Optimal Strategy Analysis of Two-Phase, N-Policy of M/EK/1 Queuing System with System Break -Downs and Balking

This Paper deals with the economic behaviour of the M/Ek/1 queue with server start-up, two-phases of compulsory service, and server breakdowns during both batch and individual services with balking under N-policy. The first phase of service is a batch service to all existing customers in the queue and the second phase of service is to each customer in the batch i

INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes

Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers

An effective novel patient specific Gaussian template based scheme for somatosensory evoked potential detection

Somatosensory evoked potentials (SSEPs) have been widely used for intra-operative neurophysiological monitoring (IONM) in surgeries for scoliosis and spinal cord related surgical procedures. Current technological trends show that at least 200-300 trials are required to generate a readable SSEP signal. A novel signal processing approach is outlined in the article, which aims at reducing the number of trials required for SSEP generation using only 30 trials. The analysis was performed on data recorded in seven patients undergoing surgery, where the posterior tibial nerve was stimulated and the SSEP response was recorded from scalp EEG using two bipolar electrodes, C 3 -C 4 and C Z -F Z . The time latencies of the P37 and the N45 peaks are detected along with the peak-to-peak amplitudes. The time latencies are detected with a mean accuracy greater than 95%. Also, the P37 and N45 peak latencies and the peak-to-peak amplitude were found to be consistent throughout the surgical procedure within the 10% and 50% clinical limits set for the time latencies and the peak-to-peak amplitude, respectively

Monotherapy and Dual Combination Therapies Based on Olmesartan: A Comprehensive Strategy to Improve Blood Pressure Control

Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged binding to AT1 receptor compared to other molecules within the same class. These characteristics produce effective and sustained blood pressure reductions in hypertensive patients at different cardiovascular risk profile with a good tolerability profile. After a brief description of the pharmacological characteristics of olmesartan, we will provide a thorough overview of the clinical studies that investigated its efficacy and safety in the clinical management of hypertensive patients both in monotherapy and in dual combination therapies with either thiazide diuretics or calcium channel blockers. These studies demonstrated that olmesartan-based antihypertensive strategy may indeed provide sustained BP control over the 24-h period in a wide proportion of hypertensive patients, thus contributing to a substantial progress in hypertension management. Finally, since growing evidence suggest that olmesartan may also exert potential favourable effects at vascular level, thereby antagonizing the vascular inflammatory process involved in the development and progression of atherosclerosis, the main clinical studies addressing this issue will be also discussed