The role of syn-eruptive vesiculation on explosive basaltic activity at Mt. Etna, Italy

We investigated the dynamics of explosive activity at Mt. Etna between 31 August and 15 December 2006 by combining vesicle studies in the erupted products with measurements of the gas composition at the active, summit crater. The analysed scoria clasts present large, connected vesicles with complex shapes and smaller, isolated, spherical vesicles, the content of which increases in scoriae from the most explosive events. Gas geochemistry reports CO2/SO2 and SO2/HCl ratios supporting a deep-derived gas phase for fire-fountain activity. By integrating results from scoria vesiculation and gas analysis we find that the highest energy episodes of Mt. Etna activity in 2006 were driven by a previously accumulated CO2-rich gas phase but we highlight the lesser role of syn-eruptive vesicle nucleation driven by water exsolution during ascent. We conclude that syn-eruptive vesiculation is a common process in Etnean magmas that may promote a deeper conduit magma fragmentation and increase ash formation

The role of syn-eruptive vesiculation on explosive basaltic activity at Mt. Etna, Italy

We investigated the dynamics of explosive activity at Mt. Etna between 31 August and 14 December 2006 by combining vesicle studies in the erupted products with measurements of the gas composition at the active, summit crater. The analysed scoria clasts present large, connected vesicles with complex shapes and smaller, isolated, spherical vesicles, the content of which increases in scoriae from the most explosive events. Gas geochemistry reports CO2/SO2 and SO2/HCl ratios supporting a deep-derived gas phase for fire-fountain activity. By integrating results from scoria vesiculation and gas analysis we find that the highest energy episodes of Mt. Etna activity in 2006 were driven by a previously accumulated CO2-rich gas phase but we highlight the lesser role of syn-eruptive vesicle nucleation driven by water exsolution during ascent. We conclude that syn-eruptive vesiculation is a common process in Etnean magmas that may promote a deeper conduit magma fragmentation and increase ash formatio

Structural analysis of the intrinsically disordered splicing factor Spp2 and its binding to the DEAH-box ATPase Prp2.

The spliceosome consists of five small RNAs and more than 100 proteins. Almost 50% of the human spliceosomal proteins were predicted to be intrinsically disordered or to contain disordered regions, among them the G-patch protein Spp2. The G-patch region of Spp2 binds to the DEAH-box ATPase Prp2, and both proteins together are essential for promoting the transition from the Bact to the catalytically active B* spliceosome. Here we show by circular dichroism and nuclear magnetic resonance (NMR) spectroscopy that Spp2 is intrinsically disordered in solution. Crystal structures of a complex consisting of Prp2-ADP and the G-patch domain of Spp2 demonstrate that the G-patch gains a defined fold when bound to Prp2. While the N-terminal region of the G-patch always folds into an α-helix in five different crystal structures, the C-terminal part is able to adopt two alternative conformations. NMR studies further revealed that the N-terminal part of the Spp2 G-patch, which is the most conserved region in different G-patch proteins, transiently samples helical conformations, possibly facilitating a conformational selection binding mechanism. The structural analysis unveils the role of conserved residues of the G-patch in the dynamic interaction mode of Spp2 with Prp2, which is vital to maintain the binding during the Prp2 domain movements needed for RNA translocation

Review of Ground Systems Development and Operations (GSDO) Tools for Verifying Command and Control Software

The Exploration Systems Development (ESD) Standing Review Board (SRB) requested the NASA Engineering and Safety Center (NESC) conduct an independent review of the plan developed by Ground Systems Development and Operations (GSDO) for identifying models and emulators to create a tool(s) to verify their command and control software. The NESC was requested to identify any issues or weaknesses in the GSDO plan. This document contains the outcome of the NESC review

Azathioprine Biotransformation in Young Patients with Inflammatory Bowel Disease: Contribution of Glutathione-S Transferase M1 and A1 Variants

The contribution of candidate genetic variants involved in azathioprine biotransformation on azathioprine efficacy and pharmacokinetics in 111 young patients with inflammatory bowel disease was evaluated. Azathioprine doses, metabolites thioguanine-nucleotides (TGN) and methylmercaptopurine-nucleotides (MMPN) and clinical effects were assessed after at least 3 months of therapy. Clinical efficacy was defined as disease activity score below 10. Candidate genetic variants (TPMT rs1142345, rs1800460, rs1800462, GSTA1 rs3957357, GSTM1, and GSTT1 deletion) were determined by polymerase chain reaction (PCR) assays and pyrosequencing. Statistical analysis was performed using linear mixed effects models for the association between the candidate variants and the pharmacological variables (azathioprine doses and metabolites). Azathioprine metabolites were measured in 257 samples (median 2 per patient, inter-quartile range IQR 1-3). Clinical efficacy at the first evaluation available resulted better in ulcerative colitis than in Crohn's disease patients (88.0% versus 52.5% responders, p = 0.0003, linear mixed effect model, LME). TGN concentration and the ratio TGN/dose at the first evaluation were significantly higher in responder. TPMT rs1142345 variant (4.8% of patients) was associated with increased TGN (LME p = 0.0042), TGN/dose ratio (LME p < 0.0001), decreased azathioprine dose (LME p = 0.0087), and MMPN (LME p = 0.0011). GSTM1 deletion (58.1% of patients) was associated with a 18.5% decrease in TGN/dose ratio and 30% decrease in clinical efficacy. GSTA1 variant (12.8% of patients) showed a trend (p = 0.049, LME) for an association with decreased clinical efficacy; however, no significant effect on azathioprine pharmacokinetics could be detected. In conclusion, GSTs variants are associated with azathioprine efficacy and pharmacokinetics

Assessing maternal alcohol consumption in pregnancy : does phosphatidylethanol measured from day 5 newborn blood spot cards have any value? An observational, population-based study

Objective Prenatal alcohol exposure (PAE) places children at risk of fetal alcohol spectrum disorder (FASD) but ascertainment of PAE is problematic. Early intervention for children at risk of FASD may help mitigate long-term difficulties. Phosphatidylethanol (PEth), a metabolite of alcohol, is incorporated into red cell membranes and can be measured in dried blood spot (DBS) cards. In the UK, DBS samples are collected on day 5 for routine newborn screening. We sought to examine if PEth measured from DBS correlates with postnatal maternal self-report of alcohol consumption in pregnancy. Design Observational population-based study. Comparison of infant PEth concentration and self-report of maternal alcohol use during pregnancy.Setting Large maternity unit in Glasgow, Scotland. Participants All singleton mother–infant dyads delivered during each fourth consecutive 24-hour period.Interventions Mother: direct, confidential, immediate postnatal interview by a single researcher examining alcohol use during pregnancy. Infant: one extra DBS collected coincident with routine newborn screening if bleeding continued. Results 92.5% of eligible mothers agreed to participate. 510 DBS were obtained of which 502 were successfully analysed. 216 (43%) samples contained PEth at a concentration of ≥8 ng/mL and 148 (29.5%) at ≥20 ng/mL. The sensitivity of PEth ≥8 ng/mL and ≥20 ng/mL in identifying women who self-reported modest alcohol use after 36 weeks’ gestation was 50% and 36.4%, respectively. Conclusion PEth measured from DBS obtained on day 5 of life does not reliably identify modest PAE after 36 weeks’ gestation from maternal self-report. Data are available upon reasonable request

Prevalence and management of familial hypercholesterolemia in patients with coronary artery disease: The heredity survey

Background and aims Familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low density lipoprotein cholesterol (LDL-C) predisposing to premature cardiovascular disease. Its prevalence varies and has been estimated around 1 in 200\u2013500. The Heredity survey evaluated the prevalence of potential FH and the therapeutic approaches among patients with established coronary artery disease (CAD) or peripheral artery disease (PAD) in which it is less well documented. Methods Data were collected in patients admitted to programs of rehabilitation and secondary prevention in Italy. Potential FH was estimated using Dutch Lipid Clinic Network (DLCN) criteria. Potential FH was defined as having a total score 65 6. Results Among the 1438 consecutive patients evaluated, the prevalence of potential FH was 3.7%. The prevalence was inversely related to age, with a putative prevalence of 1:10 in those with 8) had the highest percentages of patients after an ACS (75% vs 52.5% in the whole study population). At discharge, most patients were on high intensity statin therapy, but despite this, potential FH group still had a higher percentage of patients with LDL-C levels not at target and having a distance from the target higher than 50%. Conclusions Among patients with established coronary heart disease, the prevalence of potential FH is higher than in the general population; the results suggest that a correct identification of potential FH, especially in younger patients, may help to better manage their high cardiovascular risk