Genotype imputation accuracy in a F2 pig population using high density and low density SNP panels

Background: F2 resource populations have been used extensively to map QTL segregating between pig breeds. A limitation associated with the use of these resource populations for fine mapping of QTL is the reduced number of founding individuals and recombinations of founding haplotypes occurring in the population. These limitations, however, become advantageous when attempting to impute unobserved genotypes using within family segregation information. A trade-off would be to re-type F2 populations using high density SNP panels for founding individuals and low density panels (tagSNP) in F2 individuals followed by imputation. Subsequently a combined meta-analysis of several populations would provide adequate power and resolution for QTL mapping, and could be achieved at relatively low cost. Such a strategy allows the wealth of phenotypic information that has previously been obtained on experimental resource populations to be further mined for QTL identification. In this study we used experimental and simulated high density genotypes (HD-60K) from an F2 cross to estimate imputation accuracy under several genotyping scenarios. Results: Selection of tagSNP using physical distance or linkage disequilibrium information produced similar imputation accuracies. In particular, tagSNP sets averaging 1 SNP every 2.1 Mb (1,200 SNP genome-wide) yielded imputation accuracies (IA) close to 0.97. If instead of using custom panels, the commercially available 9K chip is used in the F2, IA reaches 0.99. In order to attain such high imputation accuracy the F0 and F1 generations should be genotyped at high density. Alternatively, when only the F0 is genotyped at HD, while F1 and F2 are genotyped with a 9K panel, IA drops to 0.90. Conclusions: Combining 60K and 9K panels with imputation in F2 populations is an appealing strategy to re-genotype existing populations at a fraction of the cost.Fil: Gualdron Duarte, Jose Luis. Michigan State University; Estados Unidos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bates, Ronald O.. Michigan State University; Estados UnidosFil: Ernst, Catherine W.. Michigan State University; Estados UnidosFil: Raney, Nancy E.. Michigan State University; Estados UnidosFil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Steibel, Juan P.. Michigan State University; Estados Unido

Risco de Recidiva a 5 Anos Após Excisão Convencional de um Carcinoma Basocelular

Introduction: Basal cell carcinomas are mostly treated surgically, mostly by surgery with postoperative histopathologic margin evaluation (“conventional surgery”), but large long-term data regarding recurrence by completeness of excisions is limited. Methods: Retrospective cohort study of basal cell carcinomas treated by conventional surgery at different medical specialties in a large tertiary centre, between 2008 and 2014. Survival analysis with a Cox proportional-hazards was performed, stratified by completeness of excision (complete excision/incomplete excision) and adjusted to several potentially confounding covariates. Results: A total of 2876 basal cell carcinomas were identified, of which 2306 (2100 primary, 206 recurrent) were considered eligible for analysis. During the 5-years of follow-up, there were 80 (4%) recurrences among 1980 complete excisions (16/1000 cases-year) and 83 (23.9%) recurrences among 348 incomplete excisions (100/1000 cases-year). Survival analysis was performed with multivariable adjustment. In the final adjusted model, we identified an association between relapse and re-intervention on recurrent tumors [adjusted Hazard Ratio (HR) 2.20 (95% Confidence interval (IC), 1.26-3.84), p=0.006], a wrong preoperative clinical diagnosis/surgery devoid of preoperative biopsy [adjusted HR 2.75 (95% CI, 1.68-4.5), p<0.001], treatment prior to 2012 [adjusted HR 1.47 (95% IC, 1.06-2.05), p<0.021] and surgery on a high-risk location, accordingly to the NCCN stratification [adjusted HR 2.18 (95% CI, 1.08-4.40), p<0.030]. By specific anatomic location, the likelihood of recurrence was especially high in the nose [adjusted HR 3.18 (95% CI 1.71-5.87), p<0.001] and eyelids [adjusted HR 3.08 (95% CI, 1.32-7.17), p=0.009]. There was also a trend towards higher recurrence in aggressive histological subtypes [adjusted HR 1.43 (95% CI 0.99-2.07), p<0.058]. Conclusion: Recurrent basal cell carcinomas, regardless of location, and primary basal cell carcinomas on high-risk locations of the face, especially on the eyelids and nose, should be considered to have a higher and independent likelihood of recurrence, even on “complete excisions” evaluated by histopathology. On the other hand, wait-andsee approaches in incompletely excised BCCs should be considered against a significant 5-year risk of relapse (1 in 10 lesions).Introdução: O tratamento dos carcinomas basocelulares é maioritariamente cirúrgico, sobretudo por cirurgia com avaliação histopatológica pós-operatória da margem (cirurgia convencional), mas os dados a longo-prazo relativos a recidiva de acordo com o resultado histológico da margem (excisão completa versus excisão incompleta, mantida em follow-up) são limitados. Métodos: Estudo coorte retrospetivo dos carcinomas basocelulares tratados por cirurgia convencional e por diferentes especialidades médico-cirúrgicas num centro terciário, entre 2008 e 2014. Realizou-se uma análise multivariada com uma regressão de Cox, estratificada pelo resultado da avaliação histológica da margem (excisão completa/incompleta) e ajustada a várias variáveis recolhidas. Resultados: Um total de 2876 carcinomas basocelulares foram identificados, dos quais 2306 [2100 primários, 206 recidivantes (primeira recidiva)] foram considerados elegíveis para análise. Nos 5 anos de follow-up, verificaram-se 80 (4%) recidivas entre os 1959 tumores completamente excisados (16/1000 casos-ano), contrastando com 83 (23,9%) recidivas em 347 excisões incompletas (100/1000 casos-ano). Foi realizada uma análise de sobrevida ajustada. No modelo final, ajustado, multivariado, foi identificada associação entre recidiva e intervenção cirúrgica a tumores recorrentes [hazard ratio (HR) ajustado 2,20 (Intervalo confiança (IC) 95%, 1,26-3,84), p=0,006], cirurgia com diagnóstico pré-operatório errado/ausência de realização de biópsia prévia [HR ajustado 2,75 (IC 95%, 1,68-4,5), p<0,001], tratamento prévio a 2012 [HR ajustado 1,47 (CI 95%, 1,06- 2,05), p<0,021] e cirurgia em localização de alto-risco, de acordo com a classificação NCCN [HR ajustado 2,18 (IC 95%, 1,08- 4,40), p<0,030]. Por localização anatómica específica, a probabilidade de recidiva a longo-prazo é especialmente elevada se a cirurgia for na pirâmide nasal [HR ajustado 3,18 (IC 95%, 1,71-5,87), p<0,001] ou nas pálpebras [HR ajustado 3,08 (CI 95%, 1,32-7,17), p=0,009]. Verificou-se também uma tendência para maior recidiva nos subtipos histológicos agressivos [HR ajustado 1,43 (IC 95%, 0,99-2,07), p<0,058]. Conclusão: Os carcinomas basocelulares recorrentes, independentemente da localização, e os carcinomas basocelulares primários em localizações de alto-risco da face, particularmente na pirâmide nasal e nas pálpebras, determinam um risco de recidiva superior e independente a longo-prazo, mesmo nas excisões “completas”. Por outro lado, as estratégias wait-and-see nos carcinomas basocelulares incompletamente excisados devem ponderar o risco de recidiva aos 5 anos (1 in 10 lesões)

Rapid screening for phenotype-genotype associations by linear transformations of genomic evaluations

Background: Currently, association studies are analysed using statistical mixed models, with marker effects estimated by a linear transformation of genomic breeding values. The variances of marker effects are needed when performing the tests of association. However, approaches used to estimate the parameters rely on a prior variance or on a constant estimate of the additive variance. Alternatively, we propose a standardized test of association using the variance of each marker effect, which generally differ among each other. Random breeding values from a mixed model including fixed effects and a genomic covariance matrix are linearly transformed to estimate the marker effects. Results: The standardized test was neither conservative nor liberal with respect to type I error rate (false-positives), compared to a similar test using Predictor Error Variance, a method that was too conservative. Furthermore, genomic predictions are solved efficiently by the procedure, and the p-values are virtually identical to those calculated from tests for one marker effect at a time. Moreover, the standardized test reduces computing time and memory requirements. The following steps are used to locate genome segments displaying strong association. The marker with the highest − log(p-value) in each chromosome is selected, and the segment is expanded one Mb upstream and one Mb downstream of the marker. A genomic matrix is calculated using the information from those markers only, which is used as the variance-covariance of the segment effects in a model that also includes fixed effects and random genomic breeding values. The likelihood ratio is then calculated to test for the effect in every chromosome against a reduced model with fixed effects and genomic breeding values. In a case study with pigs, a significant segment from chromosome 6 explained 11% of total genetic variance. Conclusions: The standardized test of marker effects using their own variance helps in detecting specific genomic regions involved in the additive variance, and in reducing false positives. Moreover, genome scanning of candidate segments can be used in meta-analyses of genome-wide association studies, as it enables the detection of specific genome regions that affect an economically relevant trait when using multiple populations.Fil: Gualdron Duarte, Jose Luis. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cantet, Rodolfo Juan Carlos. Universidad de Buenos Aires. Facultad de Agronomia. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bates, Ronald O.. Michigan State University; Estados UnidosFil: Ernst, Catherine W.. Michigan State University; Estados UnidosFil: Raney, Nancy E.. Michigan State University; Estados UnidosFil: Steibel, Juan P.. Michigan State University; Estados Unido

Viral and Atypical Bacterial Detection in Acute Respiratory Infection in Children Under Five Years

Acute respiratory infection (ARI) is a leading cause of morbidity and mortality in children worldwide. This study aimed to determine the viral and atypical bacterial causes of different severities and clinical manifestations of ARI in preschool children from low-income families in North-East Brazil.Clinical/demographic data and nasopharyngeal aspirates (NPA) were prospectively collected from children <5 years presenting with ARI over one year to a paediatric A&E department. Disease severity was grouped according to presence of lower respiratory tract signs, need for hospital admission and need for oxygen. Clinical manifestation of ARI was based on discharge diagnosis from hospital with four conditions predominating: bronchiolitis, pneumonia, episodic viral wheeze/asthma and upper respiratory tract infection. Multiplex PCR was used to detect 17 common respiratory viral and atypical bacterial pathogens in NPA.407 children with a median age of eight months were recruited. Pathogens were detected in 85·5% samples with co-infection being particularly common (39·5%). Respiratory Syncytial Virus (RSV; 37%), Adenoviruses (AdV; 25%), Rhinoviruses (hRV; 19%), Bocavirus (hBoV; 19%), human Meta-pneumovirus (hMPV; 10%) and Mycoplasma pneumoniae (Mpp; 10%) were most prevalent. Detection and co-infection rates were similar in all severities and clinical manifestations of ARI apart from RSV, which was associated with more severe disease and specifically more severe cases of bronchiolitis, and Mpp, which was associated with more severe cases of pneumonia. Mpp was detected in 17% of children admitted to hospital with pneumonia.This study underlines the importance of viral and atypical bacterial pathogens in ARI in pre-school children and highlights the complex epidemiology of these pathogens in this age group. Generally, viruses and atypical bacteria were detected in all severities and clinical manifestations of ARI but RSV and Mpp were associated with more severe cases of bronchiolitis and pneumonia respectively

Chemical and nano-mineralogical study for determining potential uses of legal Colombian gold mine sludge: Experimental evidence

The present study is focused on the chemical and nano-mineralogical characterization of sludge from gold mine activities, in order to put forward diverse solution alternatives, where lack of knowledge has been found. The sample was collected from “La Estrella” mine of Suarez, located in Department of Cauca, south-west Colombia. The sludge micro-structure and chemical composition were analyzed using a high resolution transmission electron microscopy (HR-TEM) equipped with a dispersive X-ray detector (EDS). X-ray diffraction technique was employed to identify the mineralogical phases present in the sludge. Additional mineralogical characterization was done by using RAMAN spectroscopy. Main findings points to its potential to be used as a fertilizer, this is why, mine sludge contains macronutrients such as P, Ca and S, together with micronutrients like Cu. However, the presence of goethite could decrease the mobilization of nutrients to soils, thus additional alternatives, for instance, a mixture with humus or another material containing Humic Acids should be done, in order to minimizing its retention effect. Additionally, another possible uses to explore could be as construction and ceramic material or in the wastewater treatment for nutrient retention and organic material removal. Rutile (TiO2 nanoparticles) particles have been also detected, what could cause health concern due to its nanoparticle toxic character, mainly during gold extraction process

Evaluación de politicas de gestión de inventarios de medicamentos para un sistema multinivel y multiproducto en el hospital universitario de la samaritana (hus)

The research analyzed the efficiency of inventory management process in a multilevel system with M-suppliers, a one warehouse (BC), and four retails for supply chain for drugs at the University Hospital of the Samaritana, In order to determine the appropriate order from the central warehouse to suppliers and pharmacies from auxiliary to the central warehouse, minimizing the total cost of inventory investment and in turn the percentage of the number of days with quantities missing. Of the computational results obtained in the initial validation it is concluded that the application of the proposed model generates a saving of 50% in the total investment costs and 95% in the number of days with missing for auxiliary pharmacies.&nbsp;En la investigación se analizó la eficiencia del proceso de gestión de inventarios en un sistema multinivel con M-proveedores, una bodega central (BC), y cuatro minoristas para la cadena de abastecimiento de medicamentos del Hospital Universitario de la Samaritana, con el objetivo de determinar las cantidades adecuadas de pedido desde la bodega central hacia sus proveedores y desde las farmacias auxiliares hacia la bodega central, minimizando el costo total de inversión en inventario y a su vez el porcentaje del número de días con unidades faltantes. De los resultados computacionales obtenidos en la validación inicial se concluye, que la aplicación del modelo propuesto genera un ahorro del 50% en los costos totales de inversión y 95% en el número de días con faltantes para las farmacias auxiliares.&nbsp; &nbsp

Manual de producción de enmiendas orgánicas para restablecer la fertilidad del suelo

La gran cantidad de residuos generados como parte del proceso productivo agrícola, hacen necesario un mejor manejo de estos, a fin de incorporar nutrientes al suelo, lo cual representa una gran oportunidad. Es en este contexto se desarrolla el “Manual de producción de enmiendas orgánicas para restablecer la fertilidad del suelo”, el cual presenta información científica y práctica relevante para la producción de enmiendas de fácil fabricación, ofreciendo alternativas eficientes y de bajo costo que pueden ser aplicables por los pequeños agricultores

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis

© 2010 Cascão et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA). Methods: Cytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed. Results: VERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1b and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern. Conclusions: VERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.This work was supported by a grant from Sociedade Portuguesa de Reumatologia/Schering-Plough 2005. RAM and RC were funded by Fundação para a Ciência e a Tecnologia (FCT) SFRH/BD/30247/2006 and SFRH/BD/40513/2007, respectively. MMS-C was funded by Marie Curie Intra-European Fellowship PERG-2008-239422 and a EULAR Young Investigator Award

Concurrent agreement between an anthropometric model to predict thigh volume and dual-energy X-Ray absorptiometry assessment in female volleyball players aged 14-18 years

© 2016 The Author(s).Background: A variety of performance outputs are strongly determined by lower limbs volume and composition in children and adolescents. The current study aimed to examine the validity of thigh volume (TV) estimated by anthropometry in late adolescent female volleyball players. Dual-energy X-ray absorptiometry (DXA) measures were used as the reference method. Methods: Total and regional body composition was assessed with a Lunar DPX NT/Pro/MD+/Duo/Bravo scanner in a cross-sectional sample of 42 Portuguese female volleyball players aged 14-18 years (165.2 ± 0.9 cm; 61.1 ± 1.4 kg). TV was estimated with the reference method (TV-DXA) and with the anthropometric method (TV-ANTH). Agreement between procedures was assessed with Deming regression. The analysis also considered a calibration of the anthropometric approach. Results: The equation that best predicted TV-DXA was: -0.899 + 0.876 × log10 (body mass) + 0.113 × log10 (TV-ANTH). This new model (NM) was validated using the predicted residual sum of squares (PRESS) method (R2PRESS = 0.838). Correlation between the reference method and the NM was 0.934 (95%CI: 0.880-0.964, Sy·x = 0.325 L). Conclusions: A new and accurate anthropometric method to estimate TV in adolescent female volleyball players was obtained from the equation of Jones and Pearson alongside with adjustments for body mass