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PubMed1999

Genetics and child psychiatry: I Advances in quantitative and molecular genetics.

Advances in quantitative psychiatric genetics as a whole are reviewed with respect to conceptual and methodological issues in relation to statistical model fitting, new genetic designs, twin and adoptee studies, definition of the phenotype, pervasiveness of genetic influences, pervasiveness of environmental influences, shared and nonshared environmental effects, and nature-nurture interplay. Advances in molecular genetics are discussed in relation to the shifts in research strategies to investigate multifactorial disorders (affected relative linkage designs, association strategies, and quantitative trait loci studies); new techniques and identified genetic mechanisms (expansion of trinucleotide repeats, genomic imprinting, mitochondrial DNA, fluorescent in-situ hybridisation, behavioural phenotypes, and animal models); and the successful localisation of genes.

Adolescent↗

PubMed1991

Prediction of graduate dietetic internship appointments in Canada.

A statistical model of dietetic intern selection was developed from a profile of selection criteria that was obtained in a 1988 survey of Canadian graduate dietetic internship directors. The model was composed of four clusters of variables that resulted from the most frequently used selection criteria: academic performance, work experience, communication skills, and extracurricular activities. Data from a convenience sample of 39 dietetic intern applicants were analyzed, using principal components analysis and discriminant analysis, to test the model's power to predict success in obtaining an internship appointment. In descending order, the criteria with the greatest predictive powers were: academic performance; extracurricular activities; and supervisory, teaching, or instructing types of work experience. The model accounted for 41% of the differences between those who were successful and those who were not successful in obtaining internship appointments in 1989 and correctly classified 30 of 39 subjects. These results provide baseline data on the predictive power of some criteria used for selecting dietetic interns. These findings suggest the need for a replication study with a randomized national sample to crossvalidate the results obtained in this exploratory research.

Canada↗

PubMedDate not supplied

A statistical evaluation of the Youden Matched-Pairs Procedure.

AOAC INTERNATIONAL currently permits investigators to use the Youden Matched-Pairs Procedure to obtain estimates of the method performance indicators repeatability and reproducibility (S(r) and SR, respectively). This report explains the statistical model assumptions upon which the procedure is based, provides validity tests for several of these assumptions, explains conditions under which Youdens' "precision error" is not consistent with precision estimate S(r) or SR as defined by AOAC INTERNATIONAL, and indicates when precision estimates based on the procedure should be interpreted with caution or should not be used.

Laboratories↗

PubMed1999

Analysis of time-to-pregnancy data.

Statistical models for time-to-pregnancy data are usually formulated in discrete time. Two approaches were surveyed, including methods of accounting for both known heterogeneity (covariates, possibly time-dependent) and unknown heterogeneity (frailty). Delicate censoring and truncation patterns arose for prospective and, particularly, retrospective sampling designs. The inclusion of several pregnancies per couple presents new challenges and possibilities.

Cross-Sectional Studies↗

PubMed1989

Making use of patient survey data.

Scientific measurement and management of patient satisfaction is a necessary part of retaining satisfied customers. This, the first in a series of three articles on patient surveys, shows how to use a general statistical model to quantify the patient experiences that most affect perceptions of quality or satisfaction and the likelihood of patients returning to your hospital.

Consumer Behavior↗

PubMed1999

Statistical method for the estimation of cerebral blood flow using the Kety-Schmidt technique.

The Kety-Schmidt technique for the measurement of cerebral blood flow (CBF) has been in use for many years, but efficient statistical methods for producing estimates of CBF have received little attention. This paper proposes simple statistical models for this problem and explores their properties using data from a recent study of severe head injury in children. The method, which can readily be implemented on a personal computer, allows the uncertainty in the estimate of CBF to be quantified.

Cerebrovascular Circulation↗

PubMed1999

Intelligent split menus for data entry: a simulation study in general practice medicine.

A compelling notion in menu design is that a few of the most frequently selected items should be placed as a hot list at the top of the menu. A few researchers have explored this type of interface control, known as a split menu, and have investigated the identification of the hot-list items by statistical analysis of past data. We extend the technique to automated development of dynamic hot-lists for entry of medication data in a General Practice setting. Using clinical data from 113,000 visits, a statistical model is developed and evaluated by simulated data entry of cases held back from training. Simulated SOAP note entry shows 12-item hot lists to hold over 70% of desired drug and diagnosis selections. Intelligent split menus should improve user efficiency if current selection methods require 3 seconds or more per item. A demonstration prototype can be downloaded over the Web.

Artificial Intelligence↗

PubMed1999

Biological dosimetry of chernobyl cleanup workers: inclusion of data on age and smoking provides improved radiation dose estimates.

We report the results of a study of chromosome translocations in 126 Russian subjects who participated in the cleanup activities at Chernobyl and another 53 subjects, from other places in Russia, who were not exposed at Chernobyl. In agreement with our earlier study, we find increased translocation frequencies among the exposed compared to Russian controls. We describe statistical methods for estimating the dose of ionizing radiation determined by scoring chromosome translocations found in circulating lymphocytes sampled several years after exposure. Two statistical models were fitted to the data. One model assumed that translocation frequencies followed an overdispersed Poisson distribution. The second model assumed that translocation frequencies followed a negative binomial distribution. In addition, the effects of radiation exposure were modeled as additive or as multiplicative to the effects of age and smoking history. We found that the negative binomial model fit the data better than the overdispersed Poisson model. We could not distinguish between the additive and the multiplicative model with our data. Individual dose estimates ranged from 0 (for 43 subjects) to 0.56 Gy (mean 0.14 Gy) under the multiplicative model and from 0 to 0.95 Gy (mean 0.15 Gy) under the additive model. Dose estimates were similar under the two models when the number of translocations was less than 4 per 100 cells. The additive model tended to estimate larger doses when the number of translocations was greater than 4 per 100 cells. We also describe a method for estimating upper 95% tolerance bounds for numbers of translocations in unexposed individuals. We found that inclusion of data on age and smoking history was important for dose estimation. Ignoring these factors could result in gross overestimation of exposures, particularly in older subjects who smoke.

Adult↗

PubMed2000

Screening for trisomies 21 and 18 with maternal serum placental isoferritin p43 component.

A component of placental isoferritin, p43, is an immuno-regulatory protein associated with suppression of the immune system. Maternal serum p43 levels increase throughout pregnancy and low serum levels have been associated with various pathological pregnancies, particularly those with a defect of placentation. We measured maternal serum p43 retrospectively in banked samples from 42 Down syndrome, 20 Edwards' syndrome and 281 unaffected pregnancies to assess its screening potential in both the first and second trimesters. The median maternal serum p43 level in Down syndrome was 1.58 times higher than that in the unaffected pregnancies (p=0.01, two-tail). The median level was slightly, but not significantly, reduced in Edwards' syndrome. Statistical modelling, including parameters for alpha-fetoprotein, free beta-human chorionic gonadotrophin, and unconjugated oestriol suggested that it might have a role in Down syndrome screening when combined with two or three of these markers. Larger scale studies are now needed.

Chorionic Gonadotropin, beta Subunit, Human↗

PubMed2000

Estimating birth prevalence of Down's syndrome.

BACKGROUND: Estimates of maternal age-specific prevalence of Down's syndrome are needed for the assessment of environmental factors, for counselling and monitoring screening programmes. The estimates should relate to populations of women who have not received prenatal screening. This is normally achieved by using data collected before the widespread use of screening. The problem of under-ascertainment in some data-sets has been recognised in the literature, but has not been dealt with satisfactorily in the statistical models used to estimate live-birth prevalence. METHODS: In this paper we develop a model that takes explicit account of under-ascertainment and apply this model to data from nine published studies. The primary aim of our analysis is to provide an improved model for live-birth prevalence. A secondary aim is to examine the ascertainment rates in the nine studies. RESULTS: The proposed model provides a good fit to all but one of the nine studies, although exclusion of this study does not affect the estimated risks. The estimate of risk weighted across the maternal age distribution is 1.41 in 1000 live-births [90% confidence interval (CI) 1.37-1.49]. DISCUSSION: Comparing this figure with those obtained from published rate schedules suggests that the proposed model predicts rates that are some 10% higher than those obtained when ascertainment is assumed to be complete in all studies. The predicted rates are similar to those calculated when only those studies known to have high levels of acertainment are included.

Adolescent↗

PubMed2000

Changes in left ventricular function and mass during serial investigations after valve replacement for aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The potential for left ventricular hypertrophy regression and associated functional improvements may well be the underlying mechanism of results in general after valve replacement for aortic stenosis. The study aim was to investigate preoperative predictors and the time course of such ventricular changes. METHODS: Forty-six patients (mean age 61 years; range: 24-82 years) with aortic stenosis were prospectively followed with serial investigations (Doppler echocardiography, radionuclide ventriculography) at eight days (n = 43), three months (n = 42) and 18 months (n = 39) after valve replacement with a mechanical valve (19-29 mm). The postoperative course of left ventricular ejection fraction (EF), fast filling fraction, mass index and end-diastolic volume index (EDVi) was analyzed in an independent increments statistical model for repeated measurements. RESULTS: EF rose marginally, from 59+/-15% preoperatively to 64+/-16% (p <0.05) at 18 months, independently related to preoperative EF (p = 0.0001) and fast filling fraction (p = 0.0001). Changes in fast filling fraction were similarly predicted by the preoperative starting point (p = 0.003) and by preoperative left ventricular systolic radius:wall thickness ratio (p = 0.0002) with an inverse relation (the larger the chamber and the poorer its contractility, the lower the postoperative fast filling fraction). Mass index was independently related to the time point of postoperative measurement, indicating continuing regression of hypertrophy, from 200+/-66 g/m2 preoperatively to 148+/-49 g/m2 at 18 months (p <0.0001), when only 18% of the patients had normal mass index. Mass index was also independently related to preoperative left ventricular end-systolic dimension index (p = 0.0008) with a constant influence, and systolic wall stress (p = 0.0009) which was modified by time: the influence of wall stress was significant at eight days, weak at three months, and pronounced at 18 months. Left ventricular EDVi after surgery was inversely related to preoperative EF modified by time. Associated coronary artery disease, size of the prosthetic valve, and peak gradient across the valve (mean 15 mmHg; range: 7-26 mmHg at 18 months) did not influence any of the four target variables. CONCLUSION: We conclude that left ventricular response to valve replacement for aortic stenosis is predictable. A significant reduction in hypertrophy occurs during the first 18 postoperative months, but to a normal ventricular mass in only a minority of patients. Insufficient regression of hypertrophy was related to indices of irreversible myocardial disease, which also prevented functional ventricular improvement despite successful valve replacement and a hemodynamically well functioning valve.

Aortic Valve Stenosis↗

PubMed2001

Estimates of maternal mortality for 1995.

OBJECTIVE: To present estimates of maternal mortality in 188 countries, areas, and territories for 1995 using methodologies that attempt to improve comparability. METHODS: For countries having data directly relevant to the measurement of maternal mortality, a variety of adjustment procedures can be applied depending on the nature of the data used. Estimates for countries lacking relevant data may be made using a statistical model fitted to the information from countries that have data judged to be of good quality. Rather than estimate the Maternal Mortality Ratio (MMRatio) directly, this model estimates the proportion of deaths of women of reproductive age that are due to maternal causes. Estimates of the number of maternal deaths are then obtained by applying this proportion to the best available figure of the total number of deaths among women of reproductive age. FINDINGS: On the basis of this exercise, we have obtained a global estimate of 515,000 maternal deaths in 1995, with a worldwide MMRatio of 397 per 100,000 live births. The differences, by region, were very great, with over half (273,000 maternal deaths) occurring in Africa (MMRatio: > 1000 per 100,000), compared with a total of only 2000 maternal deaths in Europe (MMRatio: 28 per 100,000). Lower and upper uncertainty bounds were also estimated, on the basis of which the global MMRatio was unlikely to be less than 234 or more than 635 per 100,000 live births. These uncertainty bounds and those of national estimates are so wide that comparisons between countries must be made with caution, and no valid conclusions can be drawn about trends over a period of time. CONCLUSION: The MMRatio is thus an imperfect indicator of reproductive health because it is hard to measure precisely. It is preferable to use process indicators for comparing reproductive health between countries or across time periods, and for monitoring and evaluation purposes.

Cross-Cultural Comparison↗

PubMed2001

Design issues and sample size when exposure measurement is inaccurate.

Measurement error often leads to biased estimates and incorrect tests in epidemiological studies. These problems can be corrected by design modifications which allow for refined statistical models, or in some situations by adjusted sample sizes to compensate a power reduction. The design options are mainly an additional replication or internal validation study. Sample size calculations for these designs are more complex, since usually there is no unique design solution to obtain a prespecified power. Thus, additionally to a power requirement, an optimal design should also fulfill the criteria of minimizing overall costs. In this review corresponding strategies and formulae are described and appraised.

Bias↗

PubMedDate not supplied

Review of the development, validation, and application of predictive instruments in interventional cardiology.

Within the last few years, risk assessment has become an integral part of clinical practice, particularly for thoracic surgery and interventional procedures. Risk assessment statistical models are being used in medical decision making, quality improvement tools, and as aids to patient counseling. This literature review was conducted to evaluate the types of predictive models and outcomes measures that have been examined, and methods used in development, validation, and application of these models. A Medline search performed to identify articles (limited to human studies) published in English from 1980 to 1999 resulted in 89 articles, of which 71 were evaluable. Populations studied for model development included patients undergoing coronary artery bypass graft (CABG), percutaneous transluminal coronary revascularization (PTCR), cardiac catheterization, or stenting procedures and patients with angina or stroke. The models were equally developed from a single center versus multicenter and from retrospective databases versus prospective studies. In terms of model perspectives, only three of the models measured cost or cost-effectiveness as the outcome; the remainder considered only clinical outcomes. The most commonly reported types of predictive models were developed using logistic regression and Bayesian techniques, followed by neural networks, rule-based artificial intelligence, simultaneous equation system, and multiple linear regression. Factors to consider when developing or evaluating a predictive model include uniformity of definitions of outcomes, uniformity of definitions of variables, completeness of data, number and frequency of variables, timeliness and source of data, development population characteristics, development and testing (validation) cohorts, and calibration and discrimination. Application of these models to an individual patient can spur quality improvement efforts that can lead to dramatic, system-wide improvements in outcomes.

Cardiovascular Diseases↗

PubMed2001

Evaluate multiple adverse events in crossover design bioequivalence clinical trials.

AIM: To establish a statistical model to appropriately evaluate the relationship between clinical adverse event and treatment. METHODS: By splitting the duration of each treatment period into several time intervals (use day as unit), a clinical adverse event was sampled in each time interval as presented or not presented. The number of presented cases was added for each time interval, and time of subjects spent in each time interval was cumulated as person days. The onset of a clinical adverse event and its duration were represented as repeatedly measured count data. By using the generalized linear mixed model with fixed- and random-effects, the relative rate of clinical adverse events relative to different treatments was modeled by the generalized estimate equation (GEE) technique. RESULTS: Example shows that not only the onset of adverse events, but also its duration and total person-days subjects spent in study would influence the relative rate of clinic adverse events. CONCLUSION: Our proposed approach is a good alternative and supplemental method for evaluating clinical adverse events.

Clinical Trials as Topic↗

PubMed2001

Evaluating UMLS strings for natural language processing.

The National Library of Medicine's Unified Medical Language System (UMLS) is a rich source of knowledge in the biomedical domain. The UMLS is used for research and development in a range of different applications, including natural language processing (NLP). In this paper we investigate the nature of the strings found in the UMLS Metathesaurus and evaluate them for their usefulness in NLP. We begin by identifying a number of properties that might allow us to predict the likelihood of a given string being found or not found in a corpus. We use a statistical model to test these predictors against our corpus, which is derived from the MEDLINE database. For one set of properties the model correctly predicted 77% of the strings that do not belong to the corpus, and 85% of the strings that do belong to the corpus. For another set of properties the model correctly predicted 96% of the strings that do not belong to the corpus and 29% of the strings that do belong to the corpus.

MEDLINE↗

PubMed2002

Dissemination of regional rainfall analysis in design and analysis of urban drainage at un-gauged locations.

A research program in Denmark on statistical modelling of rainfall has resulted in a model for regional distribution of rainfall extremes. The results show that extreme rainfalls critical to the hydraulic function of urban drainage systems and the pollution discharge are subject to a significant regional variation of extreme rainfalls throughout the country. This has implications for design and analysis of all practical problems related to urban drainage, since the rainfall data so far recommended as input to engineering analyses underestimates the problems. Consequently, the Danish Water Pollution Control Committee has issued a statement recommending a new engineering practice. The dissemination of the research results proved to be difficult due to lack of understanding of the concepts of the new paradigm by practitioners. The traditional means of communication was supplemented by user-friendly spreadsheets and easy access to rainfall data as well as giving courses on the new paradigm. This has eased the implementation of the new concepts greatly.

Cities↗

PubMed2001

Navigation and thermophotovoltaic activity by hornets at different light conditions: the influence of UVB blockers.

The aim of the present investigation was two-fold: a) to observe the homing of the Oriental hornet, Vespa orientalis (Hymenoptera, Vespinae) from different distances; and b) to study the photothermoelectric activity of hornet cuticle obtained from the subjects of goal (a) and kept frozen for a number of days prior to its testing. In both the above mentioned phases of the investigation, an attempt was made to assess how the covering of the hornets' cuticle with Ultra Violet B (UVB) blockers affects their activity as compared to the control. Flying hornets were observed to return to the nest from distances of up to 7 km, once they had learned the way back. However, covering of the cuticle with UVB blockers increases the percentage of 'non-returners' to nearly 100%. Covering the cuticle completely or partly with a number of UVB blockers (except for Sisley) proves lethal for the hornets within 24 hours. A statistical model on homing is proposed of the effect of range, of covering with UVB blockers and covering ocelli with Tippex. In the wing of the hornet there is increase in the electric current with rise in the temperature and decrease in the current upon drop of the temperature, but light has no effect on this alar (wing) current. Contrariwise, the body cuticle of the hornet responds to both temperature and illumination in terms of its electric current. Coating of the cuticle with UVB blockers causes in the wing (under all conditions of illumination) and in the cuticle (only in the dark) a moderation in the amplitude of the photothermoelectric current.

Animals↗