Optimization of high precision stereotactic body radiotherapy with photons and ions for non-small-cell-lung cancer

This work presents a contribution in two different aspects required for the implementation of scanned-beam particle therapy for lung tumors. The first part of this work investigates the reproducibility of the calculated particle therapy dose distribution for early stage non-small cell lung cancer (NSCLC) tumors in a clinical scenario. These calculations were carried out based on data sets of patients treated with single dose photon stereotactic body radiotherapy (SBRT) under high frequency jet ventilation (HFJV) in order to achieve near-total tumor fixation. A dosimetric evaluation of calculated proton and carbon ion plans was performed, to fulfill clinical plan acceptance criteria with emphasis on target coverage. By simulating the inter-fractional anatomical changes in a short time scale between planning and delivery-time anatomies as imaged by the planning and localization computed tomography (CT) data sets, we carried out an investigation of the deterioration in target coverage. The anatomical changes (e.g. tumor position, patient setup) were quantified through water equivalent path length (WEPL) calculations within the beam entrance channels and correlated with the loss in dosimetric coverage. In addition, we identified beam and planning settings, which also help to reduce dosimetric deterioration, such as best choice of beam angle, higher number of beams, larger spot sizes and larger allowances for beam spots outside the target. We demonstrated reproducible tumor fixations through HFJV. Such technique warranted excellent target coverage in proton SBRT in the majority of the investigated patients. However, for a minor number of cases, unacceptable dosimetric deviations were observed, illustrating the need for imaging prior to each dose delivery with dedicated protocols, together with the development of intervention thresholds in case of anatomical discrepancies based on their potential impact on the dose distribution. HFJV seems a suitable technique to reduce interplay effects. Newer assisted ventilation techniques which do not require use of anesthesia might be more suitable for fractionated radiotherapy. Biological treatment planning for carbon ion therapy requires a model of the radiobiological effects of high linear energy transfer (LET) radiation. One approach in the context of scanned beam ion therapy is built upon the local effect model (LEM). Within this approach, the description of the radiosensitivity and the behavior versus fractionated photon radiotherapy of both tumor and normal tissue requires input of α/β ratios, usually obtained from in vitro studies. Obtaining tumor-specific, realistic, clinical α/β values is urgently required. This topic is also relevant in hypofractionated photon radiotherapy, where there is an ongoing discussion, if the linear-quadratic (LQ) model represents adequately dose responses at high doses per fraction or if the linear-quadratic-linear (LQ-L) correction is necessary, and which α/β ratio describes better the fractionation effect for NSCLC tumors. The second part of this work presents a review of local control data of early stage NSCLC and models of these dose response data using the LQ and LQ-L approaches. Both, the LQ and LQ-L models can be fitted to clinical normo- and hypofractionated NSCLC outcome data. The LQ-L model yielded a significant value for the Dt of 11.0 Gy for the model based on biologically effective dose (BED) at the isocenter with α/β equal to 10 Gy for the full hypofractionation range; it produced a comparable tumor control probability (TCP) fit to the LQ model. We found a clear dose-effect relationship, which in the high BED region was weaker due to considerable dispersion in the data. For the application of BED (α/β=10 Gy) in the range of 100–150 Gy in three fractions or more, the differences in isoeffects predicted by both models can be neglected. Our findings therefore do not allow us to suggest use of the LQ-L model for an improved fitting compared to the LQ model of local control data in case of hypofractionation. A tentative analysis to establish the optimal α/β ratio in the frame of the LQ model for the full fractionation range did not produce significant estimates, although it showed a trend for α/β values lower than 10 Gy

The Complexity of angel-daemons and game isomorphism

The analysis of the computational aspects of strategic situations is a basic field in Computer Sciences. Two main topics related to strategic games have been developed. First, introduction and analysis of a class of games (so called angel/daemon games) designed to asses web applications, have been considered. Second, the problem of isomorphism between strategic games has been analysed. Both parts have been separately considered. Angel-Daemon Games A service is a computational method that is made available for general use through a wide area network. The performance of web-services may fluctuate; at times of stress the performance of some services may be degraded (in extreme cases, to the point of failure). In this thesis uncertainty profiles and Angel-Daemon games are used to analyse servicebased behaviours in situations where probabilistic reasoning may not be appropriate. In such a game, an angel player acts on a bounded number of ¿angelic¿ services in a beneficial way while a daemon player acts on a bounded number of ¿daemonic¿ services in a negative way. Examples are used to illustrate how game theory can be used to analyse service-based scenarios in a realistic way that lies between over-optimism and over-pessimism. The resilience of an orchestration to service failure has been analysed - here angels and daemons are used to model services which can fail when placed under stress. The Nash equilibria of a corresponding Angel-Daemon game may be used to assign a ¿robustness¿ value to an orchestration. Finally, the complexity of equilibria problems for Angel-Daemon games has been analysed. It turns out that Angel-Daemon games are, at the best of our knowledge, the first natural example of zero-sum succinct games. The fact that deciding the existence of a pure Nash equilibrium or a dominant strategy for a given player is Sp 2-complete has been proven. Furthermore, computing the value of an Angel-Daemon game is EXP-complete. Thus, matching the already known complexity results of the corresponding problems for the generic families of succinctly represented games with exponential number of actions. Game Isomorphism The question of whether two multi-player strategic games are equivalent and the computational complexity of deciding such a property has been addressed. Three notions of isomorphisms, strong, weak and local have been considered. Each one of these isomorphisms preserves a different structure of the game. Strong isomorphism is defined to preserve the utility functions and Nash equilibria. Weak isomorphism preserves only the player preference relations and thus pure Nash equilibria. Local isomorphism preserves preferences defined only on ¿close¿ neighbourhood of strategy profiles. The problem of the computational complexity of game isomorphism, which depends on the level of succinctness of the description of the input games but it is independent of the isomorphism to consider, has been shown. Utilities in games can be given succinctly by Turing machines, boolean circuits or boolean formulas, or explicitly by tables. Actions can be given also explicitly or succinctly. When the games are given in general form, an explicit description of actions and a succinct description of utilities have been assumed. It is has been established that the game isomorphism problem for general form games is equivalent to the circuit isomorphism when utilities are described by Turing Machines; and to the boolean formula isomorphism problem when utilities are described by formulas. When the game is given in explicit form, it is has been proven that the game isomorphism problem is equivalent to the graph isomorphism problem. Finally, an equivalence classes of small games and their graphical representation have been also examined.Postprint (published version

Induction of type I interferon by RNA viruses: cellular receptors and their substrates

Virus recognition and induction of interferon (IFN) are critical components of the innate immune system. The Toll-like receptor (TLR) and RIG-I-like receptor families have been characterized as key players in RNA virus detection. Signaling cascades initiated by these receptors are crucial for establishment of an IFN signaling mediated antiviral state in infected and neighboring cells and containment of virus replication as well as initiation of the adaptive immune response. In this review, we focus on the diverse and overlapping functions of these receptors, their physiological importance, and respective viral inducers. We highlight the roles of TRL3, TLR7/8, retinoic acid inducible gene I, melanoma differentiation-associated gene 5, and the RNA molecules responsible for activating these viral sensors

Sol-Gel Immobilisation of Lipases: Towards Active and Stable Biocatalysts for the Esterification of Valeric Acid

Alkyl esters are high added value products useful in a wide range of industrial sectors. A methodology based on a simple sol-gel approach (biosilicification) is herein proposed to encapsulate enzymes in order to design highly active and stable biocatalysts. Their performance was assessed through the optimization of valeric acid esterification evaluating the effect of different parameters (biocatalyst load, presence of water, reaction temperature and stirring rate) in different alcoholic media, and comparing two different methodologies: conventional heating and microwave irradiation. Ethyl valerate yields were in the 80–85% range under optimum conditions (15 min, 12% m/v biocatalyst, molar ratio 1:2 of valeric acid to alcohol). Comparatively, the biocatalysts were slightly deactivated under microwave irradiation due to enzyme denaturalisation. Biocatalyst reuse was attempted to prove that good reusability of these sol-gel immobilised enzymes could be achieved under conventional heating

The Complexity of game isomorphism

We address the question of whether two multiplayer strategic games are equivalent and the computational complexity of deciding such a property. We introduce two notions of isomorphisms, strong and weak. Each one of those isomorphisms preserves a different structure of the game. Strong isomorphisms are defined to preserve the utility functions and Nash equilibria. Weak isomorphisms preserve only the player's preference relations and thus pure Nash equilibria. We show that the computational complexity of the game isomorphism problem depends on the level of succinctness of the description of the input games but it is independent on which of the two types of isomorphisms is considered. Utilities in games can be given succinctly by Turing machines, boolean circuits or boolean formulas, or explicitly by tables. Actions can be given also explicitly or succinctly. When the games are given in general form, we asume a explicit description of actions and a succinct description of utilities. We show that the game isomorphism problem for general form games is equivalent to the circuit isomorphism when utilities are described by TMs and to the boolean formula isomorphism problem when utilities are described by formulas. When the game is given in explicit form, we show that the game isomorphism problem is equivalent to the graph isomorphism problem.Postprint (published version

Procedimientos de control de costos y gastos para reducir los gastos del servicio de transporte de carga pesada de la empresa de Transportes Uceda SAC Trujillo 2017. Revisión de la literatura

RESUMEN Existen procedimientos de control de costos para una reducción de los costos y gastos que se dan en los diferentes servicios que las empresas tienen a ofrecer, en este caso en el servicio de transporte de carga pesada que realiza la EMPRESA DE TRANSPORTES UCEDA SAC. El objetivo de la presente investigación es realizar una revisión sistemática de las características de los proyectos de investigación de diferentes universidades nacionales o internacionales, públicas o privadas sobre cuáles son los costos y gastos que tienen las empresas y que métodos o procedimientos son guías para efectuar una reducción y un control sobre ellos, que en un futuro se convierta en ahorro de dinero, tiempo y mejora para su rentabilidad. Para este estudio se hizo una revisión de libros relacionados a los costos y gastos obteniendo así un mejor entendimiento de las definiciones que son utilizadas en el proyecto como las variables de la investigación y también la encontró información relacionada con las variables asociadas que si contribuyen a la investigación. PALABRAS CLAVES: Procedimientos de control, revisión sistemática, reducción de costos y gastos

Attitudes of nursing degree students towards end of life processes. A cultural approach (Spain-Senegal)

Introduction The concept of death is abstract, complex and has a number of meanings. Thus, its understanding and the approach taken to it depend, to a large extent, on aspects such as age, culture, training and religion. Nursing students have regular contact with the process of death and so it is of great interest to understand the attitudes they have towards it. As we live in a plural society it is even more interesting to not only understand the attitudes of Spanish students but, also, those of students coming from other countries. In the present article, we seek to identify and compare the attitudes held by nursing degree students at Hekima-Santé University (Senegal) and the University of Huelva (Spain) about end of life processes. The study identifies elements that condition attitudes and coping with death, whilst considering curricular differences with regards to specific end of life training. Method A descriptive, cross-sectional and multi-center study was conducted. The overall sample (N = 142) was divided into groups: Hekima-Santé University (Dakar, Senegal) and the University of Huelva (Huelva, Spain). The measurement instruments used were an ad-hoc questionnaire and Bugen´s Coping with Death Scale. Results Statistically significant differences (p = 0.005, 95%CI) were found in relation to overall Bugen Scale scores. We can confirm that specialized end of life training (University of Huelva, Spain) did not lead to better coping when compared with a population whose academic curriculum did not provide specific training and who engaged in more religious practices (Hekima-Santé University, Senegal). Conclusions In cultures where religion not only influences the spiritual dimension of the individual, but acts in the ethical and moral system and consequently in the economic, educational and family sphere, the accompaniment at the end of life transcends the formative plane. Considering the plural society in which we live, the training that integrates the Degree in Nursing with regard to the care of the final process, must be multidimensional in which spirituality and faith are integrated, working emotional and attentional skills, as well as cultural competence strategies in this process

Mechanochemical Preparation of Novel Polysaccharide-Supported Nb2O5 Catalysts

Polysaccharides extracted from natural sources can be used as starting material for the preparation of nanoparticle supported composites. A novel family of bio-nanocomposites was mechanochemically synthesized by using niobium oxide and enzymatically produced polysaccharides. The structural, textural and surface properties of nanomaterials, were determined by X-Ray diffraction (XRD), nitrogen adsorption-desorption (N_2 porosimetry), pulse chromatography, infrared spectroscopy (ATR-IR) and dynamic light scattering (DLS). Selective oxidation of isoeugenol to vanillin was carried out to demonstrate the catalytic activity of the Nb-polysaccharides nanocomposites. Interestingly, most of our material showed high conversion of isoeugenol (60–70%) with selectivity to vanillin over 40%. The optimum conversion and selectivity were achieved with a reaction time between 8 and 24 h

Effect of Bay Leaves Essential Oil Concentration on the Properties of Biodegradable Carboxymethyl Cellulose-Based Edible Films

Films containing bay leaves essential oils (BEOs) were prepared and evaluated for edible packaging applications. The BEOs were extracted by the Soxhlet method, using ethanol or methanol as organic solvent. Then, films were prepared by “solvent casting” technique using carboxymethyl cellulose (CMC), with different concentrations for the as-obtained BEOs (from 1% to 30% wt.). The resulting films were characterized to evaluate their physical (thickness, moisture content, water solubility and water vapor permeability), optical (transparency and UV-light barrier), mechanical (tensile strength and elongation at break), antioxidant and antimicrobiological properties Attractive films were obtained for food active packaging applications, as they presented a high antioxidant activity (up to 99%) and total phenolic content, and good barrier properties against water vapor (50% improved of CMC) in the case of CMC-film containing 15% wt. ethanolic extract. Related to optical properties, UV-light barrier effect was increased (almost 100% of protection) avoiding typical lipids oxidation in food systems. High water solubility (93%) was also found, ensuring also their biodegradability. Moreover, it was demonstrated that developed films inhibit microorganisms’ growth (Escherichia coli and Candida glabrata), this avoiding an early food oxidation