Análisis de elementos viga-columna en régimen no lineal con deformación por cortante

El hormigón estructural sigue siendo sin duda uno de los materiales más utilizados en construcción debido a su resistencia, rigidez y flexibilidad para diseñar estructuras. El cálculo de estructuras de hormigón, utilizando vigas y vigas-columna, es complejo debido a los fenómenos de acoplamiento entre esfuerzos y al comportamiento no lineal del material. Los modelos más empleados para su análisis son el de Bernoulli-Euler y el de Timoshenko, indicándose en la literatura la conveniencia de usar el segundo cuando la relación canto/luz no es pequeña o los elementos están fuertemente armados. El objetivo fundamental de esta tesis es el análisis de elementos viga y viga-columna en régimen no lineal con deformación por cortante, aplicando el concepto de Pieza Lineal Equivalente (PLE). Concepto éste que consiste básicamente en resolver el problema de una pieza en régimen no lineal, transformándolo en uno lineal equivalente, de modo que ambas piezas tengan la misma deformada y los mismos esfuerzos. Para ello, se hizo en primer lugar un estudio comparado de: las distintas propuestas que aplican la deformación por cortante, de los distintos modelos constitutivos y seccionales del hormigón estructural y de los métodos de cálculo no lineal aplicando el método de elementos finitos (MEF). Teniendo en cuenta que la resolución del problema no lineal se basa en la resolución de sucesivos problemas lineales empleando un proceso de homotopía, los problemas lineales de la viga y viga-columna de Timoshenko, se resuelven mediante MEF, utilizando soluciones nodalmente exactas (SNE) y acción repartida equivalente de cualquier orden. Se obtiene así, con muy pocos elementos finitos, una excelente aproximación de la solución, no sólo en los nodos sino en el interior de los elementos. Se introduce el concepto PLE para el análisis de una barra, de material no lineal, sometida a acciones axiales, y se extiende el mismo para el análisis no lineal de vigas y vigas-columna con deformación por cortante. Cabe señalar que para estos últimos, la solución de una pieza en régimen no lineal es igual a la de una en régimen lineal, cuyas rigideces son constantes a trozos, y donde además hay que añadir momentos y cargas puntuales ficticias en los nodos, así como, un momento distribuido ficticio en toda la pieza. Se han desarrollado dos métodos para el análisis: uno para problemas isostáticos y otro general, aplicable tanto a problemas isostáticos como hiperestáticos. El primero determina de entrada la PLE, realizándose a continuación el cálculo por MEF-SNE de dicha pieza, que ahora está en régimen lineal. El general utiliza una homotopía que transforma de manera iterativa, unas leyes constitutivas lineales en las leyes no lineales del material. Cuando se combina con el MEF, la pieza lineal equivalente y la solución del problema original quedan determinadas al final de todo el proceso. Si bien el método general es un procedimiento próximo al de Newton- Raphson, presenta sobre éste la ventaja de permitir visualizar las deformaciones de la pieza en régimen no lineal, de manera tanto cualitativa como cuantitativa, ya que es posible observar en cada paso del proceso la modificación de rigideces (a flexión y cortante) y asimismo la evolución de las acciones ficticias. Por otra parte, los resultados obtenidos comparados con los publicados en la literatura, indican que el concepto PLE ofrece una forma directa y eficiente para analizar con muy buena precisión los problemas asociados a vigas y vigas-columna en las que por su tipología los efectos del cortante no pueden ser despreciados. ABSTRACT The structural concrete clearly remains the most used material in construction due to its strength, rigidity and structural design flexibility. The calculation of concrete structures using beams and beam-column is complex as consequence of the coupling phenomena between stresses and of its nonlinear behaviour. The models most commonly used for analysis are the Bernoulli-Euler and Timoshenko. The second model is strongly recommended when the relationship thickness/span is not small or in case the elements are heavily reinforced. The main objective of this thesis is to analyse the beam and beam-column elements with shear deformation in nonlinear regime, applying the concept of Equivalent Linear Structural Element (ELSE). This concept is basically to solve the problem of a structural element in nonlinear regime, transforming it into an equivalent linear structural element, so that both elements have the same deformations and the same stresses. Firstly, a comparative study of the various proposals of applying shear deformation, of various constitutive and sectional models of structural concrete, and of the nonlinear calculation methods (using finite element methods) was carried out. Considering that the resolution of nonlinear problem is based on solving the successive linear problem, using homotopy process, the linear problem of Timoshenko beam and beam-columns is resolved by FEM, using the exact nodal solutions (ENS) and equivalent distributed load of any order. Thus, the accurate solution approximation can be obtained with very few finite elements for not only nodes, but also for inside of elements. The concept ELSE is introduced to analyse a bar of nonlinear material, subjected to axial forces. The same bar is then used for other nonlinear beam and beam-column analysis with shear deformation. It is noted that, for the last analyses, the solution of a structural element in nonlinear regime is equal to that of linear regime, in which the piecewise-stiffness is constant, the moments and fictitious point loads need to be added at nodes of each element, as well as the fictitious distributed moment on element. Two methods have been developed for analysis: one for isostatic problem and other more general, applicable for both isostatic and hiperstatic problem. The first method determines the ELSE, and then the calculation of this piece is performed by FEM-ENS that now is in linear regime. The general method uses the homotopy that transforms iteratively linear constitutive laws into nonlinear laws of material. When combined with FEM, the ELSE and the solution of the original problem are determined at the end of the whole process. The general method is well known as a procedure closed to Newton-Raphson procedure but presents an advantage that allows displaying deformations of the piece in nonlinear regime, in both qualitative and quantitative way. Since it is possible to observe the modification of stiffness (flexural and shear) in each step of process and also the evolution of the fictitious actions. Moreover, the results compared with those published in the literature indicate that the ELSE concept offers a direct and efficient way to analyze with very good accuracy the problems associated with beams and beams columns in which, by typology, the effects of shear cannot be neglected.

Exploring strategic farming choices to respond to mitigation and adaptation to climate change

Las alteraciones del sistema climático debido al aumento de concentraciones de gases de efecto invernadero (GEI) en la atmósfera, tendrán implicaciones importantes para la agricultura, el medio ambiente y la sociedad. La agricultura es una fuente importante de emisiones de gases de efecto invernadero (globalmente contribuye al 12% del total de GEI), y al mismo tiempo puede ser parte de la solución para mitigar las emisiones y adaptarse al cambio climático. Las acciones frente al desafío del cambio climático deben priorizar estrategias de adaptación y mitigación en la agricultura dentro de la agenda para el desarrollo de políticas. La agricultura es por tanto crucial para la conservación y el uso sostenible de los recursos naturales, que ya están sometidos a impactos del cambio climático, al mismo tiempo que debe suministrar alimentos para una población creciente. Por tanto, es necesaria una coordinación entre las actuales estrategias de política climática y agrícola. El concepto de agricultura climáticamente inteligente ha surgido para integrar todos estos servicios de la producción agraria. Al evaluar opciones para reducir las amenazas del cambio climático para la agricultura y el medio ambiente, surgen dos preguntas de investigación: • ¿Qué información es necesaria para definir prácticas agrarias inteligentes? • ¿Qué factores influyen en la implementación de las prácticas agrarias inteligentes? Esta Tesis trata de proporcionar información relevante sobre estas cuestiones generales con el fin de apoyar el desarrollo de la política climática. Se centra en sistemas agrícolas Mediterráneos. Esta Tesis integra diferentes métodos y herramientas para evaluar las alternativas de gestión agrícola y políticas con potencial para responder a las necesidades de mitigación y adaptación al cambio climático. La investigación incluye enfoques cuantitativos y cualitativos e integra variables agronómicas, de clima y socioeconómicas a escala local y regional. La investigación aporta una recopilación de datos sobre evidencia experimental existente, y un estudio integrado sobre el comportamiento de los agricultores y las posibles alternativas de cambio (por ejemplo, la tecnología, la gestión agrícola y la política climática). Los casos de estudio de esta Tesis - el humedal de Doñana (S España) y la región de Aragón (NE España) - permiten ilustrar dos sistemas Mediterráneos representativos, donde el uso intensivo de la agricultura y las condiciones semiáridas son ya una preocupación. Por este motivo, la adopción de estrategias de mitigación y adaptación puede desempeñar un papel muy importante a la hora de encontrar un equilibrio entre la equidad, la seguridad económica y el medio ambiente en los escenarios de cambio climático. La metodología multidisciplinar de esta tesis incluye una amplia gama de enfoques y métodos para la recopilación y el análisis de datos. La toma de datos se apoya en la revisión bibliográfica de evidencia experimental, bases de datos públicas nacionales e internacionales y datos primarios recopilados mediante entrevistas semi-estructuradas con los grupos de interés (administraciones públicas, responsables políticos, asesores agrícolas, científicos y agricultores) y encuestas con agricultores. Los métodos de análisis incluyen: meta-análisis, modelos de gestión de recursos hídricos (modelo WAAPA), análisis multicriterio para la toma de decisiones, métodos estadísticos (modelos de regresión logística y de Poisson) y herramientas para el desarrollo de políticas basadas en la ciencia. El meta-análisis identifica los umbrales críticos de temperatura que repercuten en el crecimiento y el desarrollo de los tres cultivos principales para la seguridad alimentaria (arroz, maíz y trigo). El modelo WAAPA evalúa el efecto del cambio climático en la gestión del agua para la agricultura de acuerdo a diferentes alternativas políticas y escenarios climáticos. El análisis multicriterio evalúa la viabilidad de las prácticas agrícolas de mitigación en dos escenarios climáticos de acuerdo a la percepción de diferentes expertos. Los métodos estadísticos analizan los determinantes y las barreras para la adopción de prácticas agrícolas de mitigación. Las herramientas para el desarrollo de políticas basadas en la ciencia muestran el potencial y el coste para reducir GEI mediante las prácticas agrícolas. En general, los resultados de esta Tesis proporcionan información sobre la adaptación y la mitigación del cambio climático a nivel de explotación para desarrollar una política climática más integrada y ayudar a los agricultores en la toma de decisiones. Los resultados muestran las temperaturas umbral y la respuesta del arroz, el maíz y el trigo a temperaturas extremas, siendo estos valores de gran utilidad para futuros estudios de impacto y adaptación. Los resultados obtenidos también aportan una serie de estrategias flexibles para la adaptación y la mitigación a escala local, proporcionando a su vez una mejor comprensión sobre las barreras y los incentivos para su adopción. La capacidad de mejorar la disponibilidad de agua y el potencial y el coste de reducción de GEI se han estimado para estas estrategias en los casos de estudio. Estos resultados podrían ayudar en el desarrollo de planes locales de adaptación y políticas regionales de mitigación, especialmente en las regiones Mediterráneas. ABSTRACT Alterations in the climatic system due to increased atmospheric concentrations of greenhouse gas emissions (GHG) are expected to have important implications for agriculture, the environment and society. Agriculture is an important source of GHG emissions (12 % of global anthropogenic GHG), but it is also part of the solution to mitigate emissions and to adapt to climate change. Responses to face the challenge of climate change should place agricultural adaptation and mitigation strategies at the heart of the climate change agenda. Agriculture is crucial for the conservation and sustainable use of natural resources, which already stand under pressure due to climate change impacts, increased population, pollution and fragmented and uncoordinated climate policy strategies. The concept of climate smart agriculture has emerged to encompass all these issues as a whole. When assessing choices aimed at reducing threats to agriculture and the environment under climate change, two research questions arise: • What information defines smart farming choices? • What drives the implementation of smart farming choices? This Thesis aims to provide information on these broad questions in order to support climate policy development focusing in some Mediterranean agricultural systems. This Thesis integrates methods and tools to evaluate potential farming and policy choices to respond to mitigation and adaptation to climate change. The assessment involves both quantitative and qualitative approaches and integrates agronomic, climate and socioeconomic variables at local and regional scale. The assessment includes the collection of data on previous experimental evidence, and the integration of farmer behaviour and policy choices (e.g., technology, agricultural management and climate policy). The case study areas -- the Doñana coastal wetland (S Spain) and the Aragón region (NE Spain) – illustrate two representative Mediterranean regions where the intensive use of agriculture and the semi-arid conditions are already a concern. Thus the adoption of mitigation and adaptation measures can play a significant role for reaching a balance among equity, economic security and the environment under climate change scenarios. The multidisciplinary methodology of this Thesis includes a wide range of approaches for collecting and analysing data. The data collection process include revision of existing experimental evidence, public databases and the contribution of primary data gathering by semi-structured interviews with relevant stakeholders (i.e., public administrations, policy makers, agricultural advisors, scientist and farmers among others) and surveys given to farmers. The analytical methods include meta-analysis, water availability models (WAAPA model), decision making analysis (MCA, multi-criteria analysis), statistical approaches (Logistic and Poisson regression models) and science-base policy tools (MACC, marginal abatement cost curves and SOC abatement wedges). The meta-analysis identifies the critical temperature thresholds which impact on the growth and development of three major crops (i.e., rice, maize and wheat). The WAAPA model assesses the effect of climate change for agricultural water management under different policy choices and climate scenarios. The multi-criteria analysis evaluates the feasibility of mitigation farming practices under two climate scenarios according to the expert views. The statistical approaches analyses the drivers and the barriers for the adoption of mitigation farming practices. The science-base policy tools illustrate the mitigation potential and cost effectiveness of the farming practices. Overall, the results of this Thesis provide information to adapt to, and mitigate of, climate change at farm level to support the development of a comprehensive climate policy and to assist farmers. The findings show the key temperature thresholds and response to extreme temperature effects for rice, maize and wheat, so such responses can be included into crop impact and adaptation models. A portfolio of flexible adaptation and mitigation choices at local scale are identified. The results also provide a better understanding of the stakeholders oppose or support to adopt the choices which could be used to incorporate in local adaptation plans and mitigation regional policy. The findings include estimations for the farming and policy choices on the capacity to improve water supply reliability, abatement potential and cost-effective in Mediterranean regions.

KDIGO-based acute kidney injury criteria operate differently in hospitals and the community—findings from a large population cohort

ACKNOWLEDGEMENTS We acknowledge the data management support of Grampian Data Safe Haven (DaSH) and the associated financial support of NHS Research Scotland, through NHS Grampian investment in the Grampian DaSH. S.S. is supported by a Clinical Research Training Fellowship from the Wellcome Trust (Ref 102729/Z/13/Z). We also acknowledge the support from The Farr Institute of Health Informatics Research. The Farr Institute is supported by a 10-funder consortium: Arthritis Research UK, the British Heart Foundation, Cancer Research UK, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the Medical Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates) and the Wellcome Trust (MRC Grant Nos: Scotland MR/K007017/1).

A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers

BRCA1 and BRCA2 carriers are at increased risk for both breast and ovarian cancer, but estimates of lifetime risk vary widely, suggesting their penetrance is modified by other genetic and/or environmental factors. The BRCA1 and BRCA2 proteins function in DNA repair in conjunction with RAD51. A preliminary report suggested that a single nucleotide polymorphism in the 5′ untranslated region of RAD51 (135C/G) increases breast cancer risk in BRCA1 and BRCA2 carriers. To investigate this effect we studied 257 female Ashkenazi Jewish carriers of one of the common BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) mutations. Of this group, 164 were affected with breast and/or ovarian cancer and 93 were unaffected. RAD51 genotyping was performed on all subjects. Among BRCA1 carriers, RAD51-135C frequency was similar in healthy and affected women [6.1% (3 of 49) and 9.9% (12 of 121), respectively], and RAD-135C did not influence age of cancer diagnosis [Hazard ratio (HR) = 1.18 for disease in RAD51-135C heterozygotes, not significant]. However, in BRCA2 carriers, RAD51-135C heterozygote frequency in affected women was 17.4% (8 of 46) compared with 4.9% (2 of 41) in unaffected women (P = 0.07). Survival analysis in BRCA2 carriers showed RAD51-135C increased risk of breast and/or ovarian cancer with an HR of 4.0 [95% confidence interval 1.6–9.8, P = 0.003]. This effect was largely due to increased breast cancer risk with an HR of 3.46 (95% confidence interval 1.3–9.2, P = 0.01) for breast cancer in BRCA2 carriers who were RAD51-135C heterozygotes. RAD51 status did not affect ovarian cancer risk. These results show RAD51-135C is a clinically significant modifier of BRCA2 penetrance, specifically in raising breast cancer risk at younger ages.

Estado nutricional aos 20 anos como fator de risco para incidência precoce de doenças crônicas não transmissíveis entre adultos de 30 a 49 anos

Introdução: O excesso de peso em adultos jovens está associado ao desenvolvimento de doenças crônicas não transmissíveis (DCNT) e à diminuição da qualidade de vida e ao aumento da mortalidade precoce. A transição da adolescência para a fase adulta é o período de maior risco para a incidência da obesidade. Objetivo: Estimar o efeito o índice de massa corpora (IMC) aos 20 anos sobre a incidência de DCNT em adultos brasileiros com idade entre 30 a 49 anos. Métodos: Foram selecionados 12.079 indivíduos de 30 a 49 anos da Pesquisa Nacional de Saúde (PNS), realizada no ano de 2013. O modelo adotado para determinação das DCNT foi aquele proposto pela Organização Mundial de Saúde. A incidência das DCNT (hipertensão, doenças cardiovasculares, diabetes e câncer, entre outras), informada pela data do diagnóstico, foi modelada como função do IMC aos 20 anos. Os indivíduos sem a doença até o presente foram considerados como censura. As estimativas de sobrevida foram calculadas com o método de Kaplan-Meier (KM) para cada uma das doenças, estratificada por sexo e ajustada por escolaridade. A análise dos fatores de risco para as doenças foi feita utilizando-se o modelo de riscos proporcionais de Cox. Resultados: Nas curvas de sobrevida KM, indivíduos com IMC >=25kg/m² apresentaram incidência mais elevada e precoce de DCNT, principalmente hipertensão, diabetes e depressão. A idade mediana para incidência do diabetes em obesos foi de 47 anos para homens e 48 anos para mulheres. A incidência da hipertensão arterial foi 4,2 por mil com sobrevida mediana de 48 e 44 anos em mulheres com excesso de peso e obesidade, respectivamente. Dentre os fatores de risco associados as DCNT, o tabagismo em idade precoce foi associado à incidência de depressão. Conclusão: O excesso de peso em adultos jovens aumenta a incidência precoce de DCNT, com efeitos negativos na qualidade de vida, lazer e produtividade, além de aumentar a demanda por serviços de saúde. Torna-se necessário que a intervenção para redução dessas doenças seja direcionada para o período da infância e adolescência com ações que promovam a redução da exposição desses indivíduos à alimentação de má qualidade e incentivo a prática de atividade, não uso do tabaco e consumo moderado de álcool.

A nova família de distribuições odd log-logística: teoria e aplicações

Neste trabalho, foi proposta uma nova família de distribuições, a qual permite modelar dados de sobrevivência quando a função de risco tem formas unimodal e U (banheira). Ainda, foram consideradas as modificações das distribuições Weibull, Fréchet, half-normal generalizada, log-logística e lognormal. Tomando dados não-censurados e censurados, considerou-se os estimadores de máxima verossimilhança para o modelo proposto, a fim de verificar a flexibilidade da nova família. Além disso, um modelo de regressão locação-escala foi utilizado para verificar a influência de covariáveis nos tempos de sobrevida. Adicionalmente, conduziu-se uma análise de resíduos baseada nos resíduos deviance modificada. Estudos de simulação, utilizando-se de diferentes atribuições dos parâmetros, porcentagens de censura e tamanhos amostrais, foram conduzidos com o objetivo de verificar a distribuição empírica dos resíduos tipo martingale e deviance modificada. Para detectar observações influentes, foram utilizadas medidas de influência local, que são medidas de diagnóstico baseadas em pequenas perturbações nos dados ou no modelo proposto. Podem ocorrer situações em que a suposição de independência entre os tempos de falha e censura não seja válida. Assim, outro objetivo desse trabalho é considerar o mecanismo de censura informativa, baseado na verossimilhança marginal, considerando a distribuição log-odd log-logística Weibull na modelagem. Por fim, as metodologias descritas são aplicadas a conjuntos de dados reais.

Influence of drill speed and feed rate on bone damage

Implant failures and postoperative complications are often associated to the bone drilling. Estimation and control of drilling parameters are critical to prevent mechanical damage to the bone tissues. For better performance of the drilling procedures, it is essential to understand the mechanical behaviour of bones that leads to their failures and consequently to improve the cutting conditions. This paper investigates the effect of drill speed and feed-rate on mechanical damage during drilling of solid rigid foam materials, with similar mechanical properties to the human bone. Experimental tests were conducted on biomechanical blocks instrumented with strain gauges to assess the drill speed and feed-rate influence. A three-dimensional dynamic finite element model to predict the bone stresses, as a function of drilling conditions, drill geometry and bone model, was developed. These simulations incorporate the dynamic characteristics involved in the drilling process. The element removal scheme is taken into account and allows advanced simulations of tool penetration and material removal. Experimental and numerical results show that generated stresses in the material tend to increase with tool penetration. Higher drill speed leads to an increase of von-Mises stresses and strains in the solid rigid foams. However, when the feed-rate is higher, the stresses and strains are lower. The numerical normal stresses and strains are found to be in good agreement with experimental results. The models could be an accurate analysis tool to simulate the stresses distribution in the bone during the drilling process.

The dynamics of leniency application and the knock-on effect of cartel enforcement. Bruegel Working Paper 2016/02, February 2016

The authors study the timing of leniency applications using a novel application of multi-spell discrete-time survival analysis for a sample of cartels prosecuted by the European Commission between 1996 and 2014. The start of a Commission investigation does not affect the rate by which conspirators apply for leniency in the market investigated, but increases the rate of application in separate markets in which a conspirator in the investigated market also engaged in collusion. The revision of the Commission’s leniency programme in 2002 increased the rate of pre-investigation applications. Our results shed light on enforcement efforts against cartels and other forms of

NETGRAF: a computer graphics aid to the operation and interpretation of NETSIM, a traffic simulation model. Part 1: overview and experimental results. Final report.

Transportation Department, Office of University Research, Washington, D.C.

NETGRAF: a computer graphics aid to the operation and interpretation of NETSIM, a traffic simulation model. Part 3: programmer's guide.

Transportation Department, Office of University Research, Washington, D.C.

The prognostic value of a nomogram for exercise capacity in women

BACKGROUND: Recent studies have demonstrated that exercise capacity is an independent predictor of mortality in women. Normative values of exercise capacity for age in women have not been well established. Our objectives were to construct a nomogram to permit determination of predicted exercise capacity for age in women and to assess the predictive value of the nomogram with respect to survival. METHODS: A total of 5721 asymptomatic women underwent a symptom-limited, maximal stress test. Exercise capacity was measured in metabolic equivalents (MET). Linear regression was used to estimate the mean MET achieved for age. A nomogram was established to allow the percentage of predicted exercise capacity to be estimated on the basis of age and the exercise capacity achieved. The nomogram was then used to determine the percentage of predicted exercise capacity for both the original cohort and a referral population of 4471 women with cardiovascular symptoms who underwent a symptom-limited stress test. Survival data were obtained for both cohorts, and Cox survival analysis was used to estimate the rates of death from any cause and from cardiac causes in each group. RESULTS: The linear regression equation for predicted exercise capacity (in MET) on the basis of age in the cohort of asymptomatic women was as follows: predicted MET = 14.7 - (0.13 x age). The risk of death among asymptomatic women whose exercise capacity was less than 85 percent of the predicted value for age was twice that among women whose exercise capacity was at least 85 percent of the age-predicted value (P<0.001). Results were similar in the cohort of symptomatic women. CONCLUSIONS: We have established a nomogram for predicted exercise capacity on the basis of age that is predictive of survival among both asymptomatic and symptomatic women. These findings could be incorporated into the interpretation of exercise stress tests, providing additional prognostic information for risk stratification.

Lifestyle still predicts mortality in older men with established vascular disease

Background. It is uncertain whether accepted associations between health behaviors and mortality are pertinent to elderly people. No previous studies have examined the patterns of lifestyle in elderly men with and without clinically evident vascular disease by using a lifestyle score to predict survival. Methods. We measured prevalence of a healthy lifestyle (four or more healthy behaviors out of eight) and examined survival in 11,745 men aged 65-83 years participating in a randomized population-based trial of screening for abdominal aortic aneurysm in Perth, Western Australia. After stratifying participants into five groups according to history and symptoms of vascular disease, we compared survival of men in each subgroup with that of 'healthy' men with no history or symptoms of vascular disease. Results. Invitations to screening produced a corrected response of 70.5%. After adjusting for age and place of birth, having an unhealthy lifestyle was associated with an increase of 20% in the likelihood of death from any cause within 5 years (95% CI: 10-30%). This pattern was consistently evident across subgroups defined by history of vascular disease, but was less evident for deaths from vascular disease. Conclusions. Our results highlight the importance of maintaining a healthy lifestyle through to old age, regardless of history of vascular disease. (c) 2005 Elsevier Inc. All rights reserved.

Novel markers for poor prognosis in head and neck cancer

Head and neck cancer (HNSCC) is one of the most distressing human cancers, causing pain and affecting the basic survival functions of breathing and swallowing. Mortality rates have not changed despite recent advances in radiotherapy and surgical treatment. We have compared the expression of over 13,000 unique genes in 7 cases of matched HNSCC and normal oral mucosa. Of the 1,260 genes that showed statistically significant differences in expression between normal and tumor tissue at the mRNA level, the three top ranking of the top 5% were selected for further analysis by immunohistochemistry on paraffin sections,. along with the tumor suppressor genes p16 and p53, in a total of 62 patients including 55 for whom >4-year clinical data was available. Using univariate and multivariate survival analysis, we identified SPARC/osteonectin as a powerful independent prognostic marker for short disease-free interval (DFI) (p < 0.002) and poor overall survival (OS) (p = 0.018) of HNSCC patients. In combination with other ECM proteins found in our analysis, PAI-1 and uPA, the association with DFI and OS became even more significant (p < 0.001). Our study represents the first instance of SPARC as an independent prognostic marker in HNSCC.

Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer

Objectives. Gene expression profiling has provided many insights into tumor progression but translation to clinical practice has been limited. We have previously identified a list of potential markers by the differences of expression profiling of seven matched head and neck cancer (HNSCC) tumors with autologous normal oral mucosa (NOM). Alpha B-crystallin (CRYAB) was in the top 5% of genes identified with statistically significant differences in expression between tumor and NOM at the mRNA level. The objective was to confirm this in routine paraffin sections at the protein level. Study Design: The level of alpha B-crystallin was determined in tumors of 62 HNSCC patients whose prognosis was known for 5 years. Methods. Immunohistochemical detection of alpha B-crystallin expression was performed on HNSCC paraffin sections. Results. Univariate survival analysis identified lack of alpha B-crystallin staining as an independent prognostic marker for disease-free interval (P < 0.001) and overall survival (P < 0.002) of HNSCC patients over the 5-year observation period. Notably, all 13 patients (100%), including 5 patients with nodal disease whose tumors lacked alpha B-crystallin had no recurrences (P < 0.001). Nineteen of 27 node-negative patients stained positive for alpha B-crystallin and seven of the 19 (36.8%) had recurrences. Conclusion: Presence or absence of expression of alpha B-crystallin was a powerful marker for prognosis in this series of patients.

Family structure and age at menarche: A children-of-twins approach

Girls who grow up in households with an unrelated adult male reach menarche earlier than peers, a finding hypothesized to be an evolutionary strategy for families under stress. The authors tested the alternative hypothesis that nonrandom selection into stepfathering due to shared environmental and/or genetic predispositions creates a spurious relation between stepfathering and early menarche. Using the unique controls for genetic and shared environmental experiences offered by the children-of-twins design, the authors found that cousins discordant for stepfathering did not differ in age of menarche. Moreover, controlling for mother's age of menarche eliminated differences in menarcheal age associated with stepfathering in unrelated girls. These findings strongly suggest selection, and not causation, accounts for the relationship between stepfathering and early menarche.