Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

Genome-wide association study of major recurrent depression in the U.K. population.

OBJECTIVE: Studies of major depression in twins and families have shown moderate to high heritability, but extensive molecular studies have failed to identify susceptibility genes convincingly. To detect genetic variants contributing to major depression, the authors performed a genome-wide association study using 1,636 cases of depression ascertained in the U.K. and 1,594 comparison subjects screened negative for psychiatric disorders. METHOD: Cases were collected from 1) a case-control study of recurrent depression (the Depression Case Control [DeCC] study; N=1346), 2) an affected sibling pair linkage study of recurrent depression (probands from the Depression Network [DeNT] study; N=332), and 3) a pharmacogenetic study (the Genome-Based Therapeutic Drugs for Depression [GENDEP] study; N=88). Depression cases and comparison subjects were genotyped at Centre National de Génotypage on the Illumina Human610-Quad BeadChip. After applying stringent quality control criteria for missing genotypes, departure from Hardy-Weinberg equilibrium, and low minor allele frequency, the authors tested for association to depression using logistic regression, correcting for population ancestry. RESULTS: Single nucleotide polymorphisms (SNPs) in BICC1 achieved suggestive evidence for association, which strengthened after imputation of ungenotyped markers, and in analysis of female depression cases. A meta-analysis of U.K. data with previously published results from studies in Munich and Lausanne showed some evidence for association near neuroligin 1 (NLGN1) on chromosome 3, but did not support findings at BICC1. CONCLUSIONS: This study identifies several signals for association worthy of further investigation but, as in previous genome-wide studies, suggests that individual gene contributions to depression are likely to have only minor effects, and very large pooled analyses will be required to identify them.

Making land-use fit to planning goals. Weaknesses and opportunities within the Swiss land management regime

In Switzerland, the issue of land consumption has made it to the front of the political agenda in recent years. Studies conducted on a national level have concluded that there is an excess of land zoned for construction (ARE, 2008), which is seen as contributing to urban sprawl. This situation is looked upon as a failure of the Federal Law on Spatial Planning (LAT, 1979) and there is a political push to change it in order to reinforce zoning regulations. In this article, we look on the issue from a different angle. While there may be large quantities of land zoned for construction, in many urban areas land actually available for development is scarce. Building on the idea that planning's efficiency is linked to its capacity of influencing actual land-use, we focus on how this situation can be dealt with within the current Swiss institutional context.

A new case constructing adelid moth from Chile (Lepidoptera)

A new case constructing adelid moth from Chile (Lepidoptera). The adult and larva of Ceromitia tubulifolia sp. nov. are described and illustrated. The larvae seem to be associated with sclerophyllous forest of central Chile. The larvae make a protective case from of a piece of leaf. The name phylloikos is proposed for this form of larval case. A review of the morphology and bionomics of this species are provided.

Multi-stage garnet in the internal Brianconnais basement (Ambin massif, Savoy): New petrological constraints on the blueschist-facies metamorphism in the Western Alps and tectonic implications

Three types of garnet have been distinguished in pelitic schists from an epidote-blueschist-facies unit of the Ambin and South Vanoise Brianconnais massifs on the basis of texture, chemical zoning and mineral inclusion characterization. Type-1 garnet cores with high Mn/Ca ratios are interpreted as pre-Alpine relicts, whereas Type-1 garnet rims, Type-2 inclusion-rich porphyroblasts and smaller Type-3 garnets are Alpine. The latter are all characterized by low Mn/Ca ratios and a coexisting mineral assemblage of blue amphibole, high-Si phengite, epidote and quartz. Prograde growth conditions during Alpine D-1 high-pressure (HP) metamorphism are recorded by a decrease in Mn and increase in Fe (+/-Ca) in the Type-2 garnets, culminating in peak P-T conditions of 14-16 kbar and 500degreesC in the deepest parts of the Ambin dome. The multistage growth history of Type-1 garnets indicates a polymetamorphic history for the Ambin and South Vanoise massifs; unfortunately, no age constraints are available. The new metamorphic constraints on the Alpine event in the massifs define a metamorphic T `gap' between them and their surrounding cover (Brianconnais and upper Schistes Lustres units), which experienced metamorphism only in the stability field of carpholite-lawsonite (T < 400degreesC). These data and supporting structural studies confirm that the Ambin and South Vanoise massifs are slices of `eclogitized' continental crust tectonically extruded within the Schistes Lustres units and Brianconnais covers. The corresponding tectonic contacts with top-to-east movement are responsible for the juxtaposition of lower-grade metamorphic units on the Ambin and South Vanoise massifs.

Fick's law adapted to cationic diffusion in a semi-infinite solid: application to spinel megacrystals

In alkaline lavas, the chemical zoning of megacrystals of spinel is due to the cationic exchange between the latter and the host lava. The application of Fick's law to cationic diffusion profiles allows to calculate the time these crystals have stayed in the lava. Those which are in a chemical equilibrium were in contact with the lava during 20 to 30 days, whereas megacrystals lacking this equilibrium were in contact only for 3 or 4 days. The duration of the rise of an ultrabasic nodule in the volcanic chimney was calculated by applying Stokes' law.

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10(-8)) loci, some including known iron-related genes (HFE, SLC40A1, TF, TFR2, TFRC, TMPRSS6) and others novel (ABO, ARNTL, FADS2, NAT2, TEX14). SNPs at ARNTL, TF, and TFR2 affect iron markers in HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Metamorphism on Chromite Ores from the Dobromirtsi ultramafic massif, Rhodope Mountains (SE Bulgaria)

Podiform chromitite bodies occur in highly serpentinized peridotites at Dobromirtsi Ultramafic Massif (Rhodope Mountains, southeastern Bulgaria). The ultramafic body is believed to represent a fragment of Palaeozoic ophiolite mantle. The ophiolite sequence is associated with greenschist - lower-temperature amphibolite facies metamorphosed rocks (biotitic gneisses hosting amphibolite). This association suggests that peridotites, chromitites and metamorphic rocks underwent a common metamorphic evolution. Chromitites at Dobromirtsi have been strongly altered. Their degree of alteration depends on the chromite/silicate ratio and to a lesser extent, on the size of chromitite bodies. Alteration is recorded in individual chromite grains in the form of optical and chemical zoning. Core to rim chemical trends are expressed by MgO- and Al2O3- impoverishment, mainly compensated by FeO and/or Fe2O3 increases. Such chemical variations correspond with three main alteration events. The first one was associated with ocean-floor metamorphism and was characterized by a lizardite replacement of olivine and the absence of chromite alteration. The second event took place during greenchist facies metamorphism. During this event, MgO- and SiO2-rich fluids (derived from low temperature serpentinization of olivine and pyroxenes) reacted with chromite to form chlorite; as a consequence, chromite became altered to a FeO- and Cr2O3-rich, Al2O3-poor chromite. The third event, mainly developed during lower temperature amphibolite facies metamorphism, caused the replacement of the primary and previously altered chromite by Fe2O3-rich chromite (ferritchromite).

Una nova estimació retrospectiva del VAB regional industrial. Espanya, 1860-1930

[cat] En aquest treball, es realitza una nova estimació del VAB industrial espanyol a un nivell de desagregació territorial corresponent a les províncies (NUTSIII) i les Comunitats Autònomes (NUTS II). Per assolir aquest objectiu es planteja una nova metodologia d’estimació de les xifres històriques de VAB industrial regional. Front a les aproximacions tradicionals, basades en la utilització de fonts fiscals com a forma d’aproximar la capacitat productiva industrial, en aquest treball s’ofereix una estimació que també es basa en les rendes generades per la producció industrial de les regions. Amb aquest objectiu, es fa servir la metodologia proposada per Geary i Stark (2002) i les millores proposades per Crafts (2005). La utilització d’aquesta metodologia permet elaborar una nova estimació retrospectiva del VAB industrial de les regions espanyoles a diversos talls temporals corresponents al període 1860-1930.

Etudes Coût-efficacité: ce que devraient retenir les médecins [Cost-effectiveness analyses: what doctors should know]

The resources of our heath care system are limited. Choices in the attribution of resources are necessary to ensure its stability. A cost-effectiveness analysis compares the effects of one health intervention to another, taking into account the costs (including the saved costs) and the saved life years, adjusted for the quality of life (cost-utility). Cost-effectiveness analyses should take the societal perspective and the studied intervention should be compared to a relevant intervention actually in use. Physicians, at the interface between patients and payers, are in an ideal position to interpret, or even perform cost-effectiveness analysis, and to promote the interventions that are most effective and that have a reasonable cost.

Dissolution-reprecipitation of zircon at low-temperature, high-pressure conditions (Lanzo Massif, Italy)

An eclogite facies meta-plagiogranite from the Lanzo massif (western Alps, Italy) contains crystals of zircon intimately associated with allanite. Zircon displays different microtextures ranging from pristine, euhedral, and magmatic to fractured, porous varieties with mosaic zoning, and pervasive recrystallization into euhedral microcrystals. Fractures and voids in the recrystallized zircon microcrystals are mainly filled by high-pressure Na-rich pyroxene. Electron backscattered diffraction analysis revealed a similar crystallographic orientation for primary magmatic zircon crystals and microcrystals, with less than 2 degrees misorientation among neighboring microdomains. The textural change is coupled with chemical and isotopic modifications: recrystallized zircon domains contain significantly less Th and light- to mid-REE, but are richer in Sr than magmatic zircon crystals. Magmatic zircon preserves the protolith U-Pb age of 163.5 +/- 1.7 Ma, whereas zircon microcrystals have a mean age of 55 +/- 1 Ma. The coexisting allanite also contains inclusions of Na-rich pyroxene and has chemical features (elevated Sr and Ni contents and lack of Eu anomaly) indicating formation at high pressure. Despite being associated texturally with zircon, allanite yields a younger Th-Pb age of 46.5 +/- 3.0 Ma, suggesting that the Lanzo unit remained at relatively high pressure conditions for similar to 8 m.y. Zircon recrystallization proceeded with volume reduction and loss of material to an alkaline metamorphic fluid that acted as the agent for a coupled dissolution-reprecipitation process. Recrystallization occurred with minimum transport, in a low-strain environment, and was not significantly enhanced by metamictization. The source of the fluid for zircon recrystallization is most probably related to prograde devolatilization reactions in the surrounding serpentinite.

Spatial planning to the test of property rights in Switzerland : an innovative land management approach to coordinate spatial planning goals with property rights interests

In Switzerland, the land management regime is characterized by a liberal attitude towards the institution of property rights, which is guaranteed by the Constitution. Under the present Swiss constitutional arrangement, authorities (municipalities) are required to take into account landowners' interests when implementing their spatial planning policy. In other words, the institution of property rights cannot be restricted easily in order to implement zoning plans and planning projects. This situation causes many problems. One of them is the gap between the way land is really used by the landowners and the way land should be used based on zoning plans. In fact, zoning plans only describe how landowners should use their property. There is no sufficient provision for handling cases where the use is not in accordance with zoning plans. In particular, landowners may not be expropriated for a non-conforming use of the land. This situation often leads to the opening of new building areas in greenfields and urban sprawl, which is in contradiction with the goals set into the Federal Law on Spatial Planning. In order to identify legal strategies of intervention to solve the problem, our paper is structured into three main parts. Firstly, we make a short description of the Swiss land management regime. Then, we focus on an innovative land management approach designed to implement zoning plans in accordance with property rights. Finally, we present a case study that shows the usefulness of the presented land management approach in practice. We develop three main results. Firstly, the land management approach brings a mechanism to involve landowners in planning projects. Coordination principle between spatial planning goals and landowners' interests is the cornerstone of all the process. Secondly, the land use is improved both in terms of space and time. Finally, the institution of property rights is not challenged, since there is no expropriation and the market stays free.

Una nova estimació retrospectiva del VAB regional industrial. Espanya, 1860-1930

[cat] En aquest treball, es realitza una nova estimació del VAB industrial espanyol a un nivell de desagregació territorial corresponent a les províncies (NUTSIII) i les Comunitats Autònomes (NUTS II). Per assolir aquest objectiu es planteja una nova metodologia d’estimació de les xifres històriques de VAB industrial regional. Front a les aproximacions tradicionals, basades en la utilització de fonts fiscals com a forma d’aproximar la capacitat productiva industrial, en aquest treball s’ofereix una estimació que també es basa en les rendes generades per la producció industrial de les regions. Amb aquest objectiu, es fa servir la metodologia proposada per Geary i Stark (2002) i les millores proposades per Crafts (2005). La utilització d’aquesta metodologia permet elaborar una nova estimació retrospectiva del VAB industrial de les regions espanyoles a diversos talls temporals corresponents al període 1860-1930.

GIS - Based Decision and Outreach Tools for Aggregate Source Management, September 2008

This research project combined various datasets, existing and created for this project, into an Interactive Mapping Service (IMS) for use by Iowa DOT personnel, county planning and zoning departments and the public in order to make more informed decisions regarding aggregate sources and future access to them. Iowa DOT Technical Advisory Committee meetings were held, along with public forum presentations, in order to understand better the social, ecological and economic limitations to extracting aggregate. The information needed by potential users was conveyed and integrated into a single informational source, the Aggregate Planning IMS.