Selecting committee witnesses: experts back the call for a more even gender balance

Democratic Audit recently published a new report which analysed the identity of select committee witnesses in view of their increasing prominence and influence. Our research found that there was a substantial gender imbalance between those who speak in front of committees. We asked a number of democracy experts to give their views on the research, the reasons for this disparity, the consequences for women’s role in public life and what, if anything, can be done to address the problem

Long-term responders on olaparib maintenance in high-grade serous ovarian cancer: Clinical and molecular characterization

Purpose: Maintenance therapy with olaparib has improved progression-free survival in women with high-grade serous ovarian cancer (HGSOC), particularly those harboring BRCA1/2 mutations. The objective of this study was to characterize long-term (LT) versus short-term (ST) responders to olaparib. Experimental Design: A comparative molecular analysis of Study 19 (NCT00753545), a randomized phase II trial assessing olaparib maintenance after response to platinum-based chemotherapy in HGSOC, was conducted. LT response was defined as response to olaparib/placebo > 2 years, ST as < 3 months. Molecular analyses included germline BRCA1/2 status, three-biomarker homologous recombination deficiency (HRD) score, BRCA1 methylation, and mutational profiling. Another olaparib maintenance study (Study 41; NCT01081951) was used as an additional cohort. Results: Thirty-seven LT (32 olaparib) and 61 ST (21 olaparib) patients were identified. Treatment was significantly associated with outcome (P < 0.0001), with more LT patients on olaparib (60.4%) than placebo (11.1%). LT sensitivity to olaparib correlated with complete response to chemotherapy (P < 0.05). In the olaparib LT group, 244 genetic alterations were detected, with TP53, BRCA1, and BRCA2 mutations being most common (90%, 25%, and 35%, respectively). BRCA2 mutations were enriched among the LT responders. BRCA methylation was not associated with response duration. High myriad HRD score (>42) and/or BRCA1/2 mutation was associated with LT response to olaparib. Study 41 confirmed the correlation of LT response with olaparib and BRCA1/2 mutation. Conclusions: Findings show that LT response to olaparib may be multifactorial and related to homologous recombination repair deficiency, particularly BRCA1/2 defects. The type of BRCA1/2 mutation warrants further investigation. (C) 2017 AACR

The state of research in teaching and learning in sport and exercise science: a scoping review.

Evidence based pedagogy in Higher Education (HE) requires accessible collation of evidence. This study aims to collate and map the evidence that exists in teaching the unique discipline of sport and exercise science (SES). A systematic search of three electronic databases (SportDiscus; Web of Science; ERIC) for peer reviewed original articles evaluating pedagogical approaches in SES related disciplines in HE was performed. Abstracts and subsequent full-text articles were screened by dual reviewers and data extracted (article characteristics, topic and outcome measures). Literature quality was assessed using the Mixed Methods Appraisal Tool (MMAT). 44,447 articles were identified, 509 eligible for full text assessment and 156 for inclusion. Most were conducted in the USA, UK and Spain. Study designs were primarily quantitative although qualitative and mixed methods approaches were evident. Articles were published in a large range of journals, 88 in total, with a single publication in 62 journals. The most common topic category was student experience, followed by teaching methods. Articles on eLearning, student learning and achievement and attainment were also prevalent. MMAT quality checks revealed 61% were deemed high quality and 25% satisfactory. Aside the surge of literature on the impact of Covid-19 the research is diverse, without a saturation of any facet of pedagogic research in the SES field. Further research specific to SES students is required in all areas however, there are specific gaps in terms of research on 'diversity and inclusion' and 'access to higher education' which need to be filled

RNA-Seq Differentiates Tumour and Host mRNA Expression Changes Induced by Treatment of Human Tumour Xenografts with the VEGFR Tyrosine Kinase Inhibitor Cediranib.

Pre-clinical models of tumour biology often rely on propagating human tumour cells in a mouse. In order to gain insight into the alignment of these models to human disease segments or investigate the effects of different therapeutics, approaches such as PCR or array based expression profiling are often employed despite suffering from biased transcript coverage, and a requirement for specialist experimental protocols to separate tumour and host signals. Here, we describe a computational strategy to profile transcript expression in both the tumour and host compartments of pre-clinical xenograft models from the same RNA sample using RNA-Seq. Key to this strategy is a species-specific mapping approach that removes the need for manipulation of the RNA population, customised sequencing protocols, or prior knowledge of the species component ratio. The method demonstrates comparable performance to species-specific RT-qPCR and a standard microarray platform, and allowed us to quantify gene expression changes in both the tumour and host tissue following treatment with cediranib, a potent vascular endothelial growth factor receptor tyrosine kinase inhibitor, including the reduction of multiple murine transcripts associated with endothelium or vessels, and an increase in genes associated with the inflammatory response in response to cediranib. In the human compartment, we observed a robust induction of hypoxia genes and a reduction in cell cycle associated transcripts. In conclusion, the study establishes that RNA-Seq can be applied to pre-clinical models to gain deeper understanding of model characteristics and compound mechanism of action, and to identify both tumour and host biomarkers

Transferability of Military-Specific Cognitive Research to Military Training and Operations

The influence of acute aerobic exercise on cognitive function is well documented (e.g., Lambourne and Tomporowski, 2010; Chang et al., 2012). However, the influence of military specific exercise on aspects of cognitive function relevant to military operations is less well understood. With the increasing physical and cognitive loads placed on military personnel (Mahoney et al., 2007), this interaction is fundamental to understanding operational performance (Russo et al., 2005). As such, ensuring the transferability of military-specific cognitive research to military training and operations, is of great importance, particularly for the development of both mitigation and enhancement strategies (see Brunyé et al., 2020). Despite this, studies have not always considered whether meaningful translations can be made. We suggest that researchers should endeavor to strike the balance between external validity and experimental control (Figure 1), and consider the concept of representative design (Pinder et al., 2011). External validity refers to the transferability of research findings from the research to the target population, whilst representative design refers to methodological approaches chosen to ensure that the experimental task constraints characterize those experienced during performance (i.e., the training or operational environment) (Pinder et al., 2011). Herein, we will focus on representative design during load carriage investigations, due to its mission criticality (Knapik and Reynolds, 2012), and it being the primary physical activity choice during military specific exercise-cognition research. Specifically, we discuss the inclusion of dual-/multi-tasking, implications of study population, cognitive task selection, and the data collection environment