An increased number of circulating γ/δ TCR + T cells in patients with chronic viral hepatitis

Abstract There is evidence that γ/δ TCR + T cells are specialized in recognizing different antigens, but their immunologic role as a second TCR is still unclear. The aim of this study was to investigate the percentage and absolute numbers of circulating γ/δ TCR + T cells in patients with chronic viral hepatitis (CVH) and to compare with HBsAg⁺, HCV healthy carriers and healthy subjects. Forty nine patients with CVH-24 with chronic active (CAH) and 25 with chronic persistent hepatitis (CPH)-, 21 HBsAg⁺, 20 HCV asymptomatic carriers and 20 healthy subjects were enrolled in the study. Lymphocyte subsets were determined after incubation with monoclonal antibodies to T total (CD5) and T γ/δ cells (γ/δ-1) using immunofluorescence microscopy. An increased number of circulating γ/δ TCR + T cells was found in patients with CVH in comparison with asymptomatic carriers and normal controls: this increase was more profound in patients with CAH, compared to CPH patients. These results indicate a correlation between circulating γ/δ TCR + T cells in CVH patients and activity and chronicity of the disease.     

Bayesian Nonparametric Modeling for Comparison of Single-Neuron Firing Intensities

Summary .  We propose a fully inferential model-based approach to the problem of comparing the firing patterns of a neuron recorded under two distinct experimental conditions. The methodology is based on nonhomogeneous Poisson process models for the firing times of each condition with flexible nonparametric mixture prior models for the corresponding intensity functions. We demonstrate posterior inferences from a global analysis, which may be used to compare the two conditions over the entire experimental time window, as well as from a pointwise analysis at selected time points to detect local deviations of firing patterns from one condition to another. We apply our method on two neurons recorded from the primary motor cortex area of a monkey's brain while performing a sequence of reaching tasks.     

A sequential test for assessing observed agreement between raters

Assessing the agreement between two or more raters is an important topic in medical practice. Existing techniques, which deal with categorical data, are based on contingency tables. This is often an obstacle in practice as we have to wait for a long time to collect the appropriate sample size of subjects to construct the contingency table. In this paper, we introduce a nonparametric sequential test for assessing agreement, which can be applied as data accrues, does not require a contingency table, facilitating a rapid assessment of the agreement. The proposed test is based on the cumulative sum of the number of disagreements between the two raters and a suitable statistic representing the waiting time until the cumulative sum exceeds a predefined threshold. We treat the cases of testing two raters' agreement with respect to one or more characteristics and using two or more classification categories, the case where the two raters extremely disagree, and finally the case of testing more than two raters' agreement. The numerical investigation shows that the proposed test has excellent performance. Compared to the existing methods, the proposed method appears to require significantly smaller sample size with equivalent power. Moreover, the proposed method is easily generalizable and brings the problem of assessing the agreement between two or more raters and one or more characteristics under a unified framework, thus providing an easy to use tool to medical practitioners.     

A Predictive Mathematical Model of Cell Cycle,Metabolism, and Apoptosis of Monoclonal Antibody‐Producing GS–NS0 Cells

The monoclonal antibody (mAb) industry is witnessing unprecedented growth, with an increasing range of new molecules and biosimilars as well as disease targets approved than ever before. Competition necessitates pharmaceutical companies to reduce development/production costs and time‐to‐market. To this aim, mathematical modeling can aid traditional experiment‐only‐based process development by reducing the design space, integrating scales, and assisting in identifying optimal operating conditions in less time and with lower expense. Mathematical models have been employed by other industries for control and optimization purposes and are important decisional tools for testing scenarios, process configurations, operating conditions, etc. Herein, a predictive, experimentally validated mathematical model that captures cellular metabolism and growth with cell cycle, cell death (apoptosis), and mAb production in GS–NS0 cells is presented. The model utilizes cellular, metabolic, and gene expression data, highlighting how multiple data sources can be integrated in one tool with the aim of optimizing mammalian cell bioprocessing.     

Risk-Adjusted Control Charts: Theory,Methods, and Applications in Health

Control charts, the most popular tool of statistical process control, appeared in the literature to ensure that an industrial process is operating only with natural variability, i.e., under statistical control. In the last decades, control charts have been also widely used to assess the quality of non-industrial processes, such as medicine and public health. Mainly in the last two decades, a modification of standard and advanced control charts appeared in the bibliography to improve the monitoring mainly of medical processes. This is the risk-adjusted control charts which take into consideration the varying health conditions of the patients. These charts are used to monitor certain medical processes such as surgeries, mortality, and doctors’ experience. In this paper, we have tried to present all the risk-adjusted control charts presented in the literature appropriately categorized. The risk-adjusted charts have been grouped into three categories: control charts for continuous variables, control charts for attributes (non-continuous variables), time-weighted control charts. The application of risk-adjusted control charts in practical medical processes is also discussed. This review paper highlights the value of the risk-adjusted control charts.