The environmental severity of large impacts on Earth is influenced by their impact trajectory. Impact direction and angle to the target plane affect the volume and depth of origin of vaporized ...target, as well as the trajectories of ejected material. The asteroid impact that formed the 66 Ma Chicxulub crater had a profound and catastrophic effect on Earth's environment, but the impact trajectory is debated. Here we show that impact angle and direction can be diagnosed by asymmetries in the subsurface structure of the Chicxulub crater. Comparison of 3D numerical simulations of Chicxulub-scale impacts with geophysical observations suggests that the Chicxulub crater was formed by a steeply-inclined (45-60° to horizontal) impact from the northeast; several lines of evidence rule out a low angle (<30°) impact. A steeply-inclined impact produces a nearly symmetric distribution of ejected rock and releases more climate-changing gases per impactor mass than either a very shallow or near-vertical impact.
A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV
) versus once-daily ...tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature.
This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case. A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity). Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data. Treatment effect, expressed as change from baseline in FEV
was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL 95% confidence interval: 28, 77). Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable. A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted. Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum.
UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient. The ITT scenario analysis and sensitivity analyses had similar results. All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO.
UMEC/VI dominated TIO/OLO (more effective and less expensive). These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting β
-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In case–control studies, colonization and infection with vancomycin-resistant enterococci have been associated with exposure to vancomycin,
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third-generation cephalosporins,
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antibiotics ...that are active against anaerobes,
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ciprofloxacin,
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and aminoglycosides.
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The microbiologic basis for these associations is not well defined. If some antibiotics promote colonization and infection more than others that are equally effective, limiting the use of these agents may limit the spread of vancomycin-resistant enterococci.
We previously examined the effect of various antibiotics on intestinal colonization with vancomycin-resistant enterococci in mice.
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In mice with established colonization, as evidenced by the high density of vancomycin-resistant enterococci in stool, . . .
Core from Hole M0077 from IODP/ICDP Expedition 364 provides unprecedented evidence for the physical processes in effect during the interaction of impact melt with rock-debris-laden seawater, ...following a large meteorite impact into waters of the Yucatán shelf. Evidence for this interaction is based on petrographic, microstructural and chemical examination of the 46.37-m-thick impact melt rock sequence, which overlies shocked granitoid target rock of the peak ring of the Chicxulub impact structure. The melt rock sequence consists of two visually distinct phases, one is black and the other is green in colour. The black phase is aphanitic and trachyandesitic in composition and similar to melt rock from other sites within the impact structure. The green phase consists chiefly of clay minerals and sparitic calcite, which likely formed from a solidified water–rock debris mixture under hydrothermal conditions. We suggest that the layering and internal structure of the melt rock sequence resulted from a single process, i.e., violent contact of initially superheated silicate impact melt with the ocean resurge-induced water–rock mixture overriding the impact melt. Differences in density, temperature, viscosity, and velocity of this mixture and impact melt triggered Kelvin–Helmholtz and Rayleigh–Taylor instabilities at their phase boundary. As a consequence, shearing at the boundary perturbed and, thus, mingled both immiscible phases, and was accompanied by phreatomagmatic processes. These processes led to the brecciation at the top of the impact melt rock sequence. Quenching of this breccia by the seawater prevented reworking of the solidified breccia layers upon subsequent deposition of suevite. Solid-state deformation, notably in the uppermost brecciated impact melt rock layers, attests to long-term gravitational settling of the peak ring.
OBJECTIVE:To determine interleukin (IL)-8 concentrations in ventricular cerebrospinal fluid from children with severe traumatic brain injury (TBI).
DESIGN:Prospective study.
SETTING:University ...children's hospital.
PATIENTS:Twenty-seven children hospitalized with severe TBI (Glasgow Coma Scale score ≤8), seven children with cerebrospinal fluid culture-positive bacterial meningitis, and twenty-four age-equivalent controls.
INTERVENTIONS:Placement of an intraventricular catheter and continuous drainage of cerebrospinal fluid.
MEASUREMENTS AND MAIN RESULTS:Median range cerebrospinal fluid IL-8 concentration in children with TBI (0-12 hrs) (4,452.5 0-20,000 pg/mL) was markedly greater than that in controls (14.5 0-250) (p < .0001) and equivalent to concentrations in children with meningitis (5,300 1,510-22,000 pg/mL) (p = .33). Cerebrospinal fluid IL-8 remained increased in children with severe TBI for up to 108 hrs after injury. Univariate logistic regression analysis demonstrated an association between cerebrospinal fluid IL-8 and child abuse (p = .07) and mortality (p = .01). Multivariate analysis demonstrated a strong, independent association between cerebrospinal fluid IL-8 and mortality (p = .01).
CONCLUSIONS:The data are consistent with an acute inflammatory component of TBI in children and suggest an association between cerebrospinal fluid IL-8 and outcome after TBI. IL-8 may represent a potential target for anti-inflammatory therapy.
The degree of dietary generalism among consumers has important consequences for population, community, and ecosystem processes, yet the effects on consumer fitness of mixing food types have not been ...examined comprehensively. We conducted a meta-analysis of 161 peer-reviewed studies reporting 493 experimental manipulations of prey diversity to test whether diet mixing enhances consumer fitness based on the intrinsic nutritional quality of foods and consumer physiology. Averaged across studies, mixed diets conferred significantly higher fitness than the average of single-species diets, but not the best single prey species. More than half of individual experiments, however, showed maximal growth and reproduction on mixed diets, consistent with the predicted benefits of a balanced diet. Mixed diets including chemically defended prey were no better than the average prey type, opposing the prediction that a diverse diet dilutes toxins. Finally, mixed-model analysis showed that the effect of diet mixing was stronger for herbivores than for higher trophic levels. The generally weak evidence for the nutritional benefits of diet mixing in these primarily laboratory experiments suggests that diet generalism is not strongly favored by the inherent physiological benefits of mixing food types, but is more likely driven by ecological and environmental influences on consumer foraging.
Joint International Ocean Discovery Program and International Continental Scientific Drilling Program Expedition 364 drilled into the peak ring of the Chicxulub impact crater. We present P-wave ...velocity, density, and porosity measurements from Hole M0077A that reveal unusual physical properties of the peak-ring rocks. Across the boundary between post-impact sedimentary rock and suevite (impact melt-bearing breccia) we measure a sharp decrease in velocity and density, and an increase in porosity. Velocity, density, and porosity values for the suevite are 2900–3700 m/s, 2.06–2.37 g/cm3, and 20–35%, respectively. The thin (25 m) impact melt rock unit below the suevite has velocity measurements of 3650–4350 m/s, density measurements of 2.26–2.37 g/cm3, and porosity measurements of 19–22%. We associate the low velocity, low density, and high porosity of suevite and impact melt rock with rapid emplacement, hydrothermal alteration products, and observations of pore space, vugs, and vesicles. The uplifted granitic peak ring materials have values of 4000–4200 m/s, 2.39–2.44 g/cm3, and 8–13% for velocity, density, and porosity, respectively; these values differ significantly from typical unaltered granite which has higher velocity and density, and lower porosity. The majority of Hole M0077A peak-ring velocity, density, and porosity measurements indicate considerable rock damage, and are consistent with numerical model predictions for peak-ring formation where the lithologies present within the peak ring represent some of the most shocked and damaged rocks in an impact basin. We integrate our results with previous seismic datasets to map the suevite near the borehole. We map suevite below the Paleogene sedimentary rock in the annular trough, on the peak ring, and in the central basin, implying that, post impact, suevite covered the entire floor of the impact basin. Suevite thickness is 100–165 m on the top of the peak ring but 200 m in the central basin, suggesting that suevite flowed downslope from the collapsing central uplift during and after peak-ring formation, accumulating preferentially within the central basin.
•Chicxulub peak-ring rocks have low velocities and densities, and high porosities.•Physical property values indicate considerable damage of granitoid peak-ring rocks.•Suevite flowed downslope during and after peak-ring formation.
OBJECTIVESTo determine concentrations of circulating adhesion molecules endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 in children ...with sepsis-induced multiple organ failure (MOF), and to determine associations among increased concentrations of these circulating adhesion molecules and important outcome measures.
DESIGNProspective study.
SETTINGUniversity pediatric intensive care unit.
PATIENTSA total of 77 consecutive children with sepsis and 14 acutely ill children without sepsis.
INTERVENTIONSPlasma E-selectin, ICAM-1, and VCAM-1 concentrations and organ failure index (indicating number of failed organ systems) were determined in 77 children on days 1 and 3 of sepsis, and in 14 control children on pediatric intensive care unit day 1. Multivariate logistic regression analysis was used to determine associations between adhesion molecule concentrations and clinically relevant outcome measures.
MEASUREMENTS AND RESULTSPlasma concentrations of E-selectin, ICAM-1, and VCAM-1 were increased in children with sepsis vs. control on day 1 (p < .05). Plasma VCAM-1 (but not ICAM-1 or E-selectin) was increased in children with more than three organ failures vs. children with less than three organ failures (p < .05). Plasma ICAM-1 and VCAM-1 (but not E-selectin) concentrations independently predicted number of organs failed and development of more than three organ failures. Plasma ICAM-1 and VCAM-1 also predicted mortality and development of sequential (pulmonary/hepatic/renal) MOF (p < .05).
CONCLUSIONSThe pronounced and persistent increase in plasma VCAM-1 and ICAM-1 that occurs in children with sepsis and persistent MOF may indicate a phenotypic change in endothelium toward a more proinflammatory state. Alternatively, the source for these adhesion molecules may be activated leukocytes and other cell types. Future studies are required to determine the role of ICAM-1 and VCAM-1 in the pathogenesis of sepsis-induced MOF.
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