Identification and support of autistic individuals within the UK Criminal Justice System: a practical approach based upon professional consensus with input from lived experience.

BACKGROUND: Autism spectrum disorder (hereafter referred to as autism) is characterised by difficulties with (i) social communication, social interaction, and (ii) restricted and repetitive interests and behaviours. Estimates of autism prevalence within the criminal justice system (CJS) vary considerably, but there is evidence to suggest that the condition can be missed or misidentified within this population. Autism has implications for an individual's journey through the CJS, from police questioning and engagement in court proceedings through to risk assessment, formulation, therapeutic approaches, engagement with support services, and long-term social and legal outcomes. METHODS: This consensus based on professional opinion with input from lived experience aims to provide general principles for consideration by United Kingdom (UK) CJS personnel when working with autistic individuals, focusing on autistic offenders and those suspected of offences. Principles may be transferable to countries beyond the UK. Multidisciplinary professionals and two service users were approached for their input to address the effective identification and support strategies for autistic individuals within the CJS. RESULTS: The authors provide a consensus statement including recommendations on the general principles of effective identification, and support strategies for autistic individuals across different levels of the CJS. CONCLUSION: Greater attention needs to be given to this population as they navigate the CJS.

Student nurses' views of participating in an intergenerational café with older people.

BACKGROUND: Within the context of global ageing, older people will require health care during times in their later lives. As most nurses will care for older people across a variety of care settings, it is crucial that older people and nurses can work together in partnership. In preparation for this, it is important to develop intergenerational learning innovations for student nurses and older people. An online intergenerational discussion café was developed to provide an opportunity for older people and student nurses to meet and get to know each other. OBJECTIVES: 1) Evaluate the effectiveness of an intergenerational discussion café as a way of facilitating intergenerational learning, 2) Elicit participants' views on whether intergenerational learning had occurred. DESIGN: Ethically approved survey research. SETTINGS: Tertiary education institution. PARTICIPANTS: Third year student nurses (n = 50) across three BSc Nursing pre-registration degree programmes enrolled on a shared community care module. METHODS: Post-café, student nurses were invited via email to voluntarily participate in the research and to complete an anonymous online survey. Questionnaire return implied consent. Fifty student nurses (n = 50) participated in the post café survey. Descriptive statistical analysis of Likert scale quantitative data and thematic analysis of open-ended questions was undertaken. RESULTS: Participants reported that the intergenerational cafés were well organised, worked well and strongly agreed that the cafés were helpful in facilitating student nurses and older people to connect socially and share views. Results also showed that participants felt they got to know a lot about older people and that they were in many ways quite similar to older people. CONCLUSIONS: This study provides valuable information on the use of intergenerational cafés as a means of facilitating intergenerational learning. Findings indicate that it was a positive learning experience for participants.

A realist evaluation of an enhanced court-based liaison and diversion service for defendants with neurodevelopmental disorders.

BACKGROUND: In England, court-based mental health liaison and diversion (L&D) services work across courts and police stations to support those with severe mental illness and other vulnerabilities. However, the evidence around how such services support those with neurodevelopmental disorders (NDs) is limited. AIMS: This study aimed to evaluate, through the lens of court and clinical staff, the introduction of a L&D service for defendants with NDs, designed to complement the existing L&D service. METHODS: A realist evaluation was undertaken involving multiple agencies based within an inner-city Magistrates' Court in London, England. We developed a logic model based on the initial programme theory focusing on component parts of the new enhanced service, specifically training, screening, signposting and interventions. We conducted semi-structured interviews with the court staff, judiciary and clinicians from the L&D service. RESULTS: The L&D service for defendants with NDs was successful in identifying and supporting the needs of those defendants. Benefits of this service included knowledge sharing, awareness raising and promoting good practice such as making reasonable adjustments. However, there were challenges for the court practitioners and clinicians in finding and accessing local specialist community services. CONCLUSION: A L&D service developed for defendants with NDs is feasible and beneficial to staff and clinicians who worked in the court setting leading to good practice being in place for the defendants. Going forward, a local care pathway would need to be agreed between commissioners and stakeholders including the judiciary to ensure timely and equitable access to local services by both defendants and practitioners working across diversion services for individuals with NDs.

Facilitating intergenerational learning between older people and student nurses: An integrative review.

AIM: To examine the literature on intergenerational learning between older people and student nurses. BACKGROUND: Intergenerational activities offer opportunities for intergenerational learning and help reduce ageism. There are several older person/school children intergenerational learning initiatives. However, there is less known about how intergenerational learning occurs in nurse education programmes outside of service provision. METHODS: Whittemore and Knafl's (2005) integrative review framework was used to guide the review process. Population, intervention, context and outcome (PICO) was used to develop the review question, search strategy and inclusion/exclusion criteria. Database (CINAHL, Cochrane library, Medline, PubMed, Scopus and PsychInfo) searches and hand searching occurred from 2012 to 2023. Screening, appraisal and data extraction was undertaken according to Prisma guidelines. RESULTS: Nine papers were included (North American (n = 5), Canadian (n = 1) Chinese (n = 2), Taiwanese (n = 1)). Mixed methods designs were included. Four themes were identified: 1) Seeing beyond first glance; 2) Connecting and getting to know each other; 3) Learning together; and 4) Challenges for intergenerational learning. CONCLUSION: This review demonstrates the relevance of intergenerational learning in nurse education and highlights the importance of embedding initiatives which will promote and support mutual learning. Innovative intergenerational initiatives enable students to explore their underlying attitudes and views in a way that they may not be able to in the more traditional service and care giving learning situations.

Perceived burden and need for support among caregivers of cancer patients.

BACKGROUND: The aims of this study were to examine (1) the perceived burden among caregivers and identify those in risk of high burden and (2) the need for support among caregivers and identify associated factors. MATERIALS AND METHODS: Cancer patients who participated in an educational program at the Montebello Center (MBC) in Norway between May 2021 and February 2022 were asked to invite a caregiver to answer a questionnaire. The caregiving burden was assessed with the Caregivers Reaction Assessment (CRA) that consists of 24 questions scored from 1 (strongly disagree) to 5 (strongly agree), covering five domains. A mean sum score was calculated for each domain. Higher subscale scores indicate higher levels of burden, except for caregiver esteem where a high score indicates a low burden. Need for support was assessed with 13 questions. RESULTS: Of 464 invitations, 185 caregivers responded (response 40%), median age was 58.0 years and 58% were male. Caregiver burden mean scores were: 2.6 (SD 1.03) for Impact on schedule, 2.1 (SD 0.79) for Lack of family support, 2.1 (SD 0.76) for Impact on health, 2.0 (SD 0.86) for Impact on finances, and 4.2 (SD 0.47) for Caregiver esteem. Female caregivers, younger, higher education, having comorbidities, caring for patients having recurrence of cancer, and shorter time since diagnosis were associated with higher burden measured on individual subscales of the CRA. Most reported needs were information about: cancer, late effects and rehabilitation services and support from peers and professionals to cope with the new situation. Younger, caregiver comorbidity and recurrence of cancer of the patient were associated with more needs. CONCLUSIONS: The results indicate that caregivers of cancer patients participating at the MBC report moderate caregiver burden, however, numerous caregivers reported need for support within several areas. Our findings need to be confirmed in a larger unselected group.

Physical Activity in Multiple Myeloma: A Review of the Current Literature.

One of the major issues patients with multiple myeloma (MM) suffer from is bone instability and the resulting difficulties that come along with it, such as pain and immobility. Few studies have been performed in this patient group to investigate the effects of physical exercise on outcomes such as muscle strength, quality of life, fatigue, and pain. A PubMed search was conducted by entering the search terms "multiple myeloma" and "exercise," and "multiple myeloma" and "physical activity" that yielded 178 and 218 manuscripts, respectively. Limiting the search results to clinical trials left 13 and 14 manuscripts, respectively, and 7 studies (1 retrospective chart review, 1 questionnaire study, and 5 prospective clinical trials). The majority of these studies (5) were published in the past decade. The outcomes of several studies of exercise in MM show that physical exercise is feasible for MM patients. Compared with the control groups, the most active participants show better outcomes, such as improvements in their blood counts and in quality-of-life parameters such as fatigue, pain, sleep, and mood. One trial found that MM patients were in much poorer condition than people in a normative standard group. Some of the reported outcomes of exercise in MM have been promising but need to be substantiated in a broader setting with more diverse participants, for a longer duration, and include more endpoints. Due to the disease-inherent risk of bone-related complications, an individualized, supervised training protocol could be a preferable tool.

SO2 and copper tolerance exhibit an evolutionary trade-off in Saccharomyces cerevisiae.

Copper tolerance and SO2 tolerance are two well-studied phenotypic traits of Saccharomyces cerevisiae. The genetic bases of these traits are the allelic expansion at the CUP1 locus and reciprocal translocation at the SSU1 locus, respectively. Previous work identified a negative association between SO2 and copper tolerance in S. cerevisiae wine yeasts. Here we probe the relationship between SO2 and copper tolerance and show that an increase in CUP1 copy number does not always impart copper tolerance in S. cerevisiae wine yeast. Bulk-segregant QTL analysis was used to identify variance at SSU1 as a causative factor in copper sensitivity, which was verified by reciprocal hemizygosity analysis in a strain carrying 20 copies of CUP1. Transcriptional and proteomic analysis demonstrated that SSU1 over-expression did not suppress CUP1 transcription or constrain protein production and provided evidence that SSU1 over-expression induced sulfur limitation during exposure to copper. Finally, an SSU1 over-expressing strain exhibited increased sensitivity to moderately elevated copper concentrations in sulfur-limited medium, demonstrating that SSU1 over-expression burdens the sulfate assimilation pathway. Over-expression of MET 3/14/16, genes upstream of H2S production in the sulfate assimilation pathway increased the production of SO2 and H2S but did not improve copper sensitivity in an SSU1 over-expressing background. We conclude that copper and SO2 tolerance are conditional traits in S. cerevisiae and provide evidence of the metabolic basis for their mutual exclusivity. These findings suggest an evolutionary driver for the extreme amplification of CUP1 observed in some yeasts.

The potential unintended consequences of Mental Health Act reforms in England and Wales on people with intellectual disability and/or autism.

The draft Mental Health Bill, which amends the Mental Health Act 1983 for England and Wales, proposes protections for people with intellectual disability and/or autism (ID/A) to prevent detention in hospital in the absence of mental illness. This editorial critically appraises the positive impact and unintended consequences of the proposed reforms for people with ID/A.

Mental health and well-being of unpaid caregivers: a cross-sectional survey protocol.

INTRODUCTION: Unpaid caregiving, care provided by family/friends, is a public health issue of increasing importance. COVID-19 worsened the mental health conditions of unpaid caregivers, increasing substance/drug use and early development of chronic disease. The impact of the intersections of race and ethnicity, sex, age and gender along with unpaid care work and caregivers' health and well-being is unknown. The aim of this study is to describe the inequities of caregiver well-being across the intersections of race and ethnicity, sex, age and gender using a cross-sectional survey design. METHODS AND ANALYSIS: We are collaborating with unpaid caregivers and community organisations to recruit a non-probability sample of unpaid caregivers over 18 years of age (n=525). Recruitment will focus on a target sample of 305 South Asian, Chinese and Black people living in Canada, who represent 60% of the Canadian racial and ethnic populations. The following surveys will be combined into one survey: Participant Demographic Form, Caregiver Well-Being Index, interRAI Self-report of Carer Needs and the GENESIS (GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond-Premature Acute Coronary Syndrome) PRAXY Questionnaire. Sample characteristics will be summarised using descriptive statistics. The scores from the Caregiver Well-Being Index will be dichotomised into fair/poor and good/excellent. A two-stage analytical strategy will be undertaken using logistic regression to model fair/poor well-being and good/excellent well-being according to the following axes of difference set a priori: sex, race and ethnicity, gender identity, age, gender relations, gender roles and institutionalised gender. The first stage of analysis will model the main effects of each factor and in the second stage of analysis, interaction terms will be added to each model. ETHICS AND DISSEMINATION: The University of Toronto's Health Sciences Research Ethics Board granted approval on 9 August 2022 (protocol number: 42609). Knowledge will be disseminated in pamphlets/infographics/email listservs/newsletters and journal articles, conference presentation and public forums, social media and through the study website. TRIAL REGISTRATION NUMBER: This is registered in the Open Sciences Framework with a Registration DOI as follows: https://doi.org/10.17605/OSF.IO/PB9TD.

Adults with Intellectual Disability and Autism Spectrum Disorder: What Is the Evidence around the Use of Polypharmacy.

A review on the mental health needs of adults with intellectual disability (ID) and autism spectrum disorder (ASD) published just over 10 years ago found a limited evidence base for pharmacological intervention in this group. The aim of this paper was therefore to review the evidence in the subsequent 10 years, with a focus on polypharmacy use in adults who have both ID and ASD. A critical literature review of key papers published from 2009 to 2021 was undertaken on adults with both ID and ASD and related to psychopharmacology, polypharmacy, antipsychotics, antidepressants, mood stabilisers and anxiolytics interventions in improving symptoms. After excluding articles for lack of relevance, a review with a focus on the use of polypharmacy was carried out on the retrieved results. Four papers were identified as relevant to adults with both ID and ASD. Three main themes were identified in the review, including the application of pharmacogenetics, the influence of national policy on prescribing practices and safety concerns in a population with multiple health comorbidities. The past decade has produced a small increase in the evidence base on psychopharmacology use in adults with ID and ASD. However, more evidence on the effectiveness and impact of long-term polypharmacy use is required.

DNA sensor-associated type I interferon signaling is increased in ulcerative colitis and induces JAK-dependent inflammatory cell death in colonic organoids.

DNA sensor pathways can initiate inflammasome, cell death, and type I interferon (IFN) signaling in immune-mediated inflammatory diseases (IMIDs), including type I interferonopathies. We investigated the involvement of these pathways in the pathogenesis of ulcerative colitis (UC) by analyzing the expression of DNA sensor, inflammasome, and type I IFN biomarker genes in colonic mucosal biopsy tissue from control (n = 31), inactive UC (n = 31), active UC (n = 33), and a UC single-cell RNA-Seq dataset. The effects of type I IFN (IFN-ß), IFN-γ, and TNF-α on gene expression, cytokine production, and cell death were investigated in human colonic organoids. In organoids treated with cytokines alone, or in combination with NLR family pyrin domain-containing 3 (NLRP3), caspase, or JAK inhibitors, cell death was measured, and supernatants were assayed for IL-1ß/IL-18/CXCL10. The expression of DNA sensor pathway genes-PYHIN family members [absent in melanoma 2 (AIM2), IFI16, myeloid cell nuclear differentiation antigen (MNDA), and pyrin and HIN domain family member 1 (PYHIN1)- as well as Z-DNA-binding protein 1 (ZBP1), cyclic GMP-AMP synthase (cGAS), and DDX41 was increased in active UC and expressed in a cell type-restricted pattern. Inflammasome genes (CASP1, IL1B, and IL18), type I IFN inducers [stimulator of interferon response cGAMP interactor 1 (STING), TBK1, and IRF3), IFNB1, and type I IFN biomarker genes (OAS2, IFIT2, and MX2) were also increased in active UC. Cotreatment of organoids with IFN-ß or IFN-γ in combination with TNFα increased expression of IFI16, ZBP1, CASP1, cGAS, and STING induced cell death and IL-1ß/IL-18 secretion. This inflammatory cell death was blocked by the JAK inhibitor tofacitinib but not by inflammasome or caspase inhibitors. Increased type I IFN activity may drive elevated expression of DNA sensor genes and JAK-dependent but inflammasome-independent inflammatory cell death of colonic epithelial cells in UC.NEW & NOTEWORTHY This study found that patients with active UC have significantly increased colonic gene expression of cytosolic DNA sensor, inflammasome, STING, and type I IFN signaling pathways. The type I IFN, IFN-ß, in combination with TNF-α induced JAK-dependent but NLRP3 and inflammasome-independent inflammatory cell death of colonic organoids. This novel inflammatory cell death phenotype is relevant to UC immunopathology and may partially explain the efficacy of the JAKinibs tofacitinib and upadacitinib in patients with UC.

Defendants with intellectual disability and autism spectrum conditions: the perspective of clinicians working across three jurisdictions.

The treatment of vulnerable defendants by criminal justice systems or correctional systems varies within and between countries. The purpose of this paper is to examine three legal jurisdictions - New South Wales in Australia; Norway; England and Wales - to understand the extent of variation in practice within the court systems for defendants with intellectual disabilities (ID) and/or autism spectrum conditions (ASC). Two of the jurisdictions had a process for screening in place, either in police custody or at court, but this was not universally implemented across each jurisdiction. All three jurisdictions had a process for supporting vulnerable defendants through the legal system. Across the three jurisdictions, there was variation in disposal options from a mandatory care setting to hospital treatment to a custodial sentence for serious offences. This variation requires further international exploration to ensure the rights of defendants with ID or ASC are understood and safeguarded.

Severe mental illness, common mental disorders, and neurodevelopmental conditions amongst 9088 lower court attendees in London, UK.

BACKGROUND: Court Mental Health Liaison and Diversion Services (CMHLDS) have developed in some countries as a response to the over-representation of mental illness and other vulnerabilities amongst defendants presenting to criminal justice (or correctional) systems. This study examined the characteristics and rates of mental disorder of 9088 defendants referred to CMHLDS. METHOD: The study analysed service level data, obtained from the National Health Service's mental health data set, to examine characteristics relating to gender, ethnicity and comorbidity of common mental and neurodevelopmental disorders at five CMHLDS across London between September 2015 and April 2017. RESULTS: The sample included 7186 males (79.1%) and 1719 females (18.9%), the gender of 183 (2%) were not recorded. Of those referred, 6616 (72.8%) presented with an identifiable mental disorder and 503 (5.5%) with a neurodevelopmental disorder (NDD). Significantly higher rates of schizophrenia were reported amongst Black defendants (n = 681; 37.2%) and Asian defendants (n = 315; 29%), while higher rates of depression were found amongst White defendants (n = 1007; 22.1%). Substance misuse was reported amongst 2813 defendants (31%), and alcohol misuse amongst 2111 (23.2%), with significantly high rates of substance and alcohol misuse amongst defendants presenting with schizophrenia or personality disorder. CONCLUSIONS: This is one of the largest studies to examine mental health needs and vulnerabilities amongst defendants presenting to CMHLDS. It will enable an improved understanding of the required service designs and resources required to manage the healthcare pathways for people attending CMHLDS.

Transatlantic Collaborations: Baccalaureate Nursing Students' Experiences of Participating in a Semester-Long Study Abroad Program.

AIM: The aim of this study was to describe students' experiences during a 15-week semester involving clinical placement in an Irish university. BACKGROUND: Internationalization is promoted and facilitated through study abroad initiatives within nurse education. Collaborations were developed between one university in the United States, an Irish university, and service partners. This study abroad initiative involved planning logistics, curriculum learning opportunities, and negotiating clinical placement in meeting state professional requirements. METHOD: A qualitative descriptive approach was used. Following ethical approval, 19 fourth-year students participated in focus group and individual semistructured interviews. Data analysis followed a thematic approach. RESULTS: Connecting our worlds details a process of acclimatizing, navigating learning, and using person-centered practices, illustrating meaningful learning in a journey of personal and professional development. CONCLUSION: Moving beyond the rhetoric of globalization is critical in future proofing initiatives in developing nursing practitioners while balancing potential safety risks in a post-COVID-19 era.

General hospital specialists' attitudes toward psychiatry: a cross-sectional survey in seven countries.

OBJECTIVE: Psychiatric comorbidities are common in physical illness and significantly affect health outcomes. Attitudes of general hospital doctors toward psychiatry are important as they influence referral patterns and quality of care. Little is known about these attitudes and their cultural correlates. The aim of this study was to identify attitudes toward psychiatry among general hospital specialists in relation to culture of the practice setting and other clinician factors (gender, age, seniority and specialty). METHODS: A cross-sectional, descriptive study was carried out in seven countries (New Zealand, China, Sri Lanka, Russia, Israel, Brazil, the Netherlands). Data were collected from senior medical staff of various disciplines using an updated version of Mayou and Smith's (1986) self-administered questionnaire. RESULTS: A total of 889 hospital doctors participated. While favourable attitudes toward both psychiatric consultation and management were endorsed by a majority, significant differences were also observed between countries. Subgroup differences were mostly confined to gender, acuity of practice setting and specialty. For example, female doctors in Russia (χ2=7.7, p=0.0056), China (χ2=9.2, p=0.0025) and the Netherlands (χ2=5.7, p=0.0174) endorsed more positive attitudes compared with their male counterparts, but this gender effect was not replicated in the total sample. Chronic care specialists were overall more inclined to manage patients' emotional problems compared with those working in acute care (χ2=70.8, p (adjusted)<0.0001), a significant finding seen also in individual countries (China, New Zealand, the Netherlands, Russia). Physicians were more favourably disposed toward psychiatry compared with other specialists, especially surgeons, in all countries except Israel. CONCLUSIONS: This study adds to evidence for the association of medical attitudes with individual clinician factors and demonstrates that the influence of these factors varies by country. Understanding these issues may help to overcome barriers and improve quality of care provided to general hospital patients.

Analysis of Transcriptomic Response to SO2 by Oenococcus oeni Growing in Continuous Culture.

To successfully complete malolactic fermentation (MLF), Oenococcus oeni must overcome wine stress conditions of low pH, high ethanol, and the presence of SO2. Failure to complete MLF may result in detrimental effects to the quality and stability of the resulting wines. Research efforts to date have focused on elucidating the mechanisms and genetic features that confer the ability to withstand low pH and high ethanol concentrations on O. oeni; however, the responses to SO2 stress are less well defined. This study focused on characterizing the transcriptional response of O. oeni to SO2 challenge during cultivation in a continuous system at wine-like pH (3.5). This experimental design allowed the precise discrimination of transcriptional changes linked to SO2 stress from responses associated with growth stage and cultivation parameters. Differential gene expression analysis revealed major transcriptional changes following SO2 exposure and suggested that this compound primarily interacts with intracellular proteins, DNA, and the cell envelope of O. oeni. The molecular chaperone hsp20, which has a demonstrated function in the heat, ethanol, and acid stress response, was highly upregulated, confirming its additional role in the response of this species to SO2 stress. This work also reports the first nanopore-based complete genome assemblies for O. oeni. IMPORTANCE Malolactic fermentation is an indispensable step in the elaboration of most wines and is generally performed by Oenococcus oeni, a Gram-positive heterofermentative lactic acid bacterium species. While O. oeni is tolerant to many of the wine stresses, including low pH and high ethanol concentrations, it has high sensitivity to SO2, an antiseptic and antioxidant compound regularly used in winemaking. Understanding the physiological changes induced in O. oeni by SO2 stress is essential for the development of more robust starter cultures and methods for their use. This study describes the main transcriptional changes induced by SO2 stress in the wine bacterium O. oeni and provides foundational understanding on how this compound interacts with the cellular components and the induced protective mechanisms of this species.

Evaluation of a liaison and diversion Court Mental Health Service for defendants with neurodevelopmental disorders.

AIM: Neurodevelopmental disorders (NDD) may present as neuropsychiatric problems as well as impairments of motor, cognitive, social and communication functioning. This study describes the introduction of a specialist service with expertise in NDD into an existing court mental health liaison and diversion service to determine if the service would impact on the health needs or disposal outcomes of defendants. METHODS: We examined referrals of defendants with NDD disorders over 30-months at a London Magistrates' Court. The pre-existing Court Mental Health (CMH) service was enhanced to provide additional expertise and hereafter referred to as the CMH + NDD Service. Baseline data including gender, ethnicity, remands and the rates of mental disorders was collected from the CMH Service using the existing minimum mental health service dataset. This was compared with data collected from the CMH + NDD Service. RESULTS: We found the following rates of NDD 9.5 % (n = 43) for the CMH service, and 9.5 % (n = 79) for the CMH + NDD service. Although overall the rates were the same the number of defendants with a single NDD diagnosis was increased in the CMH + NDD service with ADHD 10 %, ASD and ID 4% higher, the rates of comorbid NDD decreased in the CMH + NDD service compared to baseline. Specific disorders such as depression were recorded at higher rates for NDD defendants in both phases, however, this did not reach significance. In contrast, schizophrenia and delusional disorders, alcohol and substance use were observed at much higher in the non-NDD defendants during both phases of the study. The rates of diagnosis of schizophrenia and delusional disorders increased for the NDD group within the CMH + NDD service. Following the first court appearance, there was a 10 % reduction in custodial remands for defendants with NDD who were seen by the CMH + NDD service (34.2 %, n = 25 in the CMH + NDD service vs 43.8 %, n = 14 in the CMH service). CONCLUSION: The study found it is possible to successfully integrate practitioners with expertise of NDD into existing liaison and diversion services. This service enhancement demonstrated modest evidence of service effectiveness, including an increase in the detection of comorbid mental illness and a reduction in custodial remands for defendants with NDD. Further work needs to be completed to examine how this model can be rolled out across multiple courts and in particular, a cost-benefit analysis is required to understand whether an approach involving a cluster of Courts, as opposed to a single site is the most effective approach for this group of defendants.

TNF-α synergises with IFN-γ to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells.

Rewiring of host cytokine networks is a key feature of inflammatory bowel diseases (IBD) such as Crohn's disease (CD). Th1-type cytokines-IFN-γ and TNF-α-occupy critical nodes within these networks and both are associated with disruption of gut epithelial barrier function. This may be due to their ability to synergistically trigger the death of intestinal epithelial cells (IECs) via largely unknown mechanisms. In this study, through unbiased kinome RNAi and drug repurposing screens we identified JAK1/2 kinases as the principal and nonredundant drivers of the synergistic killing of human IECs by IFN-γ/TNF-α. Sensitivity to IFN-γ/TNF-α-mediated synergistic IEC death was retained in primary patient-derived intestinal organoids. Dependence on JAK1/2 was confirmed using genetic loss-of-function studies and JAK inhibitors (JAKinibs). Despite the presence of biochemical features consistent with canonical TNFR1-mediated apoptosis and necroptosis, IFN-γ/TNF-α-induced IEC death was independent of RIPK1/3, ZBP1, MLKL or caspase activity. Instead, it involved sustained activation of JAK1/2-STAT1 signalling, which required a nonenzymatic scaffold function of caspase-8 (CASP8). Further modelling in gut mucosal biopsies revealed an intercorrelated induction of the lethal CASP8-JAK1/2-STAT1 module during ex vivo stimulation of T cells. Functional studies in CD-derived organoids using inhibitors of apoptosis, necroptosis and JAKinibs confirmed the causative role of JAK1/2-STAT1 in cytokine-induced death of primary IECs. Collectively, we demonstrate that TNF-α synergises with IFN-γ to kill IECs via the CASP8-JAK1/2-STAT1 module independently of canonical TNFR1 and cell death signalling. This non-canonical cell death pathway may underpin immunopathology driven by IFN-γ/TNF-α in diverse autoinflammatory diseases such as IBD, and its inhibition may contribute to the therapeutic efficacy of anti-TNFs and JAKinibs.

Self-harm and Mental Health Characteristics of Prisoners with elevated rates of autistic traits.

BACKGROUND: Prevalence studies among prisoners have found rates of 1-4% for autism spectrum disorder (ASD) or autistic traits. However, little is known about those prisoners with high levels of autistic traits. AIM: This aim of this study was to compare the mental health characteristics of prisoners with autistic traits with neurotypical prisoners not screening positive for neurodevelopmental disorders. METHOD: The study recruited 240 male prisoners from a London prison and screened for autism spectrum disorder using the Autism Quotient (AQ) 20 and 10, and Autism Diagnostic Observation Schedule (ADOS). The Mini International Neuropsychiatric Interview was used to assess for depression, anxiety, self-harm behavior and suicide. RESULTS: Screening using the AQ identified 46 prisoners with significant autistic traits, with 12 meeting the diagnostic threshold for ASD using the ADOS. Those screening positive with autistic traits were significantly more likely to have thought about self-harm and suicide in the past month than neurotypical prisoners and have a comorbid mental disorder. They were also significantly more likely to report having attempted suicide during their lifetime compared to neurotypical peers at a rate of 64.9 % compared to 11.6 % for the neurotypical prisoners. CONCLUSION: Prisoners with elevated levels of autistic traits were more likely to report self-harm, suicidal thoughts and were more vulnerable to a range of mental disorders than neurotypical prisoners. There is a need for more evidence on the experience of autistic prisoners to inform how pathways should work to improve health outcomes through increased awareness and access to screening and subsequent diagnosis which currently prisons are currently not set up for.