizing an automated two-step fitting process conducted within a Bayesian framework. We previously showed that at pH 6.0 the protein data is best modelled by a redox reaction of two separate, stepwise one-electron, one-proton transfers with slightly "crossed" apparent reduction potentials that incorporate electron and proton transfer terms ( E app 2 0 > E app 1 0 ). Remarkably, rather than collapsing to a concerted two-electron redox reaction at more extreme pH, the same two-stepwise one-electron transfer model with E app 2 0 > E app 1 0 continues to provide the best fit to FTACV data measured across a proton concentration range from pH 4.0 to pH 9.0. A similar, small level of crossover in reversible potentials is also displayed in overall two-electron transitions in other proteins and enzymes, and this provides access to a small but finite amount of the one electron reduced intermediate state.

Nothing so practical as theory: a rapid review of the use of behaviour change theory in family planning interventions involving men and boys.

BACKGROUND: There is growing recognition of the need for interventions that effectively involve men and boys to promote family planning behaviours. Evidence suggests that the most effective behavioural interventions in this field are founded on theoretical principles of behaviour change and gender equality. However, there are few evidence syntheses on how theoretical approaches are applied in this context that might guide best practice in intervention development. This review addresses this gap by examining the application and reporting of theories of behaviour change used by family planning interventions involving men and boys. METHODS: We adopted a systematic rapid review approach, scoping findings of a previously reported evidence and gap map of intervention reviews (covering 2007-2018) and supplementing this with searches of academic databases and grey literature for reviews and additional studies published between 2007 and 2020. Studies were eligible for inclusion if their title, abstract or keywords referred to a psychosocial or behavioural intervention targeting family planning behaviours, involved males in delivery, and detailed their use of an intervention theory of change. RESULTS: From 941 non-duplicate records identified, 63 were eligible for inclusion. Most records referenced interventions taking place in low- and middle-income countries (65%). There was a range of intervention theories of change reported, typically targeting individual-level behaviours and sometimes comprising several behaviour change theories and strategies. The most commonly identified theories were Social Cognitive Theory, Social Learning Theory, the Theory of Planned Behaviour, and the Information-Motivation-Behaviour Skills (IMB) Model. A minority of records explicitly detailed gender-informed elements within their theory of change. CONCLUSION: Our findings highlight the range of prevailing theories of change used for family planning interventions involving men and boys, and the considerable variability in their reporting. Programmers and policy makers would be best served by unified reporting and testing of intervention theories of change. There remains a need for consistent reporting of these to better understand how complex interventions that seek to involve men and boys in family planning may lead to behaviour change.

Family planning (FP) programmes aim to enable people to achieve their desired family size. Successful programmes are essential for encouraging better health outcomes for individuals and families. Historically, FP programmes have focused on the sexual and reproductive health and rights of women and girls, and while this is necessary, it has also contributed to the exclusion of men and boys from FP programmes. There is growing evidence to suggest, however, that involving men and boys in FP may increase its uptake and improve health outcomes for all. However, we still know relatively little about the best ways to involve men and boys in FP programmes in order to ensure success. Research is ongoing to rectify this.When we look at public health behaviour change programmes in general, we find that many successful programmes incorporate theories of behaviour change into their design. These theories guide the kinds of activities and materials that the programme employs in order to promote behaviour change. In the field of FP, there is little information about the kinds of behaviour change theories that might be used to design programmes. This review aimed to address this by reviewing the global literature on FP programmes that involved men and boys to identify relevant behaviour-change theories. We found a range of theories that will be of use to programme planners. We also found, however, that there was lots of variability in the way theories were reported. We make recommendations for how this problem might be resolved.

Barely sufficient practices in scientific computing.

The importance of software to modern research is well understood, as is the way in which software developed for research can support or undermine important research principles of findability, accessibility, interoperability, and reusability (FAIR). We propose a minimal subset of common software engineering principles that enable FAIRness of computational research and can be used as a baseline for software engineering in any research discipline.

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial.

BACKGROUND: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation). METHODS: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK. We enrolled patients (aged >18 years) with indolent non-Hodgkin lymphoma who had histological confirmation of follicular lymphoma or marginal zone lymphoma requiring radical or palliative radiotherapy. No limit on performance status was stipulated, and previous chemotherapy or radiotherapy to another site was permitted. Radiotherapy target sites were randomly allocated (1:1) either 24 Gy in 12 fractions or 4 Gy in two fractions using minimisation and stratified by histology, treatment intent, and study centre. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Patients, treating clinicians, and investigators were not masked to random assignments. The primary endpoint was time to local progression in the irradiated volume based on clinical and radiological evaluation and analysed on an intention-to-treat basis. The non-inferiority threshold aimed to exclude the chance that 4 Gy was more than 10% inferior to 24 Gy in terms of local control at 2 years (HR 1·37). Safety (in terms of adverse events) was analysed in patients who received any radiotherapy and who returned an adverse event form. FoRT is registered with ClinicalTrials.gov, NCT00310167, and the ISRCTN Registry, ISRCTN65687530, and this report represents the long-term follow-up. FINDINGS: Between April 7, 2006, and June 8, 2011, 614 target sites in 548 patients were randomly assigned either 24 Gy in 12 fractions (n=299) or 4 Gy in two fractions (n=315). At a median follow-up of 73·8 months (IQR 61·9-88·0), 117 local progression events were recorded, 27 in the 24 Gy group and 90 in the 4 Gy group. The 2-year local progression-free rate was 94·1% (95% CI 90·6-96·4) after 24 Gy and 79·8% (74·8-83·9) after 4 Gy; corresponding rates at 5 years were 89·9% (85·5-93·1) after 24 Gy and 70·4% (64·7-75·4) after 4 Gy (hazard ratio 3·46, 95% CI 2·25-5·33; p<0·0001). The difference at 2 years remains outside the non-inferiority margin of 10% at -13·0% (95% CI -21·7 to -6·9). The most common events at week 12 were alopecia (19 [7%] of 287 sites with 24 Gy vs six [2%] of 301 sites with 4 Gy), dry mouth (11 [4%] vs five [2%]), fatigue (seven [2%] vs five [2%]), mucositis (seven [2%] vs three [1%]), and pain (seven [2%] vs two [1%]). No treatment-related deaths were reported. INTERPRETATION: Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment. FUNDING: Cancer Research UK.

Recent advances and future perspectives for automated parameterisation, Bayesian inference and machine learning in voltammetry.

Advanced data analysis tools such as mathematical optimisation, Bayesian inference and machine learning have the capability to revolutionise the field of quantitative voltammetry. Nowadays such approaches can be implemented routinely with widely available, user-friendly modern computing languages, algorithms and high speed computing to provide accurate and robust methods for quantitative comparison of experimental data with extensive simulated data sets derived from models proposed to describe complex electrochemical reactions. While the methodology is generic to all forms of dynamic electrochemistry, including the widely used direct current cyclic voltammetry, this review highlights advances achievable in the parameterisation of large amplitude alternating current voltammetry. One significant advantage this technique offers in terms of data analysis is that Fourier transformation provides access to the higher order harmonics that are almost devoid of background current. Perspectives on the technical advances needed to develop intelligent data analysis strategies and make them generally available to users of voltammetry are provided.