Homicide and public security indicator trends in the city of Sao Paulo between 1996 and 2008: a time-series ecological study

The scope of this paper was to analyze the association between homicides and public security indicators in Sao Paulo between 1996 and 2008, after monitoring the unemployment rate and the proportion of youths in the population. A time-series ecological study for 1996 and 2008 was conducted with Sao Paulo as the unit of analysis. Dependent variable: number of deaths by homicide per year. Main independent variables: arrest-incarceration rate, access to firearms, police activity. Data analysis was conducted using Stata. IC 10.0 software. Simple and multivariate negative binomial regression models were created. Deaths by homicide and arrest-incarceration, as well as police activity were significantly associated in simple regression analysis. Access to firearms was not significantly associated to the reduction in the number of deaths by homicide (p>0,05). After adjustment, the associations with both the public security indicators were not significant. In Sao Paulo the role of public security indicators are less important as explanatory factors for a reduction in homicide rates, after adjustment for unemployment rate and a reduction in the proportion of youths. The results reinforce the importance of socioeconomic and demographic factors for a change in the public security scenario in Sao Paulo.

ENVIRONMENTAL TOBACCO SMOKE INDUCES OXIDATIVE STRESS IN DISTINCT BRAIN REGIONS OF INFANT MICE

Environmental tobacco smoke (ETS) leads to the death of 600,000 nonsmokers annually and is associated with disturbances in antioxidant enzyme capacity in the adult rodent brain. However, little is known regarding the influence of ETS on brain development. The aim of this study was to determine levels of malonaldehyde (MDA) and 3-nitrotyrosine (3-NT), as well as enzymatic antioxidant activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), and superoxide dismutase (SOD), in distinct brain structures. BALB/c mice were exposed to ETS twice daily for 1 h from postnatal day 5 through postnatal day 18. Acute exposure was performed for 1 h on postnatal day 18. Mice were euthanized either immediately (0) or 3 h after the last exposure. Immediately after an acute exposure there were higher GR and GST activities and MDA levels in the hippocampus, higher GPx and SOD activities in the prefrontal cortex, and higher GST activity and MDA levels in the striatum and cerebellum. Three hours later there was an increase in SOD activity and MDA levels in the hippocampus and a decrease in the activity of all enzymes in the prefrontal cortex. Immediately after final repeated exposure there were elevated levels of GST and GR activity and decreased GPx activity in the hippocampus. Moreover, a rise was found in GPx and GST activities in the prefrontal cortex and increased GST and GPx activity in the striatum and cerebellum, respectively. After 3 h the prefrontal cortex showed elevated GR and GST activities, and the striatum displayed enhanced GST activity. Data showed that enzymatic antioxidant system in the central nervous system responds to ETS differently in different regions of the brain and that a form of adaptation occurs after several days of exposure.

Resveratrol reduces myofibroblast arrhythmogenicity

Background: Among grape skin polyphenols, trans-resveratrol (RES) has been reported to slow the development of cardiac fibrosis and to affect myofibroblast (MFB) differentiation. Because MFBs induce slow conduction and ectopic activity following heterocellular gap junctional coupling to cardiomyocytes, we investigated whether RES and its main metabolites affect arrhythmogenic cardiomyocyte-MFB interactions. Methods: Experiments were performed with patterned growth strands of neonatal rat ventricular cardiomyocytes coated with cardiac MFBs. Impulse propagation characteristics were measured optically using voltage-sensitive dyes. Long-term video recordings served to characterize drug-related effects on ectopic activity. Data are given as means ± S.D. (n = 4–20). Results: Exposure of pure cardiomyocyte strands to RES at concentrations up to 10 µmol/L had no significant effects on impulse conduction velocity (θ) and maximal action potential upstroke velocities (dV/dtmax). By contrast, in MFB-coated strands exhibiting slow conduction, RES enhanced θ with an EC50 of ~10 nmol/L from 226 ± 38 to 344 ± 24 mm/s and dV/dtmax from 48 ± 7 to 69 ± 2%APA/ms, i.e., to values of pure cardiomyocyte strands (347 ± 33 mm/s; 75 ± 4%APA/ms). Moreover, RES led to a reduction of ectopic activity over the course of several hours in heterocellular preparations. RES is metabolized quickly in the body; therefore, we tested the main known metabolites for functional effects and found them similarly effective in normalizing conduction with EC50s of ~10 nmol/L (3-OH-RES), ~20 nmol/L (RES-3-O-β-glucuronide) and ~10 nmol/L (RES-sulfate), respectively. At these concentrations, neither RES nor its metabolites had any effects on MFB morphology and α-smooth muscle actin expression. This suggests that the antiarrhythmic effects observed were based on mechanisms different from a change in MFB phenotype. Conclusions: The results demonstrate that RES counteracts MFB-dependent arrhythmogenic slow conduction and ectopic activity at physiologically relevant concentrations. Because RES is rapidly metabolized following intestinal absorption, the finding of equal antiarrhythmic effectiveness of the main RES metabolites warrants their inclusion in future studies of potentially beneficial effects of these substances on the heart.

Phenotypic and molecular characterization of hyperpigmented group B Streptococci.

Group B Streptococcus (GBS) causes invasive infections in neonates, older adults and patients with comorbidities. β-hemolysin/cytolysin is an important GBS virulence factor. It is encoded by the cyl operon and confers GBS hemolytic activity. Isolates displaying hyperpigmentation are typically hyperhemolytic. Comparison of clonally identical isolates displaying different levels of pigmentation has shown transcriptional dysregulation due to mutations in components of the control of the virulence S/R (CovS/R) regulatory system. In addition, hyperpigmented isolates show decreased CAMP factor and decreased capsule thickness. In analogy to findings in group A Streptococcus, a pivotal role of CovS/R has been proposed in the host-pathogen interaction of invasive GBS infection. However, corresponding investigations on multiple clinical GBS isolates have not been performed. We prospectively collected hyperpigmented isolates found in a diagnostic laboratory and performed phenotypic, molecular and transcriptional analyses. In the period from 2008 to 2012, we found 10 isolates obtained from 10 patients. The isolates reflected both invasive pathogens and colonizers. In three cases, clonally identical but phenotypically different variants were also found. Hence, the analyses included 13 isolates. No capsular serotype was found to be significantly more frequent. Bacterial pigments were analyzed via spectrophotometry and for their hemolytic activity. Data obtained for typical absorbance spectra peaks correlated significantly with hemolytic activity. Molecular analysis of the cyl operon showed that it was conserved in all isolates. The covR sequence displayed mutations in five isolates; in one isolate, the CovR binding site to cylX was abrogated. Our results on clinical isolates support previous findings on CovR-deficient isogenic mutants, but suggest that - at least in some clinical isolates - for β-hemolysin/cytolysin and CAMP factor production, other molecular pathways may be involved.

L-mimosine increases the production of vascular endothelial growth factor in human tooth slice organ culture model.

AIM To assess the pro-angiogenic and pro-inflammatory capacity of the dentine-pulp complex in response to the prolyl hydroxylase inhibitor L-mimosine in a tooth slice organ culture model. METHODOLOGY Human teeth were sectioned transversely into 600-μm-thick slices and cultured in medium supplemented with serum and antibiotics. Then, pulps were stimulated for 48 h with L-mimosine. Pulps were subjected to viability measurements based on formazan formation in MTT assays. In addition, histological evaluation of pulps was performed based on haematoxylin and eosin staining. Culture supernatants were subjected to immunoassays for vascular endothelial growth factor (VEGF) to determine the pro-angiogenic capacity and to immunoassays for interleukin (IL)-6 and IL-8 to assess the pro-inflammatory response. Interleukin-1 served as pro-inflammatory control. Echinomycin was used to inhibit hypoxia-inducible factor-1 (HIF-1) alpha activity. Data were analysed using Student's t-test and Mann-Whitney U test. RESULTS Pulps within tooth slices remained vital upon L-mimosine stimulation as indicated by formazan formation and histological evaluation. L-mimosine increased VEGF production when normalized to formazan formation in the pulp tissue of the tooth slices (P < 0.05). This effect on VEGF was reduced by echinomycin (P < 0.01). Changes in normalized IL-6 and IL-8 levels upon treatment with L-mimosine did not reach the level of significance (P > 0.05), whilst treatment with IL-1, which served as positive control, increased IL-6 (P < 0.05) and IL-8 levels (P < 0.05). CONCLUSIONS The prolyl hydroxylase inhibitor L-mimosine increased VEGF production via HIF-1 alpha in the tooth slice organ culture model whilst inducing no prominent increase in IL-6 and IL-8. Pre-clinical studies will reveal if these in vitro effects translate into dental pulp regeneration.

Análisis y modelización de la dinámica emergente durante el proceso de difusión de información en las redes sociales de internet

Durante la actividad diaria, la sociedad actual interactúa constantemente por medio de dispositivos electrónicos y servicios de telecomunicaciones, tales como el teléfono, correo electrónico, transacciones bancarias o redes sociales de Internet. Sin saberlo, masivamente dejamos rastros de nuestra actividad en las bases de datos de empresas proveedoras de servicios. Estas nuevas fuentes de datos tienen las dimensiones necesarias para que se puedan observar patrones de comportamiento humano a grandes escalas. Como resultado, ha surgido una reciente explosión sin precedentes de estudios de sistemas sociales, dirigidos por el análisis de datos y procesos computacionales. En esta tesis desarrollamos métodos computacionales y matemáticos para analizar sistemas sociales por medio del estudio combinado de datos derivados de la actividad humana y la teoría de redes complejas. Nuestro objetivo es caracterizar y entender los sistemas emergentes de interacciones sociales en los nuevos espacios tecnológicos, tales como la red social Twitter y la telefonía móvil. Analizamos los sistemas por medio de la construcción de redes complejas y series temporales, estudiando su estructura, funcionamiento y evolución en el tiempo. También, investigamos la naturaleza de los patrones observados por medio de los mecanismos que rigen las interacciones entre individuos, así como medimos el impacto de eventos críticos en el comportamiento del sistema. Para ello, hemos propuesto modelos que explican las estructuras globales y la dinámica emergente con que fluye la información en el sistema. Para los estudios de la red social Twitter, hemos basado nuestros análisis en conversaciones puntuales, tales como protestas políticas, grandes acontecimientos o procesos electorales. A partir de los mensajes de las conversaciones, identificamos a los usuarios que participan y construimos redes de interacciones entre los mismos. Específicamente, construimos una red para representar quién recibe los mensajes de quién y otra red para representar quién propaga los mensajes de quién. En general, hemos encontrado que estas estructuras tienen propiedades complejas, tales como crecimiento explosivo y distribuciones de grado libres de escala. En base a la topología de estas redes, hemos indentificado tres tipos de usuarios que determinan el flujo de información según su actividad e influencia. Para medir la influencia de los usuarios en las conversaciones, hemos introducido una nueva medida llamada eficiencia de usuario. La eficiencia se define como el número de retransmisiones obtenidas por mensaje enviado, y mide los efectos que tienen los esfuerzos individuales sobre la reacción colectiva. Hemos observado que la distribución de esta propiedad es ubicua en varias conversaciones de Twitter, sin importar sus dimensiones ni contextos. Con lo cual, sugerimos que existe universalidad en la relación entre esfuerzos individuales y reacciones colectivas en Twitter. Para explicar los factores que determinan la emergencia de la distribución de eficiencia, hemos desarrollado un modelo computacional que simula la propagación de mensajes en la red social de Twitter, basado en el mecanismo de cascadas independientes. Este modelo nos permite medir el efecto que tienen sobre la distribución de eficiencia, tanto la topología de la red social subyacente, como la forma en que los usuarios envían mensajes. Los resultados indican que la emergencia de un grupo selecto de usuarios altamente eficientes depende de la heterogeneidad de la red subyacente y no del comportamiento individual. Por otro lado, hemos desarrollado técnicas para inferir el grado de polarización política en redes sociales. Proponemos una metodología para estimar opiniones en redes sociales y medir el grado de polarización en las opiniones obtenidas. Hemos diseñado un modelo donde estudiamos el efecto que tiene la opinión de un pequeño grupo de usuarios influyentes, llamado élite, sobre las opiniones de la mayoría de usuarios. El modelo da como resultado una distribución de opiniones sobre la cual medimos el grado de polarización. Aplicamos nuestra metodología para medir la polarización en redes de difusión de mensajes, durante una conversación en Twitter de una sociedad políticamente polarizada. Los resultados obtenidos presentan una alta correspondencia con los datos offline. Con este estudio, hemos demostrado que la metodología propuesta es capaz de determinar diferentes grados de polarización dependiendo de la estructura de la red. Finalmente, hemos estudiado el comportamiento humano a partir de datos de telefonía móvil. Por una parte, hemos caracterizado el impacto que tienen desastres naturales, como innundaciones, sobre el comportamiento colectivo. Encontramos que los patrones de comunicación se alteran de forma abrupta en las áreas afectadas por la catástofre. Con lo cual, demostramos que se podría medir el impacto en la región casi en tiempo real y sin necesidad de desplegar esfuerzos en el terreno. Por otra parte, hemos estudiado los patrones de actividad y movilidad humana para caracterizar las interacciones entre regiones de un país en desarrollo. Encontramos que las redes de llamadas y trayectorias humanas tienen estructuras de comunidades asociadas a regiones y centros urbanos. En resumen, hemos mostrado que es posible entender procesos sociales complejos por medio del análisis de datos de actividad humana y la teoría de redes complejas. A lo largo de la tesis, hemos comprobado que fenómenos sociales como la influencia, polarización política o reacción a eventos críticos quedan reflejados en los patrones estructurales y dinámicos que presentan la redes construidas a partir de datos de conversaciones en redes sociales de Internet o telefonía móvil. ABSTRACT During daily routines, we are constantly interacting with electronic devices and telecommunication services. Unconsciously, we are massively leaving traces of our activity in the service providers’ databases. These new data sources have the dimensions required to enable the observation of human behavioral patterns at large scales. As a result, there has been an unprecedented explosion of data-driven social research. In this thesis, we develop computational and mathematical methods to analyze social systems by means of the combined study of human activity data and the theory of complex networks. Our goal is to characterize and understand the emergent systems from human interactions on the new technological spaces, such as the online social network Twitter and mobile phones. We analyze systems by means of the construction of complex networks and temporal series, studying their structure, functioning and temporal evolution. We also investigate on the nature of the observed patterns, by means of the mechanisms that rule the interactions among individuals, as well as on the impact of critical events on the system’s behavior. For this purpose, we have proposed models that explain the global structures and the emergent dynamics of information flow in the system. In the studies of the online social network Twitter, we have based our analysis on specific conversations, such as political protests, important announcements and electoral processes. From the messages related to the conversations, we identify the participant users and build networks of interactions with them. We specifically build one network to represent whoreceives- whose-messages and another to represent who-propagates-whose-messages. In general, we have found that these structures have complex properties, such as explosive growth and scale-free degree distributions. Based on the topological properties of these networks, we have identified three types of user behavior that determine the information flow dynamics due to their influence. In order to measure the users’ influence on the conversations, we have introduced a new measure called user efficiency. It is defined as the number of retransmissions obtained by message posted, and it measures the effects of the individual activity on the collective reacixtions. We have observed that the probability distribution of this property is ubiquitous across several Twitter conversation, regardlessly of their dimension or social context. Therefore, we suggest that there is a universal behavior in the relationship between individual efforts and collective reactions on Twitter. In order to explain the different factors that determine the user efficiency distribution, we have developed a computational model to simulate the diffusion of messages on Twitter, based on the mechanism of independent cascades. This model, allows us to measure the impact on the emergent efficiency distribution of the underlying network topology, as well as the way that users post messages. The results indicate that the emergence of an exclusive group of highly efficient users depends upon the heterogeneity of the underlying network instead of the individual behavior. Moreover, we have also developed techniques to infer the degree of polarization in social networks. We propose a methodology to estimate opinions in social networks and to measure the degree of polarization in the obtained opinions. We have designed a model to study the effects of the opinions of a small group of influential users, called elite, on the opinions of the majority of users. The model results in an opinions distribution to which we measure the degree of polarization. We apply our methodology to measure the polarization on graphs from the messages diffusion process, during a conversation on Twitter from a polarized society. The results are in very good agreement with offline and contextual data. With this study, we have shown that our methodology is capable of detecting several degrees of polarization depending on the structure of the networks. Finally, we have also inferred the human behavior from mobile phones’ data. On the one hand, we have characterized the impact of natural disasters, like flooding, on the collective behavior. We found that the communication patterns are abruptly altered in the areas affected by the catastrophe. Therefore, we demonstrate that we could measure the impact of the disaster on the region, almost in real-time and without needing to deploy further efforts. On the other hand, we have studied human activity and mobility patterns in order to characterize regional interactions on a developing country. We found that the calls and trajectories networks present community structure associated to regional and urban areas. In summary, we have shown that it is possible to understand complex social processes by means of analyzing human activity data and the theory of complex networks. Along the thesis, we have demonstrated that social phenomena, like influence, polarization and reaction to critical events, are reflected in the structural and dynamical patterns of the networks constructed from data regarding conversations on online social networks and mobile phones.

La reutilización de efluentes depurados en España: retrospectiva, desarrollo del marco normativo, estudio de las tecnologías de regeneración frente a los biorreactores de membrana y sus costes en función del uso

La reutilización de efluentes depurados siempre ha sido una opción en lugares con déficit coyuntural o estructural de recursos hídricos, se haya o no procedido a la regulación y planificación de esta práctica. La necesidad se crea a partir de las demandas de una zona, normalmente riego agrícola, que ven un mejor desarrollo de su actividad por contar con este recurso. España es el país de la UE que más caudal reutiliza, y está dentro de los diez primeros a nivel mundial. La regulación de esta práctica por el RD 1620/2007, ayudó a incorporar la reutilización de efluentes depurados a la planificación hidrológica como parte de los programas de medidas, con objeto de mitigar presiones, como son las extracciones de agua superficial y subterránea, o mejoras medioambientales evitando un vertido. El objeto de este trabajo es conocer la situación de la reutilización de efluentes depurados en España, los diferentes escenarios y planteamientos de esta actividad, el desarrollo del marco normativo y su aplicabilidad, junto a los tratamientos que permiten alcanzar los límites de calidad establecidos en la normativa vigente, en función de los distintos usos. Además, se aporta un análisis de costes de las distintas unidades de tratamiento y tipologías de líneas de regeneración, tanto de las utilizadas después de un tratamiento secundario como de otras opciones de depuración, como son los biorreactores de membrana (MBRs). Para el desarrollo de estos objetivos, en primer lugar, se aborda el conocimiento de la situación de la reutilización en España a través de una base de datos diseñada para cubrir todos los aspectos de esta actividad: datos de la estación depuradora de aguas residuales (EDAR), de la estación regeneradora (ERA), caudales depurados, reutilizados, volúmenes utilizados y ubicación de los distintos usos, tipos de líneas de tratamiento, calidades del agua reutilizada, etc. Las principales fuentes de información son las Confederaciones Hidrográficas (CCHH) a través de las concesiones de uso del agua depurada, las entidades de saneamiento y depuración de las distintas comunidades autónomas (CCAA), ayuntamientos, Planes Hidrológicos de Cuenca (PHC) y visitas a las zonas más emblemáticas. Además, se revisan planes y programas con el fin de realizar una retrospectiva de cómo se ha ido consolidando y desarrollando esta práctica en las distintas zonas de la geografía española. Se han inventariado 322 sistemas de reutilización y 216 tratamientos de regeneración siendo el más extendido la filtración mediante filtro arena seguido de una desinfección mediante hipoclorito, aunque este tratamiento se ha ido sustituyendo por un físico-químico con decantación lamelar, filtro de arena y radiación ultravioleta, tratamiento de regeneración convencional (TRC), y otros tratamientos que pueden incluir membranas, tratamientos de regeneración avanzados (TRA), con dosificación de hipoclorito como desinfección residual, para adaptarse al actual marco normativo. El uso más extendido es el agrícola con el 70% del caudal total reutilizado, estimado en 408 hm3, aunque la capacidad de los tratamientos de regeneración esperada para 2015, tras el Plan Nacional de Reutilización de Aguas (PNRA), es tres veces superior. Respecto al desarrollo normativo, en las zonas donde la reutilización ha sido pionera, las administraciones competentes han ido desarrollando diferentes recomendaciones de calidad y manejo de este tipo de agua. El uso agrícola, y en zonas turísticas, el riego de campos de golf, fueron los dos primeros usos que tuvieron algún tipo de recomendación incluso reglamentación. Esta situación inicial, sin una normativa a nivel estatal ni recomendaciones europeas, creó cierta incertidumbre en el avance de la reutilización tanto a nivel de concesiones como de planificación. En la actualidad sigue sin existir una normativa internacional para la reutilización y regeneración de efluentes depurados. Las recomendaciones de referencia a nivel mundial, y en concreto para el uso agrícola, son las de la OMS (Organización Mundial de la Salud) publicadas 1989, con sus posteriores revisiones y ampliaciones (OMS, 2006). Esta norma combina tratamientos básicos de depuración y unas buenas prácticas basadas en diferentes niveles de protección para evitar problemas sanitarios. Otra normativa que ha sido referencia en el desarrollo del marco normativo en países donde se realiza esta práctica, son las recomendaciones dadas por la Agencia Medioambiente Estadunidense (USEPA, 2012) o las publicadas por el Estado de California (Título 22, 2001). Estas normas establecen unos indicadores y valores máximos dónde el tratamiento de regeneración es el responsable de la calidad final en función del uso. Durante 2015, la ISO trabajaba en un documento para el uso urbano donde se muestra tanto los posibles parámetros que habría que controlar como la manera de actuar para evitar posibles riesgos. Por otro lado, la Comisión Europea (CE) viene impulsando desde el 2014 la reutilización de aguas depuradas dentro del marco de la Estrategia Común de Implantación de la Directiva Marco del Agua, y fundamentalmente a través del grupo de trabajo de “Programas de medidas”. Para el desarrollo de esta iniciativa se está planteando sacar para 2016 una guía de recomendaciones que podría venir a completar el marco normativo de los distintos Estados Miembros (EM). El Real Decreto 1620/2007, donde se establece el marco jurídico de la reutilización de efluentes depurados, tiende más a la filosofía implantada por la USEPA, aunque la UE parece más partidaria de una gestión del riesgo, donde se establecen unos niveles de tolerancia y unos puntos de control en función de las condiciones socioeconómicas de los distintos Estados, sin entrar a concretar indicadores, valores máximos o tratamientos. Sin embargo, en la normativa estadounidense se indican una serie de tratamientos de regeneración, mientras que, en la española, se hacen recomendaciones a este respecto en una Guía sin validez legal. Por tanto, queda sin regular los procesos para alcanzar estos estándares de calidad, pudiendo ser éstos no apropiados para esta práctica. Es el caso de la desinfección donde el uso de hipoclorito puede generar subproductos indeseables. En la Guía de recomendaciones para la aplicación del RD, publicada por el Ministerio de Agricultura y Medioambiente (MAGRAMA) en 2010, se aclaran cuestiones frecuentes sobre la aplicación del RD, prescripciones técnicas básicas para los sistemas de reutilización, y buenas prácticas en función del uso. Aun así, el RD sigue teniendo deficiencias en su aplicación siendo necesaria una revisión de la misma, como en las frecuencias de muestreo incluso la omisión de algunos parámetros como huevos de nematodos que se ha demostrado ser inexistentes tras un tratamiento de regeneración convencional. En este sentido, existe una tendencia a nivel mundial a reutilizar las aguas con fines de abastecimiento, incluir indicadores de presencia de virus o protozoos, o incluir ciertas tecnologías como las membranas u oxidaciones avanzadas para afrontar temas como los contaminantes emergentes. Otro de los objetivos de este trabajo es el estudio de tipologías de tratamiento en función de los usos establecidos en el RD 1620/2007 y sus costes asociados, siendo base de lo establecido a este respecto en la Guía y PNRA anteriormente indicados. Las tipologías de tratamiento propuestas se dividen en líneas con capacidad de desalar y las que no cuentan con una unidad de desalación de aguas salobres de ósmosis inversa o electrodiálisis reversible. Se realiza esta división al tener actuaciones en zonas costeras donde el agua de mar entra en los colectores, adquiriendo el agua residual un contenido en sales que es limitante en algunos usos. Para desarrollar este objetivo se han estudiado las unidades de tratamiento más implantadas en ERAs españolas en cuanto a fiabilidad para conseguir determinada calidad y coste, tanto de implantación como de explotación. El TRC, tiene un coste de implantación de 28 a 48 €.m-3.d y de explotación de 0,06 a 0,09 €. m-3, mientras que, si se precisara desalar, este coste se multiplica por diez en la implantación y por cinco en la explotación. En caso de los usos que requieren de TRA, como los domiciliarios o algunos industriales, los costes serían de 185 a 398 €.m-3.d en implantación y de 0,14 a 0,20 €.m-3 en explotación. En la selección de tecnologías de regeneración, la capacidad del tratamiento en relación al coste es un indicador fundamental. Este trabajo aporta curvas de tendencia coste-capacidad que sirven de herramienta de selección frente a otros tratamientos de regeneración de reciente implantación como son los MBR, u otros como la desalación de agua de mar o los trasvases entre cuencas dentro de la planificación hidrológica. En España, el aumento de las necesidades de agua de alta calidad en zonas con recursos escasos, aumento de zonas sensibles como puntos de captación para potables, zonas de baño o zonas de producción piscícola, y en ocasiones, el escaso terreno disponible para la implantación de nuevas plantas depuradoras (EDARs), han convertido a los MBRs, en una opción dentro del marco de la reutilización de aguas depuradas. En este trabajo, se estudia esta tecnología frente a los TRC y TRA, aportando igualmente curvas de tendencia coste-capacidad, e identificando cuando esta opción tecnológica puede ser más competitiva frente a los otros tratamientos de regeneración. Un MBR es un tratamiento de depuración de fangos activos donde el decantador secundario es sustituido por un sistema de membranas de UF o MF. La calidad del efluente, por tanto, es la misma que el de una EDAR seguida de un TRA. Los MBRs aseguran una calidad del efluente para todos los usos establecidos en el RD, incluso dan un efluente que permite ser directamente tratado por las unidades de desalación de OI o EDR. La implantación de esta tecnología en España ha tenido un crecimiento exponencial, pasando de 13 instalaciones de menos de 5.000 m3. d-1 en el 2006, a más de 55 instalaciones en operación o construcción a finales del 2014, seis de ellas con capacidades por encima de los 15.000 m3. d-1. Los sistemas de filtración en los MBR son los que marcan la operación y diseño de este tipo de instalaciones. El sistema más implantado en España es de membrana de fibra hueca (MFH), sobre todo para instalaciones de gran capacidad, destacando Zenon que cuenta con el 57% de la capacidad total instalada. La segunda casa comercial con mayor número de plantas es Kubota, con membranas de configuración placa plana (MPP), que cuenta con el 30 % de la capacidad total instalada. Existen otras casas comerciales implantadas en MBR españoles como son Toray, Huber, Koch o Microdym. En este documento se realiza la descripción de los sistemas de filtración de todas estas casas comerciales, aportando información de sus características, parámetros de diseño y operación más relevantes. El estudio de 14 MBRs ha posibilitado realizar otro de los objetivos de este trabajo, la estimación de los costes de explotación e implantación de este tipo de sistemas frente a otras alternativas de tratamiento de regeneración. En este estudio han participado activamente ACA y ESAMUR, entidades públicas de saneamiento y depuración de Cataluña y Murcia respectivamente, que cuentan con una amplia experiencia en la explotación de este tipo de sistemas. Este documento expone los problemas de operación encontrados y sus posibles soluciones, tanto en la explotación como en los futuros diseños de este tipo de plantas. El trabajo concluye que los MBRs son una opción más para la reutilización de efluentes depurados, siendo ventajosos en costes, tanto de implantación como de explotación, respecto a EDARs seguidas de TRA en capacidades por encima de los 10.000 m3.d-1. ABSTRACT The reuse of treated effluent has always been an option in places where a situational or structural water deficit exists, whether regulatory and/or planning efforts are completed or not. The need arises from the demand of a sector, commonly agricultural irrigation, which benefits of this new resource. Within the EU, Spain is ahead in the annual volume of reclaimed water, and is among the top ten countries at a global scale. The regulation of this practice through the Royal Decree 1620/2007 has helped to incorporate the water reuse to the hydrological plans as a part of the programme of measures to mitigate pressures such as surface or ground water extraction, or environmental improvements preventing discharges. The object of this study is to gain an overview of the state of the water reuse in Spain, the different scenarios and approaches to this activity, the development of the legal framework and its enforceability, together with the treatments that achieve the quality levels according to the current law, broken down by applications. Additionally, a cost analysis of technologies and regeneration treatment lines for water reclamation is performed, whereas the regeneration treatment is located after a wastewater treatment or other options such as membrane bioreactors (MBR). To develop the abovementioned objectives, the state of water reuse in Spain is studied by means of a database designed to encompass all aspects of the activity: data from the wastewater treatment plants (WWTP), from the water reclamation plants (WRP), the use of reclaimed water, treated water and reclaimed water annual volumes and qualities, facilities and applications, geographic references, technologies, regeneration treatment lines, etc. The main data providers are the River Basin authorities, through the concession or authorization for water reuse, (sanitary and wastewater treatment managers from the territorial governments, local governments, Hydrological Plans of the River Basins and field visits to the main water reuse systems. Additionally, a review of different plans and programmes on wastewater treatment or water reuse is done, aiming to put the development and consolidation process of this activity in the different regions of Spain in perspective. An inventory of 322 reuse systems and 216 regeneration treatments has been gathered on the database, where the most extended regeneration treatment line was sand filtration followed by hypochlorite disinfection, even though recently it is being replaced by physical–chemical treatment with a lamella settling system, depth sand filtration, and a disinfection with ultraviolet radiation and hypochlorite as residual disinfectant, named conventional regeneration treatment (CRT), and another treatment that may include a membrane process, named advanced regeneration treatment (ART), to adapt to legal requirements. Agricultural use is the most extended, accumulating 70% of the reclaimed demand, estimated at 408 hm3, even though the expected total capacity of WRPs for 2015, after the implementation of the National Water Reuse Plan (NWRP) is three times higher. According to the development of the water reuse legal framework, there were pioneer areas where competent authorities developed different quality and use recommendations for this new resource. Agricultural use and golf course irrigation in touristic areas were the first two uses with recommendations and even legislation. The initial lack of common legislation for water reuse at a national or European level created some doubts which affected the implementation of water reuse, both from a planning and a licensing point of view. Currently there is still a lack of common international legislation regarding water reuse, technologies and applications. Regarding agricultural use, the model recommendations at a global scale are those set by the World Health Organization published in 1989, and subsequent reviews and extensions about risk prevention (WHO, 2006). These documents combine wastewater treatments with basic regeneration treatments reinforced by good practices based on different levels of protection to avoid deleterious health effects. Another relevant legal reference for this practices has been the Environmental Protection Agency of the US (USEPA, 2012), or those published by the State of California (Title 22, 2001). These establish indicator targets and maximum thresholds where regeneration treatment lines are responsible for the final quality according to the different uses. During 2015, the ISO has worked on a document aimed at urban use, where the possible parameters to be monitored together with risk prevention have been studied. On the other hand, the European Commission has been promoting the reuse of treated effluents within the Common Implementation Strategy of the Water Framework Directive, mainly through the work of the Programme of Measures Working Group. Within this context, the publication of a recommendation guide during 2016 is intended, as a useful tool to fill in the legal gaps of different Member States on the matter. The Royal Decree 1620/2007, where the water reuse regulation is set, resembles the principles of the USEPA more closely, even though the EU shows a tendency to prioritize risk assessment by establishing tolerance levels and thresholds according to socioeconomic conditions of the different countries, without going into details of indicators, maximum thresholds or treatments. In contrast, in the US law, regeneration treatments are indicated, while in the Spanish legislation, the only recommendations to this respect are compiled in a non-compulsory guide. Therefore, there is no regulation on the different treatment lines used to achieve the required quality standards, giving room for inappropriate practices in this respect. This is the case of disinfection, where the use of hypochlorite may produce harmful byproducts. In the recommendation Guide for the application of the Royal Decree (RD), published by the Ministry of Agriculture and Environment (MAGRAMA) in 2010, clarifications of typical issues that may arise from the application of the RD are given, as well as basic technical parameters to consider in reuse setups, or good practices according to final use. Even so, the RD still presents difficulties in its application and requires a review on issues such as the sampling frequency of current quality parameters or even the omission of nematode eggs indicator, which have been shown to be absent after CRT. In this regard, there is a global tendency to employ water reuse for drinking water, including indicators for the presence of viruses and protozoans, or to include certain technologies such as membranes or advanced oxidation processes to tackle problems like emerging pollutants. Another of the objectives of this study is to provide different regeneration treatment lines to meet the quality requirements established in the RD 1620/2007 broken down by applications, and to estimate establishment and operational costs. This proposal has been based on what is established in the above mentioned Guide and NWRP. The proposed treatment typologies are divided in treatment trains with desalination, like reverse osmosis or reversible electrodialisis, and those that lack this treatment for brackish water. This separation is done due to coastal facilities, where sea water may permeate the collecting pipes, rising salt contents in the wastewater, hence limiting certain uses. To develop this objective a study of the most common treatment units set up in Spanish WRPs is conducted in terms of treatment train reliability to obtain an acceptable relationship between the required quality and the capital and operational costs. The CRT has an establishment cost of 28 to 48 €.m-3.d and an operation cost of 0.06 to 0.09 €.m-3, while, if desalination was required, these costs would increase tenfold for implementation and fivefold for operation. In the cases of uses that require ART, such as residential or certain industrial uses, the costs would be of 185 to 398 €.m-3.d for implementation and of 0.14 to 0.20 €.m-3 for operation. When selecting regeneration treatment lines, the relation between treatment capacity and cost is a paramount indicator. This project provides cost-capacity models for regeneration treatment trains. These may serve as a tool when selecting between different options to fulfill water demands with MBR facilities, or others such as sea water desalination plants or inter-basin water transfer into a water planning framework. In Spain, the requirement for high quality water in areas with low resource availability, the increasing number of sensitive zones, such as drinking water extraction, recreational bathing areas, fish protected areas and the lack of available land to set up new WWTPs, have turned MBRs into a suitable option for water reuse. In this work this technology is analyzed in contrast to CRT and ART, providing cost-capacity models, and identifying when and where this treatment option may outcompete other regeneration treatments. An MBR is an activated sludge treatment where the secondary settling is substituted by a membrane system of UF or MF. The quality of the effluent is, therefore, comparable to that of a WWTP followed by an ART. MBRs ensure a sufficient quality level for the requirements of the different uses established in the RD, even producing an effluent that can be directly treated in OI or EDR processes. The implementation of this technology in Spain has grown exponentially, growing from 13 facilities with less than 5000 m3.d-1 in 2006 to above 55 facilities operating by the end of 2014, 6 of them with capacities over 15000 m3.d-1. The membrane filtration systems for MBR are the ones that set the pace of operation and design of this type of facilities. The most widespread system in Spain is the hollow fiber membrane configuration, especially on high flow capacities, being Zenon commercial technology, which mounts up to 57% of the total installed capacity, the main contributor. The next commercial technology according to plant number is Kubota, which uses flat sheet membrane configuration, which mounts up to 30% of the total installed capacity. Other commercial technologies exist within the Spanish MBR context, such as Toray, Huber, Koch or Microdym. In this document an analysis of all of these membrane filtration systems is done, providing information about their characteristics and relevant design and operation parameters. The study of 14 full scale running MBRs has enabled to pursue another of the objectives of this work: the estimation of the implementation and operation costs of this type of systems in contrast to other regeneration alternatives. Active participation of ACA and ESAMUR, public wastewater treatment and reuse entities of Cataluña and Murcia respectively, has helped attaining this objective. A number of typical operative problems and their possible solutions are discussed, both for operation and plant design purposes. The conclusion of this study is that MBRs are another option to consider for water reuse, being advantageous in terms of both implementation and operational costs, when compared with WWTPs followed by ART, when considering flow capacities above 10000 m3.d-1.

Molecular Characterization of an Arabidopsis Gene Encoding Hydroperoxide Lyase, a Cytochrome P-450 That Is Wound Inducible1

Hydroperoxide lyase (HPL) cleaves lipid hydroperoxides to produce volatile flavor molecules and also potential signal molecules. We have characterized a gene from Arabidopsis that is homologous to a recently cloned HPL from green pepper (Capsicum annuum). The deduced protein sequence indicates that this gene encodes a cytochrome P-450 with a structure similar to that of allene oxide synthase. The gene was cloned into an expression vector and expressed in Escherichia coli to demonstrate HPL activity. Significant HPL activity was evident when 13S-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid was used as the substrate, whereas activity with 13S-hydroperoxy-9(Z),11(E)-octadecadienoic acid was approximately 10-fold lower. Analysis of headspace volatiles by gas chromatography-mass spectrometry, after addition of the substrate to E. coli extracts expressing the protein, confirmed enzyme-activity data, since cis-3-hexenal was produced by the enzymatic activity of the encoded protein, whereas hexanal production was limited. Molecular characterization of this gene indicates that it is expressed at high levels in floral tissue and is wound inducible but, unlike allene oxide synthase, it is not induced by treatment with methyl jasmonate.

Referral patterns in a global store-and-forward telemedicine system

We examined the nature of the referral patterns in the email telemedicine network operated by the Swinfen Charitable Trust with a view to informing long-term resource planning. Over the first six years of operation, 62 hospitals from 19 countries registered with the Trust in order to be able to refer cases for specialist advice; 55 of these hospitals (89%) actually referred cases during this period. During the first six years of operation, nearly 1000 referrals were submitted and answered, from a wide range of specialty areas. Between July 2002 and March 2005 the referral rate rose from 127 to 318 cases per year. The median length of time required to provide a specialist's response was 2.3 days during the first 12 months and 1.8 days during the last 12 months. Five hospitals submitted cases for more than four years (together sending a total of 493 cases). Their activity data showed a trend to declining referral rates over the four-year period, which may represent successful knowledge transfer. There is some evidence that over the last three years the growth in demand has been exponential, while the growth in resources available (i.e. specialists) has been linear, a situation which cannot continue for very long before demand outstrips supply.

Synthesis and biological properties of 2-phenylbenzothiazole derivatives

2-Phenylbenzothiazoles have structural similarities to the antioestrogenic 2-phenylindole, zindoxifene and to the oestrogenic isoflavone, genistein which also inhibits tyrosine kinases. Hydroxylated 2-phenylbenzothiazole derivatives were therefore produced and tested for oestrogenic and tyrosine kinase inhibitory activity. Synthesis of methoxy substituted 2-phenylbenzothiazoles was via the Jacobson method, demethylation being effected by boron tribromide at -70oC. Three amino substituted 2-phenylbenzothiazoles were also synthesised and tested for activity. Data is presented for oestrogen receptor binding activity, aromatase inhibitory activity, epidermal growth factor receptor tyrosine kinase (EGFRTK) inhibitory activity and cytotoxicity to ANN-1, 3T3, MCF-7 and WIDR cells. Oestrogen receptor binding affinity (RBA) was shown by five of the nine compounds tested. 2-(4-hydroxy)-6-hydroxybenzo-thiazole was the most active of the benzothiazoles tested (RBA 0.7). This is low but comparable to that of genistein. EGFRTK inhibitory activity was shown by four of the six benzothiazole derivatives tested; activity was comparable to that of genistein. Cytotoxicity assays have shown no selective toxicity of 2-phenylbenzothiazoles to any of the cell lines tested. Toxicity to MCF-7 cells was similar to that for other cell lines despite some compounds showing oestrogen receptor binding capacity. Amino-substituted 2-phenylbenzothiazoles showed selective toxicity towards transformed ANN-1 cells compared to normal 3T3 cells but the mechanism of this selectivity has not been established. Molecular modelling techniques, including CHEM-X, QUANTA and MOPAC were used to compare known ATP-competitive tyrosine kinase inhibitors with a model of ATP built from the crystal structure of the ATP-phosphoglycerate kinase complex. Structural features thought to be important to kinase inhibition were found and used to suggest further 2-phenylbenzothiazole analogues which may have improved activity.

Information and behavioural instruction along the health-care pathway:the perspective of people undergoing hernia repair surgery and the role of formal and informal information sources

Provision of information and behavioural instruction has been demonstrated to improve recovery after surgery. However, patients draw on a range of information sources and it is important to establish which sources patients use and how this influences perceptions and behaviour as they progress along the surgical pathway. In this qualitative, exploratory and longitudinal study, the use of information and instruction were explored from the perspective of people undergoing inguinal hernia repair surgery. Seven participants undergoing inguinal hernia repair surgery were interviewed using semi-structured interviews 2 weeks before surgery and 2 weeks and 4 months post-surgery. Nineteen interviews were conducted in total. Topic guides included sources of knowledge, reasons for help-seeking and opting for surgery and factors influencing return to activity. Data were analysed thematically according to Interpretative Phenomenological Analysis. Participants sought information from a range of sources, focusing on informal information sources before surgery and using information and instruction from health-care professionals post-surgery. This information influenced behaviours including deciding to undergo surgery, use of pain medication and returning to usual activity. Anxiety and help-seeking resulted when unexpected post-surgical events occurred such as extensive bruising. Findings were consistent with psychological and sociological theories. Overall, participants were positive about the information and instruction they received but expressed a desire for more timely information on post-operative adverse events.

Stone temperature and moisture variability under temperate environmental conditions: implications for sandstone weathering

Temperature and moisture conditions are key drivers of stone weathering processes in both natural and built environments. Given their importance in the breakdown of stone, a detailed understanding of their temporal and spatial variability is central to understanding present-day weathering behaviour and for predicting how climate change may influence the nature and rates of future stone decay.
Subsurface temperature and moisture data are reported from quarry fresh Peakmoor Sandstone samples exposed during summer (June–July) and late autumn / early winter (October–December) in a mid-latitude, temperate maritime environment. These data demonstrate that the subsurface thermal response of sandstone comprises numerous short-term (minutes), low magnitude fluctuations superimposed upon larger-scale diurnal heating and cooling cycles with distinct aspect-related differences. The short-term fluctuations create conditions in the outer 5–10 mm of stone that are much more ‘energetic’ in comparison to the more subdued thermal cycling that occurs deeper within the sandstone samples.
Data show that moisture dynamics are equally complex with a near-surface region (5–10 mm) in which frequent moisture cycling takes place and this, combined with the thermal dynamism exhibited by the same region may have significant implications for the nature and rate of weathering activity. Data indicate that moisture input from rainfall, particularly when it is wind-driven, can travel deep into the stone where it can prolong the time of wetness. This most often occurs during wetter winter months when moisture input is high and evaporative loss is low but can happen at any time during the year when the hydraulic connection between near-surface and deeper regions of the stone is disrupted with subsequent loss of moisture from depth slowing as it becomes reliant on vapour diffusion alone.
These data illustrate the complexity of temperature and moisture conditions in sandstone exposed to the ‘moderate’ conditions of a temperate maritime environment. They highlight differences in thermal and moisture cycling between near-surface (5–10 mm) and deeper regions within the stone and contribute towards a better understanding of the development of structural and mineralogical heterogeneity between the stone surface and substrate.

Objective Methods for Characterizing Physical Exposures which may contribute to Work-related Musculoskeletal Disorders in Agricultural Workers

Thesis (Ph.D.)--University of Washington, 2016-08

How much walking should be advocated for good health in adolescent girls?

Background: It is currently not known how much walking should be advocated for good health in adolescent girls. The aim of this study was therefore to recommend health referenced standards for step defined physical activity relating to appropriate health criterion/indicators in a group of adolescent girls. Method: Two hundred and thirty adolescent girls aged between 12-15years volunteered to take part in the study. Each participant undertook measurements (BMI, waist circumference, % body fat and blood pressure) to define health status. Activity data were collected by pedometer and used to assess daily step counts and accumulated daily activity time over seven consecutive days. Results: Individuals classified as ‘healthy’ did not take significantly more steps·day−1 nor spend more time in moderate intensity activity than individuals classified as at health risk or with poor health profiles. Conclusion: ‘Healthy’ adolescent girls do not walk significantly more in term of steps·day−1 or time spent in activity than girls classified as ‘unhealthy’. This could suggest that adolescent girls may not walk enough to stratify health and health related outcomes and as a result the data could not be used to inform an appropriate step guideline for this population.

Computational and experimental study of the behavior of cyano-based ionic liquids in aqueous solution

The solvation of cyano- (CN-) based ionic liquids (ILs) and their capacity to establish hydrogen bonds (H-bonds) with water was studied by means of experimental and computational approaches. Experimentally, water activity data were measured for aqueous solutions of ILs based on 1-butyl-3-methylimidazolium ([BMIM](+)) cation combined with one of the following anions: thiocyanate ([SCN](-)), dicyanamide ([DCA](-)), or tricyanomethanide ([TCM](-)), and of 1-ethyl-3-methylimidazolium tetracyanoborate ([EMIM][TCB]). From the latter data, water activity coefficients were estimated showing that [BMIM][SCN] and [BMIM][DCA], unlike [BMIM][TCM] and [EMIM][TCB], are able to establish favorable interactions with water. Computationally, the conductor like screening model for real solvents (COSMO-RS) was used to estimate the water activity coefficients which compare well with the experimental ones. From the COSMO-RS results, it is suggested that the polarity of each ion composing the ILs has a strong effect on the solvation phenomena. Furthermore, classical molecular dynamics (MD) simulations were performed for obtaining an atomic level picture of the local molecular neighborhood of the different species. From the experimental and computational data it is showed that increasing the number of CN groups in the ILs' anions does not enhance their ability to establish H-bonds with water but decreases their polarities, being [BMIM][DCA] and [BMIM][SCN] the ones presenting higher propensity to interact.