Blood–Brain Barrier Transporters: Opportunities for Therapeutic Development in Ischemic Stroke

Globally, stroke is a leading cause of death and long-term disability. Over the past decades, several efforts have attempted to discover new drugs or repurpose existing therapeutics to promote post-stroke neurological recovery. Preclinical stroke studies have reported successes in identifying novel neuroprotective agents; however, none of these compounds have advanced beyond a phase III clinical trial. One reason for these failures is the lack of consideration of blood–brain barrier (BBB) transport mechanisms that can enable these drugs to achieve efficacious concentrations in ischemic brain tissue. Despite the knowledge that drugs with neuroprotective properties (i.e., statins, memantine, metformin) are substrates for endogenous BBB transporters, preclinical stroke research has not extensively studied the role of transporters in central nervous system (CNS) drug delivery. Here, we review current knowledge on specific BBB uptake transporters (i.e., organic anion transporting polypeptides (OATPs in humans; Oatps in rodents); organic cation transporters (OCTs in humans; Octs in rodents) that can be targeted for improved neuroprotective drug delivery. Additionally, we provide state-of-the-art perspectives on how transporter pharmacology can be integrated into preclinical stroke research. Specifically, we discuss the utility of in vivo stroke models to transporter studies and considerations (i.e., species selection, co-morbid conditions) that will optimize the translational success of stroke pharmacotherapeutic experiments.     

Modeling improvements in booster seat use: a discrete choice conjoint experiment

Automobile crashes are the leading cause of death in children aged 1–14 years. Many children, however, are not properly restrained in safety seats that reduce serious injury and death. This study used a discrete choice conjoint experiment to study factors influencing the decision to use booster seats. Parents of 1714 children aged 4–9 years from nine Canadian provinces completed choice tasks presenting experimentally varied combinations of 15 4-level booster seat promotion attributes. Latent class analysis yielded three segments of parents. The choices of the Benefit Sensitive segment (50%) were most sensitive to the injury prevention benefits of booster seats. The choices of parents in the Context Sensitive segment (33.5%) were more likely to be influenced by installation complexity, oppositional behavior, and the prospect that their child may be teased for riding in booster seats. Parents in the High Risk segment (16.5%) were younger, less educated, and less knowledgeable about vehicle safety legislation. They anticipated fewer benefits, expected more barriers and were less likely to use booster seats. Simulations suggest that consistent enforcement coupled with advertising focusing on injury prevention and the use of booster seats by other parents would increase adoption.     

Vibration-based crack prediction on a beam model using hybrid butterfly optimization algorithm with artificial neural network

Vibration-based damage detection methods have become widely used because of their advantages over traditional methods. This paper presents a new approach to identify the crack depth in steel beam structures based on vibration analysis using the Finite Element Method (FEM) and Artificial Neural Network (ANN) combined with Butterfly Optimization Algorithm (BOA). ANN is quite successful in such identification issues, but it has some limitations, such as reduction of error after system training is complete, which means the output does not provide optimal results. This paper improves ANN training after introducing BOA as a hybrid model (BOA-ANN). Natural frequencies are used as input parameters and crack depth as output. The data are collected from improved FEM using simulation tools (ABAQUS) based on different crack depths and locations as the first stage. Next, data are collected from experimental analysis of cracked beams based on different crack depths and locations to test the reliability of the presented technique. The proposed approach, compared to other methods, can predict crack depth with improved accuracy.     

From outpost to outback: project career paths in Australia

With the growth in project management as a form of work organisation in many sectors of the economy has come the significant rise in the number of project managers and project team members. This change in work organisation brings issues in forging career paths and determining career support in work situations that are often dynamic, short lived and intense. In the relatively small but substantially robust Australian economy, a unique labour market and the tyranny of distance bring their own difficulties. Innovative and collaborative project structures and increasing prevalence of contract work provide both challenges and opportunities for new career pathways in many industries. A growing percentage of Australia's workforce is employed in project-based or project-oriented organisations, leading to the claim that Australia is a project-based economy. This provided a context for our research into the career paths and the issues of career management for project managers working in a project based economy. Using in-depth interviews with project managers from three industry areas we found generational and gender differences in experiences of work, workplace support and mentoring for career development. For a continued strong performance in this economy, organisations that employ project personnel will need to consider how they will ensure the supply of high quality project professionals into the future.     

Human Response to Emergency Communication: A Review of Guidance on Alerts and Warning Messages for Emergencies in Buildings

The purpose of this article is to provide guidance on enhancing human response to emergency communication. This guidance can, in turn, help engineers improve the design of emergency notification and messaging systems, which, as a result, can help inform occupant response, reduce occupant evacuation time, and increase occupant safety. The article begins with a literature review on how people respond to emergencies. The Protective Action Decision Model, which describes the decision-making process that precedes human response in disaster events, is used as a framework for the literature collected as part of this review. This model is divided into three pre-decisional and five decisional processes. The method used to create the guidance document is then explained, including the six steps taken to review the literature collected (from 162 engineering and social science sources), generate findings from this literature, and compile the key statements found in the guidance document. Guidance on alerts, visual/audible warnings and dissemination of warning messages are provided. These are organized according to alert/warning type and dissemination method. The findings of the literature review include five guidance statements on alerts, 16 guidance statements on visual warnings, seven guidance statements on audible warnings and eight guidance statements on the dissemination of warning messages. Finally, guidance on emergency message testing, including language, readability and fire drills as a means of response testing, is provided. It is envisioned that this guidance will inform practitioners on the design of future emergency communications and subsequently enhances evacuee performance through a better understanding of the manner in which emergency information is processed and the tools available to provide such information.     

Lean heptane and propane combustion in a non-catalytic parallel-plate counter-flow reactor

Small scale lean combustors, in conjunction with mechanical and electrical conversion devices, have the potential to meet increasing portable power needs. This study examines the combustion of lean premixed fuels in a mesoscale, heat-recirculating parallel-plate counter-flow reactor. The reactor utilizes internal heat recirculation to produce temperatures in excess of the adiabatic flame temperature, known as superadiabatic combustion. As a result of these elevated temperatures, burning velocities above adiabatic values and extension of flammability limits, including stable operation at very lean equivalence ratios, may be attained. Combustor stability and emissions of carbon monoxide, nitrogen oxides, and unburned hydrocarbons have been previously studied for lean combustion of methane in the counter-flow reactor. This study examines lean combustion of two increasingly complex fuels, propane and heptane, due to the logistical importance of both gaseous and liquid fuels. Stability ranges and emissions measurements are presented for the counter-flow reactor operating on these fuels, and the results are compared to previously measured emissions for lean methane. Stability ranges of the counter-flow reactor operating on lean propane and heptane are also compared to those in the rich regime. Further analysis of the results for lean methane, propane and heptane combustion utilizes peak reactor wall temperatures as an indicator of favorable operating conditions, and highlights the importance of superadiabatic operation for achieving large turn-down ratios and low levels of emissions.     

Using non-food information to identify food-choice segment membership

Food companies, governments, and societal organizations use an increasing number of food-choice motives to persuade consumers to buy food products, and the question which combinations of motives matter for which type of consumer has become of central relevance. In this study, we use a concomitant mixture-modeling approach to uncover consumer segments in terms of food-choice motives, using a nationwide sample in the Netherlands. The results reveal seven segments with distinct profiles and demonstrate that age and membership of environmental organizations play an essential role in segment membership probabilities. Our findings support the idea that information about non-food-related consumer behavior improves the identification of segments. In an additional analysis, we demonstrate how organizational membership also provides an effective way to access consumer segments as compared to diverse media outlets. We discuss the implications of our findings for segmentation practice.     

Extracting local mechanical properties of steel bars by means of instrumented flat indentation

The evaluation of local mechanical properties of metal parts can be used for the prediction of forming and cutting forces during the following working stages. In order to show the feasibility of using indentation tests for work-piece characterization, C40 steel disks were cut from an extruded bar and machined by facing operation under different conditions. Indentation tests were carried out with 1 mm and 2 mm diameter indenters made of tungsten carbide; yield strength and indentation pressure values were extracted along the diameter of each disk. For the first time, indentation results were used to extract local mechanical properties of steel bars as a function of their process conditions: it was observed that small pins gave information on the effect of the machining process whereas large pins were more suitable to evaluate work-piece bulk properties.