Antiresorptive drugs (bisphosphonates), atypical fractures and rebound effect: new evidence of similitude

Background: Homeopathy is based on treatment by similitude ('like cures like') administering to sick individuals substances that cause similar symptoms in healthy individuals, employing the secondary and paradoxical action of the organism as therapeutic response. This vital or homeostatic reaction of the organism can be scientifically explained by the rebound effect of drugs, resulting in worsening of symptoms after suspension of treatment. Bisphosphonates (BPs) reduce 'typical' fractures in patients with osteoporosis, but recent studies report 'atypical' fractures of the femur after stopping the BPs, a rebound effect may be the causal mechanism. Method: Review of the literature concerning the relationship between atypical femoral fractures and antiresorptive drugs (bisphosphonates), identifying the pathogenesis of this adverse event. Results: Several studies have described multiple cases of 'atypical' low-impact subtrochanteric stress fractures or complete fractures of the femur. These fractures are often bilateral, preceded by pain in the affected thigh, may have a typical X-ray appearance, and may delayed healing. Rebound of osteoclastic activity after suspension of antiresorptive drugs is a plausible mechanism to explain this phenomenon. Conclusion: As for other classes of drugs, the rebound effect of antiresorptive drugs supports Hahnemann's similitude principle (primary action of the drugs followed by secondary and opposite action of the organism), and clarifies this 'unresolved' issue. Unfortunately, the rebound effect is little discussed among health professionals, depriving them of important knowledge ensure safe management of drugs. Homeopathy (2012) 101, 231-242.

Estudio de opciones reales para decisiones de inversión en un proyecto minero de nueva ejecución

El objetivo principal es desarrollar la metodología de opciones reales para evaluar la posible puesta en marcha de un proyecto minero. Para esto, el proyecto se divide en dos partes: En la primera parte, con carácter teórico se analizan las inversiones desde el punto de vista tradicional, comparando la problemática de estas valoraciones en ambientes de incertidumbre y flexibilidad operativa. Se analizan las opciones financieras y se comparan con las opciones reales, en cuanto a similitudes y problemáticas. Se desarrollan también los procesos estocásticos que afectan a las variables del proyecto de inversión. Se explican además, las metodologías para el cálculo de las opciones reales, incluido el cálculo de la volatilidad de las mismas. En una segunda parte, se estudia el yacimiento aurífero de Corcoesto, para el cual se realiza la simulación del plan de negocio según las características necesarias para la explotación, donde los ingresos se modelizan mediante un movimiento geométrico browniano para simular el comportamiento del precio de la onza de oro. Se elige un desarrollo de árboles binomiales para estimar el valor futuro del proyecto, a la vez que se establece un intervalo de precios de la opción para adquirir el proyecto minero. Este intervalo estará determinado por las incertidumbres del proyecto calculadas según las metodologías de Copeland y Antikarov, y Heraht y Park. Abstract This project is aimed mainly to develop real options theory to assess a mining project start-up. The project is divided in two documents: The first document with theorical content, investments are analyzed from the clasical point of view, comparing the advantages and disadvantages of this appraisal in high uncertainity and operational flexibility conditions. Financial options are analyzed and compared to real options, in both similarities and problematics. Stochastical process that affect the project variables are also developed. Methods for estimating real options value, including the methods for volatility estimation are commented. In the second document, the Corcoesto gold deposit has been studied. A bussines plan simulation has been maked according to the characteristics of the extraction, where incomes have been simulated with a geometrical Brownian movement to estimate the gold onze behaviour. The binomial tree method has been generated to study the future project value, as well as a range of option prices, for adquiring the mine project. This interval is determined by the project uncertainity calculated with the theories from Copeland and Antikarov and Herath and Park

The System of Quality Prediction on the Basis of a Fuzzy Data and Psychography of the Experts

The system of development unstable processes prediction is given. It is based on a decision-tree method. The processing technique of the expert information is offered. It is indispensable for constructing and processing by a decision-tree method. In particular data is set in the fuzzy form. The original search algorithms of optimal paths of development of the forecast process are described. This one is oriented to processing of trees of large dimension with vector estimations of arcs.

Experience of Development and Application of Expert Systems for Economic Macroparameters Forecasting and Operation

In this article there are considered problems of forecasting economical macroparameters, and in the first place, index of inflation. Concept of development of synthetical forecasting methods which use directly specified expert information as well as calculation result on the basis of objective economical and mathematical models for forecasting separate “slowly changeable parameters” are offered. This article discusses problems of macroparameters operation on the basis of analysis of received prognostic magnitude.

Cognitive dissonance and the effect of acceptance of methodology, beliefs about religion, religious orientation, and dogmatism on the success of university students in a religious studies course

The problem investigated was negative effects on the ability of a university student to successfully complete a course in religious studies resulting from conflict between the methodologies and objectives of religious studies and the student's system of beliefs. Using Festinger's theory of cognitive dissonance as a theoretical framework, it was hypothesized that completing a course with a high level of success would be negatively affected by (1) failure to accept the methodologies and objectives of religious studies (methodology), (2) holding beliefs about religion that had potential conflicts with the methodologies and objectives (beliefs), (3) extrinsic religiousness, and (4) dogmatism. The causal comparative method was used. The independent variables were measured with four scales employing Likert-type items. An 8-item scale to measure acceptance of the methodologies and objectives of religious studies and a 16-item scale to measure holding of beliefs about religion having potential conflict with the methodologies were developed for this study. These scales together with a 20-item form of Rokeach's Dogmatism Scale and Feagin's 12-item Religious Orientation Scale to measure extrinsic religiousness were administered to 144 undergraduate students enrolled in randomly selected religious studies courses at Florida International University. Level of success was determined by course grade with the 27% of students receiving the highest grades classified as highly successful and the 27% receiving the lowest grades classified as not highly successful. A stepwise discriminant analysis produced a single significant function with methodology and dogmatism as the discriminants. Methodology was the principal discriminating variable. Beliefs and extrinsic religiousness failed to discriminate significantly. It was concluded that failing to accept the methodologies and objectives of religious studies and being highly dogmatic have significant negative effects on a student's success in a religious studies course. Recommendations were made for teaching to diminish these negative effects.

Differential effects of single -sex versus coed education on the mathematical reasoning ability, verbal reasoning ability, and self-concept of high school girls

This study explored the differential effects of single-sex versus coed education on the cognitive and affective development of young women in senior year of high school. The basic research question was: What are the differential effects of single-sex versus coed education on the development of mathematical reasoning ability, verbal reasoning ability, or self-concept of high school girls?^ This study was composed of two parts. In the first part, the SAT verbal and mathematical ability scores were recorded for those subjects in the two schools from which the sample populations were drawn. The second part of the study required the application of the Piers-Harris Children's Self-Concept Scale to subjects in each of the two sample populations. The sample schools were deliberately selected to minimize between group differences in the populations. One was an all girls school, the other coeducational.^ The research design employed in this study was the causal-comparative method, used to explore causal relationships between variables that already exist. Based on a comprehensive analysis of the data produced by this research, no significant difference was found to exist between the mean scores of the senior girls in the single-sex school and the coed school on the SAT 1 verbal reasoning section. Nor was any significant difference found to exist between the mean scores of the senior girls in the single-sex school and the coed school on the SAT 1 mathematical reasoning section. Finally, no significant difference between the mean total scores of the senior girls in the single-sex school and the coed school on the Piers-Harris Children's Self-Concept Scale was found to exist.^ Contrary to what many other studies have found in the past about single-sex schools and their advantages for girls, this study found no support for such advantages in the cognitive areas of verbal and mathematical reasoning as measured by the SAT or in the affective area of self-concept as measured by the Piers-Harris Children's Self-Concept Scale. ^

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Field lab: Entrepreneurial and innovative ventures

Real options as an alternative methodology to assess investment projects

This paper aims to broaden the applicability of the assessment methodology of investment projects through real options as a key element for investment decision making -- Traditional project valuation methodologies are described and their gaps, which special characteristic is uncertainty, are presented -- A parallel between financial and real options that could be used for valuation is made, using the binomial tree method -- Finally, a case study in the construction sector shows a project valuation using expand and waiting options

A study of the cambial zone and conductive phloem of common beech (Fagus sylvatica L.) using an image analysis method. I. Influence of tree age on the structure

Quantification is a major problem when using histology to study the influence of ecological factors on tree structure. This paper presents a method to prepare and to analyse transverse sections of cambial zone and of conductive phloem in bark samples. The following paper (II) presents the automated measurement procedure. Part I here describes and discusses the preparation method, and the influence of tree age on the observed structure. Highly contrasted images of samples extracted at breast height during dormancy were analysed with an automatic image analyser. Between three young (38 years) and three old (147 years) trees, age-related differences were identified by size and shape parameters, at both cell and tissue levels. In the cambial zone, older trees had larger and more rectangular fusiform initials. In the phloem, sieve tubes were also larger, but their shape did not change and the area for sap conduction was similar in both categories. Nevertheless, alterations were limited, and demanded statistical analysis to be identified and ascertained. The physiological implications of the structural changes are discussed.

A validated method using RP-HPLC for quantification of reserpine in the Brazilian tree Rauvolfia sellowii Müll. Arg. (Apocynaceae)

This study describes a simple, fast and reproducible method using RP-HPLC-UV, in a gradient system, for quantification of reserpine in Rauvolfia sellowii stem bark. The analysis were carried out on a C18 column; mobile phase was water and acetonitrile, and separations were carried out in 10 min, flow rate of 1.0 mL min-1, 25 ºC and 268 nm. The validation data showed that the method was specific, accurate, precise and robust. Results were linear over a range of 0.625-40.0 μg mL-1, and the mean recovery was 95.1%. The amount of reserpine found in the dried stem bark was 0.01% (m/m).

DNA variation in a 13-Mb region including the F9 gene: inferring the genealogical history and causal role of a hemophilia B mutation (IVS 5+13 A -> G)

About 5.5% of all UK hemophilia B patients have the base substitution IVS 5+13 A-->G as the only change in their factor (F)IX gene (F9). This generates a novel donor splice site which fits the consensus better than the normal intron 5 donor splice. Use of the novel splice site should result in a missense mutation followed by the abnormal addition of four amino acids to the patients' FIX. In order to explain the prevalence of this mutation, its genealogical history is examined. Analysis of restriction fragment length polymorphism in the 21 reference UK individuals (from different families) with the above mutation showed identical haplotypes in 19 while two differed from the rest and from each other. In order to investigate the history of the mutation and to verify that it had occurred independently more than once, the sequence variation in 1.5-kb segments scattered over a 13-Mb region including F9 was examined in 18 patients and 15 controls. This variation was then analyzed with a recently developed Bayesian approach that reconstructs the genealogy of the gene investigated while providing evidence of independent mutations that contribute disconnected branches to the genealogical tree. The method also provides minimum estimates of the age of the mutation inherited by the members of coherent trees. This revealed that 17 or 18 mutant genes descend from a founder who probably lived 450 years ago, while one patient carries an independent mutation. The independent recurrence of the IVS5+13 A-->G mutation strongly supports the conclusion that it is the cause of these patients' mild hemophilia.

A new method for inoculation of fruit with Guignardia citricarpa, the causal agent of citrus black spot

Citrus black spot (CBS) is a fungal disease, caused by Guignardia citricarpa, that has a high economic impact on citrus. Although G. citricarpa has been associated with black spot of citrus, an adequate pathogenicity test is still not available. Thus, our objective was to develop and evaluate a simple, safe, and practical pathogenicity test. We used fruits from Pera-Rio and Valencia sweet orange trees from two different orchards, located in the State of São Paulo, Brazil. Inoculation was performed by placing six disks colonized by G. citricarpa, onto the peel of healthy fruits, previously bagged. In the Pera-Rio sweet orange grove, initial symptoms of the false melanose type resulting from the inoculations were observed 55 days after inoculation (dai). In the Valencia grove, initial symptoms also of the false melanose type resulting from the inoculations occurred 73 dai. A total of 92.8% and 86.6% of the Pera Rio and Valencia fruits inoculated, respectively, showed symptoms of CBS. Citrus black spot symptoms were not observed in any of the control fruits.

Precipitation over the past four centuries in the Dieshan Mountains as inferred from tree rings: An introduction to an HHT-based method

To improve our understanding of the Asian monsoon system, we developed a hydroclimate reconstruction in a marginal monsoon shoulder region for the period prior to the industrial era. Here, we present the first moisture sensitive tree-ring chronology, spanning 501 years for the Dieshan Mountain area, a boundary region of the Asian summer monsoon in the northeastern Tibetan Plateau. This reconstruction was derived from 101 cores of 68 old-growth Chinese pine (Pinus tabulaeformis) trees. We introduce a Hilbert–Huang Transform (HHT) based standardization method to develop the tree-ring chronology, which has the advantages of excluding non-climatic disturbances in individual tree-ring series. Based on the reliable portion of the chronology, we reconstructed the annual (prior July to current June) precipitation history since 1637 for the Dieshan Mountain area and were able to explain 41.3% of the variance. The extremely dry years in this reconstruction were also found in historical documents and are also associated with El Niño episodes. Dry periods were reconstructed for 1718–1725, 1766–1770 and 1920–1933, whereas 1782–1788 and 1979–1985 were wet periods. The spatial signatures of these events were supported by data from other marginal regions of the Asian summer monsoon. Over the past four centuries, out-of-phase relationships between hydroclimate variations in the Dieshan Mountain area and far western Mongolia were observed during the 1718–1725 and 1766–1770 dry periods and the 1979–1985 wet period.

Instrumental variable method for the causal relationship between soluble receptor for advanced glycation end-products (sRAGE) and risk of pancreatic cancer

This thesis project is motivated by the potential problem of using observational data to draw inferences about a causal relationship in observational epidemiology research when controlled randomization is not applicable. Instrumental variable (IV) method is one of the statistical tools to overcome this problem. Mendelian randomization study uses genetic variants as IVs in genetic association study. In this thesis, the IV method, as well as standard logistic and linear regression models, is used to investigate the causal association between risk of pancreatic cancer and the circulating levels of soluble receptor for advanced glycation end-products (sRAGE). Higher levels of serum sRAGE were found to be associated with a lower risk of pancreatic cancer in a previous observational study (255 cases and 485 controls). However, such a novel association may be biased by unknown confounding factors. In a case-control study, we aimed to use the IV approach to confirm or refute this observation in a subset of study subjects for whom the genotyping data were available (178 cases and 177 controls). Two-stage IV method using generalized method of moments-structural mean models (GMM-SMM) was conducted and the relative risk (RR) was calculated. In the first stage analysis, we found that the single nucleotide polymorphism (SNP) rs2070600 of the receptor for advanced glycation end-products (AGER) gene meets all three general assumptions for a genetic IV in examining the causal association between sRAGE and risk of pancreatic cancer. The variant allele of SNP rs2070600 of the AGER gene was associated with lower levels of sRAGE, and it was neither associated with risk of pancreatic cancer, nor with the confounding factors. It was a potential strong IV (F statistic = 29.2). However, in the second stage analysis, the GMM-SMM model failed to converge due to non- concaveness probably because of the small sample size. Therefore, the IV analysis could not support the causality of the association between serum sRAGE levels and risk of pancreatic cancer. Nevertheless, these analyses suggest that rs2070600 was a potentially good genetic IV for testing the causality between the risk of pancreatic cancer and sRAGE levels. A larger sample size is required to conduct a credible IV analysis.^