Multi-column multi-layer computational model of neocortex

We present a multi-layer multi-column computational model of neocortex that is built based on the activity and connections of known neuronal cell types and includes activity-dependent short term plasticity. This model, a network of spiking neurons, is validated by showing that it exhibits activity close to biology in terms of several characteristics: (1) proper laminar flow of activity; (2) columnar organization with focality of inputs; (3) low-threshold-spiking (LTS) and fast-spiking (FS) neurons function as observed in normal cortical circuits; and (4) different stages of epileptiform activity can be obtained with either increasing the level of inhibitory blockade, or simulation of NMDA receptor enhancement. The aim of this research is to provide insight into the fundamental properties of vertical and horizontal inhibition in neocortex and their influence on epileptiform activity. The developed model was used to test novel ideas about modulation of inhibitory neuronal types in a developmentally malformed cortex. The novelty of the proposed research includes: (1) design and implementation of a multi-layer multi-column model of the cortex with multiple neuronal types and short-time plasticity, (2) modification of the Izhikevich neuron model in order to model biological maximum firing rate property, (3) generating local field potential (LFP) and EEG signals without modeling multiple neuronal compartments, (4) modeling several known conditions to validate that the cortex model matches the biology in several aspects,(5) modeling different abnormalities in malformed cortex to test existing and to generate novel hypotheses

Impact of HbA1c Measurement on Hospital Readmission Rates: Analysis of 70,000 Clinical Database Patient Records

Management of hyperglycemia in hospitalized patients has a significant bearing on outcome, in terms of both morbidity and mortality. However, there are few national assessments of diabetes care during hospitalization which could serve as a baseline for change. This analysis of a large clinical database (74 million unique encounters corresponding to 17 million unique patients) was undertaken to provide such an assessment and to find future directions which might lead to improvements in patient safety. Almost 70,000 inpatient diabetes encounters were identified with sufficient detail for analysis. Multivariable logistic regression was used to fit the relationship between the measurement of HbA1c and early readmission while controlling for covariates such as demographics, severity and type of the disease, and type of admission. Results show that the measurement of HbA1c was performed infrequently (18.4%) in the inpatient setting. The statistical model suggests that the relationship between the probability of readmission and the HbA1c measurement depends on the primary diagnosis. The data suggest further that the greater attention to diabetes reflected in HbA1c determination may improve patient outcomes and lower cost of inpatient care

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049