989 resultados para Modos de falha I, II, III


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BACKGROUND: Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for. METHODS: In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression. RESULTS: The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison. CONCLUSION: Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data.

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PURPOSE: To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS: Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS: After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION: Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

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O trabalho foi desenvolvido com os objetivos de testar, dentre vários extratores de micronutrientes do solo, qual é o mais adequado para avaliar a disponibilidade de Mn em solos sob sistema de semeadura direta (SSD); estudar, com auxílio da ressonância paramagnética eletrônica (RPE), a interação do Mn com os ácidos húmicos (AH) de solos de locais com e sem constatações de deficiência desse nutriente, e avaliar em quais das frações do solo (trocável, orgânica, óxido e residual) estava ligado o Mn, após sua aplicação no solo. Quatro locais foram selecionados para o estudo (Local I: Faz. Santa Rosa; II e III: Faz. Novo Horizonte e IV: Campo Experimental da Fundação ABC). Os Locais I, II e III situam-se em Tibagi, PR, e o Local IV, em Castro (PR). De modo geral, as doses de Mn aplicadas elevaram os teores de Mn nos solos, mas a concentração e a quantidade de Mn acumuladas pelas plantas de soja foram pouco influenciadas. Os teores de Mn nas frações trocável, orgânica e óxido das amostras do Local I aumentaram com as doses de Mn aplicadas no solo, tendo a maior elevação ocorrido na fração orgânica. Nessa fração, os teores aumentaram de 5,4 mg kg-1, na testemunha, para 35,1 mg kg-1, com a aplicação da maior dose. Os sinais de Mn não foram detectados por RPE nas amostras sólidas de AH (pH 3,0). A quantificação de Mn nessas amostras, após digestão nítrico-perclórica, juntamente com a observação de Mn por RPE, em amostras de AH em solução (pH 2,4), confirmou a hipótese de que o Mn presente nas amostras de AH estava na forma de ligações muito estáveis com os grupos funcionais (provavelmente carboxílicos) do AH. A ausência de efeito do Mn na produtividade da soja pode ser devida à complexação do nutriente pela MO. De forma geral, o DTPA-TEA foi o extrator mais adequado na avaliação da disponibilidade de Mn à soja.

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New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

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New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

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The opportunistic ubiquitous pathogen Pseudomonas aeruginosa strain PAOl is a versatile Gram-negative bacterium that has the extraordinary capacity to colonize a wide diversity of ecological niches and to cause severe and persistent infections in humans. To ensure an optimal coordination of the genes involved in nutrient utilization, this bacterium uses the NtrB/C and/or the CbrA/B two-component systems, to sense nutrients availability and to regulate in consequence the expression of genes involved in their uptake and catabolism. NtrB/C is specialized in nitrogen utilization, while the CbrA/B system is involved in both carbon and nitrogen utilization and both systems activate their target genes expression in concert with the alternative sigma factor RpoN. Moreover, the NtrB/C and CbrA/B two- component systems regulate the secondary metabolism of the bacterium, such as the production of virulence factors. In addition to the fine-tuning transcriptional regulation, P. aeruginosa can rapidly modulate its metabolism using small non-coding regulatory RNAs (sRNAs), which regulate gene expression at the post-transcriptional level by diverse and sophisticated mechanisms and contribute to the fast physiological adaptability of this bacterium. In our search for novel RpoN-dependent sRNAs modulating the nutritional adaptation of P. aeruginosa PAOl, we discovered NrsZ (Nitrogen regulated sRNA), a novel RpoN-dependent sRNA that is induced under nitrogen starvation by the NtrB/C two-component system. NrsZ has a unique architecture, formed of three similar stem-loop structures (SL I, II and II) separated by variant spacer sequences. Moreover, this sRNA is processed in short individual stem-loop molecules, by internal cleavage involving the endoribonuclease RNAse E. Concerning NrsZ functions in P. aeruginosa PAOl, this sRNA was shown to trigger the swarming motility and the rhamnolipid biosurfactants production. This regulation is due to the NrsZ-mediated activation of rhlA expression, a gene encoding for an enzyme essential for swarming motility and rhamnolipids production. Interestingly, the SL I structure of NrsZ ensures its regulatory function on rhlA expression, suggesting that the similar SLs are the functional units of this modular sRNA. However, the regulatory mechanism of action of NrsZ on rhlA expression activation remains unclear and is currently being investigated. Additionally, the NrsZ regulatory network was investigated by a transcriptome analysis, suggesting that numerous genes involved in both primary and secondary metabolism are regulated by this sRNA. To emphasize the importance of NrsZ, we investigated its conservation in other Pseudomonas species and demonstrated that NrsZ is conserved and expressed under nitrogen limitation in Pseudomonas protegens Pf-5, Pseudomonas putida KT2442, Pseudomonas entomophila L48 and Pseudomonas syringae pv. tomato DC3000, strains having different ecological features, suggesting an important role of NrsZ in the adaptation of Pseudomonads to nitrogen starvation. Interestingly the architecture of the different NrsZ homologs is similarly composed by SL structures and variant spacer sequences. However, the number of SL repetitions is not identical, and one to six SLs were predicted on the different NrsZ homologs. Moreover, NrsZ is processed in short molecules in all the strains, similarly to what was previously observed in P. aeruginosa PAOl, and the heterologous expression of the NrsZ homologs restored rhlA expression, swarming motility and rhamnolipids production in the P. aeruginosa NrsZ mutant. In many aspects, NrsZ is an atypical sRNA in the bacterial panorama. To our knowledge, NrsZ is the first described sRNA induced by the NtrB/C. Moreover, its unique modular architecture and its processing in similar short SL molecules suggest that NrsZ belongs to a novel family of bacterial sRNAs. -- L'agent pathogène opportuniste et ubiquitaire Pseudomonas aeruginosa souche PAOl est une bactérie Gram négative versatile ayant l'extraordinaire capacité de coloniser différentes niches écologiques et de causer des infections sévères et persistantes chez l'être humain. Afin d'assurer une coordination optimale des gènes impliqués dans l'utilisation de différents nutriments, cette bactérie se sert de systèmes à deux composants tel que NtrB/C et CbrA/B afin de détecter la disponibilité des ressources nutritives, puis de réguler en conséquence l'expression des gènes impliqués dans leur importation et leur catabolisme. Le système NtrB/C régule l'utilisation des sources d'azote alors que le système CbrA/B est impliqué à la fois dans l'utilisation des sources de carbone et d'azote. Ces deux systèmes activent l'expression de leurs gènes-cibles de concert avec le facteur sigma alternatif RpoN. En outre, NtrB/C et CbrA/B régulent aussi le métabolisme secondaire, contrôlant notamment la production d'importants facteurs de virulence. En plus de toutes ces régulations génétiques fines ayant lieu au niveau transcriptionnel, P. aeruginosa est aussi capable de moduler son métabolisme en se servant de petits ARNs régulateurs non-codants (ARNncs), qui régulent l'expression génétique à un niveau post- transcriptionnel par divers mécanismes sophistiqués et contribuent à rendre particulièrement rapide l'adaptation physiologique de cette bactérie. Au cours de nos recherches sur de nouveaux ARNncs dépendant du facteur sigma RpoN et impliqués dans l'adaptation nutritionnelle de P. aeruginosa PAOl, nous avons découvert NrsZ (Nitrogen regulated sRNA), un ARNnc induit par la cascade NtrB/C-RpoN en condition de carence en azote. NrsZ a une architecture unique, composée de trois structures en tige- boucle (TB I, II et III) hautement similaires et séparées par des « espaceurs » ayant des séquences variables. De plus, cet ARNnc est clivé en petits fragments correspondant au trois molécules en tige-boucle, par un processus de clivage interne impliquant l'endoribonucléase RNase E. Concernant les fonctions de NrsZ chez P. aeruginosa PAOl, cet ARNnc est capable d'induire la motilité de type « swarming » et la production de biosurfactants, nommés rhamnolipides. Cette régulation est due à l'activation par NrsZ de l'expression de rhlA, un gène essentiel pour la motilité de type swarming et pour la production de rhamnolipides. Étonnamment, la structure TB I est capable d'assurer à elle seule la fonction régulatrice de NrsZ sur l'expression de rhlA, suggérant que ces molécules TBs sont les unités fonctionnelles de cet ARNnc modulaire. Cependant, le mécanisme moléculaire par lequel NrsZ active l'expression de rhlA demeure à ce jour incertain et est actuellement à l'étude. En plus, le réseau de régulations médiées par NrsZ a été étudié par une analyse de transcriptome qui a indiqué que de nombreux gènes impliqués dans le métabolisme primaire ou secondaire seraient régulés par NrsZ. Pour accentuer l'importance de NrsZ, nous avons étudié sa conservation dans d'autres espèces de Pseudomonas. Ainsi, nous avons démontré que NrsZ est conservé et exprimé en situation de carence d'azote par les souches Pseudomonas protegens Pf-5, Pseudomonas putida KT2442, Pseudomonas entomophila L48, Pseudomonas syringae pv. tomato DC3000, quatre espèces ayant des caractéristiques écologiques très différentes, suggérant que NrsZ joue un rôle important dans l'adaptation du genre Pseudomonas envers la carence en azote. Chez toutes les souches étudiées, les différents homologues de NrsZ présentent une architecture similaire faite de TBs conservées et d'espaceurs. Cependant, le nombre de TBs n'est pas identique et peut varier de une à six copies selon la souche. Les différentes versions de NrsZ sont clivées en petites molécules dans ces quatre souches, comme il a été observé chez P. aeruginosa PAOl. De plus, l'expression hétérologue des différentes variantes de NrsZ est capable de restaurer l'expression de rhlA, la motilité swarming et la production de rhamnolipides dans une souche de P. aeruginosa dont nrsZ a été inactivé. Par bien des aspects, NrsZ est un ARNnc atypique dans le monde bactérien. À notre connaissance, NrsZ est le premier ARNnc décrit comme étant régulé par le système NtrB/C. De plus, son unique architecture modulaire et son clivage en petites molécules similaires suggèrent que NrsZ appartient à une nouvelle famille d'ARNncs bactériens.

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A maioria dos estudos relacionados à agregação do solo associa o efeito de manejos ou tipos de uso da terra ao teor de matéria orgânica. No entanto, a avaliação de microrganismos e seus processos, feita diretamente em estruturas indeformadas do solo, permite maior entendimento do real efeito de diferentes tipos de manejos exercidos sobre esse. Assim, o objetivo deste trabalho foi avaliar modificações impostas por diferentes tipos de uso da terra (pastagem, mata de eucalipto, mata com araucária, plantio convencional com cenoura e plantio convencional com abóbora) em atributos químicos (pH, Ca, Mg, Al, P, K, S e matéria orgânica) e físicos (diâmetro médio geométrico - DMG, diâmetro médio ponderado - DMP, densidade do solo e densidade de partículas) e na qualidade microbiana (atividade e carbono microbianos, micélio extrarradicular total de fungos micorrízicos arbusculares e quociente metabólico - qCO2) de classes de tamanho de agregados (I- 4,00 a 2,36 mm; II- 2,36 a 1,18 mm; III- 1,18 a 0,60 mm; IV- 0,60 a 0,30 mm; e V- 0,30 a 0,15 mm) de um Latossolo Vermelho-Amarelo, no sul de Minas Gerais. Os resultados evidenciaram que os tipos de uso da terra interferem na formação, no tamanho e na qualidade microbiana dos agregados. Em agregados menores (classes IV e V), há redução de micélio extrarradicular de fungos e biomassa microbiana e aumento da atividade e do quociente metabólico, independentemente do tipo de uso da terra. A qualidade microbiana de agregados maiores do solo sob mata de araucária, com tamanho entre 0,60 e 4,00 mm (I, II e III), é semelhante a todas as classes de tamanho de agregados do solo sob mata de eucalipto, enquanto a de agregados menores de 0,60 mm (IV e V) é semelhante a todas de tamanho de agregados da pastagem. Agregados do cultivo convencional, diferentemente dos demais tipos de uso da terra, apresentam baixa qualidade microbiana e relação com a fertilidade do solo.

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A identificação de padrões de variabilidade dos atributos do solo permite o uso e a ocupação do solo de maneira sustentável. O objetivo deste trabalho foi delimitar áreas de manejo específico utilizando ferramentas matemáticas, suscetibilidade magnética e modelos de paisagem. A área de estudo localiza-se no município de Guariba, SP. Escolheu-se uma área de 110 ha, onde foram identificadas e mapeadas três superfícies geomórficas (I, II e III). Na área, foram coletadas 204 amostras de solo em uma transeção, nas profundidades de 0,00-0,20 e 0,60-0,80 m. Foram determinados o pH em CaCl2, os teores de areia, argila, matéria orgânica, P, Ca, Mg, K, H+Al, e calculados SB, CTC e V. A suscetibilidade magnética (SM) foi medida com o auxílio de uma balança analítica. Os limites matemáticos da técnica Split Moving Windows Dissimilarity Analysis (SMWDA) utilizando as informações da suscetibilidade magnética ficaram próximos aos limites de campo identificados com base nos modelos de paisagem. A utilização conjunta da suscetibilidade magnética, dos modelos matemáticos e de paisagem permitiu identificar diferentes áreas de manejo, locais com diferentes teores de argila e níveis de fertilidade do solo. A susceptibilidade magnética pode ser adotada como alternativa para identificar e mapear unidades de manejo.

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Because of low incidence, mixed study populations and paucity of clinical and histological data, the management of adult brainstem gliomas (BSGs) remains non-standardized. We here describe characteristics, treatment and outcome of patients with exclusively histologically confirmed adult BSGs. A retrospective chart review of adults (age >18 years) was conducted. BSG was defined as a glial tumor located in the midbrain, pons or medulla. Characteristics, management and outcome were analyzed. Twenty one patients (17 males; median age 41 years) were diagnosed between 2004 and 2012 by biopsy (n = 15), partial (n = 4) or complete resection (n = 2). Diagnoses were glioblastoma (WHO grade IV, n = 6), anaplastic astrocytoma (WHO grade III, n = 7), diffuse astrocytoma (WHO grade II, n = 6) and pilocytic astrocytoma (WHO grade I, n = 2). Diffuse gliomas were mainly located in the pons and frequently showed MRI contrast enhancement. Endophytic growth was common (16 vs. 5). Postoperative therapy in low-grade (WHO grade I/II) and high-grade gliomas (WHO grade III/IV) consisted of radiotherapy alone (three in each group), radiochemotherapy (2 vs. 6), chemotherapy alone (0 vs. 2) or no postoperative therapy (3 vs. 1). Median PFS (24.1 vs. 5.8 months; log-rank, p = 0.009) and mOS (30.5 vs. 11.5 months; log-rank, p = 0.028) was significantly better in WHO grade II than in WHO grade III/IV tumors. Second-line therapy considerably varied. Histologically verification of adult BSGs is feasible and has an impact on postoperative treatment. Low-grade gliomas can simple be followed or treated with radiotherapy alone. Radiochemotherapy with temozolomide can safely be prescribed for high-grade gliomas without additional CNS toxicities.

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New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

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BACKGROUND: While the assessment of analytical precision within medical laboratories has received much attention in scientific enquiry, the degree of as well as the sources causing variation between them remains incompletely understood. In this study, we quantified the variance components when performing coagulation tests with identical analytical platforms in different laboratories and computed intraclass correlations coefficients (ICC) for each coagulation test. METHODS: Data from eight laboratories measuring fibrinogen twice in twenty healthy subjects with one out of 3 different platforms and single measurements of prothrombin time (PT), and coagulation factors II, V, VII, VIII, IX, X, XI and XIII were analysed. By platform, the variance components of (i) the subjects, (ii) the laboratory and the technician and (iii) the total variance were obtained for fibrinogen as well as (i) and (iii) for the remaining factors using ANOVA. RESULTS: The variability for fibrinogen measurements within a laboratory ranged from 0.02 to 0.04, the variability between laboratories ranged from 0.006 to 0.097. The ICC for fibrinogen ranged from 0.37 to 0.66 and from 0.19 to 0.80 for PT between the platforms. For the remaining factors the ICC's ranged from 0.04 (FII) to 0.93 (FVIII). CONCLUSIONS: Variance components that could be attributed to technicians or laboratory procedures were substantial, led to disappointingly low intraclass correlation coefficients for several factors and were pronounced for some of the platforms. Our findings call for sustained efforts to raise the level of standardization of structures and procedures involved in the quantification of coagulation factors.

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New economic geography models show that there may be a strong relationship between economic integration and the geographical concentration of industries. Nevertheless, this relationship is neither unique nor stable, and may follow a ?-shaped pattern in the long term. The aim of the present paper is to analyze the evolution of the geographical concentration of manufacturing across Spanish regions during the period 1856-1995. We construct several geographical concentration indices for different points in time over these 140 years. The analysis is carried out at two levels of aggregation, in regions corresponding to the NUTS-II and NUTS-III classifications. We confirm that the process of economic integration stimulated the geographical concentration of industrial activity. Nevertheless, the localization coefficients only started to fall after the beginning of the integration of the Spanish Economy into the international markets in the mid-70s, and this new path was not interrupted by Spain¿s entry in the European Union some years later

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Num período de dez anos (1980 a 1989), foi conduzido, na Embrapa-Centro Nacional de Pesquisa de Trigo (CNPT), em Passo Fundo, RS, experimento reunindo quatro sistemas de rotação de culturas para trigo (Triticum aestivum L.): sistema I (trigo/soja); sistema II (trigo/soja, colza/soja, cevada/soja e tremoço ou serradela/milho); sistema III (trigo/soja, trevo vesiculoso/trevo vesiculoso, trevo vesiculoso/milho, de 1980 a 1983, e trigo/soja, aveia branca/soja e ervilhaca/milho, de 1984 a 1989); e sistema IV (trigo/soja, colza/soja, linho/soja e tremoço ou serradela/milho). Utilizou-se o delineamento de blocos ao acaso, com quatro repetições e parcelas com área útil de 120 m². No presente trabalho, mostra-se a análise de risco naquele período. Foram aplicados dois tipos de análise na receita líquida dos sistemas: análise da média variância e análise de risco (distribuição de probabilidade acumulada e dominância estocástica). Pela análise da média variância da receita líquida, os sistemas II e IV foram superiores aos sistemas I e III. Pelo método da dominância estocástica, o sistema II apresentou- se como a melhor alternativa de produção a ser oferecida aos agricultores, do ponto de vista de lucratividade e menor risco.

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Foram estimadas repetibilidades (r) e herdabilidades (h²) de características reprodutivas de três populações de galinhas para corte do Setor de Aves da ESALQ/USP Piracicaba, SP. Cento e quinze galinhas foram inseminadas segundo um esquema hierárquico, com sêmen de 23 galos amostrados das populações I, II e III no experimento E1 e de outros 23 galos no experimento E2. Foram utilizadas quatro incubações, ou blocos, em cada experimento. Estimativas de r e h² foram obtidas dentro de experimento, pela análise de variância de médias de galinha em cada incubação. As estimativas de r da produção de ovos (POST) foram significativas (P<0,01) e iguais a 0,19±0,05 e 0,32±0,04 nos experimentos E1 e E2, respectivamente. Quanto a eclodibilidade (ECLOD), as h² estimadas de componentes de variância de galos foram 0,14±0,14 no E1 (P>0,05) e 0,26±0,17 no E2 (P<0,05). No tocante a nascimento de pintos (NASC), as h² estimadas (P<0,05) foram 0,18±0,15 (E1) e 0,26±0,17 (E2). No entanto, h² estimadas com base em componentes de fêmea foram significativas (P<0,01) e maiores: no tocante a ECLOD, as estimativas foram 0,77±0,09 e 0,48±0,20 no experimento E1 e E2, respectivamente, e 0,58±0,21 e 0,48±0,20 quanto a nascimento (NASC). Os resultados confirmam que ECLOD e NASC apresentam variabilidade genética aditiva baixa.