Injury, Interiority, and Isolation in Men’s Suicidality

Men’s high suicide rates have been linked to individual risk factors including history of being abused as a child, single marital status, and financial difficulties. While it has also been suggested that the normative influences of hegemonic masculinities are implicated in men’s suicide, the gendered experiences of male suicidality are poorly understood. In the current photovoice study, 20 men who previously had suicidal thoughts, plans, and/or attempts were interviewed as a means to better understanding the connections between masculinities and their experiences of suicidality. The study findings revealed injury, interiority, and isolation as interconnected themes characterizing men’s suicidality. Injury comprised an array of childhood and/or cumulative traumas that fueled men’s ruminating thoughts inhibiting recovery and limiting hopes for improved life quality. In attempting to blunt these traumas, many men described self-injuring through the overuse of alcohol and other drugs. The interiority theme revealed how suicidal thoughts can fuel hopelessness amid summonsing remedies from within. The challenges to self-manage, especially when experiencing muddled thinking and negative thought were evident, and led some participants to summons exterior resources to counter suicidality. Isolation included separateness from others, and was linked to abandonment issues and not having a job and/or partner. Self-isolating also featured as a protection strategy to avoid troubling others and/or reducing exposure to additional noxious stimuli. The study findings suggest multiple intervention points and strategies, the majority of which are premised on promoting men’s social connectedness. The destigmatizing value of photovoice methods is also discussed

Health of people experiencing co-occurring homelessness, imprisonment, substance use, sex work and/or severe mental illness in high-income countries: a systematic review and meta-analysis

Background: People affected by homelessness, imprisonment, substance use, sex work or severe mental illness experience substantial excess ill health and premature death. Though these experiences often co-occur, health outcomes associated with their overlap have not previously been reviewed. We synthesised existing evidence on mortality, morbidity, self-rated health and quality of life among people affected by more than one of these experiences. Methods: In this systematic review and meta-analysis, we searched Medline, Embase, and PsycINFO for peer-reviewed English-language observational studies from high-income countries published between 1 January 1998 and 11 June 2018. Two authors undertook independent screening, with risk of bias assessed using a modified Newcastle-Ottawa Scale. Findings were summarised by narrative synthesis and random-effect meta-analysis. Results: From 15 976 citations, 2517 studies underwent full-text screening, and 444 were included. The most common exposure combinations were imprisonment/substance use (31% of data points) and severe mental illness/substance use (27%); only 1% reported outcomes associated with more than two exposures. Infections were the most common outcomes studied, with blood-borne viruses accounting for 31% of all data points. Multiple exposures were associated with poorer outcomes in 80% of data points included (sign test for effect direction, p<0.001). Meta-analysis suggested increased all-cause mortality among people with multiple versus fewer exposures (HR: 1.57 and 95% CI: 1.38 to 1.77), though heterogeneity was high. Conclusion: People affected by multiple exclusionary processes experience profound health inequalities, though there are important gaps in the research landscape. Addressing the health needs of these populations is likely to require co-ordinated action across multiple sectors, such as healthcare, criminal justice, drug treatment, housing and social security

EMBR-25. Genome-wide genetic and epigenetic assessment of group 4 Medulloblastoma for improved, biomarker driven, prognostication and risk-stratification

Introduction: Medulloblastoma (MB) is the most common malignant brain tumour in children. The most frequent molecular subgroup, Group 4 (MBGrp4) accounts for ~35/40% of cases, however it has the least understood underlying biology. Clinical outcomes are heterogeneous in MBGrp4 and are not accounted for by established clinico-pathological risk factors. There is now a requirement for a comprehensive study of MBGrp4, considering established clinico-pathological features and novel molecular biomarkers to enhance risk-stratification and identify novel therapeutic targets. Methods: A clinically-annotated, retrospective MBGrp4 discovery cohort (n = 420) was generated from UK CCLG institutions, collaborating European centres and SIOP-UKCCSG-PNET3 and HIT-SIOP-PNET4 clinical trials. Contemporary, multi-omics profiling was performed. Focal and arm level copy number aberrations (CNAs) were determined from molecular inversion probe (MIP) or DNA methylation array which additionally provided next generation non-WNT/non-SHH (Grp3/Grp4) subtype classifications. Targeted next-generation DNA sequencing was performed to overlay the mutational landscape. Survival modelling was carried out with patients >3 years old who received craniospinal irradiation. Results: MBGrp4 subtypes were assigned to 88% of tumours with available data. Subtype VIII was strongly associated with i17q (p<0.0001). The favourable-risk cytogenetic signature (2 or 3 of; chromosome 7 gain, chromosome 8 loss and/or chromosome 11 loss) associated with both subtypes VI and VII (p<0.0001). MYCN amplifications were strongly associated with subtype V (p<0.0001) in addition to 16q loss (p<0.0001). The high-risk CNA group was enriched for mutations in genes involved in chromatin remodelling (p<0.0001). Risk factors were identified from multivariate survival modelling. Subtype and CNA groups contributed to improved risk-stratification models that outperformed current clinical schemes. Conclusion: Comprehensive genetic and epigenetic profiling in this large retrospective cohort has improved our understanding of the molecular and clinical heterogeneity within MBGrp4. Incorporation of molecular biomarkers improved risk-stratification for MBGrp4

Identification of carbon dioxide in an exoplanet atmosphere

Carbon dioxide (CO2) is a key chemical species that is found in a wide range of planetary atmospheres. In the context of exoplanets, CO2 is an indicator of the metal enrichment (that is, elements heavier than helium, also called ‘metallicity’), and thus the formation processes of the primary atmospheres of hot gas giants. It is also one of the most promising species to detect in the secondary atmospheres of terrestrial exoplanets. Previous photometric measurements of transiting planets with the Spitzer Space Telescope have given hints of the presence of CO2, but have not yielded definitive detections owing to the lack of unambiguous spectroscopic identification. Here we present the detection of CO2 in the atmosphere of the gas giant exoplanet WASP-39b from transmission spectroscopy observations obtained with JWST as part of the Early Release Science programme. The data used in this study span 3.0–5.5 micrometres in wavelength and show a prominent CO2 absorption feature at 4.3 micrometres (26-sigma significance). The overall spectrum is well matched by one-dimensional, ten-times solar metallicity models that assume radiative–convective–thermochemical equilibrium and have moderate cloud opacity. These models predict that the atmosphere should have water, carbon monoxide and hydrogen sulfide in addition to CO2, but little methane. Furthermore, we also tentatively detect a small absorption feature near 4.0 micrometres that is not reproduced by these models

The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT).

Hyper-phosphorylated tau accumulates as insoluble fibrils in Alzheimers disease (AD) and related dementias. The strong correlation between phosphorylated tau and disease has led to an interest in understanding how cellular factors discriminate it from normal tau. Here, we screen a panel of chaperones containing tetratricopeptide repeat (TPR) domains to identify those that might selectively interact with phosphorylated tau. We find that the E3 ubiquitin ligase, CHIP/STUB1, binds 10-fold more strongly to phosphorylated tau than unmodified tau. The presence of even sub-stoichiometric concentrations of CHIP strongly suppresses aggregation and seeding of phosphorylated tau. We also find that CHIP promotes rapid ubiquitination of phosphorylated tau, but not unmodified tau, in vitro. Binding to phosphorylated tau requires CHIPs TPR domain, but the binding mode is partially distinct from the canonical one. In cells, CHIP restricts seeding by phosphorylated tau, suggesting that it could be an important barrier in cell-to-cell spreading. Together, these findings show that CHIP recognizes a phosphorylation-dependent degron on tau, establishing a pathway for regulating the solubility and turnover of this pathological proteoform

Measurements of Regolith Thicknesses on Enceladus: Uncovering the Record of Plume Activity

Data herein are associated with the corresponding manuscript Martin et al. 2022 submitted for publication to Icarus.  Supplemental data files include high-resolution .png version of all figures, as well as data files in both .txt and .xlsx format for the data included in Figures 2, 5, 6, 7, 8, and 9.  These data also include GIS shapefiles of the updated pit chain map, as well as modeled depsotion rates from Southworth et al. [2019].</p