Uncoupled and coupled approaches to predict macrocrack initiation in fiber reinforced ceramic matrix composites

International audienceLocalized fiber pull-out is one of the fracture features of fiber reinforced ceramic matrix composites. The onset of this mechanism is predicted by using Continuum Damage Mechanics, and corresponds to a localization of the deformations. After deriving two damage models from a uni-axial bundle approach, and criteria at localization, different axisymmetric configurations are analyzed through two different approaches to predict macrocrack initiation

Localization due to damage in fiber-reinforced composites

International audienceFiber pull-out is one of the fracture features of fiber-reinforced ceramic matrix composites. The onset of this mechanism is predicted by using Continuum Damage Mechanics, and corresponds to a localization of the deformations. Alter deriving two damage models from a uniaxial bundle approach, different configurations are analysed through analytical and numerical (F.E. calculations) methods. For one model some very simple criteria can be derived, whereas for the second one none of these criteria can be derived and the general criterion of localization has to be used

Tumour necrosis factor (TNF) and interleukin-1 (IL-1) induce muscle proteolysis through different mechanisms

The purpose of this study was to test the hypothesis that muscle proteolysis induced by TNF or IL-1 is mediated by glucocorticoids. Rats were treated with 300 μg kg−1 of recombinant human preparations of IL-1α (rIL-1α) or TNFα (rTNFα) divided into three equal intraperitoneal doses given over 16 h. Two hours before each cytokine injection, rats were given 5 mg kg−1 of the glucocorticoid receptor blocker mifepristone RU 38486, by gavage or were gavaged with the vehicle. Eighteen hours after the first cytokine injection, total and myofibrillar protein breakdown rates were determined in incubated extensor digitorum longus muscles as release of tyrosine and 3-methylhistidine, respectively. Total and myofibrillar proteolytic rates were increased following injection of rIL-1α or rTNFα. Proteolysis induced by rIL-1α was not altered by treatment with RU 38486. In contrast, the glucocorticoid receptor blocker inhibited the proteolytic effect of rTNFα. The results suggest that the proteolytic effect of TNF is mediated by glucocorticoids and that IL-1 induces muscle proteolysis through a glucocorticoid independent pathway

Influence of Blood-Brain Barrier Integrity on Brain Protein Biomarker Clearance in Severe Traumatic Brain Injury: A Longitudinal Prospective Study.

Brain protein biomarker clearance to blood in traumatic brain injury (TBI) is not fully understood. The aim of this study was to analyze the effect that a disrupted blood-brain barrier (BBB) had on biomarker clearance. Seventeen severe TBI patients admitted to Karolinska University Hospital were prospectively included. Cerebrospinal fluid (CSF) and blood concentrations of S100 calcium binding protein B (S100B) and neuron-specific enolase (NSE) were analyzed every 6-12 h for ∼1 week. Blood and CSF albumin were analyzed every 12-24 h, and BBB integrity was assessed using the CSF:blood albumin quotient (QA). We found that time-dependent changes in the CSF and blood levels of the two biomarkers were similar, but that the correlation between the biomarkers and QA was lower for NSE (ρ = 0.444) than for S100B (ρ = 0.668). Because data were longitudinal, we also conducted cross correlation analyses, which indicated a directional flow and lag-time of biomarkers from CSF to blood. For S100B, this lag-time could be ascribed to BBB integrity, whereas for NSE it could not. Upon inferential modelling, using generalized least square estimation (S100B) or linear mixed models (NSE), QA (p = 0.045), time from trauma (p < 0.001), time from trauma2 (p = 0.023), and CSF biomarker levels (p = 0.008) were independent predictors of S100B in blood. In contrast, for NSE, only time from trauma was significant (p < 0.001). These findings are novel and important, but must be carefully interpreted because of different characteristics between the two proteins. Nonetheless, we present the first data that indicate that S100B and NSE are cleared differently from the central nervous system, and that both the disrupted BBB and additional alternative pathways, such as the recently described glymphatic system, may play a role. This is of importance both for clinicians aiming to utilize these biomarkers and for the pathophysiological understanding of brain protein clearance, but warrants further examination

Weight velocity in addition to latest weight does not improve the identification of wasting, or the prediction of stunting and mortality: a longitudinal analysis using data from Malawi, South Africa, and Pakistan

Background In low/middle-income countries, most nutritional assessments use the latest weights, without reference to growth trajectory. Objective This study explores whether velocity, in addition to the latest weight, improves the prediction of wasting, stunting or mortality in the first two years of life. Methods We analysed a combined data set with weight and height data collected monthly in the first year of 3447 children from Pakistan, Malawi, South Africa, with height and survival recorded till 24 months. The main exposures were weight-for-age z-score (WAZ) at the end of each 2-month period and weight velocity-for-age z-score (WVZ2) across that period. The outcomes were wasting, stunting or all-cause mortality in the next 1-2 months. As a sensitivity analysis, we also used WVZ over 6 months (WVZ6), with matching WAZ. Cox proportional hazard models with repeated growth measures were used to study the association between exposures and mortality. Mixed Poisson models were used for stunting and wasting. Results Children who were already stunted or wasted were most likely to remain so. WVZ2 was associated with a lower risk of subsequent stunting (RR 0.95; 95% CI 0.93-0.96), but added minimal prediction (difference in AUC = 0.004) compared to a model including only WAZ. Similarly, WVZ2 was associated with wasting (RR 0.74; 95% CI 0.72-0.76) but the prediction was only marginally greater than for WAZ (difference in AUC = 0.015). Compared to WAZ, WVZ6 was less predictive for both wasting and stunting. Low WVZ6 (but not WVZ2) was associated with increased mortality (HR 0.75, 95% CI 0.67-0.85), but added marginal only prediction to a model including WAZ alone (difference in C = 0.015). Conclusions The key anthropometric determinant of impending wasting, stunting, and mortality appears to be how far below the normal range the child’s weight is, rather than how they reached that position

Use of GRADE for assessment of evidence about prognosis: rating confidence in estimates of event rates in broad categories of patients.

Summary pointsMain concepts- The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) approach defines quality of evidence as confidence in effect estimates; this conceptualization can readily be applied to bodies of evidence estimating the risk of future of events (that is, prognosis) in broadly defined populations- In the field of prognosis, a body of observational evidence (including single arms of randomized controlled trials) begins as high quality evidence- The five domains GRADE considers in rating down confidence in estimates of treatment effect—that is, risk of bias, imprecision, inconsistency, indirectness, and publication bias—as well as the GRADE criteria for rating up quality, also apply to estimates of the risk of future of events from a body of prognostic studies- Applying these concepts to systematic reviews of prognostic studies provides a useful approach to determine confidence in estimates of overall prognosis in broad populationsLay summary- The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to rating confidence in the results of research studies was initially developed for therapeutic questions- The GRADE approach considers study design (randomized trials versus non-randomized designs), risk of bias, inconsistency, imprecision, indirectness, and publication bias; size and trend in the effect are also considered- Observational studies looking at patients’ prognosis may provide robust estimates of the likelihood of undesirable or desirable outcomes in both treated and untreated patients- Patients will often find this information helpful in understanding the likely course of their disease, in planning their future, and in engaging in shared decision making with their healthcare providers- In a previous article, we examined factors that affect confidence in estimates of baseline risk (the risk of bad outcomes in untreated patients), providing examples of how this might influence the confidence in estimates of absolute treatment effect- This paper provides guidance for the use of the GRADE approach to determine confidence in estimates of future events in systematic reviews of prognostic studies in broad categories of patient

Ecosystem Stewardship: Sustainability Strategies for a Rapidly Changing Planet

Ecosystem stewardship is an action-oriented framework intended to foster social-ecological sustainability of a rapidly changing planet. Recent developments identify three strategies that make optimal use of current understanding in an environment of inevitable uncertainty and abrupt change: reducing the magnitude of, and exposure and sensitivity to, known stresses; focusing on proactive policies that shape change; and avoiding or escaping unsustainable social-ecological traps. All social-ecological systems are vulnerable to recent and projected changes but have sources of adaptive capacity and resilience that can sustain ecosystem services and human well-being through active ecosystem stewardship