Lifetime cardiovascular management of patients with previous Kawasaki disease.

Kawasaki disease (KD) is an inflammatory disorder of young children, associated with vasculitis of the coronary arteries with subsequent aneurysm formation in up to one-third of untreated patients. Those who develop aneurysms are at life-long risk of coronary thrombosis or the development of stenotic lesions, which may lead to myocardial ischaemia, infarction or death. The incidence of KD is increasing worldwide, and in more economically developed countries, KD is now the most common cause of acquired heart disease in children. However, many clinicians in the UK are unaware of the disorder and its long-term cardiac complications, potentially leading to late diagnosis, delayed treatment and poorer outcomes. Increasing numbers of patients who suffered KD in childhood are transitioning to the care of adult services where there is significantly less awareness and experience of the condition than in paediatric services. The aim of this document is to provide guidance on the long-term management of patients who have vascular complications of KD and guidance on the emergency management of acute coronary complications. Guidance on the management of acute KD is published elsewhere

Genome-wide association study for bone strength in laying hens

Bone fracture in egg laying hens is a growing welfare and economic concern in the industry. Although environmental conditions and management (especially nutrition) can exacerbate it, the primary cause of bone weakness and the resulting fractures is believed to have a genetic basis. To test this hypothesis, we performed a genome-wide association study to identify the loci associated with bone strength in laying hens. Genotype and phenotype data were obtained from 752 laying hens belonging to the same pure line population. These hens were genotyped for 580,961 SNPs, with 232,021 SNPs remaining after quality control. Each of the SNPs were tested for association with tibial breaking strength using the family-based score test for association. A total of 52 SNPs across chromosomes 1, 3, 8, and 16 were significantly associated with tibial breaking strength with the genome-wide significance threshold set as a corrected P value of 10e−5. Based on the local linkage disequilibrium around the significant SNPs, 5 distinct and novel QTLs were identified on chromosomes 1 (2 QTLs), 3 (1 QTL), 8 (1 QTL) and 16 (1 QTL). The strongest association was detected within the QTL region on chromosome 8, with the most significant SNP having a corrected P value of 4e−7. A number of candidate genes were identified within the QTL regions, including the BRD2 gene that is required for normal bone physiology. Bone-related pathways involving some of the genes were also identified including chloride channel activity, which regulates bone reabsorption, and intermediate filament organization, which plays a role in the regulation of bone mass. Our result supports previous studies that suggest that bone strength is highly regulated by genetics. It is therefore possible to reduce bone fractures in laying hens through genetic selection and ultimately improve hen welfare.</p

Genetics of tibia bone properties of crossbred commercial laying hens in different housing systems

Osteoporosis and bone fractures are a severe problem for the welfare of laying hens, with genetics and environment, such as housing system, each making substantial contributions to bone strength. In this work, we performed genetic analyses of bone strength, bone mineral density, and bone composition, as well as body weight, in 860 commercial crossbred laying hens from 2 different companies, kept in either furnished cages or floor pens. We compared bone traits between housing systems and crossbreds and performed a genome-wide association study of bone properties and body weight. As expected, the 2 housing systems produced a large difference in bone strength, with layers housed in floor pens having stronger bones. These differences were accompanied by differences in bone geometry, mineralization, and chemical composition. Genome scans either combining or independently analyzing the 2 housing systems revealed no genome-wide significant loci for bone breaking strength. We detected 3 loci for body weight that were shared between the housing systems on chromosomes 4, 6, and 27 (either genome-wide significant or suggestive) and these coincide with associations for bone length. In summary, we found substantial differences in bone strength, content, and composition between hens kept in floor pens and furnished cages that could be attributed to greater physical activity in pen housing. We found little evidence for large-effect loci for bone strength in commercial crossbred hens, consistent with a highly polygenic architecture for bone strength in the production environment. The lack of consistent genetic associations between housing systems in combination with the differences in bone phenotypes could be due to gene-by-environment interactions with housing system or a lack of power to detect shared associations for bone strength

No evidence that selection for egg production persistency causes loss of bone quality in laying hens

Background The physiological adaptations that have evolved for egg laying make hens susceptible to bone fractures and keel bone damage. In modern laying hen breeds, longer periods of egg laying could result in a greater risk of poor bone quality, and selection for increased egg production has frequently been stated to be a cause. However, the existing literature does not support this hypothesis. To test the hypothesis that egg production is associated with quality, breaking strength and density of bone, genetic correlations between these traits were estimated in White Leghorn and Rhode Island Red breeds. Genetic correlations of cortical and medullary bone material chemical properties with bone quality were also estimated, in order to identify methods to improve bone quality with appropriately targeted measurement of key traits. Results Estimates of heritability for bone quality traits were moderate (0.19-0.59) for both White Leghorn and Rhode Island Red breeds, except for the keel bone trait, which had a heritability estimate equal to zero. There was no evidence for genetic or phenotypic relationships between post-peak egg production and bone quality. In the White Leghorn breed, the estimate of the genetic correlation between pre-peak production/age at first egg and bone quality was significant and negative (- 0.7 to - 0.4). Estimates of heritability of thermogravimetric measurements of tibial medullary bone mineralisation were significant (0.18-0.41), as were estimates of their genetic correlations with tibia breaking strength and density (0.6-0.9). Conclusions The low genetic correlation of post-peak egg production with bone quality suggests that selection for increased persistency of egg production may not adversely affect bone quality. Onset of puberty and mineralisation of the medullary bone, which is a specialised adaptation for egg laying, were identified as important factors associated with the quality of the skeleton later during egg production. These are traits for which genetic, as well as environmental and management factors can positively impact the overall quality of the skeleton of laying hens

Genetics of tibia bone properties of crossbred commercial laying hens in different housing systems

Osteoporosis and bone fractures are a severe problem for the welfare of laying hens, with genetics and environment, such as housing system, each making substantial contributions to bone strength. In this work, we performed genetic analyses of bone strength, bone mineral density, and bone composition, as well as body weight, in 860 commercial crossbred laying hens from 2 different companies, kept in either furnished cages or floor pens. We compared bone traits between housing systems and crossbreds and performed a genome-wide association study of bone properties and body weight. As expected, the 2 housing systems produced a large difference in bone strength, with layers housed in floor pens having stronger bones. These differences were accompanied by differences in bone geometry, mineralization, and chemical composition. Genome scans either combining or independently analyzing the 2 housing systems revealed no genome-wide significant loci for bone breaking strength. We detected 3 loci for body weight that were shared between the housing systems on chromosomes 4, 6, and 27 (either genome-wide significant or suggestive) and these coincide with associations for bone length. In summary, we found substantial differences in bone strength, content, and composition between hens kept in floor pens and furnished cages that could be attributed to greater physical activity in pen housing. We found little evidence for large-effect loci for bone strength in commercial crossbred hens, consistent with a highly polygenic architecture for bone strength in the production environment. The lack of consistent genetic associations between housing systems in combination with the differences in bone phenotypes could be due to gene-by-environment interactions with housing system or a lack of power to detect shared associations for bone strength

Modelling direct and indirect water requirements of construction

Water consumed directly by the construction industry is known to be of little importance. However, water consumed in the manufacture of goods and services required by construction may be significant in the context of a building\u27s life cycle water requirements and the national water budget. This paper evaluates the significance of water embodied in the construction of individual buildings. To do this, an input-output-based hybrid embodied water analysis was undertaken on 17 Australian non-residential case studies. It was found that there is a considerable amount of water embodied in construction. The highest value was 20.1 kilolitres (kL)/m2 gross floor area (GFA), representing many times the enclosed volume of the building, and many years worth of operational water. The water required by the main construction process is minimal. However, the water embodied in building materials is considerable. These findings suggest that the selection of elements and materials has a great impact on a building\u27s embodied water. This research allows the construction industry to evaluate design and construction in broad environmental terms to select options that might be cost neutral or possibly cost positive while retaining their environmental integrity. The research suggests policies focused on operational water consumption alone are inadequate. <br /

An eQTL in the cystathionine beta synthase gene is linked to osteoporosis in laying hens

Background Skeletal damage is a challenge for laying hens because the physiological adaptations required for egg laying make them susceptible to osteoporosis. Previously, we showed that genetic factors explain 40% of the variation in end of lay bone quality and we detected a quantitative trait locus (QTL) of large effect on chicken chromosome 1. The aim of this study was to combine data from the commercial founder White Leghorn population and the F2 mapping population to fine-map this QTL and understand its function in terms of gene expression and physiology. Results Several single nucleotide polymorphisms on chromosome 1 between 104 and 110 Mb (galGal6) had highly significant associations with tibial breaking strength. The alternative genotypes of markers of large effect that flanked the region had tibial breaking strengths of 200.4 vs. 218.1 Newton (P < 0.002) and, in a subsequent founder generation, the higher breaking strength genotype was again associated with higher breaking strength. In a subsequent generation, cortical bone density and volume were increased in individuals with the better bone genotype but with significantly reduced medullary bone quality. The effects on cortical bone density were confirmed in a further generation and was accompanied by increased mineral maturity of the cortical bone as measured by infrared spectrometry and there was evidence of better collagen cross-linking in the cortical bone. Comparing the transcriptome of the tibia from individuals with good or poor bone quality genotypes indicated four differentially-expressed genes at the locus, one gene, cystathionine beta synthase (CBS), having a nine-fold higher expression in the genotype for low bone quality. The mechanism was cis-acting and although there was an amino-acid difference in the CBS protein between the genotypes, there was no difference in the activity of the enzyme. Plasma homocysteine concentration, the substrate of CBS, was higher in the poor bone quality genotype. Conclusions Validated markers that predict bone strength have been defined for selective breeding and a gene was identified that may suggest alternative ways to improve bone health in addition to genetic selection. The identification of how genetic variants affect different aspects of bone turnover shows potential for translational medicine