Local Heat Application for the Treatment of Buruli Ulcer: Results of a Phase II Open Label Single Center Non Comparative Clinical Trial.

BACKGROUND Buruli ulcer (BU) is a necrotizing skin disease most prevalent among West African children. The causative organism, Mycobacterium ulcerans, is sensitive to temperatures above 37°C. We investigated the safety and efficacy of a local heat application device based on phase change material. METHODS In a phase II open label single center noncomparative clinical trial (ISRCTN 72102977) under GCP standards in Cameroon, laboratory confirmed BU patients received up to 8 weeks of heat treatment. We assessed efficacy based on the endpoints 'absence of clinical BU specific features' or 'wound closure' within 6 months ("primary cure"), and 'absence of clinical recurrence within 24 month' ("definite cure"). RESULTS Of 53 patients 51 (96%) had ulcerative disease. 62% were classified as World Health Organization category II, 19% each as category I and III. The average lesion size was 45 cm(2). Within 6 months after completion of heat treatment 92.4% (49 of 53, 95% confidence interval [CI], 81.8% to 98.0%) achieved cure of their primary lesion. At 24 months follow-up 83.7% (41 of 49, 95% CI, 70.3% to 92.7%) of patients with primary cure remained free of recurrence. Heat treatment was well tolerated; adverse effects were occasional mild local skin reactions. CONCLUSIONS Local thermotherapy is a highly effective, simple, cheap and safe treatment for M. ulcerans disease. It has in particular potential as home-based remedy for BU suspicious lesions at community level where laboratory confirmation is not available. CLINICAL TRIALS REGISTRATION ISRCT 72102977.

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06)

BACKGROUND Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, number NCT00544700.

Induction chemoradiation in stage IIIA/N2 non-small-cell lung cancer: a phase 3 randomised trial

BACKGROUND One of the standard options in the treatment of stage IIIA/N2 non-small-cell lung cancer is neoadjuvant chemotherapy and surgery. We did a randomised trial to investigate whether the addition of neoadjuvant radiotherapy improves outcomes. METHODS We enrolled patients in 23 centres in Switzerland, Germany and Serbia. Eligible patients had pathologically proven, stage IIIA/N2 non-small-cell lung cancer and were randomly assigned to treatment groups in a 1:1 ratio. Those in the chemoradiotherapy group received three cycles of neoadjuvant chemotherapy (100 mg/m(2) cisplatin and 85 mg/m(2) docetaxel) followed by radiotherapy with 44 Gy in 22 fractions over 3 weeks, and those in the control group received neoadjuvant chemotherapy alone. All patients were scheduled to undergo surgery. Randomisation was stratified by centre, mediastinal bulk (less than 5 cm vs 5 cm or more), and weight loss (5% or more vs less than 5% in the previous 6 months). The primary endpoint was event-free survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00030771. FINDINGS From 2001 to 2012, 232 patients were enrolled, of whom 117 were allocated to the chemoradiotherapy group and 115 to the chemotherapy group. Median event-free survival was similar in the two groups at 12·8 months (95% CI 9·7-22·9) in the chemoradiotherapy group and 11·6 months (8·4-15·2) in the chemotherapy group (p=0·67). Median overall survival was 37·1 months (95% CI 22·6-50·0) with radiotherapy, compared with 26·2 months (19·9-52·1) in the control group. Chemotherapy-related toxic effects were reported in most patients, but 91% of patients completed three cycles of chemotherapy. Radiotherapy-induced grade 3 dysphagia was seen in seven (7%) patients. Three patients died in the control group within 30 days after surgery. INTERPRETATION Radiotherapy did not add any benefit to induction chemotherapy followed by surgery. We suggest that one definitive local treatment modality combined with neoadjuvant chemotherapy is adequate to treat resectable stage IIIA/N2 non-small-cell lung cancer. FUNDING Swiss State Secretariat for Education, Research and Innovation (SERI), Swiss Cancer League, and Sanofi.

Lee O. Case's "Elements of the Phase Rule", Chapter 1, One component systems

One component systems are treated from the point of view of the Gibbs' phase rule.

Endemic tuberculosis, the homeless, and public transportation: A merging of geographical information systems surveillance and the Houston Tuberculosis Initiative Surveillance project

To reach the goals established by the Institute of Medicine (IOM) and the Centers for Disease Control's (CDC) STOP TB USA, measures must be taken to curtail a future peak in Tuberculosis (TB) incidence and speed the currently stagnant rate of TB elimination. Both efforts will require, at minimum, the consideration and understanding of the third dimension of TB transmission: the location-based spread of an airborne pathogen among persons known and unknown to each other. This consideration will require an elucidation of the areas within the U.S. that have endemic TB. The Houston Tuberculosis Initiative (HTI) was a population-based active surveillance of confirmed Houston/Harris County TB cases from 1995–2004. Strengths in this dataset include the molecular characterization of laboratory confirmed cases, the collection of geographic locations (including home addresses) frequented by cases, and the HTI time period that parallels a decline in TB incidence in the United States (U.S.). The HTI dataset was used in this secondary data analysis to implement a GIS analysis of TB cases, the locations frequented by cases, and their association with risk factors associated with TB transmission. ^ This study reports, for the first time, the incidence of TB among the homeless in Houston, Texas. The homeless are an at-risk population for TB disease, yet they are also a population whose TB incidence has been unknown and unreported due to their non-enumeration. The first section of this dissertation identifies local areas in Houston with endemic TB disease. Many Houston TB cases who reported living in these endemic areas also share the TB risk factor of current or recent homelessness. Merging the 2004–2005 Houston enumeration of the homeless with historical HTI surveillance data of TB cases in Houston enabled this first-time report of TB risk among the homeless in Houston. The homeless were more likely to be US-born, belong to a genotypic cluster, and belong to a cluster of a larger size. The calculated average incidence among homeless persons was 411/100,000, compared to 9.5/100,000 among housed. These alarming rates are not driven by a co-infection but by social determinants. The unsheltered persons were hospitalized more days and required more follow-up time by staff than those who reported a steady housing situation. The homeless are a specific example of the increased targeting of prevention dollars that could occur if TB rates were reported for specific areas with known health disparities rather than as a generalized rate normalized over a diverse population. ^ It has been estimated that 27% of Houstonians use public transportation. The city layout allows bus routes to run like veins connecting even the most diverse of populations within the metropolitan area. Secondary data analysis of frequent bus use (defined as riding a route weekly) among TB cases was assessed for its relationship with known TB risk factors. The spatial distribution of genotypic clusters associated with bus use was assessed, along with the reported routes and epidemiologic-links among cases belonging to the identified clusters. ^ TB cases who reported frequent bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis, yet 75% of bus riders were genotypically clustered, indicating recent transmission, compared to 56% of non-bus riders (OR=2.4, 95%CI(2.0, 2.8), p<0.001). Bus riders had a mean cluster size of 50.14 vs. 28.9 (p<0.001). Second order spatial analysis of clustered fingerprint 2 (n=122), a Beijing family cluster, revealed geographic clustering among cases based on their report of bus use. Univariate and multivariate analysis of routes reported by cases belonging to these clusters found that 10 of the 14 clusters were associated with use. Individual Metro routes, including one route servicing the local hospitals, were found to be risk factors for belonging to a cluster shown to be endemic in Houston. The routes themselves geographically connect the census tracts previously identified as having endemic TB. 78% (15/23) of Houston Metro routes investigated had one or more print groups reporting frequent use for every HTI study year. We present data on three specific but clonally related print groups and show that bus-use is clustered in time by route and is the only known link between cases in one of the three prints: print 22. (Abstract shortened by UMI.)^

Non-isoprenoidal intact polar lipids, isoprenoidal and non-isoprenoidal core lipids, isoprenoidal intact polar lipids of the Black Sea site GeoB15105 sampled during Meteor cruise M84/1 in February 2011

This PhD thesis focused on the analysis and application of microbial membrane lipids as biomarkers in marine sediments. Existing protocols for lipid extraction from marine sediments and biomass were modified. In addition, recent protocols based on high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS) as well as state-of-the-art mass spectrometric analysis by quadrupole time-of-flight (MSqTOF) and the triple quadrupole (MSQQQ) mass spectrometer were used to investigate matrix effects and evaluate the reliability of quantitative analysis in marine environmental samples. The improved lipid extraction and quantification were used to analyze Black Sea water column and sediments samples to a depth of 8 meters from site GeoB 15105 taken during cruise M84/1 (DARCSEAS) with R/V Meteor to apply lipid analysis in benthic bio systems. With this component specific differentiation between planktonic and benthic lipid signature we assessed possible lipid sources. Here, this high detail lipid fingerprinting allowed us to observe changes in the head group and lipid core structures of the intact polar lipids according to the geochemical zonation.

(Table 1) Isotopic and geochemical parameters of gas phase from underground fluids of the Baikal rift and its framing

Results of studying isotopic composition of helium in underground fluids of the Baikal-Mongolian region during the last quarter of XX century are summarized. Determinations of 3He/4He ratio in 139 samples of gas phase from fluids, collected at 104 points of the Baikal rift zone and adjacent structures are given. 3He/4He values lie within the range from 1x10**-8 (typical for crustal radiogenic helium) to 1.1x10**-5 (close to typical MORB reservoir). Repeated sampling in some points during more than 20 years showed stability of helium isotopic composition in time in each of them at any level of 3He/4He values. There is no systematic differences of 3He/4He in samples from surface water sources and deeper intervals of boreholes in the same areas. Universal relationship between isotopic composition of helium and general composition of gas phase is absent either, but the minimum 3He/4He values occurred in methane gas of hydrocarbon deposits, whereas in nitrogen and carbon dioxide gases of helium composition varied (in the latter maximum 3He/4He values have been measured). According to N2/Ar_atm ratio nitrogen gases are atmospheric. In carbonic gas fN2/fNe ratio indicates presence of excessive (non-atmogenic) nitrogen, but the attitude CO2/3He differs from one in MORB. Comparison of helium isotopic composition with its concentration and composition of the main components of gas phase from fluids shows that it is formed under influence of fractionation of components with different solubility in the gas-water system and generation/consumption of reactive gases in the crust. Structural and tectonic elements of the region differ from the spectrum of 3He/4He values. At the pre-Riphean Siberian Platform the mean 3He/4He = (3.6+/-0.9)x10**- 8 is very close to radiogenic one. In the Paleozoic crust of Khangay 3He/4He = (16.3+/-4.6)x10**-8, and the most probable estimate is (12.3+/-2.9)x10**-8. In structures of the eastern flank of the Baikal rift zone (Khentei, Dauria) affected by the Mz-Kz activization 3He/4He values range from 4.4x10**-8 to 2.14x10**-6 (average 0.94x10**-6). Distribution of 3He/4He values across the strike of the Baikal rift zone indicates advective heat transfer from the mantle not only in the rift zone, but also much further to the east. In fluids of the Baikal rift zone range of 3He/4He values is the widest: from 4x10**-8 to 1.1x10**-5. Their variations along the strike of the rift zone are clearly patterned, namely, decrease of 3He/4He values in both directions from the Tunka depression. Accompanied by decrease in density of conductive heat flow and in size of rift basins, this trend indicates decrease in intensity of advective heat transfer from the mantle to peripheral segments of the rift zone. Comparing this trend with data on other continental rift zones and mid-ocean ridges leads to the conclusion about fundamental differences in mechanisms of interaction between the crust and the mantle in these environments.

Imaging systems application of multichannel configurations

While multichannel configurations are well established for non-imaging applications, they have not been used yet for imaging applications. In this paper we present for the first time some of multichannel designs for imaging systems. The multichannel comprises discontinuous optical sections which are called channels. The phase-space representation of the bundle of rays going from the object to the image is discontinuous between channels. This phase-space ray-bundle flow is divided in as many paths as channels there are but it is a single wavefront both at the source and the target. Typically, these multichannel systems are at least formed by three optical surfaces: two of them have discontinuities (either in the shape or in the shape derivative) while the last is a smooth one. Optical surfaces discontinuities cause at the phase space the wave front split in separate paths. The number of discontinuities is the same in the two first surfaces: Each channel is defined by the smooth surfaces in between discontinuities, so the surfaces forming each separate channel are all smooth. Aplanatic multichannel designs are also shown and used to explain the design procedure.

Bio-inspired FPGA Architecture for Self-Calibration of an Image Compression Core based on Wavelet Transforms in Embedded Systems

A generic bio-inspired adaptive architecture for image compression suitable to be implemented in embedded systems is presented. The architecture allows the system to be tuned during its calibration phase. An evolutionary algorithm is responsible of making the system evolve towards the required performance. A prototype has been implemented in a Xilinx Virtex-5 FPGA featuring an adaptive wavelet transform core directed at improving image compression for specific types of images. An Evolution Strategy has been chosen as the search algorithm and its typical genetic operators adapted to allow for a hardware friendly implementation. HW/SW partitioning issues are also considered after a high level description of the algorithm is profiled which validates the proposed resource allocation in the device fabric. To check the robustness of the system and its adaptation capabilities, different types of images have been selected as validation patterns. A direct application of such a system is its deployment in an unknown environment during design time, letting the calibration phase adjust the system parameters so that it performs efcient image compression. Also, this prototype implementation may serve as an accelerator for the automatic design of evolved transform coefficients which are later on synthesized and implemented in a non-adaptive system in the final implementation device, whether it is a HW or SW based computing device. The architecture has been built in a modular way so that it can be easily extended to adapt other types of image processing cores. Details on this pluggable component point of view are also given in the paper.

Conceptual framework for the design, implementation and validation of psychomotor skills’ assessment systems in minimally invasive surgery

Las técnicas de cirugía de mínima invasión (CMI) se están consolidando hoy en día como alternativa a la cirugía tradicional, debido a sus numerosos beneficios para los pacientes. Este cambio de paradigma implica que los cirujanos deben aprender una serie de habilidades distintas de aquellas requeridas en cirugía abierta. El entrenamiento y evaluación de estas habilidades se ha convertido en una de las mayores preocupaciones en los programas de formación de cirujanos, debido en gran parte a la presión de una sociedad que exige cirujanos bien preparados y una reducción en el número de errores médicos. Por tanto, se está prestando especial atención a la definición de nuevos programas que permitan el entrenamiento y la evaluación de las habilidades psicomotoras en entornos seguros antes de que los nuevos cirujanos puedan operar sobre pacientes reales. Para tal fin, hospitales y centros de formación están gradualmente incorporando instalaciones de entrenamiento donde los residentes puedan practicar y aprender sin riesgos. Es cada vez más común que estos laboratorios dispongan de simuladores virtuales o simuladores físicos capaces de registrar los movimientos del instrumental de cada residente. Estos simuladores ofrecen una gran variedad de tareas de entrenamiento y evaluación, así como la posibilidad de obtener información objetiva de los ejercicios. Los diferentes estudios de validación llevados a cabo dan muestra de su utilidad; pese a todo, los niveles de evidencia presentados son en muchas ocasiones insuficientes. Lo que es más importante, no existe un consenso claro a la hora de definir qué métricas son más útiles para caracterizar la pericia quirúrgica. El objetivo de esta tesis doctoral es diseñar y validar un marco de trabajo conceptual para la definición y validación de entornos para la evaluación de habilidades en CMI, en base a un modelo en tres fases: pedagógica (tareas y métricas a emplear), tecnológica (tecnologías de adquisición de métricas) y analítica (interpretación de la competencia en base a las métricas). Para tal fin, se describe la implementación práctica de un entorno basado en (1) un sistema de seguimiento de instrumental fundamentado en el análisis del vídeo laparoscópico; y (2) la determinación de la pericia en base a métricas de movimiento del instrumental. Para la fase pedagógica se diseñó e implementó un conjunto de tareas para la evaluación de habilidades psicomotoras básicas, así como una serie de métricas de movimiento. La validación de construcción llevada a cabo sobre ellas mostró buenos resultados para tiempo, camino recorrido, profundidad, velocidad media, aceleración media, economía de área y economía de volumen. Adicionalmente, los resultados obtenidos en la validación de apariencia fueron en general positivos en todos los grupos considerados (noveles, residentes, expertos). Para la fase tecnológica, se introdujo el EVA Tracking System, una solución para el seguimiento del instrumental quirúrgico basado en el análisis del vídeo endoscópico. La precisión del sistema se evaluó a 16,33ppRMS para el seguimiento 2D de la herramienta en la imagen; y a 13mmRMS para el seguimiento espacial de la misma. La validación de construcción con una de las tareas de evaluación mostró buenos resultados para tiempo, camino recorrido, profundidad, velocidad media, aceleración media, economía de área y economía de volumen. La validación concurrente con el TrEndo® Tracking System por su parte presentó valores altos de correlación para 8 de las 9 métricas analizadas. Finalmente, para la fase analítica se comparó el comportamiento de tres clasificadores supervisados a la hora de determinar automáticamente la pericia quirúrgica en base a la información de movimiento del instrumental, basados en aproximaciones lineales (análisis lineal discriminante, LDA), no lineales (máquinas de soporte vectorial, SVM) y difusas (sistemas adaptativos de inferencia neurodifusa, ANFIS). Los resultados muestran que en media SVM presenta un comportamiento ligeramente superior: 78,2% frente a los 71% y 71,7% obtenidos por ANFIS y LDA respectivamente. Sin embargo las diferencias estadísticas medidas entre los tres no fueron demostradas significativas. En general, esta tesis doctoral corrobora las hipótesis de investigación postuladas relativas a la definición de sistemas de evaluación de habilidades para cirugía de mínima invasión, a la utilidad del análisis de vídeo como fuente de información y a la importancia de la información de movimiento de instrumental a la hora de caracterizar la pericia quirúrgica. Basándose en estos cimientos, se han de abrir nuevos campos de investigación que contribuyan a la definición de programas de formación estructurados y objetivos, que puedan garantizar la acreditación de cirujanos sobradamente preparados y promocionen la seguridad del paciente en el quirófano. Abstract Minimally invasive surgery (MIS) techniques have become a standard in many surgical sub-specialties, due to their many benefits for patients. However, this shift in paradigm implies that surgeons must acquire a complete different set of skills than those normally attributed to open surgery. Training and assessment of these skills has become a major concern in surgical learning programmes, especially considering the social demand for better-prepared professionals and for the decrease of medical errors. Therefore, much effort is being put in the definition of structured MIS learning programmes, where practice with real patients in the operating room (OR) can be delayed until the resident can attest for a minimum level of psychomotor competence. To this end, skills’ laboratory settings are being introduced in hospitals and training centres where residents may practice and be assessed on their psychomotor skills. Technological advances in the field of tracking technologies and virtual reality (VR) have enabled the creation of new learning systems such as VR simulators or enhanced box trainers. These systems offer a wide range of tasks, as well as the capability of registering objective data on the trainees’ performance. Validation studies give proof of their usefulness; however, levels of evidence reported are in many cases low. More importantly, there is still no clear consensus on topics such as the optimal metrics that must be used to assess competence, the validity of VR simulation, the portability of tracking technologies into real surgeries (for advanced assessment) or the degree to which the skills measured and obtained in laboratory environments transfer to the OR. The purpose of this PhD is to design and validate a conceptual framework for the definition and validation of MIS assessment environments based on a three-pillared model defining three main stages: pedagogical (tasks and metrics to employ), technological (metric acquisition technologies) and analytical (interpretation of competence based on metrics). To this end, a practical implementation of the framework is presented, focused on (1) a video-based tracking system and (2) the determination of surgical competence based on the laparoscopic instruments’ motionrelated data. The pedagogical stage’s results led to the design and implementation of a set of basic tasks for MIS psychomotor skills’ assessment, as well as the definition of motion analysis parameters (MAPs) to measure performance on said tasks. Validation yielded good construct results for parameters such as time, path length, depth, average speed, average acceleration, economy of area and economy of volume. Additionally, face validation results showed positive acceptance on behalf of the experts, residents and novices. For the technological stage the EVA Tracking System is introduced. EVA provides a solution for tracking laparoscopic instruments from the analysis of the monoscopic video image. Accuracy tests for the system are presented, which yielded an average RMSE of 16.33pp for 2D tracking of the instrument on the image and of 13mm for 3D spatial tracking. A validation experiment was conducted using one of the tasks and the most relevant MAPs. Construct validation showed significant differences for time, path length, depth, average speed, average acceleration, economy of area and economy of volume; especially between novices and residents/experts. More importantly, concurrent validation with the TrEndo® Tracking System presented high correlation values (>0.7) for 8 of the 9 MAPs proposed. Finally, the analytical stage allowed comparing the performance of three different supervised classification strategies in the determination of surgical competence based on motion-related information. The three classifiers were based on linear (linear discriminant analysis, LDA), non-linear (support vector machines, SVM) and fuzzy (adaptive neuro fuzzy inference systems, ANFIS) approaches. Results for SVM show slightly better performance than the other two classifiers: on average, accuracy for LDA, SVM and ANFIS was of 71.7%, 78.2% and 71% respectively. However, when confronted, no statistical significance was found between any of the three. Overall, this PhD corroborates the investigated research hypotheses regarding the definition of MIS assessment systems, the use of endoscopic video analysis as the main source of information and the relevance of motion analysis in the determination of surgical competence. New research fields in the training and assessment of MIS surgeons can be proposed based on these foundations, in order to contribute to the definition of structured and objective learning programmes that guarantee the accreditation of well-prepared professionals and the promotion of patient safety in the OR.

Advances in the Simultaneous Multiple Surface optical design method for imaging and non-imaging applications

Classical imaging optics has been developed over centuries in many areas, such as its paraxial imaging theory and practical design methods like multi-parametric optimization techniques. Although these imaging optical design methods can provide elegant solutions to many traditional optical problems, there are more and more new design problems, like solar concentrator, illumination system, ultra-compact camera, etc., that require maximum energy transfer efficiency, or ultra-compact optical structure. These problems do not have simple solutions from classical imaging design methods, because not only paraxial rays, but also non-paraxial rays should be well considered in the design process. Non-imaging optics is a newly developed optical discipline, which does not aim to form images, but to maximize energy transfer efficiency. One important concept developed from non-imaging optics is the “edge-ray principle”, which states that the energy flow contained in a bundle of rays will be transferred to the target, if all its edge rays are transferred to the target. Based on that concept, many CPC solar concentrators have been developed with efficiency close to the thermodynamic limit. When more than one bundle of edge-rays needs to be considered in the design, one way to obtain solutions is to use SMS method. SMS stands for Simultaneous Multiple Surface, which means several optical surfaces are constructed simultaneously. The SMS method was developed as a design method in Non-imaging optics during the 90s. The method can be considered as an extension to the Cartesian Oval calculation. In the traditional Cartesian Oval calculation, one optical surface is built to transform an input wave-front to an out-put wave-front. The SMS method however, is dedicated to solve more than 1 wave-fronts transformation problem. In the beginning, only 2 input wave-fronts and 2 output wave-fronts transformation problem was considered in the SMS design process for rotational optical systems or free-form optical systems. Usually “SMS 2D” method stands for the SMS procedure developed for rotational optical system, and “SMS 3D” method for the procedure for free-form optical system. Although the SMS method was originally employed in non-imaging optical system designs, it has been found during this thesis that with the improved capability to design more surfaces and control more input and output wave-fronts, the SMS method can also be applied to imaging system designs and possesses great advantage over traditional design methods. In this thesis, one of the main goals to achieve is to further develop the existing SMS-2D method to design with more surfaces and improve the stability of the SMS-2D and SMS-3D algorithms, so that further optimization process can be combined with SMS algorithms. The benefits of SMS plus optimization strategy over traditional optimization strategy will be explained in details for both rotational and free-form imaging optical system designs. Another main goal is to develop novel design concepts and methods suitable for challenging non-imaging applications, e.g. solar concentrator and solar tracker. This thesis comprises 9 chapters and can be grouped into two parts: the first part (chapter 2-5) contains research works in the imaging field, and the second part (chapter 6-8) contains works in the non-imaging field. In the first chapter, an introduction to basic imaging and non-imaging design concepts and theories is given. Chapter 2 presents a basic SMS-2D imaging design procedure using meridian rays. In this chapter, we will set the imaging design problem from the SMS point of view, and try to solve the problem numerically. The stability of this SMS-2D design procedure will also be discussed. The design concepts and procedures developed in this chapter lay the path for further improvement. Chapter 3 presents two improved SMS 3 surfaces’ design procedures using meridian rays (SMS-3M) and skew rays (SMS-1M2S) respectively. The major improvement has been made to the central segments selections, so that the whole SMS procedures become more stable compared to procedures described in Chapter 2. Since these two algorithms represent two types of phase space sampling, their image forming capabilities are compared in a simple objective design. Chapter 4 deals with an ultra-compact SWIR camera design with the SMS-3M method. The difficulties in this wide band camera design is how to maintain high image quality meanwhile reduce the overall system length. This interesting camera design provides a playground for the classical design method and SMS design methods. We will show designs and optical performance from both classical design method and the SMS design method. Tolerance study is also given as the end of the chapter. Chapter 5 develops a two-stage SMS-3D based optimization strategy for a 2 freeform mirrors imaging system. In the first optimization phase, the SMS-3D method is integrated into the optimization process to construct the two mirrors in an accurate way, drastically reducing the unknown parameters to only few system configuration parameters. In the second optimization phase, previous optimized mirrors are parameterized into Qbfs type polynomials and set up in code V. Code V optimization results demonstrates the effectiveness of this design strategy in this 2-mirror system design. Chapter 6 shows an etendue-squeezing condenser optics, which were prepared for the 2010 IODC illumination contest. This interesting design employs many non-imaging techniques such as the SMS method, etendue-squeezing tessellation, and groove surface design. This device has theoretical efficiency limit as high as 91.9%. Chapter 7 presents a freeform mirror-type solar concentrator with uniform irradiance on the solar cell. Traditional parabolic mirror concentrator has many drawbacks like hot-pot irradiance on the center of the cell, insufficient use of active cell area due to its rotational irradiance pattern and small acceptance angle. In order to conquer these limitations, a novel irradiance homogenization concept is developed, which lead to a free-form mirror design. Simulation results show that the free-form mirror reflector has rectangular irradiance pattern, uniform irradiance distribution and large acceptance angle, which confirm the viability of the design concept. Chapter 8 presents a novel beam-steering array optics design strategy. The goal of the design is to track large angle parallel rays by only moving optical arrays laterally, and convert it to small angle parallel output rays. The design concept is developed as an extended SMS method. Potential applications of this beam-steering device are: skylights to provide steerable natural illumination, building integrated CPV systems, and steerable LED illumination. Conclusion and future lines of work are given in Chapter 9. Resumen La óptica de formación de imagen clásica se ha ido desarrollando durante siglos, dando lugar tanto a la teoría de óptica paraxial y los métodos de diseño prácticos como a técnicas de optimización multiparamétricas. Aunque estos métodos de diseño óptico para formación de imagen puede aportar soluciones elegantes a muchos problemas convencionales, siguen apareciendo nuevos problemas de diseño óptico, concentradores solares, sistemas de iluminación, cámaras ultracompactas, etc. que requieren máxima transferencia de energía o dimensiones ultracompactas. Este tipo de problemas no se pueden resolver fácilmente con métodos clásicos de diseño porque durante el proceso de diseño no solamente se deben considerar los rayos paraxiales sino también los rayos no paraxiales. La óptica anidólica o no formadora de imagen es una disciplina que ha evolucionado en gran medida recientemente. Su objetivo no es formar imagen, es maximazar la eficiencia de transferencia de energía. Un concepto importante de la óptica anidólica son los “rayos marginales”, que se pueden utilizar para el diseño de sistemas ya que si todos los rayos marginales llegan a nuestra área del receptor, todos los rayos interiores también llegarán al receptor. Haciendo uso de este principio, se han diseñado muchos concentradores solares que funcionan cerca del límite teórico que marca la termodinámica. Cuando consideramos más de un haz de rayos marginales en nuestro diseño, una posible solución es usar el método SMS (Simultaneous Multiple Surface), el cuál diseña simultáneamente varias superficies ópticas. El SMS nació como un método de diseño para óptica anidólica durante los años 90. El método puede ser considerado como una extensión del cálculo del óvalo cartesiano. En el método del óvalo cartesiano convencional, se calcula una superficie para transformar un frente de onda entrante a otro frente de onda saliente. El método SMS permite transformar varios frentes de onda de entrada en frentes de onda de salida. Inicialmente, sólo era posible transformar dos frentes de onda con dos superficies con simetría de rotación y sin simetría de rotación, pero esta limitación ha sido superada recientemente. Nos referimos a “SMS 2D” como el método orientado a construir superficies con simetría de rotación y llamamos “SMS 3D” al método para construir superficies sin simetría de rotación o free-form. Aunque el método originalmente fue aplicado en el diseño de sistemas anidólicos, se ha observado que gracias a su capacidad para diseñar más superficies y controlar más frentes de onda de entrada y de salida, el SMS también es posible aplicarlo a sistemas de formación de imagen proporcionando una gran ventaja sobre los métodos de diseño tradicionales. Uno de los principales objetivos de la presente tesis es extender el método SMS-2D para permitir el diseño de sistemas con mayor número de superficies y mejorar la estabilidad de los algoritmos del SMS-2D y SMS-3D, haciendo posible combinar la optimización con los algoritmos. Los beneficios de combinar SMS y optimización comparado con el proceso de optimización tradicional se explican en detalle para sistemas con simetría de rotación y sin simetría de rotación. Otro objetivo importante de la tesis es el desarrollo de nuevos conceptos de diseño y nuevos métodos en el área de la concentración solar fotovoltaica. La tesis está estructurada en 9 capítulos que están agrupados en dos partes: la primera de ellas (capítulos 2-5) se centra en la óptica formadora de imagen mientras que en la segunda parte (capítulos 6-8) se presenta el trabajo del área de la óptica anidólica. El primer capítulo consta de una breve introducción de los conceptos básicos de la óptica anidólica y la óptica en formación de imagen. El capítulo 2 describe un proceso de diseño SMS-2D sencillo basado en los rayos meridianos. En este capítulo se presenta el problema de diseñar un sistema formador de imagen desde el punto de vista del SMS y se intenta obtener una solución de manera numérica. La estabilidad de este proceso se analiza con detalle. Los conceptos de diseño y los algoritmos desarrollados en este capítulo sientan la base sobre la cual se realizarán mejoras. El capítulo 3 presenta dos procedimientos para el diseño de un sistema con 3 superficies SMS, el primero basado en rayos meridianos (SMS-3M) y el segundo basado en rayos oblicuos (SMS-1M2S). La mejora más destacable recae en la selección de los segmentos centrales, que hacen más estable todo el proceso de diseño comparado con el presentado en el capítulo 2. Estos dos algoritmos representan dos tipos de muestreo del espacio de fases, su capacidad para formar imagen se compara diseñando un objetivo simple con cada uno de ellos. En el capítulo 4 se presenta un diseño ultra-compacto de una cámara SWIR diseñada usando el método SMS-3M. La dificultad del diseño de esta cámara de espectro ancho radica en mantener una alta calidad de imagen y al mismo tiempo reducir drásticamente sus dimensiones. Esta cámara es muy interesante para comparar el método de diseño clásico y el método de SMS. En este capítulo se presentan ambos diseños y se analizan sus características ópticas. En el capítulo 5 se describe la estrategia de optimización basada en el método SMS-3D. El método SMS-3D calcula las superficies ópticas de manera precisa, dejando sólo unos pocos parámetros libres para decidir la configuración del sistema. Modificando el valor de estos parámetros se genera cada vez mediante SMS-3D un sistema completo diferente. La optimización se lleva a cabo variando los mencionados parámetros y analizando el sistema generado. Los resultados muestran que esta estrategia de diseño es muy eficaz y eficiente para un sistema formado por dos espejos. En el capítulo 6 se describe un sistema de compresión de la Etendue, que fue presentado en el concurso de iluminación del IODC en 2010. Este interesante diseño hace uso de técnicas propias de la óptica anidólica, como el método SMS, el teselado de las lentes y el diseño mediante grooves. Este dispositivo tiene un límite teórica en la eficiencia del 91.9%. El capítulo 7 presenta un concentrador solar basado en un espejo free-form con irradiancia uniforme sobre la célula. Los concentradores parabólicos tienen numerosas desventajas como los puntos calientes en la zona central de la célula, uso no eficiente del área de la célula al ser ésta cuadrada y además tienen ángulos de aceptancia de reducido. Para poder superar estas limitaciones se propone un novedoso concepto de homogeneización de la irrandancia que se materializa en un diseño con espejo free-form. El análisis mediante simulación demuestra que la irradiancia es homogénea en una región rectangular y con mayor ángulo de aceptancia, lo que confirma la viabilidad del concepto de diseño. En el capítulo 8 se presenta un novedoso concepto para el diseño de sistemas afocales dinámicos. El objetivo del diseño es realizar un sistema cuyo haz de rayos de entrada pueda llegar con ángulos entre ±45º mientras que el haz de rayos a la salida sea siempre perpendicular al sistema, variando únicamente la posición de los elementos ópticos lateralmente. Las aplicaciones potenciales de este dispositivo son varias: tragaluces que proporcionan iluminación natural, sistemas de concentración fotovoltaica integrados en los edificios o iluminación direccionable con LEDs. Finalmente, el último capítulo contiene las conclusiones y las líneas de investigación futura.

Optical systems design using the SMS method and optimizations

Resumen El diseño de sistemas ópticos, entendido como un arte por algunos, como una ciencia por otros, se ha realizado durante siglos. Desde los egipcios hasta nuestros días los sistemas de formación de imagen han ido evolucionando así como las técnicas de diseño asociadas. Sin embargo ha sido en los últimos 50 años cuando las técnicas de diseño han experimentado su mayor desarrollo y evolución, debido, en parte, a la aparición de nuevas técnicas de fabricación y al desarrollo de ordenadores cada vez más potentes que han permitido el cálculo y análisis del trazado de rayos a través de los sistemas ópticos de forma rápida y eficiente. Esto ha propiciado que el diseño de sistemas ópticos evolucione desde los diseños desarrollados únicamente a partir de la óptica paraxial hasta lo modernos diseños realizados mediante la utilización de diferentes técnicas de optimización multiparamétrica. El principal problema con el que se encuentra el diseñador es que las diferentes técnicas de optimización necesitan partir de un diseño inicial el cual puede fijar las posibles soluciones. Dicho de otra forma, si el punto de inicio está lejos del mínimo global, o diseño óptimo para las condiciones establecidas, el diseño final puede ser un mínimo local cerca del punto de inicio y lejos del mínimo global. Este tipo de problemática ha llevado al desarrollo de sistemas globales de optimización que cada vez sean menos sensibles al punto de inicio de la optimización. Aunque si bien es cierto que es posible obtener buenos diseños a partir de este tipo de técnicas, se requiere de muchos intentos hasta llegar a la solución deseada, habiendo un entorno de incertidumbre durante todo el proceso, puesto que no está asegurado el que se llegue a la solución óptima. El método de las Superficies Múltiples Simultaneas (SMS), que nació como una herramienta de cálculo de concentradores anidólicos, se ha demostrado como una herramienta también capaz utilizarse para el diseño de sistemas ópticos formadores de imagen, aunque hasta la fecha se ha utilizado para el diseño puntual de sistemas de formación de imagen. Esta tesis tiene por objeto presentar el SMS como un método que puede ser utilizado de forma general para el diseño de cualquier sistema óptico de focal fija o v afocal con un aumento definido así como una herramienta que puede industrializarse para ayudar al diseñador a afrontar de forma sencilla el diseño de sistemas ópticos complejos. Esta tesis está estructurada en cinco capítulos: El capítulo 1, es un capítulo de fundamentos donde se presentan los conceptos fundamentales necesarios para que el lector, aunque no posea una gran base en óptica formadora de imagen, pueda entender los planteamientos y resultados que se presentan en el resto de capítulos El capitulo 2 aborda el problema de la optimización de sistemas ópticos, donde se presenta el método SMS como una herramienta idónea para obtener un punto de partida para el proceso de optimización. Mediante un ejemplo aplicado se demuestra la importancia del punto de partida utilizado en la solución final encontrada. Además en este capítulo se presentan diferentes técnicas que permiten la interpolación y optimización de las superficies obtenidas a partir de la aplicación del SMS. Aunque en esta tesis se trabajará únicamente utilizando el SMS2D, se presenta además un método para la interpolación y optimización de las nubes de puntos obtenidas a partir del SMS3D basado en funciones de base radial (RBF). En el capítulo 3 se presenta el diseño, fabricación y medidas de un objetivo catadióptrico panorámico diseñado para trabajar en la banda del infrarrojo lejano (8-12 μm) para aplicaciones de vigilancia perimetral. El objetivo presentado se diseña utilizando el método SMS para tres frentes de onda de entrada utilizando cuatro superficies. La potencia del método de diseño utilizado se hace evidente en la sencillez con la que este complejo sistema se diseña. Las imágenes presentadas demuestran cómo el prototipo desarrollado cumple a la perfección su propósito. El capítulo 4 aborda el problema del diseño de sistemas ópticos ultra compactos, se introduce el concepto de sistemas multicanal, como aquellos sistemas ópticos compuestos por una serie de canales que trabajan en paralelo. Este tipo de sistemas resultan particularmente idóneos para él diseño de sistemas afocales. Se presentan estrategias de diseño para sistemas multicanal tanto monocromáticos como policromáticos. Utilizando la novedosa técnica de diseño que en este capítulo se presenta el diseño de un telescopio de seis aumentos y medio. En el capítulo 5 se presenta una generalización del método SMS para rayos meridianos. En este capítulo se presenta el algoritmo que debe utilizarse para el diseño de cualquier sistema óptico de focal fija. La denominada optimización fase 1 se vi introduce en el algoritmo presentado de forma que mediante el cambio de las condiciones iníciales del diseño SMS que, aunque el diseño se realice para rayos meridianos, los rayos skew tengan un comportamiento similar. Para probar la potencia del algoritmo desarrollado se presenta un conjunto de diseños con diferente número de superficies. La estabilidad y potencia del algoritmo se hace evidente al conseguirse por primera vez el diseño de un sistema de seis superficies diseñado por SMS. vii Abstract The design of optical systems, considered an art by some and a science by others, has been developed for centuries. Imaging optical systems have been evolving since Ancient Egyptian times, as have design techniques. Nevertheless, the most important developments in design techniques have taken place over the past 50 years, in part due to the advances in manufacturing techniques and the development of increasingly powerful computers, which have enabled the fast and efficient calculation and analysis of ray tracing through optical systems. This has led to the design of optical systems evolving from designs developed solely from paraxial optics to modern designs created by using different multiparametric optimization techniques. The main problem the designer faces is that the different optimization techniques require an initial design which can set possible solutions as a starting point. In other words, if the starting point is far from the global minimum or optimal design for the set conditions, the final design may be a local minimum close to the starting point and far from the global minimum. This type of problem has led to the development of global optimization systems which are increasingly less sensitive to the starting point of the optimization process. Even though it is possible to obtain good designs from these types of techniques, many attempts are necessary to reach the desired solution. This is because of the uncertain environment due to the fact that there is no guarantee that the optimal solution will be obtained. The Simultaneous Multiple Surfaces (SMS) method, designed as a tool to calculate anidolic concentrators, has also proved useful for the design of image-forming optical systems, although until now it has occasionally been used for the design of imaging systems. This thesis aims to present the SMS method as a technique that can be used in general for the design of any optical system, whether with a fixed focal or an afocal with a defined magnification, and also as a tool that can be commercialized to help designers in the design of complex optical systems. The thesis is divided into five chapters. Chapter 1 establishes the basics by presenting the fundamental concepts which the reader needs to acquire, even if he/she doesn‟t have extensive knowledge in the field viii of image-forming optics, in order to understand the steps taken and the results obtained in the following chapters. Chapter 2 addresses the problem of optimizing optical systems. Here the SMS method is presented as an ideal tool to obtain a starting point for the optimization process. The importance of the starting point for the final solution is demonstrated through an example. Additionally, this chapter introduces various techniques for the interpolation and optimization of the surfaces obtained through the application of the SMS method. Even though in this thesis only the SMS2D method is used, we present a method for the interpolation and optimization of clouds of points obtained though the SMS3D method, based on radial basis functions (RBF). Chapter 3 presents the design, manufacturing and measurement processes of a catadioptric panoramic lens designed to work in the Long Wavelength Infrared (LWIR) (8-12 microns) for perimeter surveillance applications. The lens presented is designed by using the SMS method for three input wavefronts using four surfaces. The powerfulness of the design method used is revealed through the ease with which this complex system is designed. The images presented show how the prototype perfectly fulfills its purpose. Chapter 4 addresses the problem of designing ultra-compact optical systems. The concept of multi-channel systems, such as optical systems composed of a series of channels that work in parallel, is introduced. Such systems are especially suitable for the design of afocal systems. We present design strategies for multichannel systems, both monochromatic and polychromatic. A telescope designed with a magnification of six-and-a-half through the innovative technique exposed in this chapter is presented. Chapter 5 presents a generalization of the SMS method for meridian rays. The algorithm to be used for the design of any fixed focal optics is revealed. The optimization known as phase 1 optimization is inserted into the algorithm so that, by changing the initial conditions of the SMS design, the skew rays have a similar behavior, despite the design being carried out for meridian rays. To test the power of the developed algorithm, a set of designs with a different number of surfaces is presented. The stability and strength of the algorithm become apparent when the first design of a system with six surfaces if obtained through the SMS method.

A method for revealing phase space structures of general time dependent dynamical systems

In this paper we develop new techniques for revealing geometrical structures in phase space that are valid for aperiodically time dependent dynamical systems, which we refer to as Lagrangian descriptors. These quantities are based on the integration, for a finite time, along trajectories of an intrinsic bounded, positive geometrical and/or physical property of the trajectory itself. We discuss a general methodology for constructing Lagrangian descriptors, and we discuss a “heuristic argument” that explains why this method is successful for revealing geometrical structures in the phase space of a dynamical system. We support this argument by explicit calculations on a benchmark problem having a hyperbolic fixed point with stable and unstable manifolds that are known analytically. Several other benchmark examples are considered that allow us the assess the performance of Lagrangian descriptors in revealing invariant tori and regions of shear. Throughout the paper “side-by-side” comparisons of the performance of Lagrangian descriptors with both finite time Lyapunov exponents (FTLEs) and finite time averages of certain components of the vector field (“time averages”) are carried out and discussed. In all cases Lagrangian descriptors are shown to be both more accurate and computationally efficient than these methods. We also perform computations for an explicitly three dimensional, aperiodically time-dependent vector field and an aperiodically time dependent vector field defined as a data set. Comparisons with FTLEs and time averages for these examples are also carried out, with similar conclusions as for the benchmark examples.