Side effects of genome structural changes.

The first extensive catalog of structural human variation was recently released. It showed that large stretches of genomic DNA that vary considerably in copy number were extremely abundant. Thus it is conceivable that they play a major role in functional variation. Consistently, genomic insertions and deletions were shown to contribute to phenotypic differences by modifying not only the expression levels of genes within the aneuploid segments but also of normal copy-number neighboring genes. In this report, we review the possible mechanisms behind this latter effect.

Rare genomic structural variants in complex disease: lessons from the replication of associations with obesity.

The limited ability of common variants to account for the genetic contribution to complex disease has prompted searches for rare variants of large effect, to partly explain the 'missing heritability'. Analyses of genome-wide genotyping data have identified genomic structural variants (GSVs) as a source of such rare causal variants. Recent studies have reported multiple GSV loci associated with risk of obesity. We attempted to replicate these associations by similar analysis of two familial-obesity case-control cohorts and a population cohort, and detected GSVs at 11 out of 18 loci, at frequencies similar to those previously reported. Based on their reported frequencies and effect sizes (OR≥25), we had sufficient statistical power to detect the large majority (80%) of genuine associations at these loci. However, only one obesity association was replicated. Deletion of a 220 kb region on chromosome 16p11.2 has a carrier population frequency of 2×10(-4) (95% confidence interval [9.6×10(-5)-3.1×10(-4)]); accounts overall for 0.5% [0.19%-0.82%] of severe childhood obesity cases (P = 3.8×10(-10); odds ratio = 25.0 [9.9-60.6]); and results in a mean body mass index (BMI) increase of 5.8 kg.m(-2) [1.8-10.3] in adults from the general population. We also attempted replication using BMI as a quantitative trait in our population cohort; associations with BMI at or near nominal significance were detected at two further loci near KIF2B and within FOXP2, but these did not survive correction for multiple testing. These findings emphasise several issues of importance when conducting rare GSV association, including the need for careful cohort selection and replication strategy, accurate GSV identification, and appropriate correction for multiple testing and/or control of false discovery rate. Moreover, they highlight the potential difficulty in replicating rare CNV associations across different populations. Nevertheless, we show that such studies are potentially valuable for the identification of variants making an appreciable contribution to complex disease.

Schistosoma mansoni: structural damage after treatment with oxamniquine

The effects of a single dose (100 mg/kg-body weight of mouse) of oxamniquine on the worm's tegument and paranchyma in relation to the process of immunological granulomatous reaction of the host's liver are described under light and electron microscopy (EM). The lesions caused by the drug are sequentially and simultaneously described in form of swelling, surface bulble and disruption with erosions. Ulceration in the tubercules with loss of spines is often more extensive and severe in male worms and concentration of host's mononuclear cells is observed. The possible role of host's immune response is discussed.

Price level convergence, purchasing power parity and multiple structural breaks: an application to US cities

This article provides a fresh methodological and empirical approach for assessing price level convergence and its relation to purchasing power parity (PPP) using annual price data for seventeen US cities. We suggest a new procedure that can handle a wide range of PPP concepts in the presence of multiple structural breaks using all possible pairs of real exchange rates. To deal with cross-sectional dependence, we use both cross-sectional demeaned data and a parametric bootstrap approach. In general, we find more evidence for stationarity when the parity restriction is not imposed, while imposing parity restriction provides leads toward the rejection of the panel stationar- ity. Our results can be embedded on the view of the Balassa-Samuelson approach, but where the slope of the time trend is allowed to change in the long-run. The median half-life point estimate are found to be lower than the consensus view regardless of the parity restriction.

Structural analysis of Turtle mountain (Alberta) using digital elevation model: Toward a progressive failure

In 1903, the eastern slope of Turtle Mountain (Alberta) was affected by a 30 M m3-rockslide named Frank Slide that resulted in more than 70 casualties. Assuming that the main discontinuity sets, including bedding, control part of the slope morphology, the structural features of Turtle Mountain were investigated using a digital elevation model (DEM). Using new landscape analysis techniques, we have identified three main joint and fault sets. These results are in agreement with those sets identified through field observations. Landscape analysis techniques, using a DEM, confirm and refine the most recent geology model of the Frank Slide. The rockslide was initiated along bedding and a fault at the base of the slope and propagated up slope by a regressive process following a surface composed of pre-existing discontinuities. The DEM analysis also permits the identification of important geological structures along the 1903 slide scar. Based on the so called Sloping Local Base Level (SLBL) an estimation was made of the present unstable volumes in the main scar delimited by the cracks, and around the south area of the scar (South Peak). The SLBL is a method permitting a geometric interpretation of the failure surface based on a DEM. Finally we propose a failure mechanism permitting the progressive failure of the rock mass that considers gentle dipping wedges (30°). The prisms or wedges defined by two discontinuity sets permit the creation of a failure surface by progressive failure. Such structures are more commonly observed in recent rockslides. This method is efficient and is recommended as a preliminary analysis prior to field investigation.

Qualités psychométriques de la version française de la TAS-20 et prévalence de l'alexithymie chez 264 adolescents tout-venant [The 20-item Toronto alexithymia scale: structural validity, internal consistency and prevalence of alexithymia in a Swiss adolescent sample]

L'objectif de cette étude est d'examiner la structure factorielle et la consistance interne de la TAS-20 sur un échantillon d'adolescents (n = 264), ainsi que de décrire la distribution des caractéristiques alexithymiques dans cet échantillon. La structure à trois facteurs de la TAS-20 a été confirmée par notre analyse factorielle confirmatoire. La consistance interne, mesurée à l'aide d'alpha de Cronbach, est acceptable pour le premier facteur (difficulté à identifier les sentiments (DIF)), bonne pour le second (difficulté à verbaliser les sentiments (DDF)), mais en revanche, faible pour le troisième facteur (pensées orientées vers l'extérieur (EOT)). Les résultats d'une Anova mettent en évidence une tendance linéaire indiquant que plus l'âge augmente plus le niveau d'alexithymie (score total TAS-20), la difficulté à identifier les sentiments et les pensées orientées vers l'extérieur diminuent. En ce qui concerne la prévalence de l'alexithymie, on remarque en effet que 38,5 % des adolescents de moins de 16 ans sont considérés comme alexithymiques, contre 30,1 % des 16-17 ans et 22 % des plus de 17 ans. Notre étude indique donc que la TAS-20 est un instrument adéquat pour évaluer l'alexithymie à l'adolescence, tout en suggérant quelques précautions étant donné l'aspect développemental de cette période.

Structural Breaks in the Real Exchange Rate and Real Interest Rate Relationship

In this paper we empirically examine the relationship between the real exchange rate and real interest rate differentials using recent econometric methods robust to potential structural breaks. Generally, our study provides evidence of this relationship in the long-run context. More specifically, we first focus on the UK-US relationship, and interestingly find limited evidence of this long-run relationship using traditional methods. But when an approach robust to endogenously determined structural breaks is employed, we find evidence that the real interest rate differential is an important determinant of the real exchange rate. Secondly, in order to investigate the relevance of structural shifts in a more global context, we carry out multiple country analysis. While providing evidence of this long-run relationship, European data suggest that the presence of structural breaks is not very common across countries and is indeed country-specific.

A New Test of the Real Interest Rate Parity Hypothesis: Bounds Approach and Structural Breaks

We test the real interest rate parity hypothesis using data for the G7 countries over the period 1970-2008. Our contribution is two-fold. First, we utilize the ARDL bounds approach of Pesaran et al. (2001) which allows us to overcome uncertainty about the order of integration of real interest rates. Second, we test for structural breaks in the underlying relationship using the multiple structural breaks test of Bai and Perron (1998, 2003). Our results indicate significant parameter instability and suggest that, despite the advances in economic and financial integration, real interest rate parity has not fully recovered from a breakdown in the 1980s.

Structural Interactions in Spatial Panels

Until recently, much effort has been devoted to the estimation of panel data regression models without adequate attention being paid to the drivers of diffusion and interaction across cross section and spatial units. We discuss some new methodologies in this emerging area and demonstrate their use in measurement and inferences on cross section and spatial interactions. Specifically, we highlight the important distinction between spatial dependence driven by unobserved common factors and those based on a spatial weights matrix. We argue that, purely factor driven models of spatial dependence may be somewhat inadequate because of their connection with the exchangeability assumption. Limitations and potential enhancements of the existing methods are discussed, and several directions for new research are highlighted.

Analog Modelling of N-S anticlines of the External Sierras (Jaca basin, Southern Pyrenees)

Report for the scientific sojourn carried out at the Uppsala Universitet, Sweden, from April to July the 2007. Two series of analogue models are used to explore ductile-frictional contrasts of the basal décollement in the development of oblique and transverse structures simultaneously to thin-skinned shortening. These models simulate the evolution of the Central External Sierras (Southern Pyrenees, Spain), which constitute the frontal emerging part of the southernmost Pyrenean thrust sheet. They are characterized by the presence of transverse N-S to NW-SE anticlines, which are perpendicular to the Pyrenean structural trend and developed in the hangingwall of the Santo Domingo thrust system, detaching on an unevenly distributed Triassic materials (evaporitic-dolomitic interfingerings). Model setup performs a décollement made by three patches of silicone neighbouring pure brittle sand. Model series A test the thickness ratio between overburden and décollement. Model series B test the width of frictional detachment areas. Model results show how deformation reaches further in areas detached on ductile layer whereas frictional décollement areas assimilate the strain by means of an additional uplift. This replicates the structural style of Central External Sierras: higher structural relief of N-S anticlines with regard to orogen-parallel structures, absence of a representative ductile décollement in the core, tilting towards the orogen and foreland-side closure not thrusted by the frontal emerging South-Pyrenean thrust.

Equilibrium Exchange Rate Determination and Multiple Structural Changes

The large appreciation and depreciation of the US dollar in the 1980s stimulated an important debate on the usefulness of unit root tests in the presence of structural breaks. In this paper, we propose a simple model to describe the evolution of the real exchange rate. We then propose a more general smooth transition (STR) function than has hitherto been employed, which is able to capture structural changes along the (long-run) equilibrium path, and show that this is consistent with our economic model. Our framework allows for a gradual adjustment between regimes and allows for under- and/or over-valued exchange rate adjustments. Using monthly and quarterly data for up to twenty OECD countries, we apply our methodology to investigate the univariate time series properties of CPI-based real exchange rates with both the U.S. dollar and German mark as the numeraire currencies. The empirical results show that, for more than half of the quarterly series, the evidence in favour of the stationarity of the real exchange rate was clearer in the sub-sample period post-1980.

A Comparison Of Forecasting Procedures For Macroeconomic Series: The Contribution Of Structural Break Models

This paper compares the forecasting performance of different models which have been proposed for forecasting in the presence of structural breaks. These models differ in their treatment of the break process, the parameters defining the model which applies in each regime and the out-of-sample probability of a break occurring. In an extensive empirical evaluation involving many important macroeconomic time series, we demonstrate the presence of structural breaks and their importance for forecasting in the vast majority of cases. However, we find no single forecasting model consistently works best in the presence of structural breaks. In many cases, the formal modeling of the break process is important in achieving good forecast performance. However, there are also many cases where simple, rolling OLS forecasts perform well.

A Comparison Of Forecasting Procedures For Macroeconomic Series: The Contribution Of Structural Break Models

This paper compares the forecasting performance of different models which have been proposed for forecasting in the presence of structural breaks. These models differ in their treatment of the break process, the parameters defining the model which applies in each regime and the out-of-sample probability of a break occurring. In an extensive empirical evaluation involving many important macroeconomic time series, we demonstrate the presence of structural breaks and their importance for forecasting in the vast majority of cases. However, we find no single forecasting model consistently works best in the presence of structural breaks. In many cases, the formal modeling of the break process is important in achieving good forecast performance. However, there are also many cases where simple, rolling OLS forecasts perform well.