Opportunities and challenges of a novel cardiac output response to stress (CORS) test to enhance diagnosis of heart failure in primary care: qualitative study.

OBJECTIVE: To explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care. DESIGN: Qualitative study using semistructured in-depth interviews which were audio recorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach. SETTING: Newcastle upon Tyne, UK. PARTICIPANTS: Fourteen healthcare professionals (six males, eight females) from primary (general practitioners (GPs), nurses, healthcare assistant, practice managers) and secondary care (consultant cardiologists). RESULTS: Four themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that the adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include: establishment of clinical utility, suitability for immobile patients and cost implication to GP practices. CONCLUSION: The development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose; however, factors such as cost effectiveness, diagnostic accuracy and seamless implementation in primary care have to be fully explored.This study was funded by the UK Medical Research Council Confidence in Concept Scheme grant to DGJ (grant no. BH161161). SC and NO are supported by the European Horizon 2020 research and innovation programme under grant agreement no 777204. SG is supported by the NIHR MEDTEch In Vitro Diagnostics. DGJ is supported by the UK Research Councils’ Newcastle Centre for Ageing and Vitality (grant no. L016354)

Comparison of proteomic responses as global approach to antibiotic mechanism of action elucidation

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. New antibiotics are urgently needed to address the mounting resistance challenge. In early drug discovery, one of the bottlenecks is the elucidation of targets and mechanisms. To accelerate antibiotic research, we provide a proteomic approach for the rapid classification of compounds into those with precedented and unprecedented modes of action. We established a proteomic response library of Bacillus subtilis covering 91 antibiotics and comparator compounds, and a mathematical approach was developed to aid data analysis. Comparison of proteomic responses (CoPR) allows the rapid identification of antibiotics with dual mechanisms of action as shown for atypical tetracyclines. It also aids in generating hypotheses on mechanisms of action as presented for salvarsan (arsphenamine) and the antirheumatic agent auranofin, which is under consideration for repurposing. Proteomic profiling also provides insights into the impact of antibiotics on bacterial physiology through analysis of marker proteins indicative of the impairment of cellular processes and structures. As demonstrated for trans-translation, a promising target not yet exploited clinically, proteomic profiling supports chemical biology approaches to investigating bacterial physiology

Physical education undergraduate students’ perceptions of their learning using the jigsaw learning method

Recognising the limited research around the use of cooperative learning in higher education, this case study sought to explore physical education students’ perceptions of learning using the jigsaw learning method. It examined the impact of two different aesthetic activities and two different groupings on students’ perceptions of their learning. A purposive sample of 36 third-year undergraduates was selected for the study. Data were collected using focus group interviews and reflective journals. Inductive analysis illustrated students’ perceptions of their own and others’ abilities, students’ empathy towards their peers, and how their perceptions of gymnastics and dance impacted on their perceptions of learning. Students felt that heterogeneous and friendship groupings have the potential to encourage high-order social and cognitive learning. However, those students with limited psychomotor abilities appear to be better served in friendship groupings to facilitate such learning. Students also favoured the ‘structured’ nature of gymnastics in comparison to dance for their own teaching and learning purposes. Irrespective of aesthetic activity or grouping utilised, students felt their psychomotor learning was limited. It is recommended that university staff consider using a mixture of groupings with a single cohort dependent on the practical ability of students and the use of more ‘structured’ activities. In doing so, students’ perceptions of their social, cognitive and psychomotor learning may improve and thereby encourage greater and more effective use of this innovative method in schools

Homogenization via formal multiscale asymptotics and volume averaging: How do the two techniques compare?

A wide variety of techniques have been developed to homogenize transport equations in multiscale and multiphase systems. This has yielded a rich and diverse field, but has also resulted in the emergence of isolated scientific communities and disconnected bodies of literature. Here, our goal is to bridge the gap between formal multiscale asymptotics and the volume averaging theory. We illustrate the methodologies via a simple example application describing a parabolic transport problem and, in so doing, compare their respective advantages/disadvantages from a practical point of view. This paper is also intended as a pedagogical guide and may be viewed as a tutorial for graduate students as we provide historical context, detail subtle points with great care, and reference many fundamental works

The earliest thymic T cell progenitors sustain B cell and myeloid lineage potential

The stepwise commitment from hematopoietic stem cells in the bone marrow to T lymphocyte-restricted progenitors in the thymus represents a paradigm for understanding the requirement for distinct extrinsic cues during different stages of lineage restriction from multipotent to lineage-restricted progenitors. However, the commitment stage at which progenitors migrate from the bone marrow to the thymus remains unclear. Here we provide functional and molecular evidence at the single-cell level that the earliest progenitors in the neonatal thymus had combined granulocyte-monocyte, T lymphocyte and B lymphocyte lineage potential but not megakaryocyte-erythroid lineage potential. These potentials were identical to those of candidate thymus-seeding progenitors in the bone marrow, which were closely related at the molecular level. Our findings establish the distinct lineage-restriction stage at which the T cell lineage-commitment process transits from the bone marrow to the remote thymus. © 2012 Nature America, Inc. All rights reserved

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223