Considering Quality of a Service in an Intentional Approach

International audienceThe success of service-based applications is based on service technologies such as Web services. Nevertheless, the benefits of the Service-Oriented Architecture (SOA) remain mainly at the software level, since business people are often unable to fully exploit its benefits due to their unfamiliarity with such software level technology. The intentional Service-Oriented Architecture (iSOA) suggests a move from the function-driven SOA to intention-driven SOA in order to provide service description understandable by business practitioners. However, such transposition from business to implementation level should also consider Quality of Service (QoS) aspects. In this paper, we propose modeling the Quality of intentional Service (QoiS) by introducing the quality goals and their qualitative and quantitative evaluation. We also propose populating the intentional service registry of the iSOA architecture with the QoiS description

Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo

BACKGROUND: Tissue plasminogen activator (tPA) exerts multiple functions in the central nervous system, depending on the partner with which it interacts. In particular, tPA acts as a positive neuromodulator of N-methyl-D-aspartate glutamatergic receptors (NMDAR). At the molecular level, it has been proposed that the pro-neurotoxicity mediated by tPA might occur through extrasynaptic NMDAR containing the GluN2D subunit. Thus, selective antagonists targeting tPA/GluN2D-containing NMDAR signaling would be of interest to prevent noxious effects of tPA. RESULTS: Here, we compared three putative antagonists of GluN2D-containing NMDAR and we showed that the new compound UBP145 ((2R*,3S*)-1-(9-bromophenan-threne-3-carbonyl)piperazine-2,3-dicarboxylic acid) is far more selective for GluN2D subunits than memantine and PPDA (phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid). Indeed, in vitro, in contrast to the two other compounds, UBP145 prevented NMDA toxicity only in neurons expressing GluN2D (ie, in cortical but not hippocampal neurons). Furthermore, in cultured cortical neurons, UBP145 fully prevented the pro-excitotoxic effect of tPA. In vivo, we showed that UBP145 potently prevented the noxious action of exogenous tPA on excitotoxic damages. Moreover, in a thrombotic stroke model in mice, administration of UBP145 prevented the deleterious effect of late thrombolysis by tPA. CONCLUSIONS: In conclusion, tPA exerts noxious effects on neurons by acting on GluN2D-containing NMDAR and pharmacological antagonists of GluN2D-containing NMDAR could be used to prevent the ability of tPA to promote neurotoxicity

Tissue plasminogen activator prevents white matter damage following stroke

Tissue plasminogen activator protects white matter from stroke-induced lesions via the EGF-like domain and independent of proteolytic activity by promoting oligodendrocyte survival

Impact of Skills for Change Program on metabolic control, diet and physical activity levels in adults with type 2 diabetes: A cluster randomized trial

Background: Type 2 diabetes mellitus is highly prevalent in the Arab Gulf countries. Despite this, limited culturally-adapted lifestyle intervention studies have been conducted in this region. Methods: In this culturally adapted 12-month cluster randomized trial, 382 patients with type 2 diabetes, aged 20–70 years were recruited from 6 public healthcare centers (3 interventions and 3 controls) in Al Ain, United Arab Emirates. The primary outcome of this study was a change in hemoglobin A1c (HbA1c). The secondary outcomes were Body Mass Index (BMI), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, total cholesterol, dietary intake, and physical activity levels. A diet and physical activity intervention, guided by the social cognitive theory, was delivered individually and in group format to the intervention group. The control group continued receiving only their usual diabetes management care. The data were collected at baseline and 1 year after participation. Results: The mean baseline HbA1c levels of the control and the intervention groups were 7.45 ± 0.11% and 7.81 ± 0.11%, respectively. At the end of the 12-month intervention, there was no significant difference in the changes of mean HbA1c between the intervention and the control groups. On the other hand, BMI and daily caloric intake were significantly decreased in the intervention compared to the control group by 1.18 kg/m2 (95% CI: -1.78 − -0.60) and 246 kcal (95% CI: -419.52 − -77.21), respectively, after controlling for age, gender, education, marital status, duration since diabetes diagnosis, diabetes treatment, treatment clinic, and baseline values. Sitting time during the week-end was significantly lower, difference 52.53 minutes (95% CI: 93.93 − -11.14). Conclusions: This community-based lifestyle intervention for patients with baseline HbA1c <8% did not result in a significant decrease of HbA1c but reduced caloric intake, body weight, and weekend inactivity after controlling for the covariates. Trial registration: This trial was registered on February 11, 2020 with Clinicaltrials.gov (NCT04264793)

DFT-assisted spectroscopic studies on the coordination of small ligands to palladium: from isolated ions to nanoparticles

A combination of experimental spectroscopies (UV–vis and Fourier-transform infrared) and computational modeling was used to investigate the coordination of small ligands (aminopropanol and propanediol) to Pd species during the metal nanoparticle formation process. Differences emerged between O- (propanediol) and N-containing (aminopropanol) ligands. In particular, a strong interaction between the NH amino group and Pd2+ ions could be inferred on the basis of spectroscopic evidences, which was corroborated by theoretical simulations, which confirmed the preferential coordination of aminopropanol through the NH group. This interaction seems to potentially cause the aminopropanol ligand to control the particle shape through a selective blocking of Pd(100) facets, which promote the growth on the Pd(111) facets

Cenas Urbanas Performance e política nas ruas de Florianópolis

TCC (graduação) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Curso de Ciências Sociais.A escolha da rua como espaço para realização das performances dos grupos ERRO Grupo, Grupo Experiência Trânsito e Corpo (E.T.C.) e Coletivo Urbe, na cidade de Florianópolis, apresenta-se como um modo não-convencional do fazer artístico. O presente trabalho pretende, a partir de uma participação observante (WACQUANT, 2002), investigar e explorar os elementos que compõem as práticas artísticas desses grupos, buscando compreender em que medida tais elementos possuem um sentido político. Desse modo, as questões que guiam esta pesquisa são: Por que fazer da rua um palco? Por que esse espaço é, afinal, importante para os artistas que nele se apresentam? Em que medida esta é uma escolha política? As experiências vivenciadas mostram que tais sentidos políticos se relacionam com lo político (MOUFFE, 2011), isto é, referem-se à escolha estética que, em alguma medida, define esses grupos substantivamente. Essa escolha desdobra-se em aspectos que serão analisados nesta pesquisa, como por exemplo, os lugares em que as performances acontecem; a forma como os grupos se apropriam do mesmo e como isso afeta a performance; as dualidades ator/personagem e ator/espectador; e seus textos dramatúrgicos; elementos estes que, de alguma forma, são desconstruídos nessas experiências. Observamos que, embora apresentem diferenças, as práticas artísticas de tais grupos podem ser compreendidas a partir de um mesmo sentido político, representado por um conjunto de atributos que constituem suas performances.The choice of having the street where the performances take place, as made by the groups ERRO Grupo, Grupo Experiência Trânsito e Corpo (E.T.C.) e Coletivo Urbe, in Florianópolis, is an unconventional way of doing art. The present work intends, from an observant participation (WACQUANT, 2002), to investigate and explore the elements that compose the artistic practices of these groups, trying to understand to what extent these elements have a political meaning. Thus, the questions that guide this research are: Why make the street a stage? Why is this space, after all, important for the artists who present themselves in it? To what extent is this a political choice? Experiences during fieldwork show that these political meanings are related to lo político (MOUFFE, 2011), that is, they refer to the aesthetic choice that, to some extent, defines these groups substantively. This choice unfolds into aspects that will be analyzed in this research, for example, the places in which the performances take place; how the groups appropriate it and how it affects performance; the dualities actor / character and actor / spectator; and their dramaturgical texts; elements that are somehow deconstructed in these experiences. We observe that, although there might be differences among the artistic practices of such groups, they can be understood from the same political sense, represented by a set of attributes that constitute their performances

Genetic Association and Expression Studies Indicate a Role of Toll-Like Receptor 8 in Pulmonary Tuberculosis

Despite high rates of exposure, only 5–10% of people infected with Mycobacterium tuberculosis will develop active tuberculosis (TB) disease, suggesting a significant role for genetic variation in the human immune response to this infection. Here, we studied TB association and expression of 18 genes involved in the Toll-like receptor (TLR) pathways. Initially, we genotyped 149 sequence polymorphisms in 375 pulmonary TB patients and 387 controls from Indonesia. We found that four polymorphisms in the TLR8 gene on chromosome X showed evidence of association with TB susceptibility in males, including a non-synonymous polymorphism rs3764880 (Met1Val; P = 0.007, odds ratio (OR) = 1.8, 95% c.i. = 1.2–2.7). We genotyped these four TLR8 polymorphisms in an independent collection of 1,837 pulmonary TB patients and 1,779 controls from Russia and again found evidence of association in males (for rs3764880 P = 0.03, OR = 1.2, 95% c.i. = 1.02–1.48). Combined evidence for association is P = 1.2×10−3–6×10−4. In addition, a quantitative PCR analysis indicated that TLR8 transcript levels are significantly up-regulated in patients during the acute phase of disease (P = 9.36×10−5), relative to baseline levels following successful chemotherapy. A marked increase in TLR8 protein expression was also observed directly in differentiated macrophages upon infection with M. bovis bacille Calmette-Guérin (BCG). Taken together, our results provide evidence, for the first time, of a role for the TLR8 gene in susceptibility to pulmonary TB across different populations

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation