Factors associated with serum CA19-9 levels among healthy children: a cross-sectional study

Abstract\ud \ud \ud \ud Background\ud CA19-9 is a tumor marker mainly used for biliary tract, pancreas and colorectum. Since the marker applies usually for adults, the normal range of serum CA19-9 among children has been rarely reported. This is the first study reporting the distribution of serum CA19-9 levels among cancer-free children as well as their parents, taking into account the Lewis and secretor gene polymorphism and physical growth.\ud \ud \ud \ud Methods\ud Study subjects were 972 apparently healthy Japanese Brazilians including 476 children aged from 1 to 19 years.\ud \ud \ud \ud Results\ud The comparisons in five-year age groups demonstrated that the mean values of serum CA19-9 was lower in the boys than in the girls, and higher in younger age groups; 22.5 U/ml for 1–4 year-old (n=13), 17.4 U/ml for 5–9 year-old (n=36), 15.5 U/ml for 10–14 year-old (n=96) and 10.2 U/ml for 15–19 year-old (n=74) in boys, and 25.3 U/ml (n=11), 27.1 U/ml (n=50), 17.7 U/ml (n=105) and 13.5 U/ml (n=59) in girls, respectively. The difference in those geometric means was statistically significant among four age groups (p=0.006, ANOVA adjusted for sex). After Lewis and secretor genotypes, which are definitive factors of serum CA19-9, were taken into account, geometric mean of serum CA19-9 was associated with any of BMI (p<0.001), height (p<0.001) and weight (p<0.001) among children excluding those with le/le genotype. The associations were still significant when age was adjusted.\ud \ud \ud \ud Conclusions\ud Serum CA19-9 values were higher among children than among adults, and influenced by sex, height, weight, and BMI even after the adjustment for age as well as Le and Se genotypes.This study was supported in part by a Grant-in-Aid for Scientific Research on Special Priority Areas of Cancer from the Japanese Ministry of Education, Culture, Sports, Science, and Technology. We are grateful to Ms. Yoko Mitsuda and Ms. Keiko Shibata for their technical assistance

Simulation techniques for cosmological simulations

Modern cosmological observations allow us to study in great detail the evolution and history of the large scale structure hierarchy. The fundamental problem of accurate constraints on the cosmological parameters, within a given cosmological model, requires precise modelling of the observed structure. In this paper we briefly review the current most effective techniques of large scale structure simulations, emphasising both their advantages and shortcomings. Starting with basics of the direct N-body simulations appropriate to modelling cold dark matter evolution, we then discuss the direct-sum technique GRAPE, particle-mesh (PM) and hybrid methods, combining the PM and the tree algorithms. Simulations of baryonic matter in the Universe often use hydrodynamic codes based on both particle methods that discretise mass, and grid-based methods. We briefly describe Eulerian grid methods, and also some variants of Lagrangian smoothed particle hydrodynamics (SPH) methods.Comment: 42 pages, 16 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 12; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke

Mutagenesis and Functional Studies with Succinate Dehydrogenase Inhibitors in the Wheat Pathogen Mycosphaerella graminicola

A range of novel carboxamide fungicides, inhibitors of the succinate dehydrogenase enzyme (SDH, EC 1.3.5.1) is currently being introduced to the crop protection market. The aim of this study was to explore the impact of structurally distinct carboxamides on target site resistance development and to assess possible impact on fitness

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P = 9.2 x 10(-20)), ER-negative BC (P = 1.1 x 10(-13)), BRCA1-associated BC (P = 7.7 x 10(-16)) and triple negative BC (P-diff = 2 x 10(-5)). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P = 2 x 10(-3)) and ABHD8 (PPeer reviewe

Improving the Pipeline for Developing and Testing Pharmacological Treatments in Pregnancy

In a Perspective, Lucy Chappell and Anna David discuss ways to develop and test pharmacological treatments in pregnancy

Factors associated with serum CA19-9 levels among healthy children: a cross-sectional study

BACKGROUND: CA19-9 is a tumor marker mainly used for biliary tract, pancreas and colorectum. Since the marker applies usually for adults, the normal range of serum CA19-9 among children has been rarely reported. This is the first study reporting the distribution of serum CA19-9 levels among cancer-free children as well as their parents, taking into account the Lewis and secretor gene polymorphism and physical growth. METHODS: Study subjects were 972 apparently healthy Japanese Brazilians including 476 children aged from 1 to 19 years. RESULTS: The comparisons in five-year age groups demonstrated that the mean values of serum CA19-9 was lower in the boys than in the girls, and higher in younger age groups; 22.5 U/ml for 1–4 year-old (n=13), 17.4 U/ml for 5–9 year-old (n=36), 15.5 U/ml for 10–14 year-old (n=96) and 10.2 U/ml for 15–19 year-old (n=74) in boys, and 25.3 U/ml (n=11), 27.1 U/ml (n=50), 17.7 U/ml (n=105) and 13.5 U/ml (n=59) in girls, respectively. The difference in those geometric means was statistically significant among four age groups (p=0.006, ANOVA adjusted for sex). After Lewis and secretor genotypes, which are definitive factors of serum CA19-9, were taken into account, geometric mean of serum CA19-9 was associated with any of BMI (p<0.001), height (p<0.001) and weight (p<0.001) among children excluding those with le/le genotype. The associations were still significant when age was adjusted. CONCLUSIONS: Serum CA19-9 values were higher among children than among adults, and influenced by sex, height, weight, and BMI even after the adjustment for age as well as Le and Se genotypes

Factors associated with serum CA19-9 levels among healthy children: a cross-sectional study

Abstract Background CA19-9 is a tumor marker mainly used for biliary tract, pancreas and colorectum. Since the marker applies usually for adults, the normal range of serum CA19-9 among children has been rarely reported. This is the first study reporting the distribution of serum CA19-9 levels among cancer-free children as well as their parents, taking into account the Lewis and secretor gene polymorphism and physical growth. Methods Study subjects were 972 apparently healthy Japanese Brazilians including 476 children aged from 1 to 19 years. Results The comparisons in five-year age groups demonstrated that the mean values of serum CA19-9 was lower in the boys than in the girls, and higher in younger age groups; 22.5 U/ml for 1–4 year-old (n=13), 17.4 U/ml for 5–9 year-old (n=36), 15.5 U/ml for 10–14 year-old (n=96) and 10.2 U/ml for 15–19 year-old (n=74) in boys, and 25.3 U/ml (n=11), 27.1 U/ml (n=50), 17.7 U/ml (n=105) and 13.5 U/ml (n=59) in girls, respectively. The difference in those geometric means was statistically significant among four age groups (p=0.006, ANOVA adjusted for sex). After Lewis and secretor genotypes, which are definitive factors of serum CA19-9, were taken into account, geometric mean of serum CA19-9 was associated with any of BMI (p<0.001), height (p<0.001) and weight (p<0.001) among children excluding those with le/le genotype. The associations were still significant when age was adjusted. Conclusions Serum CA19-9 values were higher among children than among adults, and influenced by sex, height, weight, and BMI even after the adjustment for age as well as Le and Se genotypes