The Effect of Selective Heart Rate Slowing in Heart Failure with Preserved Ejection Fraction

Acknowledgments Dr Ashrafian acknowledges support from the BHF Center of Research Excellence, Oxford, UK. The research was also supported by the National Institute for Health Research Oxford Biomedical Research Center Program and by the National Institute for Health Research Rare Diseases Translational Research Collaboration (NIHR RD-TRC)

Vascular defects and spinal cord hypoxia in spinal muscular atrophy

© 2015 American Neurological Association. Funded by The Euan MacDonald Center for Motor Neurone Disease Research The SMA Trust Muscular Dystrophy UK The SMA Trust The SMA Trust Motor Neurone Disease Association National Institute for Health Research Great Ormond Street Hospital Biomedical Research Center Medical Research Council Great Ormond Street Hospital Charity

Longitudinal diffusion tensor imaging in dementia with Lewy bodies and Alzheimer's disease

Copyright © 2016 Elsevier Ltd. All rights reserved. Acknowledgements The study was supported by the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge, and the NIHR Biomedical Research Unit in Dementia and the Biomedical Research Centre awarded to Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. Elijah Mak was in receipt of a Gates Cambridge PhD studentship.

The Hippo effector TAZ (WWTR1) transforms myoblasts and its abundance is associated with reduced survival in embryonal rhabdomyosarcoma

Acknowledgements This study was funded by Sarcoma UK, Friends of Anchor and the Medical Research Council grant number 99477 awarded to HW and PSZ. This work was also supported, in part, by NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research, and the Chris Lucas Trust, UK. We also thank the CCLG Tissue Bank for access to samples, and contributing CCLG centres, including members of the ECMC paediatric network. The CCLG Tissue Bank is funded by Cancer Research UK and CCLG. In addition we would like to thank Prof KunLiang Guan and Prof Malcolm Logan for kindly providing constructs

Altered fibrinolysis in autosomal dominant thrombomodulin associated coagulopathy

The NIHR BioResource-Rare Diseases and the ThromboGenomics sequencing projects are supported by the National Institute for Health Research (NIHR; http://www.nihr.ac.uk). KB is an NIHR academic clinical fellow. SKW is supported by a Medical Research Council (MRC) Clinical Training Fellowship (MR/K023489/1). KS and ET are supported by the NIHR BioResource Rare Diseases. CSW and NJM are supported by the British Heart Foundation (FS/11/2/28579). ADM is supported by the NIHR Bristol Cardiovascular Biomedical Research Unit.

Important factors in predicting mortality outcome from stroke : findings from the Anglia Stroke Clinical Network Evaluation Study

The Anglia Stroke Clinical Network Evaluation Study (ASCNES) is funded by the National Institute for Health Research (NIHR) Research for Patient Benefit Programme (PB-PG-1208-18240). This paper presents independent research funded by the NIHR under its Research for Patient Benefit (RfPB) programme (Grant Reference Number PB-PG-1208-18240). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. EAW receives funding support from the NIHR Biomedical Research Centre award to Cambridge

Costs, quality of life and cost-effectiveness of open and arthroscopic repair for rotator cuff tears : economic evaluation alongside the UKUFF trial

FUNDING & ACKNOWLEDGEMENTS This project was funded by the NIHR Health Technology Assessment programme (project number 05/47/02) and is published in full in Health Technology Assessment; Vol. 19, No. 80. Further information available at: http://www.nets.nihr.ac.uk/projects/hta/054702 This paper presents independent research commissioned by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA programme or the Department of Health. Due to the confidential nature of the trial data supporting this publication not all of the data can be made accessible to other researchers. Please contact the UKUFF study principal investigator Andrew Carr (andrew.carr@ndorms.ox.ac.uk) for more information. The authors wish to thank the UKUFF trial collaborators for their contribution in managing the conduct of the trial, and for their comments on the interim economic results: Marion Campbell and Hannah Bruhn (Centre for Healthcare Randomised Trials, HSRU, University of Aberdeen), Jonathan Rees MD and David Beard (NDORMS, University of Oxford; NIHR Oxford Biomedical Research Centre), Jane Moser (NDORMS, University of Oxford), Raymond Fitzpatrick and Jill Dawson (NDPH, University of Oxford).

Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer's disease and dementia with Lewy bodies

Acknowledgments We thank Craig Lambert for his help in processing the MRS data. The study was funded by the Sir Jules Thorn Charitable Trust (grant ref: 05/JTA) and was supported by the National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre and the Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust and Newcastle University and the NIHR Biomedical Research Centre and Biomedical Research Unit in Dementia based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Placental vascularity and markers of angiogenesis in relation to prenatal growth status in overnourished adolescent ewes

Acknowledgments Supported by the Wellcome Trust project grant 088208 (DJC), Wellbeing of Women research training fellowship 318 (DJC), Scottish Government Work package 4.2 (JMW, JSM and RPA), National Institute for Health Research University College London Hospitals Biomedical Research Centre (ALD) and Hatch ProjectND01748 (DAR).

The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma

Acknowledgements This study was funded by Sarcoma UK, Friends of Anchor and the Medical Research Council grant number 99477 awarded to HW and PSZ. This work was also supported, in part, by NHS funding to the NIHR Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research, and the Chris Lucas Trust, UK. We also thank the CCLG Tissue Bank for access to samples, and contributing CCLG centres, including members of the ECMC paediatric network. The CCLG Tissue Bank is funded by Cancer Research UK and CCLG. In addition we would like to thank Prof KunLiang Guan and Prof Malcolm Logan for kindly providing constructs

The Evolution of Chimpanzee Sanctuaries in the United States

Chimpanzees are native only to the jungles of equatorial Africa, but for the last hundred years, they have also lived in captivity in the United States, most commonly in biomedical research laboratories, but also at Air Force bases for experiments for the space program, at accredited and unaccredited zoos, at circuses, as performers in Hollywood and even in private homes and backyards as pets. But that has been gradually evolving over the last few decades, as more and more chimpanzees move to newly-established chimpanzee sanctuaries. That transition was already underway even before the announcement by the National Institutes of Health (NIH) last year that it will retire all of its remaining chimpanzees from labs to sanctuaries. By thoroughly examining the evolution of these sanctuaries leading up to that seminal decision, along with the many challenges they face, including money, medical care, conflicting philosophies on the treatment of animals and the pitfalls that have led other sanctuaries to the brink of ruin, we can take away a better understanding of why chimpanzee sanctuaries are needed and why caretakers of other animal species are now looking to the chimpanzee sanctuary movement as a model to show how animals can be cared for in retirement.

An R-package for the Estimation and Testing of Multiple Covariates and Biomarker Interactions for Survival Data Based on Local Partial Likelihood

When we study the variables that a ffect survival time, we usually estimate their eff ects by the Cox regression model. In biomedical research, e ffects of the covariates are often modi ed by a biomarker variable. This leads to covariates-biomarker interactions. Here biomarker is an objective measurement of the patient characteristics at baseline. Liu et al. (2015) has built up a local partial likelihood bootstrap model to estimate and test this interaction e ffect of covariates and biomarker, but the R code developed by Liu et al. (2015) can only handle one variable and one interaction term and can not t the model with adjustment to nuisance variables. In this project, we expand the model to allow adjustment to nuisance variables, expand the R code to take any chosen interaction terms, and we set up many parameters for users to customize their research. We also build up an R package called "lplb" to integrate the complex computations into a simple interface. We conduct numerical simulation to show that the new method has excellent fi nite sample properties under both the null and alternative hypothesis. We also applied the method to analyze data from a prostate cancer clinical trial with acid phosphatase (AP) biomarker.

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial.

BACKGROUND: EGFR overexpression occurs in 27-55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. METHODS: In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 1-21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 1-21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. FINDINGS: Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade ≥ 3 neutropenia 35 [13%] vs 74 [28%]). INTERPRETATION: Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. FUNDING: Amgen, UK National Institute for Health Research Biomedical Research Centre.

STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies

Incomplete reporting has been identified as a major source of avoidable waste in biomedical research.
Essential information is often not provided in study reports, impeding the identification, critical
appraisal, and replication of studies. To improve the quality of reporting of diagnostic accuracy
studies, the Standards for Reporting Diagnostic Accuracy (STARD) statement was developed. Here
we present STARD 2015, an updated list of 30 essential items that should be included in every
report of a diagnostic accuracy study. This update incorporates recent evidence about sources of
bias and variability in diagnostic accuracy and is intended to facilitate the use of STARD. As such,
STARD 2015 may help to improve completeness and transparency in reporting of diagnostic accuracy
studies.

Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

Monocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an integrative analysis we have discovered that selective demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in independent PCa cohorts. This demethylation is associated with expression of isoforms differing only in 5'-UTR translational control motifs, providing one contributing mechanism for MCT2 protein overexpression in PCa. Genes co-expressed with SLC16A7/MCT2 also clustered in oncogenic-related pathways and effectors of these signalling pathways were found to bind at the SLC16A7/MCT2 gene locus. Finally, MCT2 knock-down attenuated the growth of PCa cells. The present study unveils an unexpected epigenetic regulation of SLC16A7/MCT2 isoforms and identifies a link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related gene (ERG) and other oncogenic pathways in PCa. These results underscore the importance of combining data from epigenetic, transcriptomic and protein level changes to allow more comprehensive insights into the mechanisms underlying protein expression, that in our case provide additional weight to MCT2 as a candidate biomarker and molecular target in PCa.