Towards modelling X-ray reverberation in AGN: Piecing together the extended corona

Models of X-ray reverberation from extended coronae are developed from general relativistic ray tracing simulations. Reverberation lags between correlated variability in the directly observed continuum emission and that reflected from the accretion disc arise due to the additional light travel time between the corona and reflecting disc. X-ray reverberation is detected from an increasing sample of Seyfert galaxies and a number of common properties are observed, including a transition from the characteristic reverberation signature at high frequencies to a hard lag within the continuum component at low frequencies, as well a pronounced dip in the reverberation lag at 3keV. These features are not trivially explained by the reverberation of X-rays originating from simple point sources. We therefore model reverberation from coronae extended both over the surface of the disc and vertically. Causal propagation through its extent for both the simple case of constant velocity propagation and propagation linked to the viscous timescale in the underlying accretion disc is included as well as stochastic variability arising due to turbulence locally on the disc. We find that the observed features of X-ray reverberation in Seyfert galaxies can be explained if the long timescale variability is dominated by the viscous propagation of fluctuations through the corona. The corona extends radially at low height over the surface of the disc but with a bright central region in which fluctuations propagate up the black hole rotation axis driven by more rapid variability arising from the innermost regions of the accretion flow

EGRINs (Environmental Gene Regulatory Influence Networks) in Rice That Function in the Response to Water Deficit, High Temperature, and Agricultural Environments

Environmental gene regulatory influence networks (EGRINs) coordinate the timing and rate of gene expression in response to environmental signals. EGRINs encompass many layers of regulation, which culminate in changes in accumulated transcript levels. Here, we inferred EGRINs for the response of five tropical Asian rice (Oryza sativa) cultivars to high temperatures, water deficit, and agricultural field conditions by systematically integrating time-series transcriptome data, patterns of nucleosome-free chromatin, and the occurrence of known cis-regulatory elements. First, we identified 5447 putative target genes for 445 transcription factors (TFs) by connecting TFs with genes harboring known cis-regulatory motifs in nucleosome-free regions proximal to their transcriptional start sites. We then used network component analysis to estimate the regulatory activity for each TF based on the expression of its putative target genes. Finally, we inferred an EGRIN using the estimated transcription factor activity (TFA) as the regulator. The EGRINs include regulatory interactions between 4052 target genes regulated by 113 TFs. We resolved distinct regulatory roles for members of the heat shock factor family, including a putative regulatory connection between abiotic stress and the circadian clock. TFA estimation using network component analysis is an effective way of incorporating multiple genome-scale measurements into network inference

A Cross-Sectional Study of People with Epilepsy and Neurocysticercosis in Tanzania: Clinical Characteristics and Diagnostic Approaches.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa

Accelerated tibial fracture union in the third trimester of pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>We present a case of accelerated tibial fracture union in the third trimester of pregnancy. This is of particular relevance to orthopaedic surgeons, who must be made aware of the potentially accelerated healing response in pregnancy and the requirement for prompt treatment.</p> <p>Case presentation</p> <p>A 40 year old woman at 34 weeks gestational age sustained a displaced fracture of the tibial shaft. This was initially treated conservatively in plaster with view to intra-medullary nailing postpartum. Following an emergency caesarean section, the patient was able to fully weight bear without pain 4 weeks post injury, indicating clinical union. Radiographs demonstrated radiological union with good alignment and abundant callus formation. Fracture union occurred within 4 weeks, less than half the time expected for a conservatively treated tibial shaft fracture.</p> <p>Conclusion</p> <p>Long bone fractures in pregnancy require clear and precise management plans as fracture healing is potentially accelerated. Non-operative treatment is advisable provided satisfactory alignment of the fracture is achieved.</p

Severe pulmonary arterial hypertension is characterized by increased neutrophil elastase and relative elafin deficiency

BACKGROUND: Preclinical evidence implicates neutrophil elastase (NE) in PAH pathogenesis, and the NE inhibitor elafin is under early therapeutic investigation. RESEARCH QUESTION: Are circulating NE and elafin levels abnormal in PAH and associated with clinical severity? STUDY DESIGN/METHODS: . In an observational Stanford University PAH cohort (N=249), plasma NE and elafin were measured in comparison to healthy controls (N=106) then related to clinical features and relevant ancillary biomarkers. Cox regression models were fitted with cubic spline functions to associate NE and elafin with survival. To validate prognostic relationships, we analyzed two United Kingdom cohorts (N=75, N=357). Mixed effects models evaluated NE and elafin changes during disease progression. Finally, we studied effects of NE/elafin balance on pulmonary artery endothelial cells (PAECs) from PAH patients. RESULTS: Relative to controls, patients had increased NE (205.1 [123.6-387.3] vs. 97.6 [74.4-126.6] ng/mL, P168.5 ng/mL portended increased mortality risk after adjustment for known clinical predictors (HR 2.52, CI 1.36-4.65, P=0.003) or prognostic cytokines (HR 2.63, CI 1.42-4.87, P=0.001), and NE added incremental value to established PAH risk scores. Similar prognostic thresholds were identified in validation cohorts. Longitudinal NE changes tracked with clinical trends and outcomes. PAH-PAECs exhibited increased apoptosis and attenuated angiogenesis when exposed to NE at the level observed in patients' blood. Elafin rescued PAEC homeostasis, yet the required dose exceeded levels found in patients. INTERPRETATION: NE is increased and elafin deficient across PAH subtypes. NE associates with disease severity and outcomes, and this target-specific biomarker could facilitate therapeutic development of elafin

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

New Therapeutic Strategies for Systemic Sclerosis—a Critical Analysis of the Literature

Systemic sclerosis (SSc) is a multi-system disease characterized by skin fibrosis and visceral disease. Therapy is organ and pathogenesis targeted. In this review, we describe novel strategies in the treatment of SSc. Utilizing the MEDLINE and the COCHRANE REGISTRY, we identified open trials, controlled trials, for treatment of SSc from 1999 to April 2005. We used the terms scleroderma, systemic sclerosis, Raynaud's phenomenon, pulmonary hypertension, methotrexate, cyclosporin, tacrolimus, relaxin, low-dose penicillamine, IVIg, calcium channel blockers, losartan, prazocin, iloprost, N-acetylcysteine, bosentan, cyclophosphamide, lung transplantation, ACE inhibitors, anti-thymocyte globulin, and stem cell transplantation. Anecdotal reports were omitted

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Traditional beliefs and practices in the postpartum period in Fujian Province, China: a qualitative study

<p>Abstract</p> <p>Background</p> <p><it>Zuo yuezi </it>is the month postpartum in China associated with a variety of traditional beliefs and practices. We explored the current status of <it>zuo yuezi </it>from social, cultural and western medical perspectives.</p> <p>Methods</p> <p>We interviewed family members (36) and health workers (8) in Fujian Province, selecting one rural and one rapidly developing urban county. We asked about their traditional beliefs and their behaviour postpartum. We used a framework approach to identify main themes. We categorised reported behaviour against their probable effects on health, drawing on Western standards.</p> <p>Results</p> <p>Respondents reported that <it>zuo yuezi </it>was commonly practiced in urban and rural families to help the mother regain her strength and protect her future health. <it>Zuo yuezi </it>included: dietary precautions, such as eating more food and avoiding cold food; behavioural precautions, such as staying inside the home, avoiding housework and limiting visitors; hygiene precautions, such as restricting bathing and dental hygiene; and practices associated with infant feeding, including supplementary feeding and giving honeysuckle herb to the infant. Respondents reported that the main reasons for adhering to these practices were respect for tradition, and following the advice of elders. Categorised against Western medical standards, several <it>zuo yuezi </it>practices are beneficial, including eating more, eating protein rich food, avoiding housework, and daily vulval and perineal hygiene. A few are potentially harmful, including giving honeysuckle herb, and avoiding dental hygiene. Some women reported giving infants supplementary feeds, although <it>zuo yuezi </it>emphasises breast feeding.</p> <p>Conclusion</p> <p><it>Zuo yuezi </it>is an important ritual in Fujian. In medical terms, most practices are beneficial, and could be used by health staff to promote health in this period. Further research on reported potentially harmful practices, such as supplements to breast feeding, is needed.</p

Detecting differential allelic expression using high-resolution melting curve analysis: application to the breast cancer susceptibility gene CHEK2

<p>Abstract</p> <p>Background</p> <p>The gene <it>CHEK2 </it>encodes a checkpoint kinase playing a key role in the DNA damage pathway. Though <it>CHEK2 </it>has been identified as an intermediate breast cancer susceptibility gene, only a small proportion of high-risk families have been explained by genetic variants located in its coding region. Alteration in gene expression regulation provides a potential mechanism for generating disease susceptibility. The detection of differential allelic expression (DAE) represents a sensitive assay to direct the search for a functional sequence variant within the transcriptional regulatory elements of a candidate gene. We aimed to assess whether <it>CHEK2 </it>was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation in <it>BRCA1</it> or <it>BRCA2</it> had been identified.</p> <p>Methods</p> <p>We implemented an assay based on high-resolution melting (HRM) curve analysis and developed an analysis tool for DAE assessment.</p> <p>Results</p> <p>We observed allelic expression imbalance in 4 of the 41 LCLs examined. All four were carriers of the truncating mutation 1100delC. We confirmed previous findings that this mutation induces non-sense mediated mRNA decay. In our series, we ruled out the possibility of a functional sequence variant located in the promoter region or in a regulatory element of <it>CHEK2 </it>that would lead to DAE in the transcriptional regulatory milieu of freely proliferating LCLs.</p> <p>Conclusions</p> <p>Our results support that HRM is a sensitive and accurate method for DAE assessment. This approach would be of great interest for high-throughput mutation screening projects aiming to identify genes carrying functional regulatory polymorphisms.</p