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1.
Br J Cancer ; 130(8): 1261-1268, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38383704

RESUMO

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.


Assuntos
Cesárea , Neoplasias , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Reino Unido/epidemiologia , Nascido Vivo
2.
J Dairy Sci ; 103(11): 10399-10413, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32921460

RESUMO

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.


Assuntos
Bovinos , Indústria de Laticínios , Fertilidade , Lactação , Leite , Animais , Feminino , Fertilidade/genética , Quênia , Lactação/genética , Fenótipo , Gravidez
3.
Anim Genet ; 48(3): 338-348, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28211150

RESUMO

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.


Assuntos
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 , Desmame
4.
Anim Genet ; 47(1): 3-11, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26490440

RESUMO

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.


Assuntos
Cruzamento , Bovinos/genética , Seleção Genética , Maturidade Sexual/genética , Adaptação Fisiológica , Animais , Feminino , Frequência do Gene , Genômica/métodos , Genótipo , Modelos Genéticos , Linhagem , Fenótipo
5.
Front Bioinform ; 4: 1347168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38357576

RESUMO

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.

6.
J Anim Breed Genet ; 130(5): 341-8, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24074171

RESUMO

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.


Assuntos
Cruzamento , Modelos Genéticos , Fenótipo , Animais
7.
J Anim Breed Genet ; 130(4): 252-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23855627

RESUMO

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.


Assuntos
Genômica , Modelos Genéticos , Animais , Feminino , Masculino , Linhagem
8.
Animal ; 16(5): 100513, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35436647

RESUMO

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.


Assuntos
Indústria de Laticínios , Lactação , Animais , Bovinos/genética , Feminino , Quênia , Lactação/genética , Masculino , Leite , Fenótipo
9.
ESMO Open ; 7(2): 100445, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35398717

RESUMO

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.


Assuntos
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 farmacológico
10.
Nat Cell Biol ; 1(7): 444-9, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10559989

RESUMO

Here we show that the Drosophila homologue of Lissencephaly-1, DLis-1, acts together with Bicaudal-D (Bic-D), Egalitarian (Egl), dynein and microtubules to determine oocyte identity. DLis-1 is further required for nurse-cell-to-oocyte transport during oocyte growth, and for the positioning of the nucleus in the oocyte. Immunostaining of DLis-1 protein reveals a cortical localization that is independent of microtubules. DLis-1 may function in this position as a cortical anchor for the other nuclear-localization factors. DLis-1 and Bic-D are further required for nuclear localization in the developing nervous system, indicating that homologues of Bic-D, dynein and Egl-like proteins may also be involved in vertebrate neural migration and that their absence may cause a Miller-Dieker-like lissencephaly.


Assuntos
Núcleo Celular/metabolismo , Proteínas de Drosophila , Drosophila melanogaster/genética , Dineínas/metabolismo , Proteínas de Insetos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Oócitos/fisiologia , Sequência de Aminoácidos , Animais , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/metabolismo , Elementos Facilitadores Genéticos/genética , Microscopia de Fluorescência , Proteínas Associadas aos Microtúbulos/genética , Microtúbulos/metabolismo , Dados de Sequência Molecular , Neurônios/fisiologia , Oogênese/genética , Oogênese/fisiologia , Células Fotorreceptoras de Invertebrados/fisiologia , Alinhamento de Sequência
11.
J Phys Chem A ; 115(16): 3917-23, 2011 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-21241060

RESUMO

Highly nonlinear pump fluence dependence was observed in the ultrafast one-color pump-probe responses excited by 38 fs pulses resonant with the E(22) transition in a room-temperature solution of (6,5) carbon nanotubes. The differential probe transmission (ΔT/T) at the peak of the pump-probe response (τ = 20 fs) was measured for pump fluences from ∼10(13) to 10(17) photons/pulse cm(2). The onset of saturation is observed at ∼2 × 10(15) photons/pulse cm(2) (∼8 × 10(5) excitons/cm). At pump fluences >4 × 10(16) photons/pulse cm(2) (∼1.6 × 10(6) excitons/cm), ΔT/T decreases as the pump fluence increases. Analogous signal saturation behavior was observed for all measured probe delays. Despite the high exciton density at saturation, no change in the E(22) population decay rate was observed at short times (<300 fs). The pump probe signal was modeled by a third-order perturbation theory treatment that includes the effects of inhomogeneous broadening. The observed ΔT/T signal is well-fit by a pump-fluence-dependent dephasing rate linearly dependent on the number of excitons created by the pump pulse. Therefore, the observed nonlinear pump intensity dependence is attributed to the effects of quasi-elastic exciton-exciton interactions on the dephasing rates of single carbon nanotubes. The low fluence total dephasing time is 36 fs, corresponding to a homogeneous width of 36 meV (290 cm(-1)), and the derived E(22) inhomogeneous width is 68 meV (545 cm(-1)). These results are contrasted with photon-echo-derived parameters for the E(11) transition.


Assuntos
Elétrons , Nanotubos de Carbono/química , Termodinâmica , Fatores de Tempo
12.
Curr Oncol ; 21(2): e392, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24764721
13.
Curr Oncol ; 21(2): e393, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24764722
14.
Cochrane Database Syst Rev ; (1): CD003725, 2008 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-18254031

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. This incurable disease is characterised by muscle wasting and loss of walking ability leading to complete wheelchair dependence by 13 years of age. Prolongation of walking is one of the major aims of treatment. OBJECTIVES: The aim of this review was to assess whether glucocorticoid corticosteroids stabilize or improve muscle strength and walking in boys with DMD. SEARCH STRATEGY: This is an update of the Cochrane systematic review first published in 2004 (Manzur 2004). We searched the Cochrane Neuromuscular Disease Group Trials Register (August 2006) using the term 'Duchenne muscular dystrophy'. We also searched MEDLINE (January 1966 to July 2007), EMBASE (January 1980 to August 2006), CINAHL and LILACS (January 1982 to August 2006). We wrote to authors of published studies and other experts in this disease to help identify other trials, checked the references in the identified trials and hand searched the abstracts of relevant journals. SELECTION CRITERIA: Types of studies: randomised or quasi-randomised trials. TYPES OF PARTICIPANTS: all patients with a definite diagnosis of Duchenne muscular dystrophy. Types of interventions: glucocorticoids such as prednisone, prednisolone, deflazacort or others, with a minimum treatment period of three months. PRIMARY OUTCOME MEASURE: prolongation of walking (independent walking without long leg calipers). SECONDARY OUTCOME MEASURES: strength outcome measures, manual muscle strength testing using Medical Research Council strength scores, functional outcome measures and adverse events. DATA COLLECTION AND ANALYSIS: We identified six randomised controlled trials that met the inclusion criteria for our review, and one of these (Beenakker 2005) is a new addition to this update, as it was published subsequent to our first review (Manzur 2004). Two review authors independently selected the trials for the review and assessed methodological quality. Data extraction and inputting were double-checked. PRIMARY OUTCOME MEASURE: data from one small study used prolongation of walking as an outcome measure and did not show significant benefit. SECONDARY OUTCOME MEASURES: The meta-analysis of the results from four randomised controlled trials with altogether 249 participants showed that glucocorticoid corticosteroids improved muscle strength and function over six months. Improvements were seen in time taken to rise from the floor (Gowers' time), nine metres walking time, four-stair climbing time, ability to lift weights, leg function grade and forced vital capacity. One randomised controlled trial with altogether 28 participants showed that glucocorticoid corticosteroids stabilize muscle strength and function for up to two years. The most effective prednisolone regime appears to be 0.75 mg/kg/day, given in a daily dose regime. Not enough data were available to compare efficacy of prednisone with deflazacort. Adverse effects: Excessive weight gain, behavioural abnormalities, cushingoid appearance and excessive hair growth were all more common with glucocorticoid corticosteroids than placebo. Long-term adverse effects of glucocorticoid therapy could not be evaluated because of the short-term duration of the randomised studies.Non-randomised studies: A number of non-randomised studies with important efficacy and adverse effects data are tabulated and discussed. AUTHORS' CONCLUSIONS: There is evidence from randomised controlled studies that glucocorticoid corticosteroid therapy in Duchenne muscular dystrophy improves muscle strength and function in the short-term (six months to two years). The most effective prednisolone regime appears to be 0.75 mg/kg/day, given daily. In the short term, adverse effects were significantly more common but not clinically severe. Long-term benefits and hazards of glucocorticoid treatment cannot be evaluated from the currently published randomised studies. Non-randomised studies support the conclusions of functional benefits but also identify clinically significant adverse effects of long-term treatment. These benefits and adverse effects have implications for future research studies and clinical practice.


Assuntos
Corticosteroides/uso terapêutico , Glucocorticoides/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Corticosteroides/efeitos adversos , Glucocorticoides/efeitos adversos , Humanos , Masculino , Prednisolona/uso terapêutico , Prednisona/uso terapêutico , Pregnenodionas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Caminhada
15.
Curr Oncol ; 20(5): e491, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24155647
16.
Animal ; 12(3): 454-463, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28770690

RESUMO

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.


Assuntos
Modelos Genéticos , Reprodução/genética , Ovinos/genética , Animais , Cruzamento , Feminino , Determinismo Genético , Genótipo , Heterozigoto , Homozigoto , Masculino , Fenótipo , Ovinos/fisiologia
17.
J Clin Invest ; 94(1): 25-33, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7518830

RESUMO

The metabolism of the cartilage proteoglycan aggrecan was studied in patients with osteoarthritis (OA, n = 83), rheumatoid arthritis (RA, n = 127), and in controls (n = 117) using monoclonal antibody-based radioimmunoassays for glycosaminoglycans in the serum and synovial fluid (SF) to detect epitope 846 on chondroitin sulfate (probably only on recently synthesized molecules) and a keratan sulfate (KS) epitope AN9PI, present on intact and degraded molecules. Epitope 846 levels were always elevated in SF over serum (mean 38-fold in OA and 8.6-fold in RA) being highest in OA patients with the longest disease duration and greatest loss of cartilage, and lowest in RA joints with high leucocyte counts. Serum levels were more often elevated in RA (56%) than in OA (19%) and probably reflect increased aggrecan synthesis in diseased joints. KS levels were higher in SF than in serum in 69% of patients (up to 2.3-fold); levels were inversely (OA) and directly (RA) related to SF leucocyte counts. Serum KS was reduced in both diseases and in RA was inversely related to both systemic and joint inflammation markers. SF 846 levels were inversely related to SF KS in both diseases. These epitopes may provide a measure of the balance between cartilage synthesis and degradation in these diseases.


Assuntos
Artrite Reumatoide/metabolismo , Cartilagem/metabolismo , Proteínas da Matriz Extracelular , Osteoartrite/metabolismo , Proteoglicanas/análise , Líquido Sinovial/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Agrecanas , Artrite Reumatoide/etiologia , Sulfatos de Condroitina/análise , Epitopos , Feminino , Humanos , Sulfato de Queratano/análise , Lectinas Tipo C , Masculino , Pessoa de Meia-Idade , Osteoartrite/etiologia , Proteoglicanas/sangue , Proteoglicanas/imunologia
18.
Hear Res ; 349: 13-20, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27768901

RESUMO

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.


Assuntos
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/psicologia
19.
Hear Res ; 349: 4-12, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28153668

RESUMO

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.


Assuntos
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/epidemiologia
20.
J Anim Sci ; 95(5): 1879-1891, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28726993

RESUMO

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.


Assuntos
Carne Vermelha/normas , Ovinos/genética , Lã/crescimento & desenvolvimento , Animais , Austrália , Peso Corporal , Cruzamento , Feminino , Genótipo , Masculino , Fenótipo , Gravidez , Ovinos/anatomia & histologia , Ovinos/crescimento & desenvolvimento
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