Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy.

One hundred and forty-two patients with Hodgkin's disease PS I or II were treated with total or subtotal nodal irradiation as part of a prospective randomized trial in the Danish National Hodgkin Study during the period 1971-83. They were followed till death or--at the time of this analysis--from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival. Other known prognostic factors such as number of involved regions, mediastinal size, pathological stage, systemic symptoms, and ESR were related to tumour burden and lost their prognostic significance in a multivariate analysis. The only other factors of independent significance were histologic subtype and, to a lesser extent, sex. Combining tumour burden and histologic subtype made it possible to single out a group of patients with a very poor disease free survival. These patients also had a poorer survival from Hodgkin's disease and thus clearly candidates for additional initial treatment

Evidence characterizing skills, competencies, and policies in advanced nursing practice in intensive care in Europe: a scoping review protocol

Scoping Review for protocol undertaken as part of the International Nursing Advanced Competency-based Training for Intensive Care (INACTIC) project. Co-funded by the Erasmus+ Programme of the European Union

The effect of maternal anthropometric characteristics and social factors on gestational age and birth weight in Sudanese newborn infants

<p>Abstract</p> <p>Background</p> <p>In Africa low birth weight (LBW) (<2500 g), is the strongest determinant of infant morbidity and mortality. The aim of this study was to quantify the effect of maternal anthropometry, education and socio-economic status on gestational age and birth weight.</p> <p>Methods</p> <p>In 1000 Sudanese mothers with singleton births, anthropometric measurements (weight, height, mid-arm circumference) and newborn birth weight were taken within 24 hours of delivery. Furthermore, maternal education and socio-economic status were recorded. The effect of these maternal variables on gestational age and birth weight was investigated by receiver operating characteristic (ROC) curves and by multivariate logistic regression analysis.</p> <p>Results</p> <p>Although maternal height was significantly correlated (p = 0.002) with gestational age, we did not find maternal characteristics of value in determining the risk for preterm birth. Birth order was the strongest determinant of birth weight compared to other maternal characteristics. The LBW rate of first born babies of 12.2% was nearly twice that of infants of multiparous mothers. Maternal age and all maternal anthropometric measurements were positively correlated (p < 0.001) with birth weight. A maternal height of <156 cm, a maternal weight of <66 kg, a maternal mid arm circumference of <27 cm and years of education of ≤ 8 years were found to increase the relative risk of LBW but this was statistically significant only in the case of maternal height. Maternal age and BMI had no statistically significant effect on determining the risk for LBW. The social class did not affect the birth weight, while the number of years of education was positively correlated with birth weight (p = 0.01). The LBW rate decreased from 9.2% for ≤ 8 years of education to 6.0% for >12 years of education.</p> <p>Conclusion</p> <p>Birth order and maternal height were found to be the most important maternal parameters which influences birth weight and the risk for LBW. The duration of maternal education and not social class was found to significantly affect the risk for LBW.</p

Genome-wide association study of school grades identifies genetic overlap between language ability, psychopathology and creativity

Cognitive functions of individuals with psychiatric disorders differ from that of the general population. Such cognitive differences often manifest early in life as differential school performance and have a strong genetic basis. Here we measured genetic predictors of school performance in 30,982 individuals in English, Danish and mathematics via a genome-wide association study (GWAS) and studied their relationship with risk for six major psychiatric disorders. When decomposing the school performance into math and language-specific performances, we observed phenotypically and genetically a strong negative correlation between math performance and risk for most psychiatric disorders. But language performance correlated positively with risk for certain disorders, especially schizophrenia, which we replicate in an independent sample (n = 4547). We also found that the genetic variants relating to increased risk for schizophrenia and better language performance are overrepresented in individuals involved in creative professions (n = 2953) compared to the general population (n = 164,622). The findings together suggest that language ability, creativity and psychopathology might stem from overlapping genetic roots.Peer reviewe

Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies

A Genetic Investigation of Sex Bias in the Prevalence of Attention-Deficit/Hyperactivity Disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that female individuals with ADHD may be at especially high risk for certain comorbid developmental conditions (i.e., autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score analysis did not support a higher burden of ADHD common risk variants in female cases (odds ratio [confidence interval] = 1.02 [0.98–1.06], p = .28). In contrast, epidemiological sibling analyses revealed that the siblings of female individuals with ADHD are at higher familial risk for ADHD than the siblings of affected male individuals (odds ratio [confidence interval] = 1.14 [1.11–1.18], p = 1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in female individuals with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g., 6 mm biopsy), which becomes grossly under-powered as tumor volume scales. Here, we demonstrate representative sequencing (Rep-Seq) as a new method to achieve unbiased tumor tissue sampling. Rep-Seq uses fixed residual tumor material, which is homogenized and subjected to next-generation sequencing. Analysis of intratumor tumor mutation burden (TMB) variability shows a high level of misclassification using current single-biopsy methods, with 20% of lung and 52% of bladder tumors having at least one biopsy with high TMB but low clonal TMB overall. Misclassification rates by contrast are reduced to 2% (lung) and 4% (bladder) when a more representative sampling methodology is used. Rep-Seq offers an improved sampling protocol for tumor profiling, with significant potential for improved clinical utility and more accurate deconvolution of clonal structure