Separation-Resistant and Bias-Reduced Logistic Regression: STATISTICA Macro

Logistic regression is one of the most popular techniques used to describe the relationship between a binary dependent variable and a set of independent variables. However, the application of logistic regression to small data sets is often hindered by the complete or quasicomplete separation. Under the separation scenario, results obtained via maximum likelihood should not be trusted, since at least one parameter estimate diverges to infinity. Firth's approach to logistic regression is a theoretically sound procedure, which is guaranteed to arrive at finite estimates even in a separation case. Firth's procedure was also proved to significantly reduce the small sample bias of maximum likelihood estimates. The main goal of the paper is to introduce the STATISTICA macro, which performs Firth-type logistic regression

Inter-individual Variability in the Pre-clinical Drug Cardiotoxic Safety Assessment—Analysis of the Age–Cardiomyocytes Electric Capacitance Dependence

Electrical phenomena located within the plasma membrane of the mammalian cardiac cells are connected with the cells’ main physiological functions—signals processing and contractility. They were extensively studied and described mathematically in so-called Hodgkin–Huxley paradigm. One of the physiological parameters, namely cell electric capacitance, has not been analyzed in-depth. The aim of the study was to validate the mechanistic model describing the capacitive properties of cells, based on a collected experimental dataset which describes the electric capacitance of human ventricular myocytes. The gathered data was further utilized for developing an empirical correlation between a healthy individual’s age and cardiomyocyte electric capacitance

Circadian models of serum potassium, sodium, and calcium concentrations in healthy individuals and their application to cardiac electrophysiology simulations at individual level

In the article a brief description of the biological basis of the regulation of human biological clocks was presented in order to introduce the role of circadian rhythms in physiology and specifically in the pharmacological translational tools based on the computational physiology models to motivate the need to provide models of circadian fluctuation in plasma cations. The main aim of the study was to develop statistical models of the circadian rhythm of potassium, sodium, and calcium concentrations in plasma. The developed ion models were further tested by assessing their influence on QT duration (cardiac endpoint) as simulated by the biophysically detailed models of human left ventricular cardiomyocyte. The main results are model equations along with an electronic supplement to the article that contains a fully functional implementation of all models

Changes in the properties of pig manure slurry*

The paper presents the results of analyses of samples of manure from a pig farm located near Piła, Poland performed between June 2011 and May 2012 using a single sampling system. The statistical analyses of the average content of chemical and biological oxide demands, nitrogen, phosphorus, potassium, calcium and dry mass in the slurry in various seasons allowed us to draw conclusions concerning the changes in the chemical composition of the manure in specific seasons and to determine the correlations between the chemical parameters. The average content of N, BOD, P, and dry mass content tended to decrease systematically from the spring until the winter. The highest correlation coefficient, which indicates significant interdependency among the variables tested, was consistently found for COD and BOD, whereas the smallest correlation coefficient was found consistently for K and Ca and once for Ca and N

HER-3 expression in HER-2-amplified breast carcinoma

AIM OF THE STUDY: To determine whether the expression of HER-3 influences the survival of HER-2 positive patients with breast cancer (BC). MATERIAL AND METHODS: In the present work, the expression of HER-3 in a group of 35 HER-2 positive patients with BC was studied by performing immunohistochemistry (IHC) in formalin-fixed paraffin embedded tissues. RESULTS: Higher HER-3 status if estimated by IHC correlated significantly with older age of the patients. HER-3 expression did not correlate with estrogen or progesterone receptor status, pT or pN. There was also no significant difference in disease-free or overall survival (DFS and OS) between groups with different HER-3 expression, although some tendencies were seen as HER-3 expression in over 50% of cells was a factor of worse 5- and 10-year survival. CONCLUSIONS: Further studies should be performed on a larger group of patients to confirm the prognostic role of HER-3 status determined by IHC in BC

Empirical modeling of the sodium channel inhibition caused by drugs

The aim of this work was to create extended QSAR model of the relationship between sodium channel blocking activity of the particular compound and its chemical structure together with the in vitro assay conditions. Artificial neural networks (ANNs) were chosen as modeling tools. Chemoinformatics software was used for calculation of the molecular descriptors describing the structure of the interest. Drug concentration causing 50% of the channel inhibition (IC50) was used as the modeling endpoint. The data was based on the literature search and consisted of 38 drugs and 108 records. Initial number of inputs was 110 and during the sensitivity analysis was reduced to 20. ANNs models were optimized in the extended 10-fold cross-validation scheme yielding RMSE = 0.68, NRMSE = 20.7% and R2= 0.35. Best models were ANNs ensembles combining three ANNs with their outputs averaged as a collective output of the system

True left bundle branch block and long-term mortality in cardiac resynchronisation therapy patients

Background: Left bundle branch block (LBBB) is an important qualification criterion and determinant of prognosis in cardiac  resynchronisation therapy (CRT) patients.  Aims: Our goal was to investigate the long-term mortality and morbidity in a sizable cohort of patients with CRT with regard to the new strict LBBB definition proposed by Perrin.  Methods: We performed a longitudinal cohort study that included consecutive CRT patients. Primary endpoint (all-cause death) and secondary endpoint (all-cause death and hospitalisation for heart failure) were analysed. All preimplantation elec- trocardiograms were categorised as LBBB or non-LBBB according to the new definitions/criteria analysed.  Results: The survival analysis comprised 552 patients with CRT. The Perrin criteria, CRT guidelines class I indication criteria, and Strauss criteria were fulfilled in 38.9%, 79.4%, and 62.3% of all LBBB patients, respectively. During the nine-year study period, 232 patients died and the combined endpoint was met by 292 patients. The Perrin “true LBBB” definition criteria were inferior to the Strauss “complete” LBBB definition criteria in predicting survival as reflected by Kaplan-Meier survival curves (C-statistics). Multivariate Cox regression models showed that both LBBB definitions predicted mortality, however, the Perrin definition had a higher hazard ratio (HR 0.67) compared to the Strauss definition (HR 0.51).  Conclusions: It seems that the Perrin “true LBBB” criteria are not well-suited for the selection of CRT candidates. Perhaps they do not reflect the presence of a true/complete LBBB or exclude too many patients who, despite some residual conduction in the left bundle branch, responded well to CRT.

Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma : a randomized phase 3 trial

The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1–21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3–4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3–4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209