Patterns of practice of regional nodal irradiation in breast cancer: results of the European Organization for Research and Treatment of Cancer (EORTC) NOdal Radiotherapy (NORA) survey.

BACKGROUND: Predicting outcome of breast cancer (BC) patients based on sentinel lymph node (SLN) status without axillary lymph node dissection (ALND) is an area of uncertainty. It influences the decision-making for regional nodal irradiation (RNI). The aim of the NORA (NOdal RAdiotherapy) survey was to examine the patterns of RNI. METHODS: A web-questionnaire, including several clinical scenarios, was distributed to 88 EORTC-affiliated centers. Responses were received between July 2013 and January 2014. RESULTS: A total of 84 responses were analyzed. While three-dimensional (3D) radiotherapy (RT) planning is carried out in 81 (96%) centers, nodal areas are delineated in only 51 (61%) centers. Only 14 (17%) centers routinely link internal mammary chain (IMC) and supraclavicular node (SCN) RT indications. In patients undergoing total mastectomy (TM) with ALND, SCN-RT is recommend by 5 (6%), 53 (63%) and 51 (61%) centers for patients with pN0(i+), pN(mi) and pN1, respectively. Extra-capsular extension (ECE) is the main factor influencing decision-making RNI after breast conserving surgery (BCS) and TM. After primary systemic therapy (PST), 49 (58%) centers take into account nodal fibrotic changes in ypN0 patients for RNI indications. In ypN0 patients with inner/central tumors, 23 (27%) centers indicate SCN-RT and IMC-RT. In ypN1 patients, SCN-RT is delivered by less than half of the centers in patients with ypN(i+) and ypN(mi). Twenty-one (25%) of the centers recommend ALN-RT in patients with ypN(mi) or 1-2N+ after ALND. Seventy-five (90%) centers state that age is not considered a limiting factor for RNI. CONCLUSION: The NORA survey is unique in evaluating the impact of SLNB/ALND status on adjuvant RNI decision-making and volumes after BCS/TM with or without PST. ALN-RT is often indicated in pN1 patients, particularly in the case of ECE. Besides the ongoing NSABP-B51/RTOG and ALLIANCE trials, NORA could help to design future specific RNI trials in the SLNB era without ALND in patients receiving or not PST.

Operational Knowledge in Process Design

Työn tarkoituksena on selvittää, miten käyttötietämystä hyödynnetään prosessisuunnittelussa. Tavoitteena on löytää keinoja parantaa käyttötietämyksen hallintaa suunnitteluprosessin aikana ja selvittää, vaikuttaako tämä prosessisuunnittelun laatuun.Prosessisuunnittelun laatua arvioidaan seitsemällä kriteerillä, jotka ovat investointikustannukset, käyttökustannukset, turvallisuus, ympäristövaikutukset, käytettävyys, innovatiivisuus ja aikataulu. Suunnitteluprosessi jaetaan kolmeen vaiheeseen: esisuunnitteluun, perussuunnitteluun ja detaljisuunnitteluun. Prosessisuunnittelua, investointiprojektia, prosessisuunnittelun laatukriteerejä, suunnitteluprosessin eri vaiheita ja käyttötietämyksen luokittelua tarkastellaan yleisesti. Työssä selvitettiin käyttötietämyksen hyödyntämistä Kemiralla. Aluksi muotoiltiin yleisiä väittämiä käyttötietämyksen hyödyntämisestä Kemiran ulkopuolisten eri alojen asiantuntijoiden haastattelujen perusteella. Tämän jälkeen Kemiran prosessisuunnittelijat arvioivat väittämiä. Arvioiden perusteella tehtiin johtopäätöksiä yleisesti käyttötietämyksen hyödyntämisestä prosessisuunnittelussa. Seuraavaksi haastateltiin kahdessa erityyppisessä case-projektissa mukana olleita henkilöitä ja muotoiltiin yleiset väittämät näihin projekteihin sopiviksi. Projekteissa mukana olleet henkilöt arvioivat väittämiä, ja näiden arvioiden perusteella projekteja vertailtiin keskenään. Lopussa esitetään johtopäätökset kaikkien väittämien arvioiden perusteella. Johtopäätöksenä voidaan todeta, että käyttötietämystä voidaan hyödyntää kaikissa suunnittelun vaiheissa, mutta paras hyöty saadaan perus- ja detaljisuunnittelussa. Käyttötietämyksellä voidaan vaikuttaa joihinkin prosessisuunnittelun laatukriteereihin, kuten esimerkiksi käytettävyyteen ja turvallisuuteen enemmän kuin muihin. Kemiralle suositellaan nykyisten tiedonhallintamenetelmien kehittämistä, jotta käyttötietämyksen saatavuus ja sen siirtäminen paranisi. Pr

Innate and Adaptive Immunity in Orolabial Herpes Simplex

Oral mucosa is a frequent site of primary herpes simplex virus type 1 (HSV-1) infection, whereas intraoral recurrent disease is very rare. Instead, reactivation from latency predominantly results in asymptomatic HSV shedding to saliva or recurrent labial herpes (RLH) with highly individual frequency. The current study aimed to elucidate the role of human oral innate and acquired immune mechanisms in modulation of HSV infection in orolabial region. Saliva was found to neutralize HSV-1, and to protect cells from infection independently of salivary antibodies. Neutralization capacity was higher in saliva from asymptomatic HSV-seropositive individuals compared to subjects with history of RLH or seronegative controls. Neutralization was at least partially associated with salivary lactoferrin content. Further, lactoferrin and peroxidase-generated hypothiocyanite were found to either neutralize HSV-1 or interfere with HSV-1 replication, whereas lysozyme displayed no anti-HSV-1 activity. Lactoferrin was also shown to modulate HSV-1 infection by inhibiting keratinocyte proliferation. RLH susceptibility was further found to be associated with Th2 biased cytokine responses against HSV, and a higher level of anti- HSV-IgG with Th2 polarization, indicating lack of efficiency of humoral response in the control of HSV disease. In a three-dimensional cell culture, keratinocytes were found to support both lytic and nonproductive infection, suggesting HSV persistence in epithelial cells, and further emphasizing the importance of peripheral immune control of HSV. These results suggest that certain innate salivary antimicrobial compounds and Th1 type cellular responses are critically important in protecting the host against HSV disease, implying possible applications in drug, vaccine and gene therapy design.

Interaktiivinen NURBS-sovelma opetuskäyttöön

Parametriset NURBS-käyrät ja -pinnat ovat yleisiä työkaluja graafisessa mallinnuksessa, tietokoneavusteisessa suunnittelussa ja muissa sovelluksissa. NURBS-mallinnus on pääosin melko intuitiivista, mutta siinä on joitakin vaikeammin ymmärrettäviä osia. Ihminen oppii parhaiten tekemällä, minkä takia päätettiin tehdä interaktiivinen NURBS-opetussovelma, joka tutustuttaa käyttäjän NURBSien toimintaan. Sovelma toimii www-selaimessa Java-liitännäisen avulla ja hyödyntää Java OpenGL -grafiikkarajapintaa kolmiulotteisen grafiikan piirtämiseen. Sovelma on helppokäyttöinen ja opastaa käyttäjää NURBS-mallinnuksen eri osa-alueissa.

Radiaalikompressorin juoksupyörän virtauskanavan suunnittelu

Diplomityössä on tutkittu radiaalikompressorin juoksupyörän virtauskanavan suunnittelua ja esitelty yleisesti käytetyt suunnittelumenetelmät. Virtauskanavan muodon vaikutukset virtauskenttään on esitetty. Työssä on kehitetty uusi tietokoneohjelma juoksupyörän kolmiulotteisen geometrian luomiseen, yksiulotteisesta suunnittelusta saatujen päämittojen pohjalta. Ohjelmalla luotua juoksupyörän geometriaa voidaan käyttää virtaus- ja lujuusanalyyseissä. Ohjelmaan on myös liitetty kaksiulotteinen kokoonpuristuvan viskoosittoman virtauksen ratkaisija.

Families of periodic horseshoe orbits in the restricted three-body problem

We compute families of symmetric periodic horseshoe orbits in the restricted three-body problem. Both the planar and three-dimensional cases are considered and several families are found.We describe how these families are organized as well as the behavior along and among the families of parameters such as the Jacobi constant or the eccentricity. We also determine the stability properties of individual orbits along the families. Interestingly, we find stable horseshoe-shaped orbit up to the quite high inclination of 17◦

Kestomagneettigeneraattorin lämmönsiirron mallinnus tuulivoimakäytössä

Pyörivien sähkökoneiden suunnittelussa terminen suunnittelu on yhtä tärkeää kuin sähköinen ja mekaaninen suunnittelukin. Tässä diplomityössä tarkoituksena on kehittää ilmajäähdytteisten kestomagneettigeneraattorien laskentaan soveltuva lämmönsiirtymismalli, jolla staattorin lämpötilajakauma voitaisiin selvittää. Kehitetty lämmönsiirtymismalli perustuu kolmiulotteiseen äärellisen erotuksen (finite difference) menetelmään. Malli ottaa huomioon lämmönjohtumisen staattorin aktiiviosissa ja konvektion jäähdytysilmavirtaan. Mallissa on myös yksinkertainen painehäviölaskenta jäähdytysjärjestelmän komponenttien mitoittamista varten. Laskentamallilla lasketaan esimerkkitapauksena 4,3 MW:n kestomagneettigeneraattorin jäähdytystä eri toimintapisteissä. Tuloksia verrataan CFD-mallinnuksen antamiin tuloksiin sekä kokeellisten mittausten antamiin tuloksiin.

Motivational Influences on Transfer: Dimensions and Boundary Conditions

The focus of this dissertation is the motivational influences on transfer in higher education and professional training contexts. To estimate these motivational influences, the dissertation includes seven individual studies that are structured in two parts. Part I, Dimensions, aims at identifying the dimensionality of motivation to transfer and its structural relations with training-related antecedents and outcomes. Part II, Boundary Conditions, aims at testing the predictive validity of motivation theories used in contemporary training research under different study conditions. Data in this dissertation was gathered from multi-item questionnaires, which were analyzed differently in Part I and Part II. Studies in Part I employed exploratory and confirmatory factor analysis, structural equation modeling, partial least squares (PLS) path modeling, and mediation analysis. Studies in Part II used artifact distribution meta-analysis, (nested) subgroup analysis, and weighted least squares (WLS) multiple regression. Results demonstrate that motivation to transfer can be conceptualized as a three-dimensional construct, including autonomous motivation to transfer, controlled motivation to transfer, and intention to transfer, given a theoretical framework informed by expectancy theory, self-determination theory, and the theory of planned behavior. Results also demonstrate that a range of boundary conditions moderates motivational influences on transfer. To test the predictive validity of expectancy theory, social cognitive theory, and the theory of goal orientations under different study settings, a total of 17 boundary conditions were meta-analyzed, including age; assessment criterion; assessment source; attendance policy; collaboration among trainees; computer support; instruction; instrument used to measure motivation; level of education; publication type; social training context; SS/SMC bias; study setting; survey modality; type of knowledge being trained; use of a control group; and work context. Together, the findings cumulated in this thesis support the basic premise that motivation is centrally important for transfer, but that motivational influences need to be understood from a more differentiated perspective than commonly found in the literature, in order to account for several dimensions and boundary conditions. The results of this dissertation across the seven individual studies are reflected in terms of their implications for theory development and their significance for training evaluation and the design of training environments. Limitations and directions to take in future research are discussed.

Modelling of calciner in post-combustion carbon capture process

Climate change has given an impetus to research and developed new technologies to reduce significantly carbon dioxide emissions in energy production in the developed countries. The major pollution source, fossil fuels, will be used as an energy source for many decades, which provides the demand for carbon capture and storage technologies. Over recent years many new technologies has been developed and one of the most promising is calcium-looping in post-combustion carbon capture process, which use carbonation-calcination cycle to capture carbon dioxide from the flue gas of a combustion process. First pilot plant for calcium-looping process has been built in Oviedo, Spain. In this study, a three-dimensional model has been created for the calciner, which is one of the two fluidized bed reactors needed for the process. The calciner is a regenerator where the captured carbon dioxide is removed from the calcium material and then collected after the reactor. Thesis concentrates in creating the calciner 3D-model frame with CFB3D-program and testing the model with two different example cases. Used input parameters and calciner geometry are Oviedo pilot plant design parameters. The calculation results give information about the process and show that pilot plant calciner should perform as planned. This Master’s Thesis is done in participation to EU FP7 project CaOling.

Development and chemical characterization of flour obtained from the external mesocarp of "pequizeiro" fruit

The objective of this work was to develop a recommendation for the chemical peeling of pequi fruit and characterize the flour obtained from the external mesocarp of "Pequizeiro", pequi tree (Caryocar brasiliense Camb.). The technology applied to obtain the external mesocarp pequi flour included the epicarp removal with NaOH solution. The Response Surface Method was used to optimize the chemical peeling process by applying the Central Composite Rotatable Design, with eleven trials including three replicates at the central point, varying the NaOH aqueous solution concentration and fruit immersion time. The mass loss was evaluated through the analysis of variance and using bi and three dimensional graphs. The chemical characteristics of the external mesocarp pequi flour evaluated were: moisture content, ashes, proteins, lipids, total carbohydrates, dietary fiber, and some minerals. The best combination for an efficient removal of the fruit peel with the lowest mass loss was reached with 7.05 minutes of immersion in a 5.08 g.L-1 NaOH aqueous solution. This study indicated that the external mesocarp pequi flour is a food source rich in dietary fiber, carbohydrates, ashes, magnesium, calcium, manganese, and copper, but it is poor in lipids, zinc, and iron.

Modeling of allergen proteins found in sea food products

Shellfish are a source of food allergens, and their consumption is the cause of severe allergic reactions in humans. Tropomyosins, a family of muscle proteins, have been identified as the major allergens in shellfish and mollusks species. Nevertheless, few experimentally determined three-dimensional structures are available in the Protein Data Base (PDB). In this study, 3D models of several homologous of tropomyosins present in marine shellfish and mollusk species (Chaf 1, Met e1, Hom a1, Per v1, and Pen a1) were constructed, validated, and their immunoglobulin E binding epitopes were identified using bioinformatics tools. All protein models for these allergens consisted of long alpha-helices. Chaf 1, Met e1, and Hom a1 had six conserved regions with sequence similarities to known epitopes, whereas Per v1 and Pen a1 contained only one. Lipophilic potentials of identified epitopes revealed a high propensity of hydrophobic amino acids in the immunoglobulin E binding site. This information could be useful to design tropomyosin-specific immunotherapy for sea food allergies.

Näin opetan lisäävää valmistusta ja 3D-tulostusta: Pohdintoja uuden teknologian opetuksesta ja koulutuksesta

Additive manufacturing (shortened as AM), or more commonly 3D printing, consists of wide variety of different modern manufacturing technologies. AM is based on direct printing of a digital 3D model to a final product which is fabricated adding material layer by layer. This is from where term additive manufacturing has its origin. It is not only material what is added, but it is also value, properties etc. which are added. AM enables production of different and even better products compared to conventional manufacturing technologies. An estimation of potential of additive manufacturing can be gathered by considering the potential of laser cutting, which is one of the most widely used modern manufacturing technologies. This technique has been used over 40 years, and whole market around this technology is at the moment c. four billion euros and yearly growth is around 10 %. One factor affecting this success of laser cutting is that laser cutting enables radical improvements to products made of flat sheet. AM and 3D printing will do the same for three dimensional parts. Laser devices, which are at the moment used in 3D printing, are globally at the moment only around 1% of all laser devices used in any fabrication technology, so even with a cautious estimate the potential growth of at least 100 % is coming in next few years. Role of education is very important, when this kind of modern technology is industrially implemented. When both generation entering to work life and also generation who has been a while in work life understands new technology, its potential and limitations, this is the point when also product design can be rethought Potential of product design is driving force for wide use of additive manufacturing and 3D printing. Utilization of additive manufacturing and 3D printing is also opportunity for Finland and Finnish industry. This technology can save Finnish manufacturing industry. This technique has stron potential, as Finland has traditionally strong industrial know-how and good ICT knowledge.

Automatic evolution of conceptual building architectures

This thesis describes research in which genetic programming is used to automatically evolve shape grammars that construct three dimensional models of possible external building architectures. A completely automated fitness function is used, which evaluates the three dimensional building models according to different geometric properties such as surface normals, height, building footprint, and more. In order to evaluate the buildings on the different criteria, a multi-objective fitness function is used. The results obtained from the automated system were successful in satisfying the multiple objective criteria as well as creating interesting and unique designs that a human-aided system might not discover. In this study of evolutionary design, the architectures created are not meant to be fully functional and structurally sound blueprints for constructing a building, but are meant to be inspirational ideas for possible architectural designs. The evolved models are applicable for today's architectural industries as well as in the video game and movie industries. Many new avenues for future work have also been discovered and highlighted.

Enabling and Measuring Complexity in Evolving Designs using Generative Representations for Artificial Architecture

As the complexity of evolutionary design problems grow, so too must the quality of solutions scale to that complexity. In this research, we develop a genetic programming system with individuals encoded as tree-based generative representations to address scalability. This system is capable of multi-objective evaluation using a ranked sum scoring strategy. We examine Hornby's features and measures of modularity, reuse and hierarchy in evolutionary design problems. Experiments are carried out, using the system to generate three-dimensional forms, and analyses of feature characteristics such as modularity, reuse and hierarchy were performed. This work expands on that of Hornby's, by examining a new and more difficult problem domain. The results from these experiments show that individuals encoded with those three features performed best overall. It is also seen, that the measures of complexity conform to the results of Hornby. Moving forward with only this best performing encoding, the system was applied to the generation of three-dimensional external building architecture. One objective considered was passive solar performance, in which the system was challenged with generating forms that optimize exposure to the Sun. The results from these and other experiments satisfied the requirements. The system was shown to scale well to the architectural problems studied.

Optimization and validation of a new 3D-US imaging robot to detect, localize and quantify lower limb arterial stenoses

L’athérosclérose est une maladie qui cause, par l’accumulation de plaques lipidiques, le durcissement de la paroi des artères et le rétrécissement de la lumière. Ces lésions sont généralement localisées sur les segments artériels coronariens, carotidiens, aortiques, rénaux, digestifs et périphériques. En ce qui concerne l’atteinte périphérique, celle des membres inférieurs est particulièrement fréquente. En effet, la sévérité de ces lésions artérielles est souvent évaluée par le degré d’une sténose (réduction >50 % du diamètre de la lumière) en angiographie, imagerie par résonnance magnétique (IRM), tomodensitométrie ou échographie. Cependant, pour planifier une intervention chirurgicale, une représentation géométrique artérielle 3D est notamment préférable. Les méthodes d’imagerie par coupe (IRM et tomodensitométrie) sont très performantes pour générer une imagerie tridimensionnelle de bonne qualité mais leurs utilisations sont dispendieuses et invasives pour les patients. L’échographie 3D peut constituer une avenue très prometteuse en imagerie pour la localisation et la quantification des sténoses. Cette modalité d’imagerie offre des avantages distincts tels la commodité, des coûts peu élevés pour un diagnostic non invasif (sans irradiation ni agent de contraste néphrotoxique) et aussi l’option d’analyse en Doppler pour quantifier le flux sanguin. Étant donné que les robots médicaux ont déjà été utilisés avec succès en chirurgie et en orthopédie, notre équipe a conçu un nouveau système robotique d’échographie 3D pour détecter et quantifier les sténoses des membres inférieurs. Avec cette nouvelle technologie, un radiologue fait l’apprentissage manuel au robot d’un balayage échographique du vaisseau concerné. Par la suite, le robot répète à très haute précision la trajectoire apprise, contrôle simultanément le processus d’acquisition d’images échographiques à un pas d’échantillonnage constant et conserve de façon sécuritaire la force appliquée par la sonde sur la peau du patient. Par conséquent, la reconstruction d’une géométrie artérielle 3D des membres inférieurs à partir de ce système pourrait permettre une localisation et une quantification des sténoses à très grande fiabilité. L’objectif de ce projet de recherche consistait donc à valider et optimiser ce système robotisé d’imagerie échographique 3D. La fiabilité d’une géométrie reconstruite en 3D à partir d’un système référentiel robotique dépend beaucoup de la précision du positionnement et de la procédure de calibration. De ce fait, la précision pour le positionnement du bras robotique fut évaluée à travers son espace de travail avec un fantôme spécialement conçu pour simuler la configuration des artères des membres inférieurs (article 1 - chapitre 3). De plus, un fantôme de fils croisés en forme de Z a été conçu pour assurer une calibration précise du système robotique (article 2 - chapitre 4). Ces méthodes optimales ont été utilisées pour valider le système pour l’application clinique et trouver la transformation qui convertit les coordonnées de l’image échographique 2D dans le référentiel cartésien du bras robotisé. À partir de ces résultats, tout objet balayé par le système robotique peut être caractérisé pour une reconstruction 3D adéquate. Des fantômes vasculaires compatibles avec plusieurs modalités d’imagerie ont été utilisés pour simuler différentes représentations artérielles des membres inférieurs (article 2 - chapitre 4, article 3 - chapitre 5). La validation des géométries reconstruites a été effectuée à l`aide d`analyses comparatives. La précision pour localiser et quantifier les sténoses avec ce système robotisé d’imagerie échographique 3D a aussi été déterminée. Ces évaluations ont été réalisées in vivo pour percevoir le potentiel de l’utilisation d’un tel système en clinique (article 3- chapitre 5).