Complexity under stress: Integrative approaches to overdetermined vulnerabilities

Over four decades of cognitive complexity research demonstrate that higher integrative complexity (measured by the ability to differentiate and integrate multiple dimensions or perspectives on an issue) predicts more lasting, peaceful solutions to conflict. Interventions that seek to raise integrative complexity offer a promising approach to preventing various forms of intergroup conflict (e.g. sectarianism, violent extremism). However, these contexts can also be extremely stressful, and dominant theory suggests that cognitive complexity diminishes in the face of high stress. However, we know that this is not always the case, with some findings demonstrating the opposite pattern: increases in complexity under high stress. How is it that some people in the midst of stressful conflict are able to recognize multiple perspectives and solutions, while others become increasingly narrow and rigid in their thinking? The aim of this paper is to integrate these divergent findings through the broader framework of the biopsychosocial model of stress and to explore possible underlying mechanisms such as affect. Implications for intervention will also be discussed

I See! Scotland: Tackling sectarianism and promoting community psychosocial health

We developed and tested through two studies a new intervention run as a course, I SEE! Scotland, to reduce and prevent Protestant-Catholic sectarianism in Scotland, a historic inter-group conflict expressed in forms ranging from polite to violent, within a wider population that includes those who feel untouched. Designed to reflect the social ecology of Scotland and engage individuals regardless of sectarian involvement, the intervention aimed to increase cognitive complexity, measured as integrative complexity, through participatory theatre and experiential methods. We hypothesised that the confluence of experiential learning to support multiple forms of self, other, and systems awareness with narrative framing would increase integrative complexity management capacities. Tested with a diverse sample of 104 participants (secondary school staff; achieving, disruptive or vulnerable students; young adults returning to education; other professionals; prisoners; recovering drug addicts; unemployed), study one pre-post comparisons showed significant integrative complexity gains that cohered with second end of intervention integrative complexity measures, replicating results from other integrative complexity interventions despite differences in samples, conflicts, and context. Study two with twenty-eight of the one hundred and four participants showed significant pre post increases in resilience. These results predict peaceful outcomes to intergroup conflict, tackling sectarianism and promoting community psychosocial health. We note future research plans

Beyond wasted and stunted—a major shift to fight child undernutrition

Child undernutrition refers broadly to the condition in which food intake is inadequate to meet a child's needs for physiological function, growth, and the capacity to respond to illness. Since the 1970s, nutritionists have categorised undernutrition in two major ways, either as wasted (ie, low weight for height, or small mid-upper arm circumference) or stunted (ie, low height for age). This approach, although useful for identifying populations at risk of undernutrition, creates several problems: the focus is on children who have already become undernourished, and this approach draws an artificial distinction between two idealised types of undernourished children that are widely interpreted as indicative of either acute or chronic undernutrition. This distinction in turn has led to the separation of programmatic approaches to prevent and treat child undernutrition. In the past 3 years, research has shown that individual children are at risk of both conditions, might be born with both, pass from one state to the other over time, and accumulate risks to their health and life through their combined effects. The current emphasis on identifying children who are already wasted or stunted detracts attention from the larger number of children undergoing the process of becoming undernourished. We call for a major shift in thinking regarding how we assess child undernutrition, and how prevention and treatment programmes can best address the diverse causes and dynamic biological processes that underlie undernutrition

Molecular pathogenesis of proliferative verrucous leukoplakia: a systematic review

Proliferative verrucous leukoplakia (PVL) is a potentially premalignant lesion that undergoes malignant transformation in over 40% of cases. Its clinical homogeneity suggests that a single or a small number of molecular pathogenic pathways may exist. Using the Cochrane protocol for systematic reviews, we have looked at the reported evidence of the molecular aetiology and pathogenesis of PVL and compared it with that of conventional oral epithelial dysplasia (OED). Of the 43 papers studied, 19 met the inclusion criteria including 13 proteins assayed in 344 tissues, and genes investigated were TP53, p14ARF, and p16INK4A. In all studies the research objectives were defined and outcomes were clearly stated. This review has shown that the transformation of PVL does not follow the same pathway as that of OED. There was weak evidence to suggest possible correlations between DNA aneuploidy, loss of heterozygosity at locus 9p21, and specific expression of Mcm (mini chromosome maintenance) protein, to transformation of PVL. To show important or distinct pathways of this condition, further studies are needed to access the somatic genomic alterations that are found in malignancies

Multi-objective Robust Strategy Synthesis for Interval Markov Decision Processes

Interval Markov decision processes (IMDPs) generalise classical MDPs by having interval-valued transition probabilities. They provide a powerful modelling tool for probabilistic systems with an additional variation or uncertainty that prevents the knowledge of the exact transition probabilities. In this paper, we consider the problem of multi-objective robust strategy synthesis for interval MDPs, where the aim is to find a robust strategy that guarantees the satisfaction of multiple properties at the same time in face of the transition probability uncertainty. We first show that this problem is PSPACE-hard. Then, we provide a value iteration-based decision algorithm to approximate the Pareto set of achievable points. We finally demonstrate the practical effectiveness of our proposed approaches by applying them on several case studies using a prototypical tool.Comment: This article is a full version of a paper accepted to the Conference on Quantitative Evaluation of SysTems (QEST) 201

A genome-wide linkage study of mammographic density, a risk factor for breast cancer

Abstract Introduction Mammographic breast density is a highly heritable (h2 > 0.6) and strong risk factor for breast cancer. We conducted a genome-wide linkage study to identify loci influencing mammographic breast density (MD). Methods Epidemiological data were assembled on 1,415 families from the Australia, Northern California and Ontario sites of the Breast Cancer Family Registry, and additional families recruited in Australia and Ontario. Families consisted of sister pairs with age-matched mammograms and data on factors known to influence MD. Single nucleotide polymorphism (SNP) genotyping was performed on 3,952 individuals using the Illumina Infinium 6K linkage panel. Results Using a variance components method, genome-wide linkage analysis was performed using quantitative traits obtained by adjusting MD measurements for known covariates. Our primary trait was formed by fitting a linear model to the square root of the percentage of the breast area that was dense (PMD), adjusting for age at mammogram, number of live births, menopausal status, weight, height, weight squared, and menopausal hormone therapy. The maximum logarithm of odds (LOD) score from the genome-wide scan was on chromosome 7p14.1-p13 (LOD = 2.69; 63.5 cM) for covariate-adjusted PMD, with a 1-LOD interval spanning 8.6 cM. A similar signal was seen for the covariate adjusted area of the breast that was dense (DA) phenotype. Simulations showed that the complete sample had adequate power to detect LOD scores of 3 or 3.5 for a locus accounting for 20% of phenotypic variance. A modest peak initially seen on chromosome 7q32.3-q34 increased in strength when only the 513 families with at least two sisters below 50 years of age were included in the analysis (LOD 3.2; 140.7 cM, 1-LOD interval spanning 9.6 cM). In a subgroup analysis, we also found a LOD score of 3.3 for DA phenotype on chromosome 12.11.22-q13.11 (60.8 cM, 1-LOD interval spanning 9.3 cM), overlapping a region identified in a previous study. Conclusions The suggestive peaks and the larger linkage signal seen in the subset of pedigrees with younger participants highlight regions of interest for further study to identify genes that determine MD, with the goal of understanding mammographic density and its involvement in susceptibility to breast cancer

Persistence of anticancer activity in berry extracts after simulated gastrointestinal digestion and colonic fermentation

Fruit and vegetable consumption is associated at the population level with a protective effect against colorectal cancer. Phenolic compounds, especially abundant in berries, are of interest due to their putative anticancer activity. After consumption, however, phenolic compounds are subject to digestive conditions within the gastrointestinal tract that alter their structures and potentially their function. However, the majority of phenolic compounds are not efficiently absorbed in the small intestine and a substantial portion pass into the colon. We characterized berry extracts (raspberries, strawberries, blackcurrants) produced by in vitro-simulated upper intestinal tract digestion and subsequent fecal fermentation. These extracts and selected individual colonic metabolites were then evaluated for their putative anticancer activities using in vitro models of colorectal cancer, representing the key stages of initiation, promotion and invasion. Over a physiologically-relevant dose range (0–50 µg/ml gallic acid equivalents), the digested and fermented extracts demonstrated significant anti-genotoxic, anti-mutagenic and anti-invasive activity on colonocytes. This work indicates that phenolic compounds from berries undergo considerable structural modifications during their passage through the gastrointestinal tract but their breakdown products and metabolites retain biological activity and can modulate cellular processes associated with colon cancer

A prospective cohort study of biomarkers of prenatal tobacco smoke exposure: the correlation between serum and meconium and their association with infant birth weight

<p>Abstract</p> <p>Background</p> <p>The evaluation of infant meconium as a cumulative matrix of prenatal toxicant exposure requires comparison to established biomarkers of prenatal exposure.</p> <p>Methods</p> <p>We calculated the frequency of detection and concentration of tobacco smoke metabolites measured in meconium (nicotine, cotinine, and trans-3'-hydroxycotinine concentrations) and three serial serum cotinine concentrations taken during the latter two-thirds of pregnancy among 337 mother-infant dyads. We estimated the duration and intensity of prenatal tobacco smoke exposure using serial serum cotinine concentrations and calculated geometric mean meconium tobacco smoke metabolite concentrations according to prenatal exposure. We also compared the estimated associations between these prenatal biomarkers and infant birth weight using linear regression.</p> <p>Results</p> <p>We detected nicotine (80%), cotinine (69%), and trans-3'-hydroxycotinine (57%) in most meconium samples. Meconium tobacco smoke metabolite concentrations were positively associated with serum cotinine concentrations and increased with the number of serum cotinine measurements consistent with secondhand or active tobacco smoke exposure. Like serum cotinine, meconium tobacco smoke metabolites were inversely associated with birth weight.</p> <p>Conclusions</p> <p>Meconium is a useful biological matrix for measuring prenatal tobacco smoke exposure and could be used in epidemiological studies that enroll women and infants at birth. Meconium holds promise as a biological matrix for measuring the intensity and duration of environmental toxicant exposure and future studies should validate the utility of meconium using other environmental toxicants.</p

Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value=2.57x10-4) and rs9960767 (p-value=6.23x10-4). Replication in an independent sample of 16-year-olds (N=3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed