FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1

We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics

Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes

This is the final version. Available from BMC via the DOI in this record. Availability of data and materials GWAS summary data will be deposited at the EGG website (https://egg-consortium.org/) at publication. Individual study data are available from the corresponding author on reasonable request.Abstract Background: Head circumference is associated with intelligence and tracks from childhood into adulthood. Methods: We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. Results: Seven loci reached genome-wide signifcance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. Conclusions: The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.Wellcome TrustSimons FoundationWellcome TrustMRC & WTUniversity of Southern DenmarkMax Planck core societ

Gene expression profiles from discordant monozygotic twins suggest that molecular pathways are shared among multiple systemic autoimmune diseases

INTRODUCTION: The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders. METHODS: RNA microarray analyses (Agilent Human 1A(V2) 20K oligo arrays) were used to quantify gene expression in peripheral blood cells from 20 monozygotic (MZ) twin pairs discordant for SAID. Six affected probands with systemic lupus erythematosus (SLE), six with rheumatoid arthritis (RA), eight with idiopathic inflammatory myopathies (IIM), and their same-gendered unaffected twins, were enrolled. Comparisons were made between discordant twin pairs and these were also each compared to 40 unrelated control subjects (matched 2:1 to each twin by age, gender and ethnicity) using statistical and molecular pathway analyses. Relative quantitative PCR was used to verify independently measures of differential gene expression assessed by microarray analysis. RESULTS: Probands and unrelated, matched controls differed significantly in gene expression for 104 probes corresponding to 92 identifiable genes (multiple-comparison adjusted P values \u3c 0.1). Differentially expressed genes involved several overlapping pathways including immune responses (16%), signaling pathways (24%), transcription/translation regulators (26%), and metabolic functions (15%). Interferon (IFN)-response genes (IFI27, OASF, PLSCR1, EIF2AK2, TNFAIP6, and TNFSF10) were up-regulated in probands compared to unrelated controls. Many of the abnormally expressed genes played regulatory roles in multiple cellular pathways. We did not detect any probes expressed differentially in comparisons among the three SAID phenotypes. Similarly, we found no significant differences in gene expression when comparing probands to unaffected twins or unaffected twins to unrelated controls. Gene expression levels for unaffected twins appeared intermediate between that of probands and unrelated controls for 6535 probes (32% of the total probes) as would be expected by chance. By contrast, in unaffected twins intermediate ordering was observed for 84 of the 104 probes (81%) whose expression differed significantly between probands and unrelated controls. CONCLUSIONS: Alterations in expression of a limited number of genes may influence the dysregulation of numerous, integrated immune response, cell signaling and regulatory pathways that are common to a number of SAID. Gene expression profiles in peripheral blood suggest that for genes in these critical pathways, unaffected twins may be in a transitional or intermediate state of immune dysregulation between twins with SAID and unrelated controls, perhaps predisposing them to the development of SAID given the necessary and sufficient environmental exposures

Gravidez não planejada no extremo Sul do Brasil: prevalência e fatores associados

The purpose of this study was to investigate factors associated with unplanned pregnancies in Rio Grande, Rio Grande do Sul State, Brazil. A standardized questionnaire was applied in 2007 to all pregnant women in the city, including demographic characteristics, childbearing history, socioeconomic status, and prenatal and childbirth care. The study used Poisson multivariate regression analysis with robust adjustment of variance. Among the 2,557 women included in the study, 65% had not planned the current pregnancy. After adjusting for confounders, the following variables were significantly associated with unplanned pregnancy: black or mixed race, age < 20 years, single marital status, low family income, household crowding, smoking, and multiparity. Previous abortion was a protective factor against unplanned pregnancy. The high unplanned pregnancy rate, especially among women with increased risk of complications during pregnancy and childbirth, highlights the need to target healthcare programs for this group.Este estudo teve por objetivo identificar fatores associados à ocorrência de gravidez não planejada em Rio Grande, Rio Grande do Sul, Brasil. Em 2007, aplicouse questionário padronizado a todas as parturientes residentes neste município, investigando sobre características demográficas e reprodutivas maternas, nível socioeconômico da família e assistência recebida na gestação e parto. A análise ajustada foi realizada utilizando-se regressão de Poisson com ajuste robusto da variância. Dentre as 2.557 gestantes incluídas no estudo, 65% não planejaram a gravidez. Após ajuste para confundimento, as seguintes variáveis mostraram-se significativamente associadas à gravidez não planejada: cor da pele parda/preta, idade inferior a 20 anos, sem companheiro, baixa renda familiar, aglomeração familiar, tabagismo e mais de um parto. Abortamento prévio mostrou-se protetor para a gravidez não planejada. A elevada ocorrência de gravidez não planejada, sobretudo entre aquelas com maiores riscos de complicações durante a gestação e o parto, indica a necessidade de se estabelecerem programas de saúde à atenção desta população