Clinical effectiveness of dolutegravir in the treatment of HIV/AIDS

Huda Taha,1 Archik Das,2 Satyajit Das1,3 1Integrated Sexual Health Service Coventry and Warwickshire Partnership NHS Trust, Coventry, 2School of Medicine, Birmingham University, Birmingham, 3Coventry University, Coventry, UK Abstract: Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI), which has now been licensed to be used in different countries including the UK. Earlier studies have demonstrated that DTG when used with nucleoside backbone in treatment-naïve and -experienced patients has been well tolerated and demonstrated virological suppression comparable to other INSTIs and superiority against other first-line agents, including efavirenz and boosted protease inhibitors. Like other INSTIs, DTG uses separate metabolic pathways compared to other antiretrovirals and is a minor substrate for CYP-450. It does not appear to have a significant interaction with drugs, which uses the CYP-450 system. Nonetheless, it uses renal solute transporters that may potentially inhibit the transport of other drugs and can have an effect on the elimination of other drugs. However, the impact of this mechanism appears to be very minimal and insignificant clinically. The side effect profiles of DTG are similar to raltegravir and have been found to be well tolerated. DTG has a long plasma half-life and is suitable for once daily use without the need for a boosting agent. DTG has all the potential to be used as a first-line drug in combination with other nucleoside backbones, especially in the form of a single tablet in combination with abacavir and lamivudine. The purpose of this review article is to present the summary of the available key information about the clinical usefulness of DTG in the treatment of HIV infection. Keywords: dolutegravir, integrase inhibitors, HIV, antiretroviral, treatmen

Efecto del grado de hidrólisis sobre las propiedades funcionales de proteínas de semillas oleaginosas

Hydrolyzing soybean, sesame, and ricebran meals with papain and bromelain enzymes under previously determined optimum conditions was accomplished. Aliquots were withdrawn from the bulk hydrolysates at different time intervals to determine the rate of enzymatic degradation,as well as the degree of hydrolysis of the hydrolysates at different time intervals. Twelve hydrolysates were then chosen with low and high degree of hydrolysis. They also represented hydrolysates from the three substrates hydrolysed with the two enzymes used. Some functional properties of the twelve hydrolysates were examined and then an attempt to correlate the functional properties with the degree of hydrolysis was done. The investigated functional properties included: wettability, dispersibility, flowability, bulk density,nitrogen solubility index,water absorption capacity, oil holding capacity, gelation, thermostability, emulsifying capacity and foam stability.Results showed a direct relation between increasing degree of hydrolysis and nitrogen solubility and dispersibility. Wettability, flowability and emulsifying capacity gave better results with low degree of hydrolysis.Se ha efectuado la hidrólisis de harinas de haba de soja, sésamo y germen de arroz con las enzimas papaina y bromelaina bajo condiciones óptimas previamente determinadas. Se sacaron alicuotas de los hidrolizados a diferentes intervalos de tiempo para determinar la velocidad de degradación enzimática, así como el grado de hidrólisis de los hidrolizados. Con estos datos se eligieron doce hidrolizados con bajo y alto grado de hidrólisis, que fueron representativos de los tres sustratos y los dos enzimas ensayados. Se examinaron algunas propiedades funcionales de estos doce hidrolizados y luego se llevó a cabo un intento de correlacionarlas con el grado de hidrólisis. Las propiedades funcionales investigadas incluyeron: humectabilidad, dispersabilidad, fluidez, densidad volumétrica, índice de solubilidad del nitrógeno, capacidad de absorción de agua, capacidad de retención de aceite, gelación, termoestabilidad, capacidad emulsionante y estabilidad espumante. Los resultados mostraron una relación directa entre el aumento del grado de hidrólisis y la solubilidad del nitrogéno y la dispersabilidad. La humectabilidad, la fluidez y la capacidad emulsionante dieron mejores resultados con un grado de hidrólisis bajo

Stream Fusion, to Completeness

Stream processing is mainstream (again): Widely-used stream libraries are now available for virtually all modern OO and functional languages, from Java to C# to Scala to OCaml to Haskell. Yet expressivity and performance are still lacking. For instance, the popular, well-optimized Java 8 streams do not support the zip operator and are still an order of magnitude slower than hand-written loops. We present the first approach that represents the full generality of stream processing and eliminates overheads, via the use of staging. It is based on an unusually rich semantic model of stream interaction. We support any combination of zipping, nesting (or flat-mapping), sub-ranging, filtering, mapping-of finite or infinite streams. Our model captures idiosyncrasies that a programmer uses in optimizing stream pipelines, such as rate differences and the choice of a "for" vs. "while" loops. Our approach delivers hand-written-like code, but automatically. It explicitly avoids the reliance on black-box optimizers and sufficiently-smart compilers, offering highest, guaranteed and portable performance. Our approach relies on high-level concepts that are then readily mapped into an implementation. Accordingly, we have two distinct implementations: an OCaml stream library, staged via MetaOCaml, and a Scala library for the JVM, staged via LMS. In both cases, we derive libraries richer and simultaneously many tens of times faster than past work. We greatly exceed in performance the standard stream libraries available in Java, Scala and OCaml, including the well-optimized Java 8 streams

AN EFFICIENT SPEECH GENERATIVE MODEL BASED ON DETERMINISTIC/STOCHASTIC SEPARATION OF SPECTRAL ENVELOPES

The paper presents a speech generative model that provides an efficient way of generating speech waveform from its amplitude spectral envelopes. The model is based on hybrid speech representation that includes deterministic (harmonic) and stochastic (noise) components. The main idea behind the approach originates from the fact that speech signal has a determined spectral structure that is statistically bound with deterministic/stochastic energy distribution in the spectrum. The performance of the model is evaluated using an experimental low-bitrate wide-band speech coder. The quality of reconstructed speech is evaluated using objective and subjective methods. Two objective quality characteristics were calculated: Modified Bark Spectral Distortion (MBSD) and Perceptual Evaluation of Speech Quality (PESQ). Narrow-band and wide-band versions of the proposed solution were compared with MELP (Mixed Excitation Linear Prediction) speech coder and AMR (Adaptive Multi-Rate) speech coder, respectively. The speech base of two female and two male speakers were used for testing. The performed tests show that overall performance of the proposed approach is speaker-dependent and it is better for male voices. Supposedly, this difference indicates the influence of pitch highness on separation accuracy. In that way, using the proposed approach in experimental speech compression system provides decent MBSD values and comparable PESQ values with AMR speech coder at 6,6 kbit/s. Additional subjective listening testsdemonstrate that the implemented coding system retains phonetic content and speaker’s identity. It proves consistency of the proposed approach.The paper presents a speech generative model that provides an efficient way of generating speech waveform from its amplitude spectral envelopes. The model is based on hybrid speech representation that includes deterministic (harmonic) and stochastic (noise) components. The main idea behind the approach originates from the fact that speech signal has a determined spectral structure that is statistically bound with deterministic/stochastic energy distribution in the spectrum. The performance of the model is evaluated using an experimental low-bitrate wide-band speech coder. The quality of reconstructed speech is evaluated using objective and subjective methods. Two objective quality characteristics were calculated: Modified Bark Spectral Distortion (MBSD) and Perceptual Evaluation of Speech Quality (PESQ). Narrow-band and wide-band versions of the proposed solution were compared with MELP (Mixed Excitation Linear Prediction) speech coder and AMR (Adaptive Multi-Rate) speech coder, respectively. The speech base of two female and two male speakers were used for testing. The performed tests show that overall performance of the proposed approach is speaker-dependent and it is better for male voices. Supposedly, this difference indicates the influence of pitch highness on separation accuracy. In that way, using the proposed approach in experimental speech compression system provides decent MBSD values and comparable PESQ values with AMR speech coder at 6,6 kbit/s. Additional subjective listening testsdemonstrate that the implemented coding system retains phonetic content and speaker’s identity. It proves consistency of the proposed approach

Performance of High-volume Fly Ash Self-compacting Concrete Exposed to External Sulfate Attack

The high-volume fly ash concrete, HVFAC, could be defined as any concrete mix having fly ash content larger than 50 percent of the total cementitious materials content. Due to the availability of fly ash in large quantities globally with low cost, HVFAC could be considered as a solution for the environmental impact of Portland cements. In this study the durability of two high-volume fly ash self-compacting concrete, HVFASCC, mixes exposed to the effects of two sulfate aggressive solutions was investigated. The fly ash, class F, contents for these mixes were 50 and 60 percent by weight of Portland cement. The external sulfate attack was simulated by submerging the concrete specimens in 5 percent sodium and magnesium sulfate solutions separately for 240 days. Six mixes were produced for this purpose, they were: 2 reference mixes cured in water, 2 mixes submerged in Na2SO4 solution and 2 mixes submerged in MgSO4 solution. The testing program includes: slump flow, V-funnel, L-box, weight change, XRD and the strength tests: compressive, splitting and flexural strengths. The fly ash content has a positive effect on the rheology (workability) of all tested mixtures. In other words, increasing the cement replacement level from 50 to 60 percent has enhanced the filling ability, passing ability, and segregation resistance of the investigated SCC mixes. The test results show that the magnesium solution has the higher harmful effect on all mixes than the sodium solution. The replacements of Portland cement by the assigned percentages of fly ash have significantly increased the resistance of SCC to the external sulfate attack due to lime consuming reaction

Effect of Cd Additive on the Hardness and Tensile Properties of Al-Mg-Si Alloy

The aim of this paper is to study the effect of adding Cd element to aluminum alloy series (6000) on the mechanical properties (hardness & ultimate tensile strength ) which have been studied  .A permanent  mold casting method was used for preparing the specimens of alloys by adding Cd at (0.1,0.3,0.5)% wt . to (Al-Mg-Si ) alloy. Heat treatment homogenous alloy ingots were carried out at (550ºC) for (24 hours) .These heat treatments for all specimens were conducted after cutting the ingots to the required dimensions ,solution heat treatment at (500ºC) for (1 hour) and then quenching in the water at room temperature. Then natural aging was carried out at room temperature for (90 days) ,whilst with in this period the hardness of alloys were measured at subsequent equal interval . The artificial aging for the prepared alloys was carried out, at (160and 180) ºC for an interval ranging between (5 mins. & 35 hours) .The Vickers  hardness and ultimate tensile strength were measured .The hardness and ultimate tensile strength of Cd alloys have relative improvements  by natural aging. Keywords: Cd element, (Al-Mg-Si ) alloy, homogenous, artificial& natural aging

Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival

Temperature and time-dependent effects of delayed blood processing on oxylipin concentrations in human plasma.

BACKGROUND:Oxidized derivatives of polyunsaturated fatty acids, collectively known as oxylipins, are labile bioactive mediators with diverse roles in human physiology and pathology. Oxylipins are increasingly being measured in plasma collected in clinical studies to investigate biological mechanisms and as pharmacodynamic biomarkers for nutrient-based and drug-based interventions. Whole blood is generally stored either on ice or at room temperature prior to processing. However, the potential impacts of delays in processing, and of temperature prior to processing, on oxylipin concentrations are incompletely understood. OBJECTIVE:To evaluate the effects of delayed processing of blood samples in a timeframe that is typical of a clinical laboratory setting, using typical storage temperatures, on concentrations of representative unesterified oxylipins measured by liquid chromatography-tandem mass spectrometry. DESIGN:Whole blood (drawn on three separate occasions from a single person) was collected into 5 mL purple-top potassium-EDTA tubes and stored for 0, 10, 20, 30, 60 or 120 min at room temperature or on wet ice, followed by centrifugation at 4 °C for 10 min with plasma collection. Each sample was run in duplicate, therefore there were six tubes and up to six data points at each time point for each oxylipin at each condition (ice/room temperature). Representative oxylipins derived from arachidonic acid, docosahexaenoic acid, and linoleic acid were quantified by liquid chromatography tandem mass spectrometry. Longitudinal models were used to estimate differences between temperature groups 2 h after blood draw. RESULTS:We found that most oxylipins measured in human plasma in traditional potassium-EDTA tubes are reasonably stable when stored on ice for up to 2 h prior to processing, with little evidence of auto-oxidation in either condition. By contrast, in whole blood stored at room temperature, substantial time-dependent increases in the 12-lipoxygenase-derived (12-HETE, 14-HDHA) and platelet-derived (thromboxane B2) oxylipins were observed. CONCLUSION:These findings suggest that certain plasma oxylipins can be measured with reasonable accuracy despite delayed processing for up to 2 h when blood is stored on ice prior to centrifugation. 12-Lipoxygenase- and platelet-derived oxylipins may be particularly sensitive to post-collection artifact with delayed processing at room temperature. Future studies are needed to determine impacts of duration and temperature of centrifugation on oxylipin concentrations

Acute effects of cigarette smoking in habitual smokers, a focus on endothelial function

AbstractBackgroundThe chronic effect of cigarette (cig.) smoking is well established. The acute effect of smoking abolishes the concept, argued by heavy smokers, to decrease the number of smoked cigarettes instead of quitting.AimTo detect the acute effects of cigarette smoking and the duration of these effects.Patients and methodsThirty four smokers (age 21–35years) were studied at 3 occasions; 9h after the last cig. smoking, 5min after one cig. smoking and 30min after 3 cig. smoking within 30min. They were subjected to measurement of both ventricular functions using standard and tissue Doppler imaging (TDI), aortic distensibility, stiffness and endothelial function assessment by endothelium-dependent flow-mediated dilatation (FMD) and maximum vasodilatation.ResultsAfter one cigarette smoking, we found a statistically significant effect on blood pressure, Heart Rate, FMD percent, Dilation Ratio, aortic distensibility (P=0.007), and aortic stiffness index (ASI) (P=0.01). Furthermore the LV diastolic function was significantly impaired after smoking. Despite disappearance of acute effect of 3 cig. smoking within 30min on blood pressure, Heart Rate and aortic distensibility, a significant difference was still found as regards FMD percent and dilation ratio denoting the extension of the endothelial dysfunction for more than 30min after the last cigarette.ConclusionMany acute changes occur following one cigarette smoking even in habitual smokers. Persistence of endothelial dysfunction parameters after smoking indicates the failure of circulation adaptation in response to such offense that might contribute to the precipitation of acute events in vulnerable patients