A colorectal cancer genome-wide association study in a Spanish cohort identifies two variants associated with colorectal cancer risk at 1p33 and 8p12

Background: Colorectal cancer (CRC) is a disease of complex aetiology, with much of the expected inherited risk being due to several common low risk variants. Genome-Wide Association Studies (GWAS) have identified 20 CRC risk variants. Nevertheless, these have only been able to explain part of the missing heritability. Moreover, these signals have only been inspected in populations of Northern European origin. Results: Thus, we followed the same approach in a Spanish cohort of 881 cases and 667 controls. Sixty-four variants at 24 loci were found to be associated with CRC at p-values <10-5. We therefore evaluated the 24 loci in another Spanish replication cohort (1481 cases and 1850 controls). Two of these SNPs, rs12080929 at 1p33 (P-replication=0.042; P-pooled=5.523x10(-03); OR (CI95%)=0.866(0.782-0.959)) and rs11987193 at 8p12 (P-replication=0.039; P-pooled=6.985x10(-5); OR (CI95%)=0.786(0.705-0.878)) were replicated in the second Phase, although they did not reach genome-wide statistical significance. Conclusions: We have performed the first CRC GWAS in a Southern European population and by these means we were able to identify two new susceptibility variants at 1p33 and 8p12 loci. These two SNPs are located near the SLC5A9 and DUSP4 loci, respectively, which could be good functional candidates for the association signals. We therefore believe that these two markers constitute good candidates for CRC susceptibility loci and should be further evaluated in other larger datasets. Moreover, we highlight that were these two SNPs true susceptibility variants, they would constitute a decrease in the CRC missing heritability fraction.

Alegia klasikoak euskaraz: Isopeteko, La Fontaineren eta Samaniegoren alegien berridazketen azterketa

521 p.

Interactions spatiales et auto-organisation des végétations semi-arides

Les recherches récapitulées dans cette thèse de doctorat ont porté sur les causes de l’organisation spatiale des végétations périodiques. Ces structures paysagères aux motifs réguliers, tachetés, tigrés ou labyrinthiques, d’échelle décamétrique à hectométrique, couvrant des étendues considérables sur au moins trois continents, constituent un cas d’école dans l’étude des processus endogènes présidant à l’hétérogénéité du couvert végétal. Ces structures prennent place sur un substrat homogène, mis à part la rétroaction du couvert lui-même, et sont marquées par des écotones abrupts et la persistance d’une proportion considérable de sol nu. Plusieurs modèles ont mis en avant l’existence possible d’un phénomène d’auto-organisation du couvert, qui verrait une structure d’ensemble émerger des interactions locales entre individus. Ces modèles se basent sur le jeu simultané de la consommation de la ressource (compétition) et de l’amélioration de l’un ou l’autre des éléments du bilan de la même ressource par le couvert (facilitation). La condition à l’existence d’une structure d’ensemble spatialement périodique et stable réside dans une différence entre la portée de la compétition (plus grande) et celle de la facilitation. L’apparition de ces structures est modulée par le taux de croissance biologique, qui est le reflet des contraintes extérieures telles que l’aridité, le pâturage ou la coupe de bois. Le modus operandi des interactions spatiales supposées entre individus reste largement à préciser.

Nos recherches ont été menées au sud-ouest de la République du Niger, à l’intérieur et dans les environs du parc Régional du W. Trois axes ont été explorés :(i) Une étude de la dépendance spatiale entre la structure de la végétation (biovolumes cartographiés) et les paramètres du milieu abiotique (relief, sol), sur base d’analyses spectrales et cross-spectrales par transformée de Fourier (1D et 2D). (ii) Une étude diachronique (1956, 1975 et 1996) à large échelle (3000 km²) de l’influence de l’aridité et des pressions d’origine anthropique sur l’auto-organisation des végétations périodiques, basée sur la caractérisation de la structure spatiale des paysages sur photos aériennes via la transformée de Fourier en 2D. (iii) Trois études portant sur les interactions spatiales entre individus :En premier lieu, via l’excavation des systèmes racinaires (air pulsé) ;Ensuite, par un suivi spatio-temporel du bilan hydrique du sol (blocs de gypse) ;Enfin, via le marquage de la ressource par du deutérium.

Nous avons ainsi pu établir que les végétations périodiques constituent bien un mode d’auto-organisation pouvant survenir sur substrat homogène et modulé par les contraintes climatiques et anthropiques. Un ajustement rapide entre l’organisation des végétations périodiques et le climat a pu être montrée en zone protégée. La superficie et l’organisation des végétations périodiques y ont tour à tour progressé et régressé en fonction d’épisodes secs ou humides. Par contre, en dehors de l’aire protégée, la possibilité d’une restauration du couvert semble fortement liée au taux d’exploitation des ressources végétales. Ces résultats ont d’importantes implications quant à la compréhension des interactions entre climat et écosystèmes et à l’évaluation de leurs capacités de charge. La caractérisation de la structure spatiale des végétations arides, notamment par la transformée de Fourier d’images HR, devrait être généralisée comme outil de monitoring de l’état de ces écosystèmes. Nos études portant sur les modes d’interactions spatiales ont permis de confirmer l’existence d’une facilitation à courte portée du couvert végétal sur la ressource. Cependant, cette facilitation ne semble pas s’exercer sur le terme du bilan hydrique traditionnellement avancé, à savoir l’infiltration, mais plutôt sur le taux d’évaporation (deux fois moindre à l’ombre des canopées). Ce mécanisme exclut l’existence de transferts diffusifs souterrains entre sols nu et fourrés. Des transferts inverses semblent d’ailleurs montrés par le marquage isotopique. L’étude du bilan hydrique et la cartographie du micro-relief, ainsi que la profondeur fortement réduite de la zone d’exploitation racinaire, jettent de sérieux doutes quant au rôle communément admis des transferts d’eau par ruissellement/diffusion de surface en tant que processus clé dans la compétition à distance entre les plantes. L’alternative réside dans l’existence d’une compétition racinaire de portée supérieure aux canopées. Cette hypothèse trouve une confirmation tant par les rhizosphères excavées, superficielles et étendues, que dans le marquage isotopique, montrant des contaminations d’arbustes situés à plus de 15 m de la zone d’apport. De même, l’étude du bilan hydrique met en évidence les influences simultanées et contradictoires (facilitation/compétition) des ligneux sur l’évapotranspiration.

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This PhD thesis gathers results of a research dealing with the causes of the spatial organisation of periodic vegetations. These landscape structures, featuring regular spotted, labyrinthine or banded patterns of decametric to hectometric scale, and extending over considerable areas on at least three continents, constitute a perfect study case to approach endogenous processes leading to vegetation heterogeneities. These patterns occur over homogeneous substratum, except for vegetation’s own feedbacks, and are marked by sharp ecotones and the persistence of a considerable amount of bare soil. A number of models suggested a possible case of self-organized patterning, in which the general structure would emerge from local interactions between individuals. Those models rest on the interplay of competitive and facilitative effects, relating to soil water consumption and to soil water budget enhancement by vegetation. A general necessary condition for pattern formation to occur is that negative interactions (competition) have a larger range than positive interactions (facilitation). Moreover, all models agree with the idea that patterning occurs when vegetation growth decreases, for instance as a result of reduced water availability, domestic grazing or wood cutting, therefore viewing patterns as a self-organised response to environmental constraints. However the modus operandi of the spatial interactions between individual plants remains largely to be specified.

We carried out a field research in South-West Niger, within and around the W Regional Park. Three research lines were explored: (i) The study of the spatial dependency between the vegetation pattern (mapped biovolumes) and the factors of the abiotic environment (soil, relief), on the basis of spectral and cross-spectral analyses with Fourier transform (1D and 2D). (ii) A broad scale diachronic study (1956, 1975, 1996) of the influence of aridity and human induced pressures on the vegetation self-patterning, based on the characterisation of patterns on high resolution remote sensing data via 2D Fourier transform. (iii) Three different approaches of the spatial interactions between individuals: via root systems excavation with pulsed air; via the monitoring in space and time of the soil water budget (gypsum blocks method); and via water resource labelling with deuterated water.

We could establish that periodic vegetations are indeed the result of a self-organisation process, occurring in homogeneous substratum conditions and modulated by climate and human constraints. A rapid adjustment between vegetation patterning and climate could be observed in protected zones. The area and patterning of the periodic vegetations successively progressed and regressed, following drier or wetter climate conditions. On the other hand, outside protected areas, the restoration ability of vegetation appeared to depend on the degree of vegetation resource exploitation. These results have important implications regarding the study of vegetation-climate interactions and the evaluation of ecosystems’ carrying capacities. Spatial pattern characterisation in arid vegetations using Fourier transform of HR remote sensing data should be generalised for the monitoring of those ecosystems. Our studies dealing with spatial interaction mechanisms confirmed the existence of a short range facilitation of the cover on water resource. However, this facilitation does not seem to act through the commonly accepted infiltration component, but rather on the evaporative rate (twice less within thickets). This mechanism excludes underground diffusive transfers between bare ground and vegetation. Inverse transfers were even shown by deuterium labelling. Water budget study and micro-elevation mapping, along with consistent soil shallowness, together cast serious doubts on the traditional mechanism of run-off/diffusion of surface water as a key process of the long range competition between plants. An alternative explanation lies in long range root competition. This hypothesis find support as well in the excavated root systems, shallow and wide, as in isotopic labelling, showing contaminations of shrubs located up to 15 m of the irrigated area. Water budget study also evidenced simultaneous contradictory effects (facilitation/competition) of shrubs on evapotranspiration.

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 × 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 × 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

Research activities in the MaRINET project: keeping the European marine energy development facilities at world class level

The MaRINET project aims to build a synergy in the European marine renewable energy development infrastructure network, involving a total of 28 partners across the union. Its scope extends from small to large scale testing, in both tank and field. The main activities of the project are to standardize test procedures, to provide centralized free access for European technology developers, and to innovate for improving test infrastructures and techniques.
This paper presents the work carried in this last part, which focuses on research objectives identified to be current challenges for industrial development. They are distributed in 6 topics. On the one hand are issues that concern directly one of the 3 types of energy scoped in the project: wave, tidal, and offshore wind energy. Two examples are the real time estimation of incident waves, and the measurement of turbulence in tidal flows. On the other hand, collaborative effort is drawn on aspects that are common to those technologies: electrical components, environmental monitoring, and dedicated moorings.

The institutionalisation of the European Internal Cross-Border Co-operation Policy: A first appraisal

In the space of just 20 years, internal cross-border co-operation (CBC) has transformed from a marginal issue for European integration into an important strand of the third objective of European Union's (EU's) regional policy. How might this process of transformation be explained? This study intends to reconstruct the chronology of its development through interviews and use of archival material. The emergence of the current CBC policy was not, we argue, an inevitable solution to the problem of border management but, rather, the result of a struggle between the actors of that policy sub-system. The dramatic rise of CBC is the result of a series of factors that originated with the signing of the Single European Act in 1986. The construction of CBC as a set of problems and solutions by a network of policy actors at the margins of the EU through a series of technical reports, together with the policy window opened by the appointment of the Delors Commission, allowed the launching of an innovative CBC policy which has consolidated over time.

Update on Research Activities in the MaRINET Project

The MaRINET FP7 project aims to build a synergy in the European marine renewable energy development infrastructure network, involving a total of 28 partners across the union. Its scope extends from small to large scale testing, in both tank and field. The main activities of the project are to standardize test procedures, to provide centralized free access for European technology developers, and to innovate for improving test infrastructures and techniques.
Two years to the end of the project, this paper presents an update of the work being carried in this last part. It focuses on research objectives identified to be current challenges for industrial development. They are distributed in 6 topics. On the one hand are issues directly related to one of the 3 types of energy scoped in the project: wave, tidal, and offshore wind. On the other hand, collaborative effort is drawn on aspects that are common to those technologies: electrical components, environmental monitoring, and dedicated moorings.
Theory and validation of new test techniques are presented, for example in the case of non-intrusive wave measurements. This is done in coordination with extensive experimental analysis of the phenomena implying tests, such as nonlinearities in moorings.

Outgassing Behavior of C/2012 S1 (ISON) from 2011 September to 2013 June

We report photometric observations for comet C/2012 S1 (ISON) obtained during the time period immediately after discovery (r = 6.28 AU) until it moved into solar conjunction in mid-2013 June using the UH2.2 m, and Gemini North 8 m telescopes on Mauna Kea, the Lowell 1.8 m in Flagstaff, the Calar Alto 1.2 m telescope in Spain, the VYSOS-5 telescopes on Mauna Loa Hawaii and data from the CARA network. Additional pre-discovery data from the Pan STARRS1 survey extends the light curve back to 2011 September 30 (r = 9.4 AU). The images showed a similar tail morphology due to small micron sized particles throughout 2013. Observations at submillimeter wavelengths using the James Clerk Maxwell Telescope on 15 nights between 2013 March 9 (r = 4.52 AU) and June 16 (r = 3.35 AU) were used to search for CO and HCN rotation lines. No gas was detected, with upper limits for CO ranging between 3.5-4.5 × 1027 molecules s-1. Combined with published water production rate estimates we have generated ice sublimation models consistent with the photometric light curve. The inbound light curve is likely controlled by sublimation of CO2. At these distances water is not a strong contributor to the outgassing. We also infer that there was a long slow outburst of activity beginning in late 2011 peaking in mid-2013 January (r ~ 5 AU) at which point the activity decreased again through 2013 June. We suggest that this outburst was driven by CO injecting large water ice grains into the coma. Observations as the comet came out of solar conjunction seem to confirm our models.

A collision in 2009 as the origin of the debris trail of asteroid P/2010A2

The peculiar object P/2010A2 was discovered in January 2010 and given a cometary designation because of the presence of a trail of material, although there was no central condensation or coma. The appearance of this object, in an asteroidal orbit (small eccentricity and inclination) in the inner main asteroid belt attracted attention as a potential new member of the recently recognized class of main-belt comets. If confirmed, this new object would expand the range in heliocentric distance over which main-belt comets are found. Here we report observations of P/2010A2 by the Rosetta spacecraft. We conclude that the trail arose from a single event, rather than a period of cometary activity, in agreement with independent results. The trail is made up of relatively large particles of millimetre to centimetre size that remain close to the parent asteroid. The shape of the trail can be explained by an initial impact ejecting large clumps of debris that disintegrated and dispersed almost immediately. We determine that this was an asteroid collision that occurred around 10 February 2009.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

4.11(EC) Report new instrumentation and field measuring technology for tidal currents

One of the challenges the tidal power industry faces, is the requirement of cost effective, reliable but highly accurate acquisition of flow data. Different methods are required , applications range over different spatial and temporal scales. This report assembles in the first sections, theoretical background information on acoustic Doppler Velocimetry and RADAR measurements. The use of existing expertise in field tests of marine vehicles is discussed next, followed by a discussion of issues relating to recreating field conditions in laboratory environments. The last three sections present practical applications of various methods performed in field conditions. While progress has been made over the last years, this overview highlights the challenges in full scale field measurements and knowledge gaps in the industry.

Le Spectateur français au XIXme siècle, ou Variétés morales, politiques et littéraires, recueillies des meilleurs écrits périodiques

1810 (A08,T08).

Le Spectateur français au XIXme siècle, ou Variétés morales, politiques et littéraires, recueillies des meilleurs écrits périodiques

1810 (A09,T09).

Le Spectateur français au XIXme siècle, ou Variétés morales, politiques et littéraires, recueillies des meilleurs écrits périodiques

1812 (A12,T12).