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PubMed2001

Type 1 diabetes mellitus, xerostomia, and salivary flow rates.

OBJECTIVE: The Oral Health Science Institute at the University of Pittsburgh has completed a cross-sectional epidemiologic study of 406 subjects with type 1 diabetes and 268 control subjects without diabetes that assessed the associations between oral health and diabetes. This report describes the prevalence of dry-mouth symptoms (xerostomia), the prevalence of hyposalivation in this population, and the possible interrelationships between salivary dysfunction and diabetic complications. STUDY DESIGN: The subjects with diabetes were participants in the Pittsburgh Epidemiology of Diabetes Complications study who were enrolled in an oral health substudy. Control subjects were spouses or best friends of participants or persons recruited from the community through advertisements in local newspapers. Assessments of salivary function included self-reported xerostomia measures and quantification of resting and stimulated whole saliva flow rates. RESULTS: Subjects with diabetes reported symptoms of dry mouth more frequently than did control subjects. Salivary flow rates were also impaired in the subjects with diabetes. Regression models of potential predictor variables were created for the 3 self-reported xerostomia measures and 4 salivary flow rate variables. Of the medical diabetic complications studied (ie, retinopathy, peripheral and autonomic neuropathy, nephropathy, and peripheral vascular disease), only neuropathy was found to be associated with xerostomia and decreased salivary flow measures. A report of dry-mouth symptoms was associated with current use of cigarettes, dysgeusia (report of a bad taste), and more frequent snacking behavior. Xerogenic medications and elevated fasting blood glucose concentrations were significantly associated with decreased salivary flow. Resting salivary flow rates less than 0.01 mL/min were associated with a slightly higher prevalence of dental caries. Subjects who reported higher levels of alcohol consumption were less likely to have lower rates of stimulated salivary flow. CONCLUSIONS: Subjects with type 1 diabetes who had developed neuropathy more often reported symptoms of dry mouth as well as symptoms of decreased salivary flow rates. Because of the importance of saliva in the maintenance and the preservation of oral health, management of oral diseases in diabetic patients should include a comprehensive evaluation of salivary function.

Adult↗

PubMedDate not supplied

Modelling health-related performance indices.

PRIMARY OBJECTIVE: The purpose of the present review is to critically examine the various models used to describe health-related performance indices (e.g. grip-strength, lung function, arterial blood pressure, anaerobic and aerobic power, etc.). MAIN OUTCOMES AND RESULTS: The majority of health-related performance indices are known to increase proportionally with body size and decline with age, although some, for example arterial blood pressure and cholesterol, increase with both age and excessive body weight. Historically, the confounding effects of body size and age have been controlled using multiple linear or polynomial regression models assuming a constant additive error variance. Based on maximum likelihood goodness-of-fit criterion, an alternative class of allometric models with a multiplicative error term arc shown to describe such proportional relationships more adequately in both cross-sectional and longitudinal studies. CONCLUSIONS: When modelling health-related performance indices, multiplicative, allometric models incorporate the concept of a proportional association as an integral part of its model form. Such models guarantee realistic values of health-related response variables both within and beyond the range of observations, ensuring biologically sound estimates of the response variables for subjects of all ages. After a logarithmic transformation, the models can be fitted using ordinary linear regression that will naturally help to overcome the heteroscedasticity observed in such data. However, if the logarithmic transformation fails to provide a constant error variance, an alternative approach is to model the error variance itself using log-linear regression. For longitudinal data, the use of multilevel modelling provides an alternative method of modelling error variation observed in health-related performance indices.

Adolescent↗

PubMed2003

Hypothesis testing in semiparametric additive mixed models.

We consider testing whether the nonparametric function in a semiparametric additive mixed model is a simple fixed degree polynomial, for example, a simple linear function. This test provides a goodness-of-fit test for checking parametric models against nonparametric models. It is based on the mixed-model representation of the smoothing spline estimator of the nonparametric function and the variance component score test by treating the inverse of the smoothing parameter as an extra variance component. We also consider testing the equivalence of two nonparametric functions in semiparametric additive mixed models for two groups, such as treatment and placebo groups. The proposed tests are applied to data from an epidemiological study and a clinical trial and their performance is evaluated through simulations.

Anticonvulsants↗

PubMed1998

Forty-five-year tooth survival probabilities among men in Oslo, Norway.

Changes in tooth survival probabilities over a person's lifetime have remained largely unexplored. The goal of this study was to evaluate changes in the 45-year tooth survival probabilities in a cohort of 565 Norwegian males who were examined in 1969 as young adults, and followed up into mid-life (examination years and sample sizes (n): 1971 (n = 381), 1973 (n = 292), 1975 (n = 245), 1981 (n = 228), 1988 (n = 202), and 1995 (n = 223). The results indicated that the tooth survival probabilities varied considerably both (i) among teeth within individuals, and (ii) over time. The 45-year survival probabilities for the 28 teeth fell into the following ranges: larger than 95% for incisors and cuspids; between 84% and 92% for premolars; and between 59% and 96% for molars. Over the first 4 post-eruptive decades, the tooth mortality risks (excluding orthodontic extractions) were: 1st decade, 2.0% (from 1.7 to 2.4%); 2nd decade, 0.2% (from 0.1 to 0.4%); 3rd decade, 0.6% (from 0.4 to 0.8%); and 4th decade, 1.1% (from 0.8 to 1.5%). The tooth mortality risks in the 2nd, 3rd, and 4th decades were probably somewhat underestimated (due to dropout bias), suggesting that the true underlying tooth mortality hazard function may have been V-shaped. The conclusions were that the tooth mortality hazard during the first 4 post-eruptive decades was bathtub-shaped and that it varied considerably among teeth within individuals.

Adolescent↗

PubMed1997

Effects function simulation of residential appliance field exposures.

This paper demonstrates the application of effects function analysis to residential magnetic field exposure, focusing on appliance sources and mitigation choices. Residential field exposure time series were synthesized by using a sample of background household field measurements, a model of average daily appliance use, and a small sample of EMDEX data of field exposure from 12 household strength window, sudden field changes) were simulated by using the synthesized time series data for different exposure situations, such as high and low levels of appliance use, simple avoidance, and use of a set of hypothetical "low field" appliances (50% lower fields). In particular, field exposure from the use of bedside clocks and electric blankets was examined. Results demonstrate that the choice of effects function is critical for the ranks of field sources and exposure reduction choices. For the effects function of average field strength with or without a threshold, exposure from background fields dominated exposure from all appliances except for bedside clocks and electric blankets. In the case of the field strength window effects function, the dominant field sources changed with the width of the window. For the effects function based on rapid field changes, appliance use was the major source of exposure. Because of the small sample of our data set and other simplifications, specific results should be viewed as illustrative.

Computer Simulation↗

PubMed2001

Genetic characterization of hypervariable region 1 in patients chronically infected with hepatitis C virus genotype 2.

The hypervariable region 1 (HVR1) has been most reliably identified in the genome of HCV genotype 1 isolates and thought to possibly play a role in immune evasion and development of chronic infection. There are few studies, however, of other HCV genotypes to determine if they also have such a hypervariable region present, and it is unclear whether or not there is any genotype-dependent difference in the genetic characteristics of HVR1. We determined the nucleotide sequence of 5' end of E2/NS1 region of the HCV genome spanning HVR1 of multiple genotype 1 and 2 HCV isolates and carried out a detailed genetic analysis. Similarity plots identified two hypervariable regions within the genotype 2 sequences, a larger one corresponding to HVR1 as well as a smaller 27-nucleotide region of hypervariability. The synonymous substitutions per synonymous site (ds) was greater than nonsynonymous substitutions per nonsynonymous site (dn) within genotype 1 group whereas dn and ds were similar in the genotype 2 group. Analysis of amino acid sequences revealed several conserved sites across genotype 1 and 2 (amino acid numbers 2,6, 20 and 26) and overall similar hydropathic profiles were found within two genotypes. Still, despite the hypervariability, the HVR1 showed a genotype-specific phylogenetic clustering. Thus, HVR1 appears to be conserved between genotypes in keeping with it having an important survival function. Genotype 2 appears to have a greater rate of nonsynonymous substitutions within HVR1, suggesting a greater positive evolutionary pressure.

Amino Acid Sequence↗

PubMed1998

Child neglect: relation to child temperament and family context.

Relationships among neglect and child and family characteristics were examined in a sample of 121 urban, low-income families with a child under 30 months. Maternal reports of more difficult child temperament predicted emotional neglect; family context was indirectly related, as mothers in well functioning families with more support reported their children as being less difficult. Neither child temperament nor family context was related to physical neglect.

Adult↗

PubMed2001

Variance estimation of a survival function for interval-censored survival data.

Interval-censored survival data often occur in medical studies, especially in clinical trials. In this case, many authors have considered estimation of a survival function. There is, however, relatively little discussion on estimating the variance of estimated survival functions. For right-censored data, a special case of interval-censored data, the most commonly used method for variance estimation is to use the Greenwood formula. In this paper we propose a generalization of the Greenwood formula for variance estimation of a survival function based on interval-censored data. Also a simple bootstrap approach is presented. The two methods are evaluated and compared using simulation studies and a real data set. The simulation results suggest that the methods work well.

Analysis of Variance↗

PubMed1993

Nutritional risk and survival in elderly veterans: a five-year follow-up.

The purpose of this study was to identify predictors of survival over five years in a sample of 377 elderly (age 55+) chronically ill men. Subjects were selected at baseline from consecutive appointments at a geriatric clinic and given extensive medical and psychosocial assessment. Five years later, subjects who could be located were interviewed by telephone. Interviews were completed with 194 (51.4%) subjects, 90 others were confirmed as deceased, 29 subjects could not be interviewed, and 64 more were not located although VA records did not show that any were deceased. The predictor variable of interest was the Nutritional Risk Index (NRI), a 16 item index which measures nutritional dimensions of health status. Other variables included functional health status [Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL)], mental health status [Mini-Mental Status Exam (MMSE), morale], health habits (smoking, alcohol use and exercise), use of health services (physician visits, emergency room (ER) visits, hospital stays), and demographic factors (age, income, marital status and living arrangements). Proportional hazard models showed that the variables with statistically significant direct effects on survival time were younger age, higher functional health status on IADL, non-smoking, moderate alcohol use, and perception of adequate income. Nutritional status was indirectly associated with survival.

Activities of Daily Living↗

PubMed1998

Life expectancy of children with cerebral palsy.

Risk factors for mortality of young children with cerebral palsy were studied using a sample of 12,709 children aged 0.5-3.5 years with cerebral palsy who had received services from the State of California between 1980 and 1995. The most powerful prognostic factors for survival were simple functional items: mobility and feeding skills. Once these were known, factors such as severity of mental retardation and presence of quadriplegia contributed relatively little. Children with fair motor and eating skills had good survival prospects, with 90% or more reaching adulthood, but those without such skills had much poorer prospects. Among children who were unable to lift their heads, median survival time was 7 additional years for those who were tube fed (n = 557) and 14 years for those fed entirely by others (n = 997). Although a child's approximate survival chances can be assessed from such functional classifications, we indicate the manner in which additional information on the child's condition can be used to obtain more accurate survival data.

Activities of Daily Living↗

PubMed1998

Is schizophrenia a disorder of all ages? A comparison of first episodes and early course across the life-cycle.

BACKGROUND: The heterogeneity of schizophrenic and delusional syndromes by age of onset has frequently been discussed. METHODS: The age distribution of symptoms and 5 year course was studied in a population-based first-episode sample admitted to 10 psychiatric hospitals before the age of 60 (N = 232) and in a clinical sample without age limit of consecutive first admissions to a single hospital (N = 1109), both samples with broadly diagnosed schizophrenia. RESULTS: Early-onset patients, particularly men, presented more non-specific symptoms and higher PSE-CATEGO total scores than late-onset patients. In men, symptom severity decreased with increasing age of onset. In women, it remained stable except for an increase of negative symptoms with late-onset. Only a few symptoms changed markedly with age: disorganization decreased, while paranoid and systematic delusions increased steeply across the whole age of onset range. Pronounced age- and sex-differences emerged in illness behaviour, socially negative behaviour and substance abuse. Within the group of late-onset psychoses there were continuous transitions in symptom profiles and no discrimination between schizophrenia and paranoid psychosis or late paraphrenia. The main determinant of social course was onset level of social development. Early-onset patients did not improve in social status, while late-onset patients, prior to retirement, suffered considerable decline in social status. CONCLUSIONS: Gender differences in age at onset and in age trends in symptom severity support the hypothesis of a mild protective effect of oestrogen. Social course results from an interplay between biological factors (age at onset and functional impairment) and development factors (level of social development at onset and illness behaviour).

Adolescent↗

PubMed2006

Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: a meta-analysis.

The mesial premotor cortex (pre-supplementary motor area and supplementary motor area proper), lateral premotor cortex (dorsal premotor cortex and ventral premotor cortex), and primary sensorimotor cortex (primary motor cortex and primary somatosensory cortex) have been identified as key cortical areas for sensorimotor function. However, the three-dimensional (3-D) anatomic boundaries between these regions remain unclear. In order to clarify the locations and boundaries for these six sensorimotor regions, we surveyed 126 articles describing pre-supplementary motor area, supplementary motor area proper, dorsal premotor cortex, ventral premotor cortex, primary motor cortex, and primary somatosensory cortex. Using strict inclusion criteria, we recorded the reported normalized stereotaxic coordinates (Talairach and Tournoux or MNI) from each experiment. We then computed the probability distributions describing the likelihood of activation, and characterized the shape, extent, and area of each sensorimotor region in 3-D. Additionally, we evaluated the nature of the overlap between the six sensorimotor regions. Using the findings from this meta-analysis, along with suggestions and guidelines of previous researchers, we developed the Human Motor Area Template (HMAT) that can be used for ROI analysis. HMAT is available through e-mail from the corresponding author.

Algorithms↗

PubMed2006

PKPD model of interleukin-21 effects on thermoregulation in monkeys--application and evaluation of stochastic differential equations.

PURPOSE: To describe the pharmacodynamic effects of recombinant human interleukin-21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms of heat regulation. A major effort was devoted to compare the use of ordinary differential equations (ODEs) with stochastic differential equations (SDEs) in pharmacokinetic pharmacodynamic (PKPD) modelling. METHODS: A temperature model was formulated including circadian rhythm, metabolism, heat loss, and a thermoregulatory set-point. This model was formulated as a mixed-effects model based on SDEs using NONMEM. RESULTS: The effects of IL-21 were on the set-point and the circadian rhythm of metabolism. The model was able to describe a complex set of IL-21 induced phenomena, including 1) disappearance of the circadian rhythm, 2) no effect after first dose, and 3) high variability after second dose. SDEs provided a more realistic description with improved simulation properties, and further changed the model into one that could not be falsified by the autocorrelation function. CONCLUSIONS: The IL-21 induced effects on thermoregulation in cynomolgus monkeys are explained by a biologically plausible model. The quality of the model was improved by the use of SDEs.

Algorithms↗

PubMed1998

Aging and source monitoring: cognitive processes and neuropsychological correlates.

This study shows that relative to younger adults, older adults are more adversely influenced by similar items when judging a memory's source, and the phenomenal features of their correctly and incorrectly attributed memories have greater overlap. The authors argue in accordance with the source monitoring framework that this age-related impairment in source accuracy is related to processes involved in binding features into complex memories and those involved in accessing and evaluating contextual features of memories. These processes are linked to medial temporal and frontal brain regions, respectively, as evidenced by correlations in older adults between source accuracy and neuropsychological tests often used to assess medial temporal and frontal function. The results suggest that adequate feature binding is particularly important when items from different source share similar features and access-evaluation processes are particularly important after a delay.

Adult↗

PubMed2003

Selection on coding regions determined Hox7 genes evolution.

The important role of Hox genes in determining the regionalization of the body plan of the vertebrates makes them invaluable candidates for evolutionary analyses regarding functional and morphological innovation. Gene duplication and gene loss led to a variable number of Hox genes in different vertebrate lineages. The evolutionary forces determining the conservation or loss of Hox genes are poorly understood. In this study, we show that variable selective pressures acted on Hox7 genes in different evolutionary lineages, with episodes of positive selection occurring after gene duplications. Tests for functional divergence in paralogs detected significant differentiation in a region known to modulate HOX7 protein activity. Our results show that both positive and negative selection on coding regions are influencing Hox7 genes evolution.

Amino Acid Sequence↗

PubMed2005

Comparative analysis of the Saccharomyces cerevisiae and Caenorhabditis elegans protein interaction networks.

BACKGROUND: Protein interaction networks aim to summarize the complex interplay of proteins in an organism. Early studies suggested that the position of a protein in the network determines its evolutionary rate but there has been considerable disagreement as to what extent other factors, such as protein abundance, modify this reported dependence. RESULTS: We compare the genomes of Saccharomyces cerevisiae and Caenorhabditis elegans with those of closely related species to elucidate the recent evolutionary history of their respective protein interaction networks. Interaction and expression data are studied in the light of a detailed phylogenetic analysis. The underlying network structure is incorporated explicitly into the statistical analysis. The increased phylogenetic resolution, paired with high-quality interaction data, allows us to resolve the way in which protein interaction network structure and abundance of proteins affect the evolutionary rate. We find that expression levels are better predictors of the evolutionary rate than a protein's connectivity. Detailed analysis of the two organisms also shows that the evolutionary rates of interacting proteins are not sufficiently similar to be mutually predictive. CONCLUSION: It appears that meaningful inferences about the evolution of protein interaction networks require comparative analysis of reasonably closely related species. The signature of protein evolution is shaped by a protein's abundance in the organism and its function and the biological process it is involved in. Its position in the interaction networks and its connectivity may modulate this but they appear to have only minor influence on a protein's evolutionary rate.

Animals↗

PubMed2006

Evolutionary studies on an alpha-amylase gene segment in bats and other mammals.

Comparative studies of salivary glands showed that they maybe related to the adaptive radiation of bats, especially in the family Phylostomidae. In this study we have been searching for a likely relationship between different feeding habits found in bats and possible adaptive changes in a coding segment of the alpha-amylase enzyme. We have also tested some hypothesis about the phylogenetic relationship of bats and other mammals. A 663 bp segment of the alpha-amylase gene, corresponding to the exon 4 and part of the intron c, was sequenced in nine bat species. The exon 4 was also sequenced in further ten mammalian species. The phylogenetic trees generated with different methods produced the same results. When the intron c and the exon 4 were independently analyzed, they showed distinct topologies involving the bat species Sturnira lilium, different from the traditional bat phylogeny. Phylogenetic analysis of bats, primates and rodents supports the Euarchontoglires-Laurasiatheria hypothesis about the relationship among these groups. Selection tests showed that the alpha-amylase exon 4 is under strong purifying selection, probably caused by functional constraints. The conflicting bat phylogenies could not be explained by evolutionary convergence due to adaptive forces, and the different topologies may be likely due to the retention of plesiomorphic characters or the independent acquisition by evolutionary parallelism.

Amino Acid Sequence↗

PubMed1996

Exposure-response functions in Air Force toxic risk modeling.

A new methodology for estimating the probabilistic risk from acute toxic exposures is planned as a support tool for the Air Force at the Eastern and Western Ranges. Two such methodologies are programs entitled the Launch Area Toxic Analysis program (LATRA) and the Cold Spill Toxic Risk Analysis program (COSTRA). These programs combine probabilistic models of an accident (when applicable), release cloud formation and dispersion (appropriate to the toxic substance and accounting for meteorological conditions), and new exposure-response functions (ERFs) for sensitive and normal exposed populations. These ERFs, anchored on specific exposure standards, estimate the probability of a given severity of health effect in a particular population as a function of the concentration or dose to which it is exposed. The further development and acceptance of these ERFs by the toxicology community, especially for different sensitivities, are key concerns addressed in this paper.

Accidents, Aviation↗