Frequencies and risk factors for bisphosphonate-related osteonecrosis of the jaw in cancer patients: A matched case-control study

Bisphosphonates represent a unique class of drugs that effectively treat and prevent a variety of bone-related disorders including metastatic bone disease and osteoporosis. High tolerance and high efficacy rates quickly ranked bisphosphonates as the standard of care for bone-related diseases. However, in the early 2000s, case reports began to surface that linked bisphosphonates with osteonecrosis of the jaw (ONJ). Since that time, studies conducted have corroborated the linkage. However, as with most disease states, many factors can contribute to the onset of disease. The aim of this study was to determine which comorbid factors presented an increased risk for developing ONJ in cancer patients.^ Using a case-control study design, investigators used a combination of ICD-9 codes and chart review to identify confirmed cases of ONJ at The University of Texas M. D. Anderson Cancer Center (MDACC). Each case was then matched to five controls based on age, gender, race/ethnicity, and primary cancer diagnosis. Data querying and chart review provided information on variables of interest. These variables included bisphosphonate exposure, glucocorticoids exposure, smoking history, obesity, and diabetes. Statistical analysis was conducted using PASW (Predictive Analytics Software) Statistics, Version 18 (SPSS Inc., Chicago, Illinois).^ One hundred twelve (112) cases were identified as confirmed cases of ONJ. Variables were run using univariate logistic regression to determine significance (p < .05); significant variables were included in the final conditional logistic regression model. Concurrent use of bisphosphonates and glucocorticoids (OR, 18.60; CI, 8.85 to 39.12; p < .001), current smokers (OR, 2.52; CI, 1.21 to 5.25; p = .014), and presence of diabetes (OR, 1.84; CI, 1.06 to 3.20; p = .030) were found to increase the risk for developing ONJ. Obesity was not associated significantly with ONJ development.^ In this study, cancer patients that received bisphosphonates as part of their therapeutic regimen were found to have an 18-fold increase in their risk of developing ONJ. Other factors included smoking and diabetes. More studies examining the concurrent use of glucocorticoids and bisphosphonates may be able to strengthen any correlations.^

An Economic Derivation on Trade Coefficients under the Framework of Multi-regional I-O Analysis

The gravity model, entropy model, potential type model and others like these have been adopted to formulate interregional trade coefficients under the framework of Multi-Regional I-O (MRIO) analysis. Since most of these models are based upon analogies in physics or on statistical principles, they do not provide a theoretical explanation from the view of a firm's or individual's rational and deterministic decision making. In this paper, according to the deterministic choice theory, not only is an alternative formulation of the trade coefficients presented, but also a discussion of an appropriate definition for purchasing prices indices. Since this formulation is consistent with the MRIO system, it can be employed as a useful model-building tool in multi-regional models such as the spatial CGE model.

Inflation targeting in Korea, Indonesia, Thailand, and the Philippines : the impact on business cycle synchronization between each country and the world

This paper empirically analyzes whether and to what extent the adoption of inflation targeting (IT) in Korea, Indonesia, Thailand and the Philippines has affected their business cycle synchronization with the rest of the world. By employing the dynamic conditional correlation (DCC) model developed by Engle (2002), we find that IT in Asia has little effect on international business cycle synchronization and the effect is positive in some of the countries, if any. These findings basically seem to be consistent with the evidence from relevant literature.

Parameterization of applied general equilibrium models with flexible trade specifications based on the Armington, Krugman, and Melitz models

This paper explains how the Armington-Krugman-Melitz supermodel developed by Dixon and Rimmer can be parameterized, and demonstrates that only two kinds of additional information are required in order to extend a standard trade model to include Melitz-type monopolistic competition and heterogeneous firms. Further, it is shown how specifying too much additional information leads to violations of the model constraints, necessitating adjustment and reconciliation of the data. Once a Melitz-type model is parameterized, a Krugman-type model can also be parameterized using the calibrated values in the Melitz-type model without any additional data. Sample code for the General Algebraic Modeling System (GAMS) has also been prepared to promote the innovative supermodel in the AGE community.

Desarrollo de capacidades para el liderazgo en proyectos de desarrollo rural. Aplicación a comunidades Aymaras

Los proyectos de desarrollo en el medio rural han cambiado en las últimas décadas, desde un enfoque tecnocrático y descendente, que resultó insuficiente, a otro que otorga un papel principal a las personas locales. En este contexto, los nuevos modelos de planificación y gestión de los proyectos de desarrollo a menudo incluyen entre sus objetivos el desarrollo de las capacidades locales y el liderazgo, dedicándose a ellos anualmente billones de dólares. Ambos conceptos son considerados elementos indispensables para aumentar la sostenibilidad de las acciones desde un enfoque endógeno, lo que genera un gran interés tanto desde el ámbito científico como en los debates y objetivos de los organismos internacionales. Sin embargo no existe un consenso sobre el marco conceptual del desarrollo de capacidades ni sobre las metodologías adecuadas para evaluarlo. Por otra parte, en el caso del desarrollo de liderazgo, la mayoría de los estudios e investigaciones se han centrado en entornos empresariales, siendo escasos los trabajos centrados en el ámbito rural. En dicho contexto, la complejidad se incrementa debido a que a menudo la autoridad y poder de los líderes no están dados por puestos formales, sino por relaciones sociales y vínculos de confianza. Esta investigación presenta una primera fase conceptual, que aborda el marco teórico, analizando y clarificando los conceptos de desarrollo de capacidades, competencias y liderazgo en el contexto de los proyectos de desarrollo rural. Así mismo, en esta fase se clasifican los principales instrumentos para evaluar el desarrollo de capacidades, para así definir las variables que conforman el constructo de capacidades. Además se determina la multidimensionalidad del concepto de capacidades y por ello la conveniencia de abordarlo a nivel individual y colectivo. También se analizan los distintos estilos de liderazgo para llegar a una definición propia de desarrollo de capacidades y de liderazgo adaptadas al medio rural. El marco teórico anterior permite sentar, en una segunda fase de la investigación, las bases científicas del modelo que se propone: el modelo DCL de Desarrollo de Capacidades para el Liderazgo en los proyectos de desarrollo rural. Este modelo incorpora elementos del marco conceptual Working With People (Cazorla et al., 2013), fruto de 25 años de experiencia en el ámbito de la planificación de proyectos de desarrollo rural desde el grupo de investigación GESPLAN de la Universidad Politécnica de Madrid. El modelo DCL integra metodologías cuantitativas y cualitativas y una doble escala de análisis para promover y evaluar el desarrollo de capacidades en la población local desde tres componentes: técnico-empresarial, relacional y contextual. Además el modelo DCL incorpora un proceso metodológico para poder integrar el seguimiento y la evaluación de las capacidades a lo largo del ciclo del proyecto. Finalmente, en una fase de aplicación, se acomete la validación del modelo DCL a través del caso de estudio de un proyecto de desarrollo con una organización de mujeres artesanas de comunidades aymaras de Puno (Perú). Este proyecto, que incorpora el marco conceptual WWP, integra 5 años de experiencia con comunidades aymaras desde el grupo de investigación GESPLAN. La aplicación muestra cómo el modelo DCL permite evaluar el desarrollo de capacidades para el liderazgo. Así mismo, la incorporación de los aprendizajes tras las evaluaciones de desarrollo de capacidades permite reorientar las acciones del proyecto para mejorar su planificación y gestión y producir un verdadero empoderamiento y liderazgo de la organización local. Lo anterior se traduce en un aumento de la sostenibilidad del proyecto y de la resiliencia social de la organización. ABSTRACT Development projects in rural areas have changed in recent decades, from a technocratic and top-down approach, which proved insufficient, to another that gives a major role to local people. In this context, the new models of planning and management of development projects often include among their objectives the development of local capacities and leadership and engage billions of dollars annually. Both concepts are considered essential for enhancing the sustainability of the actions from an endogenous approach, generating great interest both from the scientific field and in the debates and objectives of international organizations. However there is no consensus on the conceptual framework of capacity development and on appropriate methodologies to evaluate it. Moreover, in the case of leadership development, most of the studies and research have focused on business environments, with few studies focusing on rural areas. In this context, the complexity is increased because often the authority and power of the leaders are not given for formal positions, but by social relationships and bonds of trust. This research presents an initial conceptual phase, which addresses the theoretical framework, analyzing and clarifying the concepts of capacity development, competencies and leadership in the context of rural development projects. Also, at this stage the main instruments to assess capacity development are classified so as to define the variables that shape the capacity construct. Besides the multidimensionality of the concept of capacity is determined and therefore the convenience of addressing it at an individual and colective level. Different leadership styles are also analyzed to propose a definition of capacity development and leadership adapted to the rural environment. The above theoretical framework allows to set, in a second research phase, the scientific basis of the proposed model: the model DCL of Capacity Development for Leadership in rural development projects. This model incorporates elements of the conceptual framework Working With People (Cazorla et al., 2013), the result of 25 years of experience in the field of project planning for rural development from the research group GESPLAN of the Technical University of Madrid. The DCL model integrates quantitative and qualitative methodologies and a double scale of analysis to promote and evaluate capacity development in the local population from three components: technical-entrepreneurial, relational and contextual. Besides the DCL model incorporates a methodological process to integrate monitoring and evaluation of capacities throughout the project cycle. Finally, in an application phase, DCL model validation is undertaken through the case study of a development project with an organization of women artisans of Aymara communities in Puno (Peru). This project, that incorporates the WWP conceptual framework, integrates 5 years of experience with Aymara communities from GESPLAN research group. The application shows how the DCL model allows to assess the development of capacities for leadership. Also, the incorporation of lessons learned after monitoring and evaluation of capacity development allows to redirect actions to improve project planning and management and produce a true empowerment and leadership of the local organization. This translates into increased project sustainability and social resilience of the organization.

Proposed mechanism for stability of proteins to evolutionary mutations

It is shown that the sequence-ordering tendencies induced by design into different fast-folding, thermally stable native structures interfere. This interference results in a type of quasiorthogonality between optimal native structures, which divides sequence space into fast-folding, thermally stable families surrounded by slow-folding, low stability shells. A concrete example of this effect is provided by using a simple α carbon type model in which a complete correspondence is established between sequence and structure. It is speculated that gaps can occur in the space of protein-like sequences separating the sequence families and resulting in a mechanism for stability and diversity of protein sequence information.

The multiple phenotypes of allosteric receptor mutants.

Channel-linked neurotransmitter receptors are membrane-bound heterooligomers made up of distinct, although homologous, subunits. They mediate chemo-electrical signal transduction and its regulation via interconversion between multiple conformations that exhibit distinct pharmacological properties and biological activities. The large diversity of functional properties and the widely pleiotropic phenotypes, which arise from point mutations in their subunits (or from subunit substitutions), are interpreted in terms of an allosteric model that incorporates multiple discrete conformational states. The model predicts that three main categories of phenotypes may result from point mutations, altering selectively one (or more) of the following features: (i) the properties of individual binding sites (K phenotype), (ii) the biological activity of the ion channel (gamma phenotype) of individual conformations, or (iii) the isomerization constants between receptor conformations (L phenotype). Several nicotinic acetylcholine and glycine receptor mutants with complex phenotypes are quantitatively analyzed in terms of the model, and the analogies among phenotypes are discussed.

Estudo da solidificação equiaxial utilizando o modelo do campo de fases tridimensional.

Este trabalho apresenta um estudo da solidificação de metais puros utilizando o modelo de campo de fases. O modelo é utilizado para simular a solidificação com o intuito de obter a morfologia da interface sólido-líquido sob diversas condições de transferência de calor. Foram realizados testes de validação comparando as morfologias da interface sólido-líquido obtida com as morfologias apresentadas em trabalhos anteriores para os casos bi e tridimensionais. O modelo do campo de fases adotado consiste principalmente de duas equações diferenciais: uma para calcular a variável de campo de fases e outra para calcular o campo de temperaturas. As equações foram solucionadas numericamente para um oitavo do domínio devido a simetria do problema. Os cálculos do modelo indicam que um sólido esférico com um raio inicial menor que o raio crítico de nucleação refunde. Entretanto uma esfera de raio maior cresce. Quando o sólido inicial cresce em uma malha numérica relativamente grosseira, a forma do sólido desvia da forma esférica devido perturbações na interface sólido-líquido. Quando a malha é refinada, as perturbações não são detectadas; contudo, quando introduzidas artificialmente as perturbações crescem e distorcem o formato esférico.

Sistemas de gestão integrados como indutor para a sustentabilidade: uma análise do impacto no desempenho das organizações baseado no Triple Bottom Line.

O objetivo deste trabalho é analisar o impacto dos Sistemas de Gestão Integrados (SGI) no desempenho organizacional sob a óptica do Triple Bottom Line (TBL), verificando se esta implementação auxilia a empresa a se tornar mais sustentável. A abordagem multi-método utilizada está dividida em três partes. A primeira compreende uma revisão sistemática da literatura, tendo como base a abordagem bibliométrica. A base de dados escolhida para a seleção dos artigos que compõem a amostra foi a ISI Web of Knowledge (Web of Science). As análises conduzidas sugerem lacunas na literatura a serem pesquisadas de modo a relacionar a integração dos sistemas de gestão como meio para as organizações tornarem-se mais sustentáveis, auxiliando assim na elaboração de um modelo teórico e das hipóteses de pesquisa. Os resultados parciais obtidos ressaltam a lacuna na literatura de estudos nessa área, principalmente que contemplem a dimensão social do Triple Bottom Line. Lacunas na literatura foram identificadas também no que se refere à análise do impacto da adoção dessas abordagens normativas no desempenho organizacional. A segunda etapa da metodologia é composta por estudos de casos múltiplos em empresas de diferentes setores e que tenham implantado sistemas de gestão de maneira integrada. Os resultados obtidos mostram que a certificação auxilia no desenvolvimento de ações sustentáveis, resultando em impactos econômicos, ambientais e sociais positivos. Nesta etapa, testou-se o modelo e as hipóteses levantadas na abordagem bibliométrica. A terceira etapa da metodologia é composta por análises estatísticas de dados secundários extraídos da revista Exame ?Maiores e Melhores\'. Os dados do ano de 2014 das empresas foram tratados por meio do software MINITAB 17 ®. Por meio do teste de mediana de mood, as amostras foram testadas e apresentaram diferenças estatisticamente significativas para o desempenho das empresas em diferentes setores. De maneira geral, as empresas com SGI apresentam melhor desempenho econômico do que as demais. Com a mesma base de dados, utilizando o modelo de equações estruturais e o software Smart PLS 2.0, criou-se um diagrama de caminhos analisando os constructos (SGI) com variáveis de desempenho (Endividamento, Lucratividade, Patrimônio, Crescimento e Retorno). O modelo de equações estruturais testado apresentou força para a relação entre SGI com Endividamento, Lucratividade, Patrimônio e Crescimento. As diferentes metodologias apresentadas contribuíram para responder a hipótese e afirmar com base na amostra deste trabalho que o SGI leva as empresas a terem melhor desempenho econômico, ambiental e social (baseado no TBL).

Difference schemes for numerical solutions of lagging models of heat conduction

Non-Fourier models of heat conduction are increasingly being considered in the modeling of microscale heat transfer in engineering and biomedical heat transfer problems. The dual-phase-lagging model, incorporating time lags in the heat flux and the temperature gradient, and some of its particular cases and approximations, result in heat conduction modeling equations in the form of delayed or hyperbolic partial differential equations. In this work, the application of difference schemes for the numerical solution of lagging models of heat conduction is considered. Numerical schemes for some DPL approximations are developed, characterizing their properties of convergence and stability. Examples of numerical computations are included.

Essays in dynamic optimal taxation: working experience, unemployment scarring and poverty

This thesis investigates the design of optimal tax systems in dynamic environments. The first essay characterizes the optimal tax system where wages depend on stochastic shocks and work experience. In addition to redistributive and efficiency motives, the taxation of inexperienced workers depends on a second-best requirement that encourages work experience, a social insurance motive and incentive effects. Calibrations using U.S. data yield higher expected optimal marginal income tax rates for experienced workers for most of the inexperienced workers. They confirm that the average marginal income tax rate increases (decreases) with age when shocks and work experience are substitutes (complements). Finally, more variability in experienced workers' earnings prospects leads to increasing tax rates since income taxation acts as a social insurance mechanism. In the second essay, the properties of an optimal tax system are investigated in a dynamic private information economy where labor market frictions create unemployment that destroys workers' human capital. A two-skill type model is considered where wages and employment are endogenous. I find that the optimal tax system distorts the first-period wages of all workers below their efficient levels which leads to more employment. The standard no-distortion-at-the-top result no longer holds due to the combination of private information and the destruction of human capital. I show this result analytically under the Maximin social welfare function and confirm it numerically for a general social welfare function. I also investigate the use of a training program and job creation subsidies. The final essay analyzes the optimal linear tax system when there is a population of individuals whose perceptions of savings are linked to their disposable income and their family background through family cultural transmission. Aside from the standard equity/efficiency trade-off, taxes account for the endogeneity of perceptions through two channels. First, taxing labor decreases income, which decreases the perception of savings through time. Second, taxation on savings corrects for the misperceptions of workers and thus savings and labor decisions. Numerical simulations confirm that behavioral issues push labor income taxes upward to finance saving subsidies. Government transfers to individuals are also decreased to finance those same subsidies.

Assortative matching of exporters and importers

This paper uses the opening of the US textile/apparel market for China at the end of the Multifibre Arrangement in 2005 as a natural experiment to provide evidence for positive assortative matching of Mexican exporting firms and US importing firms by their capability. We identify three findings for liberalized products by comparing them to other textile/apparel products: (1) US importers switched their Mexican partners to those making greater preshock exports, whereas Mexican exporters switched their US partners to those making fewer preshock imports; (2) for firms who switched partners, trade volume of the old partners and the new partners are positively correlated; (3) small Mexican exporters stop exporting. We develop a model combining Becker-type matching of final producers and suppliers with the standard Melitz-type model to show that these findings are consistent with positive assortative matching but not with negative assortative matching or purely random matching. The model indicates that the findings are evidence for a new mechanism of gain from trade.

Flow regime, hydrodynamics, floc size distribution and sludge properties in activated sludge bubble column, air-lift and aerated stirred reactors

This paper presents a comparative study how reactor configuration, sludge loading and air flowrate affect flow regimes, hydrodynamics, floc size distribution and sludge solids-liquid separation properties. Three reactor configurations were studied in bench scale activated sludge bubble column reactor (BCR), air-lift reactor (ALR) and aerated stirred reactor (ASR). The ASR demonstrated the highest capacity of gas holdup and resistance, and homogeneity in flow regimes and shearing forces, resulting in producing large numbers of small and compact floes. The fluid dynamics in the ALR created regularly directed recirculation forces to enhance the gas holdup and sludge flocculation. The BCR distributed a high turbulent flow regime and non-homogeneity in gas holdup and mixing, and generated large numbers of larger and looser floes. The sludge size distributions, compressibility and settleability were significantly influenced by the reactor configurations associated with the flow regimes and hydrodynamics.

Hierarchical organisation of neuro-anatomical constraints in interlimb coordination

Based on the observation that bimanual finger tapping movements tend toward mirror symmetry with respect to the body midline, despite the synchronous activation of non-homologous muscles, F. Mechsner, D. Kerzel, G. Knoblich, and W. Prinz (2001) [Perceptual basis of bimanual coordination. Nature, 414, 69-73] suggested that the basis of rhythmic coordination is purely spatial/perceptual in nature, and independent of the neuro-anatomical constraints of the motor system. To investigate this issue further, we employed a four finger tapping task similar to that used by F. Mechsner and G. Knoblich (2004) [Do muscle matter in bimanual coordination? Journal of Experimental Psychology: Human Perception and Performance, 30, 490-503] in which six male participants were required to alternately tap combinations of adjacent pairs of index (1), middle (M) and ring (R) fingers of each hand in time with an auditory metronome. The metronome pace increased continuously from 1 Hz to 3 Hz over the course of a 30-s trial. Each participant performed three blocks of trials in which finger combination for each hand (IM or MR) and mode of coordination (mirror or parallel) were presented in random order. Within each block, the right hand was placed in one of three orientations; prone, neutral and supine. The order of blocks was counterbalanced across the six participants. The left hand maintained a prone position throughout the experiment. On the basis of discrete relative phase analyses between synchronised taps, the time at which the initial mode of coordination was lost was determined for each trial. When the right hand was prone, transitions occurred only from parallel symmetry to mirror symmetry, regardless of finger combination. In contrast, when the right hand was supine, transitions occurred only from mirror symmetry to parallel but no transitions were observed in the opposite direction. In the right hand neutral condition, mirror and parallel symmetry are insufficient to describe the modes of coordination since the hands are oriented orthogonally. When defined anatomically, however, the results in each of the three right hand orientations are consistent. That is, synchronisation of finger tapping is deter-mined by a hierarchy of control of individual fingers based on their intrinsic neuro-mechanical properties rather than on the basis of their spatial orientation. (c) 2005 Elsevier B.V. All rights reserved.

Numerical simulation of magnetite segregation in a dense medium cyclone

Numerical simulations of turbulent driven flow in a dense medium cyclone with magnetite medium have been conducted using Fluent. The predicted air core shape and diameter were found to be close to the experimental results measured by gamma ray tomography. It is possible that the Large eddy simulation (LES) turbulence model with Mixture multi-phase model can be used to predict the air/slurry interface accurately although the LES may need a finer grid. Multi-phase simulations (air/water/medium) are showing appropriate medium segregation effects but are over-predicting the level of segregation compared to that measured by gamma-ray tomography in particular with over prediction of medium concentrations near the wall. Further, investigated the accurate prediction of axial segregation of magnetite using the LES turbulence model together with the multi-phase mixture model and viscosity corrections according to the feed particle loading factor. Addition of lift forces and viscosity correction improved the predictions especially near the wall. Predicted density profiles are very close to gamma ray tomography data showing a clear density drop near the wall. The effect of size distribution of the magnetite has been fully studied. It is interesting to note that the ultra-fine magnetite sizes (i.e. 2 and 7 mu m) are distributed uniformly throughout the cyclone. As the size of magnetite increases, more segregation of magnetite occurs close to the wall. The cut-density (d(50)) of the magnetite segregation is 32 gm, which is expected with superfine magnetite feed size distribution. At higher feed densities the agreement between the [Dungilson, 1999; Wood, J.C., 1990. A performance model for coal-washing dense medium cyclones, Ph.D. Thesis, JKMRC, University of Queensland] correlations and the CFD are reasonably good, but the overflow density is lower than the model predictions. It is believed that the excessive underflow volumetric flow rates are responsible for under prediction of the overflow density. (c) 2006 Elsevier Ltd. All rights reserved.