Intra-articular administration of doxycycline in calves

Objective-To evaluate local tissue compatibility of doxycycline hyclate (DOX) in antebrachiocarpal joints of calves. Animals-10 healthy calves between 80 and 110 kg. Procedures-Calves were assigned to 2 treatment groups. Calves in groups DOX(low) and DOX(high) were administered 5 and 10 mg of DOX, respectively, locally in 1 antebrachiocarpal joint. The contralateral joint served as a control joint and was injected with 0.9% NaCl solution. General and local clinical findings were scored. Several variables were assessed in blood and synovial fluid for 9 days. Calves were euthanatized and pathologic changes and drug residues evaluated. Results-Throughout the study, none of the calves had clinical changes or abnormal hematologic values. Significant differences between treatment and control joints were evident only for matrix metalloproteinases at 0.5 hours after injection, with less activity for the DOX-treated joints in both treatment groups. Values for all synovial fluid variables, except nitric oxide, increased significantly during the first 12 to 72 hours after arthrocentesis in control and DOX-treated joints. Histologic examination revealed minimal infiltration of inflammatory cells independent of the treatment. No drug residues were detected 9 days after arthrocentesis in any tissues obtained from the liver, kidneys, fat, and skeletal muscles. Conclusions and Clinical Relevance-DOX had excellent intra-articular compatibility in healthy calves. Arthrocentesis induced a mild transient increase of inflammatory mediators in the synovial fluid. Significant decreases in matrix metalloproteinase activity in DOX-treated joints may indicate a potential chondroprotective effect of DOX.

DOUBLE VAULT COMPOSTING LATRINES IN RURAL PARAGUAY : FEASIBLE CONSTRUCTION AND OPTIMAL USE

Water resource depletion and sanitation are growing problems around the world. A solution to both of these problems is the use of composting latrines, as it requires no water and has been recommended by the World Health Organization as an improved sanitation technology. However, little analysis has been done on the decomposition process occurring inside the latrine, including what temperatures are reached and what variables most affect the composting process. Having better knowledge of how outside variables affect composting latrines can aid development workers on the choice of implementing such technology, and to better educate the users on the appropriate methods of maintenance. This report presents a full, detailed construction manual and temperature data analysis of a double vault composting latrine. During the author’s two year Peace Corps service in rural Paraguay he was involved with building twenty one composting latrines, and took detailed temperature readings and visual observations of his personal latrine for ten months. The author also took limited temperature readings of fourteen community member’s latrines over a three month period. These data points were analyzed to find correlations between compost temperatures and several variables. The two main variables found to affect the compost temperatures were the seasonal trends of the outside temperatures, and the mixing and addition of moisture to the compost. Outside seasonal temperature changes were compared to those of the compost and a linear regression was performed resulting in a R2-value of 0.89. Mixing the compost and adding water, or a water/urine mixture, resulted in temperature increases of the compost 100% of the time, with seasonal temperatures determining the rate and duration of the temperature increases. The temperature readings were also used to find events when certain temperatures were held for sufficient amounts of time to reach total pathogen destruction in the compost. Four different events were recorded when a temperature of 122°F (50°C) was held for at least 24 hours, ensuring total pathogen destruction in that area of the compost. One event of 114.8°F (46°C) held for one week was also recorded, again ensuring total pathogen destruction. Through the analysis of the temperature data, however, it was found that the compost only reached total pathogen destruction levels during ten percent of the data points. Because of this the storage time recommendation outlined by the World Health Organization should be complied with. The WHO recommends storing compost for 1.5-2 years in climates with ambient temperatures of 2-20°C (35-68°F), and for at least 1 year with ambient temperatures of 20-35°C (68-95°F). If these storage durations are obtainable the use of the double vault composting latrine is an economical and achievable solution to sanitation while conserving water resources.

Self-reported non-adherence to antiretroviral therapy repeatedly assessed by two questions predicts treatment failure in virologically suppressed patients

BACKGROUND: The aim of this study was to explore the predictive value of longitudinal self-reported adherence data on viral rebound. METHODS: Individuals in the Swiss HIV Cohort Study on combined antiretroviral therapy (cART) with RNA <50 copies/ml over the previous 3 months and who were interviewed about adherence at least once prior to 1 March 2007 were eligible. Adherence was defined in terms of missed doses of cART (0, 1, 2 or >2) in the previous 28 days. Viral rebound was defined as RNA >500 copies/ml. Cox regression models with time-independent and -dependent covariates were used to evaluate time to viral rebound. RESULTS: A total of 2,664 individuals and 15,530 visits were included. Across all visits, missing doses were reported as follows: 1 dose 14.7%, 2 doses 5.1%, >2 doses 3.8% taking <95% of doses 4.5% and missing > or =2 consecutive doses 3.2%. In total, 308 (11.6%) patients experienced viral rebound. After controlling for confounding variables, self-reported non-adherence remained significantly associated with the rate of occurrence of viral rebound (compared with zero missed doses: 1 dose, hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.72-1.48; 2 doses, HR 2.17, 95% CI 1.46-3.25; >2 doses, HR 3.66, 95% CI 2.50-5.34). Several variables significantly associated with an increased risk of viral rebound irrespective of adherence were identified: being on a protease inhibitor or triple nucleoside regimen (compared with a non-nucleoside reverse transcriptase inhibitor), >5 previous cART regimens, seeing a less-experienced physician, taking co-medication, and a shorter time virally suppressed. CONCLUSIONS: A simple self-report adherence questionnaire repeatedly administered provides a sensitive measure of non-adherence that predicts viral rebound.

A STUDY OF ZINC CONCENTRATION IN HAIR AS AN INDICATION OF ZINC IMBALANCES

Trace metal imbalances have been implicated in several disease and nutritional states. There is mounting concern to identify the nutritional balance of the trace metals needed for growth, mental acuity and physical functioning. These two factors, diseases in which trace metals show involvement and nutritional balance, have made it necessary to be able to accurately describe the trace metal balances of an individual. Although several investigators have measured the concentration of trace metals in the hair and related those observed concentrations to various disease and nutritional states, no one has satisfactorily answered the questions of whether hair is useful to determine trace metal imbalances, whether the concentrations found in hair reflect tissue or serum concentrations of the trace metals, or whether any tissue accurately reflects body status of the trace metals.^ Male mice were used to examine several tissues, heart, liver, kidney, spleen, intestine, brain, bone, hair and serum for copper and zinc concentrations. The environment and dietary intake of the animals were carefully controlled, so that environmental and physical variables were minimized. Dietary intake of zinc was varied while copper intake was held constant. Each experimental diet group was matched with a pair fed control group.^ Of the tissues examined, only the serum was indicative of an early state of zinc imbalance. Neither hair nor the other tissues examined for copper and zinc concentrations were indicative of an acute zinc imbalance in a normal mature mouse. Zinc deficiencies or excesses may manifest themself differently in the chronic imbalance state or in the weanling, aged or traumatized mouse. The tissue response to zinc imbalance may vary in these cases. ^

Identification and quantification of phytochelatins in roots of rice to long-term exposure: evidence of individual role on arsenic accumulation and translocation

Rice has the predilection to take up arsenic in the form of methylated arsenic (o-As) and inorganic arsenic species (i-As). Plants defend themselves using i-As efflux systems and the production of phytochelatins (PCs) to complex i-As. Our study focused on the identification and quantification of phytochelatins by HPLC-ICP-MS/ESI-MS, relating them to the several variables linked to As exposure. GSH, 11 PCs, and As–PC complexes from the roots of six rice cultivars (Italica Carolina, Dom Sofid, 9524, Kitrana 508, YRL-1, and Lemont) exposed to low and high levels of i-As were compared with total, i-As, and o-As in roots, shoots, and grains. Only Dom Sofid, Kitrana 508, and 9524 were found to produce higher levels of PCs even when exposed to low levels of As. PCs were only correlated to i-As in the roots (r=0.884, P <0.001). However, significant negative correlations to As transfer factors (TF) roots–grains (r= –0.739, P <0.05) and shoots–grains (r= –0.541, P <0.05), suggested that these peptides help in trapping i-As but not o-As in the roots, reducing grains’ i-As. Italica Carolina reduced i-As in grains after high exposure, where some specific PCs had a special role in this reduction. In Lemont, exposure to elevated levels of i-As did not result in higher i-As levels in the grains and there were no significant increases in PCs or thiols. Finally, the high production of PCs in Kitrana 508 and Dom Sofid in response to high As treatment did not relate to a reduction of i-As in grains, suggesting that other mechanisms such as As–PC release and transport seems to be important in determining grain As in these cultivars.

Process and pattern in cichlid radiations - inferences for understanding unusually high rates of evolutionary diversification

The cichlid fish radiations in the African Great Lakes differ from all other known cases of rapid speciation in vertebrates by their spectacular trophic diversity and richness of sympatric species, comparable to the most rapid angiosperm radiations. I review factors that may have facilitated these radiations and compare these with insights from recent work on plant radiations. Work to date suggests that it was a coincidence of ecological opportunity, intrinsic ecological versatility and genomic flexibility, rapidly evolving behavioral mate choice and large amounts of standing genetic variation that permitted these spectacular fish radiations. I propose that spatially orthogonal gradients in the fit of phenotypes to the environment facilitate speciation because they allow colonization of alternative fitness peaks during clinal speciation despite local disruptive selection. Such gradients are manifold in lakes because of the interaction of water depth as an omnipresent third spatial dimension with other fitness-relevant variables. I introduce a conceptual model of adaptive radiation that integrates these elements and discuss its applicability to, and predictions for, plant radiations.

A significant effect of the KIR ligand HLA-C on fibrosis progression in chronic C hepatitis with or without liver transplantation.

BACKGROUND & AIMS The interaction of KIR with their HLA ligands drives the activation and inhibition of natural killer (NK) cells. NK cells could be implicated in the development of liver fibrosis in chronic hepatitis C. METHODS We analysed 206 non-transplanted and 53 liver transplanted patients, selected according to their Metavir fibrosis stage. Several variables such as the number of activator KIR or the HLA ligands were considered in multinomial and logistic regression models. Possible confounding variables were also investigated. RESULTS The KIRs were not significant predictors of the fibrosis stage. Conversely, a significant reduction of the HLA-C1C2 genotype was observed in the most advanced fibrosis stage group (F4) in both cohorts. Furthermore, the progression rate of fibrosis was almost 10 times faster in the subgroup of patients after liver transplantation and HLA-C1C2 was significantly reduced in this cohort compared to non-transplanted patients. CONCLUSION This study suggests a possible role of KIR and their ligands in the development of liver damage. The absence of C1 and C2 ligands heterozygosity could lead to less inhibition of NK cells and a quicker progression to a high level of fibrosis in patients infected by HCV, especially following liver transplantation. This article is protected by copyright. All rights reserved.

Psychosocial measures reported by parents in studies of skin cancer prevention

Background. Because it is important to minimize children's sun exposure to reduce skin cancer risk, much of the extensive skin cancer prevention literature consists of studies of children's sun protection, sun avoidance and ultraviolet radiation (UVR) exposure. Little attention has been focused on the measurement of psychosocial constructs in these studies. Identification of the psychosocial correlates or determinants of children's skin cancer risk or risk-reduction behavior is critical to more fully understand and predict behavior. Furthermore, psychosocial variables may be influenced by interventions to reduce risk. Thus, it is important to examine the psychosocial measures used in studies of children's skin cancer prevention. Information on the validity and reliability of psychosocial measures may increase confidence in study findings based on these measures. In particular, self-efficacy and barriers are key constructs in several major theoretical frameworks and parental measures have been associated with children's sun protection. However, there is conceptual overlap of self-efficacy and barriers measures and little is known about the psychometric properties of these measures.^ Study Aims and Methods. The overall goal of this dissertation was to examine the measurement of psychosocial constructs relevant to children's skin cancer prevention. Because children depend primarily on their parents for skin cancer prevention, measures of parents' psychosocial constructs are the focus. Study 1 was a systematic review of parental psychosocial measures used in studies of children's sun protection, sun avoidance and UVR exposure. The specific aims of Study 1 were to (1) describe psychosocial measures reported by parents, including available information on the psychometric properties of these measures and their use in analyses and (2) provide recommendations for the development, refinement and standardized reporting of measures. ^ Study 2 examined the psychometric properties of measures of parental self-efficacy and barriers regarding children's sun protection. Melanoma patients (N=205) who were parents of children ≤ 12 years of age completed a telephone interview that included self-efficacy and barriers measures specific to sunscreen, clothing, shade and limiting time outdoors. The specific aims of Study 2 were to (1) use a confirmatory factor analytic approach to examine the factorial validity of parental self-efficacy and barriers measures, (2) examine the convergent and discriminant validity of behavior-specific measures of self-efficacy and barriers and (3) assess the reliability of item and scale measures.^ Results. In Study 1, a search of standard databases yielded 48 eligible studies. Most studies assessed only one or two psychosocial constructs. Knowledge was measured most frequently. There was little discussion of measure source, development, theoretical background or psychometric properties, besides internal consistency reliability. There was conceptual overlap of some measures. In Study 2, confirmatory factor analytic findings supported the factorial validity of the self-efficacy and barriers measures. When all eight self-efficacy and barriers measures were included in the same model, a modified eight-factor model adequately fit the data, providing preliminary evidence that the measures are distinct. Measure associations supported the convergent validity of all measures and the discriminant validity of most measures. The self-efficacy and barriers measures were reliable.^ Conclusions. Recommendations based on the literature review include developing and refining psychosocial measures based on theory. Describing a measure's theoretical basis and psychometric properties would facilitate critical evaluation. Standardized reporting of source, development, theory, construct, items and analytic role would facilitate comparison of findings, continual refinement and future applications of measures. In the validation study, self-efficacy and barriers measures were examined in a sample of parents with a personal history of melanoma. Findings suggested that these measures are valid and reliable for use in studies of children's sun protection. There was preliminary evidence that these measures are distinct but additional study is needed. ^

THE USE OF MULTIVARIATE ANALYSIS OF COVARIANCE IN EVALUATING THE COMPARABILITY OF LABORATORY DETERMINATIONS IN COOPERATIVE STUDIES

The role of clinical chemistry has traditionally been to evaluate acutely ill or hospitalized patients. Traditional statistical methods have serious drawbacks in that they use univariate techniques. To demonstrate alternative methodology, a multivariate analysis of covariance model was developed and applied to the data from the Cooperative Study of Sickle Cell Disease.^ The purpose of developing the model for the laboratory data from the CSSCD was to evaluate the comparability of the results from the different clinics. Several variables were incorporated into the model in order to control for possible differences among the clinics that might confound any real laboratory differences.^ Differences for LDH, alkaline phosphatase and SGOT were identified which will necessitate adjustments by clinic whenever these data are used. In addition, aberrant clinic values for LDH, creatinine and BUN were also identified.^ The use of any statistical technique including multivariate analysis without thoughtful consideration may lead to spurious conclusions that may not be corrected for some time, if ever. However, the advantages of multivariate analysis far outweigh its potential problems. If its use increases as it should, the applicability to the analysis of laboratory data in prospective patient monitoring, quality control programs, and interpretation of data from cooperative studies could well have a major impact on the health and well being of a large number of individuals. ^

THE IMPACT OF FAMILY HISTORY ON MEDULLARY THYROID CANCER IN MEN2A PATIENTS

The American Thyroid Association recently classified all MEN2A-associated codons into increasing risk levels A-C and stated that some patients may delay prophylactic thyroidectomy if certain criteria are met. One criterion is a less aggressive family history of MTC but whether families with the same mutated codon have variable MTC aggressiveness is not well described. We developed several novel measures of MTC aggressiveness and compared families with the same mutated codon to determine if there is significant inter-familial variability. Pedigrees of families with MEN2A were reviewed for codon mutated and proportion of RET mutation carriers with MTC. Individuals with MTC were classified as having local or distant MTC and whether they had progressive MTC. MTC status and age were assessed at diagnosis and most advanced MTC stage. For those without MTC, age was recorded at prophylactic thyroidectomy or last follow-up if the patient did not have a thyroidectomy. For each pedigree, the mean age of members without MTC, with MTC, and the proportion of RET mutation carriers with local or distant and progressive MTC were calculated. We assessed differences in these variables using ANOVA and the Fisher’s exact test. Sufficient data for analysis were available for families with mutated codons 609 (92 patients from 13 families), 618 (41 patients from 7 families), and 634 (152 patients from 13 families). The only significant differences found were the mean age of patients without MTC between families with codon 609 and 618 mutations even after accounting for prophylactic thyroidectomy (p=0.006 and 0.001, respectively), and in the mean age of MTC diagnosis between families with codon 618 and 634 mutations even after accounting for symptomatic presentation (p=0.023 and 0.014, respectively). However, these differences may be explained by generational differences in ascertainment of RET carriers and the availability of genetic testing when the proband initially presented.

Determination of polybrominated diphenyl ethers in water samples from Mendoza River Basin by HS-SPME-GC-MS/MS

Polybrominated diphenyl ethers (PBDEs) are considered persistent organic pollutants because of their ubiquity, persistence and bioaccumulation. Its harmful effects on human health and the environment, has led to its inclusion of the Stockholm Convention. Little information is found about PBDEs in abiotic systems of the South America in open literature. This paper reports the presence and concentration level of four PBDEs congeners in Mendoza River, Argentina. The selected PBDEs were: 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), 2,2',4,4',6-pentabromodiphenyl ether (BDE- 100) and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). The analytical methodology used was head space-solid phase micro extraction combined with gas chromatographymass spectrometry (HS-SPME-GC-MS/MS). Several variables, including pH, salting out, extraction technique type and extraction time were studied and optimized over the relative response the target analytes. The precision of HS-SPME-GC-MS/MS evaluated over five replicate, leading RSDs values <13%, detection limits (S/N=3) ranging from 0.03 pg ml-1 to 0.12 pg ml-1 and the calibration graph was linear with r2=0.9959. BDE-47 and BDE-100 were the predominant congeners found in the analyzed samples. Their concentrations ranged from not detected to 1.9 pg ml-1 and to 0.5 pg ml-1, respectively.

On nonlinearity in neural encoding models applied to the primary visual cortex

Within the regression framework, we show how different levels of nonlinearity influence the instantaneous firing rate prediction of single neurons. Nonlinearity can be achieved in several ways. In particular, we can enrich the predictor set with basis expansions of the input variables (enlarging the number of inputs) or train a simple but different model for each area of the data domain. Spline-based models are popular within the first category. Kernel smoothing methods fall into the second category. Whereas the first choice is useful for globally characterizing complex functions, the second is very handy for temporal data and is able to include inner-state subject variations. Also, interactions among stimuli are considered. We compare state-of-the-art firing rate prediction methods with some more sophisticated spline-based nonlinear methods: multivariate adaptive regression splines and sparse additive models. We also study the impact of kernel smoothing. Finally, we explore the combination of various local models in an incremental learning procedure. Our goal is to demonstrate that appropriate nonlinearity treatment can greatly improve the results. We test our hypothesis on both synthetic data and real neuronal recordings in cat primary visual cortex, giving a plausible explanation of the results from a biological perspective.

Desarrollo de estructuras nanofotonicas de campo cercano para intensificacion localizada de luz en celulas solares de banda intermedia - Near-field nanophotonic structures for localized light enhancement in intermediate band solar cells

This doctoral thesis explores some of the possibilities that near-field optics can bring to photovoltaics, and in particular to quantum-dot intermediate band solar cells (QD-IBSCs). Our main focus is the analytical optimization of the electric field distribution produced in the vicinity of single scattering particles, in order to produce the highest possible absorption enhancement in the photovoltaic medium in their surroundings. Near-field scattering structures have also been fabricated in laboratory, allowing the application of the previously studied theoretical concepts to real devices. We start by looking into the electrostatic scattering regime, which is only applicable to sub-wavelength sized particles. In this regime it was found that metallic nano-spheroids can produce absorption enhancements of about two orders of magnitude on the material in their vicinity, due to their strong plasmonic resonance. The frequency of such resonance can be tuned with the shape of the particles, allowing us to match it with the optimal transition energies of the intermediate band material. Since these metallic nanoparticles (MNPs) are to be inserted inside the cell photovoltaic medium, they should be coated by a thin insulating layer to prevent electron-hole recombination at their surface. This analysis is then generalized, using an analytical separation-of-variables method implemented in Mathematica7.0, to compute scattering by spheroids of any size and material. This code allowed the study of the scattering properties of wavelengthsized particles (mesoscopic regime), and it was verified that in this regime dielectric spheroids perform better than metallic. The light intensity scattered from such dielectric spheroids can have more than two orders of magnitude than the incident intensity, and the focal region in front of the particle can be shaped in several ways by changing the particle geometry and/or material. Experimental work was also performed in this PhD to implement in practice the concepts studied in the analysis of sub-wavelength MNPs. A wet-coating method was developed to self-assemble regular arrays of colloidal MNPs on the surface of several materials, such as silicon wafers, amorphous silicon films, gallium arsenide and glass. A series of thermal and chemical tests have been performed showing what treatments the nanoparticles can withstand for their embedment in a photovoltaic medium. MNPs arrays are then inserted in an amorphous silicon medium to study the effect of their plasmonic near-field enhancement on the absorption spectrum of the material. The self-assembled arrays of MNPs constructed in these experiments inspired a new strategy for fabricating IBSCs using colloidal quantum dots (CQDs). Such CQDs can be deposited in self-assembled monolayers, using procedures similar to those developed for the patterning of colloidal MNPs. The use of CQDs to form the intermediate band presents several important practical and physical advantages relative to the conventional dots epitaxially grown by the Stranski-Krastanov method. Besides, this provides a fast and inexpensive method for patterning binary arrays of QDs and MNPs, envisioned in the theoretical part of this thesis, in which the MNPs act as antennas focusing the light in the QDs and therefore boosting their absorption

Linear global instability of non-orthogonal incompressible swept attachment-line boundary layer flow

Instability of the orthogonal swept attachment line boundary layer has received attention by local1, 2 and global3–5 analysis methods over several decades, owing to the significance of this model to transition to turbulence on the surface of swept wings. However, substantially less attention has been paid to the problem of laminar flow instability in the non-orthogonal swept attachment-line boundary layer; only a local analysis framework has been employed to-date.6 The present contribution addresses this issue from a linear global (BiGlobal) instability analysis point of view in the incompressible regime. Direct numerical simulations have also been performed in order to verify the analysis results and unravel the limits of validity of the Dorrepaal basic flow7 model analyzed. Cross-validated results document the effect of the angle _ on the critical conditions identified by Hall et al.1 and show linear destabilization of the flow with decreasing AoA, up to a limit at which the assumptions of the Dorrepaal model become questionable. Finally, a simple extension of the extended G¨ortler-H¨ammerlin ODE-based polynomial model proposed by Theofilis et al.4 is presented for the non-orthogonal flow. In this model, the symmetries of the three-dimensional disturbances are broken by the non-orthogonal flow conditions. Temporal and spatial one-dimensional linear eigenvalue codes were developed, obtaining consistent results with BiGlobal stability analysis and DNS. Beyond the computational advantages presented by the ODE-based model, it allows us to understand the functional dependence of the three-dimensional disturbances in the non-orthogonal case as well as their connections with the disturbances of the orthogonal stability problem.

Implicaciones de la accesibilidad configuracional en la movilidad peatonal. El caso de Madrid = The implications of configurational accessibility in pedestrian mobility. The case of Madrid

- Resumen La hipótesis que anima esta tesis doctoral es que algunas de las características del entorno urbano, en particular las que describen la accesibilidad de su red de espacio público, podrían estar relacionadas con la proporción de viajes a pie o reparto modal, que tiene cada zona o barrio de Madrid. Uno de los puntos de partida de dicha hipótesis que el entorno urbano tiene una mayor influencia sobre los viaje a pie que en sobre otros modos de transporte, por ejemplo que en los viajes de bicicleta o en transporte público; y es que parece razonable suponer que estos últimos van a estar más condicionadas por ejemplo por la disponibilidad de vías ciclistas, en el primer caso, o por la existencia de un servicio fiable y de calidad, en el segundo. Otra de las motivaciones del trabajo es que la investigación en este campo de la accesibilidad del espacio público, en concreto la denominada “Space Syntax”, ha probado en repetidas ocasiones la influencia de la red de espacio público en cómo se distribuye la intensidad del tráfico peatonal por la trama urbana, pero no se han encontrado referencias de la influencia de dicho elemento sobre el reparto modal. De acuerdo con la hipótesis y con otros trabajos anteriores se propone una metodología basada en el análisis empírico y cuantitativo. Su objetivo es comprobar si la red de espacio público, independientemente de otras variables como los usos del suelo, incluso de las variables de ajenas entorno no construido, como las socioeconómicas, está o no relacionada estadísticamente con la proporción de peatones viajes en las zonas urbanas. Las técnicas estadísticas se utilizan para comprobar sistemáticamente la asociación de las variables del entorno urbano, denominadas variables independientes, con el porcentaje de viajes a pie, la variable dependiente. En términos generales, la metodología es similar a la usada en otros trabajos en este campo como los de CERVERÓ y KOCKLEMAN (1997), CERVERÓ y DUNCAN (2003), o para los que se utilizan principalmente en la revisión general de TRB (2005) o, más recientemente, en ZEGRAS (2006) o CHATMAN (2009). Otras opciones metodológicas, como los métodos de preferencias declaradas (ver LOUVIERE, HENSHER y SWAIT, 2000) o el análisis basado en agentes (PENN & TURNER, 2004) fueron descartados, debido a una serie de razones, demasiado extensas para ser descritas aquí. El caso de estudio utilizado es la zona metropolitana de Madrid, abarcándola hasta la M-50, es decir en su mayor parte, con un tamaño aproximado de 31x34 Km y una población de 4.132.820 habitantes (aproximadamente el 80% de la población de la región). Las principales fuentes de datos son la Encuesta Domiciliaria de Movilidad de 2004 (EDM04), del Consorcio Regional de Transportes de Madrid que es la última disponible (muestra: > 35.000 familias,> 95.000 personas), y un modelo espacial del área metropolitana, integrando el modelo para calcular los índices de Space Syntax y un Sistema de Información Geográfica (SIG). La unidad de análisis, en este caso las unidades espaciales, son las zonas de transporte (con una población media de 7.063 personas) y los barrios (con una población media de 26.466 personas). Las variables del entorno urbano son claramente el centro del estudio. Un total de 20 índices (de 21) se seleccionan de entre los más relevantes encontrados en la revisión de la producción científica en este campo siendo que, al mismo tiempo, fueran accesibles. Nueve de ellos se utilizan para describir las características de los usos del suelo, mientras que otros once se usan para describir la red de espacios públicos. Estos últimos incluyen las variables de accesibilidad configuracional, que son, como se desprende de su título, el centro del estudio propuesto. La accesibilidad configuracional es un tipo especial de accesibilidad que se basa en la configuración de la trama urbana, según esta fue definida por HILLIER (1996), el autor de referencia dentro de esta línea de investigación de Space Syntax. Además se incluyen otras variables de la red de espacio público más habituales en los estudios de movilidad, y que aquí se denominan características geométricas de los elementos de la red, tales como su longitud, tipo de intersección, conectividad, etc. Por último se incluye además una variable socioeconómica, es decir ajena al entorno urbano, para evaluar la influencia de los factores externos, pues son varios los que pueden tener un impacto en la decisión de caminar (edad, género, nivel de estudios, ingresos, tasa de motorización, etc.). La asociación entre las variables se han establecido usando análisis de correlación (bivariante) y modelos de análisis multivariante. Las primeras se calculan entre por pares entre cada una de las 21 variables independientes y la dependiente, el porcentaje de viajes a pie. En cuanto a los segundos, se han realizado tres tipos de estudios: modelo multivariante general lineal, modelo multivariante general curvilíneo y análisis discriminante. Todos ellos son capaces de generar modelos de asociación entre diversas variables, pudiéndose de esta manera evaluar con bastante precisión en qué medida cada modelo reproduce el comportamiento de la variable dependiente, y además, el peso o influencia de cada variable en el modelo respecto a las otras. Los resultados fundamentales del estudio se expresan en dos modelos finales alternativos, que demuestran tener una significativa asociación con el porcentaje de viajes a pie (R2 = 0,6789, p <0,0001), al explicar las dos terceras partes de su variabilidad. En ellos, y en general en todo el estudio realizado, se da una influencia constante de tres índices en particular, que quedan como los principales. Dos de ellos, de acuerdo con muchos de los estudios previos, corresponden a la densidad y la mezcla de usos del suelo. Pero lo más novedoso de los resultados obtenidos es que el tercero es una medida de la accesibilidad de la red de espacio público, algo de lo que no había referencias hasta ahora. Pero, ¿cuál es la definición precisa y el peso relativo de cada uno en el modelo, es decir, en la variable independiente? El de mayor peso en la mayor parte de los análisis realizados es el índice de densidad total (n º residentes + n º puestos de trabajo + n º alumnos / Ha). Es decir, una densidad no sólo de población, sino que incluye algunas de las actividades más importantes que pueden darse una zona para generar movilidad a pie. El segundo que mayor peso adquiere, llegando a ser el primero en alguno de los análisis estadísticos efecturados, es el índice de accesibuilidad configuracional denominado integración de radio 5. Se trata de una medida de la accesibilidad de la zona, de su centralidad, a la escala de, más un menor, un distrito o comarca. En cuanto al tercero, obtiene una importancia bastante menor que los anteriores, y es que representa la mezcla de usos. En concreto es una medida del equilibrio entre los comercios especializados de venta al por menor y el número de residentes (n º de tiendas especializadas en alimentación, bebidas y tabaco / n º de habitantes). Por lo tanto, estos resultados confirman buena parte de los de estudios anteriores, especialmente los relativas a los usos del suelo, pero al mismo tiempo, apuntan a que la red de espacio público podría tener una influir mayor de la comprobada hasta ahora en la proporción de peatones sobre el resto de modos de transportes. Las razones de por qué esto puede ser así, se discuten ampliamente en las conclusiones. Finalmente se puede precisar que dicha conclusión principal se refiere a viajes de una sola etapa (no multimodales) que se dan en los barrios y zonas del área metropolitana de Madrid. Por supuesto, esta conclusión tiene en la actualidad, una validez limitada, ya que es el resultado de un solo caso — Abstract The research hypothesis for this Ph.D. Thesis is that some characteristics of the built environment, particularly those describing the accessibility of the public space network, could be associated with the proportion of pedestrians in all trips (modal split), found in the different parts of a city. The underlying idea is that walking trips are more sensitive to built environment than those by other transport modes, such as for example those by bicycle or by public transport, which could be more conditioned by, e.g. infrastructure availability or service frequency and quality. On the other hand, it has to be noted that the previously research on this field, in particular within Space Syntax’s where this study can be referred, have tested similar hypothesis using pedestrian volumes as the dependent variable, but never against modal split. According to such hypothesis, research methodology is based primarily on empirical quantitative analysis, and it is meant to be able to assess whether public space network, no matter other built environment and non-built environment variables, could have a relationship with the proportion of pedestrian trips in urban areas. Statistical techniques are used to check the association of independent variables with the percentage of walking in all trips, the dependent one. Broadly speaking this methodology is similar to that of previous studies in the field such as CERVERO&KOCKLEMAN (1997), CERVERO & DUNCAN (2003), or to those used mainly in the general review of T.R.B. (2005) or, more recently in ZEGRAS (2006) or CHATMAN (2009). Other methodological options such as stated choice methods (see LOUVIERE, HENSHER & SWAIT, 2000) or agent based analysis (PENN & TURNER, 2004), were discarded, due to a number of reasons, too long to be described here. The case study is not the entire Madrid’s metropolitan area, but almost (4.132.820 inhabitants, about 80% of region´s population). Main data sources are the Regional Mobility Home Based Survey 2004 (EDM04), which is the last available (sample: >35.000 families, > 95.000 individuals), and a spatial model of the metropolitan area, developed using Space Syntax and G.I.S. techniques. The analysis unit, in this case spatial units, are both transport zones (mean population = 7.063) and neighborhoods (mean population = 26.466). The variables of the built environment are clearly the core of the study. A total of 20 (out of 21) are selected from among those found in the literature while, at the same time, being accessible. Nine out of them are used to describe land use characteristics while another eleven describe the network of public spaces. Latter ones include configurational accessibility or Space Syntax variables. This is a particular sort of accessibility related with the concept of configuration, by HILLIER (1996), one of the main authors of Space Syntax, But it also include more customary variables used in mobility research to describe the urban design or spatial structure (here public space network), which here are called geometric characteristics of the such as its length, type of intersection, conectivity, density, etc. Finally a single socioeconomic variable was included in order to assess the influence non built environment factors that also may have an impact on walking (age, income, motorization rate, etc.). The association among variables is worked out using bi-variate correlation analysis and multivariate-analysis. Correlations are calculated among the 21 independent variables and the dependent one, the percentage of walking trips. Then, three types of multi-variate studies are run: general linear, curvilinear and discriminant multi-variate analysis. The latter are fully capable of generating complex association models among several variables, assessing quite precisely to what extent each model reproduces the behavior of the dependent variable, and also the weight or influence of each variable in the model. This study’s results show a consistent influence of three particular indexes in the two final alternative models of the multi-variate study (best, R2=0,6789, p<0,0000). Not surprisingly, two of them correspond to density and mix of land uses. But perhaps more interesting is that the third one is a measure of the accessibility of the public space network, a variable less important in the literature up to now. Additional precisions about them and their relative weight could also be of some interest. The density index is not only about population but includes most important activities in an area (nº residents + nº jobs+ nº students/Ha). The configurational index (radius 5 integration) is a measure of the accessibility of the area, i.e. centrality, at the scale of, more a less, a district. Regarding the mix of land uses index, this one is a measure of the balance between retail, in fact local basic retail, and the number of residents (nº of convenience shops / nº of residents). Referring to their weights, configurational index (radius 5 integration) gets the higher standardized coefficient of the final equation. However, in the final equations, there are a higher number of indexes coming from the density or land use mix categories than from public space network enter. Therefore, these findings seem to support part of the field’s knowledge, especially those concerning land uses, but at the same time they seem to bring in the idea that the configuration of the urban grid could have an influence in the proportion of walkers (as a part of total trips on any transport mode) that do single journey trips in the neighborhoods of Madrid, Spain. Of course this conclusion has, at present, a limited validity since it’s the result of a single case. The reasons of why this can be so, are discussed in the last part of the thesis.