Assessment of the environmental toxicity and carcinogenicity of tungsten-based shot.

The toxicity of elemental tungsten released from discharged shot was assessed against previous studies that established a 1% toxic threshold for soil organisms. Extremely heavy theoretical shot loadings of 69,000 shot/ha were used to generate estimated environmental concentrations (EEC) for two brands of tungsten-based shot containing 51% and 95% tungsten. The corresponding tungsten EEC values were 6.5–13.5 mg W/kg soil, far below the 1% toxic threshold. The same shot loading in water produced tungsten EEC values of 2.1–4.4 mg W/L, levels that are not toxic under experimental conditions. Pure tungsten has not been shown to exhibit carcinogenic properties when ingested or embedded in animal tissues, but nickel, with which it is often alloyed, has known carcinogenicity. Given the large number of waterfowl that carry shot embedded in their body, it is advisable to screen lead shot substitutes for their carcinogenic potential through intra-muscular implantation

Cosmic Neutrino Pevatrons: A Brand New Pathway to Astronomy, Astrophysics, and Particle Physics

The announcement by the IceCube Collaboration of the observation of 28 cosmic neutrino candidates has been greeted with a great deal of justified excitement. The data reported so far depart by 4.3\sigma from the expected atmospheric neutrino background, which raises the obvious question: "Where in the Cosmos are these neutrinos coming from?" We review the many possibilities which have been explored in the literature to address this question, including origins at either Galactic or extragalactic celestial objects. For completeness, we also briefly discuss new physics processes which may either explain or be constrained by IceCube data.Comment: This is a review article solicited for the inaugural edition of Journal of High Energy Astrophysics (JHEAp). Matching version accepted for publicatio

Effect of individual environmental heat stress variables on training and recovery in professional team sport

Context: Exercise in hot environments increases body temperature and thermoregulatory strain. However, little is known regarding the magnitude of effect that ambient temperature (Ta), relative humidity (RH), and solar radiation individually have on team-sport athletes. Purpose: To determine the effect of these individual heat-stress variables on team-sport training performance and recovery. Methods: Professional Australian Rules Football players (N = 45) undertook 8-wk preseason training producing a total of 579 outdoor field-based observations with Ta, RH, and solar radiation recorded at every training session. External load (distance covered, in m/min; percentage high-speed running [%HSR] >14.4 km/h) was collected via a global positioning system. Internal load (ratings of perceived exertion and heart rate) and recovery (subjective ratings of well-being and heart-rate variability [root mean square of the successive differences]) were monitored throughout the training period. Mixed-effects linear models analyzed relationships between variables using standardized regression coefficients. Results: Increased solar-radiation exposure was associated with reduced distance covered (−19.7 m/min, P 85% HRmax (3.9%, P a was associated with increased distance covered (19.7 m/min, P < .001) and %HSR (3.5%, P = .005). Conclusions: The authors show the importance of considering the individual factors contributing to thermal load in isolation for team-sport athletes and that solar radiation and RH reduce work capacity during team-sport training and have the potential to slow recovery between sessions.</p

The muscle proteome reflects changes in mitochondrial function, cellular stress and proteolysis after 14 days of unilateral lower limb immobilization in active young men

Skeletal muscle unloading due to joint immobilization induces muscle atrophy, which has primarily been attributed to reductions in protein synthesis in humans. However, no study has evaluated the skeletal muscle proteome response to limb immobilization using SWATH proteomic methods. This study characterized the shifts in individual muscle protein abundance and corresponding gene sets after 3 and 14 d of unilateral lower limb immobilization in otherwise healthy young men. Eighteen male participants (25.4 ±5.5 y, 81.2 ±11.6 kg) underwent 14 d of unilateral knee-brace immobilization with dietary provision and following four-weeks of training to standardise acute training history. Participant phenotype was characterized before and after 14 days of immobilization, and muscle biopsies were obtained from the vastus lateralis at baseline (pre-immobilization) and at 3 and 14 d of immobilization for analysis by SWATH-MS and subsequent gene-set enrichment analysis (GSEA). Immobilization reduced vastus group cross sectional area (-9.6 ±4.6%, P <0.0001), immobilized leg lean mass (-3.3 ±3.9%, P = 0.002), unilateral 3-repetition maximum leg press (-15.6 ±9.2%, P <0.0001), and maximal oxygen uptake (-2.9 ±5.2%, P = 0.044). SWATH analyses consistently identified 2281 proteins. Compared to baseline, two and 99 proteins were differentially expressed (FDR <0.05) after 3 and 14 d of immobilization, respectively. After 14 d of immobilization, 322 biological processes were different to baseline (FDR <0.05, P <0.001). Most (77%) biological processes were positively enriched and characterized by cellular stress, targeted proteolysis, and protein-DNA complex modifications. In contrast, mitochondrial organization and energy metabolism were negatively enriched processes. This study is the first to use data independent proteomics and GSEA to show that unilateral lower limb immobilization evokes mitochondrial dysfunction, cellular stress, and proteolysis. Through GSEA and network mapping, we identify 27 hub proteins as potential protein/gene candidates for further exploration

Review of the 25th annual scientific meeting of the International Society for Biological Therapy of Cancer

Led by key opinion leaders in the field, the 25th Annual Meeting of the International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC) provided a scientific platform for ~500 attendees to exchange cutting-edge information on basic, clinical, and translational research in cancer immunology and immunotherapy. The meeting included keynote addresses on checkpoint blockade in cancer therapy and recent advances in therapeutic vaccination against cancer induced by Human Papilloma Virus 16. Participants from 29 countries interacted through oral presentations, panel discussions, and posters on topics that included dendritic cells and cancer, targeted therapeutics and immunotherapy, innate/adaptive immune interplay in cancer, clinical trial endpoints, vaccine combinations, countering negative regulation, immune cell trafficking to tumor microenvironment, and adoptive T cell transfer. In addition to the 50 oral presentations and >180 posters on these topics, a new SITC/iSBTc initiative to create evidence-based Cancer Immunotherapy Guidelines was announced. The SITC/iSBTc Biomarkers Taskforce announced the release of recommendations on immunotherapy biomarkers and a highly successful symposium on Immuno-Oncology Biomarkers that took place on the campus of the National Institutes of Health (NIH) immediately prior to the Annual Meeting. At the Annual Meeting, the NIH took the opportunity to publicly announce the award of the U01 grant that will fund the Cancer Immunotherapy Trials Network (CITN). In summary, the Annual Meeting gathered clinicians and scientists from academia, industry, and regulatory agencies from around the globe to interact and exchange important scientific advances related to tumor immunobiology and cancer immunotherapy

Setting maximum levels for lead in game meat in EC regulations: An adjunct to replacement of lead ammunition

Abstract: Each year, hunters from 12 of the 27 European Union (EU) countries and the UK shoot over 6 million large game mammals, 12 million rabbits and hares and over 80 million birds. They support an international game meat market worth over 1.1 thousand million Euros. Animals shot with lead ammunition frequently contain lead fragments in the carcass which contaminate meals made from game meat with concentrations of lead substantially above the maximum allowable level (ML) set by European Commission Regulation EC1881/2006 for meat from domesticated animals. This poses a health risk to frequent consumers of wild-shot game meat, with children and pregnant women being particularly vulnerable. Total replacement of lead rifle and shotgun ammunition with available non-toxic alternatives is needed for all hunting in EU nations to prevent exposure of humans and wildlife to ammunition-derived lead and to allow the depletion of the long-term environmental legacy of lead from spent ammunition. We propose that EC1881/2006 is amended to incorporate an ML for game meats as a supplementary measure to the replacement of lead ammunition. This would harmonise food safety standards for lead in meats traded across and imported into the EU

Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.

BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic

Phase 2 study of RO4929097, a gamma‐secretase inhibitor, in metastatic melanoma: SWOG 0933

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110565/1/cncr29055.pd