What if they think I\u27m crazy : clinical interventions to help adolescents manage stigma following a psychiatric hospitalization

This qualitative empirical study explores how mental health professionals intervene to help adolescents manage stigma following a psychiatric hospitalization. Twelve clinicians from Northeast public school, state department of mental health, and psychiatric hospital settings were interviewed and asked a series of questions about how they support teens in combating social stigma as they return to their communities. Interview questions addressed a variety of issues pertaining to stigma, including exploring how mental health professionals support adolescents in managing the disclosure process, assessing what resources are particularly helpful for teens in this position, and addressing differences in marginalization based on the visibility or invisibility of a young person\u27s psychiatric condition. The major findings were descriptions, amongst participants, of common individual, family, group, and community-based interventions utilized with recently hospitalized teens. Research participants discussed a number of individual interventions, including supporting the use of coping and emotion regulation skills, planning and brainstorming, normalizing the teenлђs experience, and discussing the disclosure process. Participants also discussed the importance of providing interventions aimed at improving familial, social, and community supports for recently hospitalized adolescents. Future research might directly investigate the experiences of various populations of recently hospitalized adolescents, assessing what types of familial, clinical, academic, and social supports would best support the management of stigma and the reintegration process as discussed by the teens themselves

Research in Pediatric Residency: National Experience of Pediatric Chief Residents

Objective To determine factors associated with increased research productivity, satisfaction, and perceived barriers to research within residency from the experience of pediatric chief residents. Methods An online cross-sectional survey was administered to academic year 2014–15 chief residents. Topics assessed included program demographic characteristics, career intentions, research productivity, satisfaction with research training and opportunities, and research barriers. Chi-square and Fisher exact tests were used for descriptive statistics. Multivariable logistic regression analysis was used to determine factors associated with productivity and research satisfaction. Results The response rate was 63% (165 of 261). Half (82 of 165) were productive in research. Most were satisfied with their quality of research training (55%; 90 of 165) and research opportunities (69%; 114 of 165). Chiefs reporting interest in research were 5 times more likely to be productive than those who did not (odds ratio [OR] = 5.2; 95% confidence interval [CI], 2.3–11.8). Productive chiefs were more likely to report including research time in future careers (P = .003). Most (83%; 137 of 165) thought their programs were supportive of resident research, but lack of time was frequently cited as a major barrier. Those satisfied with research opportunities were less likely to find lack of training (OR = 0.3; 95% CI, 0.1–0.7) or faculty mentorship (OR = 0.2; 95% CI, 0.0–0.9) as a major barrier. Conclusions Pediatric chief resident interest in research is strongly associated with research productivity during residency, and research productivity is strongly associated with career plans including research time. By cultivating research interest through faculty mentorship, research training, and dedicated time, pediatric residency programs might help foster early research success and, potentially lead to continued engagement with research in trainees' future careers

Exploring Ecoacoustic Trajectories in a Giant Sequoia Forest After Wildfire

Forest management strategies that create spatially diverse fire-caused disturbance outcomes, consistent with historic fire regimes, are a desired condition for fire adapted western United States forests. In this context, the temporal dynamics of forest response to fire can inform the tempo and scale of forest management, including prescribed burning. Here, we investigated the use of ecoacoustic methods to assess ecological condition in a four-year period (2016–2019) after wildfire in a giant sequoia forest landscape within Kings Canyon National Park, California, United States. Audio recorders at nine sites were deployed soon after the 2015 Rough Fire subsided. The monitoring sites were located in regions with different fire histories, representing five fire history categories. We used the Acoustic Complexity Index (ACI) to document biotic chorus complexity. This previously tested ecoacoustic index provided a daily indicator of biotic sound activity in frequencies dominated by avian calls. Patterns in ACI were evaluated using generalized additive mixed models to understand the relationship with time-since-fire and covariates that accounted for season, fire history category, and weather conditions. We showed that time-since fire and fire-history influenced patterns in ACI after accounting for season and air temperature effects. Monitoring sites where prescribed fire preceded the Rough Fire showed the highest predicted ACI and evidence for a relatively consistent seasonal pattern in ecoacoustic activity across subsequent seasons. Sites without prescribed fire and burned by the Rough Fire exhibited the most pronounced successive decreases in ACI in the first and second years after the fire. The daily temporal resolution of the ecoacoustic index also revealed phenological shifts related to time-since-fire and fire history. Sites unburned by the Rough Fire offered some context for how fire changed ecoacoustic activity post-wildfire, however evidence suggested they were also impacted by the presence of the nearby Rough Fire. The patterns in the ecoacoustic index when combined with vegetation surveys offered complementary insights into ecological dynamics of regeneration after fire. Our exploratory analysis showed that using ecoacoustic methods in wildfire monitoring offers a scalable approach to remote sensing of ecological trends. Archived recordings from the monitoring effort afford future opportunities for new or more detailed insights

The genetic landscape of high-risk neuroblastoma

Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers

De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

Activating mutations in genes encoding phosphatidylinositol 3-kinase (PI3K)-AKT pathway components cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH, OMIM 603387). Here we report that individuals with MPPH lacking upstream PI3K-AKT pathway mutations carry de novo mutations in CCND2 (encoding cyclin D2) that are clustered around a residue that can be phosphorylated by glycogen synthase kinase 3β (GSK-3β). Mutant CCND2 was resistant to proteasomal degradation in vitro compared to wild-type CCND2. The PI3K-AKT pathway modulates GSK-3β activity, and cells from individuals with PIK3CA, PIK3R2 or AKT3 mutations showed similar CCND2 accumulation. CCND2 was expressed at higher levels in brains of mouse embryos expressing activated AKT3. In utero electroporation of mutant CCND2 into embryonic mouse brains produced more proliferating transfected progenitors and a smaller fraction of progenitors exiting the cell cycle compared to cells electroporated with wild-type CCND2. These observations suggest that cyclin D2 stabilization, caused by CCND2 mutation or PI3K-AKT activation, is a unifying mechanism in PI3K-AKT–related megalencephaly syndromes

Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance

Brain malformations involving the corpus callosum are common in children with developmental disabilities. We identified DCC mutations in four families and five sporadic individuals with isolated agenesis of the corpus callosum (ACC) without intellectual disability. DCC mutations result in variable dominant phenotypes with decreased penetrance, including mirror movements and ACC associated with a favorable developmental prognosis. Possible phenotypic modifiers include the type and location of mutation and the sex of the individual

N-Alkylated Linear Heptamethine Polyenes as Potent Non-Azole Leads against Candida Albicans Fungal Infections

In this study, eighteen heptamethine dyes were synthesised and their antifungal activities were evaluated against three clinically relevant yeast species.. The eighteen dyes were placed within classes based on their core subunit i.e. 2,3,3-trimethylindolenine (5a-f), 1,1,2-trimethyl-1H-benzo[e]indole (6a-f), or 2-methylbenzothiazole (7a-f). The results presented herein imply that the three families of cyanine dyes, in particular compounds 5a-f, show high potential as selective scaffolds to treat C. albicans infections. This opens up the opportunity for further optimisation and investigation of this class compounds for potential antifungal treatment

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Canine Brachycephaly is Associated with a Retrotransposon-Mediated Missplicing of SMOC2

In morphological terms, “form” is used to describe an object’s shape and size. In dogs, facial form is stunningly diverse. Facial retrusion, the proximodistal shortening of the snout and widening of the hard palate is common to brachycephalic dogs and is a welfare concern, as the incidence of respiratory distress and ocular trauma observed in this class of dogs is highly correlated with their skull form. Progress to identify the molecular underpinnings of facial retrusion is limited to association of a missense mutation in BMP3 among small brachycephalic dogs. Here, we used morphometrics of skull isosurfaces derived from 374 pedigree and mixed-breed dogs to dissect the genetics of skull form. Through deconvolution of facial forms, we identified quantitative trait loci that are responsible for canine facial shapes and sizes. Our novel insights include recognition that the FGF4 retrogene insertion, previously associated with appendicular chondrodysplasia, also reduces neurocranium size. Focusing on facial shape, we resolved a quantitative trait locus on canine chromosome 1 to a 188-kb critical interval that encompasses SMOC2. An intronic, transposable element within SMOC2 promotes the utilization of cryptic splice sites, causing its incorporation into transcripts, and drastically reduces SMOC2 gene expression in brachycephalic dogs. SMOC2 disruption affects the facial skeleton in a dose-dependent manner. The size effects of the associated SMOC2 haplotype are profound, accounting for 36% of facial length variation in the dogs we tested. Our data bring new focus to SMOC2 by highlighting its clinical implications in both human and veterinary medicine