Bayesian inference for linear stochastic differential equations with application to biological processes

Ph. D. Thesis.Stochastic differential equations (SDEs) provide a natural framework for describing the stochasticity inherent in physical processes that evolve continuously over time. In this thesis, we consider the problem of Bayesian inference for a specific class of SDE – one in which the drift and diffusion coefficients are linear functions of the state. Although a linear SDE admits an analytical solution, the inference problem remains challenging, due to the absence of a closed form expression for the posterior density of the parameter of interest and any unobserved components. This necessitates the use of sampling-based approaches such as Markov chain Monte Carlo (MCMC) and, in cases where observed data likelihood is intractable, particle MCMC (pMCMC). When data are available on multiple experimental units, a stochastic differential equation mixed effects model (SDEMEM) can be used to further account for between-unit variation. Integrating over this additional uncertainty is computationally demanding. Motivated by two challenging biological applications arising from physiology studies of mice, the aim of this thesis is the development of efficient sampling-based inference schemes for linear SDEs. A key contribution is the development of a novel Bayesian inference scheme for SDEMEMs

Effects of secondary metal carbonate addition on the porous character of resorcinol-formaldehyde xerogels

A deeper understanding of the chemistry and physics of growth, aggregation and gelation processes involved in the formation of xerogels is key to providing greater control of the porous characteristics of such materials, increasing the range of applications for which they may be utilised. Time-resolved dynamic light scattering has been used to study the formation of resorcinol-formaldehyde gels in the presence of combinations of Group I (Na and Cs) and Group II (Ca and Ba) metal carbonates. It was found that the combined catalyst composition, including species and times of addition, is crucial in determining the end properties of the xerogels, via its effect on growth of clusters involved in formation of the gel network. Combination materials have textural characteristics within the full gamut offered by each catalyst alone; however, in addition, combination materials which retain the small pores associated with sodium carbonate catalysed xerogels exhibit a narrowing of the pore size distribution, providing an increased pore volume within an application-specific range of pore sizes. We also show evidence of pore size tunability while maintaining ionic strength, which significantly increases the potential of such systems for biological applications

Interprofessional clinical placement involving speech pathology and counselling psychology: Two students\u27 experiences

This paper examines the interprofessional learning of a speech pathology and counselling psychology student in an interprofessional placement within an institution of the Department of Corrective Services in Perth, Western Australia. The institution is a pre-release centre that promotes rehabilitation and community reintegration in which up to six women are able to have their children, aged 0–4 years of age, live with them. The students provided a program to the mothers to facilitate development of a healthy mother–child relationship and the children’s communication development. This paper utilised qualitative descriptive analysis to explore two examples of student learning and found perceived growth in the students’ clinical skills, their understanding of the other profession and the concept of interprofessional collaboration. While students experience growth in a range of placements, the journey described in this paper is unusual in both the nature of the student collaboration and the placement itself. The research highlights the importance of joint clinical placements in the development of interprofessional collaborative relationships

Miniature nitro and peroxide vapor sensors using nanoporous thin films

With the increased and continuous threat of terrorist attacks in public areas, new sensors are required to safeguard the public from home-made explosive devices. Current commercial sensors for explosive vapors are high-cost, bulky equipment not amenable to mass production, thus limiting their widespread deployment within society. We are conducting research on polymer-based microsensors that can overcome these limitations. Our devices offer an approach to the realization of low-cost sensors that can readily be placed as a network of electronic sentinels that can be permanently located in areas of public access. The polymers are chemically tailored to have a high affinity for nitro and peroxide vapors and are grown electrochemically on microelectrodes. Novel nanoporous polymer-based sensors are demonstrated with a detection level of 200 ppb of nitro vapors. In addition, a prototype reversible sensor for peroxide vapors is demonstrated to low ppm concentrations

Hair cortisol, allostatic load, and depressive symptoms in Australian Aboriginal and Torres Strait Islander people

Chronic stress and adversity are associated with poor mental health and are thought to contribute to the existing mental health gap between Aboriginal and Torres Strait Islander people and other Australians. Hair cortisol and allostatic load (AL) are indices of sustained stress and may be mediators of the effects of stress on health. The aim of this study was to examine the relationship between hair cortisol, AL, and depressive symptoms. This cross-sectional study comprised 329 Aboriginal and Torres Strait Islander adolescents and adults recruited at two health screening programs operating in three communities in north Queensland. We measured hair cortisol and calculated an AL index from 10 biomarkers. We assessed depressive symptoms with a version of the Patient Health Questionnaire-9 adapted for Aboriginal and Torres Strait Islander people (aPHQ-9). We found differences in cortisol and AL between the screening programs and communities, which were not explained by depressive symptoms. Overall aPHQ-9 scores were unrelated to hair cortisol (p = .25 and p = .94) and AL (p = .30 and p = .88) when age, gender and smoking were taken into account. However, anhedonia (p = .007) and insomnia (p = .006) sub-scores were each significantly associated with AL in one study site. Our present data did not demonstrate overall associations of stress biomarkers and multisystem dysregulation with depressive symptoms, which suggests that the relationship between cumulative stress and depression may be better explained by other factors in this population. The specific association between anhedonia and insomnia with AL indicates that chronic multisystem dysregulation plays a role in these features of depression in this population

Compound Ranking Based on a New Mathematical Measure of Effectiveness Using Time Course Data from Cell-Based Assays

The half maximal inhibitory concentration (IC50) has several limitations that make it unsuitable for examining a large number of compounds in cytotoxicity studies, particularly when multiple exposure periods are tested. This article proposes a new approach to measure drug effectiveness, which allows ranking compounds according to their toxic effects on live cells. This effectiveness measure, which combines all exposure times tested, compares the growth rates of a particular cell line in the presence of the compound with its growth rate in the presence of DMSO alone. Our approach allows measuring a wider spectrum of toxicity than the IC50 approach, and allows automatic analyses of a large number of compounds. It can be easily implemented in linear regression software, provides a comparable measure of effectiveness for each investigated compound (both toxic and non-toxic), and allows statistically testing the null hypothesis that a compound is non-toxic versus the alternative that it is toxic. Importantly, our approach allows defining an automated decision rule for deciding whether a compound is significantly toxic. As an illustration, we describe the results of a cell-based study of the cytotoxicity of 24 analogs of novobiocin, a C-terminal inhibitor of heat shock protein 90 (Hsp90); the compounds were ranked in order of cytotoxicity to a panel of 18 cancer cell lines and 1 normal cell line. Our approach may also be a good alternative to computing the half maximal effective concentration (EC50) in studies searching for compounds that promote cell growth

Identifying strategies to advance equitable implementation of co-occurring mental health and substance use disorder treatment in drug treatment courts: A study protocol

Abstract Introduction: Behavioral health treatment disparities by race and ethnicity are well documented across the criminal legal system. Despite criminal legal settings such as drug treatment courts (DTCs) increasingly adopting evidence-based programs (EBPs) to improve care, there is a dearth of research identifying strategies to advance equitable implementation of EBPs and reduce racial/ethnic treatment disparities. This paper describes an innovative approach to identify community- and provider-generated strategies to support equitable implementation of an evidence-based co-occurring mental health and substance use disorder intervention, called Maintaining Independence and Sobriety through Systems Integration, Outreach and Networking-Criminal Justice (MISSION-CJ), in DTCs. Methods/design: Guided by the Health Equity Implementation Framework, qualitative interviews and surveys will assess factors facilitating and hindering equitable implementation of MISSION-CJ in DTCs among 30 Black/African American and/or Hispanic/Latino persons served and providers. Concept mapping with sixty Black/African American and/or Hispanic/Latino persons served and providers will gather community- and provider-generated strategies to address identified barriers. Finally, an advisory board will offer iterative feedback on the data to guide toolkit development and inform equitable implementation of MISSION-CJ within DTCs. Conclusions: The paper illustrates a protocol of a study based in community-engaged research and implementation science to understand multilevel drivers of racial/ethnic disparities in co-occurring disorder treatment and identify opportunities for intervention and improvements within criminal legal settings

Is climate a risk multiplier in the Central American Dry Corridor? A CGIAR study

In this study, we investigate the climate-food security-conflict nexus in the Central American dry corridor as part of the WFP - CGIAR project "Assessing the relationship between climate, food security and conflict in Ethiopia and in the Central American Dry Corridor (CADC). Quantitative analysis on the impact of climate variability on conflict in Ethiopia and in the CADC countries". Our main findings can be summarized as follows: (1) Climate exacerbates foodinsecurity, poverty and inequalitythat can lead to more frequent conflicts. (2) The impact of climate on foodinsecurity can cascade inmultiple, wider security risks (3) There exist “climate insecurityhotspots” at sub-national levelwhere high level of climatevariability, conflict intensity anddiversity co-occur with otherexisting socio-economicinsecurities