Blocked autophagy sensitizes resistant carcinoma cells to radiation therapy.

Autophagy or "self eating" is frequently activated in tumor cells treated with chemotherapy or irradiation. Whether autophagy represents a survival mechanism or rather contributes to cell death remains controversial. To address this issue, the role of autophagy in radiosensitive and radioresistant human cancer cell lines in response to gamma-irradiation was examined. We found irradiation-induced accumulation of autophagosomes accompanied by strong mRNA induction of the autophagy-related genes beclin 1, atg3, atg4b, atg4c, atg5, and atg12 in each cell line. Transduction of specific target-siRNAs led to down-regulation of these genes for up to 8 days as shown by reverse transcription-PCR and Western blot analysis. Blockade of each autophagy-related gene was associated with strongly diminished accumulation of autophagosomes after irradiation. As shown by clonogenic survival, the majority of inhibited autophagy-related genes, each alone or combined, resulted in sensitization of resistant carcinoma cells to radiation, whereas untreated resistant cells but not sensitive cells survived better when autophagy was inhibited. Similarly, radiosensitization or the opposite was observed in different sensitive carcinoma cells and upon inhibition of different autophagy genes. Mutant p53 had no effect on accumulation of autophagosomes but slightly increased clonogenic survival, as expected, because mutated p53 protects cells by conferring resistance to apoptosis. In our system, short-time inhibition of autophagy along with radiotherapy lead to enhanced cytotoxicity of radiotherapy in resistant cancer cells.

Who is the fairest of them all? The independent effect of attractive features and self-perceived attractiveness on cooperation among women

The present paper analyzes the extent to which attractiveness-related variables affect cooperative behavior in women. Cooperativeness is evaluated through a Prisoner's Dilemma Game (PDG). We consider several morphometric variables related to attractiveness: Fluctuating Asymmetry (FA), Waist-Hip Ratio (WHR, Body Mass Index (BMI) and Facial Femininity (FF). These variables have been shown to predict human behavior. We also include as a control variable a score for Self-Perceived Attractiveness (SPA). We test differences in these variables according to behavior in the PDG. Our results reveal that low FA women cooperate less frequently in the PDG. We also find that women with lower WHR are more cooperative. This result contradicts the expected relation between WHR and behavior in the PDG. We show that this effect of WHR on cooperation operates through its influence on the expectation that participants hold on the cooperative intent of their counterpart. In addition, we show that the effect of attractive features on cooperation occurs independently of the participants' perception of their own appeal. Finally, we discuss our results in the context of the evolution of cooperative behavior and under the hypothesis that attractiveness is a reliable indicator of phenotypic quality.

Self-Confidence, Overconfidence and Prenatal Testosterone Exposure: Evidence from the Lab

This paper examines whether the degree of confidence and overconfidence in one's ability is determined biologically. In articular, we study whether foetal testosterone exposure correlates with an incentive-compatible measure of confidence within an experimental setting. We find that men (rather than women) who were exposed to high testosterone levels in their mother's womb are less likely to overestimate their actual performance, which in turn helps them to gain higher monetary rewards. Men exposed to low prenatal testosterone levels, instead, set unrealistically high expectations which results in self-defeating behaviour. These results from the lab are able to reconcile hitherto disconnected evidence from the field, by providing a link between traders'overconfidence bias, long-term financial returns and prenatal testosterone exposure.

Social norms, morals and self-interest as determinants of pro-environment behaviour.

This paper considers the role which selfish, moral and social incentives and pressures play in explaining the extent to which stated choices over pro-environment behaviours vary across individuals. The empirical context is choices over household waste contracts and recycling actions in Poland. A theoretical model is used to show how cost-based motives and the desire for a positive self- and social image combine to determine the utility from alternative choices of recycling behaviour. We then describe a discrete choice experiment designed to empirically investigate the effects such drivers have on stated choices. Using a latent class model, we distinguish three types of individual who are described as duty-orientated recyclers, budget recyclers and homo oeconomicus. These groups vary in their preferences for how frequently waste is collected, and the number of categories into which household waste must be recycled. Our results have implications for the design of future policies aimed at improving participation in recycling schemes.

Limited liability and mechanism design in procurement

In the presence of cost uncertainty, limited liability introduces the possibility of default in procurement with its associated bank-ruptcy costs. When financial soundness is not perfectly observable, we show that incentive compatibility implies that financially less sound contractors are selected with higher probability in any feasible mechanism. Informational rents are associated with unsound financial situations. By selecting the financially weakest contractor, stronger price competition (auctions) may not only increase the probability of default but also expected rents. Thus, weak conditions are suffcient for auctions to be suboptimal. In particular, we show that pooling firms with higher assets may reduce the cost of procurement even when default is costless for the sponsor.

Detecting and measuring deprivation in primary care: development, reliability and validity of a self-reported questionnaire: the DiPCare-Q.

OBJECTIVES: Advances in biopsychosocial science have underlined the importance of taking social history and life course perspective into consideration in primary care. For both clinical and research purposes, this study aims to develop and validate a standardised instrument measuring both material and social deprivation at an individual level. METHODS: We identified relevant potential questions regarding deprivation using a systematic review, structured interviews, focus group interviews and a think-aloud approach. Item response theory analysis was then used to reduce the length of the 38-item questionnaire and derive the deprivation in primary care questionnaire (DiPCare-Q) index using data obtained from a random sample of 200 patients during their planned visits to an ambulatory general internal medicine clinic. Patients completed the questionnaire a second time over the phone 3 days later to enable us to assess reliability. Content validity of the DiPCare-Q was then assessed by 17 general practitioners. Psychometric properties and validity of the final instrument were investigated in a second set of patients. The DiPCare-Q was administered to a random sample of 1898 patients attending one of 47 different private primary care practices in western Switzerland along with questions on subjective social status, education, source of income, welfare status and subjective poverty. RESULTS: Deprivation was defined in three distinct dimensions: material (eight items), social (five items) and health deprivation (three items). Item consistency was high in both the derivation (Kuder-Richardson Formula 20 (KR20) =0.827) and the validation set (KR20 =0.778). The DiPCare-Q index was reliable (interclass correlation coefficients=0.847) and was correlated to subjective social status (r(s)=-0.539). CONCLUSION: The DiPCare-Q is a rapid, reliable and validated instrument that may prove useful for measuring both material and social deprivation in primary care.

A test of long memory hypothesis based on self-similarity

This paper develops a new test of true versus spurious long memory, based on log-periodogram estimation of the long memory parameter using skip-sampled data. A correction factor is derived to overcome the bias in this estimator due to aliasing. The procedure is designed to be used in the context of a conventional test of significance of the long memory parameter, and composite test procedure described that has the properties of known asymptotic size and consistency. The test is implemented using the bootstrap, with the distribution under the null hypothesis being approximated using a dependent-sample bootstrap technique to approximate short-run dependence following fractional differencing. The properties of the test are investigated in a set of Monte Carlo experiments. The procedure is illustrated by applications to exchange rate volatility and dividend growth series.

Trends in self-reported prevalence and management of hypertension, hypercholesterolemia and diabetes in Swiss adults, 1997-2007.

Switzerland has a low mortality rate from cardiovascular diseases, but little is known regarding prevalence and management of cardiovascular risk factors (CV RFs: hypertension, hypercholesterolemia and diabetes) in the general population. In this study, we assessed 10-year trends in self-reported prevalence and management of cardiovascular risk factors in Switzerland. data from three national health interview surveys conducted between 1997 and 2007 in representative samples of the Swiss adult population (49,261 subjects overall). Self-reported CV RFs prevalence, treatment and control levels were computed. The sample was weighted to match the sex - and age distribution, geographical location and nationality of the entire adult population of Switzerland. self-reported prevalence of hypertension, hypercholesterolemia and diabetes increased from 22.1%, 11.9% and 3.3% in 1997 to 24.1%, 17.4% and 4.8% in 2007, respectively. Prevalence of self-reported treatment among subjects with CV RFs also increased from 52.1%, 18.5% and 50.0% in 1997 to 60.4%, 38.8% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Self-reported control levels increased from 56.4%, 52.9% and 50.0% in 1997 to 80.6%, 75.1% and 53.3% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. Finally, screening during the last 12 months increased from 84.5%, 86.5% and 87.4% in 1997 to 94.0%, 94.6% and 94.1% in 2007 for hypertension, hypercholesterolemia and diabetes, respectively. in Switzerland, the prevalences of self-reported hypertension, hypercholesterolemia and diabetes have increased between 1997 and 2007. Management and screening have improved, but further improvements can still be achieved as over one third of subjects with reported CV RFs are not treated.

Benzodiazepine receptor ligand influences on learning: an endogenous modulatory mechanism mediated by benzodiazepines possibly of alimentary origin

In rats pre-but not post-training ip administration of either flumazenil, a central benzodiazepine (BSD) receptor antagonist, or of n-butyl-B-carboline-carboxylate (BCCB), an inverse agonist, enhanced retention of inhibitory avoidance learning. Flumazenil vlocked the enhancing effect of BCCB, and the inhibitory effect of the BZD agonists clonazepam and diazepam also given pre-training. Post-training administration of these drugs had no effects. The peripheral BZD receptor agonist/chloride channel blocker Ro5-4864 had no effect on the inhibitory avoidance task when given ip prior to training, buth it caused enhancement when given immediately post-training either ip or icv. This effect was blocked by PK11195, a competitive antagonist of Ro5-4864. These results suggest that ther is an endogenous mechanism mediated by BZD agonists, which is sensitive to inverse agonists and that normally down-regulates the formation of memories through a mechanism involving GABA-A receptors and the corresponding chloride channels. The most likely agonists for the endogenous mechanism suggested are the diazepam-like BZDs found in brain whose origin is possibly alimentary. Levels of these BZDs in the cortex were found to sharply decrease after inhibitory acoidance training or mere exposure to the training apparatus.

Validation of the German version of the Career Adapt-Abilities Scale and its relation to orientations to happiness and work stress

Career adapt-ability has recently gained momentum as a psychosocial construct that not only has much to offer the field of career development, but also contributes to positive coping, adjustment and self-regulation through the four dimensions of concern, control, curiosity and confidence. The positive psychology movement, with concepts such as the orientations to happiness, explores the factors that contribute to human flourishing and optimum functioning. This research has two main contributions; 1) to validate a German version of the Career Adapt-Abilities Scale (CAAS), and 2) to extend the contribution of adapt-abilities to the field of work stress and explore its mediating capacity in the relation between orientations to happiness and work stress. We used a representative sample of the German-speaking Swiss working population including 1204 participants (49.8% women), aged between 26 and 56 (Mage = 42.04). Results indicated that the German version of the CAAS is valid, with overall high levels of model fit suggesting that the conceptual structure of career adapt-ability replicates well in this cultural context. Adapt-abilities showed a negative relationship to work stress, and a positive one with orientations to happiness. The engagement and pleasure scales of orientations to happiness also correlated negatively with work stress. Moreover, career adapt-ability mediates the relationship between orientations to happiness and work stress. In depth analysis of the mediating effect revealed that control is the only significant mediator. Thus control may be acting as a mechanism through which individuals attain their desired life at work subsequently contributing to reduced stress levels.

RecA-mediated annealing of single-stranded DNA and its relation to the mechanism of homologous recombination.

We demonstrate that RecA protein can mediate annealing of complementary DNA strands in vitro by at least two different mechanisms. The first annealing mechanism predominates under conditions where RecA protein causes coaggregation of single-stranded DNA (ssDNA) molecules and where RecA-free ssDNA stretches are present on both reaction partners. Under these conditions annealing can take place between locally concentrated protein-free complementary sequences. Other DNA aggregating agents like histone H1 or ethanol stimulate annealing by the same mechanism. The second mechanism of RecA-mediated annealing of complementary DNA strands is best manifested when preformed saturated RecA-ssDNA complexes interact with protein-free ssDNA. In this case, annealing can occur between the ssDNA strand resident in the complex and the ssDNA strand that interacts with the preformed RecA-ssDNA complex. Here, the action of RecA protein reflects its specific recombination promoting mechanism. This mechanism enables DNA molecules resident in the presynaptic RecA-DNA complexes to be exposed for hydrogen bond formation with DNA molecules contacting the presynaptic RecA-DNA filament.

How are temporal and social comparisons related to appraisals of self-rated health during very old age?

This study investigated the direction of effects of temporal and downward social comparisons on self-rated health in very old age. Self-rated health can either reinforce or hinder comparison processes. In the framework of the Swiss Interdisciplinary Longitudinal Study on the Oldest Old, individuals aged 80 to 84 at baseline were interviewed and followed longitudinally for 5 years. Multilevel analyses were used to test the relative importance of temporal and social comparisons on self-rated health evaluations synchronically and diachronically (with a time lag of 12 to 18 months) as well as the direction of these relative influences. Results indicate that (a) at the synchronic level, continuity temporal comparisons have more impact than downward social comparisons on self-rated health; (b) both types of comparison had an independent and positive effect on self-rated health at the diachronic level; (c) self-rated health has an independent synchronic effect on both types of comparison and an independent diachronic effect in temporal comparison.

Cultural competency of health-care providers in a Swiss University Hospital: self-assessed cross-cultural skillfulness in a cross-sectional study.

BACKGROUND: As the diversity of the European population evolves, measuring providers' skillfulness in cross-cultural care and understanding what contextual factors may influence this is increasingly necessary. Given limited information about differences in cultural competency by provider role, we compared cross-cultural skillfulness between physicians and nurses working at a Swiss university hospital. METHODS: A survey on cross-cultural care was mailed in November 2010 to front-line providers in Lausanne, Switzerland. This questionnaire included some questions from the previously validated Cross-Cultural Care Survey. We compared physicians' and nurses' mean composite scores and proportion of "3-good/4-very good" responses, for nine perceived skillfulness items (4-point Likert-scale) using the validated tool. We used linear regression to examine how provider role (physician vs. nurse) was associated with composite skillfulness scores, adjusting for demographics (gender, non-French dominant language), workplace (time at institution, work-unit "sensitized" to cultural-care), reported cultural-competence training, and cross-cultural care problem-awareness. RESULTS: Of 885 questionnaires, 368 (41.2%) returned the survey: 124 (33.6%) physicians and 244 (66.4%) nurses, reflecting institutional distribution of providers. Physicians had better mean composite scores for perceived skillfulness than nurses (2.7 vs. 2.5, p < 0.005), and significantly higher proportion of "good/very good" responses for 4/9 items. After adjusting for explanatory variables, physicians remained more likely to have higher skillfulness (β = 0.13, p = 0.05). Among all, higher skillfulness was associated with perception/awareness of problems in the following areas: inadequate cross-cultural training (β = 0.14, p = 0.01) and lack of practical experience caring for diverse populations (β = 0.11, p = 0.04). In stratified analyses among physicians alone, having French as a dominant language (β = -0.34, p < 0.005) was negatively correlated with skillfulness. CONCLUSIONS: Overall, there is much room for cultural competency improvement among providers. These results support the need for cross-cultural skills training with an inter-professional focus on nurses, education that attunes provider awareness to the local issues in cross-cultural care, and increased diversity efforts in the work force, particularly among physicians.