Genetic diversity of the Colombian Creole Sheep by using the single nucleotide polymorphisms (SNP) molecular marker

El estudio tuvo como objetivo caracterizar genéticamente la población de Ovinos Criollos de Pelo Colombiano (OCPC) de dos zonas geográficas del país, el Piedemonte Llanero (PDML) y los Valles Interandinos del Río Magdalena (VIRM). Se tomaron muestras de músculo para la extracción de ADN mediante la metodología fenol cloroformo isoamílico. El genotipado se hizo con el OvineSNP50 BeadChip Data Sheet. Los genotipos fueron analizados con el software PLINK v.1.9 en busca de relaciones de consanguinidad y parentesco. Los análisis estadísticos de los datos se realizaron con el uso de los paquetes “genepop” y “adegenet” del software R. Los resultados mostraron una heterocigosidad esperada de 0.374 para el OCPC, mientras que fue de 0.357 para la zona de PDML y de 0.396 para la zona de VIRM. Los valores para los parámetros del coeficiente de consanguinidad (Fis y Fit) fueron positivos para la población y las subpoblaciones, demostrando la existencia de consanguinidad. El valor para el Fst fue de 0.042 entre subpoblaciones definidas como zonas geográficas (p<0.001), lo que sugiere que la población analizada corresponda a dos grupos raciales. Esto es apoyado con el análisis de componentes principales donde se evidencia una tendencia de aislamiento entre los individuos para cada zona geográfica. En conclusión, se puede afirmar que, la diversidad genética de la población de Ovino Criollo de Pelo Colombiano, comparada con otras razas ovinas a nivel mundial, es elevada.The aim of this study was to genetically characterize the population of the Colombian Creole Hair Sheep (CCHS) from two geographical areas of the country, the Piedemonte Llanero (PDML) and the Interandine Valleys of the Magdalena River (VIRM). Muscle samples were taken and DNA was extracted using the phenol chloroform isoamyl methodology. Genotyping was done with the OvineSNP50 BeadChip Data Sheet. The genotypes were analysed with the PLINK v.1.9 software for relationships of consanguinity and kinship. Statistical analyses of the data were performed using the “genepop” and “adegenet” packages of the R software. The results showed an expected heterozygosity of 0.374 for the CCHS, while it was 0.357 for the PDML area and 0.396 for the VIRM zone. The values ​​for the parameters of the consanguinity coefficient (Fis and Fit) were positive for the population and subpopulations, proving the existence of consanguinity. The value for the Fst was 0.042 among subpopulations defined as geographical areas (p<0.001), which suggests that the population analysed corresponds to two breed groups. This is supported by the analysis of principal components where there is evidence of a tendency of isolation among individuals for each geographical area. In conclusion, it is valid to say that the genetic diversity of the population of Colombian Creole Hair Sheep, compared to other sheep breeds worldwide, is high

Factors and situations influencing the value of patient preference studies along the medical product lifecycle: a literature review

Industry, regulators, health technology assessment (HTA) bodies, and payers are exploring the use of patient preferences in their decision-making processes. In general, experience in conducting and assessing patient preference studies is limited. Here, we performed a systematic literature search and review to identify factors and situations influencing the value of patient preference studies, as well as applications throughout the medical product lifecyle. Factors and situations identified in 113 publications related to the organization, design, and conduct of studies, and to communication and use of results. Although current use of patient preferences is limited, we identified possible applications in discovery, clinical development, marketing authorization, HTA, and postmarketing phases. This study can inform different stakeholders on how to conduct, assess, and use patient preference studies and on when to include patient preference studies in development plans

Opportunities and challenges for the inclusion of patient preferences in the medical product life cycle: a systematic review

BACKGROUND: The inclusion of patient preferences (PP) in the medical product life cycle is a topic of growing interest to stakeholders such as academics, Health Technology Assessment (HTA) bodies, reimbursement agencies, industry, patients, physicians and regulators. This review aimed to understand the potential roles, reasons for using PP and the expectations, concerns and requirements associated with PP in industry processes, regulatory benefit-risk assessment (BRA) and marketing authorization (MA), and HTA and reimbursement decision-making. METHODS: A systematic review of peer-reviewed and grey literature published between January 2011 and March 2018 was performed. Consulted databases were EconLit, Embase, Guidelines International Network, PsycINFO and PubMed. A two-step strategy was used to select literature. Literature was analyzed using NVivo (QSR international). RESULTS: From 1015 initially identified documents, 72 were included. Most were written from an academic perspective (61%) and focused on PP in BRA/MA and/or HTA/reimbursement (73%). Using PP to improve understanding of patients' valuations of treatment outcomes, patients' benefit-risk trade-offs and preference heterogeneity were roles identified in all three decision-making contexts. Reasons for using PP relate to the unique insights and position of patients and the positive effect of including PP on the quality of the decision-making process. Concerns shared across decision-making contexts included methodological questions concerning the validity, reliability and cognitive burden of preference methods. In order to use PP, general, operational and quality requirements were identified, including recognition of the importance of PP and ensuring patient understanding in PP studies. CONCLUSIONS: Despite the array of opportunities and added value of using PP throughout the different steps of the MPLC identified in this review, their inclusion in decision-making is hampered by methodological challenges and lack of specific guidance on how to tackle these challenges when undertaking PP studies. To support the development of such guidance, more best practice PP studies and PP studies investigating the methodological issues identified in this review are critically needed

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Du FOU au FLA à l’Université française ou de la pédagogie universitaire à l’écrit scientifique spécialisé

International audienc

Entre présence et distance : enseigner et apprendre les langues à l’université à l’ère numérique

International audienceBien avant que la crise sanitaire de la COVID-19 ne vienne bouleverser les pratiques d’enseignement et d’apprentissage en forçant la dématérialisation des dispositifs, le Pôle d'Élaboration de Ressources Linguistiques (PERL) de la ComUE USPC, en précurseur, avait déjà exploré les territoires du numérique dans le cadre de l’enseignement-apprentissage des langues à l’Université. Ainsi, ces recherches réalisées avant la crise, loin d’être dépassées, offrent au contraire des clefs qui peuvent s’avérer précieuses maintenant que l’hybridation a rompu certains plafonds de verre.L’injonction institutionnelle à la nouveauté, si fréquente qu’elle s’apparente dans le champ éducatif à une « tradition de l’innovation » (Castellotti, Debono & Huver, 2017), touche particulièrement les universités. Si toutes les disciplines sont touchées, l’enseignement des langues constitue un terrain de prédilection, que ce soit dans les départements de langue, dans les Centres de ressources linguistiques, ou dans l’enseignement des langues pour spécialistes d’autres disciplines (LANSAD). Ce dernier secteur constitue depuis sa généralisation, dans la droite ligne des réformes Licence Master Doctorat (LMD), un terrain privilégié pour les innovations pédagogiques (Poteaux, 2014 ; Demaizière et Grosbois, 2014). Le LANSAD y est d’autant plus propice que son développement s’accompagne d’une forte volonté de mettre les outils technologiques au service de l’enseignement des et en langues additionnelles. Comment alors intégrer, à des degrés adaptés, le numérique à l’enseignement-apprentissage des langues-cultures, afin que chacun des acteurs de l’écosystème universitaire - l'institution, l’enseignant et/ou le tuteur et l’apprenant - en tire bénéfice ?Alors que « le confinement et l’éloignement des lieux de formation [...] a contraints [les enseignants du supérieur] à construire de nouvelles stratégies, de nouveaux dispositifs, un nouvel “environnement personnel d’enseignement et d’apprentissage” » (Audran et al., 2021 : §29), cet ouvrage bien que renvoyant à des recherches pré-pandémiques démontre son caractère contemporain. En effet, parmi “les enjeux et défis” (Koecher et Gettliffe, 2021) auxquels doivent répondre les enseignants aujourdhui, le numéro répond à un questionnement d’actualité puisqu’il vise à interroger, à travers les recherches et expérimentations pédagogiques d’enseignants-chercheurs de différentes langues étrangères les modalités et les enjeux liés à la restructuration pédagogique dans la formation en langues étrangères à l’université. Nous cherchons en effet à mieux comprendre à travers des articles à la fois épistémologiques et issus d’expérimentations comment favoriser le développement langagier et comment se former dans la société du numérique. C’est un enjeu encore plus essentiel après la crise sanitaire et la dématérialisation de tout ou partie des cursus universitaires, afin de contribuer à une réflexion critique sur la pédagogie des langues à l’Université ainsi qu’à la formation des enseignants-tuteurs en charge de ces formation

Effects of the Antidepressant Amitriptyline on Juvenile Brown Trout and Their Modulation by Microplastics

Pharmaceuticals such as antidepressants are designed to be bioactive at low concentrations. According to their mode of action, they can also influence non-target organisms due to the phylogenetic conservation of molecular targets. In addition to the pollution by environmental chemicals, the topic of microplastics (MP) in the aquatic environment came into the focus of scientific and public interest. The aim of the present study was to investigate the influence of the antidepressant amitriptyline in the presence and absence of irregularly shaped polystyrene MP as well as the effects of MP alone on juvenile brown trout (Salmo trutta f. fario). Fish were exposed to different concentrations of amitriptyline (nominal concentrations between 1 and 1000 &micro;g/L) and two concentrations of MP (104 and 105 particles/L; &lt;50 &micro;m) for three weeks. Tissue cortisol concentration, oxidative stress, and the activity of two carboxylesterases and of acetylcholinesterase were assessed. Furthermore, the swimming behavior was analyzed in situations with different stress levels. Exposure to amitriptyline altered the behavior and increased the activity of acetylcholinesterase. Moreover, nominal amitriptyline concentrations above 300 &micro;g/L caused severe acute adverse effects in fish. MP alone did not affect any of the investigated endpoints. Co-exposure caused largely similar effects such as the exposure to solely amitriptyline. However, the effect of amitriptyline on the swimming behavior during the experiment was alleviated by the higher MP concentration

Factors and Situations Affecting the Value of Patient Preference Studies : Semi-Structured Interviews in Europe and the US

Objectives: Patient preference information (PPI) is gaining recognition among the pharmaceutical industry, regulatory authorities, and health technology assessment (HTA) bodies/payers for use in assessments and decision-making along the medical product lifecycle (MPLC). This study aimed to identify factors and situations that influence the value of patient preference studies (PPS) in decision-making along the MPLC according to different stakeholders. Methods: Semi-structured interviews (n = 143) were conducted with six different stakeholder groups (physicians, academics, industry representatives, regulators, HTA/payer representatives, and a combined group of patients, caregivers, and patient representatives) from seven European countries (the United Kingdom, Sweden, Italy, Romania, Germany, France, and the Netherlands) and the United States. Framework analysis was performed using NVivo 11 software. Results: Fifteen factors affecting the value of PPS in the MPLC were identified. These are related to: study organization (expertise, financial resources, study duration, ethics and good practices, patient centeredness), study design (examining patient and/or other preferences, ensuring representativeness, matching method to research question, matching method to MPLC stage, validity and reliability, cognitive burden, patient education, attribute development), and study conduct (patients’ ability/willingness to participate and preference heterogeneity). Three types of situations affecting the use of PPS results were identified (stakeholder acceptance, market situations, and clinical situations). Conclusion: The factors and situation types affecting the value of PPS, as identified in this study, need to be considered when designing and conducting PPS in order to promote the integration of PPI into decision-making along the MPLC.IMI-PREFE

Design, Conduct, and Use of Patient Preference Studies in the Medical Product Life Cycle : A Multi-Method Study

Objectives: To investigate stakeholder perspectives on how patient preference studies (PPS) should be designed and conducted to allow for inclusion of patient preferences in decision-making along the medical product life cycle (MPLC), and how patient preferences can be used in such decision-making. Methods: Two literature reviews and semi-structured interviews (n = 143) with healthcare stakeholders in Europe and the US were conducted; results of these informed the design of focus group guides. Eight focus groups were conducted with European patients, industry representatives and regulators, and with US regulators and European/Canadian health technology assessment (HTA) representatives. Focus groups were analyzed thematically using NVivo. Results: Stakeholder perspectives on how PPS should be designed and conducted were as follows: 1) study design should be informed by the research questions and patient population; 2) preferred treatment attributes and levels, as well as trade-offs among attributes and levels should be investigated; 3) the patient sample and method should match the MPLC phase; 4) different stakeholders should collaborate; and 5) results from PPS should be shared with relevant stakeholders. The value of patient preferences in decision-making was found to increase with the level of patient preference sensitivity of decisions on medical products. Stakeholders mentioned that patient preferences are hardly used in current decision-making. Potential applications for patient preferences across industry, regulatory and HTA processes were identified. Four applications seemed most promising for systematic integration of patient preferences: 1) benefit-risk assessment by industry and regulators at the marketing-authorization phase; 2) assessment of major contribution to patient care by European regulators; 3) cost-effectiveness analysis; and 4) multi criteria decision analysis in HTA. Conclusions: The value of patient preferences for decision-making depends on the level of collaboration across stakeholders; the match between the research question, MPLC phase, sample, and preference method used in PPS; and the sensitivity of the decision regarding a medical product to patient preferences. Promising applications for patient preferences should be further explored with stakeholders to optimize their inclusion in decision-making.Jorien Veldwijk and Isabelle Huys share last authorship.IMI-PREFE