Translating government policy into practice: How new UK medical schools enact widening participation.

INTRODUCTION: Increasing the diversity of medical students, or widening participation (WP), is critical for social justice and healthcare delivery, and many governments are setting policies to encourage WP. However, establishing policy is only the first step in an educational change process: we also need to know "how" policy is enacted or how medical schools interpret and put into practice WP policy. Addressing this gap, the aim of this study was to examine policy enactment in six new UK medical schools with an explicit WP mandate. METHODS: This qualitative study, underpinned by social constructivism, used semi-structured interviews to explore the experiences of key actors (6 Deans and 14 Admissions staff) of putting policy into practice when setting up a new medical school. Data coding and analysis were initially inductive, using thematic analysis. We then applied Ball's theory of policy enactment to organise the data into four contextual dimensions of 'situation', 'professional', 'material' and 'external'. RESULTS: On the surface, there were many similarities across the six schools in terms of the four dimensions. However, how these dimensions interacted illuminated tensions and differences. For example, some schools found themselves increasingly subjected to local and extra-local rule systems, including pressure to follow host university norms and hosts struggling to accept that medical schools are heavily regulated. There were also tensions between the new medical schools and the medical education "establishment", including lack of power and being judged by overly narrow outcomes. DISCUSSION: Different contexts seem to influence the enactment of WP to medicine in different places, even in the same country, even in medical schools established at the same time. That policy enactment is a complex, non-linear process of enactment is important to acknowledge: context is critical. Our findings will inform future policies and practices that aim to increase WP in medicine.

Biomarkers from subcutaneous engineered tissues predict acute rejection of organ allografts.

Invasive graft biopsies assess the efficacy of immunosuppression through lagging indicators of transplant rejection. We report on a microporous scaffold implant as a minimally invasive immunological niche to assay rejection before graft injury. Adoptive transfer of T cells into Rag2-/- mice with mismatched allografts induced acute cellular allograft rejection (ACAR), with subsequent validation in wild-type animals. Following murine heart or skin transplantation, scaffold implants accumulate predominantly innate immune cells. The scaffold enables frequent biopsy, and gene expression analyses identified biomarkers of ACAR before clinical signs of graft injury. This gene signature distinguishes ACAR and immunodeficient respiratory infection before injury onset, indicating the specificity of the biomarkers to differentiate ACAR from other inflammatory insult. Overall, this implantable scaffold enables remote evaluation of the early risk of rejection, which could potentially be used to reduce the frequency of routine graft biopsy, reduce toxicities by personalizing immunosuppression, and prolong transplant life.

Asynchronous microexon splicing of LSD1 and PHF21A during neurodevelopment.

LSD1 histone H3K4 demethylase and its binding partner PHF21A, a reader protein for unmethylated H3K4, both undergo neuron-specific microexon splicing. The LSD1 neuronal microexon weakens H3K4 demethylation activity and can alter the substrate specificity to H3K9 or H4K20. Meanwhile, the PHF21A neuronal microexon interferes with nucleosome binding. However, the temporal expression patterns of LSD1 and PHF21A splicing isoforms during brain development remain unknown. In this work, we report that neuronal PHF21A isoform expression precedes neuronal LSD1 isoform expression during human neuron differentiation and mouse brain development. The asynchronous splicing events resulted in stepwise deactivation of the LSD1-PHF21A complex in reversing H3K4 methylation. We further show that the enzymatically inactive LSD1-PHF21A complex interacts with neuron-specific binding partners, including MYT1-family transcription factors and post-transcriptional mRNA processing proteins such as VIRMA. The interaction with the neuron-specific components, however, did not require the PHF21A microexon, indicating that the neuronal proteomic milieu, rather than the microexon-encoded PHF21A segment, is responsible for neuron-specific complex formation. These results indicate that the PHF21A microexon is dispensable for neuron-specific protein-protein interactions, yet the enzymatically inactive LSD1-PHF21A complex might have unique gene-regulatory roles in neurons.

Opportunity for a Community Health Fair Model of Bleeding Control Training.

BACKGROUND: Traumatic hemorrhage is a prevalent cause of death nationally, with >50% of civilian deaths estimated to be preventable with more timely intervention. This study investigated the efficacy of training large and diverse audiences in bleeding control methods including tourniquets in community health fair settings. METHODS: A booth was utilized for bleeding control training at community health fairs via direct demonstrations of pressure, wound packing, and commercial and improvised tourniquet application followed by hands-on practice. Participants self-rated their perceived abilities while instructors rated the participant competency. RESULTS: 117 community members participated during two fairs, though not every person completed every portion of the training. Average age was 33 (range 6-82) and the majority were female (65.0%). There was no difference in self-perceived skill compared to trainer grading of participant's ability to identify life-threatening bleeding (112 (97.4%) vs 106 (97.2%); P = 1), apply pressure (113 (98.3%) vs 106 (97.2%); P = .68), and pack a wound (102 (88.7%) vs 92 (84.4%); P = .43). No difference in difficulty was noted in placing commercial vs improvised tourniquets (16 (43%) vs 14 (45%); P = .87). However, participants were overconfident in their ability to place tourniquets compared to trainer grading, respectively (112 (98.2%) vs 100 (91.7%; P = .03)). DISCUSSION: Community fair classes provide opportunities to train large and diverse audiences in bleeding control techniques. However, participants overestimated their ability to appropriately apply tourniquets. Further investigation is needed into best educational approaches to optimize the impact of bleeding control kits that have been distributed in multiple states.

The development of a novel sexual health promotion intervention for young people with mental ill-health: the PROSPEct project.

BACKGROUND: Young people with mental ill-health experience higher rates of high-risk sexual behaviour, have poorer sexual health outcomes, and lower satisfaction with their sexual wellbeing compared to their peers. Ensuring good sexual health in this cohort is a public health concern, but best practice intervention in the area remains under-researched. This study aimed to co-design a novel intervention to address the sexual health needs of young people with mental ill-health to test its effectiveness in a future trial undertaken in youth mental health services in Melbourne, Australia. METHODS: We followed the 2022 Medical Research Council (MRC) guidelines for developing and evaluating complex interventions. This involved synthesising evidence from the 'top down' (published evidence) and 'bottom up' (stakeholder views). We combined systematic review findings with data elicited from qualitative interviews and focus groups with young people, carers, and clinicians and identified critical cultural issues to inform the development of our intervention. RESULTS: Existing evidence in the field of sexual health in youth mental health was limited but suggested the need to address sexual wellbeing as a concept broader than an absence of negative health outcomes. The Information-Motivation-Belief (IMB) model was chosen as the theoretical Framework on which to base the intervention. Interviews/focus groups were conducted with 29 stakeholders (18 clinicians, three carers, and eight young people). Synthesis of the evidence gathered resulted in the co-design of a novel intervention consisting of an initial consultation and four 60-90-minute sessions delivered individually by a young 'sex-positive' clinician with additional training in sexual health. Barriers and supports to intervention success were also identified. CONCLUSIONS: Using the MRC Framework has guided the co-design of a potentially promising intervention that addresses the sexual health needs of young people with mental ill-health. The next step is to test the intervention in a one-arm feasibility trial.

Familial hypercholesterolaemia in UK primary care: a Clinical Practice Research Datalink study of an under-recognised condition.

BACKGROUND: Studies utilising genotyping methods report the prevalence of familial hypercholesterolaemia to be as high as one in 137 of the adult population. AIM: To estimate the prevalence of familial hypercholesterolaemia measured by clinically coded diagnosis, associated treatments, and lipid measurements observed in UK primary care. DESIGN AND SETTING: This was a retrospective analysis using the Clinical Practice Research Datalink (CPRD) GOLD database. METHOD: Patients aged ≥18 years and actively registered on the index date (30 June 2018) formed the study cohort. Point prevalence of familial hypercholesterolaemia for 2018 was estimated overall and for each nation of the UK. Patients with familial hypercholesterolaemia were stratified into primary and secondary prevention groups, defined as those with/without a prior diagnosis of atherosclerotic cardiovascular disease. Prevalence estimates and extrapolations were replicated for these subgroups. Baseline demographic, lipid, and clinical characteristics for the prevalent cohort were presented. RESULTS: In total, 4048 patients with familial hypercholesterolaemia formed the study cohort. The estimated familial hypercholesterolaemia prevalence for the UK was 16.4 per 10 000 (95% confidence interval [CI] = 16.0 to 16.9). Of these, 2646 (65.4%) patients with familial hypercholesterolaemia had a recent prescription for lipid-lowering therapy. Mean lipid levels were lower for those treated with lipid-lowering therapy compared with those untreated: 5.34 mmol/L (SD 1.50) versus 6.25 mmol/L (SD 1.55) for total cholesterol and 3.15 mmol/L (SD 1.34) versus 3.96 mmol/L (SD 1.36) for low-level density lipoprotein cholesterol. CONCLUSION: The estimated prevalence of familial hypercholesterolaemia was one in 608 of the population, less than expected from other studies, which may indicate that familial hypercholesterolaemia is under-recognised in UK primary care. Over one-third of diagnosed patients were undertreated and many did not achieve target goals, placing them at risk of cardiovascular events.

Mechanism of 2'-fucosyllactose degradation by human-associated Akkermansia.

Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2'-fucosyllactose (2'-FL), may specifically drive bacterial colonization of the intestine. Recently, differential growth has been observed across multiple species of Akkermansia on various HMOs including 2'-FL. In culture, we found growth of two species, A. muciniphila MucT and A. biwaensis CSUN-19,on HMOs corresponded to a decrease in the levels of 2'-FL and an increase in lactose, indicating that the first step in 2'-FL catabolism is the cleavage of fucose. Using phylogenetic analysis and transcriptional profiling, we found that the number and expression of fucosidase genes from two glycoside hydrolase (GH) families, GH29 and GH95, vary between these two species. During the mid-log phase of growth, the expression of several GH29 genes was increased by 2'-FL in both species, whereas the GH95 genes were induced only in A. muciniphila. We further show that one putative fucosidase and a ß-galactosidase from A. biwaensis are involved in the breakdown of 2'-FL. Our findings indicate that the plasticity of GHs of human-associated Akkermansia sp. enables access to additional growth substrates present in HMOs, including 2'-FL. Our work highlights the potential for Akkermansia to influence the development of the gut microbiota early in life and expands the known metabolic capabilities of this important human symbiont.IMPORTANCEAkkermansia are mucin-degrading specialists widely distributed in the human population. Akkermansia biwaensis has recently been observed to have enhanced growth relative to other human-associated Akkermansia on multiple human milk oligosaccharides (HMOs). However, the mechanisms for enhanced growth are not understood. Here, we characterized the phylogenetic diversity and function of select genes involved in the growth of A. biwaensis on 2'-fucosyllactose (2'-FL), a dominant HMO. Specifically, we demonstrate that two genes in a genomic locus, a putative ß-galactosidase and α-fucosidase, are likely responsible for the enhanced growth on 2'-FL. The functional characterization of A. biwaensis growth on 2'-FL delineates the significance of a single genomic locus that may facilitate enhanced colonization and functional activity of select Akkermansia early in life.

"What Works" to Support LGBTQ+ Young People's Mental Health: An Intersectional Youth Rights Approach.

Despite overwhelming international evidence of elevated rates of poor mental health in LGBTQ+ youth compared to their cis-heterosexual peers, we know relatively little about effective mental health services for this population group. This study aims to produce the first early intervention model of "what works" to support LGBTQ+ youth with emerging mental health problems. Utilizing a mixed method case study, we collected data across 12 UK mental health service case study sites that involved: (a) interviews with young people, parents, and mental health practitioners (n = 93); (b) documentary analysis; (c) nonparticipant observation. The data analysis strategy was theoretical using the "explanation-building" analytical technique. Our analysis suggests an intersectional youth rights approach with 13 principles that must be enacted to provide good mental health services as advocated by the United Nations Convention on the Rights of the Child and World Health Organization. This approach should address the multiple forms of marginalization and stigmatization that LGBTQ+ youth may experience, enable informed independent decision-making, and uphold the right to freedom of safe self-expression. A rights-based approach to mental health services for LGBTQ+ young people is not prominent. This needs to change if we are to tackle this mental health inequality and improve the mental well-being of LGBTQ+ youth worldwide.

There is nothing as inconsistent as the OSFED diagnostic criteria.

Atypical anorexia nervosa (AAN), purging disorder (PD), night eating syndrome (NES), and subthreshold bulimia nervosa and binge-eating disorder (Sub-BN/BED) are the five categories that comprise the 'Other Specified Feeding or Eating Disorder' (OSFED) category in the Diagnostic and Statistical Manual for Mental Disorders (DSM-5). In this review, we examine problems with the diagnostic criteria that are currently proposed for the five OSFED types. We conclude that the existing diagnostic criteria for OSFED are deficient and fall short of accurately describing the complexity and individuality of those with these eating disorders (EDs). Therefore, to enhance the quality of life of people with OSFED, diagnostic criteria for the condition should be applied uniformly in clinical and research settings.

A new network analysis model in anorexia nervosa patients based on self-reported eating disorder symptoms, psychological distress, and cognitive flexibility.

OBJECTIVES: Cognitive flexibility and psychological distress, such as depression and anxiety, have been implicated in the aetiology of Anorexia Nervosa (AN). Despite the known associations between eating disorder (ED) symptoms, depression, anxiety, and cognitive flexibility, the specific pathways that connect these constructs are unclear. We therefore used network analysis to examine the relationship between these symptoms in an AN sample. METHODS: One hundred and ninety-three treatment-seeking individuals diagnosed with AN (95.6% female, M = 26.89 [SD = 9.45] years old) completed self-report measures assessing depression, anxiety, cognitive flexibility, and ED symptoms. To determine each symptom's influence in the network, we calculated the expected influence. RESULTS: The two relationships with the greatest edges were those between (1) weight/shape concerns and eating/dietary restraint and (2) weight/shape concerns and psychological distress (a measure that combined depression and anxiety). Cognitive flexibility was not connected to weight/shape concerns but had negative partial associations with eating concerns/dietary restraint and psychological distress. There was also a slight, non-zero connection between eating concerns/dietary restraint and psychological distress. CONCLUSIONS: The findings underscore the importance of weight/shape, eating/dietary concerns, and psychological distress in the AN network and suggest that addressing cognitive flexibility may be a useful target for eating concerns/dietary restraint and psychological distress. Future studies assessing the longitudinal course of psychopathology within the AN network structure may help in identifying whether specific symptoms function as risk factors or maintaining factors for this co-occurrence.

A trade-off between proliferation and defense in the fungal pathogen Cryptococcus at alkaline pH is controlled by the transcription factor GAT201.

Cryptococcus is a fungal pathogen whose virulence relies on proliferation in and dissemination to host sites, and on synthesis of a defensive yet metabolically costly polysaccharide capsule. Regulatory pathways required for Cryptococcus virulence include a GATA-like transcription factor, Gat201, that regulates Cryptococcal virulence in both capsule-dependent and capsule-independent ways. Here we show that Gat201 is part of a negative regulatory pathway that limits fungal survival. RNA-seq analysis found strong induction of GAT201 expression within minutes of transfer to host-like media at alkaline pH. Microscopy, growth curves, and colony forming units to test viability show that in host-like media at alkaline pH wild-type Cryptococcus neoformans yeast cells produce capsule but do not bud or maintain viability, while gat201Δ cells make buds and maintain viability, yet fail to produce capsule. GAT201 is required for transcriptional upregulation of a specific set of genes in host-like media, the majority of which are direct Gat201 targets. Evolutionary analysis shows that Gat201 is conserved within pathogenic fungi but lost in model yeasts. This work identifies the Gat201 pathway as controlling a trade-off between proliferation, which we showed is repressed by GAT201, and production of defensive capsule. The assays established here will allow characterisation of the mechanisms of action of the Gat201 pathway. Together, our findings urge improved understanding of the regulation of proliferation as a driver of fungal pathogenesis.

Development of a C3 Humanized Rat as a New Model for Evaluating Novel C3 Inhibitors.

INTRODUCTION: C3 is central for all complement activation pathways, thus making it an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or nonhuman primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly. METHODS: We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology. We thoroughly characterized the resultant human C3 humanized rats and tested the treatment efficacy of an established primate-specific C3 inhibitor in a model of complement-mediated hemolysis in the C3 humanized rats. RESULTS: We found that supplementing human C3 protein into the C3-deficient rat blood restored its complement activity, which was inhibited by rat factor H or compstatin, suggesting that human C3 is compatible to the rat complement system. The newly developed C3 humanized rats appeared healthy and expressed human but not rat C3 without detectable spontaneous C3 activation. More importantly, complement-mediated hemolysis in the C3 humanized rats was also inhibited by compstatin both in vitro and in vivo. CONCLUSION: The successfully developed C3 humanized rats provided a much-desired rodent model to evaluate novel C3 inhibitors in vivo as potential drugs.

Validating and developing a shortened version of the detail and flexibility (DFlex) questionnaire for eating disorders, anxiety and depression.

OBJECTIVE: To validate the original and a shortened version of the Detail and Flexibility (DFlex) Questionnaire. METHOD: Confirmatory factor analyses, internal consistency, and discriminant validity estimates were conducted within individuals with a diagnosis of an eating disorder (ED) (n = 124), an anxiety disorder and/or depression (n = 219), and a community sample (n = 852) (Part 1). Convergent validity of the DFlex through comparisons with the Autism Spectrum Quotient, Wisconsin Card Sorting Task, and Group Embedded Figures Task was undertaken within a combined ED and community sample (N = 68). Test-retest reliability of the DFlex was also examined across 2 years in a community sample (N = 85) (Part 2). RESULTS: The original factor structure of the DFlex was not supported. Hence, a shortened version, the DFlex-Revised, was developed. Good discriminant validity was obtained for the DFlex and DFlex-Revised, however, support for convergent validity was mixed. Finally, the 2-year test-retest reliability for the two DFlex versions was found to be low, suggesting potential malleability in construct over this timeframe. CONCLUSIONS: Further research is needed to validate the DFlex in clinical and non-clinical populations using different neurocognitive tests. Test-retest, using varied time intervals, should also be assessed.

Byproducts of inflammatory radical metabolism provide transient nutrient niches for microbes in the inflamed gut.

Louis Pasteur's experiments on tartaric acid laid the foundation for our understanding of molecular chirality, but major questions remain. By comparing the optical activity of naturally-occurring tartaric acid with chemically-synthesized paratartaric acid, Pasteur realized that naturally-occurring tartaric acid contained only L-tartaric acid while paratartaric acid consisted of a racemic mixture of D- and L-tartaric acid. Curiously, D-tartaric acid has no known natural source, yet several gut bacteria specifically degrade D-tartaric acid. Here, we investigated the oxidation of monosaccharides by inflammatory reactive oxygen and nitrogen species. We found that this reaction yields an array of alpha hydroxy carboxylic acids, including tartaric acid isomers. Utilization of inflammation- derived D- and L-tartaric acid enhanced colonization by Salmonella Typhimurium and E. coli in murine models of gut inflammation. Our findings suggest that byproducts of inflammatory radical metabolism, such as tartrate and other alpha hydroxy carboxylic acids, create transient nutrient niches for enteric pathogens and other potentially harmful bacteria. Furthermore, this work illustrates that inflammatory radicals generate a zoo of molecules, some of which may erroneously presumed to be xenobiotics.

Risk of major adverse cardiovascular events associated with elevated low-density lipoprotein cholesterol in a population with atherosclerotic cardiovascular disease with and without type 2 diabetes: a UK database analysis using the Clinical Practice Research Datalink.

OBJECTIVES: To estimate the 12-month probabilities of major adverse cardiovascular events (MACE) and non-cardiovascular death in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated low-density lipoprotein cholesterol (LDL-C). DESIGN: A retrospective database analysis. SETTING: UK primary care. PARTICIPANTS: Patients were selected from the Clinical Practice Research Datalink (Aurum) linked to Hospital Episode Statistics inpatient and Office of National Statistics mortality datasets. Patients with an ASCVD diagnosis between 01 January 2010 and 31 May 2018 and LDL-C ≥2.6 mmol/L were selected. PRIMARY OUTCOMES: Primary outcomes were 12-month risk of (1) MACE (composite of revascularisation, unstable angina, non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and (2) non-cardiovascular mortality. Kaplan-Meier survival analysis estimated the probability of each outcome. A Cox proportional hazards model explored covariates associated with MACE. RESULTS: Of 102 245 study patients, 16 501 (16.1%) had a diagnosis of type 2 diabetes (T2DM). 65.5% of those with and 49.9% of those without T2DM had a lipid-lowering therapy (LLT) 6 months prior to index diagnosis. Twelve-month probability of MACE was 7.9% for non-T2DM and 11.8% for T2DM. LDL-C was significantly associated with risk of MACE (HR=1.19 (95% CI 1.16 to 1.22) per 1 mmol/L). History of acute coronary syndrome, other coronary heart disease, stroke and T2DM significantly increased the risk of MACE. Ezetimibe (0.88 (95% CI 0.79 to 0.99)) and low-intensity statins (0.88 (95% CI 0.79 to 0.97)) were associated with reduced 12-month MACE risk.and low-intensity statins 0.88 (95% CI 0.79 to 0.97) CONCLUSION: We confirmed the association between elevated LDL-C and MACE. Many patients with ASCVD and elevated LDL-C were untreated with LLT. With the increasing demands on general practitioners, initiatives aimed at improving identification and treatment of at-risk patients within primary care should be considered.

The effectiveness of sexual assault referral centres with regard to mental health and substance use: a national mixed-methods study - the MiMoS Study.

Background: Sexual assault referral centres have been established to provide an integrated service that includes forensic examination, health interventions and emotional support. However, it is unclear how the mental health and substance use needs are being addressed. Aim: To identify what works for whom under what circumstances for people with mental health or substance use issues who attend sexual assault referral centres. Setting and sample: Staff and adult survivors in English sexual assault referral centres and partner agency staff. Design: A mixed-method multistage study using realist methodology comprising five work packages. This consisted of a systematic review and realist synthesis (work package 1); a national audit of sexual assault referral centres (work package 2); a cross-sectional prevalence study of mental health and drug and alcohol needs (work package 3); case studies in six sexual assault referral centre settings (work package 4), partner agencies and survivors; and secondary data analysis of outcomes of therapy for sexual assault survivors (work package 5). Findings: There is a paucity of evidence identified in the review to support specific ways of addressing mental health and substance use. There is limited mental health expertise in sexual assault referral centres and limited use of screening tools based on the audit. In the prevalence study, participants (n = 78) reported high levels of psychological distress one to six weeks after sexual assault referral centre attendance (94% of people had symptoms of post-traumatic stress disorder). From work package 4 qualitative analysis, survivors identified how trauma-informed care potentially reduced risk of re-traumatisation. Sexual assault referral centre staff found having someone with mental health expertise in the team helpful not only in helping plan onward referrals but also in supporting staff. Both sexual assault referral centre staff and survivors highlighted challenges in onward referral, particularly to NHS mental health care, including gaps in provision and long waiting times. Work package 5 analysis demonstrated that people with recorded sexual assault had higher levels of baseline psychological distress and received more therapy but their average change scores at end point were similar to those without sexual trauma. Limitations: The study was adversely affected by the pandemic. The data were collected during successive lockdowns when services were not operating as usual, as well as the overlay of anxiety and isolation due to the pandemic. Conclusions: People who attend sexual assault centres have significant mental health and substance use needs. However, sexual assault referral centres vary in how they address these issues. Access to follow-up support from mental health services needs to be improved (especially for those deemed to have 'complex' needs) and there is some indication that co-located psychological therapies provision improves the survivor experience. Routine data analysis demonstrated that those with sexual assault can benefit from therapy but require more intensity than those without sexual assault. Future work: Further research is needed to evaluate the effectiveness and cost-effectiveness of providing co-located psychological therapy in the sexual assault referral centres, as well as evaluating the long-term needs and outcomes of people who attend these centres. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (16/117/03) and is published in full in Health and Social Care Delivery Research; Vol. 11, No. 21. Trial registration: This trial is registered as PROSPERO 2018 CRD42018119706 and ISRCTN 18208347.

We undertook several studies including: Searching and examining published research (review). A survey that asked sexual assault referral centres how mental health and substance use are addressed. Questionnaires: survivors who had recently attended a sexual assault referral centre completed questionnaires on mental health, alcohol and drugs, and quality of life. Interviews with staff at sexual assault referral centres and survivors of assualts. Routine data: we analysed anonymous data from mental health services to compare how those with sexual assault benefit from psychological therapy. We combined the findings from all the aspects of the study to conclude that most people who attend sexual assault referral centres have significant mental health needs; however, the response to these needs is variable within sexual assault referral centres. Survivors report that the sexual assault referral centres offer a caring and supportive service, but many also reported difficulties in accessing the right support afterwards. Where there was co-located psychological therapy, there were benefits for both survivors and the wider team. We also showed that, despite high needs, people surviving sexual assault can benefit from therapies but may need more therapy than those who have not experienced sexual assault.

Protecting patients and learners: educational leadership on the fringes.

The development of high-quality clinicians takes place through immersion in clinical practice facilitated by educational supervisors with appropriate capabilities and organisational support to undertake the role. Learners give feedback on the quality of their learning experience on placement, which provides insights about the quality of clinical care received by patients.In this article, we explore the role of educational leaders in engaging with learner feedback about patient care, the challenges and tensions this generates, and the path through resolution. We use a lived example to showcase the issues raised and offer reflections on the challenges faced.

Mechanism of 2'-Fucosyllactose degradation by Human-Associated Akkermansia.

Among the first microorganisms to colonize the human gut of breastfed infants are bacteria capable of fermenting human milk oligosaccharides (HMOs). One of the most abundant HMOs, 2'-fucosyllactose (2'-FL), may specifically drive bacterial colonization of the intestine. Recently, differential growth has been observed across multiple species of Akkermansia on various HMOs including 2'FL. In culture, we found growth of two species, A. muciniphila Muc T and A. biwaensis CSUN-19, in HMOS corresponded to a decrease in the levels of 2'-FL and an increase in lactose, indicating that the first step in 2'-FL catabolism is the cleavage of fucose. Using phylogenetic analysis and transcriptional profiling, we found that the number and expression of fucosidase genes from two glycoside hydrolase (GH) families, GH29 and GH95, varies between these two species. During mid-log phase growth, the expression of several GH29 genes was increased by 2'-FL in both species, whereas the GH95 genes were induced only in A. muciniphila . We further show that one putative fucosidase and a ß-galactosidase from A. biwaensis are involved in the breakdown of 2'-FL. Our findings indicate that that plasticity of GHs of human associated Akkermansia sp. enable access to additional growth substrates present in HMOs, including 2'-FL. Our work highlights the potential for Akkermansia to influence the development of the gut microbiota early in life and expands the known metabolic capabilities of this important human symbiont. IMPORTANCE: Akkermansia are mucin degrading specialists widely distributed in the human population. Akkermansia biwaensis has recently been observed to have enhanced growth relative to other human associated Akkermansia on multiple human milk oligosaccharides (HMOs). However, the mechanisms for enhanced growth are not understood. Here, we characterized the phylogenetic diversity and function of select genes involved in growth of A. biwaensis on 2'-fucosyllactose (2'-FL), a dominant HMO. Specifically, we demonstrate that two genes in a genomic locus, a putative ß-galactosidase and α-fucosidase, are likely responsible for the enhanced growth on 2'-FL. The functional characterization of A. biwaensis growth on 2'-FL delineates the significance of a single genomic locus that may facilitate enhanced colonization and functional activity of select Akkermansia early in life.

The Association between the Police, Ambulance, Clinician Early Response (PACER) Model and Involuntary Detentions of People Living with Mental Illness: A Protocol for a Retrospective Observational Study.

Emergency services are frequently called to attend mental health incidents and are looking for innovative ways to improve their responses and reduce the burden on services. Involuntary detention of people living with mental illness is considered more frequent than necessary, leading to increased pressure on emergency departments, and is often a traumatic experience for patients. The Police, Ambulance, Clinician Early Response (PACER) model was developed in 2019 in Canberra, Australia, and seeks to reduce involuntary detentions by embedding a mental health clinician into emergency services as a mobile mental health crisis response intervention. This protocol details a retrospective cohort study that will examine the association between PACER and involuntary detentions using medical and police records and compare the results to standard ambulance and police responses. We will use relative risk and odds ratio calculations to determine the probability of being involuntarily detained or diverted from hospital; and we will describe the patient characteristics and outcomes in the PACER cohort. Results will be reported using the STROBE checklist for reporting cohort studies. This study was not registered on a publicly accessible registry.