Caffeine Consumption Contributes to Skin Intrinsic Fluorescence in Type 1 Diabetes.

Background: A variant (rs1495741) in the gene for the N-acetyltransferase 2 (NAT2) protein is associated with skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation end products and other fluorophores in the skin. Because NAT2 is involved in caffeine metabolism, we aimed to determine whether caffeine consumption is associated with SIF and whether rs1495741 is associated with SIF independently of caffeine. Materials and Methods: SIF was measured in 1,181 participants with type 1 diabetes from the Epidemiology of Diabetes Interventions and Complications study. Two measures of SIF were used: SIF1, using a 375-nm excitation light-emitting diode (LED), and SIF14 (456-nm LED). Food frequency questionnaires were used to estimate mean caffeine intake. To establish replication, we examined a second type 1 diabetes cohort. Results: Higher caffeine intake was significantly associated with higher SIF1LED 375 nm[0.6, 0.2] (P=2×10−32) and SIF14LED 456 nm[0.4, 0.8] (P=7×10−31) and accounted for 4% of the variance in each after adjusting for covariates. When analyzed together, caffeine intake and rs1495741 both remained highly significantly associated with SIF1LED 375 nm[0.6, 0.2] and SIF14LED 456 nm[0.4, 0.8]. Mean caffeinated coffee intake was also positively associated with SIF1LED 375 nm[0.6, 0.2] (P=9×10−12) and SIF14LED 456 nm[0.4, 0.8] (P=4×10−12), but no association was observed for decaffeinated coffee intake. Finally, caffeine was also positively associated with SIF1LED 375 nm[0.6, 0.2] and SIF14LED 456 nm[0.4, 0.8] (P\u3c0.0001) in the replication cohort. Conclusions: Caffeine contributes to SIF. The effect of rs1495741 on SIF appears to be partially independent of caffeine consumption. Because SIF and coffee intake are each associated with cardiovascular disease, our findings suggest that accounting for coffee and/or caffeine intake may improve risk prediction models for SIF and cardiovascular disease in individuals with diabetes

Characterization of spiraling patterns in spatial rock-paper-scissors games

The spatiotemporal arrangement of interacting populations often influences the maintenance of species diversity and is a subject of intense research. Here, we study the spatiotemporal patterns arising from the cyclic competition between three species in two dimensions. Inspired by recent experiments, we consider a generic metapopulation model comprising “rock-paper-scissors” interactions via dominance removal and replacement, reproduction, mutations, pair exchange, and hopping of individuals. By combining analytical and numerical methods, we obtain the model's phase diagram near its Hopf bifurcation and quantitatively characterize the properties of the spiraling patterns arising in each phase. The phases characterizing the cyclic competition away from the Hopf bifurcation (at low mutation rate) are also investigated. Our analytical approach relies on the careful analysis of the properties of the complex Ginzburg-Landau equation derived through a controlled (perturbative) multiscale expansion around the model's Hopf bifurcation. Our results allow us to clarify when spatial “rock-paper-scissors” competition leads to stable spiral waves and under which circumstances they are influenced by nonlinear mobility

Young adult outcomes associated with teen pregnancy among high-risk girls in a randomized controlled trial of Multidimensional Treatment Foster Care

Teen pregnancy is associated with a host of deleterious outcomes for girls, such as drug use and poor parenting. Thus, reducing teen pregnancy rates could improve long-term developmental outcomes for girls, including adjustment during young adulthood. Based on the positive effects of Multidimensional Treatment Foster Care (MTFC) relative to group care (GC) in a study of adolescent girls (significantly fewer pregnancies reported in the 2-year follow-up for MTFC girls), the present study followed this sample into young adulthood (approximately 7 years post-baseline) to examine the effects of adolescent pregnancy on young adult substance use and pregnancy-related outcomes. All participants were randomly assigned to MTFC (N = 81) or GC (N = 85) as adolescents as part of a randomized controlled trial (RCT). Results from logistic regression analyses indicated that becoming pregnant during the 2-year follow-up was significantly related to illicit drug use, miscarriage from a new pregnancy, and child welfare involvement 7 years post-baseline. In addition, baseline marijuana use predicted marijuana use at 7 years post-baseline. © 2013 Copyright Taylor and Francis Group, LLC

Depression, Rational Identity and the Educational Imperative: Concordance-Finding in Tricky Diagnostic Moments

It is well-documented, within most medical and much health psychology, that many individuals find diagnoses of depression confusing or even objectionable. Within a corpus of research and practical clinical guidance dominated by the social-cognitive paradigm, the explanation for resistance to a depression diagnosis (or advice pertaining to it) within specific interactions is bordering on the canonical; patients misunderstand depression itself, often as an output of an associated social stigma that distorts public knowledge. The best way to overcome corollary resistance in situ is, logically thus, taken to be a clarification of the true (clinical) nature of depression. In this paper, exploring the diagnosis of depression in UK primary care contexts, the social-cognitive position embedded in contemporary medical reasoning around this matter is critically addressed. It is firstly highlighted how, even in a great deal of extant public health research, the link between an individual holding “correct” medical knowledge and being actively compliant with it is far from inevitable. Secondly, and with respect to concerns around direct communication in clinical contexts, a body of research emergent of Discursive Psychology and Conversation Analysis is explored so as to shed light on how non-cognitive concerns (not least those around the local interactional management of a patient’s social identity) that can inform the manner in which ostensibly “tricky” medical talk plays-out in practice, especially in cases where a mental illness is at stake. Finally, observations are drawn together in a formal Discursive Psychological analysis of a small but highly illustrative sample of three cases where a depression diagnosis is initially questioned or disputed by a patient in primary care but, following further in-consultation activity, concordance with the diagnosis is ultimately reached—a specific issue hitherto unaddressed in either DP or CA fields. These cases specifically reveal the coordinative attention of interlocutors to immediate concerns regarding how the patient might maintain a sense of being an everyday and rational witness to their own lives; indeed, the very act of challenging the diagnosis emerges as a means by which a patient can open up conversational space within the consultation to address such issues. While the veracity of the social-cognitive model is not deemed to be without foundation herein, it is concluded that attention to local interactional concerns might firstly be accorded, such that the practical social concerns and skills of practitioners and patients alike might not be overlooked in the endeavour to produce generally applicable theories

Attenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels

Zinc finger nucleases (ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold. ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain. By changing key residues in the recognition helix of the specific DNA-binding domain, one can alter the ZFN binding specificity and thereby change the sequence to which a ZFN pair is being targeted. For these and other reasons, ZFNs are being pursued as reagents for genome modification, including use in gene therapy. In order for ZFNs to reach their full potential, it is important to attenuate the cytotoxic effects currently associated with many ZFNs. Here, we evaluate two potential strategies for reducing toxicity by regulating protein levels. Both strategies involve creating ZFNs with shortened half-lives and then regulating protein level with small molecules. First, we destabilize ZFNs by linking a ubiquitin moiety to the N-terminus and regulate ZFN levels using a proteasome inhibitor. Second, we destabilize ZFNs by linking a modified destabilizing FKBP12 domain to the N-terminus and regulate ZFN levels by using a small molecule that blocks the destabilization effect of the N-terminal domain. We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity

Projections of climate conditions that increase coral disease susceptibility and pathogen abundance and virulence

Rising sea temperatures are likely to increase the frequency of disease outbreaks affecting reef-building corals through impacts on coral hosts and pathogens. We present and compare climate model projections of temperature conditions that will increase coral susceptibility to disease, pathogen abundance and pathogen virulence. Both moderate (RCP 4.5) and fossil fuel aggressive (RCP 8.5) emissions scenarios are examined. We also compare projections for the onset of disease-conducive conditions and severe annual coral bleaching, and produce a disease risk summary that combines climate stress with stress caused by local human activities. There is great spatial variation in the projections, both among and within the major ocean basins, in conditions favouring disease development. Our results indicate that disease is as likely to cause coral mortality as bleaching in the coming decades. These projections identify priority locations to reduce stress caused by local human activities and test management interventions to reduce disease impacts

Sentiment Analysis in Social Streams

In this chapter we review and discuss the state of the art on sentiment analysis in social streams –such as web forums, micro-blogging systems, and so- cial networks–, aiming to clarify how user opinions, affective states, and intended emotional effects are extracted from user generated content, how they are modeled, and how they could be finally exploited. We explain why sentiment analysis tasks are more difficult for social streams than for other textual sources, and entail going beyond classic text-based opinion mining techniques. We show, for example, that social streams may use vocabularies and expressions that exist outside the main- stream of standard, formal languages, and may reflect complex dynamics in the opinions and sentiments expressed by individuals and communities

Critical dynamics in the evolution of stochastic strategies for the iterated Prisoner's Dilemma

The observed cooperation on the level of genes, cells, tissues, and individuals has been the object of intense study by evolutionary biologists, mainly because cooperation often flourishes in biological systems in apparent contradiction to the selfish goal of survival inherent in Darwinian evolution. In order to resolve this paradox, evolutionary game theory has focused on the Prisoner's Dilemma (PD), which incorporates the essence of this conflict. Here, we encode strategies for the iterated Prisoner's Dilemma (IPD) in terms of conditional probabilities that represent the response of decision pathways given previous plays. We find that if these stochastic strategies are encoded as genes that undergo Darwinian evolution, the environmental conditions that the strategies are adapting to determine the fixed point of the evolutionary trajectory, which could be either cooperation or defection. A transition between cooperative and defective attractors occurs as a function of different parameters such a mutation rate, replacement rate, and memory, all of which affect a player's ability to predict an opponent's behavior.Comment: 27 pages, including supplementary information. 5 figures, 4 suppl. figures. Version accepted for publication in PLoS Comp. Bio

The troubling concept of class: reflecting on our ‘failure’ to encourage sociology students to re-cognise their classed locations using autobiographical methods

The troubling concept of class: reflecting on our ‘failure’ to encourage sociology students to re-cognise their classed locations using autobiographical methods Abstract This paper provides a narrative of the four authors‟ commitment to auto/biographical methods as teachers and researchers in „new‟ universities. As they went about their work, they observed that, whereas students engage with the gendered, sexualised and racialised processes when negotiating their identities, they are reluctant or unable to conceptualise „class-ifying‟ processes as key determinants of their life chances. This general inability puzzled the authors, given the students‟ predominantly working-class backgrounds. Through application of their own stories, the authors explore the sociological significance of this pedagogical „failure‟ to account for the troubling concept of class not only in the classroom but also in contemporary society