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[Microsatellite instability of genome in cells of sporadic and hereditary carcinoma of the gastrointestinal tract].

Microsatellite instability (MIN) of human genome, i.e. instability of very short (1-5 nt) DNA tandem repeats, points to a deficiency in the mismatch repair system (MMR). To investigate the role of MMR in sporadic and hereditary carcinogenesis in the gastrointestinal tract, four types of carcinomas were compared: sporadic (GC), familial (FGC) gastric carcinoma, sporadic colorectal (CC) and hereditary nonpolyposis colorectal (HNPCC) carcinoma. No significant difference in MIN frequency was found between GC (9 out of 27) (33%) and CC (7 out of 29) (24%). In hereditary carcinoma group, MIN occurrence appeared 2-3 times as high: FGC in 7 out of 10 (70%) and HNPCC in 6 out of 8 patients (75%). No significant differences were recorded in MIN occurrence at early and later stages of the disease in all groups. Therefore, it can be suggested that disorders in the MMR develop at earlier stages of carcinogenesis and may be responsible for tumor progression.

Base Sequence↗

Technology assessment in laparoscopic general surgery and gastrointestinal endoscopy: science or convenience?

Gastrointestinal endoscopy and laparoscopic general surgery have been significantly affected by the emergence of new techniques. These two disciplines share many similarities, including the use of sophisticated and expensive technologies. Their proper assessment is essential because they are developed amidst ever-decreasing health care budgets. Gastroenterologists and general surgeons must both participate in such evaluations and feel confident in interpreting pertinent published data. The present review uses a clinician's point of view with relevant examples to discuss the methodologies adopted in technology assessment and to highlight common pitfalls encountered in study design, patient selection, timing and selection of the study, blinding, and outcome measurement. Cost and statistical considerations, as well as ethical issues, are also reviewed in the context of technology assessment.

Costs and Cost Analysis↗

Genome-wide expression studies of atherosclerosis: critical issues in methodology, analysis, interpretation of transcriptomics data.

During the past 6 years, gene expression profiling of atherosclerosis has been used to identify genes and pathways relevant in vascular (patho)physiology. This review discusses some critical issues in the methodology, analysis, and interpretation of the data of gene expression studies that have made use of vascular specimens from animal models and humans. Analysis of gene expression studies has evolved toward the genome-wide expression profiling of large series of individual samples of well-characterized donors. Despite the advances in statistical and bioinformatical analysis of expression data sets, studies have not yet fully exploited the potential of gene expression data sets to obtain novel insights into the molecular mechanisms underlying atherosclerosis. To assess the potential of published expression data, we compared the data of a CC chemokine gene cluster between 18 murine and human gene expression profiling articles. Our analysis revealed that an adequate comparison is mainly hindered by the incompleteness of available data sets. The challenge for future vascular genomic profiling studies will be to further improve the experimental design, statistical, and bioinformatical analysis and to make data sets freely accessible.

Animals↗

Some limitations on studies about the relation between gross cystic disease and risk of subsequent breast cancer.

Studies about the relationship between gross cysts and risk of subsequent carcinoma of the breast should be interpreted with caution. When the study material is limited to microscopic review of benign biopsy specimens, there is considerable chance of misclassification of cases both of those with and of those without gross cysts. Moreover, statistical analyses based on internal comparisons of such data tend to separate the influence of gross cysts from that of any associated proliferative disease process. Thus, while they may provide information about whether or not gross cysts identified under a microscope influence the risk of breast cancer, independently of other, associated pathology, they do not address the question of whether or not gross cysts serve as a marker for an increased risk of breast cancer. On the other hand, statistical analyses based on external comparisons do not allow estimates of relative risks associated with gross cysts that are clearly unaffected by other factors related to breast cancer risk. Follow-up data on over 2500 patients who consulted Dr. C. D. Haagensen for gross cystic disease of the breast provide evidence of an increased risk of breast cancer, when compared with an external standard. A microscopic biopsy review of Dr. Haagensen's benign breast cases, with and without GCD, is currently under way to classify the cases in a way that is comparable to the Dupont and Page criteria. It is hoped that a statistical analysis that incorporates these microscopic findings with the clinical information and the gross pathology will shed further light on the role of gross cysts in relation to breast cancer.

Breast Neoplasms↗

Imputing missing repeated measures data: how should we proceed?

OBJECTIVE: This paper compares six missing data methods that can be used for carrying out statistical tests on repeated measures data: listwise deletion, last value carried forward (LVCF), standardized score imputation, regression and two versions of a closest match method. METHOD: The efficacy of each was investigated under a variety of sample sizes and with differing levels of missingness. Randomly selected samples from a dataset (n = 804) were used to compare the methods using t-tests. Efficacy was defined as the closeness of the estimated t-values to the true t-values from the complete dataset. RESULTS: The results suggest a reliable and efficacious basis for imputation method for repeated measures data is to substitute a missing datum with a value from another individual who has the closest scores on the same variable measured at other timepoints, or the average value of four individuals who have the closest scores on the same variable at other timepoints. The LVCF and standardized score methods performed relatively poorly, which is of concern since these are often recommended. Listwise deletion was also an inefficient missing data method. CONCLUSIONS: Researchers should consider using closest match missing data imputation. Since listwise deletion performed poorly, is widely reported and is the default method in many statistical software packages, the findings have broad implications.

Alcoholism↗

Writing a grant proposal--part 2: research methods--part 2.

As part of a Spotlight series on grant writing by members of the Center for Clinical Investigation of the Wound Ostomy and Continence Nursing (WOCN) Society, this article completes an explanation about writing the Methods section of a grant proposal. The aim of this series is to enhance the skills of WOC nurses to increase submissions of high-quality grants related to WOC nursing science and success in garnering funding, particularly from foundation grants, such as that of the WOCN. In this article, writing about the sample and setting, power analysis, sampling and recruitment procedures, implementation and data collection procedures, statistical analysis plan, and ethical considerations are described.

Data Collection↗

RepGene: a spreadsheet template for the management of reporter gene assays.

One of the most powerful techniques in molecular biology is the controlled expression of specific proteins by transfection of eukaryotic cells. This method has become feasible and highly sensitive and, thus, suitable for high-throughput reporter gene assays in basic and applied research. Moreover, the limiting factors are neither the transfection efficiency nor the functional analysis, but rather the ability to manage complex experimental protocols when multiple genes are co-transfected and/or when the effects of several chemical compounds are investigated within the same experiment. Here, we describe an easy-to-use and highly flexible spreadsheet template intended to rationalize and expedite the organization and data management of multi-step reporter gene assays. The objectives of this spreadsheet template are the design of the transfection protocol, the coordination of the administration of test compounds, and the graphical presentation and statistical analysis of the results.

Data Display↗

HLA-B27: a registry of constitutive peptide ligands.

The very strong association of human leukocyte antigen (HLA)-B27 with spondyloarthritis might be related to its peptide-presenting properties. The natural polymorphism of this molecule influences both peptide specificity and disease susceptibility. In this study, we present a comprehensive compilation of known natural ligands of HLA-B27 arising from endogenous proteins of human cells, together with a statistical assessment of residue usage among constitutive peptide repertoires of multiple HLA-B27 subtypes. This analysis provides evidence that every peptide position, including "non-anchor" ones, may be subjected to selection on the basis of its contribution to HLA-B27 binding and also allows a quantization of residue preferences at known anchor positions. The present registry is intended as a basis on which to build up reliable criteria to assess the effect of HLA-B27 polymorphism on peptide presentation, for T-cell epitope predictions, and for molecular mimicry studies.

Amino Acid Sequence↗

Clinical trials using HIV-1 RNA-based primary endpoints: statistical analysis and potential biases.

Clinical trial endpoints based on magnitude of reduction in HIV-1 RNA levels provide an important complement to endpoints based on percentage of patients achieving complete virologic suppression. However, interpretation of magnitude of reduction can be biased by measurement limitations of virologic assays, particularly lower and upper limits of quantification. Using data from two AIDS Clinical Trials Group (ACTG) studies, widely used crude methods of analyzing HIV-1 RNA reductions were compared with methods that take into account censoring of HIV-1 RNA measurements. Such methods include Kaplan-Meier and censored regression analyses. It was found that standard crude methods of analysis consistently underestimated treatment effects. In some cases, the bias induced by crude methods masked statistically significant differences between treatment arms. Although statistically significant, adjustment for baseline HIV-1 RNA levels had little effect on estimated treatment differences. Furthermore, convenient parametric analyses performed as well as more complex nonparametric analyses. It is concluded that conveniently implemented censored data analyses should be conducted in preference to widely used crude analyses of magnitude of HIV-1 RNA reduction. To obtain complete information about virologic response to antiretroviral therapy, such analyses of magnitude of virologic response should be used to complement analyses of the percentage of patients having complete virologic suppression.

Bias↗

Counting nurses: interpreting nursing workforce statistics.

Discusses the interpretation of nursing statistics, the problem of counting how many nurses there are in the workforce, and the need to be aware of how statistics are compiled when presenting numerical data to support arguments relating to nursing and the nursing workforce. Argues that NHS workforce statistics provide considerable evidence for claiming that there is a significant decline in the number of nursing staff doing the work of nursing in the NHS. Explains that although there was an increase in the number of qualified nurses working in the NHS throughout the 1980s (over a ten-year period the number of qualified nurses increased by 22 per cent), the increase in qualified nursing staff has not compensated for the loss of student learners in the workforce. Emphasizes that during the last three years for which figures are available, however, these gains have been wiped out, and the number of qualified nurses has declined to pre-Project 2000 levels.

Data Collection↗

Definition, interpretation and calculation of cost-effectiveness acceptability curves.

This paper discusses the definition, interpretation and computation of cost-effectiveness (CE) acceptability curves. A formal definition of the CE acceptability curve based on the net benefit approach is provided. The curve can be computed using parametric or non-parametric techniques and for both computational approaches we establish a formal relation between the CE acceptability curve and statistical inference based on confidence intervals and P values in CE analysis.

Cost-Benefit Analysis↗

Statistical conclusion validity and type IV errors in rehabilitation research.

The incidence of type IV errors was examined in 71 rehabilitation research studies, including a two-way analysis of variance with a statistically significant interaction. The interpretation of the significant interaction was examined to determine whether it qualified as a type IV error. A type IV error was defined as the incorrect interpretation of a correctly rejected null hypothesis. Statistically significant interactions were classified in one of the following categories: (1) correct interpretation, (2) cell mean interpretation, (3) main effect interpretation, or (4) no interpretation. Interpretations classified as cell means or main effects were considered type IV errors. The analysis revealed that 21% of the interactions were correctly interpreted and 63% of the interactions were classified as type IV errors. The remaining 16% of the studies showed a statistically significant interaction but no interpretation. The implications of statistical conclusion validity and type IV errors are discussed, and methods to eliminate or reduce the incidence of type IV errors in rehabilitation research are presented.

Analysis of Variance↗