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At least 991 records · Page 55Linked to original sources

Assessment of risk of perinatal death in Jamaica.

Data from the Jamaican Perinatal Mortality Survey had been used to create a statistical model using logistic regression. From this a simple additive scoring system to predict perinatal death was devised and tested on the 2 cohort months of the study. The score had a theoretical range of 0-28 points, with the higher the score, the greater the likelihood of a perinatal death. For a cut-point of 7, sensitivity was 43% and specificity 84%. A cut-point of 8 resulted in 27% sensitivity and 94% specificity. Higher cut-points resulted in much reduced sensitivity but enhanced specificity (e.g. cut-point 10: 11% sensitivity, 99% specificity). However, it is likely that these estimates are optimistically high, and to achieve unbiased estimates of sensitivity and specificity the score needs to be tested on a sample of the population from which it was not derived before implementation takes place. Meanwhile, the cut-off level for implementation will depend on appropriate resources available.

Cohort Studies↗

Maize association population: a high-resolution platform for quantitative trait locus dissection.

Crop improvement and the dissection of complex genetic traits require germplasm diversity. Although this necessary phenotypic variability exists in diverse maize, most research is conducted using a small subset of inbred lines. An association population of 302 lines is now available--a valuable research tool that captures a large proportion of the alleles in cultivated maize. Provided that appropriate statistical models correcting for population structure are included, this tool can be used in association analyses to provide high-resolution evaluation of multiple alleles. This study describes the population structure of the 302 lines, and investigates the relationship between population structure and various measures of phenotypic and breeding value. On average, our estimates of population structure account for 9.3% of phenotypic variation, roughly equivalent to a major quantitative trait locus (QTL), with a high of 35%. Inclusion of population structure in association models is critical to meaningful analyses. This new association population has the potential to identify QTL with small effects, which will aid in dissecting complex traits and in planning future projects to exploit the rich diversity present in maize.

Chromosome Mapping↗

Cost-effectiveness of asthma control: an economic appraisal of the GOAL study.

BACKGROUND: The Gaining Optimal Asthma ControL (GOAL) study has shown the superiority of a combination of salmeterol/fluticasone propionate (SFC) compared with fluticasone propionate alone (FP) in terms of improving guideline defined asthma control. METHODS: Clinical and economic data were taken from the GOAL study, supplemented with data on health related quality of life, in order to estimate the cost per quality adjusted life year (QALY) results for each of three strata (previously corticosteroid-free, low- and moderate-dose corticosteroid users). A series of statistical models of trial outcomes was used to construct cost effectiveness estimates across the strata of the multinational GOAL study including adjustment to the UK experience. Uncertainty was handled using the non-parametric bootstrap. Cost-effectiveness was compared with other treatments for chronic conditions. RESULT: Salmeterol/fluticasone propionate improved the proportion of patients achieving totally and well-controlled weeks resulting in a similar QALY gain across the three strata of GOAL. Additional costs of treatment were greatest in stratum 1 and least in stratum 3, with some of the costs offset by reduced health care resource use. Cost-effectiveness by stratum was 7600 pound (95% CI: 4800-10,700 pound) per QALY gained for stratum 3; 11,000 pound (8600-14,600 pound) per QALY gained for stratum 2; and 13,700 pound (11,000-18,300 pound) per QALY gained for stratum 1. CONCLUSION: The GOAL study previously demonstrated the improvement in total control associated with the use of SFC compared with FP alone. This study suggests that this improvement in control is associated with cost-per-QALY figures that compare favourably with other uses of scarce health care resources.

Albuterol↗

The value of prior information for detection of QTL affecting longitudinal traits: an example using Von Bertalanffy growth function.

A Bayesian procedure is presented for detecting quantitative trait loci (QTL) affecting longitudinal traits. The statistical model assumes a QTL affecting the prior distribution of the parameters of a given production function, under a hierarchical Bayesian scheme. Marginal posterior distributions for the effects associated with the QTL are calculated using Markov chain Monte Carlo methods. Furthermore, the Bayesian analysis allows the use of some available relevant information that can improve the detection of the QTL substantially. To illustrate the procedure, an example of QTL detection using the Von Bertalanffy growth function is presented with a F2 pig population bred from Iberian boars and Landrace sows. Animals of the F2 population were genotyped for seven markers in chromosome 2 (SSC2). Two prior distributions for the mean effect of the parameters related with birth and adult weight were compared. On the one hand, vague prior distributions were used, and, on the other, there were assumed univariate Gaussian distributions that ensure biologically meaningful adult and birth weights on the posterior growth curves. Results from the second prior distribution supported the presence of QTL, by showing that individuals with both alleles of Iberian origin had lower rates of maturation. On the contrary, when vague priors were used, the procedure was not able to detect QTL.

Animals↗

N-3 polyunsaturated fatty acids impair lifespan but have no role for metabolism.

Although generally considered as beneficial components of dietary fats, polyunsaturated fatty acids (PUFA) have been suspected to compromise maximum lifespan (MLSP) in mammals. Specifically, high amounts of phospholipid PUFAs are thought to impair lifespan due to an increase in the susceptibility of membranes to lipid peroxidation and its damaging effect on cellular molecules. Also, there is evidence from in vitro studies suggesting that highly unsaturated PUFAs elevate basal metabolic rate (BMR). Previous comparative studies in this context were based on small sample sizes, however, and, except for one study, failed to address possible confounding influences of body weight and taxonomic relations between species. Therefore, we determined phospholipid membrane composition in skeletal muscle from 42 mammalian species to test for a relation with published data on MLSP, and with literature data on BMR (30 species). Using statistical models that adjust for the effects of body weight and phylogeny, we found that among mammals, MLSP indeed decreases as the ratio of n-3 to n-6 PUFAs increases. In contrast to previous studies, we found, however, no relation between MLSP and either membrane unsaturation (i.e. PUFA content or number of double bonds) or to the very long-chain, highly unsaturated docosahexaenoic acid (DHA). Similarly, our data set gave no evidence for any notable relation between muscle phospholipid fatty acid composition and BMR, or MLSP and BMR in mammals. These results contradict the 'membrane pacemaker theory of aging', that is, the concept of a direct link between high amounts of membrane PUFAs, elevated BMR, and thus, impaired longevity.

Animals↗

Species imperilment and spatial patterns of development in the United States.

Conservation biologists and others hypothesize that humankind's "ecological footprint" is affected not only by the sheer intensity of human activity but also by its spatial arrangement. We used a multivariate statistical model and state-level data to evaluate correlations between species imperilment and the level and spatial distribution of human settlement and infrastructure development in the United States. The level of human activity--measured by the number of people and households, incidence of roads, and intensity of nighttime lights--was significantly correlated with the ecological imperilment of species. Our regression models consistently showed that a 1% increase in the level of human activity across the United States was associated with about a 0.25% increase in the proportion of plant and animal species considered at risk of extinction by The Nature Conservancy. The distribution of human activity did not affect species imperilment. Our results point to rising levels of human activity--and not some particular (e.g., sprawling) distribution of human activity--as the most relevant anthropogenic factor explaining biodiversity loss in the United States.

Animals↗

Effects of phenytoin on cognitive-motor performance in children as a function of drug concentration, seizure type, and time of medication.

Fifty children with well-controlled seizures who were receiving phenytoin (PHT) monotherapy were tested three times at weekly intervals on a cognitive-motor test battery. The first assessment served as a practice session, and PHT was given either before or withheld until after testing to create peak and trough concentrations, respectively, in the second and third sessions. On average, PHT levels as measured in saliva were in the low therapeutic range. The experimental condition (PHT before or after test sessions) was randomized and balanced across subjects, and assessments were made with examiners blind to diagnosis and timing of PHT ingestion. A variety of statistical models was used to analyze for the effect of age, diagnosis (partial vs. generalized epilepsy), PHT order, PHT concentration (as measured in saliva), and trough/peak concentration effects. Greater age was consistently associated with better performance, but diagnosis, PHT concentration levels, and transition from trough to peak concentration days had few discernible effects on psychomotor performance. Thus, fluctuations in PHT, of the order of 50%, appear to have no or immeasurably small effects in children with well-controlled seizures receiving monotherapy in low therapeutic dosages.

Adolescent↗

Quantitative MRI biomarkers of cognitive morbidity in temporal lobe epilepsy.

PURPOSE: To determine the relation between neuropsychological morbidity, quantitative magnetic resonance imaging (MRI) measures of whole brain structure, and clinical seizure factors reflecting epilepsy cause, course, and treatment. METHODS: Quantitative MRI measurements of total (whole brain) cerebrospinal fluid (CSF) and gray- and white-matter volumes and clinical seizure features were examined in relation to summary indices of cognitive morbidity in 96 patients with temporal lobe epilepsy. MRI volumes were adjusted for intracranial volume (ICV), and cognitive scores were adjusted for age, education, and gender, based on a sample of 82 healthy controls. RESULTS: Whole-brain volumes (gray, white, and CSF) were abnormal in chronic temporal lobe epilepsy patients compared with controls and were related significantly to neuropsychological morbidity, especially total CSF. Statistical modeling demonstrated that markers of total atrophy (CSF) was the primary mediator of the relation between clinical seizure variables and neuropsychological morbidity. CONCLUSIONS: Quantitative measurements of overall brain abnormality (atrophy) in temporal lobe epilepsy are clinically meaningful markers that are associated with increased cognitive morbidity. These biomarkers appear to mediate the adverse effects of some clinical seizure variables on cognition.

Adolescent↗

Effects of alcoholic beverage server liability on traffic crash injuries.

We examined effects on the frequency of injuries due to motor vehicle crashes of a sudden change in exposure to legal liability of servers of alcoholic beverages in Texas. A multiple time-series quasi-experimental research design was used, including the Auto-Regressive Integrated Moving Average and intervention-analysis statistical models on injury data from 1978 through 1988. We controlled for the effects of several other policy changes expected to influence injury rates in Texas, and for broader nationwide changes in injury rates in the 1980s. Results revealed 6.5% and 5.3% declines in injurious traffic crashes following the filing of two major liability suits in 1983 and 1984, respectively. Sever liability is one of several important public policy tools in efforts to achieve health objectives regarding reduced injury morbidity, and mortality.

Accidents, Traffic↗

Contribution of individual items to the performance of the Norton pressure ulcer prediction scale.

OBJECTIVES: To assess the specific contribution to overall scale performance of each of the five items that constitute the Norton pressure ulcer prediction scale. DESIGN: A comparison of statistical models based on cross-sectional surveys of hospitalized patients. SETTING: An urban teaching hospital in Geneva, Switzerland. PARTICIPANTS: 2373 hospitalized patients who were free of pressure ulcers on admission. MEASUREMENTS: Norton scale items measuring activity, mobility, physical condition, mental condition, and incontinence on a 4-point scale were examined as predictors of stage 1 or greater pressure ulcers. RESULTS: A total of 245 new pressure ulcers occurred between admission and patient observation. After adjustment for other independent predictors in proportional hazards models, only the activity and mobility items remained associated significantly with the risk of pressure ulcer. A simplified 2-item scale was more strongly associated with pressure ulcer risk than was the classic 5-item Norton scale. CONCLUSIONS: Our study suggests that the activity and mobility items of the Norton scale are sufficient to express the risk of pressure ulcers in hospitalized patients. Confirmation of this finding in prospective studies is warranted.

Adolescent↗

OSHA's permissible exposure limits: regulatory compliance versus health risk.

Workplace exposures to airborne chemicals are regulated in the U.S. by the Occupational Safety and Health Administration (OSHA) via the promulgation of permissible exposure limits (PELs). These limits, usually defined as eight-hour time-weighted average values, are enforced as concentrations never to be exceeded. In the case of chronic or delayed toxicants, the PEL is determined from epidemiological evidence and/or quantitative risk assessments based on long-term mean exposures or, equivalently, cumulative lifetime exposures. A statistical model was used to investigate the relation between the compliance strategy, the PEL as a limit never to be exceeded, and the health risk as measured by the probability that an individual's long-term mean exposure concentration is above the PEL. The model incorporates within-worker and between-worker variability in exposure, and assumes the relevant distributions to be log-normal. When data are inadequate to estimate the parameters of the full model, as it is in compliance inspections, it is argued that the probability of a random measurement being above the PEL must be regarded as a lower bound on the probability that a randomly selected worker's long-term mean exposure concentration will exceed the PEL. It is concluded that OSHA's compliance strategy is a reasonable, as well as a practical, means of limiting health risk for chronic or delayed toxicants.

Air Pollutants, Occupational↗

Derivation of a defibrillator implant criterion based on probability of successful defibrillation.

Common criteria for implant of a cardioverter defibrillator include verification of a 2:1 energy safety margin or a fixed safety margin of 10 joules. These criteria have been established empirically. We present a statistically model based on defibrillation efficacy curves which may be used to establish a criterion which would meet a predetermined target. As an example, an implant criterion is derived based on a goal of 1-year sudden cardiac death survival of at least 99% by selecting an expected first-shock efficacy to meet that target. Logistic regression was performed on data from over 1,500 defibrillator implants including successful epicardial and transvenous electrode system implants as well as data from unsuccessful implants. A random sample from these curves was used to generate a representative sample of 1,000 potential implant candidates. By assuming successful defibrillation using a series of shocks at specified energies, i.e., choosing an implant criterion, the probability of successful defibrillation of the patient by a single shock at a predetermined maximum output can be established. Independent data are used to validate the model's accuracy in predicting defibrillation efficacy within the derived example.

Clinical Protocols↗

Pitfalls of the concept of incremental specificity used in comparisons of dual chamber VT/VF detection algorithms.

The concepts of incremental specificity and incremental positive predictive accuracy (PPA) have been proposed to measure the success of dual chamber cardioverter defibrillator (ICD) algorithms for tachyarrhythmia detection in improving specificity while maintaining very high sensitivity to detection of episodes of ventricular tachycardia/fibrillation (VT/VF). While dual chamber VT/VF detection algorithms differ substantially among different ICD manufacturers, they all operate as "add-on" features to the single chamber elementary detection algorithms that are based on simple criteria of increased ventricular rate. The incremental specificity and PPA characterize the performance of the dual chamber detection operation in this "add-on" mode, that is within a database of rhythm episodes all meet the simple rate-based criteria. A statistical model of hypothetical devices has been used to demonstrate that the concepts of incremental specificity and PPA are very dependent on the composition of the database used to evaluate a particular dual chamber ICD. Because some sinus tachycardia and supraventricular tachyarrhythmias with regular atrioventricular conduction are more easily discriminated from true VT/VF than other supraventricular tachyarrhythmias, the model shows that rather than the performance of the dual chamber detection functions, the major contributor to the incremental specificity may be the proportion between the "easy" and "difficult" supraventricular episodes. The algorithms used by different ICD manufacturers to detect tachyarrhythmias based on ventricular rate are known to differ substantially in the ability to differentiate true VT/VF from other tachyarrhythmias. Consequently, the databases of rhythms against which the different dual camber ICDs are tested are also different in composition of different types of supraventricular tachyarrhythmias. Therefore, the values of incremental specificity and PPA reported by different manufacturers do not have an equivalent meaning and do not offer a valid comparison of the true performance of different dual chamber ICDs.

Algorithms↗

A statistical test of the hypothesis that polyclonal intestinal tumors arise by random collision of initiated clones.

The random collision hypothesis is a mathematical idealization of intestinal tumor formation that can account for the polyclonal origin of tumors without requiring a mechanistic description of clonal interaction. Using data from recent polyclonality studies in mice, we develop a statistical procedure to test the random collision hypothesis. Elements from stochastic geometry and approximations due to Armitage (1949, Biometrika 36, 257-266) support a statistical model of tumor count data. Bayesian analysis yields the posterior distribution of the number of heterotypic tumors, from which p-values are computed to test random collision.

Animals↗

Gender specificity of geographical variation in morbid risk for schizophrenia in rural Ireland.

The morbid risk for schizophrenia was determined separately for men and women within each of 36 contiguous district electoral divisions of a rural Irish county in which all cases of schizophrenia satisfying DSM-III-R criteria had been sought. The distribution of morbid risk values for men (0.0-19.2 per 1000) was in accordance with a statistical model for random occurrences in space, while for women (0.0-38.3 per 1000) it deviated markedly from such a model; thus, morbid risk for schizophrenia showed very prominent geographical variations in women, but not in men. These findings may have a basis in factors that can show both spatial inhomogeneity and gender specificity in their consequences for schizophrenia.

Adult↗

Human basic tear fluid osmolality. II. Importance of processing strategy.

Osmolalities of 100 human inferior tear prism fluid samples collected from two subjects and 100 standard solution samples (290 mOsm/Kg) were determined from their melting-point temperatures with the Clifton Nanoliter Osmometer. Accuracy and reliability comparisons were made for endpoints obtained using a single-sample simultaneous-recalibration (SS/SR) strategy, vs a lowest-of-six periodic-recalibration (LS/PR) strategy. Tear fluid osmolality values based on the LS/PR strategy were significantly lower (hypotonic) than for the SS/SR strategy (overall mean = 302.4 and 307.8 mOsm/Kg, respectively; p < 0.0012). The mean difference (5.4 mOsm/Kg) resulted from the combined effects of machine drift and reduced reliability of endpoint determination for tear fluid in comparison to that of a homogenous standard solution. LS/PR osmolality was linearly correlated to SS/SR osmolality with a slope of 0.433 and the two endpoint strategies resulted in equivalent values at 298.4 mOsm/Kg. Eighty-four percent (84%) of individual osmolality readings were greater than 298.4 mOsm/kg, and an 'averaging-type' effect caused LS/PR osmolalities to be increasingly less than SS/SR values above this value. These outcomes from two subjects were approximated by a parallel statistical model. We suggest that physiological representation of basic human tear fluid is more accurate using the single-sample simultaneous-recalibration strategy. Basic human tear prism fluid is more hypertonic and has a greater within-subject range in normal (non-dry eye) humans than previously realized.

Humans↗

The construction and assessment of mental maps.

In investigations into the manner in which people store spatial information, experimental subjects are often asked to estimate the distances and bearings between various landmarks. Methodology is described for constructing the mental map underlying a subject's matrix of distances, and the mental map underlying a subject's matrix of bearings. Also presented are methods of comparing matrices of distances or bearings, and the mental maps constructed from them, with the geographical map; this enables an assessment of differences between them. Some statistical models of disorientation are considered, and a method of choosing between them is described.

Attention↗

Effect of specimen size and aspect ratio on the tensile properties of porcine aortic valve tissues.

The measurement of mechanical properties of biological tissues is subject to artifacts such as natural variability and inconsistency in specimen preparation. As a result, data cannot be easily compared across laboratories. To test the effects of variable specimen dimensions, we systematically modified the size and aspect ratio (AR) of porcine aortic valve tissues and measured their stiffness and extensibility. We found that: (i) as the AR of circumferential specimens increased from 1:1 to 5:1, their stiffness increased by 36% (p < 0.001) and their extensibility decreased by 21% (p < 0.001); (ii) as the AR of radial specimens increased from 0.8:1 to 4:1, their stiffness increased by 36% (p < 0.001) and their extensibility decreased by 34% (p < 0.001); (iii) as the size of circumferential specimens was reduced from 128 to 32 mm2 at fixed AR (2:1), their stiffness decreased by 6 (p = 0.05), and their extensibility increased by 17% (p < 0.001); and (iv) as the size of radial specimens was reduced from 72 to 32 mm2 at fixed AR (2:1), their stiffness decreased by 7% (p = 0.03) and their extensibility increased by 16% (p = 0.005). Thus, as specimens of constant length became narrower, they became stiffer and less extensible, and as specimens of fixed aspect ratio became smaller, they became less stiff and more extensible. Statistical models of these trends were predictive and can thus be used to integrate materials test data across different laboratories.

Animals↗