Distinctive patterns of placental lesions in preeclampsia versus fetal growth restriction and their association with fetoplacental Doppler

OBJECTIVES: The aim of this study was to describe placental histopathological findings in a large cohort of pregnancies complicated by preeclampsia and/or fetal growth restriction, and to investigate its association with fetoplacental Doppler. METHODS: This was a prospective observational study including pregnancies complicated by: 1) normotensive FGR defined as birthweight 95th centile for uterine and umbilical artery, or <5th centile for middle cerebral artery and CPR. Placental lesions were categorized to vascular (maternal/fetal side), inflammatory and other lesions according to the 2014 Amsterdam Placental Workshop Group Consensus Statement. Univariate and multiple regression analysis were performed for the comparison between the study groups. Logistic regression was used to determine abnormal Doppler association with placental lesions. RESULTS: Maternal side vascular lesions are significantly higher in PE compared to controls and normotensive FGR (PE&FGR: 73%, PE: 46%, FGR: 38% vs. controls: 31%; p=0.01) including 2 types of lesions: developmental (PE&FGR: 13%, PE: 5%, FGR: 3% vs. controls: 2%, p<0.001) and malperfusion (PE&FGR: 70%, PE: 39%, FGR: 32% vs. controls: 25%, p=0.001). In contrast, fetal side developmental lesions are significantly higher in normotensive FGR compared to controls and PE (PE&FGR: 0%, PE: 3%, FGR: 8% vs. controls 2%, p=0.001). All cases displayed lower prevalence of infectious lesions, with a high prevalence of immune lesions in PE&FGR (PE&FGR: 17.5%, PE: 7.8%, FGR: 9.8% vs. controls 9.4%, p=0.001). All fetoplacental Doppler parameters are associated with maternal side vascular lesions -mainly malperfusion- [uterine arteries mean PI (Odds ratio(OR)=2.45, 95% confidence interval (CI): 1.51 - 3.97), umbilical artery PI (OR=2.05, 95% CI: 1.02 - 4.47), middle cerebral artery PI (OR=2.75, 95% CI: 1.4 - 5.42), CPR (OR=1.75, 95% CI: 1.04 - 2.95)]. This association was evident mainly in the FGR groups -with and without PE-, being nonsignificant in controls or PE without FGR. No significant associations were observed between fetoplacental Doppler parameters and other placental lesions in any of the study groups. CONCLUSIONS: PE and FGR exhibit different patterns of placental histopathological lesions in accordance with the clinical manifestation of the placental disorder (maternal vs. fetal). Fetoplacental Doppler shows an association with placental malperfusion lesions in the maternal side, reinforcing its use as a surrogate of placental insufficiency

The workers opinions have a value in the Code of Ethics : Analysis of the contributions of workers in virtual Forum Catalan Institute of Health

The Catalan Institute of Health (CIH) is the largest health services public provider in Catalonia. "CIH Code of Ethics Virtual Forum" (CEVF), was created within the Intranet of the CIH to facilitate participation among their employees. The current study aims to: a) Analyse the CIH workers' assessment of their own, their colleagues' and the organization's observance of ethical values; b) Identify the opinions, attitudes, experiences and practices related to the ethical values from the discourse of the workers that contributed voluntarily to the CEVF. Mixed methods study with convergent parallel design : The study was conducted between May and December 2008. The average score for observance of the CE by the respondents themselves was high (over 4/5), between 3.5-4/5 for the observance by their colleagues and close to 3/5 for the CIH management. These results do not change when we compare by gender, age group and professional discipline. The comments on the values are information-rich, they mirror the ethical environment of the institution and show various ethical dilemmas and suggestions. Results show that it is feasible for a publicly funded health care organization to develop a CE with the participation of employees and the support of the management. Results underscore the relevance of this strategy for the implementation, improvement and update of the CE as a responsibility shared by all workers. Practices consistent with ethical values are rewarded by social approval, enhance employee's confidence and coherence in decision-making and improve public engagement and institutional policies

Study protocol for a randomised controlled trial: treatment of early intrauterine growth restriction with low molecular weight heparin (TRACIP)

Introduction: The incidence of intrauterine growth restriction (IUGR) is estimated at about 3% of pregnancies, and it is associated with 30% of all perinatal mortality and severe morbidity with adverse neurodevelopmental and cardiovascular health consequences in adult life. Early onset IUGR represents 20%-30% of all cases and is highly associated with severe placental insufficiency. The existing evidence suggests that low molecular weight heparin (LMWH) has effects beyond its antithrombotic action, improving placental microvessel structure and function of pregnant women with vascular obstetric complications by normalising proangiogenic and antiapoptotic protein levels, cytokines and inflammatory factors. The objective of our study is to demonstrate the effectiveness of LMWH in prolonging gestation in pregnancies with early-onset IUGR. Methods and analysis: This is a multicentre, triple-blind, parallel-arm randomised clinical trial. Singleton pregnancies qualifying for early (20-32 weeks at diagnosis) placental IUGR (according to Delphi criteria) will be randomised to subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day or placebo from inclusion at diagnosis to the time of delivery. Analyses will be based on originally assigned groups (intention-to-treat). The primary objective will be analysed by comparing gestational age and prolongation of pregnancy (days) in each group with Student's t-tests for independent samples and by comparing Kaplan-Maier survival curves (from inclusion to delivery, log-rank test). A linear regression model for gestational age at birth will consider the following covariates: gestational age at inclusion (continuous) and pre-eclampsia (binary). Ethics and dissemination: The study will be conducted in accordance with the principles of Good Clinical Practice. This study was approved by the Clinical Research Ethics Committee (CEIC) of Sant Joan de Déu Hospital, on 13 July 2017. The trial is registered in the public registry www.clinicaltrial.gov. according to Science Law 14/2011, and the results will be published in an open access journal

Effectiveness of a training intervention to improve the management of vertigo in primary care: a multicentre cluster-randomised trial, VERTAP

Background: Benign paroxysmal positional vertigo (BPPV) is the most common type of vertigo. While BPPV is best treated with canalicular repositioning manoeuvres, they are not routinely performed in primary care (PC). Methods: To evaluate the effectiveness of blended training (online and face-to-face) on the diagnosis and management of vertigo to improve adherence of family doctors to clinical practice guidelines, we designed a community multicentre cluster-randomised open-label trial with an intervention (IG) and a control (GC) group of 10 primary care teams (PCT) each. Outcome variables will be ICD-10 diagnostic codes (proportion of nonspecific diagnoses such as dizziness and vertigo versus specific diagnoses such as BPPV, vestibular neuritis, and Meniere's disease); number of referrals to ENT or neurology specialists; prescription of antivertigo agents; and duration of sick leave due to vertigo. The baseline comparability of the two study groups will be analysed to ensure homogeneity. A description of all baseline variables will be performed. Student's t-test will be used to evaluate the differences between the groups. Logistic regression multivariate analysis will be performed to study the relationship between baseline variables of professionals and centres with outcome variables. Discussion: With the improvement of the diagnosis and management of vertigo by family doctors after this training, we expect an increase in the proportion of specific diagnoses, a decrease in the prescription of antivertigo agents, a decrease in referrals to ENT or neurology specialists and a reduction in the duration of sick leave due to temporary disability. The blended training will be easily expanded within primary care services, since it is mainly delivered online, with a single face-to-face session to ensure that the manoeuvres have been adequately learned

Bullying escolar: um fenômeno multifacetado

School bullying can involve children in different ways, making them play different roles, among them, victims, bullies and bully-victims. The aim of this study was to describe how bullying occurs in high social vulnerability schools of Florianópolis metropolitan area and the roles played by students in this phenomenon. Overall, 409 children and adolescents from the 3rd to 5th grades and of two public elementary schools aged 8-16 years (X = 11.14) participated in this study. As a tool, the Olweus Questionnaire adapted to the Brazilian population was used. For data analysis, descriptive statistics and inferential statistics were applied by the Mann Whitney and Kruskal Wallis tests. As for results, 29.8% of boys and 40.5% of girls reported being victims; 32.3% of boys and 24.6% of girls reported being bullies. Victims were the most willing to help a colleague who is suffering from bullying (X = 1.54; p> 0.001), even if they do not know the victims (X = 1.57; p> 0.004). Bullies are differentiated from the group that does not participate (X = 1.73) and the group of victims (X = 2.34), being those who felt less alone (x = 1.47; p> 0.001). It was concluded that the information obtained in this study is indispensable in the search for alternatives to reduce school bullying. The strengthening of relations between school and students and a better preparation of teachers and school staff are extremely necessary to try to minimize the effects of risk factors to which these children are exposed and consequently violence at school.O bullying escolar pode envolver crianças de diferentes maneiras, fazendo com que essas assumam papéis diferenciados. Dentre estes, têm-se vítimas, agressores e vítimas-agressoras. O objetivo deste estudo foi descrever como ocorre o bullying em escolas de alta vulnerabilidade social da Grande Florianópolis e os papéis assumidos pelos alunos nesse fenômeno. Quanto ao método, participaram 409 crianças e adolescentes do terceiro ao quinto ano e da quarta à sexta série do ensino fundamental, de duas escolas públicas municipais, com idades entre 8 e 16 anos (X=11,14). Como instrumento, utilizou-se o Questionário de Olweus adaptado à população brasileira. Para a análise dos dados, empregaram-se a estatística descritiva e estatística inferencial por meio dos testes Mann Whitney e Kruskal Wallis. Quanto aos resultados, 29,8% dos meninos e 40,5% das meninas relataram terem sido vítimas; já 32,3% dos meninos e 24,6% das meninas relataram terem sido agressores. As vítimas foram as que se mostraram mais dispostas a ajudar como podem um colega que esteja sofrendo agressão (X=1,54; p>0,001), mesmo que não o conheçam (X=1,57; p>0,004). Em contrapartida, os agressores se diferenciaram do grupo que não participa (X=1,73) e do grupo das vítimas (X=2,34), sendo aqueles que menos se sentiram sozinhos (X=1,47; p>0,001). Concluiu-se que as informações obtidas neste estudo são indispensáveis na busca de alternativas para redução do bullying escolar. O fortalecimento das relações entre escola e alunos, e um maior preparo dos professores e funcionários são extremamente necessários para tentar minimizar os efeitos dos fatores de risco a que essas crianças estão expostas e consequentemente a violência na escola.CAPES - Proc. nº 0815/14-4CIEC - Centro de Investigação em Estudos da Criança, IE, UMinho (UI 317 da FCT)Projeto Estratégico da FCT: UID/CED/00317/201

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

La espectroscopia NIR en la determinación de propiedades físicas y composición química de intermedios de producción y productos acabados

Conseguir una elevada calidad en el producto acabado es un reto cada día más importante en la industria moderna. Para asegurar esta calidad los productos antes de salir al mercado, deben cumplir especificaciones estrictas establecidas tanto por organismos reguladores como por el propio mercado. Con el objetivo de proporcionar a la industria nuevas metodologías de análisis se han desarrollado diversos trabajos basados en la espectroscopia NIR. Se ha colaborado con la industria del mortero y la farmacéutica ofreciéndoles soluciones concretas a sus problemas analíticos. En el primer trabajo junto con la industria del mortero, se han desarrollado modelos de cuantificación para aditivos en morteros. Se ha desarrollado un diseño de muestras original basado en la figura del antiprisma de base hexagonal, donde se han tenido en cuenta el rango de concentración de los analitos. Para incorporar la variabilidad de los aditivos, se usó el diseño D-óptimo que proporcionó las diferentes combinaciones entre clases de aditivos. Se ha obtenido un modelo de calibración PLS para cada aditivo, presentando ambos una correcta capacidad predictiva. Los métodos desarrollados han sido validados con un conjunto de muestras externas. En un segundo estudio realizado con áridos (materia prima de los morteros), se han estudiado 2 perfiles diferentes de distribución de partículas con diferente número de puntos en la curva (número de tamices utilizado en la determinación). Se han construido 2 modelos de calibración (PLS2 y ANN) para cada curva con el objeto de obtener la mejor calidad de ajuste en términos de coeficiente de correlación entre la curva de referencia y la predicha por el modelo quimiométrico y obtener los mejores errores de predicción. Los 4 modelos de calibración proporcionan resultados estadísticamente iguales, en cuanto al error de predicción, demostrando la posibilidad de obtener curvas de distribución de tamaño de partícula a partir de datos NIR y modelos de calibración PLS2 y ANN. El uso de ANN como técnica de modelado no lineal no mejora estadísticamente los resultados. Los siguientes trabajos se han realizado para la industria farmacéutica. El principal nexo de unión es la construcción de modelos de calibración sin usar método de referencia para obtener la variable dependiente. En el primer trabajo se ha realizado un estudio de determinación de API a lo largo del proceso de fabricación estudiando las diferentes variables que pueden afectar al proceso (tamaño de partícula, forma galénica, presión de compactación y grosor de la capa de lacado) y se han propuesto diferentes estrategias que tienen por objeto construir modelos de calibración simples y adecuados para la cuantificación del API en las diferentes etapas del proceso. En el segundo y tercer trabajo para la industria farmacéutica se ha desarrollado y aplicado una nueva metodología para construir conjuntos de calibración adaptados a cada tipo de comprimido. Dicha metodología se basa en la obtención del espectro proceso calculado como diferencia entre el espectro de un comprimido de producción y el de una muestra de laboratorio en polvo de la misma composición. El conjunto de diferencias calculadas para varios comprimidos constituyen un conjunto de vectores matemáticos que definen la variabilidad del proceso. Esta matriz de variabilidad se ha adicionado a un conjunto de espectros NIR de diferentes mezclas en polvo, que cubren el rango deseado de concentración del principio activo y excipientes, dando lugar a la matriz de espectros del conjunto de calibración. Aplicando el algoritmo PLS al conjunto de calibración se construye un modelo para cada uno de los analitos. Los resultados obtenidos en la predicción tanto de API como de excipientes en comprimidos de ibuprofeno y metformina muestran errores de predicción inferiores al 1,5%.Obtaining a high quality final product constitutes a challenge with increase importance in the modern industry. The products should fulfil strict specifications established by regulatory agency just before their releasing to the market. Several new methods based on NIR spectroscopy have been developed for the industry in order to provide the optimum tools to achieve these objectives. This PhD Thesis provides the analytical knowledge to solve real industrial problems usually present in the mortar and pharmaceutical industries. Two studies have been conducted for the cement industry, with the aim of improving the value of the final product. Firstly, quantitative calibration models for additives in mortars have been developed. In order to ensure the calibration set contain natural variability of the samples, we used an experimental design to select the best representative set of samples. This novel approach is based on a hexagonal antiprism that encompasses the concentration ranges spanned by the analytes and the natural variability inherent of each additive. The D-optimality criterion has been used to obtain several combinations between additive classes. The PLS calibration models thus constructed for each additive provided accurate predictions. The ensuing analytical methods have been validated using an external sample set. Secondly, particle size distribution is a key quality attribute of mortars. Different approaches have been carried out to quantify this distribution in mortars. Two different profiles of particle size distribution have been studied and PLS2 and ANN calibration models have been calculated for each one. The objective has been to achieve the best predictive ability of the calibration models in terms of high correlation coefficient between the reference and predicted distribution curve and low prediction errors. The results obtained with the four calibration models were not statistically different. Therefore, the combined use of NIR spectroscopy and PLS2 or ANN calibration models allowed an accurately determination of particle size distribution in mortars. The use ANN for non-linear modelling of the data set has not improved the results. In the pharmaceutical field, the studies have been conducted to the determination of API at different stages of the manufacturing process and also in the final product. The main link of the following works is the development of calibration models without using reference method for determining the dependent variable. In the first work, the API concentration has been quantified throughout the entire production process of a pharmaceutical formulation. The authors have evaluated the influence of particle size, galenic form, compaction pressure and coating thickness on the NIR spectra of the sample. The eventual influence of these variables was included in the calibration model in a simple way that allowed the accurate and precise prediction of the API at the different stages of the production process. In the second and third work, a new methodology has been developed to construct calibration sets. This methodology is based on obtaining the process spectra, which is calculated by the difference between the NIR spectra for production tablets and those for laboratory samples containing the nominal concentrations of API and excipients. The body of differences thus calculated for several tablets constitutes a set of mathematical vectors that define the overall variability of the process. This new matrix is added to a set of NIR spectra for several powder mixtures spanning the desired content range for the API and excipients in order to obtain the spectral matrix for the calibration set. Applying PLS algorithm to calibration set allows constructing of calibration models for each analyte. This methodology has been applied successfully on API and excipients determination in commercial pharmaceutical tablets. In this way, tablet contents can be predicted with errors less than 1.5%

The Case of "Anis del Mono" Factory. Regenerating Coastal Heritage in Catalonia

The "IAM group" (Investigation in Mediterranean Architecture), School of Architecture LaSalle -URL, Barcelona, has developed a research project entitled "Strategies for Sustainable Regeneration of Touristic Settlements in the Mediterranean coast". The aim of this investigation is to establish sustainable recycling rules to improve the development of abandoned or obsolete public spaces and buildings on the Catalan seafront. In its aim to restore the coastal heritage, the study focuses on the Modernist factory of Anis del Mono as a case study, and proposes the optimization of existing facilities and an extension of the program with new public uses. The operation aims to establish an open dialogue with the environment, improving the relation with the sea and the city, becoming a reference on the city shoreline. The results of successfully completed architectonic projects can provide us with some universal guidelines that can be used as parameters in similar cases along the whole coast. These transformation strategies are the final goal of our research and are included at the end of the presentation

Estrategias para la regeneración sostenible de asentamientos turísticos en la costa mediterránea. Proyectos de rehabilitación arquitectónica.

La comunicación presenta los siete proyectos de rehabilitación que han resultado de las investigaciones que el grupo IAM, URL, ha desarrollado a través del proyecto I+D "Estrategias para la regeneración sostenible de asentamientos turísticos en la costa mediterránea", coordinado con la UPValencia en los años 2012-14. Dichos proyectos se han desarrollado por estudiantes del máster MPIA, arquitectos en formación doctoral, y miembros del IAM, especialistas en el proyecto arquitectónico, el territorio y la sostenibilidad. Dicha investigación propone la rehabilitación del patrimonio arquitectónico en desuso en el litoral como motor de regeneración del entorno en el que se sitúa. El primer paso fue la realización de un mapa tipológico de la costa catalana y de planos territoriales de las diferentes zonas en las que se situaban los objetos de estudio, con el objetivo de detectar las distintas problemáticas. Se definieron siete tipologías, sobre las que se desarrollaron los proyectos de regeneración: 1- Industria hotelera en las ciudades turísticas del litoral: Reforma de dos hoteles en el casco urbano de Sant Feliu de Guíxols, actualmente en proceso de subasta pública. 2- Grandes recintos de equipamiento en primera línea de costa: Antiguo Sanatorio de La Savinosa, en Tarragona, para el que se plantea un nuevo uso hotelero, cultural y de ocio. 3- Asentamientos turísticos de baja densidad: Conversión del hotel Cala Vinya, en desuso, en apartamentos tutelados, y rehabilitación de los servicios y espacios públicos comunes. 4- Usos culturales en frentes marítimos: Escenario para el festival de verano “Porta Ferrada” y marina seca enel puerto de Sant Feliu, generando nuevos espacios de paseo y ocio ligados al paisaje de la bahía. 5- Hotel emblemático: El hotel Panorama de Sant Feliu de Guíxols, singular por su enclave y su potencial para regenerar el entorno y personalizar el skyline de la ciudad. 6- Recuperación de la memoria histórica: Edificio de la destilería “Anis del Mono” en la playa de Badalona, para evitar su desaparición y mantener así un patrimonio histórico de gran valor para la ciudad. 7- Reconversión de servicios e infraestructuras: Estación de ferrocarril de Premià de Mar, con el objetivo de resolver la relación de estos pueblos con su frente marítimo, actualmente fracturada por el paso de trenes y vehículos. Los proyectos de rehabilitación de estos edificios, con la incorporación de nuevos usos ligados al turismo, han contemplado como prioritarios el mantenimiento de las características arquitectónicas y paisajísticas de los diferentes enclaves, así como la incorporación de criterios de sostenibilidad, en la construcción y en el uso, con la aplicación de sistemas pasivos de eficiencia energética. La resolución de estos casos concretos ha permitido extraer unas posibles estrategias de regeneración. El objetivo es definir unas pautas de actuación aplicables en casos parecidos, incluso por los organismos y las instituciones implicados

La Espectroscopia NIR en la determinación de propiedades físicas y composición química de intermedios de producción y productos acabados

Descripció del recurs: el 1 de febrer de 2011Conseguir una elevada calidad en el producto acabado es un reto cada día más importante en la industria moderna. Para asegurar esta calidad los productos antes de salir al mercado, deben cumplir especificaciones estrictas establecidas tanto por organismos reguladores como por el propio mercado. Con el objetivo de proporcionar a la industria nuevas metodologías de análisis se han desarrollado diversos trabajos basados en la espectroscopia NIR. Se ha colaborado con la industria del mortero y la farmacéutica ofreciéndoles soluciones concretas a sus problemas analíticos. En el primer trabajo junto con la industria del mortero, se han desarrollado modelos de cuantificación para aditivos en morteros. Se ha desarrollado un diseño de muestras original basado en la figura del antiprisma de base hexagonal, donde se han tenido en cuenta el rango de concentración de los analitos. Para incorporar la variabilidad de los aditivos, se usó el diseño D-óptimo que proporcionó las diferentes combinaciones entre clases de aditivos. Se ha obtenido un modelo de calibración PLS para cada aditivo, presentando ambos una correcta capacidad predictiva. Los métodos desarrollados han sido validados con un conjunto de muestras externas. En un segundo estudio realizado con áridos (materia prima de los morteros), se han estudiado 2 perfiles diferentes de distribución de partículas con diferente número de puntos en la curva (número de tamices utilizado en la determinación). Se han construido 2 modelos de calibración (PLS2 y ANN) para cada curva con el objeto de obtener la mejor calidad de ajuste en términos de coeficiente de correlación entre la curva de referencia y la predicha por el modelo quimiométrico y obtener los mejores errores de predicción. Los 4 modelos de calibración proporcionan resultados estadísticamente iguales, en cuanto al error de predicción, demostrando la posibilidad de obtener curvas de distribución de tamaño de partícula a partir de datos NIR y modelos de calibración PLS2 y ANN. El uso de ANN como técnica de modelado no lineal no mejora estadísticamente los resultados. Los siguientes trabajos se han realizado para la industria farmacéutica. El principal nexo de unión es la construcción de modelos de calibración sin usar método de referencia para obtener la variable dependiente. En el primer trabajo se ha realizado un estudio de determinación de API a lo largo del proceso de fabricación estudiando las diferentes variables que pueden afectar al proceso (tamaño de partícula, forma galénica, presión de compactación y grosor de la capa de lacado) y se han propuesto diferentes estrategias que tienen por objeto construir modelos de calibración simples y adecuados para la cuantificación del API en las diferentes etapas del proceso. En el segundo y tercer trabajo para la industria farmacéutica se ha desarrollado y aplicado una nueva metodología para construir conjuntos de calibración adaptados a cada tipo de comprimido. Dicha metodología se basa en la obtención del espectro proceso calculado como diferencia entre el espectro de un comprimido de producción y el de una muestra de laboratorio en polvo de la misma composición. El conjunto de diferencias calculadas para varios comprimidos constituyen un conjunto de vectores matemáticos que definen la variabilidad del proceso. Esta matriz de variabilidad se ha adicionado a un conjunto de espectros NIR de diferentes mezclas en polvo, que cubren el rango deseado de concentración del principio activo y excipientes, dando lugar a la matriz de espectros del conjunto de calibración. Aplicando el algoritmo PLS al conjunto de calibración se construye un modelo para cada uno de los analitos. Los resultados obtenidos en la predicción tanto de API como de excipientes en comprimidos de ibuprofeno y metformina muestran errores de predicción inferiores al 1,5%.Obtaining a high quality final product constitutes a challenge with increase importance in the modern industry. The products should fulfil strict specifications established by regulatory agency just before their releasing to the market. Several new methods based on NIR spectroscopy have been developed for the industry in order to provide the optimum tools to achieve these objectives. This PhD Thesis provides the analytical knowledge to solve real industrial problems usually present in the mortar and pharmaceutical industries. Two studies have been conducted for the cement industry, with the aim of improving the value of the final product. Firstly, quantitative calibration models for additives in mortars have been developed. In order to ensure the calibration set contain natural variability of the samples, we used an experimental design to select the best representative set of samples. This novel approach is based on a hexagonal antiprism that encompasses the concentration ranges spanned by the analytes and the natural variability inherent of each additive. The D-optimality criterion has been used to obtain several combinations between additive classes. The PLS calibration models thus constructed for each additive provided accurate predictions. The ensuing analytical methods have been validated using an external sample set. Secondly, particle size distribution is a key quality attribute of mortars. Different approaches have been carried out to quantify this distribution in mortars. Two different profiles of particle size distribution have been studied and PLS2 and ANN calibration models have been calculated for each one. The objective has been to achieve the best predictive ability of the calibration models in terms of high correlation coefficient between the reference and predicted distribution curve and low prediction errors. The results obtained with the four calibration models were not statistically different. Therefore, the combined use of NIR spectroscopy and PLS2 or ANN calibration models allowed an accurately determination of particle size distribution in mortars. The use ANN for non-linear modelling of the data set has not improved the results. In the pharmaceutical field, the studies have been conducted to the determination of API at different stages of the manufacturing process and also in the final product. The main link of the following works is the development of calibration models without using reference method for determining the dependent variable. In the first work, the API concentration has been quantified throughout the entire production process of a pharmaceutical formulation. The authors have evaluated the influence of particle size, galenic form, compaction pressure and coating thickness on the NIR spectra of the sample. The eventual influence of these variables was included in the calibration model in a simple way that allowed the accurate and precise prediction of the API at the different stages of the production process. In the second and third work, a new methodology has been developed to construct calibration sets. This methodology is based on obtaining the process spectra, which is calculated by the difference between the NIR spectra for production tablets and those for laboratory samples containing the nominal concentrations of API and excipients. The body of differences thus calculated for several tablets constitutes a set of mathematical vectors that define the overall variability of the process. This new matrix is added to a set of NIR spectra for several powder mixtures spanning the desired content range for the API and excipients in order to obtain the spectral matrix for the calibration set. Applying PLS algorithm to calibration set allows constructing of calibration models for each analyte. This methodology has been applied successfully on API and excipients determination in commercial pharmaceutical tablets. In this way, tablet contents can be predicted with errors less than 1.5%