Multilevel variance components and brain volume mediation of life stress on post-traumatic stress disorder symptoms in children via regularization

Alterations of volume in brain regions of interest (ROIs) are associated with post-traumatic stress disorder (PTSD). Most of the extant neuroimaging research in PTSD has studied adults. The present study extends this research by using data from children (N=11,869, M age =9.92) from the ABCD study, a multisite longitudinal long-term study of brain development and childhood health in the U.S. Traumatic events (TEs) and PTSD symptoms were measured through the K- SADS for DSM-5. Values of brain ROIs were assessed using structural MRI measures. The unidirectional model was able to detect the small differences from site variance in sMRI mediators (subc: VS\u3c.009, SE\u3c.004; cort: VS\u3c.009, SE\u3c.004). Additive genetic factors explained 23.49% of the variance in TEs, 41.73% in subcortical and 19.94% in cortical mediators, and residual 21.01% in PTSD symptoms. Environmental factors explained most of the variance in TEs (C=.61, E=.16) and PTSD symptoms (resC=.19, resE=.21), as well as unique environmental factors in the cortical mediators (cort=.66). TEs highly influenced PTSD symptoms (.92). However, the indirect effect of TEs on PTSD symptoms through the mediation of volume in brain ROIs was small to non-influential at this age (subc=-.0003-.001, cort=-.001- .002). Several estimates of mediation effects were notably higher than most. Regularization via elastic net is implemented to train the mediation model to reduce bias and noise from overfitting, and to select the ROIs with mediation effects that explain the data with increased sparsity.https://scholarscompass.vcu.edu/gradposters/1102/thumbnail.jp

Continuous cell lysis in microfluidics through acoustic and optoelectronic tweezers

A versatile platform for efficient cell lysis using a combination of acoustic and electric fields in a microchannel is presented. Cell membrane disruption is triggered by electric fields inducing electroporation and then lysis. The principle of optoelectronic tweezers (OET) is applied to control the electric field strength and a surface acoustic wave transducer is attached to an OET chip to implement acoustic tweezing (AT). The system is characterized in terms of spatial control of electric fields, single cell precision and lysi

Automated Particle Identification through Regression Analysis of Size, Shape and Colour

Rapid point of care diagnostic tests and tests to provide therapeutic information are now available for a range of specific conditions from the measurement of blood glucose levels for diabetes to card agglutination tests for parasitic infections. Due to a lack of specificity these test are often then backed up by more conventional lab based diagnostic methods for example a card agglutination test may be carried out for a suspected parasitic infection in the field and if positive a blood sample can then be sent to a lab for confirmation. The eventual diagnosis is often achieved by microscopic examination of the sample. In this paper we propose a computerized vision system for aiding in the diagnostic process; this system used a novel particle recognition algorithm to improve specificity and speed during the diagnostic process. We will show the detection and classification of different types of cells in a diluted blood sample using regression analysis of their size, shape and colour. The first step is to define the objects to be tracked by a Gaussian Mixture Model for background subtraction and binary opening and closing for noise suppression. After subtracting the objects of interest from the background the next challenge is to predict if a given object belongs to a certain category or not. This is a classification problem, and the output of the algorithm is a Boolean value (true/false). As such the computer program should be able to ”predict” with reasonable level of confidence if a given particle belongs to the kind we are looking for or not. We show the use of a binary logistic regression analysis with three continuous predictors: size, shape and color histogram. The results suggest this variables could be very useful in a logistic regression equation as they proved to have a relatively high predictive value on their own

The effects of co-workers' extra-role behaviour on individual task performance and climate perceptions

Extra-role helping, defined as assisting co-workers with their work tasks, and extra-role voice, defined as arguing for constructive change, are believed to be functional for work groups. However, the mechanisms by which helping and voice might contribute to group effectiveness have not been described in detail, and relatively little empirical research has addressed the effects that helping and voice actually have within groups, or their relationships with outcomes relevant to group effectiveness. I argue that helping and voice will have their most direct and immediate effects on fellow group members, and that these effects may influence the subsequent performance of the group as a whole. I present a cross-level model of task facilitation, which describes the impact that group level helping may have on the task performance of individual group members. I present a cross-level model of climate building, which describes the impact that group level helping and voice may have on the climate perceptions of individual group members. I test hypotheses drawn from these models in three studies. Study one was conducted with 1086 Australian air traffic controllers in 45 groups. The results provided support for the task facilitation mechanism, and showed that group level helping was positively associated with the task performance and effectiveness of individual air traffic controllers. Study two was conducted in an Australian public sector organisation employing over 4000 individuals in 177 groups. The results of this study provided support for the climate building mechanism. Group level helping was positively associated with individual perceptions of affective climate. The effects of group level voice depended on the level of goal clarity within the group. I argued that group members would perceive a greater need for voice when group goal clarity was low, and that under these circumstances, group members would attribute voice behaviour to a genuine desire to benefit the group. Under conditions of high goal clarity, however, group members would not perceive a need for voice, and so the voice behaviours would be attributed to self-serving motives to gain power, influence or resources. Results supported these arguments, with group voice having a negative effect on climate perceptions when goal clarity was high, and a positive effect on climate perceptions when goal clarity was low. In study three I examined the impact of attributions for voice behaviour directly. I conducted an experiment with 69 second year management students. Students were placed in a simulated organisational context by way of a written vignette. The level of co-worker voice and the motives for voice were manipulated within this vignette to form a two by two factorial design in which the level of voice (no voice vs. some voice) was crossed with co-worker motives (self-serving vs. altruistic). Manipulation checks showed that participants attributed the co-worker's behaviour to self serving motives in the self-serving condition, and to altruistic motives in the altruistic condition. The results showed that voice behaviour had a negative impact on climate perceptions when self-serving attributions were made. When altruistic attributions were made, the presence or absence of voice did not influence climate perceptions. The results of the three studies suggest that extra-role helping and voice form important parts of the technical, social and psychological environment in which group members work. Furthermore, this environment can have important effects on the task performance and climate perceptions of group members. To the extent that group effectiveness depends on high levels of individual task performance and positive climate perceptions, these outcomes will influence subsequent group effectiveness. I close by discussing the contribution of the task facilitation and climate building models, and the practical implications of the results obtained within this thesis

Substance Use and Depression Symptomatology: Measurement Invariance of the Beck Depression Inventory (BDI-II) among Non-Users and Frequent-Users of Alcohol, Nicotine and Cannabis

Depression is a highly heterogeneous condition, and identifying how symptoms present in various groups may greatly increase our understanding of its etiology. Importantly, Major Depressive Disorder is strongly linked with Substance Use Disorders, which may ameliorate or exacerbate specific depression symptoms. It is therefore quite plausible that depression may present with different symptom profiles depending on an individual’s substance use status. Given these observations, it is important to examine the underlying construct of depression in groups of substance users compared to non-users. In this study we use a non-clinical sample to examine the measurement structure of the Beck Depression Inventory (BDI-II) in non-users and frequent-users of various substances. Specifically, measurement invariance was examined across those who do vs. do not use alcohol, nicotine, and cannabis. Results indicate strict factorial invariance across non-users and frequent-users of alcohol and cannabis, and metric invariance across non-users and frequent-users of nicotine. This implies that the factor structure of the BDI-II is similar across all substance use groups

Skistodiaptomus pallidus (Copepoda: Diaptomidae) establishment in New Zealand natural lakes, and its effects on zooplankton community composition

The North American calanoid copepod Skistodiaptomus pallidus is an emerging invader globally, with non-indigenous populations recorded from constructed waters in New Zealand, Germany and Mexico since 2000. We examined the effects of S. pallidus establishment on the zooplankton community of a natural lake, Lake Kereta, where it was first recorded in late-2008, coincident with releases of domestically cultured grass carp (Ctenopharyngodon idella). Although not present in any of our samples prior to August 2008, S. pallidus was found in all samples collected in the subsequent five years. ANOSIM indicated zooplankton community composition significantly differed between samples collected before and after S. pallidus invasion, whether the invader was included in the analysis or not. Zooplankton species affected most greatly were the copepods Calamoecia lucasi and Mesocyclops sp., which decreased in their relative importance, and the cladocerans Bosmina meridionalis and Daphnia galeata, which increased. Rotifer species were relatively unaffected. As the length of grass carp released were >6.5 cm, direct predatory effects by this species on the zooplankton community are unlikely. Associated reductions in macrophyte biomass could explain increases in the relative abundances of planktonic cladocerans (B. meridionalis and D. galeata). However, the effect of macrophyte reduction by grass carp on zooplankton communities is considered to be limited elsewhere, while the reduced macrophyte biomass cannot explain the decrease in relative abundance of the native planktonic calanoid copepod C. lucasi. Competition between C. lucasi and S. pallidus is the most compelling explanation for the reduction in importance of the native calanoid copepod species. Skistodiaptomus pallidus appears to have undergone a “boom-and-bust” cycle in Lake Kereta, increasing in relative abundance in the first three years following establishment, before declining in importance

Manufacturing of human mesenchymal stem cells: the analytical challenges

It has been repeatedly proven that cell therapies can address many current unmet clinical treatment needs and also improve on current treatment options for various diseases, from neurological disorders to bone repair (Rosset et al. 2014; Corey et al. 2017). Though the potential of cell therapies has been demonstrated at a relatively small scale, the realisation of bringing cell based treatments to a larger market is hindered by the complexity of the product along with safety concerned and high production cost. Safety concerns can be informed with more in-depth analytical analysis of the product, however this in turn increase the costs involved in producing a cell therapy (Davie et al. 2012). Consequently the cost of analytical techniques also needs to be reduced, to address this need the area of microfluidic based bioanalytics holds much promise (Titmarsh et al. 2014). The culturing of human mesenchymal stem cells (hMSC) was used as a proof of concept model to demonstrate where improved bioanalytical and bioassay methods could be utilised in the production of cell therapies. Cells from four donors were cultured under three different oxygen environments and the conditioned medium assessed for pro-angiogenic capabilities using a tube formation bioassay and a proportion of the cytokine secretome profile measured using Luminex technology. Thorough secretome analysis it was shown that predicting cytokine levels based solely on the donor was not possible as the handling of the cells also had an influence on the secretome profile. The donor expression profiles did not behave in the same manner across all oxygen environments, for example in some donors IL-8 levels increased per cell at lower oxygen where as other donors showed a decrease per cell. While the tube formation assay showed some differences between donors in pro-angiogenic capabilities it also highlights the challenges with interpreting large data sets. The feasibility of using a microcapillary film (MCF) based enzyme-linked immunosorbent assay (ELISA) to detected two relevant cytokines, IL-8 and hepatocyte growth factor (HGF) was investigated. Following on from this work the development of a combined MCF ELISA assay with hMSC cell culture to produce a fully closed cell screening system was initiated. It was shown that it was feasible to measure IL-8 and HGF using the MCF ELISA platform but further work would need to be done to make the system more compatible with the manufacturing environment. In order to adapt the MCF to also be an hMSC culture platform the first challenge was to functionalise the Fluorinated Ethylene Propylene (FEP) surface of the MCF. It was concluded that a poly (vinyl- alcohol) (PVA) and gelatin mixture produced a homogenous coating to which a consistent level of hMSC would attach. This work was carried out on a flat surface; therefore steps were taken to adapt this knowledge into the MCF, while there was evidence of hMSCs present inside the MCF more work will need to be done to bring this concept to an established platform

Extended twin study of alcohol use in Virginia and Australia

Drinking alcohol is a normal behavior in many societies, and prior studies have demonstrated it has both genetic and environmental sources of variation. Using two very large samples of twins and their first-degree relatives (Australia ≈ 20,000 individuals from 8,019 families; Virginia ≈ 23,000 from 6,042 families), we examine whether there are differences: (1) in the genetic and environmental factors that influence four interrelated drinking behaviors (quantity, frequency, age of initiation, and number of drinks in the last week), (2) between the twin-only design and the extended twin design, and (3) the Australian and Virginia samples. We find that while drinking behaviors are interrelated, there are substantial differences in the genetic and environmental architectures across phenotypes. Specifically, drinking quantity, frequency, and number of drinks in the past week have large broad genetic variance components, and smaller but significant environmental variance components, while age of onset is driven exclusively by environmental factors. Further, the twin-only design and the extended twin design come to similar conclusions regarding broad-sense heritability and environmental transmission, but the extended twin models provide a more nuanced perspective. Finally, we find a high level of similarity between the Australian and Virginian samples, especially for the genetic factors. The observed differences, when present, tend to be at the environmental level. Implications for the extended twin model and future directions are discussed

Cross-cultural comparison of genetic and cultural transmission of smoking initiation using an extended twin kinship model

Background: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime ‘ever’ smoking measure was obtained from twins and relatives in the ‘Virginia 30,000’ sample and the ‘Australian 25,000’. Results: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. Conclusions: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI