Metabolic state alters economic decision making under risk in humans

Background: Animals' attitudes to risk are profoundly influenced by metabolic state (hunger and baseline energy stores). Specifically, animals often express a preference for risky (more variable) food sources when below a metabolic reference point (hungry), and safe (less variable) food sources when sated. Circulating hormones report the status of energy reserves and acute nutrient intake to widespread targets in the central nervous system that regulate feeding behaviour, including brain regions strongly implicated in risk and reward based decision-making in humans. Despite this, physiological influences per se have not been considered previously to influence economic decisions in humans. We hypothesised that baseline metabolic reserves and alterations in metabolic state would systematically modulate decision-making and financial risk-taking in humans. Methodology/Principal Findings: We used a controlled feeding manipulation and assayed decision-making preferences across different metabolic states following a meal. To elicit risk-preference, we presented a sequence of 200 paired lotteries, subjects' task being to select their preferred option from each pair. We also measured prandial suppression of circulating acyl-ghrelin (a centrally-acting orexigenic hormone signalling acute nutrient intake), and circulating leptin levels (providing an assay of energy reserves). We show both immediate and delayed effects on risky decision-making following a meal, and that these changes correlate with an individual's baseline leptin and changes in acyl-ghrelin levels respectively. Conclusions/Significance: We show that human risk preferences are exquisitely sensitive to current metabolic state, in a direction consistent with ecological models of feeding behaviour but not predicted by normative economic theory. These substantive effects of state changes on economic decisions perhaps reflect shared evolutionarily conserved neurobiological mechanisms. We suggest that this sensitivity in human risk-preference to current metabolic state has significant implications for both real-world economic transactions and for aberrant decision-making in eating disorders and obesity

Concurrent chemoradiotherapy for squamous cell carcinoma of the anus using a shrinking field radiotherapy technique without a boost

Chemoradiotherapy (CRT) is now widely accepted as the primary treatment modality for squamous cell cancer of the anus. While randomised trials have clearly shown CRT to be more effective than radiotherapy alone, there remains uncertainty over the optimal integration of chemotherapy and radiation. We describe a series of 50 patients treated by a site specialist gastrointestinal nonsurgical oncologist with CRT at a single UK centre. Chemotherapy comprised mitomycin C (MMC) (day 1) and 5-fluorouracil (5-FU) (days 1–4, and 29–32), concurrent with 50 Gy in 25 fractions radiation, using a two-phase shrinking field technique. A radiation boost was not planned. At a median follow-up of 48 months, 11 (22%) of the patients have failed locally, of which three have been surgically salvaged. Nine (18%) have died of anal cancer. These results are comparable with those from large randomised studies, and suggest that a two-phase shrinking field radiotherapy technique with no boost, concurrent with MMC/5-FU chemotherapy, is an effective regimen for this disease. The CRT regimen described here provides the basis for the ‘control arm’ of the current UK-randomised CRT trial in anal cancer (ACT2)

On stability of discretizations of the Helmholtz equation (extended version)

We review the stability properties of several discretizations of the Helmholtz equation at large wavenumbers. For a model problem in a polygon, a complete $k$-explicit stability (including $k$-explicit stability of the continuous problem) and convergence theory for high order finite element methods is developed. In particular, quasi-optimality is shown for a fixed number of degrees of freedom per wavelength if the mesh size $h$ and the approximation order $p$ are selected such that $kh/p$ is sufficiently small and $p = O(\log k)$, and, additionally, appropriate mesh refinement is used near the vertices. We also review the stability properties of two classes of numerical schemes that use piecewise solutions of the homogeneous Helmholtz equation, namely, Least Squares methods and Discontinuous Galerkin (DG) methods. The latter includes the Ultra Weak Variational Formulation

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

Do female association preferences predict the likelihood of reproduction?

Sexual selection acting on male traits through female mate choice is commonly inferred from female association preferences in dichotomous mate choice experiments. However, there are surprisingly few empirical demonstrations that such association preferences predict the likelihood of females reproducing with a particular male. This information is essential to confirm association preferences as good predictors of mate choice. We used green swordtails (<i>Xiphophorus helleri</i>) to test whether association preferences predict the likelihood of a female reproducing with a male. Females were tested for a preference for long- or short-sworded males in a standard dichotomous choice experiment and then allowed free access to either their preferred or non-preferred male. If females subsequently failed to produce fry, they were provided a second unfamiliar male with similar sword length to the first male. Females were more likely to reproduce with preferred than non-preferred males, but for those that reproduced, neither the status (preferred/non-preferred) nor the sword length (long/short) of the male had an effect on brood size or relative investment in growth by the female. There was no overall preference based on sword length in this study, but male sword length did affect likelihood of reproduction, with females more likely to reproduce with long- than short-sworded males (independent of preference for such males in earlier choice tests). These results suggest that female association preferences are good indicators of female mate choice but that ornament characteristics of the male are also important

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

The three-dimensional easy morphological (3-DEMO) classification of scoliosis – Part III, correlation with clinical classification and parameters

BACKGROUND: In the first part of this study we proposed a new classification approach for spinal deformities (3-DEMO classification). To be valid, a classification needs to describe adequately the phenomenon considered (construct validity): a way to verify this issue is comparison with already existing classifications (concurrent and criterion validity). AIM: To compare the 3-DEMO classification and the numerical results of its classificatory parameters with the existing clinical classifications and the Cobb degrees on the frontal and sagittal planes respectively. METHODS: 118 subjects (96 females) with adolescent idiopathic scoliosis (age 15.9 ± 3.1, 37.4 ± 12.5° Cobb) have been classified according to 3-DEMO, SRS-Ponseti, King and Lenke classifications as well as according to sagittal configuration. For all patients we computed the values of the 3-DEMO parameters and the classical Cobb degrees measurements in the frontal and sagittal planes. Statistical analysis comprised Chi Square and Regression analysis, including a multivariate stepwise regression. RESULTS: Three of the four 3-DEMO parameters (Direction, Sagittal and Frontal Shift) correlated with SRS-Ponseti, King and sagittal configuration classifications, but not with Lenke's one. Feeble correlations have been found among numerical parameters, while the stepwise regression allowed us to develop almost satisfactory models to obtain 3-DEMO parameters from classical Cobb degrees measurements. DISCUSSION: These results support the hypothesis of a possible clinical significance of the 3-DEMO classification, even if follow-up studies are needed to better understand these possible correlations and ultimately the classification usefulness. The most interesting 3D parameters appear to be Direction and mainly Phase, the latter being not at all correlated with currently existing classifications. Nevertheless, Shift cannot be easily appreciated on classical frontal and sagittal radiographs, even if it could presumably be calculated

Subjective and objective outcome in congenital clubfoot; a comparative study of 204 children

<p>Abstract</p> <p>Background</p> <p>Outcome following management of congenital talipes equinovarus (clubfoot) can be assessed in a number of ways. Bjonness stated simply that <it>"the patient is the final judge of whether he has a good foot</it>"; a purely subjective assessment. Others have employed objective measures. Combining subjective evaluation with a more objective assessment of movement and position of the foot, is likely to give a more comprehensive picture of the final result of clubfoot. The purpose of this study was to compare subjective and objective outcome following management of clubfoot, and evaluate sex differences in outcome.</p> <p>Methods</p> <p>We used a patient-administered subjective assessment of outcome following treatment of clubfoot and compared it with objective anthropometry and range of movement of the ankle to assess and compare subjective and objective outcome in clubfoot. Statistical analysis was performed using Pearson correlation coefficients. Significance was tested using Student's t-test test.</p> <p>Results</p> <p>Objective outcome can be assessed using length of the foot, calf circumference and range of movement at the ankle. These are easy to measure, reproducible, and correlate well with subjective outcome. Objective outcome is comparable for boys and girls. However, subjectively, female patients and their parents are less happy with the results of management of clubfoot.</p> <p>Conclusion</p> <p>There is a correlation between the anthropometric measures and the subjective outcome and an objective grading can be designed using foot length, calf muscle bulk and range of movement at the ankle.</p

Multiyear Climate Variability and Dengue—El Niño Southern Oscillation, Weather, and Dengue Incidence in Puerto Rico, Mexico, and Thailand: A Longitudinal Data Analysis

Michael Johansson and colleagues use wavelet analysis to show that there is limited evidence for a multiyear relationship between climate and dengue incidence in Puerto Rico, Mexico, and Thailand