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BACKGROUND: People with substance use disorders (SUDs) have increased risk of mortality but risk in sub-groups is poorly understood. METHODS: SUD cases, aged 15years or older, were identified in the South London and Maudsley Case Register which contains over 150,000 specialist mental healthcare and addictions service users linked to regular national mortality tracing. Standardized mortality ratios (SMRs) for the period 2007-2009 were calculated based on expected numbers of deaths for England and Wales in 2008 then stratified by gender, age, ethnicity, and type of substance use disorder. Life expectancies at birth were estimated. RESULTS: We detected 10,927 cases with a primary substance use disorder diagnosis prior to 2010, who were active to South London and Maudsley NHS Foundation Trust services between 2007 and 2009. Alcohol and opioid use disorders were the most common disorders (45.4% and 44.2% of the SUD cohort respectively) and were associated with increased mortality (SMRs 4.04 and 4.85 respectively). Subgroups at particularly high risk were women with opioid use disorder (SMR 7.32) and those under the age of 45years with alcohol use disorder (SMR 9.25). SMRs associated with alcohol and opioid use disorders diminished with age. Life expectancies of individuals with alcohol and opioid use disorders were reduced by 9-17years compared to national norms. CONCLUSIONS: Those under 45years with alcohol use disorder and women with opioid use disorder are at particularly high risk of mortality. More targeted health care is required to address the specific needs of these vulnerable subgroups. [ABSTRACT FROM AUTHOR]

Microplastics present myriad ecological and human health risks including serving as a vector for pathogens in human and animal food chains. However, the specific mechanisms by which pathogenic fungi colonize these microplastics have yet to be explored. In this work, we examine the opportunistic fungal pathogen, Aspergillus fumigatus , and other common soil and marine Aspergilli , which we found bind microplastics tightly. Up to 3.85+/-1.48 g microplastic plastic/g fungi were bound and flocculated for polypropylene (PP), polyethylene (PE), and polyethylene terephthalate (PET) powders and particles ranging in size from 0.05 - 5 mm. Gene knockouts revealed hydrophobins as a key biomolecule driving microplastic-fungi binding. Moreover, purified hydrophobins were still able to flocculate microplastics independent of the fungus. Our work elucidates a role for hydrophobins in fungal colonization of microplastics and highlights a potential target for mitigating the harm of microplastics through engineered fungal-microplastic interactions., Significance Statement: Microplastics pose serious ecological and human health effects by introducing pathogens and toxins into animal and human food chains. Many pathogenic microorganisms preferentially form biofilms on microplastic particles that are then ingested. Here, we demonstrate that hydrophobins, highly hydrophobic, cell surface proteins, enable microplastic binding and colonization by the opportunistic pathogen Aspergillus fumigatus and other fungi within the Aspergillus genus. Our work recognizes a novel role for hydrophobin proteins, identifying potential strategies for pathogen control and protein-based microplastics recovery.

Background: Severe mental illness (SMI), which includes schizophrenia, schizoaffective disorder and bipolar disorder, has profound health impacts, even in the elderly., Aims: To evaluate relative risk of hospital admission and length of hospital stay for physical illness in elders with SMI., Method: To construct a population-based retrospective cohort observed from April 2007 to March 2016, data from a case registry with full but de-identified electronic health records were retrieved for patients of the South London and Maudsley NHS Foundation Trust, the single secondary mental healthcare service provider in south-east London. We compared participants with SMI aged >60 years old with the general population of the same age and residing in the same areas through data linkage by age-, sex- and fiscal-year-standardised admission ratios (SARs) for primary diagnoses at hospital discharge. Furthermore, we compared the duration of hospital stay with an age-, sex- and cause-of-admission-matched random group by linear regression for major causes of admission., Results: In total, records for 4175 older people with SMI were obtained, relating to 10 342 admission episodes, showing an overall SAR for all physical illnesses of 5.15 (95% CI: 5.05, 5.25). Among the top causes of admission, SARs ranged from 3.87 for circulatory system disorders (ICD-10 codes: I00-I99) to 6.99 for genitourinary system or urinary conditions (N00-N39). Specifically, the diagnostic group of 'symptoms, signs and findings, not elsewhere classified' (R00-R99) had an elevated SAR of 6.56 (95% CI: 6.22, 6.90). Elders with SMI also had significantly longer hospital stays than their counterparts in the general population, especially for digestive system illnesses (K00-K93), after adjusting for confounding., Conclusions: Poorer overall physical health and specific patterns were identified in elders with SMI.

To assess the psychosocial functioning concerning obsessive-compulsive symptoms (OCS) and/or obsessive-compulsive disorder (OCD) comorbidity in people with schizophrenia, schizoaffective disorder, or bipolar disorder diagnosed in a large case register database in Southeast London. Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) register using Clinical Record Interactive Search (CRIS) system, a platform allowing research on full but de-identified electronic health records for secondary and tertiary mental healthcare services. Information of schizophrenia, schizoaffective disorder, bipolar disorder diagnosis and OCS/OCD status was ascertained from structural or free-text fields through natural language processing (NLP) algorithms based on artificial intelligence techniques during the observation window of January 2007 to December 2016. Associations between comorbid OCS/OCD and recorded Health of the Nation Outcome Scales (HoNOS) for problems with activities of daily living (ADLs), living conditions, occupational and recreational activities, and relationships were estimated by logistic regression with socio-demographic confounders controlled. Of 15,412 subjects diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder, 2,358 (15.3%) experienced OCS without OCD, and 2,586 (16.8%) had OCD recorded. The presence of OCS/OCD was associated with more problems with relationships (adj.OR = 1.34, 95% CI: 1.25-1.44), ADLs (adj.OR = 1.31, 95%CI: 1.22-1.41), and living conditions (adj.OR = 1.31, 95% CI: 1.22-1.41). Sensitivity analysis revealed similar outcomes. Comorbid OCS/OCD was associated with poorer psychosocial functioning in people with schizophrenia, schizoaffective disorder, or bipolar disorder. This finding highlights the importance of identification and treatment of comorbid OCS among this vulnerable patient group.

The North Temperate Lakes Long-Term Ecological Research (NTL-LTER) program has been extensively used to improve understanding of how aquatic ecosystems respond to environmental stressors, climate fluctuations, and human activities. Here, we report on the metagenomes of samples collected between 2000 and 2019 from Lake Mendota, a freshwater eutrophic lake within the NTL-LTER site. We utilized the distributed metagenome assembler MetaHipMer to coassemble over 10 terabases (Tbp) of data from 471 individual Illumina-sequenced metagenomes. A total of 95,523,664 contigs were assembled and binned to generate 1,894 non-redundant metagenome-assembled genomes (MAGs) with ≥50% completeness and ≤10% contamination. Phylogenomic analysis revealed that the MAGs were nearly exclusively bacterial, dominated by Pseudomonadota (Proteobacteria, N = 623) and Bacteroidota (N = 321). Nine eukaryotic MAGs were identified by eukCC with six assigned to the phylum Chlorophyta. Additionally, 6,350 high-quality viral sequences were identified by geNomad with the majority classified in the phylum Uroviricota. This expansive coassembled metagenomic dataset provides an unprecedented foundation to advance understanding of microbial communities in freshwater ecosystems and explore temporal ecosystem dynamics., (© 2024. The Author(s).)

Schizophyllum commune is a mushroom-forming fungus notable for its distinctive fruiting bodies with split gills. It is used as a model organism to study mushroom development, lignocellulose degradation and mating type loci. It is a hypervariable species with considerable genetic and phenotypic diversity between the strains. In this study, we systematically phenotyped 16 dikaryotic strains for aspects of mushroom development and 18 monokaryotic strains for lignocellulose degradation. There was considerable heterogeneity among the strains regarding these phenotypes. The majority of the strains developed mushrooms with varying morphologies, although some strains only grew vegetatively under the tested conditions. Growth on various carbon sources showed strain-specific profiles. The genomes of seven monokaryotic strains were sequenced and analyzed together with six previously published genome sequences. Moreover, the related species Schizophyllum fasciatum was sequenced. Although there was considerable genetic variation between the genome assemblies, the genes related to mushroom formation and lignocellulose degradation were well conserved. These sequenced genomes, in combination with the high phenotypic diversity, will provide a solid basis for functional genomics analyses of the strains of S. commune., 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., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Zygnematophyceae are the algal sisters of land plants. Here we sequenced four genomes of filamentous Zygnematophyceae, including chromosome-scale assemblies for three strains of Zygnema circumcarinatum. We inferred traits in the ancestor of Zygnematophyceae and land plants that might have ushered in the conquest of land by plants: expanded genes for signaling cascades, environmental response, and multicellular growth. Zygnematophyceae and land plants share all the major enzymes for cell wall synthesis and remodifications, and gene gains shaped this toolkit. Co-expression network analyses uncover gene cohorts that unite environmental signaling with multicellular developmental programs. Our data shed light on a molecular chassis that balances environmental response and growth modulation across more than 600 million years of streptophyte evolution., (© 2024. The Author(s).)

Purpose: The aim of this study was to assess objective and subjective breathing changes in adult patients who underwent maxillary skeletal expansion with the mini-implant-supported maxillary skeletal expander (MSE)., Methods: Twenty-nine patients (mean age 18.1 ± 4.3 years) who underwent expansion using the MSE were compared pre- and posttreatment and with a control group (mean age 19.9 ± 2.6 years) to assess objective and subjective functional breathing changes. Objective measurements of the airway including peak nasal inspiratory flow (PNIF) and peak oral inspiratory flow (POIF) were measured utilizing the In-Check medical device (Clement Clarke, Harlow, United Kingdom). Patients reported subjective breathing assessment utilizing the visual analog scale (VAS). Intragroup comparisons were performed with Wilcoxon tests and intergroup comparison with Mann-Whitney U tests. Spearman correlation coefficients were calculated among the studied variables (P < 0.05)., Results: Following MSE treatment, there were significantly higher values for PNIF total (P < 0.0001), PNIF right (P < 0.0001), PNIF left (P < 0.0001), and POIF (P < 0.01) compared to pretreatment and control group results. Also, patients reported a significant decrease in troubled breathing as measured by the VAS for breathing through the right nostril (P < 0.01), left nostril (P < 0.001), and both nostrils (P < 0.01). Comparing the objective and subjective variables for both the pre-MSE or post-MSE groups, the results indicated no significant correlation between total PNIF and total VAS. However, the values had significant correlations between PNIF and VAS on each side when the patients were asked to block one nostril., Conclusions: Objective functional breathing measurements were increased immediately after treatment with MSE. Subjective functional breathing measurements changes were significantly higher after MSE treatment and compared with the control group. MSE presents a nonsurgical alternative to achieving orthopedic expansion in adult patients which may provide a benefit for patients with nasal airway obstruction., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The association between sugar-sweetened beverages intake and colorectal cancer (CRC) remains controversial. A metaanalysis was performed to clarify the correlation between sugar-sweetened beverages and CRC risk/mortality. A systematic literature search was conducted in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Sinomed (CBM), Wanfang Data Knowledge Service Platform, and China Science and Technology Journal VIP database. Articles were restricted to be available in any language until March 31, 2022. The highest exposed categories were used to calculate the pooled relative risks (RR) values. Pooled relative risks (RR) and 95% confidence intervals (CI) were used to estimate the association of sugar-sweetened beverages with CRC risk and mortality. Heterogeneity was assessed with the Cochran Q statistic and quantified with the I2 statistic. A total of 17 studies (6 case-control and 11 cohort) involving 557,391 subjects were included in this meta-analysis. The pooled RRs for CRC incidence and mortality among people taking sugar-sweetened beverages were 1.17 (95% CI: 1.07-1.28) and 1.13 (95% CI: 0.99-1.29), respectively. In subgroup analysis, a correlation was found in the distal colon with a pooled RR of 1.41 (95% CI: 1.10-1.80). There was no correlation in the proximal colon with a pooled RR of 1.58 (95% CI: 0.79-3.17). We found statistically significant associations between CRC incidence and sugar-sweetened beverages intake in North America and Oceania, with pooled RRs of 1.16 (95% CI: 1.00-1.33) and 1.32 (95% CI: 1.13-1.55), respectively. In sensitivity analysis, after excluding each study and calculating heterogeneity and effect sizes, there was still a correlation between sugar-sweetened beverages intake and CRC risk. This meta-analysis suggests that sugar-sweetened beverages intake may increase CRC risk, independent of CRC mortality. Whether CRC risk increases with increased sugar-sweetened beverage intake needs further investigation in the future. This meta-analysis aimed to indicate the relationship between sugar-sweetened beverages intake and the risk and mortality of colorectal cancer. A total of 17 studies involving 557,391 subjects were included. The results showed that sugar-sweetened beverages may increase the risk of colorectal cancer but may not be associated with colorectal cancer mortality., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Severity of personality disorder is an important determinant of future health. However, this key prognostic variable is not captured in routine clinical practice. Using a large clinical data-set, we explored the predictive validity of items from the Health of Nation Outcome Scales (HoNOS) as potential indicators of personality disorder severity. For 6912 patients with a personality disorder diagnosis, we examined associations between HoNOS items relating to core personality disorder symptoms (self-harm, difficulty in interpersonal relationships, performance of occupational and social roles, and agitation and aggression) and future health service use. Compared with those with no self-harm problem, the total healthcare cost was 2.74 times higher (95% CI 1.66-4.52; P < 0.001) for individuals with severe to very severe self-harm problems. Other HoNOS items did not demonstrate clear patterns of association with service costs. Self-harm may be a robust indicator of the severity of personality disorder, but further replication work is required.

Despite associations between alcohol use and suicidal acts, little research measures prognoses of alcohol-using patients treated by Crisis Resolution Teams (CRTs), an intensive community-based intervention. We estimated the association of alcohol use amongst patients accepted following suicidal acts or ideation in four London-based Crisis Resolution Teams, with death-by-any-cause or recontact with crisis care. We analysed the electronic health records of 1615 CRT patients accepted following suicidal acts or ideation over 38 months, following STROBE guidelines. Using logistic regression we estimated the association of alcohol use (indicated by risk-assessment, AUDIT, or ICD-10 diagnosis) with death-or-recontact at (i) 30-days and (ii) 1-year after treatment start, adjusted for age, sex, ethnicity, psychiatric diagnosis, and severity of need. Hazardous, harmful, or dependent drinking was identified in 270 cases at baseline (16.7%); 73 (4.5%) were alcohol dependent. By 1-year, 622 patients (38.5%) had recontacted crisis care or died. After adjustment, alcohol use at a hazardous, harmful, or dependent level was not associated with increased odds of death-or-recontact at 30-days (AOR 1.17, 95%CI 0.73, 1.88) or 1-year (AOR 1.17, 95%CI 0.85, 1.60). Patients with hazardous, harmful, and dependent alcohol use are a small proportion of CRT patients, despite being more commonly encountered in emergency settings from which patients may be referred to CRTs, indicating a potential gap in provision. Those who are included in CRTs are not at increased risk of death-or-recontact within 1 year of treatment, suggesting that their inclusion can work, at least in a sample with predominantly hazardous or harmful alcohol use., (© 2023 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd.)

The Fusarium oxysporum species complex (FOSC) includes both plant and human pathogens that cause devastating plant vascular wilt diseases and threaten public health. Each F. oxysporum genome comprises core chromosomes (CCs) for housekeeping functions and accessory chromosomes (ACs) that contribute to host-specific adaptation. This study inspects global transcription factor profiles (TFomes) and their potential roles in coordinating CC and AC functions to accomplish host-specific interactions. Remarkably, we found a clear positive correlation between the sizes of TFomes and the proteomes of an organism. With the acquisition of ACs, the FOSC TFomes were larger than the other fungal genomes included in this study. Among a total of 48 classified TF families, 14 families involved in transcription/translation regulations and cell cycle controls were highly conserved. Among the 30 FOSC expanded families, Zn2-C6 and Znf&#95;C2H2 were most significantly expanded to 671 and 167 genes per family including well-characterized homologs of Ftf1 (Zn2-C6) and PacC (Znf&#95;C2H2) that are involved in host-specific interactions. Manual curation of characterized TFs increased the TFome repertoires by 3% including a disordered protein Ren1. RNA-Seq revealed a steady pattern of expression for conserved TF families and specific activation for AC TFs. Functional characterization of these TFs could enhance our understanding of transcriptional regulation involved in FOSC cross-kingdom interactions, disentangle species-specific adaptation, and identify targets to combat diverse diseases caused by this group of fungal pathogens.

Purpose: Accidents are the most common cause of death among UK military personnel. It is a common misconception in the general public that accidental injuries are always the result of random events, however research suggests that mental health problems and the increased levels of risky behaviour in military personnel may play a role. The objective of this study was to further our understanding of injuries and deaths not related to deployment by examining the associations of mental health, alcohol misuse and smoking with inpatient admission to hospital for accidents and injuries, and attendance to accident and emergency (A&E) departments., Methods: Data on all hospital admissions for accidents and injuries and A&E attendance at NHS hospitals in England, Scotland and Wales were linked to data on self-reported mental health problems, alcohol misuse and smoking from a large, representative UK military cohort of serving and ex-serving personnel (n = 8,602). Logistic regression was used to examine the associations between having a hospital admission for an accident or injury with self-reported mental health problems, alcohol misuse and smoking. Cox proportional-hazards regression was then conducted to assess the associations of mental health problems, alcohol misuse and smoking with time to hospital admission for an accident or injury. Finally, negative binomial regression was used to examine associations between the number of A&E attendances with mental health problems, alcohol misuse and smoking., Results: Personnel reporting symptoms of common mental disorder (CMD) or probable post-traumatic stress disorder (PTSD) were more likely to have an admission to hospital for an accident or injury (fully adjusted odds ratio 1.39, 95% confidence interval [CI] 1.05-1.84), than those who did not report these symptoms, and also had more attendances to A&E (fully adjusted incidence rate ratio [IRR] 1.32, 95% CI 1.16-1.51). A&E attendances were also more common in personnel who were smokers (fully adjusted IRR 1.21, 95% CI 1.09-1.35) following adjustment for demographic, military and health characteristics., Conclusions: The findings suggest that accidents and injuries among military personnel are not always random events and that there are health and behavioural factors, including poor mental health and smoking, which are associated (with small effect sizes) with an increased risk of being involved in an accident. Clinicians treating individuals attending hospital after an accident should consider their healthcare needs holistically, including issues related to mental health and health damaging behaviours., Competing Interests: RDH has received research funding from Roche, Pfizer, Janssen, Lundbeck and In-Silico-Bioscience. SW at the time of this work was an advisor to the British Army in psychiatry and a trustee of Combat Stress. This work was undertaken prior to NTF’s appointment to the Independent Group Advising on the Release of Data. NTF is a trustee of one military related charity. DL is a reservist in the UK Armed Forces. ZC, SL, PM, MJ and LG declare that they have no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Chui 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.)

Background: Studies show ethnic inequalities in rates of involuntary admission and types of clinical care (such as psychological therapies). However, few studies have investigated if there is a relationship between clinical care practices and ethnic inequalities in involuntary admission., Aims: This study investigated the impact of ethnicity and clinical care on involuntary admission and the potential mediation effects of prior clinical care., Method: In this retrospective cohort study, we used data from the electronic records of the South London and Maudsley NHS Foundation Trust and identified patients with a first hospital admission between January 2008 and May 2021. Logistic regression and mediation analyses were used to investigate the association between ethnicity and involuntary admission, and whether clinical care, in the 12 months preceding admission, mediates the association., Results: Compared with White British people, higher odds of involuntary admission were observed among 10 of 14 minority ethnic groups; with more than twice the odds observed among people of Asian Chinese, of Asian Bangladeshi and of any Black background. There were some ethnic differences in clinical care prior to admission, but these had a minimal impact on the inequalities in involuntary admission. More out-patient appointments and home treatment were associated with higher odds of involuntary admission, whereas psychological therapies and having a care plan were associated with reduced odds of involuntary admission., Conclusions: Ethnic inequalities in involuntary admission persist after accounting for potential mediating effects of several types and frequencies of clinical care. Promoting access to psychological therapies and ensuring that care plans are in place may reduce involuntary admissions.

Background: There is evidence of heterogeneity within treatment-resistant schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and others becoming treatment-resistant after an initial response period. These groups may have different aetiologies., Aim: This study investigates sociodemographic and clinical correlates of early onset of TRS., Method: Employing a retrospective cohort design, we do a secondary analysis of data from a cohort of people with TRS attending the South London and Maudsley. Regression analyses were conducted to identify the correlates of the length of treatment to TRS. Predictors included the following: gender, age, ethnicity, problems with positive symptoms, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics., Results: In a cohort of 164 people with TRS (60% were men), the median length of treatment to TRS was 3 years and 8 months. We observed no cut-off on the length of treatment until TRS presentation differentiating between early and late TRS (i.e. no bimodal distribution). Having mild to very severe problems with hallucinations and delusions at the treatment start was associated with earlier TRS (~19 months earlier). In sensitivity analyses, including only complete cases (subject to selection bias), treatment with a long-acting injectable antipsychotic was additionally associated with later TRS (~15 months later)., Conclusion: Our findings do not support a clear separation between early and late TRS but rather a continuum of the length of treatment before TRS onset. Having mild to very severe problems with positive symptoms at treatment start predicts earlier onset of TRS.

Purpose: Deficits in neuro-cognitive function are not uncommon for patients who have undergone surgical removal of brain tumors. Our goal is to evaluate the safety and efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a non-invasive tool for the treatment of neuro-cognitive dysfunctions following craniotomy., Methods: We present a retrospective review of individualized rTMS in twelve patients from Cingulum Health from December 2019 to July 2021 who presented with neuro-cognitive deficits following craniotomy. Multiple cortical targets were selected based on the patient's neurological disorder, associated networks, and anomalies in the functional connectivity of the brain as determined by machine-learning. TMS treatment was performed for five consecutive days. EuroQol quality of life (EQ-5D), functional extremity scales, and neuropsychiatric questionnaires related to the patient's deficit were assessed prior to, after, and during two-month follow-up of rTMS treatment., Results: Nine patients had unilateral functional deficits in either upper, lower, or both limbs. One patient reported post-operative depression, another experienced short term memory difficulties, and a third reported hypobulia. All twelve patients reported significantly improved EQ5D after rTMS treatment and during follow-up. More than half of the patients with lower and upper functional deficits had a 9-point improvement during follow-up. In the patient who developed depression, an 88% reduction in depressive symptoms based on the Beck's Depression Inventory (BDI) was observed during follow-up. No adverse events, such as seizures, occurred., Conclusion: The personalized functional connectivity approach to rTMS treatment may be effective and safe for patients with post-craniotomy neuro-cognitive dysfunction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Although frequently reported in psychosis, obsessive-compulsive symptoms (OCS) are often not recognized and thus undertreated. We aimed to estimate the prevalence of OCS and obsessive-compulsive disorder (OCD) in patients with schizophrenia, schizoaffective disorder, or bipolar disorder in clinical records and identify clinical associations of OCS co-occurrence., Methods: Data were retrieved from the South London and Maudsley NHS Foundation Trust Biomedical Research Centre case register. The study population was restricted to individuals diagnosed with schizophrenia ( ICD F20.x), schizoaffective disorder ( ICD F25.x), or bipolar disorder ( ICD F31.x) between 2007 and 2015. OCS and OCD were ascertained from structural fields and via Natural Language Processing software applied to free-text records. Clinical characteristics were obtained from Health of the Nation Outcome Scales for the analyses on associations between clinical characteristics and OCS/OCD status using logistic regressions with confounders considered., Results: 22,551 cases of schizophrenia, schizoaffective disorder, or bipolar disorder were identified in the observation window. Among these, 5,179 (24.0%) were identified as having OCS (including an OCD diagnosis) and 2,574 (11.9%) specifically with comorbid OCD. OCS/OCD was associated with an increased likelihood of recorded aggressive behavior (OR = 1.18; 95% CI, 1.10-1.26), cognitive problems (OR = 1.21; 95% CI, 1.13-1.30), hallucinations and delusions (OR = 1.11; 95% CI, 1.04-1.20), and physical problems (OR = 1.17; 95% CI, 1.09-1.26)., Conclusions: OCS and OCD are frequently recorded for patients with schizophrenia, schizoaffective disorder, and bipolar disorder and are associated with more severe psychiatric clinical characteristics. Automated information extraction tools hold potential to improve recognition and treatment of co-occurring OCS/OCD for psychosis., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Objectives: To develop a prognostic tool of treatment resistant schizophrenia (TRS) in a large and diverse clinical cohort, with comprehensive coverage of patients using mental health services in four London boroughs., Methods: We used the Least Absolute Shrinkage and Selection Operator (LASSO) for time-to-event data, to develop a risk prediction model from the first antipsychotic prescription to the development of TRS, using data from electronic health records., Results: We reviewed the clinical records of 1,515 patients with a schizophrenia spectrum disorder and observed that 253 (17%) developed TRS. The Cox LASSO survival model produced an internally validated Harrel's C index of 0.60. A Kaplan-Meier curve indicated that the hazard of developing TRS remained constant over the observation period. Predictors of TRS were: having more inpatient days in the three months before and after the first antipsychotic, more community face-to-face clinical contact in the three months before the first antipsychotic, minor cognitive problems, and younger age at the time of the first antipsychotic., Conclusions: Routinely collected information, readily available at the start of treatment, gives some indication of TRS but is unlikely to be adequate alone. These results provide further evidence that earlier onset is a risk factor for TRS., Competing Interests: RDH, HS have received research funding from Roche, Pfizer, Janssen and H Lundbeck. GKS and DFdF have received research funding from Janssen and H Lundbeck. JHM has received research funding from H Lundbeck for this study. SES is employed on a grant held by Cardiff University from Takeda for work unrelated to the analysis reported here. SRC, NB are employees of H Lundbeck. BJK is employee of Lundbeck Pharmaceuticals LLC. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Clozapine is the only licenced medication for treating treatment-resistant schizophrenia. Previous studies have suggested unequal rates of clozapine treatment by ethnicity among individuals with schizophrenia-spectrum disorders. One previous review has investigated this topic but was restricted to studies from the USA. This current review aims to synthesise the international literature regarding ethnic disparities in clozapine prescription amongst individuals with schizophrenia-spectrum disorders. We searched CINAHL, PubMed, Medline, Embase, APA PsycINFO and Open Grey and reviewed studies reporting on the proportion of service-users prescribed clozapine separately for different ethnic groups, in individuals with a primary diagnosis of schizophrenia or any schizophrenia-spectrum disorders. A narrative synthesis was conducted to integrate information from included studies. The review was registered in PROSPERO (Number: CRD42020221731). From 24 studies, there is strong, consistent evidence that Black and Hispanic service-users in the UK and the USA are significantly less likely to receive clozapine than White/Caucasian service-users after controlling for multiple demographic and clinical potential confounders. In New Zealand, Māori service-users were reported to be more likely to receive clozapine than those of White/European ethnicity. There is mixed evidence regarding Asian service-users in the UK. The mentioned disparities were observed in studies with TRS and non-TRS cohorts. The results imply that access to clozapine treatment varies among ethnic groups. These findings raise an ethical concern as they suggest a compromise of the standards of care in schizophrenia treatment practices. Interventions are needed to reduce clozapine prescribing disparities among ethnic communities.

Aims: Research shows persistent ethnic inequities in mental health experiences and outcomes, with a higher incidence of illnesses among minoritised ethnic groups. People with psychosis have an increased risk of multiple long-term conditions (MLTC; multimorbidity). However, there is limited research regarding ethnic inequities in multimorbidity in people with psychosis. This study investigates ethnic inequities in physical health multimorbidity in a cohort of people with psychosis., Methods: In this retrospective cohort study, using the Clinical Records Interactive Search (CRIS) system, we identified service-users of the South London and Maudsley NHS Trust with a schizophrenia spectrum disorder, and then additional diagnoses of diabetes, hypertension, low blood pressure, overweight or obesity and rheumatoid arthritis. Logistic and multinomial logistic regressions were used to investigate ethnic inequities in odds of multimorbidity (psychosis plus one physical health condition), and multimorbidity severity (having one or two physical health conditions, or three or more conditions), compared with no additional health conditions (no multimorbidity), respectively. The regression models adjusted for age and duration of care and investigated the influence of gender and area-level deprivation., Results: On a sample of 20 800 service-users with psychosis, aged 13-65, ethnic differences were observed in the odds for multimorbidity. Controlling for sociodemographic factors and duration of care, compared to White British people, higher odds of multimorbidity were found for people of Black African [adjusted Odds Ratio = 1.41, 95% Confidence Intervals (1.23-1.56)], Black Caribbean [aOR = 1.79, 95% CI (1.58-2.03)] and Black British [aOR = 1.64, 95% CI (1.49-1.81)] ethnicity. Reduced odds were observed among people of Chinese [aOR = 0.61, 95% CI (0.43-0.88)] and Other ethnic [aOR = 0.67, 95% CI (0.59-0.76)] backgrounds. Increased odds of severe multimorbidity (three or more physical health conditions) were also observed for people of any Black background., Conclusions: Ethnic inequities are observed for multimorbidity among people with psychosis. Further research is needed to understand the aetiology and impact of these inequities. These findings support the provision of integrated health care interventions and public health preventive policies and actions.

Purpose: Clozapine is the most effective intervention for treatment-resistant schizophrenia (TRS). Several studies report ethnic disparities in clozapine treatment. However, few studies restrict analyses to TRS cohorts alone or address confounding by benign ethnic neutropenia. This study investigates ethnic equity in access to clozapine treatment for people with treatment-resistant schizophrenia spectrum disorder., Methods: A retrospective cohort study, using information from 11 years of clinical records (2007-2017) from the South London and Maudsley NHS Trust. We identified a cohort of service-users with TRS using a validated algorithm. We investigated associations between ethnicity and clozapine treatment, adjusting for sociodemographic factors, psychiatric multi-morbidity, substance misuse, neutropenia, and service-use., Results: Among 2239 cases of TRS, Black service-users were less likely to be receive clozapine compared with White British service-users after adjusting for confounders (Black African aOR = 0.49, 95% CI [0.33, 0.74], p = 0.001; Black Caribbean aOR = 0.64, 95% CI [0.43, 0.93], p = 0.019; Black British aOR = 0.61, 95% CI [0.41, 0.91], p = 0.016). It was additionally observed that neutropenia was not related to treatment with clozapine. Also, a detention under the Mental Health Act was negatively associated clozapine receipt, suggesting people with TRS who were detained are less likely to be treated with clozapine., Conclusion: Black service-users with TRS were less likely to receive clozapine than White British service-users. Considering the protective effect of treatment with clozapine, these inequities may place Black service-users at higher risk for hospital admissions and mortality., (© 2022. The Author(s).)

Background: Individuals with autism spectrum disorder (ASD) are at particularly high risk of suicide and suicide attempts. Presentation to a hospital with self-harm is one of the strongest risk factors for later suicide. We describe the use of a novel data linkage between routinely collected education data and child and adolescent mental health data to examine whether adolescents with ASD are at higher risk than the general population of presenting to emergency care with self-harm., Methods: A retrospective cohort study was conducted on the population aged 11-17 resident in four South London boroughs between January 2009 and March 2013, attending state secondary schools, identified in the National Pupil Database (NPD). Exposure data on ASD status were derived from the NPD. We used Cox regression to model time to first self-harm presentation to the Emergency Department (ED)., Results: One thousand twenty adolescents presented to the ED with self-harm, and 763 matched to the NPD. The sample for analysis included 113,286 adolescents (2.2% with ASD). For boys only, there was an increased risk of self-harm associated with ASD (adjusted hazard ratio 2·79, 95% CI 1·40-5·57, P<0·01). Several other factors including school absence, exclusion from school and having been in foster care were also associated with a higher risk of self-harm., Conclusions: This study provides evidence that ASD in boys, and other educational, social and clinical factors, are risk factors for emergency presentation with self-harm in adolescents. These findings are an important step in developing early recognition and prevention programmes., (© 2022. The Author(s).)

Background: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment., Methods: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors' predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale., Results: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model's optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data., Conclusions: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.

Clozapine, an antipsychotic, is associated with increased susceptibility to infection with COVID-19, compared to other antipsychotics. Here, we investigate associations between clozapine treatment and increased risk of adverse outcomes of COVID-19, namely COVID-related hospitalisation, intensive care treatment, and death, amongst patients taking antipsychotics with schizophrenia-spectrum disorders. Using the clinical records of South London and Maudsley NHS Foundation Trust, we identified 157 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders, were taking antipsychotics (clozapine or other antipsychotics) at the time of COVID-19 pandemic in the UK and had a laboratory-confirmed COVID-19 infection. The following health outcomes were measured: COVID-related hospitalisation, COVID-related intensive care treatment and death. We tested associations between clozapine treatment and each outcome using logistic regression models, adjusting for gender, age, ethnicity, neighbourhood deprivation, obesity, smoking status, diabetes, asthma, bronchitis and hypertension using propensity scores. Of the 157 individuals who developed COVID-19 while on antipsychotics (clozapine or other antipsychotics), there were 28% COVID-related hospitalisations, 8% COVID-related intensive care treatments and 8% deaths of any cause during the 28 days follow-up period. amongst those taking clozapine, there were 25% COVID-related hospitalisations, 7% COVID-related intensive care treatments and 7% deaths. In both unadjusted and adjusted analyses, we found no significant association between clozapine and any of the outcomes. Thus, we found no evidence that patients with clozapine treatment at time of COVID-19 infection had increased risk of hospitalisation, intensive care treatment or death, compared to non-clozapine antipsychotic-treated patients. However, further research should be considered in larger samples to confirm this., Competing Interests: Declaration of Competing Interest RDH has received research funding from Roche, Pfizer, Janssen, and Lundbeck. DFF has received research funding from Janssen and Lundbeck. JHM has received research funding from Lundbeck. JTT has received research funding from Bristol-Meyers-Squibb. RS declares research support in the last 36 months from Janssen, GSK and Takeda., (Copyright © 2022. Published by Elsevier B.V.)

Although secondary metabolites are typically associated with competitive or pathogenic interactions, the high bioactivity of endophytic fungi in the Xylariales, coupled with their abundance and broad host ranges spanning all lineages of land plants and lichens, suggests that enhanced secondary metabolism might facilitate symbioses with phylogenetically diverse hosts. Here, we examined secondary metabolite gene clusters (SMGCs) across 96 Xylariales genomes in two clades (Xylariaceae s.l. and Hypoxylaceae), including 88 newly sequenced genomes of endophytes and closely related saprotrophs and pathogens. We paired genomic data with extensive metadata on endophyte hosts and substrates, enabling us to examine genomic factors related to the breadth of symbiotic interactions and ecological roles. All genomes contain hyperabundant SMGCs; however, Xylariaceae have increased numbers of gene duplications, horizontal gene transfers (HGTs) and SMGCs. Enhanced metabolic diversity of endophytes is associated with a greater diversity of hosts and increased capacity for lignocellulose decomposition. Our results suggest that, as host and substrate generalists, Xylariaceae endophytes experience greater selection to diversify SMGCs compared with more ecologically specialised Hypoxylaceae species. Overall, our results provide new evidence that SMGCs may facilitate symbiosis with phylogenetically diverse hosts, highlighting the importance of microbial symbioses to drive fungal metabolic diversity., (© 2021 The Authors. New Phytologist © 2021 New Phytologist Foundation. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Marine fungi remain poorly covered in global genome sequencing campaigns; the 1000 fungal genomes (1KFG) project attempts to shed light on the diversity, ecology and potential industrial use of overlooked and poorly resolved fungal taxa. This study characterizes the genomes of three marine fungi: Emericellopsis sp. TS7, wood-associated Amylocarpus encephaloides and algae-associated Calycina marina. These species were genome sequenced to study their genomic features, biosynthetic potential and phylogenetic placement using multilocus data. Amylocarpus encephaloides and C. marina were placed in the Helotiaceae and Pezizellaceae (Helotiales), respectively, based on a 15-gene phylogenetic analysis. These two genomes had fewer biosynthetic gene clusters (BGCs) and carbohydrate active enzymes (CAZymes) than Emericellopsis sp. TS7 isolate. Emericellopsis sp. TS7 (Hypocreales, Ascomycota) was isolated from the sponge Stelletta normani. A six-gene phylogenetic analysis placed the isolate in the marine Emericellopsis clade and morphological examination confirmed that the isolate represents a new species, which is described here as E. atlantica. Analysis of its CAZyme repertoire and a culturing experiment on three marine and one terrestrial substrates indicated that E. atlantica is a psychrotrophic generalist fungus that is able to degrade several types of marine biomass. FungiSMASH analysis revealed the presence of 35 BGCs including, eight non-ribosomal peptide synthases (NRPSs), six NRPS-like, six polyketide synthases, nine terpenes and six hybrid, mixed or other clusters. Of these BGCs, only five were homologous with characterized BGCs. The presence of unknown BGCs sets and large CAZyme repertoire set stage for further investigations of E. atlantica. The Pezizellaceae genome and the genome of the monotypic Amylocarpus genus represent the first published genomes of filamentous fungi that are restricted in their occurrence to the marine habitat and form thus a valuable resource for the community that can be used in studying ecological adaptions of fungi using comparative genomics., (© 2021. The Author(s).)

Background: Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia., Aims: To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK., Method: Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use., Results: Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73-3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14-2.72)., Conclusions: These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.

Background: Alcohol use is a multidimensional risk factor for suicidal behaviour. However, suicide prevention strategies often take 'one-size-fits-all' approaches to alcohol use, reflecting an evidence base built on unidimensional measures. Latent Class Analysis can use a range of measures to differentiate distinct patterns of alcohol using behaviour and their associated risks., Methods: We analysed Electronic Health Record data from 650 suicidal adults detained for up to 36 h using police powers (Section 136 of the Mental Health Act 1983, amended 2007) to facilitate psychiatric assessment at a Health-Based Place of Safety, a dedicated emergency psychiatric care centre in London, UK. We conducted a Latent Class Analysis of alcohol using behaviours at first detention, and used multivariable logistic regression to estimate the association of each identified latent class with subsequent death or recontact with emergency psychiatric care over a median follow-up of 490 days, adjusting for sex, age and past-year psychiatric diagnosis., Results: Three classes of alcohol use were identified: low risk drinkers, heavy episodic drinkers and dependent drinkers. The dependent drinking class had twice the odds of death or recontact with emergency psychiatric care as the low risk drinking class (OR 2.32, 95 %CI 1.62-3.32, p < 0.001). Conversely, the heavy episodic drinking class was associated with lower odds of death or recontact than the low risk drinking class (OR 0.66, 95 %CI 0.53-0.81, p < 0.001)., Conclusions: The risk of adverse outcomes after a suicide attempt are not uniform for different alcohol use classes. Clinical assessment and suicide prevention efforts should be tailored accordingly., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aureobasidium pullulans is an extremotolerant, cosmopolitan yeast-like fungus that successfully colonises vastly different ecological niches. The species is widely used in biotechnology and successfully applied as a commercial biocontrol agent against postharvest diseases and fireblight. However, the exact mechanisms that are responsible for its antagonistic activity against diverse plant pathogens are not known at the molecular level. Thus, it is difficult to optimise and improve the biocontrol applications of this species. As a foundation for elucidating biocontrol mechanisms, we have de novo assembled a high-quality reference genome of a strongly antagonistic A. pullulans strain, performed dual RNA-seq experiments, and analysed proteins secreted during the interaction with the plant pathogen Fusarium oxysporum . Based on the genome annotation, potential biocontrol genes were predicted to encode secreted hydrolases or to be part of secondary metabolite clusters (e.g., NRPS-like, NRPS, T1PKS, terpene, and β-lactone clusters). Transcriptome and secretome analyses defined a subset of 79 A. pullulans genes (among the 10,925 annotated genes) that were transcriptionally upregulated or exclusively detected at the protein level during the competition with F. oxysporum . These potential biocontrol genes comprised predicted secreted hydrolases such as glycosylases, esterases, and proteases, as well as genes encoding enzymes, which are predicted to be involved in the synthesis of secondary metabolites. This study highlights the value of a sequential approach starting with genome mining and consecutive transcriptome and secretome analyses in order to identify a limited number of potential target genes for detailed, functional analyses., Competing Interests: Conflict of Interest: The authors declare no conflict of interest., (Copyright: © 2021 Rueda-Mejia et al.)

Background: Gender disparities in treatment are apparent across many areas of healthcare. There has been little research into whether clozapine prescription, the first-line treatment for treatment-resistant schizophrenia (TRS), is affected by patient gender., Methods: This retrospective cohort study identified 2244 patients with TRS within the South London and Maudsley NHS Trust, by using a bespoke method validated against a gold-standard, manually coded, dataset of TRS cases. The outcome and exposures were identified from the free-text using natural language processing applications (including machine learning and rules-based approaches) and from information entered in structured fields. Multivariable logistic regression was carried out to calculate the odds ratios for clozapine prescription according to patients' gender, and adjusting for numerous potential confounders including sociodemographic, clinical (e.g., psychiatric comorbidities and substance use), neutropenia, functional factors (e.g., problems with occupation), and clinical monitoring., Results: Clozapine was prescribed to 77% of the women and 85% of the men with TRS. Women had reduced odds of being prescribed clozapine as compared to men after adjusting for all factors included in the present study (adjusted OR: 0.66; 95% CI 0.44-0.97; p = 0.037)., Conclusion: Women with TRS are less likely to be prescribed clozapine than men with TRS, even when considering the effects of multiple clinical and functional factors. This finding suggests there could be gender bias in clozapine prescription, which carries ramifications for the relatively poorer care of women with TRS regarding many outcomes such as increased hospitalisation, mortality, and poorer quality of life., Competing Interests: Declaration of competing interest RDH and HS have received research funding from Roche, Pfizer, Janssen and H. Lundbeck A/S. GKS and DFdF have received research funding from Janssen and H. Lundbeck A/S. JHM has received research funding from H. Lundbeck A/S. RP has received research funds from Janssen and consultancy fees from Induction Healthcare and Holmusk. AS and EWW have no conflicts of interest to report., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Although no drugs are licensed for the treatment of personality disorder, pharmacological treatment in clinical practice remains common., Aims: This study aimed to estimate the prevalence of psychotropic drug use and associations with psychological service use among people with personality disorder., Method: Using data from a large, anonymised mental healthcare database, we identified all adult patients with a diagnosis of personality disorder and ascertained psychotropic medication use between 1 August 2015 and 1 February 2016. Multivariable logistic regression models were constructed, adjusting for sociodemographic, clinical and service use factors, to examine the association between psychological services use and psychotropic medication prescribing., Results: Of 3366 identified patients, 2029 (60.3%) were prescribed some form of psychotropic medication. Patients using psychological services were significantly less likely to be prescribed psychotropic medication (adjusted odds ratio 0.48, 95% CI 0.39-0.59, P<0.001) such as antipsychotics, benzodiazepines and antidepressants. This effect was maintained following several sensitivity analyses. We found no difference in the risk for mood stabiliser (adjusted odds ratio 0.79, 95% CI 0.57-1.10, P = 0.169) and multi-class psychotropic use (adjusted odds ratio 0.80, 95% CI 0.60-1.07, P = 0.133) between patients who did and did not use psychological services., Conclusions: Psychotropic medication prescribing is common in patients with personality disorder, but significantly less likely in those who have used psychological services. This does not appear to be explained by differences in demographic, clinical and service use characteristics. There is a need to develop clear prescribing guidelines and conduct research in clinical settings to examine medication effectiveness for this population.

Background: Patient-reported outcome measures (PROMs) are important tools to inform patients, clinicians and policy-makers about clinical need and the effectiveness of any given treatment. Consistent PROM use can promote early symptom detection, help identify unexpected treatment responses and improve therapeutic engagement. Very few studies have examined associations between patient characteristics and PROM data collection., Methods: We used the electronic mental health records for 28,382 children and young people (aged 4-17 years) accessing Child and Adolescent Mental Health Services (CAMHS) across four South London boroughs between the 1st of January 2008 to the 1st of October 2017. We examined the completion rates of the caregiver Strengths and Difficulties Questionnaire (SDQ), a ubiquitous PROM for CAMHS at baseline and 6-month follow-up., Results and Conclusions: SDQs were present for approximately 40% (n = 11,212) of the sample at baseline, and from these, only 8% (n = 928) had a follow-up SDQ. Patterns of unequal PROM collection by sociodemographic factors were identified: males were more likely (aOR 1.07, 95% CI 1.01-1.13), whilst older age (aOR 0.87, 95% CI 0.87-0.88), Black (aOR 0.79 95% CI 0.74-0.84) and Asian ethnicity (aOR 0.75 95% CI 0.66-0.86) relative to White ethnicity, and residence within the most deprived neighbourhood (aOR 0.87 95% CI 0.80-0.94) were less likely to have a record of baseline SDQ. Similar results were found in the sub-group (n = 11,212) with follow-up SDQ collection. Our findings indicate systematic differences in the currently available PROMS data and highlights which groups require increased focus if we are to gain equitable PROM collection. We need to ensure representative PROM collection for all individuals accessing treatment, regardless of ethnic or socioeconomic background; biased data have adverse ramifications for policy and service level decision-making., (© 2020 The Authors. Child and Adolescent Mental Health published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Algae are a diverse, polyphyletic group of photosynthetic eukaryotes spanning nearly all eukaryotic lineages of life and collectively responsible for ∼50% of photosynthesis on Earth. Sequenced algal genomes, critical to understanding their complex biology, are growing in number and require efficient tools for analysis. PhycoCosm (https://phycocosm.jgi.doe.gov) is an algal multi-omics portal, developed by the US Department of Energy Joint Genome Institute to support analysis and distribution of algal genome sequences and other 'omics' data. PhycoCosm provides integration of genome sequence and annotation for >100 algal genomes with available multi-omics data and interactive web-based tools to enable algal research in bioenergy and the environment, encouraging community engagement and data exchange, and fostering new sequencing projects that will further these research goals., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Mycorrhizal fungi are mutualists that play crucial roles in nutrient acquisition in terrestrial ecosystems. Mycorrhizal symbioses arose repeatedly across multiple lineages of Mucoromycotina, Ascomycota, and Basidiomycota. Considerable variation exists in the capacity of mycorrhizal fungi to acquire carbon from soil organic matter. Here, we present a combined analysis of 135 fungal genomes from 73 saprotrophic, endophytic and pathogenic species, and 62 mycorrhizal species, including 29 new mycorrhizal genomes. This study samples ecologically dominant fungal guilds for which there were previously no symbiotic genomes available, including ectomycorrhizal Russulales, Thelephorales and Cantharellales. Our analyses show that transitions from saprotrophy to symbiosis involve (1) widespread losses of degrading enzymes acting on lignin and cellulose, (2) co-option of genes present in saprotrophic ancestors to fulfill new symbiotic functions, (3) diversification of novel, lineage-specific symbiosis-induced genes, (4) proliferation of transposable elements and (5) divergent genetic innovations underlying the convergent origins of the ectomycorrhizal guild.

Background: Since the recent conflicts in Iraq and Afghanistan, the short-term focus of military healthcare research has been on the consequences of deployment for mental health and on those wounded or injured in combat. Now that these conflicts have ended for the UK Armed Forces, it is important to consider the longer term physical and mental health consequences, and just as importantly, the links between these. The aims of this study were to determine the most common physical conditions requiring a hospital admission in UK military personnel and whether they were more common in personnel with a mental health condition, smokers, and/or those misusing alcohol compared to those without., Methods: Data linkage of a prospective UK military cohort study to electronic admitted patient care records for England, Wales and Scotland. Nine thousand nine hundred ninety military personnel completed phase 2 of a military cohort study (56% response rate, data collected from 2007 to 2009), with analyses restricted to 86% of whom provided consent for linkage to healthcare records (n = 8602). Ninety percent were male and the mean age at phase 2 was 36 years. The outcome was physical non communicable diseases (NCDs) requiring a hospital admission which occurred after phase 2 of the cohort when the mental health, smoking and alcohol use exposure variables had been assessed until the end of March 2014., Results: The most common NCDs requiring a hospital admission were gastrointestinal disorders 5.62% (95% Confidence Intervals (CI) 5.04, 6.19) and joint disorders 5.60% (95% CI 5.02, 6.18). Number of NCDs requiring a hospital admission was significantly higher in those with a common mental disorder (Hazard ratio (HR) 1.40 (95% CI 1.16-1.68), post-traumatic stress disorder (HR 1.78 (95% CI 1.32-2.40)) and in current smokers (HR 1.35 (95% CI 1.12-1.64) compared to those without the disorder, and non-smokers, respectively., Conclusions: Military personnel with a mental health problem are more likely to have an inpatient hospital admission for NCDs compared to those without, evidencing the clear links between physical and mental health in this population.

Objectives: Linkage of electronic health records (EHRs) to Hospital Episode Statistics (HES)-Office for National Statistics (ONS) mortality data has provided compelling evidence for lower life expectancy in people with severe mental illness. However, linkage error may underestimate these estimates. Using a clinical sample (n=265 300) of individuals accessing mental health services, we examined potential biases introduced through missed matching and examined the impact on the association between clinical disorders and mortality., Setting: The South London and Maudsley NHS Foundation Trust (SLaM) is a secondary mental healthcare provider in London. A deidentified version of SLaM's EHR was available via the Clinical Record Interactive Search system linked to HES-ONS mortality records., Participants: Records from SLaM for patients active between January 2006 and December 2016., Outcome Measures: Two sources of death data were available for SLaM participants: accurate and contemporaneous date of death via local batch tracing (gold standard) and date of death via linked HES-ONS mortality data. The effect of linkage error on mortality estimates was evaluated by comparing sociodemographic and clinical risk factor analyses using gold standard death data against HES-ONS mortality records., Results: Of the total sample, 93.74% were successfully matched to HES-ONS records. We found a number of statistically significant administrative, sociodemographic and clinical differences between matched and unmatched records. Of note, schizophrenia diagnosis showed a significant association with higher mortality using gold standard data (OR 1.08; 95% CI 1.01 to 1.15; p = 0.02) but not in HES-ONS data (OR 1.05; 95% CI 0.98 to 1.13; p = 0.16). Otherwise, little change was found in the strength of associated risk factors and mortality after accounting for missed matching bias., Conclusions: Despite significant clinical and sociodemographic differences between matched and unmatched records, changes in mortality estimates were minimal. However, researchers and policy analysts using HES-ONS linked resources should be aware that administrative linkage processes can introduce error., Competing Interests: Competing interests: RDH has received research funding from Roche, Pfizer, Janssen and Lundbeck. The other authors have declared that no competing interests exist., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Trends in detention under the Mental Health Act 1983 in two major London secondary mental healthcare providers were explored using patient-level data in a historical cohort study between 2007-2008 and 2016-2017. An increase in the number of detention episodes initiated per fiscal year was observed at both sites. The rise was accompanied by an increase in the number of active patients; the proportion of active patients detained per year remained relatively stable. Findings suggest that the rise in the number of detentions reflects the rise of the number of people receiving secondary mental healthcare.

Background: Bulimia nervosa (BN) is associated with increased mortality. Frequent comorbidities of BN include substance use disorders, affective disorders and personality disorders (PD). These comorbidities may add an additional risk for mortality., Methods: We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders over an observation period from January 2007 to March 2016 for 1501 people with BN using anonymised health records data from the South London and Maudsley NHS Foundation Trust (SLaM), retrieved through its Clinical Records Interactive Search (CRIS) data resource. Mortality was ascertained through monthly linkages to the nationwide tracing system administered by the Office for National Statistics (ONS). We used Cox proportional hazards regression to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Multivariable analyses were also performed to estimate effects when controlling for confounding of age, sex, ethnicity, borough, marital status and deprivation score., Results: A total of 18 patients with BN died during the observation period. The standardised mortality ratio (SMR) for our study cohort (against the population of England and Wales in 2012 as a standard) was 2.52 (95% CI 1.49-3.97). Cox regressions revealed significant associations of mortality with older age and male gender. Comorbid PD (HR: 3.36; 95% CI 1.05-10.73) was significantly associated with all-cause mortality, even after controlling for demographic and socioeconomic covariates., Conclusions: These results highlight increased mortality in patients with BN and the importance of recognising and treating PDs in patients with BN.

Anorexia nervosa (AN) is found associated with increased mortality. Frequent comorbidities of AN include substance use disorders (SUD), affective disorders (AD) and personality disorders (PD). We investigated the influence of these psychiatric comorbidities on all-cause mortality with demographic and socioeconomic factors considered as confounders in the observation window between January 2007 and March 2016 for 1970 people with AN, using data from the case register of the South London and Maudsley (SLaM) NHS Foundation Trust, an almost monopoly-secondary mental healthcare service provider in southeast London. We retrieved data from its Clinical Records Interactive Search (CRIS) system as data source. Mortality was ascertained through nationwide tracing by the UK Office for National Statistics (ONS) linked to CRIS database on a monthly basis. A total of 43 people with AN died during the observation period. Standardized Mortality Ratio (SMR) with England and Wales population in 2012 as standard population for our study cohort was 5.21 (95% CI 3.77, 7.02). In univariate analyses, the comorbidity of SUD or PD was found to significantly increase the relative risks of mortality (HRs = 3.10, 95% CI 1.21, 7.92; and 2.58, 95% CI 1.23, 5.40, respectively). After adjustment for demographic and socioeconomic covariates as confounders, moderately but not significantly elevated risks were identified for SUD (adjusted HR = 1.39, 95% CI 0.53, 3.65) and PD (adjusted HR = 1.58, 95% CI 0.70, 3.56). These results suggest an elevated mortality in people with AN, which might be, at least partially, explained by the existence of the comorbidities SUD or PD.

Background: Insight into the effect of clozapine is limited by a lack of controlling for confounding variables in current research. Our objective was to investigate the association between clozapine prescribed at discharge, following an inpatient episode, and risk of readmission into secondary mental health services in patients with schizophrenia and schizoaffective disorder, controlling extensively for confounding variables., Methods: Clinical records from 3651 patients were analysed in a retrospective observational cohort study. Cox proportional-hazards regression models were used to assess the risk of hospital readmission. A series of sensitivity analyses were also conducted. Propensity score methods were used to address confounding-by-indication., Results: Patients on clozapine ( n=202) had a reduced risk of readmission compared with patients on other antipsychotics (adjusted hazard ratio=0.79; 95% confidence interval: 0.64-0.99; p=0.043). Clozapine also had a protective effect on risk of readmission when compared with olanzapine (adjusted hazard ratio 0.76; 95% confidence interval: 0.60-0.96; p=0.021). The effect size remained consistent after adjusting for an array of possible confounders, as well as using propensity scores to address confounding-by-indication. A statistically significant result was also noted in all but two sensitivity analyses., Conclusion: Our findings suggest that clozapine is associated with a reduced risk of readmission into secondary mental health services.

Objective: Large-scale epidemiological studies have demonstrated a protective effect of clozapine on mortality in people with schizophrenia. Clozapine is reserved for use in patients with treatment-resistant schizophrenia (TRS), but evidence of clozapine's effect on mortality exclusively within TRS samples is inconclusive. Hence, we aimed to investigate the effect of clozapine use on all-cause mortality in TRS patients., Methods: A historical patient cohort sample of 2837 patients, who met criteria for TRS between 1 Jan 2008 and 1 Jan 2016, were selected from the South London and Maudsley NHS Foundation Trust (SLAM) electronic health records (EHR). The national Zaponex Treatment Access System (ZTAS) mandatory monitoring system linked to the SLAM EHR was used to distinguish which patients were initiated on clozapine (n = 1025). Cox proportional hazard models were used, adjusting for sociodemographics, clinical monitoring, mental and physical illness severity and functional status., Results: After controlling for potential confounders, the protective effect of clozapine on all-cause mortality was significant (adjusted hazard ratio 0.61; 95% confidence interval 0.38-0.97; P = 0.04)., Conclusions: Clozapine reduces the risk of mortality in patients who meet criteria for TRS. We provide further evidence that improving access to clozapine in TRS is likely to reduce the mortality gap in schizophrenia., (© 2018 The Authors. Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.)

The prevalence of negative symptoms (NS) at first episode of early-onset psychosis (EOP), and their effect on psychosis prognosis is unclear. In a sample of 638 children with EOP (aged 10-17 y, 51% male), we assessed (1) the prevalence of NS at first presentation to mental health services and (2) whether NS predicted eventual development of multiple treatment failure (MTF) prior to the age of 18 (defined by initiation of a third trial of novel antipsychotic due to prior insufficient response, intolerable adverse-effects or non-adherence). Data were extracted from the electronic health records held by child inpatient and community-based services in South London, United Kingdom. Natural Language Processing tools were used to measure the presence of Marder Factor NS and antipsychotic use. The association between presenting with ≥2 NS and the development of MTF over a 5-year period was modeled using Cox regression. Out of the 638 children, 37.5% showed ≥2 NS at first presentation, and 124 (19.3%) developed MTF prior to the age of 18. The presence of NS at first episode was significantly associated with MTF (adjusted hazard ratio 1.62, 95% CI 1.07-2.46; P = .02) after controlling for a number of potential confounders including psychosis diagnostic classification, positive symptoms, comorbid depression, and family history of psychosis. Other factors associated with MTF included comorbid autism spectrum disorder, older age at first presentation, Black ethnicity, and family history of psychosis. In EOP, NS at first episode are prevalent and may help identify a subset of children at higher risk of responding poorly to antipsychotics.

Background: Serious mental illness (SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder) is associated with worse general health. However, admissions to general hospitals have received little investigation. We sought to delineate frequencies of and causes for non-psychiatric hospital admissions in SMI and compare with the general population in the same area., Methods: Records of 18 380 individuals with SMI aged ⩾20 years in southeast London were linked to hospitalisation data. Age- and gender-standardised admission ratios (SARs) were calculated by primary discharge diagnoses in the 10th edition of the World Health Organization International Classification of Diseases (ICD-10) codes, referencing geographic catchment data., Results: Commonest discharge diagnosis categories in the SMI cohort were urinary conditions, digestive conditions, unclassified symptoms, neoplasms, and respiratory conditions. SARs were raised for most major categories, except neoplasms for a significantly lower risk. Hospitalisation risks were specifically higher for poisoning and external causes, injury, endocrine/metabolic conditions, haematological, neurological, dermatological, infectious and non-specific ('Z-code') causes. The five commonest specific ICD-10 diagnoses at discharge were 'chronic renal failure' (N18), a non-specific code (Z04), 'dental caries' (K02), 'other disorders of the urinary system' (N39), and 'pain in throat and chest' (R07), all of which were higher than expected (SARs ranging 1.57-6.66)., Conclusion: A range of reasons for non-psychiatric hospitalisation in SMI is apparent, with self-harm, self-neglect and/or reduced healthcare access, and medically unexplained symptoms as potential underlying explanations.

Background: Computer-modelling approaches have the potential to predict the interactions between different antipsychotics and provide guidance for polypharmacy., Aims: To evaluate the accuracy of the quantitative systems pharmacology platform to predict parkinsonism side-effects in patients prescribed antipsychotic polypharmacy., Methods: Using anonymized data from South London and Maudsley NHS Foundation Trust electronic health records we applied quantitative systems pharmacology, a neurophysiology-based computer model of humanized neuronal circuits, to predict the risk for parkinsonism symptoms in patients with schizophrenia prescribed two concomitant antipsychotics. The performance of the quantitative systems pharmacology model was compared with the performance of simple parameters such as: combination of affinity constants (1/K sum ); sum of D 2 R occupancies (D 2 R) and chlorpromazine equivalent dose., Results: We identified 832 patients with schizophrenia who were receiving two antipsychotics for six or more months, between 1 January 2007 and 31 December 2014. The area under the receiver operating characteristic (AUROC) curve for the quantitative systems pharmacology model was 0.66 ( p = 0.01), while AUROCs for D 2 R, 1/K sum and chlorpromazine equivalent dose were 0.52 ( p = 0.350), 0.53 ( p = 0.347) and 0.52 ( p = 0.330) respectively., Conclusion: Our results indicate that quantitative systems pharmacology has the potential to predict the risk of parkinsonism associated with antipsychotic polypharmacy from minimal source information, and thus might have potential decision-support applicability in clinical settings.