Globular Cluster Systems in Brightest Cluster Galaxies. III: Beyond Bimodality

We present new deep photometry of the rich globular cluster (GC) systems around the Brightest Cluster Galaxies UGC 9799 (Abell 2052) and UGC 10143 (Abell 2147), obtained with the HST ACS and WFC3 cameras. For comparison, we also present new reductions of similar HST/ACS data for the Coma supergiants NGC 4874 and 4889. All four of these galaxies have huge cluster populations (to the radial limits of our data, comprising from 12000 to 23000 clusters per galaxy). The metallicity distribution functions (MDFs) of the GCs can still be matched by a bimodal-Gaussian form where the metal-rich and metal-poor modes are separated by ~0.8 dex, but the internal dispersions of each mode are so large that the total MDF becomes very broad and nearly continuous from [Fe/H] = -2.4 to Solar. There are, however, significant differences between galaxies in the relative numbers of \emph{metal-rich} clusters, suggesting that they underwent significantly different histories of mergers with massive, gas-rich halos. Lastly, the proportion of metal-poor GCs rises especially rapidly outside projected radii R > 4 R_eff, suggesting the importance of accreted dwarf satellites in the outer halo. Comprehensive models for the formation of GCs as part of the hierarchical formation of their parent galaxies will be needed to trace the systematic change in structure of the MDF with galaxy mass, from the distinctly bimodal form in smaller galaxies up to the broad continuum that we see in the very largest systems.Comment: In press for Astrophysical Journa

adjuvant mitotane for adrenocortical cancer working through uncertainty

The Journal of Clinical Endocrinology & Metabolism recently published a commentary by Huang and Fojo (1) offering a skeptical view on the efficacy of mitotane as an adjunctive postsurgical measure in patients with adrenocortical cancer (ACC). Their commentary focused on outlining the limitations of our recent study which indicated that adjuvant mitotane may prolong recurrence-free survival (RFS) in patients with radically resected ACC (2). However, we do not agree with several of their conclusions and believe that it is of interest to present our view for a balanced and comprehensive coverage of this important matter. Inprinciple,weagreewithHuangandFojothatourstudysuffers from the important limitation of a retrospective analysis; thus our investigation should be considered as hypothesis generating and certainly does not provide conclusive evidence. This problem has been clearly acknowledged in the paper, and we cautiously concluded that our study should renew interest in adjuvant therapy, whereas prospective, randomized trials will be needed to confirm the efficacyof adjuvantmitotane treatment (2).However, the rarity of ACC precluded organization of a randomized trial either in an adjuvantsettingor inpatientswithadvancedACC(3).Nonetheless, mitotane has been used for treating patients with ACC since the 1960s and is the only drug approved for ACC by the U.S. Food and Drug Administration and the European Medicines Evaluation Agency (4). In this scenario, a study including all consecutive patients treated postoperatively with mitotane in some centers and all consecutive patients left untreated after operation in other centers is thebestway toobtainexplorativedataon theefficacyofadjuvant mitotane, provided that the two groups are comparable. In our study, in fact, mitotane was recommended on the basis of the treatmentpolicyof thecenter, independentof thecharacteristicsofeither the tumorsor thepatients, and this is amajoradvantageminimizing selection bias as compared with other studies that had less clear treatment assignments (5). The major criticism of Huang and Fojo (1) is that we did not demonstrate any benefit on overall survival (OS) for patients treated adjuvantly. However, this is not correct because the hazard ratio of death of the German cohort of nontreated patients was nonsignificantly higher than mitotane-treated patients in univariate analysis, but the difference became significant in multivariate analysis after adjusting for imbalances in prognostic factors (the German cohort included more patients with stage I and II ACC than the Italian cohort of mitotane-treated patients). Even when we accept that the effect of adjuvant mitotane on OS was less impressive than on RFS, we disagree that prolonging a disease-free status is not a clinically meaningful objective even without extending significantly duration of life. In addition, there is a long-standing debate on the most appropriate endpoint for adjuvant trials, and both OS and RFS have been suggested. Analysis of RFS has the advantage of needing a shorter follow-up and being directly related to the treatment tested. The most important disadvantage of RFS is its close relationship to the frequency and quality of evaluation. Bias in follow-up or ascertainment of outcome in observational retrospective series is well recognized, and we have acknowledged this potential limit of our study. However, the follow-up procedures were highly comparable among the different centers and included imaging evaluation of the chest and abdomen every 6 months until disease progression or the end of the study period (2). Even if survival has to be considered as the reference end-point, it may not be a direct result of the study drug because it may be strongly influenced by subsequent treatments and oncologists are increasingly considering RFS as a valid surrogate for OS (6). However, this relationship has never been demonstrated specifically in ACC patients. Another criticism is derived from an ill-conceived reanalysis of our data. Huang and Fojo (1) aimed at demonstrating that the time interval between ACC recurrence and death is higher in patients treated adjuvantly than patients left untreated after surgery. Thus, they assumed important differences in tumor biology of the different cohorts. This conclusion comes from subtracting median time to recurrence from median survival observed in th

Sudden cardiac death after robbery: Homicide or natural death?

Tako-Tsubo is one of a number of rare acquired cardiomyopathies that are characterized by left ventricular dyskinesia and symptomatology typical of acute myocardial infarction (AMI). The most important feature is that the clinical features are triggered by a severe physical or emotional stress. The authors describe the story of a woman, who was brutally assaulted by two men during a house robbery and died from sudden heart failure 8 hours later, after being taken to hospital. External examination revealed no macroscopic alteration of the inner organs, whereas microscopy showed contraction bands with myocardial necrosis, subendocardial and interstitial neutrophil infiltration and fibrosis. These findings were consistent with death due to stress cardiomyopathy even in the absence of previous heart disease. The robbers were convicted of homicide and sentenced to eighteen years in prison

Methodological Differences in the Interpretation of Fatigue Data from Repeated Maximal Effort Knee Extensions

Background: Isokinetic fatigue protocols are commonly used in both research as well as in kinesiology education. However, fatigue quantification methods vary between studies. Objective: Therefore, the purpose of this study was to determine how fatigue quantification methods affect data interpretation and which methods may be most appropriate. Method: In this study, we quantified fatigue from a repeated maximal effort isokinetic knee extension test using different methods, as seen in published research. Nine healthy males and nine healthy females performed 50 concentric knee extensions at 180°•s-1. For each repetition, torque was quantified as either peak torque (PT), torque at the mid-point of the range of motion, and torque integrated over the full, middle 30° range of motion, and isokinetic range of motion. Fatigue Index was quantified using either the first and last three or five repetitions or the peak and last three or five repetitions. Torque slopes were quantified using all repetitions or repetitions that occurred at and beyond the repetition at which the greatest torque value occurred. Results: There was a significant inverse relationship between angle at PT and repetition number. Measures of fatigue were overestimated when torque integral over the isokinetic range of motion was utilized. When the first three or first five repetitions were utilized for Fatigue Index calculations, fatigue was underestimated. Conclusion: Results suggest that torque integral over the full range of motion is likely the best representation of strength or work. Also, researchers should omit the first few repetitions from their quantification of Fatigue Index or torque slope

The home-court advantage in NCAA Division-I men’s basketball

The purpose of the present study was to examine the differences in game-related statistics between home and away games at the NCAA Division-I level of men’s basketball competition. The data scraping technique was used to obtain publicly available box scores during the 2018-19 competitive season. Throughout this period, 2181 home and 2205 away box scores were randomly selected across 353 teams, regardless of the winning or losing game outcome. The findings of the present study revealed that the game-related statistics influenced by the game location, listed in descending order of magnitude, were: assists (AS), personal fouls (PF), field-goal percentage (FG%), free-throw attempts (FTA), blocks (BL), defensive rebounds (DRB), turnovers (TO), steals (ST), and three-point shooting percentage (3P%). During home games, the teams tended to display better decision-making processes (i.e., more AS and ST, and less TO), defensive performance (i.e., more DRB and BL), shooting efficiency (i.e., greater FT% and 3P%), and minimize tactical errors (i.e., less PF and more FTA). Overall, these findings suggest that playing on a home-court provides a significant advantage in securing the desired game outcome and provides insight into what game-related statistics contribute most to this effect

Electrostatic Switching Controls Channel Dynamics of the Sensor Protein VirB10 in A. tumefaciens Type IV Secretion System

Type IV secretion systems are large nanomachines assembled across the bacterial cell envelope for effector translocation and conjugation. VirB10 traverses the inner and outer membranes, sensing cellular signals for coordinating the conformational switch for pilus biogenesis and/or secretion. Mutations uncoupling secretion from pilus biogenesis were identified in Agrobacterium tumefaciens VirB10 including a gating defect mutation G272R that made VirB10 unresponsive to intracellular ATP, causing unregulated secretion of VirE2 in a contact-independent manner. Comparative long-timescale molecular dynamics of the wild type and G272R mutant of the A. tumefaciens VirB10_{CTD} tetradecamer reveals how the G272R mutation locks the oligomer in a rigid conformation by swapping the ionic interactions between the loops from the β-barrel close to the inner leaflet of the outer membrane. This electrostatic switching changes the allosteric communication pathway from the extracellular loop to the base of the barrel, suggesting that the local conformational dynamics in the loops can gate information across VirB10