612 resultados para Paramount


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OBJECTIVE: Imaging during a period of minimal myocardial motion is of paramount importance for coronary MR angiography (MRA). The objective of our study was to evaluate the utility of FREEZE, a custom-built automated tool for the identification of the period of minimal myocardial motion, in both a moving phantom at 1.5 T and 10 healthy adults (nine men, one woman; mean age, 24.9 years; age range, 21-32 years) at 3 T. CONCLUSION: Quantitative analysis of the moving phantom showed that dimension measurements approached those obtained in the static phantom when using FREEZE. In vitro, vessel sharpness, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were significantly improved when coronary MRA was performed during the software-prescribed period of minimal myocardial motion (p < 0.05). Consistent with these objective findings, image quality assessments by consensus review also improved significantly when using the automated prescription of the period of minimal myocardial motion. The use of FREEZE improves image quality of coronary MRA. Simultaneously, operator dependence can be minimized while the ease of use is improved.

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Des del 1995 el Consell Europeu ha promogut l’aprenentatge d’una segona llengua a través d’una altra àrea en el que coneixem per CLIL (Contingut i Llengua Integrats en l’Aprenentatge) o en altres paraules: “una activitat en la qual l’aprenentatge d’una llengua estrangera és utilitzada com una eina per l’aprenentatge d’una àrea no linguística en la qual llengua i contingut tenen un mateix paper” (Marsh, 2002). Tot I així, “ensenyar una àrea a través d’una llengua estrangera no és el mateix que la integració de llengua i contingut”. CLIL comporta altres implicacions metodològiques pel que fa a la planificació, estratègies didàctiques i particularment al rol del docent. De fet, són aquests factors els que componen l’èxit o el fracàs en l’implementació de CLIL. i per aquest motiu pretenc analitzar i descriure les diferències entre una sessió de CLIL i una de llengua anglesa. Aquesta investigació és un estudi de cas que vol oferir una mirada a les diferències entre una unitat de CLIL i una de llengua anglesa portades a terme en un grup de 3r de primària a l’escola de Sant Miquel dels Sants (Vic) pel que fa a la planificació, les estratègies i actuacions del docent.

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Modeling the mechanisms that determine how humans and other agents choose among different behavioral and cognitive processes-be they strategies, routines, actions, or operators-represents a paramount theoretical stumbling block across disciplines, ranging from the cognitive and decision sciences to economics, biology, and machine learning. By using the cognitive and decision sciences as a case study, we provide an introduction to what is also known as the strategy selection problem. First, we explain why many researchers assume humans and other animals to come equipped with a repertoire of behavioral and cognitive processes. Second, we expose three descriptive, predictive, and prescriptive challenges that are common to all disciplines which aim to model the choice among these processes. Third, we give an overview of different approaches to strategy selection. These include cost‐benefit, ecological, learning, memory, unified, connectionist, sequential sampling, and maximization approaches. We conclude by pointing to opportunities for future research and by stressing that the selection problem is far from being resolved.

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Insect societies are paramount examples of cooperation, yet they also harbor internal conflicts whose resolution depends on the power of the opponents. The male-haploid, female-diploid sex-determining system of ants causes workers to be more related to sisters than to brothers, whereas queens are equally related to daughters and sons. Workers should thus allocate more resources to females than to males, while queens should favor an equal investment in each sex. Female-biased sex allocation and manipulation of the sex ratio during brood development suggest that workers prevail in many ant species. Here, we show that queens of Formica selysi strongly influenced colony sex allocation by biasing the sex ratio of their eggs. Most colonies specialized in the production of a single sex. Queens in female-specialist colonies laid a high proportion of diploid eggs, whereas queens in male-specialist colonies laid almost exclusively haploid eggs, which constrains worker manipulation. However, the change in sex ratio between the egg and pupae stages suggests that workers eliminated some male brood, and the population sex-investment ratio was between the queens' and workers' equilibria. Altogether, these data provide evidence for an ongoing conflict between queens and workers, with a prominent influence of queens as a result of their control of egg sex ratio.

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BACKGROUND: We conducted a retrospective analysis of administration of nonoccupational HIV post-exposure prophylaxis (nPEP) in a single centre where tracing and testing of the source of exposure were carried out systematically over a 10-year period. METHODS: Files of all nPEP requests between 1998 and 2007 were reviewed. Characteristics of the exposed and source patients, the type of exposure, and clinical and serological outcomes were analysed. RESULTS: nPEP requests increased by 850% over 10 years. Among 910 events, 58% were heterosexual exposures, 15% homosexual exposures, 6% sexual assaults and 20% nonsexual exposures. In 208 events (23%), the source was reported to be HIV positive. In the remaining cases, active source tracing enabled 298 HIV tests to be performed (42%) and identified 11 HIV infections (3.7%). nPEP was able to be avoided or interrupted in 31% of 910 events when the source tested negative. Of 710 patients who started nPEP, 396 (56%) reported side effects, among whom 39 (5%) had to interrupt treatment. There were two HIV seroconversions, and neither was attributed to nPEP failure. CONCLUSIONS: nPEP requests increased over time. HIV testing of the source person avoided nPEP in 31% of events and was therefore paramount in the management of potential HIV exposures. Furthermore, it allowed active screening of populations potentially at risk for undiagnosed HIV infection, as shown by the increased HIV prevalence in these groups (3.7%) compared with a prevalence of 0.3% in Switzerland as a whole.

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An overview of ocular implants with therapeutic application potentials is provided. Various types of implants can be used as slow release devices delivering locally the needed drug for an extended period of time. Thus, multiple periocular or intraocular injections of the drug can be circumvented and secondary complications minimized. The various compositions of polymers fulfilling specific delivery goals are described. Several of these implants are undergoing clinical trials while a few are already commercialized. Despite the paramount progress in design, safety and efficacy, the place of these implants in our clinical therapeutic arsenal remains limited. Miniaturization of the implants allowing for their direct injection without the need for a complicated surgery is a necessary development avenue. Particulate systems which can be engineered to target specifically certain cells or tissues are another promising alternative. For ocular diseases affecting the choroid and outer retina, transscleral or intrasscleral implants are gaining momentum.

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Glutamate transport through astrocytic excitatory amino-acid transporters (EAAT)-1 and EAAT-2 is paramount for neural homeostasis. EAAT-1 has been reported in secreted extracellular microvesicles (eMV, such as exosomes) and because the protein kinase C (PKC) family controls the sub-cellular distribution of EAATs, we have explored whether PKCs drive EAATs into eMV. Using rat primary astrocytes, confocal immunofluorescence and ultracentrifugation on sucrose gradient we here report that PKC activation by phorbol myristate acetate (PMA) reorganizes EAAT-1 distribution and reduces functional [(3)H]-aspartate reuptake. Western-blots show that EAAT-1 is present in eMV from astrocyte conditioned medium, together with NaK ATPase and glutamine synthetase all being further increased after PMA treatment. However, nanoparticle tracking analysis reveals that PKC activation did not change particle concentration. Functional analysis indicates that eMV have the capacity to reuptake [(3)H]-aspartate. In vivo, we demonstrate that spinal astrocytic reaction induced by peripheral nerve lesion (spared nerve injury, SNI) is associated with a phosphorylation of PKC δ together with a shift of EAAT distribution ipsilaterally. Ex vivo, spinal explants from SNI rats release eMV with an increased content of NaK ATPase, EAAT-1 and EAAT-2. These data indicate PKC and cell activation as important regulators of EAAT-1 incorporation in eMV, and raise the possibility that microvesicular EAAT-1 may exert extracellular functions. Beyond a putative role in neuropathic pain, this phenomenon may be important for understanding neural homeostasis and a wide range of neurological diseases associated with astrocytic reaction as well as non-neurological diseases linked to eMV release.

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Expression of tissue-specific homing molecules directs antigen-experienced T cells to particular peripheral tissues. In studies using soluble antigens that focused on skin and gut, antigen-presenting cells (APCs) within regional lymphoid tissues were proposed to be responsible for imprinting homing phenotypes. Whether this occurs in other sites and after physiologic antigen processing and presentation is unknown. We define in vivo imprinting of distinct homing phenotypes on monospecific T cells responding to antigens expressed by tumors in intracerebral, subcutaneous, and intraperitoneal sites with efficient brain-tropism of CD8 T cells crossprimed in the cervical lymph nodes (LNs). Multiple imprinting programs could occur simultaneously in the same LN when tumors were present in more than one site. Thus, the identity of the LN is not paramount in determining the homing phenotype; this critical functional parameter is dictated upstream at the site of antigen capture by crosspresenting APCs.

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The attraction of walking as a pastime has grown enormously in Switzerland over the past few years. Synonym of health and well-being, this activity carries some risks which more and more patients are questioning; answering these questions is not always obvious, so we wanted to tackle the subject. Risks linked to certain animals will be covered. One of these risks is insect stings, particularly wasps and bees. This is a major problem which affects the whole population and more seriously those who are allergic, accounting for around 5% of the population. Another problem: snake bites. In Switzerland, there are about 20-25 bites each year. Poisoning from these can be divided into two categories: local or systemic. The effects are multiple and diverse, ranging from renal failure to discrasia to hypovolemic shock. Pre-hospitalisation measures are of paramount importance in the treatment.

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Tämän tutkielman tarkoituksena on selvittää, miten tietojohtamisen konseptia voidaansoveltaa asiakassuhteiden hallinnassa. Tutkimusmenetelmänä olen käyttänyt kirjallisuustutkimusta, jota on täydennetty yhdellä tapaustutkimuksella. Tietojohtaminen voidaan jakaa kahteen osakokonaisuuteen: tietämyksen hallintaan ja tietohallintoon. Tietämyksen hallinta käsittää ihmiset ja organisaation, kun taas tietohallinto käsittää tietojärjestelmät ja sovellukset. Tätä jaottelua voidaan soveltaa myös asiakassuhteiden (asiakkuuksien) hallintaan. Asiakkuuden hallinta voidaansamaan tapaan jakaa asiakastietämyksen hallintaan ja sitä tukevaan tietohallintoon. Näin ollen tietojohtamisen kehittämiseen rakennetut mallit ja menetelmät ovat sovellettavissa myös asiakkuuden hallinnan kehittämiseen. Tietojohtamisen konseptin ja tapaustutkimuksen pohjalta johtamani asiakkuuden hallinnan konsepti poikkeaa jonkin verran yleisesti käytetyistä asiakkuuden hallinnan teoreettisista malleista. Konseptini arkkitehtuuri perustuu visioon, muutosta kuvaaviin strategioihin sekä yhteisesti sovittuihin mittareihin, joilla asiakkuuden hallinnan eriosa-alueiden tarkoituksenmukaisuutta ja tehokkuutta arvioidaan. Keskeisenä tavoitteena on varmistaa asiakastietämyksen kartuttaminen ja tehokas hyödyntäminen kaikissa asiakasrajapinnoissa. Tähän päästään yhdistämällä asiakasprosessit ja organisaation omat toimintaprosessit mahdollisimman saumattomaksi kokonaisuudeksi mm. tietohallinnon palveluja ja monikanavaisuuden ideaa hyödyntämällä. Asiakkuuden hallinnan kehittämisen kannalta on tärkeää ymmärtää, millaisia mahdollisuuksia tietojohtamisen eri mallit ja yleisemmin koko tietoyhteiskuntakehitys antavat organisaatioiden kilpailukyvyn tehostamiseen. Keskeistä on luoda edellytykset tiedon vapaalle virralle, verkostoitumiselle ja innovaatioille unohtamatta kuitenkaan analyysin ja systemaattisten toimintatapojen merkitystä yrityksen toiminnan kokonaisuudessa

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There is a widespread agreement from patient and professional organisations alike that the safety of stem cell therapeutics is of paramount importance, particularly for ex vivo autologous gene therapy. Yet current technology makes it difficult to thoroughly evaluate the behaviour of genetically corrected stem cells before they are transplanted. To address this, we have developed a strategy that permits transplantation of a clonal population of genetically corrected autologous stem cells that meet stringent selection criteria and the principle of precaution. As a proof of concept, we have stably transduced epidermal stem cells (holoclones) obtained from a patient suffering from recessive dystrophic epidermolysis bullosa. Holoclones were infected with self-inactivating retroviruses bearing a COL7A1 cDNA and cloned before the progeny of individual stem cells were characterised using a number of criteria. Clonal analysis revealed a great deal of heterogeneity among transduced stem cells in their capacity to produce functional type VII collagen (COLVII). Selected transduced stem cells transplanted onto immunodeficient mice regenerated a non-blistering epidermis for months and produced a functional COLVII. Safety was assessed by determining the sites of proviral integration, rearrangements and hit genes and by whole-genome sequencing. The progeny of the selected stem cells also had a diploid karyotype, was not tumorigenic and did not disseminate after long-term transplantation onto immunodeficient mice. In conclusion, a clonal strategy is a powerful and efficient means of by-passing the heterogeneity of a transduced stem cell population. It guarantees a safe and homogenous medicinal product, fulfilling the principle of precaution and the requirements of regulatory affairs. Furthermore, a clonal strategy makes it possible to envision exciting gene-editing technologies like zinc finger nucleases, TALENs and homologous recombination for next-generation gene therapy.

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In Seychelles, comprehensive tobacco control legislation enacted in 2009, and subsequent regulations, ban smoking in all enclosed places (defined as any area under a fixed or transient roof). A survey in October-November 2014 assessed i) the compliance to the Act and these regulations in 63 restaurants, bars or discotheques and ii) knowledge of the Tobacco control Act and these regulations of supervisors and managers of these hospitality premises; (47 agreed to answer). No person was found smoking in 92% of all premises. However, "no smoking" signs did not conform to regulations in >70% of premises, and ashtrays were seen in 17% of enclosed premises. All supervisors and managers (100%) knew that smoking is banned in enclosed premises but <15% knew the fines liable to persons, respective owners of enclosed places, when a person smokes in an enclosed premise. Furthermore, 60% of supervisors were not aware that no smoking signs must comply with a specific regulation and 40% were not aware that ashtrays are not permitted in enclosed premises. In conclusion, the positive finding is that few persons smoke in restaurants, bars and discotheques, but the survey also showed that several aspects of regulations for tobacco control in enclosed premises are not well implemented. This calls for further information campaigns targeting both the public and the managers of hospitality premises, but also for strengthening enforcement measures, including fines for offenses. Scaling up comprehensive tobacco control measures, including full enforcement of clean air policy, is of paramount importance to meet the national target of 30% reduction of the smoking prevalence between 2010 and 2025.

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Les traités scientifiques ne font que depuis peu d'années l'objet d'études en histoire des sciences. Pourtant, ces traités ont énormément à apporter car ils renseignent sur la manière de raisonner des auteurs, ainsi que sur le développement d'une discipline. Dans ce travail de doctorat, différents traités des maladies du système nerveux ont été dépouillés, notamment le traité de Sémiologie des affections du système nerveux (1914) de Jules Dejerine (1849-1917). Ce traité a été analysé de trois manières différentes. Il a tout d'abord été comparé à une édition précédente publiée sous forme de chapitre (1901), révélant un large remodelage du contenu du traité, suggérant une évolution rapide de la discipline neurologique en l'espace de quelques années. Deuxièmement, l'analyse de la Sémiologie a permis de recréer un réseau de professionnels avec qui Jules Dejerine était en contact et, en parcourant les livres publiés par ces auteurs, il a été possible de décrire de quelle manière ces auteurs se citent mutuellement. Finalement, ces livres contiennent de nombreuses illustrations, qui sont associées à la notion de « preuve » : les auteurs utilisent des images sous forme de dessins, de photographies ou de schémas qui illustrent des patients ou des pièces anatomiques pour « montrer » la maladie ou la lésion. Chaque illustration a un rôle à jouer pour décrire la lésion, montrer la progression de la maladie et elle aide le médecin à poser le diagnostic. Grâce à ces trois axes de recherche, un traité devient un outil de travail dynamique, qui évolue au fil des rééditions, influencé par les critiques et commentaires retrouvés dans d'autres traités et articles, et par les progrès accomplis dans la discipline traitée. Des, passages et certaines images de l'ouvrage circulent également de traité en traité et véhiculent l'autorité de l'auteur de ces passages et images qui en viennent à représenter la maladie. Ce transfert d'images joue également un rôle dans la standardisation du diagnostic et dans l'unification de la neurologie à travers le monde occidental au début du XXe siècle, une période charnière pour l'histoire de la médecine. -- Au début du XXe siècle, la neurologie est une jeune spécialité médicale qui se développe rapidement. Les différents médecins publient des traités, communiquent entre eux et échangent leurs données. Un traité scientifique est un outil de travail dynamique qui évolue avec les rééditions et le développement d'une discipline. Ces ouvrages recèlent toutes sortes d'informations et leur analyse ne fait que depuis peu de temps l'objet d'études en histoire des sciences. Ces traités regorgent notamment d'illustrations qui sont associées à la notion de « preuve » : les auteurs utilisent des images sous forme de dessins, de photographies ou de schémas qui représentent des patients ou des pièces anatomiques afin de « montrer » la maladie ou la lésion. Chaque illustration a un rôle à jouer pour décrire la pathologie, montrer la progression de la maladie et elle aide le médecin à poser le diagnostic. Les auteurs des traités, qui viennent d'Europe et d'Amérique du Nord, se citent mutuellement, permettant au lecteur de recréer leur réseau de professionnels au niveau international. De plus, comme ces auteurs réutilisent les observations et les illustrations des autres, celles-ci circulent de traité en traité et en viennent à représenter la maladie. Ce transfert d'images joue également un rôle dans la standardisation du diagnostic et dans l'unification de la neurologie à travers le monde occidental au début du XXe siècle, une période charnière pour l'histoire de la médecine. -- Until recently, the study of textbooks has been neglected in the history of the sciences. However, textbooks can provide fruitful sources of information regarding the way authors work and the development of a particular discipline. This dissertation reviews editions of a single textbook, the Sémiologie des affections du système nerveux (1914) by Jules Dejerine (1849-1917). This textbook enabled the description of three axes of research. Firstly, by comparing the book to a first edition published as a chapter, one can acknowledge an extensive remodeling of the content of the book, suggesting a vast increase in knowledge over time. Secondly, by looking at the authors that Dejerine quotes repeatedly, it becomes possible to recreate his professional network, to review the works of these authors and to determine how they cross-reference each other. Thirdly, these textbooks contain numerous medical illustrations, which are linked with the concept of "proof;" the authors demonstrate a willingness to "show" the lesion or the pathology by publishing an image. Drawings, schematic representations, radiographies, or photographs of patients or of anatomical preparations all have their own purpose in describing the lesion and the progression of the disease. They assist in the diagnosis of the pathology. By looking at all of these aspects, it is therefore possible to conclude that a neurological textbook is a dynamic object that evolves through re-editions, comments and references found in other textbooks and by the circulations of parts of these books, such as the images. The illustrations also carry the author's authority, since their ongoing use claims that the work by the owner of the image has been endorsed by others. At the same time, it validates the borrowers' arguments. By using medical illustrations from different authors worldwide, the authors are also making a claim to a common language, to a similar way of examining patients, and about how much they depend on medical imagery to prove their points. In that sense, by focusing upon these textbooks, one can affirm that neurology already existed as a worldwide specialty at the turn of the twentieth century. Much more than mere accompaniments to the text, images were of paramount importance to the unification of neurology.

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Wide-range spectral coverage of blazar-type active galactic nuclei is of paramount importance for understanding the particle acceleration mechanisms assumed to take place in their jets. The Major Atmospheric Gamma Imaging Cerenkov (MAGIC) telescope participated in three multiwavelength (MWL) campaigns, observing the blazar Markarian (Mkn) 421 during the nights of April 28 and 29, 2006, and June 14, 2006. Aims. We analyzed the corresponding MAGIC very-high energy observations during 9 nights from April 22 to 30, 2006 and on June 14, 2006. We inferred light curves with sub-day resolution and night-by-night energy spectra. Methods. MAGIC detects γ-rays by observing extended air showers in the atmosphere. The obtained air-shower images were analyzed using the standard MAGIC analysis chain. Results. A strong γ-ray signal was detected from Mkn 421 on all observation nights. The flux (E > 250 GeV) varied on night-by-night basis between (0.92±0.11) × 10-10 cm-2 s-1 (0.57 Crab units) and (3.21±0.15) × 10-10 cm-2 s-1 (2.0 Crab units) in April 2006. There is a clear indication for intra-night variability with a doubling time of 36± min on the night of April 29, 2006, establishing once more rapid flux variability for this object. For all individual nights γ-ray spectra could be inferred, with power-law indices ranging from 1.66 to 2.47. We did not find statistically significant correlations between the spectral index and the flux state for individual nights. During the June 2006 campaign, a flux substantially lower than the one measured by the Whipple 10-m telescope four days later was found. Using a log-parabolic power law fit we deduced for some data sets the location of the spectral peak in the very-high energy regime. Our results confirm the indications of rising peak energy with increasing flux, as expected in leptonic acceleration models.

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BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.