Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: Results from the randomised, placebo-controlled avodart after radical therapy for Prostate Cancer Study (ARTS)

Background: Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical recurrence is controversial. Objective: To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy. Design, setting, and participants: Randomised, double-blind, placebo-controlled trial in 294 men from 64 centres across 9 European countries. Intervention: The 5α-reductase inhibitor, dutasteride. Outcome measurements and statistical analysis: The primary end point was time to PSA doubling from start of randomised treatment, analysed by log-rank test stratified by previous therapy and investigative-site cluster. Secondary end points included time to disease progression and the proportion of subjects with disease progression. Results and limitations: Of the 294 subjects randomised (147 in each treatment group), 187 (64%) completed 24 mo of treatment and 107 discontinued treatment prematurely (71 [48%] of the placebo group, 36 [24%] of the dutasteride group). Dutasteride significantly delayed the time to PSA doubling compared with placebo after 24 mo of treatment (p < 0.001); the relative risk (RR) reduction was 66.1% (95% confidence interval [CI], 50.35-76.90) for the overall study period. Dutasteride also significantly delayed disease progression (which included PSA- and non-PSA-related outcomes) compared with placebo (p < 0.001); the overall RR reduction in favour of dutasteride was 59% (95% CI, 32.53-75.09). The incidence of adverse events (AEs), serious AEs, and AEs leading to study withdrawal were similar between the treatment groups. A limitation was that investigators were not blinded to PSA levels during the study. Conclusions: Dutasteride delayed the biochemical progression of PCa in patients with biochemical failure after radical therapy for clinically localised disease. The safety and tolerability of dutasteride were generally consistent with previous experience. Clinical trial registry: ClinicalTrials.gov, NCT00558363

Seasonal drought limits tree species across the Neotropics

Within the tropics, the species richness of tree communities is strongly and positively associated with precipitation. Previous research has suggested that this macroecological pattern is driven by the negative effect of water-stress on the physiological processes of most tree species. This process implies that the range limits of taxa are defined by their ability to occur under dry conditions, and thus in terms of species distributions it predicts a nested pattern of taxa distribution from wet to dry areas. However, this ‘dry-tolerance’ hypothesis has yet to be adequately tested at large spatial and taxonomic scales. Here, using a dataset of 531 inventory plots of closed canopy forest distributed across the Western Neotropics we investigated how precipitation, evaluated both as mean annual precipitation and as the maximum climatological water deficit, influences the distribution of tropical tree species, genera and families. We find that the distributions of tree taxa are indeed nested along precipitation gradients in the western Neotropics. Taxa tolerant to seasonal drought are disproportionally widespread across the precipitation gradient, with most reaching even the wettest climates sampled; however, most taxa analysed are restricted to wet areas. Our results suggest that the ‘dry tolerance’ hypothesis has broad applicability in the world's most species-rich forests. In addition, the large number of species restricted to wetter conditions strongly indicates that an increased frequency of drought could severely threaten biodiversity in this region. Overall, this study establishes a baseline for exploring how tropical forest tree composition may change in response to current and future environmental changes in this region

Connecting the data landscape of long-term ecological studies: The SPI-Birds data hub

The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database (www.spibirds.org)\u2014a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration

Primordial Nucleosynthesis for the New Cosmology: Determining Uncertainties and Examining Concordance

Big bang nucleosynthesis (BBN) and the cosmic microwave background (CMB) have a long history together in the standard cosmology. The general concordance between the predicted and observed light element abundances provides a direct probe of the universal baryon density. Recent CMB anisotropy measurements, particularly the observations performed by the WMAP satellite, examine this concordance by independently measuring the cosmic baryon density. Key to this test of concordance is a quantitative understanding of the uncertainties in the BBN light element abundance predictions. These uncertainties are dominated by systematic errors in nuclear cross sections. We critically analyze the cross section data, producing representations that describe this data and its uncertainties, taking into account the correlations among data, and explicitly treating the systematic errors between data sets. Using these updated nuclear inputs, we compute the new BBN abundance predictions, and quantitatively examine their concordance with observations. Depending on what deuterium observations are adopted, one gets the following constraints on the baryon density: OmegaBh^2=0.0229\pm0.0013 or OmegaBh^2 = 0.0216^{+0.0020}_{-0.0021} at 68% confidence, fixing N_{\nu,eff}=3.0. Concerns over systematics in helium and lithium observations limit the confidence constraints based on this data provide. With new nuclear cross section data, light element abundance observations and the ever increasing resolution of the CMB anisotropy, tighter constraints can be placed on nuclear and particle astrophysics. ABRIDGEDComment: 54 pages, 20 figures, 5 tables v2: reflects PRD version minor changes to text and reference

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

Prevalencia de esofagitis eosinofílica: estudio multicéntrico en población pediátrica evaluada en 36 centros de gastroenterología de América Latina

Introducción y objetivo: La esofagitis eosinofílica es una enfermedad crónica, mediada inmunológicamente, descrita en series y publicaciones alrededor del mundo. En los últimos 20 años diversos estudios han intentado evaluar la incidencia y prevalencia de la enfermedad. El objetivo del presente trabajo es estimar la prevalencia de esofagitis eosinofílica en un grupo de niños atendidos en 36 centros de gastroenterología pediátrica de 10 países latinoamericanos. Materiales y métodos: A través de un protocolo multicéntrico, observacional y transversal se estimó la prevalencia de período de esofagitis eosinofílica entre los niños atendidos en consulta externa y sometidos a endoscopia superior diagnóstica por cualquier motivo en 36 centros de 10 países latinoamericanos durante un período de 3 meses. Resultados: Entre abril y junio de 2016 108 casos de esofagitis eosinofílica fueron evaluados. Asimismo, un promedio de 29,253 consultas ambulatorias y 4,152 endoscopias superiores de carácter diagnóstico fueron realizadas en los 36 centros participantes. La tasa de prevalencia de esofagitis eosinofílica en la población estudiada (n = 29,253) fue de 3,69 casos × 1,000 (IC 95%: 3.04 a 4.44) y entre los niños sometidos a endoscopia superior de rutina (n = 4,152) fue de 26 x 1,000 (IC 95%: 22.6 a 29.4). Conclusión: La tasa general de prevalencia de período de esofagitis eosinofílica en un grupo de niños evaluados en 36 centros latinoamericanos de gastroenterología pediátrica resultó de 3,69 × 1,000, y entre aquellos sometidos a endoscopia fue de 26 × 1,000. La prevalencia mostró una importante variabilidad entre los países y centros participantes. Este es el primer estudio de prevalencia de esofagitis eosinofílica pediátrica en Latinoamérica. Abstract: Introduction and objective: Eosinophilic esophagitis is a chronic, immune-mediated disease described in case series and publications worldwide. Over the past twenty years, the authors of different studies have attempted to evaluate its incidence and prevalence. The objetive of the present study was to estimate the prevalence of eosinophilic esophagitis in a group of children seen at 36 pediatric gastroenterology centers in ten Latin American countries. Materials and methods: A multicenter, observational, and cross-sectional study was conducted that estimated the period prevalence of eosinophilic esophagitis in children seen at outpatient consultation and that underwent diagnostic upper gastrointestinal endoscopy for any indication at 36 centers in 10 Latin American countries, within a 3-month time frame. Results: Between April and June 2016, 108 cases of eosinophilic esophagitis were evaluated. Likewise, an average of 29,253 outpatient consultations and 4,152 diagnostic upper gastrointestinal endoscopies were carried out at the 36 participating centers. The period prevalence of eosinophilic esophagitis in the population studied (n = 29,253) was 3.69 cases × 1,000 (95% CI: 3.04 to 4.44), and among the children that underwent routine upper gastrointestinal endoscopy (n = 4,152), it was 26 x 1,000 (95% CI: 22.6 to 29.4). Conclusions: The general period prevalence of eosinophilic esophagitis in a group of children evaluated at 36 Latin American pediatric gastroenterology centers was 3.69 × 1,000, and in the children that underwent endoscopy, it was 26 × 1,000. There was important prevalence variability between the participating countries and centers. The present analysis is the first study conducted on the prevalence of pediatric eosinophilic esophagitis in Latin America. Palabras clave: Esofagitis, Eosinofílica, Niños, Prevalencia, Latinoamérica, Keywords: Esophagitis, Eosinophilic, Children, Prevalence, Latin Americ