On the role of theory and modeling in neuroscience

In recent years, the field of neuroscience has gone through rapid experimental advances and extensive use of quantitative and computational methods. This accelerating growth has created a need for methodological analysis of the role of theory and the modeling approaches currently used in this field. Toward that end, we start from the general view that the primary role of science is to solve empirical problems, and that it does so by developing theories that can account for phenomena within their domain of application. We propose a commonly-used set of terms - descriptive, mechanistic, and normative - as methodological designations that refer to the kind of problem a theory is intended to solve. Further, we find that models of each kind play distinct roles in defining and bridging the multiple levels of abstraction necessary to account for any neuroscientific phenomenon. We then discuss how models play an important role to connect theory and experiment, and note the importance of well-defined translation functions between them. Furthermore, we describe how models themselves can be used as a form of experiment to test and develop theories. This report is the summary of a discussion initiated at the conference Present and Future Theoretical Frameworks in Neuroscience, which we hope will contribute to a much-needed discussion in the neuroscientific community

Conservation genetics of the annual hemiparasitic plant Melampyrum sylvaticum (Orobanchaceae) in the UK and Scandinavia

Melampyrum sylvaticum is an endangered annual hemiparasitic plant that is found in only 19 small and isolated populations in the United Kingdom (UK). To evaluate the genetic consequences of this patchy distribution we compared levels of diversity, inbreeding and differentiation from ten populations from the UK with eight relatively large populations from Sweden and Norway where the species is more continuously distributed. We demonstrate that in both the UK and Scandinavia, the species is highly inbreeding (global F IS = 0.899). Levels of population differentiation were high (F’ST = 0.892) and significantly higher amongst UK populations (F’ST = 0.949) than Scandinavian populations (F’ST = 0.762; P < 0.01). The isolated populations in the UK have, on average, lower genetic diversity (allelic richness, proportion of loci that are polymorphic, gene diversity) than Scandinavian populations, and this diversity difference is associated with the smaller census size and population area of UK populations. From a conservation perspective, the naturally inbreeding nature of the species may buffer the species against immediate effects of inbreeding depression, but the markedly lower levels of genetic diversity in UK populations may represent a genetic constraint to evolutionary change. In addition, the high levels of population differentiation suggest that gene flow among populations will not be effective at replenishing lost variation. We thus recommend supporting in situ conservation management with ex situ populations and human-mediated seed dispersal among selected populations in the UK

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14–8.23; P < 0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19–3.77; P = 0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08–3.47; P = 0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10–5.50; P = 0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30–0.72; P = 0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01–1.04; P < 0.001) and age (OR, 1.17; 95% CI, 1.08–1.26; P < 0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54–0.69) and a specificity of 0.63 (95% CI, 0.59–0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.Supplemental Table S1. Number of dogs included from each institution and years reviewed.Supplemental Table S2. Included breeds.Supplemental Table S3. Distribution of various reasons given for performing cholecystectomy in the 179 subclinical dogs with gallbladder mucocele (GBM).Supplemental Table S4. Distribution of clinical signs associated with systemic illness in 982 dogs with gallbladder mucocele.Supplemental Table S5. Distribution of reasons for death in-hospital (i.e. euthanized and died) in 179 dogs with gallbladder mucocele that underwent cholecystectomy.http://www.elsevier.com/locate/tvjlhj2020Companion Animal Clinical Studie

Reconciling the stratigraphy and depositional history of the Lycian orogen-top basins, SW Anatolia

Terrestrial fossil records from the SWAnatolian basins are crucial both for regional correlations and palaeoenvironmental reconstructions. By reassessing biostratigraphic constraints and incorporating new fossil data, we calibrated and reconstructed the late Neogene andQuaternary palaeoenvironments within a regional palaeogeographical framework. The culmination of the Taurides inSWAnatolia was followed by a regional crustal extension from the late Tortonian onwards that created a broad array of NE-trending orogen-top basins with synchronic associations of alluvial fan, fluvial and lacustrine deposits. The terrestrial basins are superimposed on the upper Burdigalian marine units with a c. 7 myr of hiatus that corresponds to a shift from regional shortening to extension. The initial infill of these basins is documented by a transition from marginal alluvial fans and axial fluvial systems into central shallow-perennial lakes coinciding with a climatic shift from warm/humid to arid conditions. The basal alluvial fan deposits abound in fossil macro-mammals of an early Turolian (MN11–12; late Tortonian) age. The Pliocene epoch in the region was punctuated by subhumid/humid conditions resulting in a rise of local base levels and expansion of lakes as evidenced by marsh-swamp deposits containing diverse fossilmammal assemblages indicating late Ruscinian (lateMN15; late Zanclean) ageWe are grateful for the support of the international bilateral project between The Scientific and Technological Research Council of Turkey (TUBITAK) and The Russian Scientific Foundation (RFBR) with grant a number of 111Y192. M.C.A. is grateful to the Turkish Academy of Sciences (TUBA) for a GEBIP (Young Scientist Award) grant. T.K. and S.M. are grateful to the Ege University Scientific Research Center for the TTM/002/2016 and TTM/001/2016 projects. M.C.A., H.A., S.M. and M.B. have obtained Martin and Temmick Fellowships at Naturalis Biodiversity Center (Leiden). F.A.D. is supported by a Mehmet Akif Ersoy University Scientific Research Grant. T.A.N. is supported by an Alexander-von-Humboldt Scholarship. L.H.O. received support from TUBITAK under the 2221 program for visiting scientists

BLSE hospitalière en France : comprendre pour contrôler

Extended-spectrum β-lactamases enterobacteria (ESBL-PE) have increasingly been reported in France and worldwide. Moreover, ESBL-PE dissemination is a problem in health care facilities and is associated with higher morbidity and mortality rates, as well as higher hospital costs. Currently, infection control measures are based on the respect of standard precautions for all patients (including hand hygiene) and the implementation of contact precaution for patients carrying multidrug-resistant organisms (MDROs) including ESBL-PE. The objective of this research project was to study the epidemiology of ESBL-PE, from transmission, acquisition, carriage to infection in French hospitals. Data for the project was obtained through local surveillance of ESBL-PE in a Parisian hospital and a cross-sectional survey of ESBL-PE carriage conducted in 2016. The first part of the study describes the evolution of methicillin-resistant Staphylococcus aureus (MRSA) and ESBL-PE acquisition in two intensive care units, using surveillance data between 1997 and 2015. Results showed that colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs. The second part of the study presents the results of a cross-sectional survey. We found that 17% of patients were digestive carrier of ESBL-PE, and most of them had not been previously identified as carrier. Greater age, recent travel abroad, exposition to antibiotics and prolonged hospitalization were associated with ESBL-PE carriage. These results suggest reinforcing standard precautions rather than contact precautions for controlling the spread of ESBL-PE. In the third part of the study concerning infection, from prospective surveillance of surgical wound infection following cardiac surgery, we determined risk factors for surgical wound infection with ESBL-PE: previous intensive care unit admission during the preceding 6 months, postoperative intensive care unit stay longer than 5 days, and being born outside France. Our results suggest that ESBL-PE should be considered for pre-emptive antibiotic therapy in patients with one of these risk factors. This work provides new insights into the hospital epidemiology of ESBL-PE in France, that might influence French infection control policies, by considering for instance to reinforce standard precautions rather than contact precautions.La situation épidémiologique des entérobactéries productrices de β-lactamases à spectre étendu (EBLSE) évolue rapidement en France et dans le monde. De plus, la dissémination des EBLSE est un problème dans les établissements de soins et occasionne une augmentation des taux de morbidité et de mortalité ainsi que des coûts associés aux soins. Actuellement, les mesures de prévention reposent sur le respect des précautions standard pour tous les patients (dont l’hygiène des mains) et la mise en place des précautions complémentaires contact pour les patients porteurs de bactéries multi-résistantes dont les EBLSE. Cette thèse a pour objectif d’améliorer les connaissances épidémiologiques sur les processus de dissémination, d’acquisition, de colonisation puis d’infection à EBLSE dans les hôpitaux français. Ce travail s’est appuyé sur des données de surveillance des EBLSE dans un hôpital parisien, et d’une enquête de prévalence de portage réalisée en 2016. Dans une première partie sur l’acquisition, à partir des données de surveillance des Staphylococcus aureus résistants à la méticilline (SARM) et des EBLSE entre 1997 et 2015 dans 2 réanimations, nous avons montré que la pression de colonisation impactait les acquisitions d’EBLSE mais pas de SARM. Ceci suggère que les mesures de prévention doivent être adaptées à la bactérie multi-résistante. Dans une deuxième partie sur l’étape de colonisation, à partir d’une enquête de prévalence, 17 % des patients étaient colonisés à EBLSE et la majorité n’était pas connue. Les facteurs de portage d’EBLSE étaient un âge supérieur à 65 ans, un retour de voyage à l’étranger récent, une exposition aux antibiotiques et une hospitalisation prolongée. Ce travail suggère qu’il est nécessaire de renforcer les précautions standard pour tous les patients afin de maitriser la diffusion des EBLSE. Dans une troisième partie sur l’étape d’infection, à partir des données de surveillance des infections sternales en chirurgie cardiaque, les facteurs d’infection à EBLSE étaient une admission en réanimation dans les 6 mois, une hospitalisation post-opératoire en réanimation prolongée et être né hors France. Ces résultats suggèrent que chez des patients présentant un de ces facteurs de risque, l’antibiothérapie préemptive devrait prendre en compte une infection à EBLSE. Ce travail de thèse offre un nouvel éclairage sur l’épidémiologie hospitalière des EBLSE en France. Ces données pourraient permettre de faire évoluer les recommandations françaises vers un renforcement des précautions standard aux dépens des précautions complémentaires contact

BLSE hospitalière en France : comprendre pour contrôler

Extended-spectrum β-lactamases enterobacteria (ESBL-PE) have increasingly been reported in France and worldwide. Moreover, ESBL-PE dissemination is a problem in health care facilities and is associated with higher morbidity and mortality rates, as well as higher hospital costs. Currently, infection control measures are based on the respect of standard precautions for all patients (including hand hygiene) and the implementation of contact precaution for patients carrying multidrug-resistant organisms (MDROs) including ESBL-PE. The objective of this research project was to study the epidemiology of ESBL-PE, from transmission, acquisition, carriage to infection in French hospitals. Data for the project was obtained through local surveillance of ESBL-PE in a Parisian hospital and a cross-sectional survey of ESBL-PE carriage conducted in 2016. The first part of the study describes the evolution of methicillin-resistant Staphylococcus aureus (MRSA) and ESBL-PE acquisition in two intensive care units, using surveillance data between 1997 and 2015. Results showed that colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs. The second part of the study presents the results of a cross-sectional survey. We found that 17% of patients were digestive carrier of ESBL-PE, and most of them had not been previously identified as carrier. Greater age, recent travel abroad, exposition to antibiotics and prolonged hospitalization were associated with ESBL-PE carriage. These results suggest reinforcing standard precautions rather than contact precautions for controlling the spread of ESBL-PE. In the third part of the study concerning infection, from prospective surveillance of surgical wound infection following cardiac surgery, we determined risk factors for surgical wound infection with ESBL-PE: previous intensive care unit admission during the preceding 6 months, postoperative intensive care unit stay longer than 5 days, and being born outside France. Our results suggest that ESBL-PE should be considered for pre-emptive antibiotic therapy in patients with one of these risk factors. This work provides new insights into the hospital epidemiology of ESBL-PE in France, that might influence French infection control policies, by considering for instance to reinforce standard precautions rather than contact precautions.La situation épidémiologique des entérobactéries productrices de β-lactamases à spectre étendu (EBLSE) évolue rapidement en France et dans le monde. De plus, la dissémination des EBLSE est un problème dans les établissements de soins et occasionne une augmentation des taux de morbidité et de mortalité ainsi que des coûts associés aux soins. Actuellement, les mesures de prévention reposent sur le respect des précautions standard pour tous les patients (dont l’hygiène des mains) et la mise en place des précautions complémentaires contact pour les patients porteurs de bactéries multi-résistantes dont les EBLSE. Cette thèse a pour objectif d’améliorer les connaissances épidémiologiques sur les processus de dissémination, d’acquisition, de colonisation puis d’infection à EBLSE dans les hôpitaux français. Ce travail s’est appuyé sur des données de surveillance des EBLSE dans un hôpital parisien, et d’une enquête de prévalence de portage réalisée en 2016. Dans une première partie sur l’acquisition, à partir des données de surveillance des Staphylococcus aureus résistants à la méticilline (SARM) et des EBLSE entre 1997 et 2015 dans 2 réanimations, nous avons montré que la pression de colonisation impactait les acquisitions d’EBLSE mais pas de SARM. Ceci suggère que les mesures de prévention doivent être adaptées à la bactérie multi-résistante. Dans une deuxième partie sur l’étape de colonisation, à partir d’une enquête de prévalence, 17 % des patients étaient colonisés à EBLSE et la majorité n’était pas connue. Les facteurs de portage d’EBLSE étaient un âge supérieur à 65 ans, un retour de voyage à l’étranger récent, une exposition aux antibiotiques et une hospitalisation prolongée. Ce travail suggère qu’il est nécessaire de renforcer les précautions standard pour tous les patients afin de maitriser la diffusion des EBLSE. Dans une troisième partie sur l’étape d’infection, à partir des données de surveillance des infections sternales en chirurgie cardiaque, les facteurs d’infection à EBLSE étaient une admission en réanimation dans les 6 mois, une hospitalisation post-opératoire en réanimation prolongée et être né hors France. Ces résultats suggèrent que chez des patients présentant un de ces facteurs de risque, l’antibiothérapie préemptive devrait prendre en compte une infection à EBLSE. Ce travail de thèse offre un nouvel éclairage sur l’épidémiologie hospitalière des EBLSE en France. Ces données pourraient permettre de faire évoluer les recommandations françaises vers un renforcement des précautions standard aux dépens des précautions complémentaires contact

ESBL in French hospitals : understanding in order to control

La situation épidémiologique des entérobactéries productrices de β-lactamases à spectre étendu (EBLSE) évolue rapidement en France et dans le monde. De plus, la dissémination des EBLSE est un problème dans les établissements de soins et occasionne une augmentation des taux de morbidité et de mortalité ainsi que des coûts associés aux soins. Actuellement, les mesures de prévention reposent sur le respect des précautions standard pour tous les patients (dont l’hygiène des mains) et la mise en place des précautions complémentaires contact pour les patients porteurs de bactéries multi-résistantes dont les EBLSE. Cette thèse a pour objectif d’améliorer les connaissances épidémiologiques sur les processus de dissémination, d’acquisition, de colonisation puis d’infection à EBLSE dans les hôpitaux français. Ce travail s’est appuyé sur des données de surveillance des EBLSE dans un hôpital parisien, et d’une enquête de prévalence de portage réalisée en 2016. Dans une première partie sur l’acquisition, à partir des données de surveillance des Staphylococcus aureus résistants à la méticilline (SARM) et des EBLSE entre 1997 et 2015 dans 2 réanimations, nous avons montré que la pression de colonisation impactait les acquisitions d’EBLSE mais pas de SARM. Ceci suggère que les mesures de prévention doivent être adaptées à la bactérie multi-résistante. Dans une deuxième partie sur l’étape de colonisation, à partir d’une enquête de prévalence, 17 % des patients étaient colonisés à EBLSE et la majorité n’était pas connue. Les facteurs de portage d’EBLSE étaient un âge supérieur à 65 ans, un retour de voyage à l’étranger récent, une exposition aux antibiotiques et une hospitalisation prolongée. Ce travail suggère qu’il est nécessaire de renforcer les précautions standard pour tous les patients afin de maitriser la diffusion des EBLSE. Dans une troisième partie sur l’étape d’infection, à partir des données de surveillance des infections sternales en chirurgie cardiaque, les facteurs d’infection à EBLSE étaient une admission en réanimation dans les 6 mois, une hospitalisation post-opératoire en réanimation prolongée et être né hors France. Ces résultats suggèrent que chez des patients présentant un de ces facteurs de risque, l’antibiothérapie préemptive devrait prendre en compte une infection à EBLSE. Ce travail de thèse offre un nouvel éclairage sur l’épidémiologie hospitalière des EBLSE en France. Ces données pourraient permettre de faire évoluer les recommandations françaises vers un renforcement des précautions standard aux dépens des précautions complémentaires contact.Extended-spectrum β-lactamases enterobacteria (ESBL-PE) have increasingly been reported in France and worldwide. Moreover, ESBL-PE dissemination is a problem in health care facilities and is associated with higher morbidity and mortality rates, as well as higher hospital costs. Currently, infection control measures are based on the respect of standard precautions for all patients (including hand hygiene) and the implementation of contact precaution for patients carrying multidrug-resistant organisms (MDROs) including ESBL-PE. The objective of this research project was to study the epidemiology of ESBL-PE, from transmission, acquisition, carriage to infection in French hospitals. Data for the project was obtained through local surveillance of ESBL-PE in a Parisian hospital and a cross-sectional survey of ESBL-PE carriage conducted in 2016. The first part of the study describes the evolution of methicillin-resistant Staphylococcus aureus (MRSA) and ESBL-PE acquisition in two intensive care units, using surveillance data between 1997 and 2015. Results showed that colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs. The second part of the study presents the results of a cross-sectional survey. We found that 17% of patients were digestive carrier of ESBL-PE, and most of them had not been previously identified as carrier. Greater age, recent travel abroad, exposition to antibiotics and prolonged hospitalization were associated with ESBL-PE carriage. These results suggest reinforcing standard precautions rather than contact precautions for controlling the spread of ESBL-PE. In the third part of the study concerning infection, from prospective surveillance of surgical wound infection following cardiac surgery, we determined risk factors for surgical wound infection with ESBL-PE: previous intensive care unit admission during the preceding 6 months, postoperative intensive care unit stay longer than 5 days, and being born outside France. Our results suggest that ESBL-PE should be considered for pre-emptive antibiotic therapy in patients with one of these risk factors. This work provides new insights into the hospital epidemiology of ESBL-PE in France, that might influence French infection control policies, by considering for instance to reinforce standard precautions rather than contact precautions

Influence de l'usage des fluoroquinolones sur l'acquisition de Staphylococcus aureus résistant à la méticilline

PARIS-BIUP (751062107) / SudocSudocFranceF