21,433 research outputs found
Effects of ignoring inbreeding in model-based accuracy for BLUP and SSGBLUP
[EN] Model-based accuracy, defined as the theoretical correlation between true and estimated breeding value, can be obtained for each individual as a function of its prediction error variance (PEV) and inbreeding coefficient F, in BLUP, GBLUP and SSGBLUP genetic evaluations. However, for computational convenience, inbreeding is often ignored in two places. First, in the computation of reliability = 1-PEV/(1 + F). Second, in the set-up, using Henderson's rules, of the inverse of the pedigree-based relationship matrix A. Both approximations have an effect in the computation of model-based accuracy and result in wrong values. In this work, first we present a reminder of the theory and extend it to SSGBLUP. Second, we quantify the error of ignoring inbreeding with real data in three scenarios: BLUP evaluation and SSGBLUP in Uruguayan dairy cattle, and BLUP evaluations in a line of rabbit closed for >40 generations with steady increase of inbreeding up to an average of 0.30. We show that ignoring inbreeding in the set-up of the A-inverse is equivalent to assume that non-inbred animals are actually inbred. This results in an increase of apparent PEV that is negligible for dairy cattle but considerable for rabbit. Ignoring inbreeding in reliability = 1-PEV/(1 + F) leads to underestimation of reliability for BLUP evaluations, and this underestimation is very large for rabbit. For SSGBLUP in dairy cattle, it leads to both underestimation and overestimation of reliability, both for genotyped and non-genotyped animals. We strongly recommend to include inbreeding both in the set-up of A-inverse and in the computation of reliability from PEVs.FEDER; INRA; Universidad Nacional de Lomas de Zamora; European Unions' Horizon 2020 Research & Innovation Programme, Grant/Award Number: No772787Aguilar, I.; Fernandez, EN.; Blasco Mateu, A.; Ravagnolo, O.; Legarra, A. (2020). Effects of ignoring inbreeding in model-based accuracy for BLUP and SSGBLUP. Journal of Animal Breeding and Genetics. 137(4):356-364. https://doi.org/10.1111/jbg.12470S3563641374Bijma, P. (2012). Accuracies of estimated breeding values from ordinary genetic evaluations do not reflect the correlation between true and estimated breeding values in selected populations. Journal of Animal Breeding and Genetics, 129(5), 345-358. doi:10.1111/j.1439-0388.2012.00991.xChristensen, O. F., Madsen, P., Nielsen, B., Ostersen, T., & Su, G. (2012). Single-step methods for genomic evaluation in pigs. Animal, 6(10), 1565-1571. doi:10.1017/s1751731112000742Colleau, J.-J., Palhière, I., Rodríguez-Ramilo, S. T., & Legarra, A. (2017). A fast indirect method to compute functions of genomic relationships concerning genotyped and ungenotyped individuals, for diversity management. Genetics Selection Evolution, 49(1). doi:10.1186/s12711-017-0363-9Edel, C., Pimentel, E. C. G., Erbe, M., Emmerling, R., & Götz, K.-U. (2019). Short communication: Calculating analytical reliabilities for single-step predictions. Journal of Dairy Science, 102(4), 3259-3265. doi:10.3168/jds.2018-15707Fernández, E. N., Sánchez, J. P., Martínez, R., Legarra, A., & Baselga, M. (2017). Role of inbreeding depression, non-inbred dominance deviations and random year-season effect in genetic trends for prolificacy in closed rabbit lines. Journal of Animal Breeding and Genetics, 134(6), 441-452. doi:10.1111/jbg.12284Golden, B. L., Brinks, J. S., & Bourdon, R. M. (1991). A performance programmed method for computing inbreeding coefficients from large data sets for use in mixed-model analyses. Journal of Animal Science, 69(9), 3564-3573. doi:10.2527/1991.6993564xGroeneveld E. Kovac M. &Wang T.(1990).PEST a general purpose BLUP package for multivariate prediction and estimation. Proceedings of the 4th World Congress on Genetics Applied to Livestock Production Edinburgh 13 488–491.Henderson, C. R. (1975). Best Linear Unbiased Estimation and Prediction under a Selection Model. Biometrics, 31(2), 423. doi:10.2307/2529430Henderson, C. R. (1976). A Simple Method for Computing the Inverse of a Numerator Relationship Matrix Used in Prediction of Breeding Values. Biometrics, 32(1), 69. doi:10.2307/2529339Legarra, A., Aguilar, I., & Colleau, J. J. (2020). Short communication: Methods to compute genomic inbreeding for ungenotyped individuals. Journal of Dairy Science, 103(4), 3363-3367. doi:10.3168/jds.2019-17750Legarra, A., Aguilar, I., & Misztal, I. (2009). A relationship matrix including full pedigree and genomic information. Journal of Dairy Science, 92(9), 4656-4663. doi:10.3168/jds.2009-2061Legarra A. Lourenco D. A. L. &Vitezica Z. G.(2018).Bases for genomic prediction. Retrieved fromhttp://genoweb.toulouse.inra.fr/~alegarra/Masuda, Y., Aguilar, I., Tsuruta, S., & Misztal, I. (2015). Technical note: Acceleration of sparse operations for average-information REML analyses with supernodal methods and sparse-storage refinements1,2. Journal of Animal Science, 93(10), 4670-4674. doi:10.2527/jas.2015-9395Matilainen, K., Strandén, I., Aamand, G. P., & Mäntysaari, E. A. (2018). Single step genomic evaluation for female fertility in Nordic Red dairy cattle. Journal of Animal Breeding and Genetics, 135(5), 337-348. doi:10.1111/jbg.12353Mehrabani-Yeganeh, H., Gibson, J. P., & Schaeffer, L. R. (2000). Including coefficients of inbreeding in BLUP evaluation and its effect on response to selection. Journal of Animal Breeding and Genetics, 117(3), 145-151. doi:10.1046/j.1439-0388.2000.00241.xMeyer, K. (2007). WOMBAT—A tool for mixed model analyses in quantitative genetics by restricted maximum likelihood (REML). Journal of Zhejiang University SCIENCE B, 8(11), 815-821. doi:10.1631/jzus.2007.b0815Misztal, I., & Wiggans, G. R. (1988). Approximation of Prediction Error Variance in Large-Scale Animal Models. Journal of Dairy Science, 71, 27-32. doi:10.1016/s0022-0302(88)79976-2Mrode, R. A., & Thompson, R. (Eds.). (2005). Linear models for the prediction of animal breeding values. doi:10.1079/9780851990002.0000Pryce, J. E., Gonzalez-Recio, O., Nieuwhof, G., Wales, W. J., Coffey, M. P., Hayes, B. J., & Goddard, M. E. (2015). Hot topic: Definition and implementation of a breeding value for feed efficiency in dairy cows. Journal of Dairy Science, 98(10), 7340-7350. doi:10.3168/jds.2015-9621Sargolzaei, M., Chesnais, J. P., & Schenkel, F. S. (2014). A new approach for efficient genotype imputation using information from relatives. BMC Genomics, 15(1), 478. doi:10.1186/1471-2164-15-478Strandén, I., Matilainen, K., Aamand, G. P., & Mäntysaari, E. A. (2017). Solving efficiently large single-step genomic best linear unbiased prediction models. Journal of Animal Breeding and Genetics, 134(3), 264-274. doi:10.1111/jbg.12257Ten Napel J. Vandenplas J. Lidauer M. Stranden I. Taskinen M. Mäntysaari E. Veerkamp R. F.(2017).MiXBLUP user‐friendly software for large genetic evaluation systems–Manual V2. Retrived from:https://www.mixblup.eu/documents/Manual%20MiXBLUP%202.1_June%202017_V2.pdfTier B. Schneeberger M. Hammond K. &Fuchs W. C.(1991).Determining the accuracy of estimated breeding values in multiple trait animal models. Proceedings of the 9th AAABG Conference 239–242Van Vleck, L. D. (1993). Variance of prediction error with mixed model equations when relationships are ignored. Theoretical and Applied Genetics, 85(5), 545-549. doi:10.1007/bf00220912VanRaden, P. M. (2008). Efficient Methods to Compute Genomic Predictions. Journal of Dairy Science, 91(11), 4414-4423. doi:10.3168/jds.2007-0980Xiang, T., Christensen, O. F., & Legarra, A. (2017). Technical note: Genomic evaluation for crossbred performance in a single-step approach with metafounders1. Journal of Animal Science, 95(4), 1472-1480. doi:10.2527/jas.2016.115
Why do some asthma patients respond poorly to glucocorticoid therapy?
Glucocorticosteroids are the first-line therapy for controlling airway inflammation in asthma. They bind intracellular glucocorticoid receptors to trigger increased expression of anti-inflammatory genes and suppression of pro-inflammatory gene activation in asthmatic airways. In the majority of asthma patients, inhaled glucocorticoids are clinically efficacious, improving lung function and preventing exacerbations. However, 5–10 % of the asthmatic population respond poorly to high dose inhaled and then systemic glucocorticoids. These patients form a category of severe asthma associated with poor quality of life, increased morbidity and mortality, and constitutes a major societal and health care burden. Inadequate therapeutic responses to glucocorticoid treatment is also reported in other inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease; however, asthma represents the most studied steroid-refractory disease. Several cellular and molecular events underlying glucocorticoid resistance in asthma have been identified involving abnormalities of glucocorticoid receptor signaling pathways. These events have been strongly related to immunological dysregulation, genetic, and environmental factors such as cigarette smoking or respiratory infections. A better understanding of the multiple mechanisms associated with glucocorticoid insensitivity in asthma phenotypes could improve quality of life for people with asthma but would also provide transferrable knowledge for other inflammatory diseases. In this review, we provide an update on the molecular mechanisms behind steroid-refractory asthma. Additionally, we discuss some therapeutic options for treating those asthmatic patients who respond poorly to glucocorticoid therapy
Fusion-Fission of 16O+197Au at Sub-Barrier Energies
The recent discovery of heavy-ion fusion hindrance at far sub-barrier
energies has focused much attention on both experimental and theoretical
studies of this phenomenon. Most of the experimental evidence comes from
medium-heavy systems such as Ni+Ni to Zr+Zr, for which the compound system
decays primarily by charged-particle evaporation. In order to study heavier
systems, it is, however, necessary to measure also the fraction of the decay
that goes into fission fragments. In the present work we have, therefore,
measured the fission cross section of 16O+197Au down to unprecedented far
sub-barrier energies using a large position sensitive PPAC placed at backward
angles. The preliminary cross sections will be discussed and compared to
earlier studies at near-barrier energies. No conclusive evidence for
sub-barrier hindrance was found, probably because the measurements were not
extended to sufficiently low energies.Comment: Fusion06 - Intl. Conf. on Reaction Mechanisms and Nuclear Structure
at the Coulomb Barrier, San Servolo, Venezia, Italy, March 19-223, 2006 5
pages, 4 figure
Variability of Pennsylvanian-Permian Carbonate Associations and Implications for NW Pangea Palaeogeography, East-Central British Columbia, Canada
Different stages of Pennsylvanian-Permian carbonate sedimentation in east-central British Columbia record a complex history of changing environments influenced by evolving palaeogeography and climate. Newly recognized tectonically controlled features affected the distribution and variability of carbonate associations, providing new interpretations for this portion of the west coast of Pangea. Both a heterozoan (cool water) and photozoan (warm-water) association were identified on either side of a palaeogeographic high here informally termed “Tipinahokan Peninsula”. Cool water carbonates were located outboard, or to the west of this high, an area influenced by upwelling waters. Inboard of this high, a warm, protected sea developed, here termed “Kisosowin Sea”. This configuration and palaeolatitude is similar to that of Baja California, Mexico and the Sea of Cortéz, providing a good modern analog for these deposits where warm water carbonates grow at latitudes otherwise dominated by cool water deposits. The warm sea provided a place for a photozoan association to develop during the Permian when the low latitude NW coast of Pangea was dominated by cool water carbonates
Quantum turbulence at finite temperature: the two-fluids cascade
To model isotropic homogeneous quantum turbulence in superfluid helium, we
have performed Direct Numerical Simulations (DNS) of two fluids (the normal
fluid and the superfluid) coupled by mutual friction. We have found evidence of
strong locking of superfluid and normal fluid along the turbulent cascade, from
the large scale structures where only one fluid is forced down to the vorticity
structures at small scales. We have determined the residual slip velocity
between the two fluids, and, for each fluid, the relative balance of inertial,
viscous and friction forces along the scales. Our calculations show that the
classical relation between energy injection and dissipation scale is not valid
in quantum turbulence, but we have been able to derive a temperature--dependent
superfluid analogous relation. Finally, we discuss our DNS results in terms of
the current understanding of quantum turbulence, including the value of the
effective kinematic viscosity
Flow Induced Organization and Memory of a Vortex Lattice
We report on experiments probing the evolution of a vortex state in response
to a driving current in 2H-NbSe crystals. By following the vortex motion
with fast transport measurements we find that the current enables the system to
reorganize and access new configurations. During this process the system
exhibits a long-term memory: if the current is turned off the vortices freeze
in place remembering their prior motion. When the current is restored the
motion resumes where it stopped. The experiments provide evidence for a
dynamically driven structural change of the vortex lattice and a corresponding
dynamic phase diagram that contains a previously unknown regime where the
critical current can be either or by applying an
appropriate driving current.Comment: 5 pages, 4figure
Public knowledge, attitudes, social distance and reported contact regarding people with mental illness 2009-2015
Objective To investigate whether public knowledge, attitudes, desire for social distance and reported contact in relation to people with mental health problems have improved in England during the Time to Change (TTC) programme to reduce stigma and discrimination 2009–2015. Methods Using data from an annual face-to-face survey of a nationally representative sample of adults, we analysed longitudinal trends in the outcomes with regression modelling using standardised scores of the measures overall and by age and gender subgroups. Results There were improvements in all outcomes. The improvement for knowledge was 0.17 standard deviation units in 2015 compared to 2009 (95% CI 0.10, 0.23); for attitudes 0.20 standard deviation units (95% CI 0.14, 0.27) and for social distance 0.17 standard deviation units (95% CI 0.11, 0.24). Survey year for 2015 vs. 2009 was associated with a higher likelihood of reported contact (OR 1.32, 95% CI 1.13, 1.53). Statistically significant interactions between year and age suggest the campaign had more impact on the attitudes of the target age group (25–45) than those aged over 65 or under 25. Women's reported contact with people with mental health problems increased more than did men's. Conclusion The results provide support for the effectiveness of TTC
Engagement in activities and occupations by people who have experienced psychosis : a metasynthesis of lived experience
Water incident related hospital activity across England between 1997/8 and 2003/4: a retrospective descriptive study
Every year in the United Kingdom, 10,000 people will die from accidental injury and the treatment of these injuries will cost the NHS £2 billion and the consequences of injuries received at home cost society a further £25 billion [1]. Non-fatal injuries result in 720,000 people being admitted to hospital a year and more than six million visits to accident and emergency departments each year [2]. Drowning is the second leading cause of unintentional injury mortality globally behind road traffic injuries. It is estimated that a total of 409, 272 people drown each year [3]. This equates to a global incident rate of 7.4 deaths per 100, 000 people worldwide and relates to a further 1.3 million Disability Adjusted Life Years (DALYs) which are lost as a result of premature death or disability [4].
'Death' represents only the tip of the injury "iceberg" [5]. For every life lost from an injury, many more people are admitted to hospital, attend accident and emergency departments or general practitioners, are rescued by search and rescue organisations or resolve the situation themselves. It is estimated that 1.3 million people are injured as a result of near drowning episodes globally and that many more hundreds of thousands of people are affected through incidents and near misses but there are no accurate data [4].
The United Kingdom has reported a variable drowning fatality rate, the injury chart book reports a rate of 1.0 – 1.5 per 100,000 [6] and other studies suggest a rate as low as 0.5 per 100, 000 population [7] for accidental drowning and submersion, based on the International Classification of Disease 10 code W65 – 74, however, the problem is even greater and these Global Burden of Disease (GDB) figures are an underestimate of all drowning deaths, since they exclude drownings due to cataclysms (floods), water related transport accidents, assaults and suicide [3]. A recent study in Scotland highlighted this underestimation in drowning fatality data and found that the overall death rate due to drownings in Scotland 3.26 per 100,000 [8]. Even though drowning fatality rates in the United Kingdom vary, little is known about the people who are admitted to hospital after an incident either in or on water. This paper seeks to address this gap in our knowledge through the investigation of the data available on those admitted to NHS hospitals in England
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