This review traces the examination of autonomic, cardiovascular, and respiratory derangements associated with seizure activity in the clinical and preclinical literature generally, and in the ...author's animal model specifically, and concludes with the author's views on the potential mechanisms for sudden death in epilepsy (SUDEP). An animal model that employs kainic acid-induced seizures on a background of urethane anesthesia has permitted unprecedented access to the behavior of autonomic, cardiovascular, and respiratory systems during seizure activity. The result is a detailed description of the major causes of death and how this animal model can be used to develop and test preventative and interventional strategies. A critical translational step was taken when the rat data were shown to directly parallel data from definite SUDEP cases in the clinical literature. The reasons why ventricular fibrillation as a cause of death is so rarely reported and tools for verifying that seizure-associated laryngospasm can induce obstructive apnea as a cause of death are discussed in detail. Many details of the specific kinetics of activation of brainstem neurons serving autonomic and respiratory function remain to be elucidated, but the boundary conditions described in this review provide an excellent framework for more focused studies. A number of studies conducted in animal models of seizure activity and in epilepsy patients have contributed information on the autonomic, cardiovascular, and respiratory consequences of seizure activity spreading through hypothalamus and brainstem to the periphery. The result is detailed information on the systemic impact of seizure spread and the development of an understanding of the essential mechanistic features of sudden unexpected death in epilepsy (SUDEP). This review summarizes translation of data obtained from animal models to biomarkers that are useful in evaluating data from epilepsy patients.
A spatial time-dependent reliability model is developed for a RC beam subject to corrosion-induced pitting corrosion, for shear and flexural limit states. The analysis considers the spatial and ...time-dependent variability of pitting corrosion, structural resistance and load effects. The amount of corrosion loss can significantly affect the mechanical behaviour of reinforcement, namely low corrosion loss can result in ductile yielding, whereas a higher corrosion loss can result in brittle fracture. The progression from ductile to brittle behaviour is spatially and time-dependent. To estimate how such phenomena affects structural reliability the structural resistance of reinforcement is modelled as either (i) perfectly ductile parallel system or (ii) perfectly brittle parallel system. It was found that the probability of failure assuming brittle reinforcement behaviour is up to 450% higher than assuming ductile behaviour.
Characterization of tumors utilizing next‐generation sequencing methods, including assessment of the number of somatic mutations (tumor mutational burden TMB), is currently at the forefront of the ...field of personalized medicine. Recent clinical studies have associated high TMB with improved patient response rates and survival benefit from immune checkpoint inhibitors; hence, TMB is emerging as a biomarker of response for these immunotherapy agents. However, variability in current methods for TMB estimation and reporting is evident, demonstrating a need for standardization and harmonization of TMB assessment methodology across assays and centers. Two uniquely placed organizations, Friends of Cancer Research (Friends) and the Quality Assurance Initiative Pathology (QuIP), have collaborated to coordinate efforts for international multistakeholder initiatives to address this need. Friends and QuIP, who have partnered with several academic centers, pharmaceutical organizations, and diagnostic companies, have adopted complementary, multidisciplinary approaches toward the goal of proposing evidence‐based recommendations for achieving consistent TMB estimation and reporting in clinical samples across assays and centers. Many factors influence TMB assessment, including preanalytical factors, choice of assay, and methods of reporting. Preliminary analyses highlight the importance of targeted gene panel size and composition, and bioinformatic parameters for reliable TMB estimation. Herein, Friends and QuIP propose recommendations toward consistent TMB estimation and reporting methods in clinical samples across assays and centers. These recommendations should be followed to minimize variability in TMB estimation and reporting, which will ensure reliable and reproducible identification of patients who are likely to benefit from immune checkpoint inhibitors.
•We compared six analytical methods BFI values to a mass balance method, the CMB method.•One of six analytical methods, power function method best matched mass balance method.•Five un-calibrated ...analytical base flow methods did not match the mass balance method.•After calibration, analytical methods closely matched the mass balance method.
Base flow is the ground water contribution to stream flow. Many activities, such as water resource management, calibrating hydrological and climate models, and studies of basin hydrology, require good estimates of base flow. The base flow component of stream flow is usually determined by separating a stream hydrograph into two components, base flow and runoff. Analytical methods, mathematical functions or algorithms used to calculate base flow directly from discharge, are the most widely used base flow separation methods and are often used without calibration to basin or gage-specific parameters other than basin area. In this study, six analytical methods are compared to a mass balance method, the conductivity mass-balance (CMB) method. The base flow index (BFI) values for 35 stream gages are obtained from each of the seven methods with each gage having at least two consecutive years of specific conductance data and 30years of continuous discharge data. BFI is cumulative base flow divided by cumulative total discharge over the period of record of analysis. The BFI value is dimensionless, and always varies from 0 to 1. Areas of basins used in this study range from 27km2 to 68,117km2.
BFI was first determined for the uncalibrated analytical methods. The parameters of each analytical method were then calibrated to produce BFI values as close to the CMB derived BFI values as possible. One of the methods, the power function (aQb+cQ) method, is inherently calibrated and was not recalibrated. The uncalibrated analytical methods have an average correlation coefficient of 0.43 when compared to CMB-derived values, and an average correlation coefficient of 0.93 when calibrated with the CMB method. Once calibrated, the analytical methods can closely reproduce the base flow values of a mass balance method. Therefore, it is recommended that analytical methods be calibrated against tracer or mass balance methods.
Review of Mel Stanfill, Exploiting fandom: How the media industry seeks to manipulate fans. Iowa City: University of Iowa Press, 2019, paperback, $75 (262p), ISBN 978-1609386238.
•Blast-resistant design using Ultra-high Performance Concrete (UHPC) columns.•Explosive ordnance and terrorism blast scenarios were considered.•Probability of major damage for a UHPC column varies ...from 1 × 10−2 to 1 × 10−5.•Decision metrics were target reliabilities and cost-benefit assessment.•Risk reducing benefit of blast-resistant UHPC columns can be considerable.
In conventional structural protective design against blast loads conservative structural designs are anticipated. However, unknown factors that include threat uncertainty, blast load variation, construction methods, material quality, etc., could impact the accuracy of assessment and design, sometimes even leading to an overestimation of structural capacity to explosive blast effects or an underestimation of actual blast pressures. In the present study, structural safety and reliability analyses of Ultra-high Performance Concrete (UHPC) columns under varying blast scenarios are performed. The variation in column dimensions, steel reinforcement, UHPC material strength, explosive range and mass, and numerical and blast load model errors are considered. The peak reflected pressure and impulse from the selected blast scenarios are derived based on variation in the explosive mass and standoff distance. Failure probabilities of columns made of this emerging high performance concrete material are then estimated. It was found that for a UHPC column designed for blast the probability of major damage given an explosive blast load varies from 1 × 10−2 to 1 × 10−5 for explosive ordnance and terrorism blast scenarios. This provides a reasonable margin of safety against major structural damage. It was also found that the risk reducing benefit of blast-resistant UHPC columns can be considerable.
► We study the effects of climate change on the durability of corroding RC structures. ► Simplified climate models including climate change scenarios are presented. ► Climate change could reduce RC ...durability significantly. ► The time-to-failure and service life decrease by up to 31% or 15years, respectively. ► We outlined the needs for an optimal risk-based selection of adaptation strategies.
Chloride ingress and carbonation cause corrosion of reinforced concrete (RC) structures affecting its operational life. Experimental evidence indicates that these deterioration processes are highly influenced by CO2 emissions and climatic conditions in the surrounding environment – i.e., temperature, humidity, etc. Since studies on global warming announce changes in climate, the impact of changing climate on RC durability should also be considered. This paper links RC deterioration mechanisms to CO2 emissions and global warming. Based on various studies on climate change, models for estimating the effect of CO2 emissions and temperature/humidity changes due to global warming are described. Furthermore, various scenarios of global warming that can be used to assess the effect of climate change in structural reliability are proposed. The proposed approach is then illustrated with a numerical example that calculates the probability of failure of a RC bridge beam for future climate scenarios. The paper then outlines some adaptation strategies, particularly focusing on the needs for risk-based selection of optimal adaptation measures.
•New stochastic model for casualty risks to fragmentation hazard.•Probabilistic models of fragment generation, trajectories, and human vulnerability.•Numerical simulations for fragment densities and ...casualty risks.•Safety evacuation distance obtained based on the casualty risks.
Fatalities and injuries are mainly attributed to primary fragmentation if accidental or malevolent detonation of high-explosive munitions occurs in an open space. This study aims to develop a simulation-based approach to assess individual casualty risks from primary fragments naturally generated by detonation of high-explosive munitions, which enables a stochastic characterization of fragment generation, trajectories, modelling uncertainties, and human vulnerability. The proposed method is demonstrated by a numerical example estimating the fatality and injury risks for an individual in a standing position exposed to the detonation of a single 105 mm projectile. The results suggest that, as expected, the individual fatality and injury risks decrease with an increasing stand-off distance. At a stand-off distance greater than 40 m, an individual is more likely to suffer injuries rather than fatality. The safety distance obtained from the present study is 97 m which is close to but less conservative than a safety distance of 104 m in existing literature and standards.
•Probabilistic modelling of construction defects in housing.•Bayesian approach combining expert opinion, HRA method and limited defect data.•Integration of construction defect model into wind ...fragility assessment.•Considerable effect of construction defects on roof cladding fragility is predicted.
Post-damage observations reveal that construction error is one of the major contributors to roof damage for houses subjected to extreme winds. In this study, a Bayesian approach was developed to probabilistically quantify the construction defect rates in roof connections, which enables a systematic integration of expert judgement, human reliability analysis (HRA) techniques and limited construction defect data. The reductions of uplift capacities for defective roof connections were also probabilistically modelled based on experimental evidence and engineering judgement. The developed construction defect model was incorporated in a reliability-based fragility method to assess the wind damage to metal roof cladding and timber roof trusses for contemporary houses in non-cyclonic regions of Australia. It was found that, the effects of construction defects are significant for the predicted roof cladding fragility, whereas for roof truss fragility, such effects are lower.
Atmospheric CO2 is a major cause of reinforcement corrosion in bridges, buildings, wharves, and other concrete infrastructure in Australia, United States, United Kingdom and most other countries. The ...increase in CO2 levels associated with global warming will increase the likelihood of carbonation-induced corrosion. Moreover, temperature rises will increase corrosion rates. Clearly, the impact of climate change on existing and new infrastructure is considerable, as corrosion damage is disruptive to society and costly to repair. The paper describes a probabilistic and reliability-based approach that predicts the probability of corrosion initiation and damage (severe cracking) for concrete infrastructure subjected to carbonation and chloride-induced corrosion resulting from elevated CO2 levels and temperatures. The atmospheric CO2 concentration and local temperature and relative humidity changes with time over the next 100 years in the Australian cities of Sydney and Darwin are projected based on nine General Circulation Models (GCMs) under (i) high CO2 emission scenario, (ii) medium CO2 emission scenario, and (iii) CO2 emission reduction scenario based on policy intervention. The probabilistic analysis included the uncertainty of CO2 concentration, deterioration processes, material properties, dimensions, and predictive models. It was found that carbonation-induced damage risks can increase by over 400% over a time period to 2100 for some regions in Australia. Damage risks for chloride-induced corrosion increase by no more than 15% over the same time period due to temperature increase, but without consideration of ocean acidity change in marine exposure. Corrosion loss of reinforcement is not significant. The results were most sensitive to increases in atmospheric CO2.
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