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To slow the spread of COVID-19 many mental health providers transitioned to telehealth delivery of trauma-focused treatment for maltreated children. However, these providers faced myriad challenges, including equitable access to equipment and technical demands of telehealth software. Training clinics overseeing pre-doctoral clinical psychology interns experienced the added challenge of providing quality supervision and training via telehealth. This study involves a retrospective application of the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to describe the innovative adaptation to a telehealth service delivery model in a training clinic providing evidence-based trauma-focused treatment to children and their families. Mixed methods data from clinic records and intern evaluations indicate that compared to pre-COVID (February 2019 – February 2020), during early COVID (April 2020 – April 2021) more patients accessed clinic services, interns reported fewer hours of individual supervision, and interns reported greater satisfaction with their training experiences. Implications for ongoing provision of telehealth services are discussed. [ABSTRACT FROM AUTHOR]

To improve water access while working and contribute to fewer heat-related illnesses (HRI), backpack hydration systems were provided to over 200 farmworkers to use during the 2022 growing season. Acceptability of the water intake intervention was assessed among farmworkers in eastern North Carolina, USA. With a pre-established community–university partnership, the acceptability of the intervention was assessed using a cross-sectional survey. The backpack brand selected included a 3-liter water bladder and attached drinking hose. Data analysis included descriptive and correlation statistics. Among 47 male, migrant farmworkers, most (90%) reported the hydration backpack to be acceptable or completely acceptable to workplace fluid intake. Most (53%) reported using the backpack some of the time, compared to 28% who used it often. The participants reported an average of 4.8 (SD 2.2) liters of water intake from the backpack on a typical workday. Most reported the backpack improved the quantity and frequency of their water consumption. This study was an important first step in implementation of hydration backpack systems as an HRI-preventative intervention among farmworkers. Future interventional studies could assess the efficacy of the backpacks on health outcomes, including incidence of dehydration and symptoms of HRI. [ABSTRACT FROM AUTHOR]

What conditions enable novel intellectual contributions to diffuse and become integrated into later scientific work? Prior work tends to focus on whole cultural products, such as patents and articles, and emphasizes external social factors as important. This article focuses on concepts as reflections of ideas, and we identify the combined influence that social factors and internal intellectual structures have on ideational diffusion. To develop this perspective, we use computational techniques to identify nearly 60,000 new ideas introduced over two decades (1993 to 2016) in the Web of Science and follow their diffusion across 38 million later publications. We find new ideas diffuse more widely when they socially and intellectually resonate. New ideas become core concepts of science when they reach expansive networks of unrelated authors, achieve consistent intellectual usage, are associated with other prominent ideas, and fit with extant research traditions. These ecological conditions play an increasingly decisive role later in an idea's career, after their relations with the environment are established. This work advances the systematic study of scientific ideas by moving beyond products to focus on the content of ideas themselves and applies a relational perspective that takes seriously the contingency of their success. [ABSTRACT FROM AUTHOR]

Sustaining sports-related head impacts has been reported to result in neurological changes that potentially lead to later-life neurological disease. Advanced neuroimaging techniques have been used to detect subtle neurological effects resulting from head impacts, even after a single competitive season. The current study used resting-state functional magnetic resonance imaging to assess changes in functional connectivity of the frontoparietal network, a brain network responsible for executive functioning, in collegiate club ice hockey players over one season. Each player was scanned before and after the season and wore accelerometers to measure head impacts at practices and home games throughout the season. We examined pre- to post-season differences in connectivity within the frontoparietal and default mode networks, as well as the relationship between the total number of head impacts sustained and changes in connectivity. We found a significant interaction between network region of interest and time point (p =.016), in which connectivity between the left and right posterior parietal cortex seed regions increased over the season (p <.01). Number of impacts had a significant effect on frontoparietal network connectivity, such that more impacts were related to greater connectivity differences over the season (p =.042). Overall, functional connectivity increased in ice hockey athletes over a season between regions involved in executive functioning, and sensory integration, in particular. Furthermore, those who sustained more impacts had the greatest changes in connectivity. Consistent with prior findings in resting-state sports-related head impact literature, these findings have been suggested to represent brain injury. Highlights Functional connectivity of the frontoparietal network significantly increased between the pre- and post-season, which may be a compensatory mechanism driven by neural tissue injury caused by repetitive head impacts. Changes in frontoparietal network connectivity are related to head impact exposure, measured as the number of head impacts sustained in a single season. Functional connectivity of the default mode network did not change over an ice hockey season. [ABSTRACT FROM AUTHOR]

Objectives: In response to a surge of drug overdoses involving polysubstance use among Atlanta service industry workers that resulted in the deaths of five people in the Atlanta area in the summer of 2021, a local community of harm reductionists and nurses organized opioid education and naloxone distribution (OEND) training sessions specifically customized for service industry workers in Atlanta. After the sessions, the nurses and harm reductionists asked attendants to participate in a study concerning their response to overdoses. The reason nurses and harm reductionists conducted the study was to determine the efficacy of OEND training adapted for those working in the service industries as well as to evaluate and possibly modify the training sessions for future use. This pre‐post study examined if and how participants' knowledge and attitudes toward an opioid‐involved overdose changed after engaging with the OEND training. If the study determined that the sessions were successful in teaching service industry workers how to mitigate the immediate and devastating effects of overdose, we recommend expanding and implementing both adaptable training sessions like the OEND training referenced, as well as accompanying studies to improve the training sessions' effectiveness. Design: The pre‐post study used convenience sampling to recruit participants in emergent OEND training. Participants completed an abbreviated version the Opioid Overdose Attitudes Scale (OOAS) which measured how, and to what degree, they changed their attitudes towards overdoses and their responses to them. Participants also completed an abbreviated version of the Opioid Overdose Knowledge Scale (OOKS) which measured how effectively the OEND increased their knowledge when it came to properly responding to an overdose, which included implementing naloxone as part of immediate rehabilitation treatment. Paired nonparametric tests assessed changes in participants' OOAS/OOKS scores. Results: A total of 161 individuals attended, and 72 consented to be in the study. The sample predominately consisted of white (76.4%) and female (66.7%) adults whose age averaged 34.3 years. Attitude and knowledge score improvements were statistically significant: approximately 11 points (p <.001) and 3 points (p <.001), respectively. Conclusions: This rapidly implemented training was associated with improving attitudes and knowledge about responding to an opioid‐involved overdose. We recommend expanding the scope of studies like these in order to develop and examine effective, dynamic, and targeted OEND training tailored towards specific community groups and situations, such as polysubstance overdose among service industry workers. As the opioid epidemic worsens, it is critical to equip community members themselves with the skills and tools to recognize and respond to opioid overdoses as a frontline prevention to overdose deaths. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) genetics studies have identified a coding variant within ABI3 gene that increases the risk of developing AD. Recently, we demonstrated that deletion of the Abi3 gene locus dramatically exacerbates AD neuropathology in a transgenic mouse model of amyloidosis. In the course of this AD project, we unexpectedly found that deletion of the Abi3 gene locus resulted in a dramatic obese phenotype in non-transgenic mice. Here, we report our investigation into this serendipitous metabolic finding. Specifically, we demonstrate that mice with deletion of the Abi3 gene locus (Abi3􀀀=􀀀) have dramatically increased body weight and body fat. Further, we determined that Abi3􀀀=􀀀 mice have impaired energy expenditure. Additionally, we found that deletion of the Abi3 gene locus altered gene expression within the hypothalamus, particularly within immune-related pathways. Subsequent immunohistological analysis of the central nervous system (CNS) revealed that microglia number and area were decreased specifically within the mediobasal hypothalamus of Abi3􀀀=􀀀 mice. Altogether, this investigation establishes the functional importance of the Abi3 gene locus in the regulation of systemic metabolism and maintenance of healthy body weight. While our previous findings indicated the importance of Abi3 in neurodegeneration, this study indicates that Abi3 related functions are also essential for metabolic regulation. [ABSTRACT FROM AUTHOR]

Background: Severe mental illness (SMI) is associated with increased stroke risk, but little is known about how SMI relates to stroke prognosis and receipt of acute care.Aims: To determine the association between SMI and stroke outcomes and receipt of process-of-care quality indicators (such as timely admission to stroke unit).Method: We conducted a cohort study using routinely collected linked data-sets, including adults with a first hospital admission for stroke in Scotland during 1991-2014, with process-of-care quality indicator data available from 2010. We identified pre-existing schizophrenia, bipolar disorder and major depression from hospital records. We used logistic regression to evaluate 30-day, 1-year and 5-year mortality and receipt of process-of-care quality indicators by pre-existing SMI, adjusting for sociodemographic and clinical factors. We used Cox regression to evaluate further stroke and vascular events (stroke and myocardial infarction).Results: Among 228 699 patients who had had a stroke, 1186 (0.5%), 859 (0.4%), 7308 (3.2%) had schizophrenia, bipolar disorder and major depression, respectively. Overall, median follow-up was 2.6 years. Compared with adults without a record of mental illness, 30-day mortality was higher for schizophrenia (adjusted odds ratio (aOR) = 1.33, 95% CI 1.16-1.52), bipolar disorder (aOR = 1.37, 95% CI 1.18-1.60) and major depression (aOR = 1.11, 95% CI 1.05-1.18). Each disorder was also associated with marked increased risk of 1-year and 5-year mortality and further stroke and vascular events. There were no clear differences in receipt of process-of-care quality indicators.Conclusions: Pre-existing SMI was associated with higher risks of mortality and further vascular events. Urgent action is needed to better understand and address the reasons for these disparities. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the effects of a ketone ester (KE)-supplemented diet on energy expenditure (EE) and adiposity in mice housed at 23 °C versus thermoneutrality (30 °C), in which sympathetic nervous system activity is diminished.Methods: Thirty-two 10-week-old male C57BL/6J mice were assigned to 1 of 4 groups (n = 8 per group): 30% KE diet + 23 °C (KE23), control (CON) diet + 23 °C (CON23), 30% KE diet + 30 °C (KE30), or CON diet + 30 °C (CON30). CON mice were pair-fed to the average intake of mice consuming the KE diet (ad libitum) for 8 weeks. Body composition and components of energy balance were measured at completion of the study.Results: CON23 (mean ± SD, 26.0 ± 1.6 g) and CON30 (29.7 ± 1.4 g) mice weighed more than KE groups (P < 0.03 for both) and were also different from each other (CON23 vs. CON30, P < 0.01). However, KE23 (23.4 ± 2.7 g) and KE30 (23.1 ± 1.9 g) mice were not different in body weight. As expected, food intake at 30 °C (2.0 ± 0.3 g/d) was lower than at 23 °C (2.6 ± 0.3 g/d, P < 0.01). Diet did not influence resting and total EE, but mice housed at 30 °C had lower EE compared with mice at 23 °C (P < 0.01).Conclusions: Dietary KEs attenuate body weight gain at standard (23 °C) and thermoneutral (30 °C) housing temperatures, and this effect is not mediated by increased EE under these conditions. [ABSTRACT FROM AUTHOR]

Objective: Surgical manipulations of adipose tissue by removal, or partial lipectomy, have demonstrated body fat compensation and recovered body weight, suggesting that the body is able to resist changes to body composition. However, the mechanisms underlying these observations are not well understood. The purpose of this scoping review is to provide an update on what is currently known about the regulation of energetics and body fat after surgical manipulations of adipose tissue in small mammals.Methods: PubMed and Scopus were searched to identify 64 eligible studies. Outcome measures included body fat, body weight, food intake, and circulating biomarkers.Results: Surgeries performed included lipectomy (72%) or transplantation (12%) in mice (35%), rats (35%), and other small mammals. Findings suggested that lipectomy did not have consistent long-term effects on reducing body weight and fat because regain occurred within 12 to 14 weeks post surgery. Hence, biological feedback mechanisms act to resist long-term changes of body weight or fat. Furthermore, whether this weight and fat regain occurred because of "passive" and "active" regulation under the "set point" or "settling point" theories cannot fully be discerned because of limitations in study designs and data collected.Conclusions: The regulation of energetics and body fat are complex and dynamic processes that require further studies of the interplay of genetic, physiological, and behavioral factors. [ABSTRACT FROM AUTHOR]

Globally, there is increasing recognition that agricultural workers are at risk for chronic kidney disease of unknown etiology (CKD u). Recurrent heat exposure, physical exertion, dehydration, muscle damage, and inflammation are hypothesized to contribute to the development of CKD u, but the relative importance of these processes and the interactions among them remain unclear. Moreover, there is a need to identify biomarkers that could distinguish individuals who are at greatest risk for kidney damage to target preventative interventions for CKD u. In this study, we evaluated dehydration and markers of inflammation, muscle damage, and renal function in agricultural workers at a non-workday baseline assessment. Urine specific gravity and kidney function were measured before and after work shifts on three subsequent days, and heat index, core body temperature, and heart rate were monitored during the work shifts. A combination of direct comparisons and machine learning algorithms revealed that reduced levels of uromodulin and sodium in urine and increased levels of interleukin-6 and C-reactive protein in serum were indicative of dehydration at baseline, and that dehydration, high body mass index, reduced urine uromodulin, and increased serum interleukin-6, C-reactive protein, and lipopolysaccharide-binding protein at baseline were predictive of acute kidney injury on subsequent workdays. Our findings suggest a method for identifying agricultural workers at greatest risk for kidney injury and reveal potential mechanisms responsible for this process, including pathways overlapping in dehydration and kidney injury. These results will guide future studies confirming these mechanisms and introducing interventions to protect kidney health in this vulnerable population. [ABSTRACT FROM AUTHOR]

Recent research suggests genetic variation in the Klotho locus may modify the association between APOE ɛ4 and cognitive impairment. We tested for associations and interactions between these genotypes versus risk of dementia, cognitive abilities, and brain structure in older UK Biobank participants. Klotho status was indexed with rs9536314 heterozygosity (versus not), in unrelated people with versus without APOE ɛ4 genotype, corrected for various confounders. APOE ɛ4 associated with increased risk of dementia, worse cognitive abilities, and brain structure. Klotho was associated with better reasoning. There were no interactions; potentially suggesting an age- and pathology-dependent Klotho effect. [ABSTRACT FROM AUTHOR]

Objective: Despite the known health benefits of weight loss among persons with obesity, observational studies have reported that cycles of weight loss and regain, or weight cycling, are associated with increased mortality. To study whether weight loss must be sustained to achieve health and longevity benefits, we performed a randomized controlled feeding study of weight cycling in mice.Methods: In early adult life, obese mice were randomized to ad libitum feeding to sustain obesity, calorie restriction to achieve a "normal" or intermediate body weight, or weight cycling (repeated episodes of calorie restriction and ad libitum refeeding). Body weight, body composition, and food intake were followed longitudinally until death. A subsample of mice was collected from each group for determination of adipose cell size, serum analytes, and gene expression.Results: Weight loss significantly reduced adipose mass and adipocyte size in both sexes, whereas weight cycling animals regained body fat and cell size during refeeding. Sustained weight loss resulted in a dose-dependent decrease in mortality compared with ad libitum feeding.Conclusions: Weight cycling significantly increased life-span relative to remaining with obesity and had a similar benefit to sustained modest weight loss. [ABSTRACT FROM AUTHOR]

Background: Psychiatric disorders are associated with increased risk of ischaemic heart disease (IHD) and stroke, but it is not known whether the associations or the role of sociodemographic factors have changed over time.Aims: To investigate the association between psychiatric disorders and IHD and stroke, by time period and sociodemographic factors.Method: We used Scottish population-based records from 1991 to 2015 to create retrospective cohorts with a hospital record for psychiatric disorders of interest (schizophrenia, bipolar disorder or depression) or no record of hospital admission for mental illness. We estimated incidence and relative risks of IHD and stroke in people with versus without psychiatric disorders by calendar year, age, gender and area-based deprivation level.Results: In all cohorts, incidence of IHD (645 393 events) and stroke (276 073 events) decreased over time, but relative risks decreased for depression only. In 2015, at the mean age at event onset, relative risks were 2- to 2.5-fold higher in people with versus without a psychiatric disorder. Age at incidence of outcome differed by cohort, gender and socioeconomic status. Relative but not absolute risks were generally higher in women than men. Increasing deprivation conveys a greater absolute risk of IHD for people with bipolar disorder or depression.Conclusions: Despite declines in absolute rates of IHD and stroke, relative risks remain high in those with versus without psychiatric disorders. Cardiovascular disease monitoring and prevention approaches may need to be tailored by psychiatric disorder and cardiovascular outcome, and be targeted, for example, by age and deprivation level. [ABSTRACT FROM AUTHOR]

Background: Directed acyclic graphs (DAGs) are popular tools for identifying appropriate adjustment strategies for epidemiological analysis. However, a lack of direction on how to build them is problematic. As a solution, we propose using a combination of evidence synthesis strategies and causal inference principles to integrate the DAG-building exercise within the review stages of research projects. We demonstrate this idea by introducing a novel protocol: 'Evidence Synthesis for Constructing Directed Acyclic Graphs' (ESC-DAGs)'.Methods: ESC-DAGs operates on empirical studies identified by a literature search, ideally a novel systematic review or review of systematic reviews. It involves three key stages: (i) the conclusions of each study are 'mapped' into a DAG; (ii) the causal structures in these DAGs are systematically assessed using several causal inference principles and are corrected accordingly; (iii) the resulting DAGs are then synthesised into one or more 'integrated DAGs'. This demonstration article didactically applies ESC-DAGs to the literature on parental influences on offspring alcohol use during adolescence.Conclusions: ESC-DAGs is a practical, systematic and transparent approach for developing DAGs from background knowledge. These DAGs can then direct primary data analysis and DAG-based sensitivity analysis. ESC-DAGs has a modular design to allow researchers who are experienced DAG users to both use and improve upon the approach. It is also accessible to researchers with limited experience of DAGs or evidence synthesis. [ABSTRACT FROM AUTHOR]

Background: Nomograms are graphical calculating devices used to predict risk of malignant transformation (MT) or response to treatment during cancer management. To date, a nomogram has not been used to predict clinical outcome during oral potentially malignant disorder (PMD) treatment. The aim of this study was to create a nomogram for use by clinicians to predict the probability of MT, thereby facilitating accurate assessment of risk and objective decision-making during individual patient management.Methods: Clinico-pathological data from a previously treated cohort of 590 newly presenting PMD patients were reviewed and clinical outcomes categorized as disease free, persistent PMD or MT. Multiple logistic regression was used to predict the probability of MT in the cohort using age, gender, lesion type, site and incision biopsy histopathological diagnoses. Internal validation and calibration of the model was performed using the bootstrap method (n = 1000), and bias-corrected indices of model performance were computed.Results: Potentially malignant disorders were predominantly leukoplakias (79%), presenting most frequently at floor of mouth and lateral tongue sites (51%); 99 patients (17%) developed oral squamous cell carcinoma during the study period. The nomogram performed well when MT predictions were compared with patient outcome data, demonstrating good bias-corrected discrimination and calibration (Dxy  = 0.58; C = 0.790), with a sensitivity of 87% and specificity 63%, and a positive predictive value of 32% and negative predictive value 96%.Conclusion: The "Newcastle Nomogram" has been developed to predict the probability of MT in PMD, based on an internally validated statistical model. Based upon readily available and patient-specific clinico-pathological data, it provides clinicians with a pragmatic diagrammatic aid for clinical decision-making during diagnosis and management of PMD. [ABSTRACT FROM AUTHOR]

Background: People with bipolar disorder typically require long-term pharmacological treatment to prevent episodes of depression or mania. However, evidence-based guidelines are often not followed by prescribers and, in some countries, prescribing of lithium is in decline. Polypharmacy is also common in bipolar disorder.AimsTo employ a data linkage approach to describe and evaluate prescribing patterns in bipolar disorder in Scotland between 2009 and 2016.Method: By linking prescribing data to the electronic Scottish Morbidity Records, we identified a cohort of 23 135 patients with bipolar disorder who were prescribed psychotropic medication between 2009 and 2016. We examined trends in proportions of patients prescribed each of six drug categories. Random effects logistic models examined change in prescribing over years of interest.Results: The most common form of treatment was antidepressant monotherapy (24.96%), with only 5.90% of patients receiving lithium monotherapy. Prescribing of antipsychotics and anti-epileptics increased from 2009 to 2016 (antipsychotics: odds ratio 1.16, 95% CI 1.15-1.18; anti-epileptics: odds ratio 1.34, 95% CI 1.32-1.36), whereas prescribing of lithium decreased (odds ratio 0.83, 95% CI 0.82-0.85). Prescribing of valproate decreased from 2009-2016 in women, but increased in men (women: odds ratio 0.93, 95% CI 0.90-0.97; men: odds ratio 1.11, 95% CI 1.04-1.18).Conclusions: Antidepressant monotherapy was the most common form of treatment for bipolar disorder in Scotland and prescribing of lithium has declined between 2009 and 2016. The findings are concerning and represent a gap between treatment guidelines and clinical practice.Declaration of interestNone. [ABSTRACT FROM AUTHOR]

Acarbose, an alpha-glucosidase inhibitor used in treating type 2 diabetes, impairs complex carbohydrate digestion and absorption and extends life span in mice (without a requisite reduction in food intake). To assess sex-differential effects coincident with calorie restriction versus a nonrestricted longevity enhancing intervention, we evaluated the metabolite profiles (by liquid chromatography-mass spectroscopy) from livers and cecal contents of C57BL/6J mice (n = 4/sex/group), which were maintained for 10 months under one of the three diet treatments: ad libitum control diet (CON), ad libitum control diet containing 0.1% acarbose (ACA), or 40% calorie restriction using the control diet (CR). Principal component analysis revealed sex-differential profiles with ACA in livers. Of the identified metabolites (n = 621) in liver, CR significantly altered ~44% (males:187↑/131↓, females:74↑/148↓) compared with CON, in contrast with ACA (M:165↑/61↓, F:52↑/60↓). Dissimilarity in ACA-F liver metabolites was observed for ~50% of common metabolites from ACA-M and CR-M/F. CR resulted in fewer significant cecal metabolite differences (n = 615 metabolites; M:86↑/66↓, F:51↑/48↓ vs CON), relative to ACA treatment (M:32↑/189↓, F:36↑/137↓). Metabolomic profiling identifies sex-differential and tissue-specific effects with amino acid metabolism sub-pathways including those involving tryptophan, branch-chain and sulfur amino acids, and the urea cycle, as well as bile acid, porphyrin, and cofactor metabolism pathways. [ABSTRACT FROM AUTHOR]

The study examined a new child report measure of maternal support following child sexual abuse. One hundred and forty-six mother–child dyads presenting for a forensic evaluation completed assessments including standardized measures of adjustment. Child participants also responded to 32 items considered for inclusion in a new measure, the Maternal Support Questionnaire–Child Report (MSQ-CR). Exploratory factor analysis of the Maternal Support Questionnaire–Child Report resulted in a three factor, 20-item solution: Emotional Support (9 items), Skeptical Preoccupation (5 items), and Protection/Retaliation (6 items). Each factor demonstrated adequate internal consistency. Construct and concurrent validity of the new measure were supported in comparison to other trauma-specific measures. The Maternal Support Questionnaire–Child Report demonstrated sound psychometric properties. Future research is needed to determine whether the Maternal Support Questionnaire–Child Report provides a more sensitive approximation of maternal support following disclosure of sexual abuse, relative to measures of global parent–child relations and to contextualize discrepancies between mother and child ratings of maternal support. [ABSTRACT FROM PUBLISHER]

Purpose: Prophylactic cranial irradiation (PCI) involves giving radiation to the entire brain with the goals of reducing the incidence of brain metastasis and improving overall survival. Experimentally, we have demonstrated that PCI prevents brain metastases in a breast cancer mouse model. We developed a computational model to expand on and aid in the interpretation of our experimental results.Methods and Materials: MATLAB was used to develop a computational model of brain metastasis and PCI in mice. Model input parameters were optimized such that the model output would match the experimental number of metastases per mouse from the unirradiated group. An independent in vivo-limiting dilution experiment was performed to validate the model. The effect of whole brain irradiation at different measurement points after tumor cells were injected was evaluated in terms of the incidence, number of metastases, and tumor burden and was then compared with the corresponding experimental data.Results: In the optimized model, the correlation between the number of metastases per mouse and the experimental fits was >95. Our attempt to validate the model with a limiting dilution assay produced 99.9% correlation with respect to the incidence of metastases. The model accurately predicted the effect of whole-brain irradiation given 3 weeks after cell injection but substantially underestimated its effect when delivered 5 days after cell injection. The model further demonstrated that delaying whole-brain irradiation until the development of gross disease introduces a dose threshold that must be reached before a reduction in incidence can be realized.Conclusions: Our computational model of mouse brain metastasis and PCI correlated strongly with our experiments with unirradiated mice. The results further suggest that early treatment of subclinical disease is more effective than irradiating established disease. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is highly prevalent and a significant source of disability, yet its genetic and environmental risk factors are poorly understood. Its relationship with major depressive disorder (MDD) is of particular importance. We sought to test the contribution of genetic factors and shared and unique environment to risk of chronic pain and its correlation with MDD in Generation Scotland: Scottish Family Health Study (GS:SFHS). We then sought to replicate any significant findings in the United Kingdom Biobank study.Methods and Findings: Using family-based mixed-model analyses, we examined the contribution of genetics and shared family environment to chronic pain by spouse, sibling, and household relationships. These analyses were conducted in GS:SFHS (n = 23,960), a family- and population-based study of individuals recruited from the Scottish population through their general practitioners. We then examined and partitioned the correlation between chronic pain and MDD and estimated the contribution of genetic factors and shared environment in GS:SFHS. Finally, we used data from two independent genome-wide association studies to test whether chronic pain has a polygenic architecture and examine whether genomic risk of psychiatric disorder predicted chronic pain and whether genomic risk of chronic pain predicted MDD. These analyses were conducted in GS:SFHS and repeated in UK Biobank, a study of 500,000 from the UK population, of whom 112,151 had genotyping and phenotypic data. Chronic pain is a moderately heritable trait (heritability = 38.4%, 95% CI 33.6% to 43.9%) that is significantly concordant in spouses (variance explained 18.7%, 95% CI 9.5% to 25.1%). Chronic pain is positively correlated with depression (ρ = 0.13, 95% CI 0.11 to 0.15, p = 2.72x10-68) and shows a tendency to cluster within families for genetic reasons (genetic correlation = 0.51, 95%CI 0.40 to 0.62, p = 8.24x10-19). Polygenic risk profiles for pain, generated using independent GWAS data, were associated with chronic pain in both GS:SFHS (maximum β = 6.18x10-2, 95% CI 2.84 x10-2 to 9.35 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 5.68 x 10-2, 95% CI 4.70x10-2 to 6.65x10-2, p < 3x10-4). Genomic risk of MDD is also significantly associated with chronic pain in both GS:SFHS (maximum β = 6.62x10-2, 95% CI 2.82 x10-2 to 9.76 x10-2, p = 4.3x10-4) and UK Biobank (maximum β = 2.56x10-2, 95% CI 1.62x10-2 to 3.63x10-2, p < 3x10-4). Limitations of the current study include the possibility that spouse effects may be due to assortative mating and the relatively small polygenic risk score effect sizes.Conclusions: Genetic factors, as well as chronic pain in a partner or spouse, contribute substantially to the risk of chronic pain for an individual. Chronic pain is genetically correlated with MDD, has a polygenic architecture, and is associated with polygenic risk of MDD. [ABSTRACT FROM AUTHOR]

Background: Brain metastasis poses a major treatment challenge and remains an unmet clinical need. Finding novel therapies to prevent and treat brain metastases requires an understanding of the biology and molecular basis of the process, which currently is constrained by a dearth of experimental models and specific therapeutic targets.Methods: Green Fluorescent Protein (GFP)-labeled breast cancer cells were injected via tail vein into SCID/Beige mice (n = 10-15 per group), and metastatic colonization to the brain and lung was evaluated eight weeks later. Knockdown and overexpression of miR-141 were achieved with lentiviral vectors. Serum levels of miR-141 were measured from breast cancer patients (n = 105), and the association with clinical outcome was determined by Kaplan-Meier method. All statistical tests were two-sided.Results: Novel brain metastasis mouse models were developed via tail vein injection of parental triple-negative and human epidermal growth factor receptor 2 (HER2)-overexpressing inflammatory breast cancer lines. Knockdown of miR-141 inhibited metastatic colonization to brain (miR-141 knockdown vs control: SUM149, 0/8 mice vs 6/9 mice,P= .009; MDA-IBC3, 2/14 mice vs 10/15 mice,P= .007). Ectopic expression of miR-141 in nonexpressing MDA-MB-231 enhanced brain metastatic colonization (5/9 mice vs 0/10 mice,P= .02). Furthermore, high miR-141 serum levels were associated with shorter brain metastasis-free survival (P= .04) and were an independent predictor of progression-free survival (hazard ratio [HR] = 4.77, 95% confidence interval [CI] = 2.61 to 8.71,P< .001) and overall survival (HR = 7.22, 95% CI = 3.46 to 15.06,P< .001).Conclusions: Our study suggests miR-141 is a regulator of brain metastasis from breast cancer and should be examined as a biomarker and potential target to prevent and treat brain metastases. [ABSTRACT FROM AUTHOR]

Background: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC).Methods: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes.Results: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04).Conclusions: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The relative contribution of demographic, lifestyle and medication factors to the association between affective disorders and cardiometabolic diseases is poorly understood.Aims: To assess the relationship between cardiometabolic disease and features of depresion and bipolar disorder within a large population sample.Method: Cross-sectional study of 145 991 UK Biobank participants: multivariate analyses of associations between features of depression or bipolar disorder and five cardiometabolic outcomes, adjusting for confounding factors.Results: There were significant associations between mood disorder features and 'any cardiovascular disease' (depression odds ratio (OR) = 1.15, 95% CI 1.12-1.19; bipolar OR = 1.28, 95% CI 1.14-1.43) and with hypertension (depression OR = 1.15, 95% CI 1.13-1.18; bipolar OR = 1.26, 95% CI 1.12-1.42). Individuals with features of mood disorder taking psychotropic medication were significantly more likely than controls not on psychotropics to report myocardial infarction (depression OR = 1.47, 95% CI 1.24-1.73; bipolar OR = 2.23, 95% CI 1.53-3.57) and stroke (depression OR = 2.46, 95% CI 2.10-2.80; bipolar OR = 2.31, 95% CI 1.39-3.85).Conclusions: Associations between features of depression or bipolar disorder and cardiovascular disease outcomes were statistically independent of demographic, lifestyle and medication confounders. Psychotropic medication may also be a risk factor for cardiometabolic disease in individuals without a clear history of mood disorder. [ABSTRACT FROM AUTHOR]

Background: Comorbid chronic pain and depression is a challenging dyad of conditions to manage in primary care and reporting has shown to vary by ethnic group. Whether the relationship between depression and chronic pain varies by ethnicity is unclear. This study aims to explore chronic pain and depression reporting across ethnic groups and examine whether this association differs, independently of potential confounding factors. Methods: Cross-sectional study of UK Biobank participants with complete data on chronic pain and probable lifetime history of depression, who reported their ethnic group as White, Asian/Asian British or Black/Black British. Chronic pain classification: present if participants had ≥ 1 site of body pain (up to seven sites or "pain all over the body" could be selected) that lasted ≥ 3 months; extent of chronic pain categories: 0, 1, 2-3, 4-7 sites or pain all over the body. Probable depression classification: an algorithm of low mood, anhedonia and help-seeking behaviour. Relationship between depression and presence/extent of chronic pain assessed using logistic/ multinomial regression models (odds ratio (OR); relative risk ratio (RRR), 95 % confidence intervals), adjusted for sociodemographic, lifestyle, and morbidity factors; and a final adjustment for current depressive symptoms. Results: The number of participants eligible for inclusion was 144,139: 35,703 (94 %) White, 4539 (3 %) Asian, and 3897 (3 %) Black. Chronic pain was less (40.5 %, 45.8 %, 45.0 %, respectively) and depression more (22.1 %, 12.9 %, 13.8 %, respectively) commonly reported in White participants than Asian and Black participants. Statistically significant associations between depression and presence/extent of chronic pain persisted following adjustment for potential confounding variables; this relationship was strongest for Black participants (presence of chronic pain: OR 1.86 (1.52, 2.27); RRR 1 site 1.49 (1.16, 1.91), 2-3 sites 1.98 (1.53, 2.56), 4-7 sites 3.23 (2.09, 4.99), pain all over the body 3.31 (2.05, 5.33). When current depressive symptoms were considered these relationships were attenuated. Conclusions: Chronic pain and depression reporting varies across ethnic groups. Differences in health seeking behaviour between ethnic groups may impact on the results reported. Clinicians, particularly in primary care, need to be aware of the cultural barriers within certain ethic groups to expressing concern over mood and to consider their approach accordingly. [ABSTRACT FROM AUTHOR]

The purpose of this investigation is to describe the characteristics of professional and preprofessional learners who registered for and completed TF-CBT Web, a modular, web-based training program designed to promote the dissemination of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) and to demonstrate the feasibility of this method of dissemination. Between October 1, 2005, and October 1, 2012, a total of 123,848 learners registered for TF-CBT Web, of whom 98,646 (79.7%) initiated the learning activities by beginning the first module pretest. Of those, 67,201 (68.1%) completed the full training. Registrants hailed from 130 countries worldwide, and they had varied educational backgrounds, professional identities (both professional and preprofessional), and a range of experience working with child trauma victims. Learners who were from the United States, students, those with master's degrees, and those with fewer years of experience working with child trauma victims tended to have the highest course completion rates. Learners displayed significant increases in knowledge about each component of TF-CBT, based on module pretest and posttest scores. The advantages and limitations of this web-based training program evaluation are discussed, while important implications for the use of web-based trainings are reviewed. [ABSTRACT FROM AUTHOR]

Neurodevelopmental disorders are recognized to be relatively common in developing countries but little data exist for planning effective prevention and intervention strategies. In particular, data on autism spectrum disorders are lacking. For application in Uganda, we developed a 23-question screener (23Q) that includes the Ten Questions screener and additional questions on autism spectrum disorder behaviors. We then conducted household screening of 1169 children, 2–9 years of age, followed by clinical assessment of children who screened positive and a sample of those who screened negative to evaluate the validity of the screener. We found that 320 children (27% of the total) screened positive and 68 children received a clinical diagnosis of one or more moderate to severe neurodevelopmental disorders (autism spectrum disorder; cerebral palsy; epilepsy; cognitive, speech and language, hearing, or vision impairment), including 8 children with autism spectrum disorders. Prevalence and validity of the screener were evaluated under different statistical assumptions. Sensitivity of the 23Q ranged from 0.55 to 0.80 and prevalence for ≥1 neurodevelopmental disorders from 7.7/100 children to 12.8/100 children depending on which assumptions were used. The combination of screening positive on both autism spectrum disorders and Ten Questions items was modestly successful in identifying a subgroup of children at especially high risk of autism spectrum disorders. We recommend that autism spectrum disorders and related behavioral disorders be included in studies of neurodevelopmental disorders in low-resource settings to obtain essential data for planning local and global public health responses. [ABSTRACT FROM PUBLISHER]

Background: Offspring of mothers with depression are at heightened risk of psychiatric disorder. Many mothers with depression have comorbid psychopathology. How these co-occurring problems affect child outcomes has rarely been considered.Aims: To consider whether the overall burden of co-occurring psychopathology in mothers with recurrent depression predicts new-onset psychopathology in offspring.Method: Mothers with recurrent depression and their adolescent offspring (9-17 years at baseline) were assessed in 2007 and on two further occasions up to 2011. Mothers completed questionnaires assessing depression severity, anxiety, alcohol problems and antisocial behaviour. Psychiatric disorder in offspring was assessed using the Child and Adolescent Psychiatric Assessment.Results: The number of co-occurring problems in mothers (0, 1 or 2+) predicted new-onset offspring disorder (odds ratio (OR) = 1.80, 95% CI 1.17-2.77, P = 0.007). Rates varied from 15.7 to 34.8% depending on the number of co-occurring clinical problems. This remained significant after controlling for maternal depression severity (OR = 1.73, 95% CI 1.03-2.89, P = 0.040).Conclusions: The burden of co-occurring psychopathology among mothers with recurrent depression indexes increased risk of future onset of psychiatric disorder for offspring. This knowledge can be used in targeting preventive measures in children at high risk of psychiatric disorder. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop an efficient way to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]- tyrosine ( 99mTc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with 99mTc with high radiochemical purity (>95%). Cellular uptake of 99mTc-N4-Tyrosine was much higher than that of 99mTc- N4 and the clinical gold standard 18F-2-deoxy-2-fluoro-glucose (18F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although 99mTc-N4-Tyrosine appeared to be inferior to 18F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. 99mTc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging. [ABSTRACT FROM AUTHOR]

The nitro group of 2-nitroimidazole (NIM) enters the tumor cells and is bioreductively activated and fixed in the hypoxia cells. 1,4, 8,11-tetraazacyclotetradecane (N4) has shown to be a stable chelator for 99mTc. The present study was aimed to develop 99mTc-cyclam- 2-nitroimidazole ( 99mTc-N4-NIM) for tumor hypoxia imaging. N4-NIM precursor was synthesized by reacting N4-oxalate and 1,3-dibromopropane-NIM, yielded 14% (total synthesis). Cell uptake of 99mTc-N4-NIM and 99mTc-N4 was obtained in 13762 rat mammary tumor cells and mesothelioma cells in 6-well plates. Tissue distribution of 99mTc-N4-NIM was evaluated in breasttumor-bearing rats at 0.5-4 hrs. Tumor oxygen tension was measured using an oxygen probe. Planar imaging was performed in the tumor-bearing rat and rabbit models. Radiochemical purity of 99mTc-N4-NIM was >96% by HPLC. Cell uptake of 99mTc-N4-NIM was higher than 99mTc-N4 in both cell lines. Biodistribution of 99mTc-N4-NIM showed increased tumor-to-blood and tumor-tomuscle count density ratios as a function of time. Oxygen tension in tumor tissue was 6-10mmHg compared to 40-50mmHg in normal muscle tissue. Planar imaging studies confirmed that the tumors could be visualized clearly with 99mTc-N4-NIM in animal models. Efficient synthesis of N4-NIM was achieved. 99mTc-N4-NIM is a novel hypoxic probe and may be useful in evaluating cancer therapy. [ABSTRACT FROM AUTHOR]

Activation of hedgehog (HH) pathway signaling is observed in many tumors. Due to a feedback loop, the HH receptor Patched (PTCH-1) is over expressed in tumors with activated HH signaling. Therefore, we sought to radiolabel the PTCH-1 ligand sonic (SHH) for detection of cancer cells with canonical HH activity. Receptor binding of 131I-SHH was increased in cell lines with high HH pathway activation. Our findings also show that PTCH-1 receptor expression is decreased upon treatment with HH signaling inhibitors, and receptor binding of 131I-SHH is significantly decreased following treatment with cyclopamine. In vivo imaging and biodistribution studies revealed significant accumulation of 131I-SHH within tumor tissue as compared to normal organs. Tumor-to- muscle ratios were approximately 8 : 1 at 5 hours, while tumor to blood and tumor to bone were 2 : 1 and 5 : 1, respectively. Significant uptake was also observed in liver and gastrointestinal tissue. These studies show that 131I-SHH is capable of in vivo detection of breast tumors with high HH signaling. We further demonstrate that the hedgehog receptor PTCH-1 is downregulated upon treatment with hedgehog inhibitors. Our data suggests that radiolabeled SHH derivatives may provide a method to determine response to SHH-targeted therapies. [ABSTRACT FROM AUTHOR]

Many rodent experiments have assessed effects of diets, drugs, genes, and other factors on life span. A challenge with such experiments is their long duration, typically over 3.5 years given rodent life spans, thus requiring significant time costs until answers are obtained. We collected longevity data from 15 rodent studies and artificially truncated them at 2 years to assess the extent to which one will obtain the same answer regarding mortality effects. When truncated, the point estimates were not significantly different in any study, implying that in most cases, truncated studies yield similar estimates. The median ratio of variances of coefficients for truncated to full-length studies was 3.4, implying that truncated studies with roughly 3.4 times as many rodents will often have equivalent or greater power. Cost calculations suggest that shorter studies will be more expensive but perhaps not so much to not be worth the reduced time. [ABSTRACT FROM PUBLISHER]

Background: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples.Aims: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes.Methods: Following PRISMA guidelines, we searched EMBASE, Medline and PsycINFO (from August 2009 - 14th March 2016) and references of included studies. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate.Results: Twenty-five studies were included. Overall, both polygenic risk scores were associated with other psychiatric disorders (not the discovery sample disorder) such as depression, schizophrenia and bipolar disorder, greater symptom severity of depression, membership of a creative profession and greater educational attainment. Both depression and bipolar polygenic risk scores explained small amounts of variance in most phenotypes (< 2%).Limitations: Many studies did not report standardised effect sizes. This prevented us from conducting a meta-analysis.Conclusions: Polygenic risk scores for BD and MDD are associated with a range of phenotypes and outcomes. However, they only explain a small amount of the variation in these phenotypes. Larger discovery and adequately powered target samples are required to increase power of the PRS approach. This could elucidate how genetic risk for bipolar disorder and depression is manifest and contribute meaningfully to stratified medicine. [ABSTRACT FROM AUTHOR]

Background: Depression is highly heterogeneous in its clinical presentation. Those with attention deficit/hyperactivity disorder (ADHD) may be at risk of a more chronic and impairing depression compared to those with depression alone according to studies of young people. However, no studies to date have examined ADHD in recurrently depressed adults in mid-life.Method: In a sample of women in mid-life (n=148) taken from a UK based prospective cohort of adults with a history of recurrent depression, we investigated the prevalence of ADHD and the association of ADHD with clinical features of depression.Results: 12.8% of the recurrently depressed women had elevated ADHD symptoms and 3.4% met DSM-5 diagnostic criteria for ADHD. None of the women reported having a diagnosis of ADHD from a medical professional. ADHD symptoms were associated with earlier age of depression onset, higher depression associated impairment, a greater recurrence of depressive episodes and increased persistence of subthreshold depression symptoms over the study period, higher levels of irritability and increased risk of self-harm or suicide attempt. ADHD symptoms were associated with increased risk of hospitalisation and receiving non-first-line antidepressant medication.Limitations: ADHD was measured using a questionnaire measure. We focussed on mothers in a longitudinal study of recurrent depression, so the findings may not apply to males or other groups.Conclusions: Higher ADHD symptoms appear to index a worse clinical presentation for depression. Clinical implications include that in women with early onset, impairing and recurrent depression, the possibility of underlying ADHD masked by depression needs to be considered. [ABSTRACT FROM AUTHOR]

Purpose: Oral oncolytics are an increasingly important treatment option for cancer. These agents often fall within the pharmacy benefit, with the potential for increased out-of-pocket (OOP) cost burden for patients. The purpose of this study was to evaluate patient OOP payments for oral oncolytic therapies in US managed care plans. Materials and Methods: Patients age ≥ 18 years who received one of 21 oral oncolytics were identified in 2009 US claims; the first oral therapy was the index therapy. OOP payments were calculated as the allowed amount (dollar amount a health plan allows for a therapy, including member liability) minus the paid amount (dollar amount paid by a health plan). Patient characteristics were provided, and per-claim OOP payments were evaluated for each of the 21 therapies in aggregate and stratified by payer type and index therapy. Results: A total of 6,094 patients who received at least one oral oncolytic therapy were identified. Mean age was 53 years; 54% were women; 77% had a commercial payer; prevalent cancer diagnoses included breast, colorectal, glioblastoma, and lung. Mean OOP payments were highest for dasatinib ($527; median, $36) and lowest for cyclophosphamide ($15; median, $10). Medicare Risk patients had higher mean OOP payments for most therapies compared with commercial, Medicaid, and self-insured patients. Conclusion: Among 21 oral oncolytics, average OOP cost ranged from $15 to $500. These results confirm previous findings showing OOP payments differing widely among oral oncolytic options. As cost for therapy becomes a greater part of treatment decisions, an understanding of patient OOP cost will be critical in informing choices. [ABSTRACT FROM AUTHOR]

Background: Studying the phenotypic manifestations of increased genetic liability for Bipolar Disorder (BD) can increase understanding of this disorder.Aims: We assessed whether genetic risk for BD was associated with childhood psychopathology and features of hypomania in young adulthood within a large population-based birth cohort.Methods: We used data from the second Psychiatric Genetics Consortium Genome Wide Association Study (GWAS) for Bipolar Disorder to construct a polygenic risk score (PRS) for each individual in the Avon Longitudinal Study of Parents and Children (ALSPAC). Linear and logistic regression models were used to assess associations between the BD-PRS and emotional/behavioural difficulties, attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) traits in childhood, as well as hypomania in early adulthood (sample sizes from 2654 to 6111).Results: The BD-PRS was not associated with total hypomania score, but was weakly associated with a binary measure of hypomania (OR = 1.13, 95%CI 0.98,1.32; p = 0.097), and particularly at higher hypomania symptom thresholds (strongest evidence OR = 1.33, 95%CI 1.07, 1.65; p = 0.01). The BD-PRS was also associated with ADHD (OR = 1.31, 95%CI 1.10, 1.57; p = 0.018), but not with other childhood psychopathology.Limitations: The PRS only captures common genetic variation and currently explains a relatively small proportion of the variance for BD.Conclusions: The BD-PRS was associated with ADHD in childhood, and weakly with adult hypomania, but not with other psychopathology examined. Our findings suggest that genetic risk for BD does not appear to manifest in childhood to the same extent as schizophrenia genetic risk has been reported to do. [ABSTRACT FROM AUTHOR]

Background: Adolescent depression is common and leads to distress and impairment for individuals/families. Treatment/prevention guidelines stress the need for good information and evidence-based psychosocial interventions. There has been growing interest in psychoeducational interventions (PIs), which broadly deliver accurate information about health issues and self-management.Objective, Methods: Systematic search of targeted PIs as part of prevention/management approaches for adolescent depression. Searches were undertaken independently in PubMed, PsycINFO, EMBASE, guidelines, reviews (including Cochrane), and reference lists. Key authors were contacted. No restrictions regarding publishing dates.Results: Fifteen studies were included: seven targeted adolescents with depression/depressive symptoms, eight targeted adolescents 'at risk' e.g. with a family history of depression. Most involved family/group programmes; others included individual, school-based and online approaches. PIs may affect understanding of depression, identification of symptoms, communication, engagement, and mental health outcomes.Conclusion, Practice Implications: PIs can have a role in preventing/managing adolescent depression, as a first-line or adjunctive approach. The limited number of studies, heterogeneity in formats and evaluation, and inconsistent approach to defining PI, make it difficult to compare programmes and measure overall effectiveness. Further work needs to establish an agreed definition of PI, develop/evaluate PIs in line with frameworks for complex interventions, and analyse their active components. [ABSTRACT FROM AUTHOR]

Background: There is limited understanding of the symptomatic development of bipolar disorder from childhood to early adulthood.Aims: We assessed whether borderline personality disorder traits, ADHD, and emotional, behavioural and social difficulties during childhood were associated with hypomania assessed in young adulthood.Method: We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine associations between measures of childhood psychopathology and lifetime hypomanic features assessed at age 22-23 years using the Hypomania Checklist-32 (HCL-32; n = 3372). We also conducted a factor analysis of the HCL to identify latent constructs underlying hypomania, and the extent to which childhood psychopathology was associated with these.Results: We identified two factors of the HCL corresponding to energy/mood and risk-taking/irritability. There was evidence of association between childhood borderline personality disorder traits and both hypomania factors, with evidence that the association was stronger with the risk-taking/irritability factor. All individual borderline traits, with the exception of fear of abandonment, were associated with hypomania. There was also evidence of association between most other measures of childhood psychopathology (ADHD, hyperactivity, conduct problems, peer relationship problems and reduced prosocial behaviour) and the risk-taking/irritability factor, but much less consistent evidence of association with the energy/mood factor.Limitations: The HCL cannot diagnose bipolar disorder and may be subject to reporting bias.Conclusions: A broad range of childhood psychopathologies may represent early markers of risk for hypomania. Further studies are required to understand the mechanisms underlying these associations, and to inform earlier detection of bipolar disorder. [ABSTRACT FROM AUTHOR]

Gamified interventions exploit the motivational characteristics of a game in order to provide prevention information and promote behavior change. Despite the modest effect sizes observed in increasingly popular web-based personalized normative feedback (PNF) alcohol interventions for college students, previous research has yet to consider how gamification might be used to enhance efficacy. This study examines whether a novel, gamified PNF intervention format, which includes a point-based reward system, the element of chance, and personal icons to visually represent users, is more effective in reducing short-term alcohol use than the standard web-based style of PNF currently used on college campuses. Two-hundred and thirty-seven college students were randomly assigned to receive either a standard brief, web-based PNF alcohol intervention or the same alcohol intervention components delivered within a Facebook-connected social game called CampusGANDR (Gamified Alcohol Norm Discovery and Readjustment). In both study conditions participants answered identical questions about their perceptions of peer drinking norms and own drinking and then received the same PNF slides. Two weeks following PNF delivery, participants again reported their perceptions of peers' alcohol use and own drinking. Students in the CampusGANDR condition reported significantly reduced peer drinking norms and alcohol use at the two-week follow-up relative to students who received identical PNF delivered by standard online survey. Further, a mediation model demonstrated that this effect was driven by larger reductions in perceived drinking norms among participants assigned to receive CampusGANDR, relative to control. As web-based PNF is becoming an increasingly universal prevention strategy, findings from this study suggest gamification may represent one method by which intervention efficacy could be substantially improved. The potential methodological and economic benefits associated with gamified PNF interventions are emphasized and directions for future research are discussed. [ABSTRACT FROM AUTHOR]

Background: Previous reviews have identified medium-large group differences in cognitive performance in adults with bipolar disorder (BD) compared to healthy peers, but the proportion with clinically relevant cognitive impairment has not yet been established. This review aimed to quantify the prevalence of cognitive impairment in euthymic adults with BD, and to describe sociodemographic, clinical and other factors that are significantly associated with cognitive impairment.Methods: Systematic literature review. The population was euthymic community-dwelling adults with BD, aged 18-70 years, and recruited consecutively or randomly. The outcome was cognitive impairment, relative to healthy population norms. Electronic databases and reference lists of relevant articles were searched, and authors were contacted. Original cross-sectional studies published in peer-reviewed English-language journals from January 1994 to February 2015 were included. Methodological bias and reporting bias were assessed using standard tools. A narrative synthesis is presented together with tables and forest plots.Results: Thirty articles were included, of which 15 contributed prevalence data. At the 5th percentile impairment threshold, prevalence ranges were: executive function 5.3-57.7%; attention/working memory 9.6-51.9%; speed/reaction time 23.3-44.2%; verbal memory 8.2-42.1%; visual memory 11.5-32.9%. More severe or longstanding illness and antipsychotic medication were associated with greater cognitive impairment.Limitations: The synthesis was limited by heterogeneity in cognitive measures and impairment thresholds, precluding meta-analysis.Conclusions: Cognitive impairment affects a substantial proportion of euthymic adults with BD. Future research with more consistent measurement and reporting will facilitate an improved understanding of cognitive impairment burden in BD. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested a possible link between exposure to influenza in utero and bipolar disorder in adulthood. Using data from a prospective birth cohort, we aimed to test for an association between exposure to gestational influenza and the experience of hypomania assessed in early adulthood.Methods: We used data on 2957 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). The two main outcomes of interest were hypomania, assessed using the Hypomania Checklist (HCL-32) at age 22-23, and 'hypomania plus previous psychotic experiences (PE)'. Maternally-reported gestational influenza was the exposure of interest. Multivariable logistic regression was used and estimates of association were adjusted for a range of possible confounding factors, including maternal smoking in pregnancy.Results: Relative to controls, rates of exposure to gestational influenza were higher for participants with hypomania (24.0%) and for participants with 'hypomania plus PE' (34.2%), but univariate and multivariable analyses of an association between gestational influenza and hypomania (with and without previous PE) were not significant.Limitations: The response rate to those who were sent the HCL-32 questionnaire was 36.8%. As a result, some analyses may have been under-powered to detect a true effect. Influenza infection during pregnancy was self-reported by mothers.Conclusions: In this prospective population study, gestational influenza was not identified as a clear risk factor for lifetime hypomania or for 'hypomania with PEs' in young adult offspring. It is possible that previous reports of an association between gestational influenza and bipolar disorder in adulthood have been confounded by factors such as maternal smoking during pregnancy. [ABSTRACT FROM AUTHOR]