Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis

Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 × 10-27) and subpleural ILAs (P = 1.6 × 10-29). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 × 10-8) and FCF1P3 (rs73199442, P = 4.8 × 10-8) with ILAs, and near HTRE1 (rs7744971, P = 4.2 × 10-8) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones

Whole-farm profit and the optimum maternal liveweight profile of Merino ewe flocks lambing in winter and spring are influenced by the effects of ewe nutrition on the progeny's survival and lifetime wool production

Profitability of sheep production systems in southern Australia is optimised at a stocking rate that provides adequate nutrition for breeding ewes and enables efficient utilisation of grown pasture and supplements. In this paper we used bio-economic modelling to develop optimum liveweight1 profiles for spring-lambing Merino ewes in different environments. The modelling included the impacts of the ewe liveweight profile on the production of the ewe and the survival and lifetime wool production of her progeny. Fifteen ewe liveweight profiles were analysed for each region to determine the profitability of varying ewe liveweight at joining, varying rate of loss of liveweight after joining and the rate of gain in liveweight from the minimum to lambing. The analyses support the hypotheses that whole-farm profitability is sensitive to the liveweight profile of Merino ewe flocks and that there is a liveweight profile that maximises whole-farm profit. The variation between the most and least profitable ewe liveweight profile was $690002 per farm ($14.30/ewe) for south-west Victoria, $51000 per farm ($8.70/ewe) for Great Southern Western Australia and $33300 per farm ($9.70/ewe) for southern New South Wales. The changes in profit were due to differences in costs of feeding to achieve the ewe liveweight profile and its influence on the production of both the ewes and their progeny. Failure to include the impacts of liveweight profile on progeny survival and lifetime wool production incorrectly identifies the optimum ewe liveweight profile and provided inaccurate estimates of profitability. The optimum liveweight profiles for ewes lambing in spring were similar for all three regions and insensitive to changing commodity prices, pasture productivity and management. The optimum profile was to join ewes at ∼90% of the standard reference weight of the genotype, lose a small amount of weight after joining and regain weight in late pregnancy to return to the joining weight by lambing. Regaining the liveweight lost in early pregnancy by lambing is the most important target to achieve. The cost per farm of missing this liveweight target by 1 kg was $13000 ($2.60/ewe) for south-west Victoria, $8900 ($1.45/ewe) for Great Southern Western Australia and $5500 ($1.65/ewe) for southern New South Wales. By contrast, the cost per farm of missing the joining target by 1 kg was $5500 for south-west Victoria and less than$2000 across the other two regions. Whole-farm profit increased with increasing stocking rate up to an optimum and regardless of stocking rate there is an additional opportunity to increase whole-farm profit by up to 15% by managing ewes to achieve the optimum liveweight profile. This indicates that the optimum liveweight profile should be achieved by increasing the level of grain feeding and altering the timing of utilising the farm feed resources rather than manipulating stocking rate

Economic value of pregnancy scanning and optimum nutritional management of dry, single - and twin-bearing Merino ewes

The nutritional requirements of twin-bearing ewes are ∼25% greater than those of ewes with single fetuses during late pregnancy and nearly twice those of non-pregnant ewes. Underfeeding ewes, resulting in liveweight loss during late pregnancy, can have adverse effects on the production and survival of both the lamb and the ewe, and improving twin-lamb survival is critical to improving the overall reproductive performance of the National Merino flock. Scanning for pregnancy status and litter size allows for more precise management of the nutrition of the ewe flock according to the different nutritional needs of dry, single- and twin-bearing ewes. In the present paper, we tested the hypothesis that it is profitable to identify pregnancy status and litter size, and the optimum nutrition profiles are different for dry, single- and twin-bearing ewes. We tested this by examining a range of nutrition strategies for flocks where only the dry ewes were identified, or for flocks where the single- and twin-bearing ewes were identified. A MIDAS model set up for the Hamilton region in south-western Victoria was used for this analysis as it represents the whole flock and it includes a powerful feed-budgeting module that optimises animal and pasture management across the whole farm. The survival and production of the single- and twin-born progeny was adjusted on the basis of the liveweight profile of the single- and twin-bearing ewes. Our hypothesis was supported and profitability was increased by approximately AU$4630/farm or AU$0.80/ewe, by scanning ewes for pregnancy status and litter size, and the optimum liveweight profiles were different for dry, single- and twin-bearing ewes. The majority of the increase in profit was due to identifying litter size and being able to differentially manage the single- and twin-bearing ewes. When ewes are scanned for pregnancy status and litter size, the most profitable combination of profiles involves all ewes losing 4 kg in early pregnancy and single-bearing ewes regaining the 4 kg to lamb at their standard reference weight, twin-bearing ewes gaining 8 kg to lamb above their standard reference weight and dry ewes losing a further 4 kg to be 8 kg lighter than their standard reference weight at lambing time

Trattato dei Disturbi di Personalità. A cura di John M. Oldham, Andrew E. Skodol, Donna S. Bender

Risultato del lavoro di più di 70 autori, riuniti sotto la prestigiosa sigla dell’American Psychiatric Publishing, questo è il trattato sui disturbi di personalità più completo e aggiornato. Organizzato in sei parti – concetti di base, valutazione clinica, eziologia, trattamento, problemi e popolazioni particolari, nuovi sviluppi e indicazioni future – prende in considerazione le teorie più recenti e i risultati della ricerca ed è al tempo stesso una guida clinica e un testo di riferimento non solo per psichiatri, psicologi e medici ma anche per accademici e studenti

An international comparison of power meter calibrations conducted in 1987

NRC publication: Ye

An international comparison of power meter calibrations conducted in 1987

NRC publication: Ye