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Exploring the Current Practices,Costs and Benefits of FAIR Implementation in Pharmaceutical Research and Development:A Qualitative Interview Study

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Data Intelligence 2021年第4期3卷 507-527页

作者： Ebtisam Alharbi Rigina Skeva Nick Juty caroline Jay Carole Goble School of Computer Science University of ManchesterManchesterManchester M139PLUK College of Computer and Information Systems Umm Al-Qura UniversityMeccaMakkah 21421Saudi Arabia

The findable,accessible,interoperable,reusable(FAIR)principles for scientific data management and stewardship aim to facilitate data reuse at scale by both humans and *** and development(R&D)in the pharmaceutical industry is becoming increasingly data driven,but managing its data assets according to FAIR principles remains costly and *** date,little scientific evidence exists about how FAIR is currently implemented in practice,what its associated costs and benefits are,and how decisions are made about the retrospective FAIRification of data sets in pharmaceutical R&*** paper reports the results of semi-structured interviews with 14 pharmaceutical professionals who participate in various stages of drug R&D in seven pharmaceutical *** thematic analysis identified three primary themes of the benefits and costs of FAIRification,and the elements that influence the decision-making process for FAIRifying legacy data *** collectively acknowledged the potential contribution of FAIRification to data reusability in diverse research domains and the subsequent potential for *** costs,however,were still considered a barrier by participants,with the need for considerable expenditure in terms of resources,and cultural *** decisions were made about FAIRification was influenced by legal and ethical considerations,management commitment,and data *** findings have significant implications for those in the pharmaceutical R&D industry who are engaged in driving FAIR implementation,and for external parties who seek to better understand existing practices and challenges.

关键词： FAIR FAIRification Retrospective FAIRification Pharmaceutical R&D Cost-benefit Decision-making process

Pricing formulae for derivatives in insurance using Malliavin calculus

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Probability, Uncertainty and Quantitative Risk 2018年第1期3卷 210-228页

作者： caroline Hillairet Ying Jiao Anthony Reveillac ENSAE Universite Paris Saclay CREST5 avenue Henry Le Chatelier91120 PalaiseauFrance Universite Claude Bernard-Lyon1 Institutde Science Financiere et d’Assurances69007 Lyon France INSA de Toulouse IMT UMR CNRS 5219Universite de Toulouse135 avenue de Rangueil 31077 Toulouse Cedex 4 France

In this paper,we provide a valuation formula for different classes of actuar-ial and financial contracts which depend on a general loss process by using Malliavin *** to the celebrated Black-Scholes formula,we aim to express the expected cash flow in terms of a building *** former is related to the loss process which is a cumulated sum indexed by a doubly stochastic Poisson process of claims allowed to be dependent on the intensity and the jump times of the count-ing *** example,in the context of stop-loss contracts,the building block is given by the distribution function of the terminal cumulated loss taken at the Value at Risk when computing the expected shortfall risk measure.

关键词： Cox processes Pricing formulae Insurance derivatives Malliavincalculus

Liver biopsy in a district general hospital:Changes over two decades

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World Journal of Gastroenterology 2007年第40期13卷 5336-5342页

作者： Wing-Kin Syn caroline Bruckner-Holt Adam Farmer Sarah Howdle Jeffrey Bateman Liver and Hepatobiliary Unit Queen Elizabeth HospitalBirminghamB 15 2THUnited Kingdom Department of Gastroenterology Princess Royal HospitalTelfordUnited Kingdom Department of Gastroenterology City HospitalBirminghamUnited Kingdom Department of Radiology Princess Royal HospitalYelfordUnited Kingdom

AIM： To study liver biopsy practice over two decades in a district general hospital in the United Kingdom.METHODS： We identified all patients who had at least one liver biopsy between 1986 and 2006 from the databases of the radiology and gastroenterology departments. Subjects with incomplete clinical data were excluded from the study.RESULTS： A total of 103 liver biopsies were performed. Clinical data was available for 88 patients, with 95 biopsies. Between 1986 and 1996, 18 （95%） out of the 19 liver biopsies performed were blind and 6 （33%） were for primary biliary cirrhosis. Between 1996 and 2006, 14 （18%） out of 76 biopsies were blind; and the indications were abnormal liver tests （33%）, hepatitis C （12%） and targeted-biopsies （11%）. Liver biopsies were unhelpful in 5 （50） subjects. Pain was the most common complication of liver biopsy （5%）. No biopsy-related mortality was reported. There was a trend towards more technical failures and complications with the blind biopsy technique.CONCLUSION： Liver biopsies performed in small district hospitals are safe and useful for diagnostic and staging purposes. Abnormal liver tests, non-alcoholic fatty liver disease and targeted biopsies are increasingly common indications. Ultrasound-guided liver biopsies are now the preferred method and are associated with fewer complications.

关键词： Complication District general Indication Liver biopsy Non-alcoholic fatty liver

Oxidative stress physiology in relation to life history traits of a free-living vertebrate:the spotted snow skink,Niveoscincus ocellatus

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Integrative Zoology 2011年第2期6卷 140-149页

作者： caroline ISAKSSON Geoffrey M.WHILE Mats OLSSON Jan KOMDEUR Erik WAPSTRA University of Groningen Animal Ecology GroupHarenThe Netherlands University of Wollongong School of Biological SciencesWollongongNew South Wales University of Tasmania School of ZoologyHobartTasmaniaAustralia

Recent research suggests that oxidative stress,via its links to metabolism and senescence,is a key mechanism linking life history traits such as fecundity and growth with survival;however,this has rarely been put under empirical scrutiny within free-living *** a wild population of live-bearing skinks,we explored how plasma antioxidant activity(OXY),reactive oxidative metabolites(ROM),and the estimated oxidative stress index are associated with female and male life *** found that male skinks have a significantly higher ROM and estimated oxidative stress index than female skinks,but this was not accompanied by a sex difference in *** sexes showed a non-linear association between OXY and age,indicating that the oldest and youngest individuals had the lowest ***,female skinks with high OXY showed a decreased probability of survival to the following ***,we found no significant associations between female reproductive investment(litter size or litter mass)or parturition date(***)and oxidative ***,our results offer mixed support for a role of oxidative stress in mediating life history traits and suggest that future studies need to explore oxidative stress during vitellogenesis in addition to using an intra-individual approach to understand the cost of reproduction and patterns of aging.

关键词： antioxidants life history Niveoscincus ocellatus oxidative stress reptile

Early detection and prevention of pancreatic cancer:Is it really possible today?

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World Journal of Gastroenterology 2014年第34期20卷 12118-12131页

作者： Marco Del Chiaro Ralf Segersvrd Matthias Lohr caroline Verbeke Division of Surgery Department of Clinical ScienceIntervention and Technology (CLINTEC)Karolinska Institute141 86 StockholmSweden Division of Pathology Department of Laboratory MedicineKarolinska Institute141 86 StockholmSweden

Pancreatic cancer is the 4th leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established. In particular, individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5- to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer. The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery. Considering the risk associated with pancreatic surgery, the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals, but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms, or early cancer. Currently, results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions, nor do they define the outcome of the surgical treatment of these lesions. For this reason, surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial. However, the acquisition of a deeper understanding of this complex area, together with the increasing request for screening and treatment by individuals at risk, will usher pancreatologists into a new era of preemptive pancreatic surgery. Along with the growing demand to treat individuals with precancerous lesions, the need for low-risk investigation, low-morbidity operation and a minimally invasive approach becomes increasingly pressing. All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.

关键词： Preemptive pancreatic surgery Cystic tumors of the pancreas Familial pancreatic cancer Early detection Pancreas cancer screening

The Challenging Place of Natural Hazards in Disaster Risk Reduction Conceptual Models:Insights from Central Africa and the European Alps

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International Journal of Disaster Risk Science 2020年第3期11卷 316-332页

作者： caroline Michellier Patrick Pigeon André Paillet Théodore Trefon Olivier Dewitte Francois Kervyn Natural Hazards Service Royal Museum for Central Africa3080 TervurenBelgium EDYTEM Laboratory Universite de Savoie-Mont-Blanc73376 Le Bourget du lacFrance Geodynamics and Mineral Resources Service Royal Museum for Central Africa3080 TervurenBelgium

Based on a literature review and two case studies,this article presents the difficulties inherent in the main disaster risk reduction conceptual *** method used to highlight such evidence is to compare two programs on disaster risk reduction with mainstream conceptual *** authors participated in these programs,which were confronted with the need to integrate contributions and insights from both earth and social *** analysis found that the existing main conceptual models were unable to do justice to disaster risk reduction *** finding encouraged us to critique these *** effort led us to present possible solutions to compensate for the shortcomings of current models while taking into account the contextualization and dynamics of phenomena,as well as grappling with the more explicit integration of hazards and hazard risk into model design.

关键词： Central Africa Conceptual models Disaster risk reduction Natural hazards Northern French Alps

Human viral pathogens are pervasive in wastewater treatment center aerosols

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Journal of Environmental Sciences 2018年第5期30卷 45-53页

作者： Evelyne Brisebois Marc Veillette Vanessa Dion-Dupont Jacques Lavoie Jacques Corbeil AlexANDer Culley caroline Duchaine Universite Laval Pavillon Alexandre Vachon1045ave de la MedecineQuebecQC GIVOA6Canada CRIUCPQ 2725 Chemin Sainte-FoyQuebecQC GIV 4G5Canada IRSST 505 Boulevard de Maisonneuve OMontréalQCH3A 3C2Canada CRCHU 2705 Boulevard LaurierRC-709QuébecQCG1V 4G2Canada

Wastewater treatment center（WTC） workers may be vulnerable to diseases caused by viruses, such as the common cold, influenza and gastro-intestinal infections. Although there is a substantial body of literature characterizing the microbial community found in wastewater, only a few studies have characterized the viral component of WTC aerosols,despite the fact that most diseases affecting WTC workers are of viral origin and that some of these viruses are transmitted through the air. In this study, we evaluated in four WTCs the presence of 11 viral pathogens of particular concern in this milieu and used a metagenomic approach to characterize the total viral community in the air of one of those WTCs. The presence of viruses in aerosols in different locations of individual WTCs was evaluated and the results obtained with four commonly used air samplers were *** detected four of the eleven viruses tested, including human adenovirus（h Ad V）,rotavirus, hepatitis A virus（HAV） and Herpes Simplex virus type 1（HSV1）. The results of the metagenomic assay uncovered very few viral RNA sequences in WTC aerosols, however sequences from human DNA viruses were in much greater relative abundance.

关键词： Airborne viruses Air sampling Wastewater treatment plants Viral metagenomics

Erlotinib inhibits progression to dysplasia in a colitis-associated colon cancer model

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World Journal of Gastroenterology 2011年第44期17卷 4858-4866页

作者： Beatriz Pagán Angel A Isidro Myrella L Cruz Domenico Coppola caroline B Appleyard Department of Physiology and Pharmacology Ponce School of Medicine Department of Anatomic Pathology H.Lee Moffitt Cancer Center and Research Institute

AIM:To investigate the role of epidermal growth factor receptor(EGFR) in colitis-associated dysplasia using the EGFR tyrosine kinase inhibitor ***:Sprague-Dawley rats received trinitrobenzene sulfonic acid(TNBS;30 mg in 50% ethanol,ic),followed 6 wk later by reactivation with TNBS(5 mg/kg,iv) for 3 *** induce colitis-associated dysplasia,rats then received TNBS(iv) twice a week for 10 *** group received erlotinib(10 mg/kg,ip) for 1 wk before the start of the reactivation of the colitis and 2 wk after(21 d);the rest received the *** rats were euthanized,the colons were removed and analyzed for damage and expression of the EGFR downstream effectors Erk1/2 and ***:Ninety percent of the vehicle-treated animals had dysplasia in any region of the ***-treated animals had a significant decrease in the incidence of dysplasia compared to vehicle-treated animals in all regions of the colon(50.00% ± 11.47% vs 90.00% ± 10.00% in proximal,P < 0.05;15.00% ± 8.19% vs 50.00% ± 16.67% in mid,P < 0.05;and 20.00% ± 9.17% vs 70.00% ± 15.28% in distal,P < 0.01).Erlotinib-treated animals also had reduced cell proliferation,reduced active Erk1/2,and reduced c-Myc in colon epithelium compared with the vehicle-treated *** vitro,erlotinib treatment was shown to markedly decrease c-Myc and pErk1/2 levels in rat epithelial *** of rat epithelial cells was stimulated by epidermal growth factor and inhibited by erlotinib(P < 0.05).CONCLUSION:Erlotinib can decrease the development of colitis-associated dysplasia,suggesting a potential therapeutic use for erlotinib in patients with long-standing colitis.

关键词： Animal model Epidermal growth factor receptor Colitis Dysplasia Erlotinib

Vitellogenin expression in the oilseed rape pest Meligethes aeneus

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Insect Science 2019年第2期26卷 274-282页

作者： caroline Kaiser Christina Lazaridou Karl-Martin Vagn Jen sen Rodrigo Labouriau Michael Kristenseni Department of Agroecology Aarhus University Slagelse Denmark Department of Agricultural Technology Alexander Technological Educational Institute of Thessaloniki Thessaloniki Greece Department of Mathematics Aarhus University Aarhus C Denmark

When investigating insecticide resistance of pest insects, for example, the pollen beetle Meligethes aeneus, it is relevant to differentiate toxicological and molecular genetic data between male and female specimens. A molecular sex determination method would allow resistance testing to be run without prior sorting of the samples. A one-step quantitative RT-PCR method for quantification of the yolk protein vitellogenin expression in the pollen beetle was established. The expression level of vitellogenin relative to tubulin was determined. Pollen beetles were tested at different time points during their development to determine if vitellogenin is a reliable molecular marker for detection of sexually mature females. The differentiation between females and males by relative expression of vitellogenin to tubulin is conditional regarding the life cycle. Sexually mature females and males could easily be distinguished, whereas immature specimens could not be seperated. Vitellogenin expression is a successful marker for identification of sexually mature pollen beetles. Females from the spring populations showed vitellogenin expression when the temperature was above 10.2°C. Further, detailed observations of vitellogenin throughout the spring indicated a strong relationship between daily temperatures and vitellogenin expression, which is an indicator of oviposition ability.

关键词： Brassicogethes aeneus egg yolk protein gene expression oilseed rape oviposition pollen beetle qRT-PCR