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PubMed2006

A workflow spatial scan statistic.

We propose a modification of the spatial scan statistic that takes account of workflow, which is the movement of individuals between home and work. The objective is to detect clusters of disease in situations where exposure occurs in the workplace, but only home address is available for analysis. In these situations, application of the usual spatial scan statistic does not account for possible differences between home and work address, thereby reducing the power of detection. We describe an extension to the usual spatial scan statistic that uses workflow data to search for disease clusters resulting from workplace exposure. We also present results from simulations that demonstrate the increased power of the workflow scan statistic over the usual scan statistic for detecting clusters arising from exposures in the workplace.

Anthrax↗
PubMed1988

Overweight and pregnancy complications.

The association between increased prepregnancy weight for height and seven pregnancy complications was studied in a multi-racial sample of more than 4100 recent deliveries. Body mass indices were calculated and used to classify women as average weight (90-119 percent of ideal or BMI 19.21-25.60), moderately overweight (120-135 percent ideal or BMI 25.61-28.90), and very overweight (greater than 135 percent ideal or BMI greater than 28.91) prior to pregnancy. Compared to women of average weight for height, very overweight women had a higher risk of diabetes, hypertension, pregnancy-induced hypertension and primary cesarean section delivery. Moderately overweight women were also at higher risk than average for diabetes, pregnancy-induced hypertension and primary cesarean deliveries but the relative risks were of a smaller magnitude than for very overweight women. With women of average prepregnancy body mass as reference, moderately elevated, but not significant relative risks were found for perinatal mortality in the very overweight group, for urinary tract infections in both overweight groups, and a decreased risk for anemia was found in the very overweight group. However, post-hoc power analyses indicated that the number of overweight women in the sample did not allow adequate statistical power to detect these small differences in risk. To overcome limitations associated with low statistical power, the results of three recent studies of these outcomes in very overweight pregnant women were combined and summarized using Mantel-Haenzel techniques. This second, larger analysis suggested that very overweight women are at significantly higher risk for all seven outcomes studied. Summary results for moderately overweight women could not be calculated, since only two of the studies had evaluated moderately overweight women separately. These latter results support other findings that both moderate overweight and very overweight are risk factors during pregnancy, with the highest risk occurring in the heaviest group. Although these results indicate that moderate overweight is a risk factor during pregnancy, additional studies are needed to confirm the impact of being 20-35 percent above ideal weight prior to pregnancy. The results of this analysis also imply that since the baseline incidence of many perinatal complications is low, studies relating overweight and pregnancy complications should include large enough samples of overweight women so that there is adequate statistical power to reliably detect differences in complication rates.

Adolescent↗
PubMed2005

A constrained-likelihood approach to marker-trait association studies.

Marker-trait association analysis is an important statistical tool for detecting DNA variants responsible for genetic traits. In such analyses, an analysis model of the mean genetic effects of the genotypes is often specified. For instance, the effect of the disease allele on the trait is often specified to be dominant, recessive, additive, or multiplicative. Although this model-based approach is powerful when the analysis model is correctly specified, it has been found to have low power sometimes when the specified model is incorrect. We introduce an approach that does not require the specification of a particular genetic model. This approach is built upon a constrained maximum likelihood in which the mean genetic effect of the heterozygous genotype is required to not exceed those of the two homozygous genotypes. The asymptotic distribution of the likelihood-ratio statistic is derived for two special cases. A simulation study suggests that this new approach has power comparable to that of the model-based method when the analysis model is correctly specified. This approach uses one marker at a time (i.e., it is a single-marker analysis). However, given the latest findings that powerful inferential procedures for haplotype analyses can be constructed from single-marker analyses, we expect this approach to be useful for haplotype analyses.

Alleles↗
PubMed2004

Meta-analysis: apolipoprotein E genotypes and risk for coronary heart disease.

BACKGROUND: Apolipoprotein E (apoE) genotypes play critical roles in lipid metabolism and are believed to influence risk for coronary heart disease (CHD). Despite many population studies, however, the impact of apoE polymorphism on risk for CHD remains uncertain. PURPOSE: To qualitatively and quantitatively assess the evidence regarding the relation of apoE polymorphism to CHD risk. DATA SOURCES: All relevant reports and references from original and review papers published from 1966 to January 2004. STUDY SELECTION: Predefined criteria were used to identify 48 relevant studies. DATA EXTRACTION: A summary database that contained variables of study design, study sample and ethnicity, sex, apoE genotypes, CHD end points, plasma lipid levels, and other CHD risk factors was developed. DATA SYNTHESIS: The authors qualitatively evaluated many potential sources of heterogeneity. To quantify the extent of heterogeneity and assess the consistency of apoE-CHD associations, stratified analyses were conducted using the classic random-effects model. To further incorporate uncertainty due to between-study variation, the pooled odds ratios (ORs) and 95% credible intervals (CrIs) were estimated by using a Bayesian hierarchical model. Finally, the robustness of the pooled estimates was tested in multiple sensitivity analyses. Compared with individuals with the epsilon3/3 genotype, carriers of the apoE epsilon4 allele had a 42% higher risk for CHD (OR, 1.42 [95% CrI, 1.26 to 1.61]). The epsilon2 allele had no significant association with CHD risk (OR, 0.98 [CrI, 0.66 to 1.46]). LIMITATIONS: This meta-analysis did not include unpublished data or studies published in languages other than English. CONCLUSIONS: Inadequate statistical power, differences in geographic and ethnic background, allele frequency, sex, CHD phenotypes, study design, and potential gene-environment interactions may have contributed to the conflicting results of previous studies. The apoE epsilon4 allele is a significant risk factor for CHD.

Apolipoproteins E↗
PubMed1998

The Conconi test: a controversial concept for the determination of the anaerobic threshold in young rowers.

In order to examine the validity of Conconi's heart rate threshold (ATHR) during rowing ergometry, in accordance with the new recommendations of Conconi, ten young rowers (age 17.5 [SD 1.7] years; height 182.5 [SD 5.9]cm; body mass 77.0 [SD 10.6] kg) were submitted - at random and within 48-72 h - to two progressive incremental exercise tests on a rowing ergometer. In the first test, the heart rate threshold (ATHR) was determined during a ramp-like incremental test. In a second test, the lactate method (150W + 50W x 3 min(-1)) was used to determine the 4 mmol x l(-1) threshold (AT4) and the individual anaerobic threshold (IAT). Subsequently, each subject performed within 48-72 h after the second progressive incremental exercise test a 30 min prolonged exercise test (PET) at the power output corresponding to ATHR to demonstrate whether or not a steady state in blood lactate concentration ([La-]bSS) could be maintained. Friedmann's analysis of variance, Wilcoxon signed ranks test and Spearman rank correlation coefficient (rs) were used as statistical tools. Significant lower values for power output (p < 0.01 ) and heart rate (HR) (p < 0.01) were found at IAT as compared to AT4 and ATHR. No relationships were found between ATHR on the one hand and AT4 and IATon the other hand, neither for power output (rs=0.27 and -0.09), nor for HR (rs=0.08 and -0.08). Coefficients of correlation between AT4 and IAT were respectively 0.68 (p < 0.05) for power output and 0.79 (p < 0.01) for HR. During PET only four out of 10 rowers reached the target time of 30 min at ATHR power output and only one rower showed a lactate steady state. From our results we can conclude that power output at ATHR is overestimated and cannot be used for the prescription of endurance training in rowing. The ATHR does not reflect the anaerobic threshold and is therefore not relevant for monitoring continuous endurance training in rowing.

Adolescent↗
PubMed1988

Biological applications of the SAS system: an overview.

The SAS system provides biologists with a flexible, easy to use software package for data analysis. Through a combination of data management tools, a wide variety of pre-programmed procedures for sorting, graphing, and statistical analysis and a sophisticated programming language, SAS software can perform all analytical needs for most problems. The recent availability of SAS software on mainframes other than IBM, and more recently on the microcomputer, means that most scientists can have access to the software. In this review we discuss the structure of the SAS language and demonstrate its power in the analysis of biological problems. Although to a lesser extent now than originally, the SAS system is statistically oriented and a working knowledge of statistics is recommended before using its statistical capabilities. However, all biologists will find its data management and summarization capabilities very useful.

Biology↗
PubMed1983

Errors, Types I and II.

The practicing physician and the clinical investigator regularly confront therapeutic trials, diagnostic tests, and other hypothesis-testing situations. The clinical literature increasingly displays statistical notations and concepts related to decision making in medicine. For these reasons, the physician is obligated to have some familiarity with the principles behind the null hypothesis, Type I and II errors, statistical power, and related elements of hypothesis testing.

Clinical Laboratory Techniques↗
PubMed2000

A comparison between flow cytometric assessment of S-phase fraction and Nottingham histologic grade as prognostic instruments in breast cancer.

Flow cytometric DNA analysis with assessment of S-phase fraction and DNA ploidy was compared to Nottingham histologic grade. The study population consisted of 654 patients who presented between 1987 and 1996 with primary operable breast cancer and whose tumours had been analysed for S-phase fraction and DNA ploidy at the time of surgery. Grade, tumour size, node status, steroid receptor status, age, S-phase fraction and DNA ploidy were analysed univariately and multi-variately in a Cox proportional hazard analysis. In the univariate analyses all parameters were statistically significantly associated with breast cancer mortality during the follow-up period of 2-11 years. The most powerful predictor of death from breast cancer in the multiple regression analysis was grade. Patients with grade 1 tumours have excellent prognosis. We conclude that tumour grade is a strong prognostic indicator applicable to all breast cancer patients, regardless of size and nodal status, and advocate its general use.

Adult↗
PubMed2000

Microleakage of resin-based composite restorations with ceramic inserts.

PURPOSE: To evaluate dye penetration of proximal vertical slot resin-based composite (RBC) restorations as a function of cavity size and restorative material employed (RBC, ceramic inserts with low-viscosity resin, and RBC with low-viscosity resin liner). Microleakage was measured using rank scoring and linear measurement of dye penetration and ANOVA and non-parametric tests were used to evaluate the statistical significance of the results. MATERIALS AND METHODS: Ninety erupted crack- and caries-free mandibular third molars, extracted for orthodontic reasons, were used. Proximal vertical slots were prepared on the mesial surfaces of the teeth using diamond instruments at high speed under distilled water coolant. Teeth were placed randomly into nine groups. Three sizes of diamond burs of an ultrasonic cavity preparation system were used under low energy in order to standardize cavity size and shape, each tip size being used in 30 different teeth. The gingival margins were prepared 1 mm above the cemento-enamel junction. Specimens were etched, prepared with bonding agent, restored using three different materials, and immersed in a 50% AgNO3 solution for 8 hrs and sectioned to evaluate the dye penetration. RESULTS: Statistical analysis revealed no statistically significant differences among the nine groups.

Acid Etching, Dental↗
PubMed2004

A single institutional phase III trial of preoperative chemotherapy with hyperfractionation radiotherapy plus surgery versus surgery alone for resectable esophageal squamous cell carcinoma.

BACKGROUND: We conducted a prospective randomized controlled trial comparing surgery alone (S) with concurrent chemoradiotherapy followed by surgery (CRT-S) for resectable esophageal squamous cell carcinoma (SCC) based on our previous report. PATIENTS AND METHODS: One hundred and one patients with stage II/III esophageal SCC were randomized to receive either S (50 patients) or CRT-S (51 patients). The chemoradiotherapy (CRT) consisted of cisplatin 60 mg/m(2) intravenously (i.v.) on day 1, 5-fluorouracil (5-FU) 1000 mg/m(2) i.v. on days 2-5, cisplatin 60 mg/m(2) i.v. on day 22 combined with radiation therapy (45.6 Gy, 1.2 Gy b.i.d. on days 1-28). Surgery was performed 3-4 weeks after radiotherapy was completed. For patients with disease that was stable or responsive to CRT, three additional cycles of chemotherapy (cisplatin 60 mg/m(2) i.v. on day 1, 5-FU 1000 mg/m(2) on days 2-5 every 4 weeks) were given after surgical resection. RESULTS: The median age was 62 years. The toxicity of CRT was acceptable and did not affect the post-operative morbidity and the duration of hospital stay. Clinical response was 86% including 21% of complete response (CR) rate. Pathological CR was achieved in 43% [95% confidence interval (CI) 27-59] of the patients who underwent surgery after CRT. At a median follow-up of 25 months, median overall survival (OS) was 27.3 months in S and 28.2 months in CRT-S (P = 0.69). Event-free survival (EFS) at 2 years was 51% in S and 49% in CRT-S (P = 0.93). This trial, which was statistically powered to detect a relatively large difference in 2-year survival rate from 30% to 50% with 80% power, was discontinued at interim analysis because of the unexpectedly high drop-out rate for esophagectomy (31%) and resultant excessive locoregional failure rate in CRT-S arm (22% versus 12%, P = 0.31), though it was not statistically significant. CONCLUSION: Although preoperative CRT induced high clinical and pathological response, there was no statistically significant benefit in OS and EFS.

Adult↗
PubMed2004

Confirmation of the HPCX prostate cancer predisposition locus in large Utah prostate cancer pedigrees.

Several genetic predisposition loci for prostate cancer have been identified through linkage analysis, and it is now generally recognized that no single gene is responsible for more than a small proportion of prostate cancers. However, published confirmations of these loci have been few, and failures to confirm have been frequent. The genetic etiology of prostate cancer is clearly complex and includes significant genetic heterogeneity, phenocopies, and reduced penetrance. Powerful analyses that involve robust statistics and methods to reduce genetic heterogeneity are therefore necessary. We have performed linkage analysis on 143 Utah pedigrees for the previously published Xq27-28 (HPCX) prostate cancer susceptibility locus. We employed a robust multipoint statistic (TLOD) and a novel splitting algorithm to reduce intra-familial heterogeneity by iteratively removing the top generation from the large Utah pedigrees. In a dataset containing pedigrees having no more than five generations, we observed a multipoint TLOD of 2.74 (P=0.0002), which is statistically significant after correction for multiple testing. For both the full-structure pedigrees (up to seven generations) and the smaller sub-pedigrees, the linkage evidence was much reduced. This study thus represents the first significant confirmation of HPCX (Xq27-28) and argues for the continued utility of large pedigrees in linkage analyses for complex diseases.

Chromosome Mapping↗
PubMed2006

Meta-analysis in neuropsychology: an introduction.

This special issue is an introduction to meta-analytic approaches, methods, and findings in neuropsychology. The six articles that comprise this issue include a review article, one article examining the statistical power of a specific research literature, and four new meta-analyses on neuropsychological topics. Together these articles provide a user-friendly introduction to meta-analysis in neuropsychology and are designed to assist the clinician in using and applying findings from these studies to their own research and/or clinical work.

Humans↗
PubMed2003

[Common biostatistical errors in clinical studies].

Roughly half to two third of all published biomedical studies that use statistical methods contain unacceptable errors. The present article points at common errors that may be avoided without requiring profound statistical knowledge. These errors mainly concern the minimal number of patients and sample size (statistical power), agreement between aim and conclusion, distribution of data as well as description of location and variability of data. An analysis of 150 papers in the New England Journal of Medicine and in Circulation demonstrates that these errors can also commonly be found in respected journals after statistical peer review. Editors of biomedical journals could reduce the problem by means of statistical guidelines.

Biometry↗
PubMed2003

Power-law time distribution of large earthquakes.

We study the statistical properties of time distribution of seismicity in California by means of a new method of analysis, the diffusion entropy. We find that the distribution of time intervals between a large earthquake (the main shock of a given seismic sequence) and the next one does not obey Poisson statistics, as assumed by the current models. We prove that this distribution is an inverse power law with an exponent mu=2.06+/-0.01. We propose the long-range model, reproducing the main properties of the diffusion entropy and describing the seismic triggering mechanisms induced by large earthquakes.

Journal Article↗
PubMed1998

Cardiac autonomic dysfunction in survivors of acute lymphoblastic leukemia in childhood.

The purpose of this study was to investigate autonomic regulation of neurocardiac function in survivors of acute lymphoblastic leukemia (ALL) in childhood, through power spectral and time domain analyses of the heart rate variability signal. Studies were conducted on 34 unselected patients and 34 age matched controls. Patients were in remission, off therapy for at least 20 months and from high risk (HR, n=21) and standard risk (SR, n=13) groups as described by Dana-Farber Cancer Institute protocols 87-01 and 91-01. Twenty-nine patients had received cranial irradiation, 7 on a hyperfractionated schedule. Power spectral analysis of the heart rate (PS/HRV) was performed on 30 min heart rate time series and time domain statistics were computed from 24 h Holter recordings. Left ventricular function was assessed by measuring ejection and shortening fractions on echocardiography. All such measures were normal. Analysis of PS/HRV revealed that the supine low frequency: high frequency (LF:HF) area ratio was elevated in patients compared to controls. Changes in the LF and HF power on standing were attenuated in the patients compared to controls. Circadian analysis revealed a depressed diurnal rhythm of heart rate in the patients. Those from the SR group showed greater reduction of the LF power response to orthostatic stress and a reduced circadian rhythm of the heart rate compared to those with HR ALL. Patients from the HR group showed reductions in both HF and LF power responses to orthostasis compared to controls. Elevated supine LF power and depressed circadian variation in the HF power band were evident only in female subjects. Patients who received standard cranial irradiation had higher LF:HF area ratio and diminished LF and HF power responses to orthostatic stress than did subjects in the hyperfractionated group. These findings suggest that the autonomic nervous regulation of the heart is compromised in patients treated for ALL in childhood even when resting echocardiographic measures provide no evidence of cardiac decompensation. The extent of neurocardiac dysfunction is influenced by risk status, gender and schedule of cranial irradiation.

Adolescent↗
PubMed1999

Comparison of asynchronous versus synchronous arm crank ergometry.

STUDY DESIGN: A direct comparison of synchronous versus asynchronous arm crank ergometry has not been carried out previously. Therefore, a comparative research design was employed. OBJECTIVE: To assess the physiological responses of arm cranking when performed asynchronously (arms moving opposite to each other) versus synchronously (both arms moving in the same direction simultaneously). SETTING: A university hospital setting in Galveston, Texas, USA. METHODS: Seventeen individuals between the ages of 19 and 53 years were studied, 11 with paraplegia and six with no apparent disability. Two maximal arm crank graded exercise tests were performed with the subject seated in a wheelchair. Testing consisted of both arms (1) asynchronously (reciprocally) pushing and pulling the crank handles and (2) pushing and pulling the crank handles synchronously. Each test consisted of 2 min stages starting at 20 W and increasing 10 W per stage thereafter until exhaustion. Heart rate, oxygen consumption, and minute ventilation were measured and recorded during each stage. Blood lactate levels were monitored before and after each test. Statistical analysis was performed using the multivariate Hotelling's T2 followed by post hoc univariate tests. RESULTS: Greater power and longer test times (both groups, P<0.05) and higher post test blood lactates (nondisabled P<0.01, paraplegic P<0.05) were achieved with asynchronous cranking versus synchronous cranking. While submaximal responses were similar between the two modes of cranking, there was a tendency for all variables to be lower with asynchronous. All subjects preferred asynchronous rather than synchronous cranking. CONCLUSION: Despite few statistically significant differences, based on the subjective reports from all subjects, we believe there is a clinically significant difference between the two modes of cranking. The results suggest that the mode of cranking may have implications for arm crank testing, training, and functional locomotion in individuals with lower extremity impairments.

Adult↗
PubMed2000

Cancer of the tongue in patients less than forty.

INTRODUCTION: It is the opinion of many surgeons that the biologic potential of cancer that develops in young people is different compared with older patients. Prior reports on small series of patients addressing this issue have inadequate statistical power to resolve the question. METHODS: By use of the techniques of meta-analysis, patients less than 40 years old who had undergone treatment of squamous cell carcinoma (SCC) of the oral tongue were examined. Twenty-eight patients who were encountered in the Department of Otolaryngology, University of Pittsburgh School of Medicine, and 94 patients were identified in the literature for a total of 122 patients <40 years old. A control group of 150 patients, aged 40 years and older treated for SCC of the oral tongue between 1982 and 1994 was identified. RESULTS: Three-year disease-free survival in the group of patients aged less than 40 was 53.3% compared with 3-year disease free survivorship of 55.0% in the older cohort of patients. CONCLUSION: These data strongly suggest that the outcomes of treatment for SCC of the oral tongue in young patients are similar compared with patients older than 40 with similar extent of disease.

Adolescent↗
PubMed1995

Comparison of additive and multiplicative models for reproductive risk factors and post-menopausal breast cancer.

The mathematical multistage model of carcinogenesis proposed by Breslow and Day indicates that if hormonal risk factors for breast cancer are late-stage carcinogens then the use of an additive model (excess absolute risk) should be preferrable to the present standard use of the multiplicative model (excess relative risk). To test different models, information from a large prospective study of 431,604 women aged 45-74 years in 1970 with follow-up to 1985 on reproductive factors and post-menopausal breast cancer mortality was used to compute goodness-of-fit statistics. The relative risk function, ranging from multiplicative to additive, was explored by changing the exponent in a power transformation. The analysis found evidence of better fit by the additive compared with the multiplicative models, consistent with the proposed mathematical model.

Aged↗