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Background: A significant proportion of inflammatory bowel disease (IBD) patients fail to respond to advanced therapies. Combining advanced therapies may improve treatment outcome. This study aimed to assess the effectiveness, adverse events, and costs associated with combining advanced therapies in IBD patients., Methods: Combination advanced therapy was defined as the concurrent use of two biological agents or one biological agent with a small molecule therapy. Clinical data, including disease characteristics, treatment regimens, and adverse events, were collected from electronic patient records. Clinical response rates, biochemical markers, and treatment costs were evaluated., Results: The study included 109 IBD patients receiving combination advanced therapies from 9 academic centers in Ireland. Corticosteroid-free clinical response rates at 12 weeks and 52 weeks were 39 % and 38 %, respectively. Adverse events occurred in 26 % of therapeutic trials, with disease-related events being the most common. Notably, there were 3 cases of non-melanomatous skin cancer and 10 infectious complications. The annual cost of maintenance therapy for combination advanced therapies ranged from €17,560 to €30,724 per patient., Conclusion: Combination advanced therapies demonstrated effectiveness and acceptable safety profiles in a cohort of treatment-refractory IBD patients. Further large, prospective trials are required to definitively evaluate the role of combination advanced therapies in IBD., Competing Interests: Conflicts of interest There are no conflicts of interest pertaining to this paper., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

In November 2023, the Department of Health and Social Care published guidance, entitled 'Baroness Hollins' Final Report: My Heart Breaks - Solitary Confinement in Hospital Has no Therapeutic Benefit for People with a Learning Disability and Autistic People'. The report's commendable analysis of the problems and identification of the areas where practice should be improved is unfortunately not matched by many of its recommendations, which appear to be contrary to evidence-based approaches. The concerns are wide-ranging, from the use of the term 'solitary confinement' for current long-term segregation (LTS) and seclusion, to presumption that all LTS and seclusion is bad, to holding clinicians (mainly psychiatrists) responsible for events beyond their locus of control. Importantly, there is a no guidance on how to practically deliver the recommendations in an evidence-based manner. This Feature critically appraises the report, to provide a comprehensive summary outlining potential positive impacts, identifying specific concerns and reflecting on best practice going forward.

Aim: To determine the barriers, facilitators and effectiveness of using an intergenerational café to enable intergenerational learning., Design: Implementation science using the 'Consolidated Framework for Implementation Research' framework., Methods: Ethical approval for this research was granted by the University of Limerick. Online intergenerational cafés were held with older people and student nurses. Original data were collected through surveys and facilitator reflections. Participants were invited post-café to participate in the study. Student nurses (n = 50) and older people (n = 49) participated in an anonymous online survey, and facilitators (n = 7) took part in a peer focus group on planning and co-ordinating the cafés. Post hoc 'CFIR' analysis comprised secondary data analysis through mapping descriptive statistics and thematically analysed data to codebooks derived from CFIR domains and constructs., Results: Barriers and facilitators to café implementation were identified. Organisational factors are important for effective implementation. More students felt that the purpose, topics and running of the café were clear and organised. In contrast, more older people wanted additional time in the discussion groups. Technical difficulties (e.g., computer, logging on) were identified by some as a barrier to participation. Overall, having a clear purpose and topics along with an online approach facilitated implementation. All participants supported the café innovation as a way of increasing intergenerational learning. Facilitators worked effectively as a team to ensure the smooth running of the cafés. The analysis helped determine the effectiveness of the intervention., Conclusion: These cafés facilitated mutual learning and understanding and were well received by participants., Implications for the Profession And/or Patient Care: Intergenerational cafés can support intergenerational learning., Impact: Intergenerational cafés facilitated intergenerational learning., Reporting Method: SRQR/EQUATOR., Patient or Public Contribution: There was no patient/public contribution., (© 2024 The Author(s). Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Background: Patients with inflammatory bowel disease (IBD) in clinical and endoscopic remission may still experience disease relapse. Therefore, there is a need to identify outcome predictors. Recently, the role of neutrophils in predicting outcomes in ulcerative colitis (UC) has been highlighted. Furthermore, the impairment of intestinal barrier plays a key role in forecasting disease outcomes in IBD., Objective: This observational study aimed to assess the predictive role of neutrophils according to tissue localization and intestinal barrier protein expression in IBD., Methods: IBD patients in clinical remission who underwent colonoscopy between January 2020 and June 2022 at two tertiary referral centres were enrolled. Patients with Mayo Endoscopic Score ≤1 (UC) and Simple Endoscopic Score ≤6 (Crohn's disease) were included. Histological activity was assessed using validated scores. Experienced pathologists evaluated neutrophil localization in the epithelium and lamina propria and immunohistochemical expression of Claudin-2 and junctional adhesion molecule A (JAM-A)., Results: Of 60 UC and 76 CD patients, 59.7% had histological activity. 25.8% of patients developed an adverse outcome within 12 months. Neutrophils in the epithelium predicted adverse outcomes for UC (hazard ratio [HR] 5.198, p = 0.01) and CD (HR 4.377, p = 0.03) patients in endoscopic remission. Claudin-2 expression correlated with endoscopic and histological activity and predicted outcomes in UC. Similar results were found for JAM-A in CD despite this protein showing less specificity as a barrier predictor of outcome., Conclusion: This study highlights the potential role of epithelial neutrophil localization and Claudin-2 'leaky gut' expression as tools for predicting IBD outcomes and guiding further patient-tailored therapy., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Specialist forensic community teams for people with intellectual disability and/or autism have been developed, but little is known about their extent and delivery., Aims: To describe specialist forensic community teams for people with intellectual disability and/or autism across the UK., Method: An online survey was sent to representatives of each UK Trust/Health Board providing adult mental health and/or intellectual disability services. Questions covered the availability, structure and activities of specialist community forensic services. Quantitative data were summarised and associations between access to specialist forensic teams and care were tested with Chi-squared tests. Thematic analysis of free-text survey responses was used to understand the challenges of providing community forensic mental health services for this group., Results: A total of 49 out of 78 (63%) eligible Trusts/Health Boards responded, of which 25 (51%) had access to a specialist forensic community team. Teams operated either as part of a single Trust/Board ( n = 13) or over a larger regional footprint ( n = 12). The availability of specialist forensic community teams was associated with better access to offence-related interventions (χ 2 = 15.1002, P < 0.005) and co-production of patient care plans (χ 2 = 7.8726, P = 0.005). Respondents reported a wide variation in availability, expertise and perceived quality of community services. The availability of secure and generic in-patient beds, commissioning and legal barriers were also significant challenges in providing appropriate care., Conclusions: Coverage of specialist community forensic teams is not universal. There are indications that such teams are associated with improved care processes, but further work is needed to establish longer-term outcomes and the optimal model of care.

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., (© 2024. The Author(s).)

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., (© 2023 The Authors. Criminal Behaviour and Mental Health published by John Wiley & Sons Ltd.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Note as a point of information: This integrative review paper was prepared as part of a larger research project funded by the University of Limerick, Health Research Institute/Health Implementation Science Technology, Limerick, Ireland., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

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.

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., Competing Interests: The authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright: © 2023 Onetto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (© 2023 Harborside™.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

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-β), 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-1β/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-β or IFN-γ in combination with TNFα increased expression of IFI16 , ZBP1 , CASP1 , cGAS , and STING induced cell death and IL-1β/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-β, 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.

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., (© 2022. The Author(s).)

Purpose: This paper aims to examine effective diagnostic and treatment pathways for attention deficit hyperactivity disorder (ADHD) in prison settings given the high prevalence of ADHD and comorbidities in the prison population., Design/methodology/approach: Two studies were carried out in two separate prisons in London. Firstly, data were collected to understand the prevalence of ADHD and the comorbidities. The second study used quality improvement (QI) methodology to assess the impact of a diagnostic and treatment pathway for prisoners with ADHD., Findings: Of the prisoners, 22.5% met the diagnostic criteria for ADHD. Nearly half of them were screened positive for autistic traits, with a higher prevalence of mental disorders among prisoners with ADHD compared to those without. The QI project led to a significant increase in the number of prisoners identified as requiring ADHD assessment but a modest increase in the number of prisoners diagnosed or treated for ADHD., Originality/value: Despite various challenges, an ADHD diagnostic and treatment pathway was set up in a prison using adapted QI methodology. Further research is needed to explore the feasibility of routine screening for ADHD in prison and examine at a national level the effectiveness of current ADHD prison pathways., (© Emerald Publishing Limited.)

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., (Copyright © 2021. Published by Elsevier Ltd.)

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 (χ 2 =7.7, p=0.0056), China (χ 2 =9.2, p=0.0025) and the Netherlands (χ 2 =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 (χ 2 =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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

To successfully complete malolactic fermentation (MLF), Oenococcus oeni must overcome wine stress conditions of low pH, high ethanol, and the presence of SO 2 . 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 SO 2 stress are less well defined. This study focused on characterizing the transcriptional response of O. oeni to SO 2 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 SO 2 stress from responses associated with growth stage and cultivation parameters. Differential gene expression analysis revealed major transcriptional changes following SO 2 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 SO 2 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 SO 2 , an antiseptic and antioxidant compound regularly used in winemaking. Understanding the physiological changes induced in O. oeni by SO 2 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 SO 2 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.

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., (© 2021. The Author(s).)

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., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite calls for cross-cultural research, Minority world perspectives still dominate death and bereavement studies, emphasizing individualized emotions and neglecting contextual diversities. In research concerned with contemporary African societies, on the other hand, death and loss are generally subsumed within concerns about AIDS or poverty, with little attention paid to the emotional and personal significance of a death. Here, we draw on interactionist sociology to present major themes from a qualitative study of family deaths in urban Senegal, theoretically framed through the duality of meanings-in-context. Such themes included family and community as support and motivation; religious beliefs and practices as frameworks for solace and (regulatory) meaning; and material circumstances as these are intrinsically bound up with emotions. Although we identify the experience of (embodied, emotional) pain as a common response across Minority and Majority worlds, we also explore significant divergencies, varying according to localized contexts and broader power dynamics.

Summary: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Proteins of the BCL-2 family are evolutionarily conserved modulators of apoptosis that function as sensors of cellular integrity. Over the past three decades multiple BCL-2 family members have been identified, many of which are now fully incorporated into regulatory networks governing the mitochondrial apoptotic pathway. For some, however, an exact role in cell death signalling remains unclear. One such 'orphan' BCL-2 family member is BCL-G (or BCL2L14). In this study we analysed gastrointestinal expression of human BCL-G in health and disease states, and investigated its contribution to inflammation-induced tissue damage by exposing intestinal epithelial cells (IEC) to IFN-γ and TNF-α, two pro-inflammatory mediators associated with gut immunopathology. We found that both BCL-G splice variants - BCL-G S (short) and BCL-G L (long) - were highly expressed in healthy gut tissue, and that their mRNA levels decreased in active inflammatory bowel diseases (for BCL-G S ) and colorectal cancer (for BCL-G S/L ). In vitro studies revealed that IFN-γ and TNF-α synergised to upregulate BCL-G S/L and to trigger apoptosis in colonic epithelial cell lines and primary human colonic organoids. Using RNAi, we showed that synergistic induction of IEC death was STAT1-dependent while optimal expression of BCL-G S/L required STAT1, NF-κB/p65 and SWI/SNF-associated chromatin remodellers BRM and BRG1. To test the direct contribution of BCL-G to the effects of IFN-γ and TNF-α on epithelial cells, we used RNAi- and CRISPR/Cas9-based perturbations in parallel with isoform-specific overexpression of BCL-G, and found that BCL-G was dispensable for Th1 cytokine-induced apoptosis of human IEC. Instead, we discovered that depletion of BCL-G differentially affected secretion of inflammatory chemokines CCL5 and CCL20, thus uncovering a non-apoptotic immunoregulatory function of this BCL-2 family member. Taken together, our data indicate that BCL-G may be involved in shaping immune responses in the human gut in health and disease states through regulation of chemokine secretion rather than intestinal apoptosis.

Background: Research into neurodevelopmental disorders in adult offenders has tended to be disorder specific, so hindering service planning for a group of offenders with similar vulnerabilities., Aim: To examine vulnerabilities for mental illness and self-harming behaviours among male prisoners screening positive for a range of neurodevelopmental difficulties-including but not confined to disorders of intellectual ability, attention deficit hyperactivity, and in the autistic spectrum., Method: In a cross-sectional study, prisoners who screened positive for neurodevelopmental difficulties were compared to prisoners who screened negative for the same on indicators of suicide-related and self-harm behaviours, mental illness, and substance misuse using the Mini International Neuropsychiatric Interview (MINI)., Results: Of 87 prisoners who screened positive for neurodevelopmental difficulties, 69 had full MINI mental health data. In comparison with 69 neurotypical men in the same prison, the neurodevelopmental difficulties group was significantly more likely to have thought about self-harm and suicide in the last month and to have significantly higher rates of concurrent mental disorders including psychosis, anxiety, depression, personality disorder, and substance dependency disorders., Conclusions: This is one of the first studies to examine the mental health of adults with neurodevelopmental difficulties in a prison setting. This group, unlike those who meet diagnostic threshold, is not routinely considered by mental health or correctional services. The study found prisoners with neurodevelopmental difficulties showed greater vulnerability to mental disorder and thoughts of suicide and suicide-related behaviours than other prisoners. Accordingly, we recommend routine early screening across the criminal justice system for any neurodevelopmental difficulties to inform decision-making on the most appropriate disposal and support., (© 2020 John Wiley & Sons, Ltd.)

Aotearoa New Zealand is a country of just under 5 million people with a diverse population, the main ethnic groups being of European descent and Maori. There are well-developed public and private healthcare systems. As in other countries, Aotearoa New Zealand has closed the large institutions and developed community-based services for people with intellectual disability. Aotearoa New Zealand has specific legislation for people with intellectual disability presenting to the criminal justice system and has unusually and explicitly excluded people with intellectual disability from mental health legislation since 1992. Partly as a result, most health professional training schemes have little focus on issues for people with intellectual and developmental disabilities. Therefore, one of the main challenges over the coming decade will be to ensure there is a sufficient workforce of psychiatrists and other professionals who have the training and expertise to work with people with intellectual disability requiring mental health and forensic services.

Background: There is little evidence to guide pharmacological treatment in adults with Down syndrome and Alzheimer's disease. Aims To investigate the effect of cholinesterase inhibitors or memantine on survival and function in adults with Down syndrome and Alzheimer's disease., Method: This was a naturalistic longitudinal follow-up of a clinical cohort of 310 people with Down syndrome diagnosed with Alzheimer's disease collected from specialist community services in England., Results: Median survival time (5.59 years, 95% CI 4.67-6.67) for those on medication (n = 145, mainly cholinesterase inhibitors) was significantly greater than for those not prescribed medication (n = 165) (3.45 years, 95% CI 2.91-4.13, log-rank test P<0.001). Sequential assessments demonstrated an early effect in maintaining cognitive function., Conclusions: Cholinesterase inhibitors appear to offer benefit for people with Down syndrome and Alzheimer's disease that is comparable with sporadic Alzheimer's disease; a trial to test the effect of earlier treatment (prodromal Alzheimer's disease) in Down syndrome may be indicated. Declaration of interest A.S. has undertaken consulting for Ono Pharmaceuticals, outside the submitted work. Z.W. has received a consultancy fee and grant from GE Healthcare, outside the submitted work.

Introduction: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), often leading to an impaired quality of life in affected patients. Current treatment modalities include antitumour necrosis factor (anti-TNF) monoclonal antibodies (mABs) including infliximab, adalimumab and golimumab (GLM). Several recent retrospective and prospective studies have demonstrated that fixed dosing schedules of anti-TNF agents often fails to consistently achieve adequate circulating therapeutic drug levels (DL) with consequent risk of immunogenicity treatment failure and potential risk of hospitalisation and colectomy in patients with UC.The design of GLM dose Optimisation to Adequate Levels to Achieve Response in Colitis aims to address the impact of dose escalation of GLM immediately following induction and during the subsequent maintenance phase in response to suboptimal DL or persisting inflammatory burden as represented by raised faecal calprotectin (FCP)., Aim: The primary aim of the study is to ascertain if monitoring of FCP and DL of GLM to guide dose optimisation (during maintenance) improves rates of patient continuous clinical response and reduces disease activity in UC., Methods and Analysis: A randomised, multicentred two-arm trial studying the effect of dose optimisation of GLM based on FCP and DL versus treatment as per SMPC. Eligible patients will be randomised in a 1:1 ratio to 1 of 2 treatment groups and shall be treated over a period of 46 weeks., Ethics and Dissemination: The study protocol was approved by the Research Ethics committee of St. Vincent's University Hospital. The results will be published in a peer-reviewed journal and shared with the worldwide medical community., Trial Registration Numbers: EudraCT number: 2015-004724-62; Clinicaltrials.gov Identifier: NCT0268772; Pre-results., Competing Interests: Competing interests: None declared.

Background: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade., Objective: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these., Methods: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England. Survival times when considering different risk factors were calculated., Results: The mean age of diagnosis was 55.80 years, SD 6.29. Median survival time after diagnosis was 3.78 years, and median age at death was approximately 60 years. Survival time was associated with age of diagnosis, severity of intellectual disability, living status, anti-dementia medication status, and history of epilepsy. Age at diagnosis and treatment status remained predictive of survival time following adjustment., Conclusion: This study provides the best estimate of survival in dementia within the DS population to date, and is in keeping with previous estimates from smaller studies in the DS population. This study provides important estimates and insights into possible predictors of survival and age of diagnosis of AD in adults with DS, which will inform selection of participants for treatment trials in the future.

Autism spectrum disorder (ASD) frequently co-occurs with intellectual disability (ID) and often remains undiagnosed until adulthood. The Social Communication Questionnaire (SCQ) is a widely used measure to screen for ASD. To improve the utility of the SCQ for adults with ID, the aim of this study was to develop an ID-specific and adult appropriate algorithm for the SCQ using a core set of valid items. These items were identified in one sample (N = 226) and further cross-validated in a second, independent sample (N = 225) from Germany, England and the U.S. The newly developed algorithm has 24 items compared with the 40 items in the original instrument. The reduced item core set yielded similar diagnostic validity as the original algorithm with good sensitivity values (0.81-0.89) and low specificity values (0.62-0.72). Overall, these results suggest that the removed items may not carry diagnostically relevant information in adults with ID; thus, excluding these items may result in a more efficient and age-appropriate screening measure for this population. However, due to the low specificity values, a comprehensive assessment is essential for a final diagnostic assignment. Autism Res 2017, 10: 1481-1490. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., (© 2017 International Society for Autism Research, Wiley Periodicals, Inc.)

Background: There is limited empirical information on service-level outcome domains and indicators for the large number of people with intellectual disabilities being treated in forensic psychiatric hospitals., Aims: This study identified and developed the domains that should be used to measure treatment outcomes for this population., Method: A systematic review of the literature highlighted 60 studies which met eligibility criteria; they were synthesised using content analysis. The findings were refined within a consultation and consensus exercises with carers, patients and experts., Results: The final framework encompassed three a priori superordinate domains: (a) effectiveness, (b) patient safety and (c) patient and carer experience. Within each of these, further sub-domains emerged from our systematic review and consultation exercises. These included severity of clinical symptoms, offending behaviours, reactive and restrictive interventions, quality of life and patient satisfaction., Conclusions: To index recovery, services need to measure treatment outcomes using this framework., Declaration of Interest: None., Copyright and Usage: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY) licence.

Diagnosing Autism Spectrum Disorders (ASD) is important throughout the lifespan. The objective was to investigate the transcultural diagnostic validity of the Social Communication Questionnaire (SCQ) in a clinical sample of 451 adults with Intellectual Developmental Disorder (IDD) with and without ASD in Germany, the U.S.A. and Great Britain. Variables associated with higher SCQ sum-scores were higher levels of IDD, male gender, a diagnosis of ASD and the study site (Germany > U.S.A > G.B.). An ROC analysis revealed a cut-score of 13, which resulted in a sensitivity of 0.87 and a specificity of 0.58. It is recommended to adjust the cut-score according to level of IDD and gender. Further research is needed to align diagnostic assignment of ASD across different sites and countries.

The aim of this consensus statement was to discuss transition of patients with ADHD from child to adult healthcare services, and formulate recommendations to facilitate successful transition. An expert workshop was convened in June 2012 by the UK Adult ADHD Network (UKAAN), attended by a multidisciplinary team of mental health professionals, allied professionals and patients. It was concluded that transitions must be planned through joint meetings involving referring/receiving services, patients and their families. Negotiation may be required to balance parental desire for continued involvement in their child's care, and the child's growing autonomy. Clear transition protocols can maintain standards of care, detailing relevant timeframes, responsibilities of agencies and preparing contingencies. Transition should be viewed as a process not an event, and should normally occur by the age of 18, however flexibility is required to accommodate individual needs. Transition is often poorly experienced, and adherence to clear recommendations is necessary to ensure effective transition and prevent drop-out from services.

Chylothorax is characterized by an accumulation of lymphatic fluid in the pleural cavity due to damage to the thoracic duct. The aetiology can be traumatic or non-traumatic. Goitre is a rare cause of chylothorax with only eight cases previously described in the literature including only one case causing a bilateral chylothorax. This report describes a patient with bilateral chylothorax secondary to substernal goitre, which was successfully treated, and discusses this very rare case in light of the available literature., Learning Points: Pleural ultrasound and aspiration is important in bilateral pleural effusions unresponsive to diuretic treatment, or of dubious origin.The aetiology, diagnosis and treatment of a chylothorax are described.Goitre can cause chylothorax by damaging the thoracic duct., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Chromosomal copy-number variations (CNVs) are a class of genetic variants highly implicated in the aetiology of neurodevelopmental disorders, including intellectual disabilities (ID), schizophrenia and autism spectrum disorders (ASD). Yet the majority of adults with idiopathic ID presenting to psychiatric services have not been tested for CNVs. We undertook genome-wide chromosomal microarray analysis (CMA) of 202 adults with idiopathic ID recruited from community and in-patient ID psychiatry services across England. CNV pathogenicity was assessed using standard clinical diagnostic methods and participants underwent comprehensive medical and psychiatric phenotyping. We found an 11% yield of likely pathogenic CNVs (22/202). CNVs at recurrent loci, including the 15q11-q13 and 16p11.2-p13.11 regions were most frequently observed. We observed an increased frequency of 16p11.2 duplications compared with those reported in single-disorder cohorts. CNVs were also identified in genes known to effect neurodevelopment, namely NRXN1 and GRIN2B. Furthermore deletions at 2q13, 12q21.2-21.31 and 19q13.32, and duplications at 4p16.3, 13q32.3-33.3 and Xq24-25 were observed. Routine CMA in ID psychiatry could uncover ~11% new genetic diagnoses with potential implications for patient management. We advocate greater consideration of CMA in the assessment of adults with idiopathic ID presenting to psychiatry services.

Objective: Dementia is a common clinical presentation among older adults with Down syndrome. The presentation of dementia in Down syndrome differs compared with typical Alzheimer's disease. The performance of manualised dementia criteria in the International Classification of Diseases (ICD)-10 and Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (DSM-IV-TR) is uncertain in this population.We aimed to determine the concurrent validity and reliability of clinicians' diagnoses of dementia against ICD-10 and DSM-IV-TR diagnoses. Validity of clinical diagnoses were also explored by establishing the stability of diagnoses over time., Methods: We used clinical data from memory assessments of 85 people with Down syndrome, of whom 64 (75.3%) had a diagnosis of dementia. The cases of dementia were presented to expert raters who rated the case as dementia or no dementia using ICD-10 and DSM-IV-TR criteria and their own clinical judgement., Results: We found that clinician's judgement corresponded best with clinically diagnosed cases of dementia, identifying 84.4% cases of clinically diagnosed dementia at the time of diagnosis. ICD-10 criteria identified 70.3% cases, and DSM-IV-TR criteria identified 56.3% cases at the time of clinically diagnosed dementia. Over time, the proportion of cases meeting ICD-10 or DSM-IV-TR diagnoses increased, suggesting that experienced clinicians used their clinical knowledge of dementia presentation in Down syndrome to diagnose the disorder at an earlier stage than would have been possible had they relied on the classic description contained in the diagnostic systems., Conclusions: Clinical diagnosis of dementia in Down syndrome is valid and reliable and can be used as the standard against which new criteria such as the DSM-5 are measured., (Copyright © 2014 John Wiley & Sons, Ltd.)

Although epidemiological findings support a role for vitamin K status in the improvement of bone indices in adult patients with Crohn's disease (CD), this needs to be confirmed in double-blind, randomised controlled trials (RCT) with phylloquinone (vitamin K1). By conducting two RCT, the present study aimed to first establish whether supplementation with 1000 μg of phylloquinone daily near-maximally suppresses the percentage of undercarboxylated osteocalcin in serum (%ucOC; marker of vitamin K status) in adult patients with CD currently in remission as it does in healthy adults and second determine the effect of supplementation with phylloquinone at this dose for 12 months on the indices of bone turnover and bone mass. The initial dose-ranging RCT was conducted in adult patients with CD (n 10 per group) using 0 (placebo), 1000 or 2000 μg of phylloquinone daily for 2 weeks. In the main RCT, the effect of placebo v. 1000 μg vitamin K/d (both co-administered with Ca (500 mg/d) and vitamin D3 (10 μg/d)) for 12 months (n 43 per group) on the biochemical indices of bone turnover (determined by enzyme immunoassay) and bone mass (determined by dual-energy X-ray absorptiometry) were investigated. At baseline, the mean %ucOC was 47 %, and this was suppressed upon supplementation with 1000 μg of phylloquinone daily ( - 81 %; P< 0·01) and not suppressed further by 2000 μg of phylloquinone daily. Compared with the placebo, supplementation with 1000 μg of phylloquinone daily for 12 months had no significant effect (P>0·1) on bone turnover markers or on the bone mass of the lumbar spine or femur, but modestly increased (P< 0·05) the bone mass of the total radius. Despite near maximal suppression of serum %ucOC, supplementation with 1000 μg of phylloquinone daily (with Ca and vitamin D3) had no effect on the indices of bone health in adult CD patients with likely vitamin K insufficiency.

Wine styles are defined by complex and highly diverse chemical compositions. Evidence suggests that some of this complexity is determined by the choice of yeast strain used in fermentation. There are hundreds of different commercially available wine yeast strains that, potentially, provide a means by which winemakers can tailor their wines for different consumer market segments. In this study we evaluated the impacts of fermenting Shiraz must with different yeast strains, with a focus on chemical composition and tannin content of the finished wines. Principal Component Analysis (PCA) of the wines indicated that choice of yeast strain had a strong influence on a number of wine compositional parameters, including tannin. In three fermentation experiments, across two vintages and using different winemaking protocols, a compelling case for yeast strain 'signature' was evident. The results demonstrate that there is an opportunity to use commercial wine yeast diversity to modulate red wine composition and, by implication, the style of finished wines., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Ireland has become a multicultural society in just over a decade, with non-Irish nationals comprising 12% of the population. The challenge for nurses working in the Irish healthcare system is to provide culturally appropriate care to this diverse population. This paper reports on a qualitative descriptive study exploring nurses' experiences of communicating with people from diverse cultures, and focuses on language barriers and the use of interpreters. The findings indicate that communicating with people who do not share the same first language is challenging, in particular the participants (nurses) were concerned about their ability to make a comprehensive assessment that ultimately forms the basis for quality care provision. The use of interpreters can inform the assessment process, but there are challenges in accessing and utilising these services. Further continuing education is required to promote culturally appropriate care. There is a need for increased discussion between nurses and interpreters to maximise communication with patients.

The central concern of this paper is that there has been a move within British sociology to subsume (or sometimes, even replace) the concept of 'family' within ideas about personal life, intimacy and kinship. It calls attention to what will be lost sight of by this conceptual move: an understanding of the collective whole beyond the aggregation of individuals; the creation of lacunae that will be (partially) filled by other disciplines; and engagement with policy developments and professional practices that focus on 'family' as a core, institutionalized, idea. While repudiating the necessity (and indeed, pointing out the dangers) of providing any definitive answer to definitions of 'family', the paper calls for critical reflection on the implications of these conceptual moves., (© London School of Economics and Political Science 2012.)

Background: Oenococcus oeni, a member of the lactic acid bacteria, is one of a limited number of microorganisms that not only survive, but actively proliferate in wine. It is also unusual as, unlike the majority of bacteria present in wine, it is beneficial to wine quality rather than causing spoilage. These benefits are realised primarily through catalysing malolactic fermentation, but also through imparting other positive sensory properties. However, many of these industrially-important secondary attributes have been shown to be strain-dependent and their genetic basis it yet to be determined., Results: In order to investigate the scale and scope of genetic variation in O. oeni, we have performed whole-genome sequencing on eleven strains of this bacterium, bringing the total number of strains for which genome sequences are available to fourteen. While any single strain of O. oeni was shown to contain around 1800 protein-coding genes, in-depth comparative annotation based on genomic synteny and protein orthology identified over 2800 orthologous open reading frames that comprise the pan genome of this species, and less than 1200 genes that make up the conserved genomic core present in all of the strains. The expansion of the pan genome relative to the coding potential of individual strains was shown to be due to the varied presence and location of multiple distinct bacteriophage sequences and also in various metabolic functions with potential impacts on the industrial performance of this species, including cell wall exopolysaccharide biosynthesis, sugar transport and utilisation and amino acid biosynthesis., Conclusions: By providing a large cohort of sequenced strains, this study provides a broad insight into the genetic variation present within O. oeni. This data is vital to understanding and harnessing the phenotypic variation present in this economically-important species.

Oenococcus kitaharae is only the second member of the genus Oenococcus to be identified and is the closest relative of the industrially important wine bacterium Oenococcus oeni. To provide insight into this new species, the genome of the type strain of O. kitaharae, DSM 17330, was sequenced. Comparison of the sequenced genomes of both species show that the genome of O. kitaharae DSM 17330 contains many genes with predicted functions in cellular defence (bacteriocins, antimicrobials, restriction-modification systems and a CRISPR locus) which are lacking in O. oeni. The two genomes also appear to differentially encode several metabolic pathways associated with amino acid biosynthesis and carbohydrate utilization and which have direct phenotypic consequences. This would indicate that the two species have evolved different survival techniques to suit their particular environmental niches. O. oeni has adapted to survive in the harsh, but predictable, environment of wine that provides very few competitive species. However O. kitaharae appears to have adapted to a growth environment in which biological competition provides a significant selective pressure by accumulating biological defence molecules, such as bacteriocins and restriction-modification systems, throughout its genome.