The relationship between androgens and days per month of period pain, pelvic pain, headache, and TLR4 responsiveness of peripheral blood mononuclear cells in young women with dysmenorrhoea

Purpose: Women bear a disproportionate burden of persistent pain conditions when compared to men. To determine whether the hormonal environment affects the clinical experience of pain, as measured by the days per month of pelvic pain (DPelvicPM), period pain (DPeriodPM), headache (DHeadachePM) or the in vitro EC50 for Interleukin-1β (IL-1β) release following TLR4 stimulation with Lipopolysaccharide from Peripheral Blood Mononuclear Cells (PBMCs). Findings were stratified according to use or non-use of the oral contraceptive pill. Patients and Methods: Fifty-six women aged 16-35 years, with minimal or severe dysmenorrhea, and use or non-use of the OC, were enrolled. Blood was collected on two occasions in a single menstrual cycle: Days 1-2 and Days 7-10. Hormonal analysis for testosterone, dihydrotestosterone, dehydroepiandrosterone, Androstenedione, 3α-Androstanediol, 3β-androstanediol, estradiol, estrone, 17α-hydroxyprogesterone, progesterone, cortisol and sex-hormone binding globulin was undertaken using ultra-sensitive Liquid Chromatography Mass-Spectrometry (LC-MS). PBMCs were exposed to lipopolysaccharide (LPS) and the resulting Interleukin-1β output was determined. Results: Non-users of the OC showed a strongly inverse correlation between a reducing free androgen index (FAI) and increasing DPelvicPM (p=0.0032), DPeriodPM (p=0.013), DHeadachePM (p=0.041). Non-users of the OC showed a significant increase in DPelvicPM (p=0.049) on Days 7-10. Modestly significant associations were found between reduced androgens and potentiated LPS-induced IL-1β (lower EC50). Conclusion: This is the first study to investigate the relationship between the hormonal environment and activation of the immune system in young women with dysmenorrhoea-related pain conditions. Low androgen levels were consistently associated with increased pain. Translational implications for the findings are discussed.Susan F Evans, Yuen Kwok, Ann Solterbeck, Carmen Pyragius, Mary Louise Hull, Mark R Hutchinson, Paul Rola

Estimation of Airborne Vapor Concentrations of Oil Dispersants COREXIT™ EC9527A and EC9500A, Volatile Components Associated with the Deepwater Horizon Oil Spill Response and Clean-up Operations

The Deepwater Horizon (DWH) drilling unit explosion above the Macondo oil well on 20 April 2010 caused the release of approximately 4.9 million barrels (779 million L) of oil into the Gulf of Mexico. As part of a larger spill response and clean-up effort, approximately 1.84 million gallons (6.81 million L) of chemical dispersants COREXIT™ EC9500A and COREXIT™ EC9527A were applied to the resultant oil slicks through spraying on the water surface by plane and by vessel and through injection at the release source near the seabed. The GuLF STUDY is investigating the health effects of workers involved in the oil spill response and clean-up after the DWH explosion, and estimates of possible exposure to chemical dispersants were needed. Exposures were estimated to the volatile components of COREXIT™ EC9500A [petroleum distillates, hydrotreated light, and propylene glycol (PG)] and of COREXIT™ EC9527A [2-butoxyethanol (2-BE) and PG] using two of AIHA IHMOD2.0© mathematical modeling tools along with the dispersants' chemical and physical properties. Monte Carlo simulations were used to reflect uncertainty in input parameters with both the two-box, constant emission model and the near and mid field plume model for indoor and outdoor activities, respectively. Possible exposure scenarios considered various evaporation rates, sizes of the dispersant pool, wind speeds, and ventilation rates. For the two-box model, mean near field exposure estimates to 2-BE ranged from 0.9 to 5.7 ppm, while mean far field estimated exposures ranged from 0.3 to 3.5 ppm. Estimates of mean near field plume model exposures ranged from 0.01 to 3.7 ppm at 2.5 ft from the source, and <0.01 to 0.3 ppm at 10 ft from the source. Estimated exposures to PG were approximately 10% of the calculated 2-BE exposures and exposures to petroleum distillates about 40% higher than the 2-BE estimates. Results indicate that compared with current occupational exposure guidelines, overexposure to petroleum distillates and PG probably did not occur in our study, but under some conditions, for short periods, exposure to 2-BE may have exceeded the limits for peak exposures. These estimates were developed for use in job-exposure matrices to estimate exposures of workers having contact with dispersant vapors for the GuLF STUDY

Viral Load Distribution in SARS Outbreak

Airborne transmission may have resulted in an outbreak of SARS in Hong Kong

Theory of a Higher Order Phase Transition: Superconducting Transition in BKBO

We describe here the properties expected of a higher (with emphasis on the order fourth) order phase transition. The order is identified in the sense first noted by Ehrenfest, namely in terms of the temperature dependence of the ordered state free energy near the phase boundary. We have derived an equation for the phase boundary in terms of the discontinuities in thermodynamic observables, developed a Ginzburg-Landau free energy and studied the thermodynamic and magnetic properties. We also discuss the current status of experiments on $Ba_{0.6}K_{0.4}BiO_3$ and other $BiO_3$ based superconductors, the expectations for parameters and examine alternative explanations of the experimental results.Comment: 18 pages, no figure

Modeled Air Pollution from In Situ Burning and Flaring of Oil and Gas Released Following the Deepwater Horizon Disaster

The GuLF STUDY, initiated by the National Institute of Environmental Health Sciences, is investigating the health effects among workers involved in the oil spill response and clean-up (OSRC) after the Deepwater Horizon (DWH) explosion in April 2010 in the Gulf of Mexico. Clean-up included in situ burning of oil on the water surface and flaring of gas and oil captured near the seabed and brought to the surface. We estimated emissions of PM2.5 and related pollutants resulting from these activities, as well as from engines of vessels working on the OSRC. PM2.5 emissions ranged from 30 to 1.33e6 kg per day and were generally uniform over time for the flares but highly episodic for the in situ burns. Hourly emissions from each source on every burn/flare day were used as inputs to the AERMOD model to develop average and maximum concentrations for 1-, 12-, and 24-h time periods. The highest predicted 24-h average concentrations sometimes exceeded 5000 μg m-3 in the first 500 m downwind of flaring and reached 71 μg m-3 within a kilometer of some in situ burns. Beyond 40 km from the DWH site, plumes appeared to be well mixed, and the predicted 24-h average concentrations from the flares and in situ burns were similar, usually below 10 μg m-3. Structured averaging of model output gave potential PM2.5 exposure estimates for OSRC workers located in various areas across the Gulf. Workers located nearest the wellhead (hot zone/source workers) were estimated to have a potential maximum 12-h exposure of 97 μg m-3 over the 2-month flaring period. The potential maximum 12-h exposure for workers who participated in in situ burns was estimated at 10 μg m-3 over the ~3-month burn period. The results suggest that burning of oil and gas during the DWH clean-up may have resulted in PM2.5 concentrations substantially above the U.S. National Ambient Air Quality Standard for PM2.5 (24-h average = 35 μg m-3). These results are being used to investigate possible adverse health effects in the GuLF STUDY epidemiologic analysis of PM2.5 exposures

Assessing Exposures from the Deepwater Horizon Oil Spill Response and Clean-up

The GuLF Study is investigating adverse health effects from work on the response and clean-up after the Deepwater Horizon explosion and oil release. An essential and necessary component of that study was the exposure assessment. Bayesian statistical methods and over 135 000 measurements of total hydrocarbons (THC), benzene, ethylbenzene, toluene, xylene, and n-hexane (BTEX-H) were used to estimate inhalation exposures to these chemicals for >3400 exposure groups (EGs) formed from three exposure determinants: job/activity/task, location, and time period. Recognized deterministic models were used to estimate airborne exposures to particulate matter sized 2.5 μm or less (PM2.5) and dispersant aerosols and vapors. Dermal exposures were estimated for these same oil-related substances using a model modified especially for this study from a previously published model. Exposures to oil mist were assessed using professional judgment. Estimated daily THC arithmetic means (AMs) were in the low ppm range (<25 ppm), whereas BTEX-H exposures estimates were generally <1000 ppb. Potential 1-h PM2.5 air concentrations experienced by some workers may have been as high as 550 μg m-3. Dispersant aerosol air concentrations were very low (maximum predicted 1-h concentrations were generally <50 μg m-3), but vapor concentrations may have exceeded occupational exposure excursion guidelines for 2-butoxyethanol under certain circumstances. The daily AMs of dermal exposure estimates showed large contrasts among the study participants. The estimates are being used to evaluate exposure-response relationships in the GuLF Study

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Search for black holes and other new phenomena in high-multiplicity final states in proton-proton collisions at root s=13 TeV

Peer reviewe