257 research outputs found

    Virtual Maltreatment: Sexualisation and Social Media Abuse in Sport.

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    Virtual maltreatment is a rapidly emerging and highly significant issue within contemporary sport. This study examines such behaviour by exploring the negative social media attention that tennis player Maria Sharapova received during the 2015 Wimbledon tennis championships. Using a netnographic approach, an analysis of two popular social media platforms (Facebook and Twitter) was conducted to examine the social commentary surrounding this athlete during the event. Three primary themes emerged from the analysis of data on these platforms: ‘admiration of her physical beauty and/or sexualisation’; ‘threatening physical and/or sexual contact’ and ‘emotionally ridiculing and/or criticising’. These findings demonstrate how social media provides a space for unregulated physical and sexual abuse of female athletes in a way that traditional sports media does not. Virtual abuse and maltreatment is identified as a significant social problem which requires further consideration in academic literature

    Seasonal variation and impact of waste-water lagoons as larval habitat on the population dynamics of Culicoides sonorensis (Diptera:Ceratpogonidae) at two dairy farms in northern California.

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    The Sacramento (northern Central) Valley of California (CA) has a hot Mediterranean climate and a diverse ecological landscape that is impacted extensively by human activities, which include the intensive farming of crops and livestock. Waste-water ponds, marshes, and irrigated fields associated with these agricultural activities provide abundant larval habitats for C. sonorensis midges, in addition to those sites that exist in the natural environment. Within this region, C. sonorensis is an important vector of bluetongue (BTV) and related viruses that adversely affect the international trade and movement of livestock, the economics of livestock production, and animal welfare. To characterize the seasonal dynamics of immature and adult C. sonorensis populations, abundance was monitored intensively on two dairy farms in the Sacramento Valley from August 2012- to July 2013. Adults were sampled every two weeks for 52 weeks by trapping (CDC style traps without light and baited with dry-ice) along N-S and E-W transects on each farm. One farm had large operational waste-water lagoons, whereas the lagoon on the other farm was drained and remained dry during the study. Spring emergence and seasonal abundance of adult C. sonorensis on both farms coincided with rising vernal temperature. Paradoxically, the abundance of midges on the farm without a functioning waste-water lagoon was increased as compared to abundance on the farm with a waste-water lagoon system, indicating that this infrastructure may not serve as the sole, or even the primary larval habitat. Adult midges disappeared from both farms from late November until May; however, low numbers of parous female midges were detected in traps set during daylight in the inter-seasonal winter period. This latter finding is especially critical as it provides a potential mechanism for the "overwintering" of BTV in temperate regions such as northern CA. Precise documentation of temporal changes in the annual abundance and dispersal of Culicoides midges is essential for the creation of models to predict BTV infection of livestock and to develop sound abatement strategies

    Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy

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    Autophagy is a cell-protective and degradative process that recycles damaged and long-lived cellular components. Cancer cells are thought to take advantage of autophagy to help them to cope with the stress of tumorigenesis; thus targeting autophagy is an attractive therapeutic approach. However, there are currently no specific inhibitors of autophagy. ULK1, a serine/threonine protein kinase, is essential for the initial stages of autophagy, and here we report that two compounds, MRT67307 and MRT68921, potently inhibit ULK1 and ULK2 in vitro and block autophagy in cells. Using a drug-resistant ULK1 mutant, we show that the autophagy-inhibiting capacity of the compounds is specifically through ULK1. ULK1 inhibition results in accumulation of stalled early autophagosomal structures, indicating a role for ULK1 in the maturation of autophagosomes as well as initiation

    Mobility of the SecA 2-helix-finger is not essential for polypeptide translocation via the SecYEG complex

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    The bacterial ATPase SecA and protein channel complex SecYEG form the core of an essential protein translocation machinery. The nature of the conformational changes induced by each stage of the hydrolytic cycle of ATP and how they are coupled to protein translocation are not well understood. The structure of the SecA–SecYEG complex revealed a 2-helix-finger (2HF) of SecA in an ideal position to contact the substrate protein and push it through the membrane. Surprisingly, immobilization of this finger at the edge of the protein channel had no effect on translocation, whereas its imposition inside the channel blocked transport. This analysis resolves the stoichiometry of the active complex, demonstrating that after the initiation process translocation requires only one copy each of SecA and SecYEG. The results also have important implications on the mechanism of energy transduction and the power stroke driving transport. Evidently, the 2HF is not a highly mobile transducing element of polypeptide translocation

    Pollen exposure and hospitalization due to asthma exacerbations: daily time series in a European city.

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    Exposure to pollen can contribute to increased hospital admissions for asthma exacerbation. This study applied an ecological time series analysis to examine associations between atmospheric concentrations of different pollen types and the risk of hospitalization for asthma in London from 2005 to 2011. The analysis examined short-term associations between daily pollen counts and hospital admissions in the presence of seasonal and long-term patterns, and allowed for time lags between exposure and admission. Models were adjusted for temperature, precipitation, humidity, day of week, and air pollutants. Analyses revealed an association between daily counts (continuous) of grass pollen and adult hospital admissions for asthma in London, with a 4-5-day lag. When grass pollen concentrations were categorized into Met Office pollen 'alert' levels, 'very high' days (vs. 'low') were associated with increased admissions 2-5 days later, peaking at an incidence rate ratio of 1.46 (95%, CI 1.20-1.78) at 3 days. Increased admissions were also associated with 'high' versus 'low' pollen days at a 3-day lag. Results from tree pollen models were inconclusive and likely to have been affected by the shorter pollen seasons and consequent limited number of observation days with higher tree pollen concentrations. Future reductions in asthma hospitalizations may be achieved by better understanding of environmental risks, informing improved alert systems and supporting patients to take preventive measures

    Gefitinib and <i>EGFR</i> Gene Copy Number Aberrations in Esophageal Cancer

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    Purpose: The cancer esophagus gefitinib (COG) trial demonstrated improved progression free survival with the Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI), gefitinib relative to placebo in advanced esophageal cancer patients with disease progression after chemotherapy. Rapid and durable responses were observed in a minority. We hypothesised that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Patients and Methods: A pre-specified blinded molecular analysis of COG trial tumours was conducted to compare efficacy of gefitinib to placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF and PIK3CA mutation status. EGFR CNG was determined by fluorescent insitu hybridisation (FISH) using pre-specified criteria and EGFR FISH positive defined as high polysomy or amplification. Results: Biomarker data were available for 340 patients. In EGFR FISH positive tumours (20.2%) overall survival was improved with gefitinib compared to placebo (hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.35, 1.00 p=0.05). In EGFR FISH negative tumours there was no difference in overall survival with gefitinib compared to placebo (HR for death, 0.90, 95% CI 0.69, 1.18 p=0.46). EGFR amplification (7.2%) patients gained greatest benefit from gefitinib (HR for death, 0.21; 95% CI 0.07-0.64; p=0.006). There was no difference in overall survival for gefitinib versus placebo for patients with EGFR, KRAS, BRAF and PIK3CA mutations, or for any mutation versus none. Conclusion: EGFR CNG assessed by FISH appears to identify a subgroup of esophageal cancer patients who may benefit from gefitinib as a second line treatment, and suggests that anti-EGFR 3 therapies should be investigated in prospective clinical trials in different settings in EGFR FI SH positive, and in particular EGFR amplified, esophageal cancer

    Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

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    BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre
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