Duration of untreated psychosis and social function: 1-year follow-up study of first-episode schizophrenia.

BACKGROUND: In first-episode schizophrenia, longer duration of untreated psychosis (DUP) predicts poorer outcomes. AIMS: To address whether the relationship between DUP and outcome is a direct causal one or the result of association between symptoms and/or cognitive functioning and social functioning at the same time point. METHOD: Symptoms, social function and cognitive function were assessed in 98 patients with first-episode schizphrenia at presentation and 1 year later. RESULTS: There was no significant clinical difference between participants with short and long DUP at presentation. Linear regression analyses revealed that longer DUP significantly predicted more severe positive and negative symptoms and poorer social function at 1 year, independent of scores at presentation. Path analyses revealed independent direct relationships between DUP and social function, core negative symptoms and positive symptoms. There was no significant association between DUP and cognition. CONCLUSIONS: Longer DUP predicts poor social function independently of symptoms. The findings underline the importance of taking account of the phenomenological overlap between measures of negative symptoms and social function when investigating the effects of DUP

External Workloads Vary by Position and Game Result in US-based Professional Soccer Players

International Journal of Exercise Science 16(6): 688-699, 2023. Professional soccer is a physically demanding sport that requires players to be highly trained. Advances using GPS allow the tracking of external workloads for individual players in practice and competition, however, there is a lack of evidence on how these measures impact match results. Therefore, we analyzed external workloads by player position and determined if they vary depending on the result of competitive matches. External workloads were analyzed in professional soccer players (n = 25) across 28 competitive games. One-way ANOVA determined if workloads varied by position (striker – ST, wide midfielder - WM, central midfielder – CM, wide defender - WD, central defender – CD) or across games won (n = 8), lost (n = 13) or tied (n = 7). Repeated-measures ANOVA assessed differences in workloads specific to each position in each of the result categories. Statistical significance was set at p \u3c 0.05. Across all games, more high-speed and very-high speed running was done by ST and WD compared to CD (p \u3c 0.001) and CM (p \u3c 0.001 - 0.02). Whole-team data showed no differences in any external workload variable with respect to match result (p \u3e 0.05), however, in games won ST did more very high-speed running than in losing games (p = 0.03) and defending players did more high and very high-speed running in games tied vs. those won or lost (p \u3c 0.05). Whole-team external workloads do not vary depending on the match result; however, high speed running may be a differentiating factor at the positional level. Coaches should consider position-specific analysis when examining player workloads

And then there was one: a camera trap survey of the declining population of African elephants in Knysna, South Africa

Conservation agencies rely on accurate wildlife population estimates to inform management practices. The importance of accuracy increases with smaller, threatened populations, but so too does the challenge in achieving it, especially for evasive species in low-visibility terrain. Non-invasive survey techniques have been successfully applied in such conditions; however, each technique bears a unique set of limitations and often deliver different results. The shy Knysna elephants (Loxodonta africana) occur at extremely low numbers in difficult terrain, and the past few decades have seen debates raging about their numbers, fuelled in part by differing survey outcomes, although a decline has been apparent over the last 150 years. We surveyed the known range of the Knysna elephant population for 15 months (July 2016 – October 2017), using camera traps, and identified one adult female elephant. The reliability of using camera trapping for surveying animal populations in conditions such as the Knysna elephant is compared with the previous faecal DNA genotyping survey. We conclude that this population has declined to a single individual and discuss the implications for local conservation authorities. Additionally, we highlight the importance of designing rigorous survey approaches where only a few individual animals are present.The South African National Parks’ (SANParks) Garden Route National Park management teamhttp://www.sawma.co.zahj2020Mammal Research Institut

Non-Invasive Imaging of Cysteine Cathepsin Activity in Solid Tumors Using a 64Cu-Labeled Activity-Based Probe

The papain family of cysteine cathepsins are actively involved in multiple stages of tumorigenesis. Because elevated cathepsin activity can be found in many types of human cancers, they are promising biomarkers that can be used to target radiological contrast agents for tumor detection. However, currently there are no radiological imaging agents available for these important molecular targets. We report here the development of positron emission tomography (PET) radionuclide-labeled probes that target the cysteine cathepsins by formation of an enzyme activity-dependent bond with the active site cysteine. These probes contain an acyloxymethyl ketone (AOMK) functional group that irreversibly labels the active site cysteine of papain family proteases attached to a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) tag for labeling with 64Cu for PET imaging studies. We performed biodistribution and microPET imaging studies in nude mice bearing subcutaneous tumors expressing various levels of cysteine cathepsin activity and found that the extent of probe uptake by tumors correlated with overall protease activity as measured by biochemical methods. Furthermore, probe signals could be reduced by pre-treatment with a general cathepsin inhibitor. We also found that inclusion of a Cy5 tag on the probe increased tumor uptake relative to probes lacking this fluorogenic dye. Overall, these results demonstrate that small molecule activity-based probes carrying radio-tracers can be used to image protease activity in living subjects

Emerging school sport development policy, practice and governance in England: Big Society, autonomy and decentralisation

International interest in developing mass sports participation through systems of school and community sports development has become a growing field of public leisure policy interest. This research paper considers the policy change from School Sport Partnerships to the new 2012 School Games model of networked partnerships to establish characteristics of the changes in governance modes and implications from practice in England. The research project is based on a regional case study drawing upon indepth,face-to-face interviews with key public policy stakeholders to inform an analysis of change. Initial findings indicate that the emergent networks are characterised by more networked-based mode of governance than previous hierarchical models present under UK New Labour. The study also shows the fragility of a reliance on partnership structures and the potential implications for incongruence in delivering policy outcomes and improving access to physical activity and school sport opportunities

Cross-tissue, single-cell stromal atlas identifies shared pathological fibroblast phenotypes in four chronic inflammatory diseases

BackgroundPro-inflammatory fibroblasts are critical for pathogenesis in rheumatoid arthritis, inflammatory bowel disease, interstitial lung disease, and Sjögren’s syndrome and represent a novel therapeutic target for chronic inflammatory disease. However, the heterogeneity of fibroblast phenotypes, exacerbated by the lack of a common cross-tissue taxonomy, has limited our understanding of which pathways are shared by multiple diseases.MethodsWe profiled fibroblasts derived from inflamed and non-inflamed synovium, intestine, lungs, and salivary glands from affected individuals with single-cell RNA sequencing. We integrated all fibroblasts into a multi-tissue atlas to characterize shared and tissue-specific phenotypes.FindingsTwo shared clusters, CXCL10+CCL19+ immune-interacting and SPARC+COL3A1+ vascular-interacting fibroblasts, were expanded in all inflamed tissues and mapped to dermal analogs in a public atopic dermatitis atlas. We confirmed these human pro-inflammatory fibroblasts in animal models of lung, joint, and intestinal inflammation.ConclusionsThis work represents a thorough investigation into fibroblasts across organ systems, individual donors, and disease states that reveals shared pathogenic activation states across four chronic inflammatory diseases.FundingGrant from F. Hoffmann-La Roche (Roche) AG

Global Spatial Risk Assessment of Sharks Under the Footprint of Fisheries

Effective ocean management and conservation of highly migratory species depends on resolving overlap between animal movements and distributions and fishing effort. Yet, this information is lacking at a global scale. Here we show, using a big-data approach combining satellite-tracked movements of pelagic sharks and global fishing fleets, that 24% of the mean monthly space used by sharks falls under the footprint of pelagic longline fisheries. Space use hotspots of commercially valuable sharks and of internationally protected species had the highest overlap with longlines (up to 76% and 64%, respectively) and were also associated with significant increases in fishing effort. We conclude that pelagic sharks have limited spatial refuge from current levels of high-seas fishing effort. Results demonstrate an urgent need for conservation and management measures at high-seas shark hotspots and highlight the potential of simultaneous satellite surveillance of megafauna and fishers as a tool for near-real time, dynamic management

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council