Multi-Scale Simulation Modeling for Prevention and Public Health Management of Diabetes in Pregnancy and Sequelae

Diabetes in pregnancy (DIP) is an increasing public health priority in the Australian Capital Territory, particularly due to its impact on risk for developing Type 2 diabetes. While earlier diagnostic screening results in greater capacity for early detection and treatment, such benefits must be balanced with the greater demands this imposes on public health services. To address such planning challenges, a multi-scale hybrid simulation model of DIP was built to explore the interaction of risk factors and capture the dynamics underlying the development of DIP. The impact of interventions on health outcomes at the physiological, health service and population level is measured. Of particular central significance in the model is a compartmental model representing the underlying physiological regulation of glycemic status based on beta-cell dynamics and insulin resistance. The model also simulated the dynamics of continuous BMI evolution, glycemic status change during pregnancy and diabetes classification driven by the individual-level physiological model. We further modeled public health service pathways providing diagnosis and care for DIP to explore the optimization of resource use during service delivery. The model was extensively calibrated against empirical data.Comment: 10 pages, SBP-BRiMS 201

Biological and technical variables affecting immunoassay recovery of cytokines from human serum and simulated vaginal fluid: A multicenter study

The increase of proinflammatory cytokines in vaginal secretions may serve as a surrogate marker of unwanted inflammatory reaction to microbicide products topically applied for the prevention of sexually transmitted diseases, including HIV-1. Interleukin (IL)-1β and IL-6 have been proposed as indicators of inflammation and increased risk of HIV-1 transmission; however, the lack of information regarding detection platforms optimal for vaginal fluids and interlaboratory variation limit their use for microbicide evaluation and other clinical applications. This study examines fluid matrix variants relevant to vaginal sampling techniques and proposes a model for interlaboratory comparisons across current cytokine detection technologies. IL-1β and IL-6 standards were measured by 12 laboratories in four countries, using 14 immunoassays and four detection platforms based on absorbance, chemiluminescence, electrochemiluminescence, and fluorescence. International reference preparations of cytokines with defined biological activity were spiked into (1) a defined medium simulating the composition of human vaginal fluid at pH 4.5 and 7.2, (2) physiologic salt solutions (phosphate-buffered saline and saline) commonly used for vaginal lavage sampling in clinical studies of cytokines, and (3) human blood serum. Assays were assessed for reproducibility, linearity, accuracy, and significantly detectable fold difference in cytokine level. Factors with significant impact on cytokine recovery were determined by Kruskal−Wallis analysis of variance with Dunn’s multiple comparison test and multiple regression models. All assays showed acceptable intra-assay reproducibility; however, most were associated with significant interlaboratory variation. The smallest reliably detectable cytokine differences (P < 0.05) derived from pooled interlaboratory data varied from 1.5- to 26-fold depending on assay, cytokine, and matrix type. IL-6 but not IL-1β determinations were lower in both saline and phosphate-buffered saline as compared to vaginal fluid matrix, with no significant effect of pH. The (electro)chemiluminescence-based assays were most discriminative and consistently detected <2-fold differences within each matrix type. The Luminex-based assays were less discriminative with lower reproducibility between laboratories. These results suggest the need for uniform vaginal sampling techniques and a better understanding of immunoassay platform differences and cross-validation before the biological significance of cytokine variations can be validated in clinical trials. This investigation provides the first standardized analytic approach for assessing differences in mucosal cytokine levels and may improve strategies for monitoring immune responses at the vaginal mucosal interface

PAUSED for thought? Using verbal protocol analysis to understand the situational and temporal cues in the decision-making of residential burglars

Using verbal protocol analysis (VPA) alongside semi-structured interviews, this research aimed to explicate the situational dynamics that inform the decision-making and target selection of residential burglars. Focusing on the VPA method, novel to criminological research, the paper considers the contribution of this empirical approach for studying the decision-making of offenders in situ. The findings reveal a series of cues, encapsulated in the ‘PAUSED’ model, that are drawn upon by residential burglars to assess the suitability of a target; determining whether it is profitable, accessible, uninterruptible, surveillable, escapable and/or dishonourable. The PAUSED model is unpacked to articulate a collection of visual stimuli that serve to disrupt and suspend the otherwise rapid flow of target appraisal. Discussion of the strengths and limitations of the VPA method, and how it can compliment other approaches to understanding the decision-making of residential burglars, is provided

Strong interface-induced spin-orbit coupling in graphene on WS2

Interfacial interactions allow the electronic properties of graphene to be modified, as recently demonstrated by the appearance of satellite Dirac cones in the band structure of graphene on hexagonal boron nitride (hBN) substrates. Ongoing research strives to explore interfacial interactions in a broader class of materials in order to engineer targeted electronic properties. Here we show that at an interface with a tungsten disulfide (WS2) substrate, the strength of the spin-orbit interaction (SOI) in graphene is very strongly enhanced. The induced SOI leads to a pronounced low-temperature weak anti-localization (WAL) effect, from which we determine the spin-relaxation time. We find that spin-relaxation time in graphene is two-to-three orders of magnitude smaller on WS2 than on SiO2 or hBN, and that it is comparable to the intervalley scattering time. To interpret our findings we have performed first-principle electronic structure calculations, which both confirm that carriers in graphene-on-WS2 experience a strong SOI and allow us to extract a spin-dependent low-energy effective Hamiltonian. Our analysis further shows that the use of WS2 substrates opens a possible new route to access topological states of matter in graphene-based systems.Comment: Originally submitted version in compliance with editorial guidelines. Final version with expanded discussion of the relation between theory and experiments to be published in Nature Communication

Global and local concerns: What attitudes and beliefs motivate farmers to mitigate and adapt to climate change?

In response to agriculture\u27s vulnerability and contribution to climate change, many governments are developing initiatives that promote the adoption of mitigation and adaptation practices among farmers. Since most climate policies affecting agriculture rely on voluntary efforts by individual farmers, success requires a sound understanding of the factors that motivate farmers to change practices. Recent evidence suggests that past experience with the effects of climate change and the psychological distance associated with people\u27s concern for global and local impacts can influence environmental behavior. Here we surveyed farmers in a representative rural county in California\u27s Central Valley to examine how their intention to adopt mitigation and adaptation practices is influenced by previous climate experiences and their global and local concerns about climate change. Perceived changes in water availability had significant effects on farmers\u27 intention to adopt mitigation and adaptation strategies, which were mediated through global and local concerns respectively. This suggests that mitigation is largely motivated by psychologically distant concerns and beliefs about climate change, while adaptation is driven by psychologically proximate concerns for local impacts. This match between attitudes and behaviors according to the psychological distance at which they are cognitively construed indicates that policy and outreach initiatives may benefit by framing climate impacts and behavioral goals concordantly; either in a global context for mitigation or a local context for adaptation

Mobilising knowledge between practitioners and researchers to iteratively refine a complex intervention (DAFNEplus) pre-trial: protocol for a structured, collaborative working group process.

Background: Randomised controlled trials (RCTs) of complex interventions often begin with a pilot phase to test the proposed methods and refine the intervention before it is trialled. Although the Medical Research Council (MRC) recommends regular communication between the practitioners delivering the intervention and the researchers evaluating it during the pilot phase, there is a lack of practical guidance about how to undertake this aspect of pre-trial work. This paper describes a novel structured process for collaborative working, which we developed to iteratively refine a complex intervention prior to an RCT. We also describe an in-built qualitative study to learn lessons about how this approach could be used by future study teams. Methods: This work forms part of a broader research programme to develop and trial a complex intervention for people with type 1 diabetes, called DAFNEplus. The intervention is being piloted in three National Health Service (NHS) diabetes centres in two waves, with refinements being incrementally implemented between each wave in response to real-time, collective learning (combining practitioner experience, process evaluation data and patient and public involvement via an advisory group). A structured 'Collaborative Working Group' (CWG) process, comprising monthly teleconferences and four strategically timed face-to-face meetings, is being used to identify and respond systematically to emerging implementation challenges and research findings. The group involves 25 members of the study team, including the multi-disciplinary practitioners delivering the intervention, the research teams conducting the process evaluation, the study manager and Chief Investigator. An in-built qualitative study comprising documentary analysis of meeting materials, discourse analysis of meeting transcripts, reflexive note taking, and thematic analysis of focus groups and interviews with CWG members is being undertaken to explore how the CWG works and how its processes and procedures might be improved. Discussion: The CWG process offers a potential model for collaborative working in future pre-trial pilot phases and intervention development studies that operationalises MRC guidance to progressively develop a complex intervention and foster shared ownership through genuine collaboration. The findings from the qualitative study will provide insight into how to best support collaborative working to achieve optimal intervention design

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse