Improved VMAT planning for head and neck tumors with an advanced optimization algorithm

OBJECTIVE In this study, the "Progressive Resolution Optimizer PRO3" (Varian Medical Systems) is compared to the previous version "PRO2" with respect to its potential to improve dose sparing to the organs at risk (OAR) and dose coverage of the PTV for head and neck cancer patients. MATERIALS AND METHODS For eight head and neck cancer patients, volumetric modulated arc therapy (VMAT) treatment plans were generated in this study. All cases have 2-3 phases and the total prescribed dose (PD) was 60-72Gy in the PTV. The study is mainly focused on the phase 1 plans, which all have an identical PD of 54Gy, and complex PTV structures with an overlap to the parotids. Optimization was performed based on planning objectives for the PTV according to ICRU83, and with minimal dose to spinal cord, and parotids outside PTV. In order to assess the quality of the optimization algorithms, an identical set of constraints was used for both, PRO2 and PRO3. The resulting treatment plans were investigated with respect to dose distribution based on the analysis of the dose volume histograms. RESULTS For the phase 1 plans (PD=54Gy) the near maximum dose D2% of the spinal cord, could be minimized to 22±5 Gy with PRO3, as compared to 32±12Gy with PRO2, averaged for all patients. The mean dose to the parotids was also lower in PRO3 plans compared to PRO2, but the differences were less pronounced. A PTV coverage of V95%=97±1% could be reached with PRO3, as compared to 86±5% with PRO2. In clinical routine, these PRO2 plans would require modifications to obtain better PTV coverage at the cost of higher OAR doses. CONCLUSION A comparison between PRO3 and PRO2 optimization algorithms was performed for eight head and neck cancer patients. In general, the quality of VMAT plans for head and neck patients are improved with PRO3 as compared to PRO2. The dose to OARs can be reduced significantly, especially for the spinal cord. These reductions are achieved with better PTV coverage as compared to PRO2. The improved spinal cord sparing offers new opportunities for all types of paraspinal tumors and for re-irradiation of recurrent tumors or second malignancies.

Usability and Acceptability of ASSESS MS: Assessment of Motor Dysfunction in Multiple Sclerosis Using Depth-Sensing Computer Vision

Background: Sensor-based recordings of human movements are becoming increasingly important for the assessment of motor symptoms in neurological disorders beyond rehabilitative purposes. ASSESS MS is a movement recording and analysis system being developed to automate the classification of motor dysfunction in patients with multiple sclerosis (MS) using depth-sensing computer vision. It aims to provide a more consistent and finer-grained measurement of motor dysfunction than currently possible. Objective: To test the usability and acceptability of ASSESS MS with health professionals and patients with MS. Methods: A prospective, mixed-methods study was carried out at 3 centers. After a 1-hour training session, a convenience sample of 12 health professionals (6 neurologists and 6 nurses) used ASSESS MS to capture recordings of standardized movements performed by 51 volunteer patients. Metrics for effectiveness, efficiency, and acceptability were defined and used to analyze data captured by ASSESS MS, video recordings of each examination, feedback questionnaires, and follow-up interviews. Results: All health professionals were able to complete recordings using ASSESS MS, achieving high levels of standardization on 3 of 4 metrics (movement performance, lateral positioning, and clear camera view but not distance positioning). Results were unaffected by patients’ level of physical or cognitive disability. ASSESS MS was perceived as easy to use by both patients and health professionals with high scores on the Likert-scale questions and positive interview commentary. ASSESS MS was highly acceptable to patients on all dimensions considered, including attitudes to future use, interaction (with health professionals), and overall perceptions of ASSESS MS. Health professionals also accepted ASSESS MS, but with greater ambivalence arising from the need to alter patient interaction styles. There was little variation in results across participating centers, and no differences between neurologists and nurses. Conclusions: In typical clinical settings, ASSESS MS is usable and acceptable to both patients and health professionals, generating data of a quality suitable for clinical analysis. An iterative design process appears to have been successful in accounting for factors that permit ASSESS MS to be used by a range of health professionals in new settings with minimal training. The study shows the potential of shifting ubiquitous sensing technologies from research into the clinic through a design approach that gives appropriate attention to the clinic environment.

Global Optimization with Sparse and Local Gaussian Process Models

We present a novel surrogate model-based global optimization framework allowing a large number of function evaluations. The method, called SpLEGO, is based on a multi-scale expected improvement (EI) framework relying on both sparse and local Gaussian process (GP) models. First, a bi-objective approach relying on a global sparse GP model is used to determine potential next sampling regions. Local GP models are then constructed within each selected region. The method subsequently employs the standard expected improvement criterion to deal with the exploration-exploitation trade-off within selected local models, leading to a decision on where to perform the next function evaluation(s). The potential of our approach is demonstrated using the so-called Sparse Pseudo-input GP as a global model. The algorithm is tested on four benchmark problems, whose number of starting points ranges from 102 to 104. Our results show that SpLEGO is effective and capable of solving problems with large number of starting points, and it even provides significant advantages when compared with state-of-the-art EI algorithms.

Multiple retinal detachment surgery: A functional outcome study. The Houston Vision Assessment Test-Retina (HVAT-Retina)

Retinal detachment is a common ophthalmologic procedure, and outcome is typically measured by a single factor-improvement in visual acuity. Health related functional outcome testing, which quantifies patient's self-reported perception of impairment, can be integrated with objective clinical findings. Based on the patient's self-assessed lifestyle impairment, the physician and patient together can make an informed decision on the treatment that is most likely to benefit the patient. ^ A functional outcome test (the Houston Vision Assessment Test-Retina; HVAT-Retina) was developed and validated in patients with multiple retinal detachments in the same eye. The HVAT-Retina divides an estimated total impairment into subcomponents: contribution of visual disability (potentially correctable by retinal detachment surgery) and nonvisual physical disabilities (co-morbidities not affected by retinal detachment surgery. ^ Seventy-six patients participated in this prospective multicenter study. Seven patients were excluded from the analysis because they were not certain of their answers. Cronbach's alpha coefficient was 0.91 for presurgery HVAT-Retina and 0.94 post-surgery. The item-to-total correlation ranged from 0.50 to 0.88. Visual impairment score improved by 9 points from pre-surgery (p = 0.0003). Physical impairment score also improved from pre-surgery (p = 0.0002). ^ In conclusion, the results of this study demonstrate that the instrument is reliable and valid in patients presenting with recurrent retinal detachments. The HVAT-Retina is a simple instrument and does not burden the patient or the health professional in terms of time or cost. It may be self-administrated, not requiring an interviewer. Because the HVAT-Retina was designed to demonstrate outcomes perceivable by the patient, it has the potential to guide the decision making process between patient and physician. ^

MBA Program Reputation: Objective Rankings for Students, Employers and Program Administrators

Widely publicized reports of fresh MBAs receiving multiple job offers with six-figure annual salaries leave a long-lasting general impression about the high quality of selected business schools. Business Week reports on a regular basis ranking of MBA programs based on subjective surveys of students and employers. This paper ranks MBA programs using objective data from three different points of view students, employers, and MBA program administrators.

Obesity and risk of multiple myeloma: A case-control study

Introduction. Several studies have reported a positive association of body mass index (BMI) with multiple myeloma; however, the period of adulthood where BMI is most important remains unclear. In addition, it is well known that body fat is associated with both sex-steroid hormone storage and with increasing insulin levels; therefore, it was hypothesized that the association between obesity and multiple myeloma may be attributed to increased aromatization of androgen in adipose tissue. Objective. The overall objective of this case-control study was to determine whether multiple myeloma cases had higher BMI and greater adult weight gain relative to healthy controls. In addition, we tested the hypothesis that hormone replacement therapy use among women will further increase the association between BMI and risk of multiple myeloma. This study used data from a pilot case-control study at M.D. Anderson Cancer Center (MDACC), entitled Etiology of multiple myeloma, directed by Dr. Sara Strom and Dr. Sergio Giralt. Methods. The pilot study recruited a total of 122 cases of histopathologically confirmed multiple myeloma from MDACC. Controls (n=183) were selected from a database of random digit dialing controls accrued in the Department of Epidemiology at MDACC and were frequency matched to the cases on age (±5 years), gender, and race/ethnicity. Demographic and risk factor information were obtained from all participants who completed a self-administered questionnaire. Items included in the questionnaire include demographic information, height and weight at age 25, 40 and current/diagnosis, medical history, family history of cancer, smoking and alcohol use. Statistical analysis. Initial descriptive analysis included Student's t-test and Pearson's chi-squared tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between the variables of interest and multiple myeloma. A multivariable model will be developed using unconditional logistic regression. Results. MM cases were 1.79 times (95% CI=0.99-3.32) more likely to have been overweight or obese (BMI > 25 kg/m2) at age 25 relative to healthy controls after controlling for age, gender, race/ethnicty, education and family history of cancer. Being overweight or obese at age 40 was not significantly associated with mutliple myeloma risk (OR=1.42, 95% CI=0.86-2.34) nor was being overweight or obses at diagnosis (OR=1.43, 95% CI=0.78, 2.63). We observed a statistically significant 2-fold increased odds of multiple myeloma in individuals who gained more than 4.7 kg during between 25 and 40 years (OR=1.97, 95% CI=1.15-3.39). When assessing HRT as a modifier of the BMI and multiple myeloma association among women (N=123), no association between obesity and MM status was observed among women who have never used HRT (OR=0.60, 95% CI=0.23-1.61; n=73). Yet among women who have ever used HRT (n=50), being overweight or obese was associated with an increase in MM risk (OR=2. 93, 95% CI=0.81-10.6) after adjusting for age; however, the association was not statistically significant. Significance. This study provides further evidence that increased BMI increases the risk of multiple myeloma. Furthermore, among women, HRT use may modify risk of disease. ^

Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody in HIV-1 infected adults

Context: Despite tremendous strides in HIV treatment over the past decade, resistance remains a major problem. A growing number of patients develop resistance and require new therapies to suppress viral replication. ^ Objective: To assess the safety of multiple administrations of the anti-CD4 receptor (anti-CD4) monoclonal antibody ibalizumab given as intravenous (IV) infusions, in three dosage regimens, in subjects infected with human immunodeficiency virus (HIV-1). ^ Design: Phase 1, multi-center, open-label, randomized clinical trial comparing the safety, pharmacokinetics and antiviral activity of three dosages of ibalizumab. ^ Setting: Six clinical trial sites in the United States. ^ Participants: A total of twenty-two HIV-positive patients on no anti-retroviral therapy or a stable failing regimen. ^ Intervention: Randomized to one of two treatment groups in Arms A and B followed by non-randomized enrollment in Arm C. Patients randomized to Arm A received 10 mg/kg of ibalizumab every 7 days, for a total of 10 doses; patients randomized to Arm B received a total of six doses of ibalizumab; a single loading dose of 10 mg/kg on Day 1 followed by five maintenance doses of 6 mg/kg every 14 days, starting at Week 1. Patients assigned to Arm C received 25 mg/kg of ibalizumab every 14 days for a total of 5 doses. All patients were followed for safety for an additional 7 to 8 weeks. ^ Main Outcome Measures: Clinical and laboratory assessments of safety and tolerability of multiple administrations of ibalizumab in HIV-infected patients. Secondary measures of efficacy include HIV-1 RNA (viral load) measurements. ^ Results: 21 patients were treatment-experienced and 1 was naïve to HIV therapy. Six patients were failing despite therapy and 15 were on no current HIV treatment. Mean baseline viral load (4.78 log 10; range 3.7-5.9) and CD4+ cell counts (332/μL; range 89-494) were similar across cohorts. Mean peak decreases in viral load from baseline of 0.99 log10(1.11 log10, and 0.96 log 10 occurred by Wk 2 in Cohorts A, B and C, respectively. Viral loads decreased by >1.0 log10 in 64%; 4 patients viral loads were suppressed to < 400 copies/mL. Viral loads returned towards baseline by Week 9 with reduced susceptibility to ibalizumab. CD4+ cell counts rose transiently and returned toward baseline. Maximum median elevations above BL in CD4+ cell counts for Cohorts A, B and C were +257, +198 and +103 cells/μL, respectively and occurred within 3 Wks in 16 of 22 subjects. The half-life of ibalizumab was 3-3.5 days and elimination was characteristic of capacity-limited kinetics. Administration of ibalizumab was well tolerated. Four serious adverse events were reported during the study. None of these events were related to study drug. Headache, nausea and cough were the most frequently reported treatment emergent adverse events and there were no laboratory abnormalities related to study drug. ^ Conclusions: Ibalizumab administered either weekly or bi-weekly was safe, well tolerated, and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.^

Motivational interviewing and feedback for college drinkers: Handling missing values with complete case analysis and multiple imputation

Objective: In this secondary data analysis, three statistical methodologies were implemented to handle cases with missing data in a motivational interviewing and feedback study. The aim was to evaluate the impact that these methodologies have on the data analysis. ^ Methods: We first evaluated whether the assumption of missing completely at random held for this study. We then proceeded to conduct a secondary data analysis using a mixed linear model to handle missing data with three methodologies (a) complete case analysis, (b) multiple imputation with explicit model containing outcome variables, time, and the interaction of time and treatment, and (c) multiple imputation with explicit model containing outcome variables, time, the interaction of time and treatment, and additional covariates (e.g., age, gender, smoke, years in school, marital status, housing, race/ethnicity, and if participants play on athletic team). Several comparisons were conducted including the following ones: 1) the motivation interviewing with feedback group (MIF) vs. the assessment only group (AO), the motivation interviewing group (MIO) vs. AO, and the intervention of the feedback only group (FBO) vs. AO, 2) MIF vs. FBO, and 3) MIF vs. MIO.^ Results: We first evaluated the patterns of missingness in this study, which indicated that about 13% of participants showed monotone missing patterns, and about 3.5% showed non-monotone missing patterns. Then we evaluated the assumption of missing completely at random by Little's missing completely at random (MCAR) test, in which the Chi-Square test statistic was 167.8 with 125 degrees of freedom, and its associated p-value was p=0.006, which indicated that the data could not be assumed to be missing completely at random. After that, we compared if the three different strategies reached the same results. For the comparison between MIF and AO as well as the comparison between MIF and FBO, only the multiple imputation with additional covariates by uncongenial and congenial models reached different results. For the comparison between MIF and MIO, all the methodologies for handling missing values obtained different results. ^ Discussions: The study indicated that, first, missingness was crucial in this study. Second, to understand the assumptions of the model was important since we could not identify if the data were missing at random or missing not at random. Therefore, future researches should focus on exploring more sensitivity analyses under missing not at random assumption.^

EPANET Input Files of New York tunnels and Pacific City used in a metamodel-based optimization study

Metamodels have proven be very useful when it comes to reducing the computational requirements of Evolutionary Algorithm-based optimization by acting as quick-solving surrogates for slow-solving fitness functions. The relationship between metamodel scope and objective function varies between applications, that is, in some cases the metamodel acts as a surrogate for the whole fitness function, whereas in other cases it replaces only a component of the fitness function. This paper presents a formalized qualitative process to evaluate a fitness function to determine the most suitable metamodel scope so as to increase the likelihood of calibrating a high-fidelity metamodel and hence obtain good optimization results in a reasonable amount of time. The process is applied to the risk-based optimization of water distribution systems; a very computationally-intensive problem for real-world systems. The process is validated with a simple case study (modified New York Tunnels) and the power of metamodelling is demonstrated on a real-world case study (Pacific City) with a computational speed-up of several orders of magnitude.

Integrated program debugging, verification, and optimization using abstract interpretation (and the Ciao system preprocessor)

The technique of Abstract Interpretation has allowed the development of very sophisticated global program analyses which are at the same time provably correct and practical. We present in a tutorial fashion a novel program development framework which uses abstract interpretation as a fundamental tool. The framework uses modular, incremental abstract interpretation to obtain information about the program. This information is used to validate programs, to detect bugs with respect to partial specifications written using assertions (in the program itself and/or in system libraries), to generate and simplify run-time tests, and to perform high-level program transformations such as multiple abstract specialization, parallelization, and resource usage control, all in a provably correct way. In the case of validation and debugging, the assertions can refer to a variety of program points such as procedure entry, procedure exit, points within procedures, or global computations. The system can reason with much richer information than, for example, traditional types. This includes data structure shape (including pointer sharing), bounds on data structure sizes, and other operational variable instantiation properties, as well as procedure-level properties such as determinacy, termination, nonfailure, and bounds on resource consumption (time or space cost). CiaoPP, the preprocessor of the Ciao multi-paradigm programming system, which implements the described functionality, will be used to illustrate the fundamental ideas.

A graph-based approach for latency modeling and optimization in multiview video encoding

We present a novel framework for encoding latency analysis of arbitrary multiview video coding prediction structures. This framework avoids the need to consider an specific encoder architecture for encoding latency analysis by assuming an unlimited processing capacity on the multiview encoder. Under this assumption, only the influence of the prediction structure and the processing times have to be considered, and the encoding latency is solved systematically by means of a graph model. The results obtained with this model are valid for a multiview encoder with sufficient processing capacity and serve as a lower bound otherwise. Furthermore, with the objective of low latency encoder design with low penalty on rate-distortion performance, the graph model allows us to identify the prediction relationships that add higher encoding latency to the encoder. Experimental results for JMVM prediction structures illustrate how low latency prediction structures with a low rate-distortion penalty can be derived in a systematic manner using the new model.

Design of a compact objective for SWIR applications

Lately the short-wave infrared (SWIR) has become very important due to the recent appearance on the market of the small detectors with a large focal plane array. Military applications for SWIR cameras include handheld and airborne systems with long range detection requirements, but where volume and weight restrictions must be considered. In this paper we present three different designs of telephoto objectives that have been designed according to three different methods. Firstly the conventional method where the starting point of the design is an existing design. Secondly we will face design starting from the design of an aplanatic system. And finally the simultaneous multiple surfaces (SMS) method, where the starting point is the input wavefronts that we choose. The designs are compared in terms of optical performance, volume, weight and manufacturability. Because the objectives have been designed for the SWIR waveband, the color correction has important implications in the choice of glass that will be discussed in detail

Optimization of the irrigation time and irrigation frequency by using Hydrus-2D and a capacitance FDR sensor

The evolution of water content on a sandy soil during the sprinkler irrigation campaign, in the summer of 2010, of a field of sugar beet crop located at Valladolid (Spain) is assessed by a capacitive FDR (Frequency Domain Reflectometry) EnviroScan. This field is one of the experimental sites of the Spanish research center for the sugar beet development (AIMCRA). The objective of the work focus on monitoring the soil water content evolution of consecutive irrigations during the second two weeks of July (from the 12th to the 28th). These measurements will be used to simulate water movement by means of Hydrus-2D. The water probe logged water content readings (m3/m3) at 10, 20, 40 and 60 cm depth every 30 minutes. The probe was placed between two rows in one of the typical 12 x 15 m sprinkler irrigation framework. Furthermore, a texture analysis at the soil profile was also conducted. The irrigation frequency in this farm was set by the own personal farmer 0 s criteria that aiming to minimizing electricity pumping costs, used to irrigate at night and during the weekend i.e. longer irrigation frequency than expected. However, the high evapotranspiration rates and the weekly sugar beet water consumption—up to 50mm/week—clearly determined the need for lower this frequency. Moreover, farmer used to irrigate for six or five hours whilst results from the EnviroScan probe showed the soil profile reaching saturation point after the first three hours. It must be noted that AIMCRA provides to his members with a SMS service regarding weekly sugar beet water requirement; from the use of different meteorological stations and evapotranspiration pans, farmers have an idea of the weekly irrigation needs. Nevertheless, it is the farmer 0 s decision to decide how to irrigate. Thus, in order to minimize water stress and pumping costs, a suitable irrigation time and irrigation frequency was modeled with Hydrus-2D. Results for the period above mentioned showed values of water content ranging from 35 and 30 (m3/m3) for the first 10 and 20cm profile depth (two hours after irrigation) to the minimum 14 and 13 (m3/m3) ( two hours before irrigation). For the 40 and 60 cm profile depth, water content moves steadily across the dates: The greater the root activity the greater the water content variation. According to the results in the EnviroScan probe and the modeling in Hydrus-2D, shorter frequencies and irrigation times are suggested.

Temperature and Photoperiod Effects on Vicia faba Phenology Simulated by CROPGRO-Fababean

Models may be useful tools to design efficient crop management practices provided they are able to accurately simulate the effect of weather variables on crop performance. The objective of this work was to accurately simulate the effects of temperature and day length on the rate of vegetative node expression, time to flowering, time to first pod, and time to physiological maturity of faba bean (Vicia faba L.) using the CROPGRO-Fababean model. Field experiments with multiple sowing dates were conducted in northwest Spain during 3 yr (17 sowing dates: 12 used for calibration and five for validation). Observed daily minimum and maximum air temperatures were within the range of ?9.0 and 39.2°C and observed photoperiods within 10.1 to 16.6 h. Optimization of thermal models to predict leaf appearance raised the base temperature (Tb) from the commonly used value of 0.0 to 3.9°C. In addition, photothermal models detected a small accelerating effect of day length on the rate of leaf appearance. Accurate prediction of the flowering date required incorporating day length, but the solved Tb approached negative values, close to ?4°C. All the reproductive phases after flowering were affected only by temperature, but postanthesis Tb was also mayor que0°C and approached values close to 8°C for time to first pod set and 5.5°C for time from first pod to physiological maturity. Our data indicated that cardinal base temperatures are not the same across all phenological phases.

Optimization of urban mobility measures to achieve win-win strategies

European cities are essential in the development of Europe as they constitute the living environment of more than 60% of the population in the European Union and are drivers of the European economy – just under 85% of the EU’s gross domestic product is produced in urban areas (EC, 2007a). The car has been one of the main factors of development during the 20th century, but it is at the same time the origin of the key problems cities have to face: traffic increase. This has resulted in chronic congestion with many adverse consequences such as air pollution and noise. This loss of environmental quality is one of the reasons for urban sprawl in European cities during recent decades. But this urban sprawl at the same time worsens the environmental conditions. We must return to the dense city, but clean and competitive, and this implies reducing car use yet provides quality transport alternatives sufficient to recover and maintain the competitiveness of cities (EC, 2007a). Consequently, European cities need to establish an urban transport strategy which helps reduce their environmental problems –mainly emissions and noise – but without decreasing their trip attraction. This aspect is very important because a loss of trip attraction would result in an increase of people moving to more disperse areas, contributing towards worsening the current situation. This thesis is an attempt to contribute solutions to this problem in two ways: 1) The first is to analyze the complementarity and possible synergies of several urban transport measures aimed at improving a modal split to a more sustainable means of transport. This analysis will focus on the three aspects already mentioned: emissions, noise and attractiveness or competitiveness. 2) Once possible synergies and complementarities have been analyzed, the second objective is to propose the best combination of these measures, in terms of level of implementation, to achieve the maximum benefit with respect to the three aspects previously established: emissions, noise and attractiveness or competitiveness. Therefore, within the wide range of measures enhancing sustainable urban transport, three of them have been be selected in this thesis to establish a methodology for achieving these objectives. The analysis will be based on the region of Madrid, which is also the case study selected for this research. Las ciudades europeas son piezas fundamentales para el desarrollo europeo, ya que son el lugar de residencia de más del 60% de la población de la unión europea así como los motores de su economía – casi el 85% del PIB europeo se produce en áreas urbanas (EC, 2007a). El coche ha sido uno de los principales motores de desarrollo de las ciudades durante el siglo XX, pero se ha terminado por convertir a su vez en uno de los principales problemas con los que tiene que lidiar las ciudades: el aumento del tráfico. Esto ha derivado en unos niveles crónicos de congestión, con multitud de efectos adversos, entre los que cabe destacar la contaminación del aire y el ruido. Esta pérdida de calidad ambiental es una de las razones que ha propiciado la dispersión urbana que han experimentado las ciudades europeas en las últimas décadas. Pero esta dispersión urbana a su vez contribuye a empeorar las condiciones ambientales de las ciudades. Debemos retornar a la ciudad densa, pero limpia y competitiva, y esto implica reducir el uso del coche, pero proporcionando alternativas de transporte que permitan recuperar y mantener la competitividad de las ciudades (EC, 2007a). Por lo tanto, las ciudades europeas necesitan encontrar una estrategia de transporte urbano que ayude a reducir sus problemas medio ambientales – principalmente ruido y emisiones – pero sin hacerlas perder atractividad o competitividad. Este aspecto tiene gran importancia porque una pérdida de la misma se traduciría en un aumento de dispersión de la población hacia áreas periféricas, contribuyendo a empeorar la situación actual. Esta tesis contribuye a solucionar este problema de dos maneras: 1) La primera, analizando la complementariedad y posibles sinergias de diferentes medidas de transporte urbano orientadas a promover un reparto modal hacia modos más sostenibles. Este análisis se centrará en los tres aspectos anteriormente citados: emisiones, ruido y atractividad o competitividad. 2) Una vez las posibles sinergias y complementariedades se han analizado, el segundo objetivo es proponer la mejor combinación de estas medidas – en términos de grado de aplicación - para lograr el máximo beneficio en lo que respecta a los tres objetivos previamente establecidos. Para ello, en esta tesis se han seleccionado una serie de medidas que permitan establecer una metodología para alcanzar estos objetivos previamente definidos. El análisis se centra en la ciudad de Madrid y su área metropolitana, la cual se ha escogido como caso de estudio para realizar esta investigación.