Safeguarding in adolescent mental health research: navigating dilemmas and developing procedures.

Mental disorders are prevalent during adolescence. Self-harm and suicide are more common in adolescents with a probable mental disorder, with one in four reporting to have attempted self-harm. Research involving adolescents is, therefore, likely to include participants experiencing mental ill health, even if mental health is not the primary focus. Researchers should adopt procedures and principles that safeguard adolescent mental health in their research practice. Yet there are gaps between theory and practice of research with adolescents in relation to their mental health, and limited guidance is available.We discuss emerging safeguarding dilemmas and procedures in adolescent mental health research. Our experiences of safeguarding adolescent mental health are grounded in the UK National Institute for Health and Care Research-funded SMART Schools Study. Drawing from this secondary school-based study, we focus on how our research team encountered and addressed a high prevalence of participants (aged 12-13 and 14-15 years) reporting thoughts and behaviours related to self-harm or suicide (24% of participants). This included reviewing our existing risk mitigation processes and consulting with several committees including young people with lived experiences of mental health.We present the SMART Schools study safeguarding approach for adolescent mental health. This encompasses key safeguarding principles, study procedures and relevant justifications. We address school and university roles and responsibilities, pupil understanding, and efficient, effective and secure communication pathways. We embed guidance throughout this article for researchers working with adolescents in the context of mental health. Lastly, we present five key recommendations to safeguard the mental health of adolescents participating in research, including (1) appointing a safeguarding lead within the research team; (2) codesigning a bespoke study safeguarding approach; (3) adopting a responsive approach to mental health safeguarding; (4) being transparent about the study mental health safeguarding approach and (5) report the implementation and outcomes of safeguarding approaches.Trial registration number ISRCTN77948572.

Associations between School-Level Disadvantage, Bullying Involvement and Children's Mental Health.

Bullying is a modifiable risk factor for poor mental health across childhood and adolescence. It is also socially patterned, with increased prevalence rates in more disadvantaged settings. The current study aimed to better understand whether school-level disadvantage is associated with different types of bullying roles, and whether it is a moderator in the association between bullying and children's mental health. Cross-sectional data were used from 4727 children aged 6-11 years, from 57 primary schools across England and Wales. The child data included previous bullying involvement and bullying role characteristics (bully, victim, bully-victim, reinforcer, defender, outsider), and the teacher-reported data included each child's mental health (emotional symptoms and externalizing) problems. School-level disadvantage was calculated from the proportion of children in the school eligible to receive free school meals (an indicator of disadvantage). Children in more disadvantaged schools were more likely to report being bully perpetrators, bully-victims, and engage less in defending behaviors during a bullying incident. Children from more disadvantaged schools who reported bullying others showed fewer emotional symptoms than those from less disadvantaged schools. There was no other evidence of moderation by school-level disadvantage between bullying roles and emotional and externalizing problems. The findings highlight the potential for school-based interventions targeting children's emotional and social development, targeting bullying, and promoting defending behaviors, particularly in more disadvantaged settings.

Acute Effect of Night Shift Work on Endothelial Function with and without Naps: A Scoping Review.

We examined the breadth and depth of the current evidence investigating napping/sleeping during night shift work and its impact on non-invasive measures of endothelial function. We used a scoping review study design and searched five databases: Ovid Medline, EMBASE, Ovid APA PsycInfo, Web of Science Core Collection, and EBSCO CINAHL. We limited our search to English language and publications from January 1980 to September 2022. Our reporting adhered to the PRISMA-ScR guidance for scoping reviews. Our search strategy yielded 1949 records (titles and abstracts) after deduplication, of which 36 were retained for full-text review. Five articles were retained, describing three observational and two experimental research studies with a total sample of 110 individuals, which examined the non-invasive indicators of endothelial function in relation to the exposure to night shift work. While there is some evidence of an effect of night shift work on the non-invasive indicators of endothelial function, this evidence is incomplete, limited to a small samples of shift workers, and is mostly restricted to one measurement technique for assessing endothelial function with diverse protocols. In addition, there is no identifiable research investigating the potential benefits of napping during night shift work on non-invasive measures of endothelial function.

Three-phase hierarchical model-based and hybrid inference.

Global commitments to mitigating climate change and halting biodiversity loss require reliable information about Earth's ecosystems. Increasingly, such information is obtained from multiple sources of remotely sensed data combined with data acquired in the field. This new wealth of data poses challenges regarding the combination of different data sources to derive the required information and assess uncertainties. In this article, we show how predictors and their variances can be derived when hierarchically nested models are applied. Previous studies have developed methods for cases involving two modeling steps, such as biomass prediction relying on tree-level allometric models and models linking plot-level field data with remotely sensed data. This study extends the analysis to cases involving three modeling steps to cover new important applications. The additional step might involve an intermediate model, linking field and remotely sensed data available from a small sample, for making predictions that are subsequently used for training a final prediction model based on remotely sensed data:•In cases where the data in the final step are available wall-to-wall, we denote the approach three-phase hierarchical model-based inference (3pHMB),•In cases where the data in the final step are available as a probability sample, we denote the approach three-phase hierarchical hybrid inference (3pHHY).

Susceptibility of the adult house fly (Diptera: Muscidae) and 3 of its principal parasitoids (Hymenoptera: Pteromalidae) to the GHA strain of Beauveria bassiana and 4 isolates from field-collected muscid flies.

House fly (Musca domestica L.) (Diptera: Muscidae) populations can negatively impact poultry layer facilities, posing a risk to human and animal health and egg food safety. House flies quickly develop resistance to traditional chemical control methods; therefore, improved biological control may provide opportunities for improved integrated pest management (IPM) programs. Biological control methods currently used include augmentative releases of pteromalid pupal parasitoids and application of the fungal entomopathogen Beauveria bassiana (Balsamo) Vuillemin. This study used bioassays to compare the impact of different B. bassiana strains on survival of house flies and of 3 species of filth fly parasitoids. The B. bassiana that were compared were 3 new field-collected isolates, an older field-collected isolate (L90), and a common commercially available strain (GHA). Flies and parasitoids were exposed to filter paper treated with 1.5 × 109 spores of each strain and a control. All field-isolated strains induced lower mean survival times in house flies than GHA did. The results for all species of parasitoids demonstrated less difference among the treatment groups and the control than in-house flies. Although there was some effect of B. bassiana exposure on parasitoid mortality, the expected spatial separation of parasitoids from areas of application may offer some protection. Using the most effective tested strains of B. bassiana and filth fly parasitoids jointly could be a biological component of an IPM plan for fly control in poultry facilities.

Smartphones, social Media and Adolescent mental well-being: the impact of school policies Restricting dayTime use-protocol for a natural experimental observational study using mixed methods at secondary schools in England (SMART Schools Study).

INTRODUCTION: Smartphone and social media use is prevalent during adolescence, with high levels of use associated with lower levels of mental well-being. Secondary schools in the UK have introduced policies that restrict daytime use of smartphones and social media, but there is no evaluation on the impact of these policies on adolescent mental well-being. The SMART Schools Study aims to determine the impact of daytime restrictions of smartphone and social media use on indicators of adolescent mental well-being, anxiety, depression, physical activity, sleep, classroom behaviour, attainment and addictive social media use. METHODS AND ANALYSIS: This is a natural experimental observational study using mixed methods. Secondary schools within a 100 mile radius of the recruiting centre in the West Midlands (UK) have been categorised into two groups: Schools that restrict (intervention) and permit (comparator) daytime use of smartphones. We aim to recruit 30 schools (20 restrictive, 10 permissive) and 1170 pupils aged 12-13 and 14-15 years. We will collect data on mental well-being, anxiety and depressive symptoms, phone and social media use, sleep and physical activity from pupil surveys, and accelerometers. Policy implementation measures and data on individual pupil factors will be collected through school staff surveys, and website/policy analysis. Six case study schools will explore individual, school and family/home factors that influence relationships between school smartphone policies, smartphone/social media use, and mental well-being. Economic evaluation will be completed through a cost-consequence analysis from an education sector perspective. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Birmingham's Research Ethics Committee (ERN_22-0723). Parents/carers of pupil participants can complete a form to opt their child out of the study. Pupil, school staff and parent/carer participants are asked to complete online/written consent (or assent). Findings will be disseminated through policy briefings, resources for schools, social media, reports, and open access publications. TRIAL REGISTRATION NUMBER: ISRCTN77948572.

Military HealthySteps Pilot Program Outcome Study.

INTRODUCTION: Military families face many unique challenges, including frequent separations, demanding work hours, and relocations. The HealthySteps (HS) program may offset these challenges utilizing the expertise of a nonclinical child development specialist called a HS specialist who offers enhanced well-child visits (WCVs), support between visits, and connections to community resources. Our study sought to identify the impact of the military HS pilot program on the timeliness of WCVs, immunizations, routine behavioral and developmental screenings, and referrals to community resources within the first 15 months of life (MOL). MATERIALS AND METHODS: We retrospectively reviewed charts of 26 HS-enrolled and 26 randomly selected age-matched non-HS-enrolled children from age 2 to 15 MOL. Demographic variables obtained include child's gender, child's birth order, mother's age, active duty parent's rank classification, and active duty parent's gender. We examined five outcomes measures aligning with the American Academy of Pediatrics health supervision, immunization, and screening recommendations and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set measures: (1) completed six or more WCVs in the first 15 MOL, (2) completed developmental screening at the 9-month WCV, (3) up to date on vaccinations at 15 MOL, (4) completed three or more postpartum depression (PPD) screens in the first 6 MOL, and (5) the total number of documented referrals to community resources within the first 15 MOL. Chi-square analysis and independent t-tests were used to compare the groups. RESULTS: There was no statistical significance (P > .05) between the HS-enrolled and control groups for all five demographic variables. A significantly higher percentage of children in the HS-enrolled group received PPD screening compared to the control group (96% vs. 73.1%, P = .021). The HS-enrolled group had a higher mean number of community resource referrals at 15 MOL of 2.46 (SD = 1.14) vs. the control group with a mean of 0.19 (SD = 0.49). None of the other outcomes showed a statistically significant difference between groups. CONCLUSIONS: The results of this study indicate the positive impacts of the military HS program on referrals to community resources and PPD screening, reflecting the HS specialist focus on the family unit. Limitations of this study include the small population size and limited demographic information resulting from the retrospective nature of the study and pilot status of the HS program. Larger prospective studies are needed to clarify the true impact of the HS program in the military health system.

Correction: Chen et al. Computational Fluid Dynamics Analysis of Alternative Ventilation Schemes in Cage-Free Poultry Housing. Animals 2021, 11, 2352.

There was an error in the original publication [...].

Numerical Simulation of Airborne Disease Spread in Cage-Free Hen Housing with Multiple Ventilation Options.

The current ventilation designs of poultry barns have been present deficiencies with respect to the capacity to protect against disease exposure, especially during epidemic events. An evolution of ventilation options is needed in the egg industry to keep pace with the advancing transition to cage-free production. In this study, we analyzed the performances of four ventilation schemes for constraining airborne disease spread in a commercial cage-free hen house using computational fluid dynamics (CFD) modeling. In total, four three-dimensional models were developed to compare a standard ventilation configuration (top-wall inlet sidewall exhaust, TISE) with three alternative designs, all with mid-wall inlet and a central vertical exhaust. A one-eighth scale commercial floor-raised hen house with 2365 hens served as the model. Each ventilation configuration simulated airflow and surrogate airborne virus particle spread, assuming the initial virus was introduced from upwind inlets. Simulation outputs predicted the MICE and MIAE models maintained a reduced average bird level at 47% and 24%, respectively, of the standard TISE model, although the MIRE model predicted comparable virus mass fraction levels with TISE. These numerical differences unveiled the critical role of centrally located vertical exhaust in removing contaminated, virus-laden air from the birds housing environment. Moreover, the auxiliary attic space in the MIAE model was beneficial for keeping virus particles above the bird-occupied floor area.

A spatial and temporal assessment of nonresponse in the national forest inventory of the U.S.

In nearly all national forest inventories (NFI), some sample plots are unable to be measured such that nonresponse may be an issue of concern. Thus, it is of particular interest to understand the phenomenon in terms of current status and temporal change in nonresponse rates and the associated spatial distribution on the landscape. In the NFI of the USA, denial of access permission on privately owned forest land and hazardous conditions has led to an overall nonresponse rate of 9.8% with some areas exceeding 20% of plots being inaccessible. Further, it was found that nearly 50% of the areas studied were exhibiting increasing rates of nonresponse over time. Comparisons between response and nonresponse plots via remote sensing characteristics suggested there may be systematic differences in some parts of the country, which may cause bias in the sample and resulting estimates. The findings indicate that improved communication strategies with private landowners are needed to reduce nonresponse rates. Due to the unlikelihood of eliminating nonresponse entirely, methods to mitigate potential nonresponse bias should be considered for incorporation into the estimation of population parameters.

The UK stand together trial: protocol for a multicentre cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of KiVa to reduce bullying in primary schools.

BACKGROUND: Reducing bullying is a public health priority. KiVa, a school-based anti-bullying programme, is effective in reducing bullying in Finland and requires rigorous testing in other countries, including the UK. This trial aims to test the effectiveness and cost-effectiveness of KiVa in reducing child reported bullying in UK schools compared to usual practice. The trial is currently on-going. Recruitment commenced in October 2019, however due to COVID-19 pandemic and resulting school closures was re-started in October 2020. METHODS: Design: Two-arm pragmatic multicentre cluster randomised controlled trial with an embedded process and cost-effectiveness evaluation. PARTICIPANTS: 116 primary schools from four areas; North Wales, West Midlands, South East and South West England. Outcomes will be assessed at student level (ages 7-11 years; n = approximately 13,000 students). INTERVENTION: KiVa is a whole school programme with universal actions that places a strong emphasis on changing bystander behaviour alongside indicated actions that provide consistent strategies for dealing with incidents of bullying. KiVa will be implemented over one academic year. COMPARATOR: Usual practice. PRIMARY OUTCOME: Student-level bullying-victimisation assessed through self-report using the extensively used and validated Olweus Bully/Victim questionnaire at baseline and 12-month follow-up. SECONDARY OUTCOMES: student-level bullying-perpetration; student mental health and emotional well-being; student level of, and roles in, bullying; school related well-being; school attendance and academic attainment; and teachers' self-efficacy in dealing with bullying, mental well-being, and burnout. SAMPLE SIZE: 116 schools (58 per arm) with an assumed ICC of 0.02 will provide 90% power to identify a relative reduction of 22% with a 5% significance level. RANDOMISATION: recruited schools will be randomised on 1:1 basis stratified by Key-Stage 2 size and free school meal status. Process evaluation: assess implementation fidelity, identify influences on KiVa implementation, and examine intervention mechanisms. Economic evaluation: Self-reported victimisation, Child Health Utility 9D, Client Service Receipt Inventory, frequency of services used, and intervention costs. The health economic analysis will be conducted from a schools and societal perspective. DISCUSSION: This two-arm pragmatic multicentre cluster randomised controlled trial will evaluate the KiVa anti-bullying intervention to generate evidence of the effectiveness, cost-effectiveness and scalability of the programme in the UK. Our integrated process evaluation will assess implementation fidelity, identify influences on KiVa implementation across England and Wales and examine intervention mechanisms. The integrated health economic analysis will be conducted from a schools and societal perspective. Our trial will also provide evidence regarding the programme impact on inequalities by testing whether KiVa is effective across the socio-economic gradient. TRIAL REGISTRATION: Trials ISRCTN 12300853 Date assigned 11/02/2020.

Computational Fluid Dynamics Analysis of Alternative Ventilation Schemes in Cage-Free Poultry Housing.

This work investigated alternative ventilation schemes to help define a proper ventilation system design in cage-free hen houses with the goal of assuring bird welfare through comfortable conditions. Computational fluid dynamics (CFD) modeling was employed to simulate indoor and outdoor airflows to quantify the effectiveness of ventilation systems in maintaining suitable and uniform living conditions at the hen level. Four three-dimensional CFD models were developed based on a full-scale floor-raised layer house, corresponding to ventilation schemes of the standard top-wall inlet, sidewall exhaust, and three alternatives: mid-wall inlet, ceiling exhaust; mid-wall inlet, ridge exhaust; and mid-wall inlet, attic exhaust with potential for pre-treatment of exhaust air. In a sophisticated and powerful achievement of the analysis, 2365 birds were individually modeled with simplified bird-shapes to represent a realistic number, body heat, and airflow obstruction of hens housed. The simulated ventilation rate for the layer house models was 1.9-2.0 m3/s (4100 ft3/min) in the desired range for cold weather (0 °C). Simulation results and subsequent analyses demonstrated that these alternative models had the capacity to create satisfactory comfortable temperature and air velocity at the hen level. A full-scale CFD model with individual hen models presented robustness in evaluating bird welfare conditions.

A proposed pediatric risk stratification method (PRiSM) for disaster preparedness.

OBJECTIVE: Children are a uniquely vulnerable population in times of disaster. Understanding the risk associated with the pediatric population is complex and involves aspects beyond just the medical needs of children. DESIGN: We reviewed current literature in two databases regarding risk and disaster preparedness in children to assess current risk stratification methodologies across multiple domains including medical, social, and educational. RESULTS: No comprehensive risk stratification tool exists that considers multiple domains. Three key domains are inter-related to a child's vulnerability in times of disaster; medical, educational, and social. We propose a pediatric risk stratification method (PRiSM) for disaster preparedness as one way to consider the three critical domains. Using existing medical, educational, and social data, our proposed framework considers all three domains to stratify children by their degree of risk in terms of disaster preparedness. PRiSM consists of a three-digit alphanumeric guide to stratify patients based on complex medical, educational, and social needs. CONCLUSION: This framework provides a possible method to risk stratify children prior to a disaster to better inform planning and responses in the future.

Eclipse stemless shoulder prosthesis vs. Univers II shoulder prosthesis: a multicenter, prospective randomized controlled trial.

BACKGROUND: Total shoulder arthroplasty is an accepted treatment for glenohumeral osteoarthritis. The Arthrex Eclipse shoulder prosthesis is a stemless, canal-sparing humeral prosthesis with bone ingrowth capacity on the trunnion, as well as through the fenestrated hollow screw, that provides both diaphyseal and metaphyseal load sharing and fixation. METHODS: Between 2013 and 2018, 16 sites in the United States enrolled 327 patients (Eclipse in 237 and Arthrex Univers II in 90). All patients had glenohumeral arthritis refractory to nonsurgical care. Strict exclusion criteria were applied to avoid confounding factors such as severe patient comorbidities, arthritis not consistent with osteoarthritis, and medical or prior surgical treatments that may have affected outcomes. Patients were randomized to the Eclipse or Univers II group via block randomization. RESULTS: In total, 149 Eclipse and 76 Univers II patients reached 2-year follow-up (139 Eclipse patients [93.3%] and 68 Univers II patients [89.5%] had complete data). The success rate using the Composite Clinical Success score was 95% in the Eclipse group vs. 89.7% in the Univers II group. No patient exhibited radiographic evidence of substantial humeral radiolucency, humeral migration, or subsidence at any point. Reoperations were performed in 7 patients (3.2%) in the Eclipse group and 3 (3.8%) in the Univers II group. CONCLUSION: The Arthrex Eclipse shoulder prosthesis is a safe and effective humeral implant for patients with glenohumeral arthritis at 2-year follow-up, with no differences in outcomes compared with the Univers II shoulder prosthesis.

Computational Fluid Dynamics Modeling of Ventilation and Hen Environment in Cage-Free Egg Facility.

Poultry facilities are going through an evolution in design due to growing demands for cage-free eggs and egg products without unified guidelines to accommodate these transitions. The goal of this study was to help builders and egg producers assess current ventilation design within cage-free production facilities for conditions that impact hen comfort and welfare. The method of evaluation was simulation of the indoor environment of a hen house via computational fluid dynamics (CFD) modeling with individual hens modeled at a typical stocking density. This paper describes the development of a three-dimensional model of a commercial floor-raised cage-free hen house that is cross-ventilated to document current environmental conditions. A one-eighth section of the barn was modeled at full-scale using existing ventilation schemes with each bird represented by a hen-shaped, heated, solid body. A conventional top-wall inlet, side-wall exhaust (TISE) ventilation configuration was modeled for this study. The simulated ventilation rate for the hen house was approximately 3 m3/h (1.77 ft3/min) per hen resulting in 7092 m3/h (4174 ft3/min) for the 2365 birds, which falls at the higher end of the desired cold weather (0 °C) ventilation range. Contours of airflow, temperature, and pressure were generated to visualize results. Three two-dimensional planes were created at representative cross-sections to evaluate the contours inside and outside the barn. Five animal-occupied zones within each of the model planes were evaluated for practical hen comfort attributes. The simulation output suggested the TISE standard ventilation system could limit air speed to a comfortable average of 0.26 m/s (51 ft/min) and the temperature could be maintained between 18 and 24 °C on average at the bird level. Additionally, the indoor static pressure difference was very uniform averaging -25 Pascal (0.1 inches of water), which falls in the normal range for a floor-raised hen house with negative-pressure ventilation during cold weather conditions. Findings confirmed that CFD modeling can be a powerful tool for studying ventilation system performance at the bird level, particularly when individual animals are modeled, to assure a comfortable indoor environment for animal welfare in poultry facilities.

Inactivation of Escherichia coli K-12 in Liquid Egg White By a Flow-through Pulsed Uv Light Treatment System.

ABSTRACT: Unpasteurized liquid egg can be contaminated with pathogenic microorganisms and may cause foodborne outbreaks. Thus, it is essential to decontaminate the liquid egg to ensure food safety. Pulsed UV light is one of the emerging technologies for food decontamination in recent years. This static treatment system has been studied previously in our laboratory. However, continuous processing using a flow-through treatment system needs to be evaluated for potential commercial applications. Therefore, in this study, a flow-through treatment system of pulsed UV light was evaluated and optimized for inactivation of Escherichia coli K12NSR for liquid egg white decontamination. Treatment factors including flow rate (40 to 80 mL/min), number of passes (one to three passes), and distance from the sample to the pulsed UV light strobe (5 to 13 cm) were optimized using response surface methodology. This methodology suggested three passes with 40 mL/min flow rate and a 5-cm distance as the optimum conditions. The model was then validated for the maximum reduction of E. coli K12NSR, which was measured as 1.57 log CFU/mL at the optimal conditions. The energy doses of the pulsed UV light and temperature changes of the liquid egg white during the treatment were measured. Furthermore, several quality parameters were assessed at the optimum treatment conditions to determine the impact of the flow-through pulsed UV processing on the quality of liquid egg white. The results showed significant differences in pH, lipid oxidation, turbidity, and color between control and pulsed UV light-treated samples (P < 0.05). However, there was no significant difference in foaming ability or foam stability between pulsed UV light-treated samples and the control. Overall, this study demonstrated the potential of flow-through pulsed UV light to decontaminate liquid egg white, but further research is needed for optimal enhancement.

Childhood physical abuse and emotional neglect are specifically associated with adult mental disorders.

Background: Childhood adversities and trauma (CAT) are associated with adult mental disorders. Nevertheless, although CAT of different domains mostly co-occurs, and co-morbidity is common, the associations between CAT and mental disorders, when taking these interrelations into account, are not well known.Aims: We aimed to study differential associations between the five core domains of CAT and current axis-I disorders, taking into consideration their interrelations.Methods: Four hundred and fifteen outpatients attending adult primary (n = 255) and psychiatric care (n = 160) were assessed with the Trauma and Distress Scale (TADS) and the Mini International Neuropsychiatric Interview (MINI). Associations between CAT core domains and diagnostic categories were examined by path analyses.Results: At least some infrequent experience of CAT (83.6%), mostly of neglect, and current mental disorders (49.4%), mostly depression, was frequent, as were co-morbidities and co-occurrence of CAT domains. Considering these interrelations in a path model of excellent fit, physical abuse predicted depressive, manic, psychotic and anxiety disorders, whereas emotional neglect predicted depressive, anxiety and substance misuse disorders.Conclusions: Of all five CAT core domains, physical abuse and emotional neglect had the strongest association with adult psychiatric disorders and might have transmitted earlier reported main effects of other CAT domains onto mental disorders.

Childhood adversity predicts persistence of suicidal thoughts differently in females and males at clinical high-risk patients of psychosis. Results of the EPOS project.

AIM: Depression and suicidal ideation (SUI) and behaviour are more prevalent in females than males, and common in clinical high-risk (CHR) patients. Childhood adversities and trauma (CAT) are associated with adult depression and SUI. The role of gender as a moderator and depression as a mediator for the effect of CAT on SUI has not been explored in CHR patients. METHODS: In all, 245 young help-seeking CHR patients were assessed for SUI (thoughts of killing themselves) with the Beck Depression Inventory at baseline, 9-month and 18-month follow-ups. At baseline, clinical depression was assessed by the Structured Clinical Interview for DSM-IV (SCID-I), and CAT by the Trauma and Distress Scale (TADS) which includes the five domains of emotional, physical and sexual abuse, emotional and physical neglect. RESULTS: CAT total and all domains except physical neglect predicted SUI over the study period. The effect of CAT on SUI was mediated via clinical depression and concurrent depression symptoms differently for females and males. In females, the effect of emotional abuse and neglect on SUI was mediated via baseline depression. In males, emotional and physical abuse had a direct effect on SUI, and the effect of sexual abuse and emotional neglect was partly mediated via concurrent depression symptoms. CONCLUSIONS: For CHR females, the effect of CAT on adult SUI is mediated via depression, while for males, CAT and its domains have mainly direct effects in maintaining SUI. These gender differences should be taken into account when treating CHR patients with SUI.

Identification of distinct conformations associated with monomers and fibril assemblies of mutant huntingtin.

The N-terminal fragments of mutant huntingtin (mHTT) misfold and assemble into oligomers, which ultimately bundle into insoluble fibrils. Conformations unique to various assemblies of mHTT remain unknown. Knowledge on the half-life of various multimeric structures of mHTT is also scarce. Using a panel of four new antibodies named PHP1-4, we have identified new conformations in monomers and assembled structures of mHTT. PHP1 and PHP2 bind to epitopes within the proline-rich domain (PRD), whereas PHP3 and PHP4 interact with motifs formed at the junction of polyglutamine (polyQ) and polyproline (polyP) repeats of HTT. The PHP1- and PHP2-reactive epitopes are exposed in fibrils of mHTT exon1 (mHTTx1) generated from recombinant proteins and mHTT assemblies, which progressively accumulate in the nuclei, cell bodies and neuropils in the brains of HD mouse models. Notably, electron microscopic examination of brain sections of HD mice revealed that PHP1- and PHP2-reactive mHTT assemblies are present in myelin sheath and in vesicle-like structures. Moreover, PHP1 and PHP2 antibodies block seeding and subsequent fibril assembly of mHTTx1 in vitro and in a cell culture model of HD. PHP3 and PHP4 bind to epitopes in full-length and N-terminal fragments of monomeric mHTT and binding diminishes as the mHTTx1 assembles into fibrils. Interestingly, PHP3 and PHP4 also prevent the aggregation of mHTTx1 in vitro highlighting a regulatory function for the polyQ-polyP motifs. These newly detected conformations may affect fibril assembly, stability and intercellular transport of mHTT.