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The proliferation of extremely intense synchrotron sources has enabled ever higher-resolution structures to be obtained using data collected from smaller and often more imperfect biological crystals (Helliwell, 1984). Synchrotron beamlines now exist that are capable of measuring data from single crystals that are just a few micrometres in size. This provides renewed motivation to study and understand the radiation damage behaviour of small protein crystals. Reciprocal-space mapping and Bragg coherent diffractive imaging experiments have been performed on cryo-cooled microcrystals of hen egg-white lysozyme as they undergo radiation damage. Several well established metrics, such as intensity-loss and lattice expansion, are applied to the diffraction data and the results are compared with several new metrics that can be extracted from the coherent imaging experiments. Individually some of these metrics are inconclusive. However, combining metrics, the results suggest that radiation damage behaviour in protein micro-crystals differs from that of larger protein crystals and may allow them to continue to diffract for longer. A possible mechanism to account for these observations is proposed. [ABSTRACT FROM AUTHOR]

Introduction: Psychotic experiences (PEs) are associated with increased risk of later mental disorders and so could be valuable in prevention studies. However, to date few intervention studies have examined PEs. Given this lack of evidence, in the current study a secondary data analysis was conducted on a clustered-randomized control trial (RCT) of 3 school based interventions to reduce suicidal behaviour, to investigate if these may reduce rates of PEs, and prevent PE, at 3-month and 1-year follow-up., Methods: The Irish site of the Saving and Empowering Young Lives in Europe study, trial registration (DRKS00000214), a cluster-RCT designed to examine the effect of school-based interventions on suicidal thoughts and behaviour. Seventeen schools (n = 1096) were randomly assigned to one of three intervention arms or a control arm. The interventions included a teacher training (gate-keeper) intervention, an interactive educational (universal-education) intervention, and a screening and integrated referral (selective-indicative) intervention. The primary outcome of this secondary data-analysis was reduction in point-prevalence of PEs at 12 months. A second analysis excluding those with PEs at baseline was conducted to examine prevention of PEs. Additional analysis was conducted of change in depression and anxiety scores (comparing those with/without PEs) in each arm of the intervention. Statistical analyses were conducted using mixed-effects modelling., Results: At 12-months, the screening and referral intervention was associated with a significant reduction in PEs (OR:0.12,95%CI[0.02-0.62]) compared to the control arm. The teacher training and education intervention did not show this effect. Prevention was also observed only in the screening and referral arm (OR:0.30,95%CI[0.09-0.97]). Participants with PEs showed higher levels of depression and anxiety symptoms, compared to those without, and different responses to the screening and referral intervention & universal-education intervention., Conclusions: This study provides the first evidence for a school based intervention that reduce & prevent PEs in adolescence. This intervention is a combination of a school-based screening for psychopathology and subsequent referral intervention significantly reduced PEs in adolescents. Although further research is needed, our findings point to the effectiveness of school-based programmes for prevention of future mental health problems., (© 2023. The Author(s).)

Psychotic experiences (PE) are common in the general population, in particular in childhood, adolescence and young adulthood. PE have been shown to be associated with an increased risk for later psychotic disorders, mental disorders, and poorer functioning. Recent findings have highlighted the relevance of PE to many fields of healthcare, including treatment response in clinical services for anxiety & depression treatment, healthcare costs and service use. Despite PE relevance to many areas of mental health, and healthcare research, there remains a gap of information between PE researchers and experts in other fields. With this review, we aim to bridge this gap by providing a broad overview of the current state of PE research, and future directions. This narrative review aims to provide an broad overview of the literature on psychotic experiences, under the following headings: (1) Definition and Measurement of PE; (2) Risk Factors for PE; (3) PE and Health; (4) PE and Psychosocial Functioning; (5) Interventions for PE, (6) Future Directions.

Dendritic cells (DCs) and macrophages are at the forefront of immune responses, modifying their transcriptional programs in response to their tissue environment or immunological challenge. Posttranslational modifications of histones, such as histone H3 lysine-27 trimethylation (H3K27me3) by the Polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells. Unexpectedly, EZH2 deficiency neither prevented the deposition and maintenance of H3K27me3 in DCs nor hindered DC/macrophage homeostasis. In contrast, SUZ12 deficiency markedly impaired the capacity of DCs and macrophages to maintain H3K27me3. SUZ12 ablation induced a rapid loss of the alveolar macrophage and Langerhans cell networks under both steady state and inflammatory conditions because these cells could no longer proliferate to facilitate their self-renewal. Despite the reduced H3K27me3, DC development and function were unaffected by SUZ12 ablation, suggesting that PRC2-mediated gene repression was dispensable for DC homeostasis. Thus, the role of SUZ12 highlights the fundamentally different homeostatic mechanisms used by tissue-resident myeloid cells versus DCs.

Background: Psychotic experiences (PE) are highly prevalent in childhood and are known to be associated with co-morbid mental health disorders and functional difficulties in adolescence. However, little is known about the long-term outcomes of young people who report PE., Methods: As part of the Adolescent Brain Development Study, 211 young people were recruited in childhood (mean age 11.7 years) and underwent detailed clinical interviews, with 25% reporting PE. A 10 year follow-up study was completed and 103 participants returned (mean age 20.9 years). Structured clinical interviews for DSM-5 (SCID-5) and interviewer-rated assessments of functioning were conducted. A detailed neuropsychological battery was also administered. Analyses investigated group differences between those who had ever reported PE and controls in early adulthood., Results: The PE group was at a significantly higher risk of meeting DSM-5 criteria for a current (OR 4.08, CI 1.16-14.29, p = 0.03) and lifetime psychiatric disorder (OR 3.27, CI 1.43-7.47, p = 0.005). They were also at a significantly higher risk of multi-morbid lifetime psychiatric disorders. Significantly lower scores on current social and global functioning measures were observed for the PE group. Overall, there were no differences in neuropsychological performance between groups apart from significantly lower scores on the Stroop Word task and the Purdue Pegboard task for the PE group., Conclusions: Our findings suggest that reports of PE are associated with poorer mental health and functional outcomes in early adulthood, with some persisting cognitive and motor deficits. Young people who report such symptoms could be considered a target group for interventions to aid functional outcomes.

Background: Psychotic experiences (PEs) are reported by a significant minority of adolescents and are associated with the development of psychiatric disorders. The aims of this study were to examine associations between PEs and a range of factors including psychopathology, adversity and lifestyle, and to investigate mediating effects of coping style and parental support on associations between adversity and PEs in a general population adolescent sample., Method: Cross-sectional data were drawn from the Irish centre of the Saving and Empowering Young Lives in Europe study. Students completed a self-report questionnaire and 973 adolescents, of whom 522 (53.6%) were boys, participated. PEs were assessed using the 7-item Adolescent Psychotic Symptom Screener., Results: Of the total sample, 81 (8.7%) of the sample were found to be at risk of PEs. In multivariate analysis, associations were found between PEs and number of adverse events reported (OR 4.48, CI 1.41-14.25; p < 0.011), maladaptive/pathological internet use (OR 2.70, CI 1.30-5.58; p = 0.007), alcohol intoxication (OR 2.12, CI 1.10-4.12; p = 0.025) and anxiety symptoms (OR 4.03, CI 1.57-10.33; p = 0.004). There were small mediating effects of parental supervision, parental support and maladaptive coping on associations between adversity and PEs., Conclusion: We have identified potential risk factors for PEs from multiple domains including adversity, mental health and lifestyle factors. The mediating effect of parental support on associations between adversity and PEs suggests that poor family relationships may account for some of this mechanism. These findings can inform the development of interventions for adolescents at risk.

Objective: To systematically review evidence for the association between trauma experienced in childhood or adolescence, and the subsequent experience of affective or psychotic mental disorders in adulthood., Methods: Electronic databases (Scopus, Medline (for Ovid), EMBASE and PsychINFO) were searched for peer-reviewed, longitudinal cohort studies in the English language examining child or adolescent exposure to trauma, and adult-diagnosed depression, anxiety, psychotic disorder or bipolar disorder. A total of 23 manuscripts were retained., Results: Results revealed a significant association between the following childhood exposures and adult mental disorder: bullying (victimhood, perpetration and frequency); emotional abuse; physical neglect; parental loss; and general maltreatment (unspecified and/or multiple trauma exposure). There was some evidence of a dose-response relationship with those exposed to multiple forms of maltreatment having more than three times the odds of developing a mental disorder (Odds ratio = 3.11, 95% CI = 1.36-7.14). There was no significant association found between physical or sexual abuse and adult mental disorder; however, this is likely an artefact of how these adversities were assessed., Conclusion: There is strong evidence of an association between childhood trauma and later mental illness. This association is particularly evident for exposure to bullying, emotional abuse, maltreatment and parental loss. The evidence suggests that childhood and adolescence are an important time for risk for later mental illness, and an important period in which to focus intervention strategies., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Mental ill-health is one of the most significant health and social issues affecting young people globally. To address the mental health crisis, a number of cross-sectoral research and action priorities have been identified. These include improving mental health literacy, translating research findings into accessible public health outputs, and the use of digital technologies. There are, however, few examples of public health-oriented knowledge transfer activities involving collaborations between researchers, the Arts, and online platforms in the field of youth mental health., Objective: The primary aim of this project was to translate qualitative research findings into a series of online public mental health animations targeting young people between the ages of 16 and 25 years. A further aim was to track online social media engagement and viewing data for the animations for a period of 12 months., Methods: Qualitative data were collected from a sample of 17 youth in Ireland, aged 18-21 years, as part of the longitudinal population-based Adolescent Brain Development study. Interviews explored the life histories and the emotional and mental health of participants. The narrative analysis revealed 5 thematic findings relating to young people's emotional and mental health. Through a collaboration between research, the Arts, and the online sector, the empirical thematic findings were translated into 5 public health animations. The animations were hosted and promoted on 3 social media platforms of the Irish youth health website called SpunOut. Viewing data, collected over a 12-month period, were analyzed to determine the reach of the animations., Results: Narrative thematic analysis identified anxiety, depression, feeling different, loneliness, and being bullied as common experiences for young people. These thematic findings formed the basis of the animations. During the 12 months following the launch of the animations, they were viewed 15,848 times. A majority of views occurred during the period of the social media ad campaign at a cost of €0.035 (approximately US $0.042) per view. Animations on feeling different and being bullied accounted for the majority of views., Conclusions: This project demonstrates that online animations provide an accessible means of translating empirical research findings into meaningful public health outputs. They offer a cost-effective way to provide targeted online information about mental health, coping, and help-seeking to young people. Cross-sectoral collaboration is required to leverage the knowledge and expertise required to maximize the quality and potential reach of any knowledge transfer activities. A high level of engagement is possible by targeting non-help-seeking young people on their native social media platforms. Paid promotion is, therefore, an important consideration when budgeting for online knowledge translation and dissemination activities in health research., (©Helen Coughlan, David Quin, Kevin O'Brien, Colm Healy, Jack Deacon, Naoise Kavanagh, Niamh Humphries, Mary C Clarke, Mary Cannon. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 09.02.2021.)

Background: Psychotic experiences (PEs) are not uncommon in young people and are associated with both psychopathology and compromised global functioning. Although psychotic experiences are transient (short-lived, self-resolving and non-recurring) for most people who report them, few studies have examined the association between early transient PEs and later functioning in population samples. Additionally, studies using self-report measures of interpersonal and educational/ vocational difficulties are lacking. The aim of this study was to examine the relationship between transient psychotic experiences and self-reported interpersonal and educational/vocational difficulties in adolescence and young adulthood., Methods: Participants were 103 young people from a longitudinal population-based study cohort of mental health in Ireland. They attended for baseline clinical interviews in childhood (age 11-13) and were followed up in young adulthood (age 19-25). Participants who reported psychotic experiences at baseline but not at follow-up were classified as having transient psychotic experiences. Data from both time-points were used to examine the association between transient psychotic experiences and self-reported interpersonal and educational/ vocational difficulties in young adulthood using poisson regression modelling., Results: Young people with a history of transient psychotic experiences reported significantly higher interpersonal (adj IRR: 1.83, 95%ileCI: 1.10-3.02, p = .02) and educational/vocational (adj IRR: 2.28, 95%ileCI: 1.43-3.64, p = .001) difficulties during adolescence. However, no significant differences in interpersonal (adj IRR: 0.49, 95%ileCI: 0.10-2.30, p = .37) or educational/vocational (adj IRR: 0.88, 95%ileCI: 0.37-2.08, p = .77) difficulties were found in young adulthood. Self-reported interpersonal and educational/vocational difficulties in young people both with and without a history of transient psychotic experiences decreased between adolescence and young adulthood., Conclusions: Young people with transient psychotic experiences have increased interpersonal and educational/vocational difficulties in adolescence but these may not persist into the young adult years. This finding indicates that early psychotic experiences may not confer high risk for long-term interpersonal or educational/vocational deficits among young people who experience these phenomena transiently.

Abnormal functional connectivity (FC, the temporal synchronization of activation across distinct brain regions) of the default mode (DMN), salience (SN), central executive (CEN), and motor (MN) networks is well established in psychosis. However, little is known about FC in individuals, particularly adolescents, reporting subthreshold psychotic experiences (PE) and their trajectory over time. Thus, the aim of this study was to investigate the FC of these networks in adolescents with PE. In this population-based case-control study, 24 adolescents (mean age = 13.58) meeting the criteria for PE were drawn from a sample of 211 young people recruited and scanned for a neuroimaging study, with a follow-up scan 2 years later (n = 18, mean age = 15.78) and compared to matched controls drawn from the same sample. We compared FC of DMN, SN, CEN, and MN regions between PE and controls using whole-brain FC analyses. At both timepoints, the PE group displayed significant hypoconnectivity compared to controls. At baseline, FC in the PE group was decreased between MN and DMN regions. At follow-up, dysconnectivity in the PE group was more widespread. Over time, controls displayed greater FC changes than the PE group, with FC generally increasing between MN, DMN, and SN regions. Adolescents with PE exhibit hypoconnectivity across several functional networks also found to be hypoconnected in established psychosis. Our findings highlight the potential for studies of adolescents reporting PE to reveal early neural correlates of psychosis and support further investigation of the role of the MN in PE and psychotic disorders., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Psychotic experiences (PEs) are common in early adolescence and are associated with nonpsychotic psychopathology. However, not all adolescents with PEs have subsequent psychopathology, and vice versa. To date, factors mediating the relationship between PEs and psychopathology have been understudied. The aims of this study were to investigate the bidirectional relationship between PEs and psychopathology in adolescence and to investigate potentially malleable mediators of these relationships. Data from 2 waves (age 13 and 17 years) of Cohort '98 of the Growing Up in Ireland study were examined ( n = 6,206). Using KHB pathway decomposition, we investigated the following as potential mediators of the relationship between psychopathology and PEs: parent-child relationship (conflict and positive), self-concept, and child-peer relationship (alienation and trust). Supplementary counterfactual mediation and sensitivity analyses were conducted. Early adolescents with psychopathology had twofold increased odds of late adolescent PEs (internalizing problems: odds ratio [OR] = 2.03, 95% confidence interval [CI; 1.56, 2.62]; externalizing problems: OR = 1.99, CI [1.51, 2.60]). Parent-child conflict explained between 23% and 34% of the associations between internalizing and externalizing problems and subsequent PEs. Early adolescents with PEs had increased odds of late adolescent psychopathology (internalizing problems: OR = 2.01, CI [1.61, 2.50]; externalizing problems: OR = 1.70, CI [1.25, 2.31]). Self-concept alone accounted for 52% of the relationship between PEs and subsequent internalizing problems. There is a bidirectional heterotypic relationship between psychopathology and PEs. Parent-child conflict and self-concept are important characteristics that mediate a proportion of the relationship between PEs and psychopathology. Interventions targeting parent-child conflict in the context of psychopathology and self-concept in the context of PEs may assist in reducing the incidence of poorer outcomes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Aims: Smaller hippocampal volumes are among the most consistently reported neuroimaging findings in schizophrenia. However, little is known about hippocampal volumes in people who report psychotic experiences. This study investigated differences in hippocampal volume between young people without formal diagnoses who report psychotic experiences (PEs) and those who do not report such experiences. This study also investigated if any differences persisted over two years., Methods: A nested case-control study of 25 adolescents (mean age 13.5 years) with reported PEs and 25 matched controls (mean age 13.36 years) without PEs were drawn from a sample of 100 local schoolchildren. High-resolution T1-weighted anatomical imaging and subsequent automated cortical segmentation (Freesurfer 6.0) was undertaken to determine total hippocampal volumes. Comprehensive semi-structured clinical interviews were also performed including information on PEs, mental diagnoses and early life stress (bullying). Participants were invited for a second scan at two years., Results: 19 adolescents with PEs and 19 controls completed both scans. Hippocampal volumes were bilaterally lower in the PE group compared to the controls with moderate effects sizes both at baseline [left hippocampus p = 0.024 d = 0.736, right hippocampus p = 0.018, d = 0.738] and at 2 year follow up [left hippocampus p = 0.027 d = 0.702, right = 0.048 d = 0.659] throughout. These differences survived adjustment for co-morbid mental disorders and early life stress., Conclusions: Psychotic experiences are associated with total hippocampal volume loss in young people and this volume loss appears to be independent of possible confounders such as co-morbid disorders and early life stress., Competing Interests: The authors have declared that no competing interests exist.

Aim: Psychotic-like experiences (PEs) have been associated with childhood adversity and psychopathology. However, few studies have examined the dynamic interplay between risk and protective factors and later life outcomes in people with PEs. This study aimed to explore and compare patterns of early adverse and protective experiences and young adult outcomes in a sample of young people with a history of PEs., Method: Longitudinal qualitative data spanning nine years were collected from a general population sample of seventeen young adults who had reported PEs in early adolescence. A qualitative comparative case study design was used to explore patterns of early life experiences and young adult outcomes., Results: Four archetypal profiles of early life experiences and later outcomes were identified. Qualitative differences between types of early adverse experiences and the quality of attachment relationships were dominant discriminating factors between low-risk and at-risk archetypes for poor young adult outcomes. Experiences of multiple adversities, which included childhood trauma and occurred in the absence of secure attachment relationships was associated with the poorest young adult outcomes. The presence of secure attachment relationships was protective, even among individuals who had experienced adversity., Conclusions: Not all young people who report PEs have high levels of adversity. Those who experience multiple early adversities, childhood trauma and insecure attachment relationships are at highest risk for reoccurring PEs and poor young adult outcomes. Developing trusted attachment relationships and engaging in corrective experiences may be protective and could promote positive outcomes in youth with PEs., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Little is known about the prevalence of inconsistent trauma reporting in community samples and about its associations with psychopathology. This study aimed to assess for the first time the prevalence of inconsistent trauma reporting in a community sample of children/adolescents and to explore associations with both psychotic experiences and with psychopathology more generally., Method: A community-based sample of 86 children/adolescents (baseline mean age 11.5) were interviewed at two time points with data collected in relation to potentially traumatic events through the K-SADS. Emotional and behavioural problems were assessed at follow-up (mean age 15.7) through the Youth Self Report questionnaire while the presence of psychotic experiences was based on expert consensus post interview. Logistic regression models were used to test associations between inconsistent reporting and psychotic experiences at baseline and follow-up, with associations with emotional and behavioral problems at follow-up also assessed., Results: Overall, 16.3% of adolescents failed to report previously reported potentially traumatic events at follow-up and were therefore defined as inconsistent trauma reporters. Inconsistent reporting was associated with emotional and behavioural problems as assessed by the Youth Self Report with the exception of rule breaking behaviour and with psychotic experiences as assessed on interview., Conclusions: Inconsistent trauma reporting is associated with psychotic experiences and emotional and behavioural problems in young people and may represent an important marker for psychopathology in youth.

Background: Psychotic experiences (PEs) are commonly reported in adolescence and are associated with a range of negative outcomes. Few targets for intervention for PEs have been identified. One potential target is self-concept: an individual's beliefs about his/her personal attributes. Improvements in self-concept have been shown to reduce psychotic symptoms in patients with schizophrenia but no study has investigated the relationship between changes in self-concept and risk of PEs in the general population. We aimed to investigate: (a) the relationship between child and adolescent self-concept and adolescent PEs; and (b) whether changes in self-concept between childhood and adolescence were associated with risk of adolescent PEs., Method: Using data from age 9 and age 13 (n = 7,423) of the child cohort (Cohort'98) from the Growing Up in Ireland study we investigated the relationship between self-concept at age 9 and age 13 and PEs at age 13. PEs were measured using the Adolescent Psychotic Symptoms Screener and self-concept was measured using the Piers Harris-II. Using a stratified analysis, we investigated the relationship between change in self-concept between age 9 and age 13 and the risk of PEs at age 13. Additionally we investigated changes across the six self-concept subscales., Results: Psychotic experiences were reported by 13% of participants at age 13. 'Very low' self-concept at age 9 was associated with an increased risk of PEs at age 13 (Adjusted-OR: 2.74, CI: 1.80-4.19), and 'High' self-concept at age 9 was associated with a decreased risk of PEs at age 13 (Adjusted-OR: 0.77, CI: 0.60-0.97). The stratified analysis indicated that improvements in self-concept reduced the odds of adolescent PEs and decline in self-concept increased the odds of adolescent PEs. This effect was noted across the majority of the self-concept subscales., Conclusions: There is a strong relationship between self-concept and PEs. The antecedents of low self-concept may be a useful target for preventative psychiatry. Broad-spectrum interventions targeting self-concept in childhood may help to reduce the incidence of PEs in adolescence., (© 2019 Association for Child and Adolescent Mental Health.)

Aims: (a) To investigate the utility of childhood PE as a predictor of adolescent psychopathology while accounting for three known risk factors: childhood mental disorder; traumatic experiences and poor childhood functioning, and (b) to investigate the additive effects of including childhood PE in predictive clinical model of adolescent psychopathology., Method: The study sample comprised of 86 Irish youths who completed two waves of the "Adolescent Brain Development" study (baseline age: 11.7 and follow-up age: 15.7). At baseline, participants completed a clinical interview assessing for PE, mental disorders, traumatic experiences and global functioning in childhood. The internalizing and externalizing problems sub-scales from the Youth Self Report questionnaire were used as follow-up outcomes variables in adolescence., Results: Logistic regression analyses revealed that childhood PE was the only predictor significantly associated with both internalizing (univariate OR: 7.58, CI: 2.59-22.15; multivariate OR: 5.43, CI: 1.53-19.29) and externalizing (univariate OR: 11.76, CI: 3.70-37.41; multivariate OR: 30.39, CI: 5.28-174.80) problems in adolescence. All predictive models with PE significantly predicted adolescent outcomes (area under the curve range: 0.70-0.81; all P < 0.05) and adding PE to the models improved the predictive value for externalizing problems (P = 0.02)., Conclusion: Childhood PE is a powerful predictor of adolescent psychopathology, particularly for externalizing problems. Routine assessment of PE and targeted support for children who report PE may reduce the incidence of mental disorder in adolescence., (© 2018 John Wiley & Sons Australia, Ltd.)

Background: Psychotic experiences (PEs) are common in childhood and adolescence and their association with mental disorders is well-established. We aim to conduct a quantitative synthesis the literature on the relationship between childhood and adolescent PEs and (i) any mental disorder; and (ii) specific categories of mental disorder, while stratifying by study design., Method: Three electronic databases (PUBMED, PsycINFO and EMBASE) were searched from inception to August 2017 for all the published literature on childhood and adolescent PEs and mental disorder (outcome) in non-help-seeking community samples. Study quality was assessed using a recognised quality assessment tool for observational studies. Two authors conducted independent data extraction. Pooled odds ratios were calculated for mental disorders using random-effects models. Additional analyses were conducted investigating different categories of mental disorder while stratifying by study design., Results: Fourteen studies from 13 community samples (n = 29 517) were identified with 9.8% of participants reporting PEs. PEs were associated with a three-fold increased risk of any mental disorder [odds ratio (OR) 3.08, confidence interval (CI) 2.26-4.21, k = 12]. PEs were associated with four-fold increase risk of psychotic disorder (OR 3.96, CI 2.03-7.73, population-attributable-fraction: 23.2%, k = 5). In addition, PEs were associated with an increased risk of affective disorders, anxiety disorders, behavioural disorders and substance-use disorders. Few longitudinal studies have investigated childhood and adolescent PEs and subsequent non-psychotic disorders which limited a meaningful synthesis and interpretation of these results., Conclusion: This meta-analysis confirms that PEs are prevalent in childhood and adolescent community samples and are associated with a variety of mental disorders beyond psychotic disorders. Further longitudinal research is necessary to fully determine the longitudinal relationship between PEs and non-psychotic disorders.

Objective: To identify neuropsychological and motor changes from adolescence to early adulthood in young people with psychotic experiences (PE)., Methods: A community-based sample of 56 young people attended the study over a 9 year follow-up period. Participants were assessed over 3 time-points at T1, T2 and T3 aged x¯ = 11.69, x¯ = 15.80 and x¯ = 18.80 years respectively. PE were assessed using the Kiddie Schedule for Affective and Depressive Symptoms (K-SADS). Neuropsychological assessments, including subtests of the MATRICS battery, and motor assessments were examined at T2 and T3. Two groups were compared: those who ever reported PE during their adolescence or early adulthood (n = 21) and a healthy control group (n = 35). Further group analysis was conducted within the PE group subdividing into those with transient PE (n = 10) and those with persistent PE (n = 11)., Results: At T3, a significant group difference was found between the PE and control groups in the fine motor skill task, the Pegboard task (F = 4.8, p = .03) and the processing speed task, the Digit-Symbol Coding task (F = 5.36, p = .03). Furthermore, a significant group difference was found between the transient PE and control groups on the Digit-Symbol Coding task (F = 5.61, p = .02), while a significant group difference was found between the persistent PE and control groups on the Pegboard task (F = 7.84, p = .01)., Conclusion: This study shows that fine motor skill and processing speed deficits persist in young people who report PE, even in those with transient PE. The current research advances the knowledge about the trajectory and precursors of sub-clinical symptoms of psychosis in young people., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Dendritic cells (DCs) are can be broadly divided into conventional (cDC) and plasmacytoid (pDC) subsets. Despite the importance of this lineage diversity, its genetic basis is not fully understood. We found that conditional ablation of the Ets-family transcription factor PU.1 in DC-restricted progenitors led to increased pDC production at the expense of cDCs. PU.1 controlled many of the cardinal functions of DCs, such as antigen presentation by cDCs and type I interferon production by pDCs. Conditional ablation of PU.1 de-repressed the pDC transcriptional signature in cDCs. The combination of genome-wide mapping of PU.1 binding and gene expression analysis revealed a key role for PU.1 in maintaining cDC identity through the induction of the transcriptional regulator DC-SCRIPT. PU.1 activated DC-SCRIPT expression, which in turn promoted cDC formation, particularly of cDC1s, and repressed pDC development. Thus, cDC identity is regulated by a transcriptional node requiring PU.1 and DC-SCRIPT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Previous magnetic resonance imaging (MRI) research suggests that, prior to the onset of psychosis, high risk youths already exhibit brain abnormalities similar to those present in patients with schizophrenia., Objectives: The goal of the present study was to describe the functional organization of endogenous activation in young adolescents who report auditory verbal hallucinations (AVH) in view of the "distributed network" hypothesis of psychosis. We recruited 20 young people aged 13-16 years who reported AVHs and 20 healthy controls matched for age, gender and handedness from local schools., Methods: Each participant underwent a semi-structured clinical interview and a resting state (RS) neuroimaging protocol. We explored functional connectivity (FC) involving three different networks: 1) default mode network (DMN) 2) salience network (SN) and 3) central executive network (CEN). In line with previous findings on the role of the auditory cortex in AVHs as reported by young adolescents, we also investigated FC anomalies involving both the primary and secondary auditory cortices (A1 and A2, respectively). Further, we explored between-group inter-hemispheric FC differences (laterality) for both A1 and A2. Compared to the healthy control group, the AVH group exhibited FC differences in all three networks investigated. Moreover, FC anomalies were found in a neural network including both A1 and A2. The laterality analysis revealed no between-group, inter-hemispheric differences., Conclusions: The present study suggests that young adolescents with subclinical psychotic symptoms exhibit functional connectivity anomalies directly and indirectly involving the DMN, SN, CEN and also a neural network including both primary and secondary auditory cortical regions., Competing Interests: The authors have declared that no competing interests exist.

Aim: This study aimed to examine whether or not sexual minority youth constitute an at-risk group for nonsuicidal self-injury, suicidal ideation or suicide attempts during their emerging adult years., Methods: Using data from the Challenging Times Study, a population-based study of psychopathology and suicide in Ireland, analyses were conducted to test the associations between sexual minority status and the odds of any lifetime experience of nonsuicidal self-injury, suicidal thoughts or suicide attempts among Irish youth aged 19-24 years., Results: Sexual minority youth had 6.6-fold (95% CI 1.7-24.7) increased risk of nonsuicidal self-injury, a 5.0-fold (95% CI 1.3-18.3) increased risk of suicidal ideation, a 7.7-fold (95% CI 1.8-32.0) increased risk of suicide intent and a 6.8-fold (95% CI 1.6-27.6) increased risk of a suicide attempt during their lifetime compared to their heterosexual peers., Conclusions: This study shows that emerging adulthood is a period of risk for suicide and nonsuicidal self-injurious behaviour among sexual minority youth., (© 2015 Wiley Publishing Asia Pty Ltd.)

Three duplex molecular beacon based real-time Nucleic Acid Sequence Based Amplification (NASBA) assays have been designed and experimentally validated targeting RNA transcripts for the detection and identification of Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae respectively. Each real-time NASBA diagnostics assay includes an endogenous non-competitive Internal Amplification Control (IAC) to amplify the splice variant 1 mRNA of the Homo sapiens TBP gene from human total RNA. All three duplex real-time NASBA diagnostics assays were determined to be 100% specific for the target species tested for. Also the Limits of Detection (LODs) for the H. influenzae, N. meningitidis and S. pneumoniae duplex real-time NASBA assays were 55.36, 0.99, and 57.24 Cell Equivalents (CE) respectively. These robust duplex real-time NASBA diagnostics assays have the potential to be used in a clinical setting for the rapid (<60min) specific detection and identification of the most prominent microorganisms associated with bacterial meningitis in humans., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: The objective of this review is to report on recent developments in youth mental health incorporating all levels of severity of mental disorders encouraged by progress in the field of early intervention in psychotic disorders, research in deficiencies in the current system and social advocacy., Methods: The authors have briefly reviewed the relevant current state of knowledge, challenges and the service and research response across four countries (Australia, Ireland, the UK and Canada) currently active in the youth mental health field., Results: Here we present information on response to principal challenges associated with improving youth mental services in each country. Australia has developed a model comprised of a distinct front-line youth mental health service (Headspace) to be implemented across the country and initially stimulated by success in early intervention in psychosis; in Ireland, Headstrong has been driven primarily through advocacy and philanthropy resulting in front-line services (Jigsaw) which are being implemented across different jurisdictions; in the UK, a limited regional response has addressed mostly problems with transition from child-adolescent to adult mental health services; and in Canada, a national multi-site research initiative involving transformation of youth mental health services has been launched with public and philanthropic funding, with the expectation that results of this study will inform implementation of a transformed model of service across the country including indigenous peoples., Conclusions: There is evidence that several countries are now engaged in transformation of youth mental health services and in evaluation of these initiatives.

Haemophilus influenzae is recognised as an important human pathogen associated with invasive infections, including bloodstream infection and meningitis. Currently used molecular-based diagnostic assays lack specificity in correctly detecting and identifying H. influenzae. As such, there is a need to develop novel diagnostic assays for the specific identification of H. influenzae. Whole genome comparative analysis was performed to identify putative diagnostic targets, which are unique in nucleotide sequence to H. influenzae. From this analysis, we identified 2H. influenzae putative diagnostic targets, phoB and pstA, for use in real-time PCR diagnostic assays. Real-time PCR diagnostic assays using these targets were designed and optimised to specifically detect and identify all 55H. influenzae strains tested. These novel rapid assays can be applied to the specific detection and identification of H. influenzae for use in epidemiological studies and could also enable improved monitoring of invasive disease caused by these bacteria., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect H. influenzae in RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the smpB gene was designed to detect all serogroups of H. influenzae. The assay was validated using a panel of well-characterized Haemophilus spp. Subsequently, 44 Haemophilus clinical isolates were collected, and 36 isolates were identified as H. influenzae using a gold standard methodology that combined the results of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and a fucK diagnostic assay. Using the novel smpB diagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (n = 98) were blindly tested with the gold standard and smpB diagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel smpB assay when used directly on respiratory specimens., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Importance: Abnormal brain connectivity is thought to have a key role in the pathophysiology of schizophrenia and other psychotic disorders. White matter (WM) abnormalities have been reported in patients with schizophrenia and patients with prodromal syndromes. To our knowledge, no studies have yet reported on WM differences among adolescents who report psychotic experiences, a known vulnerability group for later severe psychopathology, including psychotic illness., Objective: To study WM differences using diffusion-weighted imaging (whole-brain and tractography analyses) in adolescents who report psychotic experiences., Design, Setting, and Participants: A population-based case-control study of 28 adolescents 13 to 16 years old who reported psychotic experiences and a matched sample of 28 adolescents who did not report psychotic experiences drawn from a sample of 212 young people recruited from primary schools in North Dublin and Kildare, Ireland. The study dates were 2008 to 2011., Interventions: High-angular resolution diffusion-weighted imaging data were used to conduct whole-brain WM analysis using tract-based spatial statistics. Based on this exploratory analysis, a tractography-based approach with constrained spherical deconvolution was performed., Results: Compared with control group participants, adolescents who reported psychotic experiences showed WM differences bilaterally in striatal regions in proximity to the putamen (increased fractional anisotropy, P = .01, false discovery rate corrected), and tractography identified significant WM differences bilaterally in the uncinate fasciculus (increased fractional anisotropy in the right [P = .001] and axial diffusivity in the left [P = .01] uncinate fasciculus, respectively). Similar patterns of WM differences between groups survived adjustment for other psychopathology, indicating some specificity for psychotic experiences. Exploratory along-tract analyses showed WM differences between groups in the frontal projections of the right inferior fronto-occipital fasciculus (reduced radial diffusivity in approximately 32% of the tract segment [P ≤ .0001] and increased fractional anisotropy in approximately 16% of the tract segment [P ≤ .0009])., Conclusions and Relevance: In a population-based study of adolescents reporting psychotic experiences, we found a number of WM differences in the region of the putamen located between the inferior fronto-occipital fasciculus and the uncinate fasciculus and in the left parietal regions that include the fiber bundle of the superior longitudinal fasciculus. These findings suggest that subtle structural changes to WM microstructure are not merely a consequence of disorder but may index vulnerability to psychosis even at a very early age.

Psychotic experiences are far more common in the population than psychotic disorder. They are associated with a number of adverse outcomes but there has been little research on associations with functioning and distress. We wished to investigate functioning and distress in a community sample of adolescents with psychotic experiences. Two hundred and twelve school-going adolescents were assessed for psychotic experiences, mental distress associated with these experiences, global (social/occupational) functioning on the Children's Global Assessment Scale, and a number of candidate mediator variables, including psychopathology, suicidality, trauma (physical and sexual abuse and exposure to domestic violence) and neurocognitive functioning. Seventy five percent of participants who reported psychotic experiences reported that they found these experiences distressing (mean score for severity of distress was 6.9 out of maximum 10). Participants who reported psychotic experiences had poorer functioning than participants who did not report psychotic experiences (respective means: 68.6, 81.9; OR=0.25, 95% CI=0.14-0.44). Similarly, participants with an Axis-1 psychiatric disorder who reported psychotic experiences had poorer functioning than participants with a disorder who did not report psychotic experiences (respective means: 61.8, 74.5; OR=0.28, 95% CI=0.12-0.63). Candidate mediator variables explained some but not all of the relationship between psychotic experiences and functioning (OR=0.48, 95% CI=0.22-1.05, P<0.07). Young people with psychotic experiences have poorer global functioning than those who do not, even when compared with other young people with psychopathology (but who do not report psychotic experiences). A disclosure of psychotic experiences should alert treating clinicians that the individual may have significantly more functional disability than suggested by the psychopathological diagnosis alone., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: This study investigated the prevalence of DSM-IV Axis 1 mental disorders, deliberate self-harm and suicidal ideation in a sample of Irish adolescents aged 11-13 years., Methods: A total of 1131 students was surveyed for general psychopathology using the Strengths and Difficulties Questionnaire. Following this, a representative sample of 212 adolescents was assessed for mental disorders, deliberate self-harm and suicidal ideation using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children., Results: 14.6% of the sample met criteria for a borderline score and 6.9% for an abnormal score on the Strengths and Difficulties Questionnaire. Following clinical diagnostic interviews, 27.4% of participants received a current diagnosis of an Axis 1 disorder and 36.8% received a lifetime diagnosis, those rates falling to 15.4% and 31.2% respectively when specific phobias were excluded., Conclusions: Findings from this study reveal that Irish adolescents aged 11-13 years are experiencing high levels of mental ill-health., (Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)