Increased survival with enzalutamide in prostate cancer after chemotherapy

Contains fulltext : 108324.pdf (publisher's version ) (Open Access)BACKGROUND: Enzalutamide (formerly called MDV3100) targets multiple steps in the androgen-receptor-signaling pathway, the major driver of prostate-cancer growth. We aimed to evaluate whether enzalutamide prolongs survival in men with castration-resistant prostate cancer after chemotherapy. METHODS: In our phase 3, double-blind, placebo-controlled trial, we stratified 1199 men with castration-resistant prostate cancer after chemotherapy according to the Eastern Cooperative Oncology Group performance-status score and pain intensity. We randomly assigned them, in a 2:1 ratio, to receive oral enzalutamide at a dose of 160 mg per day (800 patients) or placebo (399 patients). The primary end point was overall survival. RESULTS: The study was stopped after a planned interim analysis at the time of 520 deaths. The median overall survival was 18.4 months (95% confidence interval [CI], 17.3 to not yet reached) in the enzalutamide group versus 13.6 months (95% CI, 11.3 to 15.8) in the placebo group (hazard ratio for death in the enzalutamide group, 0.63; 95% CI, 0.53 to 0.75; P<0.001). The superiority of enzalutamide over placebo was shown with respect to all secondary end points: the proportion of patients with a reduction in the prostate-specific antigen (PSA) level by 50% or more (54% vs. 2%, P<0.001), the soft-tissue response rate (29% vs. 4%, P<0.001), the quality-of-life response rate (43% vs. 18%, P<0.001), the time to PSA progression (8.3 vs. 3.0 months; hazard ratio, 0.25; P<0.001), radiographic progression-free survival (8.3 vs. 2.9 months; hazard ratio, 0.40; P<0.001), and the time to the first skeletal-related event (16.7 vs. 13.3 months; hazard ratio, 0.69; P<0.001). Rates of fatigue, diarrhea, and hot flashes were higher in the enzalutamide group. Seizures were reported in five patients (0.6%) receiving enzalutamide. CONCLUSIONS: Enzalutamide significantly prolonged the survival of men with metastatic castration-resistant prostate cancer after chemotherapy. (Funded by Medivation and Astellas Pharma Global Development; AFFIRM ClinicalTrials.gov number, NCT00974311.)

The effects of desert pavements (gravel mulch) on soil micro-hydrology

The effect of desert pavements (gravel mulch) on near surface soil micro-hydrology has been inadequately studied. Micro-hydrology in arid ecosystems occurs due to a daily non rainfall atmospheric water cycle, consisting of an input phase (dew, fog, vapour adsorption) and an evaporation phase. A winter comparative study between a bare soil (control) and gravel mulch using the automated microlysimeter approach was conducted in Stellenbosch, South Africa in 2008. Results showed that dew deposition and direct water vapour adsorption were significantly higher into bare soil compared to gravel mulch. In contrast, however, soil moisture from rain persists for a longer time under gravel mulch compared to bare soil. This result suggests that the greatest impact of gravel mulch on soil micro-hydrology is towards conserving moisture and could explain why the treatment is used in dry-land agriculture in Mediterranean regions. © 2011 Springer Basel AG

A method for direct assessment of the "non rainfall" atmospheric water cycle: Input and evaporation from the soil

"Non rainfall" atmospheric water (dew, fog, vapour adsorption) supplies a small amount of water to the soil surface that may be important for arid soil micro-hydrology and ecology. Research into the direct effects of this water on soil is, however, lacking due to instrument and technical constraints. We report on the design, development, construction and findings of an automated microlysimeter instrument to directly measure this soil water cycle in Stellenbosch, South Africa during winter. Performance of the microlysimeter was satisfactory and results obtained were compared to literature and fell within the expected range. "Non rainfall" atmospheric water input into bare soil (river sand) was between 0.88 and 1.10 mm per night while evaporation was between 1.39 and 2.71 mm per day. The study also attempted to differentiate the composition of "non rainfall" atmospheric water and results showed that vapour adsorption contributed the bulk of this input. © 2011 Springer Basel AG

Age alters cardiac autonomic modulations during and following exercise-induced heat stress in females

The aim of this study was to examine the effect of natural ageing on heart rate variability during and following exercise-induced heat stress in females. Eleven young (∼24 years) and 13 older (∼51 years), habitually active females completed an experimental session consisting of baseline rest, moderate intensity intermittent exercise (four 15-min bouts separated by 15-min recovery) and 1-hour of final recovery in a hot and dry (35°C, 20% relative humidity) environment. Respiratory and heart rate recordings were continuously logged with 10-min periods analysed at the end of: baseline rest; each of the exercise and recovery bouts; and during the 1-hour final recovery period. Comparisons over time during exercise and recovery, and between groups were conducted via two-way repeated-measures ANCOVAs with rest values as the covariate. During baseline rest, older females exhibited lower heart rate variability compared to young females with similar levels of respiration and most (∼71-79%) heart rate variability measures during repeated exercise and recovery. However, older females exhibited heart rate variability metrics suggestive of greater parasympathetic modulation (greater long axis of Poincare plot, cardiac vagal index; lower low-high frequency ratio) during repeated exercise with lower indices during the latter stage of prolonged recovery (less very low frequency component, Largest Lyapunov Exponent; greater cardiac sympathetic index). The current study documented several unique, age-dependent differences in heart rate variability, independent of respiration, during and following exercise-induced heat stress for females that may assist in the detection of normal heat-induced adaptations as well as individuals vulnerable to heat stress. © 2018, © 2018 Taylor & Francis

Computer Vision Tool and Technician as First Reader of Lung Cancer Screening CT Scans

To implement a cost-effective low-dose computed tomography (LDCT) lung cancer screening program at the population level, accurate and efficient interpretation of a large volume of LDCT scans is needed. The objective of this study was to evaluate a workflow strategy to identify abnormal LDCT scans in which a technician assisted by computer vision (CV) software acts as a first reader with the aim to improve speed, consistency, and quality of scan interpretation.Without knowledge of the diagnosis, a technician reviewed 828 randomly batched scans (136 with lung cancers, 556 with benign nodules, and 136 without nodules) from the baseline Pan-Canadian Early Detection of Lung Cancer Study that had been annotated by the CV software CIRRUS Lung Screening (Diagnostic Image Analysis Group, Nijmegen, The Netherlands). The scans were classified as either normal (no nodules \geq1 mm or benign nodules) or abnormal (nodules or other abnormality). The results were compared with the diagnostic interpretation by Pan-Canadian Early Detection of Lung Cancer Study radiologists.The overall sensitivity and specificity of the technician in identifying an abnormal scan were 97.8\% (95\% confidence interval: 96.4-98.8) and 98.0\% (95\% confidence interval: 89.5-99.7), respectively. Of the 112 prevalent nodules that were found to be malignant in follow-up, 92.9\% were correctly identified by the technician plus CV compared with 84.8\% by the study radiologists. The average time taken by the technician to review a scan after CV processing was 208 ± 120 seconds.Prescreening CV software and a technician as first reader is a promising strategy for improving the consistency and quality of screening interpretation of LDCT scans