Characteristics and circumstances of rail suicides in England 2019-2021: A cluster analysis and autopsy study.

BACKGROUND: Around 4 % of all suicide deaths in Great Britain occur on the railways. This exploratory study was designed to increase understanding of the individuals that take their lives in this way, and the circumstances of their death. METHOD: Data were obtained from fatality investigation files compiled by the British Transport Police (BTP) relating to suspected suicides on the mainline railway in England from April 2019 to March 2021. Cluster analysis was carried out to identify grouped associations of characteristics and circumstances relating to rail suicide. RESULTS: A total of 436 files were analysed, representing 93 % of all suspected railway suicides during this period. Cluster analysis identified four groups of almost equal size, distinguished principally by age, living arrangements, employment status and location of death. The study is novel in the way it integrates individual characteristics and circumstances of death. The identified clusters may provide a multidimensional way of conceptualising suicide risk that could inform more targeted interventions at rail locations. LIMITATIONS: A high proportion of missing data means that the findings need to be interpreted with caution. It also restricted the multivariate analysis to those categories of information for which sufficient information was available. CONCLUSION: The characteristics and circumstances of suicide deaths on the railways are complex and multifaceted. The typology identified in this study may help to target preventative strategies prior to the incident as well as at different location types.

Fatigue after CriTical illness (FACT): Co-production of a self-management intervention to support people with fatigue after critical illness.

PURPOSE: Fatigue is a common and debilitating problem in patients recovering from critical illness. To address a lack of evidence-based interventions for people with fatigue after critical illness, we co-produced a self-management intervention based on self-regulation theory. This article reports the development and initial user testing of the co-produced intervention. METHODS: We conducted three workshops with people experiencing fatigue after critical illness, family members, and healthcare professionals to develop a first draft of the FACT intervention, designed in web and electronic document formats. User testing and interviews were conducted with four people with fatigue after critical illness. Modifications were made based on the findings. RESULTS: Participants found FACT acceptable and easy to use, and the content provided useful strategies to manage fatigue. The final draft intervention includes four key topics: (1) about fatigue which discusses the common characteristics of fatigue after critical illness; (2) managing your energy with the 5 Ps (priorities, pacing, planning, permission, position); (3) strategies for everyday life (covering physical activity; home life; leisure and relationships; work, study, and finances; thoughts and feelings; sleep and eating); and (4) goal setting and making plans. All material is presented as written text, videos, and supplementary infographics. FACT includes calls with a facilitator but can also be used independently. CONCLUSIONS: FACT is a theory driven intervention co-produced by patient, carer and clinical stakeholders and is based on contemporary available evidence. Its development illustrates the benefits of stakeholder involvement to ensure interventions are informed by user needs. Further testing is needed to establish the feasibility and acceptability of FACT. IMPLICATIONS FOR CLINICAL PRACTICE: The FACT intervention shows promise as a self-management tool for people with fatigue after critical illness. It has the potential to provide education and strategies to patients at the point of discharge and follow-up.

A Three-Dimensional Primary Cortical Culture System Compatible with Transgenic Disease Models, Virally Mediated Fluorescence, and Live Microscopy.

In vitro cell culture models can offer high-resolution and high-throughput experimentation of cellular behaviors. However, in vitro culture approaches often fail to fully recapitulate complex cell processes involving synergistic interactions between heterogeneous neural cell populations and the surrounding neural microenvironment. Here, we describe the formation of a three-dimensional primary cortical cell culture system compatible with live confocal microscopy.

Allocation of authorship and patient enrollment among global clinical trials in oncology.

BACKGROUND: Oncology randomized controlled trials (RCTs) are increasingly global in scope. Whether authorship is equitably shared between investigators from high-income countries (HIC) and low-middle/upper-middle incomes countries (LMIC/UMIC) is not well described. The authors conducted this study to understand the allocation of authorship and patient enrollment across all oncology RCTs conducted globally. METHODS: A cross-sectional retrospective cohort study of phase 3 RCTs (published 2014-2017) that were led by investigators in HIC and recruited patients in LMIC/UMIC. FINDINGS: During 2014-2017, 694 oncology RCTs were published; 636 (92%) were led by investigators from HIC. Among these HIC-led trials, 186 (29%) enrolled patients in LMIC/UMIC. One-third (33%, 62 of 186) of RCTs had no authors from LMIC/UMIC. Forty percent (74 of 186) of RCTs reported patient enrollment by country; in 50% (37 of 74) of these trials, LMIC/UMIC contributed <15% of patients. The relationship between enrollment and authorship proportion is very strong and is comparable between LMIC/UMIC and HIC (Spearman's ρ LMIC/UMIC 0.824, p < .001; HIC 0.823, p < .001). Among the 74 trials that report country enrollment, 34% (25 of 74) have no authors from LMIC/UMIC. CONCLUSIONS: Among trials that enroll patients in HIC and LMIC/UMIC, authorship appears to be proportional to patient enrollment. This finding is limited by the fact that more than half of RCTs do not report enrollment by country. Moreover, there are important outliers as a significant proportion of RCTs had no authors from LMIC/UMIC despite enrolling patients in these countries. The findings in this study reflect a complex global RCT ecosystem that still underserves cancer control outside high-income settings.

Non-pharmacological interventions for self-management of fatigue in adults: An umbrella review of potential interventions to support patients recovering from critical illness.

PURPOSE: Fatigue is a common symptom after critical illness. However, evidence-based interventions for fatigue after critical illness are lacking. We aimed to identify interventions to support self-management of fatigue caused by physical conditions and assess their effectiveness and suitability for adaptation for those with fatigue after critical illness. MATERIALS AND METHODS: We conducted an umbrella review of systematic reviews. Databases included CINAHL, PubMed, Medline, PsycINFO, British Nursing Index (BNI), Web of Science, Cochrane Database of Systematic Reviews (CDSR), JBI Evidence Synthesis Database, and PROSPERO register. Included reviews were appraised using the JBI Checklist for Systematic Reviews and Research Syntheses. Results were summarised narratively. RESULTS: Of the 672 abstracts identified, 10 met the inclusion criteria. Reviews focused on cancer (n = 8), post-viral fatigue (n = 1), and Systemic Lupus Erythematosus (SLE) (n = 1). Primary studies often did not address core elements of self-management. Positive outcomes were reported across all reviews, and interventions involving facilitator support appeared to be most effective. CONCLUSIONS: Self-management can be effective at reducing fatigue symptoms and improving quality of life for physical conditions and has clear potential for supporting people with fatigue after critical illness, but more conclusive data on effectiveness and clearer definitions of self-management are required.

Access G-AP: development of an accessible goal setting and action planning resource for stroke survivors with aphasia.

PURPOSE: Goal setting is key to stroke rehabilitation, but access for people with aphasia is challenging. Based on the Goal setting and Action Planning (G-AP) framework, we developed an accessible goal setting resource (Access G-AP). METHODS: Access G-AP was designed using a three-phase, user-centred design process. Phase 1: Access G-AP Draft A was designed using evidence-based recommendations. Phase 2: Draft A was reviewed by stroke survivors with aphasia (focus groups 1&2) and rehabilitation staff (questionnaire). Phase 3: Suggested recommendations informed Access G-AP Draft B, which was further reviewed by stroke survivors with aphasia (focus group 3). The final version of Access G-AP was approved by stroke survivors with aphasia at a debrief meeting. Data were analysed using content analysis. RESULTS: Recommended design improvements included reducing text, adding bullet points, and diversifying images. Both participant groups highlighted that Access G-AP should be used collaboratively to support stroke survivor involvement. Staff recommended Access G-AP training and additional resources to support stroke survivors with severe aphasia. CONCLUSIONS: Access G-AP was co-developed to support people with aphasia to access and engage in stroke rehabilitation goal setting. Further research is required to establish the feasibility of Access G-AP in clinical practice.IMPLICATIONS FOR REHABILITATIONEvidence-based accessible formatting strategies and an iterative design process can inform the design of accessible goal setting resources.Accessible goal setting materials should be relevant to stroke survivors with aphasia and responsive to their needs.Rehabilitation staff require training and support to use accessible goal setting resources (like Access G-AP) with stroke survivors with aphasia, especially those with severe aphasia.Evaluation of the feasibility of Access G-AP in clinical practice is now required.

Early childhood caries sequelae and relapse rates in an Australian public dental hospital.

BACKGROUND: Early childhood caries (ECC) remains one of the most prevalent childhood diseases in Australia, disproportionately affecting disadvantaged populations. AIM: To investigate the ECC experience including risk factors, incidence of caries, pain and infection as well as relapse rates of caries and secondary dental general anaesthesia (GA). DESIGN: A retrospective cohort study included dental records of children with ECC, aged <72 months at an Australian public dental hospital paediatric dentistry department from 2013 to 2015 (n = 102). Dental caries, pain, infection, referral patterns, demographic and caries risk factor data were recorded for 24 months. Descriptive statistics were used for patient characteristics and clinical data, and Kaplan-Meier curves and parametric exponential survival models for time-to-event series. RESULTS: The study population demonstrated higher-than-national average dmft and disease progression at baseline. Major risk factors for the development of caries, pain and infection were daily consumption of sweetened beverages, poor oral hygiene, residing in lower socio-economic areas, older age and being male. Rates of caries relapse and new referral for secondary treatment under general anaesthesia were relatively high. CONCLUSION: A high degree of ECC progression and recurrence in this population indicates a need for a more comprehensive approach to ECC addressing multilevel root causes and systemic risk factors.

Does behavioural parent training reduce internalising symptoms (or not) among children with externalising problems? Systematic review and meta-analysis.

Behaviour parent training (BPT) is known to effectively reduce child externalising problems. However, evidence for BPT to have secondary benefits for reducing internalising symptoms remains unclear. To address this, electronic databases (PsycINFO, MEDLINE, EMBASE, CINAHL, and SCOPUS) were systematically searched for studies examining internalising outcomes from BPT among children aged 2-12 years with clinically elevated externalizing problems. Outcomes for internalising problems following BPT were analysed by meta-analysis. Of 9105 studies identified, 24 studies met the eligibility criteria. Results from meta-analysis demonstrated a significant small treatment effect size (g = - 0.41) for reducing internalising symptoms immediately after treatment. Studies showed moderate heterogeneity (I2 = 44%). Moderation analyses indicated that the overall treatment effect was robust against variations in treatment and study design characteristics. However, a review of individual study methods indicate that these results are limited by significant heterogeneity and limitations in clinical assessment. Overall, the results suggest that BPT programmes for reducing externalising problems have the potential to improve internalising outcomes, but that there is limited information to determine the reliability of these effects, highlighting the need for further investigation.

Gender equality eliminates gender gaps in engagement with female-stereotypic domains.

Although prior work reveals that gender bias against women produces gender gaps favoring men in science, technology, engineering, and mathematics engagement, research has yet to explore whether gender bias against men produces gender gaps favoring women in health care, early education, and domestic (HEED) engagement. Supporting preregistered predictions, results from an online study with MTurkers (N = 296) and a laboratory study with college students (N = 275) revealed that men expressed less sense of belonging, positivity toward, and aspirations to participate in HEED (and anticipated more discrimination) than did women when exposed to the reality of antimale gender biases in these domains. However, when told that HEED displays gender equality, men's engagement matched women's. Moderated mediation analyses revealed the importance of sense of belonging (and to a lesser extent, anticipated discrimination) in explaining why gender bias leads men to express less HEED positivity and aspirations than women. The current research thus provided novel evidence suggesting that gender bias contributes to men's underrepresentation in HEED, with important implications for broader occupational gender segregation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A European giant: a large spinosaurid (Dinosauria: Theropoda) from the Vectis Formation (Wealden Group, Early Cretaceous), UK.

Postcranial elements (cervical, sacral and caudal vertebrae, as well as ilium, rib and limb bone fragments) belonging to a gigantic tetanuran theropod were recovered from the basal unit (the White Rock Sandstone equivalent) of the Vectis Formation near Compton Chine, on the southwest coast of the Isle of Wight. These remains appear to pertain to the same individual, with enormous dimensions similar to those of the Spinosaurus holotype and exceeding those of the largest European theropods previously reported. A combination of features-including the presence of spinodiapophyseal webbing on an anterior caudal vertebra-suggest that this is a member of Spinosauridae, though a lack of convincing autapomorphies precludes the identification of a new taxon. Phylogenetic analysis supports spinosaurid affinities but we were unable to determine a more precise position within the clade weak support for a position within Spinosaurinae or an early-diverging position within Spinosauridae were found in some data runs. Bioerosion in the form of curved tubes is evident on several pieces, potentially related to harvesting behaviour by coleopteran bioeroders. This is the first spinosaurid reported from the Vectis Formation and the youngest British material referred to the clade. This Vectis Formation spinosaurid is unusual in that the majority of dinosaurs from the Lower Cretaceous units of the Wealden Supergroup are from the fluviolacustrine deposits of the underlying Barremian Wessex Formation. In contrast, the lagoonal facies of the upper Barremian-lower Aptian Vectis Formation only rarely yield dinosaur material. Our conclusions are in keeping with previous studies that emphasise western Europe as a pivotal region within spinosaurid origination and diversification.

A 3Din vitromodel of the device-tissue interface: functional and structural symptoms of innate neuroinflammation are mitigated by antioxidant ceria nanoparticles.

Objective.The recording instability of neural implants due to neuroinflammation at the device-tissue interface is a primary roadblock to broad adoption of brain-machine interfaces. While a multiphasic immune response, marked by glial scaring, oxidative stress (OS), and neurodegeneration, is well-characterized, the independent contributions of systemic and local 'innate' immune responses are not well-understood. We aimed to understand and mitigate the isolated the innate neuroinflammatory response to devices.Approach.Three-dimensional primary neural cultures provide a unique environment for studying the drivers of neuroinflammation by decoupling the innate and systemic immune systems, while conserving an endogenous extracellular matrix and structural and functional network complexity. We created a three-dimensionalin vitromodel of the device-tissue interface by seeding primary cortical cells around microwires. Live imaging of both dye and Adeno-Associated Virus (AAV) - mediated functional, structural, and lipid peroxidation fluorescence was employed to characterize the neuroinflammatory response.Main results.Live imaging of microtissues over time revealed independent innate neuroinflammation, marked by increased OS, decreased neuronal density, and increased functional connectivity. We demonstrated the use of this model for therapeutic screening by directly applying drugs to neural tissue, bypassing low bioavailability through thein vivoblood brain barrier. As there is growing interest in long-acting antioxidant therapies, we tested efficacy of 'perpetual' antioxidant ceria nanoparticles, which reduced OS, increased neuronal density, and protected functional connectivity.Significance.Our three-dimensionalin vitromodel of the device-tissue interface exhibited symptoms of OS-mediated innate neuroinflammation, indicating a significant local immune response to devices. The dysregulation of functional connectivity of microcircuits surround implants suggests the presence of an observer effect, in which the process of recording neural activity may fundamentally change the neural signal. Finally, the demonstration of antioxidant ceria nanoparticle treatment exhibited substantial promise as a neuroprotective and anti-inflammatory treatment strategy.

Lipopolysaccharide-induced neuroinflammation disrupts functional connectivity and community structure in primary cortical microtissues.

Three-dimensional (3D) neural microtissues are a powerful in vitro paradigm for studying brain development and disease under controlled conditions, while maintaining many key attributes of the in vivo environment. Here, we used primary cortical microtissues to study the effects of neuroinflammation on neural microcircuits. We demonstrated the use of a genetically encoded calcium indicator combined with a novel live-imaging platform to record spontaneous calcium transients in microtissues from day 14-34 in vitro. We implemented graph theory analysis of calcium activity to characterize underlying functional connectivity and community structure of microcircuits, which are capable of capturing subtle changes in network dynamics during early disease states. We found that microtissues cultured for 34 days displayed functional remodeling of microcircuits and that community structure strengthened over time. Lipopolysaccharide, a neuroinflammatory agent, significantly increased functional connectivity and disrupted community structure 5-9 days after exposure. These microcircuit-level changes have broad implications for the role of neuroinflammation in functional dysregulation of neural networks.

Waiting list eradication in secondary care psychology: Addressing a National Health Service blind spot.

OBJECTIVES: Waiting times for secondary care psychological therapy remain a 'blind spot' in serious mental illness (SMI) provision, and their reduction is a priority within the National Health Service (NHS) Five Year Forward View. The paper describes the eradication of waiting times within a community-based NHS service and the effectiveness of strategies whilst examining help-seeking behaviour, compliance and therapeutic need. METHODS: Analyses are reported for treatment compliance and therapeutic outcomes for 208 waiting-list cohort individuals seen by the SMI psychology service over an 18-month period between October 2014 and March 2016. RESULTS: No significant clinical or demographic differentiation between individuals who successfully completed therapy compared to those who disengaged was observed. Despite an average 2.20-year waiting time, this alone did not significantly impact engagement with psychological treatment and all psychological therapies provided led to a significant clinical improvement and no individuals who completed therapy required re-referral at 12-month follow-up. CONCLUSIONS: If imposed appropriately over a suitable time frame evidence-based practice coupled with effective operationalization can result in efficient needs-led psychological provision within SMI and secondary care. Potentially debilitating waiting times for service users and other referring professionals can be avoided, whilst psychology provision retains a flexible, formulation-based and person-centred approach.

Equivocal, explicit and emergent actions of PKC isoforms in cancer.

The maturing mutational landscape of cancer genomes, the development and application of clinical interventions and evolving insights into tumour-associated functions reveal unexpected features of the protein kinase C (PKC) family of serine/threonine protein kinases. These advances include recent work showing gain or loss-of-function mutations relating to driver or bystander roles, how conformational constraints and plasticity impact this class of proteins and how emergent cancer-associated properties may offer opportunities for intervention. The profound impact of the tumour microenvironment, reflected in the efficacy of immune checkpoint interventions, further prompts to incorporate PKC family actions and interventions in this ecosystem, informed by insights into the control of stromal and immune cell functions. Drugging PKC isoforms has offered much promise, but when and how is not obvious.

Embedding an Evidence-Based Model for Suicide Prevention in the National Health Service: A Service Improvement Initiative.

Despite the improved understanding of the determinants of suicide over recent decades, the mean suicide rate within the United Kingdom (UK) has remained at 10 per 100,000 per annum, with about 28% accessing mental health services in the 12 months prior to death. In this paper, we outlined a novel systems-level approach to tackling this problem through objectively differentiating the level of severity for each suicide risk presentation and providing fast-track pathways to care for all, including life-threatening cases. An additional operational challenge addressed within the proposed model was the saturation of local crisis mental health services with approximately 150 suicidality referrals per month, including non-mental health cases. This paper discussed a service improvement initiative undertaken within a National Health Service (NHS) secondary care mental health provider's open-access 24/7 crisis and home treatment service. An organisation-wide bespoke "suicide risk triage" system utilising the Collaborative Assessment and Management of Suicidality (CAMS) was implemented across all services. The preliminary impacts on suicidality, suicide rates and service user outcomes were described.

Bidirectional neural interface: Closed-loop feedback control for hybrid neural systems.

Closed-loop neural prostheses enable bidirectional communication between the biological and artificial components of a hybrid system. However, a major challenge in this field is the limited understanding of how these components, the two separate neural networks, interact with each other. In this paper, we propose an in vitro model of a closed-loop system that allows for easy experimental testing and modification of both biological and artificial network parameters. The interface closes the system loop in real time by stimulating each network based on recorded activity of the other network, within preset parameters. As a proof of concept we demonstrate that the bidirectional interface is able to establish and control network properties, such as synchrony, in a hybrid system of two neural networks more significantly more effectively than the same system without the interface or with unidirectional alternatives. This success holds promise for the application of closed-loop systems in neural prostheses, brain-machine interfaces, and drug testing.

Dysphagia and swallowing-related quality of life in Friedreich ataxia.

Dysphagia in Friedreich ataxia (FRDA) and its impact on quality of life is not adequately understood. The objective of this study was to characterise dysphagia in FRDA and to determine the impact of swallowing dysfunction on activities, participation, and sense of well-being. Thirty-six individuals with a confirmed diagnosis of FRDA were assessed via a clinical bedside examination (CBE), the Royal Brisbane Hospital outcome measure for swallowing, an oral-motor examination and the Australian therapy outcome measures for speech and swallowing (AusTOMS). Data on swallowing function, diet modification and swallowing strategies were collated. Thirty-three (91.67 %) participants exhibited clinical signs of dysphagia according to the CBE, and all participants received ratings indicating swallowing difficulties on at least one other measure. Dysphagia in FRDA is characterised by oral and pharyngeal stage impairment relating to incoordination, weakness and spasticity. A significant positive correlation was found between the severity of impairment, activity, participation and distress/well-being on the AusTOMS, suggesting that swallowing function decreases with overall reductions in quality of life. A significant correlation was found between activity on the AusTOMS and disease duration (r = -0.283, p = 0.012). No significant correlations were found between dysphagia severity and GAA repeat length, age of onset or disease severity. Participants employing diet modification and swallowing strategies demonstrated higher dysphagia severity, activity limitations and participation restrictions. These data advocate a holistic approach to dysphagia management in FRDA. Early detection of swallowing impairment and consideration of the potential impact dysphagia has on quality of life should be key aspects in disease management.