Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European Scleroderma Trials and Research (EUSTAR) analysis.

Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12\ub13 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trial

Ten instars in the leprous grasshopper Phymateus leprosus (Fabricius, 1793) (Caelifera: Pyrgomorphidae): Maximum number recorded in the Acridoidea

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A tale of gold transport and precipitation. The genesis of a giant mesothermal Au deposit from a multidisciplinary study (Sigma deposit - Canada).

The Sigma deposit is a large network of Au-mineralized, quartz-tourmaline veins of the Archean Abitibi greenstone belt. It produced 290 t of Au, and is a proxy example of metamorphogenic, mesothermal gold deposits. Here, we combine new constraints from a multidisciplinary study of this network to propose a new genetic model. This study considers a) a 3-D geometric reconstruction of network veins; b) a mass transfer study of the tourmaline- and albite-rich hydrothermal alteration haloes; c) a petrographic, microthermometric, Raman spectroscopy, and Laser Ablation-ICP-Mass Spectrometry study of co-genetic groups of fluid inclusions; and d) a fluid-mineral equilibria study. At Sigma, the backbone of the vein network is a set of conjugated, steeply dipping, oblique-reverse shear zones with a vertical continuity of the order of kilometers. Steep veins are hosted by these shear zones, but are continuous for few hundreds of meters at best. They interconnect with vertically short splays and with small, subhorizontal extension veins. These interconnections are all gold rich (grade >25 g/t), showing that the mechanisms that controlled shear development and vein propagation controlled gold precipitation as well. About 95% of all veins are filled with quartz and tourmaline. Gold, found mostly within the veins, precipitated at all stages of vein filling and fluid-rock interaction. Co-genetic groups of fluid inclusions trapped within vein quartz host either an H2O-NaCl (aqueous) fluid or an H2O-NaCl-CO2 (aquo-carbonic) fluid. In both fluid types, liquid-rich and vapor-rich inclusions have low salinity (Liq: 4-8 wt% NaCleq; Vap:0.5-4 wt% NaCleq) and homogenization occurs mostly into the liquid and vapor phases. The distribution of Thtot within individual cogenetic groups show modes between 330 and 385 \ub0C, but the total range is much larger, being ca. 200-420 \ub0C. Microthermometric data and tests for equilibrium coexistence indicate that an \u201cimplosion\u201d re-equilibration regime affected the co-genetic groups. Accordingly, we identify the properties of the high-Thtot inclusions as those approaching the pristine fluid. These properties are consistent with unmixing of a parent H2O-NaCl-CO2 fluid at about 350-400 \ub0C and P<500 bars. Thus, in contrast with previous models, we identify aqueous and aquo-carbonic fluids as end-member fluids generated by unmixing. The ranges of Na, K, B, and Au concentrations in the two fluid types have been measured by Laser Ablation-ICP-Mass Spectrometry of single fluid inclusion, and subsequently used to estimate pH, logaH2S and logaO2 during Au precipitation. In particular, concentration of B is in the 80-2200 ppm range for the two fluid types, and Au in the 0.5-5 ppm range. Fluid-mineral equilibria at 400 \ub0C 300 bar and 400 \ub0C 3 kbar have been used to test the hypothesis of low-pressure gold deposition. Results show that this hypothesis is valid, and that fluid pressure fluctuations of few tens of bars around 300 bar might have affected gold precipitation significantly. Thus, pressure fluctuations of the parent fluid caused by interconnection of distinct vein segments may have caused fluid unmixing and massive gold precipitation at Sigma. This interpretation implies that poorly connected vein networks are also relatively inefficient in precipitating gold, and their exploration should account for these features. Combining the estimated 70000 t of B deposited within the vein network with the measured range of B concentration within the fluid inclusions, we calculate that 0.1-2.3 km3 of hydrothermal fluid deposited all the tourmaline and gold at Sigma. This suggests that only small volumes of hydrothermal fluid were probably involved in the generation of this mineralised vein network. Simple mass-balance calculations show that metamorphic devolatilization of any dehydrating pelitic or igneous rock could not be the only process generating this volume of hydrothermal fluid

Evaluation of the scientific impact of the Ebola epidemic: a systematic review

The Ebola outbreak prompted an extensive number of scientific publications, but little attention has been paid to the involvement of local scientists, distribution of research funding and related publications. We sought to systematically review publicly available information on the scientific impact of the Ebola epidemic

Cyclic fault-controlled mass transfer during gold mineralisation in carbonated ultramafites (Bisciarelle stream, Voltri Massif, Ligurian Alps)

In this work, we examine a thrust fault developed within carbonated ultramafites (lherzolite and serpentinite) of the Voltri Massif (Ligurian Alps), exposed along the Bisciarelle Stream. Different rock types characterise the damage zone of this fault, namely carbonate and chalcedony-quartz veins at the footwall and intensely fractured and hydrothermally altered lherzolite at the hangingwall. The fault core hosts unusual carbonate-coated grains (CCGs), in a ca. 50 cm-thick level, cut by chalcedony shear veins at the top. We have combined petrographic data with SEM-EDS and LA-ICP-TOFMS (Laser Ablation-ICP Time of Flight-Mass Spectrometry) analyses, and with mass transfer calculations in order to: 1) determine the chemical properties of fault core rocks, and 2) monitor chemical exchanges that took place between hydrothermal fluids flowing within the fault at the time of its slip and the host lherzolite. The used samples were collected at the fault damage zone and along a sampling profile orthogonal with respect to the fault strike. Fault core CCGs are mm to cm-sized, have a surprisingly regular round shape, and are rarely in contact with each other. The largest CCGs show complex internal textures, in which relatively thick and fibrous dolomite bands alternate with thinner, massive, and partly laminated dark carbonate bands, suggesting a cyclic growth process; the smallest CCGs show simpler internal textures. Two dimensional, multi-elemental compositional maps generated by LA-ICP-TOFMS analyses highlight systematic compositional difference between the thin massive bands and the fibrous dolomite bands; the first ones have relatively high concentrations of Mn, Al, K, Pb, Cr, Co, and Cu, whereas the second are enriched in only a small number of metals (i.e. Fe, Sr, and W). Chalcedony shear veins contain Al2O3, Na2O, and K2O in addition to SiO2, and show a peculiar enrichment in Sb, Ag, In, Pb, and Au. Mass transfer calculations show that the fluid transferred consistently volatiles (CO2 and H2O) and Sb to the rock, whereas the rock transferred Si, Fe, Co, and Cr to the fluid. Our dataset shows that the thrust hosted a gold-bearing hydrothermal fluid, which was responsible for the rhythmic growth of the CCGs. Such growth was syn-kinematic and at equilibrium with the fault fluid, but was not coupled with any substantial grain-size reduction of the fault core. Mass transfer data show that hydrothermal formation of CCGs and chalcedony was entirely fault-controlled, and that the host rock provides a poor record of this circulation. The evidence for transfer of Si, Fe, Co, and Cr from the protolith to the fluid provides a strong indication that the enrichment of these elements within CCGs and chalcedony was made possible by fluid-rock interaction. In conclusion, the occurrence of CCGs with a peculiar composition, their texture, and the lack of grain-size reduction suggest that the hydrothermal precipitation controlled the composition of the Bisciarelle fault rocks

Capabilities of automated LA-ICP-TOFMS imaging of geological samples

Element imaging aims to provide quantitative data on multi-element distributions from major to trace elements with high lateral resolution. Here, we describe a control system for laser ablation inductively coupled plasma time-of-flight mass spectrometry (LA-ICP-TOFMS) imaging with complex integration of translational stage, laser, and mass spectrometer data acquisition which was tested on glass and mineral samples. In particular, besides single pulse imaging at a laser repetition rate of 100 Hz using a 5 \u3bcm laser spot size, a hole drilling imaging approach provided higher pixel sensitivity and lower limits of detection (<1 mg kg 121 for most heavy elements) while maintaining the same lateral resolution. An optional surface cleaning pulse can be applied without additional recording of data. Furthermore, the ablation area can be adapted to specific object structures of interest and leads to significant shorter imaging times. Triggering the data acquisition for every ablation position led to binned pixel data in relation to the sample position. This simplifies the data evaluation and allows a more automated image generation. The approach presented in this study enables flexible adjustments of distinct ablation modes to a specific analytical task and provides the basis for fully automated element imaging. To test the applicability of our approach, two complex geological samples containing crystalline solids were imaged to gain insights into the distribution of trace elements that occur typically in the low mg kg 121 range. We show that both single pulse and hole drilling ablation modes allow the determination of a large number of trace elements. However, the hole drilling mode shows a superior sensitivity per pixel, which in turn provides more detailed information about the formation of geological samples

Site-Specific Investigation of the Steady-State Kinetics and Dynamics of the Multistep Binding of Bile Acid Molecules to a Lipid Carrier Protein

The investigation of multi-site ligand-protein binding and multi-step mechanisms is highly demanding. In this work, advanced NMR methodologies such as 2D (1)H-(15)N line-shape analysis, which allows a reliable investigation of ligand binding occurring on micro- to millisecond timescales, have been extended to model a two-step binding mechanism. The molecular recognition and complex uptake mechanism of two bile salt molecules by lipid carriers is an interesting example that shows that protein dynamics has the potential to modulate the macromolecule-ligand encounter. Kinetic analysis supports a conformational selection model as the initial recognition process in which the dynamics observed in the apo form is essential for ligand uptake, leading to conformations with improved access to the binding cavity. Subsequent multi-step events could be modelled, for several residues, with a two-step binding mechanism. The protein in the ligand-bound state still exhibits a conformational rearrangement that occurs on a very slow timescale, as observed for other proteins of the family. A global mechanism suggesting how bile acids access the macromolecular cavity is thus proposed