Cohort profile : InTraUterine sampling in early pregnancy (ITU), a prospective pregnancy cohort study in Finland: study design and baseline characteristics

Purpose The InTraUterine sampling in early pregnancy (ITU) is a prospective pregnancy cohort study. The overarching aim of ITU is to unravel genomic, epigenomic, transcriptomic, endocrine, inflammatory and metabolic maternal-placental-fetal mechanisms involved in the programming of health and disease after exposure to prenatal environmental adversity, such as maternal malnutrition, cardiometabolic disorders, infections, medical interventions, mental disorders and psychosocial stress. This paper describes the study protocol, design and baseline characteristics of the cohort. Participants We included 944 pregnant Finnish women, their partners and children born alive between April 2012 and December 2017. The women were recruited through the national, voluntary trisomy 21 screening between 9(+0) and 21(+6) gestational weeks. Of the participating women, 543 were screen positive and underwent fetal chromosomal testing. Test result of these women suggested no fetal chromosomal abnormality. Further, we recruited 401 women who were screen negative and who did not undergo fetal chromosomal testing. Findings to date We have collected chorionic villi and amniotic fluid from the screen-positive women; blood, urine, buccal swabs and diurnal salivary samples from all women; blood and buccal swabs from all partners; and placenta, cord blood and buccal swabs from all newborns for analyses of the genome, epigenome, transcriptome, and endocrine, inflammatory and metabolic markers. These data are coupled with comprehensive phenotypes, including questions on demographic characteristics, health and well-being of the women and their partners during pregnancy and of the women and their children at the child's age of 1.7 and 3 years. Data also come from patient records and nationwide registers covering health, lifestyle and medication data. Future plans Multiple layers of ITU data allow integrative data analyses, which translate to biomarker identification and allow risk stratification and understanding of the biological mechanisms involved in prenatal programming of health and disease.Peer reviewe

Reliability of a novel approach for reference-based cell type estimation in human placental DNA methylation studies

The placenta is a central organ during early development, influencing trajectories of health and disease. DNA methylation (DNAm) studies of human placenta improve our understanding of how its function relates to disease risk. However, DNAm studies can be biased by cell type heterogeneity, so it is essential to control for this in order to reduce confounding and increase precision. Computational cell type deconvolution approaches have proven to be very useful for this purpose. For human placenta, however, an assessment of the performance of these estimation methods is still lacking. Here, we examine the performance of a newly available reference-based cell type estimation approach and compare it to an often-used reference-free cell type estimation approach, namely RefFreeEWAS, in placental genome-wide DNAm samples taken at birth and from chorionic villus biopsies early in pregnancy using three independent studies comprising over 1000 samples. We found both reference-free and reference-based estimated cell type proportions to have predictive value for DNAm, however, reference-based cell type estimation outperformed reference-free estimation for the majority of data sets. Reference-based cell type estimations mirror previous histological knowledge on changes in cell type proportions through gestation. Further, CpGs whose variation in DNAm was largely explained by reference-based estimated cell type proportions were in the proximity of genes that are highly tissue-specific for placenta. This was not the case for reference-free estimated cell type proportions. We provide a list of these CpGs as a resource to help researchers to interpret results of existing studies and improve future DNAm studies of human placenta.Peer reviewe

LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells

Leading cells require LIMK for matrix degradation and invadopodia formation during collective cell migration

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good