991 research outputs found

    Deep Over-sampling Framework for Classifying Imbalanced Data

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    Class imbalance is a challenging issue in practical classification problems for deep learning models as well as traditional models. Traditionally successful countermeasures such as synthetic over-sampling have had limited success with complex, structured data handled by deep learning models. In this paper, we propose Deep Over-sampling (DOS), a framework for extending the synthetic over-sampling method to exploit the deep feature space acquired by a convolutional neural network (CNN). Its key feature is an explicit, supervised representation learning, for which the training data presents each raw input sample with a synthetic embedding target in the deep feature space, which is sampled from the linear subspace of in-class neighbors. We implement an iterative process of training the CNN and updating the targets, which induces smaller in-class variance among the embeddings, to increase the discriminative power of the deep representation. We present an empirical study using public benchmarks, which shows that the DOS framework not only counteracts class imbalance better than the existing method, but also improves the performance of the CNN in the standard, balanced settings

    Design fictions:a tool for debating societal, legal and ethical aspects of personal and pervasive health systems

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    The potential benefits offered by health-related technologies are counterpoised by the societal, legal and ethical challenges concomitant with the pervasive monitoring of people necessitated by such technological interventions. Through the ProtoPolicy research project we explored the production and use of design fictions as a tool for debating the societal, legal and ethical dimensions of personal health systems. Two design fictions were co-created and tested in a series of design workshops with community groups based in Lancashire and Cornwall, UK. A thematic analysis of a debate among older people from the Lancaster group on the Smart Object Therapist (SOT) design fiction highlighted societal and ethical issues relevant to personal health system design. We conclude that ethics like ‘usability’ may be usefully based on engagement with directly or indirectly implicated publics and should not be designed into innovation by experts alone

    Intergenerational effects of violence on women's perinatal wellbeing and infant health outcomes: evidence from a birth cohort study in Central Vietnam.

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    BACKGROUND: Girls exposed to violence have a high risk of being victimized as adults and are more likely than non-abused women to have children who are treated violently. This intergenerational transmission may be especially serious when women suffer violence during pregnancy and early motherhood, as it impairs maternal wellbeing and infant health and development. This study examined the intergenerational effects of being exposed to childhood maltreatment (CM) and prenatal intimate partner violence (p-IPV) on perinatal mental distress and birth outcomes in central Vietnam. METHODS: A birth cohort study in Hue City, Vietnam was conducted with 150 women in the third trimester of pregnancy (Wave 1) and 3 months after childbirth (Wave 2). Using multivariable logistic regression models, augmented inverse-probability-weighted estimators and structural equation modelling (SEM), we analyzed a theoretical model by evaluating adjusted risk differences and pathways between CM, p-IPV and subsequent perinatal adversity and indicators of infant health problems. RESULTS: One in two pregnant women experienced at least one form of CM (55.03%) and one in ten pregnant women experienced both CM and p-IPV (10.67%). Mothers who experienced p-IPV or witnessed IPV as a child were approximately twice as likely to experience poor mental health during pregnancy [ARR 1.94, 95% CI (1.20-3.15)]. Infants had a two-fold higher risk of adverse birth outcomes (low birth weight, preterm birth, admission to neonatal intensive care) [ARR 2.45 95% CI (1.42, 4.25)] if their mothers experienced any form of p-IPV, with greater risk if their mothers were exposed to both CM and p-IPV [ARR 3.45 95% CI (1.40, 8.53)]. Notably, significant pathways to p-IPV were found via adverse childhood experience (ACE) events (β = 0.13), neighborhood disorder (β = 0.14) and partner support (β = - 1.3). CONCLUSION: These results emphasize the detrimental and prolonged nature of the effect of violence during childhood and pregnancy. Exposure to childhood maltreatment and violence during pregnancy increases the risk of maternal mental health difficulties and adverse birth outcomes. Antenatal care systems need to be responsive to women's previous experiences of violence and maternal mental health. The significant protective role of partner support and social support should also be considered when designing tailored interventions to address violence during pregnancy

    Controls on gut phosphatisation : the trilobites from the Weeks Formation Lagerstätte (Cambrian; Utah)

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    Despite being internal organs, digestive structures are frequently preserved in Cambrian Lagerstätten. However, the reasons for their fossilisation and their biological implications remain to be thoroughly explored. This is particularly true with arthropods--typically the most diverse fossilised organisms in Cambrian ecosystems--where digestive structures represent an as-yet underexploited alternative to appendage morphology for inferences on their biology. Here we describe the phosphatised digestive structures of three trilobite species from the Cambrian Weeks Formation Lagerstätte (Utah). Their exquisite, three-dimensional preservation reveals unique details on trilobite internal anatomy, such as the position of the mouth and the absence of a differentiated crop. In addition, the presence of paired pygidial organs of an unknown function is reported for the first time. This exceptional material enables exploration of the relationships between gut phosphatisation and the biology of organisms. Indeed, soft-tissue preservation is unusual in these fossils as it is restricted to the digestive structures, which indicates that the gut played a central role in its own phosphatisation. We hypothesize that the gut provided a microenvironment where special conditions could develop and harboured a source of phosphorus. The fact that gut phosphatization has almost exclusively been observed in arthropods could be explained by their uncommon ability to store ions (including phosphorous) in their digestive tissues. However, in some specimens from the Weeks Formation, the phosphatisation extends to the entire digestive system, suggesting that trilobites might have had some biological particularities not observed in modern arthropods. We speculate that one of them might have been an increased capacity for ion storage in the gut tissues, related to the moulting of their heavily-mineralised carapace

    The importance of maternal insulin resistance throughout pregnancy on neonatal adiposity

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    Background: Although previous studies evaluated the association of maternal health parameters with neonatal adiposity, little is known regarding the complexity of the relationships among different maternal health parameters throughout pregnancy and its impact on neonatal adiposity. Objectives: To evaluate the direct and indirect associations between maternal insulin resistance during pregnancy, in women with obesity, and neonatal adiposity. In addition, associations between maternal fasting glucose, triglycerides (TG), non-esterified fatty acids (NEFA), and neonatal adiposity were also assessed. Methods: This is a longitudinal, secondary analysis of the DALI study, an international project conducted in nine European countries with pregnant women with obesity. Maternal insulin resistance (HOMA-IR), fasting glucose, TG, and NEFA were measured three times during pregnancy (<20, 24-28, and 35-37 weeks of gestation). Offspring neonatal adiposity was estimated by the sum of four skinfolds. Structural equation modelling was conducted to evaluate the direct and indirect relationships among the variables of interest. Results: Data on 657 mother-infant pairs (50.7% boys) were analysed. Neonatal boys exhibited lower mean sum of skinfolds compared to girls (20.3 mm, 95% CI 19.7, 21.0 vs 21.5 mm, 95% CI 20.8, 22.2). In boys, maternal HOMA-IR at <20 weeks was directly associated with neonatal adiposity (β = 0.35 mm, 95% CI 0.01, 0.70). In girls, maternal HOMA-IR at 24-28 weeks was only indirectly associated with neonatal adiposity, which implies that this association was mediated via maternal HOMA-IR, glucose, triglycerides, and NEFA during pregnancy (β = 0.26 mm, 95% CI 0.08, 0.44). Conclusions: The timing of the role of maternal insulin resistance on neonatal adiposity depends on fetal sex. Although the association was time-dependent, maternal insulin resistance was associated with neonatal adiposity in both sexes

    Mild cognitive impairment: the Manchester consensus

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    Given considerable variation in diagnostic and therapeutic practice, there is a need for national guidance on the use of neuroimaging, fluid biomarkers, cognitive testing, follow-up and diagnostic terminology in mild cognitive impairment (MCI). MCI is a heterogenous clinical syndrome reflecting a change in cognitive function and deficits on neuropsychological testing but relatively intact activities of daily living. MCI is a risk state for further cognitive and functional decline with 5–15% of people developing dementia per year. However, ~50% remain stable at 5 years and in a minority, symptoms resolve over time. There is considerable debate about whether MCI is a useful clinical diagnosis, or whether the use of the term prevents proper inquiry (by history, examination and investigations) into underlying causes of cognitive symptoms, which can include prodromal neurodegenerative disease, other physical or psychiatric illness, or combinations thereof. Cognitive testing, neuroimaging and fluid biomarkers can improve the sensitivity and specificity of aetiological diagnosis, with growing evidence that these may also help guide prognosis. Diagnostic criteria allow for a diagnosis of Alzheimer’s disease to be made where MCI is accompanied by appropriate biomarker changes, but in practice, such biomarkers are not available in routine clinical practice in the UK. This would change if disease-modifying therapies became available and required a definitive diagnosis but would present major challenges to the National Health Service and similar health systems. Significantly increased investment would be required in training, infrastructure and provision of fluid biomarkers and neuroimaging. Statistical techniques combining markers may provide greater sensitivity and specificity than any single disease marker but their practical usefulness will depend on large-scale studies to ensure ecological validity and that multiple measures, e.g. both cognitive tests and biomarkers, are widely available for clinical use. To perform such large studies, we must increase research participation amongst those with MCI

    Cancer-cell intrinsic gene expression signatures overcome intratumoural heterogeneity bias in colorectal cancer patient classification

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    Stromal-derived intratumoural heterogeneity (ITH) has been shown to undermine molecular stratification of patients into appropriate prognostic/predictive subgroups. Here, using several clinically relevant colorectal cancer (CRC) gene expression signatures, we assessed the susceptibility of these signatures to the confounding effects of ITH using gene expression microarray data obtained from multiple tumour regions of a cohort of 24 patients, including central tumour, the tumour invasive front and lymph node metastasis. Sample clustering alongside correlative assessment revealed variation in the ability of each signature to cluster samples according to patient-of-origin rather than region-of-origin within the multi-region dataset. Signatures focused on cancer-cell intrinsic gene expression were found to produce more clinically useful, patient-centred classifiers, as exemplified by the CRC intrinsic signature (CRIS), which robustly clustered samples by patient-of-origin rather than region-of-origin. These findings highlight the potential of cancer-cell intrinsic signatures to reliably stratify CRC patients by minimising the confounding effects of stromal-derived ITH

    Episodic Therapy for Genital Herpes in Sub-Saharan Africa: A Pooled Analysis from Three Randomized Controlled Trials

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    BACKGROUND: A randomized controlled trial in South Africa found a beneficial effect of acyclovir on genital ulcer healing, but no effect was seen in trials in Ghana, Central African Republic and Malawi. The aim of this paper is to assess whether the variation in impact of acyclovir on ulcer healing in these trials can be explained by differences in the characteristics of the study populations. METHODOLOGY/PRINCIPAL FINDINGS: Pooled data were analysed to estimate the impact of acyclovir on the proportion of ulcers healed seven days after randomisation by HIV/CD4 status, ulcer aetiology, size and duration before presentation; and impact on lesional HIV-1. Risk ratios (RR) were estimated using Poisson regression with robust standard errors. Of 1478 patients with genital ulcer, most (63%) had herpetic ulcers (16% first episode HSV-2 ulcers), and a further 3% chancroid, 2% syphilis, 0.7% lymphogranuloma venereum and 31% undetermined aetiology. Over half (58%) of patients were HIV-1 seropositive. The median duration of symptoms before presentation was 6 days. Patients on acyclovir were more likely to have a healed ulcer on day 7 (63% vs 57%, RR = 1.08, 95% CI 0.98-1.18), shorter time to healing (p = 0.04) and less lesional HIV-1 RNA (p = 0.03). Small ulcers (<50 mm(2)), HSV-2 ulcers, first episode HSV-2 ulcers, and ulcers in HIV-1 seropositive individuals responded best but the better effectiveness in South Africa was not explained by differences in these factors. CONCLUSIONS/SIGNIFICANCE: There may be slight benefit in adding acyclovir to syndromic management in settings where most ulcers are genital herpes. The stronger effect among HIV-1 infected individuals suggests that acyclovir may be beneficial for GUD/HIV-1 co-infected patients. The high prevalence in this population highlights that genital ulceration in patients with unknown HIV status provides a potential entry point for provider-initiated HIV testing

    Ecological homogenization of urban USA

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    Author Posting. © Ecological Society of America, 2014. This article is posted here by permission of Ecological Society of America for personal use, not for redistribution. The definitive version was published in Frontiers in Ecology and the Environment 12 (2014): 74-81, doi:10.1890/120374.A visually apparent but scientifically untested outcome of land-use change is homogenization across urban areas, where neighborhoods in different parts of the country have similar patterns of roads, residential lots, commercial areas, and aquatic features. We hypothesize that this homogenization extends to ecological structure and also to ecosystem functions such as carbon dynamics and microclimate, with continental-scale implications. Further, we suggest that understanding urban homogenization will provide the basis for understanding the impacts of urban land-use change from local to continental scales. Here, we show how multi-scale, multi-disciplinary datasets from six metropolitan areas that cover the major climatic regions of the US (Phoenix, AZ; Miami, FL; Baltimore, MD; Boston, MA; Minneapolis–St Paul, MN; and Los Angeles, CA) can be used to determine how household and neighborhood characteristics correlate with land-management practices, land-cover composition, and landscape structure and ecosystem functions at local, regional, and continental scales.We thank the MacroSystems Biology Program in the Emerging Frontiers Division of the Biological Sciences Directorate at NSF for support. The “Ecological Homogenization of Urban America” project was supported by a series of collaborative grants from this program (EF-1065548, 1065737, 1065740, 1065741, 1065772, 1065785, 1065831, 121238320). The work arose from research funded by grants from the NSF Long Term Ecological Research Program supporting work in Baltimore (DEB-0423476), Phoenix (BCS-1026865, DEB-0423704 and DEB-9714833), Plum Island (Boston) (OCE-1058747 and 1238212), Cedar Creek (Minneapolis–St Paul) (DEB-0620652), and Florida Coastal Everglades (Miami) (DBI-0620409)

    IL-10 Blocks the Development of Resistance to Re-Infection with Schistosoma mansoni

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    Despite effective chemotherapy to treat schistosome infections, re-infection rates are extremely high. Resistance to reinfection can develop, however it typically takes several years following numerous rounds of treatment and re-infection, and often develops in only a small cohort of individuals. Using a well-established and highly permissive mouse model, we investigated whether immunoregulatory mechanisms influence the development of resistance. Following Praziquantel (PZQ) treatment of S. mansoni infected mice we observed a significant and mixed anti-worm response, characterized by Th1, Th2 and Th17 responses. Despite the elevated anti-worm response in PBMC's, liver, spleen and mesenteric lymph nodes, this did not confer any protection from a secondary challenge infection. Because a significant increase in IL-10-producing CD4+CD44+CD25+GITR+ lymphocytes was observed, we hypothesised that IL-10 was obstructing the development of resistance. Blockade of IL-10 combined with PZQ treatment afforded a greater than 50% reduction in parasite establishment during reinfection, compared to PZQ treatment alone, indicating that IL-10 obstructs the development of acquired resistance. Markedly enhanced Th1, Th2 and Th17 responses, worm-specific IgG1, IgG2b and IgE and circulating eosinophils characterized the protection. This study demonstrates that blocking IL-10 signalling during PZQ treatment can facilitate the development of protective immunity and provide a highly effective strategy to protect against reinfection with S. mansoni
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