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91.
Mia C. Hikke Stine Braaen Stephane Villoing Kjartan Hodneland Corinne Geertsema Lisa Verhagen Petter Frost Just M. Vlak Espen Rimstad Gorben P. Pijlman 《Vaccine》2014
Salmonid alphavirus (SAV; also known as Salmon pancreas disease virus; family Togaviridae) causes pancreas disease and sleeping disease in Atlantic salmon and rainbow trout, respectively, and poses a major burden to the aquaculture industry. SAV infection in vivo is temperature-restricted and progeny virus is only produced at low temperatures (10–15 °C). Using engineered SAV replicons we show that viral RNA replication is not temperature-restricted suggesting that the viral structural proteins determine low-temperature dependency. The processing/trafficking of SAV glycoproteins E1 and E2 as a function of temperature was investigated via baculovirus vectors in Sf9 insect cells and by transfection of CHSE-214 fish cells with DNA constructs expressing E1 and E2. We identified SAV E2 as the temperature determinant by demonstrating that membrane trafficking and surface expression of E2 occurs only at low temperature and only in the presence of E1. Finally, a vaccination-challenge model in Atlantic salmon demonstrates the biological significance of our findings and shows that SAV replicon DNA vaccines encoding E2 elicit protective immunity only when E1 is co-expressed. This is the first study that identifies E2 as the critical determinant of SAV low-temperature dependent virion formation and defines the prerequisites for induction of a potent immune response in Atlantic salmon by DNA vaccination. 相似文献
92.
Harold M. Hudson Serigne N. Lô R. John Simes Andrew M. Tonkin Stephane Heritier 《Statistics in medicine》2014,33(10):1621-1645
Transform methods have proved effective for networks describing a progression of events. In semi‐Markov networks, we calculated the transform of time to a terminating event from corresponding transforms of intermediate steps. Saddlepoint inversion then provided survival and hazard functions, which integrated, and fully utilised, the network data. However, the presence of censored data introduces significant difficulties for these methods. Many participants in controlled trials commonly remain event‐free at study completion, a consequence of the limited period of follow‐up specified in the trial design. Transforms are not estimable using nonparametric methods in states with survival truncated by end‐of‐study censoring. We propose the use of parametric models specifying residual survival to next event. As a simple approach to extrapolation with competing alternative states, we imposed a proportional incidence (constant relative hazard) assumption beyond the range of study data. No proportional hazards assumptions are necessary for inferences concerning time to endpoint; indeed, estimation of survival and hazard functions can proceed in a single study arm. We demonstrate feasibility and efficiency of transform inversion in a large randomised controlled trial of cholesterol‐lowering therapy, the Long‐Term Intervention with Pravastatin in Ischaemic Disease study. Transform inversion integrates information available in components of multistate models: estimates of transition probabilities and empirical survival distributions. As a by‐product, it provides some ability to forecast survival and hazard functions forward, beyond the time horizon of available follow‐up. Functionals of survival and hazard functions provide inference, which proves sharper than that of log‐rank and related methods for survival comparisons ignoring intermediate events. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
93.
Yasser Khazaal Mathias van Singer Anne Chatton Sophia Achab Daniele Zullino Stephane Rothen Riaz Khan Joel Billieux Gabriel Thorens 《Journal of medical Internet research》2014,16(7)
Background
The number of medical studies performed through online surveys has increased dramatically in recent years. Despite their numerous advantages (eg, sample size, facilitated access to individuals presenting stigmatizing issues), selection bias may exist in online surveys. However, evidence on the representativeness of self-selected samples in online studies is patchy.Objective
Our objective was to explore the representativeness of a self-selected sample of online gamers using online players’ virtual characters (avatars).Methods
All avatars belonged to individuals playing World of Warcraft (WoW), currently the most widely used online game. Avatars’ characteristics were defined using various games’ scores, reported on the WoW’s official website, and two self-selected samples from previous studies were compared with a randomly selected sample of avatars.Results
We used scores linked to 1240 avatars (762 from the self-selected samples and 478 from the random sample). The two self-selected samples of avatars had higher scores on most of the assessed variables (except for guild membership and exploration). Furthermore, some guilds were overrepresented in the self-selected samples.Conclusions
Our results suggest that more proficient players or players more involved in the game may be more likely to participate in online surveys. Caution is needed in the interpretation of studies based on online surveys that used a self-selection recruitment procedure. Epidemiological evidence on the reduced representativeness of sample of online surveys is warranted. 相似文献94.
95.
The US Food and Drug Administration developed the Breakthrough Therapy designation to expedite the development and review of drugs that show a clear advantage over available therapy for serious conditions. Prior research has shown that physicians tend to misunderstand that a drug may receive a Breakthrough Therapy designation based on preliminary clinical evidence (eg, effect on a surrogate endpoint or intermediate clinical endpoint that is likely to predict clinical benefit). The objective of this article is to examine whether physicians’ familiarity with and interpretation of the Breakthrough Therapy designation have changed since a survey on the topic was published in 2016. We replicated three of the questions in that study and explored beliefs that a Breakthrough Therapy designation automatically qualifies a drug for accelerated approval. We also draw comparisons by specialization (oncologists vs. primary care physicians). In general, physicians remain more likely than not to misunderstand the Breakthrough Therapy designation. 相似文献
96.
97.
Michael T. Barbe MD Lisa Tonder MS Paul Krack MD PhD Bettina Debû MD Michael Schüpbach MD Steffen Paschen MD Till A. Dembek MD Andrea A. Kühn MD Valerie Fraix MD Christine Brefel-Courbon MD PhD Lars Wojtecki MD PhD David Maltête MD PhD Phillippe Damier MD PhD Friederike Sixel-Döring MD Daniel Weiss MD Marcus Pinsker MD PhD Tatiana Witjas MD PhD Stephane Thobois MD PhD Carmen Schade-Brittinger B.Sc Jörn Rau MSc Jean-Luc Houeto MD PhD Andreas Hartmann MD PhD Lars Timmermann MD PhD Alfons Schnitzler MD PhD Valerie Stoker MPH Marie Vidailhet MD PhD Günther Deuschl MD PhD for the EARLYSTIM study group 《Movement disorders》2020,35(1):82-90
98.
Nadya Pyatigorskaya MD Michael Sharman PhD Jean‐Christophe Corvol MD PhD Romain Valabregue PhD Lydia Yahia‐Cherif PhD Fabrice Poupon PhD Florence Cormier‐Dequaire MD Hartwig Siebner Stephan Klebe MD PhD Marie Vidailhet MD Alexis Brice MD PhD Stephane Lehéricy MD PhD 《Movement disorders》2015,30(8):1077-1084
99.
Expert consensus document on arterial stiffness: methodological issues and clinical applications. 总被引:25,自引:0,他引:25
Stephane Laurent John Cockcroft Luc Van Bortel Pierre Boutouyrie Cristina Giannattasio Daniel Hayoz Bruno Pannier Charalambos Vlachopoulos Ian Wilkinson Harry Struijker-Boudier 《European heart journal》2006,27(21):2588-2605
In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area. 相似文献
100.
Validation of the HFA‐PEFF score for the diagnosis of heart failure with preserved ejection fraction