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"Murray, David"
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Do TUNEL and Other Apoptosis Assays Detect Cell Death in Preclinical Studies?
The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay detects DNA breakage by labeling the free 3ʹ-hydroxyl termini. Given that genomic DNA breaks arise during early and late stages of apoptosis, TUNEL staining continues to be widely used as a measure of apoptotic cell death. The advantages of the assay include its relative ease of performance and the broad availability of TUNEL assay kits for various applications, such as single-cell analysis of apoptosis in cell cultures and tissue samples. However, as briefly discussed herein, aside from some concerns relating to the specificity of the TUNEL assay itself, it was demonstrated some twenty years ago that the early stages of apoptosis, detected by TUNEL, can be reversed. More recently, compelling evidence from different biological systems has revealed that cells can recover from even late stage apoptosis through a process called anastasis. Specifically, such recovery has been observed in cells exhibiting caspase activation, genomic DNA breakage, phosphatidylserine externalization, and formation of apoptotic bodies. Furthermore, there is solid evidence demonstrating that apoptotic cells can promote neighboring tumor cell repopulation (e.g., through caspase-3-mediated secretion of prostaglandin E2) and confer resistance to anticancer therapy. Accordingly, caution should be exercised in the interpretation of results obtained by the TUNEL and other apoptosis assays (e.g., caspase activation) in terms of apoptotic cell demise.
Journal Article
Adverse outcomes after total and unicompartmental knee replacement in 101 330 matched patients: a study of data from the National Joint Registry for England and Wales
Total knee replacement (TKR) or unicompartmental knee replacement (UKR) are options for end-stage osteoarthritis. However, comparisons between the two procedures are confounded by differences in baseline characteristics of patients undergoing either procedure and by insufficient reporting of endpoints other than revision. We aimed to compare adverse outcomes for each procedure in matched patients.
With propensity score techniques, we compared matched patients undergoing TKR and UKR in the National Joint Registry for England and Wales. The National Joint Registry started collecting data in April 1, 2003, and is continuing. The last operation date in the extract of data used in our study was Aug 28, 2012. We linked data for multiple potential confounders from the National Health Service Hospital Episode Statistics database. We used regression models to compare outcomes including rates of revision, revision/reoperation, complications, readmission, mortality, and length of stay.
25 334 UKRs were matched to 75 996 TKRs on the basis of propensity score. UKRs had worse implant survival both for revision (subhazard ratio [SHR] 2·12, 95% CI 1·99–2·26) and for revision/reoperation (1·38, 1·31–1·44) than TKRs at 8 years. Mortality was significantly higher for TKR at all timepoints than for UKR (30 day: hazard ratio 0·23, 95% CI 0·11–0·50; 8 year: 0·85, 0·79–0·92). Length of stay, complications (including thromboembolism, myocardial infarction, and stroke), and rate of readmission were all higher for TKR than for UKR.
In decisions about which procedure to offer, the higher revision/reoperation rate of UKR than of TKR should be balanced against a lower occurrence of complications, readmission, and mortality, together with known benefits for UKR in terms of postoperative function. If 100 patients receiving TKR received UKR instead, the result would be around one fewer death and three more reoperations in the first 4 years after surgery.
Royal College of Surgeons of England and Arthritis Research UK.
Journal Article
Bruce Springsteen : from Asbury Park, to Born to Run, to Born in the USA
\"An unprecedented look at Bruce Springsteen and the E Street Band on their path to becoming rock legends, from the group's early New Jersey Shore days in 1973, to their meteoric rise, to the band's seminal Born in the U.S.A. tour. David Gahr (1922-2008) was tapped by Columbia Records designer John Berg to shoot cover art for Springsteen's second album, The Wild, the Innocent and the E Street Shuffle. Gahr's earliest photographs of the musician showcase a youthful Bruce Springsteen, not even aged twenty-three, in New Jersey, on the eve of a career breakthrough. Gahr befriended the rising star, and from 1973 to 1986 he photographed Springsteen countless times both on and off stage. Rare captures include Springsteen recording music, performing at the famous West Village venue The Bottom Line weeks before the release of his seminal 1975 album Born to Run, and playing to legions of fans during his Born in the U.S.A. tour\"--Jacket flap.
BOOK
Myeloma Therapy for Monoclonal Gammopathy of Thrombotic Significance
Monoclonal Gammopathy of Thrombotic SignificanceA patient with serious thrombotic episodes was found to have a monoclonal gammopathy of an anti–PF4 antibody. Myeloma therapy reduced the paraprotein level and prevented further thrombotic events.
Journal Article
Review of Recent Methodological Developments in Group-Randomized Trials: Part 1—Design
In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis.
Journal Article
World War II. The Pacific
Written from a British perspective, this book discusses some of the key moments during the Pacific campaigns of World War II, along with personal anecdotes of soldiers and civilians.
Book
Review of Recent Methodological Developments in Group-Randomized Trials: Part 2—Analysis
In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have updated that review with developments in analysis of the past 13 years, with a companion article to focus on developments in design. We discuss developments in the topics of the earlier review (e.g., methods for parallel-arm GRTs, individually randomized group-treatment trials, and missing data) and in new topics, including methods to account for multiple-level clustering and alternative estimation methods (e.g., augmented generalized estimating equations, targeted maximum likelihood, and quadratic inference functions). In addition, we describe developments in analysis of alternative group designs (including stepped-wedge GRTs, network-randomized trials, and pseudocluster randomized trials), which require clustering to be accounted for in their design and analysis.
Journal Article