977 resultados para Isa Label
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Tutkimuksen tavoitteena on selvittää paikallisten metsäteollisuuteen toimittavien pienten ja keskisuurten ohjelmistoyritysten nykytilannetta, hyviä käytäntöjä ja toiminnan ongelmia. Tunnistamalla pienten ja keskisuurten ohjelmistoyritysten nykytilanne on mahdollista suunnitella konkreettisia yrityksille suunnattavia kehittämistoimenpiteitä. Työssä on keskitytty tutkimaan metsäteollisuuteen toimittavia kaakkoissuomaisia pieniä ja keskisuuria ohjelmistoyrityksiä. Työn viitekehyksenä esitellään metsäteollisuuden nykytilannetta, kehitystrendejä sekä kehitystrendien vaikutusta metsäteollisuusyritysten tietojärjestelmätarpeisiin. Lisäksi työn viitekehyksessä esitellään tutkimuksessa käytetyt kvalitatiiviset tutkimusmenetelmät.Tutkimus on luonteeltaan kvalitatiivinen eli laadullinen ja tutkimusotteeltaan deskriptiivinen eli kuvaileva. Tutkimusaineisto koostui 19 asiantuntijahaastattelusta ja dokumenttiaineistosta. Tutkimusaineiston analysoinnissa käytin aineistopohjaista meneelmää ja tapaustutkimusta. Tutkimustulosten perusteella pystyttiinkuvaamaan tutkimuksessa mukana olleille 10 paikalliselle pienelle ja keskisuurelle ohjelmistoyritykselle yhteisiä ominaisuuksia. Tämän lisäksi pystyttiin tunnistamaan ohjelmistoyrityksistä kolme erilaista tyyppiä ja luonnehtimaan kunkin tyypin nykytilannetta, hyviä käytäntöjä ja toiminnan ongelmia. Tunnistetut paikallisten pienten ja keskisuurten ohjelmistoyritysten tyypit ovat: erikoistuja, ennakoija ja keräilijä. Tutkimustulokset antavat hyvän lähtökohdan tulevaisuuden kehitystrendien tunnistamisessa ja toiminnankehitystoimenpiteiden suunnittelussa.
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The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not fitted all the gaps in our knowledge and thus, in clinical. practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence. Methods: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD. Results: Overall., 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naive patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adlimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.
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Tutkimuksessa arvioidaan millaisia kyvykkyyksiä toimijoiltavaaditaan, jotta voidaan edistää verkostoja palvelevan innovaatiopolitiikan toteutumista ja toteuttaa käytäntölähtöistä innovaatiotoimintaa. Empiirinen osa tarkastelee Päijät-Hämeen toimijoiden asenneympäristöä ja toimimisen valmiuksia käytäntölähtöisen innovaatiotoiminnan tarpeisiin sopivaksi. Osaaminen kerääntyy yliopistopaikkakunnille ulkoisten suurtuotannon etujen mukaisesti. Ne alueet, joilla ei ole yliopistoa joutuvat luomaan muunlaista innovaatiokyvykkyyttä saavuttaakseen kilpailuetua. Siksi Päijät-Hämeen visiona on tulla johtavaksi käytäntölähtöisen innovaatiotoiminnan alueeksi hyvien toimintamallien ja tehokkaiden tiedonsiirtomekanismien avulla. Tämä vaatii alueen toimijoilta mm. korkeaa absorptiivista kapasiteettia ja heikkoja linkkejä alueen ulkopuolelle. Työn empiirinen osa koostuu 12:sta puolistrukturoidusta haastattelusta sekä kyselytutkimuksesta. Tiedonluonti ja -siirto alueelle nähtiin pääasiassa tutkimusmaailman tehtävänä, mutta varianssianalyysin perusteella tutkimusmaailma ei itse nähnyt olevansa siinä asemassa. Yhteisen kielen puuttuminen tutkimus- ja käytännön työelämän väliltä nähtiin puutteena.
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The most important recent advance in the treatment of neovascular age-related macular degeneration (AMD) is the development of antivascular endothelial growth factor (anti-VEGF) therapeutic agents that preserve and improve visual acuity by arresting choroidal neovascular growth and reducing vascular permeability. Two anti-VEGF agents, ranibizumab and pegaptanib sodium, are currently approved by Swissmedic for the treatment of neovascular AMD. A third anti-VEGF agent, bevacizumab, is currently used as an off label treatment option for exsudative AMD. Other anti-VEGF agent strategies that have shown efficacy include among others, small interfering RNA agents to silence the VEGF gene and receptor and the fusion protein VEGF trap. Anti-VEGF therapies have been used successfully in the clinic, encouraging their use in the treatment of other neovascular and exudative eye diseases.
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Finnish food producers' trade with Russia has experienced profound changes since the collapse of the Soviet Union. Simultaneously, the distribution systems of foodstuffs have changed remarkably. This study sheds some light into these changes and analyses the current situation in distribution systems of foodstuffs in Russia. In addition, the study discusses the possibilities of Finnish food producers to get more of their products to the shelves of Russian food retail stores. Before the 1998 financial crisis, the import of foreign foodstuffs was booming in Russia due to the overvalued rouble. As a result of the financial crisis, food import collapsed. The export of Finnish foodstuffs to Russia has been slowly recovering during the past few years, but in the most important product categories the pre-crisis levels have so far not been reached and maybe will not be reached. In certain product categories the growth has been only marginal. It seems that starting localproduction will become increasingly important in the future. This is further encouraged by the fact that Russian consumers favour domestic food products. Russian consumers are very price conscious and demand quality in food products. The perceived price-quality ratio is an important criterion in the purchase decision.The majority of foodstuff retail is still conducted via unorganised forms of trade (e.g. kiosks and marketplaces) but modern retail chains are developing at a fast pace in Russia. They are also expected to dominate the retail trade in foodstuffs over the unorganised forms of trade in the future. This will change the distribution systems as well. The retail chains are trying to shorten the distribution chain, similarly to what has been seen in the Western countries. This together with the strengthening of retail chains is likely to shrink the role of wholesalers, as the chains increasingly want to work directly with the producers. Many large retail chains are acquiring or have already acquired a distribution centre or centres in order to boost efficiency and control the flow of products. The strengthening of the retail chains also gives them power in negotiations, which the producers and distributors have to adjust to. For example store entry fees and retail chains' own private label products pose challenges to the food producers. In the food production sector the competition is fierce, as large Russianand foreign producers want to ensure their piece of the market. The largest producers utilise their size: they invest in big marketing campaigns and are willing to pay high entry fees to retail chains in order to secure a place on the store shelves and to build a strong brand in Russia. This complicates the situation from the viewpoint of small producers. Currently, the most popular type of distribution system among the interviewed Finnish food producers is based on a network of local distributors. There is, however, a strong consensus on the importanceof starting local production in order to be a serious actor in Russia in the future. Factors that hinder the starting of local production include the lack of local infrastructure and qualified staff, and the low risk tolerance of Finnish firms. Major barriers for entry in Russia are the actions of authorities, fierce competition, fragmented market and Finnish producers' heavy production costs. The suggested strategies for increasing the market share include focusing geographically or segment-wise, introducing new products, starting local production, andcooperation between Finnish producers. Smallness was one reason why Finnish producers had to cut down their operations in Russia due to the 1998 crisis. Smaller producers had fewer resources to tolerate losses during the period of crisis. Smallness is reflected also on trade negotiations with retail chains and distributors. It makes it harder to cope with the store entry fees and to differentiatefrom the mass of products propped up by expensive advertising. Finally, it makes it harder for Finnish producers to start or expand local production, as it is more difficult for a small producer to get financing and to tolerate the increased risks. Compensating for the smallness might become the crucial factor determining the future success of Finnish food producers in the Russian market.
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This research paper focuses on the Russian food retail sector and its structure and development. At the momentit is one of the fastest growing markets today with 12.1% growth last year (2004). The growth originates from high oil price, which has been accumulated to people's wages. They are growing nominally more than 20% annually. But even though the income increases, the share of food of all retailtrade has been fairly stable with only a slight decline. Thus, the consumption is shifting to products with more quality and value. The shareof modern retail outlets is low, as the Russian retail sector is still very dispersed to traditional retail outlets such as kiosks, open markets and small grocery stores. The store chains are, however, becoming more and more significant. The biggest market for retailers is Moscow but nowadays the chains are expanding rapidly into other regions. Even though the markets have not been saturated in Moscow, the best prospects for growth are in the regions. The most important factor restricting the growth in Moscowis the availability of real estate and land plots for stores. The market is moving forward to saturation, and a consolidation process will follow. In fact, it has already started but not many acquisitions have been made so far. To this point the domestic chains have settled to form only alliances. The foreign players will be very strong in the tightening competition in the future. The problem of domestic chains is that the stores are nonstandardized, which is not cost-efficient. The chains are trying to enhance their power in price negotiations by forming purchasing alliances, introducing private label goods and using the regional expansion as a striking weapon. In order to follow the growing chains to other regions the producer must sell its products to the chains at favorable terms. Suppliers are strong in negotiations when they have a functioning distribution network, ability to JIT deliveries, proper documentationpolicies, a strong brand, reliability in deliveries and a fair price. The size of the entry ticket, i.e. the listing fee may define the shelf space a producer gets in the stores.
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Tämän tutkimuksen aiheena on tilintarkastuksen historiallinen kehittyminen Suomessa runsaan sadan vuoden aikana. Tutkimuksen tavoitteena on analysoida osakeyhtiön tilintarkastuksen kehitystä ja yhdistää vuosisadan kehityspiirteet tilintarkastuksen kokonaiskuvaksi. Tutkittava periodi alkaa 1800-luvun lopulta ja päättyy 2000-luvun taitteeseen. Tutkimuksessa tarkastellaan suomalaista tilintarkastusinstituutiota, joka jaetaan kolmeen osaan: tilintarkastusta säätelevään normistoon (normit), tilintarkastajajärjestelmään (toimijat) ja tilintarkastuksen sisältöön (tehtävät). Tutkimuksessa tavoitellaan vastauksia kysymyksiin: mitä tarkastettiin, milloin tarkastettiin, kuka tarkasti ja miten tarkastettiin eri aikakausina? Tutkimus perustuu historialliseen lähdeaineistoon, jonka muodostavat tutkimusajanjakson lainsäädäntö, lainvalmisteluasiakirjat, viranomaisten ohjeet ja päätökset, alan järjestöjen suositukset, ammattilehtien artikkelit sekä laskentatoimen ja tilintarkastuksen ammattikirjallisuus. Metodologisesti tutkimus on teoreettinen, kvalitatiivinen historiantutkimus, jossa lähdeaineistoa käsitellään lähdekriittisesti ja osittain sisältöanalyysin keinoin. Tilintarkastusta säätelevässä normistossa keskeisiä lakeja ovat olleet osakeyhtiölaki, kirjanpitolaki ja tilintarkastuslaki. Lakisääteinen tilintarkastus alkoi vuoden 1895 osakeyhtiölaista, joka uudistui vuonna 1978 ja jälleen vuonna 1997. Kirjanpitolainsäädäntö on uudistunut viidesti: 1925 ja 1928, 1945, 1973, 1993 sekä 1997. Vuoden 1994 tilintarkastuslakiin koottiin tilintarkastuksen säädökset useista laeista. Muita normistoja ovat olleet EY:n direktiivit, Kilan ohjeet, KHT-yhdistyksen suositukset, Keskuskauppakamarin säännökset ja viimeisimpinä IAS- ja ISA-standardit. Ammattimainen tilintarkastajajärjestelmä saatiin maahamme kauppiaskokousten ansiosta. Ammattimaisena tilintarkastuksen toimijana aloitti Suomen Tilintarkastajainyhdistys vuonna 1911, ja sen toimintaa jatkoi KHT-yhdistys vuodesta 1925 alkaen. Tilintarkastajien auktorisointi siirtyi Keskuskauppakamarille vuonna 1924. HTM-tilintarkastajat ovat olleet alalla vuodesta 1950 lähtien. Kauppakamarijärjestö on toiminut hyväksyttyjen tilintarkastajien valvojana koko ammattimaisen tilintarkastustoiminnan ajan. Valtion valvontaa suorittaa VALA (Valtion tilintarkastuslautakunta). Koko tutkittavan periodin ajan auktorisoitujen tilintarkastajien rinnalla osakeyhtiöiden tarkastajina ovat toimineet myös maallikot.Tilintarkastuksen tehtäviin kuului vuoden 1895 osakeyhtiölain mukaan hallinnon ja tilien tarkastus. Myöhemmin sisältö täsmentyi tilinpäätöksen, kirjanpidon ja hallinnon tarkastukseksi. Tutkimusajanjakson alussa tilintarkastus oli manuaalista kaikkien tositteiden prikkausta ja virheiden etsimistä. Myöhemmin tarkastus muuttui pistokokeiksi. Kertatarkastuksesta siirryttiin jatkuvaan valvontatarkastukseen 1900-luvun alkupuolella. Dokumentoinnista ja työpapereista alkaa olla havaintoja 1930-luvulta lähtien. Atk-tarkastus yleistyi 1970- ja 1980-luvuilla, jolloin myös riskianalyyseihin alettiin kiinnittää huomiota. Hallinnon tarkastuksen merkitys on kasvanut kaiken aikaa. Tilintarkastuskertomukset olivat tutkimusajanjakson alussa vapaamuotoisia ja sisällöltään ilmaisurikkaita ja kuvailevia. Kertomus muuttui julkiseksi vuoden 1978 osakeyhtiölain myötä. Myöhemmin KHT-yhdistyksen vakiokertomusmallit yhdenmukaistivat ja pelkistivät raportointia. Tutkimuksen perusteella tilintarkastuksen historia voidaan jakaa kolmeen kauteen, jotka ovat tilintarkastusinstituution rakentumisen kausi (1895 - 1950), vakiintumisen kausi (1951 - 1985) ja kansainvälistymisen ja julkisuuden kausi (1986 alkaen). Tutkimusajanjakson jokaisella vuosikymmenellä keskusteltiin jatkuvasti tilintarkastajien riittävyydestä, alalle pääsyn ja tutkintojen vaikeudesta, tilintarkastajien ammattitaidon tasosta,hallinnon tarkastuksen sisällöstä, tilintarkastuskertomuksesta sekä maallikkotarkastajien asemasta. 1990-luvun keskeisimmät keskusteluaiheet olivat konsultointi, riippumattomuus, odotuskuilu sekä tilintarkastuksen taso ja laadunvalvonta. Analysoitaessa tilintarkastuksen muutoksia runsaan sadan vuoden ajalta voidaan todeta, että tilintarkastuksen ydintehtävät eivät juurikaan ole muuttuneet vuosikymmenien kuluessa. Osakeyhtiön tilintarkastus on edelleenkin laillisuustarkastusta. Sen tarkoituksena on yhä kirjanpidon, tilinpäätöksen ja hallinnon tarkastus. Tilintarkastajat valvovat osakkeenomistajien etua ja raportoivat heille tarkastuksen tuloksista. Tilintarkastuksen ulkoinen maailma sen sijaan on muuttunut vuosikymmenten saatossa. Kansainvälistyminen on lisännyt säännösten määrää, odotuksia ja vaatimuksia on nykyisin enemmän, uusi tekniikka mahdollistaa nopean tiedonkulun ja valvonta on lisääntynyt nykypäivää kohti tultaessa. Tilintarkastajan pätevyys perustuu nykyään tietotekniikan, tietojärjestelmien ja yrityksen toimialantuntemukseen. Runsaan sadan vuoden takaisen lain vaarinpitovaatimuksesta on tultu virtuaaliaikaiseen maailmaan!
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Las teorías sobre la invención histórica de la infancia y la adolescencia se han basado casi exclusivamente en fuentes occidentales (más exactamente centroeuropeas y anglosajonas), por lo que es urgente una reconceptualización en una óptica diacrónica y transcultural. Una de las conclusiones del encuentro «A criança e o jovem na America Latina», que tuvo lugar en Marilia (Brasil) en noviembre del 2001, organizado por la International Sociological Association, fue la necesidad de reconceptualizar la infancia y la juventud desde una perspectiva latinoamericana (como ámbito geográfico, académico y cultural). En este artículo proponemos retomar, en una perspectiva comparativa y como ejemplo de la riqueza y complejidad de las tareas pendientes, dos casos documentales y etnográficos recabados en nuestras propias indagaciones en México (Feixa, 1998b) y Chile (González, 2004a, 2004b), en la idea de comenzar a cursar esta «asignatura pendiente».
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A clorose variegada dos citros (CVC) é uma doença grave, causada por Xylella fastidiosa. As medidas usuais de controle mostram-se pouco eficientes ou práticas e com alto custo. Dessa forma, o uso de variedades resistentes e/ou tolerantes desponta como a alternativa mais eficiente, razão pela qual se julgou oportuna a realização deste trabalho. O presente estudo teve como objetivo avaliar o comportamento de variedades e clones de laranjas introduzidas em relação a X. fastidiosa. Foram estudados 59 variedades e clones de laranjas doces e 2 de laranjas azedas introduzidos da França, Itália e Portugal. O delineamento experimental foi o de blocos casualizados (DBC), com 62 tratamentos e 4 repetições, incluindo a variedade 'Pêra', como padrão. Cada parcela continha duas plantas, sendo uma inoculada e a outra sem inoculação. Para a inoculação do patógeno, foi empregado o método de encostia, utilizando-se de mudas infectadas. Para a avaliação da incidência da doença, utilizou-se de dados qualitativos, positivos ou negativos, enquanto para severidade empregou-se escala de notas, que foi estabelecida baseando-se nos sintomas de CVC, confirmados através dos testes de PCR. As variedades de laranjas azedas Beja e Sr. Pinto e as laranjas doces Navelina ISA 315, Navelina SRA 332 e Newhall Navel SRA 343 não apresentaram sintomas em folhas até 27 meses após a inoculação.
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This paper asks a simple question: if humans and their actions co-evolve with hydrological systems (Sivapalan et al., 2012), what is the role of hydrological scientists, who are also humans, within this system? To put it more directly, as traditionally there is a supposed separation of scientists and society, can we maintain this separation as socio-hydrologists studying a socio-hydrological world? This paper argues that we cannot, using four linked sections. The first section draws directly upon the concern of science-technology studies to make a case to the (socio-hydrological) community that we need to be sensitive to constructivist accounts of science in general and socio-hydrology in particular. I review three positions taken by such accounts and apply them to hydrological science, supported with specific examples: (a) the ways in which scientific activities frame socio-hydrological research, such that at least some of the knowledge that we obtain is constructed by precisely what we do; (b) the need to attend to how socio-hydrological knowledge is used in decision-making, as evidence suggests that hydrological knowledge does not flow simply from science into policy; and (c) the observation that those who do not normally label themselves as socio-hydrologists may actually have a profound knowledge of socio-hydrology. The second section provides an empirical basis for considering these three issues by detailing the history of the practice of roughness parameterisation, using parameters like Manning's n, in hydrological and hydraulic models for flood inundation mapping. This history sustains the third section that is a more general consideration of one type of socio-hydrological practice: predictive modelling. I show that as part of a socio-hydrological analysis, hydrological prediction needs to be thought through much more carefully: not only because hydrological prediction exists to help inform decisions that are made about water management; but also because those predictions contain assumptions, the predictions are only correct in so far as those assumptions hold, and for those assumptions to hold, the socio-hydrological system (i.e. the world) has to be shaped so as to include them. Here, I add to the ``normal'' view that ideally our models should represent the world around us, to argue that for our models (and hence our predictions) to be valid, we have to make the world look like our models. Decisions over how the world is modelled may transform the world as much as they represent the world. Thus, socio-hydrological modelling has to become a socially accountable process such that the world is transformed, through the implications of modelling, in a fair and just manner. This leads into the final section of the paper where I consider how socio-hydrological research may be made more socially accountable, in a way that is both sensitive to the constructivist critique (Sect. 1), but which retains the contribution that hydrologists might make to socio-hydrological studies. This includes (1) working with conflict and controversy in hydrological science, rather than trying to eliminate them; (2) using hydrological events to avoid becoming locked into our own frames of explanation and prediction; (3) being empirical and experimental but in a socio-hydrological sense; and (4) co-producing socio-hydrological predictions. I will show how this might be done through a project that specifically developed predictive models for making interventions in river catchments to increase high river flow attenuation. Therein, I found myself becoming detached from my normal disciplinary networks and attached to the co-production of a predictive hydrological model with communities normally excluded from the practice of hydrological science.
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Background: Although randomized clinical trials (RCTs) are considered the gold standard of evidence, their reporting is often suboptimal. Trial registries have the potential to contribute important methodologic information for critical appraisal of study results. Methods and Findings: The objective of the study was to evaluate the reporting of key methodologic study characteristics in trial registries. We identified a random sample (n = 265) of actively recruiting RCTs using the World Health Organization International Clinical Trials Registry Platform (ICTRP) search portal in 2008. We assessed the reporting of relevant domains from the Cochrane Collaboration’s ‘Risk of bias’ tool and other key methodological aspects. Our primary outcomes were the proportion of registry records with adequate reporting of random sequence generation, allocation concealment, blinding, and trial outcomes. Two reviewers independently assessed each record. Weighted overall proportions in the ICTRP search portal for adequate reporting of sequence generation, allocation concealment, blinding (including and excluding open label RCT) and primary outcomes were 5.7% (95% CI 3.0–8.4%), 1.4% (0–2.8%), 41% (35–47%), 8.4% (4.1–13%), and 66% (60–72%), respectively. The proportion of adequately reported RCTs was higher for registries that used specific methodological fields for describing methods of randomization and allocation concealment compared to registries that did not. Concerning other key methodological aspects, weighted overall proportions of RCTs with adequately reported items were as follows: eligibility criteria (81%), secondary outcomes (46%), harm (5%) follow-up duration (62%), description of the interventions (53%) and sample size calculation (1%). Conclusions: Trial registries currently contain limited methodologic information about registered RCTs. In order to permit adequate critical appraisal of trial results reported in journals and registries, trial registries should consider requesting details on key RCT methods to complement journal publications. Full protocols remain the most comprehensive source of methodologic information and should be made publicly available.
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PURPOSE: To optimize and preliminarily evaluate a three-dimensional (3D) radial balanced steady-state free precession (bSSFP) arterial spin labeled (ASL) sequence for nonenhanced MR angiography (MRA) of the extracranial carotid arteries. MATERIALS AND METHODS: The carotid arteries of 13 healthy subjects and 2 patients were imaged on a 1.5 Tesla MRI system using an undersampled 3D radial bSSFP sequence providing a scan time of ∼4 min and 1 mm(3) isotropic resolution. A hybridized scheme that combined pseudocontinuous and pulsed ASL was used to maximize arterial coverage. The impact of a post label delay period, the sequence repetition time, and radiofrequency (RF) energy configuration of pseudocontinuous labeling on the display of the carotid arteries was assessed with contrast-to-noise ratio (CNR) measurements. Faster, higher undersampled 2 and 1 min scans were tested. RESULTS: Using hybridized ASL MRA and a 3D radial bSSFP trajectory, arterial CNR was maximized with a post label delay of 0.2 s, repetition times ≥ 2.5 s (P < 0.05), and by eliminating RF energy during the pseudocontinuous control phase (P < 0.001). With higher levels of undersampling, the carotid arteries were displayed in ≤ 2 min. CONCLUSION: Nonenhanced MRA using hybridized ASL with a 3D radial bSSFP trajectory can display long lengths of the carotid arteries with 1 mm(3) isotropic resolution. J. Magn. Reson. Imaging 2015;41:1150-1156. © 2014 Wiley Periodicals, Inc.
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OBJECTIVE: To assess safety up to 1 year of follow-up associated with prasugrel and clopidogrel use in a prospective cohort of patients with acute coronary syndromes (ACS). METHODS: Between 2009 and 2012, 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort, among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines. Patients with ST-elevation myocardial infarction (STEMI) preferentially received prasugrel, while those with non-STEMI, a history of stroke or transient ischaemic attack, age ≥75 years, or weight <60 kg received clopidogrel or reduced dose of prasugrel to comply with the prasugrel label. RESULTS: After adjustment using propensity scores, the primary end point of clinically relevant bleeding events (defined as the composite of Bleeding Academic Research Consortium, BARC, type 3, 4 or 5 bleeding) at 1 year, occurred at a similar rate in both patient groups (prasugrel/clopidogrel: 3.8%/5.5%). Stratified analyses in subgroups including patients with STEMI yielded a similar safety profile. After adjusting for baseline variables, no relevant differences in major adverse cardiovascular and cerebrovascular events were observed at 1 year (prasugrel/clopidogrel: cardiac death 2.6%/4.2%, myocardial infarction 2.7%/3.8%, revascularisation 5.9%/6.7%, stroke 1.0%/1.6%). Of note, this study was not designed to compare efficacy between prasugrel and clopidogrel. CONCLUSIONS: In this large prospective ACS cohort, patients treated with prasugrel according to current guidelines (ie, in patients without cerebrovascular disease, old age or underweight) had a similar safety profile compared with patients treated with clopidogrel. CLINICAL TRIAL REGISTRATION NUMBER: SPUM-ACS: NCT01000701; COMFORTABLE AMI: NCT00962416.
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This study examines the proportions of regenerative and collateral sprouting to the skin after peripheral nerve injury. Methods: In the first experimental paradigm, primary afferent neurones were pre-labelled with Diamidino Yellow (DY), injected in digit 3, followed by sciatic nerve section and repair. After three months of regeneration, digit 3 was re-injected with Fast Blue (FB) to label regernating cells. Fluoro-Gold (FG) was applied to the femoral (FEM) and musculocutaneous (MC) nervers four days later to quantify their contribution to the innveration. In the second experimental paradigm, sciatic nerve was first sectioned and repaired. Three months later, the sciatic was resected, and digit 3 injected with FB. After four more days, FEM and MC were resected and FG injected in all digits. Results: Neurones in dorsal root ganglion (DRG) L5 had a higher rate of correct reinnervation of digit 3 (44-72%) than neurones in DRG L4 (14-44%). Like in control cases, only occasional axons were traced from the FEM and MC. In the second experiment, only occasional labelled neurones appeared. Conclusions: The results indicate differences in the capacity for correct peripheral sensory reinnvervation between segmental levels and that in this model collateral sprouting was practically non-existent compared to regenerative sprouting.
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Capsule application of Diamidino Yellow (DY) to the cut end of the sciatic nerve immediately followed by capsule application of Fast Blue (FB) resulted in approximate to 95% double-labelled dorsal root ganglion neurones (DRGn) and motoneurones (Mn). Nerve injection of DY followed either immediately or 2 months later by capsule application of FB resulted in approximate to 90% double-labelled DRGn and Mn, indicating that DY and FB label similar populations of DRGn and Mn, and that insignificant DY fading occurred during this period. Inversing the order of application, however, i.e. nerve injection of FB followed immediately by capsule application of DY, resulted in double labelling in only approximate to 10% of the DRGn and Mn. These percentages increased to 70% of the DRGn and 60% of the Mn when the FB injection was followed 1 or 2 months after by the DY application, indicating that DY uptake is blocked by recent administration of FB. The results indicate that DY and FB might be useful for sequential labelling before and after nerve injury as a tool to investigate the accuracy of sensory and motor regeneration.