26 research outputs found

    Моделирование изменения цен финансовых активов

    Get PDF
    В работе представлена модель процесса изменения цен финансовых активов на рынке. Описан путь построения модели, ее экономическая интерпретация, найдены моменты процесса и исследовано его поведение в предельном случае. Для сравнения с данной моделью приведены примеры некоторых других существующих моделей.У рoботi представлена модель процесу змiни цiн фiнансових активiв на ринку. Описано шлях побудови моделi, її економiчна iнтерпретацiя, знайдено моменти процесу, дослiджено його поведiнку у граничному випадку. Для порiвняння з даною моделлю наведено приклади деяких iнших моделей, що iснують.A model of process for financial assets — prices changing on market is presented. The way of the model’s construction is described, its economic interpretation, a moments of the process are obtained, its behavior in limit case is investigated. For comparison with the given model examples of other models are presented

    Isotype specific antibody responses to Mycobacterium Avium subspecies Paratuberculosis antigens are associated with the use of biological therapy in Inflammatory Bowel Disease

    Get PDF
    Background: The role of Mycobacterium avium paratuberculosis [MAP] in inflammatory bowel disease [IBD], especially Crohn’s disease [CD] is controversial due conflicting results and lack of reproducibility and standardised tests. The current study focuses on the role of MAP in disease progression and genetic susceptibility, as MAP is likely one of many factors involved in the complex pathogenesis of IBD, potentially affecting a subgroup depending on genetic susceptibility.Methods: Serum from 812 patients was evaluated with seven immunoglobulin [Ig] isotype-specific serology tests assessing humoral response to three different MAP antigens. For each of these in total 21 tests, the intra-assay and inter-assay coefficients were used to evaluate test accuracy. Reliable assays were subsequently analysed in relation to disease characteristics and need for biologic therapy/surgery. Genome-wide genotyping was available for all participants. Genetic determinants of humoral response to MAP antigens were evaluated using genome-wide association analysis and polygenic risk scores [PRS].Results: High IgA or IgM response to MAP2609 was associated with increased use of biologic therapy in CD and ulcerative colitis [UC] [odds ratios 2.69; 95% confidence interval 1.44–5.01; and 2.60, 1.46–4.64, respectively]. No associations were seen for risk of surgery [p-values > 0.29]. We could not identify genetic determinants nor polygenic risk scores for MAP response with genome-wide significance.Conclusions: Extensive assays for serological response to MAP were evaluated using stringent criteria for reliability. Increased IgA and IgM response to MAP antigens was seen in patients exposed to biologic therapy, but no genetic determinants underlying this humoral response were found

    Efficient Direct and Limited Environmental Transmission of SARS-CoV-2 Lineage B.1.22 in Domestic Cats

    Get PDF
    The susceptibility of domestic cats to infection with SARS-CoV-2 has been demonstrated by several experimental studies and field observations. We performed an extensive study to further characterize the transmission of SARS-CoV-2 between cats, through both direct and indirect contact. To that end, we estimated the transmission rate parameter and the decay parameter for infectivity in the environment. Using four groups of pair-transmission experiment, all donor (inoculated) cats became infected, shed virus, and seroconverted, while three out of four direct contact cats got infected, shed virus, and two of those seroconverted. One out of eight cats exposed to a SARS-CoV-2-contaminated environment became infected but did not seroconvert. Statistical analysis of the transmission data gives a reproduction number R0 of 2.18 (95% CI = 0.92 to 4.08), a transmission rate parameter b of 0.23 day21 (95% CI = 0.06 to 0.54), and a virus decay rate parameter m of 2.73 day21 (95% CI = 0.77 to 15.82). These data indicate that transmission between cats is efficient and can be sustained (R0 . 1), however, the infectiousness of a contaminated environment decays rapidly (mean duration of infectiousness 1/2.73 days). Despite this, infections of cats via exposure to a SARS-CoV-2-contaminated environment cannot be discounted if cats are exposed shortly after contamination. IMPORTANCE This article provides additional insight into the risk of infection that could arise from cats infected with SARS-CoV-2 by using epidemiological models to determine transmission parameters. Considering that transmission parameters are not always provided in the literature describing transmission experiments in animals, we demonstrate that mathematical analysis of experimental data is crucial to estimate the likelihood of transmission. This article is also relevant to animal health professionals and authorities involved in risk assessments for zoonotic spill-overs of SARS-CoV-2. Last but not least, the mathematical models to calculate transmission parameters are applicable to analyze the experimental transmission of other pathogens between animals

    Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats

    Get PDF
    Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations

    Immunization of young heifers with staphylococcal immune evasion proteins before natural exposure to Staphylococcus aureus induces a humoral immune response in serum and milk

    Get PDF
    Background: Staphylococcus aureus, a leading cause of mastitis in dairy cattle, causes severe mastitis and/or chronic persistent infections with detrimental effects on the cows' wellbeing, lifespan and milk production. Despite years of research there is no effective vaccine against S. aureus mastitis. Boosting of non-protective pre-existing immunity to S. aureus, induced by natural exposure to S. aureus, by vaccination may interfere with vaccine efficacy. The aim was to assess whether experimental immunization of S. aureus naïve animals results in an immune response that differs from immunity following natural exposure to S. aureus. Results: First, to define the period during which calves are immunologically naïve for S. aureus, Efb, LukM, and whole-cell S. aureus specific serum antibodies were measured in a cohort of newborn calves by ELISA. Rising S. aureus specific antibodies indicated that from week 12 onward calves mounted an immune response to S. aureus due to natural exposure. Next, an experimental immunization trial was set up using 8-week-old heifer calves (n = 16), half of which were immunized with the immune evasion molecules Efb and LukM. Immunization was repeated after one year and before parturition and humoral and cellular immunity specific for Efb and LukM was determined throughout the study. Post-partum, antibody levels against LukM and EfB were significantly higher in serum, colostrum and milk in the experimentally immunized animals compared to animals naturally exposed to S. aureus. LukM specific IL17a responses were also significantly higher in the immunized cows post-partum. Conclusions: Experimental immunization with staphylococcal immune evasion molecules starting before natural exposure resulted in significantly higher antibody levels against Efb and LukM around parturition in serum as well as the site of infection, i.e. in colostrum and milk, compared to natural exposure to S. aureus. This study showed that it is practically feasible to vaccinate S. aureus naïve cattle and that experimental immunization induced a humoral immune response that differed from that after natural exposure only.</p

    Faecal microbiota composition based random forest model predicts Mycobacterium Avium subsp. Paratuberculosis (MAP) shedding severity in cattle

    No full text
    Paratuberculosis is a devastating infectious disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). The development of the paratuberculosis clinical symptoms in cattle could take up to a few years and vastly differs between individuals in severity of the symptoms and shedding of the pathogen in the environment. Identification of high shedding animals that significantly increase the burden of the pathogen in a farm environment is essential for paratuberculosis control and minimization of economic losses. Widely used methods for detection and quantification of MAP, such as culturing and PCR based techniques rely on direct presence of the pathogen in a sample and have little to no predictive value for the disease development. In the current study we investigated possibility of prediction of the shedding severity through the life of a cow based on fecal microbiota composition. Twenty calves were experimentally infected with MAP and fecal samples were collected biweekly up to four years of age. All collected samples were subjected to culturing on the selective media to obtain data about shedding severity. Faecal microbiota were profiled in a subset of samples that reflects important time points in cattle husbandry. Using faecal microbiota composition and shedding intensity data we build a random forest classifier for prediction of the animals shedding status. We found that machine learning approaches applied to microbial composition can be used to classify cows that are severely shedding MAP into the environment. However, classification accuracy strongly correlates with age of the animals and use of samples from older individuals results higher precision of classification. Classification model based on samples from the first 12 month of life showed AUC between 0.78 and 0.79, where is model based on samples from animals older than 24 month showed AUC between 0.91 and 0.92 (95% CI). . We also showed that only a relatively small number of microbial taxa are important for classification and could be considered as biomarkers. The study provides evidence for the link between microbiota composition and severity of MAP infection and shedding, as well as lays ground for development of predictive diagnostic tools based on the microbiota composition

    Faecal microbiota composition based random forest model predicts Mycobacterium Avium subsp. Paratuberculosis (MAP) shedding severity in cattle

    No full text
    Paratuberculosis is a devastating infectious disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). The development of the paratuberculosis clinical symptoms in cattle could take up to a few years and vastly differs between individuals in severity of the symptoms and shedding of the pathogen in the environment. Identification of high shedding animals that significantly increase the burden of the pathogen in a farm environment is essential for paratuberculosis control and minimization of economic losses. Widely used methods for detection and quantification of MAP, such as culturing and PCR based techniques rely on direct presence of the pathogen in a sample and have little to no predictive value for the disease development. In the current study we investigated possibility of prediction of the shedding severity through the life of a cow based on fecal microbiota composition. Twenty calves were experimentally infected with MAP and fecal samples were collected biweekly up to four years of age. All collected samples were subjected to culturing on the selective media to obtain data about shedding severity. Faecal microbiota were profiled in a subset of samples that reflects important time points in cattle husbandry. Using faecal microbiota composition and shedding intensity data we build a random forest classifier for prediction of the animals shedding status. We found that machine learning approaches applied to microbial composition can be used to classify cows that are severely shedding MAP into the environment. However, classification accuracy strongly correlates with age of the animals and use of samples from older individuals results higher precision of classification. Classification model based on samples from the first 12 month of life showed AUC between 0.78 and 0.79, where is model based on samples from animals older than 24 month showed AUC between 0.91 and 0.92 (95% CI). . We also showed that only a relatively small number of microbial taxa are important for classification and could be considered as biomarkers. The study provides evidence for the link between microbiota composition and severity of MAP infection and shedding, as well as lays ground for development of predictive diagnostic tools based on the microbiota composition

    Short lifespans of memory T-cells in bone marrow, blood, and lymph nodes suggest that T-cell memory is maintained by continuous self-renewal of recirculating cells

    No full text
    Memory T-cells are essential to maintain long-term immunological memory. It is widely thought that the bone marrow (BM) plays an important role in the long-term maintenance of memory T-cells. There is controversy however on the longevity and recirculating kinetics of BM memory T-cells. While some have proposed that the BM is a reservoir for long-lived, non-circulating memory T-cells, it has also been suggested to be the preferential site for memory T-cell self-renewal. In this study, we used in vivo deuterium labeling in goats to simultaneously quantify the average turnover rates-and thereby expected lifespans-of memory T-cells from BM, blood and lymph nodes (LN). While the fraction of Ki-67 positive cells, a snapshot marker for recent cell division, was higher in memory T-cells from blood compared to BM and LN, in vivo deuterium labeling revealed no substantial differences in the expected lifespans of memory T-cells between these compartments. Our results support the view that the majority of memory T-cells in the BM are self-renewing as fast as those in the periphery, and are continuously recirculating between the blood, BM, and LN.</p

    Classification and prediction of Mycobacterium Avium subsp. Paratuberculosis (MAP) shedding severity in cattle based on young stock heifer faecal microbiota composition using random forest algorithms

    Get PDF
    BACKGROUND: Bovine paratuberculosis is a devastating infectious disease caused by Mycobacterium avium subsp. paratuberculosis (MAP). The development of the paratuberculosis in cattle can take up to a few years and vastly differs between individuals in severity of the clinical symptoms and shedding of the pathogen. Timely identification of high shedding animals is essential for paratuberculosis control and minimization of economic losses. Widely used methods for detection and quantification of MAP, such as culturing and PCR based techniques rely on direct presence of the pathogen in a sample and have little to no predictive value concerning the disease development. In the current study, we investigated the possibility of predicting MAP shedding severity in cattle based on the faecal microbiota composition. Twenty calves were experimentally infected with MAP and faecal samples were collected biweekly up to four years of age. All collected samples were subjected to culturing on selective media to obtain data about shedding severity. Faecal microbiota was profiled in a subset of samples (n = 264). Using faecal microbiota composition and shedding intensity data a random forest classifier was built for prediction of the shedding status of the individual animals. RESULTS: The results indicate that machine learning approaches applied to microbial composition can be used to classify cows into groups by severity of MAP shedding. The classification accuracy correlates with the age of the animals and use of samples from older individuals resulted in a higher classification precision. The classification model based on samples from the first 12 months of life showed an AUC between 0.78 and 0.79 (95% CI), while the model based on samples from animals older than 24 months showed an AUC between 0.91 and 0.92 (95% CI). Prediction for samples from animals between 12 and 24 month of age showed intermediate accuracy [AUC between 0.86 and 0.87 (95% CI)]. In addition, the results indicate that a limited number of microbial taxa were important for classification and could be considered as biomarkers. CONCLUSIONS: The study provides evidence for the link between microbiota composition and severity of MAP infection and shedding, as well as lays ground for the development of predictive diagnostic tools based on the faecal microbiota composition

    Effects of Age and Environment on Adaptive Immune Responses to Mycobacterium avium subsp. paratuberculosis (MAP) Vaccination in Dairy Goats in Relation to Paratuberculosis Control Strategies

    No full text
    Paratuberculosis infection is caused by Mycobacterium avium subsp. paratuberculosis (MAP). In the Netherlands, 75% herd level prevalence of caprine paratuberculosis has been estimated, and vaccination is the principal control strategy applied. Most goat dairy farms with endemic paratuberculosis systematically vaccinate goat kids in the first months of life with a commercially available whole cell MAP vaccine. We hypothesized that the development of adaptive immune responses in goats vaccinated at young age depends on the environment they are raised in, and this has implications for the application of immune diagnostic tests in vaccinated dairy goats. We evaluated the early immune response to vaccination in young goat kids sourced from a MAP unsuspected non-vaccinated herd and raised in a MAP-free environment. Subsequently we compared these with responses observed in birth year and vaccination matched adult goats raised on farms with endemic paratuberculosis. Results indicated that initial adaptive immune responses to vaccination are limited in a MAP-free environment. In addition, adult antibody positive vaccinated goats raised in a MAP endemic environment are less likely to be IS900 PCR-positive as compared to antibody negative herd mates. We conclude that test-and-cull strategies in a vaccinated herd are currently not feasible using available immune diagnostic tests
    corecore