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PURPOSE: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

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BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

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BACKGROUND: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. METHODS: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA < 2.5 ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS ≤ 7[3 + 4]), TS ≤ pT2) and high risk (GS≥ 7[4 + 3], TS > pT2) PCa. Statistical analyses were done using SAS. RESULTS: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P < 0.0001) and PR (P = 0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P = 0.034). CONCLUSION: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

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INTRODUCTION: Epididymitis in patients with anorectal malformation (ARM) represents a unique problem because unlike the general population, an underlying urinary tract problem is frequently identified. We review our experience with epididymitis in ARM population with an emphasis on examining urologic outcomes. MATERIALS AND METHODS: We performed a retrospective review of male patients with ARM cared for from 1980 to 2010. Clinical and pathologic variables recorded included age at presentation, recurrence, associated urologic anomalies, incidence of ureteral fusion with mesonephric ductal structures, glomerular filtration rate and urodynamic parameters. RESULTS: Twenty-six patients were identified with documented episodes of epididymitis. Renal injury was noted in five patients (19%), all of whom were diagnosed with neurogenic bladder (NGB) several years after anorectoplasty. NGB was found in ten patients (38%) in our series. Ectopic insertion of ureter into a mesonephric ductal structure was discovered in five patients (19%). Twelve patients (46%) had recurrent episodes of epididymitis, with seven of these patients (58%) being diagnosed with NGB. Two patients in the pubertal group presented with a history of epididymitis and complained of ejaculatory pain. CONCLUSION: Epididymitis in a patient with ARM warrants a comprehensive urologic investigation, particularly in recurrent episodes. Attempts at surgical intervention (e.g. vasectomy) should be avoided until functional assessment of the urinary tract has occurred. Failure to recognize this association may lead to potentially avoidable complications and morbidity. Long term urological follow up of these patients is warranted to identify at risk patients and minimize renal deterioration.

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Introduction Epididymitis in patients with anorectal malformation (ARM) represents a unique problem because unlike the general population, an underlying urinary tract problem is frequently identified. We review our experience with epididymitis in ARM population with an emphasis on examining urologic outcomes. Materials and Methods We performed a retrospective review of male patients with ARM cared for from 1980 to 2010. Clinical and pathologic variables recorded included age at presentation, recurrence, associated urologic anomalies, incidence of ureteral fusion with mesonephric ductal structures, glomerular filtration rate and urodynamic parameters. Results Twenty-six patients were identified with documented episodes of epididymitis. Renal injury was noted in five patients (19%), all of whom were diagnosed with neurogenic bladder (NGB) several years after anorectoplasty. NGB was found in ten patients (38%) in our series. Ectopic insertion of ureter into a mesonephric ductal structure was discovered in five patients (19%). Twelve patients (46%) had recurrent episodes of epididymitis, with seven of these patients (58%) being diagnosed with NGB. Two patients in the pubertal group presented with a history of epididymitis and complained of ejaculatory pain. Conclusion Epididymitis in a patient with ARM warrants a comprehensive urologic investigation, particularly in recurrent episodes. Attempts at surgical intervention (e.g. vasectomy) should be avoided until functional assessment of the urinary tract has occurred. Failure to recognize this association may lead to potentially avoidable complications and morbidity. Long term urological follow up of these patients is warranted to identify at risk patients and minimize renal deterioration .

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Difficulty in characterizing the relationship between climatic variability and climate change vulnerability arises when we consider the multiple scales at which this variation occurs, be it temporal (from minute to annual) or spatial (from centimetres to kilometres). We studied populations of a single widely distributed butterfly species, Chlosyne lacinia, to examine the physiological, morphological, thermoregulatory and biophysical underpinnings of adaptation to tropical and temperate climates. Microclimatic and morphological data along with a biophysical model documented the importance of solar radiation in predicting butterfly body temperature. We also integrated the biophysics with a physiologically based insect fitness model to quantify the influence of solar radiation, morphology and behaviour on warming impact projections. While warming is projected to have some detrimental impacts on tropical ectotherms, fitness impacts in this study are not as negative as models that assume body and air temperature equivalence would suggest. We additionally show that behavioural thermoregulation can diminish direct warming impacts, though indirect thermoregulatory consequences could further complicate predictions. With these results, at multiple spatial and temporal scales, we show the importance of biophysics and behaviour for studying biodiversity consequences of global climate change, and stress that tropical climate change impacts are likely to be context-dependent.

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This study compares incidence and mortality of penile cancer in Puerto Rico (PR) with other racial/ethnic groups in the United States (US) and evaluates the extent in which socioeconomic position index (SEP) or its components influence incidence and mortality in PR.

Age-standardized rates were calculated for incidence and mortality based on data from the PR Cancer Registry and the US National Cancer Institute's Surveillance, Epidemiology and End Results program, using the direct method.

PR men had approximately 3-fold higher incidence of penile cancer as compared to non-Hispanic white (Standardized rate ratio [SRR]: 3.33; 95%CI=2.80-3.95). A higher incidence of penile cancer was also reported in PR men as compared to non-Hispanic blacks and Hispanics men. Mortality from penile cancer was also higher for PR men as compared to all other ethnic/racial groups. PR men in the lowest SEP index had 70% higher incidence of penile cancer as compared with those PR men in the highest SEP index. However, the association was marginally significant (SRR: 1.70; 95%CI=0.97, 2.87). Only low educational attainment was statistically associated with higher penile cancer incidence (SRR: 2.18; 95%CI=1.42-3.29).

Although penile cancer is relatively uncommon, our results support significant disparities in the incidence and mortality rates among men in PR. Low educational attainment might influence the high incidence of penile cancer among PR men. Further studies are strongly recommended to explore these disparities. .

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OBJECTIVE: Prostate cancer is the most common cancer and the most common cause of cancer death among men in Puerto Rico (PR). Socioeconomic and racial/ethnic disparities with regard to prostate cancer incidence have been reported in the United States of America (US); however, detailed information regarding health disparities in PR is scarce. METHODS: Age-standardized rates for prostate cancer incidence and mortality were calculated based on the world standard population using data from the PR Central Cancer Registry and the National Cancer Institute SEER program. The age-specific relative risks were calculated using Poisson regression models. In addition, incidence and mortality rates in PR were compared by socioeconomic position (SEP) at the municipal level. RESULTS: For the period from 1992 to 2004, the incidence and mortality trends of prostate cancer decreased in all racial/ethnic groups except for PR men and US Hispanics (USH). Non-Hispanic whites (NHW), non-Hispanic blacks (NHB), and USH had higher incidence of prostate cancer than did PR men; however, PR men aged 85+ yrs and USH aged 45-54 yrs/85+ yrs, respectively, had higher incidences than did NHW and USH. Nonetheless, men in PR had a higher mortality than did USH and NHW. PR men aged 55-64 years with the highest SEP had a 40% higher mortality of prostate cancer than did those with the lowest SEP. CONCLUSION: Areas of concern include the higher mortality of prostate cancer in PR as compared with the USH and NHW in the US. Further research should be performed to guide the design and implementation of prostate cancer prevention and education programs that can increase early detection in PR men.

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PURPOSE: This study compares incidence and mortality of penile cancer in Puerto Rico (PR) with other racial/ethnic groups in the United States (US) and evaluates the extent in which socioeconomic position index (SEP) or its components influence incidence and mortality in PR. MATERIALS AND METHODS: Age-standardized rates were calculated for incidence and mortality based on data from the PR Cancer Registry and the US National Cancer Institute's Surveillance, Epidemiology and End Results program, using the direct method. RESULTS: PR men had approximately 3-fold higher incidence of penile cancer as compared to non-Hispanic white (Standardized rate ratio [SRR]: 3.33; 95%CI=2.80-3.95). A higher incidence of penile cancer was also reported in PR men as compared to non-Hispanic blacks and Hispanics men. Mortality from penile cancer was also higher for PR men as compared to all other ethnic/racial groups. PR men in the lowest SEP index had 70% higher incidence of penile cancer as compared with those PR men in the highest SEP index. However, the association was marginally significant (SRR: 1.70; 95%CI=0.97, 2.87). Only low educational attainment was statistically associated with higher penile cancer incidence (SRR: 2.18; 95%CI=1.42-3.29). CONCLUSIONS: Although penile cancer is relatively uncommon, our results support significant disparities in the incidence and mortality rates among men in PR. Low educational attainment might influence the high incidence of penile cancer among PR men. Further studies are strongly recommended to explore these disparities.

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Phycodnaviruses have a significant role in modulating the dynamics of phytoplankton, thereby influencing community structure and succession, nutrient cycles and potentially atmospheric composition because phytoplankton fix about half the carbon dioxide (CO(2)) on the planet, and some algae release dimethylsulphoniopropionate when lysed by viruses. Despite their ecological importance and widespread distribution, relatively little is known about the evolutionary history, phylogenetic relationships and phylodynamics of the Phycodnaviruses from freshwater environments. Herein we provide novel data on Phycodnaviruses from the largest river system on earth--the Amazon Basin--that were compared with samples from different aquatic systems from several places around the world. Based on phylogenetic inference using DNA polymerase (pol) sequences we show the presence of distinct populations of Phycodnaviridae. Preliminary coarse-grained phylodynamics and phylogeographic inferences revealed a complex dynamics characterized by long-term fluctuations in viral population sizes, with a remarkable worldwide reduction of the effective population around 400 thousand years before the present (KYBP), followed by a recovery near to the present time. Moreover, we present evidence for significant viral gene flow between freshwater environments, but crucially almost none between freshwater and marine environments.

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Biological impacts of climate warming are predicted to increase with latitude, paralleling increases in warming. However, the magnitude of impacts depends not only on the degree of warming but also on the number of species at risk, their physiological sensitivity to warming and their options for behavioural and physiological compensation. Lizards are useful for evaluating risks of warming because their thermal biology is well studied. We conducted macrophysiological analyses of diurnal lizards from diverse latitudes plus focal species analyses of Puerto Rican Anolis and Sphaerodactyus. Although tropical lowland lizards live in environments that are warm all year, macrophysiological analyses indicate that some tropical lineages (thermoconformers that live in forests) are active at low body temperature and are intolerant of warm temperatures. Focal species analyses show that some tropical forest lizards were already experiencing stressful body temperatures in summer when studied several decades ago. Simulations suggest that warming will not only further depress their physiological performance in summer, but will also enable warm-adapted, open-habitat competitors and predators to invade forests. Forest lizards are key components of tropical ecosystems, but appear vulnerable to the cascading physiological and ecological effects of climate warming, even though rates of tropical warming may be relatively low.

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BACKGROUND: There is a paucity of information regarding prostate cancer (PCa) risk factors among Hispanics, the fastest-growing ethnic group in the United States. METHODS: This population-based case-control study included 176 Texas men of Mexican descent with PCa and 174 age- and ethnicity-matched controls. Demographic, lifetime occupational history, family history of cancer, lifestyle (e.g., smoking, alcohol, diet, and recreational physical activity) and anthropometric information were collected by personal interviews. Chemical exposure and physical activity were determined using job-exposure matrices for each reported job. RESULTS: Logistic regression models adjusted for relevant covariates were used to evaluate their independent effects. Compared to controls, cases were three times more likely to work in jobs with high agrichemical exposure (OR = 3.44, 95% CI 1.84-6.44), and 54% less likely to work in jobs with moderate/high occupational physical activity (OR = 0.46, 95% CI 0.28-0.77). In analyses stratified by stage, cases with organ-confined PCa were three times more likely to have high agrichemical exposure (OR = 3.39, 9%CI 1.68-6.84), and 56% less likely to have moderate/high levels of occupational physical activity (OR = 0.44, 95% CI 0.26-0.76). Increased risk of being diagnosed with advanced PCa was associated with obesity at time of diagnosis (OR = 2.50, 95% CI 1.20-5.20) and high levels of agrichemical exposure (OR = 4.65, 95% CI 1.97-10.97), but not with occupational physical activity. CONCLUSIONS: This case-control study, the first conducted in a homogeneous Hispanic population, identified modifiable PCa risk factors, such as physical activity and agrichemical exposure, which may be useful in developing interventions for this understudied population.

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Apoptosis, a genetically encoded program that results in cell death, represents a fundamental biologic concept that has relevance to a wide range of dermatologic processes. This review discusses the basic biology of apoptosis and its relevance to cutaneous disease.

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Neuroendocrine and catecholamine dysfunctions in depression may be linked by corticotropin-releasing factor (CRF) effects on locus coeruleus (LC) neurons. One consequence of CRF hypersecretion in depression would be persistent elevated levels of LC discharge and diminished responses to phasic sensory stimuli. The hypothesis that antidepressants could reverse these changes was tested by characterizing effects of pharmacologically distinct antidepressants on LC sensory-evoked discharge, LC activation by stress, and LC activation by CRF. The most consistent effect of all of the antidepressants tested was a decrease in LC sensory-evoked discharge after acute administration. However, tolerance occurs to these effects after chronic administration. With chronic administration each of the antidepressants produced effects which could potentially interfere with CRF function in the LC. Desmethylimipramine and mianserin attenuated LC activation by a stressor which requires endogenous CRF, suggesting that these antidepressants attenuate stress-elicited release of CRF and perhaps the hypersecretion that occurs in depression. The serotonin reuptake inhibitor, sertraline (SER), enhanced the signal-to-noise ratio of the LC sensory response, an effect opposite to that of CRF. Thus, SER could serve as a functional antagonist of CRF that is hypersecreted in depression. The finding that three pharmacologically distinct antidepressants share the potential to interfere with CRF function in the LC implies that this may be an important common mechanism for antidepressant activity.

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A 2-year (1981-82) prospective study was undertaken to determine the incidence of morbidity and mortality related to anaesthesia at the University Hospital of the West Indies. Data was obtained from all patients subjected to anaesthesia relating to their pre-operative, intra-operative and post-operative (recovery room or ICU) course and, in relevant instances, the convalescent ward. A total of 8,334 anaesthetics were administered and the ages of the patients ranged from 3 days to 96 years (mean 36 years). Three hundred and sixty patients (4.31 per cent) developed a complication as a result of anaesthesia and, of these, 12 patients (0.14 per cent of the total) died. Five patients died following post-operative cardio-respiratory arrest whereas 6 patients died of intra-operative arrhythmia and/or hypotension. One patient, a 1-year old child, died post-operatively of hypoxic brain damage. The incidence of various organ system involvement among non-fatal complications were as follows: respiratory (45 percent), cardiovascular (32 percent), musculo-skeletal (3 percent) central nervous (<1 percent). Respiratory complications included laryngospasm and/or bronchospasm (49 percent), post-operative respiratory obstruction (15 percent), post-operative respiratory insufficiency (19 percent), pulmonary oedema following aspiration (4 percent). Fifty-five patients needed post-operative mechanical ventilation in the ICU. Aspiration of stomach contents occurred in 6 instances and 5 of these patients involved anaesthesia for emergency caesarean section. All of these patients improved with supportive therapy (AU)

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Coral reefs of north Jamaica, normally sheltered, were severely damaged by Hurricane Allen, the strongest Caribbean hurricane of this century. Immediate studies were made at Discovery Bay, where reef populations were already known in some detail. Data are presented to show how damage varied with the position and orientation of the substraturn and with the shape, size, and mechanical properties of exposed organisms. Data collected over succeeding weeks showed striking differences in the ability of organisms to heal and survive.

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