126 research outputs found

    Supervised and Unsupervised Learning of Audio Representations for Music Understanding

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    In this work, we provide a broad comparative analysis of strategies for pre-training audio understanding models for several tasks in the music domain, including labelling of genre, era, origin, mood, instrumentation, key, pitch, vocal characteristics, tempo and sonority. Specifically, we explore how the domain of pre-training datasets (music or generic audio) and the pre-training methodology (supervised or unsupervised) affects the adequacy of the resulting audio embeddings for downstream tasks. We show that models trained via supervised learning on large-scale expert-annotated music datasets achieve state-of-the-art performance in a wide range of music labelling tasks, each with novel content and vocabularies. This can be done in an efficient manner with models containing less than 100 million parameters that require no fine-tuning or reparameterization for downstream tasks, making this approach practical for industry-scale audio catalogs. Within the class of unsupervised learning strategies, we show that the domain of the training dataset can significantly impact the performance of representations learned by the model. We find that restricting the domain of the pre-training dataset to music allows for training with smaller batch sizes while achieving state-of-the-art in unsupervised learning -- and in some cases, supervised learning -- for music understanding. We also corroborate that, while achieving state-of-the-art performance on many tasks, supervised learning can cause models to specialize to the supervised information provided, somewhat compromising a model's generality

    Prioritization of mycotoxins for risk management action based on both public health risk and mitigation efficacy

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    There is a large and progressively growing number of mycotoxins with new potential concerns and implications on consumer protection. The classical approach to risk management is to deal with each emerging hazard individually, leading to both overload and lack of coherence in terms of an overall riskbased approach. The development of mitigation strategies should prioritize mycotoxins that regularly occur at undesirable levels in commonly consumed commodities, wherein both the toxicological profiles and effectiveness of mitigation are understood with a reasonable degree of certainty. The ultimate goal of mycotoxin mitigation is to prevent adverse health effects caused by foodborne exposure to mycotoxins, while preserving nutritional and organoleptic quality of food. The International Life Sciences Institute Europe (ILSI Europe) Food Contaminants Task Force is firmly committed to contributing to the understanding of the issues of mycotoxins affecting the different points of the food chain. This presentation will illustrate a recent new activity that is devoted to establishing a framework for the prioritization of mycotoxins found in food following a risk-based approach (decision tree). Based on the evidence and scale of risk to consumers, and the potential for risk mitigation, the framework will enable the differentiation between mycotoxins where risk management action is both warranted and likely to be effective based on available evidence. Through case-studies, this framework will also highlight potential knowledge gaps. The proposed activity is therefore devoted to delineating the right path for scaling and prioritizing mycotoxins in terms of risk-ranking and consequent mitigation opportunities.info:eu-repo/semantics/publishedVersio

    Pregnancy outcome following gestational exposure to azithromycin

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    BACKGROUND: Azithromycin is an azalide antibiotic with an extensive range of indications and has become a common treatment option due to its convenient dosing regimen and therapeutic advantages. Human studies addressing gestational use of azithromycin have primarily focused on antibiotic efficacy rather than fetal safety. Our primary objective was to evaluate the possibility of teratogenic risk following gestational exposure to azithromycin. METHODS: There were 3 groups of pregnant women enrolled in our study: 1) women who took azithromycin. 2) women exposed to non-teratogenic antibiotics for similar indications, and 3) women exposed to non-teratogenic agents. They were matched for gestational age at time of call, maternal age, cigarette and alcohol consumption. Rates of major malformations and other endpoints of interest were compared among the three groups. RESULTS: Pregnancy outcome of 123 women in each group was ascertained. There were no statistically significant differences among the three groups in the rates of major malformations; 3.4% (exposed) versus 2.3% (disease matched) and 3.4% (non teratogen) or any other endpoints that were examined. In the azithromycin group, 88 (71.6%) women took the drug during the first trimester CONCLUSION: Results suggest that gestational exposure to azithromycin is not associated with an increase in the rate of major malformations above the baseline of 1–3%. Our data adds to previous research showing that macrolide antibiotics, as a group, are generally safe in pregnancy and provides an evidence-based option for health professionals caring for populations with chlamydia

    Pharmacodynamic evaluation of commonly prescribed oral antibiotics against respiratory bacterial pathogens

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    <p>Abstract</p> <p>Background</p> <p>Upper and lower respiratory tract infections (RTIs) account for a substantial portion of outpatient antibiotic utilization. However, the pharmacodynamic activity of commonly used oral antibiotic regimens has not been studied against clinically relevant pathogens. The objective of this study was to assess the probability of achieving the requisite pharmacodynamic exposure for oral antibacterial regimens commonly prescribed for RTIs in adults against bacterial isolates frequently involved in these processes (<it>S. pneumoniae</it>, <it>H. influenzae</it>, and <it>M. catharralis</it>).</p> <p>Methods</p> <p>Using a 5000-subject Monte Carlo simulation, the cumulative fractions of response (CFR), (i.e., probabilities of achieving requisite pharmacodynamic targets) for the most commonly prescribed oral antibiotic regimens, as determined by a structured survey of medical prescription patterns, were assessed against local respiratory bacterial isolates from adults in São Paulo collected during the same time period. Minimal inhibitory concentration (MIC) of 230 isolates of <it>Streptococcus pneumoniae </it>(103), <it>Haemophilus influenzae </it>(98), and <it>Moraxella catharralis </it>(29) from a previous local surveillance were used.</p> <p>Results</p> <p>The most commonly prescribed antibiotic regimens were azithromycin 500 mg QD, amoxicillin 500 mg TID, and levofloxacin 500 mg QD, accounting for 58% of the prescriptions. Varied doses of these agents, plus gatifloxacin, amoxicillin-clavulanate, moxifloxacin, and cefaclor made up the remaining regimens. Utilizing aggressive pharmacodynamic exposure targets, the only regimens to achieve greater than 90% CFR against all three pathogens were amoxicillin/amoxicillin-clavulanate 500 mg TID (> 91%), gatifloxacin 400 mg QD (100%), and moxifloxacin 400 mg QD (100%). Considering <it>S. pneumoniae </it>isolates alone, azithromycin 1000 mg QD also achieved greater than 90% CFR (91.3%).</p> <p>Conclusions</p> <p>The only regimens to achieve high CFR against all three pathogen populations in both scenarios were gatifloxacin 400 mg QD, moxifloxacin 400 mg QD, and amoxicillin-clavulanate 500 mg TID. These data suggest the need for reconsideration of empiric antibiotic regimen selection among adult patients with RTIs in the São Paulo area. Additionally, this type of study could be used to optimize prescribing patterns in specific regions in light of emerging resistance.</p

    Induction of Membrane Ceramides: A Novel Strategy to Interfere with T Lymphocyte Cytoskeletal Reorganisation in Viral Immunosuppression

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    Silencing of T cell activation and function is a highly efficient strategy of immunosuppression induced by pathogens. By promoting formation of membrane microdomains essential for clustering of receptors and signalling platforms in the plasma membrane, ceramides accumulating as a result of membrane sphingomyelin breakdown are not only essential for assembly of signalling complexes and pathogen entry, but also act as signalling modulators, e. g. by regulating relay of phosphatidyl-inositol-3-kinase (PI3K) signalling. Their role in T lymphocyte functions has not been addressed as yet. We now show that measles virus (MV), which interacts with the surface of T cells and thereby efficiently interferes with stimulated dynamic reorganisation of their actin cytoskeleton, causes ceramide accumulation in human T cells in a neutral (NSM) and acid (ASM) sphingomyelinase–dependent manner. Ceramides induced by MV, but also bacterial sphingomyelinase, efficiently interfered with formation of membrane protrusions and T cell spreading and front/rear polarisation in response to β1 integrin ligation or αCD3/CD28 activation, and this was rescued upon pharmacological or genetic ablation of ASM/NSM activity. Moreover, membrane ceramide accumulation downmodulated chemokine-induced T cell motility on fibronectin. Altogether, these findings highlight an as yet unrecognised concept of pathogens able to cause membrane ceramide accumulation to target essential processes in T cell activation and function by preventing stimulated actin cytoskeletal dynamics

    20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

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    The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

    Państwo, gospodarka, społeczeństwo w integrującej się Europie TOM 3

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    Ze wstępu: "1 maja 2004 przyniesie radykalną zmianą sytuacji dotychczasowych kandydatów do Unii Europejskiej. Z roli aplikanta i petenta przekształcą się we współdecydenta. Już dziś z przyszłymi członkami konsultuje się większość kwestii wymagających strategicznych decyzji. Przez ostatnie dziesięć lat wysiłek polityczny i intelektualny był skierowany na uzyskanie członkostwa Unii, a w ostatnim okresie negocjacji - na osiągnięcie najlepszych według polityków i ekonomistów warunków akcesji. 1 ten etap mamy już za sobą. Pora zacząć patrzeć przed siebie, lecz niejako petent, ale kraj współodpowiedzialny za dalsze funkcjonowanie i rozwój powiększonej Unii. Z tej perspektywy istotnajest analiza gospodarki europejskiej, z którąjuż dziś gospodarka państw kandydackich, także Polski, jest silnie powiązana. Wiedza na ten temat jest uboga i ograniczona do przeglądu bieżących wskaźników makroekonomicznych. Zarówno w ośrodkach rządowych, jak i pozarządowych dominuje podejście analizujące, co z konkretnego wydarzenia w innym kraju wynika dla gospodarki polskiej. Stanowczo nie wystarczy to do pełnienia odpowiedzialnej roli współdecydenta. Potrzebna jest pogłębiona wiedza na temat gospodarki europejskiej jako całości i poszczególnych krajów, a także najważniejszych partnerów handlowych i gospodarczych zjednoczonej Europy. Konieczne są pogłębione prace studialne dotyczące mechanizmów międzynarodowych, gdyż organy unijne będą się zajmować w najbliższych latach dalszym rozwojem europejskiego jednolitego Rynku, rywalizacją gospodarczą z USA i krajami azjatyckimi, liberalizacjąhandlu światowego."(...

    Seasonal variations of the digestive tract of the Eurasian beaver castor fiber.

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    Forage availability for wild rodents varies with season. In turn, the composition of food can affect morphometric parameters of the digestive tract. This study was performed in Eurasian beavers (Castor fiber) whose population was close to extinction in most Eurasian countries, but has now increased. Due to the previous low number of studies, information about the effect of forage availability on the digestive tract morphology has previously been lacking. This study was performed using beavers captured from the natural environment during three seasons of different forage availability: winter, summer and autumn. It was found that the diet of the beaver varied during the year; in winter it was dominated by woody material consisting of willow shoots, whereas in summer the diet was primarily herbs, grass and leaves. Season also affected the mass of digested contents of the digestive tract. The digestive content increased in the caecum and colon in winter and autumn, when poor-quality food dominated the beaver's diet. The results indicated that the digestive tract parameters of beavers varied based on the composition of available forage
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