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PubMed2000

Establishing the relation between detrended fluctuation analysis and power spectral density analysis for stochastic processes

Stochastic fractal signals can be characterized by the Hurst coefficient H, which is related to the exponents of various power-law statistics characteristic of these processes. Two techniques widely used to estimate H are spectral analysis and detrended fluctuation analysis (DFA). This paper examines the analytical link between these two measures and shows that they are related through an integral transform. Numerical simulations confirm this relationship for ideal synthesized fractal signals. Their performance as estimators of H is compared based on a mean square error criterion and found to be similar. DFA measures are derived for physiological signals of heartbeat R-R intervals through the integral transform of a spectral density estimate. These agree with directly calculated DFA estimates, indicating that the relationship holds for signals with nonideal fractal properties. It is concluded that DFA and spectral measures provide equivalent characterizations of stochastic signals with long-term correlation.

Journal Article↗
PubMed1989

[Meta-analysis on randomized trials comparing the results of low-molecular weight heparins to those of fractioned heparins in the prevention of deep venous thrombosis].

The main reason for using low molecular weight heparin (LMWH) is its capacity to keep the antithrombotic effect of standard non-fractioned heparin (NFH) while reducing its hemorrhagic power. Various studies comparing LMWH to NFH gave contradictory results, so we carried out a meta-analysis of randomized trials comparing these two treatments in prevention of deep-vein thrombosis (DVT) (and in prevention of deep-vein thrombosis or pulmonary embolism). From a selection of ten trials we could not show any significant difference in the DVT rates, as well as for the whole of surgical indications as for the subgroups of abdominal and orthopedic surgery. The weighted global difference between the DVT rates is so low that, in spite of the use of meta-analysis, the power is clearly insufficient. The hemorrhagic risk is not statistically reduced as well for the whole of surgical indications as for the subgroups.

Heparin↗
PubMed2025

CoverM: read alignment statistics for metagenomics.

SUMMARY: Genome-centric analysis of metagenomic samples is a powerful method for understanding the function of microbial communities. Calculating read coverage is a central part of analysis, enabling differential coverage binning for recovery of genomes and estimation of microbial community composition. Coverage is determined by processing read alignments to reference sequences of either contigs or genomes. Per-reference coverage is typically calculated in an ad-hoc manner, with each software package providing its own implementation and specific definition of coverage. Here we present a unified software package CoverM which calculates several coverage statistics for contigs and genomes in an ergonomic and flexible manner. It uses "Mosdepth arrays" for computational efficiency and avoids unnecessary I/O overhead by calculating coverage statistics from streamed read alignment results. AVAILABILITY AND IMPLEMENTATION: CoverM is free software available at https://github.com/wwood/coverm. CoverM is implemented in Rust, with Python (https://github.com/apcamargo/pycoverm) and Julia (https://github.com/JuliaBinaryWrappers/CoverM_jll.jl) interfaces.

Metabolomics↗
PubMed1996

Monitoring and analysis of outcome studies.

Monitoring technology appears to be advancing at a rare that exceeds our ability to assess its effectiveness. RCTs are often poorly designed and lacks statistical power. Even high-quality RCTs may not provide inferences that can be generalized across all patient populations. Alternative methods of technology assessment, such as closed claims analysis, meta-analysis, and statistical process control, also have limitations. PORTs using a standard model of combined techniques are beginning to solve some of the more common methodological problems. The future of technology assessment relies on the ability to conduct large-scale cohort studies from routine practice settings. In terms of intraoperative monitors, this may require production of a complete and valid database of all monitored variables that can compared to a complete and valid database of all monitored variables that can be compared to a complete and valid database of appropriate outcome indicators. National standard for collection of data need to be developed. At this time, professional societies should focus more on developing guidelines for technology assessment than on guidelines for technology utilization.

Cohort Studies↗
PubMed1980

Methodological issues in short-term motor memory research.

Four methodological issues identified and studied by short-term motor memory researchers were examined in this paper: (a) the distributions of three commonly used measures of error (AE, CE, and VE); (b) statistical analysis of these scores as dependent measures in an experiment; (c) within-cell and experiment-wise estimates of the reliability of CE; and (d) the power of the statistical test with CE as the dependent measure. The first two sub-problems were explored theoretically, while the latter two were subjected to empirical examination using four data sets from previously published experiments. The distributions of AE and VE scores were described as non-normal under certain conditions, while the CE score distribution was shown to be normal. Therefore analyses of these three dependent measures may require different statistical procedures. In light of this information, the assumptions affecting estimates of reliability and power in an experimental framework were examined. Based on an analysis of the four data sets, a strategy was proposed in which a relatively small number of subjects could be utilized in an experiment without sacrificing desired experimental controls.

Journal Article↗
PubMed2006

Treatment of varicocele in subfertile men: The Cochrane Review--a contrary opinion.

OBJECTIVE: A recent Cochrane meta-analysis of randomised clinical trials (RCTs) concluded that surgical or radiological treatment of varicocele in men from couples with otherwise unexplained subfertility cannot be recommended. The aim of the present study is to address criticisms of this review carrying out a critical analysis of all available RCTs. MATERIALS AND METHODS: The eight randomised clinical trials selected in the last Cochrane Library systematic review have been evaluated. All RCTs including patients either with normal semen analysis or subclinical varicocele have been excluded. Inclusion criteria, number and clinical characteristics of randomised patients, and outcomes reported in terms of pregnancy rate one year after randomisation have been described in the remaining studies. RESULTS: Only 3/8 RCTs included patients with abnormal semen analysis and palpable varicocele. Overall 120 patients in the treatment group and 117 in the control group were randomised. The studies turned out to be heterogeneous in terms of inclusion criteria and clinical characteristics of the analysed patients. Their methodological quality and statistical power have to be considered poor. Moreover, the "as treated" cumulative analysis showed a significant increase in pregnancy rate in patients who underwent varicocele treatment (36.4%) compared with the control group (20%) (p = 0.009). CONCLUSIONS: The RCTs included in the last Cochrane review concerning the efficacy of varicocele treatment in subfertile couples were heterogeneous and methodologically poor. The pooling of these studies cannot result in a good quality meta-analysis. The Cochrane meta-analysis conclusions should not support guidelines recommendation against varicocele treatment in subfertile patients. Data from ongoing studies should provide more information in this topic.

Adult↗
PubMed2003

Insulin glargine: a systematic review of a long-acting insulin analogue.

BACKGROUND: Insulin glargine is the first long-acting basal insulin analogue indicated for subcutaneous administration once daily at bedtime in adults with type 1 or type 2 diabetes mellitus and pediatric patients aged > or = 6 years with type 1 diabetes. It differs in structure from native human insulin by 3 amino acids, a structural modification that provides a delayed onset of action and a constant, peakless effect that has a duration of at least 24 hours. OBJECTIVE: The goal of this article was to help determine the current place in therapy of insulin glargine by reviewing all available efficacy and tolerability data published since its introduction onto the market. METHODS: Relevant English-language articles were identified through searches of MEDLINE, PubMed, and EMBASE from 1966 to October 2002 and PREMEDLINE for November 2002. The search terms used were insulin, analogs, analogues, diabetes mellitus, glargine, HOE901, HOE-901, efficacy, safety, comparative study, treatment outcome, and case report. The reference lists of the identified articles were searched for additional relevant publications. Pharmacokinetic and pharmacodynamic data were reviewed and summarized. All large clinical trials (> or = 100 patients) evaluating the efficacy and tolerability of insulin glargine in patients with type 1 or type 2 diabetes were included in the review. Studies were compared in terms of their designs, primary and secondary efficacy parameters (glycosylated hemoglobin [HbA(1c)], fasting plasma glucose [FPG] and/or fasting blood glucose [FBG] level, incidence of hypoglycemia), and tolerability assessments. RESULTS: Fourteen trials met the criteria for inclusion in this review, 7 of them published only in abstract form. All were multicenter, randomized, open-label, parallel-group trials conducted in Europe or the United States, and ranged in duration from 4 to 52 weeks. They compared insulin glargine with neutral protamine Hagedorn (NPH) insulin given once or twice daily in >5000 patients with type 1 or type 2 diabetes, or in insulin-naive patients with type 2 diabetes that was poorly controlled by oral antidiabetic agents. Insulin doses were individually titrated to achieve a target FBG level < or =120 mg/dL (6.7 mmol/L). The studies were typically statistically underpowered to detect a significant difference in HbA(1c) between treatment groups; only 3 trials were of an adequate size to have 90% statistical power to detect a mean 0.5% difference in HbA(1c). Furthermore, analysis of the data from these trials was associated with a number of methodologic problems relating to inconsistencies in reporting. Given these limitations, the available data suggest that insulin glargine treatment produces statistically significant reductions in FPG or FBG levels at end point both compared with baseline and compared with NPH insulin (P < 0.001) without achieving overall significant improvements in HbA(1c) values. However, a recent abstract of a small 52-week trial in patients with type 1 diabetes reported a 0.4% additional decrease in HbA(1c) with insulin glargine treatment compared with NPH insulin. Patients have reported greater treatment satisfaction with insulin glargine compared with NPH insulin. The findings varied regarding weight gain, overall incidence of hypoglycemia, and incidence of nocturnal hypoglycemia. Currently, the cost of insulin glargine is twice that of NPH insulin on a per-unit basis. CONCLUSIONS: As a basal insulin replacement, insulin glargine administered once daily demonstrates a steady time-action profile over 24 hours without a pronounced peak. Based on the evidence from published clinical trials, insulin glargine appears to have equal clinical efficacy to NPH insulin, produces similar reductions in HbA(1c), and is associated with lower FPG and FBG levels and a consistent and significant reduction in the incidence of nocturnal hypoglycemia in patients with type 2 diabetes.

Clinical Trials as Topic↗
PubMed2007

Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass.

UNLABELLED: Several genome-wide scans have been performed to detect loci that regulate BMD, but these have yielded inconsistent results, with limited replication of linkage peaks in different studies. In an effort to improve statistical power for detection of these loci, we performed a meta-analysis of genome-wide scans in which spine or hip BMD were studied. Evidence was gained to suggest that several chromosomal loci regulate BMD in a site-specific and sex-specific manner. INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic fracture risk. Several genome-wide scans have been performed in an attempt to detect loci that regulate BMD, but there has been limited replication of linkage peaks between studies. In an attempt to resolve these inconsistencies, we conducted a collaborative meta-analysis of genome-wide linkage scans in which femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied. MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD and by sex. For each study, genomic bins of 30 cM were defined and ranked according to the maximum LOD score they contained. While various densitometers were used in different studies, the ranking approach that we used means that the results are not confounded by the fact that different measurement devices were used. Significance for high average rank and heterogeneity was obtained through Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this exhibited high heterogeneity and the effect was specific for women. Other significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12-q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3 (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33, 14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in average ranks of bins between men and women and the loci that regulated BMD in men and women and at different sites were largely distinct. CONCLUSIONS: This large-scale meta-analysis provided evidence for replication of several QTLs identified in previous studies and also identified a QTL on chromosome 18p11-q12.3, which had not been detected by individual studies. However, despite the large sample size, none of the individual loci identified reached genome-wide significance.

Bone Density↗
PubMedDate not supplied

The affected-pedigree-member method: power to detect linkage.

The affected-pedigree-member (APM) method of linkage analysis is a nonparametric statistic for testing for nonindependent segregation of a marker to affected members of a pedigree. We present here results of a simulation study evaluating the power of the APM method to detect linkage. We have systematically explored, by computer simulation, the effect of a variety of factors on the power to detect linkage using the single-locus APM statistic. These factors include mode of inheritance, marker polymorphism, the distance between marker and disease, phenocopy rate, heterogeneity, and misspecified marker allele frequencies. We also evaluated the relative power obtained under fixed-structure sampling and sequential sampling. For a dominant disease, sequential sampling led to increased power as compared to fixed-structure sampling, while for a recessive disease, there was no clear advantage in sampling beyond nuclear families.

Alleles↗
PubMed1987

Predictors of atherosclerosis in the Honolulu Heart Program. II. Adjustment for autopsy bias.

Although autopsy is considered the final word on many medical questions, there has long been concern over possible bias in inference about a living population from analysis of autopsy material. Focus of the present paper is on the relationship between results obtainable only at autopsy and risk factors recorded as part of a prospective study of the entire "target population." Since pathologies are sure to be overrepresented in an autopsy sample compared to the target population, the dependence of autopsy scores upon risk factors may be distorted in the autopsy sample. The present paper proposes a method of adjustment for this bias. When both autopsy sample and target population can be stratified by major disease categories, under certain assumptions of equal effect, adjustment similar to the direct method for age adjustment may be applied. If, in addition, dependence can be characterized accurately by linear regression of both autopsy score and disease category frequency onto risk factors, then a very convenient calculation produces adjusted regression coefficients. This "parametric" method usually provides the most convenient results, with the greatest statistical power.

Analysis of Variance↗
PubMed2003

Modern robust data analysis methods: measures of central tendency.

Various statistical methods, developed after 1970, offer the opportunity to substantially improve upon the power and accuracy of the conventional t test and analysis of variance methods for a wide range of commonly occurring situations. The authors briefly review some of the more fundamental problems with conventional methods based on means; provide some indication of why recent advances, based on robust measures of location (or central tendency), have practical value; and describe why modern investigations dealing with nonnormality find practical problems when comparing means, in contrast to earlier studies. Some suggestions are made about how to proceed when using modern methods.

Humans↗
PubMed2005

Tissue model and preliminary analysis of microdebriders used in functional endoscopic sinus surgery.

OBJECTIVE: To develop a standardized in vitro tissue model for microdebrider comparison, and determine which microdebrider, tissue type, blade type, and suction strength is most efficient. STUDY DESIGN AND SETTING: A prospective randomized comparison of the Diego Powered Dissector and XPS 3000 Powered ENT System was conducted using a soft-tissue and a firm-tissue model. In addition to evaluating tissue aspiration with straight and angled blades, clogging rates and clearance times were measured. Both standard wall suction and liposuction were used. Basic statistical analysis and a one-way analysis of variance using confidence intervals were performed to compare outcomes. RESULTS: The aspiration of soft tissue was statistically superior to and demonstrated less clogging compared to the aspiration of firm tissue. For the "head-to-head" comparison, the XPS 3000 was statistically superior for aspirating soft tissue. When liposuction was excluded, the devices were essentially equivalent. Several notable trends that were not statistically significant were also observed. The aspiration efficiency of straight blades appeared to be superior compared to angled blades. The XPS 3000 and liposuction independently seemed to aspirate more tissue than the Diego Powered Dissector and regular suction, but at the expense of increased clogging. Finally, the Diego Powered Dissector showed a trend toward aspirating more firm tissue. CONCLUSION: Our tissue model represents a reliable and reproducible means of microdebrider comparison. A secondary analysis with a larger sample size is warranted to further validate the tissue model, to improve the power of the statistically significant results, and to better delineate the trends that were observed in the current study.

Animals↗
PubMed2006

Analysis of cell-based RNAi screens.

RNA interference (RNAi) screening is a powerful technology for functional characterization of biological pathways. Interpretation of RNAi screens requires computational and statistical analysis techniques. We describe a method that integrates all steps to generate a scored phenotype list from raw data. It is implemented in an open-source Bioconductor/R package, cellHTS (http://www.dkfz.de/signaling/cellHTS). The method is useful for the analysis and documentation of individual RNAi screens. Moreover, it is a prerequisite for the integration of multiple experiments.

Quality Control↗
PubMed1991

Data analysis and sample size issues in evaluations of community-based health promotion and disease prevention programs: a mixed-model analysis of variance approach.

The growing interest in community-based approaches to health promotion and disease prevention (HP/DP) has been accompanied by a growing need to evaluate the effectiveness of such programs. Special issues that arise in these evaluation studies include (1) entire communities are assigned to intervention and control groups, (2) only a small number of communities can usually be studied, (3) the time course of changes in behavior and other outcomes is often of interest, and (4) surveys to measure such changes over time can be conducted with either repeated cross-sectional samples or with longitudinal samples. This paper shows how these issues can be addressed under a mixed-model analysis of variance approach. This approach serves to unify several ideas in the literature on evaluation of community studies, including use of time-series regression and the question of whether the individual or the community should be the unit of analysis. We also describe how the method can be used to estimate sample size requirements, statistical power, or minimum detectable program effect.

Analysis of Variance↗
PubMed2006

Comparison of the accuracy of magnetic resonance imaging and positron emission tomography/computed tomography in the presurgical detection of lymph node metastases in patients with uterine cervical carcinoma: a prospective study.

BACKGROUND: The objective of the current study was to determine the accuracy of magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) for detecting lymph node metastases in patients with uterine cervical carcinoma compared with thin-section histopathologic results from systemic lymphadenectomy. METHODS: Twenty-two patients with International Federation of Obstetrics and Gynecology (FIGO) Stage IB-IVA cervical carcinoma who underwent both MRI and PET/CT before lymphadenectomy were included in this study. Lymphadenectomy involved removing all visible lymph nodes in the surgical fields. To enable region-specific comparisons, paraaortic and pelvic lymph nodes were divided into seven regions: the paraaortic area, both common iliac areas, both external iliac areas, and both internal iliac/obturator areas. Histopathologic evaluation of lymph nodes was the diagnostic standard. Chi-square analysis was used to compare the accuracy of MRI and PET/CT for the detection of metastatic lymph nodes. A P value < or = 0.05 was considered statistically significant. RESULTS: With MRI, the sensitivity, specificity, and accuracy rates for detecting metastatic lymph nodes in each lymph node group were 30.3% (10 of 33 lymph node groups), 92.6% (112 of 121 lymph node groups), and 72.7% (122 of 154 lymph node groups), respectively; with PET/CT, those rates were 57.6% (19 of 33 lymph node groups), 92.6% (112 of 121 lymph node groups), and 85.1% (131 of 154 lymph node groups), respectively. Statistical analysis showed that PET/CT was more sensitive than MRI (P = 0.026) but that there were no statistical differences noted with regard to specificity (P = 1.000) or accuracy (P = 0.180). Power analysis demonstrated that a sample size of 685 lymph node groups (98 patients) would be necessary to demonstrate that PET/CT was more accurate than MRI (alpha = 0.05; beta = 0.80). CONCLUSIONS: PET/CT was more sensitive than MRI for detecting lymph node metastases in patients with uterine cervical carcinoma.

Adult↗
PubMed1988

Load- and skill-related changes in segmental contributions to a weightlifting movement.

An exemplary short duration, high-power, weightlifting event was examined to determine whether the ability to lift heavier loads and whether variations in the level of skill were accompanied by quantitative changes in selected aspects of lower extremity joint power-time histories. Six experienced weightlifters, three skilled and three less skilled, performed the double-knee-bend execution of the pull in Olympic weightlifting, a movement which lasted almost 1 s. Analysis-of-variance statistics were performed on selected peak and average values of power generated by the three skilled subjects as they lifted three loads (69, 77, and 86% of their competition maximum). The results indicated that the skilled subjects lifted heavier loads by increasing the average power, but not the peak power, about the knee and ankle joints. In addition, the changes with load were more subtle than a mere quantitative scaling and also seemed to be associated with a skill element in the form of variation in the duration of the phases of power production and absorption. Similarly, statistical differences (independent t-test) due to skill did not involve changes in the magnitude of power but rather the temporal organization of the movement. Thus, the ability to successfully execute the double-knee-bend movement depends on an athlete's ability to both generate a sufficient magnitude of joint power and to organize the phases of power production and absorption into an appropriate temporal sequence.

Adolescent↗
PubMed2004

Recent trends and advances in immunodiagnostics of solid tumors.

The development of new cancer immunodiagnostic tests measuring soluble markers can be divided along the lines of single analyte measurement versus multiplex analysis. In the measurement of single analytes, newly proposed test analytes still struggle with the same issues as their predecessors; namely, can the measurement of a single biomarker be sufficiently sensitive and specific for screening the general population? Probably the best example of this challenge is in the area of bladder cancer detection, where several newly identified markers are being clinically evaluated in multicenter trials. In order to surmount this hurdle, multiplex analysis has become an increasingly important research focus. By combining the statistical power of measuring many cancer-associated analytes, it is hoped that highly specific diagnostic tests can be developed that are suitable for screening the general population. Some of the most impressive data for multiplex cancer biomarker detection derive from a non-immunologic technique - mass spectroscopy. Multiplex analysis has also recently been applied to the measurement of serum antibodies to tumor-associated antigens. Recent data link the development of antibodies to tumor-associated antigens with the presence of solid tumors. This strategy is a departure from the more traditional assay format of measuring the antigens themselves, and is another promising emerging area of investigation for the early detection of solid tumors. Solid tumor analysis by quantitative immunohistochemical staining is another rapidly growing area of cancer immunodiagnosis. This field has become especially important in the context of pharmacodiagnostics - the coupling of cancer therapy to the outcome of a test measurement from a patient biopsy. Standardization and assay reproducibility appear to be the most significant challenges in this context. In summary, developments over the past several years give reason for excitement and optimism about the potential for cancer immunodiagnostics to meaningfully impact cancer patient survival. In this review we take a fresh look at the field of cancer immunodiagnostics, to identify these recent and emerging trends that may impact on clinical practice over the next few years.

Animals↗