A phase field model for elastic-gradient-plastic solids undergoing hydrogen embrittlement

We present a gradient-based theoretical framework for predicting hydrogen assisted fracture in elastic-plastic solids. The novelty of the model lies in the combination of: (i) stress-assisted diffusion of solute species, (ii) strain gradient plasticity, and (iii) a hydrogen-sensitive phase field fracture formulation, inspired by first principles calculations. The theoretical model is numerically implemented using a mixed finite element formulation and several boundary value problems are addressed to gain physical insight and showcase model predictions. The results reveal the critical role of plastic strain gradients in rationalising decohesion-based arguments and capturing the transition to brittle fracture observed in hydrogen-rich environments. Large crack tip stresses are predicted, which in turn raise the hydrogen concentration and reduce the fracture energy. The computation of the steady state fracture toughness as a function of the cohesive strength shows that cleavage fracture can be predicted in otherwise ductile metals using sensible values for the material parameters and the hydrogen concentration. In addition, we compute crack growth resistance curves in a wide variety of scenarios and demonstrate that the model can appropriately capture the sensitivity to: the plastic length scales, the fracture length scale, the loading rate and the hydrogen concentration. Model predictions are also compared with fracture experiments on a modern ultra-high strength steel, AerMet100. A promising agreement is observed with experimental measurements of threshold stress intensity factor $K_{th}$ over a wide range of applied potentials

Hospital variation in the risk of infection after hip fracture surgery: a population-based cohort study including 29,598 patients from 2012–2017

BACKGROUND AND PURPOSE: Understanding the key drivers of hospital variation in postoperative infections after hip fracture surgery is important for directing quality improvements. Therefore, we investigated variation in the risk of any infection, and subgroups of infections including pneumonia and sepsis after hip fracture surgery. METHODS: In this nationwide population-based cohort study, all Danish patients aged ≥ 65 undergoing surgery for an incident hip fracture from 2012 to 2017 were included. Risk of postoperative infections, based on data from hospital registration (hospital-treated infections) and antibiotic dispensing (community-treated infections), were calculated using multilevel Poisson regression analysis. Hospital variation was evaluated by intra-class coefficient (ICC) and median risk ratio (MRR). RESULTS: The risk of hospital-treated infection was 15%. The risk of community-treated infection was 24%. The adjusted risk varied between hospitals from 7.8–25% for hospital-treated infection and 16–34% for community-treated infection. The ICC indicated that 19% of the adjusted variance was due to hospital level for hospital-treated infection. The ICC for community-treated infections was 13%. The MRR showed a 2-fold increased risk for the average patient acquiring a hospital-treated infection at the highest risk hospital compared with the lowest risk hospital. For community-treated infection, the MRR was 1.4. INTERPRETATION: Our results suggest that 20% of infections could be reduced by applying the top performing hospitals’ approach. Nearly a 5th of the variation was at the hospital level. This suggests a more standardized approach to avoid postoperative infection after hip fracture surgery. Hip fracture is a leading cause of hospital admission among the elderly. The 30-day mortality following hip fracture surgery has been approximately 10% during the last few years in Denmark (Pedersen et al. 2017). Higher mortality after hip fracture has been associated with a range of hospital factors (Kristensen et al. 2016, Sheehan et al. 2016) and patient factors in observational studies (Roche et al. 2005). Furthermore, variation in 30-day mortality after hip fracture surgery has been observed between Danish hospitals, but not fully explained (Kristensen et al. 2019)

Hypothalamic FTO is associated with the regulation of energy intake not feeding reward

<p>Abstract</p> <p>Background</p> <p>Polymorphism in the FTO gene is strongly associated with obesity, but little is known about the molecular bases of this relationship. We investigated whether hypothalamic FTO is involved in energy-dependent overconsumption of food. We determined FTO mRNA levels in rodent models of short- and long-term intake of palatable fat or sugar, deprivation, diet-induced increase in body weight, baseline preference for fat versus sugar as well as in same-weight animals differing in the inherent propensity to eat calories especially upon availability of diverse diets, using quantitative PCR. FTO gene expression was also studied in organotypic hypothalamic cultures treated with anorexigenic amino acid, leucine. In situ hybridization (ISH) was utilized to study FTO signal in reward- and hunger-related sites, colocalization with anorexigenic oxytocin, and c-Fos immunoreactivity in FTO cells at initiation and termination of a meal.</p> <p>Results</p> <p>Deprivation upregulated FTO mRNA, while leucine downregulated it. Consumption of palatable diets or macronutrient preference did not affect FTO expression. However, the propensity to ingest more energy without an effect on body weight was associated with lower FTO mRNA levels. We found that 4-fold higher number of FTO cells displayed c-Fos at meal termination as compared to initiation in the paraventricular and arcuate nuclei of re-fed mice. Moreover, ISH showed that FTO is present mainly in hunger-related sites and it shows a high degree of colocalization with anorexigenic oxytocin.</p> <p>Conclusion</p> <p>We conclude that FTO mRNA is present mainly in sites related to hunger/satiation control; changes in hypothalamic FTO expression are associated with cues related to energy intake rather than feeding reward. In line with that, neurons involved in feeding termination express FTO. Interestingly, baseline FTO expression appears linked not only with energy intake but also energy metabolism.</p

The global aerosol synthesis and science project (GASSP): Measurements and modeling to reduce uncertainty

This is the final version of the article. Available from American Meteorological Society via the DOI in this record.The largest uncertainty in the historical radiative forcing of climate is caused by changes in aerosol particles due to anthropogenic activity. Sophisticated aerosol microphysics processes have been included in many climate models in an effort to reduce the uncertainty. However, the models are very challenging to evaluate and constrain because they require extensive in situ measurements of the particle size distribution, number concentration, and chemical composition that are not available from global satellite observations. The Global Aerosol Synthesis and Science Project (GASSP) aims to improve the robustness of global aerosol models by combining new methodologies for quantifying model uncertainty, to create an extensive global dataset of aerosol in situ microphysical and chemical measurements, and to develop new ways to assess the uncertainty associated with comparing sparse point measurements with low-resolution models. GASSP has assembled over 45,000 hours of measurements from ships and aircraft as well as data from over 350 ground stations. The measurements have been harmonized into a standardized format that is easily used by modelers and nonspecialist users. Available measurements are extensive, but they are biased to polluted regions of the Northern Hemisphere, leaving large pristine regions and many continental areas poorly sampled. The aerosol radiative forcing uncertainty can be reduced using a rigorous model–data synthesis approach. Nevertheless, our research highlights significant remaining challenges because of the difficulty of constraining many interwoven model uncertainties simultaneously. Although the physical realism of global aerosol models still needs to be improved, the uncertainty in aerosol radiative forcing will be reduced most effectively by systematically and rigorously constraining the models using extensive syntheses of measurements.GASSP was funded by the Natural Environment Research Council (NERC) under Grants NE/J024252/1, NE/J022624/1, and NE/J023515/1; ACID-PRUF under Grants NE/I020059/1 and NE/I020148/1; the European Union BACCHUS project under Grant 603445-BACCHUS; ACTRIS under Grants 262254 and 654109; and by the UK–China Research and Innovation Partnership Fund through the Met Office Climate Science for Service Partnership (CSSP) China as part of the Newton Fund. We made use of the N8 HPC facility funded from the N8 consortium and an Engineering and Physical Sciences Research Council Grant to use ARCHER (EP/K000225/1) and the JASMIN facility (www.jasmin.ac.uk/) via the Centre for Environmental Data Analysis funded by NERC and the UK Space Agency and delivered by the Science and Technology Facilities Council. We acknowledge the following additional funding: the Royal Society Wolfson Merit Award (Carslaw); a doctoral training grant from the Natural Environment Research Council and a CASE studentship with the Met Office Hadley Centre (Regayre); the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013)/ERC Grant Agreement FP7-280025 (Stier); the Department of Energy under DE-SC0007178 (Zhang); the U.S. National Science Foundation under ATM-745986 (Snider); the NOAA Global Change Program (Nenes); NASA Global Tropospheric Experiment Program, the NASA Tropospheric Composition Program, the NASA Radiation Sciences Program, and the NASA Earth Venture Suborbital Project (Anderson); the NOAA Climate Program Office (Quinn); NSF Atmospheric Chemistry Program, the NASA Global Tropospheric Experiment, and NASA Earth Science Project Office (Clarke); German Federal Ministry of Education and Research (BMBF) CLOUD12 project Grant 01LK1222B (Kristensen); Swedish Research Council (VR), the Knut and Alice Wallenberg Foundation and the Swedish Polar Research Secretariat (SPRS) for access to the icebreaker Oden and logistical support (Leck); the Department of Energy (DE-SC0007178) and the Max Planck Society (Andreae, Poeschl); the global environment research fund of the Ministry of the Environment in Japan (2-1403), the Arctic Challenge for Sustainability (ArCS) project of the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) in Japan, and the Japan Society for the Promotion of Science (JSPS) KAKENHI (Grants JP16H01770, JP26701004, and JP26241003) (Kondo, Oshima); Lufthansa for enabling CARIBIC and the German Federal Ministry of Education and Research (BMBF) for financing the CARIBIC instruments operation as part of the Joint Project IAGOS-D (Hermann); the Collaborative Innovation Center of Climate Change supported by the Jiangsu provincial government and the JirLATEST supported by the Ministry of Education, China (Ding and Chi); the Max Planck Institute for Chemistry, Mainz, Germany (Schmale); the NOAA Atmospheric Composition and Climate Program, the NASA Radiation Sciences Program, and the NASA Upper Atmosphere Research Program supporting the NOAA SP2 BC data acquisition and analysis (Schwarz); DOE (BER/ASR) DE-SC0016559 and EPA STAR 83587701-0 (the EPA has not reviewed this manuscript and no endorsement should be inferred) (Jimenez); and Environment and Climate Change Canada (Leaitch)

Changed activation, oxygenation, and pain response of chronically painful muscles to repetitive work after training interventions: a randomized controlled trial

The aim of this randomized controlled trial was to assess changes in myalgic trapezius activation, muscle oxygenation, and pain intensity during repetitive and stressful work tasks in response to 10 weeks of training. In total, 39 women with a clinical diagnosis of trapezius myalgia were randomly assigned to: (1) general fitness training performed as leg-bicycling (GFT); (2) specific strength training of the neck/shoulder muscles (SST) or (3) reference intervention without physical exercise. Electromyographic activity (EMG), tissue oxygenation (near infrared spectroscopy), and pain intensity were measured in trapezius during pegboard and stress tasks before and after the intervention period. During the pegboard task, GFT improved trapezius oxygenation from a relative decrease of −0.83 ± 1.48 μM to an increase of 0.05 ± 1.32 μM, and decreased pain development by 43%, but did not affect resting levels of pain. SST lowered the relative EMG amplitude by 36%, and decreased pain during resting and working conditions by 52 and 38%, respectively, without affecting trapezius oxygenation. In conclusion, GFT performed as leg-bicycling decreased pain development during repetitive work tasks, possibly due to improved oxygenation of the painful muscles. SST lowered the overall level of pain both during rest and work, possibly due to a lowered relative exposure as evidenced by a lowered relative EMG. The results demonstrate differential adaptive mechanisms of contrasting physical exercise interventions on chronic muscle pain at rest and during repetitive work tasks

Geographic clustering of testicular cancer incidence in the northern part of The Netherlands

Geographic variations in testicular cancer incidence may be caused by differences in environmental factors, genetic factors, or both. In the present study, geographic patterns of age-adjusted testicular cancer incidence rates (IRs) in 12 provinces in The Netherlands in the period 1989–1995 were analysed. In addition, the age-adjusted IR of testicular cancer by degree of urbanization was evaluated. Cancer incidence data were obtained from the Netherlands Cancer Registry. The overall annual age-adjusted IR of testicular cancer in The Netherlands in the period 1989–1995 was 4.4 per 100 000 men. The province Groningen in the north of the country showed the highest annual IR with 5.8 per 100 000 men, which was higher (P < 0.05) than the overall IR in The Netherlands (incidence rate ratio (IRR) 1.3, 95% confidence interval (CI) 1.1–1.6). The highest IR in Groningen was seen for both seminomas and non-seminomas. In addition, Groningen showed the highest age-specific IRs in all relevant younger age groups (15–29, 30–44 and 45–59 years), illustrating the consistency of data. The province Friesland, also situated in the northern part of the country, showed the second highest IR of testicular cancer with 5.3 cases per 100 000 men per year (IRR 1.2, 95% Cl 1.0–1.5, not significant). This mainly resulted from the high IR of seminoma in Friesland. Analysis of age-adjusted IRs of testicular cancer by degree of urbanization in The Netherlands showed no urban–rural differences at analysis of all histological types combined, or at separate analyses of seminomas and non-seminomas. Geographic clustering of testicular cancer seems to be present in the rural north of The Netherlands with some stable founder populations, which are likely to share a relatively high frequency of genes from common ancestors including genes possibly related to testicular cancer. Although this finding does not exclude the involvement of shared environmental factors in the aetiology of testicular cancer, it may also lend support to a genetic susceptibility to testicular cancer development. Testicular cancer cases in stable founder populations seem particularly suitable for searching for testicular cancer susceptibility genes because such genes are likely to be more frequent among affected men in such populations. © 1999 Cancer Research Campaig

Population pharmacokinetics of the antimalarial amodiaquine: a pooled analysis to optimize dosing

Amodiaquine plus artesunate is the recommended antimalarial treatment in many countries where malaria is endemic. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over 3 days. Plasma concentration-time profiles for both the parent drug and the metabolite were characterized using nonlinear mixed-effects modeling. Amodiaquine pharmacokinetics were adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 months (95% confidence interval [CI], 1.5 to 3.7 months) and 3.9 months (95% CI, 2.6 to 5.3 months) after birth, assuming that the baby was born at term. Bioavailability was 22.4% (95% CI, 15.6 to 31.9%) lower at the start of treatment than during convalescence, which suggests a malaria disease effect. Neither the drug formulation nor the hemoglobin concentration had an effect on any pharmacokinetic parameters. Results from simulations showed that current manufacturer dosing recommendations resulted in low desethylamodiaquine exposure in patients weighing 8 kg, 15 to 17 kg, 33 to 35 kg, and &gt;62 kg compared to that in a typical 50-kg patient. We propose possible optimized dosing regimens to achieve similar drug exposures among all age groups, which require further validation