Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox

This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results

Individualization as driving force of clustering phenomena in humans

One of the most intriguing dynamics in biological systems is the emergence of clustering, the self-organization into separated agglomerations of individuals. Several theories have been developed to explain clustering in, for instance, multi-cellular organisms, ant colonies, bee hives, flocks of birds, schools of fish, and animal herds. A persistent puzzle, however, is clustering of opinions in human populations. The puzzle is particularly pressing if opinions vary continuously, such as the degree to which citizens are in favor of or against a vaccination program. Existing opinion formation models suggest that "monoculture" is unavoidable in the long run, unless subsets of the population are perfectly separated from each other. Yet, social diversity is a robust empirical phenomenon, although perfect separation is hardly possible in an increasingly connected world. Considering randomness did not overcome the theoretical shortcomings so far. Small perturbations of individual opinions trigger social influence cascades that inevitably lead to monoculture, while larger noise disrupts opinion clusters and results in rampant individualism without any social structure. Our solution of the puzzle builds on recent empirical research, combining the integrative tendencies of social influence with the disintegrative effects of individualization. A key element of the new computational model is an adaptive kind of noise. We conduct simulation experiments to demonstrate that with this kind of noise, a third phase besides individualism and monoculture becomes possible, characterized by the formation of metastable clusters with diversity between and consensus within clusters. When clusters are small, individualization tendencies are too weak to prohibit a fusion of clusters. When clusters grow too large, however, individualization increases in strength, which promotes their splitting.Comment: 12 pages, 4 figure

Pre-Stressor Interference Control and Intrusive Memories

Although intrusive imagery is a common response in the aftermath of a stressful or traumatic event, only a minority of trauma victims show persistent re-experiencing and related psychopathology. Individual differences in pre-trauma executive control possibly play a critical role. Therefore, this study investigated whether a relatively poor pre-stressor ability to resist proactive interference in working memory might increase risk for experiencing undesirable intrusive memories after being exposed to a stressful event. Non-clinical participants (N = 85) completed a modified version of a widely used test of interference control in working memory (CVLT; Kramer and Delis 1991) and subsequently watched an emotional film fragment. Following presentation of the fragment, intrusive memories were recorded in a 1-week diary and at a follow up session 7 days later. A relatively poor ability to resist proactive interference was related to a relatively high frequency of film-related intrusive memories. This relationship was independent of neuroticism and gender. These findings are consistent with the idea that a pre-morbid deficit in the ability to resist proactive interference reflects a vulnerability factor for experiencing intrusive memories after trauma exposure

O6-methylguanine-DNA-methyltransferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma

In a retrospective study, O6-methylguanine-DNA-methyltransferase (MGMT) expression was analysed by immunohistochemistry using monoclonal human anti-MGMT antibody in melanoma metastases in patients receiving dacarbazine (DTIC) as single-drug therapy or as part of combination chemotherapy with DTIC–vindesine or DTIC–vindesine–cisplatin. The correlation of MGMT expression levels with clinical response to chemotherapy was investigated in 79 patients with metastatic melanoma. There was an inverse relationship between MGMT expression and clinical response to DTIC-based chemotherapy (P=0.05). Polymorphisms in the coding region of the MGMT gene were also investigated in tumours from 52 melanoma patients by PCR/SSCP and nucleotide sequence analyses. Single-nucleotide polymorphisms (SNPs) in exon 3 (L53L and L84F) and in exon 5 (I143V/K178R) were identified. There were no differences in the frequencies of these polymorphisms between these melanoma patients and patients with familial melanoma or healthy Swedish individuals. Functional analysis of variants MGMT-I143V and -I143V/K178R was performed by in vitro mutagenesis in Escherichia coli. There was no evidence that these variants decreased the MGMT DNA repair activity compared to the wild-type protein. All melanoma patients with the MGMT 53/84 polymorphism except one had tumours with high MGMT expression. There was no significant correlation between any of the MGMT polymorphisms and clinical response to chemotherapy, although an indication of a lower response rate in patients with SNPs in exon 5 was obtained. Thus, MGMT expression appears to be more related to response to chemotherapy than MGMT polymorphisms in patients with metastatic melanoma

Why are we not flooded by involuntary thoughts about the past and future? Testing the cognitive inhibition dependency hypothesis

© The Author(s) 2018In everyday life, involuntary thoughts about future plans and events occur as often as involuntary thoughts about the past. However, compared to involuntary autobiographical memories (IAMs), such episodic involuntary future thoughts (IFTs) have become a focus of study only recently. The aim of the present investigation was to examine why we are not constantly flooded by IFTs and IAMs given that they are often triggered by incidental cues while performing undemanding activities. One possibility is that activated thoughts are suppressed by the inhibitory control mechanism, and therefore depleting inhibitory control should enhance the frequency of both IFTs and IAMs. We report an experiment with a between-subjects design, in which participants in the depleted inhibition condition performed a 60-min high-conflict Stroop task before completing a laboratory vigilance task measuring the frequency of IFTs and IAMs. Participants in the intact inhibition condition performed a version of the Stroop task that did not deplete inhibitory control. To control for physical and mental fatigue resulting from performing the 60-min Stroop tasks in experimental conditions, participants in the control condition completed only the vigilance task. Contrary to predictions, the number of IFTs and IAMs reported during the vigilance task, using the probe-caught method, did not differ across conditions. However, manipulation checks showed that participants’ inhibitory resources were reduced in the depleted inhibition condition, and participants were more tired in the experimental than in the control conditions. These initial findings suggest that neither inhibitory control nor physical and mental fatigue affect the frequency of IFTs and IAMs.Peer reviewedFinal Published versio

Dissociable Components of Cognitive Control: An Event-Related Potential (ERP) Study of Response Inhibition and Interference Suppression

Background: Cognitive control refers to the ability to selectively attend and respond to task-relevant events while resisting interference from distracting stimuli or prepotent automatic responses. The current study aimed to determine whether interference suppression and response inhibition are separable component processes of cognitive control. Methodology/Principal Findings: Fourteen young adults completed a hybrid Go/Nogo flanker task and continuous EEG data were recorded concurrently. The incongruous flanker condition (that required interference suppression) elicited a more centrally distributed topography with a later N2 peak than the Nogo condition (that required response inhibition). Conclusions/Significance: These results provide evidence for the dissociability of interference suppression and response inhibition, indicating that taxonomy of inhibition is warranted with the integration of research evidence from neuroscience

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Khat Use Is Associated with Impaired Working Memory and Cognitive Flexibility

Rationale Khat consumption has increased during the last decades in Eastern Africa and has become a global phenomenon spreading to ethnic communities in the rest of the world, such as The Netherlands, United Kingdom, Canada, and the United States. Very little is known, however, about the relation between khat use and cognitive control functions in khat users. Objective We studied whether khat use is associated with changes in working memory (WM) and cognitive flexibility, two central cognitive control functions. Methods Khat users and khat-free controls were matched in terms of sex, ethnicity, age, alcohol and cannabis consumption, and IQ (Raven's progressive matrices). Groups were tested on cognitive flexibility, as measured by a Global-Local task, and on WM using an N-back task. Result Khat users performed significantly worse than controls on tasks tapping into cognitive flexibility as well as monitoring of information in WM. Conclusions The present findings suggest that khat use impairs both cognitive flexibility and the updating of information in WM. The inability to monitor information in WM and to adjust behavior rapidly and flexibly may have repercussions for daily life activities

Extraordinary Molecular Evolution in the PRDM9 Fertility Gene

Recent work indicates that allelic incompatibility in the mouse PRDM9 (Meisetz) gene can cause hybrid male sterility, contributing to genetic isolation and potentially speciation. The only phenotype of mouse PRDM9 knockouts is a meiosis I block that causes sterility in both sexes. The PRDM9 gene encodes a protein with histone H3(K4) trimethyltransferase activity, a KRAB domain, and a DNA-binding domain consisting of multiple tandem C2H2 zinc finger (ZF) domains. We have analyzed human coding polymorphism and interspecies evolutionary changes in the PRDM9 gene. The ZF domains of PRDM9 are evolving very rapidly, with compelling evidence of positive selection in primates. Positively selected amino acids are predominantly those known to make nucleotide specific contacts in C2H2 zinc fingers. These results suggest that PRDM9 is subject to recurrent selection to change DNA-binding specificity. The human PRDM9 protein is highly polymorphic in its ZF domains and nearly all polymorphisms affect the same nucleotide contact residues that are subject to positive selection. ZF domain nucleotide sequences are strongly homogenized within species, indicating that interfinger recombination contributes to their evolution. PRDM9 has previously been assumed to be a transcription factor required to induce meiosis specific genes, a role that is inconsistent with its molecular evolution. We suggest instead that PRDM9 is involved in some aspect of centromere segregation conflict and that rapidly evolving centromeric DNA drives changes in PRDM9 DNA-binding domains