Histopathological Features of Aspirated Thrombi after Primary Percutaneous Coronary Intervention in Patients with ST-Elevation Myocardial Infarction

BACKGROUND: Plaque disruption with superimposed thrombus is the predominant mechanism responsible for the onset of acute coronary syndromes. Studies have shown that plaque disruption and thrombotic occlusion are frequently separated in time. We established the histopathological characteristics of material aspirated during primary percutaneous coronary intervention (PCI) in a large consecutive ST-elevation myocardial infarction (STEMI) population. METHODOLOGY/PRINCIPAL FINDINGS: Thrombus aspiration during primary PCI was performed in 1,362 STEMI patients. Thrombus age was classified as fresh (<1 day), lytic (1-5 days), or organized (>5 day). Further, the presence of plaque was documented. The histopathological findings were related to the clinical, angiographic, and procedural characteristics. Material could be aspirated in 1,009 patients (74%). Components of plaque were found in 395 of these patients (39%). Fresh thrombus was found in 577 of 959 patients (60%) compared to 382 patients (40%) with lytic or organized thrombi. Distal embolization was present in 21% of patients with lytic thrombus compared to 12% and 15% of patients with fresh or organized thrombus. CONCLUSIONS/SIGNIFICANCE: Material could be obtained in 74% of STEMI patients treated with thrombus aspiration during primary PCI. In 40% of patients thrombus age is older than 24 h, indicating that plaque disruption and thrombus formation occur significantly earlier than the onset of symptoms in many patients

Saamelaisten oikeuksien toteutuminen: kansainvälinen oikeusvertaileva tutkimus

Saamelaisten oikeuksien eteenpäin vieminen Suomessa on kohdannut haasteita. Tämä tutkimus pyrkii vastaamaan valtioneuvoston määrittelemään tietotarpeeseen, joka liittyy erityisesti saamelaisten maa- ja osallistumisoikeuksiin sekä saamelaismääritelmään. Kyseessä on kansainvälinen oikeusvertaileva tutkimus, joka pyrkii tarjoamaan uutta tietoa sekä kansainvälisen alkuperäiskansaoikeuden kehityksestä että siitä, miten muissa aiheen kannalta keskeisissä valtioissa on ratkaistu alkuperäiskansojen oikeuksiin liittyviä kysymyksiä. Tutkimusraportti koostuu neljästä pääosiosta. Ensimmäinen osio tarkastelee saamelaisten oikeusasemaa Suomessa sekä siihen liittyviä ehdotuksia, joita tarkastellaan kansainvälisen oikeuden luomien velvoitteiden näkökulmasta. Toinen kokonaisuus pitää sisällään saamelaismääritelmän problematiikan tarkastelua kansainvälisen oikeuden sekä korkeimman hallinto-oikeuden tapauskäytännön valossa, sisältäen myös kuvauksen saamelaisuuden määrittelyyn liittyvien kiistojen taustoista ja syistä. Kolmas pääosio keskittyy alkuperäiskansojen kansainvälisoikeudellisen aseman ja oikeuksien kehitykseen pääfokuksena ns. ennakkosuostumuksen periaate (FPIC). Tämä osio pitää sisällään myös ILO sopimus 169:n sisältämien maaoikeuksien analyysiin. Neljäs pääkokonaisuus on oikeusvertaileva osio, jossa on mukana Norjaa, Ruotsia, Uutta-Seelantia, Kanadaa ja Latinalaisen Amerikan maita koskevat maaraportit. Tämä kappalekokonaisuus sisältää myös yhteenvedon vertailun piirissä olleiden valtioiden oikeuskäytänteiden keskeisistä elementeistä, joista voidaan löytää parhaita käytänteitä Suomen saamelaisten oikeuksien toteuttamiseksi

Employment Protection and Multinational Enterprises: Theory and Evidence from Micro Data

In this paper we show, theoretically and empirically, that stronger employment protection legislation (EPL) in a host country has important and differing effects on the various activities of multinational enterprises (MNEs). Using micro data on affiliates to Swedish multinational firms in 20 countries for the period of 19651998, we find that increased stringency in EPL is associated with fewer investments in new affiliates and lower employment in existing affiliates. We also find that it is mainly affiliate exports that are affected negatively by stronger EPL, while the impact on local sales is small. This is in accordance with our theoretical model, which predicts that the impact of EPL on the costs of competing firms is likely to put affiliates at a smaller disadvantage when selling for the local market than in the production for exports

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

Abstract A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth.Abstract A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth

Genome-wide association study of placental weight identifies distinct and shared genetic influences between placental and fetal growth

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth

Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The chaos in calibrating crop models

Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of system models and has an important impact on simulated values. Here we propose and illustrate a novel method of developing guidelines for calibration of system models. Our example is calibration of the phenology component of crop models. The approach is based on a multi-model study, where all teams are provided with the same data and asked to return simulations for the same conditions. All teams are asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices.HighlightsWe propose a new approach to deriving calibration recommendations for system modelsApproach is based on analyzing calibration in multi-model simulation exercisesResulting recommendations are holistic and anchored in actual practiceWe apply the approach to calibration of crop models used to simulate phenologyRecommendations concern: objective function, parameters to estimate, software usedCompeting Interest StatementThe authors have declared no competing interest