Uncovering the hidden costs of offshoring: The interplay of complexity, organizational design, and experience

This study investigates estimation errors due to hidden costs—the costs of implementation that are neglected in strategic decision-making processes—in the context of services offshoring. Based on data from the Offshoring Research Network, we find that decision makers are more likely to make cost-estimation errors given increasing configuration and task complexity in captive offshoring and offshore outsourcing, respectively. Moreover, we show that experience and a strong orientation toward organizational design in the offshoring strategy reduce the cost-estimation errors that follow from complexity. Our findings contribute to research on the effectiveness of sourcing and global strategies by stressing the importance of organizational design and experience in dealing with increasing complexity

Promiscuous Targeting of Cellular Proteins by Vpr Drives Systems-Level Proteomic Remodeling in HIV-1 Infection.

HIV-1 encodes four "accessory proteins" (Vif, Vpr, Vpu, and Nef), dispensable for viral replication in vitro but essential for viral pathogenesis in vivo. Well characterized cellular targets have been associated with Vif, Vpu, and Nef, which counteract host restriction and promote viral replication. Conversely, although several substrates of Vpr have been described, their biological significance remains unclear. Here, we use complementary unbiased mass spectrometry-based approaches to demonstrate that Vpr is both necessary and sufficient for the DCAF1/DDB1/CUL4 E3 ubiquitin ligase-mediated degradation of at least 38 cellular proteins, causing systems-level changes to the cellular proteome. We therefore propose that promiscuous targeting of multiple host factors underpins complex Vpr-dependent cellular phenotypes and validate this in the case of G2/M cell cycle arrest. Our model explains how Vpr modulates so many cell biological processes and why the functional consequences of previously described Vpr targets, identified and studied in isolation, have proved elusive.This work was supported by the Wellcome Trust (PRF 210688/Z/18/Z to PJL), the MRC (CSF MR/P008801/1 to NJM), NHSBT (WPA15-02 to NJM), the NIHR Cambridge BRC, and a Wellcome Trust Strategic Award to the CIMR

A report from the NIHR UK working group on remote trial delivery for the COVID-19 pandemic and beyond

Abstract Background Prior to the COVID-19 pandemic, the majority of clinical trial activity took place face to face within clinical or research units. The COVID-19 pandemic resulted in a significant shift towards trial delivery without in-person face-to-face contact or “Remote Trial Delivery”. The National Institute of Health Research (NIHR) assembled a Remote Trial Delivery Working Group to consider challenges and enablers to this major change in clinical trial delivery and to provide a toolkit for researchers to support the transition to remote delivery. Methods The NIHR Remote Trial Delivery Working Group evaluated five key domains of the trial delivery pathway: participant factors, recruitment, intervention delivery, outcome measurement and quality assurance. Independent surveys were disseminated to research professionals, and patients and carers, to ascertain benefits, challenges, pitfalls, enablers and examples of good practice in Remote Trial Delivery. A toolkit was constructed to support researchers, funders and governance structures in moving towards Remote Trial Delivery. The toolkit comprises a website encompassing the key principles of Remote Trial Delivery, and a repository of best practice examples and questions to guide research teams. Results The patient and carer survey received 47 respondents, 34 of whom were patients and 13 of whom were carers. The professional survey had 115 examples of remote trial delivery practice entered from across England. Key potential benefits included broader reach and inclusivity, the ability for standardisation and centralisation, and increased efficiency and patient/carer convenience. Challenges included the potential exclusion of participants lacking connectivity or digital skills, the lack of digitally skilled workforce and appropriate infrastructure, and validation requirements. Five key principles of Remote Trial Delivery were proposed: national research standards, inclusivity, validity, cost-effectiveness and evaluation of new methodologies. Conclusions The rapid changes towards Remote Trial Delivery catalysed by the COVID-19 pandemic could lead to sustained change in clinical trial delivery. The NIHR Remote Trial Delivery Working Group provide a toolkit for researchers recommending five key principles of Remote Trial Delivery and providing examples of enablers. </jats:sec

Recommendations for exercise adherence measures in musculoskeletal settings : a systematic review and consensus meeting (protocol)

Background: Exercise programmes are frequently advocated for the management of musculoskeletal disorders; however, adherence is an important pre-requisite for their success. The assessment of exercise adherence requires the use of relevant and appropriate measures, but guidance for appropriate assessment does not exist. This research will identify and evaluate the quality and acceptability of all measures used to assess exercise adherence within a musculoskeletal setting, seeking to reach consensus for the most relevant and appropriate measures for application in research and/or clinical practice settings. Methods/design: There are two key stages to the proposed research. First, a systematic review of the quality and acceptability of measures used to assess exercise adherence in musculoskeletal disorders; second, a consensus meeting. The systematic review will be conducted in two phases and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to ensure a robust methodology. Phase one will identify all measures that have been used to assess exercise adherence in a musculoskeletal setting. Phase two will seek to identify published and unpublished evidence of the measurement and practical properties of identified measures. Study quality will be assessed against the COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. A shortlist of best quality measures will be produced for consideration during stage two: a meeting of relevant stakeholders in the United Kingdom during which consensus on the most relevant and appropriate measures of exercise adherence for application in research and/or clinical practice settings will be sought. Discussion: This study will benefit clinicians who seek to evaluate patients’ levels of exercise adherence and those intending to undertake research, service evaluation, or audit relating to exercise adherence in the musculoskeletal field. The findings will impact upon new research studies which aim to understand the factors that predict adherence with exercise and which test different adherence-enhancing interventions. PROSPERO reference: CRD4201300621

Functional proteomic atlas of HIV infection in primary human CD4+ T cells.

Viruses manipulate host cells to enhance their replication, and the identification of cellular factors targeted by viruses has led to key insights into both viral pathogenesis and cell biology. In this study, we develop an HIV reporter virus (HIV-AFMACS) displaying a streptavidin-binding affinity tag at the surface of infected cells, allowing facile one-step selection with streptavidin-conjugated magnetic beads. We use this system to obtain pure populations of HIV-infected primary human CD4+ T cells for detailed proteomic analysis, and quantitate approximately 9000 proteins across multiple donors on a dynamic background of T cell activation. Amongst 650 HIV-dependent changes (q < 0.05), we describe novel Vif-dependent targets FMR1 and DPH7, and 192 proteins not identified and/or regulated in T cell lines, such as ARID5A and PTPN22. We therefore provide a high-coverage functional proteomic atlas of HIV infection, and a mechanistic account of host factors subverted by the virus in its natural target cell

Poorly differentiated carcinoma arising from adenolymphoma of the parotid gland

BACKGROUND: There is only one previous case report of a poorly differentiated carcinoma arising from an adenolymphoma of the parotid gland (Warthin's tumour). The absence of clinical symptoms, and the aspecificity of the radiological pattern make the diagnosis very difficult. CASE PRESENTATION: We here report the case of a 73-year-old man with Warthin's tumour who was brought to our attention because of a swelling in the parotid region. CONCLUSIONS: In this case with an atypical clinical presentation, the intra-operative examination of a frozen section of the parotid mass allowed us to diagnose the malignant tumour correctly and consequently undertake its radical excision

Precision Orbit of δ Delphini and Prospects for Astrometric Detection of Exoplanets

This is the author accepted manuscript. The final version is available from American Astronomical Society / IOP Publishing via the DOI in this record.Combining visual and spectroscopic orbits of binary stars leads to a determination of the full 3D orbit, individual masses, and distance to the system. We present a full analysis of the evolved binary system δ Delphini using astrometric data from the MIRC and PAVO instruments on the CHARA long-baseline interferometer, 97 new spectra from the Fairborn Observatory, and 87 unpublished spectra from the Lick Observatory. We determine the full set of orbital elements for δ Del, along with masses of 1.78 ± 0.07 M ⊙ and 1.62 ± 0.07 M ⊙ for each component, and a distance of 63.61 ± 0.89 pc. These results are important in two contexts: for testing stellar evolution models and for defining the detection capabilities for future planet searches. We find that the evolutionary state of this system is puzzling, as our measured flux ratios, radii, and masses imply a ~200 Myr age difference between the components, using standard stellar evolution models. Possible explanations for this age discrepancy include mass transfer scenarios with a now-ejected tertiary companion. For individual measurements taken over a span of two years, we achieve 2 M J on orbits >0.75 au around individual components of hot binary stars via differential astrometry.This work is based upon observations obtained with the Georgia State University Center for High Angular Resolution Astronomy Array at Mount Wilson Observatory. The CHARA Array is supported by the National Science Foundation under Grants No. AST-1211929 and AST-1411654. Institutional support has been provided from the GSU College of Arts and Sciences and the GSU Office of the Vice President for Research and Economic Development. This research has made use of the Jean-Marie Mariotti Center SearchCal service2 . JDM and TG wish to gratefully acknowledge support by NASA XRP Grant NNX16AD43G. Astronomy at Tennessee State University is supported by the state of Tennessee through its Centers of Excellence program. SK acknowledges support from an European Research Council Starting Grant (Grant Agreement No. 639889) and STFC Rutherford Fellowship (ST/J004030/1). D.H. acknowledges support by the National Aeronautics and Space Administration under Grant NNX14AB92G issued through the Kepler Participating Scientist Program. TRW acknowledges the support of the Villum Foundation (research grant 10118)