Explore the vast range of titles available.

Purpose This study aimed to develop and evaluate the Newbridge Prognosis Score (NPS), a prognostic questionnaire designed for use by a multidisciplinary team (MDT) when an anorexia nervosa (AN) patient is discharged from an inpatient treatment facility for eating disorders. The tool integrates the collective judgment of MDT members to predict short-term outcomes in adolescents with AN, focusing on physical, psychological, and behavioural factors and systematically assessing psychopathology, weight, and continued treatment needs. This information is intended to guide individualized community support, enhance post-discharge recovery, and aid in the allocation of limited community-based resources. Methods A group of adolescent girls and boys undergoing inpatient treatment for AN participated in the study. In addition, a matched control sub-sample was created. Upon discharge, the multidisciplinary team scored the Newbridge Prognosis Score (NPS), and follow-up data were collected 6 months later from the young person and/or their parents or carers. Results The NPS significantly correlates with key recovery items, such as weight maintenance, lower eating disorder psychopathology, subsequent need for readmission and engagement in follow-up. Higher NPS scores predict poorer outcomes, such as more severe psychopathology, lower weight or weight loss and higher readmission risk at follow-up. Psychological factors are strong predictors of post-discharge prognosis, with the suggestion that those sufferers may require enhanced psychological support. The NPS is more effective at predicting long-term readmission risk than short-term outcomes. However, the NPS explained only a proportion of the variance in these outcomes and sensitivity in predicting readmission within the matched control sample was mixed. Conclusions The NPS shows promise as a potential tool for predicting short-term outcomes following AN treatment. While promising, further refinement of the tool is needed, prior to being validated for use in clinical practice. Level of evidence Level III. Evidence obtained from a well-designed cohort or case-controlled analytic studies.

Background The relationship between anorexia nervosa (AN) and family disturbance has been a subject of debate since its first description. What began as a clear view of the pathologically disturbed family causing AN has become ever more complex over the decades. Objective The aim of this review is to explore the literature to examine the changes and evolution of clinical opinion around family dysfunction and AN over the last 20 years. Methods A narrative review of heterogeneous studies in peer-reviewed publications sourced from the major databases, including PubMed and ScienceDirect, to illuminate the topic of family distress and AN by highlighting the conflicting and complementary ways it has been studied. Results This review has highlighted the complexity of the relationship between anorectic sufferers and their families. It has explored the literature about parental burden, emotions and cognitive mechanisms together with parental attitudes about weight and shape. It is clear that there is no consistent psycho-social pathology in families which has been shown to be causative. However, over the last twenty years, research has highlighted the distress and family dysfunction caused by having to look after an anoretic child with poor mentalisation skills, insecure attachment and emotion dysregulation. Conclusion The area has become clearer over the last 20 years; research suggests a bi-directional relationship between AN and family dysfunction, with difficult dynamics becoming entrenched within the family. This is best addressed, the consensus suggests, by specialist family therapy and carer skills interventions. Longitudinal research is needed to definitively answer the question with rigorous scientific certainty. EMB rating Level V. Level of evidence Level I: Evidence obtained from: at least one properly designed randomized controlled trials; systematic reviews and meta-analyses; experimental studies. Level II: Evidence obtained from well-designed controlled trials without randomization. Level III: Evidence obtained from well-designed cohort or case-control analytic studies. Level IV: Evidence obtained from with multiple time series analysis such as case studies. Dramatic results in uncontrolled trials might also be regarded as this type of evidence. Level V: Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

A correction to this paper has been published: https://doi.org/10.1007/s40519-021-01185-6

Anti-HBe seroconversion and HBsAg loss are important therapeutic endpoints in patients with hepatitis B virus (HBV) infection. Quantitative measures of hepatitis B surface antigen (qHBsAg) and e antigen (qHBeAg) have been identified as potentially useful indicators of therapeutic response in HBV monoinfection. The aim of this study was to examine serological change including quantitative biomarkers in HIV-HBV coinfected patients initiating HBV active antiretroviral therapy (ART). HIV-HBV coinfected individuals from Thailand were followed for up to 168 weeks post ART. Rates and associations of qualitative serological change were determined. Longitudinal changes in qHBsAg and qHBeAg were measured and their utility as predictors of response examined. Forty seven patients were included of whom 27 (57%) were HBeAg positive at baseline. Median CD4 count was 48 cells/mm(3). Over a median follow-up of 108 weeks 48% (13/27) lost HBeAg, 12/27 (44%) achieved anti-HBe seroconversion and 13% (6/47) HBsAg loss. Anti-HBe seroconversion was associated with higher baseline ALT (p = 0.034), lower qHBsAg (p = 0.015), lower qHBeAg (p = 0.031) and greater HBV DNA decline to week 24 (p = 0.045). Sensitivity and specificity for qHBsAg and qHBeAg decline of >0.5 log at week 12 and >1.0 log at week 24 were high for both anti-HBe seroconversion and HBsAg loss. Rates of serological change in these HIV-HBV coinfected individuals with advanced immunodeficiency initiating HBV-active ART were high. Baseline and on treatment factors were identified that were associated with a greater likelihood of subsequent anti-HBe seroconversion, including both quantitative HBsAg and HBeAg, suggesting these biomarkers may have utility in this clinical setting.

GLP-1 receptor agonists have neurotrophic properties in in-vitro and in-vivo models of Parkinson's disease and results of epidemiological studies and small randomised trials have suggested possible benefits for risk and progression of Parkinson's disease. We aimed to establish whether the GLP-1 receptor agonist, exenatide, could slow the rate of progression of Parkinson's disease. We did a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial at six research hospitals in the UK. Participants were aged 25–80 years with a diagnosis of Parkinson's disease, were at Hoehn and Yahr stage 2·5 or less when on dopaminergic treatment, and were on dopaminergic treatment for at least 4 weeks before enrolment. Participants were randomly assigned (1:1) using a web-based system with minimisation according to Hoehn and Yahr stage and study site to receive extended-release exenatide 2 mg by subcutaneous pen injection once per week over 96 weeks, or visually identical placebo. All participants and all research team members at study sites were masked to randomisation allocation. The primary outcome was the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score, off dopaminergic medication at 96 weeks, analysed in the intention-to-treat population using a linear mixed modelling approach. This study is registered with ISRCTN (14552789), EudraCT (2018-003028-35), and ClinicalTrials.gov (NCT04232969). Between Jan 23, 2020, and April 23, 2022, 215 participants were screened for eligibility, of whom 194 were randomly assigned to exenatide (n=97) or placebo (n=97). 56 (29%) participants were female and 138 (71%) were male. 92 participants in the exenatide group and 96 in the placebo group had at least one follow-up visit and were included in analyses. At 96 weeks, MDS-UPDRS III OFF-medication scores had increased (worsened) by a mean of 5·7 points (SD 11·2) in the exenatide group, and by 4·5 points (SD 11·4) points in the placebo group (adjusted coefficient for the effect of exenatide 0·92 [95% CI –1·56 to 3·39]; p=0·47). Nine (9%) participants in the exenatide group had at least one serious adverse event compared with 11 (11%) in the placebo group. Our findings suggest that exenatide is safe and well tolerated. We found no evidence to support exenatide as a disease-modifying treatment for people with Parkinson's disease. Studies with agents that show better target engagement or in specific subgroups of patients are needed to establish whether there is any support for the use of GLP-1 receptor agonists for Parkinson's disease. National Institute for Health and Care Research and Cure Parkinson's.

Increasing numbers of genes are being implicated in Mendelian disorders and incorporated into clinical test panels. However, lack of evidence supporting the gene-disease relationship can hinder interpretation. We explored the utility of testing 51 additional genes for hypertrophic cardiomyopathy (HCM), one of the most commonly tested Mendelian disorders. Using genome sequencing data from 240 sarcomere gene negative HCM cases and 6229 controls, we undertook case-control and individual variant analyses to assess 51 genes that have been proposed for HCM testing. We found no evidence to suggest that rare variants in these genes are prevalent causes of HCM. One variant, in a single case, was categorized as likely to be pathogenic. Over 99% of variants were classified as a variant of uncertain significance (VUS) and 54% of cases had one or more VUS. For almost all genes, the gene-disease relationship could not be validated and lack of evidence precluded variant interpretation. Thus, the incremental diagnostic yield of extending testing was negligible, and would, we propose, be outweighed by problems that arise with a high rate of uninterpretable findings. These findings highlight the need for rigorous, evidence-based selection of genes for clinical test panels.

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily, which controls programs regulating cell proliferation, differentiation, and apoptosis. We have identified an unexpected role for GR in mitosis. We discovered that specifically modified GR species accumulate at the mitotic spindle during mitosis in a distribution that overlaps with Aurora kinases. We found that Aurora A was required to mediate mitosis-driven GR phosphorylation, but not recruitment of GR to the spindle. GR was necessary for mitotic progression, with increased time to complete mitosis, frequency of mitotic aberrations, and death in mitosis observed following GR knockdown. Complementation studies revealed an essential role for the GR ligand-binding domain, but no clear requirement for ligand binding in regulating chromosome segregation. The GR N-terminal domain, and specifically phosphosites S203 and S211, were not required. Reduced GR expression results in a cell cycle phenotype, with isolated cells from mouse and human subjects showing changes in chromosome content over prolonged passage. Furthermore, GR haploinsufficient mice have an increased incidence of tumor formation, and, strikingly, these tumors are further depleted for GR, implying additional GR loss as a consequence of cell transformation. We identified reduced GR expression in a panel of human liver, lung, prostate, colon, and breast cancers. We therefore reveal an unexpected role for the GR in promoting accurate chromosome segregation during mitosis, which is causally linked to tumorigenesis, making GR an authentic tumor suppressor gene. Significance We have discovered a role for the glucocorticoid receptor (GR) in coordinating cell division. We find enrichment of GR to mitotic spindles and demonstrate that GR knockdown causes accumulation of mitotic defects, including delayed anaphase, ternary chromosome segregation, and death in mitosis. Mitotic GR function requires the ligand-binding domain but not ligand binding, revealing a nontranscriptional and ligand-independent mechanism of action. Analysis of GR haploinsufficient cells and tissues reveals increased aneuploidy and DNA damage, and mice show an increased incidence of tumors in vivo, with further GR loss within those incident tumors. We also identify reduced GR expression in several common human cancers, thereby implicating GR as a novel tumor suppressor gene.

Introduction There is currently no published data on the effectiveness of DAA treatment for elimination of HCV infection in HIV‐infected populations at a population level. However, a number of relevant studies and initiatives are emerging. This research aims to report cascade of care data for emerging HCV elimination initiatives and studies that are currently being evaluated in HIV/HCV co‐infected populations in the context of implementation science theory. Methods HCV elimination initiatives and studies in HIV co‐infected populations that are currently underway were identified. Context, intervention characteristics and cascade of care data were synthesized in the context of implementation science frameworks. Results Seven HCV elimination initiatives and studies were identified in HIV co‐infected populations, mainly operating in high‐income countries. Four were focused mainly on HCV elimination in HIV‐infected gay and bisexual men (GBM), and three included a combination of people who inject drugs (PWID), GBM and other HIV‐infected populations. None were evaluating treatment delivery in incarcerated populations. Overall, HCV RNA was detected in 4894 HIV‐infected participants (range within studies: 297 to 994): 48% of these initiated HCV treatment (range: 21% to 85%; within studies from a period where DAAs were broadly available the total is 57%, range: 36% to 74%). Among studies with treatment completion data, 96% of 1109 initiating treatment completed treatment (range: 94% to 99%). Among those who could be assessed for sustained virological response at 12 weeks (SVR12), 1631 of 1757 attained SVR12 (93%, range: 86% to 98%). Conclusions Early results from emerging research on HCV elimination in HIV‐infected populations suggest that HCV treatment uptake is higher than reported levels prior to DAA treatment availability, but approximately half of patients remain untreated. These results are among diagnosed populations and additional effort is required to increase diagnosis rates. Among those who have initiated treatment, completion and SVR rates are promising. More data are required in order to evaluate the effectiveness of these elimination programmes in the long term, assess which intervention components are effective, and whether they need to be tailored to particular population groups.

Neptune-sized planets exhibit a wide range of compositions and densities, depending on factors related to their formation and evolution history, such as the distance from their host stars and atmospheric escape processes. They can vary from relatively low-density planets with thick hydrogen–helium atmospheres 1 , 2 to higher-density planets with a substantial amount of water or a rocky interior with a thinner atmosphere, such as HD 95338 b (ref.  3 ), TOI-849 b (ref.  4 ) and TOI-2196 b (ref.  5 ). The discovery of exoplanets in the hot-Neptune desert 6 , a region close to the host stars with a deficit of Neptune-sized planets, provides insights into the formation and evolution of planetary systems, including the existence of this region itself. Here we show observations of the transiting planet TOI-1853 b, which has a radius of 3.46 ± 0.08 Earth radii and orbits a dwarf star every 1.24 days. This planet has a mass of 73.2 ± 2.7 Earth masses, almost twice that of any other Neptune-sized planet known so far, and a density of 9.7 ± 0.8 grams per cubic centimetre. These values place TOI-1853 b in the middle of the Neptunian desert and imply that heavy elements dominate its mass. The properties of TOI-1853 b present a puzzle for conventional theories of planetary formation and evolution, and could be the result of several proto-planet collisions or the final state of an initially high-eccentricity planet that migrated closer to its parent star. Observations of the super-massive Neptune-sized transiting planet TOI-1853 b show a mass almost twice that of any other Neptune-sized planet known so far and a bulk density implying that heavy elements dominate its mass.

The 2013–2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics. Frequent dispersal and short-lived local transmission clusters fuelled the 2013–2016 Ebola virus epidemic in Guinea, Liberia and Sierra Leone. Evolution of an epidemic Understanding how and why viruses spread during epidemics is crucial for planning how to prevent and respond to future threats. Andrew Rambaut and colleagues provide an overview of the genetic epidemiology of the 2013–2016 epidemic caused by Ebola virus in West Africa. By analysing more than 1,600 Ebola virus genomes, the authors determine the factors that were important in the spread of the epidemic and also explain why the virus did not spread into neighbouring countries.