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PubMed1992

The epidemiology of genetic epidemiology.

Familial aggregation for disease is important; strong familial risk factors must exist even if the increased risk to a relative of an affected individual is modest. It is in practice difficult, however, to conduct studies in genetic epidemiology which conform to strict epidemiological principles. For twin studies there are two major questions: Are twins 'no different' from the population on which inference is to be made? Are study twins 'no different' to twins in the population? The importance of each question of bias depends on the scientific question, the trait(s) studied, and sampling issues. The strength of the twin design is its ability to refute the null hypothesis that genetic factors do not explain variation in a trait. Following the Popperian paradigm, alternate hypotheses should be considered in depth (both theoretically and empirically), with a design and sample size sufficient to exclude not just naive explanations. More sophisticated statistical techniques are now being applied, so the philosophy, assumptions, and limitations of statistical modelling must be appreciated. The concept of 'heritability' has, in the past, been misunderstood and misused. New advances in DNA technology promise to revolutionise epidemiological thinking, and so case-control-pedigree designs may well become standard tools. The strengths and limitations of studies based on related individuals as the sampling unit are discussed.

Adult↗

PubMed1990

Segregation ratios within Segregation Distorter lines of Drosophila melanogaster conform to a beta-binomial distribution.

Segregation Distorter (SD) chromosomes are preferentially recovered from SD/SD+ males due to the dysfunction of sperm bearing the SD+ chromosome. The proportion of offspring bearing the SD chromosome is given the symbol k. The nature of the frequency distribution of k was examined by comparing observed k distributions produced by six different SD chromosomes, each with a different mean, with k distributions predicted by two different statistical models. The first model was one where the k of all males with a given SD chromosome were considered to be equal prior to the determination of those gametes which produce viable zygotes. In this model the only source of variation of k would be binomial sampling. The results rigorously demonstrated for the first time that the observed k distributions did not fit the prediction that the only source of variation was binomial sampling. The next model tested was that the prior distribution of segregation ratios conformed to a beta distribution, such that the distribution of k would be a beta-binomial distribution. The predicted distributions of this model did not differ significantly from the observed distributions of k in five of the six cases examined. The sixth case probably failed to fit a beta-binomial distribution due to a major segregating modifier. The demonstration that the prior distribution of segregation ratios of SD lines can generally be approximated with a beta distribution is crucial for the biometrical analysis of segregation distortion.

Animals↗

PubMed2006

Genetic mapping of allometric scaling laws.

Many biological processes, from cellular metabolism to population dynamics, are characterized by particular allometric scaling relationships between rate and size (power laws). A statistical model for mapping specific quantitative trait loci (QTLs) that are responsible for allometric scaling laws has been developed. We present an improved model for allometric mapping of QTLs based on a more general allometry equation. This improved model includes two steps: (1) use model II regression analysis to estimate the parameters underlying universal allometric scaling laws, and (2) substitute the estimated allometric parameters in the mixture-based mapping model to obtain the estimation of QTL position and effects. This model has been validated by a real example for a mouse F2 progeny, in which two QTLs were detected on different chromosomes that determine the allometric relationship between growth rate and body weight.

Algorithms↗

PubMed2002

Estimating the distribution of worm burden and egg excretion of Schistosoma japonicum by risk group in Sichuan Province, China.

During autumn 2000 an extensive cross-sectional survey of the prevalence of Schistosomiasis japonicum was conducted among about 4000 villagers within 20 villages in the Anning River Valley located in the southwestern Sichuan Province. Two procedures were used to assess infection status, the Kato-Katz thick smear procedure and a miracidia hatch test. Whereas the Kato-Katz procedure provides information on both prevalence and intensity, the hatch test provides only prevalence data, albeit on a much larger volume of stool. In addition, we performed Kato-Katz smears for 15 consecutive samples on a subset of 15 individuals. The proportion of both hatch-test and Kato-Katz positive individuals in the larger cross-sectional survey was 25%. The goal of the study was to estimate both the egg and worm distributions among risk groups using both the hatch and Kato-Katz tests from the cross-sectional data and the repeated Kato-Katz smears from the longitudinal data sets. As a prelude to parameter estimation, individuals were classified into risk groups by natural village and occupation; the proportion of Kato-Katz positive subjects among the risk groups varied from 10% to 60%. We used the statistical model of de Vlas et al. (1992) and Bayesian techniques to derive both estimates of and inference about the worm and egg distribution parameters. The parameter estimates imply (1) similar eggs per gram stool (e.p.g.) per worm pair compared with earlier estimates, (2) a range of worm burdens among the risk groups and (3) estimates of risk heterogeneity within groups is sensitive to prior information on the within-person variability in egg excretion.

Age Factors↗

PubMed2000

Dynamics of natural immunity caused by subclinical infections, case study on Haemophilus influenzae type b (Hib).

Natural immunity to Haemophilus influenzae type b (Hib) is based primarily on antibodies that are thought to develop in response to subclinical infections. Wide use of conjugated Hib vaccines could lead to decreases in circulating Hib bacteria, thereby diminishing antibody levels in the unvaccinated. We applied a statistical model to estimate the duration of natural immunity to Hib under different forces of infection. Prior to the introduction of conjugated Hib vaccines, new Hib infections were estimated to occur once in 4 years and the antibody concentration to stabilize at a level around 1 microg/ml. In the absence of new stimuli, i.e. infection, 57% of the unvaccinated population would become susceptible to invasive disease (antibody levels < 0.15 microg/ml) in 10 years. Due to an interaction between the force of infection and the duration of immunity, in some situations numbers of invasive infections could increase in unvaccinated cohorts. This theoretical scenario has yet to be observed in practice.

Adolescent↗

PubMed1990

Serological study of the epidemiology of mumps virus infection in north-west England.

Serum samples from individuals of a wide age range, collected in northwest England in 1984 and 1986, provide the basis for an analysis of the epidemiology of mumps virus infection. A radial haemolysis test yielding quantitative antibody measurements was used to screen samples for mumps-specific IgG. Analyses of resultant age-seroprevalence profiles, using statistical models, revealed an age-related pattern in the rate of infection per susceptible similar to that observed for other childhood infections. This rate, or force of infection, was low in young children, high in older children, and low in adults. In addition, the serological surveys provide evidence for time-dependent changes (both epidemic and longer-term) in the rate of mumps virus transmission. The longer-term changes, reflected in the pattern of the age-acquisition of specific antibodies, are supported by evidence from case notification data. The implications of temporal changes in incidence to the interpretation and design of serological surveys are considered.

Adolescent↗

PubMed2001

Use of the chronic disease score to measure comorbidity in the Canadian Study of Health and Aging.

Most older adults have multiple chronic diseases. Consideration of these conditions can improve the performance of statistical models in epidemiological analyses. The Chronic Disease Score (CDS) is a measure of comorbidity derived from medication usage, which may have some advantages over measures derived from other sources. The calculation of the CDS from data contained in the Canadian Study of Health and Aging (CSHA) is described. This measure can be used to estimate comorbidity within the CSHA database.

Aged↗

PubMed2003

Contemporary longitudinal methods for the study of trauma and posttraumatic stress disorder.

Traditional methods for analyzing trends in longitudinal data have typically emphasized average group change over time. In this article, we propose multilevel, regression-based methods for examining inter-individual differences in intra-individual change and apply these methods to research in trauma and posttraumatic stress disorder (PTSD). The outcome or dependent variable of interest is reconceptualized as an index of dynamic change reflecting the trend or trajectory of an individual's PTSD symptom severity scores across time. A basic statistical model is presented, and analyses and findings are demonstrated with an existing database used in previously published studies. The methods offer promise for future study of the natural course of PTSD chronicity or recovery, risk and resilience factors that influence individual growth or decline, and critical timepoints for intervention.

Adaptation, Psychological↗

PubMedDate not supplied

Epidemiology in community psychiatric research: common uses and methodological issues.

OBJECTIVE: Epidemiological principles underpin much medical research particularly that concerned with the planning and evaluation of health services, including research in community and social psychiatry. The aim of this paper is to review some of the common uses of epidemiology in community psychiatric research and to discuss some methodological issues that arise frequently in epidemiological research in community settings. METHODS: This is a review of the relevant literature and of the work currently in progress in the department of psychological medicine of the university of Wales College of Medicine. RESULTS: Among the many uses of epidemiology in health care, four are especially relevant in community psychiatric settings: the assessment of the mental health needs of the population (four approaches are described: the collection of routine data, surveys of existing patients, surveys of the general population and statistical modelling), the identification of risk factors of disease, the contribution to prevention and the assessment of the clinical effectiveness of health care interventions. The most important methodological issues include causal inference which in epidemiology takes the form of explaining the association between an exposure and disease (chance, bias, confounding, reverse causality and causality), the issue of confounding and how to adjust for it and issues arising in the context of specific study designs. CONCLUSION: Epidemiology has become a set of methods used to investigate a wide range of clinical questions. Population based research is an essential part of clinical research but epidemiological knowledge is also needed by clinicians in order to critically appraise and interpret the scientific literature.

Bias↗

PubMed1997

Effect of additional unpaired bases on the stability of three-way DNA junctions studied by fluorescence techniques.

Fluorescence melting experiments were carried out to determine the relative stability of three-way DNA junctions with and without extrahelical adenine nucleotides in one strand at the branch point of the junction (i.e., An bulges where n = 0, 1, 2, and 3). The oligonucleotides were labeled with chromophores at the 5' ends of the strands. The progress of the thermal denaturation was followed by monitoring the fluorescence intensities and anisotropies of the dyes and the fluorescence resonance energy transfer between the two dyes. The results of the thermal denaturation experiments are interpreted and discussed in terms of either two-state thermodynamic models or statistical models for the thermal denaturation. The junctions all melt at the same temperature (at equal concentrations) within the error of the Tm determination, regardless of the presence, or absence, of the bulge. It is suggested that the denaturation of the helical arms begins primarily at the free ends of the helical arms and proceeds toward the branch point. The junctions, all which have 10 base pairs in each arm, possess thermal denaturation characteristics similar to duplexes with 20 arms. This leads to the proposition that for these junctions an important molecular parameter that controls the stability of the junctions is the number of base pairs between neighboring arms. The melting profiles obtained by monitoring the tetramethylrhodamine fluorescence are found to depend strongly on the nucleotide sequence in the single-stranded region.

Base Composition↗

PubMedDate not supplied

QSAR--how good is it in practice? Comparison of descriptor sets on an unbiased cross section of corporate data sets.

The quality of QSAR (Quantitative Structure-Activity Relationships) predictions depends on a large number of factors including the descriptor set, the statistical method, and the data sets used. Here we study the quality of QSAR predictions mainly as a function of the data set and descriptor type using partial least squares as the statistical modeling method. The study makes use of the fact that we have access to a large number of data sets and to a variety of different QSAR descriptors. The main conclusions are that the quality of the predictions depends both on the data set and the descriptor used. The quality of the predictions correlates positively with the size of the data set and the range of biological activities. There is no clear dependence of the quality of the predictions on the complexity of the data set. All of the descriptors tested produced useful predictions for some of the data sets. None of the descriptors is best for all data sets; it is therefore necessary to test in each individual case, which descriptor produces the best model. In our tests, 2D fragment based descriptors usually performed better than simpler descriptors based on augmented atom types. Possible reasons for these observations are discussed.

Models, Statistical↗

PubMed2007

Reactions of nitrogen monoxide on cobalt cluster ions: reaction enhancement by introduction of hydrogen.

Absolute cross sections for NO chemisorption, NO decomposition, and cluster dissociation in the collision of a nitrogen monoxide molecule, NO, with cluster ions Con+ and ConH+ (n=2-5) were measured as a function of the cluster size, n, in a beam-gas geometry in a tandem mass spectrometer. Size dependency of the cross sections and the change of the cross sections by introduction of H to Con+ (effect of H-introduction) are explained by a statistical model based on the RRK theory, with the aid of the energetics obtained by a DFT calculation. It was found that the reactions are governed by the energetics rather than dynamics. For instance, Co3+ does not react appreciably with NO because the reactions are endothermic, while Co3H+ does because the reaction becomes exothermic by the H-introduction.

Catalysis↗

PubMed2006

Adsorption and spontaneous rupture of vesicles composed of two types of lipids.

To analyze the adsorption of single vesicles composed of two types of lipids (e.g., zwitterionic and positively charged lipids or zwitterionic and negatively charged lipids), we propose a statistical model taking into account lipid-surface interactions, lipid-lipid lateral interactions, and vesicle bending energy. Our treatment specifies how these parameters govern vesicle adsorption, shows how the radius of the vesicle-surface contact area may depend on the vesicle composition, and clarifies the conditions for vesicle rupture.

Adsorption↗

PubMedDate not supplied

From precursor to final peptides: a statistical sequence-based approach to predicting prohormone processing.

Predicting the final neuropeptide products from neuropeptides genes has been problematic because of the large number of enzymes responsible for their processing. The basic processing of 22 Aplysia californica prohormones representing 750 cleavage sites have been analyzed and statistically modeled using binary logistic regression analyses. Two models are presented that predict cleavage probabilities at basic residues based on prohormone sequence. The complex model has a correct classification rate of 97%, a sensitivity of 97%, and a specificity of 96% when tested on the Aplysia dataset.

Amino Acid Sequence↗

PubMedDate not supplied

Improving solubility of Shewanella oneidensis MR-1 and Clostridium thermocellum JW-20 proteins expressed into Esherichia coli.

Low solubility of proteins overexpressed in E. coli is a frequent problem in high-throughput structural genomics. To improve solubility of proteins from mesophilic Shewanella oneidensis MR-1 and thermophilic Clostridium thermocellum JW20, an approach was attempted that included a fusion of the target protein to a maltose-binding protein (MBP) and a decrease of induction temperature. The MBP was selected as the most efficient solubilizing carrier when compared to a glutathione S-transferase and a Nus A protein. A tobacco etch virus (TEV) protease recognition site was introduced between fused proteins using a double polymerase-chain reaction and four primers. In this way, 79 S. oneidensis proteins have been expressed in one case with an N-terminal 30-residue tag and in another case as a fusion protein with MBP. A foreign tag might significantly affect the properties of the target polypeptide. At 37 degrees C and 18 degrees C induction temperatures, only 5 and 17 tagged proteins were soluble, respectively. In fusion with MBP 4, 34, and 38 proteins were soluble upon induction at 37 degrees, 28 degrees, and 18 degrees C, respectively. The MBP is assumed to increase stability and solubility of a target protein by changing both the mechanism and the cooperativity of folding/unfolding. The 66 C. thermocellum proteins were expressed as fusion proteins with MBP. Induction at 37 degrees, 28 degrees, and 18 degrees C produced 34, 57, and 60 soluble proteins, respectively. The higher solubility of C. thermocellum proteins in comparison with the S. oneidensis proteins under similar conditions of induction correlates with the thermophilicity of the host. The two-factor Wilkinson-Harrison statistical model was used to identify soluble and insoluble proteins. Theoretical and experimental data showed good agreement for S. oneidensis proteins; however, the model failed to identify soluble/insoluble Clostridium proteins. A suggestion has been made that the Wilkinson-Harrison model is not applicable to C. thermocellum proteins because it did not account for the peculiarities of protein sequences from thermophiles.

Amino Acid Sequence↗

PubMed1998

Predicting patients' utilities from quality of life items: an improved scoring system for the UBQ-H.

The Utility-based Quality of Life--Heart Questionnaire (UBQ-H) is a cardiovascular extension of the Health Measurement Questionnaire. It is a multidimensional instrument that can be scored to yield a utility estimate using the Rosser Index and a classification algorithm developed for the Health Measurement Questionnaire. The aim of this study was to employ a statistical modelling approach to devise an improved scoring system. A sample of 201 cardiovascular patients completed the UBQ-H and assessed the utility of their own health state using standard gamble and time trade-off questions in an interview. Two new scoring methods were devised by regressing the UBQ-H data against patients' self-assessed utilities. The new methods gave utility estimates that correlated with angina/dyspnoea grades, life satisfaction scores and General Health Questionnaire (GHQ) scores. In a second sample of 1,112 cardiovascular patients, the UBQ-H utilities were able to distinguish between patients who had/had not experienced an adverse event (e.g. myocardial infarction) and were responsive to changes in health over time. The new scoring methods were not particularly more sensitive to quality of life effects than the original method based on the Rosser Index. However, they produced significantly lower estimates and more accurately reflected patients' self-assessed utilities.

Cardiovascular Diseases↗

PubMed1999

Comparison of statistical methods to predict the time to complete a series of surgical cases.

We present a statistical model for predicting the time to complete a series of successive, elective surgical cases. The use of sample means of case times and turnover times when scheduling cases does not minimize the operating room labor costs associated with errors in predicting times to complete series of cases. The problem of minimizing associated labor costs (both under and over utilization) can be converted to the problem of least absolute deviation regression. The dependent variables are the times to complete series of cases. The independent variables are the numbers of cases in each series that are in various categories (i.e., combinations of scheduled procedures and surgeons). Although the computational method is preferred on theoretical grounds to that involving sample means, application of both methods shows that the more practical method is to use the sample means of previous case times and turnovers.

Elective Surgical Procedures↗

PubMed1998

Gallbladder volume: comparison of diabetics and controls.

Diabetics are known to have an increased prevalence of gallstones. The aim of this study was to investigate whether diabetics have increased gallbladder volumes that would predispose to stasis, nucleation of cholesterol crystals, and gallstone formation. The gallbladder volume of 271 diabetic subjects and 277 controls was determined by ultrasound using the ellipse formula. Gallbladder volume was also determined by the sum of the cylinders method in 143 cases with a strong correlation (r = 0.89) between the two methods. Using analysis of variance, gallbladder volume was influenced by both diabetic type (NIDDM = 33.68 cm3, IDDM = 26.84 cm3, controls = 29.05 cm3; P = 0.018) and the presence of gallstones (gallstones = 32.04 cm3, no gallstones = 27.58 cm3; P = 0.018). The variation in gallbladder volume between NIDDM, IDDM, and control subjects was influenced by the presence of gallstones (P = 0.024, interaction term from ANOVA). Significant differences (P < 0.001) were only found between NIDDM vs IDDM and NIDDM vs control in the nongallstone group (NIDDM = 34.33 cm3, IDDM = 25.08 cm3, control = 25.17 cm3). Males had significantly larger gallbladder volumes than females: 31.98 cm3 vs 27.74 cm3 (P = 0.023). After the inclusion of BMI, HDL cholesterol, triglyceride, and age in a statistical model with gender and diabetic type in those without gallstones, significant differences were still found between NIDDM and IDDM (P = 0.013) and NIDDM and controls (P = 0.005), demonstrating that NIDDM is an independent predictor for increased gallbladder volume.

Adult↗