Determinants of youth attitudes and skills towards which drinking/driving prevention programs should be directed. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Criminal violence, biological correlates and determinants : a selected bibliography /

Includes indexes.

Determinants of effective unit performance : research on measuring and managing unit training readiness /

Mode of access: Internet.

A time series analysis of the growth and determinants of union/nonunion relative wage effects, 1967-1977 /

"April 1981."

Mapping the determinants in owl monkey CD4 and CCR5 that allow entry of early-stage HIV-1 Env variants

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

Social and behavioural determinants of early childhood caries

Background: To investigate the association between selected social and behavioural (infant feeding and preventive dental practices) variables and the presence of early childhood caries in preschool children within the north Brisbane region. Methods: A cross sectional sample of 2515 children aged four to five years were examined in a preschool setting using prevalence (percentage with caries) and severity (dmft) indices. A self-administered questionnaire obtained information regarding selected social and behavioural variables. The data were modelled using multiple logistic regression analysis at the 5 per cent level of significance. Results: The final explanatory model for caries presence in four to five year old children included the variables breast feeding from three to six months of age (OR=0.7, CI=0.5, 1.0), sleeping with the bottle (OR=1.9, CI=1.5, 2.4), sipping from the bottle (OR=1.6, CI=1.2, 2.0), ethnicity other than Caucasian (OR=1.9, CI=1.4, 2.5), annual family income $20,000-$35,000 (OR = 1.7, CI=1.3, 2.3) and annual family income less than $20,000 (OR=2.1, CI=1.5, 2.8). Conclusion: A statistical model for early childhood caries in preschool children within the north Brisbane region has been constructed using selected social and behavioural determinants. Epidemiological data can be used for improved public oral health service planning and resource allocation within the region.

Do the Genetic or Environmental Determinants of Anxiety and Depression Change with Age? A Longitudinal Study of Australian Twins

Because the determinants of anxiety and depression in late adolescence and early adulthood may differ from those in later life, we investigated the temporal stability and magnitude of genetic and environmental correlates of symptoms of anxiety and depression across the life span. Data were collected from a population-based Australian sample of 4364 complete twin pairs and 777 singletons aged 20 to 96 years who were followed-up over three studies between 1980 and 1996. Each study contained the 14-item self-report DSSI/sAD scale which was used to measure recently experienced symptoms of anxiety and depression. Symptom scores were then divided and assigned to age intervals according to each subject's age at time of participation. We fitted genetic simplex models to take into account the longitudinal nature of the data. For male anxiety and depression, the best fitting simplex models comprised a single genetic innovation at age 20 which was transmitted, and explained genetic variation in anxiety and depression at ages 30, 40, 50 and 60. Most of the lifetime genetic variation in female anxiety and depression could also be explained by innovations at age 20 which were transmitted to all other ages; however, there were also smaller age-dependent genetic innovations at 30 for anxiety and at 40 and 70 for depression. Although the genetic determinants of anxiety and depression appear relatively stable across the life-span for males and females, there is some evidence to support additional mid-life and late age gene action in females for depression. The fact that mid-life onset for anxiety occurs one decade before depression is also consistent with a causal relationship (anxiety leading to depression) between these conditions. These findings have significance for large scale depression prevention projects.

Expression and biochemical analysis of the entire HIV-2 gp41 ectodomain: determinants of stability map to N- and C-terminal sequences outside the 6-helix bundle core

The folding of HIV gp41 into a 6-helix bundle drives virus-cell membrane fusion. To examine the structural relationship between the 6-helix bundle core domain and other regions of gp41, we expressed in Escherichia coli, the entire ectodomain of HIV-2(ST) gp41 as a soluble, trimeric maltose-binding protein (MBP)/gp41 chimera. Limiting proteolysis indicated that the Cys-591-Cys-597 disulfide-bonded region is outside a core domain comprising two peptides, Thr-529-Trp-589 and Val-604-Ser-666. A biochemical examination of MBP/gp41 chimeras encompassing these core peptides; indicated that the N-terminal polar segment, 521-528, and C-terminal membrane-proximal segment, 658-666, cooperate in stabilizing the ectodomain. A functional interaction between sequences outside the gp41 core may contribute energy to membrane fusion. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Common E protein determinants for attenuation of glycosaminoglycan-binding variants of Japanese encephalitis and West Nile viruses

Natural isolates and laboratory strains of West Nile virus (WNV) and Japanese encephalitis virus (JEV) were attenuated for neuroinvasiveness in mouse models for flavivirus encephalitis by serial passage in human adenocarcinoma (SW13) cells. The passage variants displayed a small-plaque phenotype, augmented affinity for heparin-Sepharose, and a marked increase in specific infectivity for SW13 cells relative to the respective parental viruses, while the specific infectivity for Vero cells was not altered. Therefore, host cell adaptation of passage variants was most likely a consequence of altered receptor usage for virus attachment-entry with the involvement of cell surface glycosaminoglycans (GAG) in this process. In vivo blood clearance kinetics of the passage variants was markedly faster and viremia was reduced relative to the parental viruses, suggesting that affinity for GAG (ubiquitously present on cell surfaces and extracellular matrices) is a key determinant for the neuroinvasiveness of encephalitic flaviviruses. A difference in pathogenesis between WNV and JEV, which was reflected in more efficient growth in the spleen and liver of the WNV parent and passage variants, accounted for a less pronounced loss of neuroinvasiveness of GAG binding variants of WNV than JEV. Single gain-of-net-positive-charge amino acid changes at E protein residue 49, 138, 306, or 389/390, putatively positioned in two clusters on the virion surface, define molecular determinants for GAG binding and concomitant virulence attenuation that are shared by the JEV serotype flaviviruses.

Assessment of arginine 97 and lysine 72 as determinants of substrate specificity in cytochrome P450 2C9 (CYP2C9)

CYP2C9 is distinguished by a preference for substrates bearing a negative charge at physiological pH. Previous studies have suggested that CYP2C9 residues R97 and K72 may play roles in determining preference for anionic substrates by interaction at the active site or in the access channel. The aim of the present study was to assess the role of these two residues in determining substrate selectivity. R97 and K72 were substituted with negative, uncharged polar and hydrophobic residues using a degenerate polymerase chain reaction-directed strategy. Wild-type and mutant enzymes were expressed in bicistronic format with human cytochrome P450 reductase in Escherichia coli. Mutation of R97 led to a loss of holoenzyme expression for R97A, R97V, R97L, R97T, and R97E mutants. Low levels of hemoprotein were detected for R97Q, R97K, R97I, and R97P mutants. Significant apoenzyme was observed, suggesting that heme insertion or protein stability was compromised in R97 mutants. These observations are consistent with a structural role for R97 in addition to any role in substrate binding. By contrast, all K72 mutants examined (K72E, K72Q, K72V, and K72L) could be expressed as hemoprotein at levels comparable to wild-type. Type I binding spectra were obtained with wildtype and K72 mutants using diclofenac and ibuprofen. Mutation of K72 had little or no effect on the interaction with these substrates, arguing against a critical role in determining substrate specificity. Thus, neither residue appears to play a role in determining substrate specificity, but a structural role for R97 can be proposed consistent with recently published crystallographic data for CYP2C9 and CYP2C5.

Determinants of functional capacity in patients with chronic heart failure: Role of filling pressure and systolic and diastolic function

Background Previous work suggesting a better correlation of diastolic than systolic function with exercise capacity in heart failure may reflect the -relative insensitivity and load-dependence of ejection fraction (EF). We sought the correlation of new and more sensitive methods of quantifying systolic and diastolic function and filling pressure with functional capacity. Methods We studied 155 consecutive exercise tests on 95 patients with congestive heart failure (81 male, aged 62 +/- 10 years), who underwent resting 2-climensional echocardiography and tissue Doppler imaging before and after measurement of maximum oxygen uptake (peak VO2)Results The resting EF was 3 1 % 10% and a peak VO(2)was 13 +/- 5 mL/kg/min; the majority of these patients (80%) had an ischemic cardiornyopathy. Resting EF (r 0.14, P =.09) correlated poorly with peak VO2 and mean systolic (r = 0.23, P =.004) and diastolic tissue velocities (r 0.18, P =.02). Peak EF was weakly correlated with the mean systolic (r = 0.18, P =.02) and diastolic velocities (r = 0.16, P <.04). The mean sum of systolic and diastolic velocities in both annuli (r = 0.30, P <.001) and E/Ea ratio (r 0.31, P <.001) were better correlated with peak VO2 Prediction of peak VO2 was similar with models based on models of filling pressure (R = 0.61), systolic factors (R = 0.63), and diastolic factors (R 0.59), although a composite model of filling pressure, systolic and diastolic function was a superior predictor of peak VO2 (R 0.69; all P<.001). Conclusions The reported association of diastolic rather than systolic function with functional capacity may have reflected the limitations of EF. Functional capacity appears related not only to diastolic function, but also to systolic function and filling pressure, and is most closely associated with a combination of these factors.

Identifying the energy gap: Magnitude and determinants of 5-year weight gain in midage women

Objective: The aims of this study were to estimate average yearly weight gain in midage women and to identify the determinants of weight gain and gaining weight at double the average rate. Research Methods and Procedures: The study sample comprised 8071 participants (45 to 55 years old) in the Australian Longitudinal Study on Women's Health who completed mailed surveys in 1996, 1998, and 2001. Results: On average, the women gained almost 0.5 kg per year [average 2.42 kg (95% confidence interval, 2.29 to 2.54) over 5 years]. In multivariate analyses, variables associated with energy balance (physical activity, sitting time, and energy intake), as well as quitting smoking, menopause/hysterectomy, and baseline BMI category were significantly associated with weight gain, but other behavioral and demographic characteristics were not. After adjustment for all of the other biological and behavioral variables, the odds of gaining weight at about twice the average rate (> 5 kg over 5 years) were highest for women who quit smoking (odds ratio = 2.94; 95% confidence interval, 2.17, 3.96). There were also independent relationships between the odds of gaining > 5 kg and lower levels of habitual physical activity, more time spent sitting, energy intake (but only in women with BMI > 25 at baseline), menopause transition, and hysterectomy. Discussion: The average weight gain equates with an energy imbalance of only about 10 kcal or 40 kJ per day, which suggests that small sustained changes in the modifiable behavioral variables could prevent further weight gain.