Fibrin fragment D-dimer and the risk of future venous thrombosis

Plasma D-dimer concentration rises more than 100-fold during acute deep vein thrombosis, but there are no prospective data concerning D-dimer as a risk factor for incident venous thrombosis in a general population. Incident venous thrombosis was ascertained in 2 prospective observational studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Of 21 690 participants enrolled between 1987 and 1993, after 8 years of follow-up, D-dimer was measured using baseline stored plasma of 307 participants who developed venous thrombosis and 616 who did not. Relative to the first quintile of the distribution of D-dimer, the age-adjusted odds ratios for future venous thrombosis for the second to fifth quintiles of D-dimer were 1.6, 2.3, 2.3, and 4.2, respectively (P for trend < .0001). Following added adjustment for sex, race, body mass index, factor V Leiden, prothrombin 20210A, and elevated factor VIII coagulant activity (factor VIII:c), these odds ratios were 1.5, 2.1, 1.9, and 3.0, respectively (P for trend < .0001). Among those with idiopathic thrombosis or secondary thrombosis unrelated to cancer, the adjusted fifth quintile odds ratios were 3.5 and 4.8, respectively. By contrast, D-dimer in the fifth versus first quintile was not related to occurrence of cancer-associated thrombosis (odds ratio, 1.1). Odds ratios for elevated D-dimer were consistently elevated in subgroups defined by age, sex, race, duration of follow-up, and thrombosis type (deep vein thrombosis or pulmonary embolus). D-dimer is strongly and positively related to the occurrence of future venous thrombosis

D4.1. Technologies and tools for corpus creation, normalization and annotation

The objectives of the Corpus Acquisition and Annotation (CAA) subsystem are the acquisition and processing of monolingual and bilingual language resources (LRs) required in the PANACEA context. Therefore, the CAA subsystem includes: i) a Corpus Acquisition Component (CAC) for extracting monolingual and bilingual data from the web, ii) a component for cleanup and normalization (CNC) of these data and iii) a text processing component (TPC) which consists of NLP tools including modules for sentence splitting, POS tagging, lemmatization, parsing and named entity recognition

Thrombomodulin Ala455Val Polymorphism and the risk of cerebral infarction in a biracial population: the Stroke Prevention in Young Women Study

BACKGROUND: The genes encoding proteins in the thrombomodulin-protein C pathway are promising candidate genes for stroke susceptibility because of their importance in thrombosis regulation and inflammatory response. Several published studies have shown that the Ala455Val thrombomodulin polymorphism is associated with ischemic heart disease, but none has examined the association with stroke. Using data from the Stroke Prevention in Young Women Study, we sought to determine the association between the Ala455Val thrombomodulin polymorphism and the occurrence of ischemic stroke in young women. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. We compared 141 cases of first ischemic stroke (44% black) among women 15 to 44 years of age with 210 control subjects (35% black) who were identified by random digit dialing and frequency matched to the cases by age and geographical region of residence. Data on historical risk factors were collected by standardized interview. Genotyping of the thrombomodulin Ala455Val polymorphism was performed by pyrosequencing. RESULTS: The A allele (frequency = 0.85) was associated with stroke under the recessive model. After adjustment for age, race, cigarette smoking, hypertension, and diabetes, the AA genotype, compared with the AV and VV genotypes combined, was significantly associated with stroke (odds ratio 1.9, 95% CI 1.1–3.3). The AA genotype was more common among black than white control subjects (81% versus 68%) but there was no significant interaction between the risk genotype and race (adjusted odds ratio 2.7 for blacks and 1.6 for whites). A secondary analysis removing all probable (n = 16) and possible (n = 15) cardioembolic strokes demonstrated an increased association (odds ratio 2.2, 95% CI 1.2–4.2). CONCLUSIONS: Among women aged 15 to 44 years, the AA genotype is more prevalent among blacks than whites and is associated with increased risk of early onset ischemic stroke. Removing strokes potentially related to cardioembolic phenomena increased this association. Further studies are needed to determine whether this polymorphism is functionally related to thrombomodulin expression or whether the association is due to population stratification or linkage to a nearby functional polymorphism

TReND in Africa: Toward a Truly Global (Neuro)science Community.

TReND is a volunteer-scientist run charity dedicated to promoting research and education on the African continent. Focusing on neuroscience, we discuss approaches to address some of the factors that currently stifle Africa's scientific development and our experience in implementing them

Genetic variants in TLR2 and TLR4 are associated with markers of monocyte activation: the Atherosclerosis Risk in Communities MRI Study

Markers of monocyte activation play a critical role in atherosclerosis, but little is known about the genetic influences on cellular levels. Therefore, we investigated the influence of genetic variants in monocyte differentiation antigen (CD14), toll-like receptor-4 (TLR4), toll-like receptor-2 (TLR2), and myeloperoxidase (MPO) on monocyte surface receptor levels. The study sample consisted of 1,817 members of a biracial cohort of adults from the Atherosclerosis Risk in Communities Carotid MRI Study. Monocyte receptors were measured using flow cytometry on fasting whole blood samples. TLR2 rs1816702 genotype was significantly associated with CD14+/TLR2+ percent of positive cells (%) and median fluorescence intensity (MFI) in whites but not in blacks (p < 0.001). Specifically, the presence of the minor T-allele was associated with increased receptor levels. In blacks, TLR4 rs5030719 was significantly associated with CD14+/TLR4+ monocytes (MFI) with mean ± SE intensities of 16.7 ± 0.05 and 16.0 ± 0.14 for GG and GT/TT genotypes, respectively (p < 0.001). Variants in TLR2 and TLR4 were associated with monocyte receptor levels of TLR2 and TLR4, respectively, in a biracial cohort of adults. To our knowledge, this is the first study to look at associations between variants in the toll-like receptor family and toll-like receptor levels on monocytes

The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula

MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent a series of upgrades, involving the exchange of the MAGIC-I camera and its trigger system, as well as the upgrade of the readout system of both telescopes. We use observations of the Crab Nebula taken at low and medium zenith angles to assess the key performance parameters of the MAGIC stereo system. For low zenith angle observations, the standard trigger threshold of the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula flux in 50 h of observations. The angular resolution, defined as the sigma of a 2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while the energy resolution is 16%. We also re-evaluate the effect of the systematic uncertainty on the data taken with the MAGIC telescopes after the upgrade. We estimate that the systematic uncertainties can be divided in the following components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle Physic

The 2009 multiwavelength campaign on Mrk 421: Variability and correlation studies

Aims: We perform an extensive characterization of the broadband emission of Mrk 421, as well as its temporal evolution, during the non-flaring (low) state. The high brightness and nearby location (z = 0.031) of Mrk 421 make it an excellent laboratory to study blazar emission. The goal is to learn about the physical processes responsible for the typical emission of Mrk 421, which might also be extended to other blazars that are located farther away and hence are more difficult to study. Methods: We performed a 4.5-month multi-instrument campaign on Mrk 421 between January 2009 and June 2009, which included VLBA, F-GAMMA, GASP-WEBT, Swift, RXTE, Fermi-LAT, MAGIC, and Whipple, among other instruments and collaborations. This extensive radio to very-high-energy (VHE; E> 100 GeV) γ-ray dataset provides excellent temporal and energy coverage, which allows detailed studies of the evolution of the broadband spectral energy distribution. Results: Mrk421 was found in its typical (non-flaring) activity state, with a VHE flux of about half that of the Crab Nebula, yet the light curves show significant variability at all wavelengths, the highest variability being in the X-rays. We determined the power spectral densities (PSD) at most wavelengths and found that all PSDs can be described by power-laws without a break, and with indices consistent with pink/red-noise behavior. We observed a harder-when-brighter behavior in the X-ray spectra and measured a positive correlation between VHE and X-ray fluxes with zero time lag. Such characteristics have been reported many times during flaring activity, but here they are reported for the first time in the non-flaring state. We also observed an overall anti-correlation between optical/UV and X-rays extending over the duration of the campaign. Conclusions: The harder-when-brighter behavior in the X-ray spectra and the measured positive X-ray/VHE correlation during the 2009 multi-wavelength campaign suggests that the physical processes dominating the emission during non-flaring states have similarities with those occurring during flaring activity. In particular, this observation supports leptonic scenarios as being responsible for the emission of Mrk 421 during non-flaring activity. Such a temporally extended X-ray/VHE correlation is not driven by any single flaring event, and hence is difficult to explain within the standard hadronic scenarios. The highest variability is observed in the X-ray band, which, within the one-zone synchrotron self-Compton scenario, indicates that the electron energy distribution is most variable at the highest energies.Fil: Aleksic, J.. IFAE; EspañaFil: Ansoldi, S.. Università di Udine; ItaliaFil: Antonelli, L. A.. INAF National Institute for Astrophysics; ItaliaFil: Antoranz, P.. Università di Siena; ItaliaFil: Babic, A.. University of Rijeka; CroaciaFil: Bangale, P.. Max-Planck-Institut für Physik; AlemaniaFil: Barres de Almeida, U.. Max-Planck-Institut für Physik; AlemaniaFil: Barrio, J. A.. Universidad Complutense de Madrid; EspañaFil: Becerra Gonzalez, J.. Inst. de Astrofísica de Canarias; EspañaFil: Bednarek, W.. University of Lodz; PoloniaFil: Berger, K.. Inst. de Astrofísica de Canarias; EspañaFil: Bernardini, E.. Deutsches Elektronen-Synchrotron (DESY); AlemaniaFil: Bijand, A.. ETH Zurich; SuizaFil: Blanch, O.. IFAE; EspañaFil: Bock, R. K.. Max-Planck-Institut für Physik; AlemaniaFil: Bonnefoy, S.. Universidad Complutense; EspañaFil: Bonnoli, G.. INAF National Institute for Astrophysics; ItaliaFil: Borracci, F.. Max-Planck-Institut für Physik; AlemaniaFil: Bretz, T.. Universität Würzburg,; AlemaniaFil: Carmona, E.. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas; EspañaFil: Carosi, A.. INAF National Institute for Astrophysics; EspañaFil: Carreto Fidalgo, D.. Universität Würzburg; AlemaniaFil: Colin, P.. Max-Planck-Institut für Physik; AlemaniaFil: Colombo, E.. Inst. de Astrofísica de Canarias; EspañaFil: Contreras, J. L.. Universidad Complutense; EspañaFil: Cortina, J.. IFAE; EspañaFil: Covino, S.. INAF National Institute for Astrophysics; ItaliaFil: Pichel, Ana Carolina. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: The Magic Collaboration.Fil: The Veritas Collaboration

Unprecedented study of the broadband emission of Mrk 421 during flaring activity in March 2010

Context. Because of its proximity, Mrk 421 is one of the best sources on which to study the nature of BL Lac objects. Its proximity allows us to characterize its broadband spectral energy distribution (SED). Aims. The goal is to better understand the mechanisms responsible for the broadband emission and the temporal evolution of Mrk 421. These mechanisms may also apply to more distant blazars that cannot be studied with the same level of detail. Methods. A flare occurring in March 2010 was observed for 13 consecutive days (from MJD 55 265 to MJD 55 277) with unprecedented wavelength coverage from radio to very high energy (VHE; E> 100 GeV) γ-rays with MAGIC, VERITAS, Whipple, Fermi-LAT, MAXI, RXTE, Swift, GASP-WEBT, and several optical and radio telescopes. We modeled the day-scale SEDs with one-zone and two-zone synchrotron self-Compton (SSC) models, investigated the physical parameters, and evaluated whether the observed broadband SED variability can be associated with variations in the relativistic particle population. Results. The activity of Mrk 421 initially was high and then slowly decreased during the 13-day period. The flux variability was remarkable at the X-ray and VHE bands, but it was minor or not significant at the other bands. The variability in optical polarization was also minor. These observations revealed an almost linear correlation between the X-ray flux at the 2–10 keV band and the VHE γ-ray flux above 200 GeV, consistent with the γ-rays being produced by inverse-Compton scattering in the Klein-Nishina regime in the framework of SSC models. The one-zone SSC model can describe the SED of each day for the 13 consecutive days reasonably well, which once more shows the success of this standard theoretical scenario to describe the SEDs of VHE BL Lacs such as Mrk 421. This flaring activity is also very well described by a two-zone SSC model, where one zone is responsible for the quiescent emission, while the other smaller zone, which is spatially separated from the first, contributes to the daily variable emission occurring at X-rays and VHE γ-rays. The second blob is assumed to have a smaller volume and a narrow electron energy distribution with 3 × 104<γ< 6 × 105, where γ is the Lorentz factor of the electrons. Such a two-zone scenario would naturally lead to the correlated variability at the X-ray and VHE bands without variability at the optical/UV band, as well as to shorter timescales for the variability at the X-ray and VHE bands with respect to the variability at the other bands. Conclusions. Both the one-zone and the two-zone SSC models can describe the daily SEDs via the variation of only four or five model parameters, under the hypothesis that the variability is associated mostly with the underlying particle population. This shows that the particle acceleration and cooling mechanism that produces the radiating particles might be the main mechanism responsible for the broadband SED variations during the flaring episodes in blazars. The two-zone SSC model provides a better agreement with the observed SED at the narrow peaks of the low- and high-energy bumps during the highest activity, although the reported one-zone SSC model could be further improved by varying the parameters related to the emitting region itself (δ, B and R), in addition to the parameters related to the particle population.Fil: Aleksic, J.. IFAE; EspañaFil: Ansoldi, S.. Università di Udine; ItaliaFil: Antonelli, L. A.. INAF National Institute for Astrophysics; ItaliaFil: Antoranz, P.. Università di Siena; ItaliaFil: Babic, A.. University of Rijeka; CroaciaFil: Bangale, P.. Max-Planck-Institut für Physik; AlemaniaFil: Barres de Almeida, U.. Max-Planck-Institut für Physik; AlemaniaFil: Barrio, J. A.. Universidad Complutense de Madrid; EspañaFil: Becerra Gonzalez, J.. Inst. de Astrofísica de Canarias; EspañaFil: Bednarek, W.. University of Łódź,; PoloniaFil: Bernardini, E.. Deutsches Elektronen-Synchrotron (DESY); AlemaniaFil: Biasuzzi, B.. Università di Udine; ItaliaFil: Biland, A.. ETH Zurich; SuizaFil: Blanch, O.. IFAE; EspañaFil: Boller, A.. ETH Zurich; SuizaFil: Bonnefoy, S.. Universidad Complutense de Madrid; EspañaFil: Bonnoli, G.. INAF National Institute for Astrophysics ; ItaliaFil: Borracci, F.. Max-Planck-Institut für Physik; AlemaniaFil: Bretz, T.. Universität Würzburg ; AlemaniaFil: Carmona, E.. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas ; EspañaFil: Carosi, A.. INAF National Institute for Astrophysics; ItaliaFil: Colin, P.. Max-Planck-Institut für Physik; AlemaniaFil: Colombo, E.. Inst. de Astrofísica de Canarias; EspañaFil: Contreras, J. L.. Universidad Complutense; EspañaFil: Cortina, J.. IFAE; EspañaFil: Covino, S.. INAF National Institute for Astrophysics; ItaliaFil: Da Vela, P.. Università di Siena; ItaliaFil: Dazzi, F.. Max-Planck-Institut für Physik; AlemaniaFil: Pichel, Ana Carolina. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: Rovero, Adrian Carlos. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: The Veritas Collaboration.Fil: The MAGIC Collaboration

Multiwavelength observations of Mrk 501 in 2008

Context. Blazars are variable sources on various timescales over a broad energy range spanning from radio to very high energy (>100 GeV, hereafter VHE). Mrk 501 is one of the brightest blazars at TeV energies and has been extensively studied since its first VHE detection in 1996. However, most of the γ-ray studies performed on Mrk 501 during the past years relate to flaring activity, when the source detection and characterization with the available γ-ray instrumentation was easier toperform. Aims: Our goal is to characterize the source γ-ray emission in detail, together with the radio-to-X-ray emission, during the non-flaring (low) activity, which is less often studied than the occasional flaring (high) activity. Methods: We organized a multiwavelength (MW) campaign on Mrk 501 between March and May 2008. This multi-instrument effort included the most sensitive VHE γ-ray instruments in the northern hemisphere, namely the imaging atmospheric Cherenkov telescopes MAGIC and VERITAS, as well as Swift, RXTE, the F-GAMMA, GASP-WEBT, and other collaborations and instruments. This provided extensive energy and temporal coverage of Mrk 501 throughout the entire campaign. Results: Mrk 501 was found to be in a low state of activity during the campaign, with a VHE flux in the range of 10%-20% of the Crab nebula flux. Nevertheless, significant flux variations were detected with various instruments, with a trend of increasing variability with energy and a tentative correlation between the X-ray and VHE fluxes. The broadband spectral energy distribution during the two different emission states of the campaign can be adequately described within the homogeneous one-zone synchrotron self-Compton model, with the (slightly) higher state described by an increase in the electron number density. Conclusions: The one-zone SSC model can adequately describe the broadband spectral energy distribution of the source during the two months covered by the MW campaign. This agrees with previous studies of the broadband emission of this source during flaring and non-flaring states. We report for the first time a tentative X-ray-to-VHE correlation during such a low VHE activity. Although marginally significant, this positive correlation between X-ray and VHE, which has been reported many times during flaring activity, suggests that the mechanisms that dominate the X-ray/VHE emission during non-flaring-activity are not substantially different from those that are responsible for the emission during flaring activity.Fil: Aleksic, J.. IFAE; EspañaFil: Ansoldi, S.. Università di Udine; ItaliaFil: Antonelli, L. A.. INAF National Institute for Astrophysics; ItaliaFil: Antoranz, P.. Università di Siena; ItaliaFil: Babic, A.. University of Rijeka ; Croacia. University of Split; CroaciaFil: Bangale, P.. Max-Planck-Institut für Physik; AlemaniaFil: Barres de Almeida, U.. Max-Planck-Institut für Physik; AlemaniaFil: Barrio, J. A.. Universidad Complutense de Madrid; EspañaFil: Becerra Gonzalez, J.. Inst. de Astrofísica de Canarias; EspañaFil: Bednarek, W.. University of Lodz; PoloniaFil: Berger, K.. Inst. de Astrofísica de Canarias; EspañaFil: Bernardini, E.. Deutsches Elektronen-Synchrotron (DESY); AlemaniaFil: Biland, A.. ETH Zurich; SuizaFil: Blanch, O.. IFAE; EspañaFil: Bock, R. K.. Max-Planck-Institut für Physik; AlemaniaFil: Bonnefoy, S.. Universidad Complutense de Madrid; EspañaFil: Bonnoli, G.. INAF National Institute for Astrophysics; ItaliaFil: Borracci, F.. Max-Planck-Institut für Physik; AlemaniaFil: Bretz, T.. Universität Würzburg; Alemania. Now at École polytechnique fédérale de Lausanne (EPFL); SuizaFil: Carmona, E.. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas; EspañaFil: Carosi, A.. INAF National Institute for Astrophysics; ItaliaFil: Carreto Fidalgo, D.. Universität Würzburg; AlemaniaFil: Colin, P.. Max-Planck-Institut für Physik; AlemaniaFil: Colombo, E.. Inst. de Astrofísica de Canarias; EspañaFil: Contreras, J. L.. Universidad Complutense de Madrid; EspañaFil: Cortina, J.. IFAE; EspañaFil: Covino, S.. INAF National Institute for Astrophysics; ItaliaFil: Da Vela, P.. Università di Siena; ItaliaFil: Dazzi, F.. Università di Udine; ItaliaFil: Pichel, Ana Carolina. Consejo Nacional de Investigaciónes Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Astronomía y Física del Espacio. - Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Astronomía y Física del Espacio; ArgentinaFil: The MAGIC collaboration.Fil: The VERITAS collaboration

Common Variants in MAGI2 Gene Are Associated with Increased Risk for Cognitive Impairment in Schizophrenic Patients

Schizophrenia is a complex psychiatric disorder characterized by positive symptoms, negative symptoms, and cognitive impairment. MAGI2, a relatively large gene (∼1.5 Mbps) that maps to chromosome 7q21, is involved in recruitment of neurotransmitter receptors such as AMPA- and NMDA-type glutamate receptors. A genetic association study designed to evaluate the association between MAGI2 and cognitive performance or schizophrenia has not been conducted. In this case-control study, we examined the relationship of single nucleotide polymorphism (SNP) variations in MAGI2 and risk for schizophrenia in a large Japanese sample and explored the potential relationships between variations in MAGI2 and aspects of human cognitive function related to glutamate activity. Based on the result of first schizophrenia genome-wide association study in a Japanese population (JGWAS), we selected four independent SNPs and performed an association study using a large independent Japanese sample set (cases 1624, controls 1621). Wisconsin Card Sorting Test (WCST) was used to evaluate executive function in 114 cases and 91 controls. We found suggestive evidence for genetic association of common SNPs within MAGI2 locus and schizophrenia in Japanese population. Furthermore in terms of association between MAGI2 and cognitive performance, we observed that genotype effect of rs2190665 on WCST score was significant (p = 0.034) and rs4729938 trended toward significance (p = 0.08). In conclusion, although we could not detect strong genetic evidence for association of common variants in MAGI2 and increased schizophrenia risk in a Japanese population, these SNPs may increase risk of cognitive impairment in schizophrenic patients