Microlensing Constraints on Broad Absorption and Emission Line Flows in the Quasar H1413+117

We present new integral field spectroscopy of the gravitationally lensed broad absorption line (BAL) quasar H1413+117, covering the ultraviolet to visible rest-frame spectral range. We observe strong microlensing signatures in lensed image D, and we use this microlensing to simultaneously constrain both the broad emission and broad absorption line gas. By modeling the lens system over the range of probable lensing galaxy redshifts and using on a new argument based on the wavelength-independence of the broad line lensing magnifications, we determine that there is no significant broad line emission from smaller than ~20 light days. We also perform spectral decomposition to derive the intrinsic broad emission line (BEL) and continuum spectrum, subject to BAL absorption. We also reconstruct the intrinsic BAL absorption profile, whose features allow us to constrain outflow kinematics in the context of a disk-wind model. We find a very sharp, blueshifted onset of absorption of 1,500 km/s in both C IV and N V that may correspond to an inner edge of a disk-wind's radial outflow. The lower ionization Si IV and Al III have higher-velocity absorption onsets, consistent with a decreasing ionization parameter with radius in an accelerating outflow. There is evidence of strong absorption in the BEL component which indicates a high covering factor for absorption over two orders of magnitude in outflow radius.Comment: 29 pages, 8 figure

The Toll-Like receptor adaptor TRIF contributes to otitis media pathogenesis and recovery

<p>Abstract</p> <p>Background</p> <p>Toll-like receptor (TLR) signalling is crucial for innate immune responses to infection. The involvement of TLRs in otitis media (OM), the most prevalent childhood disease in developed countries, has been implicated by studies in middle ear cell lines, by association studies of TLR-related gene polymorphisms, and by altered OM in mice bearing mutations in TLR genes. Activated TLRs signal via two alternative intracellular signaling molecules with differing effects; MyD88 (Myeloid differentiation primary response gene 88) inducing primarily interleukin expression and TRIF (Tir-domain-containing adaptor inducing interferon β) mediating type I interferon (IFN) expression. We tested the hypothesis that TRIF and type I IFN signaling play a role in OM, using a murine model of OM induced by non-typeable <it>Haemophilus influenzae </it>(NTHi). The ME inflammatory response to NTHi was examined in wild-type (WT) and TRIF-/- mice by qPCR, gene microarray, histopathology and bacterial culture.</p> <p>Results</p> <p>Expression of TRIF mRNA was only modesty enhanced during OM, but both type I IFN signalling genes and type I IFN-inducible genes were significantly up-regulated in WT mice. TRIF-deficient mice showed reduced but more persistent mucosal hyperplasia and less leukocyte infiltration into the ME in response to NTHi infection than did WT animals. Viable bacteria could be cultured from MEs of TRIF-/- mice for much longer in the course of disease than was the case for middle ears of WT mice.</p> <p>Conclusion</p> <p>Our results demonstrate that activation of TRIF/type I IFN responses is important in both the pathogenesis and resolution of NTHi-induced OM.</p

Catestatin induces glycogenesis by stimulating the phosphoinositide 3-kinase-AKT pathway

Aim: Defects in hepatic glycogen synthesis contribute to post-prandial hyperglycaemia in type 2 diabetic patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA 352-372) improves glucose tolerance in insulin-resistant mice. Here, we seek to determine whether CST induces hepatic glycogen synthesis. Methods: We determined liver glycogen, glucose-6-phosphate (G6P), uridine diphosphate glucose (UDPG) and glycogen synthase (GYS2) activities; plasma insulin, glucagon, noradrenaline and adrenaline levels in wild-type (WT) as well as in CST knockout (CST-KO) mice; glycogen synthesis and glycogenolysis in primary hepatocytes. We also analysed phosphorylation signals of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-dependent kinase-1 (PDK-1), GYS2, glycogen synthase kinase-3β (GSK-3β), AKT (a kinase in AKR mouse that produces Thymoma)/PKB (protein kinase B) and mammalian/mechanistic target of rapamycin (mTOR) by immunoblotting. Results: CST stimulated glycogen accumulation in fed and fasted liver and in primary hepatocytes. CST reduced plasma noradrenaline and adrenaline levels. CST also directly stimulated glycogenesis and inhibited noradrenaline and adrenaline-induced glycogenolysis in hepatocytes. In addition, CST elevated the levels of UDPG and increased GYS2 activity. CST-KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role of CST in hepatic glycogenesis. CST improved insulin signals downstream of IR and IRS-1 by enhancing phospho-AKT signals through the stimulation of PDK-1 and mTORC2 (mTOR Complex 2, rapamycin-insensitive complex) activities. Conclusions: CST directly promotes the glycogenic pathway by (a) reducing glucose production, (b) increasing glycogen synthesis from UDPG, (c) reducing glycogenolysis and (d) enhancing downstream insulin signalling

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

We conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Weekend effect: analysing temporal trends in solid organ donation

Background: Research suggests patients treated over weekends experience poorer outcomes. Only one US-based study explored this weekend effect in organ donation, specifically the kidney discard rate. In Australia potential donors are referred to a donation service, and donation proceeds if family consent is granted and the donor is deemed medically suitable to donate. Organ procurement occurs when utilization is almost certain hence discard rates are much lower than in the USA. We aimed to characterize the effect of weekend referral on organ donation in Australia. Methods: We retrospectively reviewed all New South Wales Organ and Tissue Donation Service logs from 2010 to 2016. Our primary outcome was progression to organ procurement, and secondary outcomes were family consent and meeting medical suitability thresholds. We used logistic regression with random effects adjusting for clustering of referral hospitals. Results: Of 3496 potential donors referred for consideration, 694 (20%) progressed to organ procurement. There were fewer referrals on weekends (average 415 versus 588 for weekdays). However, donation rates were no lower for weekend compared to weekday referrals (adjusted OR 1.17; 95% CI 0.95, 1.44). Family consent (adjusted OR 1.20; 95% CI 1.00, 1.44) and medical suitability (adjusted OR 1.15; 95% CI 0.96, 1.38) were not lower for weekend compared to weekday referrals. Similar results were found for all sensitivity analyses conducted. Conclusions: In Australia, the donation pathway operates consistently throughout the week, with donation no less likely to proceed on weekends and holidays. This finding contrasts with findings in the USA

The Veterans Health Administration: Quality, Value, Accountability, and Information as Transforming Strategies for Patient-Centered Care

Abstract Countries around the world are in need of electronic medical record (EMR) systems that meet their specific needs. This paper describes briefly the benefits of EMRs in developing countries. It focuses on the basic EMR information, including types of EMRs, components of EMRs, and already existing EMRs, in order to establish which EMR systems would be feasible and effective for specific situations. Electronic Medical Record Systems for Developing Countries: Review Structure of Systems A. Data Model • Flat file structures (spread-sheet like) as compared with relational databases B. Networks • Stand-alone • Systems which are deployed on a single machine • Local area networks • Wide area network solutions • Deployed across a much larger area Discussion When choosing which electronic medical record system to implement, one should consider the following factors: population, location, and availability of resources. OpenMRS may be the best choice for today&apos;s EMR

Poisson-de Rham homology of hypertoric varieties and nilpotent cones

We prove a conjecture of Etingof and the second author for hypertoric varieties, that the Poisson-de Rham homology of a unimodular hypertoric cone is isomorphic to the de Rham cohomology of its hypertoric resolution. More generally, we prove that this conjecture holds for an arbitrary conical variety admitting a symplectic resolution if and only if it holds in degree zero for all normal slices to symplectic leaves. The Poisson-de Rham homology of a Poisson cone inherits a second grading. In the hypertoric case, we compute the resulting 2-variable Poisson-de Rham-Poincare polynomial, and prove that it is equal to a specialization of an enrichment of the Tutte polynomial of a matroid that was introduced by Denham. We also compute this polynomial for S3-varieties of type A in terms of Kostka polynomials, modulo a previous conjecture of the first author, and we give a conjectural answer for nilpotent cones in arbitrary type, which we prove in rank less than or equal to 2.Comment: 25 page

Antihypertensive Treatment for Kidney Transplant Recipients

Background: In some nontransplant populations, effects of different antihypertensive drug classes vary. Relative effects in kidney transplant recipients are uncertain. Objectives: To assess comparative effects of different classes of antihypertensive agents in kidney transplant recipients. Search strategy: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, conference proceedings and reference lists of identified studies were searched. Selection criteria: Randomised controlled trials of any antihypertensive agent applied to kidney transplant recipients for at least two weeks were included. Data collection and analysis: Data was extracted by two investigators independently. Study quality, transplant outcomes and other patient centred outcomes were assessed using random effects meta-analysis. Risk ratios (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, both with 95% confidence intervals (CI) were calculated. Stratified analyses and meta-regression were used to investigate heterogeneity. Main results: We identified 60 studies, enrolling 3802 recipients. Twenty-nine studies (2262 participants) compared calcium channel blockers (CCB) to placebo/no treatment, 10 studies (445 participants) compared angiotensin converting enzyme inhibitors (ACEi) to placebo/no treatment and seven studies (405 participants) compared CCB to ACEi. CCB compared to placebo/no treatment (plus additional agents in either arm as required) reduced graft loss (RR 0.75, 95% CI 0.57 to 0.99) and improved glomerular filtration rate (GFR), (MD, 4.45 mL/min, 95% CI 2.22 to 6.68). Data on ACEi versus placebo/no treatment were inconclusive for GFR (MD -8.07 mL/min, 95% CI -18.57 to 2.43), and variable for graft loss, precluding meta-analysis. In direct comparison with CCB, ACEi decreased GFR (MD -11.48 mL/min, 95% CI -5.75 to -7.21), proteinuria (MD -0.28 g/24 h, 95% CI -0.47 to -0.10), haemoglobin (MD -12.96 g/L, 95% CI -5.72 to -10.21) and increased hyperkalaemia (RR 3.74, 95% CI 1.89 to 7.43). Graft loss data were inconclusive (RR 7.37, 95% CI 0.39 to 140.35). Other drug comparisons were compared in small numbers of participants and studies. Authors' conclusions: These data suggest that CCB may be preferred as first line agents for hypertensive kidney transplant recipients. ACEi have some detrimental effects in kidney transplant recipients. More high quality studies reporting patient centred outcomes are required