Safety and efficacy of fixed-dose combination rilpivirine-tenofovir-emtricitabine (RPV/TDF/FTC) in treatment-experienced patients infected with HIV-1

Purpose of the study: Rilpivirine (RPV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) which has shown non-inferiority to efavirenz (EFV) in terms of efficacy and safety profiles. The vast majority of clinical data has been performed in the treatment naïve population and has not been studied in depth in treatment-experienced patients. We sought to explore the safety and efficacy of RPV/TDF/FTC in treatment-experienced patients attending our clinics. Methods: HIV-infected individuals commenced on RPV/TDF/FTC from December 2011 to June 2012 were retrospectively identified from a patient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated. At baseline, 1 month and 3 month time points the following laboratory results were compared using the Kruskal-Wallis test: CD4 count, HIV viral load, amino transferase (ALT), cholesterol, triglyceride and HDL/cholesterol ratio. Summary of results: Sixty-five patients (4 female) were identified. Median age was 38 years (range: 25–73). Fifty-six patients were treatment experienced (2 re-start); 39 on NNRTI-based (33 on EFV), 10 on PI-based and 4 on other regimens. 9 patients were naïve to treatment. The reasons for switch are illustrated in Fig. 1. Fifty-four patients had HIV-RNA-1<40 copies/mL at the time of switch and all remained undetectable at 3 months. At baseline, the median CD4 count was 555 cells/mm3 (range: 209–1586) in the switch group, which increased significantly to 638 cells/mm3 (p<0.005) 3 months after switch. Switch to RPV/TDF/FTC had a favorable effect on lipid profile. At baseline the median cholesterol, triglyceride and HDL/cholesterol ratio levels were 4.8 mmol/L, 1.78 mmol/L and 4.37 respectively. At 1 month post-switch this decreased to 4.5 mmol/L, 1.65 mmol/L and 4.24 and at 3 months post-switch decreased to 4.1 mmol/L, 1.44 mmol/L and 4.04. Median HIV-RNA-1 in treatment-naïve patients (n=9) at baseline was 50298 copies/mL, at 1 month four patients had HIV-RNA-1<40 copies/mL and at 3 months eight patients had HIV-RNA-1<40 copies/mL. RPV/TDF/FTC had no favourable effect on lipid profile in treatment-naïve group and had no effect on ALT levels in either the switch or the treatment-naïve group. Conclusion: In this cohort, RPV/TDF/FTC has been shown to have a safe virological efficacy and safety profile as a switch therapy for patients suppressed on their current standard of care and are experiencing adverse events

Optimal motion control and vibration suppression of flexible systems with inaccessible outputs

This work addresses the optimal control problem of dynamical systems with inaccessible outputs. A case in which dynamical system outputs cannot be measured or inaccessible. This contradicts with the nature of the optimal controllers which can be considered without any loss of generality as state feedback control laws for systems with linear dynamics. Therefore, this work attempts to estimate dynamical system states through a novel state observer that does not require injecting the dynamical system outputs onto the observer structure during its design. A linear quadratic optimal control law is then realized based on the estimated states which allows controlling motion along with active vibration suppression of this class of dynamical systems with inaccessible outputs. Validity of the proposed control framework is evaluated experimentally

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Appendicoumbilical Fistula: A Rare Reason for Neonatal Umbilical Mass

The normal umbilicus is a simple structure, but the intrauterine development of the umbilicus is highly complex. Neonatal umbilical mass anomalies usually represent failure of obliteration of the vitelline duct or the allantois which results in persistence of remnants, which can lead to a wide variety of disorders. In this paper, we present a case of an appendicoumbilical fistula in a neonate along with the differential diagnosis and management options. Embryologic explanation of the etiology was discussed with the possible association with different forms of malpositioning and rotation of the gut

From von Neumann architecture and Atanasoff’s ABC to Neuromorphic Computation and Kasabov’s NeuCube. Part II: Applications

Spatio/Spector-Temporal Data (SSTD) analyzing is a challenging task, as temporal features may manifest complex interactions that may also change over time. Making use of suitable models that can capture the “hidden” interactions and interrelationship among multivariate data, is vital in SSTD investigation. This chapter describes a number of prominent applications built using the Kasabov’s NeuCube-based Spiking Neural Network (SNN) architecture for mapping, learning, visualization, classification/regression and better understanding and interpretation of SSTD

Explaining Exchange Rate Forecasts with Macroeconomic Fundamentals Using Interpretive Machine Learning

The complexity and ambiguity of financial and economic systems, along with frequent changes in the economic environment, have made it difficult to make precise predictions that are supported by theory-consistent explanations. Interpreting the prediction models used for forecasting important macroeconomic indicators is highly valuable for understanding relations among different factors, increasing trust towards the prediction models, and making predictions more actionable. In this study, we develop a fundamental-based model for the Canadian-U.S. dollar exchange rate within an interpretative framework. We propose a comprehensive approach using machine learning to predict the exchange rate and employ interpretability methods to accurately analyze the relationships among macroeconomic variables. Moreover, we implement an ablation study based on the output of the interpretations to improve the predictive accuracy of the models. Our empirical results show that crude oil, as Canada's main commodity export, is the leading factor that determines the exchange rate dynamics with time-varying effects. The changes in the sign and magnitude of the contributions of crude oil to the exchange rate are consistent with significant events in the commodity and energy markets and the evolution of the crude oil trend in Canada. Gold and the TSX stock index are found to be the second and third most important variables that influence the exchange rate. Accordingly, this analysis provides trustworthy and practical insights for policymakers and economists and accurate knowledge about the predictive model's decisions, which are supported by theoretical considerations

Sedation and Analgesia in Intensive Care: A Comparison of Fentanyl and Remifentanil

Optimal sedation and analgesia are of key importance in intensive care. The aim of this study was to assess the quality of sedoanalgesia and outcome parameters in regimens containing midazolam and either fentanyl or remifentanil. A prospective, randomized, open-label, controlled trial was carried out in the ICU unit of a large teaching hospital in Istanbul over a 9-month period. Thirty-four patients were randomly allocated to receive either a remifentanil-midazolam regimen (R group, n = 17) or a fentanyl-midazolam regimen (F group, n = 17). A strong correlation between Riker Sedation-Agitation Scale (SAS) and Ramsey Scale (RS) measurements was observed. Comparatively, remifentanil provided significantly more potent and rapid analgesia based on Behavioral-Physiological Scale (BPS) measurements and a statistically nonsignificantly shorter time to discharge. On the other hand, remifentanil also caused a significantly sharper fall in heart rate within the first six hours of treatment

Combined chemotherapy in 76 children with non-Hodgkin's lymphoma excluding Burkitt's lymphoma.

From January 1983 to December 1986 seventy-six previously untreated children with non-Hodgkin's lymphoma (NHL) were treated by combination chemotherapy. Burkitt's lymphoma patients were ineligible. The treatment regimens include intermittent chemotherapy and for non-localized patients, prophylactic central nervous system chemotherapy. Intrathoracic non-Hodgkin's lymphoma patients also had cranial prophylactic radiotherapy. Sixty-six patients (86.8%) achieved complete remission. Two year failure-free survival rate was 82.1% for localized (stage I and II) NHL and 53.3% for non-localized (stage III and IV) NHL patients. Failure-free survival did not differ significantly for the two major histologic diagnoses, but two year survival rate was lower in diffuse poorly differentiated lymphoblastic than undifferentiated non-Burkitt's lymphoma (50% versus 66.8% respectively). Failure-free survival rate was 53.7% in mediastinal disease and, 73.2% in abdominal disease at 24 months. Relapse rate was higher in mediastinal cases (46.1%) than primary abdominal cases (24.3%) at 24 months. Eleven (13.5%) died of treatment related sepsis. Although the overall survival rate was 72.4% at 2 years we need novel or more intensive programmes for mediastinal and non-localized disease