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Cell size is a complex trait that responds to developmental and environmental cues. Quantitative size analysis of mutant strain collections disrupted for protein kinases and transcriptional regulators in the pathogenic yeast Candida albicans uncovered 66 genes that altered cell size, few of which overlapped with known size genes in the budding yeast Saccharomyces cerevisiae. A potent size regulator specific to C. albicans was the conserved p38/HOG MAPK module that mediates the osmostress response. Basal HOG activity inhibited the SBF G1/S transcription factor complex in a stress-independent fashion to delay the G1/S transition. The HOG network also governed ribosome biogenesis through the master transcriptional regulator Sfp1. Hog1 bound to the promoters and cognate transcription factors for ribosome biogenesis regulons and interacted genetically with the SBF G1/S machinery, and thereby directly linked cell growth and division. These results illuminate the evolutionary plasticity of size control and identify the HOG module as a nexus of cell cycle and growth regulation.

BACKGROUND: Molecular barcode arrays provide a powerful means to analyze cellular phenotypes in parallel through detection of short (20-60 base) unique sequence tags, or "barcodes", associated with each strain or clone in a collection. However, costs of current methods for microarray construction, whether by in situ oligonucleotide synthesis or ex situ coupling of modified oligonucleotides to the slide surface are often prohibitive to large-scale analyses. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that unmodified 20mer oligonucleotide probes printed on conventional surfaces show comparable hybridization signals to covalently linked 5'-amino-modified probes. As a test case, we undertook systematic cell size analysis of the budding yeast Saccharomyces cerevisiae genome-wide deletion collection by size separation of the deletion pool followed by determination of strain abundance in size fractions by barcode arrays. We demonstrate that the properties of a 13K unique feature spotted 20 mer oligonucleotide barcode microarray compare favorably with an analogous covalently-linked oligonucleotide array. Further, cell size profiles obtained with the size selection/barcode array approach recapitulate previous cell size measurements of individual deletion strains. Finally, through atomic force microscopy (AFM), we characterize the mechanism of hybridization to unmodified barcode probes on the slide surface. CONCLUSIONS/SIGNIFICANCE: These studies push the lower limit of probe size in genome-scale unmodified oligonucleotide microarray construction and demonstrate a versatile, cost-effective and reliable method for molecular barcode analysis.

Background: Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by Borrelia infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide. Methods: Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence in situ hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue. Results: Autopsy tissue evaluation demonstrated Borrelia in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by Borrelia-induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia. Conclusions: Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas.

Abstract Background Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. Methods The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40–79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0–20 and categorised as 0–4, 5–9, 10–14, and 15–20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. Results Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0–4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15–20. After adjustment compared to those with normal sleep duration (6–9 h), those with a short (

Evidence of congenital transmission of Lyme disease from mother to fetus has been investigated since the 1980s. This study reports the results of a retrospective analysis of 31 studies described in 27 papers published in a 2018 review article. Analysis of these identified statistically probable transmission in 13 (42%) of the 31 studies and possible transmission in 2 (6%). Most studies included mothers who had been treated with antimicrobials. When no antimicrobials were used, 74% of the pregnancies had adverse outcomes. When oral antimicrobials were used, 29% of pregnancies had adverse outcomes. When intravenous (IV) antimicrobials were used, adverse outcomes dropped to 12% of the pregnancies. This is a six-fold reduction in risk compared with no antimicrobial treatment. Some studies did not define whether oral or IV antimicrobials were used. When these results were included, adverse outcomes were 30 times higher for untreated mothers. Adverse outcomes included deaths, heart anomalies, and preterm births.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct clinicopathologic entity. Currently, there is a paucity of randomized prospective data to inform on optimal front-line chemoimmunotherapy (CIT) and use of consolidative mediastinal radiation (RT). To assess if distinct CIT approaches are associated with disparate survival outcomes, we performed a systematic review and meta-analysis comparing dose-intensive (DI-CIT) versus standard CIT for the front-line treatment of PMBCL. Standard approach (S-CIT) was defined as R-CHOP-21/CHOP-21, with or without RT. DI-CIT were defined as regimens with increased frequency, dose, and/or number of systemic agents. We reviewed data on 4,068 patients (2,517 DI-CIT; 1,551 S-CIT) with a new diagnosis of PMBCL. Overall survival for DI-CIT patients was 88% (95% CI: 85-90) compared to 80% for the S-CIT cohort (95% CI: 74-85). Meta-regression revealed an 8% overall survival (OS) benefit for the DI-CIT group (P

Two models were developed to estimate Lyme borreliosis (LB) cases. One was based on the seroprevalence of Borrelia infections in human samples. This model used corrections for false negative and false positive results from published test sensitivity and specificity measures. A second model based on Borrelia infections in sentinel dogs was used to quantify the prevalence of Lyme disease Borrelia infections in humans; the reference baseline for this model was human and canine infections in Germany. A comparison of the two models is shown and differences discussed. The relationships between incidence, prevalence and total infection burden for LB were derived from published data and these were used in both models to calculate annual incidence, prevalence and total LB infections. The modelling was conservative and based on medical insurance records coded for erythema migrans. Linear model growth rates were used in place of the commonly adopted exponential growth. The mean of the two models was used to create estimates for various countries and continents. Examples from the analyses for LB estimated for 2018 include: incidence – USA 473,000/year, Germany 471,000/year, France 434,000/year and UK 132,000/year; prevalence – USA 2.4 million, Germany 2.4 million, France 2.2 million and UK 667,000; total infections – USA 10.1 million, Germany 10.0 million, France 9.3 million and UK 2.8 million. Estimates for the world for 2018 are: incidence 12.3 million/year; prevalence 62.1 million; and total infection burden 262.0 million. These figures are far higher than officially published data and reflect not only the underestimation of diagnosed cases, which is acknowledged by health agencies, but also undiagnosed and misdiagnosed cases.

A fixed-target approach to high-throughput room-temperature serial synchrotron crystallography with oscillation is described. Patterned silicon chips with microwells provide high crystal-loading density with an extremely high hit rate. The microfocus, undulator-fed beamline at CHESS, which has compound refractive optics and a fast-framing detector, was built and optimized for this experiment. The high-throughput oscillation method described here collects 1–5° of data per crystal at room temperature with fast (10° s−1) oscillation rates and translation times, giving a crystal-data collection rate of 2.5 Hz. Partial datasets collected by the oscillation method at a storage-ring source provide more complete data per crystal than still images, dramatically lowering the total number of crystals needed for a complete dataset suitable for structure solution and refinement – up to two orders of magnitude fewer being required. Thus, this method is particularly well suited to instances where crystal quantities are low. It is demonstrated, through comparison of first and last oscillation images of two systems, that dose and the effects of radiation damage can be minimized through fast rotation and low angular sweeps for each crystal.

Osteoarthritis is a painful, disabling condition which is increasing in prevalence as a result of an ageing population. With no recognized disease-limiting therapeutics, arthroplasty of the hip and knee is the most common and effective treatment for lower limb osteoarthritis, however lower limb arthroplasty has a finite life-span and a proportion of patients will require revision arthroplasty. With increasing life expectancy and an increasing proportion of younger (

A network of high-frequency radars (HFRs) has been deployed around Taiwan. The wide-area data coverage is dedicated to revealing near real-time sea-surface current information. This paper investigates three primary objectives: (1) describing the seasonal current synoptic variability; (2) determining the influence of wind forcing; (3) describing the tidal current field pattern and variability. Sea surface currents derived from HFR data include both geostrophic components and wind-driven components. This study explored vector complex correlations between the HFR time series and wind, which was sufficient to identify high-frequency components, including an Ekman balance among the surface currents and wind. Regarding the characteristics of mesoscale events and the tidal field, a year-long high-resolution surface dataset was utilized to observe the current–eddy–tide interactions over four seasons. The harmonic analysis results derived from surface currents off of northeastern Taiwan during 2013 are presented. The results agree well with the tidal parameters estimated from tide-gauge station observations. The analysis shows that this region features a strong, mixed, mainly semidiurnal tide. Continued monitoring by a variety of sensors (e.g., satellite and HFR) would improve the understanding of the circulation in the region.

One of the most critical but still poorly understood aspects of eukaryotic cell proliferation is the basis for commitment to cell division in late G1 phase, called Start in yeast and the Restriction Point in metazoans. In all species, a critical cell size threshold coordinates cell growth with cell division and thereby establishes a homeostatic cell size. While a comprehensive survey of cell size genetic determinism has been performed in the saprophytic yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, very little is known in pathogenic fungi. As a number of critical Start regulators are haploinsufficient for cell size, we applied a quantitative analysis of the size phenome, using elutriation-barcode sequencing methodology, to 5639 barcoded heterozygous deletion strains of the opportunistic yeast Candida albicans. Our screen identified conserved known regulators and biological processes required to maintain size homeostasis in the opportunistic yeast C. albicans. We also identified novel C. albicans-specific size genes and provided a conceptual framework for future mechanistic studies. Interestingly, some of the size genes identified were required for fungal pathogenicity suggesting that cell size homeostasis may be elemental to C. albicans fitness or virulence inside the host.

The spirochetal bacterium Borrelia miyamotoi is a human pathogen and has been identified in many countries throughout the world. This study reports for the first time the presence of Borrelia miyamotoi in Ireland, and confirms prior work with the detection of B. garinii and B. valaisiana infected ticks. Questing Ixodes ricinus nymph samples were taken at six localities within Ireland. DNA extraction followed by Sanger sequencing was used to identify the species and strains present in each tick. The overall rate of borrelial infection in the Irish tick population was 5%, with a range from 2% to 12% depending on the locations of tick collection. The most prevalent species detected was B. garinii (70%) followed by B. valaisiana (20%) and B. miyamotoi (10%). Knowledge of Borrelia species prevalence is important and will guide appropriate selection of antigens for serology test kit manufacture, help define the risk of infection, and allow medical authorities to formulate appropriate strategies and guidelines for diagnosis and treatment of Borrelia diseases.

In vitro cell based models have been invaluable tools for studying cell behaviour and for investigating drug disposition, toxicity and potential adverse effects of administered drugs. Within this drug discovery pipeline, the ability to assess and prioritise candidate compounds as soon as possible offers a distinct advantage. However, the ability to apply this approach to a cell culture study is limited by the need to provide an accurate, in vitro-like, microenvironment in conjunction with a low cost and high-throughput screening (HTS) methodology. Although the geometry and/or alignment of cells has been reported to have a profound influence on cell growth and differentiation, only a handful of studies have directly compared the growth of a single cell line on different shaped multiwell plates the most commonly used substrate for HTS, in vitro, studies. Herein, the impact of various surface geometries (flat, round and v-shaped 96 well plates), as well as fixed volume growth media and fixed growth surface area have been investigated on the characteristics of three commonly used human cell lines in biopharmaceutical research and development, namely ARPE-19 (retinal epithelial), A549 (alveolar epithelial) and Malme-3M (dermal fibroblastic) cells. The effect of the surface curvature on cells was characterised using a combination of a metabolic activity assay (CellTiter AQ/MTS), LDH release profiles (CytoTox ONE) and absolute cell counts (Guava ViaCount), respectively. In addition, cell differentiation and expression of specific marker proteins were determined using flow cytometry. These in vitro results confirmed that surface topography had a significant effect (p < 0.05) on cell activity and morphology. However, although specific marker proteins were expressed on day 1 and 5 of the experiment, no significant differences were seen between the different plate geometries (p < 0.05) at the later time point. Accordingly, these results highlight the impact of substrate geometry on the culture of a cell line and the influence it has on the cells' correct growth and differentiation characteristics. As such, these results provide important implications in many aspects of cell biology the development of a HTS, in vitro, cell based systems to further investigate different aspects of toxicity testing and drug delivery.

Reliability is a key consideration when microgrid technology is implemented in military applications. Droop control provides a simple option without requiring communication between microgrid components, increasing the control system reliability. However, traditional droop control does not allow the microgrid to utilize much of the power available from a solar resource. This paper applies an optimal multidimensional droop control strategy for a solar resource connected in a microgrid at a military patrol base. Simulation and hardware-in-the-loop experiments of a sample microgrid show that much more power from the solar resource can be utilized, while maintaining the system’s bus voltage around a nominal value, and still avoiding the need for communication between the various components.

Previous studies have evidenced an association between gastroesophageal reflux and esophageal adenocarcinoma (EA). It is unknown to what extent these associations vary by population, age, sex, body mass index, and cigarette smoking, or whether duration and frequency of symptoms interact in predicting risk. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) allowed an in-depth assessment of these issues.Detailed information on heartburn and regurgitation symptoms and covariates were available from five BEACON case-control studies of EA and esophagogastric junction adenocarcinoma (EGJA). We conducted single-study multivariable logistic regressions followed by random-effects meta-analysis. Stratified analyses, meta-regressions, and sensitivity analyses were also conducted.Five studies provided 1,128 EA cases, 1,229 EGJA cases, and 4,057 controls for analysis. All summary estimates indicated positive, significant associations between heartburn/regurgitation symptoms and EA. Increasing heartburn duration was associated with increasing EA risk; odds ratios were 2.80, 3.85, and 6.24 for symptom durations of

IntroductionBody mass index is known to be positively associated with an increased risk of adenocarcinomas of the esophagus, yet there is there limited evidence on whether physical activity or sedentary behavior affects risk of histology- and site-specific upper gastrointestinal cancers. We used the NIH-AARP Diet and Health Study to assess these exposures in relation to esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric non-cardia adenocarcinoma (GNCA).MethodsSelf-administered questionnaires were used to elicit physical activity and sedentary behavior exposures at various age periods. Cohort members were followed via linkage to the US Postal Service National Change of Address database, the Social Security Administration Death Master File, and the National Death Index. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 percent confidence intervals (95%CI).ResultsDuring 4.8 million person years, there were a total of 215 incident ESCCs, 631 EAs, 453 GCAs, and 501 GNCAs for analysis. Strenuous physical activity in the last 12 months (HR(>5 times/week vs. never)=0.58, 95%CI: 0.39, 0.88) and typical physical activity and sports during ages 15-18 years (p for trend=0.01) were each inversely associated with GNCA risk. Increased sedentary behavior was inversely associated with EA (HR(5-6 hrs/day vs. ConclusionsWe find evidence for an inverse association between physical activity and GNCA risk. Associations between body mass index and adenocarcinomas of the esophagus do not appear to be related to physical activity and sedentary behavior.

Abstract The association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.

Ancestry-related differences in immunobiology may explain the health disparities observed in prostate cancer patients, with men of African origin bearing the highest prostate cancer burden. By measuring immune-related proteins in serum samples, here the authors report that systemic cytokines linked to suppression of tumor immunity are upregulated in men of African ancestry and associated with reduced survival.

Abstract The natural history of patients with myelodysplastic syndrome (MDS) is dependent upon the presence and magnitude of diverse genetic and molecular aberrations. The International Prognostic Scoring System (IPSS) and revised IPSS (IPSS‐R) are the most widely used classification and prognostic systems; however, somatic mutations are not currently incorporated into these systems, despite evidence of their independent impact on prognosis. Our manuscript reviews prognostic information for TP53, EZH2, DNMT3A, ASXL1, RUNX1, SRSF2, CBL, IDH 1/2, TET2, BCOR, ETV6, GATA2, U2AF1, ZRSR2, RAS, STAG2, and SF3B1. Mutations in TP53, EZH2, ASXL1, DNMT3A, RUNX1, SRSF2, and CBL have extensive evidence for their negative impact on survival, whereas SF3B1 is the lone mutation carrying a favorable prognosis. We use the existing literature to propose the incorporation of somatic mutations into the IPSS‐R. More data are needed to define the broad spectrum of other genetic lesions, as well as the impact of variant allele frequencies, class of mutation, and impact of multiple interactive genomic lesions. We postulate that the incorporation of these data into MDS prognostication systems will not only enhance our therapeutic decision making but lead to targeted treatment in an attempt to improve outcomes in this formidable disease.

ObjectiveTo assess the longitudinal associations of socioeconomic position (SEP) with functional limitations and knee joint replacement surgery (JRS) in people with symptomatic knee osteoarthritis (OA), and whether body mass index (BMI) mediated these relationships.MethodsData came from the English Longitudinal Study of Ageing, a national longitudinal panel study of adults aged ≥50 years. A total of 1,499 participants (62.3% female; mean age 66.5 (standard deviation (SD) 9.4) years; 47.4% obese) self-reporting an OA diagnosis and knee pain, with at least one BMI measurement were included. Mixed effect models estimated longitudinal associations of each SEP variable (education, occupation, income, wealth and deprivation index) and obesity (BMI ≥30.0 kg/m2) with repeated measures of functional limitations. Cox regression analyses estimated associations between SEP indicators and obesity at baseline and risk of knee JRS at follow-up. Structural equation modeling estimated any mediating effects of BMI on these relationships.ResultsLower SEP and obesity at baseline were associated with increased odds of functional limitations in people with knee OA [e.g., difficulty walking 100 yards: no qualification vs. degree adjOR 4.33 (95% CI 2.20, 8.55) and obesity vs. no obesity adjOR 3.06 (95% CI 2.14, 4.37); similar associations were found for the other SEP indicators]. A small proportion of the association between lower SEP and functional limitations could be explained by BMI (6.2–12.5%). Those with lower income, lower wealth and higher deprivation were less likely to have knee JRS [e.g., adjHR most vs. least deprived 0.37 (95% CI 0.19, 0.73)]; however, no clear association was found for education and occupation. Obesity was associated with increased hazards of having knee JRS [adjHR 1.87 (95% CI 1.32, 2.66)]. As the direction of the associations for SEP and obesity with knee JRS were in opposite directions, no mediation analyses were performed.ConclusionsLower SEP was associated with increased odds of functional limitations but lower hazards of knee JRS among people with knee OA, potentially indicating underutilization of JRS in those with lower SEP. Obesity partially mediated the relationship between lower SEP and increased odds of functional limitations, suggesting adiposity as a potential interventional target.

Purpose: Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods: We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results: We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion: We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.

Task-based functional magnetic resonance imaging (fMRI) has been used to examine neuroanatomical and functional changes following mild traumatic brain injury (mTBI). Prior studies have lacked consistency in identifying common regions of altered neural activity during cognitive tasks. This may be partly due to differences in task paradigm, patient heterogeneity, and methods of fMRI analysis. We conducted a meta-analysis using an activation likelihood estimation (ALE) method to identify regions of differential brain activation in patients with mTBI compared to healthy controls. We included experiments that performed scans from acute to subacute time points post-injury. The seven included studies recruited a total sample of 174 patients with mTBIs and 139 control participants. The results of our coordinate based meta-analysis revealed a single cluster of reduced activation within the right middle frontal gyrus (MFG) that differentiated mTBI from healthy controls. We conclude that the cognitive impairments in memory and attention typically reported in mTBI patients may be associated with a deficit in the right MFG, which impacts the recruitment of neural networks important for attentional control. Keywords: Concussion, Mild traumatic brain injury, Cognition, Functional MRI, Neuroimaging, Activation likelihood estimation

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

Esophageal adenocarcinoma (EA) is characterized by a strong male predominance. Sex steroid hormones have been hypothesized to underlie this sex disparity, but no population-based study to date has examined this potential association.Using mass spectrometry and ELISA, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in plasma from males- 172 EA cases and 185 controls-within the Factors Influencing the Barrett/Adenocarcinoma Relationship (FINBAR) Study, a case-control investigation conducted in Northern Ireland and Ireland. Multivariable adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA.Higher androgen:estrogen ratio metrics were associated with increased odds of EA (e.g., testosterone:estradiol ratio ORQ4 v. Q1 = 2.58, 95%CI = 1.23-5.43; Ptrend = 0.009). All estrogens and androgens were associated with significant decreased odds of EA. When restricted to individuals with minimal to no decrease in body mass index, the size of association for the androgen:estrogen ratio was not greatly altered.This first study of sex steroid hormones and EA provides tentative evidence that androgen:estrogen balance may be a factor related to EA. Replication of these findings in prospective studies is needed to enhance confidence in the causality of this effect.

This paper presents two control strategies: (i) An optimal exergy destruction (OXD) controller and (ii) a decentralized power apportionment (DPA) controller. The OXD controller is an analytical, closed-loop optimal feedforward controller developed utilizing exergy analysis to minimize exergy destruction in an AC inverter microgrid. The OXD controller requires a star or fully connected topology, whereas the DPA operates with no communication among the inverters. The DPA presents a viable alternative to conventional P − ω / Q − V droop control, and does not suffer from fluctuations in bus frequency or steady-state voltage while taking advantage of distributed storage assets necessary for the high penetration of renewable sources. The performances of OXD-, DPA-, and P − ω / Q − V droop-controlled microgrids are compared by simulation.

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation and the risk of hormone-related cancers. Here we evaluated whether single nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism and regulation (N=1100), as well as SNPs associated with circulating sex steroid concentrations as identified by genome-wide association studies (N=17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction=4.0x10-5; q-value=0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR=0.62 95% CI: 0.41, 0.93), and high use of dicamba (OR=0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic or antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.

An association between testosterone therapy (TT) and cardiovascular disease has been reported and TT use is increasing rapidly.We conducted a cohort study of the risk of acute non-fatal myocardial infarction (MI) following an initial TT prescription (N = 55,593) in a large health-care database. We compared the incidence rate of MI in the 90 days following the initial prescription (post-prescription interval) with the rate in the one year prior to the initial prescription (pre-prescription interval) (post/pre). We also compared post/pre rates in a cohort of men prescribed phosphodiesterase type 5 inhibitors (PDE5I; sildenafil or tadalafil, N = 167,279), and compared TT prescription post/pre rates with the PDE5I post/pre rates, adjusting for potential confounders using doubly robust estimation.In all subjects, the post/pre-prescription rate ratio (RR) for TT prescription was 1.36 (1.03, 1.81). In men aged 65 years and older, the RR was 2.19 (1.27, 3.77) for TT prescription and 1.15 (0.83, 1.59) for PDE5I, and the ratio of the rate ratios (RRR) for TT prescription relative to PDE5I was 1.90 (1.04, 3.49). The RR for TT prescription increased with age from 0.95 (0.54, 1.67) for men under age 55 years to 3.43 (1.54, 7.56) for those aged ≥ 75 years (p trend = 0.03), while no trend was seen for PDE5I (p trend = 0.18). In men under age 65 years, excess risk was confined to those with a prior history of heart disease, with RRs of 2.90 (1.49, 5.62) for TT prescription and 1.40 (0.91, 2.14) for PDE5I, and a RRR of 2.07 (1.05, 4.11).In older men, and in younger men with pre-existing diagnosed heart disease, the risk of MI following initiation of TT prescription is substantially increased.

Assessment of cancer incidence trends within the U.S. have mostly relied upon Surveillance, Epidemiology, and End Results (SEER) data, with implicit inference that such is representative of the general population. However, many cancer policy decisions are based at a more granular level. To help inform such, analyses of regional cancer incidence data are needed. Leveraging the unique resource of National Program of Cancer Registries (NPCR)-SEER, we assessed whether regional rates and trends of esophageal cancer significantly deviated from national estimates.From NPCR-SEER, we extracted cancer case counts and populations for whites aged 45-84 years by calendar year, histology, sex, and census region for the period 1999-2008. We calculated age-standardized incidence rates (ASRs), annual percent changes (APCs), and male-to-female incidence rate ratios (IRRs).This analysis included 65,823 esophageal adenocarcinomas and 27,094 esophageal squamous cell carcinomas diagnosed during 778 million person-years. We observed significant geographic variability in incidence rates and trends, especially for esophageal adenocarcinomas in males: ASRs were highest in the Northeast (17.7 per 100,000) and Midwest (18.1). Both were significantly higher than the national estimate (16.0). In addition, the Northeast APC was 62% higher than the national estimate (3.19% vs. 1.97%). Lastly, IRRs remained fairly constant across calendar time, despite changes in incidence rates.Significant regional variations in esophageal cancer incidence trends exist in the U.S. Stable IRRs may indicate the predominant factors affecting incidence rates are similar in men and women.

Solution-processed films of 1,4,8,11,15,18,22,25-octakis(hexyl) copper phthalocyanine (CuPc6) were utilized as an active semiconducting layer in the fabrication of organic field-effect transistors (OFETs) in the bottom-gate configurations using chemical vapour deposited silicon dioxide (SiO2) as gate dielectrics. The surface treatment of the gate dielectric with a self-assembled monolayer of octadecyltrichlorosilane (OTS) resulted in values of 4×10−2 cm2 V−1 s−1 and 106 for saturation mobility and on/off current ratio, respectively. This improvement was accompanied by a shift in the threshold voltage from 3 V for untreated devices to -2 V for OTS treated devices. The trap density at the interface between the gate dielectric and semiconductor decreased by about one order of magnitude after the surface treatment. The transistors with the OTS treated gate dielectrics were more stable over a 30-day period in air than untreated ones.