A modelling framework for the prediction of the herd-level probability of infection from longitudinal data

International audienceThe collective control programmes (CPs) that exist for many infectious diseases of farm animals rely on the application of diagnostic testing at regular time intervals for the identification of infected animals or herds. The diversity of these CPs complicates the trade of animals between regions or countries because the definition of freedom from infection differs from one CP to another. In this paper, we describe a statistical model for the prediction of herd-level probabilities of infection from longitudinal data collected as part of CPs against infectious diseases of cattle. The model was applied to data collected as part of a CP against bovine viral diarrhoea virus (BVDV) infection in Loire-Atlantique, France. The model represents infection as a herd latent status with a monthly dynamics. This latent status determines test results through test sensitivity and test specificity. The probability of becoming status positive between consecutive months is modelled as a function of risk factors (when available) using logistic regression. Modelling is performed in a Bayesian framework, using either Stan or JAGS. Prior distributions need to be provided for the sensitivities and specificities of the different tests used, for the probability of remaining status positive between months as well as for the probability of becoming positive between months. When risk factors are available, prior distributions need to be provided for the coefficients of the logistic regression, replacing the prior for the probability of becoming positive. From these prior distributions and from the longitudinal data, the model returns posterior probability distributions for being status positive for all herds on the current month. Data from the previous months are used for parameter estimation. The impact of using different prior distributions and model implementations on parameter estimation was evaluated. The main advantage of this model is its ability to predict a probability of being status positive in a month from inputs that can vary in terms of nature of test, frequency of testing and risk factor availability/presence. The main challenge in applying the model to the BVDV CP data was in identifying prior distributions, especially for test characteristics, that corresponded to the latent status of interest, i.e. herds with at least one persistently infected (PI) animal. The model is available on Github as an R package (https://github.com/AurMad/STOCfree) and can be used to carry out output-based evaluation of disease CPs

Analysing algorithms and data sources for the tissue-specific reconstruction of liver healthy and cancer cells

Genome-Scale Metabolic Models (GSMMs), mathematical representations of the cell metabolism in different organisms including humans, are resourceful tools to simulate metabolic phenotypes and understand associated diseases, such as obesity, diabetes and cancer. In the last years, different algorithms have been developed to generate tissue-specific metabolic models that simulate different phenotypes for distinct cell types. Hepatocyte cells are one of the main sites of metabolic conversions, mainly due to their diverse physiological functions. Most of the liver's tissue is formed by hepatocytes, being one of the largest and most important organs regarding its biological functions. Hepatocellular carcinoma is, also, one of the most important human cancers with high mortality rates. In this study, we will analyze four different algorithms (MBA, mCADRE, tINIT and FASTCORE) for tissue-specific model reconstruction, based on a template model and two types of data sources: transcriptomics and proteomics. These methods will be applied to the reconstruction of metabolic models for hepatocyte cells and HepG2 cancer cell line. The models will be analyzed and compared under different perspectives, emphasizing their functional analysis considering a set of metabolic liver tasks. The results show that there is no ``ideal'' algorithm. However, with the current analysis, we were able to retrieve knowledge about the metabolism of the liver.This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER-006684), BioTecNorte operation (NORTE01-0145-FEDER-000004) and Search-ON2: Revitalization of HPC infrastructure of UMinho, (NORTE-07-0162-FEDER-000086), all funded by European Regional Development Fund under the scope of Norte2020—Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition

Vampires in the village Žrnovo on the island of Korčula: following an archival document from the 18th century

Središnja tema rada usmjerena je na raščlambu spisa pohranjenog u Državnom arhivu u Mlecima (fond: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) koji se odnosi na događaj iz 1748. godine u korčulanskom selu Žrnovo, kada su mještani – vjerujući da su se pojavili vampiri – oskvrnuli nekoliko mjesnih grobova. U radu se podrobno iznose osnovni podaci iz spisa te rečeni događaj analizira u širem društvenom kontekstu i prate se lokalna vjerovanja.The main interest of this essay is the analysis of the document from the State Archive in Venice (file: Capi del Consiglio de’ Dieci: Lettere di Rettori e di altre cariche) which is connected with the episode from 1748 when the inhabitants of the village Žrnove on the island of Korčula in Croatia opened tombs on the local cemetery in the fear of the vampires treating. This essay try to show some social circumstances connected with this event as well as a local vernacular tradition concerning superstitions

Mortalities due to constipation and dystocia caused by intraperitoneal radio-transmitters in Eurasian lynx (Lynx lynx)

Three lynx (Lynx lynx) were found dead following complications after a surgically implanted free floating intraperitoneal radio-transmitter became lodged within the pelvic canal. Two yearling lynx died due to consequences following severe constipation as the transmitter compressed the colon. Both were emaciated, with no abdominal or intrapelvic fat, which allowed the transmitter implant to fit into the pelvic canal. An adult female lynx died of dystocia when the pelvic birth canal was blocked by the transmitter when parturition began, leading to uterine rupture and subsequent peritonitis. A total of 41 lynx was implanted with this type of intraperitoneal transmitter in Scandinavia 1997-2002. After the three transmitter-associated mortalities, the transmitter type used in lynx cubs was exchanged for another model, and further fatalities due to the implants have not been documented