101 research outputs found
Numerical Modelling Approaches for the Analysis of Earthquake Triggered Landslides
Different numerical approaches for the analysis of earthquake triggered landslides are studied. Improved simplified models are developed and their performance for evaluating the response of natural slopes subjected to earthquakes is studied. Using more sophisticated numerical techniques the influence of several factors such as the hydro mechanical behavior assumptions, 1D vs. 2D geometry, and the input motion are assessed. 2D computations have shown that the kinematics of the slope motion is largely affected by the geometry of the slope. As far as the soil behavior is concerned, the results indicate that introduction of progressive yielding in the soil model provides larger displacement, progressive pore-pressure generation and more diffuse deformation. For the input motion, the number of peaks and their amplitudes have been identified as being the mains factors for irreversible displacements
Impacts of changes in groundwater recharge on the isotopic composition and geochemistry of seasonally ice-covered lakes: insights for sustainable management
Lakes are under increasing pressure due to widespread anthropogenic impacts
related to rapid development and population growth. Accordingly, many lakes
are currently undergoing a systematic decline in water quality. Recent
studies have highlighted that global warming and the subsequent changes in
water use may further exacerbate eutrophication in lakes. Lake evolution
depends strongly on hydrologic balance, and therefore on groundwater
connectivity. Groundwater also influences the sensitivity of lacustrine
ecosystems to climate and environmental changes, and governs their
resilience. Improved characterization of groundwater exchange with lakes is
needed today for lake preservation, lake restoration, and sustainable
management of lake water quality into the future. In this context, the aim of
the present paper is to determine if the future evolution of the climate, the
population, and the recharge could modify the geochemistry of lakes (mainly
isotopic signature and quality via phosphorous load) and if the isotopic
monitoring of lakes could be an efficient tool to highlight the variability
of the water budget and quality.
Small groundwater-connected lakes were chosen to simulate changes in water
balance and water quality expected under future climate change scenarios,
namely representative concentration pathways (RCPs) 4.5 and 8.5. Contemporary
baseline conditions, including isotope mass balance and geochemical
characteristics, were determined through an intensive field-based research
program prior to the simulations. Results highlight that future lake
geochemistry and isotopic composition trends will depend on four main
parameters: location (and therefore climate conditions), lake catchment size
(which impacts the intensity of the flux change), lake volume (which impacts
the range of variation), and lake G index (i.e., the percentage of
groundwater that makes up total lake inflows), the latter being the dominant
control on water balance conditions, as revealed by the sensitivity of lake
isotopic composition. Based on these model simulations, stable isotopes
appear to be especially useful for detecting changes in recharge to lakes
with a G index of between 50 and 80âŻ%, but response is non-linear.
Simulated monthly trends reveal that evolution of annual lake isotopic
composition can be dampened by opposing monthly recharge fluctuations. It is
also shown that changes in water quality in groundwater-connected lakes
depend significantly on lake location and on the intensity of recharge
change
Safety of atmospheric storage tanks during accidental explosions
International audienceThe occurrence of a chain reaction from blast on atmospheric storage tanks in oil and chemical facilities is hard to predict. The current French practice for SEVESO facilities ignores projectiles and assumes a critical peak overpressure value observed from accident data. This method could lead to conservative or dangerous assessments. This study presents various simple mechanical models to facilitate quick effective assessment of risk analysis, the results of which are compared with the current practice. The damage modes are based on experience of the most recent accidents in France. Uncertainty propagation methods are used in order to evaluate the sensitivity and the failure probability of global tank models for a selection of overpressure signatures. The current work makes use of these evaluations to demonstrate the importance of a dynamic analysis to study domino effects in accidents.L'occurrence de réaction en chaßne, dite réaction par effets dominos, sur les réservoirs de stockage atmosphérique suite à une explosion accidentelle dans les installations pétrochimiques est difficile à prévoir. La pratique actuelle française pour les installations SEVESO consiste à ignorer les projectiles et à assumer une valeur de surpression maximale admissible pour les effets de souffle. Cette méthode est susceptible de conduire à des évaluations conservatrices ou dangereuses. Cette étude présente divers modÚles mécaniques simples pouvant permettre une évaluation efficace et rapide des risques d'effet dominos. Les modes de comportement des réservoirs sont basées sur l'expérience des plus récents accidents en France. Plusieurs méthodes de propagation des incertitudes sont utilisées afin d'évaluer les sensibilités et la probabilité de défaillance des modÚles de réservoir pour une sélection de signaux de surpression. L'étude aboutie sur la sélection de paramÚtres et de modÚles dynamiques pertinents pour l'étude des effets dominos
Impacts of changes in groundwater recharge on the isotopic composition and geochemistry of seasonally ice-covered lakes: insights for sustainable management
Lakes are under increasing pressure due to widespread anthropogenic impacts
related to rapid development and population growth. Accordingly, many lakes
are currently undergoing a systematic decline in water quality. Recent
studies have highlighted that global warming and the subsequent changes in
water use may further exacerbate eutrophication in lakes. Lake evolution
depends strongly on hydrologic balance, and therefore on groundwater
connectivity. Groundwater also influences the sensitivity of lacustrine
ecosystems to climate and environmental changes, and governs their
resilience. Improved characterization of groundwater exchange with lakes is
needed today for lake preservation, lake restoration, and sustainable
management of lake water quality into the future. In this context, the aim of
the present paper is to determine if the future evolution of the climate, the
population, and the recharge could modify the geochemistry of lakes (mainly
isotopic signature and quality via phosphorous load) and if the isotopic
monitoring of lakes could be an efficient tool to highlight the variability
of the water budget and quality.
Small groundwater-connected lakes were chosen to simulate changes in water
balance and water quality expected under future climate change scenarios,
namely representative concentration pathways (RCPs) 4.5 and 8.5. Contemporary
baseline conditions, including isotope mass balance and geochemical
characteristics, were determined through an intensive field-based research
program prior to the simulations. Results highlight that future lake
geochemistry and isotopic composition trends will depend on four main
parameters: location (and therefore climate conditions), lake catchment size
(which impacts the intensity of the flux change), lake volume (which impacts
the range of variation), and lake G index (i.e., the percentage of
groundwater that makes up total lake inflows), the latter being the dominant
control on water balance conditions, as revealed by the sensitivity of lake
isotopic composition. Based on these model simulations, stable isotopes
appear to be especially useful for detecting changes in recharge to lakes
with a G index of between 50 and 80âŻ%, but response is non-linear.
Simulated monthly trends reveal that evolution of annual lake isotopic
composition can be dampened by opposing monthly recharge fluctuations. It is
also shown that changes in water quality in groundwater-connected lakes
depend significantly on lake location and on the intensity of recharge
change
âI h 8 uâ: Findings from a five-year study of text and e-mail bullying
Copyright @ 2010 British Educational Research Association. The final version of this article is available at the link below.This study charts reports of nasty or threatening text and e-mail messages received by students in academic years 7 and 8 (11-13 years of age) attending 13 secondary schools in the North of England between 2002-2006. Annual surveys were undertaken on behalf of the local education authority (LEA) to monitor bullying. Results indicated that, over five years, the number of pupils receiving one or more nasty or threatening text messages or e-mails increased significantly, particularly among girls. However, receipt of frequent nasty or threatening text and e-mail messages remained relatively stable. For boys, being a victim of direct-physical bullying was associated with receiving nasty or threatening text and e-mail messages; for girls it was being unpopular among peers. Boys received more hate-related messages and girls were primarily the victims of name-calling, Findings are discussed with respect to theoretical and policy developments, and recommendations for future research are offered
Topical NSAIDs for acute pain: a meta-analysis
BACKGROUND: A previous systematic review reported that topical NSAIDs were effective in relieving pain in acute conditions like sprains and strains, with differences between individual drugs for efficacy. More trials, a better understanding of trial quality and bias, and a reclassification of certain drugs necessitate a new review. METHODS: Studies were identified by searching electronic databases and writing to manufacturers. We selected randomised double blind trials comparing topical NSAID with either placebo or another active treatment in adults with acute pain, and extracted dichotomous information approximating to a 50% reduction in pain at one week, together with details of adverse events and withdrawals. Relative benefit and number-needed-to-treat (NNT), and relative risk and number-needed-to-harm (NNH) were calculated, with sensitivity analyses where appropriate to investigate differences between individual drugs and aspects of trial design. RESULTS: Twenty-six double blind placebo controlled trials had information from 2,853 patients for evaluation of efficacy. Topical NSAID was significantly better than placebo in 19 of the 26 trials, with a pooled relative benefit of 1.6 (95% confidence interval 1.4 to 1.7), and NNT of 3.8 (95% confidence interval 3.4 to 4.4) compared with placebo for the outcome of half pain relief at seven days. Results were not affected by outcome reported, or condition treated, but smaller trials yielded a larger estimate of efficacy. Indirect comparisons of individual topical NSAIDs showed that ketoprofen was significantly better than all other topical NSAIDs, while indomethacin was barely distinguished from placebo. Three trials, with 433 patients, compared topical with oral NSAID (two trials compared the same drug, one compared different drugs) and found no difference in efficacy. Local adverse events, systemic adverse events, or withdrawals due to an adverse event were rare, and no different between topical NSAID and placebo. CONCLUSIONS: Topical NSAIDs were effective and safe in treating acute painful conditions for one week
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19
Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15â20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5â528.7, P = 1.1 Ă 10â4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3â8.2], P = 2.1 Ă 10â4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1â2635.4], P = 3.4 Ă 10â3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3â8.4], P = 7.7 Ă 10â8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 Ă 10â5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old
Autoantibodies against type I IFNs in patients with life-threatening COVID-19
Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men
Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs
Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population
C. PRESL) at the transcriptional level.
This paper investigates differences in gene expression among the two Thlaspi caerulescens ecotypes La Calamine (LC) and Lellingen (LE) that have been shown to differ in metal tolerance and metal uptake. LC originates from a metalliferous soil and tolerates higher metal concentrations than LE which originates from a non-metalliferous soil. The two ecotypes were treated with different levels of zinc in solution culture, and differences in gene expression were assessed through application of a cDNA microarray consisting of 1,700 root and 2,700 shoot cDNAs. Hybridisation of root and shoot cDNA from the two ecotypes revealed a total of 257 differentially expressed genes. The regulation of selected genes was verified by quantitative reverse transcriptase polymerase chain reaction. Comparison of the expression profiles of the two ecotypes suggests that LC has a higher capacity to cope with reactive oxygen species and to avoid the formation of peroxynitrite. Furthermore, increased transcripts for the genes encoding for water channel proteins could explain the higher Zn tolerance of LC compared to LE. The higher Zn tolerance of LC was reflected by a lower expression of the genes involved in disease and defence mechanisms. The results of this study provide a valuable set of data that may help to improve our understanding of the mechanisms employed by plants to tolerate toxic concentrations of metal in the soil
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