Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p

Prognostic value of histopathologic traits independent of stromal tumor-infiltrating lymphocyte levels in chemotherapy-naïve patients with triple-negative breast cancer

Background: In the absence of prognostic biomarkers, most patients with early-stage triple-negative breast cancer (eTNBC) are treated with combination chemotherapy. The identification of biomarkers to select patients for whom treatment de-escalation or escalation could be considered remains an unmet need. We evaluated the prognostic value of histopathologic traits in a unique cohort of young, (neo)adjuvant chemotherapy-naïve patients with early-stage (stage I or II), node-negative TNBC and long-term follow-up, in relation to stromal tumor-infiltrating lymphocytes (sTILs) for which the prognostic value was recently reported. Materials and methods: We studied all 485 patients with node-negative eTNBC from the population-based PARADIGM cohort which selected women aged &lt;40 years diagnosed between 1989 and 2000. None of the patients had received (neo)adjuvant chemotherapy according to standard practice at the time. Associations between histopathologic traits and breast cancer-specific survival (BCSS) were analyzed with Cox proportional hazard models. Results: With a median follow-up of 20.0 years, an independent prognostic value for BCSS was observed for lymphovascular invasion (LVI) [adjusted (adj.) hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.49-3.69], fibrotic focus (adj. HR 1.61, 95% CI 1.09-2.37) and sTILs (per 10% increment adj. HR 0.75, 95% CI 0.69-0.82). In the sTILs &lt;30% subgroup, the presence of LVI resulted in a higher cumulative incidence of breast cancer death (at 20 years, 58%; 95% CI 41% to 72%) compared with when LVI was absent (at 20 years, 32%; 95% CI 26% to 39%). In the ≥75% sTILs subgroup, the presence of LVI might be associated with poor survival (HR 11.45, 95% CI 0.71-182.36, two deaths). We confirm the lack of prognostic value of androgen receptor expression and human epidermal growth factor receptor 2 -low status. Conclusions: sTILs, LVI and fibrotic focus provide independent prognostic information in young women with node-negative eTNBC. Our results are of importance for the selection of patients for de-escalation and escalation trials.</p

Impact of global warming on beef cattle production cost in Brazil

Global warming is affecting agribusiness in its economic aspects. Therefore, the prediction of the evolution of Brazilian beef cattle production cost was made using the IPCC forecast scenario for global warming. The methodology consisted of two steps: (i) the development of a fuzzy model that estimated the grazing land capacity (RP) decrease risk as a function of the changes in the average total rain index, air temperature and increase in extension of the dry season; and (ii) the design of an algorithm for predicting the decrease in production as function of the RPfuzzy model, that results in the impact in beef cattle productivity, and consequent increase in production costs. Historical environmental data from important producing counties in the Cerrado were organized and a set of fuzzy Gaussian functions were developed, and three possible settings (optimistic, medium and pessimistic) were considered. The decrease in beef cattle productivity was estimated using the losses in production due to the increase in air temperature and vulnerability of pasture capacity. The boundary settings for the total increase of production cost scenario used the number of animals per area of grazing land, the adoption of grain supplement and its future scenario; and the result output function pointed to a threshold within a variation from an increase in production cost of 80% (optimistic) to 160% (pessimistic). Under the optimistic scenario the total cost of Brazilian beef cattle production in the Cerrado became near to US$2.88 kg-1, while in the pessimistic scenario this cost reached US$ 4.16 kg-1, challenging the international competitiveness of this economic segment.O aquecimento global afeta o agronegócio em seus aspectos econômicos. Foi feita previsão daevolução do custo de produção de carne bovina brasileira usando a predição de aquecimento global do IPCC. A metodologia consistiu de duas etapas: (i) o desenvolvimento de modelo fuzzy que estimou o risco de decréscimo da capacidade de pastagens (RP) em função das mudanças no índice pluviométrico total, na temperatura do ar e na extensão da estação de seca; e (ii) o desenvolvimento de um algoritmo para predição do decréscimo da produção em função de um modelo fuzzy de RP que resulte no impacto na produtividade bovina de corte e conseqüente aumento no custo de produção. Foram organizados os dados históricos de fatores ambientais dos municípios importante produção no Cerrado e um conjunto de funções Gaussianas fuzzy foi desenvolvido e três estimativas possíveis (otimista, média e negativa) foram consideradas. O decréscimo na produtividade do gado foi estimado usando as perdas de produção devido ao acréscimo da temperatura bem como da vulnerabilidade da capacidade de pastagem. O estabelecimento dos limites para o cenário do acréscimo do custo de produção usou o número de unidade animal por área de pastagem, a adoção de suplemento de grãos e o cenário de produção futura; e o resultado da função de saída apontou para uma variação do acréscimo do custo de produção de 80% (otimista) até 160% (pessimista). Sob o cenário otimista, o custo total da produção brasileira de carne bovina no Cerrado chega a US$2,88 kg-1, enquanto no cenário pessimista este custo pode atingir US$ 4,16 kg-1, o que pode comprometer a competitividade internacional do setor

Broilers' Toes Asymmetry And Walking Ability Assesment [assimetria Dos Pés De Frangos De Corte E Medida De Habilidade Locomotora]

Economy due to its technological advancement, which associated to the development of genetic strains of high growth may cause deviation in the growth rate and harm production. Morphological asymmetry has been pointed as an indicator of welfare, as maintained the pattern that leads to balance, the broiler chicken would have its normal locomotion characteristics, freely reaching water and feed. Thus, the objective of this research was to verify the possibility of using morphological asymmetry for evaluating walking ability of broiler chicken. The research was done in the Technology Center, at UNICAMP. The experiment was made using biomechanics analysis and following, the toes were measured. Results found did not show asymmetry useful for determining the locomotion ability of broiler chicken. New studies are recommended in order to search for other correlations that might help to estimate at field level, the locomotion difficulties of broiler chicken.294538546Bizeray, D., Faure, J.M., Leterrier, C., Faire marcher lê poulet: pourquoi et comment (2004) INRA Producion Animale, 17 (1), pp. 45-57. , MontpellierBizeray, D., Laterrier, C., Constantin, P., Picard, M., Faure, J.M., Early locomotor behaviour in genetic stocks of chickens with different growth rates (2000) Applied Animal Behaviour Science, 68 (2), pp. 231-242. , BristolBokkers, E.A.M., Koene, P., Behaviour of fast and slow growing broilers to 12 weeks of age and the physical consequences (2003) Applied Animal Behaviour Science, 81 (2), pp. 59-72. , BristolBroom, D.M., Behaviour and welfare in relation to pathology (2006) Applied Animal Behaviour Science, 97 (1), pp. 73-83. , BristolCarvalho, R.R., Bucklin, R.A., Shearer, J.K., Shearer, L., Effects of trimming on dairy cattle hoof weight bearing and pressure distributions during the stance phase (2005) Transactions of the ASAE, 48 (4), pp. 1.653-1.659. , St. JosephCoor, S.A., McCorquodale, C.C., Gentle, M.J., Gait analysis of poultry (1998) Research in Veterinary Science, 65 (1), pp. 233-238. , SaskatoonDawkins, M.S., Donnelly, C.A., Jones, T.A., Chicken welfare is influenced more by housing conditions than by stocking density (2004) Nature, 427 (6972), pp. 342-344. , CambridgeDongen, S.V., Molenberghs, G., Matthysen, E., The statistical analysis of fluctuating asymmetry: REML estimation of a mixed regression model (1999) Journal of Evolution Biology, 12 (2), pp. 94-102. , BaselHall, A.L., The effect of stocking density on the welfare and behaviour of broiler chickens reared commercially (2001) Animal Welfare, 10 (2), pp. 23-40. , EdinburghKestin, S.C., Knowles, T.G., Tinch, A.E., Gregory, G., Prevalence of leg weakness in broiler chickens and its relationship with genotype (1992) Veterinary Record, 2 (131), pp. 190-194. , LondonKestin, S.C., Su, G., Sorensen, P., Different commercial broiler crosses have different susceptibilities to leg weakness (1999) Poultry Science, 78 (8), pp. 1.085-1.090. , SavoyKnierim, U., Dongen, S.V., Forkman, B., Tuyttens, F.A.M., Spinka, M., Campo, J.L., Weissengruber, G.E., Fluctuating asymmetry as an animal welfare indicator - A review of methodology and validity (2007) Physiology & Behavior, 92 (2), pp. 398-421. , Tarrytown(2006), MINITAB Inc. Minitab 15.1.0.0. State College: Minitab IncMoller, A., Manning, J., Growth and developmental instability (2003) The Veterinary Journal, 166 (1), pp. 19-27. , Amsterdamvan Nuffel, A., van Poucke, E., van Dongen, S., Lens, L., Tuyttens, F.A.M., Measuring fluctuating asymmetry in broilers, p. 2008. , http://www.ilvo.vlaanderen.be/documents/fluctasbroilers.pdf, Disponível em, Acesso em: 10 junvan Nuffel, A., Tuyttens, F.A.M., van Dongen, S., Talloen, W.E., van Poucke, E., Sonck, B., Lens, L., Fluctuating asymmetry in broiler chickens: A decision protocol for trait selection in seven measuring methods (2007) Poultry Science, 86 (3), pp. 2.555-2.568. , SavoyOviedo-Rondón, E.O., (2008) Predisposing factors that affect walking ability in turkeys and broilers, , http://www.ces.ncsu.edu/depts/poulsci/conference_proceedings/nutrition_c onference/2007/oviedo_2007.pdf, Disponível em, Acesso em: 12 maiovan Poucke, E., van Nuffel, A., van Dongen, S., Sonck, B., Lens, L., Tuyttens, F.A.M., Experimental stress does not increase fluctuating asymmetry of broiler chickens at slaughter age (2007) Poultry Science, 86 (10), pp. 2.110-2.116. , LangfordReiter, K., Kutriz, B., Behavior and leg weakness in different broiler breeds (2001) Archiv fur Geflügelkunde, 65 (2), pp. 137-141. , BerlinSanotra, G., Anotra, S., Damkjer, J., Lund, J., Vestergaard, K.S., Influence of light-dark schedules and stocking density on behaviour, risk of leg problems and occurrence of chronic fear in broilers (2002) British Poultry Science, 43 (3), pp. 344-354. , LondonSorensen, P., Su, G., Kestin, S.C., Effects of age and stocking density on leg weakness in broiler chickens (2000) Poultry Science, 79 (6), pp. 864-870. , SavoyTuyttens, F.A.M., Measures of developmental instability as integrated, a-posteriori indicators of farm animal welfare: a review (2003) Animal Welfare, 12 (10), pp. 535-540. , South MimmosWeeks, C.A., Danbury, T.D., Davies, H.C., Hunt, P., Kestin, S.C., The behaviour of broiler chickens and its modification by lameness (2000) Applied Animal Behaviour Science, 67 (1-2), pp. 111-125. , Bristo

Cell Cytoskeleton and Tether Extraction

We perform a detailed investigation of the force × deformation curve in tether extraction from 3T3 cells by optical tweezers. Contrary to conventional wisdom about tethers extracted from cells, we find that actin filaments are present within them, so that a revised theory of tether pulling from cells is called for. We also measure steady and maximum tether force values significantly higher than previously published ones for 3T3 cells. Possible explanations for these differences are investigated. Further experimental support of the theory of force barriers for membrane tube extension is obtained. The potential of studies on tether pulling force × deformation for retrieving information on membrane-cytoskeleton interaction is emphasized