Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10^–6) with replication at Bonferroni-corrected P < 8.6 x 10^–4. Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10^–4). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood–derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat–associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.

We conducted a two-sample Mendelian randomisation study to investigate the causal associations of type 2 diabetes mellitus (T2DM) with risk of overall cancer and 22 site-specific cancers. Summary-level data for cancer were extracted from the Breast Cancer Association Consortium and UK Biobank. Genetic predisposition to T2DM was associated with higher odds of pancreatic, kidney, uterine and cervical cancer, lower odds of oesophageal cancer and melanoma, but not associated with 16 other site-specific cancers or overall cancer. The odds ratios (95% confidence interval) were 1.13 (1.04, 1.22), 1.08 (1.00, 1.17), 1.08 (1.01, 1.15), 1.07 (1.01, 1.15), 0.89 (0.81, 0.98), and 0.93 (0.89, 0.97) for pancreatic, kidney, uterine, cervical, and oesophageal cancer and melanoma, respectively. The association between T2DM and pancreatic cancer was also observed in a meta-analysis of this and a previous Mendelian randomisation study (odds ratio 1.08; 1.02, 1.14; p=0.009). There was limited evidence supporting causal associations between fasting glucose and cancer. Genetically predicted fasting insulin levels were positively associated with cancers of the uterus, kidney, pancreas and lung. The present study found causal detrimental effects of T2DM on several cancers. We suggested to reinforce the cancers screening in T2DM patients to enable the early detection of cancer.

The increasing prevalence of type 2 diabetes poses a major challenge to societies worldwide. Blood-based factors like serum proteins are in contact with every organ in the body to mediate global homeostasis and may thus directly regulate complex processes such as aging and the development of common chronic diseases. We applied a data-driven proteomics approach, measuring serum levels of 4,137 proteins in 5,438 elderly Icelanders and identified 536 proteins associated with prevalent and/or incident type 2 diabetes. We validated a subset of the observed associations in an independent case-control study of type 2 diabetes. These protein associations provide novel biological insights into the molecular mechanisms that are dysregulated prior to and following the onset of type 2 diabetes and can be detected in serum. A bi-directional two-sample Mendelian randomization analysis indicated that serum changes of at least 23 proteins are downstream of the disease or its genetic liability, while 15 proteins were supported as having a causal role in type 2 diabetes.

We only sell high-quality marijuana which is approved by the authorities taking care of the medical sector. The medical marijuana bought from us will never land you in trouble and you will receive your order on time and in a discrete way.

OLIEVENHOUTBOS, South Africa (AP) — Thousands of people stood in line for hours on Saturday in a South African township waiting for handouts of food. The scene has repeated for days in one of the world’s most unequal countries as...

Joseph Henson
Jan 1, 2016; 39:130-138
IDF-ADA Translational Symposium

The Chicago Dental Society and its members donated thousands of personal protective equipment to front-line health care workers in response to the COVID-19 pandemic.

OBJECTIVE

To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation.

There is so much that is peculiar, irregular, silly, or downright twisted in mathematical verbiage that, certainly, we could all benefit from some soul-searching on the language of our culture. Some of mathematics usage is confusing (e. g. overuse of … Continue reading →

This recipe features on Foodie Tuesday, a weekly segment on 774 Drive with Raf Epstein, 3.30PM, shared by Dan Hunter, chef and owner of Otways' restaurant Brae.

Kathy Tsaples, author of Sweet Greek Life, shared this recipe on Foodie Tuesday, a weekly segment on ABC Radio Melbourne's Drive program at 3.30pm.

Kathy Tsaple, author of Sweet Greek Life, shared this recipe on Foodie Tuesday, a weekly segment on ABC Radio Melbourne's Drive program at 3.30pm.

Gayle Lorenzi
Sep 1, 2010; 28:157-162
Bridges to Excellence

"Life's beauty is inseparable from its fragility," says psychologist Susan David. In a special virtual conversation, she shares wisdom on how to build resilience, courage and joy in the midst of the coronavirus pandemic. Responding to listeners' questions from across the globe, she offers ways to talk to your children about their emotions, keep focus during the crisis and help those working on the front lines. (This virtual conversation is part of the TED Connects series, hosted by head of TED Chris Anderson and current affairs curator Whitney Pennington Rodgers. Recorded March 23, 2020)

Muslims.

Aboriginal Australians -- Land tenure.

Menopause.

Paris : O. Doin, 1890.

Stuttgart : F. Enke, 1902.

Breslau : Preuss & Junger, 1897.

Berlin : T. Trautwein, 1842.

Berlin : A. Hirschwald, 1896.

London : Smith, Elder, 1881.

Edinburgh : Oliver and Boyd, 1888.

London : Philadelphia, 1890.

As Oklahoma teachers prepare for day four of their statewide walkout, here's a guide to the larger picture of teacher protests.

A Paris (rue St Jacques au dessus de la fontaine St Severin aux 2 colonnes) : chez Jacques Chereau, [between 1700 and 1799?]

Stuttgart : In Kommission: Wissenschaftliche Verlagsgesellschaft, 2019.

This paper presents a new open source Python framework for causal discovery from observational data and domain background knowledge, aimed at causal graph and causal mechanism modeling. The cdt package implements an end-to-end approach, recovering the direct dependencies (the skeleton of the causal graph) and the causal relationships between variables. It includes algorithms from the `Bnlearn' and `Pcalg' packages, together with algorithms for pairwise causal discovery such as ANM.

We consider the problem of learning causal models from observational data generated by linear non-Gaussian acyclic causal models with latent variables. Without considering the effect of latent variables, the inferred causal relationships among the observed variables are often wrong. Under faithfulness assumption, we propose a method to check whether there exists a causal path between any two observed variables. From this information, we can obtain the causal order among the observed variables. The next question is whether the causal effects can be uniquely identified as well. We show that causal effects among observed variables cannot be identified uniquely under mere assumptions of faithfulness and non-Gaussianity of exogenous noises. However, we are able to propose an efficient method that identifies the set of all possible causal effects that are compatible with the observational data. We present additional structural conditions on the causal graph under which causal effects among observed variables can be determined uniquely. Furthermore, we provide necessary and sufficient graphical conditions for unique identification of the number of variables in the system. Experiments on synthetic data and real-world data show the effectiveness of our proposed algorithm for learning causal models.

Given a response $Y$ and a vector $X = (X^1, dots, X^d)$ of $d$ predictors, we investigate the problem of inferring direct causes of $Y$ among the vector $X$. Models for $Y$ that use all of its causal covariates as predictors enjoy the property of being invariant across different environments or interventional settings. Given data from such environments, this property has been exploited for causal discovery. Here, we extend this inference principle to situations in which some (discrete-valued) direct causes of $ Y $ are unobserved. Such cases naturally give rise to switching regression models. We provide sufficient conditions for the existence, consistency and asymptotic normality of the MLE in linear switching regression models with Gaussian noise, and construct a test for the equality of such models. These results allow us to prove that the proposed causal discovery method obtains asymptotic false discovery control under mild conditions. We provide an algorithm, make available code, and test our method on simulated data. It is robust against model violations and outperforms state-of-the-art approaches. We further apply our method to a real data set, where we show that it does not only output causal predictors, but also a process-based clustering of data points, which could be of additional interest to practitioners.

In this paper we introduce a statistical model, called additively faithful directed acyclic graph (AFDAG), for causal learning from observational data. Our approach is based on additive conditional independence (ACI), a recently proposed three-way statistical relation that shares many similarities with conditional independence but without resorting to multi-dimensional kernels. This distinct feature strikes a balance between a parametric model and a fully nonparametric model, which makes the proposed model attractive for handling large networks. We develop an estimator for AFDAG based on a linear operator that characterizes ACI, and establish the consistency and convergence rates of this estimator, as well as the uniform consistency of the estimated DAG. Moreover, we introduce a modified PC-algorithm to implement the estimating procedure efficiently, so that its complexity is determined by the level of sparseness rather than the dimension of the network. Through simulation studies we show that our method outperforms existing methods when commonly assumed conditions such as Gaussian or Gaussian copula distributions do not hold. Finally, the usefulness of AFDAG formulation is demonstrated through an application to a proteomics data set.

We develop an encompassing framework for matching, covariate balancing, and doubly-robust methods for causal inference from observational data called generalized optimal matching (GOM). The framework is given by generalizing a new functional-analytical formulation of optimal matching, giving rise to the class of GOM methods, for which we provide a single unified theory to analyze tractability and consistency. Many commonly used existing methods are included in GOM and, using their GOM interpretation, can be extended to optimally and automatically trade off balance for variance and outperform their standard counterparts. As a subclass, GOM gives rise to kernel optimal matching (KOM), which, as supported by new theoretical and empirical results, is notable for combining many of the positive properties of other methods in one. KOM, which is solved as a linearly-constrained convex-quadratic optimization problem, inherits both the interpretability and model-free consistency of matching but can also achieve the $sqrt{n}$-consistency of well-specified regression and the bias reduction and robustness of doubly robust methods. In settings of limited overlap, KOM enables a very transparent method for interval estimation for partial identification and robust coverage. We demonstrate this in examples with both synthetic and real data.

Datasets in sleep science present challenges for machine learning algorithms due to differences in recording setups across clinics. We investigate two deep transfer learning strategies for overcoming the channel mismatch problem for cases where two datasets do not contain exactly the same setup leading to degraded performance in single-EEG models. Specifically, we train a baseline model on multivariate polysomnography data and subsequently replace the first two layers to prepare the architecture for single-channel electroencephalography data. Using a fine-tuning strategy, our model yields similar performance to the baseline model (F1=0.682 and F1=0.694, respectively), and was significantly better than a comparable single-channel model. Our results are promising for researchers working with small databases who wish to use deep learning models pre-trained on larger databases.

Xiaoqin Wang, Li Yin.

Source: The Annals of Statistics, Volume 48, Number 1, 138--160.

Abstract:
In sequential causal inference, two types of causal effects are of practical interest, namely, the causal effect of the treatment regime (called the sequential causal effect) and the blip effect of treatment on the potential outcome after the last treatment. The well-known $G$-formula expresses these causal effects in terms of the standard parameters. In this article, we obtain a new $G$-formula that expresses these causal effects in terms of the point observable effects of treatments similar to treatment in the framework of single-point causal inference. Based on the new $G$-formula, we estimate these causal effects by maximum likelihood via point observable effects with methods extended from single-point causal inference. We are able to increase precision of the estimation without introducing biases by an unsaturated model imposing constraints on the point observable effects. We are also able to reduce the number of point observable effects in the estimation by treatment assignment conditions.

Michael E. Sobel, Martin A. Lindquist.

Source: The Annals of Applied Statistics, Volume 14, Number 1, 452--472.

Abstract:
Neuroscientists often use functional magnetic resonance imaging (fMRI) to infer effects of treatments on neural activity in brain regions. In a typical fMRI experiment, each subject is observed at several hundred time points. At each point, the blood oxygenation level dependent (BOLD) response is measured at 100,000 or more locations (voxels). Typically, these responses are modeled treating each voxel separately, and no rationale for interpreting associations as effects is given. Building on Sobel and Lindquist ( J. Amer. Statist. Assoc. 109 (2014) 967–976), who used potential outcomes to define unit and average effects at each voxel and time point, we define and estimate both “point” and “cumulated” effects for brain regions. Second, we construct a multisubject, multivoxel, multirun whole brain causal model with explicit parameters for regions. We justify estimation using BOLD responses averaged over voxels within regions, making feasible estimation for all regions simultaneously, thereby also facilitating inferences about association between effects in different regions. We apply the model to a study of pain, finding effects in standard pain regions. We also observe more cerebellar activity than observed in previous studies using prevailing methods.

Fan Li, Fan Li.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2389--2415.

Abstract:
Causal or unconfounded descriptive comparisons between multiple groups are common in observational studies. Motivated from a racial disparity study in health services research, we propose a unified propensity score weighting framework, the balancing weights, for estimating causal effects with multiple treatments. These weights incorporate the generalized propensity scores to balance the weighted covariate distribution of each treatment group, all weighted toward a common prespecified target population. The class of balancing weights include several existing approaches such as the inverse probability weights and trimming weights as special cases. Within this framework, we propose a set of target estimands based on linear contrasts. We further develop the generalized overlap weights, constructed as the product of the inverse probability weights and the harmonic mean of the generalized propensity scores. The generalized overlap weighting scheme corresponds to the target population with the most overlap in covariates across the multiple treatments. These weights are bounded and thus bypass the problem of extreme propensities. We show that the generalized overlap weights minimize the total asymptotic variance of the moment weighting estimators for the pairwise contrasts within the class of balancing weights. We consider two balance check criteria and propose a new sandwich variance estimator for estimating the causal effects with generalized overlap weights. We apply these methods to study the racial disparities in medical expenditure between several racial groups using the 2009 Medical Expenditure Panel Survey (MEPS) data. Simulations were carried out to compare with existing methods.

Chanmin Kim, Michael J. Daniels, Joseph W. Hogan, Christine Choirat, Corwin M. Zigler.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1927--1956.

Abstract:
Emission control technologies installed on power plants are a key feature of many air pollution regulations in the US. While such regulations are predicated on the presumed relationships between emissions, ambient air pollution and human health, many of these relationships have never been empirically verified. The goal of this paper is to develop new statistical methods to quantify these relationships. We frame this problem as one of mediation analysis to evaluate the extent to which the effect of a particular control technology on ambient pollution is mediated through causal effects on power plant emissions. Since power plants emit various compounds that contribute to ambient pollution, we develop new methods for multiple intermediate variables that are measured contemporaneously, may interact with one another, and may exhibit joint mediating effects. Specifically, we propose new methods leveraging two related frameworks for causal inference in the presence of mediating variables: principal stratification and causal mediation analysis. We define principal effects based on multiple mediators, and also introduce a new decomposition of the total effect of an intervention on ambient pollution into the natural direct effect and natural indirect effects for all combinations of mediators. Both approaches are anchored to the same observed-data models, which we specify with Bayesian nonparametric techniques. We provide assumptions for estimating principal causal effects, then augment these with an additional assumption required for causal mediation analysis. The two analyses, interpreted in tandem, provide the first empirical investigation of the presumed causal pathways that motivate important air quality regulatory policies.

Fuhlbohm (Family)

Fuhlbohm (Family)

Some Democrats took "Believe Women" literally until Joe Biden was accused. Now they're relearning that guilt-by-accusation doesn't serve justice.

Pantelis Samartsidis, Shaun R. Seaman, Anne M. Presanis, Matthew Hickman, Daniela De Angelis.

Source: Statistical Science, Volume 34, Number 3, 486--503.

Abstract:
Researchers are often challenged with assessing the impact of an intervention on an outcome of interest in situations where the intervention is nonrandomised, the intervention is only applied to one or few units, the intervention is binary, and outcome measurements are available at multiple time points. In this paper, we review existing methods for causal inference in these situations. We detail the assumptions underlying each method, emphasize connections between the different approaches and provide guidelines regarding their practical implementation. Several open problems are identified thus highlighting the need for future research.

Nicole Bohme Carnegie.

Source: Statistical Science, Volume 34, Number 1, 90--93.

Abstract:
With a thorough exposition of the methods and results of the 2016 Atlantic Causal Inference Competition, Dorie et al. have set a new standard for reproducibility and comparability of evaluations of causal inference methods. In particular, the open-source R package aciccomp2016, which permits reproduction of all datasets used in the competition, will be an invaluable resource for evaluation of future methodological developments. Building upon results from Dorie et al., we examine whether a set of potential modifications to Bayesian Additive Regression Trees (BART)—multiple chains in model fitting, using the propensity score as a covariate, targeted maximum likelihood estimation (TMLE), and computing symmetric confidence intervals—have a stronger impact on bias, RMSE, and confidence interval coverage in combination than they do alone. We find that bias in the estimate of SATT is minimal, regardless of the BART formulation. For purposes of CI coverage, however, all proposed modifications are beneficial—alone and in combination—but use of TMLE is least beneficial for coverage and results in considerably wider confidence intervals.

Ehud Karavani, Tal El-Hay, Yishai Shimoni, Chen Yanover.

Source: Statistical Science, Volume 34, Number 1, 86--89.

Abstract:
Data competitions proved to be highly beneficial to the field of machine learning, and thus expected to provide similar advantages in the field of causal inference. As participants in the 2016 and 2017 Atlantic Causal Inference Conference (ACIC) data competitions and co-organizers of the 2018 competition, we discuss the strengths of simulation-based competitions and suggest potential extensions to address their limitations. These suggested augmentations aim at making the data generating processes more realistic and gradually increase in complexity, allowing thorough investigations of algorithms’ performance. We further outline a community-wide competition framework to evaluate an end-to-end causal inference pipeline, beginning with a causal question and a database, and ending with causal estimates.