Research Inefficiency in Degenerative Cervical Myelopathy: Findings of a Systematic Review on Research Activity Over the Past 20 Years.

STUDY DESIGN: Scoping review. OBJECTIVE: To describe activity, themes and trends in degenerative cervical myelopathy (DCM) research over the past 20 years with a view to considering DCM research inefficiency. METHODS: A systematic review of MEDLINE and Embase for "Cervical" AND "Myelopathy" was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and December 31, 2015 were considered eligible. Country of origin, number of papers published, number of patients studied, research theme, and year of publication were assessed. Comparison was made between developed and developing countries. RESULTS: A total of 1485 papers and 4 117 051 patients were included. Japan published more papers (450) than any other country while the United States studied the greatest number of patients (3 674 737). Over 99.4% of papers and 78.6% of patients were from developed countries. The number of papers (r = 0.96, P < .001) and patients (r = 0.83 P < .001) studied each year increased significantly overall and for both developed (r = 0.93, P < .001; r = 0.81, P < .001) and developing countries (r = 0.90, P < .001; r = 0.87, P < .001). Surgery was the most prevalent theme (58.3% papers; 55.7% patients) for developed and developing countries. Research from developing countries showed greater thematic variability. CONCLUSIONS: DCM research activity is increasing internationally, with surgery remaining the focus. Research output has predominantly been from developed countries; however, the rate of growth for developed and developing countries is comparable

Electrophysiological stimulation of excised rat muscle elicits a measurable change in tissue sodium concentration using 23Na-MRI

Changes in the tissue sodium gradient play an important role in cell signalling such as at the neuromuscular junction and as part of neuronal action potentials. 23Na-MRI has the ability to measure the macroscopic sodium distribution. In this study we investigated the changes in tissue sodium in an electrically stimulated and freshly excised rat leg muscle.This work was supported by CRUK [C8742/A18097]. This is a contribution from the Cancer Imaging Centre in Cambridge & Manchester, which is funded by the EPSRC and Cancer Research UK. We would like to express our gratitude to the Experimental Cancer Medicine Centres (ECMC) for continued support. JK receives funding support from GlaxoSmithKline

Safe Tumbling of Heavy Objects Using a Two-Cable Crane

In heavy industries, large, heavy objects must be tumbled to access features on their bottoms and sides for assembly and maintenance. Traditional manual operations using a single-cable crane are high-risk, and difficult for less experienced workers. Automating the tumbling process is made challenging due to the presence of kinematic and static singularities which are shown to occur when a single-cable crane loses control over the block being tumbled. Here, an autonomous method for safely tumbling a heavy block sitting on a surface using a two-cable crane is presented. Two winches controlling a pair of cables on a crane are coordinated in such a way that a) the block cannot slip on the floor, b) the block is not lifted into the air, and c) the block is under quasi-static balanced control at all times. A control algorithm for coordinating the two winches is developed for safely tumbling a block without slipping or becoming airborne as well as for eliminating the effect of singularities. A small-scale prototype is developed and the control algorithm is implemented and evaluated experimentally.S.M

Evidence synthesis summary formats for clinical guideline development group members: a mixed-methods systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]

Introduction: Evidence syntheses, often in the form of systematic reviews, are essential for clinical guideline development and informing changes to health policies. However, clinical guideline development groups (CGDG) are multidisciplinary, and participants such as policymakers, healthcare professionals and patient representatives can face obstacles when trying to understand and use evidence synthesis findings. Summary formats to communicate the results of evidence syntheses have become increasingly common, but it is currently unclear which format is most effective for different stakeholders. This mixed-methods systematic review (MMSR) evaluates the effectiveness and acceptability of different evidence synthesis summary formats for CGDG members. Methods: This protocol follows guidance from the Joanna Briggs Institute on MMSRs and is reported according to the Preferred Reporting Items for Systematic Reviews (PRISMA)-P guideline. A comprehensive search of six databases will be performed with no language restrictions. Primary outcomes are those relating to the effectiveness and preferences for and attitudes towards the different summary formats. We will include qualitative research and randomised controlled trials. Two reviewers will perform title, abstract, and full-text screening. Independent double-extraction of study characteristics and critical appraisal items will be undertaken using a standardised form. We will use a convergent segregated approach to analyse quantitative and qualitative data separately; results will then be integrated. Discussion: The results of this systematic review will provide an overview of the effectiveness and acceptability of different summary formats for evidence synthesis findings. These findings can be helpful for those in or communicating to guideline development groups. The results can also inform the development and pilot-testing of summary formats for evidence summaries.</p

Evidence synthesis summary formats for clinical guideline development group members: a mixed-methods systematic review protocol [version 2; peer review: 2 approved]

Introduction: Evidence syntheses, often in the form of systematic reviews, are essential for clinical guideline development and informing changes to health policies. However, clinical guideline development groups (CGDG) are multidisciplinary, and participants such as policymakers, healthcare professionals and patient representatives can face obstacles when trying to understand and use evidence synthesis findings. Summary formats to communicate the results of evidence syntheses have become increasingly common, but it is currently unclear which format is most effective for different stakeholders. This mixed-methods systematic review (MMSR) evaluates the effectiveness and acceptability of different evidence synthesis summary formats for CGDG members. Methods: This protocol follows guidance from the Joanna Briggs Institute on MMSRs and is reported according to the Preferred Reporting Items for Systematic Reviews (PRISMA)-P guideline. A comprehensive search of six databases will be performed with no language restrictions. Primary outcomes are those relating to the effectiveness and preferences for and attitudes towards the different summary formats. We will include qualitative research and randomised controlled trials. Two reviewers will perform title, abstract, and full-text screening. Independent double-extraction of study characteristics and critical appraisal items will be undertaken using a standardised form. We will use a convergent segregated approach to analyse quantitative and qualitative data separately; results will then be integrated. Discussion: The results of this systematic review will provide an overview of the effectiveness and acceptability of different summary formats for evidence synthesis findings. These findings can be helpful for those in or communicating to guideline development groups. The results can also inform the development and pilot-testing of summary formats for evidence summaries.</p

The curative management of synchronous rectal and prostate cancer

Objective: Neoadjuvant &amp;quot;long-course&amp;quot; chemoradiation is considered a standard of care in locally advanced rectal cancer. In addition to prostatectomy, external beam radiotherapy and brachytherapy with or without androgen suppression (AS) are well established in prostate cancer management. A retrospective review of ten cases was completed to explore the feasibility and safety of applying these standards in patients with dual pathology. To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. Methods: Eligible patients had synchronous histologically proven locally advanced rectal cancer (defined as cT3-4Nx; cTxN1-2) and non-metastatic prostate cancer (pelvic nodal disease permissible). Curative treatment was delivered to both sites simultaneously. Follow-up was as per institutional guidelines. Acute and late toxicities were reviewed, and a literature search performed. Results: Pelvic external beam radiotherapy (RT) 45-50.4 Gy was delivered concurrent with 5-fluorouracil (5FU). Prostate total dose ranged from 70.0 to 79.2Gy. No acute toxicities occurred, excluding AS-induced erectile dysfunction. Nine patients proceeded to surgery, and one was managed expectantly. Three relapsed with metastatic colorectal cancer, two with metastatic prostate cancer. Five patients have no evidence of recurrence, and four remain alive with metastatic disease. With a median follow-up of 2.2 years (range 1.2-6.3 years), two significant late toxicities occurred; G3 proctitis in a patient receiving palliative bevacizumab and a G3 anastomotic stricture precluding stoma reversal. Conclusion: Patients proceeding to synchronous radical treatment of both primary sites should receive 45-50.4Gy pelvic RT with infusional 5FU. Prostate dose escalation should be given with due consideration to the potential impact of prostate cancer on patient survival, as increasing dose may result in significant late morbidity. Review of published series explores the possibility of prostate brachytherapy as an alternative method of boost delivery. Frequent use of bevacizumab in metastatic rectal cancer may compound late rectal morbidity in this cohort. Advances in knowledge: To our knowledge, this is the largest case series of synchronous rectal and prostate cancers treated with curative intent. This article contributes to the understanding of how best to approach definitive treatment in these patients

Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer

Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.Tumours with homologous recombination (HR) defects become sensitive to PARPi. Here, the authors show that androgen receptor (AR) regulates HR and AR inhibition activates the PARP pathway in vivo, thus inhibition of both AR and PARP is required for effective treatment of high risk prostate cancer.</p