4,651 research outputs found

    Explaining deep neural networks: A survey on the global interpretation methods

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    A substantial amount of research has been carried out in Explainable Artificial Intelligence (XAI) models, especially in those which explain the deep architectures of neural networks. A number of XAI approaches have been proposed to achieve trust in Artificial Intelligence (AI) models as well as provide explainability of specific decisions made within these models. Among these approaches, global interpretation methods have emerged as the prominent methods of explainability because they have the strength to explain every feature and the structure of the model. This survey attempts to provide a comprehensive review of global interpretation methods that completely explain the behaviour of the AI models. We present a taxonomy of the available global interpretations models and systematically highlight the critical features and algorithms that differentiate them from local as well as hybrid models of explainability. Through examples and case studies from the literature, we evaluate the strengths and weaknesses of the global interpretation models and assess challenges when these methods are put into practice. We conclude the paper by providing the future directions of research in how the existing challenges in global interpretation methods could be addressed and what values and opportunities could be realized by the resolution of these challenges

    Conserved Quantities in Noncommutative Principal Chiral Model with Wess-Zumino Term

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    We construct noncommutative extension of U(N) principal chiral model with Wess-Zumino term and obtain an infinite set of local and non-local conserved quantities for the model using iterative procedure of Brezin {\it et.al} \cite{BIZZ}. We also present the equivalent description as Lax formalism of the model. We expand the fields perturbatively and derive zeroth- and first-order equations of motion, zero-curvature condition, iteration method, Lax formalism, local and non-local conserved quantities.Comment: 14 Page

    Low-dose aspirin for the prevention of preterm delivery in nulliparous women with a singleton pregnancy (ASPIRIN): a randomised, double-blind, placebo-controlled trial.

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    BACKGROUND: Preterm birth remains a common cause of neonatal mortality, with a disproportionately high burden in low-income and middle-income countries. Meta-analyses of low-dose aspirin to prevent pre-eclampsia suggest that the incidence of preterm birth might also be decreased, particularly if initiated before 16 weeks of gestation. METHODS: ASPIRIN was a randomised, multicountry, double-masked, placebo-controlled trial of low-dose aspirin (81 mg daily) initiated between 6 weeks and 0 days of pregnancy, and 13 weeks and 6 days of pregnancy, in nulliparous women with an ultrasound confirming gestational age and a singleton viable pregnancy. Participants were enrolled at seven community sites in six countries (two sites in India and one site each in the Democratic Republic of the Congo, Guatemala, Kenya, Pakistan, and Zambia). Participants were randomly assigned (1:1, stratified by site) to receive aspirin or placebo tablets of identical appearance, via a sequence generated centrally by the data coordinating centre at Research Triangle Institute International (Research Triangle Park, NC, USA). Treatment was masked to research staff, health providers, and patients, and continued until 36 weeks and 7 days of gestation or delivery. The primary outcome of incidence of preterm birth, defined as the number of deliveries before 37 weeks\u27 gestational age, was analysed in randomly assigned women with pregnancy outcomes at or after 20 weeks, according to a modified intention-to-treat (mITT) protocol. Analyses of our binary primary outcome involved a Cochran-Mantel-Haenszel test stratified by site, and generalised linear models to obtain relative risk (RR) estimates and associated confidence intervals. Serious adverse events were assessed in all women who received at least one dose of drug or placebo. This study is registered with ClinicalTrials.gov, NCT02409680, and the Clinical Trial Registry-India, CTRI/2016/05/006970. FINDINGS: From March 23, 2016 to June 30, 2018, 14 361 women were screened for inclusion and 11 976 women aged 14-40 years were randomly assigned to receive low-dose aspirin (5990 women) or placebo (5986 women). 5780 women in the aspirin group and 5764 in the placebo group were evaluable for the primary outcome. Preterm birth before 37 weeks occurred in 668 (11·6%) of the women who took aspirin and 754 (13·1%) of those who took placebo (RR 0·89 [95% CI 0·81 to 0·98], p=0·012). In women taking aspirin, we also observed significant reductions in perinatal mortality (0·86 [0·73-1·00], p=0·048), fetal loss (infant death after 16 weeks\u27 gestation and before 7 days post partum; 0·86 [0·74-1·00], p=0·039), early preterm delivery (\u3c34 \u3eweeks; 0·75 [0·61-0·93], p=0·039), and the incidence of women who delivered before 34 weeks with hypertensive disorders of pregnancy (0·38 [0·17-0·85], p=0·015). Other adverse maternal and neonatal events were similar between the two groups. INTERPRETATION: In populations of nulliparous women with singleton pregnancies from low-income and middle-income countries, low-dose aspirin initiated between 6 weeks and 0 days of gestation and 13 weeks and 6 days of gestation resulted in a reduced incidence of preterm delivery before 37 weeks, and reduced perinatal mortality. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development

    Development of the global network for women\u27s and children\u27s health research\u27s socioeconomic status index for use in the network\u27s sites in low and lower middle-income countries

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    Background: Socioeconomic status (SES) is an important determinant of health globally and an important explanatory variable to assess causality in epidemiological research. The 10th Sustainable Development Goal is to reduce disparities in SES that impact health outcomes globally. It is easier to study SES in high-income countries because household income is representative of the SES. However, it is well recognized that income is poorly reported in low- and middle- income countries (LMIC) and is an unreliable indicator of SES. Therefore, there is a need for a robust index that will help to discriminate the SES of rural households in a pooled dataset from LMIC.Methods: The study was nested in the population-based Maternal and Neonatal Health Registry of the Global Network for Women\u27s and Children\u27s Health Research which has 7 rural sites in 6 Asian, sub-Saharan African and Central American countries. Pregnant women enrolling in the Registry were asked questions about items such as housing conditions and household assets. The characteristics of the candidate items were evaluated using confirmatory factor analyses and item response theory analyses. Based on the results of these analyses, a final set of items were selected for the SES index.Results: Using data from 49,536 households of pregnant women, we reduced the data collected to a 10-item index. The 10 items were feasible to administer, covered the SES continuum and had good internal reliability and validity. We developed a sum score-based Item Response Theory scoring algorithm which is easy to compute and is highly correlated with scores based on response patterns (r = 0.97), suggesting minimal loss of information with the simplified approach. Scores varied significantly by site (p \u3c 0.001). African sites had lower mean SES scores than the Asian and Central American sites. The SES index demonstrated good internal consistency reliability (Cronbach\u27s alpha = 0.81). Higher SES scores were significantly associated with formal education, more education, having received antenatal care, and facility delivery (p \u3c 0.001).Conclusions: While measuring SES in LMIC is challenging, we have developed a Global Network Socioeconomic Status Index which may be useful for comparisons of SES within and between locations. Next steps include understanding how the index is associated with maternal, perinatal and neonatal mortality. Trial Registration NCT01073475 Socioeconomic status (SES) is an important determinant of health globally, and improving SES is important to reduce disparities in health outcomes. It is easier to study SES in high-income countries because it can be measured by income and what income is spent on, but this concept does not translate easily to low and middle income countries. We developed a questionnaire that includes 10 items to determine SES in low-resource settings that was added to an ongoing Maternal and Neonatal Health Registry that is funded by the National Institutes of Child Health and Human Development\u27s Global Network. The Registry includes sites that collect outcomes of pregnancies in women and their babies in rural areas in 6 countries in South Asia, sub-Saharan Africa and Central America. The Registry is population based and tracks women from early in pregnancy to day 42 post-partum. The questionnaire is easy to administer and has good reliability and validity. Next steps include understanding how the index is associated with maternal, fetal and neonatal mortality

    Opposing effects ofApoe/Apoa1double deletion on amyloid-β pathology and cognitive performance in APP mice

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    Producción CientíficaATP binding cassette transporter A1 (encoded by ABCA1) regulates cholesterol efflux from cells to apolipoproteins A-I and E (ApoA-I and APOE; encoded by APOA1 and APOE, respectively) and the generation of high density lipoproteins. In Abca1 knockout mice (Abca1(ko)), high density lipoproteins and ApoA-I are virtually lacking, and total APOE and APOE-containing lipoproteins in brain substantially decreased. As the ε4 allele of APOE is the major genetic risk factor for late-onset Alzheimer's disease, ABCA1 role as a modifier of APOE lipidation is of significance for this disease. Reportedly, Abca1 deficiency in mice expressing human APP accelerates amyloid deposition and behaviour deficits. We used APP/PS1dE9 mice crossed to Apoe and Apoa1 knockout mice to generate Apoe/Apoa1 double-knockout mice. We hypothesized that Apoe/Apoa1 double-knockout mice would mimic the phenotype of APP/Abca1(ko) mice in regards to amyloid plaques and cognitive deficits. Amyloid pathology, peripheral lipoprotein metabolism, cognitive deficits and dendritic morphology of Apoe/Apoa1 double-knockout mice were compared to APP/Abca1(ko), APP/PS1dE9, and single Apoa1 and Apoe knockouts. Contrary to our prediction, the results demonstrate that double deletion of Apoe and Apoa1 ameliorated the amyloid pathology, including amyloid plaques and soluble amyloid. In double knockout mice we show that (125)I-amyloid-β microinjected into the central nervous system cleared at a rate twice faster compared to Abca1 knockout mice. We tested the effect of Apoe, Apoa1 or Abca1 deficiency on spreading of exogenous amyloid-β seeds injected into the brain of young pre-depositing APP mice. The results show that lack of Abca1 augments dissemination of exogenous amyloid significantly more than the lack of Apoe. In the periphery, Apoe/Apoa1 double-knockout mice exhibited substantial atherosclerosis and very high levels of low density lipoproteins compared to APP/PS1dE9 and APP/Abca1(ko). Plasma level of amyloid-β42 measured at several time points for each mouse was significantly higher in Apoe/Apoa1 double-knockout then in APP/Abca1(ko) mice. This result demonstrates that mice with the lowest level of plasma lipoproteins, APP/Abca1(ko), have the lowest level of peripheral amyloid-β. Unexpectedly, and independent of amyloid pathology, the deletion of both apolipoproteins worsened behaviour deficits of double knockout mice and their performance was undistinguishable from those of Abca1 knockout mice. Finally we observed that the dendritic complexity in the CA1 region of hippocampus but not in CA2 is significantly impaired by Apoe/Apoa1 double deletion as well as by lack of ABCA1. In conclusion: (i) plasma lipoproteins may affect amyloid-β clearance from the brain by the 'peripheral sink' mechanism; and (ii) deficiency of brain APOE-containing lipoproteins is of significance for dendritic complexity and cognition

    Investigation on the aerosol performance of dry powder inhalation hypromellose capsules with different lubricant levels

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    HPMC capsules are made by a dipping process and a surface lubricant for the mould pins is an essential processing aid for removing dried capsules shells. For the purpose of this study, the level was determined by quantifying methyloleate (MO) a component found in the lubricant but not in the hypromellose capsules. Here we investigated the influence of the lubricant, low (10.81 μg/capsule = 60 mg/kg MO), medium (15.97 μg/capsule = 90 mg/kg MO) and high (23.23 μg/capsule = 127 mg/kg MO) content on powder (binary mixture of salbutamol: lactose, 1:50 w/w) aerosolization properties was investigated. Results indicated significantly lower emitted dose from capsules with 60 mg/kg MO. Furthermore, the 90 and 127 mg/kg MO level of lubricant capsules produced almost double the Fine Particle Dose & Fine Particle Fraction compared with the low level of lubricant. The data indicates that lubricant level within capsules has an influence on deposition profiles and amount of drug remaining in capsule and inhaler device after actuation. It is suggested lubricant levels greater than 60 mg/kg MO per capsule are required to minimise powder retention within capsules and maximise deposition profiles. AFM (atomic force microscopy) data suggest that internal surface roughness may be related with this phenomena

    Prevalence and determinants of anemia among women of reproductive age in Thatta Pakistan: Findings from a cross-sectional study

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    Background: Anemia is a major public health concern among women of reproductive age leading to high maternal mortality in low- and middle-income countries. Of the prior studies conducted in Pakistan, most focused on large urban areas and did not explore the determinants of anemia among women of reproductive age (WRA) across socio-demographic, dietary, reproductive, and biological domains. Thus, we aimed to study the prevalence and determinants of anemia among WRA in rural Pakistan.Methods: We conducted a cross-sectional study in the Thatta district of Pakistan from September 2018 to January 2019 and enrolled 150 non-pregnant, married women. Data collectors administered a structured questionnaire to collect sociodemographic, reproductive and dietary data from women, who also provided stool and blood samples. We classified all WRA as anemic if their hemoglobin was \u3c12.0 g/dl. We performed logistic regression analysis to calculate adjusted odds ratios (aOR) and their respective 95% CIs to assess the determinants of anemia.Results: In our study, 61.3% of the enrolled women were anemic. In the multivariable analysis, we found that factors such as serum iron levels of less than 50 μg/dl (aOR: 7.17; 95% CI (2.94, 17.47)), history of breastfeeding (aOR: 2.43; 95% CI (1.04, 5.72)), living in a katcha house (aOR: 6.61; 95% CI (2.21, 19.87)), no consumption of meat (aOR: 4.18; 95% CI (1.66, 9.96)) were significantly associated with anemia among WRA. A history of more than one abortion (aOR: 0.06; 95% CI (0.01, 0.33) appeared protective for its association with anemia.Conclusion: Our findings demonstrate a high burden of anemia and its complex determinants among WRA in rural Pakistan. A combination of nutritional and educational strategies should be designed to encourage rural women to consume iron-rich foods in their diet with an access to adequate food. Breastfeeding women should be encouraged to consume extra calories with sufficient intake of the food to continue exclusive breastfeeding and reserve the iron stores through amenorrhea to prevent themselves from becoming anemic

    Challenges of implementing an individual randomized controlled trial (women first: Preconception maternal nutrition study) in a rural study site: A case study from Pakistan

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    Persistent global disparities in maternal and neonatal outcomes associated with poor maternal nutrition provided the genesis of the Women First (WF) study, an individually randomized controlled trial on preconceptional maternal nutrition. This article describes the challenges that arose in implementing this trial related to nutrition or diet of the mother, in District Thatta-Pakistan. During different phases of the study, we encountered problems in identifying the eligible participants, taking consent from couples, randomizing participants in different arms, conducting biweekly follow-up visits on time, ensuring compliance to the intervention, and measuring the primary outcome within the 24 hours of birth. Each challenge was itself an opportunity for the research team to address the same through effective coordination and teamwork. Moreover, with adequate resources and dedicated staff with diverse backgrounds, it was possible to implement the WF study across the widely scattered geographic clusters of District Thatta. In addition, there are some broad strategies that could be applied to other studies such as very close contact either in person or at least by talking to mothers via phones and rapport with the study participants, the study leadership of country coordinator and the field supervisors to build trust between those on front lines and the study leadership. Moreover, continuous monitoring and supervision with frequent training and refreshers were also found to be more important to assure the data quality and to meet the study targets. Community meetings were also found to be very helpful and effective to follow the participants for a long time. Researchers conducting a similar type of studies particularly in rural areas can learn many lessons from such experiences. Thus, the process of implementing the study in one of the rural areas of Pakistan provides an insight into where and how similar individual randomized trials might be deployed

    Algebraic construction of the Darboux matrix revisited

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    We present algebraic construction of Darboux matrices for 1+1-dimensional integrable systems of nonlinear partial differential equations with a special stress on the nonisospectral case. We discuss different approaches to the Darboux-Backlund transformation, based on different lambda-dependencies of the Darboux matrix: polynomial, sum of partial fractions, or the transfer matrix form. We derive symmetric N-soliton formulas in the general case. The matrix spectral parameter and dressing actions in loop groups are also discussed. We describe reductions to twisted loop groups, unitary reductions, the matrix Lax pair for the KdV equation and reductions of chiral models (harmonic maps) to SU(n) and to Grassmann spaces. We show that in the KdV case the nilpotent Darboux matrix generates the binary Darboux transformation. The paper is intended as a review of known results (usually presented in a novel context) but some new results are included as well, e.g., general compact formulas for N-soliton surfaces and linear and bilinear constraints on the nonisospectral Lax pair matrices which are preserved by Darboux transformations.Comment: Review paper (61 pages). To be published in the Special Issue "Nonlinearity and Geometry: Connections with Integrability" of J. Phys. A: Math. Theor. (2009), devoted to the subject of the Second Workshop on Nonlinearity and Geometry ("Darboux Days"), Bedlewo, Poland (April 2008

    A 5.3-Kilobase Genomic Fragment from Arabidopsis thaliana Containing kin1 and cor6.6

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