Validity Of Statistical Methods Research Articles

OTHR-42. Missing data tolerant integration of proteomic datasets enables the identification and characterization of brain cancer subtypes

Investigating the proteome can add a significant layer of information to manifold existing methylation, mutation, and transcriptome data on brain tumors as proteins represent the pharmacologically addressable phenotype of a disease. Small cohorts limit the usability and validity of statistical methods, and variable technical setups and high numbers of missing values make data integration from public sources challenging. Using a newly developed framework being able to reduce batch effects without the need for data reduction or missing value imputation, we show –based on in-house and publicly available datasets- successful integration of proteomic data across different tissue types, quantification platforms, and technical setups. Exemplarily, data of a Sonic hedgehog (Shh) medulloblastoma mouse model were analyzed, showing efficient data integration independent of tissue preservation strategy or batch. We further integrated batches of publicly available data of human brain tumors, confirming proposed proteomic cancer subtypes correlating with clinical features. We show that, missing value tolerant reduction of technical variances may be helpful to identify biomarkers, proteomic signatures, and altered pathways characteristic for molecular brain cancer subtypes.

Molecular mobility changes after high-temperature, short-time pasteurization: An extended time-domain nuclear magnetic resonance screening of ewe milk

This study presents an extensive investigation on the effect of pasteurization on raw whole ewe milk. Milk samples have been analyzed, throughout lactation (from February to July), by time-domain nuclear magnetic resonance (TD-NMR), collecting the characteristic TD-NMR relaxation parameters, proton longitudinal and transverse relaxation times (1H T1 and T2). Collected data aim at integrating previous NMR works, mainly focusing on dairy model systems (casein and whey proteins solutions and gels, reconstituted skim milk) and cheese, with specific reference to the effect of heat treatments. Whole ewe milk, from a single flock (Sarda sheep breed), was daily analyzed both as untreated (raw) and heat treated with a laboratory-scaled high-temperature, short-time treatment (72°C for 15 and 20 s). Moreover, molecular dynamics in milk were investigated by TD-NMR in different periods of lactation for the first time. As a consequence of high-temperature short-time treatment, 1H T1 and T2 consistently shifted to lower values with respect to raw counterparts. Statistical analysis indicated a significant decrease of T2 in treated samples, to an extent dependent on the heat treatment duration. A subset of dedicated experiments demonstrated that the observed T2 shift is largely ascribable to protein molecular rearrangements and, to a lesser extent, to the interaction of fat globules with proteins or other nonfat components (or both). In light of the crucial importance of detecting the application of a heat treatment to milk, the results reported here suggest TD-NMR relaxation parameters were able to describe heat-induced changes in molecular dynamics and interactions of milk components in a water-rich environment. The use of TD-NMR can be considered a potential suitable technique for quality control and assurance practices in the dairy industry. Upon statistical validation of methods, the application of TD-NMR in the dairy industry would take advantage of its low cost, reliability, and robustness.

ACVIM consensus statement on the treatment of immune-mediated hemolytic anemia in dogs.

Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases.

The panacea statistical toolbox of a biomedical peer reviewer

The main role of a peer reviewer is to make judgments on the research articles by asking a number of questions to evaluate the quality of the research article. Statistics is a major part of any biomedical research article, and most reviewers gain their experiences in manuscript reviewing by undertaking it but not through an educational process. Therefore, reviewers of the biomedical journals normally do not have enough knowledge and skills to evaluate the validity of statistical methods used in biomedical research articles submitted for consideration. Hence, inappropriate statistical analysis in medical journals can lead to misleading conclusions and incorrect results. In this paper, the most common basic statistical guidelines are described that might be a road map to the biomedical reviewers. It is not meant for statisticians or medical editors who have special interest and expertise in statistical analysis.

Distinguishing Milankovitch‐Driven Processes in the Rock Record from Stochasticity Using Computer‐Simulated Stratigraphy

Repetitive patterns of facies recurrence are frequently reported from the shallow‐water sedimentary rock record and are postulated to have been driven by orbital forcing on eustatic sea level. Consequently, multiple statistical techniques have been developed to evaluate whether patterns of stratigraphic succession are more consistent with a periodic sea level signal or are stochastic. Previous studies focused on development and/or application of such methods to test empirical geological records. However, the character of such records cannot be known a priori, as deposition, erosion, and preservation influence the resultant composition, nor can those records be readily manipulated to explore the sensitivity, robustness, and overall validity of statistical methods. Here we simulate carbonate layers using computer‐modeled successions generated by periodic sea level changes. The resulting stratigraphic records were then evaluated statistically. Thickness distributions of simulated lithofacies were compared to distributions predicted for Poisson processes, which by definition are not driven by cyclical sea level changes. Our results suggest that periodic processes produce stratigraphic thickness frequencies that are difficult to distinguish from random frequencies except under high‐magnitude sea level fluctuations. Similarly, autocorrelation fails to correctly recognize cyclic patterns in such simulated records. Models with high‐magnitude sea level fluctuations (icehouse conditions) had thickness frequencies that are suggestive of orbital forcing, whereas low‐magnitude sea level fluctuations (greenhouse conditions) appeared independent even though they were modeled using Milankovitch orbital forcing. The increasing evidence based on spectral data from real rock successions suggests that Milankovitch drivers are common in both icehouse and greenhouse periods. Because statistical approaches are unsuccessful in recognizing the cyclic driver of these simulated records, we infer that it is difficult to disprove independence from real stratigraphy even when orbital forcing is controlling the rock composition. Even in the necessarily simplified world of computer simulations, the numerous factors involved in depositing stratigraphic successions work to complicate or mask any periodic signal, thus generating the appearance of stochasticity in some successions.

Validation of Statistical Methods to Compare Cancellation Rates on the Day of Surgery

Validation of Statistical Methods to Compare Cancellation Rates on the Day of Surgery

Validation of Statistical Methods to Compare Cancellation Rates on the Day of Surgery

Validation of Statistical Methods to Compare Cancellation Rates on the Day of Surgery

Application of Deming's Principles to Evaluating Professional Staff Members in R&D Services Companies

ABSTRACTThe nature of R&D services company work—long-term projects, non-repetitive activities, and highly specialized knowledge requirements—limits the validity of statistical methods used for employee performance evaluation. This article contends that employee performance appraisal systems based on statistical classification or ranking methods produce inaccurate results and cause consequent quality and productivity losses when managers apply them to technical professionals. W. E. Deming's principles for transforming Western management techniques provide the foundation for analyzing these effects and for developing more effective employee evaluation techniques.

Evaluation and validation of statistical methods for viability assays with emphasis on monte carlo experiments as applied to the limiting dilution assay

Evaluation and validation of statistical methods for viability assays with emphasis on monte carlo experiments as applied to the limiting dilution assay