Putting teeth into the developmental origins hypothesis: A longitudinal study of early childhood malnutrition, enamel hypoplasia and adolescent health in Amazonian Bolivia

Thesis (Ph.D.)--University of Washington, 2016-06

Air pollution exposure and novel biomarkers of inflammation and cardiac stress in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

Thesis (Master's)--University of Washington, 2016-06

Magnetic Devices and Techniques for the Study of Viscoelasticity of Biomaterials and Myocardial Forces

Thesis (Ph.D.)--University of Washington, 2016-06

Functional recycling of C2 domains throughout evolution: A comparative study of synaptotagmin, protein kinase C and phospholipase C by sequence, structural and modelling approaches

The C2 domain is one of the most frequent and widely distributed calcium-binding motifs. Its structure comprises an eight-stranded beta-sandwich with two structural types as if the result of a circular permutation. Combining sequence, structural and modelling information, we have explored, at different levels of granularity, the functional characteristics of several families of C2 domains. At the coarsest level,the similarity correlates with key structural determinants of the C2 domain fold and, at the finest level, with the domain architecture of the proteins containing them, highlighting the functional diversity between the various subfamilies. The functional diversity appears as different conserved surface patches throughout this common fold. In some cases, these patches are related to substrate-binding sites whereas in others they correspond to interfaces of presumably permanent interaction between other domains within the same polypeptide chain. For those related to substrate-binding sites, the predictions overlap with biochemical data in addition to providing some novel observations. For those acting as protein-protein interfaces' our modelling analysis suggests that slight variations between families are a result of not only complementary adaptations in the interfaces involved but also different domain architecture. In the light of the sequence and structural genomic projects, the work presented here shows that modelling approaches along with careful sub-typing of protein families will be a powerful combination for a broader coverage in proteomics. (C) 2003 Elsevier Ltd. All rights reserved.

A national case-control study of Ewing's sarcoma family of tumours in Australia

Limited population-based epidemiologic information is available on Ewing's sarcoma family of tumours (ESFT), a rare group of neoplasms. Several associations have been noted on a few studies but results were not consistent, except for exposure to farming among cases and their parents. Here we present the non-farm findings of a nationwide case-control study of ESFT in children and young adults in Australia. The analysis included 106 persons with confirmed ESFT and 344 population-based controls selected randomly via telephone. Information was collected by interview (84% face to face). We found a strong and significant association of ESFT with hernias, in particular hernia repaired in hospital (OR = 5.6, 95% Cl 1.3-6.4). Among other factors, there was a near doubling of risk for males, and male cases had their pubertal signs earlier (started shaving earlier) than male controls. There was also an increased risk of ESFT at higher levels of self-assessed exercise, but no other factor really stood out. For pregnancy-related factors, there was a tripling of risk for glandular fever, a doubling of risk for urinary tract infection and a near doubling of risk for X-rays during or just before pregnancy, but these estimates were not significant. In addition, there was a large number of inverse associations with medical conditions (specifically bone disorders), case exposure to medications, vaccinations and X-rays, with ultrasound during the pregnancy having the most certain effects. We conclude that, although the aetiology of ESFT remains obscure, overall there is strong evidence of an association with inguinal hernia; this can now be added to the farm-associated risk reported by others and us. The other associations reported here await replication and refinement in future studies. (C) 2003 Wiley-Liss, Inc.

A longitudinal study of employee adaptation to organizational change: The role of change-related information and change-related self-efficacy

This study examined the role of information, efficacy, and 3 stressors in predicting adjustment to organizational change. Participants were 589 government employees undergoing an 18-month process of regionalization. To examine if the predictor variables had long-term effects on adjustment, the authors assessed psychological well-being, client engagement, and job satisfaction again at a 2-year follow-up. At Time 1, there was evidence to suggest that information was indirectly related to psychological well-being, client engagement, and job satisfaction, via its positive relationship to efficacy. There also was evidence to suggest that efficacy was related to reduced stress appraisals, thereby heightening client engagement. Last, there was consistent support for the stress-buffering role of Time I self-efficacy in the prediction of Time 2 job satisfaction.

Case-only study of interactions between genetic polymorphisms of GSTM1, P1, T1 and Z1 and smoking in Parkinson's disease

Current opinion contends that complex interactions between genetic and environmental factors play a role in the etiology of Parkinson's disease (PD). Cigarette smoking is thought to reduce risk of PD, and emerging evidence suggests that genetic factors may modulate smoking's effect. We used a case-only design, an approach not previously used to study gene-environment interactions in PD, specifically to study interactions between glutathione-S-transferase (GST) gene polymorphisms and smoking in relation to PD. Four-hundred PD cases (age at onset: 60.0 +/- 10.7 years) were genotyped for common polymorphisms in GSTM1, PI, T1 and Z1 using well-established methods. Smoking exposure data were collected in face-to-face interviews. The independence of the studied GST genotypes and smoking exposure was confirmed by studying 402 healthy, aged individuals. No differences were observed in the distributions of GSTM1, T1 or Z1 polymorphisms between ever-smoked and never-smoked PD cases using logistic regression (all P > 0.43). However, GSTP1 *C haplotypes were over-represented among PD cases who ever smoked (odds ratio for interaction (ORi) = 2.00 (95% Cl: 1.11-3.60, P = 0.03)). Analysis revealed that ORi between smoking and the GSTP1-114Val carrier status increased with increasing smoking dose (P = 0.02 for trend). These data suggest that one or more GSTP1 polymorphisms may interact with cigarette smoking to influence the risk for PD. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Hospital-based case-control study of bronchiectasis in indigenous children in central Australia

Background: Childhood pneumonia has been reported to be associated with the development of bronchiectasis but there are no case-control studies that have examined this. This study examined the relationship between hospital admission for episode(s) of pneumonia and the risk of radiologically proven bronchiectasis. Methods: A medical record-based case-control study of bronchiectasis in Indigenous children was conducted in Central Australia. Controls (183), matched to cases (61) by gender, age and year of diagnosis, were Indigenous children hospitalized with other conditions. Results: There was a strong association between a history of hospitalized pneumonia and bronchiectasis [odds ratio (OR), 15.2; 95% confidence interval (95% CI) 4.4-52.7]. This was particularly evident in recurrent hospitalized pneumonia (P for trend < 0.01), severe pneumonia episodes with longer hospital stay (P for trend < 0.01), presence of atelectasis (OR 11.9; 95% CI 3.1-45.9) and requirement for oxygen (P for trend < 0.01). The overall number of pneumonia episodes, rather than its site, was associated with bronchiectasis. Although the total number of pneumonia episodes in the first year of life did not increase the risk of bronchiectasis, more severe episodes early in life did. Malnutrition, premature birth and being small for gestational age were more common findings among cases. Breast-feeding appeared to be a protective factor (OR 0.2; 95% CI 0.1-0.7). Conclusions: Although we cannot fully answer the question of why bronchiectasis is much more common in Indigenous children, we have provided strong evidence of an association between bronchiectasis and severe and recurrent pneumonia episodes in infancy and childhood.

A feasibility study of email communication between the patient's family and the specialist burns team

We investigated whether the parents of burns patients could capture suitable clinical images with a digital camera and add the necessary text information to enable the paediatric burns team to provide follow-up care via email. Four families were involved in the study, each of whom sent regular email consultations for six months. The results were very encouraging. The burns team felt confident that the clinical information in 30 of the 32 email messages (94%) they received was accurate, although in I I of these 30 cases (37%) they stated that there was room for improvement (the quality was nonetheless adequate for clinical decision making). The study also showed that low-resolution images (average size 37 kByte) were satisfactory for diagnosis. Families were able to participate in the service without intensive training and support. The user survey showed that all four families found it easy and convenient to take the digital photographs and to participate in the study. The results suggest that the technique has potential as a low-cost telemedicine service in burns follow-up, and that it requires only modest investment in equipment, training and support.

The Cotard syndrome. Report of two patients: with a review of the extended spectrum of 'délire des négations'

The Cotard syndrome is characterized by the delusion where an individual insists that he has died or part of his body has decayed. Although described classically in schizophrenia and bipolar disorder, physical disorders including migraine, tumour and trauma have also been associated with the syndrome. Two new cases are described here, the one associated with arteriovenous malformations and the other with probable multiple sclerosis. The delusion has been embarrassing to each patient. Study of such cases may have wider implications for the understanding of the psychotic interpretation of body image, for example that occurring in anorexia nervosa.

Maintaining and updating semantic context in schizophrenia: an investigation of the effects of multiple remote primes

Conflicting findings regarding the ability of people with schizophrenia to maintain and update semantic contexts have been due, arguably, to vagaries within the experimental design employed (e.g. whether strongly or remotely associated prime-target pairs have been used, what delay between the prime and the target was employed, and what proportion of related prime-target pairs appeared) or to characteristics of the participant cohort (e.g. medication status, chronicity of illness). The aim of the present study was to examine how people with schizophrenia maintain and update contextual information over an extended temporal window by using multiple primes that were either remotely associated or unrelated to the target. Fourteen participants with schizophrenia and 12 healthy matched controls were compared across two stimulus onset asynchronies (SOAs) (short and long) and two relatedness proportions (RP) (high and low) in a crossed design. Analysis of variance statistics revealed significant two- and three-way interactions between Group and SOA, Group and Condition, SOA and RP, and Group, SOA and RP. The participants with schizophrenia showed evidence of enhanced remote priming at the short SOA and low RP, combined with a reduction in the time course over which context could be maintained. There was some sensitivity to biasing contextual information at the short SOA, although the mechanism over which context served to update information appeared to be different from that in the controls. The participants with schizophrenia showed marked performance decrements at the long SOA (both low and high RP). Indices of remote priming at the short (but not the long) SOA correlated with both clinical ratings of thought disorder and with increasing length of illness. The results support and extend the hypothesis that schizophrenia is associated with concurrent increases in tonic dopamine activity and decreases in phasic dopamine activity. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Preliminary study of shunt related death in paediatric patients

Hydrocephalus is a condition commonly encountered in paediatric and adult neurosurgery and cerebrospinal fluid (CSF) shunting remains the treatment of choice for many cases. Despite improvements in shunt technology and technique, morbidity and mortality remain. The incidence of early shunt obstruction is high with later failures seen less frequently. This review aims to examine mortality associated with mechanical failure of CSF shunts within Queensland. Neurosurgical and Intensive Care databases were reviewed for cases of mortality associated with shunt failure. Eight cases were identified between the years of 1992 and 2002 with the average age at death 7.7 years. Deaths occurred on average 2 years after last shunt revision. Seven of the eight patients lived outside the metropolitan area. Shunting remains an imperfect means of treating hydrocephalus. Mortality may be encountered at any time post surgery and delays to surgical intervention influence this. Alternative measures such as third ventriculostomy or the placement of a separate access device should be considered. In the event of emergency, a spinal needle could be used to access the ventricle along the course of the ventricular catheter. (C) 2004 Elsevier Ltd. All rights reserved.

Articulatory function in hypokinetic dysarthria: An electropalatographic examination of two cases

The present study employed electropalatography (EPG) and a nonspeech measure of lingual function to examine, in detail, the articulatory production deficits of two individuals with Parkinson disease (PD) and hypokinetic dysarthria. Participants read 10 repetitions of CV words contained within the carrier phrase I saw a _ today while wearing an EPG artificial palate. Target consonants included the alveolar stop /t/, lateral approximant /l/, and the alveolar fricative /s/ in the /a/ vowel environment. The results of the two participants were compared to an age-matched control group. Examination of the perceptual features of articulatory production, lingual strength, fine force control and endurance, tongue-palate contact patterns, and segment durations were conducted. Results of the study revealed quite different articulatory deficits in the two participants. Specifically, the articulation of Participant One (P1) was characterized by a fast rate of speech, undershooting of articulatory targets, and reduced duration of consonant closures. In contrast, Participant Two (P2) demonstrated tongue-palate contact patterns indicative of impaired lingual control in the presence of both normal and increased articulatory segment durations. Potential reasons for the differing articulatory deficits were hypothesized. The current study demonstrated that assessment with EPG identified potential causes of consonant imprecision in two individuals with hypokinetic dysarthria. Directions for speech pathology intervention, salient from the results of the study, were also noted.

Mass uptake study of the diffusion of water and SBF into poly(2-hydroxyethyl methacrylate-co-tetrahydrofurfuryI methacrylate) containing aspirin or vitamin B-12

The ingress of water and Kokubo simulated body fluid (SBF) into poly (2-hydroxyethyl methacrylate) (PHEMA), and its co-polymers with tetrahydrofurduryl methacrylate (THFMA), loaded with either one of two model drugs, vitamin 1312 or aspirin, was studied by mass uptake over the temperature range 298-318 K. The polymers were studied as cylinders and were loaded with either 5 wt% or 10 wt% of the drugs. From DSC studies it was observed that vitamin B-12 behaved as a physical cross-linker restricting chain segmental mobility, and so had a small anti-plasticisation effect on PHEMA and the co-polymers rich in HEMA, but almost no effect on the T-g of co-polymers rich in THFMA. On the other hand, aspirin exhibited a plasticising effect on PHEMA and the copolymers. All of the polymers were found to absorb water and SBF according to a Fickian diffusion mechanism. The polymers were all found to swell to a greater extent in SBF than in water, which was attributed to the presence of Tris buffer in the SBF. The sorptions of the two penetrants were found to follow Fickian kinetics in all cases and the diffusion coefficients at 310 K for SBF were found to be smaller than those for water, except for the polymers containing aspirin where the diffusion coefficients were higher than for the other systems. For example, for sorption into PHEMA the diffusion coefficient for water was 1.41 X 10(-11) m(2)/s and for SBF was 0.79 x 10-11 m(2)/s, but in the presence of 5 wt% aspirin the corresponding values were 1.27 x 10(-1)1 m(2)/s and 1.25 x 10(-11) m(2)/s, respectively. The corresponding values for PHEMA loaded with 5 wt% B-12 were 1.25 x 10(-11) m(2)/s and 0.74 x 10(-11) m(2)/s, respectively.