Mentoring to reduce antisocial behaviour in childhood

The effects of social interventions need to be examined in real life situations as well as studie

Use of 3D printed connectors to redesign full face snorkeling masks in the COVID-19 era: a preliminary technical case-study

The COVID-19 pandemic resulted in severe shortages of personal protection equipment and non-invasive ventilation devices. As traditional supply chains could not meet up with the demand, makeshift solutions were developed and locally manufactured by rapid prototyping networks. Among the different global initiatives, retrofitting of full-face snorkeling masks for Non-Invasive-Ventilation (NIV) applications seems the most challenging. This article provides a systematic overview of rapid prototyped - 3D printed - designs that enable attachment of medical equipment to snorkeling masks, highlighting potential and challenges in additive manufacturing. The different NIV connector designs are compared on low-cost 3D fabrication time and costs, which allows a rapid assessment of developed connectors for health care workers in urgent need of retrofitting snorkeling masks for NIV purposes. Challenges and safety issues of the rapid prototyping approach for healthcare applications during the pandemic are discussed as well. When critical parameters such as the final product cost, geographical availability of the feedstock and the 3D printers and the medical efficiency of the rapid prototyped products are well considered before deploying decentralized 3D printing as manufacturing method, this rapid prototyping strategy contributed to reduce personal protective equipment and NIV shortages during the first wave of the COVID-19 pandemic. It is also concluded that it is crucial to carefully optimize material and printer parameter settings to realize best fitting and airtight connector-mask connections, which is heavily depending on the chosen feedstock and type of printer

Combination Early-Phase Trials of Anticancer Agents in Children and Adolescents

Trials; Anticancer agents; ChildrenEnsayos; Agentes anticancerígenos; NiñosAssajos; Agents anticancerígens; NensPURPOSE There is an increasing need to evaluate innovative drugs for childhood cancer using combination strategies. Strong biological rationale and clinical experience suggest that multiple agents will be more efficacious than monotherapy for most diseases and may overcome resistance mechanisms and increase synergy. The process to evaluate these combination trials needs to maximize efficiency and should be agreed by all stakeholders. METHODS After a review of existing combination trial methodologies, regulatory requirements, and current results, a consensus among stakeholders was achieved. RESULTS Combinations of anticancer therapies should be developed on the basis of mechanism of action and robust preclinical evaluation, and may include data from adult clinical trials. The general principle for combination early-phase studies is that, when possible, clinical trials should be dose- and schedule-confirmatory rather than dose-exploratory, and every effort should be made to optimize doses early. Efficient early-phase combination trials should be seamless, including dose confirmation and randomized expansion. Dose evaluation designs for combinations depend on the extent of previous knowledge. If not previously evaluated, limited evaluation of monotherapy should be included in the same clinical trial as the combination. Randomized evaluation of a new agent plus standard therapy versus standard therapy is the most effective approach to isolate the effect and toxicity of the novel agent. Platform trials may be valuable in the evaluation of combination studies. Patient advocates and regulators should be engaged with investigators early in a proposed clinical development pathway and trial design must consider regulatory requirements. CONCLUSION An optimized, agreed approach to the design and evaluation of early-phase pediatric combination trials will accelerate drug development and benefit all stakeholders, most importantly children and adolescents with cancer

Environmental Impact Statement for West Horton Road Extension Phase 1

West Horton Road currently dead-ends into a roundabout. The proposed action is to build an extension of road to connect the west terminus of West Horton Road to Aldrich Road to its west. The road extension would feature one traffic lane in each direction, one bike lane in each direction, and sidewalks on both sides

Isolement et caractérisation des saponosides de trois plantes de la famille des araliaceae et dracaenaceae et évaluation de leurs activités cytotoxiques sur cellules tumorales

L intérêt des substances d origine naturelle, potentiellement anti-tumorales nous a amené à nous intéresser aux saponines triterpéniques et stéroïdiques de plantes issues de la biodiversité africaine de la famille des Araliaceae et des Dracaenaceae. En effet, des études antérieures menées sur quelques plantes de ces deux familles ont conduit à l obtention de molécules complexes et originales possédant d excellentes propriétés cytotoxiques, immuno-modulatrices, anti-inflammatoires. Au vu de ces résultats nous avons entrepris des investigations pharmaco-chimiques sur Cussonia arborea (Araliaceae), Dracaena deisteliana et Dracaena arborea (Dracaenaceae), plantes médicinales couramment utilisées en pharmacopée traditionnelle africaine pour traiter différentes maladies. Les travaux menés ont conduit à l isolement de 31 composés purs en utilisant les différentes techniques analytiques du laboratoire notamment les diverses techniques de chromatographie liquide successive à pression atmosphérique, moyenne pression et flash chromatographie sur silice en phase normale et en phase inverse. Les structures ont été déterminées par les méthodes de spectrométrie de masse en source FAB et de spectroscopie de RMN 1D et 2D (COSY, TOCSY, NOESY, HMBC et HSQC). Parmi les 07 composés purs obtenus des écorces de Cussonia arborea, 5 sont des nouvelles saponines triterpéniques dont un dérivé de l acide ursolique, un dérivé de l hédéragénine et trois dérivés de l acide oléanolique, tous disubstitués en position 3 et 28 par des chaînes oligosaccharidiques. 13 composés purs sont obtenus à partir des feuilles de Cussonia arborea, dont 7 nouvelles saponines triterpéniques dérivés de l acide ursolique, de l acide 23-hydroxyursolique, de l hédéragénine et de l acide oléanolique dont 04 d entre elles sont obtenues sous forme de mélanges inséparables d isomères acide oléanolique/acide ursolique et hédéragénine/acide 23-hydroxyursolique. A partir des écorces de Dracaena arborea et des tiges de Dracaena deisteliana, nous avons isolé et caractérisé 10 saponines stéroïdiques dont 4 nouvelles et une sapogénine. Les activités de certains de ces produits purs ont été évaluées sur deux lignées de cellules cancéreuses coliques humaines HCT 116 et HT-29.The interest of the substances from natural origin, potentially antitumor led us to interest in triterpenoid and steroidal saponins of plants from the African biodiversity belonging to the Araliaceae and Dracaenaceae families of plants. Indeed, of the former studies undertaken on some plants of these two families led to obtaining complex and original molecules having excellent cytotoxic, immuno-modulating, anti-inflammatory properties. Within sight of these results we undertook pharmaco-chemical investigations on Cussonia arborea (Araliaceae), Dracaena deisteliana, and Dracaena arborea (Dracaenaceae), medicinal plants usually used in african traditional pharmacopeia to treat various diseases. The work led to the isolation of 31 pure compounds by using the various analytical techniques in particular the various chromatography techniques (CC, MPLC, TLC, flash) on silica gel, normal and reversed phases. The structures were determined by the methods of mass spectrometry (FAB, ESI, IE) and 1D (1H and 13C) and 2D (COSY, TOCSY, NOESY, HMBC and HSQC) NMR spectroscopy. Among the 07 pure compounds obtained of the barks of Cussonia arborea, 5 are new triterpenoid saponins derivatives of ursolic acid, hederagenin and three derived from the acid oleanolic, all disubstituted in position 3 and 28 by oligosaccharidic chains. 13 pure compounds were obtained from leaves of Cussonia arborea, seven of which are new triterpenoid saponins derivatives of oleanolic acid, ursolic acid, hederagenin and 23-hydroxyursolic acid of which four were obtained as mixtures of isomers oleanolic acid/ursolic acid and hederagenin/23-hydroxyursolic acid. From the bark of Dracaena arborea and stem of Dracaena deisteliana, we isolated and characterized ten steroidal saponins including 4 new and sapogenin. The activities of some of these pure products were evaluated on two cancerous lines human colic cells HCT 116 and HT-29.DIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

A novel data management platform to improve image-guided precision preclinical biological research

Objective: Preclinical biological research is mandatory for developing new drugs to investigate the toxicity and efficacy of the drug. In this paper, the focus is on radiobiological research as an example of advanced preclinical biological research. In radiobiology, recent technological advances have produced novel research platforms which can precisely irradiate targets in animals and use advanced onboard image-guidance, mimicking the clinical radiotherapy environment. These platforms greatly facilitate complex research combining several agents simultaneously (in our example, radiation and non-radiation agents). Since these modern platform can produce a large amount of wide-ranging data, one of the main impediments in preclinical research platforms is a proper data management system for preclinical studies. Methods: A preclinical data management system, inspired by current radiotherapy clinical data management systems was designed. The system was designed with InterSystems technology, i.e. a programmable Enterprise Service Bus solution. New DICOM animal imaging standards are used such as DICOM suppl. 187 for storing small animal acquisition context and the DICOM second generation course model. Results: A small animal big data warehouse environment for research is designed to work with modern image-guided precision research platforms. Its modular design includes (1) a study workflow manager, (2) a data manager, and (3) a storage manager. The system provides interfaces to, e.g. preclinical treatment planning systems and data analysis plug-ins, and guides the user efficiently through the many steps involved in preclinical research. The system manages various data source locations, and arranges access to the data centrally. Conclusion: A novel preclinical data management system can be designed to improve preclinical workflow, facilitate data exchange between researchers, and support translation to clinical trials. Advances in knowledge: A preclinical data management system such as the one proposed here would greatly benefit preparation, execution and analysis of biological experiments, and will eventually facilitate translation to clinical trials