Estimation of individual treatment effect in observational data is complicated due to the challenges of confounding and selection bias. A useful inferential framework to address this is the ...counterfactual (potential outcomes) model, which takes the hypothetical stance of asking what if an individual had received both treatments. Making use of random forests (RF) within the counterfactual framework we estimate individual treatment effects by directly modeling the response. We find that accurate estimation of individual treatment effects is possible even in complex heterogenous settings but that the type of RF approach plays an important role in accuracy. Methods designed to be adaptive to confounding, when used in parallel with out-of-sample estimation, do best. One method found to be especially promising is counterfactual synthetic forests. We illustrate this new methodology by applying it to a large comparative effectiveness trial, Project Aware, to explore the role drug use plays in sexual risk. The analysis reveals important connections between risky behavior, drug usage, and sexual risk.
It is known that behavior in childhood is associated with certain physical and mental health problems in midlife. However, there is limited evidence on the role of childhood behavior problems in the ...development of hypertension in adulthood. The present study aimed to examine whether behavior problems in childhood influenced the risk of hypertension in midlife in the United Kingdom 1958 birth cohort.
The 1958 British birth cohort comprised 17,638 individuals born in the first week of March 1958 in the United Kingdom. Behavior problems were assessed at 7, 11, and 16 years of age by parents and teachers. At age 45, blood pressure was measured and hypertension was recorded if blood pressure was ≥140/90 mm Hg or if the participants were informed by their health professionals that they had high blood pressure. Behavioral information was reported according to the Rutter Children's Behaviour Questionnaire (RCBQ) and the Bristol Social Adjustment Guide (BSAG). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine behavior problems in childhood in relation to hypertension at 45 years of age according to logistic regression analysis, with adjustment for sex, social class in childhood and adulthood, childhood cognition, birth weight, gestational age at birth, body mass index (BMI), smoking, alcohol consumption, and physical activity.
Behavior problems reported by parents at 7, 11, and 16 years were not associated with hypertension in midlife (OR, 0.93; 95% CI, 0.81, 1.07; OR, 0.95; 95% CI, 0.81, 1.11; OR, 0.98; 95% CI, 0.85, 1.12, respectively). Similarly, teacher-reported behavior problems at 7, 11, and 16 years were not associated with hypertension in midlife (OR, 0.92; 95% CI, 0.72, 1.18; OR, 0.92; 95% CI, 0.84, 1.02; OR, 1.03; 95% CI, 0.92, 1.15, respectively). Further separate analyses showed similar results for males and females.
There is no association between behavior problems in childhood and hypertension in midlife.
We have described multipotent progenitor-like cells within the major pancreatic ducts (MPDs) of the human pancreas. They express PDX1, its surrogate surface marker P2RY1, and the bone morphogenetic ...protein (BMP) receptor 1A (BMPR1A)/activin-like kinase 3 (ALK3), but not carbonic anhydrase II (CAII). Here we report the single-cell RNA sequencing (scRNA-seq) of ALK3bright+-sorted ductal cells, a fraction that harbors BMP-responsive progenitor-like cells. Our analysis unveiled the existence of multiple subpopulations along two major axes, one that encompasses a gradient of ductal cell differentiation stages, and another featuring cells with transitional phenotypes toward acinar tissue. A third potential ducto-endocrine axis is revealed upon integration of the ALK3bright+ dataset with a single-cell whole-pancreas transcriptome. When transplanted into immunodeficient mice, P2RY1⁺/ALK3bright+ populations (enriched in PDX1⁺/ALK3⁺/CAII⁻ cells) differentiate into all pancreatic lineages, including functional β-cells. This process is accelerated when hosts are treated systemically with an ALK3 agonist. We found PDX1⁺/ALK3⁺/CAII⁻ progenitor-like cells in the MPDs of types 1 and 2 diabetes donors, regardless of the duration of the disease. Our findings open the door to the pharmacological activation of progenitor cells in situ.
To assess whether there is a long-term relationship between childhood behaviour problems and type 2 diabetes in midlife. The study will also investigate whether any of such relationship is ...independent of other factors which may be associated with type 2 diabetes.
Cohort study.
A total of 9377 members of the 1958 British birth cohort participated in the biomedical survey at age 45 years. The cohort has been followed up at regular intervals in childhood (age 7, 11 and 16 years) and adulthood (23, 33, 42 and 45 years).
Information regarding childhood behaviour collected during follow-ups at ages 7, 11 and 16 years.
Type 2 diabetes assessed using HbA1c at age 45 years.
Unadjusted estimates show that teachers reported adolescent behaviour problems at age of 16 are associated with increased risk of type 2 diabetes in midlife. After adjustment for potential confounders and mediators in childhood and adulthood, a relationship was observed between the severity of adolescent behaviour problems and type 2 diabetes risk in midlife (mild behaviour problems: OR 2.17, 95% CI 1.11-4.23; severe behaviour problems: OR 4.40, 95% CI 1.14-16.99). However, no such relationship was observed between behaviour problems at 7 and 11 years and type 2 diabetes in midlife.
There is an association between adolescent behaviour problems and an increased risk of type 2 diabetes in midlife. Further molecular/genetic studies are required to understand the biological basis for this observed association.
BackgroundThe etiologies of pancytopenia in the pediatric age group remain exceedingly ubiquitous and warrant extensive hematological and interventional investigations like bone marrow biopsy. It ...varies widely from benign nutritional disorders to fatal malignancies. The present study aims to delineate the prevalence of various causes of pancytopenia in the pediatric population.MethodsThe present cross-sectional study included 96 patients between the age of one month till 15 years with pancytopenia. Study participants were evaluated for various parameters including their demographical details, clinical features, immunization history, and nature of the disorder. The prevalence of various etiologies (nutritional, neoplastic, infectious, autoimmune, and others) of pancytopenia was ascertained.ResultsOf the 96 patients, 42 (43.75%) were males with a mean age of 69.47 ± 7.12 months. Fever was present in 71.87%, arthralgias in 56.25%, weight loss in 35.41%, and failure to thrive in 18.75% of patients. The bone marrow examination revealed aplastic changes in 36 (37.50%), hyperplastic changes in 21 (21.87%), and normal cellularity in 40.62% of patients. Megaloblastic anemia was the most common nutritional cause of pancytopenia present in 21.85% of cases. Acute lymphoblastic leukemia (ALL) was the most prevalent neoplastic etiology present in 19.79% of patients. Aplastic anemia, miliary tuberculosis, parvovirus B19, and hemolytic anemia were other notable etiologies.ConclusionMegaloblastic anemia and infections like tuberculosis were common treatable etiologies of pancytopenia among the pediatric age group. ALL was the most common neoplastic etiology. Bone marrow biopsy remains crucial in elucidating the various neoplastic and nutritional etiologies of pancytopenia in children.
A Survey on Deep Learning Pouyanfar, Samira; Sadiq, Saad; Yan, Yilin ...
ACM computing surveys,
09/2019, Letnik:
51, Številka:
5
Journal Article
Recenzirano
The field of machine learning is witnessing its golden era as deep learning slowly becomes the leader in this domain. Deep learning uses multiple layers to represent the abstractions of data to build ...computational models. Some key enabler deep learning algorithms such as generative adversarial networks, convolutional neural networks, and model transfers have completely changed our perception of information processing. However, there exists an aperture of understanding behind this tremendously fast-paced domain, because it was never previously represented from a multiscope perspective. The lack of core understanding renders these powerful methods as black-box machines that inhibit development at a fundamental level. Moreover, deep learning has repeatedly been perceived as a silver bullet to all stumbling blocks in machine learning, which is far from the truth. This article presents a comprehensive review of historical and recent state-of-the-art approaches in visual, audio, and text processing; social network analysis; and natural language processing, followed by the in-depth analysis on pivoting and groundbreaking advances in deep learning applications. It was also undertaken to review the issues faced in deep learning such as unsupervised learning, black-box models, and online learning and to illustrate how these challenges can be transformed into prolific future research avenues.
Purpose: To assess whether there is a long-term relationship between childhood behaviour problems and type 2 diabetes in midlife. The study will also investigate whether any of such relationship is ...independent of other factors which may be associated with type 2 diabetes. Design: Cohort study. Participants: A total of 9377 members of the 1958 British birth cohort participated in the biomedical survey at age 45 years. The cohort has been followed up at regular intervals in childhood (age 7, 11 and 16 years) and adulthood (23, 33, 42 and 45 years). Predictor Variables: Information regarding childhood behaviour collected during follow-ups at ages 7, 11 and 16 years. Main Outcome Variables: Type 2 diabetes assessed using HbA1c at age 45 years. Results: Unadjusted estimates show that teachers reported adolescent behaviour problems at age of 16 are associated with increased risk of type 2 diabetes in midlife. After adjustment for potential confounders and mediators in childhood and adulthood, a relationship was observed between the severity of adolescent behaviour problems and type 2 diabetes risk in midlife (mild behaviour problems: OR 2.17, 95% CI 1.11-4.23; severe behaviour problems: OR 4.40, 95% CI 1.14-16.99). However, no such relationship was observed between behaviour problems at 7 and 11 years and type 2 diabetes in midlife. Conclusion: There is an association between adolescent behaviour problems and an increased risk of type 2 diabetes in midlife. Further molecular/genetic studies are required to understand the biological basis for this observed association. Keywords: type 2 diabetes, adolescent behaviour problems, 1958 British birth cohort, National Child Development Study, HbA1c
Nowadays, the world faces extreme climate changes, resulting in an increase of natural disaster events and their severities. In these conditions, the necessity of disaster information management ...systems has become more imperative. Specifically, in this paper, the problem of flood event detection from images with real-world conditions is addressed. That is, the images may be taken in several conditions, including day, night, blurry, clear, foggy, rainy, different lighting conditions, etc. All these abnormal scenarios significantly reduce the performance of the learning algorithms. In addition, many existing image classification methods use datasets that usually include high-resolution images without considering real-world noise. In this paper, we propose a new image classification framework based on adversarial data augmentation and deep learning algorithms to address the aforementioned problems. We validate the performance of the flood event detection framework on a real-world noisy visual dataset collected from social networks.
Introduction: The exocrine compartment of the pancreas has been hypothesized to harbor progenitor cells. While their existence remains the subject of debate, the widespread consensus is that any such ...putative progenitors should express the pancreatic-duodenal homeobox 1 protein (PDX1). Progenitor cell stimulation often depends on concurrent TGFb inhibition and BMP activation. We further hypothesized that PDX1-expressing putative b-cell progenitors may respond to BMP-7. Our data (1) indicate that extrainsular PDX1+/ALK3+ cells do so by proliferating and subsequently, upon BMP-7 withdrawal, differentiating in a multilineage fashion. Here we present additional mechanistic data on b-cell regeneration using a novel human pancreatic slice culture system that allows for the observation of pancreatic tissue for 2 weeks. We further show single cell RNAseq analyses of sorted ALK3+ from the human pancreas, confirming the heterogeneity of the ductal compartment.
Methods: HPS: Low melting point agarose-embedded, vibratome-sectioned live pancreatic slices were generated from human donors. Transduction with a CMV-loxP-dsRed-loxP-EGFP adenovirus + insulin promoter-Cre adenovirus was done in slices cultured atop optically clear perfluorcarbon (PFC)-based membranes. scRNAseq of ALK3+ sorted cells from human non-endocrine tissue (hNEPT, the leftover of islet isolations) was done on 1,000 cells/sample (250K reads/cell).
Conclusions: We report the use of live HPS as a novel tool for the study of pancreatic regeneration. Our preliminary results confirm the feasibility of tracing and monitoring discrete transitional events in response to BMP signalling stimulation, as well as the existence of multiple ductal populations at various degrees of differentiation in healthy donor pancreata.
References:
1. Qadir MMF, et al. P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics. Cell Reports. 2018
Disclosure
M. Qadir: None. S. Alvarez-Cubela: None. J. van Dijk: None. J. Weitz: None. S. Cechin: None. D. Klein: None. A.M. Tamayo: None. J. Almaca: None. A. Caicedo: None. I. Kusmartseva: None. H. Hiller: None. M. Beery: None. K.B. Johnson: None. Y.B. Moreno Hernandez: None. M.B. Navarro Rubio: None. S. Sadiq: None. C. Ricordi: Advisory Panel; Self; Zone Labs. A. Pugliese: None. C. Fraker: None. R. Pastori: Other Relationship; Self; Ophysio Inc. J. Domínguez-Bendala: None.
Funding
Diabetes Research Institute Foundation; Inserra Family Foundation; Fred and Mabel R. Parks Foundation; Foundation for Diabetes Research; Tonkinson Foundation; Michael J. and Katherine E. Franco Foundation; Frank Strick Foundation; Mildred Graff; National Institutes of Health (R43DK105655-01, R44DK105655-02, U01DK120393-01); Fulbright Scholarship Board/International Institute of Education (to M.M.F.Q.)
One size fits all approaches to medicine have become a thing of the past as the understanding of individual differences grows. The paper introduces a test for the presence of heterogeneity in ...treatment effects in a clinical trial. Heterogeneity is assessed on the basis of the predicted individual treatment effects (PITE) framework and a permutation test is utilized to establish if significant heterogeneity is present. We first use the novel test to show that heterogeneity in the effects of interventions exists in the Amyotrophic Lateral Sclerosis Clinical Trials. We then show, using two different predictive models (linear regression model and Random Forests) that the test has adequate type I error control. Next, we use the ALS data as the basis for simulations to demonstrate the ability of the permutation test to find heterogeneity in treatment effects as a function of both effect size and sample size. We find that the proposed test has good power to detected heterogeneity in treatment effects when the heterogeneity was due primarily to a single predictor, or when it was spread across the predictors. The predictive model, on the other hand is of secondary importance to detect heterogeneity. The non-parametric property of the permutation test can be applied with any predictive method and requires no additional assumptions to obtain PITEs.
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