41 research outputs found
\u3ci\u3eBoise Cascade Corp. v. State of Oregon\u3c/i\u3e:Signaling the End of Sovereign Immunity as a Shield for Environmental Regulation
The response of composite cylindrical shells with cutouts and subjected to internal pressure and axial compression loads
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76299/1/AIAA-1998-1768-190.pd
A numerical and experimental study of the response of selected compression-loaded composite shells with cutouts
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76998/1/AIAA-1998-1988-596.pd
Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis
Inflammation is a necessary albeit insufficient component of tumorigenesis in some cancers. Infectious agents directly implicated in tumorigenesis have been shown to induce inflammation. This process involves both the innate and adaptive components of the immune system which contribute to tumor angiogenesis, tumor tolerance and metastatic properties of neoplasms. Recently, heat-shock proteins have been identified as mediators of this inflammatory process and thus may provide a link between infection-mediated inflammation and subsequent cancer development. In this review, the role of heat-shock proteins in infection-induced inflammation and carcinogenesis will be discussed
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Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021
BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation
Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome
Parametric Study on the Response of Compression-Loaded Composite Shells With Geometric and Material Imperfections
The results of a parametric study of the effects of initial imperfections on the buckling and postbuckling response of three unstiffened thinwalled compression-loaded graphite-epoxy cylindrical shells with different orthotropic and quasi-isotropic shell-wall laminates are presented. The imperfections considered include initial geometric shell-wall midsurface imperfections, shell-wall thickness variations, local shell-wall ply-gaps associated with the fabrication process, shell-end geometric imperfections, nonuniform applied end loads, and variations in the boundary conditions including the effects of elastic boundary conditions. A high-fidelity nonlinear shell analysis procedure that accurately accounts for the effects of these imperfections on the nonlinear responses and buckling loads of the shells is described. The analysis procedure includes a nonlinear static analysis that predicts stable response characteristics of the shells and a nonlinear transient analysis that predicts unstable response characteristics
Buckling Behavior of Compression-Loaded Composite Cylindrical Shells with Reinforced Cutouts
Results from a numerical study of the response of thin-wall compression-loaded quasi-isotropic laminated composite cylindrical shells with reinforced and unreinforced square cutouts are presented. The effects of cutout reinforcement orthotropy, size, and thickness on the nonlinear response of the shells are described. A high-fidelity nonlinear analysis procedure has been used to predict the nonlinear response of the shells. The analysis procedure includes a nonlinear static analysis that predicts stable response characteristics of the shells and a nonlinear transient analysis that predicts unstable dynamic buckling response characteristics. The results illustrate how a compression-loaded shell with an unreinforced cutout can exhibit a complex nonlinear response. In particular, a local buckling response occurs in the shell near the cutout and is caused by a complex nonlinear coupling between local shell-wall deformations and in-plane destabilizing compression stresses near the cutout. In general, the addition of reinforcement around a cutout in a compression-loaded shell can retard or eliminate the local buckling response near the cutout and increase the buckling load of the shell, as expected. However, results are presented that show how certain reinforcement configurations can actually cause an unexpected increase in the magnitude of local deformations and stresses in the shell and cause a reduction in the buckling load. Specific cases are presented that suggest that the orthotropy, thickness, and size of a cutout reinforcement in a shell can be tailored to achieve improved response characteristics
High-Fidelity Nonlinear Analysis of Compression-Loaded Composite Shells
The results of an experimental and analytical study of the effects of initial imperfections on the buckling and postbuckling response of unstiffened thin-walled compression-loaded graphite-epoxy cylindrical shells are presented. The shells considered in the study have four different shell-wall laminates and two different shell-radius-to-thickness ratios. The shell-wall laminates include two different orthotropic laminates and two different quasi-isotropic laminates. The shell-radius-to-thickness ratios include shell-radius-to-thickness ratios equal to 100 and 200. The results identify the effects of traditional and nontraditional initial imperfections on the nonlinear response characteristics and buckling loads of the shells. The traditional imperfections include the geometric shell-wall mid-surface imperfections that are commonly discussed in the literature on thin shell buckling. The nontraditional imperfections include shell-wall thickness variations, local shell-wall ply-gaps associated with the fabrication process, shell-end geometric imperfections, nonuniform applied end loads, and variations in the boundary conditions including the effects of elastic boundary conditions. A high-fidelity nonlinear shell analysis procedure that accurately accounts for the effects of these traditional and nontraditional imperfections on the nonlinear response characteristics and buckling loads of the shells is described. The analysis procedure includes a nonlinear static analysis that predicts the stable response characteristics of the shells, and a nonlinear transient analysis that predicts the unstable response characteristics. The results of a local shell-wall stress analysis used to estimate failure stresses are also described
Buckling and Failure of Compression-Loaded Composite Cylindrical Shells With Geometric and Material Imperfections
The results of an experimental and numerical study of the effects of initial imperfections on the buckling response and failure of unstiffened thin-walled compression-loaded graphite-epoxy cylindrical shells are presented. The shells considered in the study have six different orthotropic or quasi-isotropic shell-wall laminates and two different shell-radius-to-thickness ratios. The numerical results include the effects of geometric shell-wall mid-surface imperfections, shell-wall thickness variations, local shell-wall ply-gaps associated with the fabrication process, shell-end geometric imperfections, nonuniform end loads, and the effects of elastic boundary conditions. Selected cylinder parameter uncertainties were also considered. Results that illustrate the effects of imperfections and uncertainties on the nonlinear response characteristics, buckling loads and failure the shells are presented. In addition, a common failure analysis is used to predict material failures in the shells