56 research outputs found
Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study
Abstract Introduction To assess the effect of canakinumab, a fully human anti-interleukin-1β antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS). Methods In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed. Results Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated. Conclusions Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL. Trial registration Clintrials.gov NCT0046598
How do surgeons decide? Conduit choice in coronary artery bypass graft surgery in the UK
OBJECTIVES
Conduits used in coronary artery bypass grafting may have significant impact on outcomes, but evidence is mixed and there is large variation in practice. This study provides insights into the opinions of the UK surgeons on conduit use and their decision-making processes.
METHODS
A questionnaire was created using the Ottawa Decision Support Framework to elicit the importance that surgeons placed on bilateral internal mammary artery grafting, skeletonization, total arterial revascularization and sequential anastomoses on a scale of 1–10. Scores ≥8 were deemed ‘important’ and ≤3 ‘not important’. Surgeons were asked to specify changes to practice in frail patients or emergencies. Additional questions included conduit type used, factors affecting decision-making and vein harvesting methods. Questionnaires were administered in person with data analysed centrally.
RESULTS
Ninety-seven consultant cardiac surgeons from 25 centres responded. Thirty-two percent surgeons routinely used radial arteries and 36% used right internal mammary artery. High-quality evidence contributed most to decision-making receiving a total of 328/960 points, with consultant experience being the second (255/960 points). There was a bimodal distribution of perceived importance of bilateral internal mammary artery use, with 29 (30%) ‘important’ and ‘not important’ scores each. 23% of surgeons found total arterial revascularization important. Most surgeons (64%) preferred pedicled mammary arteries. Twenty-six percent of surgeons considered sequential grafting to be important.
CONCLUSIONS
Low uptake of total arterial revascularization and bilateral internal mammary artery among the UK consultants may be due to the lack of high-quality evidence demonstrating a significant benefit. It is also possible that reluctance to use certain conduits may stem from low levels of exposure to conduits or inadequate training, particularly given the importance of consultant experience on decision-making
Bowhead whales overwinter in the Amundsen Gulf and Eastern Beaufort Sea
The bowhead whale is the only baleen whale endemic to the Arctic and is well adapted to this environment. Bowheads live near the polar ice edge for much of the year and although sea ice dynamics are not the only driver of their annual migratory movements, it likely plays a key role. Given the intrinsic variability of open water and ice, one might expect bowhead migratory plasticity to be high and linked to this proximate environmental factor. Here, through a network of underwater passive acoustic recorders, we document the first known occurrence of bowheads overwintering in what is normally their summer foraging grounds in the Amundsen Gulf and eastern Beaufort Sea. The underlying question is whether this is the leading edge of a phenological shift in a species' migratory behaviour in an environment undergoing dramatic shifts due to climate change
The product line engineering approach in a model-driven process
International audienceThe European CESAR project intends to provide industrial companies with a customizable systems engineering platform (a Reference Technologic Platform) that can be used across several application domains (aeronautics, automotive, industrial automation, railway, and space). This paper focuses on the work performed in the aeronautics domain and presents an innovative tooled-up approach for product line engineering used in the Thales Avionics use case. This approach implements the automatic generation of product models from variability models with the guaranty of a requirements database. Domain engineering is here developed in a model-driven process
Recommended from our members
Using two drones to simultaneously monitor visual and acoustic behaviour of gray whales (Eschrichtius robustus) in Baja California, Mexico
This study provides an initial demonstration of a combined two-UAV (Unmanned Aerial Vehicle) system for measuring the underwater source levels and behavioural context of vocal and non-vocal marine mammal signals, information that is highly ecologically-relevant in terms of understanding how a species interacts and copes with conspecifics and its acoustic environment. Although the calls of a few species are well known, major gaps exist in our knowledge about the relationship between vocal output and behavioural context, gender and age for most species. Accurate parameter estimates (e.g., typical source levels, frequency ranges, and temporal characteristics of animal sounds) relevant to their behaviour (activities such as foraging, migrating, mating, or parental care) are needed to establish use of critical habitats (when monitored by acoustics) or to assess potential effects of anthropogenic sound exposure (including reduction of the detection space of sounds used for communication). The emergence of UAVs provides new perspectives and data collection capabilities for marine mammal research. Although UAVs have been frequently exploited for visual observations of whales, most approaches for monitoring and recording sounds from individual whales are still performed using overside hydrophones from a boat or using acoustic tags attached to the animals. Laguna San Ignacio (LSI), Mexico, is one of the breeding and calving grounds of the Eastern North Pacific gray whale (Eschrichtius robustus) population. LSI area's restricted geography, combined with the short dive times of the whales, provided an excellent field laboratory to test a dual drone approach. We used two UAVs: one to obtain acoustic measurements close to the whales and another one to obtain overhead visual observations. For the acoustic drone, a hydrophone (SoundTrap) was suspended via a 2-m line to a waterproof UAV quadcopter (Swellpro), which has the ability to take off and land from the surface of water. Simultaneously, the visual drone (DJI) monitored the whales in the area. Between 27 February and 17 March 2019, we simultaneously recorded underwater gray whale sounds and visual behavioural observations. During 92 min of underwater acoustic recordings, the acoustic drone recorded 11 call types. By timesynching underwater audio with the behavioural video, we obtained new insights into the source levels and functions of various quiet underwater sound that are difficult to impossible to obtain with standard methods. To our knowledge, no studies combining overhead visual observations and underwater acoustic recordings to describe acoustic behaviour and sound parameters of calls have been previously published
Acoustic detections of Arctic marine mammals near Ulukhaktok, Northwest Territories
The Arctic marine environment is changing rapidly through a combination of sea ice loss and increased anthropogenic activity. Given these changes can affect marine animals in a variety of ways, understanding the spatial and temporal distributions of Arctic marine animals is imperative. We use passive acoustic monitoring to examine the presence of marine mammals near Ulukhaktok, Northwest Territories, Canada, from October 2016 to April 2017. We documented bowhead whale (Balaena mysticetus Linnaeus, 1758) and beluga whale (Delphinapterus leucas Pallas, 1776) vocalizations later into the autumn than expected, and we recorded bowhead whales in early April. We recorded ringed seal (Pusa hispida Schreber, 1775) vocalizations throughout our deployment, with higher vocal activity than in other studies, and with peak vocal activity in January. We recorded bearded seals (Erignathus barbatus Erxleben, 1777) throughout the deployment, with peak vocal activity in February. We recorded lower bearded seal vocal activity than other studies, and almost no vocal activity near the beginning of the spring breeding season. Both seal species vocalized more when ice concentration was high. These patterns in vocal activity document the presence of each species at this site over autumn and winter, and are a useful comparison for future monitoring.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Petits barrages et digues en sols traités : matériaux, concepts, comportement, retours d'expérience et innovation
International audienceSoil treatment with cement or lime is used in hydraulic works since for a few decades. Since 10 years, the feedback from existing structures and in-depth studies of treated soils behaviour make this technique more and more interesting for designers and owners who intend to take advantage of treated soils performance. This paper describes first the treated soil as a material: treatable soils, performance, mixing and compaction. It relates then the benefits of soil treatment for small dams. Current studies about soil treated dams, carried out in the context of the ICOLD Committee P are described. Soil treated dams are for now a concept, not completely validated yet, unlike dikes and low dams in treated soils. Studies include laboratory tests in order to select or develop a proper soil model for treated soil, and also engineering efforts to preliminary design such dams, e.g. dams with upstream watertightness system The paper also addresses the dikes topic, describing the results of the French R&D project DigueELITE about lime treated soils, and the new in-situ overtopping test. Main result of that project is that soil treatment gives to soil good resistance against surface erosion compared to non treated soil. This comes in addition to already demonstrated internal erosion resistance of treated soil. Finally, feedback from existing structures is given, such as canal, zoned dam, dike and temporary cofferdam.L'utilisation du traitement des sols dans les ouvrages hydrauliques n'est pas nouvelle, mais bénéficie actuellement d'un regain d'intérêt de la part des concepteurs et des gestionnaires. La connaissance fine du comportement des matériaux traités et de leurs applications est en plein développement et profite à la fois d'efforts de recherche récents et en cours, et du retour d'expérience d'un nombre croissant de réalisations. Cet article s'intéresse tout d'abord aux matériaux traités : sols concernés, performance des sols traités à la chaux et au ciment, conditions de préparation et mise en oeuvre de sols traités. Il développe ensuite les applications possibles des sols traités et les innovations envisagées grâce aux performances des sols traités. Le cas des barrages est abordé, dans le contexte du comité technique P de la CIGB (barrages en matériaux cimentés). En effet, au contraire des digues et des petits barrages, les barrages en sols traités ne sont à ce stade qu'un concept. Des études de validation du concept sont en cours en France dans le cadre du Groupe de travail. Elles comprennent des essais de laboratoire en vue de développer une loi de comportement rendant compte du comportement mécanique du sol traité. Par ailleurs, des propositions de conception, en barrage homogène avec masque amont, sont proposées. L'article s'intéresse également au cas des digues, en exposant le projet de recherche DigueELITE, qui a permis d'une part de préciser les fonctions essentielles que peut remplir le sol traité à la chaux, et d'autre part de développer un essai inédit de résistance à l'érosion de surface. Les résultats issus de ces essais sont particulièrement prometteurs, et confirment la tenue à l'érosion de surface du sol traité à la chaux, en plus de la résistance à l'érosion interne (érosion de conduit), déjà démontrée au laboratoire. Enfin, cet article cite quelques réalisations d'ouvrages en sol traité (chaux et ciment), parmi les plus significatives de ces dernières décennies : canaux, barrages zonés, digues, batardeaux provisoires
Petits barrages et digues en sols traités : matériaux, concepts, comportement, retours d'expérience et innovation
International audienceSoil treatment with cement or lime is used in hydraulic works since for a few decades. Since 10 years, the feedback from existing structures and in-depth studies of treated soils behaviour make this technique more and more interesting for designers and owners who intend to take advantage of treated soils performance. This paper describes first the treated soil as a material: treatable soils, performance, mixing and compaction. It relates then the benefits of soil treatment for small dams. Current studies about soil treated dams, carried out in the context of the ICOLD Committee P are described. Soil treated dams are for now a concept, not completely validated yet, unlike dikes and low dams in treated soils. Studies include laboratory tests in order to select or develop a proper soil model for treated soil, and also engineering efforts to preliminary design such dams, e.g. dams with upstream watertightness system The paper also addresses the dikes topic, describing the results of the French R&D project DigueELITE about lime treated soils, and the new in-situ overtopping test. Main result of that project is that soil treatment gives to soil good resistance against surface erosion compared to non treated soil. This comes in addition to already demonstrated internal erosion resistance of treated soil. Finally, feedback from existing structures is given, such as canal, zoned dam, dike and temporary cofferdam.L'utilisation du traitement des sols dans les ouvrages hydrauliques n'est pas nouvelle, mais bénéficie actuellement d'un regain d'intérêt de la part des concepteurs et des gestionnaires. La connaissance fine du comportement des matériaux traités et de leurs applications est en plein développement et profite à la fois d'efforts de recherche récents et en cours, et du retour d'expérience d'un nombre croissant de réalisations. Cet article s'intéresse tout d'abord aux matériaux traités : sols concernés, performance des sols traités à la chaux et au ciment, conditions de préparation et mise en oeuvre de sols traités. Il développe ensuite les applications possibles des sols traités et les innovations envisagées grâce aux performances des sols traités. Le cas des barrages est abordé, dans le contexte du comité technique P de la CIGB (barrages en matériaux cimentés). En effet, au contraire des digues et des petits barrages, les barrages en sols traités ne sont à ce stade qu'un concept. Des études de validation du concept sont en cours en France dans le cadre du Groupe de travail. Elles comprennent des essais de laboratoire en vue de développer une loi de comportement rendant compte du comportement mécanique du sol traité. Par ailleurs, des propositions de conception, en barrage homogène avec masque amont, sont proposées. L'article s'intéresse également au cas des digues, en exposant le projet de recherche DigueELITE, qui a permis d'une part de préciser les fonctions essentielles que peut remplir le sol traité à la chaux, et d'autre part de développer un essai inédit de résistance à l'érosion de surface. Les résultats issus de ces essais sont particulièrement prometteurs, et confirment la tenue à l'érosion de surface du sol traité à la chaux, en plus de la résistance à l'érosion interne (érosion de conduit), déjà démontrée au laboratoire. Enfin, cet article cite quelques réalisations d'ouvrages en sol traité (chaux et ciment), parmi les plus significatives de ces dernières décennies : canaux, barrages zonés, digues, batardeaux provisoires
2.2 A phase II trial with canakinumab, a new IL-1beta blocking monoclonal antibody (ACZ885), to evaluate preliminary dosing, safety and efficacy profile in children with systemic Juvenile Idiopathic arthritis (sJIA)
- …