Fine structural variations of alphabetaTCRs selected by vaccination with natural versus altered self-antigen in melanoma patients.

Immunotherapy of cancer is often performed with altered "analog" peptide Ags optimized for HLA class I binding, resulting in enhanced immunogenicity, but the induced T cell responses require further evaluation. Recently, we demonstrated fine specificity differences and enhanced recognition of naturally presented Ag by T cells after vaccination with natural Melan-A/MART-1 peptide, as compared with analog peptide. In this study, we compared the TCR primary structures of 1489 HLA-A*0201/Melan-A(26-35)-specific CD8 T cells derived from both cohorts of patients. Although a strong preference for TRAV12-2 segment usage was present in nearly all patients, usage of particular TRAJ gene segments and CDR3alpha composition differed slightly after vaccination with natural vs analog peptide. Moreover, TCR beta-chain repertoires were broader after natural than analog peptide vaccination. In all patients, we observed a marked conservation of the CDR3beta amino acid composition with recurrent sequences centered on a glycyl-leucyl/valyl/alanyl-glycyl motif. In contrast to viral-specific TCR repertoires, such "public" motifs were primarily expressed by nondominant T cell clonotypes, which contrasted with "private" CDR3beta signatures frequently found in T cell clonotypes that dominated repertoires of individual patients. Interestingly, no differences in functional avidity were observed between public and private T cell clonotypes. Collectively, our data indicate that T cell repertoires generated against natural or analog Melan-A peptide exhibited slightly distinct but otherwise overlapping and structurally conserved TCR features, suggesting that the differences in binding affinity/avidity of TCRs toward pMHC observed in the two cohorts of patients are caused by subtle structural TCR variations.

Factores cognitivos en la fibromialgia: el papel del autoconcepto y de los conflicots relativos a la identidad en el tratamiento psicológico de la fibromialgia

La fibromialgia es un síndrome caracterizado por la presencia de dolor músculo-esquelético generalizado, difuso y crónico. La etiología es desconocida y es diagnóstico es exclusivamente clínico. Además hasta el momento el tratamiento se centra únicamente en la reducción de síntomas. Todas estas características influyen en gran medida en la vivencia que tienen estas pacientes de la enfermedad, así como en la imagen que tienen de sí mismas. Diversos autores han enfatizado la importancia de estudiar los fenómenos relacionados con la identidad en las situaciones de dolor crónico. En este informe se presentan los dos estudios realizados durante los cuatro años de beca en torno al estudio del autoconcepto y la identidad en mujeres con fibromialgia. Ambos estudios se enmarcan dentro de la Psicología de los Constructos Personales de George Kelly y utilizan la técnica de rejilla como principal instrumento de evaluación. En el primer estudio se realiza una comparación de las medidas de construcción del sí mismo y de estructura cognitiva entre un grupo de mujeres con fibromialgia (n = 30) y un grupo de mujeres sin fibromialgia (n = 30). Encontramos que las mujeres de nuestra muestra presentan una mayor discrepancia entre el “yo actual” y el “yo ideal”, una menor adecuación percibida en los otros y mayor probabilidad de presentar algún conflicto cognitivo. Estos resultados preliminares nos llevaron a plantearnos la relación entre estos factores cognitivos y el tratamiento. Por ello, el segundo estudio consiste en un estudio de casos en el que se realiza un tratamiento individualizado (terapia cognitivo-constructivista) con cada una de las participantes y se analizan en detalle, a través de un grupo de trabajo, estos factores cognitivos y su relación con la evolución del tratamiento. Este segundo estudio sigue en curso, por lo que se presentan sólo unos resultados preliminares.

Self-Fulfilling Price Cycles

This paper presents a model of a self-fulfilling price cycle in an asset market. Price oscillates deterministically even though the underlying environment is stationary. The mechanism that we uncover is driven by endogenous variation in the investment horizons of the different market participants, informed and uninformed. On even days, the price is high; on odd days it is low. On even days, informed traders are willing to jettison their good assets, knowing that they can buy them back the next day, when the price is low. The anticipated drop in price more than offsets any potential loss in dividend. Because of these asset sales, the informed build up their cash holdings. Understanding that the market is flooded with good assets, the uninformed traders are willing to pay a high price. But their investment horizon is longer than that of the informed traders: their intention is to hold the assets they purchase, not to resell. On odd days, the price is low because the uninformed recognise that the informed are using their cash holdings to cherry-pick good assets from the market. Now the uninformed, like the informed, are investing short-term. Rather than buy-and-hold as they do with assets purchased on even days, on odd days the uninformed are buying to sell. Notice that, at the root of the model, there lies a credit constraint. Although the informed are flush with cash on odd days, they are not deep pockets. On each cherry that they pick out of the market, they earn a high return: buying cheap, selling dear. However they don't have enough cash to strip the market of cherries and thereby bid the price up.

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.

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.

Could cell membranes produce acoustic streaming? Making the case for synechococcus self-propulsion

Sir James Lighthill proposed in 1992 that acoustic streaming occurs in the inner ear, as part of the cochlear amplifier mechanism. Here we hypothesize that some of the most ancient organisms use acoustic streaming not only for self-propulsion but also to enhance their nutrient uptake. We focus on a motile strain of Synechococcus, a yanobacteria whose mechanism for self-propulsion is not known. Molecular motors could work like piezoelectric transducers acting on the crystalline structure surrounding the outer cell membrane. Our calculations show that a traveling surface acoustic wave (SAW)could account for the observed velocities. These SAW waves will also produce a non-negligible Stokes layer surrounding the cell: motion within this region being essentially chaotic. Therefore, an AS mechanism would be biologically advantageous, enhancing localized diffusion processes and consequently, chemical reactions. We believe that acoustic streaming, produced by nanometer scale membrane vibrations could be widespread in cell biology. Other possible instances are yeast cells and erythrocytes. Flows generated by acoustic streaming may also be produced by silica coated diatoms along their raphe. We note that microelectromechanical (MEMS) acoustic streaming devices were first introduced in the 1990’s. Nature may have preceded this invention by 2.7 Gyr.

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.

Differences in self-reported prevalence and management of cardiovascular risk factors in Switzerland, 2007

Purpose: To assess the prevalence of four self-reported cardiovascular risk factors (CV RFs: smoking, hypertension, dyslipidaemia and diabetes) and their reported management in seven Swiss regions (Léman, MiUelland, Zurich, North-West Switzerland, Oriental Switzerland, Central Switzerland and Tessin). Methods: National health interview survey conducted in 2007 in a representative sample of the Swiss population (17,879 subjects). Age-adjusted data on prevalence of self-reported CV RFs, treatment among participants reporting a RF, control of RFs among treated participants and CV RF screening in the last 12 months levels were computed after weighting. Results: The prevalence of hypertension was highest in North-West Switzerland (27.3%) and lowest in Central Switzerland (21.0%, p<0.001). Antihypertensive treatment was highest in Léman region (62.7%) and lowest in Oriental Switzerland (55.2%, p<0.001). Screening was higher in Tessin (89.3%) and lowest in Léman region (81.8%, p<0.001). Prevalence of dyslipidaemia was highest in Tessin and Léman region (20.7% and 20.1 %, respectively) and lowest in Oriental Switzerland (14.5%, p<0.001). Lipid-Iowering treatment was highest in Tessin and Léman region (44.3% each) and lowest in Central Switzerland (30.7%, p<0.001). Dyslipidaemia screening was highest in Tessin (76.6%) and lowest in Central Switzerland (58.6%, p<0.001). Prevalence of diabetes was highest in North-West Switzerland (5.4%) and lowest in Central Switzerland (3.3%, p<0.05). Diabetes screening was highest in Tessin (78.1%) and lowest in Oriental Switzerland (64.0%, p<0.001). Conversely, no between-region differences were found for hypertension or dyslipidaemia control (see table). Conclusion: there are significant differences between the Swiss regions in self-reported prevalence and management of CV RFs. Screening is beUer in Tessin than in the other regions.