304 research outputs found

    Multijet Background Estimation for Supersymmetry Searches and Radiation Damage Studies with the ATLAS Detector

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    This thesis documents a data-driven methodology for the estimation of the multijet background in fully hadronic final states with high missing transverse momentum within the ATLAS detector at the Large Hadron Collider. The implementation of this methodology within two analyses searching for evidence of supersymmetric particle production using 36.1 fb−1 of √s = 13 TeV proton-proton collision data is described. The two analyses described in this thesis investigate supersymmetric particle production via the strong interaction both inclusively via the superpartners of the first and second generation quarks and exclusively via the superpartners of the third generation t and b quarks. Both analyses consider the eventual decay of any produced supersymmetric particles to standard model particles and the lightest neutralino, which escapes without detection and is observed as missing momentum in the transverse plane of the detector. Additionally, an investigation into the level of radiation damage received by the ATLAS silicon Semiconductor Tracker is presented with predictions of the level of radiation damage faced over the course of the planned lifetime of the detector

    Engineering a machine learning pipeline for automating metadata extraction from longitudinal survey questionnaires

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    Data Documentation Initiative-Lifecycle (DDI-L) introduced a robust metadata model to support the capture of questionnaire content and flow, and encouraged through support for versioning and provenancing, objects such as BasedOn for the reuse of existing question items. However, the dearth of questionnaire banks including both question text and response domains has meant that an ecosystem to support the development of DDI ready Computer Assisted Interviewing (CAI) tools has been limited. Archives hold the information in PDFs associated with surveys but extracting that in an efficient manner into DDI-Lifecycle is a significant challenge.
 While CLOSER Discovery has been championing the provision of high-quality questionnaire metadata in DDI-Lifecycle, this has primarily been done manually. More automated methods need to be explored to ensure scalable metadata annotation and uplift.
 This paper presents initial results in engineering a machine learning (ML) pipeline to automate the extraction of questions from survey questionnaires as PDFs. Using CLOSER Discovery as a ‘training and test dataset’, a number of machine learning approaches have been explored to classify parsed text from questionnaires to be output as valid DDI items for inclusion in a DDI-L compliant repository.
 The developed ML pipeline adopts a continuous build and integrate approach, with processes in place to keep track of various combinations of the structured DDI-L input metadata, ML models and model parameters against the defined evaluation metrics, thus enabling reproducibility and comparative analysis of the experiments.  Tangible outputs include a map of the various metadata and model parameters with the corresponding evaluation metrics’ values, which enable model tuning as well as transparent management of data and experiments

    Engineering a machine learning pipeline for automating metadata extraction from longitudinal survey questionnaires

    Get PDF
    Data Documentation Initiative-Lifecycle (DDI-L) introduced a robust metadata model to support the capture of questionnaire content and flow, and encouraged through support for versioning and provenancing, objects such as BasedOn for the reuse of existing question items. However, the dearth of questionnaire banks including both question text and response domains has meant that an ecosystem to support the development of DDI ready Computer Assisted Interviewing (CAI) tools has been limited. Archives hold the information in PDFs associated with surveys but extracting that in an efficient manner into DDI-Lifecycle is a significant challenge.
 While CLOSER Discovery has been championing the provision of high-quality questionnaire metadata in DDI-Lifecycle, this has primarily been done manually. More automated methods need to be explored to ensure scalable metadata annotation and uplift.
 This paper presents initial results in engineering a machine learning (ML) pipeline to automate the extraction of questions from survey questionnaires as PDFs. Using CLOSER Discovery as a ‘training and test dataset’, a number of machine learning approaches have been explored to classify parsed text from questionnaires to be output as valid DDI items for inclusion in a DDI-L compliant repository.
 The developed ML pipeline adopts a continuous build and integrate approach, with processes in place to keep track of various combinations of the structured DDI-L input metadata, ML models and model parameters against the defined evaluation metrics, thus enabling reproducibility and comparative analysis of the experiments.  Tangible outputs include a map of the various metadata and model parameters with the corresponding evaluation metrics’ values, which enable model tuning as well as transparent management of data and experiments

    Analysing Longitudinal Social Science Questionnaires: Topic modelling with BERT-based Embeddings

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    Unsupervised topic modelling is a useful unbiased mechanism for topic labelling of complex longitudinal questionnaires covering multiple domains such as social science and medicine. Manual tagging of such complex datasets increases the propensity of incorrect or inconsistent labels and is a barrier to scaling the processing of longitudinal questionnaires for provision of question banks for data collection agencies. Towards this effort, we propose a tailored BERTopic framework that takes advantage of its novel sentence embedding for creating interpretable topics, and extend it with an enhanced visualisation for comparing the topic model labels with the tags manually assigned to the question literals. The resulting topic clusters uncover instances of mislabelled question tags, while also enabling showcasing the semantic shifts and evolution of the topics across the time span of the longitudinal questionnaires. The tailored BERTopic framework outperforms existing topic modelling baselines for the quantitative evaluation metrics of topic coherence and diversity, while also being 18 times faster than the next best-performing baseline

    Validation of oral fluid samples to monitor serological changes to Plasmodium falciparum: An observational study in southern Zambia

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    <p>Abstract</p> <p>Background</p> <p>In formerly endemic areas where malaria transmission has declined, levels of population immunity to <it>Plasmodium falciparum </it>provide information on continued malaria transmission and potentially susceptible populations. Traditional techniques for measuring serological responses to <it>P. falciparum </it>antigens use plasma or dried blood spots (DBS). These invasive procedures pose a biohazard and may be unacceptable to communities if performed frequently. The use of oral fluid (OF) samples to detect antibodies to <it>P. falciparum </it>antigens may be a more acceptable strategy to monitor changes in population immunity.</p> <p>Methods</p> <p>An enzyme immunoassay was optimized to detect antibodies to whole, asexual stage <it>P. falciparum </it>antigens. Optical density (OD) values from paired DBS and OF samples collected as part of a community-based survey of malaria parasitaemia were compared.</p> <p>Results</p> <p>Oral fluid and dried blood spot samples were collected from 53 participants in Southern Province, Zambia. Their ages ranged from 1 to 80 years and 45% were female. A statistically significant correlation (r = 0.79; P < 0.01) was observed between OD values from OF and DBS samples. The OF assay identified all DBS-confirmed positive and negative samples, resulting in 100% sensitivity and specificity.</p> <p>Conclusions</p> <p>Oral fluid is a valid alternative specimen for monitoring changes in antibodies to <it>P. falciparum </it>antigens. As OF collection is often more acceptable to communities, poses less of a biohazard than blood samples and can be performed by community volunteers, serological surveys using OF samples provide a strategy for monitoring population immunity in regions of declining malaria transmission.</p

    Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast.

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    BACKGROUND: The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. RESULTS: To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. CONCLUSIONS: As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

    NO formation in nucleus tractus solitarii attenuates pressor response evoked by skeletal muscle afferents

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    Li, Jianhua, and Jeffrey T. Potts. NO formation in nucleus tractus solitarii attenuates pressor response evoked by skeletal muscle afferents. Am J Physiol Heart Circ Physiol 280: H2371-H2379, 2001.-We have previously shown that static muscle contraction induces the expression of c-Fos protein in neurons of the nucleus tractus solitarii (NTS) and that some of these cells were codistributed with neuronal NADPH-diaphorase [nitric oxide (NO) synthase]-positive fibers. In the present study, we sought to determine the role of NO in the NTS in mediating the cardiovascular responses elicited by skeletal muscle afferent fibers. Static contraction of the triceps surae muscle was induced by electrical stimulation of the L7 and S1 ventral roots in anesthetized cats. Muscle contraction during microdialysis of artificial extracellular fluid increased mean arterial pressure (MAP) and heart rate (HR) 51 Ϯ 9 mmHg and 18 Ϯ 3 beats/min, respectively. Microdialysis of L-arginine (10 mM) into the NTS to locally increase NO formation attenuated the increases in MAP (30 Ϯ 7 mmHg, P Ͻ 0.05) and HR (14 Ϯ 2 beats/min, P Ͼ 0.05) during contraction. Microdialysis of D-arginine (10 mM) did not alter the cardiovascular responses evoked by muscle contraction. Microdialysis of N G -nitro-L-arginine methyl ester (2 mM) during contraction attenuated the effects of Larginine on the reflex cardiovascular responses. These findings demonstrate that an increase in NO formation in the NTS attenuates the pressor response to static muscle contraction, indicating that the NO system plays a role in mediating the cardiovascular responses to static muscle contraction in the NTS. cardiovascular responses; static muscle contraction; blood pressure; heart rate; microdialysis; L-arginine; L-NAME STUDIES HAVE DEMONSTRATED that nitric oxide (NO) synthase (NOS) is localized in discrete medullary areas (41) involved in cardiovascular regulation The evidence that the muscle afferents terminate in several laminae of the spinal cord as well as ascending to terminate in the NTS has been shown by neuroanatomic tracing studies MATERIALS AND METHODS General Surgical Preparation Experiments were performed on 25 anesthetized cats of either sex weighing 3.4-5.5 kg. The animals were anesthetized by inhalation of a halothane-oxygen mixture (2-3%). An endotracheal tube was inserted into the trachea via a tracheotomy to maintain an open airway, and the jugular vein and carotid artery were catheterized for drug administration and measurement of ABP, respectively. Anesthesia was then maintained with a mixture of ␣-chloralose (80 mg/kg) and urethane (200 mg/kg) injected intravenously. Throughout the experiment, supplemental ␣-chloralose (15 mg/kg iv) was given if the cats exhibited a corneal reflex or if they withdrew a limb in response to a noxious stimulus

    Changing individual-level risk factors for malaria with declining transmission in southern Zambia: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Malaria elimination will require that both symptomatic- and asymptomatic-infected persons be identified and treated. However, well-characterized, individual-level risk factors for malaria may not be valid in regions with declining malaria transmission. Changes in individual-level correlates of malaria infection were evaluated over three years in a region of declining malaria transmission in southern Zambia.</p> <p>Methods</p> <p>Malaria surveys were conducted in two study areas within the catchment area of Macha Hospital, Zambia in 2007 and 2008/2009. A random sample of households was identified from a digitized satellite image of the study areas. Cross-sectional surveys were conducted approximately five times throughout the year in each of the two study areas. During study visits, adults and caretakers of children were administered questionnaires and a blood sample was obtained for a rapid diagnostic test (RDT) for malaria.</p> <p>Results</p> <p>In the 2007 study area, 330 individuals were surveyed. 40.9% of participants lived in a household with at least one insecticide-treated bed net (ITN); however, only 45.2% reported sleeping under the ITN. 23.9% of participants were RDT positive. Correlates of RDT positivity included younger age, the presence of symptoms, testing during the rainy season, using an open water source, and not sleeping under an ITN. In the 2008 study area, 435 individuals were surveyed. 77.0% of participants lived in a household with at least one ITN; however, only 56.4% reported sleeping under the ITN. 8.1% of participants were RDT positive. RDT positivity was negatively correlated with the presence of symptoms within the last two weeks but positively correlated with documented fever. In 2009, 716 individuals were surveyed in the same area as 2008. 63.7% of participants lived in a household with at least one ITN; however, only 57.7% reported sleeping under the ITN. 1.5% of participants were RDT positive. Only self-reported fever was significantly correlated with RDT positivity.</p> <p>Conclusions</p> <p>With declining malaria prevalence, few individual-level characteristics were correlated with RDT positivity. This lack of correlation with individual characteristics hampers identification of individuals infected with malaria. Strategies based on ecological or environmental risk factors may be needed to target control efforts and achieve further reductions and elimination.</p

    Comparison of a PfHRP2-Based Rapid Diagnostic Test and Pcr for Malaria in a Low Prevalence Setting in Rural Southern Zambia: Implications for Elimination

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    Background: Rapid diagnostic tests (RDTs) detecting histidine-rich protein 2 (PfHRP2) antigen are used to identify individuals with Plasmodium falciparum infection even in low transmission settings seeking to achieve elimination. However, these RDTs lack sensitivity to detect low-density infections, produce false negatives for P. falciparum strains lacking pfhrp2 gene and do not detect species other than P. falciparum. Methods: Results of a PfHRP2-based RDT and Plasmodium nested PCR were compared in a region of declining malaria transmission in southern Zambia using samples from community-based, cross-sectional surveys from 2008 to 2012. Participants were tested with a PfHRP2-based RDT and a finger prick blood sample was spotted onto filter paper for PCR analysis and used to prepare blood smears for microscopy. Species-specific, real-time, quantitative PCR (q-PCR) was performed on samples that tested positive either by microscopy, RDT or nested PCR. Results: Of 3,292 total participants enrolled, 12 (0.4%) tested positive by microscopy and 42 (1.3%) by RDT. Of 3,213 (98%) samples tested by nested PCR, 57 (1.8%) were positive, resulting in 87 participants positive by at least one of the three tests. Of these, 61 tested positive for P. falciparum by q-PCR with copy numbers ≤ 2 × 103 copies/μL, 5 were positive for both P. falciparum and Plasmodium malariae and 2 were positive for P. malariae alone. RDT detected 32 (53%) of P. falciparum positives, failing to detect three of the dual infections with P. malariae. Among 2,975 participants enrolled during a low transmission period between 2009 and 2012, sensitivity of the PfHRP2-based RDT compared to nested PCR was only 17%, with specificity of \u3e99%. The pfhrp gene was detected in 80% of P. falciparum positives; however, comparison of copy number between RDT negative and RDT positive samples suggested that RDT negatives resulted from low parasitaemia and not pfhrp2 gene deletion. Conclusions: Low-density P. falciparum infections not identified by currently used PfHRP2-based RDTs and the inability to detect non-falciparum malaria will hinder progress to further reduce malaria in low transmission settings of Zambia. More sensitive and specific diagnostic tests will likely be necessary to identify parasite reservoirs and achieve malaria elimination
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