The current state of knowledge and research required around nutrition in pediatric critical illness

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A randomized trial to assess the impact of opinion leader endorsed evidence summaries on the use of secondary prevention strategies in patients with coronary artery disease: the ESP-CAD trial protocol [NCT00175240]

BACKGROUND: Although numerous therapies have been shown to be beneficial in the prevention of myocardial infarction and/or death in patients with coronary disease, these therapies are under-used and this gap contributes to sub-optimal patient outcomes. To increase the uptake of proven efficacious therapies in patients with coronary disease, we designed a multifaceted quality improvement intervention employing patient-specific reminders delivered at the point-of-care, with one-page treatment guidelines endorsed by local opinion leaders ("Local Opinion Leader Statement"). This trial is designed to evaluate the impact of these Local Opinion Leader Statements on the practices of primary care physicians caring for patients with coronary disease. In order to isolate the effects of the messenger (the local opinion leader) from the message, we will also test an identical quality improvement intervention that is not signed by a local opinion leader ("Unsigned Evidence Statement") in this trial. METHODS: Randomized trial testing three different interventions in patients with coronary disease: (1) usual care versus (2) Local Opinion Leader Statement versus (3) Unsigned Evidence Statement. Patients diagnosed with coronary artery disease after cardiac catheterization (but without acute coronary syndromes) will be randomly allocated to one of the three interventions by cluster randomization (at the level of their primary care physician), if they are not on optimal statin therapy at baseline. The primary outcome is the proportion of patients demonstrating improvement in their statin management in the first six months post-catheterization. Secondary outcomes include examinations of the use of ACE inhibitors, anti-platelet agents, beta-blockers, non-statin lipid lowering drugs, and provision of smoking cessation advice in the first six months post-catheterization in the three treatment arms. Although randomization will be clustered at the level of the primary care physician, the design effect is anticipated to be negligible and the unit of analysis will be the patient. DISCUSSION: If either the Local Opinion Leader Statement or the Unsigned Evidence Statement improves secondary prevention in patients with coronary disease, they can be easily modified and applied in other communities and for other target conditions

Caractérisation des interactions protéines-protéines au sein de polycétides synthases trans-AT inhabituelles

Polyketides are specialized metabolites produced by various organisms, including plants, bacteria, fungi, and some animals, and exhibit a wide range of therapeutic properties valuable for humans and animals (antibiotics, anticancer agents, immunosuppressants, etc.). It is therefore highly interesting to find new polyketides or modify existing structures to generate analogs with enhanced properties. In this context, a promising strategy is the synthetic biology of the enzymes responsible for their synthesis, the polyketide synthases (PKS). For this approach to be effective, it requires a detailed understanding of the structure/function relationships of these multi-enzymatic complexes. PKS are among the largest and most complex biosynthetic systems in nature: these PKS are divided into several polypeptide chains called subunits, which are further divided into modules, which are themselves subdivided into domains. Each module carries out a cycle of extension and/or modification of the polyketide via the different activities provided by its component domains. In these systems, the correct arrangement of the numerous subunits—and thus the proper transfer of the extending polyketide chain is ensured by short protein-protein interaction regions located at the C- and N-terminal ends of the subunits, called docking domains (DDs). During genetic engineering experiments, modifying the domain composition of modules has proven ineffective, leading researchers to attempt swapping modules or even entire subunits, where DDs have been very useful due to their portable nature.To deepen our understanding of docking domains and, more generally, of inter-subunit interactions within trans-AT PKS systems, we studied several interfaces within a model system. This thesis work led to the characterization of a docking interface by nuclear magnetic resonance between the two central subunits of the toblerol PKS, leading to the identification of a new type of DD within trans-AT PKS. We also showed, for the first time, that both partners of the same DD pair are intrinsically disordered regions (IDRs), allowing transient interactions with high specificity but moderate affinity. Furthermore, we identified a pair of key residues involved in interaction specificity. Together, these results help expand our knowledge for future use of docking domains in PKS engineering.During the analysis of the DD complex, we noticed that one of our partners resembles other previously identified DDs classified in another type. Following this observation, we found that certain docking domain folds are reused across multiple types, illustrating the great versatility and adaptability of α-helical DDs as docking elements, as well as the difficulty in predicting their presence and structure based solely on primary sequence analysis.Preliminary bioinformatic analyses, along with the production and purification of various putative docking domains from the PKS system responsible for synthesizing colibactin, a toxin involved in the development of human colorectal cancer, allowed us to initiate the first biophysical tests aimed at demonstrating an interaction. Unfortunately, no other interaction could be characterized, but further experiments are proposed to achieve this goal.Les polycétides sont des métabolites spécialisés produits par une multitude d'organismes dont les plantes, les bactéries, les champignons et certains animaux, et présentent une grande gamme de propriétés thérapeutiques précieuses pour l'Homme et les animaux (antibiotiques, anticancéreux, immunosuppresseurs, etc.). Il est donc très intéressant de trouver de nouveaux polycétides dans la biosphère ou de modifier les structures existantes afin de pouvoir créer des analogues aux propriétés pharmacologiques améliorées. Pour cela, une stratégie prometteuse consiste à modifier par génie génétique les enzymes responsables de leur synthèse, les polycétides synthases (PKS). Pour que cette approche soit efficace, elle nécessite une compréhension très fine des relations structure/fonction de ces complexes multienzymatiques. Les PKS font partie des systèmes biosynthétiques les plus grands et complexes du vivant : ces PKS sont divisées en plusieurs chaines polypeptidiques appelées sous-unités, elles-mêmes divisées en modules, eux-mêmes divisés en domaines. Chaque module réalise un cycle de d'extension et/ou de modification du polycétide grâce aux différentes activités portées par les domaines le composant. Dans ces systèmes, l'agencement correct des nombreuses sous-unités et donc le bon transfert de la chaine polycétidique en extension est assuré par de courtes régions d'interaction protéine-protéine situées aux extrémités C- et N-terminales des sous-unités, et appelées domaines de docking (DDs). Lors d'expériences d'ingénierie génétique, la modification de la composition en domaines de modules s'est avérée souvent inefficace, amenant les chercheurs à essayer d'échanger des modules voir des sous-unités entières où les DDs se sont révélés être très utiles grâce à leur caractère portatif.Afin d'approfondir nos connaissances sur les domaines de docking et plus généralement sur les interactions entre sous-unités au sein des PKS de type trans-AT, nous avons étudié plusieurs interfaces au sein d'un système modèle. Ces travaux de thèse ont conduit à la caractérisation d'une interface de docking par résonnance magnétique nucléaire entre les deux sous-unités centrales de la PKS toblerol, permettant l'identification d'une nouvelle type de DD au sein des PKS trans-AT. Nous avons également montré pour la première fois que les deux partenaires d'une même paire de DD sont des régions intrinsèquement désordonnées (IDR), permettant de former des interactions transitoires avec une forte spécificité mais une affinité moyenne. De plus, nous avons pu identifier un couple de résidus clé participant à la spécificité d'interaction. Conjointement, ces résultats permettent d'étoffer nos connaissances pour de futures utilisations de domaines de docking en ingénierie des PKS.Lors de l'analyse du complexe des DDs, nous nous sommes rendu compte que l'un des partenaires est semblable à d'autres DDs identifiés et classifiés dans un autre type. Suite à cette observation, nous avons remarqué que certains repliements de DDs sont réutilisés au sein de plusieurs types, illustrant la grande polyvalence et l'adaptabilité des DDs α-hélicoïdaux en tant qu'éléments de docking, ainsi que la difficulté à prédire leur présence et structuration en se basant uniquement sur la séquence primaire.Des analyses bioinformatiques préliminaires ainsi que la production et la purification des différents domaines de docking putatifs du système PKS synthétisant la colibactine, une toxine impliquée dans le développement du cancer colorectal chez l'Homme, ont permis d'initier les premiers tests biophysiques visant à mettre en évidence une interaction. Malheureusement, aucune autre interaction n'a pu être caractérisée, mais des expériences complémentaires sont proposées pour y parvenir

A Priority-Based CSMA/CA Mechanism to Support Deadline-Aware Scheduling in Home Automation Applications Using IEEE 802.15.4

The wireless sensor networks (WSNs) are characterized by several small nodes able to perform measurements on one or more parameters and to communicate with each other through several protocols. Most of home automation networks (depending on the specific application) are mainly characterized by periodic traffic flows. In soft real-time contexts, the main problem is represented by the efficient allocation of guaranteed time slots (GTSs) for periodic traffic flows transmission in IEEE 802.15.4 networks. Moreover, it is important to ensure adequate performance for those embedded devices competing for the access to the medium through the carrier sense multiple access/collision avoidance algorithm (CSMA/CA). The main aim of this paper is to show a new approach for network flows scheduling in home automation applications based on IEEE 802.15.4 wireless sensor networks. This work addresses several advantages due to the introduction of rate monotonic (RM) for guaranteed time slots (GTSs) allocation combined with priority-based CSMA/CA for latencies reduction on transmission attempts as clearly demonstrated by obtained results. </jats:p

Exploiting patterns and templates for technical documentation

There are several domains in which the documents are made of reusable pieces. Template languages have been widely studied by the document engineering community to deal with common structures and textual fragments. Though, templating mechanisms are often hidden in mainstream word-precessors and even unknown by common users. This paper presents a pattern-based language for templates, serialized in HTML and exploited in a user-friendly WYSIWYG editor for writing technical documentation. We discuss the deployment of the editor by an engineering company in the railway domain, as well as some generalized lessons learned about templates

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Performers: Johnny "Scat" DavisPiano, Voice and Chord