300 research outputs found
It is Not Black and White: A Comparison of Skin Tone by Playing Position in the Premier League and English Football
Within the present manuscript we explore the role of skin tone on playing position within English footballâs top four professional leagues. Player data (N = 4,515) was collected across five seasons (2010-2015). Results indicate that in general, darker skin toned players are more likely to operate within peripheral rather than central positions. Using both one and two-way ANOVAs, results suggest significant differences between skin tone and individual playing positions. Between league differences were, however, non-significant. Although darker skin toned players are still more likely to occupy peripheral positions, the situation is more nuanced than first thought. Instead of segregating players by central versus peripheral roles, it appears that darker skin toned players occupy positions associated with athleticism and strength. In contrast, lighter skin toned players appear to fulfill positions requiring organizational skills and creativity
Method of Food Preparation Influences Blood Glucose Response to a High-Carbohydrate Meal: A Randomised Cross-over Trial
The aim of this study was to establish the blood glucose response to different cooking methods of pasta. Participants consumed three identical meals in a random order that were freshly cooked (hot), cooled and reheated. Blood glucose concentrations were assessed before, and every 15 min after ingestion of each meal for 120 min. There was a significant interaction between temperature and time (F (8.46â372.34) = 2.75, p = 0.005), with the reheated (90 min) condition returning to baseline faster than both cold (120 min) and hot conditions. Blood glucose area under the curve (AUC) was significantly lower in the reheated (703 ± 56 mmol·Lâ1·minâ1) than the hot condition (735 ± 77 mmol·Lâ1·minâ1, t (92) = â3.36, pbonferroni = 0.003), with no significant difference with the cold condition (722 ± 62 mmol·Lâ1·minâ1). To our knowledge, the current study is the first to show that reheating pasta causes changes in post-prandial glucose response, with a quicker return to fasting levels in both the reheated and cooled conditions than the hot condition. The mechanisms behind the changes in post-prandial blood glucose seen in this study are most likely related to changes in starch structure and how these changes influence glycaemic response
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An engaged approach to exploring issues around poverty and mental health: A reflective evaluation of the research process from researchers and community partners involved in the DeStress study
Background
Involving patients, service users, carers and members of the public in research has been part of health policy and practice in the UK for the last 15 years. However, lowâincome communities tend to remain marginalized from the coâdesign and delivery of mental health research, perpetuating the potential for health inequalities. Greater understanding is therefore needed on how to meaningfully engage lowâincome communities in mental health research.
Objectives
To explore and articulate whether and how an engaged research approach facilitated knowledge coproduction relating to poverty and mental distress.
Setting
A reflective evaluation of community and researcher engagement in the DeStress study that took place in two lowâincome areas of Southâwest England.
Design
Reflective evaluation by the authors through onâgoing feedback, a focus group and firstâperson writing and discussion on experiences of working with the DeStress project, and how knowledge coproduction was influenced by an engaged research approach.
Results
An engaged research approach influenced the process and delivery of the DeStress project, creating a space where community partners felt empowered to coproduce knowledge relating to povertyârelated mental distress, treatment and the training of health professionals that would otherwise have been missed. We examine motivations for involvement, factors sustaining engagement, how coproduction influenced research analysis, findings and dissemination of outputs, and what involvement meant for different stakeholders.
Conclusion
Engaged research supported the coproduction of knowledge in mental health research with lowâincome communities which led to multiple impacts
EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen.
Chordoma is a rare malignant bone tumour with a poor prognosis and limited therapeutic options. We undertook a focused compound screen (FCS) against 1097 compounds on three well-characterized chordoma cell lines; 154 compounds were selected from the single concentration screen (1 ”m), based on their growth-inhibitory effect. Their half-maximal effective concentration (EC50 ) values were determined in chordoma cells and normal fibroblasts. Twenty-seven of these compounds displayed chordoma selective cell kill and 21/27 (78%) were found to be EGFR/ERBB family inhibitors. EGFR inhibitors in clinical development were then studied on an extended cell line panel of seven chordoma cell lines, four of which were sensitive to EGFR inhibition. Sapitinib (AstraZeneca) emerged as the lead compound, followed by gefitinib (AstraZeneca) and erlotinib (Roche/Genentech). The compounds were shown to induce apoptosis in the sensitive cell lines and suppressed phospho-EGFR and its downstream pathways in a dose-dependent manner. Analysis of substituent patterns suggested that EGFR-inhibitors with small aniline substituents in the 4-position of the quinazoline ring were more effective than inhibitors with large substituents in that position. Sapitinib showed significantly reduced tumour growth in two xenograft mouse models (U-CH1 xenograft and a patient-derived xenograft, SF8894). One of the resistant cell lines (U-CH2) was shown to express high levels of phospho-MET, a known bypass signalling pathway to EGFR. Neither amplifications (EGFR, ERBB2, MET) nor mutations in EGFR, ERBB2, ERBB4, PIK3CA, BRAF, NRAS, KRAS, PTEN, MET or other cancer gene hotspots were detected in the cell lines. Our findings are consistent with the reported (p-)EGFR expression in the majority of clinical samples, and provide evidence for exploring the efficacy of EGFR inhibitors in the treatment of patients with chordoma and studying possible resistance mechanisms to these compounds in vitro and in vivo. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland
A Simplified, Sequential, Phosphorus Fractionation Method
Hedley et al. (1982) developed what has become the most widely used (and modified), phosphorus (P) fractionation technique. It consists of sequential extraction of increasingly less phytoavailable P pools. Extracts are centrifuged at up to 25000 g (RCF) and filtered to 0.45 ÎŒm to ensure that soil is not lost between extractions. In attempting to transfer this method to laboratories with limited facilities, it was considered that access to high-speed centrifuges, and the cost of frequent filtration may prevent adoption of this P fractionation technique. The modified method presented here was developed to simplify methodology, reduce cost, and therefore increase accessibility of P fractionation technology. It provides quantitative recovery of soil between extractions, using low speed centrifugation without filtration. This is achieved by increasing the ionic strength of dilute extracts, through the addition of NaCl, to flocculate clay particles. Addition of NaCl does not change the amount of P extracted. Flocculation with low speed centrifugation produced extracts comparable with those having undergone filtration (0.025 ÎŒm). A malachite green colorimetric method was adopted for inorganic P determination, as this simple manual method provides high sensitivity with negligible interference from other anions. This approach can also be used for total P following digestion, alternatively non-discriminatory methods, such as inductively coupled plasma atomic emission spectroscopy, may be employed
The fourteenth-century poll tax returns and the study of English surname distribution
The modern-day distributions of English surnames have been considered in genealogical, historical, and philological research as possible indicators of their origins. However, many centuries have passed since hereditary surnames were first used, and so their distribution today does not necessarily reflect their original spread, misrepresenting their origins. Previously, medieval data with national coverage have not been available for a study of surname distribution, but with the recent publication of the fourteenth-century poll tax returns, this has changed. By presenting discrepancies in medieval and nineteenth-century distributions, it is shown that more recent surname data may not be a suitable guide to surname origins and can be usefully supplemented by medieval data in order to arrive at more accurate conclusions
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response.
SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells are selectively sensitive to poly (ADP-ribose) polymerase inhibitors (PARPi), independent of hotspot mutation and tumor site. SF3B1MUT cells display a defective response to PARPi-induced replication stress that occurs via downregulation of the cyclin-dependent kinase 2 interacting protein (CINP), leading to increased replication fork origin firing and loss of phosphorylated CHK1 (pCHK1; S317) induction. This results in subsequent failure to resolve DNA replication intermediates and G2/M cell cycle arrest. These defects are rescued through CINP overexpression, or further targeted by a combination of ataxia-telangiectasia mutated and PARP inhibition. In vivo, PARPi produce profound antitumor effects in multiple SF3B1MUT cancer models and eliminate distant metastases. These data provide the rationale for testing the clinical efficacy of PARPi in a biomarker-driven, homologous recombination proficient, patient population
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