Male-pattern baldness susceptibility locus at 20p11.

We conducted a genome-wide association study for androgenic alopecia in 1,125 men and identified a newly associated locus at chromosome 20p11.22, confirmed in three independent cohorts (n = 1,650; OR = 1.60, P = 1.1 x 10(-14) for rs1160312). The one man in seven who harbors risk alleles at both 20p11.22 and AR (encoding the androgen receptor) has a sevenfold-increased odds of androgenic alopecia (OR = 7.12, P = 3.7 x 10(-15)).

Restricted transgene expression in the brain with cell-type specific neuronal promoters.

Tissue-targeted expression is of major interest for studying the contribution of cellular subpopulations to neurodegenerative diseases. However, in vivo methods to investigate this issue are limited. Here, we report an analysis of the cell specificity of expression of fluorescent reporter genes driven by six neuronal promoters, with the ubiquitous phosphoglycerate kinase 1 (PGK) promoter used as a reference. Quantitative analysis of AcGFPnuc expression in the striatum and hippocampus of rodents showed that all lentiviral vectors (LV) exhibited a neuronal tropism; however, there was substantial diversity of transcriptional activity and cell-type specificity of expression. The promoters with the highest activity were those of the 67 kDa glutamic acid decarboxylase (GAD67), homeobox Dlx5/6, glutamate receptor 1 (GluR1), and preprotachykinin 1 (Tac1) genes. Neuron-specific enolase (NSE) and dopaminergic receptor 1 (Drd1a) promoters showed weak activity, but the integration of an amplification system into the LV overcame this limitation. In the striatum, the expression profiles of Tac1 and Drd1a were not limited to the striatonigral pathway, whereas in the hippocampus, Drd1a and Dlx5/6 showed the expected restricted pattern of expression. Regulation of the Dlx5/6 promoter was observed in a disease condition, whereas Tac1 activity was unaffected. These vectors provide safe tools that are more selective than others available, for the administration of therapeutic molecules in the central nervous system (CNS). Nevertheless, additional characterization of regulatory elements in neuronal promoters is still required.

Dynamics of transient pattern formation in nematic liquid crystals

We analyze the dynamics of a transient pattern formation in the Fréedericksz transition corresponding to a twist geometry. We present a calculation of the time-dependent structure factor based on a dynamical model which incorporates consistently the coupling of the director field with the velocity flow and also the effect of fluctuations. The appearance and development of a characteristic periodicity is described in terms of the time dependence of the maximum of the structure factor. We find a well-defined time for the appearance of the pattern and a subsequent stage of pattern development in which the characteristic periodicity tends to an asymptotic value.

Nonlinear effects in the dynamics of transient pattern formation in nematics

A nonlinear calculation of the dynamics of transient pattern formation in the Fréedericksz transition is presented. A Gaussian decoupling is used to calculate the time dependence of the structure factor. The calculation confirms the range of validity of linear calculations argued in earlier work. In addition, it describes the decay of the transient pattern.

Alterations in the local myocardial motion pattern in patients suffering from pressure overload due to aortic stenosis.

BACKGROUND: MR tissue tagging allows the noninvasive assessment of the locally and temporally resolved motion pattern of the left ventricle. Alterations in cardiac torsion and diastolic relaxation of the left ventricle were studied in patients with aortic stenosis and were compared with those of healthy control subjects and championship rowers with physiological volume-overload hypertrophy. METHODS AND RESULTS: Twelve aortic stenosis patients, 11 healthy control subjects with normal left ventricular function, and 11 world-championship rowers were investigated for systolic and diastolic heart wall motion on a basal and an apical level of the myocardium. Systolic torsion and untwisting during diastole were examined by use of a novel tagging technique (CSPAMM) that provides access to systolic and diastolic motion data. In the healthy heart, the left ventricle performs a systolic wringing motion, with a counterclockwise rotation at the apex and a clockwise rotation at the base. Apical untwisting precedes diastolic filling. In the athlete's heart, torsion and untwisting remain unchanged compared with those of the control subjects. In aortic stenosis patients, torsion is significantly increased and diastolic apical untwisting is prolonged compared with those of control subjects or athletes. CONCLUSIONS: Torsional behavior as observed in pressure- and volume-overloaded hearts is consistent with current theoretical findings. A delayed diastolic untwisting in the pressure-overloaded hearts of the patients may contribute to a tendency toward diastolic dysfunction.

Quality of life depends on the drinking pattern in alcohol-dependent patients.

AIMS: In patients with alcohol dependence, health-related quality of life (QOL) is reduced compared with that of a normal healthy population. The objective of the current analysis was to describe the evolution of health-related QOL in adults with alcohol dependence during a 24-month period after initial assessment for alcohol-related treatment in a routine practice setting, and its relation to drinking pattern which was evaluated across clusters based on the predominant pattern of alcohol use, set against the influence of baseline variables METHODS: The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to measure QOL at baseline and quarterly for 2 years among participants in CONTROL, a prospective observational study of patients initiating treatment for alcohol dependence. The sample consisted of 160 adults with alcohol dependence (65.6% males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected using TimeLine Follow-Back. Based on the participant's reported alcohol use, three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear regression analysis was used to identify factors that were potentially associated with the mental and physical summary MOS-SF-36 scores at each time point. RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100, norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4) at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8 (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses indicated that there was a significant association between a lower 2-year follow-up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale score ≥8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical component summary score was 48.8 (10.6) at baseline, remained stable over the follow-up and did not differ across the three clusters. Mixed-effect linear regression univariate analyses found that the average 2-year follow-up MOS-SF-36 physical score was increased (compared with mostly abstainers) in mostly heavy drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36 physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid improvement was seen in the mental dimension of QOL following treatment initiation, which was maintained during 24 months. Improvement was associated with the pattern of alcohol use, becoming close to the general population norm in patients classified as mostly abstainers, improving substantially in mostly moderate drinkers and improving only slightly in mostly heavy drinkers. The physical dimension of QOL was generally in the normal range but was not associated with drinking patterns.

The geographical concentration of industry across Spanish Regions, 1856-1995

New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

European integration, FDI and the internal geography of trade : evidence from Western European border regions

In this paper we use a gravity model to study the trade performance of French and Spanishborder regions relatively to non-border regions, over the past two decades. We find that,controlling for their size, proximity and location characteristics, border regions trade onaverage between 62% and 193% more with their neighbouring country than other regions,and twice as much if they are endowed with good cross border transport infrastructures.Despite European integration, however, this trade outperformance has fallen for the mostperipheral regions within the EU. We show that this trend was linked in part to a shift in the propensity of foreign investors to move their affiliates from the regions near their home market to the regions bordering the EU core.

Monetary integration and the cost of borrowing

With the beginning of the European Monetary Union (EMU), euro-area sovereign securities¿ adjusted spreads over Germany (corrected from the foreign exchange risk) experienced an increase that caused a lower than expected decline in borrowing costs. The objective of this paper is to study what explains that rising. In particular, if it took place a change in the price assigned by markets to domestic (credit risk and/or market liquidity) or to international risk factors. The empirical evidence supports the idea that a change in the market value of liquidity occurred with the EMU. International and default risk play a smaller role

Integración económica y localización industrial. Cataluña, la fábrica de España: ¿cuándo y por qué?

En este artículo se analizan los determinantes de la localización de la actividad industrial en España durante la segunda mitad del siglo XIX. El objetivo es estudiar la existencia de cambios en los factores explicativos de la localización, con el fin de identificar los efectos de la integración económica sobre la geografía industrial española. Para hacerlo, en primer lugar se analiza la literatura histórica existente. En segundo lugar, se describen las teorías que explican la localización de l'actividad. En tercer lugar, se realiza un análisis empírico de la localización y la concentración de la industria española al siglo XIX. A continuación, se propone un estudio econométrico de los determinantes de la localización industrial en dos cortes temporales, 1856 y 1893. Los resultados son consistentes con las teorías del comercio. Durante el decurso de la segunda mitad del siglo XIX, España paso a ser una economía integrada, la movilidad del trabajo y del capital se vio favorecida y como resultado, las diferencias relativas en las dotaciones de factores perdieron importancia en la explicación de las pautas de especialización industrial. Por el contrario, la integración económica favoreció la significación relativa de las economías de escala o de la proximidad a los mercados como elementos explicativos de la localización de la industria, favoreciendo, de esta manera, la aglomeración de la actividad industrial

Financial Integration, Trade Openness and International Transmission

[cat] Com afecten l’obertura comercial i financera a la volatilitat macroeconòmica? La literatura existent, tant empírica com teòrica, no ha assolit encara un consens. Aquest article usa un model microfonamentat de dos països simètrics amb entrada endògena d’empreses per estudiar-ho. L’anàlisis es du a terme per tres règims econòmics diferents amb diferents nivells d’integració internacional: una economia tancada, una autarquia financera i una integració plena. Es consideren diversos nivells d’obertura comercial, en forma de biaix domèstic de la demanda i l’economia pot patir pertorbacions en la productivitat del treball i en innovació. El model conclou que la incertesa macroeconòmica, representada principalment per la volatilitat del consum, la producció i la relació real d’intercanvi internacional, depèn del grau d’obertura i del tipus de pertorbació.

Influence of bedrock structures on the spatial pattern of erosional landforms in small alpine catchments

Structural settings and lithological characteristics are traditionally assumed to influence the development of erosional landforms, such as gully networks and rock couloirs, in steep mountain rock basins. The structural control of erosion of two small alpine catchments of distinctive rock types is evaluated by comparing the correspondences between the orientations of their gullies and rock couloirs with (1) the sliding orientations of potential slope failures mechanisms, and (2) the orientation of the maximum joint frequency, this latter being considered as the direction exploited primarily by erosion and mass wasting processes. These characteristic orientations can be interpreted as structural weaknesses contributing to the initiation and propagation of erosion. The morphostructural analysis was performed using digital elevation models and field observations. The catchment comprised of magmatic intrusive rocks shows a clear structural control, mostly expressed through potential wedges failure. Such joint configurations have a particular geometry that encourages the development of gullies in hard rock, e.g. through enhanced gravitational and hydrological erosional processes. In the catchment underlain by sedimentary rocks, penetrative joints that act as structural weaknesses seem to be exploited by gullies and rock couloirs. However, the lithological setting and bedding configuration prominently control the development of erosional landforms, and influence not only the local pattern of geomorphic features, but the general morphology of the catchment. The orientations of the maximum joint frequency are clearly associated with the gully network, suggesting that its development is governed by anisotropy in rock strength. These two catchments are typical of bedrock-dominated basins prone to intense processes of debris supply. This study suggests a quantitative approach for describing the relationship between bedrock jointing and geomorphic features geometry. Incorporation of bedrock structure can be relevant when studying processes governing the transfer of clastic material, for the assessment of sediment yields and in landforms evolution models.