HIV-associated lipodystrophy (HIVLD) syndrome is a condition comprising abnormalities in distribution of body fat and metabolism of lipids and glucose that arises in HIV-infected patients on long-term antiretroviral therapy. This thesis describes clinical research into aspects of the natural history and treatment of HIVLD, as well as molecular research into its pathogenesis centred on subcutaneous adipose tissue. Results demonstrate HIVLD to be a treatment-induced syndrome characterised by initial gains in body fat followed by selective, progressive loss of limb fat. Exposure to thymidineanalogue nucleoside reverse transcriptase inhibitors (tNRTI) induces lipoatrophy through mitochondrial dysfunction of which inhibition of mitochondrial RNA expression, rather than mitochondrial DNA depletion, is an early feature. Mitochondrial dysfunction is associated with decreases in expression of peroxisome proliferatoractivated receptor gamma (PPAR??), an adipocyte transcription factor, which helps explain how tNRTI exposure leads to the loss of adipocyte function. Once established, lipoatrophy is characterised by mitochondrial DNA depletion, although this depletion occurs throughout the mitochondrial genome, suggesting an underlying cause other than inhibition of DNA polymerase gamma. HIVLD is a difficult syndrome to treat. Lipoatrophy is resistant to treatment with rosiglitazone, an agonist of PPAR??, which is ineffective in the setting of ongoing tNRTI therapy and mitochondrial dysfunction. Dyslipidaemia is also difficult to treat as use of pravastatin in the setting of ongoing exposure to protease inhibitors results in only modest declines in fasting cholesterol concentrations. Gains in central fat, such as that seen in patients with buffalo hump, are associated with insulin resistance and diabetes, but only occur in a relatively small percentage of treated patients, suggesting a role for genetic factors in its development. Use of strategies such as avoidance of tNRTI in firstline ART, genetic screening to identify those at risk of toxicities and targeted selection of interventions in subgroups of affected patients, may help prevent this syndrome occurring and better treat those patients in which it has already occurred.

Methadone is currently the most widely used agent to manage opioid dependence, but clinical experience has highlighted some limitations with its use. In particular, a relatively high proportion of patients complain of breakthrough withdrawal symptoms ( non - holding ) at apparently adequate methadone doses. Levo - alpha - acetylmethadol ( LAAM ) is a long acting opioid that is likely to benefit methadone non - holders ; however, relatively little is known about its pharmacology at steady state. The primary aim of this thesis was to evaluate LAAM as an alternative maintenance pharmacotherapy to methadone for the treatment of non - holders ; subsidiary aims were to elucidate the pharmacodynamics and pharmacokinetics of LAAM and its active metabolites ( nor - and dinor - LAAM ), and to examine the in vitro activity of LAAM, nor - and dinor - LAAM. Sixteen methadone maintenance patients ( non - holders = 8 ) were recruited to participate in a randomised, crossover trial of LAAM and methadone. At steady state there were two testing sessions ( 24 h for methadone and 48 h for LAAM ) that featured the concurrent measurement of plasma drug concentrations and both subjective and physiological indices of opioid effect. Cognitive and psychomotor functions were also assessed once during each inter - dosing interval study. Ten age - and gender - matched controls were also tested. The peak magnitude of methadone ' s and LAAM ' s effects were similar. Compared to methadone, LAAM was associated with more stable and less severe withdrawal and mood disturbance. The general pattern of symptom complaints and cognitive function was similar for both drugs. Severity of mood disturbance and withdrawal was similar in holders on methadone and LAAM, but was greater in non - holders when they were taking methadone than LAAM. In comparison to plasma ( R ) - ( - ) methadone, plasma nor - and dinor - LAAM concentrations fluctuated little over the dosing interval. Furthermore, nor - and dinor - LAAM were both more potent in the guinea - pig ileum bioassay, and had greater affinity for mu opioid receptors in receptor binding studies, than LAAM. In conclusion, LAAM converted methadone non - holders into LAAM holders. It is proposed that it is the relatively flat plasma concentration - time profile for nor - and dinor - LAAM that confer stability of opioid effect, minimising withdrawal. Therefore, LAAM may have a role in selected patients, whose response to methadone is suboptimal. / Thesis (Ph.D.)--School of Medical Sciences, 2006.

Graduation date: 2005

M.S. / Materials Science and Engineering / The most fundamental step in the development of a predictive model for microstructure and residual stress distribution in steels is the accurate representation of the transient temperature field. Three constituents of a database of thermophysical properties, namely the thermal conductivity, volumetric specific heat capacity and convective heat transfer coefficient, were isolated and their effects quantified on the accuracy of temperature field predictions using finite element analysis (FEA). The most critical parameter in the heat transfer process was ultimately identified to be the temperature dependent convective heat transfer coefficient. It was determined using an inverse heat transfer method, which was successfully applied to accurately establish the thermal boundary conditions for an arbitrary 3D steel geometry. The temperature dependency of the volumetric specific heat capacity in the transformation range of temperatures has to be known a priori, for which a reliable model describing alloy dependent reaction kinetics has to be developed first. Thermal conductivity and its dependency on temperature have secondary effects on the accuracy of FEA predictions. The impact of the outcome of this study lies in its relevance to the heat treatment industry.

Abstract PURPOSE: The aim of this study was to describe and compare possible differences regarding selected prognostic factors for disability between patients with non-specific chronic pain who were about to start a multidisciplinary treatment program (MMR), either within primary care (MMR1) or hospital care (MMR2). METHODS: The study had a descriptive and comparative cross sectional design. Eighty-nine patients were recruited consecutively when they were about to start their team treatment (50 in MMR1,39 in MMR2). The measurements were; Evaluation of self-reported self-efficacy for eight daily activities (STIVA-8), The Pain Belief Screening Instrument (PBSI) and Hospital Anxiety and Depression Scale (HADS). RESULTS: The study found some significant differences between the answers from patients in MMR1 and those from patients in MMR2. For instance, patients in MMR2 estimated lower self-efficacy according to STIVA-8 than patients in MMR1. Also, there were fewer low risk patients and more high risk patients in MMR2 than in MMR1 regarding pain intensity according to PBSI. In addition to this, there were fewer patients without depression and more with moderate depression in MMR2 than in MMR1 according to HADS. No significant differences could be shown for either anxiety according to HADS or for low- and high risk regarding activity disability according to PBSI. No significant differences could be found when pain intensity was measured with mean values on a scale from 0-10. CONCLUSIONS: Patients in MMR2 experienced more negative consequences from their pain disease than patients in MMR1. Systematic use of standardized self-reported instruments for selected prognostic factors could be helpful when screening for complexity and make it easier to decide whether the rehabilitation should be within MMR1 or MMR2 for patients in need of MMR. / Sammanfattning SYFTE: Syftet med denna studie var att beskriva och jämföra om patienter med långvarig smärtproblematik inom primärvård (MMR1) respektive specialiserad sjukhusvård (MMR2), som stod i begrepp att påbörja multimodal smärtrehabilitering (MMR), skattade olika avseende ett antal prognostiska faktorer för funktionsförmåga. METOD: Studien hade en deskriptiv och komparativ tvärsnittsdesign. Åttionio konsekutivt tillfrågade patienter deltog (50 i MMR1, 39 i MMR2). Datainsamlingen gjordes vid start av MMR med tre självskattningsformulär; Skattning av tilltro till sin förmåga att utföra åtta specificerade vardagsaktiviteter (STIVA-8), The Pain Belief Screening Instrument (PBSI) och Hospital Anxiety and Depression Scale (HADS). RESULTAT: Studien visade statistiskt signifikanta skillnader avseende att patienterna i MMR2 skattade lägre tilltro till sin förmåga enligt STIVA-8, det var färre andel lågriskpatienter och större andel högriskpatienter i MMR2 avseende smärtintensitet enligt PBSI samt färre andel patienter utan depression i MMR2 och fler med måttliga depressionsbesvär i MMR2 enligt HADS. Inga signifikanta skillnader kunde visas avseende låg- och högrisk för aktivitetsbegränsning enligt PBSI och inte heller för ångest enligt HADS. När smärtintensitet beräknades med medelvärde på skalan 0-10 fanns inga signifikanta skillnader. KONKLUSION: Patienterna i MMR2 skattade mer negativa konsekvenser av sin smärtsjukdom än i MMR1. Systematisk användning av skattningsformulär som ringar in olika prognostiska faktorer bör kunna underlätta selektion och sortering vid val av vårdnivå för patienter i behov av MMR.

The need for rehabilitation of bridges has become a critical challenge due to aging and an increase in traffic loads. Many of these bridges are exceeding their design fatigue life. Since many of these bridges are structurally deficient, they need to be rehabilitated or replaced by a new bridge. The most susceptible and weak parts of steel bridges to cracks and fatigue are the welds, due to the presence of high stress concentrations, tensile residual stresses, and imperfections as a result of the welding process. Inspection and repair of welds are difficult and elimination of welded details is not possible in steel bridge construction. Ultrasonic impact treatment (UIT) is a promising and innovative post-weld treatment (PWT) method for improving the fatigue performance of existing welded steel and steel-concrete composite structures such as highway bridges. The fatigue resistance of treated joints is enhanced by improving the geometry of the weld toe, and introducing compressive residual stresses. However, a lack of tools for quality assurance has slowed UIT’s adoption by bridge authorities. The current study was undertaken to examine the fatigue performance of structural steel welds subjected to UIT at various levels, including intentional under-treatment and over-treatment, and to relate the fatigue performance of the treated welds to geometric and metallurgical properties measured to control the treatment quality. The last objective was to use the laboratory results to develop acceptance criteria for the quality control of UIT in bridge applications. Fatigue tests of non-load carrying fillet welded attachments were conducted on properly treated, under-treated, and over-treated weld toes. Statistical analyses of the fatigue life data were performed and crack growth was monitored using the alternating current potential drop (ACPD) method. Measurement of local properties (such as weld toe geometry, local hardness, and residual stresses) and examination of the weld toe microstructure were also performed on the untreated and treated welds. The effects of weld toe geometry on the local stresses in the untreated and treated welds were also investigated using elastic finite element analysis (FEA) to obtain the stress concentration factor (SCF) for the different treatment cases and to examine the changes in the SCF for the different weld toe geometries. Based on the statistical analysis performed in this research, the results illustrated that UIT significantly improved the fatigue lives of weld details regardless of the investigated level of treatment quality. The fatigue lives of welded details under constant amplitude (CA) loading and constant amplitude loading with under-loads (CA-UL) were increased up to 30 and 27 times respectively. On average, the fatigue life of the treated weld details was slightly lower under CA-UL than under CA loading. Treatment quality had little impact on the mean of the S-N curves. However, it did impact the design (95% survival probability) S-N curves, with the curve associated with a proper treatment slightly higher than the curves for poor or unknown treatment quality. Local near-surface microhardness and compressive residual stresses were greatest for the over-treated welded details, followed by the properly treated and then the under-treated welded details. Increasing the treatment speed resulted in a greater reduction in the surface microhardness and compressive residual stresses than decreasing the treatment intensity. Finite element analyses showed that changes in weld toe geometry due to UIT can cause a decrease in the SCF near the surface of the treated weld toe. The SCF was the lowest for the properly treated steel specimens and slightly higher for the under-treated specimens. For the over-treated specimens, the SCFs were nearly as high as for the untreated weld. The SCF increases as the thickness of the flange increased up to 19 mm. With further flange thickness increase to 38 mm, the SCF did not change substantially. The work presented herein demonstrated that indent depth measurements from the base metal side, commonly used for quality control, may not identify over-treatment on their own. Indent depth measurements from both the weld and the base metal sides, obtained by measurement of weld toe impressions, offer a good alternative means for identifying over-treatment. However, for identifying under-treatment, indent depth measurements should be used in conjunction with visual inspection for traces of the original weld toe.

Treatment dropout is a pervasive phenomenon that can preclude clients from benefiting fully from psychotherapy. Research efforts to understand the phenomenon in the preceding decades yielded few consistent results. The investigation of intrinsic client and therapist factors gave way to the more recent exploration of dynamic therapeutic process factors potentially influencing the dropout process. The availability of periodic treatment outcome measurement instruments has helped client-focused research explore the effects of treatment response as a process factor on aspects of psychotherapy. As an added benefit, real-time treatment response measures, such as the Outcome Questionnaire, offer the possibility of timely adjustment in clinical intervention to meet evolving client needs and enhance therapeutic treatment. This present study primarily sought to explore the relationship between psychotherapy dropout and treatment response patterns in terms of clients' psychosocial well-being as measured by the Outcome Questionnaire. The results suggest that treatment response patterns alone may not effectively predict dropout probabilities. Even so, the measure's sub-component assessing the client's subjective experience of symptom distress is shown to be more accurate in predicting dropout than the composite Outcome Questionnaire measure or any other component scale. This finding conceivably highlights the relative importance of symptom distress in the dropout process for the sampled clients. Those clients reporting higher levels of symptom distress appeared to be associated with greater probabilities of dropout termination. Additionally, prior research has recognized a likely mediated relationship between higher client educational attainment and lower dropout probabilities - a trend also observed in this study's sampled population. As one of its expressed intents, this study examined educational attainment's moderating effect on the relationship between aspects of client treatment response and dropout probabilities. While showing educational attainment to be a relevant factor in assessing dropout risks, the analysis results indicate that this client characteristic variable's interactional effect on the evaluated treatment response pattern feature is weak and statistically nonsignificant. The present study contributes to the research literature through providing some clarification to the importance of treatment response in the prediction of psychotherapy client dropout.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 373-387). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 373-387). Also available on the Internet.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences