Late side-effects after curative intent radiotherapy: Identification of hypersensitive patients for personalized strategy.

Radiation therapy undeniably enhances local control and thus improves overall survival in cancer patients. However, some long-term cancer survivors (less than 10%) develop severe late radio-induced toxicities altering their quality of life. Therefore, there is a need to identify patients who are sensitive to those toxicities and who could benefit from adapted care. In this review, we address all available techniques aiming to detect patients' hyper-radiosensitivity and present the scientific rationales these techniques are based on.

THE USEFUL SIDE OF AMBIVALENCE: Ambivalent attitudes can be adaptive and socially valued

En s'inspirant de la littérature récente qui a dépeint l'ambivalence comme étant adaptative et en lien avec des comportements stratégiques, cette thèse examine le versant utile des attitudes ambivalentes. Elle met tout d'abord en évidence que son expression peut-être sciemment contrôlée et mise en avant pour des raisons d'auto-présentation. De plus, elle démontre que les individus peuvent présenter une attitude ambivalente afin de gagner l'approbation sociale sur un objet d'attitude controversé alors que l'inverse a été observé sur des objets consensuels (Première ligne de recherche). Cette thèse a également révélé que l'expression d'attitudes ambivalentes pouvait amener à être valorisé socialement. En effet, contrairement à des attitudes plus tranchées (pro-normatives ou contre-normatives), les attitudes ambivalentes ont été évaluées de façon plus importante sur la dimension de l'utilité sociale (une dimension qui indique la compétence d'autrui ou encore la propension à évoluer dans la hiérarchie sociale). La valorisation de l'ambivalence n'est apparue que sur la dimension de l'utilité sociale et non sur la dimension de la désirabilité sociale (une dimension qui indique la sympathie d'autrui ainsi que la propension à être apprécié socialement). De plus, ce résultat a été observé sur des thèmes controversés et non sur des thèmes consensuels (Seconde ligne de recherche). Dans l'ensemble cette thèse soutient une approche de l'ambivalence comme donnant lieu à des bénéfices. Elle peut également ouvrir la voie à l'étude de l'ambivalence en lien avec la pensée critique. - Drawing on the recent literature that portrayed ambivalence as being adaptive and linked with strategic behaviors, this thesis examines the useful side of ambivalent attitudes. It first revealed that the expression of ambivalent attitudes could be controlled and purposely displayed for self-presentational concerns. Furthermore, it demonstrated that people could put ambivalence forward to gain social approval when expressing it on controversial social issues, whereas the opposite was true on consensual social issues (First line of research). The thesis also revealed that the expression of ambivalent attitudes could lead to be socially valued. Indeed, contrary to clear-cut attitudes (either pro-normative or counter-normative attitudes), ambivalent attitudes have been evaluated the highest on the social utility dimension (a dimension indicating people's competence as well as the extent to which they are likely to climb in social hierarchy). The valorization of ambivalent attitudes only appeared on social utility and not on social desirability (a dimension indicating people's niceness as well as the extent to which they are likely to be socially appreciated). This effect was true on controversial social issues but not on consensual ones (Second line of research). Overall, this thesis provides support for an approach that conceives attitudinal ambivalence as leading to benefits. It also may open avenues for the study of ambivalence in relation with critical thinking.

FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals

We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information.

Implantació d'un sistema SCADA en una cèl·lula flexible de fabricació

La Universitat de Vic disposa, entre altres equips, d’una cèl·lula flexible de fabricació, del fabricant Festo, que simula un procés de formació de palets amb els productes que es disposen en un magatzem intermedi. Aquesta cèl·lula està composta de quatre estacions de muntatge diferenciades (càrrega de palets, càrrega de plaques, magatzem intermedi i transport). Cada una disposa d'un PLC SIEMENS S7-300 per la seva automatització, i tots aquests es troben interconnectats amb una xarxa industrial Profibus. L'objectiu d'aquest projecte és implantar el sistema SCADA Vijeo Citect pel control i supervisió de l'estació magatzem d'aquesta cèl·lula flexible de fabricació, establint també un intercanvi de dades entre l'SCADA i el Microsoft Access, per poder ser utilitzat per la docència. Aquest projecte s'ha desenvolupat en cinc fases diferents: 1. La primera fase s'ha dedicat a l'automatització pròpiament de l'estació magatzem a partir de l'autòmat programable Siemens S7-300 i complint amb les necessitats plantejades. 2. En la segona fase s'ha programat i establert la comunicació per l'intercanvi de dades (lectura i escriptura) entre el sistema SCADA Vijeo Citect i la base de dades de Microsoft Access. 3. En la tercera fase s'ha elaborat i programat l'entorn gràfic de supervisió i control del procés a partir del sistema SCADA Vijeo Citect. 4. En la quarta fase s'ha instal·lat un OPC Server en el PC i s'ha establert la comunicació entre el PLC i el sistema SCADA. 5. Finalment s'ha anat revisant i depurant les diferents programacions i comunicacions per tal de que el sistema funcioni com a un conjunt.

Development of Non-Petroleum Based Binders for Use in Flexible Pavements, TR-594, 2010

Most bituminous adhesives or binders that are used for pavement materials are derived primarily from fossil fuels. With petroleum oil reserves becoming depleted and the drive to establish a bio-based economy, there is a push to produce binders from alternative sources, particularly from biorenewable resources. However, until now, no research has studied the applicability of utilizing bio-oils as a bitumen replacement (100% replacement) in the pavement industry. The main objective of this research was to test various properties of bio-oils in order to determine the applicability of using bio-oils as binders in the pavement industry. The overall conclusions about the applicability of using bio-oils as bio-binders in the pavement industry can be summarized as follows: 1. Bio-oils cannot be used as bio-binders/pavement materials without any heat pre-treatment/upgrading procedure. 2. Current testing standards and specifications, especially Superpave procedures, should be modified to comply with the properties of bio-binders. 3. The temperature range of the viscous behavior for bio-oils may be lower than that of bitumen binders by about 30°–40° C. 4. The rheological properties of the unmodified bio-binders vary in comparison to bitumen binders, but the rheological properties of these modified bio-binders change significantly upon adding polymer modifiers. 5. The high-temperature performance grade for the developed bio-binders may not vary significantly from that of the bitumen binders, but the low-temperature performance grade may vary significantly

Investigation of Uplift Failures in Flexible Pipe Culverts, HR-306, 1990

This study was precipitated by several failures of flexible pipe culverts due to apparent inlet floatation. A survey of Iowa County Engineers revealed 31 culvert failures on pipes greater than 72" diameter in eight Iowa counties within the past five years. No special hydrologic, topography, and geotechnical environments appeared to be more susceptible to failure. However, most failures seemed to be on pipes flowing in inlet control. Geographically, most of the failures were in the southern and western sections of Iowa. The forces acting on a culvert pipe are quantified. A worst case scenario, where the pipe is completely plugged, is evaluated to determine the magnitude of forces that must be resisted by a tie down or headwall. Concrete headwalls or slope collars are recommended for most pipes over 4 feet in diameter.

The ager tarraconensis project (right side of river Francoli) (PAT): the application of geophysical survey to identify rural Roman settlement typologies

The methodology of the ager Tarraconensis project also included geophysical surveys aiming to distinguish different categories of rural settlements. Two geophysical techniques (resistivity and magnetometry) were combined to reveal traces of unearth structures from a selection of sites identified from the field survey. Results of geophysical surveys of these seven sites as well as conclusions obtained from this approach are discussed here.

Reflective Crack Mitigation Guide for Flexible Pavements, TR-641, 2015

Reflective cracks form in pavements when hot-mix asphalt (HMA) overlays are placed over jointed and/or severely cracked rigid and flexible pavements. In the first part of the research, survival analysis was conducted to identify the most appropriate rehabilitation method for composite pavements and to evaluate the influence of different factors on reflective crack development. Four rehabilitation methods, including mill and fill, overlay, heater scarification (SCR), and rubblization, were analyzed using three performance indicators: reflective cracking, international roughness index (IRI), and pavement condition index (PCI). It was found that rubblization can significantly retard reflective cracking development compared to the other three methods. No significant difference for PCI was seen among the four rehabilitation methods. Heater scarification showed the lowest survival probability for both reflective cracking and IRI, while an overlay resulted in the poorest overall pavement condition based on PCI. In addition, traffic level was found not to be a significant factor for reflective cracking development. An increase in overlay thickness can significantly delay the propagation of reflective cracking for all four treatments. Soil types in rubblization pavement sites were assessed, and no close relationship was found between rubblized pavement performance and subgrade soil condition. In the second part of the research, the study objective was to evaluate the modulus and performance of four reflective cracking treatments: full rubblization, modified rubblization, crack and seat, and rock interlayer. A total of 16 pavement sites were tested by the surface wave method (SWM), and in the first four sites both falling weight deflectometer (FWD) and SWM were conducted for a preliminary analysis. The SWM gave close concrete layer moduli compared to the FWD moduli on a conventional composite pavement. However, the SWM provided higher moduli for the rubblized concrete layer. After the preliminary analysis, another 12 pavement sites were tested by the SWM. The results showed that the crack and seat method provided the highest moduli, followed by the modified rubblization method. The full rubblization and the rock interlayer methods gave similar, but lower, moduli. Pavement performance surveys were also conducted during the field study. In general, none of the pavement sites had rutting problems. The conventional composite pavement site had the largest amount of reflective cracking. A moderate amount of reflective cracking was observed for the two pavement sites with full rubblization. Pavements with the rock interlayer and modified rubblization treatments had much less reflective cracking. It is recommended that use of the modified rubblization and rock interlayer treatments for reflective cracking mitigation are best.

Development of Non-Petroleum-Based Binders for Use in Flexible Pavements – Phase II, TR-650, 2015

Bio-binders can be utilized as asphalt modifiers, extenders, and replacements for conventional asphalt in bituminous binders. From the rheology results of Phase I of this project, it was found that the bio-binders tested had good performance, similar to conventional asphalt, except at low temperatures. Phase II of this project addresses this shortcoming and evaluates the Superpave performance of laboratory mixes produced with the enhanced bio-binders. The main objective of this research was to develop a bio-binder capable of replacing conventional asphalt in flexible pavements by incorporating ground tire rubber (GTR) into bio-oil derived from fast pyrolysis of agriculture and forestry residues. The chemical compatibility of the new bio-binder with GTR was assessed, and the low-temperature performance of the bio-binders was enhanced by the use of GTR. The newly developed binder, which consisted of 80 percent conventional binder and 20 percent rubber-modified bio-oil (85 percent bio-oil with 15 percent GTR), was used to produce mixes at two different air void contents, 4 and 7 percent. The laboratory performance test results showed that the performance of the newly developed bio-binder mixes is as good as or better than conventional asphalt mixes for fatigue cracking, rutting resistance, moisture sensitivity, and low-temperature cracking. These results need to be validated in field projects in order to demonstrate adequate performance for this innovative and sustainable technology for flexible pavements.

Multisensory Integration: Flexible Use of General Operations.

Research into the anatomical substrates and "principles" for integrating inputs from separate sensory surfaces has yielded divergent findings. This suggests that multisensory integration is flexible and context dependent and underlines the need for dynamically adaptive neuronal integration mechanisms. We propose that flexible multisensory integration can be explained by a combination of canonical, population-level integrative operations, such as oscillatory phase resetting and divisive normalization. These canonical operations subsume multisensory integration into a fundamental set of principles as to how the brain integrates all sorts of information, and they are being used proactively and adaptively. We illustrate this proposition by unifying recent findings from different research themes such as timing, behavioral goal, and experience-related differences in integration.

Iontophoresis: from the lab to the bed side.

Pioneer work on iontophoresis undertaken by David Maurice during the 1970s and 1980s laid the initial groundwork for its potential implementation as a promising ocular therapeutic modality. A better understanding of tissue interactions within the eye during electric current application, along with better designs of drug delivery devices have enabled us to pursue David Maurice's original ideas and take them from the bench to the bed side. In the present study we demonstrate the potential application of an iontophoresis device (Eyegate, Optis, France) for the treatment of certain human eye diseases. Seventeen patients received a penetrating keratoplasty (PKP) at various intervals before presentation with active graft rejection in our clinic and were treated using this iontophoresis device. Methylprednisolone sodium succinate (MP) 62.5 mg/ml was infused within the Eyegate ocular probe container and an electrical current of 1.5 mA was delivered for 4 min with the negative pole connected to the ocular probe. Patients were treated on an ambulatory basis and received a standard course of three iontophoresis applications given once a day over 3 consecutive days. After treatment, 15 of the 17 treated eyes (88%) demonstrated a complete reversal of the rejection processes. In two eyes, only a partial and temporary improvement was observed. The mean best corrected visual acuity of all 17 patients during the last follow up visit was 0.37 +/- 0.2 compared to 0.06 +/- 0.05 before initiation of the iontophoresis treatment. The mean follow-up time was 13.7 months with a range of 5-29 months for the 17 patients. No significant side-effects associated with the iontophoresis treatment were observed. Thus, for the management of active corneal graft rejection, iontophoresis of MP can be an alternative to very frequent instillations of eye drops, or to pulsed intravenous therapy of corticosteroids.

Structural macro factors and the affine term structure of interest rates

This work consists of three essays investigating the ability of structural macroeconomic models to price zero coupon U.S. government bonds. 1. A small scale 3 factor DSGE model implying constant term premium is able to provide reasonable a fit for the term structure only at the expense of the persistence parameters of the structural shocks. The test of the structural model against one that has constant but unrestricted prices of risk parameters shows that the exogenous prices of risk-model is only weakly preferred. We provide an MLE based variance-covariance matrix of the Metropolis Proposal Density that improves convergence speeds in MCMC chains. 2. Affine in observable macro-variables, prices of risk specification is excessively flexible and provides term-structure fit without significantly altering the structural parameters. The exogenous component of the SDF is separating the macro part of the model from the term structure and the good term structure fit has as a driving force an extremely volatile SDF and an implied average short rate that is inexplicable. We conclude that the no arbitrage restrictions do not suffice to temper the SDF, thus there is need for more restrictions. We introduce a penalty-function methodology that proves useful in showing that affine prices of risk specifications are able to reconcile stable macro-dynamics with good term structure fit and a plausible SDF. 3. The level factor is reproduced most importantly by the preference shock to which it is strongly and positively related but technology and monetary shocks, with negative loadings, are also contributing to its replication. The slope factor is only related to the monetary policy shocks and it is poorly explained. We find that there are gains in in- and out-of-sample forecast of consumption and inflation if term structure information is used in a time varying hybrid prices of risk setting. In-sample yield forecast are better in models with non-stationary shocks for the period 1982-1988. After this period, time varying market price of risk models provide better in-sample forecasts. For the period 2005-2008, out of sample forecast of consumption and inflation are better if term structure information is incorporated in the DSGE model but yields are better forecasted by a pure macro DSGE model.