Magnetic local time dependence of geomagnetic disturbances contributing to the AU and AL indices

The Auroral Electrojet (AE) indices, which are composed of four indices (AU, AL, AE, and AO), are calculated from the geomagnetic field data obtained at 12 geomagnetic observatories that are located in geomagnetic latitude (GMLAT) of 61.7°-70°. The indices have been widely used to study magnetic activity in the auroral zone. In the present study, we examine magnetic local time (MLT) dependence of geomagnetic field variations contributing to the AU and AL indices. We use 1-min geomagnetic field data obtained in 2003. It is found that both AU and AL indices have two ranges of MLT (AU: 15:00-22:00MLT, ~06:00 MLT; and AL: ~02:00 MLT, 09:00-12:00 MLT) contributing to the index during quiet periods and one MLT range (AU: 15:00-20:00MLT, and AL: 00:00-06:00 MLT) during disturbed periods. These results are interpreted in terms of various ionospheric current systems, such as, Sqp, Sq, and DP2

The jet and circumburst stellar wind of GRB 980519

We present extensive multi-colour (UBVR_CI_C) photometry of the optical afterglow of GRB 980519. Upon discovery, 8.3 hours after the burst, the source was decaying as a power law, (t-t_GRB)^alpha, with a rapid decay rate alpha_1 = - 1.73+-0.04. About 13 hours after the burst a steepening of the light-curve to alpha_2 = -2.22+-0.04 was observed. Within the framework of current afterglow models, we argue that the rapid initial decline, the `break' in the light curve, and the spectral properties of the afterglow are best interpreted as being due to a collimated ultra-relativistic jet of fixed opening angle expanding into an inhomogeneous medium. In this scenario, we find that the circumburst medium has a density structure that goes as r^(-2.05+-0.22). This is characteristic of a preexisting wind expelled from a massive star. A possible physical scenario is that the progenitor star collapsed to form a black hole (i.e., a `collapsar'), producing the observed burst and afterglow. However, the supernova signature expected in the light curve in such a scenario is not detected. This either implies that the redshift of GRB980519 is greater than 1.5 or that supernovae accompanying GRBs are not standard candles.Comment: 11 pages, including 2 tables and 3 figures. Accepted for publication in ApJ, part

Effect of Intraduodenal Bile and Na-Taurodeoxycholate on Exocrine Pancreatic Secretion and on Plasma Levels of Secretin, Pancreatic Polypeptide, and Gastrin in Man

The effect of intraduodenally administered cattle bile (CB) and Na-taurodeoxycholate (TDC) on basal pancreatic secretion and plasma levels of secretin, pancreatic polypeptide (PP), and gastrin were investigated on two separate days in 10 fasting volunteers. Doses of 2-6 g CB and 20&600 mg TDC were given intraduodenally at 65-min intervals. Volume, bicarbonate, lipase, trypsin, amylase, and bilirubin were measured in 10-min fractions of duodenal juice, and GI peptides determined by radioimmunoassay. CB and TDC enhanced significantly and dose-dependently volume, bicarbonate and enzyme secretion, and plasma secretin and PP levels. In contrast, plasma gastrin showed only a marginal increase. We conclude that the hydrokinetic effect of intraduodenal CB and TDC is at least partially mediated by secretin. Gastrin could be ruled out as a mediator of the ecbolic effect, whereas other GI peptides, primarily CCK, and/or neural mechanisms must be considered possible mediators. Both pathways may also play a role in the PP release

The Afterglow and Complex Environment of the Optically Dim Burst GRB 980613

We report the identification of the optical afterglow of GRB 980613 in R- and I-band images obtained between 16 and 48 hr after the gamma-ray burst. Early near-infrared (NIR) H and K\u27 observations are also reported. The afterglow was optically faint (R ≈ 23) at discovery but did not exhibit an unusually rapid decay (power-law decay slope α \u3c 1.8 at 2 σ). The optical/NIR spectral index (βRH \u3c 1.1) was consistent with the optical-to-X-ray spectral index (βRX ≈ 0.6), indicating a maximal reddening of the afterglow of ≈0.45 mag in R. Hence, the dimness of the optical afterglow was mainly due to the fairly flat spectral shape rather than internal reddening in the host galaxy. We also present late-time Hubble Space Telescope/Space Telescope Imaging Spectrograph images of the field in which GRB 980613 occurred, obtained 799 days after the burst. These images show that GRB 980613 was located close to a very compact, blue V = 26.1 object inside a complex region consisting of star-forming knots and/or interacting galaxy fragments. Therefore, GRB 980613 constitutes a strong case for the association of cosmological gamma-ray bursts with star-forming regions

Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation.

Efst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesLumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10(-12)) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH.European Commission National Institutes of Healt

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.publishedVersio

Clear cell chondrosarcoma of the head and neck

Clear cell chondrosarcoma is a rare variant of chondrosarcoma that mostly involves the end of long bones. However, nine cases have been reported in the head and neck: four in larynx, two in nasal septum, two in maxilla and one in the skull. These cases form the basis of this review. Head and neck cases accounts for less than 5% of Clear cell chondrosarcomas in the whole body and the larynx is the most common place. The histological findings of head and neck cases are consistent with general features of this entity in the whole body and nearly all tumors in this case series had a component of conventional chondrosarcoma. Clear cell chondrosarcoma is an intracompartmental tumor and retains "Grenz zone" just beneath the epithelium. Therefore, the overlying mucosa remained intact in all laryngeal cases. Nasal tumor caused ballooning of the septum and the maxillary lesion did not involve the oral mucosa. This tumor presents various radiographic features in the head and neck area. Chondroblastoma, chondroma, osteoblastoma, osteosarcoma and metastatic renal cell carcinoma are included in the histologic differential diagnoses. Differentiation from chondroblastic osteosarcoma is important in the maxilla. A wide resection is adequate in most cases. However, some laryngeal cases show tendency to recur. Clear cell chondrosarcoma is a slow growing tumor and this necessitates a long time follow-up of patients. Due to the extreme rarity in the head and neck, diagnosis of Clear cell chondrosarcoma in this area, must be confirmed by histochemical and immunohistochemical studies

Roadmap to DILI research in Europe. A proposal from COST action ProEuroDILINet

\ua9 2024 The AuthorsIn the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI

Association of COMT genotypes with S-COMT promoter methylation in growth-discordant monozygotic twins and healthy adults

<p>Abstract</p> <p>Background</p> <p>Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and estrogen metabolism. Recently, COMT haplotypes rather than the single polymorphism Val158Met have been reported to underlie differences in protein expression by modulating mRNA secondary structure. So far, studies investigating the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly focused on phenotypical aspects, and results have been controversial.</p> <p>Methods</p> <p>We assessed S-COMT promoter methylation in saliva and blood derived DNA with regard to early pre- and postnatal growth as well as to genotype for polymorphisms rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4 years), who were discordant for intrauterine development due to severe feto-fetal-transfusion syndrome. Methylation levels of two previously reported partially methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP HPLC) assay.</p> <p>Results</p> <p>Overall, we observed a high variability of S-COMT promoter methylation, which did not correlate with individual differences in the pre- or postnatal growth pattern. Within the twin pairs however we noted a distinct similarity that could be linked to underlying COMT genotypes. This association was subsequently confirmed in a cohort of 93 unrelated adult controls. Interestingly, 158Val-alleles were found at both ends of the epigenotypical range, which is in accordance with a recently proposed model of COMT haplotypes corresponding to a continuum of phenotypical variability.</p> <p>Conclusion</p> <p>The strong heritable component of S-COMT promoter methylation found in our study needs to be considered in future approaches that focus on interactions between COMT epigenotype and phenotype.</p