Background Metastatic castration-resistant prostate cancer is enriched in DNA damage response (DDR) gene aberrations. The TOPARP-B trial aims to prospectively validate the association between DDR gene aberrations and response to olaparib in metastatic castration-resistant prostate cancer.Methods In this open-label, investigator-initiated, randomised phase 2 trial following a selection (or pick-thewinner) design, we recruited participants from 17 UK hospitals. Men aged 18 years or older with progressing metastatic castration-resistant prostate cancer previously treated with one or two taxane chemotherapy regimens and with an Eastern Cooperative Oncology Group performance status of 2 or less had tumour biopsies tested with targeted sequencing. Patients with DDR gene aberrations were randomly assigned (1:1) by a computer-generated minimisation method, with balancing for circulating tumour cell count at screening, to receive 400 mg or 300 mg olaparib twice daily, given continuously in 4-week cycles until disease progression or unacceptable toxicity. Neither participants nor investigators were masked to dose allocation. The primary endpoint of confirmed response was defined as a composite of all patients presenting with any of the following outcomes: radiological objective response (as assessed by Response Evaluation Criteria in Solid Tumors 1.1), a decrease in prostate-specific antigen (PSA) of 50% or more (PSA50) from baseline, or conversion of circulating tumour cell count (from ≥5 cells per 7•5 mL blood at baseline to <5 cells per 7•5 mL blood). A confirmed response in a consecutive assessment after at least 4 weeks was required for each component. The primary analysis was done in the evaluable population. If at least 19 (43%) of 44 evaluable patients in a dose cohort responded, then the dose cohort would be considered successful. Safety was assessed in all patients who received at least one dose of olaparib. This trial is registered at ClinicalTrials.gov, NCT01682772. Recruitment for the trial has completed and follow-up is ongoing. Findings 711 patients consented for targeted screening between April 1, 2015, and Aug 30, 2018. 161 patients had DDR gene aberrations, 98 of whom were randomly assigned and treated (49 patients for each olaparib dose), with 92 evaluable for the primary endpoint (46 patients for each olaparib dose). Median follow-up was 24•8 months (IQR 16•7-35•9). Confirmed composite response was achieved in 25 (54•3%; 95% CI 39•0-69•1) of 46 evaluable patients in the 400 mg cohort, and 18 (39•1%; 25•1-54•6) of 46 evaluable patients in the 300 mg cohort. Radiological response was achieved in eight (24•2%; 11•1-42•3) of 33 evaluable patients in the 400 mg cohort and six (16•2%; 6•2-32•0) of 37 in the 300 mg cohort; PSA50 response was achieved in 17 (37•0%; 23•2-52•5) of 46 and 13 (30•2%; 17•2-46•1) of 43; and circulating tumour cell count conversion was achieved in 15 (53•6%; 33•9-72•5) of 28 and 13 (48•1%; 28•7-68•1) of 27. The most common grade 3-4 adverse event in both cohorts was anaemia (15 [31%] ...

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Ten athletes with distal biceps tendon ruptures that had been anatomically repaired with a double-incision techniques were reviewed to determine their functional recovery. All of the patients were men, with an average age of 40 years (range, 25 to 49). Eight of the 10 patients were weight lifters or body builders, and 7 had participated on a competitive level at some point in their athletic careers. Six injured their dominant extremity, and 4 their nondominant extremity. Isokinetic muscle testing of supination and flexion was performed in 8 patients and the results were compared to a control group. Followup averaged 50 months (range, 12 to 105). Patients uniformly graded their subjective results as excellent, with a group mean rating of 9.75 on a 10-point scale. All athletes returned to full, unlimited activity. The contour of the biceps muscle was restored in all cases. Isokinetic muscle testing demonstrated that in those patients with a repaired dominant extremity, supination strength and endurance was normal; in flexion, they had normal strength, but averaged 20% less endurance. Testing of the group that had the nondominant extremity repaired revealed a supination strength deficit of 25%, but normal endurance. Flexion strength and endurance were essentially normal in this group. Anatomic repair of a distal biceps tendon rupture gives consistently excellent subjective and good objective results in athletes, particularly for those sports with high strength demands such as weight lifting and body building. Rehabilitation of the operated arm, especially the repaired nondominant extremity, should be emphasized.

Flow cytometry can be used to obtain high-resolution estimates of nuclear DNA content (8,12,27). Much of the work in this area has been confined to clinical studies in the human, but the technology has been extended to organisms such as pocket gophers (241, triploid trout ( 2 3 , side-necked turtles (61, sex-reversed horses (16), and oysters (1).In these and similar studies, the DNA content of target cells is quantified relative to a standard DNA content in cells from a reference species (13,14,28). Standards may be used as internal references, when target cells and reference cells are mixed together and assayed simultaneously, or as external references, when target cells and cells from the reference species are analyzed independently. When external references are used, the flow cytometer must be checked for equilibration between analyses.The standard can be used for several calculations. The standard can be assigned a known DNA mass, against which picogram quantities of nuclear DNA from target cells can be estimated directly (15). Alternatively, a standard could be used as an internal reference in the analysis of individual samples, following which the reference is cancelled during estimation of a DNA Index. An internal reference would also be cancelled during the calculation of picogram quantities of nuclear DNA relative to a separate standard that has a known DNA mass (and a known relationship to the internal reference). These last two calculations do not require knowledge of the precise DNA mass of the internal reference.Because the use of reference standards provides a relative measure of DNA content, it is crucial that the reference cells and the target cells have a similar DNA content to minimize possible zero shift error (28) and, in the case of a n internal reference, that the values for the reference and target cells do not overlap.In order to gather information relating to the selection of reference standards for use in flow cytometry, we have surveyed a wide spectrum of taxa representing each of the major vertebrate classes. Here we present the results of our survey in 45 species. These species were selected because of their broad distribution and general accessibility, and because they provide an array of fluorescence peaks spanning the range of DNA masses that might be encountered in comparative studies. ~~~