UNIVERSITIES AS GENDERED ORGANIZATIONS: A SOCIOLOGICAL APPROACH TO STUDYING CAMPUS RESPONSES TO SEXUAL ASSAULT

Sexual assault remains a prevalent crime on college campuses, leaving institutions of higher education with the task of responding to allegations of sexual assault semi-regularly. While a lot of research examines students’ perceptions of their universities’ responses, the ways in which different university units collaborate in their responses remain unstudied. In my dissertation, I apply Acker’s theory of gendered organizations to study universities as a gendered organization comprised of multiple differently gendered organizations that respond to allegations of sexual assault. Drawing on data from a media audit, policy analysis, and interviews, I analyze in what ways and in what contexts gendering occurs in sexual assault policies and practices at two universities in the Pacific Northwest. Across these studies, I find that gendering infrequently occurs within university policy text. Instead, gendering occurs within federal and state guidelines that, in turn, influence university policy. Moreover, I find differences in approaches to the same federal guidelines based on state climate. I follow these studies with an explanation of my findings, their scientific contribution, and directions for future research

Advancements in Monte Carlo Dose Calculations for Prostate and Breast Permanent Implant Brachytherapy

Monte Carlo (MC) simulations of radiation transport may provide more accurate estimates of dose delivered to permanent implant brachytherapy patients compared to the clinical AAPM TG-43 dose calculation paradigm. However, MC dose calculations are burdened by sensitivity to required modelling assumptions, especially with low energy photon sources typical of permanent implant brachytherapy (20-30 keV). MC simulations require a detailed virtual model of the patient, often derived from post-treatment CT images containing imaging artifacts due to the brachytherapy sources present during image acquisition. For the first time, several metallic artifact reduction algorithms, of varied approach, are explored in phantom and clinical prostate brachytherapy CT images to determine their ability to mitigate artifacts and to quantify their sensitivity on dose calculations. Permanent implant breast brachytherapy is a challenge to model due to the radiologically different adipose and fibrogland soft tissues in and near the treatment volume. Further, the geometry of breast treatments is especially non-water like suggesting the clinical TG-43 dose calculation paradigm may yield significantly inaccurate results. The dose calculation sensitivity due to metallic artifact reduction, tissue differentiation approach and simulated tissue composition are explored in permanent implant breast brachytherapy clinical patient data, in addition to presenting differences between realistic and TG-43 conditions for target and organ-at-risk dosimetric endpoints. This work presents the largest cohort of permanent implant prostate brachytherapy MC dose calculations published to-date, providing quantitative differences between realistic and TG-43 conditions and a detailed sensitivity analysis of organ-at-risk simulated tissue composition, calcification modelling approach and calcification tissue composition. Clinical radiotherapy is increasingly considering radiobiological endpoints to judge treatment quality. Various radiobiological indices are evaluated using a large cohort of prostate brachytherapy dose calculations to explore the differences between these models and differences between applying TG-43 or realistic tissue MC dose calculations. This work identifies challenges related to applying dose calculations in heterogeneous tissue models to existing radiobiological models. The contributions of this thesis improve the understanding of realistic brachytherapy dose calculations, pave the way for the clinical adoption of Monte Carlo dose calculations and challenge and build upon the current frontier of radiobiological modelling for permanent implant brachytherapy

<i>C-elegans</i> model identifies genetic modifiers of alpha-synuclein inclusion formation during aging

Inclusions in the brain containing alpha-synuclein are the pathological hallmark of Parkinson's disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a &lt;i&gt;C-elegans&lt;/i&gt; model that makes it possible to monitor, in living animals, the formation of alpha-synuclein inclusions. In worms of old age, inclusions contain aggregated alpha-synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in alpha-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between alpha-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson's disease and other alpha-synuclein related disorders

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms

Peer reviewe

High-efficiency laser fabrication of drag reducing riblet surfaces on pre-heated Teflon

Bio-inspired surfaces are able to decrease friction with fluids and gases. The most recognizable are shark-skin-like riblet surface structures. Such bio-inspired surfaces can be formed by the laser ablation technique. In this work, bio-inspired riblet surfaces with grooves were formed using picosecond ultraviolet laser ablation on pre-heated polytetrafluoroethylene (PTFE) at various sample temperatures. The ablation of hot PTFE was found to be 30% more efficient than the conventional laser structuring at the room temperature. The friction of structured PTFE surfaces with the flowing air was investigated by using drag a measurement setup. Results show the decrease of friction force by 6% with dimensionless riblet spacing around 14-20

Towards clinical application of RayStretch for heterogeneity corrections in LDR permanent 125-I prostate brachytherapy

Purpose: RayStretch is a simple algorithm proposed for heterogeneity corrections in low-dose-rate brachytherapy. It is built on top of TG-43 consensus data, and it has been validated with Monte Carlo (MC) simulations. In this study, we take a real clinical prostate implant with 71 125I seeds as reference and we apply RayStretch to analyze its performance in worst-case scenarios. Methods and Materials: To do so, we design two cases where large calcifications are located in the prostate lobules. RayStretch resilience under various calcification density values is also explored. Comparisons against MC calculations are performed. Results: Dose-volume histogram-related parameters like prostate D90, rectum D2cc, or urethra D10 obtained with RayStretch agree within a few percent with the detailed MC results for all cases considered. Conclusions: The robustness and compatibility of RayStretch with commercial treatment planning systems indicate its applicability in clinical practice for dosimetric corrections in prostate calcifications. Its use during intraoperative ultrasound planning is foreseen

Reduced cerebellum volume and ataxia-like motoric phenotype in transgenic mouse, carrier of human CYP2C19 gene

Introduction: CYP2C19 transgenic mouse (2C19TG) is generated by the insertion of 12 copies of the human CYP2C19 gene into mouse genome. This animal model is a tool to study the neurodevelopmental role of CYP2C19 in vivo, since this enzyme is expressed in the foetal brains of 2C19TG mice and humans. Previous studies [1,2] showed anxiety and depression-like behaviour in these mice, while the aim of this study was to characterize the motoric function of the 2C19TG mouse. Methods: Whole brain dopamine concentration was measured in the brain homogenate of 23 adult mice by the HPLC-MS method. Motoric function in 50 mutant and 43 control mice of both genders was tested by the rotarod and beam walking tests. Beam walking test was repeated after treatment with dopaminergic receptor antagonists, Ecopipam (0.1 mg/kg) and Raclopride (0.25 mg/kg) as a follow-up. The sections of 10 6-month old and 8 15-months old mice were stained with anti-tyrosine hydroxylase antibody and the number of dopaminergic neurons was counted on histological slides under microscope. Next, after transcardial perfusion of 30 2C19TG and 30 control mice of both genders with contrast agent (4% Paraformaldehyde, 0.05M Gadoteridole, 0.01M Phosphate buffered saline, pH=7.4), cranium containing the whole brain was scanned overnight by the 9.4T MRI scanner. The volumes of 39 brain regions were quantified according to the mouse brain atlas [3]. Student's t-test and two-way ANOVA were used to evaluate statistical significance of between-group differences. Results: Adult 2C19TG mice are hyperdopaminergic, as they exhibit 15% increased dopamine concentration (p<0.001). They also show hyperkinetic motoric phenotype with the ataxia-like walking pattern and pathological clasping reflex. In the beam walking test 2C19TG mice had 20% longer beam crossing time (p=0.007) and 60% more paw slips (p<0.001) then the controls, and this motoric impairment could not be improved with antidopaminergic drugs. Both younger and older 2C19TG mice exhibited only a marginal reduction in the number of dopaminergic neurons of both substantia nigra and ventral tegmental area in a subset of coronal sections. This was confirmed by the gadolinium-enhanced neuroimaging that showed no change in substantia nigra volume in 2C19TG mice. On the other hand, significant differences in volume were identified in 11 regions, including cerebellum (-8.3% p<0.001) and striatum (+3.0%, p<0.001), which are the regions connected with the motoric function. The volumetric changes were detected in the hippocampus (-1.3%, p=0.027), amygdala (+2.8%, p<0.001), septum (+3.3%, p=0.014) and nucleus accumbens (+3.5, p=0.004) of 2C19TG mice. These brain regions are involved in emotional and motivational functions. Conclusion: Ataxia-like motoric phenotype in 2C19TG transgenic mice is probably caused by changes in cerebellum, while hyperdopaminergism is most likely the compensatory adaptation, whereas the changes in the hippocampus, amygdala, septum, and nucleus accumbens may be connected with the mutants’ depression-like phenotype and susceptibility to stress. Therefore, CYP2C19 transgenic mouse in potentially useful model of hyperkinetic disorders, and our findings hint at the possible impact of CYP2C19 enzyme on the development of the several brain regions involved in motor and emotional functioning.33rd ECNP Congress – Vienna 202

Cytochrome P450 in Pharmacogenetics: An Update

cited By 1Interindividual variability in drug disposition is a major cause of lack of efficacy and adverse effects of drug therapies. The majority of hepatically cleared drugs are metabolized by cytochrome P450 (CYP) enzymes, mainly in families CYP1, CYP2, and CYP3. Genes encoding these enzymes are highly variable with allele distribution showing considerable differences between populations. Genetic variability of especially CYP2C9, CYP2C19, CYP2D6, and CYP3A5 is known to have clear clinical impact on drugs that are metabolized by these enzymes. CYP1A2, CYP2A6, CYP2B6, CYP2C8, and CYP3A4 all show variability that affects pharmacokinetics of drugs as well, but so far the evidence regarding their clinical implications is not as conclusive. In this review, we provide an up-to-date summary of the pharmacogenetics of the major human drug-metabolizing CYP enzymes, focusing on clinically significant examples. © 2018 Elsevier Inc.Peer reviewe

Erratum: Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment (Molecular psychiatry (2016))

This corrects the article DOI: 10.1038/mp.2016.204