258 research outputs found

    An assessment on potential long-term health effects caused by antibiotic resistance marker genes in genetically modified organisms based on antibiotic usage and resistance patterns in Norway.

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    Source at https://vkm.no/Usage of antibiotics selects for resistant bacteria, resulting in reduced treatment options, and increased morbidity and mortality from microbial infections. Development of resistance in susceptible bacteria can occur through spontaneous mutation or horizontal gene transfer (HGT). Our current understanding of resistance development in bacterial pathogens is more descriptive than predictive in nature. That is, whereas the acquisition or development of new resistance determinants in bacteria can be retrospectively described relatively easily at the molecular, species and geographical distribution levels, the initial horizontal transfer events, the resistance gene donor, and the environmental location and conditions that produced the first generation of the resistant bacteria remain largely unknown. Without this latter knowledge and without a clear understanding of directional selection and genetic drift in natural bacterial populations, it is impossible to predict accurately further resistance development occurring through HGT. Some of the antibiotic resistance marker (ARM) genes used in the production of genetically modified organisms (GMO) encode resistance to antibiotics in clinical and veterinary use. Thus, concerns have been raised that the large-scale release of such genes in commercialized GMOs may increase the rate of, and broaden the locations where, bacteria horizontally acquire resistance genes

    Vascular responses to radiotherapy and androgen-deprivation therapy in experimental prostate cancer

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    Background: Radiotherapy (RT) and androgen-deprivation therapy (ADT) are standard treatments for advanced prostate cancer (PC). Tumor vascularization is recognized as an important physiological feature likely to impact on both RT and ADT response, and this study therefore aimed to characterize the vascular responses to RT and ADT in experimental PC. Methods: Using mice implanted with CWR22 PC xenografts, vascular responses to RT and ADT by castration were visualized in vivo by DCE MRI, before contrast-enhancement curves were analyzed both semi-quantitatively and by pharmacokinetic modeling. Extracted image parameters were correlated to the results from ex vivo quantitative fluorescent immunohistochemical analysis (qIHC) of tumor vascularization (9 F1), perfusion (Hoechst 33342), and hypoxia (pimonidazole), performed on tissue sections made from tumors excised directly after DCE MRI. Results: Compared to untreated (Ctrl) tumors, an improved and highly functional vascularization was detected in androgen-deprived (AD) tumors, reflected by increases in DCE MRI parameters and by increased number of vessels (VN), vessel density ( VD), and vessel area fraction ( VF) from qIHC. Although total hypoxic fractions ( HF) did not change, estimated acute hypoxia scores ( AHS) – the proportion of hypoxia staining within 50 μm from perfusion staining – were increased in AD tumors compared to in Ctrl tumors. Five to six months after ADT renewed castration-resistant (CR) tumor growth appeared with an even further enhanced tumor vascularization. Compared to the large vascular changes induced by ADT, RT induced minor vascular changes. Correlating DCE MRI and qIHC parameters unveiled the semi-quantitative parameters area under curve ( AUC) from initial time-points to strongly correlate with VD and VF, whereas estimation of vessel size ( VS) by DCE MRI required pharmacokinetic modeling. HF was not correlated to any DCE MRI parameter, however, AHS may be estimated after pharmacokinetic modeling. Interestingly, such modeling also detected tumor necrosis very strongly. Conclusions: DCE MRI reliably allows non-invasive assessment of tumors’ vascular function. The findings of increased tumor vascularization after ADT encourage further studies into whether these changes are beneficial for combined RT, or if treatment with anti-angiogenic therapy may be a strategy to improve the therapeutic efficacy of ADT in advanced PC.publishedVersio

    A Kernel to Exploit Informative Missingness in Multivariate Time Series from EHRs

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    A large fraction of the electronic health records (EHRs) consists of clinical measurements collected over time, such as lab tests and vital signs, which provide important information about a patient's health status. These sequences of clinical measurements are naturally represented as time series, characterized by multiple variables and large amounts of missing data, which complicate the analysis. In this work, we propose a novel kernel which is capable of exploiting both the information from the observed values as well the information hidden in the missing patterns in multivariate time series (MTS) originating e.g. from EHRs. The kernel, called TCKIM_{IM}, is designed using an ensemble learning strategy in which the base models are novel mixed mode Bayesian mixture models which can effectively exploit informative missingness without having to resort to imputation methods. Moreover, the ensemble approach ensures robustness to hyperparameters and therefore TCKIM_{IM} is particularly well suited if there is a lack of labels - a known challenge in medical applications. Experiments on three real-world clinical datasets demonstrate the effectiveness of the proposed kernel.Comment: 2020 International Workshop on Health Intelligence, AAAI-20. arXiv admin note: text overlap with arXiv:1907.0525

    Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

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    Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

    UTTALELSE OM PIONEER HI-BRED/MYCOGEN SEEDS GENMODIFISERTE MAIS 59122x1507xNK603 (EFSA/GMO/UK/2005/21)

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    Source at https://vkm.no/Vurderingen av den genmodifiserte herbicidresistente og insektstolerante maishybriden 59122x1507xNK603 fra Pioneer Hi-Bred/Mycogen Seeds er utført av Faggruppe for genmodifiserte organismer under Vitenskapskomiteen for mattrygghet. Mattilsynet (MT) ber Vitenskapskomiteen for mattrygghet om å vurdere den genmodifiserte maishybriden 59122x1507xNK603 til bruk i næringsmidler og fôrvarer

    UTTALELSE OM PIONEER HI-BRED/MYCOGEN SEEDS GENMODIFISERT MAIS 1507x59122 (EFSA/GMO/NL/2005/15)

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    Source at https://vkm.no/Vurderingen av den genmodifiserte herbicidresistente og insektstolerante maislinjen 1507x59122 fra Pioneer Hi-Bred/Mycogen Seeds er utført av Faggruppe for genmodifiserte organismer under Vitenskapskomiteen for mattrygghet. Mattilsynet (MT) ber Vitenskapskomiteen for mattrygghet om å vurdere den genmodifiserte maislinjen 1507x59122 til bruk i næringsmidler og fôrvarer
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