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Background: Studies looking at associations between environmental chemicals and child behaviour usually consider only one exposure or family of exposures. Objective: This study explores associations between prenatal exposure to a wide range of environmental chemicals and child behaviour. Methods: We studied 708 mother-child pairs from five European cohorts recruited in 2003-2009. We assessed 47 exposure biomarkers from eight chemical exposure families in maternal blood or urine collected during pregnancy. We used the Strengths and Difficulties Questionnaire (SDQ) to evaluate child behaviour between three and seven years of age. We assessed associations of SDQ scores with exposures using an adjusted least absolute shrinkage and selection operator (LASSO) considering all exposures simultaneously and an adjusted exposome-wide association study (ExWAS) considering each exposure independently. Results: LASSO selected only copper (Cu) as associated with externalizing behaviour. In the ExWAS, bisphenol A [BPA, incidence rate ratio (IRR): 1.06, 95% confidence interval (95%CI): 1.01;1.12] and mono-n-butyl phthalate (MnBP, IRR: 1.06, 95%CI: 1.00;1.13) were associated with greater risk of externalizing behaviour problems. Cu (IRR: 0.90, 95%CI: 0.82;0.98), perfluoroundecanoate (PFUnDA, IRR: 0.92, 95%CI: 0.84;0.99) and organochlorine compounds (OCs) were associated with lower risk of externalizing behaviour problems, however the associations with OCs were mainly seen among women with insufficient weight gain during pregnancy. Internalizing score worsen in association with exposure to diethyl thiophosphate (DETP, IRR: 1.11, 95%CI: 1.00;1.24) but the effect was driven by the smallest cohort. Internalizing score improved with increased concentration of perfluorooctane sulfonate (PFOS, IRR: 0.92, 95%CI: 0.85;1.00), however the association was driven by the two smallest cohorts with the lowest PFOS concentrations. Discussion: This study added evidence on deleterious effects of prenatal exposure to BPA and MnBP on child behaviour. Other associations should be interpreted cautiously since they were not consistent with previous studies or they have not been studied extensively.

Background: MASK-air® is an app that supports allergic rhinitis patients in disease control. Users register daily allergy symptoms and their impact on activities using visual analog scales (VASs). We aimed to assess the concurrent validity, reliability, and responsiveness of these daily VASs. Methods: Daily monitoring VAS data were assessed in MASK-air® users with allergic rhinitis. Concurrent validity was assessed by correlating daily VAS values with those of the EuroQol-5 Dimensions (EQ-5D) VAS, the Control of Allergic Rhinitis and Asthma Test (CARAT) score, and the Work Productivity and Activity Impairment Allergic Specific (WPAI-AS) Questionnaire (work and activity impairment scores). Intra-rater reliability was assessed in users providing multiple daily VASs within the same day. Test-retest reliability was tested in clinically stable users, as defined by the EQ-5D VAS, CARAT, or "VAS Work" (i.e., VAS assessing the impact of allergy on work). Responsiveness was determined in users with two consecutive measurements of EQ-5D-VAS or "VAS Work" indicating clinical change. Results: A total of 17,780 MASK-air® users, with 317,176 VAS days, were assessed. Concurrent validity was moderate-high (Spearman correlation coefficient range: 0.437-0.716). Intra-rater reliability intraclass correlation coefficients (ICCs) ranged between 0.870 (VAS assessing global allergy symptoms) and 0.937 (VAS assessing allergy symptoms on sleep). Test-retest reliability ICCs ranged between 0.604 and 0.878-"VAS Work" and "VAS asthma" presented the highest ICCs. Moderate/large responsiveness effect sizes were observed-the sleep VAS was associated with lower responsiveness, while the global allergy symptoms VAS demonstrated higher responsiveness. Conclusion: In MASK-air®, daily monitoring VASs have high intra-rater reliability and moderate-high validity, reliability, and responsiveness, pointing to a reliable measure of symptom loads.

International audience; Background: Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children.Methods: In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures.Findings: In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions.Interpretation: Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease.Funding: European Community's Seventh Framework Programme (HELIX project).

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010–2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. Mechanisms of the Development of ALL ergy; EU FP 7‐CP ‐IP ; Project No: 261357; 2010–2015

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research. This study was funded by the “Acción Transversal del Cáncer del Consejo de Ministros del 11/10/2007”, from the “Instituto de Salud Carlos III-FEDER” (PI08/1770, PI08/0533, PI11/00226), ISCIII FIS grants, and HIWATE-EU project (036224). NEH receives funding for the PhD program in Biomedicine from the “Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR FI-DGR 2013) Generalitat de Cataluña”

En aquest projecte final de carrera es presenta una part d'un estudi que encara no ha estat publicat que investiga la relació entre asma i nivell socioeconòmic, és a dir, si,per exemple, són les classes socials més baixes o més pobres les que pateixen més asma. Aquest aspecte encara no havia estat tocat per l'estudi ECRHS, i altres estudis que han investigat el tema no arriben a conclusions clares. A l'IMIM estem treballant actualment en la redacció d'un article sobre això, que inclourà part de les anàlisis que es presenten en aquest projecte final de carrera però que abarcarà també una diferenciació dels diversos tipus d'asma, com per exemple l'asma al·lèrgic o el no al·lèrgic. Aquestes anàlisis addicionals no estan inclosos en aquest projecte final de carrera perquè augmentarien molt la quantitat de treball i allargarien la finalització del projecte, i a canvi no aportarien cap novetat en termes d'anàlisi ja que la metodologia que es fa servir és la mateixa però fent servir altres variables resposta.

Existing study design formulas for longitudinal studies assume that the exposure is time invariant or that it varies in a manner that is controlled by design. However, in observational studies, the investigator does not control how exposure varies within subjects over time. Typically, a large number of exposure patterns are observed, with differences in the number of exposed periods per participant and with changes in the cross-sectional mean of exposure over time. This article provides formulas for study design calculations that incorporate these features for studies with a continuous outcome and a time-varying exposure, for cases where the effect of exposure on the response is assumed to be constant over time. We show that incorrectly using the formulas for time-invariant exposure can produce substantial overestimation of the required sample size. It is shown that the exposure mean, variance and intraclass correlation are the only additional parameters needed for exact solutions for the required sample size, if compound symmetry of residuals can be assumed, or to a good approximation if residuals follow a damped exponential correlation structure. The methods are applied to several examples. A publicly available programme to perform the calculations is provided. Research was supported, in part, by National Institutes of Health (grant number CA06516)

L'objectiu final del programa és que al finalitzar l'aplicació l'usuari sigui capaç de crear els seus propis models de regressió lineal simple, que sàpiga validar-los i que en conegui les limitacions.

Scientists and practitioners implementing citizen science projects, in which the involvement of citizens is key, often need ideas and tools that help in reaching citizens, engaging them in the project and maximizing their contributions. In this paper, we describe the creation of an open toolkit, a web-based portal citizensciencetoolkit.eu1 designed in the framework of the CitieS-Health project for the development and promotion of citizen science (CS) projects. The main focus is on projects linking urban environmental exposures and health, but it has applicability to other settings. The toolkit comprises the steps and phases during the implementation of CS activities in environmental epidemiology. A total of 28 tools are currently included, of which most were co-designed and tested within CitiesS-Health, as well as some resulting from external projects. For each tool, in addition to the details of its purpose and the specific challenges it poses, downloadable support content is available. To help facilitate inspiration and the adoption of tools provided, an illustrative step-by-step demonstration and description of its use in a CS project in a real-life setting is included, focusing on recommendations derived from the user experience. The portal is designed as a live inventory of tools, enabling interested CS practitioners not only to replicate, but also to continuously update and enrich it is content. To this end, the long-term objective of the portal is to act as a hub of resources that would enable the active inclusion of citizens in all the phases of the participatory research projects.

The short-term effects of air pollution on brain health have come under investigation only recently. Since environmental health studies are often developed entirely by scientists, citizen science is a promising approach to actively involving the public in research. However, the implementation of citizen science in environmental epidemiology has so far been underexplored. This thesis aimed to evaluate the associations between short-term exposure to air pollution and cognitive and mental health outcomes in adolescents and adults, and to explore the application and potential benefits of citizen science in environmental epidemiology. Data and co-creation activities from two Barcelona-based participatory research projects were analyzed. The findings suggest that 1) cleaning the air of a classroom does not have an impact on adolescents’ attention, 2) days of poor air quality appear to have a potentially adverse effect on attention and perceived stress in adults, and 3) applying citizen science is valuable for environmental health researchers despite some methodological challenges. Els efectes a curt termini de la contaminació de l'aire sobre la salut del cervell només s'han investigat recentment. Com que els estudis de salut ambiental solen ser desenvolupats completament per científics, la ciència ciutadana és un enfocament prometedor per implicar activament el públic en la investigació. Tanmateix, la implementació de la ciència ciutadana en epidemiologia ambiental ha estat fins ara poc explorada. Aquesta tesi tenia com a objectius: d'una banda avaluar les associacions entre l'exposició a curt termini a la contaminació de l'aire i els resultats de salut cognitiva i mental en adolescents i adults, i d'altra banda explorar l'aplicació i els beneficis potencials de la ciència ciutadana en l'epidemiologia ambiental. Es van analitzar les dades i les activitats de co-creació de dos projectes de recerca participativa a Barcelona. Els resultats suggereixen que 1) netejar l'aire d'una aula no té un impacte en l'atenció dels adolescents, 2) els dies de mala qualitat de l'aire semblen tenir un efecte potencialment advers sobre l'atenció i l'estrès percebut en adults, i 3) aplicar la ciència ciutadana és valuós per als investigadors de salut ambiental malgrat alguns reptes metodològics.

Exposure to ambient temperatures has been widely described as an important health hazard. The most studied effect of temperatures is an increase on mortality; however, there is less evidence on other health impacts. In response to climate change and associated extreme events, public health adaptation has become imperative. The Spanish Government implemented in 2004 a heat health prevention plan (HHPP). This thesis aimed to evaluate the effectiveness of the Spanish HHPP in terms of reductions in mortality and cause-specific hospitalizations, and to assess the effects of weather factors on gastroenteritis and on occupational injuries. Daily maximum and average temperature, and daily precipitation in each capital of province were used as exposure measures. Daily counts of deaths, hospitalizations for cardiovascular, cerebrovascular and respiratory diseases, hospitalizations for infectious gastroenteritis and occupational injuries registered in Spain were included as health outcomes. Our results suggested that the implementation of the HHPP has reduced extreme heat-related mortality and respiratory admissions. By contrast, an increment of moderate heat-related mortality was observed. We also found that the effects of cold temperatures on mortality and respiratory admissions experienced a decrease in the second period, although this was not observed for cardiovascular and cerebrovascular admissions. Cold and heat were also associated with higher risk of gastroenteritis admissions and occupational injuries. An important economic impact of working at non-optimum temperatures has been estimated in this thesis. We observed a protective effect of heavy precipitation on gastroenteritis admissions. This thesis showed some improvements on health outcomes after the implementation of the HHPP. Nonetheless, ambient temperatures still have an important role in increasing health hazards. Public health prevention measures should consider all range of temperatures as well as target specific actions for some vulnerable groups, such as workers or children. L'exposició a temperatures ambient ha estat àmpliament descrita com un important perill per a la salut. L'efecte més estudiat de les temperatures és un augment de la mortalitat, no obstant, l’evidència sobre altres impactes en salut és més escassa. Com a resposta al canvi climàtic i als seus esdeveniments extrems associats, mesures d'adaptació en salut pública són indispensables. El Govern espanyol va implementar el 2004 un pla de prevenció dels efectes en salut de la calor (HHPP). L’objectiu d’aquesta tesi era avaluar l'efectivitat del HHPP en quant a reducció de la mortalitat i de determinades causes específiques d’hospitalitzacions, així com avaluar els efectes dels factors climatològics en les gastroenteritis i les lesions laborals. Com a mesures d’exposició es van utilitzar la temperatura màxima i mitjana diària i la precipitació diària a cada capital de la província. Es van incloure, com a indicadors de salut, el nombre diari de defuncions, hospitalitzacions per malalties cardiovasculars, cerebrovasculars i respiratòries, hospitalitzacions per gastroenteritis infeccioses i lesions laborals registrades a Espanya. Els nostres resultats van suggerir que la implementació del HHPP va reduir la mortalitat i també els ingressos hospitalaris per malalties respiratòries relacionats amb la calor extrema. Per contra, es va observar un increment de la mortalitat relacionada amb la calor moderada. També es va constatar que els efectes de les temperatures fredes sobre la mortalitat i ingressos respiratoris van experimentar una disminució en el segon període, mentre que aquesta reducció no es va observar en els ingressos cardiovasculars i cerebrovasculars. El fred i la calor també es van associar amb un major risc d'ingressos per gastroenteritis així com de les lesions laborals. En aquesta tesi es va estimar un important impacte econòmic de treballar amb temperatures no òptimes. Es va observar un efecte protector de les precipitacions intenses en els ingressos per gastroenteritis. A més, aquesta tesi va mostrar algunes millores en salut després de la implementació del HHPP. De totes maneres, actualment les temperatures ambient suposen un perill per la salut. És necessari, per tant, que les mesures de prevenció en salut pública cobreixin tot el rang de temperatures, així com que s’estableixin accions específiques per a determinats grups vulnerables de població, com ara els/les treballadors/es o els infants.

En este proyecto se pretende hacer también el análisis de la mortalidad de la población en diferentes municipios del área metropolitana de Barcelona utilizando diversos factores e identificar patrones espaciales que justifiquen el comportamiento de la mortalidad (años 1999 a 2006) en término espaciales. . Inferir la relació estadística espacial entre la mortalitat i la proximitat a espais verds urbans. Es necessiten coneixements d'anàlisi espacial

Epidemiological evidence is limited regarding the effects of long-term exposure to traffic-related air pollution and to traffic noise on blood pressure (BP). This thesis aims at (a) assessing the long-term co-exposure to traffic-related air pollution and traffic noise and (b) evaluating and disentangling the associations of each of these trafficrelated environmental factors on hypertension, systolic and diastolic BP in the adult population of Girona city (Catalonia, Spain). We studied the spatial correlation between annual average levels of measured nitrogen dioxide (NO2) and modeled traffic noise levels (L24h and Lnight) at 83 outdoor residential locations in Girona city. We used data from the baseline examination (years 2003-2006) of a population-based cohort corresponding to 3836 participants aged 35-84. We assigned outdoor annual average levels of NO2 and traffic noise at the participants’ postal addresses with a land-use regression model and a traffic noise model, respectively. Indoor traffic Lnight levels at the bedrooms were estimated based on the noise protection elements at home. The correlation between NO2 and traffic noise was high and city area-dependent. NO2 and indoor traffic noise showed consistent and independent associations with both BP and hypertension. In contrast, the associations for NO2 could not be disentangled from those for outdoor traffic noise. We also identified potential susceptibility groups. This thesis adds to the limited evidence showing that long-term exposure to trafficrelated air pollution and to traffic noise are associated (and independently) with both BP and hypertension. Further studies are required to confirm these results., L’evidència epidemiològica és limitada en relació als efectes de l’exposició prolongada a la contaminació atmosfèrica i al soroll provinents del trànsit amb la pressió arterial (PA). Aquesta tesi té com a objectiu (a) explorar l’exposició conjunta a la contaminació atmosfèrica i al soroll del trànsit a llarg termini i (b) avaluar i separar les associacions de cadascun d’aquests dos factors ambientals amb la hipertensió i la pressió sistòlica i diastòlica a la població adulta de la ciutat mediterrània de Girona (Catalunya, Espanya). Vam estudiar la correlació espacial entre els nivells anuals mitjans de diòxid de nitrogen (NO2) mesurat i del soroll de trànsit modelitzat (L24h and Lnit) a l’exterior de 83 localitzacions residencials. Vam utilitzar les dades de l’exploració basal (anys 2003- 2006) d’una cohort poblacional corresponents a 3836 participants de 35 a 84 anys. Vam assignar els nivells mitjans anuals exteriors de NO2 i de soroll de trànsit a les adreces postals residencials de cada participant amb un model de regressió de l’ús del sòl i un model de soroll de trànsit, respectivament. Els nivells interiors de Lnit de trànsit als dormitoris es van derivar en base a les proteccions contra el soroll a casa. La correlació entre l’NO2 i el soroll del trànsit era elevada i depenia de l’àrea de la ciutat. Ambdós l’NO2 i el soroll del trànsit s’associaven consistent i independentment amb la hipertensió i la PA. En canvi, les associacions per l’NO2 no es podien deslligar de les del soroll de trànsit exterior. També vam identificar factors de susceptibilitat potencials. Aquesta tesi incrementa l’evidència escassa sobre que l’exposició prolongada a la contaminació atmosfèrica i al soroll del trànsit s’associen, i independentment, tant amb la PA com amb la hipertensió. Es requereixen més estudis per confirmar aquests resultats., La evidencia epidemiológica es limitada en relación a los efectos de la exposición prolongada a la contaminación atmosférica y al ruido procedentes del tráfico con la presión arterial (PA). Esta tesis tiene como objetivo (a) explorar la exposición conjunta a la contaminación atmosférica y al ruido del tráfico a largo plazo y (b) evaluar y separar las asociaciones de cada uno de estos dos factores ambientales con la hipertensión y la presión sistólica y diastólica en la población adulta de la ciudad mediterránea de Girona (Cataluña, España). Estudiamos la correlación espacial entre los niveles anuales medios de dióxido de nitrógeno (NO2) medido y de ruido de tráfico modelizado (L24h and Lnoche) en el exterior de 83 localizaciones residenciales. Utilizamos los datos de la exploración basal (años 2003-2006) de una cohorte poblacional correspondientes a 3836 participantes de 35 a 84 años. Asignamos los niveles medios anuales exteriores de NO2 y de ruido de tráfico a las direcciones postales residenciales de cada participante con un modelo de regresión del uso del suelo y un modelo de ruido de tráfico, respectivamente. Los niveles interiores de Lnoche de tráfico en los dormitorios se derivaron en base a las protecciones contra el ruido en casa. La correlación entre el NO2 y el ruido del tráfico era elevada y dependía del área de la ciudad. Ambos el NO2 y el ruido del tráfico se asociaban consistente e independientemente con la hipertensión y la PA. En cambio, las asociaciones para el NO2 no se podían desenredar de las del ruido de tráfico exterior. También identificamos factores de susceptibilidad potenciales. Esta tesis incrementa la evidencia escasa sobre que la exposición prolongada a la contaminación atmosférica y al ruido del tráfico se asocian, e independientemente, tanto con la PA como con la hipertensión. Se requieren más estudios para confirmar estos resultados.

En el contexto de los estudios longitudinales observacionales, hemos obtenido los valores óptimos para el número de participantes y el número de medidas repetidas que maximizan la potencia para detectar el hipotético efecto, sin rebasar un presupuesto económico determinado, o que minimizan el coste total del estudio, alcanzando una potencia determinada. Hemos considerado una variable respuesta continua, cuya estructura de covarianza se supone exponencialmente amortiguada, y una exposición binaria variable en el tiempo, tanto para un efecto agudo y transitorio de la exposición, a través de una diferencia constante en la media entre expuestos y no expuestos, como para un efecto acumulativo, a través de una diferencia linealmente divergente. Hemos derivado expresiones cerradas para la solución del problema en el caso particular en que se supone que la estructura de covarianza de la respuesta es de simetría compuesta. Los resultados mostraron la importancia de la correlación intraclase de la exposición sobre la determinación de la combinación óptima del número de participantes y el número de medidas repetidas y, por tanto, sobre la potencia o el coste optimizados. Así, la incorrecta asunción de una exposición constante conduce a resultados sesgados en el cálculo del tamaño de la muestra y de la potencia o el coste del estudio. También analizamos la sensibilidad de los resultados a la presencia de datos faltantes debido al abandono de participantes durante el seguimiento, al cambio de la estructura de covarianza de la respuesta y a una prevalencia de la exposición variable en el tiempo. Como ejemplo, ilustramos algunos de estos resultados aplicando nuestros métodos en un estudio real. Además, proporcionamos el paquete de R optimalAllocation para realizar todos los cálculos necesarios para obtener la combinación óptima del número de participantes y el número de medidas repetidas In the context of observational longitudinal studies, the aim of this work is to obtain optimal values of the number of participants and the number of repeated measurements that maximize the power to detect the hypothesized effect, given the total financial cost of the study

This thesis contributes to the characterization of the spatial distribution of NO2, heavy metals and UFP in Girona, to the methodology in air pollution exposure assessment studying different markers of traffic-related air pollution, measurement instruments and protocols, as well as to the development of the LUR technique identifying potential bias in the resulting coefficients of the health model and practical solutions to avoid them. Finally, this thesis added to the evidence that long-term exposure to traffic-related air pollution is associated with atherosclerosis and identified potential susceptibility factors for the Mediterranean population., Esta tesis contribuye a la caracterización de la distribución espacial del NO2, los metales pesados y las UFP en Girona, a la metodología de la evaluación de la exposición a contaminación atmosférica habiendo estudiado diferentes marcadores de contaminación por tráfico, instrumentos de medida y protocolos, así como al desarrollo de la técnica de modelos LUR para los que se identificaron sesgos potenciales sobre la estimación del efecto sobre la salud de dicha exposición y aporta soluciones prácticas para evitarlos. Finalmente, esta tesis añade a la evidencia de que la exposición a largo plazo a la contaminación procedente del tráfico se asocia a la aterosclerosis e identifica factores de susceptibilidad potenciales para la población mediterránea.

En epidemiologia ambiental es te com a objectiu el mesurar l'exposició individual als contaminants ambientals (en aigua, aire, etc ). La impossibilitat de prendre aquesta mesura directament fa que s'hagin de fer servir tècniques estadístiques per a obtenir-la. Objectiu: Trobar un bon model d'ajust del pes al néixer del nadó. Comparar el model lineal, model lineal amb bootstrap i el model jeràrquic a l'hora d'estimar l'exposició individual al NO2.En epidemiologia ambiental es te com a objectiu el mesurar l'exposició individual als contaminants ambientals (en aigua, aire, etc ). La impossibilitat de prendre aquesta mesura directament fa que s'hagin de fer servir tècniques estadístiques per a obtenir-la. L'objectiu és trobar un bon model d'ajust del pes al néixer del nadó i comparar el model lineal, model lineal amb bootstrap i el model jeràrquic a l'hora d'estimar l'exposició individual al NO2.