Improved and standardized method for assessing years lived with disability after burns and its application to estimate the non-fatal burden of disease of burn injuries in Australia, New Zealand and the Netherlands

Background: Burden of disease estimates are an important resource in public health. Currently, robust estimates are not available for the burn population. Our objectives are to adapt a refined methodology (INTEGRIS method) to burns and to apply this new INTEGRIS-burns method to estimate, and compare, the burden of disease of burn injuries in Australia, New Zealand and the Netherlands. Methods: Existing European and Western-Australian health-related quality of life (HRQL) datasets were combined to derive disability weights for three homogenous burn injury groups based on percentage total body surface area (%TBSA) burned. Subsequently, incidence data from Australia, New Zealand, and the Netherlands from 2010 to 2017 were used to compute annual non-fatal burden of disease estimates for each of these three countries. Non-fatal burden of disease was measured by years lived with disability (YLD). Results: The combined dataset included 7159 HRQL (EQ-5D-3 L) outcomes from 3401 patients. Disability weights ranged from 0.046 (subgroup  24 months post-burn) to 0.497 (subgroup > 20% TBSA burned 0–1 months post-burn). In 2017 the non-fatal burden of disease of burns for the three countries (YLDs/100,000 inhabitants) was 281 for Australia, 279 for New Zealand and 133 for the Netherlands. Conclusions: This project established a method for more precise estimates of the YLDs of burns, as it is the only method adapted to the nature of burn injuries and their recovery. Compared to previous used methods, the INTEGRIS-burns method includes improved disability weights based on severity categorization of burn patients; a better substantiated proportion of patients with lifelong disability based; and, the application of burn specific recovery timeframes. Information derived from the adapted method can be used as input for health decision making at both the national and international level. Future studies should investigate whether the application is valid in low- and middle- income countries

Hierarchically-coupled hidden Markov models for learning kinetic rates from single-molecule data

We address the problem of analyzing sets of noisy time-varying signals that all report on the same process but confound straightforward analyses due to complex inter-signal heterogeneities and measurement artifacts. In particular we consider single-molecule experiments which indirectly measure the distinct steps in a biomolecular process via observations of noisy time-dependent signals such as a fluorescence intensity or bead position. Straightforward hidden Markov model (HMM) analyses attempt to characterize such processes in terms of a set of conformational states, the transitions that can occur between these states, and the associated rates at which those transitions occur; but require ad-hoc post-processing steps to combine multiple signals. Here we develop a hierarchically coupled HMM that allows experimentalists to deal with inter-signal variability in a principled and automatic way. Our approach is a generalized expectation maximization hyperparameter point estimation procedure with variational Bayes at the level of individual time series that learns an single interpretable representation of the overall data generating process.Comment: 9 pages, 5 figure

Structural analysis of Salmonella enterica effector protein SopD

Salmonella outer protein D (SopD) is a type III secreted virulence effector protein from Salmonella enterica. Full-length SopD and SopD lacking 16 amino acids at the N-terminus (SopDDeltaN) have been expressed as fusions with GST in Escherichia coli, purified with a typical yield of 20-30 mg per litre of cell culture and crystallized. Biophysical characterization has been carried out mainly on SopDDeltaN. Analytical size exclusion chromatography shows that SopDDeltaN is monomeric and probably globular in aqueous solution. The secondary structure composition, calculated from the CD spectrum, is mixed (38% alpha-helix and 26% beta-strand). Sequence analysis indicates that SopD contains a coiled coil motif, as found in numerous other type III secretion system-associated proteins. This suggests that SopD has the potential for one or more heterotypic protein-protein interactions. Limited trypsin digestion of SopDDeltaN, monitored by both one-dimensional proton NMR spectroscopy and SDS-PAGE, shows that the protein has a large, protease-resistant core domain of 286 amino acid residues. This single-domain architecture suggests that SopD lacks a cognate chaperone. In crystallization trials, SopDDeltaN produced better crystals than either full-length SopD or trypsin-digested SopDDeltaN. Diffraction to 3.0 Angstrom resolution has so far been obtained from crystals of SopDDeltaN

Variability and spectral classification of LMC giants: results from DENIS and EROS

We present the first cross-identifications of sources in the near-infrared DENIS survey and in the micro-lensing EROS survey in a field of about 0.5 square degrees around the optical center (OC) of the Large Magellanic Cloud. We analyze the photometric history of these stars in the EROS data base and obtain light-curves for about 800 variables. Most of the stars are long period variables (Miras and Semi-Regulars), a few Cepheids are also present. We also present new spectroscopic data on 126 asymptotic giant branch stars in the OC field, 30 previously known and 96 newly discovered by the DENIS survey. The visible spectra are used to assign a carbon- (C-) or oxygen-rich (O-rich) nature to the observed stars on the basis of the presence of molecular bands of TiO, VO, CN, C2. For the remaining of the stars we used the (J-Ks) color to determine whether they are O-rich or C-rich. Plotting Log(period) versus Ks we find three very distinct period-luminosity relations, mainly populated by Semi-Regular of type a (SRa), b (SRb) and Mira variables. Carbon-rich stars occupy mostly the upper part of these relations. We find that 65% of the asymptotic giant branch population are long period variables (LPVs).Comment: 9 pages, 7 figures, 4 tables (2 via CDS), accepted by A&A journa

Time-resolved, multi-color photometry and spectroscopy of Virgo 4 (OU Vir): a high orbital inclination, short orbital period dwarf nova

We present multi-color photometry and time resolved spectroscopy of OU Vir. The analysis of the quiescent light curve shows that OU Vir is characterized by i) strong cycle-to-cycle brightness variations, and ii) hot spot modulated light curve with grazing eclipse of the impact region. Colors are derived both in- and out- of eclipse. The time-resolved spectroscopy allows us to produce the radial velocity curve from the H$\alpha$ accretion disk emission line which possibly reveals only weak evidence for hot spot line emission. The hot spot is believed to be a turbulent optically thick region, producing mostly continuum emission.Comment: 8 pages (including figures), 7 figures. To Be published in A&

Hydrodynamics of the stream-disk impact in interacting binaries

We use hydrodynamic simulations to provide quantitative estimates of the effects of the impact of the accretion stream on disks in interacting binaries. For low accretion rates, efficient radiative cooling of the hotspot region can occur, and the primary consequence of the stream impact is stream overflow toward smaller disk radii. The stream is well described by a ballistic trajectory, but larger masses of gas are swept up and overflow at smaller, but still highly supersonic, velocities. If cooling is inefficient, overflow still occurs, but there is no coherent stream inward of the disk rim. Qualitatively, the resulting structure appears as a bulge extending downstream along the disk rim. We calculate the mass fraction and velocity of the overflowing component as a function of the important system parameters, and discuss the implications of the results for X-ray observations and doppler tomography of cataclysmic variables, low-mass X-ray binaries and supersoft X-ray sources.Comment: 16 pages, including 8 figures. 1 color figure as a jpeg. ApJ, in pres

Carbon-rich dust production in metal-poor galaxies in the Local Group

We have observed a sample of 19 carbon stars in the Sculptor, Carina, Fornax, and Leo I dwarf spheroidal galaxies with the Infrared Spectrograph on the Spitzer Space Telescope. The spectra show significant quantities of dust around the carbon stars in Sculptor, Fornax, and Leo I, but little in Carina. Previous comparisons of carbon stars with similar pulsation properties in the Galaxy and the Magellanic Clouds revealed no evidence that metallicity affected the production of dust by carbon stars. However, the more metal-poor stars in the current sample appear to be generating less dust. These data extend two known trends to lower metallicities. In more metal-poor samples, the SiC dust emission weakens, while the acetylene absorption strengthens. The bolometric magnitudes and infrared spectral properties of the carbon stars in Fornax are consistent with metallicities more similar to carbon stars in the Magellanic Clouds than in the other dwarf spheroidals in our sample. A study of the carbon budget in these stars reinforces previous considerations that the dredge-up of sufficient quantities of carbon from the stellar cores may trigger the final superwind phase, ending a star's lifetime on the asymptotic giant branch.Comment: ApJ, in press, 21 pages, 12 figures. Replaced Fig 12, corrected two reference

Destructive effects of murine arthritogenic antibodies to type II collagen on cartilage explants in vitro

Certain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilage. Bovine cartilage explants were cultured over 21 days in the presence of two arthritogenic mAbs to CII (CIIC1 or M2139), a non-arthritogenic mAb to CII (CIIF4) or a control mAb (GAD6). Penetration of cartilage by mAb was determined by immunofluorescence on frozen sections and correlated with changes to the extracellular matrix and chondrocytes by morphometric analysis of sections stained with toluidine blue. The effects of mAbs on matrix components were examined by Fourier transform infrared microspectroscopy (FTIRM). A possible role of Fc-binding was investigated using F(ab)(2 )from CIIC1. All three mAbs to CII penetrated the cartilage explants and CIIC1 and M2139, but not CIIF4, had adverse effects that included proteoglycan loss correlating with mAb penetration, the later development in cultures of an abnormal superficial cellular layer, and an increased proportion of empty chondrons. FTIRM showed depletion and denaturation of CII at the explant surface in the presence of CIIC1 or M2139, which paralleled proteoglycan loss. The effects of F(ab)(2 )were greater than those of intact CIIC1. Our results indicate that mAbs to CII can adversely affect preformed cartilage, and that the specific epitope on CII recognised by the mAb determines both arthritogenicity in vivo and adverse effects in vitro. We conclude that antibodies to CII can have pathogenic effects that are independent of inflammatory mediators or Fc-binding