Enzyme replacement therapy with galsulfase for mucopolysaccharidosis type vi

Background Mucopolysaccharidosis type VI or Maroteaux-Lamy syndrome is a rare genetic disorder caused by the deficiency of arylsulphatase B. The resultant accumulation of dermatan sulphate causes lysosomal damage. The clinical symptoms are related to skeletal dysplasia (i.e. short stature and degenerative joint disease). Other manifestations include cardiac disease, impaired pulmonary function, ophthalmological complications, hepatosplenomegaly, sinusitis, otitis, hearing loss and sleep apnea. Intellectual impairment is generally absent. Clinical manifestation is typically by two or three years of agehowever, slowly progressive cases may not present until adulthood. Enzyme replacement therapy with galsulfase is considered a new approach for treating mucopolysaccharidosis type VI. Objectives To evaluate the effectiveness and safety of treating mucopolysaccharidosis VI by enzyme replacement therapy with galsulfase compared to other interventions, placebo or no intervention. Search methods Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register, in CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease and ClinicalTrials.gov. Date of the last search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 05 February 2016. Selection criteria Randomized and quasi-randomized controlled clinical studies of enzyme replacement therapy with galsulfase compared to other interventions or placebo. Data collection and analysis Two authors independently screened the studies, assessed the risk of bias and extracted data. Main results One study was included involving 39 participants who received either enzyme replacement therapy with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered to be of overall unclear quality, since the authors did not report how both the allocation generation and concealment were performed. The key finding at 24 weeks in the 12-minute walk test was a statistically significant mean difference of 92.00 meters between the two groups in favour of the galsulfase group (95% confidence interval 11.00 to 172.00). While week 24 results for the three-minute stair climb demonstrated some improvement in the treatment group as compared to the placebo group, this was not significant, mean difference 5.70 (95% confidence interval -0.10 to 11.50). A significant decrease in the urinary glycosaminoglycan levels was observed in favour of the galsulfase group at 24 weeks, mean difference -227.00 (95% confidence interval -264.00 to -190.00). In general, the dose of galsulfase was well tolerated and there were no significant differences in relation to adverse events. These events include drug-related adverse events, serious and severe adverse events, those during infusion, drug-related adverse events during infusion, and deaths. More infusion-related reactions were observed in the galsulfase group and were managed with interruption or slowing of infusion rate or administration of antihistamines or corticosteroids drugs. No deaths occurred during the study. Authors' conclusions The results of one small study (based on 24-week randomised phase of the study and prior to the open-label extension) demonstrated that galsulfase is more effective than placebo in people with MPS VI, with significant improvements in the 12-minute walk test and a reduction in urinary glycosaminoglycans. There were no significant changes in cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects. Further studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy with galsulfase.Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, Brazilian Cochrane Centre, São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Emergency Medicine and Evidence Based Medicine, São Paulo, São Paulo, BrazilCentro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, Brazilian Cochrane Centre, São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Emergency Medicine and Evidence Based Medicine, São Paulo, São Paulo, BrazilWeb of Scienc

Experimental and computational study of the energetics of hydantoin and 2-thiohydantoin

This work reports an experimental and a theoretical study of two imidazolidine derivatives, hydantoin (CAS No. 461-72-3) and 2-thiohydantoin (CAS No. 503-87-7). The standard (p degrees = 0.1 MPa) molar energies of combustion of hydantoin and 2-thiohydantoin were measured by static and rotating bomb combustion calorimetry, respectively. The standard molar enthalpies of sublimation, at T = 298.15 K, were derived from the temperature dependence of the vapour pressures of these compounds, measured by the Knudsen-effusion technique, and from high temperature Calvet microcalorimetry. The conjugation of these experimental results enables the calculation of the standard molar enthalpies of formation in the gaseous state, at T = 298.15 K, which are discussed in terms of structural contributions. We have also estimated the gas-phase enthalpy of formation from high-level ab initio molecular orbital calculations at the G3MP2B3 level of theory, being the computed values in good agreement with the experimental ones. Furthermore, this composite approach was also used to obtain information about the gas-phase basicities, proton and electron affinities and adiabatic ionization enthalpies

Preliminary assessment of cardiac short term safety and efficacy of manganese chloride for cardiovascular magnetic resonance in humans

<p>Abstract</p> <p>Background</p> <p>Manganese based agents are intracellular and accumulate inside myocytes allowing for different imaging strategies compared to gadolinium contrasts. While previous agents release manganese very slowly in the circulation, MnCl₂allows for rapid Mn2⁺uptake in myocytes, creating a memory effect that can be potentially explored. Data on animal models are very encouraging but the safety and efficacy of this approach in humans has not yet been investigated. Therefore, our objectives were to study the safety and efficacy of a rapid infusion of manganese chloride (MnCl₂) for cardiovascular magnetic resonance (CMR) in humans.</p> <p>Methods</p> <p>Fifteen healthy volunteers underwent a CMR scan on a 1.5 T scanner. Before the infusion, cardiac function was calculated and images of a short axis mid-ventricular slice were obtained using a 2D and 3D gradient-echo inversion recovery (GRE-IR) sequence, a phase-sensitive IR sequence and a single breath-hold segmented IR prepared steady-state precession acquisition for T₁calculations. MnCl₂was infused over three minutes at a total dose of 5 μMol/kg. Immediately after the infusion, and at 15 and 30 minutes later, new images were obtained and cardiac function re-evaluated.</p> <p>Results</p> <p>There was a significant decrease in T₁values compared to baseline, sustained up to 30 minutes after the MnCl₂infusion (pre,839 ± 281 ms; 0 min, 684 ± 99; 15 min, 714 ± 168; 30 min, 706 ± 172, P = 0.003). The 2D and 3D GRE-IR sequence showed the greatest increase in signal-to-noise ratio compared to the other sequences (baseline 6.6 ± 4.2 and 9.7 ± 5.3; 0 min, 11.3 ± 4.1 and 15.0 ± 8.7; 15 min, 10.8 ± 4.0 and 16.9 ± 10.2; 30 min, 10.6 ± 5.2 and 16.5 ± 8.3, P < 0.001 for both). There was a slight increase in systolic pressure and heart rate after three and four minutes of the infusion with normalization of these parameters thereafter. Patients showed good tolerance to MnCl₂with no major adverse events, despite all reporting transient facial flush.</p> <p>Conclusions</p> <p>In the short term, MnCl₂appears safe for human use. It effectively decreases myocardium T₁, maintaining this effect for a relatively long period of time and allowing for the development of new imaging strategies in CMR, especially in ischemia research.</p

Uma Ontologia para Apoiar Discussões de Riscos em Projetos de Software

Um gerenciamento de riscos efetivo em projetos de software é importante para garantir que os fatores que podem impactar no sucesso e na qualidade de um sistema desenvolvido estão sob controle. Além disso, melhorar a comunicação entre participantes de um projeto, bem como integrar suas diferentes experiências e perspectivas sobre este domínio de problema é imprescindível. O objetivo deste trabalho é demonstrar como explorar a representação de um domínio de conhecimento por meio de ontologias para suportar a identificação e análise colaborativa de riscos em projetos de software. Para isso, a ontologia proposta foi criada para apoiar o desenvolvimento de atividades de gerenciamento de riscos tipicamente envolvidas nestas discussões colaborativas de riscos

Enhancing Energy Production with Exascale HPC Methods

High Performance Computing (HPC) resources have become the key actor for achieving more ambitious challenges in many disciplines. In this step beyond, an explosion on the available parallelism and the use of special purpose processors are crucial. With such a goal, the HPC4E project applies new exascale HPC techniques to energy industry simulations, customizing them if necessary, and going beyond the state-of-the-art in the required HPC exascale simulations for different energy sources. In this paper, a general overview of these methods is presented as well as some specific preliminary results.The research leading to these results has received funding from the European Union's Horizon 2020 Programme (2014-2020) under the HPC4E Project (www.hpc4e.eu), grant agreement n° 689772, the Spanish Ministry of Economy and Competitiveness under the CODEC2 project (TIN2015-63562-R), and from the Brazilian Ministry of Science, Technology and Innovation through Rede Nacional de Pesquisa (RNP). Computer time on Endeavour cluster is provided by the Intel Corporation, which enabled us to obtain the presented experimental results in uncertainty quantification in seismic imagingPostprint (author's final draft

Evaluation of the new modular biogents BG-Pro mosquito trap in comparison to CDC, EVS, BG-Sentinel, and BG-Mosquitaire traps

Mosquito surveillance is an essential component of mosquito control and mosquito traps are a universally employed tool to monitor adult populations. The objective of this paper was to evaluate the new modular Biogents BG-Pro mosquito trap (BGP) and compare its performance to 4 widely used traps for adult mosquitoes: the BG-Sentinel (BGS), the BG Mosquitaire (BGM), the CDC miniature light trap (CDC), and the encephalitis vector survey trap (EVS). One semi-field and 9 field Latin square trials were performed in 7 countries. Results showed that the collection performance of the BGP was equivalent to or exceeded that of the BGS, BGM, CDC, and EVS traps in head-to-head comparisons. The BGP uses 35% less power than the CDC and 75% less than the BGS and BGM. This lower power consumption allows it to run at 5 V for 2 days using a small lightweight 10,000-mAh rechargeable power bank. The BG-Pro is an excellent alternative for the surveillance of mosquito species that are usually monitored with BG-Sentinel, CDC, or EVS traps