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PubMed2001

DF-analyses of heritability with double-entry twin data: asymptotic standard errors and efficient estimation.

In this paper we establish the asymptotic distribution of DeFries Fulker (1985) regression estimates for heritability and shared environmental influences with double-entry twin data. A simple formula to estimate the covariance matrix of the coefficients in DF-regressions is provided, and applications to simulated data and Danish twin data show that this method can substantially increase the statistical power of the analyses. We also provide an 'efficient DF-analysis' that yields more precise estimates when additional covariates are included among the explanatory variables.

Adult↗
PubMed2002

Digital dermoscopy analysis of atypical pigmented skin lesions: a stepwise logistic discriminant analysis approach.

BACKGROUND: Digital microscopy is a non-invasive diagnostic technique enabling determination of characteristics that cannot be appreciated by direct observation. If correctly applied, this technique can be useful for the diagnosis of pigmented skin lesions. PURPOSE: To evaluate the utility of digital microscopy for analysing atypical benign and malignant pigmented skin lesions exploiting digital numerical filtering and automatic measurements. METHODS: Forty-eight parameters were identified as possible discriminating variables, and were grouped in four categories: geometries, colours, textures, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. RESULTS: The high quality of the digital image made it possible to observe diagnostic signs in pigmented skin lesion images, acquired by the present technique, in great detail. Specially designed filtering enhanced certain diagnostic patterns. Stepwise discriminant analysis selected only 10 variables (the means of these variables were higher in melanomas than in nevi). CONCLUSIONS: The combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing atypical nevi and early melanoma.

Diagnosis, Computer-Assisted↗
PubMed2004

Analytical and statistical methods to evaluate microsatellite allelic imbalance in small amounts of DNA.

Microsatellite analysis is a powerful tool for the assessment of genetic instability and loss of heterozygosity in cancer cells. However, most human tumors harbor significant numbers of normal cells, which may contribute to false-negative results. Recent techniques based on fluorescently labeled primers and semiautomated capillary electrophoresis of polymerase chain reaction (PCR) products allow a reliable quantitative assessment of (PCR) products while requiring very small numbers of cells. We report a highly sensitive protocol for the semiautomated analysis of allelic imbalance based on time-release PCR and capillary electrophoresis. With this protocol, as few as 100 cells can be used to reliably assess allelic imbalance (AI) in DNA samples. Using a panel of seven microsatellite markers, we determined allelic variation in a large set of heterozygous lymphocyte DNA samples and examined the use of different statistical analysis techniques. Using these statistical approaches, we describe a calibration method to evaluate AI from microsatellite results. Using a simple formula, cutoff points at preset confidence levels are used to decide whether allelic imbalance exists in a given sample at the loci under investigation. Our method allows the reliable detection of AI with very small amounts of DNA, and is sufficiently quantitative to assess allelic ratios in nonclonal tissue specimens.

Allelic Imbalance↗
PubMed2001

Haplotype frequency distribution and discriminatory power of two mtDNA fragments in a marine pelagic teleost (Atlantic herring, Clupea harengus).

Two regions of the mtDNA of Atlantic herring (Clupea harengus), ND3/4 and ND5/6, were surveyed by RFLP analysis to assess the effects of marker variability on the power of statistical tests. Although haplotype diversity was similar, marked differences in the number of common haplotypes were observed between the two regions, with ND3/4 having a more even distribution of haplotype frequencies. ND3/4 also revealed higher differentiation among samples than ND5/6, similar to previously published microsatellite data of the same samples. The data suggested that the highly skewed haplotype distribution of many mtDNA markers may be one of the reasons for the less frequent detection of population differentiation compared to microsatellites. Pooling ('binning') of related haplotypes did not increase differentiation revealed by each mtDNA region individually, but greatly strengthened geographical patterns shown by both regions combined. The data provided evidence for genetic differentiation of Icelandic herring from other north-eastern Atlantic stocks, and indicated genetic differences between Baltic and Celtic Sea herring. However, mtDNA data failed to confirm previously reported differences between Barents Sea herring, Norwegian fjord populations and Norwegian spring spawners.

Animals↗
PubMed2003

[VIII: Statistics in medical publications: check lists for authors].

The "Material and Methods" section of clinical research papers should reference major aspects concerning statistical planning and evaluation of the study design and the resulting clinical data. Particular focus is laid on the listing of methods for description and significance evaluation of the trial data, as well as on design-associated study determinants (randomisation and masking strategy, response rate evaluation, primary endpoints, power and sample size determination, multiple testing, software and methods for statistical analysis). Suggestions for the minimum content to be mentioned in a trial publication are listed in author check lists and are illustrated by means of the study synopsis of a randomised clinical trial on the rotation stability of two lens haptics.

Authorship↗
PubMed2005

Prediction of active sites for protein structures from computed chemical properties.

MOTIVATION: Identification of functional information for a protein from its three-dimensional (3D) structure is a major challenge in genomics. The power of theoretical microscopic titration curves (THEMATICS), when coupled with a statistical analysis, provides a method for high-throughput screening for identification of catalytic sites and binding sites with high accuracy and precision. The method requires only the 3D structure of the query protein as input, but it performs as well as other methods that depend on sequence alignments and structural similarities.

Bacterial Proteins↗
PubMed2006

Identification of two novel quantitative trait loci for pre-eclampsia susceptibility on chromosomes 5q and 13q using a variance components-based linkage approach.

Pre-eclampsia/eclampsia (PE/E) is a common and serious disorder of human pregnancy that is associated with substantial maternal and perinatal morbidity and mortality. The suspected aetiology of PE/E is complex, with susceptibility being attributable to multiple environmental factors and a large genetic component. By assuming that the underlying liability towards PE/E susceptibility is inherently quantitative, any PE/E susceptibility gene would represent a quantitative trait locus (QTL). This assumption enables a more refined and powerful variance components procedure using a threshold model for our PE/E statistical analysis. Using this more efficient linkage approach, we have now re-analysed our previously completed Australian/New Zealand genome scan data to identify two novel PE/E susceptibility QTLs on chromosomes 5q and 13q. We have obtained strong evidence of linkage on 5q with a peak logarithm-of-odds (LOD) score of 3.12 between D5S644 and D5S433 [at approximately 121 centimorgan (cM)] and strong evidence of linkage on 13q with a peak LOD score of 3.10 between D13S1265 and D13S173 (at approximately 123 cM). Objective identification and prioritization of positional candidate genes using the quantitative bioinformatics program GeneSniffer revealed highly plausible PE/E candidate genes encoding aminopeptidase enzymes and a placental peptide hormone on the 5q QTL and two type IV collagens on the 13q QTL regions, respectively.

Analysis of Variance↗
PubMed2001

Pharmacologic neuroprotection in experimental spinal cord ischemia: a systematic review.

Various surgical procedures may cause temporary interruption of spinal cord blood supply and may result in irreversible ischemic injury and neurological deficits. The cascade of events that leads to neuronal death following ischemia may be amenable to pharmacological manipulations that aim to increase the tolerable duration of ischemia. Many agents have been evaluated in experimental spinal cord ischemia (SCI). In order to investigate whether an agent is available that justifies clinical evaluation, the literature on pharmacological neuroprotection in experimental SCI was systematically reviewed to assess the neuroprotective efficacy of the various agents. In addition, the strength of the evidence for neuroprotection was investigated by analyzing the methodology. The authors used a systematic review to conduct this evaluation. The included studies were analyzed for neuroprotection and methodology. In order to be able to compare the various agents for neuroprotective efficacy, relative risks and confidence intervals were calculated from the data in the results sections. A total of 103 studies were included. Seventy-nine different agents were tested. Only 14 of the agents tested did not afford protection at all. A large variation was observed in the experimental models to produce SCI. This variation limited comparison of the individual agents. In 48 studies involving 31 single agents, the relative risks and confidence intervals could be calculated. An analysis of the methodology revealed poor temperature management and lack of statistical power in the majority of the 103 studies. The results suggest that numerous agents may protect the spinal cord from transient ischemia. However, poor temperature management and lack of statistical power severely weakened the evidence. Consequently, clinical evaluation of pharmacological neuroprotection in surgical procedures that carry a risk of ischemic spinal cord damage is not justified on the basis of this study.

Animals↗
PubMed2005

A note on P-values under group sequential testing and nonproportional hazards.

Group sequential designs are often used for periodically assessing treatment efficacy during the course of a clinical trial. Following a group sequential test, P-values computed under the assumption that the data were gathered according to a fixed sample design are no longer uniformly distributed under the null hypothesis of no treatment effect. Various sample space orderings have been proposed for computing proper P-values following a group sequential test. Although many of the proposed orderings have been compared in the setting of time-invariant treatment effects, little attention has been given to their performance when the effect of treatment within an individual varies over time. Our interest here is to compare two of the most commonly used methods for computing proper P-values following a group sequential test, based upon the analysis time (AT) and Z-statistic orderings, with respect to resulting power functions when treatment effects on survival are delayed. Power under the AT ordering is shown to be heavily influenced by the presence of a delayed treatment effect, while power functions corresponding to the Z-statistic ordering remain robust under time-varying treatment effects.

Algorithms↗
PubMed2005

Risk factors for epistaxis on British racecourses: evidence for locomotory impact-induced trauma contributing to the aetiology of exercise-induced pulmonary haemorrhage.

REASONS FOR PERFORMING STUDY: The proposed biological mechanisms for exercise-induced pulmonary haemorrhage (EIPH) are many and varied. Better knowledge of risk factors should lead to achievable measures to reduce the incidence. OBJECTIVES: To identify risk factors associated with epistaxis following racing in UK Thoroughbreds, to gain possible insights into the pathogenesis of the condition and to investigate the association between epistaxis and race finishing position. METHODS: The association of epistaxis occurring on UK racecourses between 1996 and 1998 with a wide range of race-, horse- and start-level variables was examined in multivariable mixed effect logistic regression analyses. Four multivariable analyses were conducted, one for all race types considered collectively and one each for flat, hurdle and steeplechase race types considered separately. RESULTS: Risk of epistaxis was significantly increased for hurdle and steeplechase race types compared to both flat and National Hunt flat races. In 3 of the 4 final models, there was a significant biological trend for increasing risk of epistaxis with increasing ground hardness ('going') and accumulated years spent racing. However, in flat races epistaxis was such a rare outcome (0.33 cases per 1000 starts) that this subset analysis had insufficient power to measure the detectable effect of 'going' as statistically significant. Horses with epistaxis were significantly more likely to have a poorer finishing position than those without blood at the nostrils. CONCLUSIONS: Findings were consistent with the theory that locomotory impact-induced trauma contributes to exercise-induced epistaxis. Further validation of this hypothesis through application of similar methods to endoscopically visible EIPH and through biomechanical studies is warranted. POTENTIAL RELEVANCE: Knowledge of significant risk factors should allow formulation of practical measures, such as track watering, to reduce the risks of EIPH and epistaxis in racehorses.

Animals↗
PubMed1999

[Effectiveness of pinaverium bromide therapy on colonic motility disorders in irritable bowel syndrome].

The special patterns of the slow wave activity in irrittable bowel syndrome by means of surface electromyography were examined and the effect of pinaverium bromide on the symptoms and on the colonic motility in this disease was estimated. Twenty two patients with irritable bowel syndrome and 7 healthy controls were selected to the study. The clinical symptoms were abdominal pain and bloating in all patients, constipation in 9, and diarrhoea in 6 cases. Surface electromyography was carried out before and on the 14th day of the treatment with pinaverium bromide (50 mg t. i. d). The colonic motility was analysed in a 2 hour fasting and a 2 hour postprandial period following a standard (800 kCal) meal. The slow wave frequency of 0.01-0.04 Hz were selected and analysed. The mean frequency of activity peaks (n/10 min) and power-index (area under curve, microV 10 min) were measured. For statistical analysis Student's t-test was applied. Electromyogram of patients with irritable bowel syndrome showed a significant increase of the measured colonic motility parameters both in fasting and postprandial states. Fourteen days of pinaverium bromide treatment was able to significantly reduce the intensity of the colonic motor activity. Administration of pinaverium bromide completely released in 6 and significantly improved the abdominal pain in other 12 patients, while the bloating disappeared in 12 and was significantly improved in 5 from 22 patients. Pinaverium bromide was able to normalise the stool frequency: the weekly number of stools was decreased from 16 to 7 in the patients complaining diarrhoea ant it was increased from 2 to 6 in the patients with constipation.

Calcium Channel Blockers↗
PubMed1999

Strategic issues in the design and interpretation of studies on metabolic polymorphisms and cancer.

This chapter describes in a simple way the most important issues of epidemiological design, with emphasis on studies on metabolic polymorphisms. Different options are offered to the researcher who approaches a molecular epidemiology study. Case-control studies and cohort studies have different and sometimes complementary advantages and disadvantages. The sources of bias and the choice of controls, with specific problems in the context of investigations on metabolic polymorphisms, are key issues. Confounding is an issue that needs further clarification in the field, partly because of the lack of complete biological knowledge on the complex relationships between exposure, markers of susceptibility, and cancer. Metabolic polymorphisms are correctly interpreted as effect modifiers of the exposure-disease relationship. This interpretation implies that studies should be planned in order to have sufficient statistical power and that an interactive term should be modelled in the statistical analysis.

Bias↗
PubMed1978

[Piracetam and vigilance. A study of EEG changes and clinical effects in gerontopsychiatric patients (author's transl)].

The electroencephalographic and clinical effects of piracetam were studied in a group of 11 hospitalized gerontopsychiatric patients treated with a daily dosage of 4.8 g for 8--13 months. The EEG was evaluated by power spectral analysis, followed by a principal component analysis of frequency parameters. The statistical analysis of the resulting factor scores shows that piracetam induces significant EEG changes: decrease of slow frequencies, augmentation and acceleration of alpha-activity and increase of beta-activity. These EEG changes, indicating an increase in vigilance, correspond clinically to an improvement of communicative behavior and cognitive functioning.

Aged↗
PubMedDate not supplied

The Statistical Package for the Social Sciences (SPSS) as an adjunct to pharmacokinetic analysis.

Computer techniques for numerical analysis are well known to pharmacokineticists. Powerful techniques for data file management have been developed by social scientists but have, in general, been ignored by pharmacokineticists because of their apparent lack of ability to interface with pharmacokinetic programs. Extensive use has been made of the Statistical Package for the Social Sciences (SPSS) for its data handling capabilities, but at the same time, techniques have been developed within SPSS to interface with pharmacokinetic programs of the users' choice and to carry out a variety of user-defined pharmacokinetic tasks within SPSS commands, apart from the expected variety of statistical tasks. Because it is based on a ubiquitous package, this methodology has all of the benefits of excellent documentation, interchangeability between different types and sizes of machines and true portability of techniques and data files. An example is given of the total management of a pharmacokinetic study previously reported in the literature by the authors.

Computers↗
PubMed2003

The effect of finasteride on the expression of vascular endothelial growth factor and microvessel density: a possible mechanism for decreased prostatic bleeding in treated patients.

PURPOSE: Several studies have confirmed the benefit of finasteride in limiting hematuria from benign prostatic hyperplasia. Vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, and microvessel density have been independently evaluated in the mechanism of decreased bleeding observed in patients treated with finasteride. We evaluated the expression of VEGF and suburethral prostatic microvessel density in patients with benign prostatic hyperplasia treated with finasteride. MATERIALS AND METHODS: The study included 24 patients undergoing prostatic surgery for benign disease, of whom 12 were given finasteride for a minimum of 6 weeks before surgery and the remaining 12 served as controls. Sections from the prostatic urothelium and hyperplastic prostate were individually stained for CD34 specific for nascent blood vessels and VEGF. Analysis of each specimen was performed in a blinded fashion. Microvessel density was calculated by counting the number of positively stained blood vessels on 10 consecutive, nonoverlapping, high power fields within the suburethral and hyperplastic prostate compartments. VEGF expression was examined by immunohistochemistry. Statistical analysis of the results was performed using Student's t test. RESULTS: Prostatic suburethral VEGF expression and microvessel density were significantly lower in the finasteride group compared to controls (p <0.05). Differences in VEGF expression and microvessel density at the level of the hyperplastic prostate were not found to be significantly different between the 2 groups. CONCLUSIONS Decreased expression of VEGF by finasteride inhibits angiogenesis and significantly decreases microvessel density in prostatic suburethral tissue. This sequential relationship provides histochemical insight into the mechanism by which finasteride reduces prostatic urethral bleeding.

Aged↗
PubMed1997

Microsatellite diversity and the demographic history of modern humans.

We have examined differences in diversity at 60 microsatellite loci among human population samples from three major continental groups to evaluate the hypothesis of greater African diversity in this rapidly evolving class of loci. Application of a statistical test that assumes equal mutation rates at all loci fails to demonstrate differences in microsatellite diversity, while a randomization test that does not make this assumption finds that Africans have significantly greater microsatellite diversity (P < 10(-8)) than do Asians and Europeans. Greater African diversity is most apparent at loci with smaller overall variance in allele size, suggesting that the record of population history has been erased at repeat loci with higher mutation rates. A power analysis shows that only 35-40 microsatellites are needed to establish this difference statistically, demonstrating the considerable evolutionary information contained in these systems. On average, African populations have approximately 20% greater microsatellite diversity than do Asian and European populations. A comparison of continental diversity differences in microsatellites and mtDNA sequences suggests earlier demographic expansion of the ancestors of Africans.

Africa↗
PubMed2005

Corneal topography in thyroid orbitopathy after orbital irradiation.

PURPOSE: The orbital tonus changes in thyroid orbitopathy, so it may be expected that corneal topographic results also change. Orbital irradiation may reduce the orbital tonus, and thus, it may affect the topographic changes. Corneal topographic results were examined before and after orbital irradiation in patients with thyroid orbitopathy to determine whether there was a difference. METHODS: Twenty eyes of 10 patients with thyroid orbitopathy were included in this study. Corneal topography was performed with Topographic Modeling System 2 (Tomey). The refractive power of the corneal curvature was measured at the center of the corneal apex and in each of the eight quadrants, 1.5 mm and 3 mm from the corneal apex, on the corneal topographer. A total dose of 20 Gy was given in 10 fractions over 2 weeks to the orbital structures sparing the lens, and corneal topography was performed 6 weeks and 8 months later. The measures of the refractive power of the cornea were taken again. Repeated-measures analysis of variance was used to evaluate the differences between the measures. RESULTS: There were no statistically significant differences in refractive power of the cornea in the topographic maps obtained before the radiotherapy and the two follow-up examinations after the radiotherapy. CONCLUSIONS: Thyroid orbitopathy is an orbital disease and may affect corneal topographic results. Orbital irradiation reduces or eliminates pathogenic orbital lymphocyte infiltration, thereby reducing orbital and extraocular muscle edema in patients with thyroid orbitopathy. In the current study group, corneal topographic changes were observed minimally as a result of the orbital irradiation, but they were not statistically significant.

Adult↗
PubMed2002

Classification tree analysis: a statistical tool to investigate risk factor interactions with an example for colon cancer (United States).

OBJECTIVE: Classification tree analysis is a potentially powerful tool for investigating multilevel interactions. Within the context of colon cancer etiology it may help identify disease pathways and evaluate important interactions of risk factors. METHODS: We apply classification tree analysis as a statistical method to investigate interactions of risk factors for colon cancer. We use data collected from a population-based case-control study of newly diagnosed cases of colon cancer (N = 4403 cases and controls). RESULTS: Our results indicate that, as expected, there are many factors that influence colon cancer risk, and that they interact on many levels. We find that the most important factor is the utilization of aspirin and/or non-steroidal anti-inflammatory drugs (NSAID), with those taking this medication having lower risk. Family history appears as a level two modifying factor when NSAID are not used, whereas Western diet is the second factor when NSAID are taken. The final tree has six levels, contains several modifying factors and correctly classifies case or control status for 60.8% (95% CI 59.4-62.2) of all individuals. CONCLUSIONS: Our results suggest that risk factors work together to determine disease risk. By accounting for interactions between risk factors we become better able to dissect disease pathways and determine those risk factors that increase susceptibility to disease. Our results highlight the importance of designing studies so that interactions can be addressed.

Adult↗