Hydrogen embrittlement is a complex phenomenon, involving several length- and timescales, that affects a large class of metals. It can significantly reduce the ductility and load-bearing capacity and ...cause cracking and catastrophic brittle failures at stresses below the yield stress of susceptible materials. Despite a large research effort in attempting to understand the mechanisms of failure and in developing potential mitigating solutions, hydrogen embrittlement mechanisms are still not completely understood. There are controversial opinions in the literature regarding the underlying mechanisms and related experimental evidence supporting each of these theories. The aim of this paper is to provide a detailed review up to the current state of the art on the effect of hydrogen on the degradation of metals, with a particular focus on steels. Here, we describe the effect of hydrogen in steels from the atomistic to the continuum scale by reporting theoretical evidence supported by quantum calculation and modern experimental characterisation methods, macroscopic effects that influence the mechanical properties of steels and established damaging mechanisms for the embrittlement of steels. Furthermore, we give an insight into current approaches and new mitigation strategies used to design new steels resistant to hydrogen embrittlement.
There is an increasing desire in the railway industry to improve the longevity of wheels and rails without reducing performance in other ways (e.g. worsening passenger comfort). One way of reducing ...track and wheel wear is to reduce the primary yaw stiffness, significantly diminishing the costs associated with maintenance and emergency repairs, resulting however in reduced passenger comfort and high-speed stability. This paper, using a two-axle railway vehicle case study, demonstrates the potential of using passive, inerter-based suspensions to concurrently improve ride comfort and reduce track wear. The industrial parameter
is used to quantify the frictional energy lost at the contact patch under curving conditions, and the lateral RMS carbody acceleration is used to quantify passenger comfort under straight running conditions, with lateral track disturbances taken from real track data. Optimisation results conclude that, with the default yaw stiffness value, compared with the default spring-damper configuration in the primary lateral suspension, employing beneficial inerter-based configurations can improve passenger comfort by up to 43%. If the yaw stiffness is reduced such that the track wear is improved, similar improvements in passenger comfort can still be achieved with lateral inerter-based suspensions; for example, an improvement of 33% can still be achieved with a 50% reduction in yaw stiffness. Furthermore, when an inerter-based lateral suspension is used together with a Hall-Bush longitudinal suspension, the passenger comfort rises to 40%, which relates to a 25% improvement when compared with a non-inerter lateral plus Hall-Bush longitudinal setup.
This study describes a simple parameterization to estimate regionally averaged changes in surface ozone due to past or future changes in anthropogenic precursor emissions based on results from 14 ...global chemistry transport models. The method successfully reproduces the results of full simulations with these models. For a given emission scenario it provides the ensemble mean surface ozone change, a regional source attribution for each change, and an estimate of the associated uncertainty as represented by the variation between models. Using the Representative Concentration Pathway (RCP) emission scenarios as an example, we show how regional surface ozone is likely to respond to emission changes by 2050 and how changes in precursor emissions and atmospheric methane contribute to this. Surface ozone changes are substantially smaller than expected with the SRES A1B, A2 and B2 scenarios, with annual global mean reductions of as much as 2 ppb by 2050 vs. increases of 4-6 ppb under SRES, and this reflects the assumptions of more stringent precursor emission controls under the RCP scenarios. We find an average difference of around 5 ppb between the outlying RCP 2.6 and RCP 8.5 scenarios, about 75% of which can be attributed to differences in methane abundance. The study reveals the increasing importance of limiting atmospheric methane growth as emissions of other precursors are controlled, but highlights differences in modelled ozone responses to methane changes of as much as a factor of two, indicating that this remains a major uncertainty in current models.
Understanding the surface O3 response over a “receptor” region to emission changes over a foreign “source” region is key to evaluating the potential gains from an international approach to abate ...ozone (O3) pollution. We apply an ensemble of 21 global and hemispheric chemical transport models to estimate the spatial average surface O3 response over east Asia (EA), Europe (EU), North America (NA), and south Asia (SA) to 20% decreases in anthropogenic emissions of the O3 precursors, NOx, NMVOC, and CO (individually and combined), from each of these regions. We find that the ensemble mean surface O3 concentrations in the base case (year 2001) simulation matches available observations throughout the year over EU but overestimates them by >10 ppb during summer and early fall over the eastern United States and Japan. The sum of the O3 responses to NOx, CO, and NMVOC decreases separately is approximately equal to that from a simultaneous reduction of all precursors. We define a continental‐scale “import sensitivity” as the ratio of the O3 response to the 20% reductions in foreign versus “domestic” (i.e., over the source region itself) emissions. For example, the combined reduction of emissions from the three foreign regions produces an ensemble spatial mean decrease of 0.6 ppb over EU (0.4 ppb from NA), less than the 0.8 ppb from the reduction of EU emissions, leading to an import sensitivity ratio of 0.7. The ensemble mean surface O3 response to foreign emissions is largest in spring and late fall (0.7–0.9 ppb decrease in all regions from the combined precursor reductions in the three foreign regions), with import sensitivities ranging from 0.5 to 1.1 (responses to domestic emission reductions are 0.8–1.6 ppb). High O3 values are much more sensitive to domestic emissions than to foreign emissions, as indicated by lower import sensitivities of 0.2 to 0.3 during July in EA, EU, and NA when O3 levels are typically highest and by the weaker relative response of annual incidences of daily maximum 8‐h average O3 above 60 ppb to emission reductions in a foreign region (<10–20% of that to domestic) as compared to the annual mean response (up to 50% of that to domestic). Applying the ensemble annual mean results to changes in anthropogenic emissions from 1996 to 2002, we estimate a Northern Hemispheric increase in background surface O3 of about 0.1 ppb a−1, at the low end of the 0.1–0.5 ppb a−1 derived from observations. From an additional simulation in which global atmospheric methane was reduced, we infer that 20% reductions in anthropogenic methane emissions from a foreign source region would yield an O3 response in a receptor region that roughly equals that produced by combined 20% reductions of anthropogenic NOx, NMVOC, and CO emissions from the foreign source region.
Objectives
We aimed to update data on the prevalence and incidence of systemic lupus erythematosus (SLE) in the Medicare population and describe associated outcomes.
Methods
This observational study ...used Medicare 20% random sample data 2007–2016 to estimate SLE prevalence and incidence 2009–2016. The study population included patients aged ≥18 years (stratified by <65 and ≥65 years) with Medicare fee-for-service coverage. The SLE definition was based on a published and validated algorithm. All-cause death, hospitalizations, and kidney disease incidence were defined for a prevalent SLE cohort 2011–2015. Unadjusted event rates during 5-year follow-up were reported per 100 patient-years.
Results
The study included > 5 million eligible patients for each year 2009–2016. There were 19,518 (10,898, aged ≥65; 8620, aged <65) in 2016, extrapolated to 97,590 (54,490 aged ≥65; 43,100 aged <65) in the overall 2016 Medicare population. Age- and sex-adjusted prevalence rates (per 100,000 Medicare population) ranged from 301.1 in 2009 to 366.6 in 2016, all ages, and 184.0–239.9, ≥65 years. There were 2614 (1844 aged ≥65; 770 aged <65) incident patients in 2016; age-/sex-adjusted incidence rates (per 100,000 Medicare population) ranged from 46.9 in 2009 to 49.0 in 2016, all ages, and 37.5–40.8, ≥65. Five-year unadjusted mortality, elderly vs. younger, was 8.8 vs. 3.8, morbidity 34.5 vs. 32.4, and kidney disease incidence 19.8 vs. 18.0 per 100 patient-years.
Conclusions
Prevalence rates steadily increased while incidence was relatively stable 2009–2016. Our data should be interpreted with caution due to our elderly study population.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
As part of the Hemispheric Transport of Air Pollution (HTAP; http:// www.htap.org) project, we analyze results from 15 global and 1 hemispheric chemical transport models and compare these to Clean ...Air Status and Trends Network (CASTNet) observations in the United States (US) for 2001. Using the policy-relevant maximum daily 8-h average ozone (MDA8 O3) statistic, the multi-model ensemble represents the observations well (mean r2=0.57, ensemble bias = +4.1 ppbv for all US regions and all seasons) despite a wide range in the individual model results. Correlations are strongest in the northeastern US during spring and fall (r2=0.68); and weakest in the midwestern US in summer (r2=0.46). However, large positive mean biases exist during summer for all eastern US regions, ranging from 10–20 ppbv, and a smaller negative bias is present in the western US during spring (~3 ppbv). In nearly all other regions and seasons, the biases of the model ensemble simulations are ≤5 ppbv. Sensitivity simulations in which anthropogenic O3-precursor emissions (NOx + NMVOC + CO + aerosols) were decreased by 20% in four source regions: East Asia (EA), South Asia (SA), Europe (EU) and North America (NA) show that the greatest response of MDA8 O3 to the summed foreign emissions reductions occurs during spring in the West (0.9 ppbv reduction due to 20% emissions reductions from EA + SA + EU). East Asia is the largest contributor to MDA8 O3 at all ranges of the O3 distribution for most regions (typically ~0.45 ppbv) followed closely by Europe. The exception is in the northeastern US where emissions reductions in EU had a slightly greater influence than EA emissions, particularly in the middle of the MDA8 O3 distribution (response of ~0.35 ppbv between 35–55 ppbv). EA and EU influences are both far greater (about 4x) than that from SA in all regions and seasons. In all regions and seasons O3-precursor emissions reductions of 20% in the NA source region decrease MDA8 O3 the most – by a factor of 2 to nearly 10 relative to foreign emissions reductions. The O3 response to anthropogenic NA emissions is greatest in the eastern US during summer at the high end of the O3 distribution (5–6 ppbv for 20% reductions). While the impact of foreign emissions on surface O3 in the US is not negligible – and is of increasing concern given the recent growth in Asian emissions – domestic emissions reductions remain a far more effective means of decreasing MDA8 O3 values, particularly those above 75 ppb (the current US standard).
Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety ...profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin.
Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course.
DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages.
DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832).
Health system responsiveness is related to the way and the environment in which individuals are treated during their health system interaction. Generally, patients who are members of ethnic minority ...(EM) groups encounter more challenges in receiving healthcare services and bear a disproportionate burden of diseases compared with most counterparts. We aimed to compare the health system responsiveness perceived by South Asian (SA) EM people with that of local Chinese people in Hong Kong.
The cross-sectional survey sample comprised 575 SA and 494 Chinese individuals. The health system responsiveness module of the World Health Survey 2002 was used for data collection.
We used propensity score weighting method to balance the two groups. Simple and multiple regressions were used to compare the perceived outpatient and inpatient health system responsiveness between SA and Chinese participants, respectively, before and after adjustment for demographics. All estimates were accompanied by 95% confidence intervals, and two-sided tests were conducted with significance concluded by a P value < 0∙05.
Compared with the Chinese participants, the SA participants reported generally lower health system responsiveness for outpatient and inpatient services. The top three mean score difference (SA-Chinese) for outpatient care included autonomy (−0.78, P < 0.001), communication (−0.67, P < 0.001), and choice (−0.53, P < 0.001), and the top three mean score difference for inpatient care included communication (−0.90, P < 0.001), autonomy (−0.82, P < 0.001), and choice (−0.61, P < 0.01). In addition, SA participants also experienced lower responsiveness in access to community support (−0.81, P < 0.001) during hospitalization but perceived higher quality of basic amenities (0.29, P < 0.001) and confidentiality (0.44, P < 0.01) in outpatient settings.
SA participants in an urbanized Chinese-oriented society reported generally lower health system responsiveness compared with the local Chinese group; however, SA participants perceived higher confidentiality and quality of basic amenities in their outpatient experience. Concerted efforts from healthcare providers and policymakers are required to improve the existing healthcare system for users of members of EM groups.
•Low health system responsiveness for South Asian (SA) patients compared to Chinese.•Difficulties with communication, patient autonomy and to choose healthcare provider.•Higher quality of basic amenities and confidentiality in outpatient settings.
Implementation of pharmacogenetics (PGx) and individualization of drug therapy is supposed to obviate adverse drug reactions or therapy failure. Health care professionals (HCPs) use drug labels (DLs) ...as reliable information about drugs. We analyzed the Swiss DLs to give an overview on the currently available PGx instructions. We screened 4306 DLs applying natural language processing focusing on drug metabolism (pharmacokinetics) and we assigned PGx levels following the classification system of PharmGKB. From 5979 hits, 2564 were classified as PGx-relevant affecting 167 substances. 55% (n = 93) were classified as "actionable PGx". Frequently, PGx information appeared in the pharmacokinetics section and in DLs of the anatomic group "nervous system". Unstandardized wording, appearance of PGx information in different sections and unclear instructions challenge HCPs to identify and interpret PGx information and translate it into practice. HCPs need harmonization and standardization of PGx information in DLs to personalize drug therapies and tailor pharmaceutical care.
The original paper contains a mistake in the acronym AIDE. The AIDE acronym mistake occurs in the title of the section heading and in the following text on p. 6276, and in the text in the section ...“Discussion and outlook on the HE mechanisms” on p. 6277.
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