Moderators of resistance-based exercise programs\u27 effect on sarcopenia-related measures in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis

Introduction: Older men with prostate cancer are commonly affected by reductions in lean mass and physical function following androgen deprivation therapy (ADT). Resistance-based exercise programs are critical to counteract the musculoskeletal toxicities derived from prostate cancer treatment and aging. However, there is significant variability in the effects of exercise interventions. Examining demographic and clinical moderators of exercise effects in this patient group can assist in identifying which subgroups of patients benefit most. Therefore, we examined the effects and moderators of resistance-based exercise programs on sarcopenia-related outcomes that included lean mass, skeletal muscle index, physical function, and muscle strength in older men with prostate cancer. Materials and Methods: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. For the present study, we included data from trials that examined the effects of supervised resistance-based exercise interventions on lean mass outcomes, muscle strength, and physical function in patients with prostate cancer previously or currently treated with ADT. Linear mixed models were undertaken to analyse the effects of resistance-based exercise programs considering the clustering of patients within studies. Effects were evaluated by regressing the study group on the post-intervention value of the outcome adjusted for the baseline value, while potential moderators were examined by adding the moderator and its interaction term into the regression model. Results: A total of 560 patients with prostate cancer (age: 69.5 ± 7.8 yrs.; body mass index: 28.6 ± 4.0 kg.m−2) previously or currently treated with ADT were included. Resistance-based exercise programs resulted in significant effects on whole-body and appendicular lean mass and the skeletal muscle index (P \u3c 0.05), with improvements observed across different characteristics. Improvements were also observed in 400-m walk and 6-m backwards tandem walk (P \u3c 0.05), with patients presenting with lower baseline levels deriving greater exercise effects on 400-m walk (−19.4 s, 95% confidence interval [CI]: −36.6 to −2.3) and 6-m backwards tandem walk tests (−3.0 s, 95% CI: −5.7 to −0.3). For relative muscle strength, significant exercise effects were observed, with greater effects in younger patients (0.35 kg.kg−1, 95% CI: 0.22 to 0.48). Discussion: Resistance-based exercise programs effectively improve well-known markers of sarcopenia in men with prostate cancer, with specific subgroups of patients, such as those younger and presenting with lower baseline levels of physical function, deriving greater effects on muscle strength and physical function, respectively

Effects and moderators of exercise medicine on cardiometabolic outcomes in men with prostate cancer previously or currently undergoing androgen deprivation therapy: An individual patient data meta-analysis

Purpose: To examine the effects and moderators of exercise effects on cardiometabolic outcomes in men with prostate cancer previously or currently undergoing androgen deprivation therapy (ADT). Results: Seven trials including 560 patients were examined. Exercise resulted in significant effects on whole-body and regional fat mass (P ≤ 0.001). For whole-body fat mass, significant exercise effects were observed in patients who were unmarried (−1.4 kg, P \u3c 0.05) and who presented with higher fat mass levels (−1.0 kg, P \u3c 0.05). For diastolic blood pressure and low-density lipoprotein (LDL), younger (−4.7 mmHg, P \u3c 0.05) and older patients (−0.2 mmol.l-1, P \u3c 0.10) achieved greater effects, respectively. Regarding high-density lipoprotein (HDL), patients undertaking ADT + prostatectomy + radiotherapy derived significant exercise effects (0.3 mmol.l-1, P \u3c 0.05). Conclusions: Exercise effectively reduces fat mass across subgroups of men undergoing or following ADT with different characteristics. For diastolic blood pressure, HDL and LDL, groups based on age and treatment history could be specifically targeted with exercise medicine

Imaging Cool Giant Planets in Reflected Light: Science Investigations and Synergy with Habitable Planets

Planned astronomical observatories of the 2020s will be capable of obtaining reflected light photometry and spectroscopy of cool extrasolar giant planets. Here we explain that such data are valuable both for understanding the origin and evolution of giant planets as a whole and for preparing for the interpretation of similar datasets from potentially habitable extrasolar terrestrial planets in the decades to follow.Comment: Science white paper submitted to the Astro 2020 Decadal Survey on Astronomy and Astrophysics. Replace version to fix typo in co-signer name and add figure credit

The Critical, Strategic Importance of Adaptive Optics-Assisted Ground-Based Telescopes for the Success of Future NASA Exoplanet Direct Imaging Missions

Ground-based telescopes coupled with adaptive optics (AO) have been playing a leading role in exoplanet direct imaging science and technological development for the past two decades and will continue to have an indispensable role for the next decade and beyond. Over the next decade, extreme AO systems on 8-10m telescopes will 1) mitigate risk for WFIRST-CGI by identifying numerous planets the mission can spectrally characterize, 2) validate performance requirements and motivate improvements to atmosphere models needed to unambiguously characterize solar system-analogues from space, and 3) mature novel technological innovations useful for space. Extremely Large Telescopes can deliver the first thermal infrared (10 $\mu m$) images of rocky planets around Sun-like stars and identify biomarkers. These data provide a future NASA direct imaging flagship mission (i.e. HabEx, LUVOIR) with numerous exo-Earth candidates and critical ancillary information to help clarify whether these planets are habitable.Comment: 5 pages, 3 figures; Astro2020 Decadal Survey submission; argues for strategic NASA support of ground-based exoplanet direct imaging science programs and tech development. arXiv admin note: substantial text overlap with arXiv:1803.0545

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome

Objective: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS).Background: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist.Material and Methods: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated.Results: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9 +/- 3.1 vs MILR 226 +/- 4.0, P=0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P=0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P=0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P=0.015), posthepatectomy liver failure (0.6% vs 4.3%, P=0.008), and bile leaks (2.2% vs 6.4%, P=0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P=0.002) and day 3 (3.1% vs 11.4%, P<0.001); hospital stay was significantly shorter (5.8 +/- 1.9 vs 7.5 +/- 1.7, P<0.001). There was no significant difference in overall survival and disease-free survival.Conclusions: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible

Regulatory sites for splicing in human basal ganglia are enriched for disease-relevant information

Genome-wide association studies have generated an increasing number of common genetic variants associated with neurological and psychiatric disease risk. An improved understanding of the genetic control of gene expression in human brain is vital considering this is the likely modus operandum for many causal variants. However, human brain sampling complexities limit the explanatory power of brain-related expression quantitative trait loci (eQTL) and allele-specific expression (ASE) signals. We address this, using paired genomic and transcriptomic data from putamen and substantia nigra from 117 human brains, interrogating regulation at different RNA processing stages and uncovering novel transcripts. We identify disease-relevant regulatory loci, find that splicing eQTLs are enriched for regulatory information of neuron-specific genes, that ASEs provide cell-specific regulatory information with evidence for cellular specificity, and that incomplete annotation of the brain transcriptome limits interpretation of risk loci for neuropsychiatric disease. This resource of regulatory data is accessible through our web server, http://braineacv2.inf.um.es/

Identification of additional risk loci for stroke and small vessel disease: a meta-analysis of genome-wide association studies

BACKGROUND: Genetic determinants of stroke, the leading neurological cause of death and disability, are poorly understood and have seldom been explored in the general population. Our aim was to identify additional loci for stroke by doing a meta-analysis of genome-wide association studies. METHODS: For the discovery sample, we did a genome-wide analysis of common genetic variants associated with incident stroke risk in 18 population-based cohorts comprising 84 961 participants, of whom 4348 had stroke. Stroke diagnosis was ascertained and validated by the study investigators. Mean age at stroke ranged from 45·8 years to 76·4 years, and data collection in the studies took place between 1948 and 2013. We did validation analyses for variants yielding a significant association (at p<5 × 10(-6)) with all-stroke, ischaemic stroke, cardioembolic ischaemic stroke, or non-cardioembolic ischaemic stroke in the largest available cross-sectional studies (70 804 participants, of whom 19 816 had stroke). Summary-level results of discovery and follow-up stages were combined using inverse-variance weighted fixed-effects meta-analysis, and in-silico lookups were done in stroke subtypes. For genome-wide significant findings (at p<5 × 10(-8)), we explored associations with additional cerebrovascular phenotypes and did functional experiments using conditional (inducible) deletion of the probable causal gene in mice. We also studied the expression of orthologs of this probable causal gene and its effects on cerebral vasculature in zebrafish mutants. FINDINGS: We replicated seven of eight known loci associated with risk for ischaemic stroke, and identified a novel locus at chromosome 6p25 (rs12204590, near FOXF2) associated with risk of all-stroke (odds ratio [OR] 1·08, 95% CI 1·05-1·12, p=1·48 × 10(-8); minor allele frequency 21%). The rs12204590 stroke risk allele was also associated with increased MRI-defined burden of white matter hyperintensity-a marker of cerebral small vessel disease-in stroke-free adults (n=21 079; p=0·0025). Consistently, young patients (aged 2-32 years) with segmental deletions of FOXF2 showed an extensive burden of white matter hyperintensity. Deletion of Foxf2 in adult mice resulted in cerebral infarction, reactive gliosis, and microhaemorrhage. The orthologs of FOXF2 in zebrafish (foxf2b and foxf2a) are expressed in brain pericytes and mutant foxf2b(-/-) cerebral vessels show decreased smooth muscle cell and pericyte coverage. INTERPRETATION: We identified common variants near FOXF2 that are associated with increased stroke susceptibility. Epidemiological and experimental data suggest that FOXF2 mediates this association, potentially via differentiation defects of cerebral vascular mural cells. Further expression studies in appropriate human tissues, and further functional experiments with long follow-up periods are needed to fully understand the underlying mechanisms