Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

Sorveglianza dell’infezione da virus dell’epatite E (HEV) in Italia: from farm to table

L'epatite E è una malattia umana con caratteristiche di epatite acuta, causata da un ssRNA virus (HEV). Nel 1997, HEV è stato identificato per la prima volta nei suini (SwHEV). In seguito, diverse evidenze, tra cui la vicinanza genetica tra ceppi umani e suini, suggerirono la trasmissione zoonotica del virus. Nella presente tesi, l’identificazione di SwHEV è stata condotta mediante ricerca di porzioni di genoma virale attraverso RT-PCR. Dal 2011 al 2013, sono stati analizzati 343 campioni fecali (da 19 allevamenti) e 70 bili (da 2 macelli) prelevati da altrettanti suini, in diverse Regioni italiane. E’ stato inoltre condotto uno studio retrospettivo su 78 feci (da 3 allevamenti) raccolte nel 2000. Il virus è stato identificato nel 24,5% e 19,2% delle feci raccolte rispettivamente nel 2011-2013 e nel 2000. Nessuna bile è risultata positiva. Mediante sequenziamento del genoma intero di uno dei virus identificati, è stata condotta l’analisi filogenetica per valutarne il grado di correlazione con alti ceppi suini e umani. La presenza di HEV è stata valutata lungo la filiera di produzione suina, dal macello al punto vendita. Trentaquattro campioni di feci, fegato e muscolo sono stati raccolti in un macello da altrettanti suini sani (età:6-7 mesi). Quattordici feci e 2 fegati, sono risultati positivi per HEV. Sono state prelevate 129 salsicce sia allo stabilimento di trasformazione sia alla vendita, ma nessuna è risultata positiva. La presenza di HEV è stata valutata anche nelle salsicce di fegato, fresche e secche, acquistate presso una macelleria. Il genoma virale è stato rilevato nel 22,2% delle salsicce fresche e nel 4,3 % di quelle secche ma la vitalità del virus non è stata dimostrata. In conclusione, lo studio condotto ha confermato l’ampia circolazione di HEV nei suini e la possibile contaminazione dei prodotti carnei derivati, confermando la necessità di una continua sorveglianza.

Optimisation of chemical lysis protocol for point-of-care leukocyte differentiation

The full blood cell (FBC) count is the most common indicator of diseases. At present hematology analyzers are used for the blood cell characterization, but, recently, there has been interest in using techniques that take advantage of microscale devices and intrinsic properties of cells for increased automation and decreased cost. Microfluidic technologies offer solutions to handling and processing small volumes of blood (2-50 uL taken by finger prick) for point-of-care(PoC) applications. Several PoC blood analyzers are in use and may have applications in the fields of telemedicine, out patient monitoring and medical care in resource limited settings. They have the advantage to be easy to move and much cheaper than traditional analyzers, which require bulky instruments and consume large amount of reagents. The development of miniaturized point-of-care diagnostic tests may be enabled by chip-based technologies for cell separation and sorting. Many current diagnostic tests depend on fractionated blood components: plasma, red blood cells (RBCs), white blood cells (WBCs), and platelets. Specifically, white blood cell differentiation and counting provide valuable information for diagnostic purposes. For example, a low number of WBCs, called leukopenia, may be an indicator of bone marrow deficiency or failure, collagen- vascular diseases, disease of the liver or spleen. The leukocytosis, a high number of WBCs, may be due to anemia, infectious diseases, leukemia or tissue damage. In the laboratory of hybrid biodevices, at the University of Southampton,it was developed a functioning micro impedance cytometer technology for WBC differentiation and counting. It is capable to classify cells and particles on the base of their dielectric properties, in addition to their size, without the need of labeling, in a flow format similar to that of a traditional flow cytometer. It was demonstrated that the micro impedance cytometer system can detect and differentiate monocytes, neutrophils and lymphocytes, which are the three major human leukocyte populations. The simplicity and portability of the microfluidic impedance chip offer a range of potential applications in cell analysis including point-of-care diagnostic systems. The microfluidic device has been integrated into a sample preparation cartridge that semi-automatically performs erythrocyte lysis before leukocyte analysis. Generally erythrocytes are manually lysed according to a specific chemical lysis protocol, but this process has been automated in the cartridge. In this research work the chemical lysis protocol, defined in the patent US 5155044 A, was optimized in order to improve white blood cell differentiation and count performed by the integrated cartridge.

[Microbiological point of care tests]

It is well known that the early initiation of a specific antiinfective therapy is crucial to reduce the mortality in severe infection. Procedures culturing pathogens are the diagnostic gold standard in such diseases. However, these methods yield results earliest between 24 to 48 hours. Therefore, severe infections such as sepsis need to be treated with an empirical antimicrobial therapy, which is ineffective in an unknown fraction of these patients. Today's microbiological point of care tests are pathogen specific and therefore not appropriate for an infection with a variety of possible pathogens. Molecular nucleic acid diagnostics such as polymerase chain reaction (PCR) allow the identification of pathogens and resistances. These methods are used routinely to speed up the analysis of positive blood cultures. The newest PCR based system allows the identification of the 25 most frequent sepsis pathogens by PCR in parallel without previous culture in less than 6 hours. Thereby, these systems might shorten the time of possibly insufficient antiinfective therapy. However, these extensive tools are not suitable as point of care diagnostics. Miniaturization and automating of the nucleic acid based method is pending, as well as an increase of detectable pathogens and resistance genes by these methods. It is assumed that molecular PCR techniques will have an increasing impact on microbiological diagnostics in the future.

Point-of-care testing in the cardiovascular operating theatre

Point-of-care testing (POCT) remains under scrutiny by healthcare professionals because of its ill-tried, young history. POCT methods are being developed by a few major equipment companies based on rapid progress in informatics and nanotechnology. Issues as POCT quality control, comparability with standard laboratory procedures, standardisation, traceability and round robin testing are being left to hospitals. As a result, the clinical and operational benefits of POCT were first evident for patients on the operating table. For the management of cardiovascular surgery patients, POCT technology is an indispensable aid. Improvement of the technology has meant that clinical laboratory pathologists now recognise the need for POCT beyond their high-throughput areas.

Effective water treatment for rural communities in Suriname : a comparison of point-of-use ceramic filters and centralized treatment with sand filters

For countless communities around the world, acquiring access to safe drinking water is a daily challenge which many organizations endeavor to meet. The villages in the interior of Suriname have been the focus of many improved drinking water projects as most communities are without year-round access. Unfortunately, as many as 75% of the systems in Suriname fail within several years of implementation. These communities, scattered along the rivers and throughout the jungle, lack many of the resources required to sustain a centralized water treatment system. However, the centralized system in the village of Bendekonde on the Upper Suriname River has been operational for over 10 years and is often touted by other communities. The Bendekonde system is praised even though the technology does not differ significantly from other failed systems. Many of the water systems that fail in the interior fail due to a lack of resources available to the community to maintain the system. Typically, the more complex a system becomes, so does the demand for additional resources. Alternatives to centralized systems include technologies such as point-of-use water filters, which can greatly reduce the necessity for outside resources. In particular, ceramic point-of-use water filters offer a technology that can be reasonably managed in a low resource setting such as that in the interior of Suriname. This report investigates the appropriateness and effectiveness of ceramic filters constructed with local Suriname clay and compares the treatment effectiveness to that of the Bendekonde system. Results of this study showed that functional filters could be produced from Surinamese clay and that they were more effective, in a controlled laboratory setting, than the field performance of the Bendekonde system for removing total coliform. However, the Bendekonde system was more successful at removing E. coli. In a life-cycle assessment, ceramic water filters manufactured in Suriname and used in homes for a lifespan of 2 years were shown to have lower cumulative energy demand, as well as lower global warming potential than a centralized system similar to that used in Bendekonde.

The effect of long-term water table manipulations on vegetation, pore water, substrate quality, and carbon cycling in a Northern poor fen peatland

Northern peatlands are large reservoirs of soil organic carbon (C). Historically peatlands have served as a sink for C since decomposition is slowed primarily because of a raised water table (WT) that creates anoxic conditions. Climate models are predicting dramatic changes in temperature and precipitation patterns for the northern hemisphere that contain more than 90% of the world’s peatlands. It is uncertain whether climate change will shift northern peatlands from C sequestering systems to a major global C source within the next century because of alterations to peatland hydrology. This research investigated the effects of 80 years of hydrological manipulations on peatland C cycling in a poor fen peatland in northern Michigan. The construction of an earthen levee within the Seney National Wildlife Refuge in the 1930’s resulted in areas of raised and lowered WT position relative to an intermediate WT site that was unaltered by the levee. We established sites across the gradient of long-term WT manipulations to examine how decadal changes in WT position alter peatland C cycling. We quantified vegetation dynamics, peat substrate quality, and pore water chemistry in relation to trace gas C cycling in these manipulated areas as well as the intermediate site. Vegetation in both the raised and lowered WT treatments has different community structure, biomass, and productivity dynamics compared to the intermediate site. Peat substrate quality exhibited differences in chemical composition and lability across the WT treatments. Pore water dissolved organic carbon (DOC) concentrations increased with impoundment and WT drawdown. The raised WT treatment DOC has a low aromaticity and is a highly labile C source, whereas WT drawdown has increased DOC aromaticity. This study has demonstrated a subtle change of the long-term WT position in a northern peatland will induce a significant influence on ecosystem C cycling with implications for the fate of peatland C stocks.

Enterprise Integration of Smart Objects using Semantic Service Descriptions

Integrating physical objects (smart objects) and enterprise IT systems is still a labor intensive, mainly manual task done by domain experts. On one hand, enterprise IT backend systems are based on service oriented architectures (SOA) and driven by business rule engines or business process execution engines. Smart objects on the other hand are often programmed at very low levels. In this paper we describe an approach that makes the integration of smart objects with such backends systems easier. We introduce semantic endpoint descriptions based on Linked USDL. Furthermore, we show how different communication patterns can be integrated into these endpoint descriptions. The strength of our endpoint descriptions is that they can be used to automatically create REST or SOAP endpoints for enterprise systems, even if which they are not able to talk to the smart objects directly. We evaluate our proposed solution with CoAP, UDP and 6LoWPAN, as we anticipate the industry converge towards these standards. Nonetheless, our approach also allows easy integration with backend systems, even if no standardized protocol is used.

A Demonstration of Mobility Prediction as a Service in Cloudified LTE Networks

Location prediction has attracted a significant amount of research effort. Being able to predict users’ movement benefits a wide range of communication systems, including location-based service/applications, mobile access control, mobile QoS provision, and resource management for mobile computation and storage management. In this demo, we present MOBaaS, which is a cloudified Mobility and Bandwidth prediction services that can be instantiated, deployed, and disposed on-demand. Mobility prediction of MOBaaS provides location predictions of a single/group user equipments (UEs) in a future moment. This information can be used for self-adaptation procedures and optimal network function configuration during run-time operations. We demonstrate an example of real-time mobility prediction service deployment running on OpenStack platform, and the potential benefits it bring to other invoking services.

'Reform' of the British national health service after the election of a labour government: Understanding the policy development process

The policy development process leading to the Labour government's white paper of December 1997—The new NHS: Modern, Dependable—is the focus of this project and the public policy development literature is used to aid in the understanding of this process. Policy makers who had been involved in the development of the white paper were interviewed in order to acquire a thorough understanding of who was involved in this process and how they produced the white paper. A theoretical framework is used that sorts policy development models into those that focus on knowledge and experience, and those which focus on politics and influence. This framework is central to understanding the evidence gathered from the individuals and associations that participated in this policy development process. The main research question to be asked in this project is to what extent do either of these sets of policy development models aid in understanding and explicating the process by which the Labour government's policies were developed. The interview evidence, along with published evidence, show that a clear pattern of policy change emerged from this policy development process, and the Knowledge-Experience and Politics-Influence policy making models both assist in understanding this process. The early stages of the policy development process were characterized as hierarchical and iterative, yet also very collaborative among those participating, with knowledge and experience being quite prevalent. At every point in the process, however, informal networks of political influence were used and noted to be quite prevalent by all of the individuals interviewed. The later stages of the process then became increasingly noninclusive, with decisions made by a select group of internal and external policy makers. These policy making models became an important tool with which to understand the policy development process. This Knowledge-Experience and Politics-Influence dichotomy of policy development models could therefore be useful in analyzing other types of policy development. ^

Performance recovery from exercise: A review from a statistical point of view

Background. Research into methods for recovery from fatigue due to exercise is a popular topic among sport medicine, kinesiology and physical therapy. However, both the quantity and quality of studies and a clear solution of recovery are lacking. An analysis of the statistical methods in the existing literature of performance recovery can enhance the quality of research and provide some guidance for future studies. Methods: A literature review was performed using SCOPUS, SPORTDiscus, MEDLINE, CINAHL, Cochrane Library and Science Citation Index Expanded databases to extract the studies related to performance recovery from exercise of human beings. Original studies and their statistical analysis for recovery methods including Active Recovery, Cryotherapy/Contrast Therapy, Massage Therapy, Diet/Ergogenics, and Rehydration were examined. Results: The review produces a Research Design and Statistical Method Analysis Summary. Conclusion: Research design and statistical methods can be improved by using the guideline from the Research Design and Statistical Method Analysis Summary. This summary table lists the potential issues and suggested solutions, such as, sample size calculation, sports specific and research design issues consideration, population and measure markers selection, statistical methods for different analytical requirements, equality of variance and normality of data, post hoc analyses and effect size calculation.^

Modeling of the Division Point of Different Propagation Mechanisms in the Near-Region Within Arched Tunnels

An accurate characterization of the near-region propagation of radio waves inside tunnels is of practical importance for the design and planning of advanced communication systems. However, there has been no consensus yet on the propagation mechanism in this region. Some authors claim that the propagation mechanism follows the free space model, others intend to interpret it by the multi-mode waveguide model. This paper clarifies the situation in the near-region of arched tunnels by analytical modeling of the division point between the two propagation mechanisms. The procedure is based on the combination of the propagation theory and the three-dimensional solid geometry. Three groups of measurements are employed to verify the model in different tunnels at different frequencies. Furthermore, simplified models for the division point in five specific application situations are derived to facilitate the use of the model. The results in this paper could help to deepen the insight into the propagation mechanism within tunnel environments.

Optimización de la composición del hueco de fachada en materia de eficiencia energética. Propuesta de indicador como herramienta para el análisis integral del elemento acristalado = Energy performance optimization of window systems. Proposal of an indicator as a tool for an integrated analysis of glazing

La hipótesis de esta tesis es: "La optimización de la ventana considerando simultáneamente aspectos energéticos y aspectos relativos a la calidad ambiental interior (confort higrotérmico, lumínico y acústico) es compatible, siempre que se conozcan y consideren las sinergias existentes entre ellos desde las primeras fases de diseño". En la actualidad se desconocen las implicaciones de muchas de las decisiones tomadas en torno a la ventana; para que su eficiencia en relación a todos los aspectos mencionados pueda hacerse efectiva es necesaria una herramienta que aporte más información de la actualmente disponible en el proceso de diseño, permitiendo así la optimización integral, en función de las circunstancias específicas de cada proyecto. En la fase inicial de esta investigación se realiza un primer acercamiento al tema, a través del estado del arte de la ventana; analizando la normativa existente, los componentes, las prestaciones, los elementos experimentales y la investigación. Se observa que, en ocasiones, altos requisitos de eficiencia energética pueden suponer una disminución de las prestaciones del sistema en relación con la calidad ambiental interior, por lo que surge el interés por integrar al análisis energético aspectos relativos a la calidad ambiental interior, como son las prestaciones lumínicas y acústicas y la renovación de aire. En este punto se detecta la necesidad de realizar un estudio integral que incorpore los distintos aspectos y evaluar las sinergias que se dan entre las distintas prestaciones que cumple la ventana. Además, del análisis de las soluciones innovadoras y experimentales se observa la dificultad de determinar en qué medida dichas soluciones son eficientes, ya que son soluciones complejas, no caracterizadas y que no están incorporadas en las metodologías de cálculo o en las bases de datos de los programas de simulación. Por lo tanto, se plantea una segunda necesidad, generar una metodología experimental para llevar a cabo la caracterización y el análisis de la eficiencia de sistemas innovadores. Para abordar esta doble necesidad se plantea la optimización mediante una evaluación del elemento acristalado que integre la eficiencia energética y la calidad ambiental interior, combinando la investigación teórica y la investigación experimental. En el ámbito teórico, se realizan simulaciones, cálculos y recopilación de información de distintas tipologías de hueco, en relación con cada prestación de forma independiente (acústica, iluminación, ventilación). A pesar de haber partido con un enfoque integrador, resulta difícil esa integración detectándose una carencia de herramientas disponible. En el ámbito experimental se desarrolla una metodología para la evaluación del rendimiento y de aspectos ambientales de aplicación a elementos innovadores de difícil valoración mediante la metodología teórica. Esta evaluación consiste en el análisis comparativo experimental entre el elemento innovador y un elemento estándar; para llevar a cabo este análisis se han diseñado dos espacios iguales, que denominamos módulos de experimentación, en los que se han incorporado los dos sistemas; estos espacios se han monitorizado, obteniéndose datos de consumo, temperatura, iluminancia y humedad relativa. Se ha realizado una medición durante un periodo de nueve meses y se han analizado y comparado los resultados, obteniendo así el comportamiento real del sistema. Tras el análisis teórico y el experimental, y como consecuencia de esa necesidad de integrar el conocimiento existente se propone una herramienta de evaluación integral del elemento acristalado. El desarrollo de esta herramienta se realiza en base al procedimiento de diagnóstico de calidad ambiental interior (CAI) de acuerdo con la norma UNE 171330 “Calidad ambiental en interiores”, incorporando el factor de eficiencia energética. De la primera parte del proceso, la parte teórica y el estado del arte, se obtendrán los parámetros que son determinantes y los valores de referencia de dichos parámetros. En base a los parámetros relevantes obtenidos se da forma a la herramienta, que consiste en un indicador de producto para ventanas que integra todos los factores analizados y que se desarrolla según la Norma UNE 21929 “Sostenibilidad en construcción de edificios. Indicadores de sostenibilidad”. ABSTRACT The hypothesis of this thesis is: "The optimization of windows considering energy and indoor environmental quality issues simultaneously (hydrothermal comfort, lighting comfort, and acoustic comfort) is compatible, provided that the synergies between these issues are known and considered from the early stages of design ". The implications of many of the decisions made on this item are currently unclear. So that savings can be made, an effective tool is needed to provide more information during the design process than the currently available, thus enabling optimization of the system according to the specific circumstances of each project. The initial phase deals with the study from an energy efficiency point of view, performing a qualitative and quantitative analysis of commercial, innovative and experimental windows. It is observed that sometimes, high-energy efficiency requirements may mean a reduction in the system's performance in relation to user comfort and health, that's why there is an interest in performing an integrated analysis of indoor environment aspects and energy efficiency. At this point a need for a comprehensive study incorporating the different aspects is detected, to evaluate the synergies that exist between the various benefits that meet the window. Moreover, from the analysis of experimental and innovative windows, a difficulty in establishing to what extent these solutions are efficient is observed; therefore, there is a need to generate a methodology for performing the analysis of the efficiency of the systems. Therefore, a second need arises, to generate an experimental methodology to perform characterization and analysis of the efficiency of innovative systems. To address this dual need, the optimization of windows by an integrated evaluation arises, considering energy efficiency and indoor environmental quality, combining theoretical and experimental research. In the theoretical field, simulations and calculations are performed; also information about the different aspects of indoor environment (acoustics, lighting, ventilation) is gathered independently. Despite having started with an integrative approach, this integration is difficult detecting lack available tools. In the experimental field, a methodology for evaluating energy efficiency and indoor environment quality is developed, to be implemented in innovative elements which are difficult to evaluate using a theoretical methodology This evaluation is an experimental comparative analysis between an innovative element and a standard element. To carry out this analysis, two equal spaces, called experimental cells, have been designed. These cells have been monitored, obtaining consumption, temperature, luminance and relative humidity data. Measurement has been performed during nine months and results have been analyzed and compared, obtaining results of actual system behavior. To advance this optimization, windows have been studied from the point of view of energy performance and performance in relation to user comfort and health: thermal comfort, acoustic comfort, lighting comfort and air quality; proposing the development of a methodology for an integrated analysis including energy efficiency and indoor environment quality. After theoretical and experimental analysis and as a result of the need to integrate existing knowledge, a comprehensive evaluation procedure for windows is proposed. This evaluation procedure is developed according to the UNE 171330 "Indoor Environmental Quality", also incorporating energy efficiency and cost as factors to evaluate. From the first part of the research process, outstanding parameters are chosen and reference values of these parameters are set. Finally, based on the parameters obtained, an indicator is proposed as windows product indicator. The indicator integrates all factors analyzed and is developed according to ISO 21929-1:2011"Sustainability in building construction. Sustainability indicators. Part 1: Framework for the development of indicators and a core set of indicators for buildings".