Description: Motivation Single cell transcriptional profiling opens up a new avenue in studying the functional role of cell-to-cell variability in physiological processes. The analysis of single cell expression profiles creates new challenges due to the distributive nature of the data and the stochastic dynamics of gene transcription process. The reconstruction of gene regulatory networks (GRNs) using single cell transcriptional profiles is particularly challenging, especially when directed gene-gene relationships are desired. Results We developed SINCERITIES (SINgle CEll Regularized Inference using TIme-stamped Expression profileS) for the inference of GRNs from single cell transcriptional profiles. We focused on time-stamped cross-sectional expression data, commonly generated from transcriptional profiling of single cells collected at multiple time points after cell stimulation. SINCERITIES recovers directed regulatory relationships among genes by employing regularized linear regression (ridge regression), using temporal changes in the distributions of gene expressions. Meanwhile, the modes of the gene regulations (activation and repression) come from partial correlation analyses between pairs of genes. We demonstrated the efficacy of SINCERITIES in inferring GRNs using in silico time-stamped single cell expression data and single cell transcriptional profiles of THP-1 monocytic human leukemia cells. The case studies showed that SINCERITIES could provide accurate GRN predictions, significantly better than other GRN inference algorithms such as TSNI, GENIE3 and JUMP3. Moreover, SINCERITIES has a low computational complexity and is amenable to problems of extremely large dimensionality. Finally, an application of SINCERITIES to single cell expression data of T2EC chicken erythrocytes pointed to BATF as a candidate novel regulator of erythroid development. Availability and implementation MATLAB and R version of SINCERITIES are freely available from the following websites: http://www.cabsel.ethz.ch/tools/sincerities.html and https://github.com/CABSEL/SINCERITIES . The single cell THP-1 and T2EC transcriptional profiles are available from the original publications ( Kouno et al. , 2013 ; Richard et al. , 2016 ). The in silico single cell data are available on SINCERITIES websites. Contact rudi.gunawan@chem.ethz.ch Supplementary information Supplementary dataSupplementary data are available at Bioinformatics online.

Description: Objective To identify factors influencing general practitioners' (GPs’) decisions about whether or not to remain in direct patient care in general practice and what might help to retain them in that role. Design Qualitative, in-depth, individual interviews exploring factors related to GPs leaving, remaining in and returning to direct patient care. Setting South West England, UK. Participants 41 GPs: 7 retired; 8 intending to take early retirement; 11 who were on or intending to take a career break; 9 aged under 50 years who had left or were intending to leave direct patient care and 6 who were not intending to leave or to take a career break. Plus 19 stakeholders from a range of primary care-related professional organisations and roles. Results Reasons for leaving direct patient care were complex and based on a range of job-related and individual factors. Three key themes underpinned the interviewed GPs’ thinking and rationale: issues relating to their personal and professional identity and the perceived value of general practice-based care within the healthcare system; concerns regarding fear and risk, for example, in respect of medical litigation and managing administrative challenges within the context of increasingly complex care pathways and environments; and issues around choice and volition in respect of personal social, financial, domestic and professional considerations. These themes provide increased understanding of the lived experiences of working in today’s National Health Service for this group of GPs. Conclusion Future policies and strategies aimed at retaining GPs in direct patient care should clarify the role and expectations of general practice and align with GPs’ perception of their own roles and identity; demonstrate to GPs that they are valued and listened to in planning delivery of the UK healthcare; target GPs’ concerns regarding fear and risk, seeking to reduce these to manageable levels and give GPs viable options to support them to remain in direct patient care.

Description: Author(s): H. Miao, W. H. Brito, Z. P. Yin, R. D. Zhong, G. D. Gu, P. D. Johnson, M. P. M. Dean, S. Choi, G. Kotliar, W. Ku, X. C. Wang, C. Q. Jin, S.-F. Wu, T. Qian, and H. Ding Here, we use angle-resolved photoemission spectroscopy to study superconductivity that emerges in two extreme cases, from a Fermi-liquid phase (LiFeAs) and an incoherent bad-metal phase ( FeTe 0.55 Se 0.45 ). We find that although the electronic coherence can strongly reshape the single-particle spectral... [Phys. Rev. B 98, 020502(R)] Published Mon Jul 09, 2018

Description: Objectives To assess acceptability and feasibility of trial processes and the Rehabilitation Training (ReTrain) intervention including an assessment of intervention fidelity. Design A two-group, assessor-blinded, randomised controlled trial with parallel mixed methods process and economic evaluations. Setting Community settings across two sites in Devon. Participants Eligible participants were: 18 years old or over, with a diagnosis of stroke and with self-reported mobility issues, no contraindications to physical activity, discharged from National Health Service or any other formal rehabilitation programme at least 1 month before, willing to be randomised to either control or ReTrain and attend the training venue, possessing cognitive capacity and communication ability sufficient to participate. Participants were individually randomised (1:1) via a computer-generated randomisation sequence minimised for time since stroke and level of functional disability. Only outcome assessors independent of the research team were blinded to group allocation. Interventions ReTrain comprised (1) an introductory one-to-one session; (2) ten, twice-weekly group classes with up to two trainers and eight clients; (3) a closing one-to-one session, followed by three drop-in sessions over the subsequent 3 months. Participants received a bespoke home-based training programme. All participants received treatment as usual. The control group received an exercise after stroke advice booklet. Outcome measures Candidate primary outcomes included functional mobility and physical activity. Results Forty-five participants were randomised (ReTrain=23; Control=22); data were available from 40 participants at 6 months of follow-up (ReTrain=21; Control=19) and 41 at 9 months of follow-up (ReTrain=21; Control=20). We demonstrated ability to recruit and retain participants. Participants were not burdened by the requirements of the study. We were able to calculate sample estimates for candidate primary outcomes and test procedures for process and health economic evaluations. Conclusions All objectives were fulfilled and indicated that a definitive trial of ReTrain is feasible and acceptable. Trial registration number NCT02429180 ; Results.