Treatment Intensification in Patients With Kawasaki Disease and Coronary Aneurysm at Diagnosis.

BackgroundCoronary artery aneurysms (CAA) are a serious complication of Kawasaki disease. Treatment with intravenous immunoglobulin (IVIg) within 10 days of fever onset reduces the risk of CAA from 25% to <5%. Corticosteroids and infliximab are often used in high-risk patients or those with CAA at diagnosis, but there are no data on their longer-term impact on CAA.MethodsRetrospective multicenter study including children who had CAA with a z score ≥2.5 and <10 at time of diagnosis and who received primary therapy with IVIg alone or in combination with either corticosteroids or infliximab within 10 days of onset of fever.ResultsOf 121 children, with a median age of 2.8 (range 0.1-15.5) years, 30 (25%) received primary therapy with corticosteroids and IVIg, 58 (48%) received primary therapy with infliximab and IVIg, and 33 (27%) received primary therapy with IVIg only. Median coronary z scores at the time of diagnosis did not differ among treatment groups (P = .39). Primary treatment intensification with either corticosteroids or infliximab were independent protective factors against progression of coronary size on follow-up (coefficient: -1.31 [95% confidence interval: -2.33 to -0.29]; coefficient: -1.07 [95% confidence interval: -1.95 to -0.19], respectively).ConclusionsAmong a high-risk group of patients with Kawasaki disease with CAA on baseline echocardiography, those treated with corticosteroids or infliximab in addition to IVIg had less progression in CAA size compared with those treated with IVIg alone. Prospective randomized trials are needed to determine the best adjunctive treatment of patients who present with CAA

The DRIFT Dark Matter Experiments

The current status of the DRIFT (Directional Recoil Identification From Tracks) experiment at Boulby Mine is presented, including the latest limits on the WIMP spin-dependent cross-section from 1.5 kg days of running with a mixture of CS2 and CF4. Planned upgrades to DRIFT IId are detailed, along with ongoing work towards DRIFT III, which aims to be the world's first 10 m3-scale directional Dark Matter detector.Comment: Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 201

The consequences of tobacco tax on household health and fi nances in rich and poor smokers in China: an extended cost-eff ectiveness analysis

Background In China, there are more than 300 million male smokers. Tobacco taxation reduces smoking-related premature deaths and increases government revenues, but has been criticised for disproportionately aff ecting poorer people. We assess the distributional consequences (across diff erent wealth quintiles) of a specifi c excise tax on cigarettes in China in terms of both fi nancial and health outcomes. Methods We use extended cost-eff ectiveness analysis methods to estimate, across income quintiles, the health benefi ts (years of life gained), the additional tax revenues raised, the net fi nancial consequences for households, and the fi nancial risk protection provided to households, that would be caused by a 50% increase in tobacco price through excise tax fully passed onto tobacco consumers. For our modelling analysis, we used plausible values for key parameters, including an average price elasticity of demand for tobacco of –0·38, which is assumed to vary from –0·64 in the poorest quintile to –0·12 in the richest, and we considered only the male population, which constitutes the overwhelming majority of smokers in China. Findings Our modelling analysis showed that a 50% increase in tobacco price through excise tax would lead to 231 million years of life gained (95% uncertainty range 194–268 million) over 50 years (a third of which would be gained in the lowest income quintile), a gain of US$703 billion ($616–781 billion) of additional tax revenues from the excise tax (14% of which would come from the lowest income quintile, compared with 24% from the highest income quintile). The excise tax would increase overall household expenditures on tobacco by $376 billion ($232–505 billion), but decrease these expenditures by $21 billion (–$83 to $5 billion) in the lowest income quintile, and would reduce expenditures on tobacco-related disease by$24·0 billion ($17·3–26·3 billion, 28 income quintile). Finally, it would provide fi nancial risk protection worth$1·8 billion ($1·2–2·3 billion), mainly concentrated (74%) in the lowest income quintile. Interpretation Increased tobacco taxation can be a pro-poor policy instrument that brings substantial health and fi nancial benefi ts to households in China

Virtual screening for inhibitors of the human TSLP:TSLPR interaction

The pro-inflammatory cytokine thymic stromal lymphopoietin (TSLP) plays a pivotal role in the pathophysiology of various allergy disorders that are mediated by type 2 helper T cell (Th2) responses, such as asthma and atopic dermatitis. TSLP forms a ternary complex with the TSLP receptor (TSLPR) and the interleukin-7-receptor subunit alpha (IL-7Ra), thereby activating a signaling cascade that culminates in the release of pro-inflammatory mediators. In this study, we conducted an in silico characterization of the TSLP: TSLPR complex to investigate the drugability of this complex. Two commercially available fragment libraries were screened computationally for possible inhibitors and a selection of fragments was subsequently tested in vitro. The screening setup consisted of two orthogonal assays measuring TSLP binding to TSLPR: a BLI-based assay and a biochemical assay based on a TSLP: alkaline phosphatase fusion protein. Four fragments pertaining to diverse chemical classes were identified to reduce TSLP: TSLPR complex formation to less than 75% in millimolar concentrations. We have used unbiased molecular dynamics simulations to develop a Markov state model that characterized the binding pathway of the most interesting compound. This work provides a proof-ofprinciple for use of fragments in the inhibition of TSLP: TSLPR complexation

Background Assay and Rejection in DRIFT

The DRIFT-IId dark matter detector is a m3-scale low-pressure TPC with directional sensitivity to WIMP-induced nuclear recoils. Its primary backgrounds were due to alpha decays from contamination on the central cathode. Efforts to reduce these backgrounds led to replacing the 20 μm wire central cathode with one constructed from 0.9 μm aluminized mylar, which is almost totally transparent to alpha particles. Detailed modeling of the nature and origin of the remaining backgrounds led to an in-situ, ppt-sensitive assay of alpha decay backgrounds from the central cathode. This led to further improvements in the thin-film cathode resulting in over 2 orders of magnitude reduction in backgrounds compared to the wire cathode. Finally, the addition of O2 to CS2 gas was found to produce multiple species of electronegative charge carriers, providing a method to determine the absolute position of nuclear recoils and reject all known remaining backgrounds while retaining a high efficiency for nuclear recoil detection

Measurement of directional range components of nuclear recoil tracks in a fiducialised dark matter detector

We present results from the first measurement of axial range components of fiducialized neutron induced nuclear recoil tracks using the DRIFT directional dark matter detector. Nuclear recoil events are fiducialized in the DRIFT experiment using temporal charge carrier separations between different species of anions in 30:10:1 Torr of CS$_2$:CF$_4$:O$_2$ gas mixture. For this measurement, neutron-induced nuclear recoil tracks were generated by exposing the detector to $^{252}$Cf source from different directions. Using these events, the sensitivity of the detector to the expected axial directional signatures were investigated as the neutron source was moved from one detector axis to another. Results obtained from these measurements show clear sensitivity of the DRIFT detector to the axial directional signatures in this fiducialization gas mode

The Drift Directional Dark Matter Experiments

The current status of the DRIFT (Directional Recoil Identification From Tracks) experiment at Boulby Mine is presented, including the latest limits on the WIMP spin-dependent cross-section from 1.5 kg days of running with a mixture of CS2 and CF4. Planned upgrades to DRIFT IId are detailed, along with ongoing work towards DRIFT III, which aims to be the world's first 10 m3-scale directional Dark Matter detector