Helical tomotherapy for the treatment of anal canal cancer: a dosimetric comparison with 3D conformal radiotherapy.

AIMS AND BACKGROUND: The standard treatment of anal canal cancer (ACC) is combined chemotherapy and radiation therapy (RT), which is complex because of the shape of the target volumes and the need to minimize the irradiation of normal pelvic structures. In this study we compared the dosimetric results of helical tomotherapy (HT) plans with traditional 3D conformal RT (3DRT) plans for the treatment of ACC. METHODS AND STUDY DESIGN: Twelve patients (median age 57 years, range 38-83; F/M 8/4) treated with HT and concurrent chemotherapy for locally advanced ACC were selected. All had histologically confirmed squamous-cell carcinoma. A clinical target volume including the tumor and pelvic and inguinal lymph nodes was treated with HT to a total dose of 36 Gy in 1.8-Gy daily fractions. Then a sequential boost of 23.4 Gy in 1.8-Gy daily fractions (total dose 59.4 Gy) was delivered to the tumor and involved nodes. For all 12 patients, 3DRT plans were generated for comparison. Treatment plans were evaluated by means of standard dose-volume histograms. Dose coverage of the planning target volumes (PTVs), homogeneity index (HI), and mean doses to organs at risk (OARs) were compared. RESULTS: The coverage of PTV was comparable between the two treatment plans. HI was better in the HT vs. 3DRT plans (1.25 and 3.57, respectively; p<0.0001). HT plans resulted in better sparing of OARs (p<0.0001). CONCLUSIONS: HT showed superior target dose conformality and significant sparing of pelvic structures compared with 3DRT. Further investigation should determine if these dosimetric improvements will improve clinical outcomes regarding locoregional control, survival, and treatment-related acute and late morbidity.

3D-suunnittelujärjestelmän ja tuotetiedonhallintajärjestelmän integrointi

3D-suunnittelujärjestelmät ovat tärkeitä työkaluja tuotetiedon luomista ja muokkaamista varten, joten niiden tehokas toiminta yhdessä tuotetiedonhallintajärjestelmien kanssa on erittäin tärkeää. 3D-suunnittelujärjestelmien kehityksen seurauksena 3D-malleihin voidaan sisällyttää entistä enemmän tuotetietoa, jolloin tehokas tiedon tallentaminen ja sen hallinta kasvattaa merkitystään. 3D-malleihin sisältyvää tietoa, kuten esimerkiksi kappaleen painoa tai geometriaa, halutaan myös tarkastella ilman tiettyä 3D-järjestelmää. Tuotetiedon hallinta on ollut jo pitkään tärkeä osa tuotteen suunnitteluprosessia. Tuotetiedon hallintaan sisältyy tiedon luomista, keräämistä ja muokkaamista koko tuotteen eliniän ajan. Näitä tietoja voivat olla esimerkiksi piirustukset, 3D-mallit, mittauspöytäkirjat, kokouspöytäkirjat, mallistoluettelot, lujuuslaskelmat, huoltoraportit jne. Tuotetiedonhallintajärjestelmä pitää huolta kaikesta tästä tiedosta ja sen kautta tuotteisiin liittyvää tietoa voidaan myös muokata ja jakaa tehokkaasti. Tässä diplomityössä tutkittiin näiden kahden järjestelmän integraation toteutusta erilaisilla menetelmillä. Työn tarkoituksena oli valita Valtra Oy:n tarkoituksiin parhaiten sopiva menetelmä tuotetiedon siirtämiseksi järjestelmien välillä tehokkaasti. Työn tuloksena annetaan suositus käytettävistä menetelmistä ja työkaluista.

Tuotteen suunnitteluketjun tehostaminen 3D-ympäristössä

Tämä diplomityö on tehty Andritz Oy:lle Washers & Filters tuoteryhmään. Työ on osa 3D-suunnittelujärjestelmän käyttöönottoprojektia. Tavoitteena on arvioida uuden laitesuunnittelujärjestelmän vaikutuksia yrityksen tietojärjestelmiin ja toimintatapoihin sekä etsiä potentiaalisia tulevaisuuden kehityskohteita. Suunnittelutietoa hyödyntäviä sidosryhmien edustajia haastattelemalla selvitettiin järjestelmille ja ohjelmistoille asetettavia vaatimuksia. Ohjelmistoihin tutustumalla saatiin käsitys niiden nykytilasta ja kehityssuunnista. 3D-geometrian hyödyntämiseen perustuvilla järjestelmillä voidaan poistaa päällekäistä työtä sekä lyhentää läpimenoaikoja suunnittelussa ja valmistuksessa sijoittamalla työvaiheita rinnakkain. Suurimmat 3D-suunnittelun edut saavutetaan tuotekehitysvaiheessa, tuotemuutoksia tehtäessä sekä valmistusprosesseja suunniteltaessa. Ongelmallisimmat osa-alueet tietojärjestelmien kehittämisessä ovat ensi-sijaisesti tiedonsiirto ohjelmistojen välillä, työntekijöiden muutosvastarinta sekä laadukkaiden järjestelmien korkea hinta. Laajojen tietojärjestelmä-projektien läpivienti on hyvin haastavaa ja onnistuminen vaatii kaikkien sidosryhmien mukana olemista ja tarkkaa projektin koordinointia.

Social justice in education : how the function of selection in educational institutions predicts support for (non)egalitarian assessment practices

Educational institutions are considered a keystone for the establishment of a meritocratic society. They supposedly serve two functions: an educational function that promotes learning for all, and a selection function that sorts individuals into different programs, and ultimately social positions, based on individual merit. We study how the function of selection relates to support for assessment practices known to harm vs. benefit lower status students, through the perceived justice principles underlying these practices. We study two assessment practices: normative assessment-focused on ranking and social comparison, known to hinder the success of lower status students-and formative assessment-focused on learning and improvement, known to benefit lower status students. Normative assessment is usually perceived as relying on an equity principle, with rewards being allocated based on merit and should thus appear as positively associated with the function of selection. Formative assessment is usually perceived as relying on corrective justice that aims to ensure equality of outcomes by considering students' needs, which makes it less suitable for the function of selection. A questionnaire measuring these constructs was administered to university students. Results showed that believing that education is intended to select the best students positively predicts support for normative assessment, through increased perception of its reliance on equity, and negatively predicts support for formative assessment, through reduced perception of its ability to establish corrective justice. This study suggests that the belief in the function of selection as inherent to educational institutions can contribute to the reproduction of social inequalities by preventing change from assessment practices known to disadvantage lowerstatus student, namely normative assessment, to more favorable practices, namely formative assessment, and by promoting matching beliefs in justice principles.

Evolution of dosage compensation under sexual selection differs between X and Z chromosomes.

Complete sex chromosome dosage compensation has more often been observed in XY than ZW species. In this study, using a population genetic model and the chicken transcriptome, we assess whether sexual conflict can account for this difference. Sexual conflict over expression is inevitable when mutation effects are correlated across the sexes, as compensatory mutations in the heterogametic sex lead to hyperexpression in the homogametic sex. Coupled with stronger selection and greater reproductive variance in males, this results in slower and less complete evolution of Z compared with X dosage compensation. Using expression variance as a measure of selection strength, we find that, as predicted by the model, dosage compensation in the chicken is most pronounced in genes that are under strong selection biased towards females. Our study explains the pattern of weak dosage compensation in ZW systems, and suggests that sexual selection plays a major role in shaping sex chromosome dosage compensation.

Cardiovascular magnetic resonance imaging techniques for motion-suppressed multi-dimensional coronary artery imaging with high spatial and temporal resolution

L'imagerie par résonance magnétique (IRM) peut fournir aux cardiologues des informations diagnostiques importantes sur l'état de la maladie de l'artère coronarienne dans les patients. Le défi majeur pour l'IRM cardiaque est de gérer toutes les sources de mouvement qui peuvent affecter la qualité des images en réduisant l'information diagnostique. Cette thèse a donc comme but de développer des nouvelles techniques d'acquisitions des images IRM, en changeant les techniques de compensation du mouvement, pour en augmenter l'efficacité, la flexibilité, la robustesse et pour obtenir plus d'information sur le tissu et plus d'information temporelle. Les techniques proposées favorisent donc l'avancement de l'imagerie des coronaires dans une direction plus maniable et multi-usage qui peut facilement être transférée dans l'environnement clinique. La première partie de la thèse s'est concentrée sur l'étude du mouvement des artères coronariennes sur des patients en utilisant la techniques d'imagerie standard (rayons x), pour mesurer la précision avec laquelle les artères coronariennes retournent dans la même position battement après battement (repositionnement des coronaires). Nous avons découvert qu'il y a des intervalles dans le cycle cardiaque, tôt dans la systole et à moitié de la diastole, où le repositionnement des coronaires est au minimum. En réponse nous avons développé une nouvelle séquence d'acquisition (T2-post) capable d'acquérir les données aussi tôt dans la systole. Cette séquence a été testée sur des volontaires sains et on a pu constater que la qualité de visualisation des artère coronariennes est égale à celle obtenue avec les techniques standard. De plus, le rapport signal sur bruit fourni par la séquence d'acquisition proposée est supérieur à celui obtenu avec les techniques d'imagerie standard. La deuxième partie de la thèse a exploré un paradigme d'acquisition des images cardiaques complètement nouveau pour l'imagerie du coeur entier. La technique proposée dans ce travail acquiert les données sans arrêt (free-running) au lieu d'être synchronisée avec le mouvement cardiaque. De cette façon, l'efficacité de la séquence d'acquisition est augmentée de manière significative et les images produites représentent le coeur entier dans toutes les phases cardiaques (quatre dimensions, 4D). Par ailleurs, l'auto-navigation de la respiration permet d'effectuer cette acquisition en respiration libre. Cette technologie rend possible de visualiser et évaluer l'anatomie du coeur et de ses vaisseaux ainsi que la fonction cardiaque en quatre dimensions et avec une très haute résolution spatiale et temporelle, sans la nécessité d'injecter un moyen de contraste. Le pas essentiel qui a permis le développement de cette technique est l'utilisation d'une trajectoire d'acquisition radiale 3D basée sur l'angle d'or. Avec cette trajectoire, il est possible d'acquérir continûment les données d'espace k, puis de réordonner les données et choisir les paramètres temporel des images 4D a posteriori. L'acquisition 4D a été aussi couplée avec un algorithme de reconstructions itératif (compressed sensing) qui permet d'augmenter la résolution temporelle tout en augmentant la qualité des images. Grâce aux images 4D, il est possible maintenant de visualiser les artères coronariennes entières dans chaque phase du cycle cardiaque et, avec les mêmes données, de visualiser et mesurer la fonction cardiaque. La qualité des artères coronariennes dans les images 4D est la même que dans les images obtenues avec une acquisition 3D standard, acquise en diastole Par ailleurs, les valeurs de fonction cardiaque mesurées au moyen des images 4D concorde avec les valeurs obtenues avec les images 2D standard. Finalement, dans la dernière partie de la thèse une technique d'acquisition a temps d'écho ultra-court (UTE) a été développée pour la visualisation in vivo des calcifications des artères coronariennes. Des études récentes ont démontré que les acquisitions UTE permettent de visualiser les calcifications dans des plaques athérosclérotiques ex vivo. Cepandent le mouvement du coeur a entravé jusqu'à maintenant l'utilisation des techniques UTE in vivo. Pour résoudre ce problème nous avons développé une séquence d'acquisition UTE avec trajectoire radiale 3D et l'avons testée sur des volontaires. La technique proposée utilise une auto-navigation 3D pour corriger le mouvement respiratoire et est synchronisée avec l'ECG. Trois échos sont acquis pour extraire le signal de la calcification avec des composants au T2 très court tout en permettant de séparer le signal de la graisse depuis le signal de l'eau. Les résultats sont encore préliminaires mais on peut affirmer que la technique développé peut potentiellement montrer les calcifications des artères coronariennes in vivo. En conclusion, ce travail de thèse présente trois nouvelles techniques pour l'IRM du coeur entier capables d'améliorer la visualisation et la caractérisation de la maladie athérosclérotique des coronaires. Ces techniques fournissent des informations anatomiques et fonctionnelles en quatre dimensions et des informations sur la composition du tissu auparavant indisponibles. CORONARY artery magnetic resonance imaging (MRI) has the potential to provide the cardiologist with relevant diagnostic information relative to coronary artery disease of patients. The major challenge of cardiac MRI, though, is dealing with all sources of motions that can corrupt the images affecting the diagnostic information provided. The current thesis, thus, focused on the development of new MRI techniques that change the standard approach to cardiac motion compensation in order to increase the efficiency of cardioavscular MRI, to provide more flexibility and robustness, new temporal information and new tissue information. The proposed approaches help in advancing coronary magnetic resonance angiography (MRA) in the direction of an easy-to-use and multipurpose tool that can be translated to the clinical environment. The first part of the thesis focused on the study of coronary artery motion through gold standard imaging techniques (x-ray angiography) in patients, in order to measure the precision with which the coronary arteries assume the same position beat after beat (coronary artery repositioning). We learned that intervals with minimal coronary artery repositioning occur in peak systole and in mid diastole and we responded with a new pulse sequence (T2~post) that is able to provide peak-systolic imaging. Such a sequence was tested in healthy volunteers and, from the image quality comparison, we learned that the proposed approach provides coronary artery visualization and contrast-to-noise ratio (CNR) comparable with the standard acquisition approach, but with increased signal-to-noise ratio (SNR). The second part of the thesis explored a completely new paradigm for whole- heart cardiovascular MRI. The proposed techniques acquires the data continuously (free-running), instead of being triggered, thus increasing the efficiency of the acquisition and providing four dimensional images of the whole heart, while respiratory self navigation allows for the scan to be performed in free breathing. This enabling technology allows for anatomical and functional evaluation in four dimensions, with high spatial and temporal resolution and without the need for contrast agent injection. The enabling step is the use of a golden-angle based 3D radial trajectory, which allows for a continuous sampling of the k-space and a retrospective selection of the timing parameters of the reconstructed dataset. The free-running 4D acquisition was then combined with a compressed sensing reconstruction algorithm that further increases the temporal resolution of the 4D dataset, while at the same time increasing the overall image quality by removing undersampling artifacts. The obtained 4D images provide visualization of the whole coronary artery tree in each phases of the cardiac cycle and, at the same time, allow for the assessment of the cardiac function with a single free- breathing scan. The quality of the coronary arteries provided by the frames of the free-running 4D acquisition is in line with the one obtained with the standard ECG-triggered one, and the cardiac function evaluation matched the one measured with gold-standard stack of 2D cine approaches. Finally, the last part of the thesis focused on the development of ultrashort echo time (UTE) acquisition scheme for in vivo detection of calcification in the coronary arteries. Recent studies showed that UTE imaging allows for the coronary artery plaque calcification ex vivo, since it is able to detect the short T2 components of the calcification. The heart motion, though, prevented this technique from being applied in vivo. An ECG-triggered self-navigated 3D radial triple- echo UTE acquisition has then been developed and tested in healthy volunteers. The proposed sequence combines a 3D self-navigation approach with a 3D radial UTE acquisition enabling data collection during free breathing. Three echoes are simultaneously acquired to extract the short T2 components of the calcification while a water and fat separation technique allows for proper visualization of the coronary arteries. Even though the results are still preliminary, the proposed sequence showed great potential for the in vivo visualization of coronary artery calcification. In conclusion, the thesis presents three novel MRI approaches aimed at improved characterization and assessment of atherosclerotic coronary artery disease. These approaches provide new anatomical and functional information in four dimensions, and support tissue characterization for coronary artery plaques.

Selection on a genetic polymorphism counteracts ecological speciation in a stick insect.

The interplay between selection and aspects of the genetic architecture of traits (such as linkage, dominance, and epistasis) can either drive or constrain speciation [1-3]. Despite accumulating evidence that speciation can progress to "intermediate" stages-with populations evolving only partial reproductive isolation-studies describing selective mechanisms that impose constraints on speciation are more rare than those describing drivers. The stick insect Timema cristinae provides an example of a system in which partial reproductive isolation has evolved between populations adapted to different host plant environments, in part due to divergent selection acting on a pattern polymorphism [4, 5]. Here, we demonstrate how selection on a green/melanistic color polymorphism counteracts speciation in this system. Specifically, divergent selection between hosts does not occur on color phenotypes because melanistic T. cristinae are cryptic on the stems of both host species, are resistant to a fungal pathogen, and have a mating advantage. Using genetic crosses and genome-wide association mapping, we quantify the genetic architecture of both the pattern and color polymorphism, illustrating their simple genetic control. We use these empirical results to develop an individual-based model that shows how the melanistic phenotype acts as a "genetic bridge" that increases gene flow between populations living on different hosts. Our results demonstrate how variation in the nature of selection acting on traits, and aspects of trait genetic architecture, can impose constraints on both local adaptation and speciation.

Disentangling the formation of contrasting tree line physiognomies combining model selection and Bayesian parameterization for simulation models.

Alpine tree-line ecotones are characterized by marked changes at small spatial scales that may result in a variety of physiognomies. A set of alternative individual-based models was tested with data from four contrasting Pinus uncinata ecotones in the central Spanish Pyrenees to reveal the minimal subset of processes required for tree-line formation. A Bayesian approach combined with Markov chain Monte Carlo methods was employed to obtain the posterior distribution of model parameters, allowing the use of model selection procedures. The main features of real tree lines emerged only in models considering nonlinear responses in individual rates of growth or mortality with respect to the altitudinal gradient. Variation in tree-line physiognomy reflected mainly changes in the relative importance of these nonlinear responses, while other processes, such as dispersal limitation and facilitation, played a secondary role. Different nonlinear responses also determined the presence or absence of krummholz, in agreement with recent findings highlighting a different response of diffuse and abrupt or krummholz tree lines to climate change. The method presented here can be widely applied in individual-based simulation models and will turn model selection and evaluation in this type of models into a more transparent, effective, and efficient exercise.

Students support demographically-based quotas with distributive justice rules favoring their selection at university

We manipulate distributive justice rules of demographic quotas in university selection. Results show that quotas involving students' need are preferred over equity and authority ranking quotas. International students also differentiate more between quotas than locals, preferring those advantaging them. This suggests that universities should consider students' need in their selection.

Feature Selection, Ranking of Each Feature and Classification for the Diagnosis of Community Acquired Legionella Pneumonia

Diagnosis of community acquired legionella pneumonia (CALP) is currently performed by means of laboratory techniques which may delay diagnosis several hours. To determine whether ANN can categorize CALP and non-legionella community-acquired pneumonia (NLCAP) and be standard for use by clinicians, we prospectively studied 203 patients with community-acquired pneumonia (CAP) diagnosed by laboratory tests. Twenty one clinical and analytical variables were recorded to train a neural net with two classes (LCAP or NLCAP class). In this paper we deal with the problem of diagnosis, feature selection, and ranking of the features as a function of their classification importance, and the design of a classifier the criteria of maximizing the ROC (Receiving operating characteristics) area, which gives a good trade-off between true positives and false negatives. In order to guarantee the validity of the statistics; the train-validation-test databases were rotated by the jackknife technique, and a multistarting procedure was done in order to make the system insensitive to local maxima.

Gene filtering with optimal threshold selection

Gene filtering is a useful preprocessing technique often applied to microarray datasets. However, it is no common practice because clear guidelines are lacking and it bears the risk of excluding some potentially relevant genes. In this work, we propose to model microarray data as a mixture of two Gaussian distributions that will allow us to obtain an optimal filter threshold in terms of the gene expression level.