9,058 research outputs found
The propositional nature of human associative learning
The past 50 years have seen an accumulation of evidence suggesting that associative learning depends oil high-level cognitive processes that give rise to propositional knowledge. Yet, many learning theorists maintain a belief in a learning mechanism in which links between mental representations are formed automatically. We characterize and highlight the differences between the propositional and link approaches, and review the relevant empirical evidence. We conclude that learning is the consequence of propositional reasoning processes that cooperate with the unconscious processes involved in memory retrieval and perception. We argue that this new conceptual framework allows many of the important recent advances in associative learning research to be retained, but recast in a model that provides a firmer foundation for both immediate application and future research
Assessing causal relationships in genomics: From Bradford-Hill criteria to complex gene-environment interactions and directed acyclic graphs
Observational studies of human health and disease (basic, clinical and epidemiological) are vulnerable to methodological problems -such as selection bias and confounding- that make causal inferences problematic. Gene-disease associations are no exception, as they are commonly investigated using observational designs. A rich body of knowledge exists in medicine and epidemiology on the assessment of causal relationships involving personal and environmental causes of disease; it includes seminal causal criteria developed by Austin Bradford Hill and more recently applied directed acyclic graphs (DAGs). However, such knowledge has seldom been applied to assess causal relationships in clinical genetics and genomics, even in studies aimed at making inferences relevant for human health. Conversely, incorporating genetic causal knowledge into clinical and epidemiological causal reasoning is still a largely unexplored area
Distinguishing cause from effect using observational data: methods and benchmarks
The discovery of causal relationships from purely observational data is a
fundamental problem in science. The most elementary form of such a causal
discovery problem is to decide whether X causes Y or, alternatively, Y causes
X, given joint observations of two variables X, Y. An example is to decide
whether altitude causes temperature, or vice versa, given only joint
measurements of both variables. Even under the simplifying assumptions of no
confounding, no feedback loops, and no selection bias, such bivariate causal
discovery problems are challenging. Nevertheless, several approaches for
addressing those problems have been proposed in recent years. We review two
families of such methods: Additive Noise Methods (ANM) and Information
Geometric Causal Inference (IGCI). We present the benchmark CauseEffectPairs
that consists of data for 100 different cause-effect pairs selected from 37
datasets from various domains (e.g., meteorology, biology, medicine,
engineering, economy, etc.) and motivate our decisions regarding the "ground
truth" causal directions of all pairs. We evaluate the performance of several
bivariate causal discovery methods on these real-world benchmark data and in
addition on artificially simulated data. Our empirical results on real-world
data indicate that certain methods are indeed able to distinguish cause from
effect using only purely observational data, although more benchmark data would
be needed to obtain statistically significant conclusions. One of the best
performing methods overall is the additive-noise method originally proposed by
Hoyer et al. (2009), which obtains an accuracy of 63+-10 % and an AUC of
0.74+-0.05 on the real-world benchmark. As the main theoretical contribution of
this work we prove the consistency of that method.Comment: 101 pages, second revision submitted to Journal of Machine Learning
Researc
Persistent environmental pollutants and risk of cardiovascular disease
Persistent chemicals emitted in the environment can have a considerable impact on
ecosystems and human health, now and in the future. One notorious group of persistent
organic pollutants (POPs) is the per- and polyfluoroalkyl substances (PFAS). Since their
production in 1940s for household and consumer products, they have accumulated in the
environment and in humans via consumption of contaminated drinking water and food.
They are hypothesized to induce metabolic disturbances, due to shared chemical
similarities with fatty acids. Consequently, PFAS may have high societal and economic
impact by increasing risk of obesity, type 2 diabetes (T2D) and cardiovascular disease
(CVD). However, reports on these associations are scarce, and the underlying molecular
pathways are still unclear. Therefore, in this PhD project, we aimed to i) investigate
associations between PFAS and risk of several cardiometabolic diseases and ii) explore
potential underlying pathways.
In Paper I, we investigated cross-sectional associations between PFAS mixtures and body
mass index (BMI) in European teenagers using meta-regression. Results showed a
tendency for inverse associations between PFAS and BMI and indicated a potential for
diverging contributions between PFAS compounds. In Paper II, using a nested casecontrol study on T2D including metabolomics data in Swedish adults, we found that PFAS
correlated positively with glycerophospholipids and diacylglycerols. But whilst
glycerophospholipids associated with lower T2D risk, diacylglycerols associated with
higher T2D risk. This indicates a potential for diverging effects on disease risk. In Paper III,
we investigated whether genetic polymorphisms in peroxisome proliferator-activated
receptor gamma coactivator-1 alpha (PPARGC1A), which encodes a master regulator of
pathways potentially disrupted by PFAS exposure, associated with secondary
cardiovascular events in a large consortium study. However, we did not find clear
evidence for such associations. In Paper IV, we assessed associations of PFAS with blood
lipids and incident CVD using case-control studies nested in two Swedish adult cohorts.
We observed overall null associations with stroke, but a tendency for inverse associations
with myocardial infarction as well as associations with higher HDL-cholesterol and lower
triglycerides, but also with higher LDL-cholesterol. In Paper V, we included OMICs data
(metabolites, proteins and genes), which linked PFAS to lower myocardial infarction risk
via lipid and inflammatory pathways. Likewise, a group of ‘old POPs’, the organochlorine
compounds (OCs), were linked to higher myocardial infarction risk via the same pathways
and to higher stroke risk via mitochondrial pathways.
Thus, although we found no evidence for associations between PFAS and increased
cardiometabolic disease risk, the overall findings indicate associations of PFAS with
metabolic disturbances, particularly lipid metabolism. This is a potential adverse effect on
human physiology and warrants further attention
Target Trial Emulation and Bias Through Missing Eligibility Data: An Application to a Study of Palivizumab for the Prevention of Hospitalization due to Infant Respiratory Illness
Target trial emulation (TTE) applies the principles of randomised controlled trials to the causal analysis of observational datasets. On challenge that is rarely considered in TTE is the sources of bias that may arise if the variables involved in the definition of eligibility into the trial are missing. We highlight patterns of bias that might arise when estimating the causal effect of a point exposure when restricting the target trial (TT) to individuals with complete eligibility data. Simulations consider realistic scenarios where the variables affecting eligibility modify the causal effect of the exposure and are Missing at Random (MAR) or Missing Not at Random (MNAR). We discuss multiple means to address these patterns of bias, namely, (i) controlling for the collider bias induced by the missing dataon eligibility, and (ii) imputing the missing values of the eligibility variables prior to selection into the TT. Results are compared to when TTE is performed ignoring the impact of missing eligibility. A study of Palivizumab, a monoclonal antibody recommended for the prevention of respiratory hospital admissions due to Respiratory Synctial Virus in high risk infants, is used for illustrations
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