Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.

PURPOSE: Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. PATIENTS AND METHODS: Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. RESULTS: In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. CONCLUSION: Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

Personalized touristic routes implementing semantic web on GIS

Nowadays, when a user is planning a touristic route is very difficult to find out which are the best places to visit. The user has to choose considering his/her preferences due to the great quantity of information it is possible to find in the web and taking into account it is necessary to do a selection, within small time because there is a limited time to do a trip. In Itiner@ project, we aim to implement Semantic Web technology combined with Geographic Information Systems in order to offer personalized touristic routes around a region based on user preferences and time situation. Using ontologies it is possible to link, structure, share data and obtain the result more suitable for user's preferences and actual situation with less time and more precisely than without ontologies. To achieve these objectives we propose a web page combining a GIS server and a touristic ontology. As a step further, we also study how to extend this technology on mobile devices due to the raising interest and technological progress of these devices and location-based services, which allows the user to have all the route information on the hand when he/she does a touristic trip. We design a little application in order to apply the combination of GIS and Semantic Web in a mobile device.

Progression of auditory discrimination based on neural decoding predicts awakening from coma.

Auditory evoked potentials are informative of intact cortical functions of comatose patients. The integrity of auditory functions evaluated using mismatch negativity paradigms has been associated with their chances of survival. However, because auditory discrimination is assessed at various delays after coma onset, it is still unclear whether this impairment depends on the time of the recording. We hypothesized that impairment in auditory discrimination capabilities is indicative of coma progression, rather than of the comatose state itself and that rudimentary auditory discrimination remains intact during acute stages of coma. We studied 30 post-anoxic comatose patients resuscitated from cardiac arrest and five healthy, age-matched controls. Using a mismatch negativity paradigm, we performed two electroencephalography recordings with a standard 19-channel clinical montage: the first within 24 h after coma onset and under mild therapeutic hypothermia, and the second after 1 day and under normothermic conditions. We analysed electroencephalography responses based on a multivariate decoding algorithm that automatically quantifies neural discrimination at the single patient level. Results showed high average decoding accuracy in discriminating sounds both for control subjects and comatose patients. Importantly, accurate decoding was largely independent of patients' chance of survival. However, the progression of auditory discrimination between the first and second recordings was informative of a patient's chance of survival. A deterioration of auditory discrimination was observed in all non-survivors (equivalent to 100% positive predictive value for survivors). We show, for the first time, evidence of intact auditory processing even in comatose patients who do not survive and that progression of sound discrimination over time is informative of a patient's chance of survival. Tracking auditory discrimination in comatose patients could provide new insight to the chance of awakening in a quantitative and automatic fashion during early stages of coma.

Oseltamivir in seasonal, avian H5N1 and pandemic 2009 A/H1N1 influenza: pharmacokinetic and pharmacodynamic characteristics.

Oseltamivir is the ester-type prodrug of the neuraminidase inhibitor oseltamivir carboxylate. It has been shown to be an effective treatment for both seasonal influenza and the recent pandemic 2009 A/H1N1 influenza, reducing both the duration and severity of the illness. It is also effective when used preventively. This review aims to describe the current knowledge of the pharmacokinetic and pharmacodynamic characteristics of this agent, and to address the issue of possible therapeutic drug monitoring. According to the currently available literature, the pharmacokinetics of oseltamivir carboxylate after oral administration of oseltamivir are characterized by mean ± SD bioavailability of 79 ± 12%, apparent clearance of 25.3 ± 7.0 L/h, an elimination half-life of 7.4 ± 2.5 hours and an apparent terminal volume of distribution of 267 ± 122 L. A maximum plasma concentration of 342 ± 83 μg/L, a time to reach the maximum plasma concentration of 4.2 ± 1.1 hours, a trough plasma concentration of 168 ± 32 μg/L and an area under the plasma concentration-time curve from 0 to 24 hours of 6110 ± 1330 μg · h/L for a 75 mg twice-daily regimen were derived from literature data. The apparent clearance is highly correlated with renal function, hence the dosage needs to be adjusted in proportion to the glomerular filtration rate. Interpatient variability is moderate (28% in apparent clearance and 46% in the apparent central volume of distribution); there is no indication of significant erratic or limited absorption in given patient subgroups. The in vitro pharmacodynamics of oseltamivir carboxylate reveal wide variation in the concentration producing 50% inhibition of influenza A and B strains (range 0.17-44 μg/L). A formal correlation between systemic exposure to oseltamivir carboxylate and clinical antiviral activity or tolerance in influenza patients has not yet been demonstrated; thus no formal therapeutic or toxic range can be proposed. The pharmacokinetic parameters of oseltamivir carboxylate after oseltamivir administration (bioavailability, apparent clearance and the volume of distribution) are fairly predictable in healthy subjects, with little interpatient variability outside the effect of renal function in all patients and bodyweight in children. Thus oseltamivir carboxylate exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics. However, there is a lack of clinical study data on naturally infected patients. In addition, the therapeutic margin of oseltamivir carboxylate is poorly defined. The usefulness of systematic therapeutic drug monitoring in patients therefore appears to be questionable; however, studies are still needed to extend the knowledge to particular subgroups of patients or dosage regimens.

Reduced learning ability as a consequence of evolutionary adaptation to nutritional stress in Drosophila melanogaster

1. Dietary conditions affect cognitive abilities of many species, but it is unclear to what extent this physiological effect translates into an evolutionary relationship. 2. A reduction of competitive ability under nutritional stress has been reported as a correlated response to selection for learning ability in Drosophila melanogaster. Here we test whether the reverse holds as well, i.e. whether an evolutionary adaptation to poor food conditions leads to a decrease in learning capacities. 3. Populations of D. melanogaster were: (i) not subject to selection (control), (ii) selected for improved learning ability, (iii) selected for survival and fast development on poor food, or (iv) subject to both selection regimes. 4. There was no detectable response to selection for learning ability. 5. Selection on poor food led to higher survival, faster development and smaller adult size as a direct response, and to reduced learning ability as a correlated response. This study supports the hypothesis that adaptation to poor nutrition is likely to trade off with the evolution of improved learning ability.

Efecte de la recurrència dels incendis sobre la vegetació i el sòl a les zons de bosc del Macizo Central Ourensano

En els últims 30 anys, el número d’incendis patits a Galicia han augmentat de manera important. En el Massís Central Ourensano l’home ha utilitzat el foc com a eina de gestió forestal per tal de permetre pasturar al bestiar i per tal de recuperar terres per a pastos i culius. Aquesta pràctica ha generat grans extensions de matollar sec europeu on hi hauria d’haver formacions boscoses. Partim de la necessitat de recuperar zones de bosc i ecosistema original i per això mesurem el comportament de les diferents espècies que trobem al matollar y al bosc en aquestes altituds davant la pertorbació que suposen els incendis recurrents. Per realitzar això s’ha mostrejat la vegetació de zones cremades en moments diferents o repetides vegades, mesurant superfície i alçades així com nombre d’individus de cada espècie. També s’han analitzat perfils del sòl per tal de conèixer amb més detall les característiques de cada zona. S’ha observat mitjançant el mostreig com per a la recuperació del matollar el factor determinant és el temps, encara que no trobem un sòl de bona qualitat i profund, en una mitjana de 8 anys trobem un matollar ben desenvolupat amb una bona diversitat d’espècies i grau de cobertura. En canvi, per tal d’arribar a un estat de la successió vegetal on trobem un bosc és necessari que existeixin comunitats arbòries a prop per tal de que arribin individus al matollar desenvolupat. Cal aleshores treballar en l’educació de la població i en la cerca d’alternatives a la gestió forestal vigent, donant èmfasi en la valoració econòmica dels ecosistemes en bon estat i facilitant que aquest bon estat proporcioni beneficis a la població local. Per això cal generar una infraestructura per atraure un turisme rural respectuós amb el medi al mateix temps que es duen altres iniciatives com la implantació de centrals de biomassa als pobles que puguin proporcionar calefacció o aigua calenta. Generant llocs de feina i estalvis a la població d’una zona on l’economia encara es basa potencialment en la ramaderia. Al mateix temps l’esforç monetari dedicat a les plantacions ha de dedicar-se a generar espais al territori amb espècies autòctones com el roure en aquells matollars que presentin condicions adients per a recuperar el bosc.

Critical ruptures in a bundle of slowly relaxing fibers

We study the damage enhanced creep rupture of disordered materials by means of a fiber bundle model. Broken fibers undergo a slow stress relaxation modeled by a Maxwell element whose stress exponent m can vary in a broad range. Under global load sharing we show that due to the strength disorder of fibers, the lifetime ʧ of the bundle has sample-to-sample fluctuations characterized by a log-normal distribution independent of the type of disorder. We determine the Monkman-Grant relation of the model and establish a relation between the rupture life tʄ and the characteristic time tm of the intermediate creep regime of the bundle where the minimum strain rate is reached, making possible reliable estimates of ʧ from short term measurements. Approaching macroscopic failure, the deformation rate has a finite time power law singularity whose exponent is a decreasing function of m. On the microlevel the distribution of waiting times is found to have a power law behavior with m-dependent exponents different below and above the critical load of the bundle. Approaching the critical load from above, the cutoff value of the distributions has a power law divergence whose exponent coincides with the stress exponent of Maxwell elements

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

OBJECTIVE: HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. METHODS: In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. RESULTS: Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. CONCLUSION: Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization.

Characterization and simulation of a CdTe detector for use in PET

The Voxel Imaging PET (VIP) Path nder project got the 4 year European Research Council FP7 grant in 2010 to prove the feasibility of using CdTe detectors in a novel conceptual design of PET scanner. The work presented in this thesis is a part of the VIP project and consists of, on the one hand, the characterization of a CdTe detector in terms of energy resolution and coincidence time resolution and, on the other hand, the simulation of the setup with the single detector in order to extend the results to the full PET scanner. An energy resolution of 0.98% at 511 keV with a bias voltage of 1000 V/mm has been measured at low temperature T=-8 ºC. The coincidence time distribution of two twin detectors has been found to be as low as 6 ns FWHM for events with energies above 500 keV under the same temperature and bias conditions. The measured energy and time resolution values are compatible with similar ndings available in the literature and prove the excellent potential of CdTe for PET applications. This results have been presented in form of a poster contribution at the IEEE NSS/MIC & RTSD 2011 conference in October 2011 in Valencia and at the iWoRID 2012 conference in July 2012 in Coimbra, Portugal. They have been also submitted for publication to "Journal of Instrumentation (JINST)" in September 2012.

An Examination of Iowa's School Liaison Program, 2001

In the early 1990’s the Chief Juvenile Court Officers (JCOs) and other key players desired to provide services, such as school support, family support, and community support to both juvenile court and at-risk youths within the school setting. With strong support from both Iowa’s Attorney General and Governor the Iowa State Legislature first appropriated funds for school liaisons in 1994. The liaison program is currently funded with 75 percent state dollars appropriated to the Department of Human Services and a minimum of 25 percent match from the local school districts. In some cases the schools do not actually match funds with “school money,” rather they may utilize community money from other sources, such as the local decategorization process. In 1994, the state legislature funded this effort at $400,000. Since that time the amount has grown to more than $3,000,000. In the early years there were just a handful of liaisons working in a few school districts, but by the beginning of the 2000-2001 school year there were 304 schools served by 147 liaisons. The cost per liaison, including salary and benefits, was estimated at approximately $34,324 including both the DHS and school contributions. It was a desire of the Chief JCOs to place the liaisons under the school districts and thus allow them to be independent of the juvenile court. Agreements were developed between the schools and juvenile court regarding employee status, funding, information sharing, and other such issues.

The curvature of the conical intersection seam: an approximate second-order analysis

We present a method for analyzing the curvature (second derivatives) of the conical intersection hyperline at an optimized critical point. Our method uses the projected Hessians of the degenerate states after elimination of the two branching space coordinates, and is equivalent to a frequency calculation on a single Born-Oppenheimer potential-energy surface. Based on the projected Hessians, we develop an equation for the energy as a function of a set of curvilinear coordinates where the degeneracy is preserved to second order (i.e., the conical intersection hyperline). The curvature of the potential-energy surface in these coordinates is the curvature of the conical intersection hyperline itself, and thus determines whether one has a minimum or saddle point on the hyperline. The equation used to classify optimized conical intersection points depends in a simple way on the first- and second-order degeneracy splittings calculated at these points. As an example, for fulvene, we show that the two optimized conical intersection points of C2v symmetry are saddle points on the intersection hyperline. Accordingly, there are further intersection points of lower energy, and one of C2 symmetry - presented here for the first time - is found to be the global minimum in the intersection space

L'intégration de la sexualité en consultation gynécologique : discordances entre les perceptions des femmes et celles des gynécologues.

Dès les années 2000, l'Office Fédéral de la Santé Publique recommande aux médecins de premier recours, dont les gynécologues, d'aborder activement la sexualité en consultation, en raison notamment de l'augmentation des infections sexuellement transmissibles asymptomatiques (1ST). Dans le même sens, comme le montrent nombre d'études, plus de 70% des patientes souhaiteraient être interrogées au sujet de leur sexualité en consultation gynécologique. Or, il semble que peu de médecins intègrent systématiquement des questions de sexualité dans leur anamnèse. La revue de la littérature relève que les recherches réalisées à ce jour ont été menées principalement à l'aide de questionnaire selon une perspective naturaliste, qui étudie la sexualité de manière décontextualisée et qui la conçoit comme un invariant biologique et par conséquent universel. Notre objectif est de saisir en profondeur les perceptions et le vécu des gynécologues et des femmes, face à l'intégration de la sexualité en consultation gynécologique. Nous avons adopté une perspective critique en psychologie de la santé (Santiago-Delefosse & Chamberlain, 2008 ; Murray, 2004a ; Lyons & Chamberlain, 2006) qui permet de privilégier d'une part, l'étude de la signification que les sujets donnent à la sexualité dans leur contexte socio-historique et, d'autre part, une vision de l'être humain comprenant des dimensions corporelles, psychologiques et sociétales (Santiago-Delefosse, 2011). Pour ce faire, nous avons utilisé un dispositif de méthodes mixtes en deux phases. Dans la première phase, nous avons mené 21 entretiens semi directifs avec des gynécologues hommes et femmes. Puis, nous avons réalisé 3 groupes focalisés (N=16) avec des femmes âgées de 23 à 65 ans. La seconde phase a consisté à créer un questionnaire, élaboré à partir des résultats de la première phase, afin d'élargir l'expérience de l'intégration de la sexualité en consultation, à une population plus diversifiée de femmes (N=421). Les données récoltées par le biais de ces trois méthodes nous ont permis d'esquisser un modèle présentant les processus en jeu dans la situation de non intégration de la sexualité en consultation gynécologique. Celui-ci relève non seulement des lacunes dans le cursus universitaire de médecine en matière de sexualité, mais également d'importantes discordances entre les gynécologues et les femmes interviewés concernant le rôle du gynécologue, la perception de l'intime, la perception d'introduire le sujet de la sexualité en consultation, ainsi que de la définition même de la sexualité. Nos résultats ouvrent sur des perspectives pratiques pour la consultation gynécologique, ainsi que sur des pistes pour des recherches futures dans l'étude de la sexualité, selon une perspective plus intégrative. -- Since the 2000's, the Swiss Federal Office of Public Health recommended primary care physicians, including gynaecologists, to actively address sexuality issues in consultation, namely because of the increasing incidence of Sexually Transmitted Infections (STI). In line with this, studies have shown that more than 70% of patients would like to be asked about their sexuality by their gynaecologist. However, physicians do not take systematically sexual histories from their patients. Literature in the field has highlighted that most research has been restricted to using questionnaires following a naturalist theoretical perspective according to which sexual behaviour is defined as biologically invariant, hence, universal. Our objective is to deepen understand perceptions from gynaecologists and women with regard to the integration of sexuality in consultations. A critical health psychology approach allows us to consider on the one hand sexuality as a construct that is inseparable from a given socio-historical context. On the other hand, this approach takes into consideration an embodied, social and psychological definition of human beings. Therefore, we used a mixed methods design that included two main research steps : First, we conducted 21 semi-structured interviews with male and female gynaecologists. In this phase, we also led 3 focus groups made up of 16 women aged from 21 to 65. Second, a survey was implemented (N= 421) based on findings stemming from the first phase. This allowed us to further analyse experiences on the integration of sexuality and to extend findings to a more diversified population of women. The data analysis allowed us to create a model that highlights the processes involved in the non integration of sexuality during gynaecological consultation. It shows a lack of training in sexology within medical programs. Moreover, it emphasises the mismatches on perceptions between gynaecologists and women concerning the gynaecologist's role ; intimacy, the issue of whether introducing sexuality topics, and finally, on the actual definition of sexuality itself. Our findings open new research perspectives for the study of sexuality by proposing a more integrative approach. They also provide practical and clinical perspectives concerning consultations in gynaecology.

Dose reconstruction in the context of tomotherapy

In vivo dosimetry is a way to verify the radiation dose delivered to the patient in measuring the dose generally during the first fraction of the treatment. It is the only dose delivery control based on a measurement performed during the treatment. In today's radiotherapy practice, the dose delivered to the patient is planned using 3D dose calculation algorithms and volumetric images representing the patient. Due to the high accuracy and precision necessary in radiation treatments, national and international organisations like ICRU and AAPM recommend the use of in vivo dosimetry. It is also mandatory in some countries like France. Various in vivo dosimetry methods have been developed during the past years. These methods are point-, line-, plane- or 3D dose controls. A 3D in vivo dosimetry provides the most information about the dose delivered to the patient, with respect to ID and 2D methods. However, to our knowledge, it is generally not routinely applied to patient treatments yet. The aim of this PhD thesis was to determine whether it is possible to reconstruct the 3D delivered dose using transmitted beam measurements in the context of narrow beams. An iterative dose reconstruction method has been described and implemented. The iterative algorithm includes a simple 3D dose calculation algorithm based on the convolution/superposition principle. The methodology was applied to narrow beams produced by a conventional 6 MV linac. The transmitted dose was measured using an array of ion chambers, as to simulate the linear nature of a tomotherapy detector. We showed that the iterative algorithm converges quickly and reconstructs the dose within a good agreement (at least 3% / 3 mm locally), which is inside the 5% recommended by the ICRU. Moreover it was demonstrated on phantom measurements that the proposed method allows us detecting some set-up errors and interfraction geometry modifications. We also have discussed the limitations of the 3D dose reconstruction for dose delivery error detection. Afterwards, stability tests of the tomotherapy MVCT built-in onboard detector was performed in order to evaluate if such a detector is suitable for 3D in-vivo dosimetry. The detector showed stability on short and long terms comparable to other imaging devices as the EPIDs, also used for in vivo dosimetry. Subsequently, a methodology for the dose reconstruction using the tomotherapy MVCT detector is proposed in the context of static irradiations. This manuscript is composed of two articles and a script providing further information related to this work. In the latter, the first chapter introduces the state-of-the-art of in vivo dosimetry and adaptive radiotherapy, and explains why we are interested in performing 3D dose reconstructions. In chapter 2 a dose calculation algorithm implemented for this work is reviewed with a detailed description of the physical parameters needed for calculating 3D absorbed dose distributions. The tomotherapy MVCT detector used for transit measurements and its characteristics are described in chapter 3. Chapter 4 contains a first article entitled '3D dose reconstruction for narrow beams using ion chamber array measurements', which describes the dose reconstruction method and presents tests of the methodology on phantoms irradiated with 6 MV narrow photon beams. Chapter 5 contains a second article 'Stability of the Helical TomoTherapy HiArt II detector for treatment beam irradiations. A dose reconstruction process specific to the use of the tomotherapy MVCT detector is presented in chapter 6. A discussion and perspectives of the PhD thesis are presented in chapter 7, followed by a conclusion in chapter 8. The tomotherapy treatment device is described in appendix 1 and an overview of 3D conformai- and intensity modulated radiotherapy is presented in appendix 2. - La dosimétrie in vivo est une technique utilisée pour vérifier la dose délivrée au patient en faisant une mesure, généralement pendant la première séance du traitement. Il s'agit de la seule technique de contrôle de la dose délivrée basée sur une mesure réalisée durant l'irradiation du patient. La dose au patient est calculée au moyen d'algorithmes 3D utilisant des images volumétriques du patient. En raison de la haute précision nécessaire lors des traitements de radiothérapie, des organismes nationaux et internationaux tels que l'ICRU et l'AAPM recommandent l'utilisation de la dosimétrie in vivo, qui est devenue obligatoire dans certains pays dont la France. Diverses méthodes de dosimétrie in vivo existent. Elles peuvent être classées en dosimétrie ponctuelle, planaire ou tridimensionnelle. La dosimétrie 3D est celle qui fournit le plus d'information sur la dose délivrée. Cependant, à notre connaissance, elle n'est généralement pas appliquée dans la routine clinique. Le but de cette recherche était de déterminer s'il est possible de reconstruire la dose 3D délivrée en se basant sur des mesures de la dose transmise, dans le contexte des faisceaux étroits. Une méthode itérative de reconstruction de la dose a été décrite et implémentée. L'algorithme itératif contient un algorithme simple basé sur le principe de convolution/superposition pour le calcul de la dose. La dose transmise a été mesurée à l'aide d'une série de chambres à ionisations alignées afin de simuler la nature linéaire du détecteur de la tomothérapie. Nous avons montré que l'algorithme itératif converge rapidement et qu'il permet de reconstruire la dose délivrée avec une bonne précision (au moins 3 % localement / 3 mm). De plus, nous avons démontré que cette méthode permet de détecter certaines erreurs de positionnement du patient, ainsi que des modifications géométriques qui peuvent subvenir entre les séances de traitement. Nous avons discuté les limites de cette méthode pour la détection de certaines erreurs d'irradiation. Par la suite, des tests de stabilité du détecteur MVCT intégré à la tomothérapie ont été effectués, dans le but de déterminer si ce dernier peut être utilisé pour la dosimétrie in vivo. Ce détecteur a démontré une stabilité à court et à long terme comparable à d'autres détecteurs tels que les EPIDs également utilisés pour l'imagerie et la dosimétrie in vivo. Pour finir, une adaptation de la méthode de reconstruction de la dose a été proposée afin de pouvoir l'implémenter sur une installation de tomothérapie. Ce manuscrit est composé de deux articles et d'un script contenant des informations supplémentaires sur ce travail. Dans ce dernier, le premier chapitre introduit l'état de l'art de la dosimétrie in vivo et de la radiothérapie adaptative, et explique pourquoi nous nous intéressons à la reconstruction 3D de la dose délivrée. Dans le chapitre 2, l'algorithme 3D de calcul de dose implémenté pour ce travail est décrit, ainsi que les paramètres physiques principaux nécessaires pour le calcul de dose. Les caractéristiques du détecteur MVCT de la tomothérapie utilisé pour les mesures de transit sont décrites dans le chapitre 3. Le chapitre 4 contient un premier article intitulé '3D dose reconstruction for narrow beams using ion chamber array measurements', qui décrit la méthode de reconstruction et présente des tests de la méthodologie sur des fantômes irradiés avec des faisceaux étroits. Le chapitre 5 contient un second article intitulé 'Stability of the Helical TomoTherapy HiArt II detector for treatment beam irradiations'. Un procédé de reconstruction de la dose spécifique pour l'utilisation du détecteur MVCT de la tomothérapie est présenté au chapitre 6. Une discussion et les perspectives de la thèse de doctorat sont présentées au chapitre 7, suivies par une conclusion au chapitre 8. Le concept de la tomothérapie est exposé dans l'annexe 1. Pour finir, la radiothérapie «informationnelle 3D et la radiothérapie par modulation d'intensité sont présentées dans l'annexe 2.

Between pluralism and majoritarianism: the European Court of Human Rights on religious symbols and education

How is it possible to square the development of a consistent Europeanapproach to religious diversity with the recognition of the sometimes-conflictiveplurality of state-religion models? The Court´s support of the liberalprinciples of separation and neutrality have either been deplored by Christianconservatives as the result of European Christophobia, or celebratedby secularists as contributing to the formation of a Europe free of religion.In contrast, the present chapter argues for a differentiated approach toEuropean jurisprudence, outlining how the Court has been oscillating betweenan appealing liberal-pluralist perspective or framework, and a questionablemajoritarian one. Both perspectives are illustrated by focusing onrepresentative decisions in the area of religious education and symbols.

Iowa Sex Offender Treatment and Supervision Task Force Report to the Iowa General Assembly, January 15, 2006

Over the last several years, lawmakers have been responding to several highly publicized child abduction, assault and murder cases. While such cases remain rare in Iowa, the public debates they have generated are having far-reaching effects. Policy makers are responsible for controlling the nature of such effects. Challenges they face stem from the need to avoid primarily politically-motivated responses and the desire to make informed decisions that recognize both the strengths and the limitations of the criminal justice system as a vehicle for promoting safe and healthy families and communities. Consensus was reached by the Task Force at its first meeting that one of its standing goals is to provide nonpartisan guidance to help avoid or fix problematic sex offense policies and practices. Setting this goal was a response to the concern over what can result from elected officials’ efforts to respond to the types of sex offender-related concerns that can easily become emotionally laden and politically charged due to the universally held abhorrence of sex crimes against children. The meetings of the Task Force and the various work groups it has formed have included some spirited and perhaps emotionally charged discussions, despite the above-stated ground rule. However, as is described in the report, the Task Force’s first set of recommendations and plans for further study were approved through consensus. It is hoped that in upcoming legislative deliberations, it will be remembered that the non-legislative members of the Task Force all agreed on the recommendations contained in this report. The topics discussed in this first report from the Task Force are limited to the study issues specifically named in H.F. 619, the Task Force’s enabling legislation. However, other topics of concern were discussed by the Task Force because of their immediacy or because of their possible relationships with one or more of the Task Force’s mandated study issues. For example, it has been reported by some probation/parole officers and others that the 2000 feet rule has had a negative influence on treatment participation and supervision compliance. While such concerns were noted, the Task Force did not take it upon itself to investigate them at this time and thus broaden the agenda it was given by the General Assembly last session. As a result, the recently reinstated 2000 feet rule, the new cohabitation/child endangerment law and other issues of interest to Task Force members but not within the scope of their charge are not discussed in the body of this report. An issue of perhaps the greatest interest to most Task Force members that was not a part of their charge was a belief in the benefit of viewing Iowa’s efforts to protect children from sex crimes with as comprehensive a platform as possible. It has been suggested that much more can be done to prevent child-victim sex crimes than would be accomplished by only concentrating on what to do with offenders after a crime has occurred. To prevent child victimization, H.F. 619 policy provisions rely largely on incapacitation and future deterrent effects of increased penalties, more restrictive supervision practices and greater public awareness of the risk presented by a segment of Iowa’s known sex offenders. For some offenders, these policies will no doubt prevent future sex crimes against children, and the Task Force has begun long-term studies to look for the desired results and for ways to improve such results through better supervision tools and more effective offender treatment. Unfortunately, much of the effects from the new policies may primarily influence persons who have already committed sex offenses against minors and who have already been caught doing so. Task Force members discussed the need for a range of preventive efforts and a need to think about sex crimes against children from other than just a “reaction- to-the-offender” perspective. While this topic is not addressed in the report that follows, it was suggested that some of the Task Force’s discussions could be briefly shared through these opening comments. Along with incapacitation and deterrence, comprehensive approaches to the prevention of child-victim sex crimes would also involve making sure parents have the tools they need to detect signs of adults with sex behavior problems, to help teach their children about warning signs and to find the support they need for healthy parenting. School, faithbased and other community organizations might benefit from stronger supports and better tools they can use to more effectively promote positive youth development and the learning of respect for others, respect for boundaries and healthy relationships. All of us who have children, or who live in communities where there are children, need to understand the limitations of our justice system and the importance of our own ability to play a role in preventing sexual abuse and protecting children from sex offenders, which are often the child’s own family members. Over 1,000 incidences of child sexual abuse are confirmed or founded each year in Iowa, and most such acts take place in the child’s home or the residence of the caretaker of the child. Efforts to prevent child sexual abuse and to provide for early interventions with children and families at risk could be strategically examined and strengthened. The Sex Offender Treatment and Supervision Task Force was established to provide assistance to the General Assembly. It will respond to legislative direction for adjusting its future plans as laid out in this report. Its plans could be adjusted to broaden or narrow its scope or to assign different priority levels of effort to its current areas of study. Also, further Task Force considerations of the recommendations it has already submitted could be called for. In the meantime, it is hoped that the information and recommendations submitted through this report prove helpful.