Doctor of Philosophy

dissertationDiffusion tensor MRI (DT-MRI or DTI) has been proven useful for characterizing biological tissue microstructure, with the majority of DTI studies having been performed previously in the brain. Other studies have shown that changes in DTI parameters are detectable in the presence of cardiac pathology, recovery, and development, and provide insight into the microstructural mechanisms of these processes. However, the technical challenges of implementing cardiac DTI in vivo, including prohibitive scan times inherent to DTI and measuring small-scale diffusion in the beating heart, have limited its widespread usage. This research aims to address these technical challenges by: (1) formulating a model-based reconstruction algorithm to accurately estimate DTI parameters directly from fewer MRI measurements and (2) designing novel diffusion encoding MRI pulse sequences that compensate for the higher-order motion of the beating heart. The model-based reconstruction method was tested on undersampled DTI data and its performance was compared against other state-of-the-art reconstruction algorithms. Model-based reconstruction was shown to produce DTI parameter maps with less blurring and noise and to estimate global DTI parameters more accurately than alternative methods. Through numerical simulations and experimental demonstrations in live rats, higher-order motion compensated diffusion-encoding was shown to successfully eliminate signal loss due to motion, which in turn produced data of sufficient quality to accurately estimate DTI parameters, such as fiber helix angle. Ultimately, the model-based reconstruction and higher-order motion compensation methods were combined to characterize changes in the cardiac microstructure in a rat model with inducible arterial hypertension in order to demonstrate the ability of cardiac DTI to detect pathological changes in living myocardium

Individual-Level Predictors of Community Aftercare Completion

The importance of prison treatment for substance-using offenders in reducing recidivism and relapse has garnered much attention and acceptance over the past 30 years. The role of community aftercare as a continuum of the treatment process has been broadly acknowledged as essential in enhancing posttreatment success. However, our understanding of individual-level factors influencing a client’s willingness to participate and engage in aftercare remains limited. This article presents findings of individual-level factors found to be associated with successful completion of aftercare among a sample of 259 ex-offenders admitted to aftercare following 12 months of in-prison drug treatment

Minimal Bystander Activation of CD8 T Cells during the Virus-induced Polyclonal T Cell Response

Acute infections with viruses such as lymphocytic choriomeningitis virus (LCMV) are associated with a massive polyclonal T cell response, but the specificities of only a small percentage of these activated T cells are known. To determine if bystander stimulation of T cells not specific to the virus plays a role in this T cell response, we examined two different systems, HY-specific T cell receptor (TCR)-transgenic mice, which have a restricted TCR repertoire, and LCMVcarrier mice, which are tolerant to LCMV. LCMV infection of HY-transgenic C57BL/6 mice induced antiviral CTLs that lysed target cells coated with two of the three immunodominant epitopes previously defined for LCMV (glycoprotein 33 and nucleoprotein 397). Although LCMV-induced cytotoxic T lymphocytes (CTLs) from C57BL/6 mice could lyse uninfected H-2k and H-2d allogeneic targets, LCMV-induced CTLs from HY mice lysed only the H-2kexpressing cells. The HY mice generated both anti-H-2k and anti-H-2d CTL in mixed leukocyte reactions, providing evidence that the generation of allospecific CTLs during acute LCMV infection is antigen specific. During the LCMV infection there was blastogenesis of the CD8+ T cell population, but the HY-specific T cells (as determined by expression of the TCR-α chain) remained small in size. To examine the potential for bystander stimulation under conditions of a very strong CTL response, T cell chimeras were made between normal and HY mice. Even in the context of a normal virus-induced CTL response, no stimulation of HY-specific T cells was observed, and HY-specific cells were diluted in number by day 9 after infection. In LCMV-carrier mice in which donor and host T cells could be distinguished by Thy1 allotypic markers, adoptive transfer of LCMV-immune T cells into LCMV-carrier mice, whose T cells were tolerant to LCMV, resulted in activation and proliferation of donor CD8 cells, but little or no activation of host CD8 cells. These results support the hypothesis that the massive polyclonal CTL response to LCMV infection is virus-specific and that bystander activation of non–virus-specific T cells is not a significant component of this response

Is Emerging Adulthood Influencing Moffitt’s Developmental Taxonomy? Adding the “Prolonged” Adolescent Offender

The study of offender trajectories has been a prolific area of criminological research. However, few studies have incorporated the influence of emerging adulthood, a recently identified stage of the life course, on offending trajectories. The present study addressed this shortcoming by introducing the prolonged adolescent offender, a low-level offender between the ages of 18 and 25 that has failed to successfully transition into adult social roles. A theoretical background based on prior research in life-course criminology and emerging adulthood is presented. Using data from the National Longitudinal Study of Adolescent Health analyses examined the relationship between indicators of traditional turning points and social bonds and low-level criminal offending and drug use. Several indicators including education, economic instability, and parental attachment were all predictive of offending and drug use

Regulation of protein kinase B and glycogen synthase kinase-3 by insulin and beta-adrenergic agonists in rat epididymal fat cells - Activation of protein kinase B by wortmannin-sensitive and -insensittve mechanisms

Previous studies using L6 myotubes have suggested that glycogen synthase kinase-3 (GSK-3) is phosphoryl ated and inactivated in response to insulin by protein kinase B (PKB, also known as Akt or RAG) (Cross, D, A, E., Alessi, D, R., Cohen, P., Andjelkovic, M., and Hemmings, B, A. (1995) Nature 378, 785-789), In the present study, marked increases in the activity of PKB have been shown to occur in insulin-treated rat epididymal fat cells with a time course compatible with the observed decrease in GSK-3 activity, Isoproterenol, acting primarily through beta(3)-adrenoreceptors, was found to decrease GSK-3 activity to a similar extent (approximately 50%) to insulin, However, unlike the effect of insulin, the inhibition of GSK by isoproterenol was not found to be sensitive to inhibition by the phosphatidylinositol 3'-kinase inhibitors, wortmannin or LY 294002, The change in GSK-3 activity brought about by isoproterenol could not be mimicked by the addition of permeant cyclic AMP analogues or forskolin to the cells, although at the concentrations used, these agents were able to stimulate lipolysis. Isoproterenol, but again not the cyclic AMP analogues, was found to increase the activity of PKB, although to a lesser extent than insulin. While wortmannin abolished the stimulation of PKB activity by insulin, it was without effect on the activation seen in response to isoproterenol, The activation of PKB by isoproterenol was not accompanied by any detectable change in the electrophoretic mobility of the protein on SDS-polyacrylamide gel electrophoresis. It would therefore appear that distinct mechanisms exist for the stimulation of PKB by insulin and isoproterenol in rat fat cells

Lung clearance index during hospital admission in school-age children with cystic fibrosis

AbstractBackgroundThere is currently limited information regarding lung clearance index (LCI) and its response to treatment of pulmonary exacerbations in CF. We aimed to examine the utility of LCI for assessing short term clinical response to IV antibiotic therapy in school-age children with CF.MethodsSubjects experiencing exacerbations and hospitalised for IV antibiotics performed both multiple breath nitrogen washout (MBNW) and spirometry on admission to hospital and prior to discharge.Results27 patients (aged 6–20years) had paired data for MBNW and spirometry. Mean LCI reduced from 12.18 to 11.65 (4.4%) by time of discharge and FEV1 z-score improved from −3.05 to −2.86 (6.2%). Overall, LCI improved in n=15 (55%) patients compared with n=18 (67%) where FEV1 improved.ConclusionsIn summary, these findings do not support the use of LCI (or indeed, FEV1) to gauge the short term clinical response to IV antibiotic therapy in school-age children with cystic fibrosis

Rebel Child Soldiering and Conflict-Related Sexual Violence

Abstract Why do some rebel groups perpetrate sexual violence in armed conflict while others do not? A growing literature explores factors impacting the occurrence of conflict-related sexual violence (CRSV). We contribute to this literature, arguing that the composition of rebel groups can provide insight into patterns of sexual violence. We contend rebel groups that use child soldiers, and especially those that rely heavily on coercive child recruitment practices, are more prone to engage in wartime sexual violence than groups who do not recruit minors. While children are rarely the ideal soldier, they have become a crucial resource for many rebel groups. Yet, their recruitment can impact internal group dynamics. Sexual violence can serve as a tool for conditioning children to violence, intragroup cohesion-building, and an instrument for combatting defection. We test this argument with data on 245 rebel groups active in armed conflicts between 1989 and 2011. We supplement the quantitative analyses with an illustrative case study on the Revolutionary United Front in Sierra Leone. Our results suggest groups that recruit child soldiers are more likely to inflict CRSV. This effect is magnified when children are recruited forcibly.</jats:p

The Application of Acoustic Measurements and Audio Recordings for Diagnosis of In-Flight Hardware Anomalies

In many cases, an initial symptom of hardware malfunction is unusual or unexpected acoustic noise. Many industries such as automotive, heating and air conditioning, and petro-chemical processing use noise and vibration data along with rotating machinery analysis techniques to identify noise sources and correct hardware defects. The NASA/Johnson Space Center Acoustics Office monitors the acoustic environment of the International Space Station (ISS) through periodic sound level measurement surveys. Trending of the sound level measurement survey results can identify in-flight hardware anomalies. The crew of the ISS also serves as a "detection tool" in identifying unusual hardware noises; in these cases the spectral analysis of audio recordings made on orbit can be used to identify hardware defects that are related to rotating components such as fans, pumps, and compressors. In this paper, three examples of the use of sound level measurements and audio recordings for the diagnosis of in-flight hardware anomalies are discussed: identification of blocked inter-module ventilation (IMV) ducts, diagnosis of abnormal ISS Crew Quarters rack exhaust fan noise, and the identification and replacement of a defective flywheel assembly in the Treadmill with Vibration Isolation (TVIS) hardware. In each of these examples, crew time was saved by identifying the off nominal component or condition that existed and in directing in-flight maintenance activities to address and correct each of these problems

Chandra High Energy Transmission Grating Spectrum of AE Aquarii

(Abridged) The results of a Chandra X-ray Observatory High-Energy Transmission Grating (HETG) observation of the nova-like cataclysmic binary AE Aqr are described. First, the X-ray spectrum is that of an optically thin multi-temperature thermal plasma; the X-ray emission lines are broad, with widths that increase with the line energy, from sigma~1 eV for O VIII to sigma~5.5 eV for Si XIV; the X-ray spectrum is reasonably well fit by a plasma model with a Gaussian emission measure distribution that peaks at log T(K)=7.16, has a width sigma=0.48, an Fe abundance equal to 0.44 times solar, and other metal (primarily Ne, Mg, and Si) abundances equal to 0.76 times solar; and for a distance d=100 pc, the total emission measure EM=8.0E53 cm^-3 and the 0.5-10 keV luminosity L_X=1.1E31 erg/s. Second, based on the f/(i+r) flux ratios of the forbidden (f), intercombination (i), and recombination (r) lines of the He alpha triplets of N VI, O VII, and Ne IX measured by Itoh et al. in the XMM-Newton Reflection Grating Spectrometer spectrum and those of O VII, Ne IX, Mg XI, and Si XIII in the Chandra HETG spectrum, either the electron density of the plasma increases with temperature by over three orders of magnitude, from n_e~6E10 cm^-3 for N VI to n_e~1E14 cm^-3 for SI XIII, and/or the plasma is significantly affected by photoexcitation. Third, the radial velocity of the X-ray emission lines varies on the white dwarf spin phase, with two oscillations per spin cycle and an amplitude K~160 km/s. These results appear to be inconsistent with the recent models of Itoh et al., Ikhsanov, and Venter & Meintjes of an extended, low-density source of X-rays in AE Aqr, but instead support earlier models in which the dominant source of X-rays is of high density and/or in close proximity to the white dwarf.Comment: 13 pages including 1 table and 11 encapsulated postscript figure (3 in color); uses emulateapj.cls and apjfonts.sty; accepted on 2009 October 1 for publication in The Astrophysical Journa