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BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.
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Cesárea , Neoplasias , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Reino Unido/epidemiologia , Nascido VivoRESUMO
EMBL-EBI provides a broad range of training in data-driven life sciences. To improve awareness and access to training course listings and to make digital learning materials findable and simple to use, the EMBL-EBI Training website, www.ebi.ac.uk/training, was redesigned and restructured. To provide a framework for the redesign of the website, the FAIR (findable, accessible, interoperable, reusable) principles were applied to both the listings of live training courses and the presentation of on-demand training content. Each of the FAIR principles guided decisions on the choice of technology used to develop the website, including the details provided about training and the way in which training was presented. Since its release the openly accessible website has been accessed by an average of 58,492 users a month. There have also been over 12,000 unique users creating accounts since the functionality was added in March 2022, allowing these users to track their learning and record completion of training. Development of the website was completed using the Agile Scrum project management methodology and a focus on user experience. This framework continues to be used now that the website is live for the maintenance and improvement of the website, as feedback continues to be collected and further ways to make training FAIR are identified. Here, we describe the process of making EMBL-EBI's training FAIR through the development of a new website and our experience of implementing Agile Scrum.
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A deterministic bio-economic model was developed to estimate economic weights for genetic improvement of lactation milk yield, fat yield, age at first calving, calving interval, mature weight and survival under low, medium and high production systems in the Tropics. Input parameters were obtained from dairy production systems in Kenya which has a tropical environment. The highest proportion of revenue is from the sale of milk followed by sale of heifers, cull cows and sale of male calves under all production systems. On the other hand, feed cost is the most important production cost followed by labour, marketing, reproduction and health costs, respectively. Economic values for the six traits were derived from a profit equation using revenue and production costs per cow per year. The economic values were then discounted using diffusion coefficients which account for differences between traits in the time when the improvement is expressed. Economic weights were robust to changes in input and output prices, changes in feeding strategies, and changes in milk and surplus heifer marketing strategies. Genetic standard deviations were multiplied by economic values to standardise the economic value of traits and to compare their potential for economic response. When expressed as proportion of their sum, these relative economic weights under the low, medium and high production systems for lactation milk yield were 51.36, 59.79 and 63.98%; for fat yield 4.50, 10.69 and 9.05%; for age at first calving 3.16, 2.66 and 0.55%; for calving interval 33.59, 19.88 and 20.05%; for mature weight 1.55, 1.34 and 1.19% and for survival rate 5.84, 5.64 and 5.18%, respectively. The predicted responses followed the same pattern as the relative economic weights. This shows that milk yield and calving interval were most important in all production systems but the value of response for traits differed between production systems with more emphasis on milk yield and less on calving interval in the high production systems. Moderate correlations were estimated between the breeding objective for the low, medium and high production systems. To maximise response in the overall breeding objective, different selection criteria are required for the three production systems.
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Indústria de Laticínios , Lactação , Animais , Bovinos/genética , Feminino , Quênia , Lactação/genética , Masculino , Leite , FenótipoRESUMO
INTRODUCTION: Pembrolizumab is an established first-line option for patients with advanced non-small-cell lung cancer (NSCLC) expressing programmed death-ligand 1 ≥50%. Durable responses are seen in a subset of patients; however, many derive little clinical benefit. Biomarkers of the systemic inflammatory response predict survival in NSCLC. We evaluated their prognostic significance in patients receiving first-line pembrolizumab for advanced NSCLC. METHODS: Patients treated with first-line pembrolizumab for advanced NSCLC with programmed death-ligand 1 expression ≥50% at two regional Scottish cancer centres were identified. Pretreatment inflammatory biomarkers (white cell count, neutrophil count, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, albumin, prognostic nutritional index) were recorded. The relationship between these and progression-free survival (PFS) and overall survival (OS) were examined. RESULTS: Data were available for 219 patients. On multivariate analysis, albumin and neutrophil count were independently associated with PFS (P < 0.001, P = 0.002, respectively) and OS (both P < 0.001). A simple score combining these biomarkers was explored. The Scottish Inflammatory Prognostic Score (SIPS) assigned 1 point each for albumin <35 g/l and neutrophil count >7.5 × 109/l to give a three-tier categorical score. SIPS predicted PFS [hazard ratio 2.06, 95% confidence interval (CI) 1.68-2.52 (P < 0.001)] and OS [hazard ratio 2.33, 95% CI 1.86-2.92 (P < 0.001)]. It stratified PFS from 2.5 (SIPS2), to 8.7 (SIPS1) to 17.9 months (SIPS0) (P < 0.001) and OS from 5.1 (SIPS2), to 12.4 (SIPS1) to 28.7 months (SIPS0) (P < 0.001). The relative risk of death before 6 months was 2.96 (95% CI 1.98-4.42) in patients with SIPS2 compared with those with SIPS0-1 (P < 0.001). CONCLUSIONS: SIPS, a simple score combining albumin and neutrophil count, predicts survival in patients with NSCLC receiving first-line pembrolizumab. Unlike many proposed prognostic scores, SIPS uses only routinely collected pretreatment test results and provides a categorical score. It stratifies survival across clinically meaningful time periods that may assist clinicians and patients with treatment decisions. We advocate validation of the prognostic utility of SIPS in this and other immune checkpoint inhibitor treatment settings.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Albuminas/uso terapêutico , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Inflamação/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológicoRESUMO
Genetic parameters for test-day milk yield, lactation persistency, and age at first calving (as a fertility trait) were estimated for the first 4 lactations in multiple-breed dairy cows in low-, medium-, and high-production systems in Kenya. Data included 223,285 test-day milk yield records from 11,450 cows calving from 1990 to 2015 in 148 herds. A multivariate random regression model was used to estimate variance and covariance components. The fixed effects in the model included herd, year, and test month, and age as a covariate. The lactation profile over days in milk (DIM) was fitted as a cubic smoothing spline. Random effects included herd, year, and test month interaction effects, genetic group effects, and additive genetic and permanent environmental effects modeled with a cubic Legendre polynomial function. The residual variance was heterogeneous with 11 classes. Consequently, the variance components were varied over the lactation and with the production system. The estimated heritability for milk yield was lower in the low-production system (0.04-0.48) than in the medium- (0.22-0.59) and high-production (0.21-0 60) systems. The genetic correlations estimated between different DIM within lactations decreased as the time interval increased, becoming negative between the ends of the lactations in the low- and medium-production systems. Low (0.05) to medium (0.60) genetic correlations were estimated among first lactation test-day milk yields across the 3 production systems. Genetic correlations between the first lactation test-day milk yield and age at first calving ranged from 0.27 to 0.49, 0 to 0.81, and -0.08 to 0.27 in the low-, medium-, and high-production systems, respectively. Medium to high heritabilities (0.17-0.44) were estimated for persistency, with moderate to high (0.30-0.87) genetic correlations between 305-d milk yield and persistency. This indicates that genetic improvement in persistency would lead to increased milk yield. The low to medium genetic correlations between test-day milk yield between production systems indicate that sires may be re-ranked between production systems. Therefore, we conclude that sires should be selected based on a genetic evaluation within the target production system.
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Bovinos , Indústria de Laticínios , Fertilidade , Lactação , Leite , Animais , Feminino , Fertilidade/genética , Quênia , Lactação/genética , Fenótipo , GravidezRESUMO
Some mutations (or 'major genes') have a desirable effect in heterozygous carriers but an undesirable effect in homozygous carriers. When these mutations affect a trait of significant economic importance, their eradication, depending on their effect and frequency, may be counterproductive. This is especially the case of major genes affecting the ovulation rate and thus the prolificacy in meat sheep populations. To manage such situations, a mating design based on the major genotypes of reproducers has to be optimized. Both the effect of the major gene and the cost of genotyping candidates at this locus influence the expected genetic progress and profitability of the breeding plan. The aim of this study was to determine the optimal combination of matings that maximizes profitability at the level of the whole population (nucleus + commercial flocks). A deterministic model was developed and, using sequential quadratic programming methodology, the optimal strategy (optimal combination of matings) that maximized the economic gain achieved by the population across a range of genotype effects and genotyping costs was determined. The optimal strategy was compared with simpler and more practical strategies based on a limited number of parental genotype mating types. Depending on the genotype effect and genotyping costs, the optimal strategy varied, such that either the heterozygous frequency and/or polygenic gain was maximized with a large number of animals genotyped, or when genotyping costs were higher, the optimization led to lower heterozygous frequency and/or polygenic gain with fewer animals genotyped. Comparisons showed that some simpler strategies were close to the optimal strategy. An overlapping model was then derived as an application of the real case of the French Lacaune meat sheep OVI-TEST breeding program. Results showed that a practical strategy based on mating non-carriers to heterozygous carriers was only slightly less effective than the optimal strategy, with a reduction in efficiency from 3% to 8%, depending on the genotyping costs. Based on only two different parental genotype mating types, this strategy would be easy to implement.
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Modelos Genéticos , Reprodução/genética , Ovinos/genética , Animais , Cruzamento , Feminino , Determinismo Genético , Genótipo , Heterozigoto , Homozigoto , Masculino , Fenótipo , Ovinos/fisiologiaRESUMO
Genetic correlations between 29 wool production and quality traits and 25 meat quality and nutritional value traits were estimated for Merino sheep from an Information Nucleus (IN). Genetic correlations among the meat quality and nutritional value traits are also reported. The IN comprised 8 flocks linked genetically and managed across a range of sheep production environments in Australia. The wool traits included over 5,000 yearling and 3,700 adult records for fleece weight, fiber diameter, staple length, staple strength, fiber diameter variation, scoured wool color, and visual scores for breech and body wrinkle. The meat quality traits were measured on samples from the and included over 1,200 records from progeny of over 170 sires for intramuscular fat (IMF), shear force of meat aged for 5 d (SF5), 24 h postmortem pH (pHLL; also measured in the , pHST), fresh and retail meat color and meat nutritional value traits such as iron and zinc levels, and long-chain omega-3 and omega-6 polyunsaturated fatty acid levels. Estimated heritabilities for IMF, SF5, pHLL, pHST, retail meat color lightness (), myoglobin, iron, zinc and across the range of long-chain fatty acids were 0.58 ± 0.11, 0.10 ± 0.09, 0.15 ± 0.07, 0.20 ± 0.10, 0.59 ± 0.15, 0.31 ± 0.09, 0.20 ± 0.09, 0.11 ± 0.09, and range of 0.00 (eicosapentaenoic, docosapentaenoic, and arachidonic acids) to 0.14 ± 0.07 (linoleic acid), respectively. The genetic correlations between the wool production and meat quality traits were low to negligible and indicate that wool breeding programs will have little or no effect on meat quality. There were moderately favorable genetic correlations between important yearling wool production traits and the omega-3 fatty acids that were reduced for corresponding adult wool production traits, but these correlations are unlikely to be important in wool/meat breeding programs because they have high SE, and the omega-3 traits have little or no genetic variance. Significant genetic correlations among the meat quality traits included IMF with SF5 (-0.76 ± 0.24), fresh meat color * (0.50 ± 0.18), and zinc (0.41 ± 0.19). Selection to increase IMF will improve meat tenderness and color which may address some of the issues with Merino meat quality. These estimated parameters allow Merino breeders to combine wool and meat objectives without compromising meat quality.
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Carne/normas , Ovinos/genética , Lã/normas , Animais , Austrália , Peso Corporal/genética , Cruzamento , Cor , Ácidos Graxos/análise , Feminino , Ferro/análise , Masculino , Valor Nutritivo/genética , Fenótipo , Ovinos/fisiologia , Zinco/análiseRESUMO
Genetic correlations between 29 wool production and quality traits and live weight and ultrasound fat depth (FAT) and eye muscle depth (EMD) traits were estimated from the Information Nucleus (IN). The IN comprised 8 genetically linked flocks managed across a range of Australian sheep production environments. The data were from a maximum of 9,135 progeny born over 5 yr from 184 Merino sires and 4,614 Merino dams. The wool traits included records for yearling and adult fleece weight, fiber diameter (FD), staple length (SL), fiber diameter CV (FDCV), scoured color, and visual scores for breech and body wrinkle. We found high heritability for the major yearling wool production traits and some wool quality traits, whereas other wool quality traits, wool color, and visual traits were moderately heritable. The estimates of heritability for live weight generally increased with age as maternal effects declined. Estimates of heritability for the ultrasound traits were also higher when measured at yearling age rather than at postweaning age. The genetic correlations for fleece weight with live weights were positive (favorable) and moderate (approximately 0.5 ± 0.1), whereas those with FD were approximately 0.3 (unfavorable). The other wool traits had lower genetic correlations with the live weights. The genetic correlations for FAT and EMD with FD and SL were positive and low, with FDCV low to moderate negative, but variable with wool weight and negligible for the other wool traits. The genetic correlations for FAT and EMD with postweaning weight were positive and high (0.61 ± 0.18 to 0.75 ± 0.14) but were generally moderate with weights at other ages. Selection for increased live weight will result in a moderate correlated increase in wool weight as well as favorable reductions in breech cover and wrinkle, along with some unfavorable increases in FD and wool yellowness but little impact on other wool traits. The ultrasound meat traits, FAT and EMD, were highly positively genetically correlated (0.8), and selection to increase them would result in a small unfavorable correlated increase in FD, moderately favorable reductions in breech cover and wrinkle, but equivocal or negligible changes in other wool traits. The estimated parameters provide the basis for calculation of more accurate Australian Sheep Breeding Values and selection indexes that combine wool and meat objectives in Merino breeding programs.
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Carne Vermelha/normas , Ovinos/genética , Lã/crescimento & desenvolvimento , Animais , Austrália , Peso Corporal , Cruzamento , Feminino , Genótipo , Masculino , Fenótipo , Gravidez , Ovinos/anatomia & histologia , Ovinos/crescimento & desenvolvimentoRESUMO
Genetic correlations between 29 wool production and quality traits and 14 whole carcass measures and carcass component traits were estimated from the Information Nucleus of 8 flocks managed across a range of Australian sheep production environments and genetically linked. Wool data were from over 5,000 Merino progeny born over 5 yr, whereas carcass data were from over 1,200 wether progeny of over 176 sires, slaughtered at about 21 kg carcass weight, on average. Wool traits included yearling and adult records for wool weight, fiber diameter, fiber diameter variation, staple strength, scoured color, and visual scores for breech and body wrinkle. Whole carcass measures included HCW, dressing percentage (DP), and various measures of fat depth and eye muscle dimensions. Carcass components were obtained by dissection, and lean meat yield (LMY) was predicted. Heritability estimates for whole carcass measures ranged from 0.12 ± 0.08 to 0.35 ± 0.10 and ranged from 0.17 ± 0.10 to 0.46 ± 0.10 for carcass dissection traits, with no evidence of important genotype × environment interactions. Genetic correlations indicated that selection for increased clean wool weight will result in reduced carcass fat (-0.17 to -0.34) and DP (-0.48 ± 0.15), with little effect on carcass muscle. Selection for lower fiber diameter will reduce HCW (-0.48 ± 0.15) as well as carcass fat (0.14 to 0.27) and muscle (0.21 to 0.50). There were high genetic correlations between live animal measures of fat and muscle depth and the carcass traits (generally greater than 0.5 in size). Selection to increase HCW (and DP) will result in sheep with fewer wrinkles on the body (-0.57 ± 0.10) and barer breeches (-0.74 ± 0.12, favorable), with minor deterioration in scoured wool color (reduced brightness and increased yellowness). Selection for reduced fat will also result in sheep with fewer body wrinkles (-0.42 to -0.79). Increasing LMY in Merinos through selection would result in a large reduction in carcass fat and DP (-0.66 to -0.84), with a smaller increase in carcass muscle and some increase in wool weight and wrinkles. Although no major antagonisms are apparent between the wool and carcass traits, developing selection indexes for dual-purpose wool and meat breeding objectives will require accurate estimates of genetic parameters to ensure that unfavorable relationships are suitably considered. The findings will aid development of dual-purpose wool and meat breeding objectives.
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Ovinos/genética , Lã/crescimento & desenvolvimento , Animais , Austrália , Peso Corporal , Cruzamento , Cor , Feminino , Genótipo , Masculino , Fenótipo , Carne Vermelha , Ovinos/crescimento & desenvolvimentoRESUMO
Economically important reproduction traits in sheep, such as number of lambs weaned and litter size, are expressed only in females and later in life after most selection decisions are made, which makes them ideal candidates for genomic selection. Accurate genomic predictions would lead to greater genetic gain for these traits by enabling accurate selection of young rams with high genetic merit. The aim of this study was to design and evaluate the accuracy of a genomic prediction method for female reproduction in sheep using daughter trait deviations (DTD) for sires and ewe phenotypes (when individual ewes were genotyped) for three reproduction traits: number of lambs born (NLB), litter size (LSIZE) and number of lambs weaned. Genomic best linear unbiased prediction (GBLUP), BayesR and pedigree BLUP analyses of the three reproduction traits measured on 5340 sheep (4503 ewes and 837 sires) with real and imputed genotypes for 510 174 SNPs were performed. The prediction of breeding values using both sire and ewe trait records was validated in Merino sheep. Prediction accuracy was evaluated by across sire family and random cross-validations. Accuracies of genomic estimated breeding values (GEBVs) were assessed as the mean Pearson correlation adjusted by the accuracy of the input phenotypes. The addition of sire DTD into the prediction analysis resulted in higher accuracies compared with using only ewe records in genomic predictions or pedigree BLUP. Using GBLUP, the average accuracy based on the combined records (ewes and sire DTD) was 0.43 across traits, but the accuracies varied by trait and type of cross-validations. The accuracies of GEBVs from random cross-validations (range 0.17-0.61) were higher than were those from sire family cross-validations (range 0.00-0.51). The GEBV accuracies of 0.41-0.54 for NLB and LSIZE based on the combined records were amongst the highest in the study. Although BayesR was not significantly different from GBLUP in prediction accuracy, it identified several candidate genes which are known to be associated with NLB and LSIZE. The approach provides a way to make use of all data available in genomic prediction for traits that have limited recording.
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Cruzamento , Genômica/métodos , Reprodução/genética , Carneiro Doméstico/genética , Animais , Feminino , Genoma , Genótipo , Tamanho da Ninhada de Vivíparos , Masculino , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único , DesmameRESUMO
The purpose of this study was to describe the prevalence of hearing loss and tinnitus in a cohort of Iraq and Afghanistan Veterans (IAV) with common post-deployment conditions, including traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and other typical post-concussive conditions such as headaches and vertigo/dizziness. This retrospective observational study used data from the national Veterans Health Administration (VA) data repository from fiscal years 2001-2014. Veteran data was included if there were at least three years of VA care, with one or more years of care in 2007 or after. We identified comorbidities that may be associated with post-deployment hearing loss or tinnitus including TBI, PTSD, depression, and common post-concussive symptoms using International Classification of Diseases, 9th Revision, Clinical Modification codes. A multinomial logistic regression analysis was used to examine conditions associated with hearing loss or tinnitus. Among IAV, 570,332 were included in the final analysis. Of these, 7.78% of these were diagnosed with hearing loss alone, 6.54% with tinnitus alone, and 6.24% with both hearing loss and tinnitus. Comorbid TBI, PTSD, and depression were significantly associated with increased rates of hearing loss, tinnitus, or both conditions together. Older individuals, males, and those with TBI, PTSD, or vertigo/dizziness were significantly more likely to have hearing loss, tinnitus, or both. In order to provide more holistic post-deployment support, this myriad of conditions should be carefully considered in the planning of clinical care and beyond.
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Campanha Afegã de 2001- , Perda Auditiva/epidemiologia , Guerra do Iraque 2003-2011 , Zumbido/epidemiologia , Saúde dos Veteranos , Adulto , Lesões Encefálicas Traumáticas/epidemiologia , Distribuição de Qui-Quadrado , Comorbidade , Depressão/epidemiologia , Feminino , Audição , Perda Auditiva/diagnóstico , Perda Auditiva/fisiopatologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Fatores de Tempo , Zumbido/diagnóstico , Zumbido/fisiopatologia , Estados Unidos/epidemiologiaRESUMO
Hearing loss is the second most common disability awarded by the U.S. Department of Veterans Affairs (VA) to former members of the U.S. uniformed services. Hearing readiness and conservation practices differ among the four largest uniformed military services (Air Force, Army, Marine Corps, and Navy). Utilizing a data set consisting of all hearing loss claims submitted to the VA from fiscal years 2003-2013, we examined characteristics of veterans submitting claims within one year of separation from military service. Our results indicate that having a hearing loss disability claim granted was significantly more likely for men, individuals over the age of 26 years at the time of the claim, individuals most recently serving in the U.S. Army, and those with at least one hearing loss diagnosis. Importantly, individuals with at least one test record in the Defense Occupational and Environmental Health Readiness System-Hearing Conservation (DOEHRS-HC) system were significantly less likely to have a hearing loss disability claim granted by the VA. Within the DOEHRS-HC cohort, those with at least one threshold shift or clinical hearing loss diagnosis while on active duty were more than two and three times more likely to have a hearing loss disability claim granted, respectively. These findings indicate that an established history of reduced hearing ability while on active duty was associated with a significantly increased likelihood of an approved hearing loss disability claim relative to VA claims without such a history. Further, our results show a persistent decreased rate of hearing loss disability awards overall. These findings support increased inclusion of personnel in DoD hearing readiness and conservation programs to reduce VA hearing loss disability awards.
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Avaliação da Deficiência , Perda Auditiva Provocada por Ruído/diagnóstico , Testes Auditivos , Audição , Militares , Doenças Profissionais/diagnóstico , United States Department of Defense , United States Department of Veterans Affairs , Ajuda a Veteranos de Guerra com Deficiência , Veteranos , Adulto , Fatores Etários , Fadiga Auditiva , Percepção Auditiva , Definição da Elegibilidade , Feminino , Perda Auditiva Provocada por Ruído/epidemiologia , Perda Auditiva Provocada por Ruído/fisiopatologia , Perda Auditiva Provocada por Ruído/psicologia , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Militares/psicologia , Ruído Ocupacional/efeitos adversos , Doenças Profissionais/epidemiologia , Doenças Profissionais/fisiopatologia , Doenças Profissionais/psicologia , Exposição Ocupacional/efeitos adversos , Valor Preditivo dos Testes , Fatores Sexuais , Fatores de Tempo , Estados Unidos/epidemiologia , Veteranos/psicologiaRESUMO
Genomic selection is becoming a standard tool in livestock breeding programs, particularly for traits that are hard to measure. Accuracy of genomic selection can be improved by increasing the quantity and quality of data and potentially by improving analytical methods. Adding genotypes and phenotypes from additional breeds or crosses often improves the accuracy of genomic predictions but requires specific methodology. A model was developed to incorporate breed composition estimated from genotypes into genomic selection models. This method was applied to age at puberty data in female beef cattle (as estimated from age at first observation of a corpus luteum) from a mix of Brahman and Tropical Composite beef cattle. In this dataset, the new model incorporating breed composition did not increase the accuracy of genomic selection. However, the breeding values exhibited slightly less bias (as assessed by deviation of regression of phenotype on genomic breeding values from the expected value of 1). Adding additional Brahman animals to the Tropical Composite analysis increased the accuracy of genomic predictions and did not affect the accuracy of the Brahman predictions.
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Cruzamento , Bovinos/genética , Seleção Genética , Maturidade Sexual/genética , Adaptação Fisiológica , Animais , Feminino , Frequência do Gene , Genômica/métodos , Genótipo , Modelos Genéticos , Linhagem , FenótipoRESUMO
A reparameterization of the multivariate linear mixed model in genetic evaluation to principal components is described. This yields an equivalent model with a sparser coefficient matrix in the mixed model equations and, thus, reduced computational requirements to solve them. It is especially advantageous for analyses incorporating genomic relationship information with many nonzero elements in the inverse of the relationship matrix. Moreover, the framework lends itself directly to dimension reduction and, thus, further computational savings by omitting genetic principal components with negligible eigenvalues. The potential impact on computational demands is illustrated for an application to single-step genomic evaluation of Australian sheep.
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Genômica/métodos , Modelos Genéticos , Análise de Componente Principal , Ovinos/genética , Animais , Cruzamento , Genoma , Modelos LinearesRESUMO
Activity and disuse of synapses are thought to influence progression of several neurodegenerative diseases in which synaptic degeneration is an early sign. Here we tested whether stimulation or disuse renders neuromuscular synapses more or less vulnerable to degeneration, using axotomy as a robust trigger. We took advantage of the slow synaptic degeneration phenotype of axotomized neuromuscular junctions in flexor digitorum brevis (FDB) and deep lumbrical (DL) muscles of Wallerian degeneration-Slow (Wld(S)) mutant mice. First, we maintained ex vivo FDB and DL nerve-muscle explants at 32°C for up to 48 h. About 90% of fibers from Wld(S) mice remained innervated, compared with about 36% in wild-type muscles at the 24-h checkpoint. Periodic high-frequency nerve stimulation (100 Hz: 1s/100s) reduced synaptic protection in Wld(S) preparations by about 50%. This effect was abolished in reduced Ca(2+) solutions. Next, we assayed FDB and DL innervation after 7 days of complete tetrodotoxin (TTX)-block of sciatic nerve conduction in vivo, followed by tibial nerve axotomy. Five days later, only about 9% of motor endplates remained innervated in the paralyzed muscles, compared with about 50% in 5 day-axotomized muscles from saline-control-treated Wld(S) mice with no conditioning nerve block. Finally, we gave mice access to running wheels for up to 4 weeks prior to axotomy. Surprisingly, exercising Wld(S) mice ad libitum for 4 weeks increased about twofold the amount of subsequent axotomy-induced synaptic degeneration. Together, the data suggest that vulnerability of mature neuromuscular synapses to axotomy, a potent neurodegenerative trigger, may be enhanced bimodally, either by disuse or by hyperactivity.
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Junção Neuromuscular/fisiopatologia , Degeneração Walleriana/fisiopatologia , Animais , Axotomia , Cálcio/metabolismo , Terapia por Estimulação Elétrica , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Junção Neuromuscular/patologia , Corrida/fisiologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiopatologia , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Nervo Tibial/lesões , Nervo Tibial/fisiopatologia , Técnicas de Cultura de Tecidos , Degeneração Walleriana/patologia , Degeneração Walleriana/prevenção & controleRESUMO
Procedures are described for estimating selection index accuracies for individual animals and expected genetic change from selection for the general case where indexes of EBVs predict an aggregate breeding objective of traits that may or may not have been measured. Index accuracies for the breeding objective are shown to take an important general form, being able to be expressed as the product of the accuracy of the index function of true breeding values and the accuracy with which that function predicts the breeding objective. When the accuracies of the individual EBVs of the index are known, prediction error variances (PEVs) and covariances (PECs) for the EBVs within animal are able to be well approximated, and index accuracies and expected genetic change from selection estimated with high accuracy. The procedures are suited to routine use in estimating index accuracies in genetic evaluation, and for providing important information, without additional modelling, on the directions in which a population will move under selection.
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Cruzamento , Modelos Genéticos , Fenótipo , AnimaisRESUMO
In single-step genomic evaluation using best linear unbiased prediction (ssGBLUP), genomic predictions are calculated with a relationship matrix that combines pedigree and genomic information. For missing pedigrees, unknown selection processes, or inclusion of several populations, a BLUP model can include unknown-parent groups (UPG) in the animal effect. For ssGBLUP, UPG equations also involve contributions from genomic relationships. When those contributions are ignored, UPG solutions and genetic predictions can be biased. Options to eliminate or reduce such bias are presented. First, mixed model equations can be modified to include contributions to UPG elements from genomic relationships (greater software complexity). Second, UPG can be implemented as separate effects (higher cost of computing and data processing). Third, contributions can be ignored when they are relatively small, but they may be small only after refinements to UPG definitions. Fourth, contributions may approximately cancel out when genomic and pedigree relationships are constructed for compatibility; however, different construction steps are required for unknown parents from the same or different populations. Finally, an additional polygenic effect that also includes UPG can be added to the model.