Solubility and diffusional uptake of hydrogen in quartz at high water pressures: Implications for hydrolytic weakening

Attempts to introduce molecular water into dry, natural quartz crystals by diffusive transport and thus weaken them hydrolytically at T = 700°–900°C and PH_2O = 400–1550 MPa have failed. Infrared spectroscopy of hydrothermally annealed single crystals of natural quartz reveals the diffusive uptake of interstitial hydrogen (resulting in hydroxyl groups) at rates similar to those previously proposed for intracrystalline water at high water pressures. The solubility of interstitial hydrogen at these conditions is independent of temperature and pressure; instead, it depends upon the initial aluminum concentration by the local charge neutrality condition [H_i·] = [Al_(Si)′]. The rate of interstitial hydrogen diffusion parallel to c is given by an Arrhenius relation with D_0 = 1.4 × 10^(−1) m^2/s and Q = 200 ± 20 kJ/mol, in close agreement with H diffusivities reported for much lower pressures (PH_2O = 2.5 MPa). Deformation experiments following hydrothermal annealing show no mechanical weakening, and the lack of any detectable broadband absorption associated with molecular water shows that the diffusion rates of structural water are much lower than those of hydrogen. These results are consistent with the available oxygen diffusion data for quartz and with the failure to observe weakening in previous studies of quartz deformation at pressures of 300–500 MPa; they call into question the rapid rates of diffusion originally suggested for the hydrolytic weakening defect. It is suggested that the observed weakening in many previous experiments was complicated by microcracking processes in response to nonhydrostatic stresses and low effective confining pressures. Extensive microcracking may provide a mechanism for molecular water to enter quartz and allow local plastic deformation to occur. It does not appear that molecular water can diffuse far enough into uncracked quartz to allow hydrolytic weakening over annealing times that are feasible in the laboratory

Estimating antibiotic coverage from linked microbiological and clinical data from the Swiss Paediatric Sepsis Study to support empiric antibiotic regimen selection.

In light of rising antibiotic resistance, better methods for selection of empiric antibiotic treatment based on clinical and microbiological data are needed. Most guidelines target specific clinical infections, and variably adjust empiric antibiotic selection by certain patient characteristics. Coverage estimates reflect the probability that an antibiotic regimen will be active against the causative pathogen once confirmed and can provide an objective basis for empiric regimen selection. Coverage can be estimated for specific infections using a weighted incidence syndromic combination antibiograms (WISCAs) framework. However, no comprehensive data combining clinical and microbiological data for specific clinical syndromes are available in Switzerland. We therefore describe estimating coverage from semi-deterministically linked routine microbiological and cohort data of hospitalised children with sepsis. Coverage estimates were generated for each hospital and separately pooling data across ten contributing hospitals for five pre-defined patient risk groups. Data from 1,082 patients collected during the Swiss Paediatric Sepsis Study (SPSS) 2011-2015 were included. Preterm neonates were the most commonly represented group, and half of infants and children had a comorbidity. 67% of neonatal sepsis cases were hospital-acquired late-onset whereas in children 76% of infections were community-acquired. Escherichia coli, Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the most common pathogens. At all hospitals, ceftazidime plus amikacin regimen had the lowest coverage, and coverage of amoxicillin plus gentamicin and meropenem were generally comparable. Coverage was improved when vancomycin was included in the regimen, reflecting uncertainty about the empirically targeted pathogen spectrum. Children with community-acquired infections had high coverage overall. It is feasible to estimate coverage of common empiric antibiotic regimens from linked data. Pooling data by patient risk groups with similar expected pathogen and susceptibility profiles may improve coverage estimate precision, supporting better differentiation of coverage between regimens. Identification of data sources, selection of regimens and consideration of pathogens to target for improved empiric coverage is important

Cortical cell stiffness is independent of substrate mechanics

Cortical stiffness is an important cellular property that changes during migration, adhesion and growth. Previous atomic force microscopy (AFM) indentation measurements of cells cultured on deformable substrates have suggested that cells adapt their stiffness to that of their surroundings. Here we show that the force applied by AFM to a cell results in a significant deformation of the underlying substrate if this substrate is softer than the cell. This ‘soft substrate effect’ leads to an underestimation of a cell’s elastic modulus when analysing data using a standard Hertz model, as confirmed by finite element modelling and AFM measurements of calibrated polyacrylamide beads, microglial cells and fibroblasts. To account for this substrate deformation, we developed a ‘composite cell–substrate model’. Correcting for the substrate indentation revealed that cortical cell stiffness is largely independent of substrate mechanics, which has major implications for our interpretation of many physiological and pathological processes

Discovery and genotyping of structural variation from long-read haploid genome sequence data

In an effort to more fully understand the full spectrum of human genetic variation, we generated deep single-molecule, real-time (SMRT) sequencing data from two haploid human genomes. By using an assembly-based approach (SMRT-SV), we systematically assessed each genome independently for structural variants (SVs) and indels resolving the sequence structure of 461,553 genetic variants from 2 bp to 28 kbp in length. We find that &gt;89% of these variants have been missed as part of analysis of the 1000 Genomes Project even after adjusting for more common variants (MAF &gt; 1%). We estimate that this theoretical human diploid differs by as much as ∼16 Mbp with respect to the human reference, with long-read sequencing data providing a fivefold increase in sensitivity for genetic variants ranging in size from 7 bp to 1 kbp compared with short-read sequence data. Although a large fraction of genetic variants were not detected by short-read approaches, once the alternate allele is sequence-resolved, we show that 61% of SVs can be genotyped in short-read sequence data sets with high accuracy. Uncoupling discovery from genotyping thus allows for the majority of this missed common variation to be genotyped in the human population. Interestingly, when we repeat SV detection on a pseudodiploid genome constructed in silico by merging the two haploids, we find that ∼59% of the heterozygous SVs are no longer detected by SMRT-SV. These results indicate that haploid resolution of long-read sequencing data will significantly increase sensitivity of SV detection.</jats:p

A Prospective Multicenter SPOG 2003 FN Study of Microbiologically Defined Infections in Pediatric Cancer Patients with Fever and Neutropenia.

BACKGROUND: Fever and neutropenia (FN) often complicate anticancer treatment and can be caused by potentially fatal infections. Knowledge of pathogen distribution is paramount for optimal patient management. METHODS: Microbiologically defined infections (MDI) in pediatric cancer patients presenting with FN by nonmyeloablative chemotherapy enrolled in a prospective multi-center study were analyzed. Effectiveness of empiric antibiotic therapy in FN episodes with bacteremia was assessed taking into consideration recently published treatment guidelines for pediatric patients with FN. RESULTS: MDI were identified in a minority (22%) of pediatric cancer patients with FN. In patients with, compared to without MDI, fever (median, 5 [IQR 3-8] vs. 2 [IQR1-3] days, p &lt; 0.001) and hospitalization (10 [6-14] vs. 5 [3-8] days, p &lt; 0.001) lasted longer, transfer to the intensive care unit was more likely (13 of 95 [14%] vs. 7 of 346 [2.0%], p &lt; 0.001), and antibiotics were given longer (10 [7-14] vs. 5 [4-7], p &lt; 0.001). Empiric antibiotic therapy in FN episodes with bacteremia was highly effective if not only intrinsic and reported antimicrobial susceptibilities were considered but the purposeful omission of coverage for coagulase negative staphylococci and enterococci was also taken into account (81% [95%CI 68 - 90] vs. 96.6% [95%CI 87 - 99.4], p = 0.004) CONCLUSIONS: MDI were identified in a minority of FN episodes but they significantly affected management and the clinical course of pediatric cancer patients. Compliance with published guidelines was associated with effectiveness of empiric antibiotic therapy in FN episodes with bacteremia

Phosphatidylinositol 3-Akt-kinase-dependent phosphorylation of p21(Waf1/Cip1) as a novel mechanism of neuroprotection by glucocorticoids

The role of glucocorticoids in the regulation of apoptosis remains incongruous. Here, we demonstrate that corticosterone protects neurons from apoptosis by a mechanism involving the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). In primary cortical neurons, corticosterone leads to a dose- and Akt-kinase-dependent upregulation with enhanced phosphorylation and cytoplasmic appearance of p21(Waf1/Cip1) at Thr 145. Exposure of neurons to the neurotoxin ethylcholine aziridinium (AF64A) results in activation of caspase-3 and a dramatic loss of p21(Waf1/Cip1) preceding apoptosis in neurons. These effects of AF64A are reversed by pretreatment with corticosterone. Corticosterone-mediated upregulation of p21(Waf1/Cip1) and neuroprotection are completely abolished by glucocorticoid and mineralocorticoid receptor antagonists as well as inhibitors of PI3- and Akt-kinase. Both germline and somatically induced p21(Waf1/Cip1) deficiency abrogate the neuroprotection by corticosterone, whereas overexpression of p21(Waf1/Cip1) suffices to protect neurons from apoptosis. We identify p21(Waf1/Cip1) as a novel antiapoptotic factor for postmitotic neurons and implicate p21(Waf1/Cip1) as the molecular target of neuroprotection by high-dose glucocorticoids

Estimating antibiotic coverage from linked microbiological and clinical data from the Swiss Paediatric Sepsis Study to support empiric antibiotic regimen selection

In light of rising antibiotic resistance, better methods for selection of empiric antibiotic treatment based on clinical and microbiological data are needed. Most guidelines target specific clinical infections, and variably adjust empiric antibiotic selection by certain patient characteristics. Coverage estimates reflect the probability that an antibiotic regimen will be active against the causative pathogen once confirmed and can provide an objective basis for empiric regimen selection. Coverage can be estimated for specific infections using a weighted incidence syndromic combination antibiograms (WISCAs) framework. However, no comprehensive data combining clinical and microbiological data for specific clinical syndromes are available in Switzerland. We therefore describe estimating coverage from semi-deterministically linked routine microbiological and cohort data of hospitalised children with sepsis. Coverage estimates were generated for each hospital and separately pooling data across ten contributing hospitals for five pre-defined patient risk groups. Data from 1,082 patients collected during the Swiss Paediatric Sepsis Study (SPSS) 2011-2015 were included. Preterm neonates were the most commonly represented group, and half of infants and children had a comorbidity. 67% of neonatal sepsis cases were hospital-acquired late-onset whereas in children 76% of infections were community-acquired. Escherichia coli, Coagulase-negative staphylococci (CoNS) and Staphylococcus aureus were the most common pathogens. At all hospitals, ceftazidime plus amikacin regimen had the lowest coverage, and coverage of amoxicillin plus gentamicin and meropenem were generally comparable. Coverage was improved when vancomycin was included in the regimen, reflecting uncertainty about the empirically targeted pathogen spectrum. Children with community-acquired infections had high coverage overall. It is feasible to estimate coverage of common empiric antibiotic regimens from linked data. Pooling data by patient risk groups with similar expected pathogen and susceptibility profiles may improve coverage estimate precision, supporting better differentiation of coverage between regimens. Identification of data sources, selection of regimens and consideration of pathogens to target for improved empiric coverage is important

Occupational Therapy Intervention with Children Survivors of War

A preventive occupational therapy program with children surviving the Kosovo conflict is examined. The objective of the program was to facilitate the emotional expression of traumatic experiences in order to prevent the development of future psychological problems. The intervention was based on a community-centred approach with spirituality as a central focus of the intervention.The Model of Human Occupation and the Occupational Performance Process Model were utilized to guide the identification and intervention of occupational performance issues.The children’s return from a land of war to a land of children demonstrates the potential of occupational therapy intervention in this field. With increasing awareness of populations facing social and political challenges, there is a growing importance of the concept of occupational justice and the need to work against occupational apartheid.Cet article décrit un programme de prévention en ergothérapie qui était destiné aux enfants ayant survécu au conflit du Kosovo. L’objectif du programme était d’aider les enfants à exprimer les émotions qu’ils avaient ressenties lors d’expériences traumatiques afin de prévenir l’apparition de problèmes psychologiques. L’intervention était basée sur une approche communautaire s’articulant autour de la spiritualité. Le Modèle de l’occupation humaine et le Modèle du processus d’intervention dans le rendement occupationnel ont été utilisés pour cibler les difficultés en matière de rendement occupationnel et pour déterminer les interventions requises. Le retour des enfants d’un monde de guerre vers le monde de l’enfance démontre la possibilité de proposer une intervention ergothérapique dans ce domaine. La conscientisation de plus en plus grand face à la détresse des populations confrontées à des problèmes politiques et sociaux entraîne une augmentation de l’importance du concept de la justice occupationnelle et du besoin de lutter contre l’apartheid occupationnel

Use of polyethylene glycol coatings for optical fibre humidity sensing

Humidity induced change in the refractive index and thickness of the polyethylene glycol (PEG) coatings are in situ investigated for a range from 10 to 95%, using an optical waveguide spectroscopic technique. It is experimentally demonstrated that, upon humidity change, the optical and swelling characteristics of the PEG coatings can be employed to build a plastic fibre optic humidity sensor. The sensing mechanism is based on the humidity induced change in the refractive index of the PEG film, which is directly coated onto a polished segment of a plastic optical fibre with dip-coating method. It is observed that PEG, which is a highly hydrophilic material, shows no monotonic linear response to humidity but gives different characteristics for various ranges of humidity levels both in index of refraction and in thickness. It undergoes a physical phase change from a semi-crystal line structure to a gel one at around 80% relative humidity. At this phase change point, a drastic decrease occurs in the index of refraction as well as a drastic increase in the swelling of the PEG film. In addition, PEG coatings are hydrogenated in a vacuum chamber. It is observed that the hydrogen has a preventing effect on the humidity induced phase change in PEG coatings. Finally, the possibility of using PEG coatings in construction of a real plastic fibre optic humidity sensor is discussed. (C) 2008 The Optical Society of Japan

Fluid Assisted Compaction and Deformation of Reservoir Lithologies

The compaction and diagenesis of sandstones that form reservoirs to hydrocarbons depend on mechanical compaction processes, fluid flow at local and regional scales, and chemical processes of dissolution, precipitation and diffusional solution transport. The compaction and distortional deformation of quartz aggregates exposed to reactive aqueous fluids have been investigated experimentally at varying critical and subcritical stress states and time scales. Pore fluid compositions and reaction rates during deformation have been measured and compared with creep rates. Relative contributions of mechanical and chemical processes to deformation and pore structure evolution have been evaluated using acoustic emission (AE) measurements and scanning electron microscope (SEM) observations. At the subcritical conditions investigated, creep rates and acoustic emission rates fit transient logarithmic creep laws. Based on AE and SEM observations, we conclude that intragranular cracking and grain rearrangement are the dominant strain mechanisms. Specimens show little evidence of stress-enhanced solution transfer. At long times under wet conditions, the dominant strain mechanism gradually shifts from critical cracking at grain contacts with high stress concentrations to fluid-assisted sub-critical cracking