PACIC Instrument: disentangling dimensions using published validation models.

OBJECTIVE: To better understand the structure of the Patient Assessment of Chronic Illness Care (PACIC) instrument. More specifically to test all published validation models, using one single data set and appropriate statistical tools. DESIGN: Validation study using data from cross-sectional survey. PARTICIPANTS: A population-based sample of non-institutionalized adults with diabetes residing in Switzerland (canton of Vaud). MAIN OUTCOME MEASURE: French version of the 20-items PACIC instrument (5-point response scale). We conducted validation analyses using confirmatory factor analysis (CFA). The original five-dimension model and other published models were tested with three types of CFA: based on (i) a Pearson estimator of variance-covariance matrix, (ii) a polychoric correlation matrix and (iii) a likelihood estimation with a multinomial distribution for the manifest variables. All models were assessed using loadings and goodness-of-fit measures. RESULTS: The analytical sample included 406 patients. Mean age was 64.4 years and 59% were men. Median of item responses varied between 1 and 4 (range 1-5), and range of missing values was between 5.7 and 12.3%. Strong floor and ceiling effects were present. Even though loadings of the tested models were relatively high, the only model showing acceptable fit was the 11-item single-dimension model. PACIC was associated with the expected variables of the field. CONCLUSIONS: Our results showed that the model considering 11 items in a single dimension exhibited the best fit for our data. A single score, in complement to the consideration of single-item results, might be used instead of the five dimensions usually described.

A new look at atrial fibrillation: lessons learned from drugs, pacing, and ablation therapies.

Atrial fibrillation (AF) is the most common arrhythmia and among the leading causes of stroke and heart failure in Western populations. Despite the increasing size of clinical trials assessing the efficacy and safety of AF therapies, achieved outcomes have not always matched expectations. Considering that AF is a symptom of many possible underlying diseases, clinical research for this arrhythmia should take into account their respective pathophysiology. Accordingly, the definition of the study populations to be included should rely on the established as well as on the new classifications of AF and take advantage from a differentiated look at the AF-electrocardiogram and from increasingly large spectrum of biomarkers. Such an integrated approach could bring researchers and treating physicians one step closer to the ultimate vision of personalized therapy, which, in this case, means an AF therapy based on refined diagnostic elements in accordance with scientific evidence gathered from clinical trials. By applying clear-cut patient inclusion criteria, future studies will be of smaller size and thus of lower cost. In addition, the findings from such studies will be of greater predictive value at the individual patient level, allowing for pinpointed therapeutic decisions in daily practice.

Structural characterization of rockfall sources in Yosemite Valley from remote sensing data and field surveys

Yosemite Valley poses significant rockfall hazard and related risk due to its glacially steepened walls and approximately 4 million visitors annually. To assess rockfall hazard, it is necessary to evaluate the geologic structure that contributes to the destabilization of rockfall sources and locate the most probable future source areas. Coupling new remote sensing techniques (Terrestrial Laser Scanning, Aerial Laser Scanning) and traditional field surveys, we investigated the regional geologic and structural setting, the orientation of the primary discontinuity sets for large areas of Yosemite Valley, and the specific discontinuity sets present at active rockfall sources. This information, combined with better understanding of the geologic processes that contribute to the progressive destabilization and triggering of granitic rock slabs, contributes to a more accurate rockfall susceptibility assessment for Yosemite Valley and elsewhere.

International business cycles, financial markets and household production

This paper investigates the properties of an international real business cycle model with household production. We show that a model with disturbances to both market and household technologies reproduces the main regularities of the data and improves existing models in matching international consumption, investment and output correlations without irrealistic assumptions on the structure of international financial markets. Sensitivity analysis shows the robustness of the results to alternative specifications of the stochastic processes for the disturbances and to variations of unmeasured parameters within a reasonable range.

Cell locations for AQP1, AQP4 and 9 in the non-human primate brain.

The presence of three water channels (aquaporins, AQP), AQP1, AQP4 and AQP9 were observed in normal brain and several rodent models of brain pathologies. Little is known about AQP distribution in the primate brain and its knowledge will be useful for future testing of drugs aimed at preventing brain edema formation. We studied the expression and cellular distribution of AQP1, 4 and 9 in the non-human primate brain. The distribution of AQP4 in the non-human primate brain was observed in perivascular astrocytes, comparable to the observation made in the rodent brain. In contrast with rodent, primate AQP1 is expressed in the processes and perivascular endfeet of a subtype of astrocytes mainly located in the white matter and the glia limitans, possibly involved in water homeostasis. AQP1 was also observed in neurons innervating the pial blood vessels, suggesting a possible role in cerebral blood flow regulation. As described in rodent, AQP9 mRNA and protein were detected in astrocytes and in catecholaminergic neurons. However additional locations were observed for AQP9 in populations of neurons located in several cortical areas of primate brains. This report describes a detailed study of AQP1, 4 and 9 distributions in the non-human primate brain, which adds to the data already published in rodent brains. This relevant species differences have to be considered carefully to assess potential drugs acting on AQPs non-human primate models before entering human clinical trials.

Allergy to betalactam antibiotics in children: a prospective follow-up study in retreated children after negative responses in skin and challenge tests.

BACKGROUND: Up to 10% of the patients in whom suspected betalactam hypersensitivity (HS) has been excluded by skin and challenge tests report suspected allergic reactions during subsequent treatments with the same or very similar betalactams. It has been suggested that the reactions may result from a resensitization induced by the challenge performed at the time of the allergological work-up. However, most patients did not undergo a second allergological work-up, to determine if the reactions resulted from betalactam HS or not. OBJECTIVES: We aimed to determine if children diagnosed nonallergic to betalactams have tolerated subsequent treatments with the initially suspected and/or other betalactams, and, in case of a reaction, if the reaction resulted from betalactam HS. Methods: We sent a questionnaire concerning the clinical history of their children to the parents of 256 children previously diagnosed nonallergic to betalactams. A second allergological work-up was performed in the children reporting suspected allergic reactions during subsequent treatments with the same and/or other betalactams. Skin tests were performed with the soluble form of the suspected (or very similar) betalactams and other betalactams from the same and other classes. Skin test responses were assessed at 15-20 min (immediate), 6-8 h (semi-late) and 48-72 h (late). Oral challenge (OC) was performed in children with negative skin tests, either at the hospital (immediate and accelerated reactions), or at home (delayed reactions). RESULTS: A response was obtained from 141 children (55.3%). Forty-eight (34%) of those children had not been treated with the betalactams for whom a diagnosis of allergy had been ruled out previously. Seven (7.5%) of the 93 children who had been treated again reported suspected allergic reactions. Skin tests and OC were performed in six of those children, and gave negative results in five children. In one child previously diagnosed nonallergic to amoxicillin associated with clavulanic acid, we diagnosed a delayed HS to clavulanic acid and a serum sickness-like disease to cefaclor. Thus, the frequency of reactions resulting from betalactam HS in children with negative skin and challenge tests is very low, and does not exceed 2.1% (2/93) if we consider that the child which refused a second allergological work-up is really allergic to betalactams. CONCLUSION: Our results in a very large number of children show that reactions presumed to result from betalactam HS are rare in children in whom the diagnosis of betalactam allergy has been ruled out previously. Moreover, they suggest that, as shown for the initial reactions, most of the reactions during subsequent treatments are rather a consequence of the infectious diseases for whom betalactams have been prescribed than a result of betalactam HS. Finally, they suggest that the risk of resensitization by OC is very low, and do not support the notion that skin testing should be repeated in children diagnosed nonallergic to betalactams.

The ins and outs of unemployment: An analysis conditional on technology shocks

We analyze how unemployment, job finding and job separation rates reactto neutral and investment-specific technology shocks. Neutral shocks increaseunemployment and explain a substantial portion of it volatility; investment-specificshocks expand employment and hours worked and contribute to hoursworked volatility. Movements in the job separation rates are responsible for theimpact response of unemployment while job finding rates for movements alongits adjustment path. The evidence warns against using models with exogenousseparation rates and challenges the conventional way of modelling technologyshocks in search and sticky price models.

Designing institutions for financial stability: Regulation and supervision by objective for the Euro area

In this paper, we discuss pros and cons ofdifferent models for financial market regulationand supervision and we present a proposal forthe re-organisation of regulatory and supervisoryagencies in the Euro Area. Our arguments areconsistent with both new theories and effectivebehaviour of financial intermediaries inindustrialized countries. Our proposed architecturefor financial market regulation is based on theassignment of different objectives or "finalities"to different authorities, both at the domesticand the European level. According to thisperspective, the three objectives of supervision- microeconomic stability, investor protectionand proper behaviour, efficiency and competition- should be assigned to three distinct Europeanauthorities, each one at the centre of a Europeansystem of financial regulators and supervisorsspecialized in overseeing the entire financialmarket with respect to a single regulatoryobjective and regardless of the subjective natureof the intermediaries. Each system should bestructured and organized similarly to the EuropeanSystem of Central Banks and work in connectionwith the central bank which would remain theinstitution responsible for price and macroeconomicstability. We suggest a plausible path to buildour 4-peak regulatory architecture in the Euro area.

Testing demographic models of effective population size.

Due to practical difficulties in obtaining direct genetic estimates of effective sizes, conservation biologists have to rely on so-called 'demographic models' which combine life-history and mating-system parameters with F-statistics in order to produce indirect estimates of effective sizes. However, for the same practical reasons that prevent direct genetic estimates, the accuracy of demographic models is difficult to evaluate. Here we use individual-based, genetically explicit computer simulations in order to investigate the accuracy of two such demographic models aimed at investigating the hierarchical structure of populations. We show that, by and large, these models provide good estimates under a wide range of mating systems and dispersal patterns. However, one of the models should be avoided whenever the focal species' breeding system approaches monogamy with no sex bias in dispersal or when a substructure within social groups is suspected because effective sizes may then be strongly overestimated. The timing during the life cycle at which F-statistics are evaluated is also of crucial importance and attention should be paid to it when designing field sampling since different demographic models assume different timings. Our study shows that individual-based, genetically explicit models provide a promising way of evaluating the accuracy of demographic models of effective size and delineate their field of applicability.

Cumulative dominance and heuristic performance in binary multi-attribute choice

Several studies have reported high performance of simple decision heuristics multi-attribute decision making. In this paper, we focus on situations where attributes are binary and analyze the performance of Deterministic-Elimination-By-Aspects (DEBA) and similar decision heuristics. We consider non-increasing weights and two probabilistic models for the attribute values: one where attribute values are independent Bernoulli randomvariables; the other one where they are binary random variables with inter-attribute positive correlations. Using these models, we show that good performance of DEBA is explained by the presence of cumulative as opposed to simple dominance. We therefore introduce the concepts of cumulative dominance compliance and fully cumulative dominance compliance and show that DEBA satisfies those properties. We derive a lower bound with which cumulative dominance compliant heuristics will choose a best alternative and show that, even with many attributes, this is not small. We also derive an upper bound for the expected loss of fully cumulative compliance heuristics and show that this is moderateeven when the number of attributes is large. Both bounds are independent of the values ofthe weights.

Psychothérapie et mécanismes de défense = Psychotherapy and defense mechanisms

Dans cet article, les auteurs mettent en dialogue deux facettes des mécanismes de défense en situation psychothérapeutique : la psychopathologie et le changement. Pour commencer, les instruments de mesure les plus utilisés sont présentés, avec un accent sur les échelles d'évaluation par un juge externe. Les conceptions de Vaillant et de Perry sont présentées et discutées. L'article se continue avec une synthèse des travaux empiriques de recherche en psychothérapie se focalisant sur les changements des mécanismes de défense au cours des psychothérapies, principalement d'orientation psychanalytique. Une réflexion autour du lien avec le concept d'alliance thérapeutique, ainsi qu'avec celui du coping complète cette synthèse. Des travaux récents concernant des psychothérapies de courte et de longue durée sont ensuite abordés. Les défenses sont également discutées du point de vue de la psychopathologie, à travers deux exemples d'études empiriques mettant en évidence des spécificités dans des troubles psychiatriques. Les retombées de ces résultats de recherche pour la pratique psychanalytique sont mentionnées tout au long de cet article de synthèse. With the present article, we aim to develop a dialogue between two aspects of defense mechanisms in psychotherapy : psychopathology and change. First, the most frequently used instruments will be presented, with a particular focus on observer-rated scales, and Vaillant's and Perry's models are sketched and discussed. Then, we review empirical research on changes in defense mechanisms over the course of psychotherapy, mainly psychoanalytic. An elaboration on the links with the concept of therapeutic alliance and the concept of coping completes this overview. Recent studies on change in short- and long-term psychotherapy are then discussed. Defense mechanisms are then examined from a psychopathology point of view, using two examples of empirical studies pointing to distinctive characteristics of mental disorders. Clinical implications for psychoanalytic practice are discussed throughout the article.

A test of the predictive validity of non-linear QALY models using time trade-off utilities

This paper presents a test of the predictive validity of various classes ofQALY models (i.e., linear, power and exponential models). We first estimatedTTO utilities for 43 EQ-5D chronic health states and next these states wereembedded in health profiles. The chronic TTO utilities were then used topredict the responses to TTO questions with health profiles. We find that thepower QALY model clearly outperforms linear and exponential QALY models.Optimal power coefficient is 0.65. Our results suggest that TTO-based QALYcalculations may be biased. This bias can be avoided using a power QALY model.

Molecular and functional characterization of a novel cardiac-specific human tropomyosin isoform.

BACKGROUND: Tropomyosin (TM), an essential actin-binding protein, is central to the control of calcium-regulated striated muscle contraction. Although TPM1alpha (also called alpha-TM) is the predominant TM isoform in human hearts, the precise TM isoform composition remains unclear. METHODS AND RESULTS: In this study, we quantified for the first time the levels of striated muscle TM isoforms in human heart, including a novel isoform called TPM1kappa. By developing a TPM1kappa-specific antibody, we found that the TPM1kappa protein is expressed and incorporated into organized myofibrils in hearts and that its level is increased in human dilated cardiomyopathy and heart failure. To investigate the role of TPM1kappa in sarcomeric function, we generated transgenic mice overexpressing cardiac-specific TPM1kappa. Incorporation of increased levels of TPM1kappa protein in myofilaments leads to dilated cardiomyopathy. Physiological alterations include decreased fractional shortening, systolic and diastolic dysfunction, and decreased myofilament calcium sensitivity with no change in maximum developed tension. Additional biophysical studies demonstrate less structural stability and weaker actin-binding affinity of TPM1kappa compared with TPM1alpha. CONCLUSIONS: This functional analysis of TPM1kappa provides a possible mechanism for the consequences of the TM isoform switch observed in dilated cardiomyopathy and heart failure patients.

Is the observed persistence spurious? A test for fractional integration versus short memory and structural breaks

Although it is commonly accepted that most macroeconomic variables are nonstationary, it is often difficult to identify the source of the non-stationarity. In particular, it is well-known that integrated and short memory models containing trending components that may display sudden changes in their parameters share some statistical properties that make their identification a hard task. The goal of this paper is to extend the classical testing framework for I(1) versus I(0)+ breaks by considering a a more general class of models under the null hypothesis: non-stationary fractionally integrated (FI) processes. A similar identification problem holds in this broader setting which is shown to be a relevant issue from both a statistical and an economic perspective. The proposed test is developed in the time domain and is very simple to compute. The asymptotic properties of the new technique are derived and it is shown by simulation that it is very well-behaved in finite samples. To illustrate the usefulness of the proposed technique, an application using inflation data is also provided.

Scale-dependent adaptive evolution and morphological convergence to climatic niche in Californian eriogonoids (Polygonaceae)

Aim Macroevolutionary patterns and processes change substantially depending on levels of taxonomic and ecological organization, and the resolution of environmental and spatial variability. In comparative methods, the resolution of environmental and spatial variability often defines the number of selective regimes used to test whether phenotypic characteristics are adaptively correlated with the environment. Here, we examine how investigator choice of the number of selective regimes, determined by varying the resolution of among-species variability in the species climatic niche (hereafter called ecological scale'), influences trait morphological diversification among Eriogonoideae species. We assess whether adaptive or neutral processes drive the evolution of several morphological traits in these species. Location South-western North America. Methods We applied a phylogenetic framework of three evolutionary models to four morphological traits and the climatic niches of Eriogonoideae (in the buckwheat family, Polygonaceae). We tested whether morphological traits evolve in relation to climate by adaptive or neutral process, and whether the resulting patterns of morphological variability are conserved or convergent across the clade. We inspected adaptive models of evolution under different levels of resolution of among-species variability of the climatic niche. Results We show that morphological traits and climate niches of Eriogonoideae species are not phylogenetically conserved. Further, adaptive evolution of phenotypic traits is specific to climatic niche occupancy across this clade. Finally, the likely evolutionary process and the level of detectable niche conservatism change depending on the resolution of environmental variability of the climatic niche. Main conclusions Our study demonstrates the need to consider both the resolution of environmental variability and alternative evolutionary models to understand the morphological diversification that accompanies divergent adaptive evolution of lineages to climatic conditions.