Comparability of clinical wear measurements by optical 3D laser scanning in two different centers.

OBJECTIVE: The purpose of this study was to compare the use of different variables to measure the clinical wear of two denture tooth materials in two analysis centers. METHODS: Twelve edentulous patients were provided with full dentures. Two different denture tooth materials (experimental material and control) were placed randomly in accordance with the split-mouth design. For wear measurements, impressions were made after an adjustment phase of 1-2 weeks and after 6, 12, 18, and 24 months. The occlusal wear of the posterior denture teeth of 11 subjects was assessed in two study centers by use of plaster replicas and 3D laser-scanning methods. In both centers sequential scans of the occlusal surfaces were digitized and superimposed. Wear was described by use of four different variables. Statistical analysis was performed after log-transformation of the wear data by use of the Pearson and Lin correlation and by use of a mixed linear model. RESULTS: Mean occlusal vertical wear of the denture teeth after 24 months was between 120μm and 212μm, depending on wear variable and material. For three of the four variables, wear of the experimental material was statistically significantly less than that of the control. Comparison of the two study centers, however, revealed correlation of the wear variables was only moderate whereas strong correlation was observed among the different wear variables evaluated by each center. SIGNIFICANCE: Moderate correlation was observed for clinical wear measurements by optical 3D laser scanning in two different study centers. For the two denture tooth materials, wear measurements limited to the attrition zones led to the same qualitative assessment.

Design of a Control Slide for Cyanoacrylate Polymerization : Application to the CA-Bluestar Sequence

Casework expercience has shown that, in some cases, long exposures of surfaces subjected to cyanoacrylate (CA) fuming had detrimental effects on the subsequent application of Bluestar. This study aimed to develop a control mechanism to monitor the amount of CA deposited prior to the subsequent treatment. A control slide bearing spots of sodium hydroxide (NaOH) of known concentrations and volume was designed and validated against both scanning electron microscopy (SEM) observations and latent print examiners' assessments of the quality of the developed marks. The control slide allows one to define three levels of development that were used to monitor the Bluestar reaction on depleting footwear marks left in diluted blood. The appropriate conditions for a successful application of both CA and Bluestar were determined.

Do orthopaedic shoes improve local dynamic stability of gait? An observational study in patients with chronic foot and ankle injuries.

BACKGROUND: Complex foot and ankle fractures, such as calcaneum fractures or Lisfranc dislocations, are often associated with a poor outcome, especially in terms of gait capacity. Indeed, degenerative changes often lead to chronic pain and chronic functional limitations. Prescription footwear represents an important therapeutic tool during the rehabilitation process. Local Dynamic Stability (LDS) is the ability of locomotor system to maintain continuous walking by accommodating small perturbations that occur naturally during walking. Because it reflects the degree of control over the gait, LDS has been advocated as a relevant indicator for evaluating different conditions and pathologies. The aim of this study was to analyze changes in LDS induced by orthopaedic shoes in patients with persistent foot and ankle injuries. We hypothesised that footwear adaptation might help patients to improve gait control, which could lead to higher LDS: METHODS: Twenty-five middle-aged inpatients (5 females, 20 males) participated in the study. They were treated for chronic post-traumatic disabilities following ankle and/or foot fractures in a Swiss rehabilitation clinic. During their stay, included inpatients received orthopaedic shoes with custom-made orthoses (insoles). They performed two 30s walking trials with standard shoes and two 30s trials with orthopaedic shoes. A triaxial motion sensor recorded 3D accelerations at the lower back level. LDS was assessed by computing divergence exponents in the acceleration signals (maximal Lyapunov exponents). Pain was evaluated with Visual Analogue Scale (VAS). LDS and pain differences between the trials with standard shoes and the trials with orthopaedic shoes were assessed. RESULTS: Orthopaedic shoes significantly improved LDS in the three axes (medio-lateral: 10% relative change, paired t-test p < 0.001; vertical: 9%, p = 0.03; antero-posterior: 7%, p = 0.04). A significant decrease in pain level (VAS score -29%) was observed. CONCLUSIONS: Footwear adaptation led to pain relief and to improved foot & ankle proprioception. It is likely that that enhancement allows patients to better control foot placement. As a result, higher dynamic stability has been observed. LDS seems therefore a valuable index that could be used in early evaluation of footwear outcome in clinical settings.

LEVERAGING SANDBOX IMMERSIVE 3D VIRTUAL WORLDS TO DEVELOP DO-IT- YOURSELF TEACHING GAMES: IMPLEMENTATION TO MARKETING CASE STUDY TEACHING IN SECOND LIFE

Games are powerful and engaging. On average, one billion people spend at least 1 hour a day playing computer and videogames. This is even more true with the younger generations. Our students have become the < digital natives >, the < gamers >, the < virtual generation >. Research shows that those who are most at risk for failure in the traditional classroom setting, also spend more time than their counterparts, using video games. They might strive, given a different learning environment. Educators have the responsibility to align their teaching style to these younger generation learning styles. However, many academics resist the use of computer-assisted learning that has been "created elsewhere". This can be extrapolated to game-based teaching: even if educational games were more widely authored, their adoption would still be limited to the educators who feel a match between the authored games and their own beliefs and practices. Consequently, game-based teaching would be much more widespread if teachers could develop their own games, or at least customize them. Yet, the development and customization of teaching games are complex and costly. This research uses a design science methodology, leveraging gamification techniques, active and cooperative learning theories, as well as immersive sandbox 3D virtual worlds, to develop a method which allows management instructors to transform any off-the-shelf case study into an engaging collaborative gamified experience. This method is applied to marketing case studies, and uses the sandbox virtual world of Second Life. -- Les jeux sont puissants et motivants, En moyenne, un milliard de personnes passent au moins 1 heure par jour jouer à des jeux vidéo sur ordinateur. Ceci se vérifie encore plus avec les jeunes générations, Nos étudiants sont nés à l'ère du numérique, certains les appellent des < gamers >, d'autres la < génération virtuelle >. Les études montrent que les élèves qui se trouvent en échec scolaire dans les salles de classes traditionnelles, passent aussi plus de temps que leurs homologues à jouer à des jeux vidéo. lls pourraient potentiellement briller, si on leur proposait un autre environnement d'apprentissage. Les enseignants ont la responsabilité d'adapter leur style d'enseignement aux styles d'apprentissage de ces jeunes générations. Toutefois, de nombreux professeurs résistent lorsqu'il s'agit d'utiliser des contenus d'apprentissage assisté par ordinateur, développés par d'autres. Ceci peut être extrapolé à l'enseignement par les jeux : même si un plus grand nombre de jeux éducatifs était créé, leur adoption se limiterait tout de même aux éducateurs qui perçoivent une bonne adéquation entre ces jeux et leurs propres convictions et pratiques. Par conséquent, I'enseignement par les jeux serait bien plus répandu si les enseignants pouvaient développer leurs propres jeux, ou au moins les customiser. Mais le développement de jeux pédagogiques est complexe et coûteux. Cette recherche utilise une méthodologie Design Science pour développer, en s'appuyant sur des techniques de ludification, sur les théories de pédagogie active et d'apprentissage coopératif, ainsi que sur les mondes virtuels immersifs < bac à sable > en 3D, une méthode qui permet aux enseignants et formateurs de management, de transformer n'importe quelle étude de cas, provenant par exemple d'une centrale de cas, en une expérience ludique, collaborative et motivante. Cette méthode est appliquée aux études de cas Marketing dans le monde virtuel de Second Life.

Design, data management, and population baseline characteristics of the PERFORM magnetic resonance imaging project.

Quantitative information from magnetic resonance imaging (MRI) may substantiate clinical findings and provide additional insight into the mechanism of clinical interventions in therapeutic stroke trials. The PERFORM study is exploring the efficacy of terutroban versus aspirin for secondary prevention in patients with a history of ischemic stroke. We report on the design of an exploratory longitudinal MRI follow-up study that was performed in a subgroup of the PERFORM trial. An international multi-centre longitudinal follow-up MRI study was designed for different MR systems employing safety and efficacy readouts: new T2 lesions, new DWI lesions, whole brain volume change, hippocampal volume change, changes in tissue microstructure as depicted by mean diffusivity and fractional anisotropy, vessel patency on MR angiography, and the presence of and development of new microbleeds. A total of 1,056 patients (men and women ≥ 55 years) were included. The data analysis included 3D reformation, image registration of different contrasts, tissue segmentation, and automated lesion detection. This large international multi-centre study demonstrates how new MRI readouts can be used to provide key information on the evolution of cerebral tissue lesions and within the macrovasculature after atherothrombotic stroke in a large sample of patients.

Development of a 3D very high-resolution seismic reflection system for lacustrine settings - a case study over a thrust fault zone in Lake Geneva

Un système efficace de sismique tridimensionnelle (3-D) haute-résolution adapté à des cibles lacustres de petite échelle a été développé. Dans le Lac Léman, près de la ville de Lausanne, en Suisse, des investigations récentes en deux dimension (2-D) ont mis en évidence une zone de faille complexe qui a été choisie pour tester notre système. Les structures observées incluent une couche mince (<40 m) de sédiments quaternaires sub-horizontaux, discordants sur des couches tertiaires de molasse pentées vers le sud-est. On observe aussi la zone de faille de « La Paudèze » qui sépare les unités de la Molasse du Plateau de la Molasse Subalpine. Deux campagnes 3-D complètes, d?environ d?un kilomètre carré, ont été réalisées sur ce site de test. La campagne pilote (campagne I), effectuée en 1999 pendant 8 jours, a couvert 80 profils en utilisant une seule flûte. Pendant la campagne II (9 jours en 2001), le nouveau système trois-flûtes, bien paramétrés pour notre objectif, a permis l?acquisition de données de très haute qualité sur 180 lignes CMP. Les améliorations principales incluent un système de navigation et de déclenchement de tirs grâce à un nouveau logiciel. Celui-ci comprend un contrôle qualité de la navigation du bateau en temps réel utilisant un GPS différentiel (dGPS) à bord et une station de référence près du bord du lac. De cette façon, les tirs peuvent être déclenchés tous les 5 mètres avec une erreur maximale non-cumulative de 25 centimètres. Tandis que pour la campagne I la position des récepteurs de la flûte 48-traces a dû être déduite à partir des positions du bateau, pour la campagne II elle ont pu être calculées précisément (erreur <20 cm) grâce aux trois antennes dGPS supplémentaires placées sur des flotteurs attachés à l?extrémité de chaque flûte 24-traces. Il est maintenant possible de déterminer la dérive éventuelle de l?extrémité des flûtes (75 m) causée par des courants latéraux ou de petites variations de trajet du bateau. De plus, la construction de deux bras télescopiques maintenant les trois flûtes à une distance de 7.5 m les uns des autres, qui est la même distance que celle entre les lignes naviguées de la campagne II. En combinaison avec un espacement de récepteurs de 2.5 m, la dimension de chaque «bin» de données 3-D de la campagne II est de 1.25 m en ligne et 3.75 m latéralement. L?espacement plus grand en direction « in-line » par rapport à la direction «cross-line» est justifié par l?orientation structurale de la zone de faille perpendiculaire à la direction «in-line». L?incertitude sur la navigation et le positionnement pendant la campagne I et le «binning» imprécis qui en résulte, se retrouve dans les données sous forme d?une certaine discontinuité des réflecteurs. L?utilisation d?un canon à air à doublechambre (qui permet d?atténuer l?effet bulle) a pu réduire l?aliasing observé dans les sections migrées en 3-D. Celui-ci était dû à la combinaison du contenu relativement haute fréquence (<2000 Hz) du canon à eau (utilisé à 140 bars et à 0.3 m de profondeur) et d?un pas d?échantillonnage latéral insuffisant. Le Mini G.I 15/15 a été utilisé à 80 bars et à 1 m de profondeur, est mieux adapté à la complexité de la cible, une zone faillée ayant des réflecteurs pentés jusqu?à 30°. Bien que ses fréquences ne dépassent pas les 650 Hz, cette source combine une pénétration du signal non-aliasé jusqu?à 300 m dans le sol (par rapport au 145 m pour le canon à eau) pour une résolution verticale maximale de 1.1 m. Tandis que la campagne I a été acquise par groupes de plusieurs lignes de directions alternées, l?optimisation du temps d?acquisition du nouveau système à trois flûtes permet l?acquisition en géométrie parallèle, ce qui est préférable lorsqu?on utilise une configuration asymétrique (une source et un dispositif de récepteurs). Si on ne procède pas ainsi, les stacks sont différents selon la direction. Toutefois, la configuration de flûtes, plus courtes que pour la compagne I, a réduit la couverture nominale, la ramenant de 12 à 6. Une séquence classique de traitement 3-D a été adaptée à l?échantillonnage à haute fréquence et elle a été complétée par deux programmes qui transforment le format non-conventionnel de nos données de navigation en un format standard de l?industrie. Dans l?ordre, le traitement comprend l?incorporation de la géométrie, suivi de l?édition des traces, de l?harmonisation des «bins» (pour compenser l?inhomogénéité de la couverture due à la dérive du bateau et de la flûte), de la correction de la divergence sphérique, du filtrage passe-bande, de l?analyse de vitesse, de la correction DMO en 3-D, du stack et enfin de la migration 3-D en temps. D?analyses de vitesse détaillées ont été effectuées sur les données de couverture 12, une ligne sur deux et tous les 50 CMP, soit un nombre total de 600 spectres de semblance. Selon cette analyse, les vitesses d?intervalles varient de 1450-1650 m/s dans les sédiments non-consolidés et de 1650-3000 m/s dans les sédiments consolidés. Le fait que l?on puisse interpréter plusieurs horizons et surfaces de faille dans le cube, montre le potentiel de cette technique pour une interprétation tectonique et géologique à petite échelle en trois dimensions. On distingue cinq faciès sismiques principaux et leurs géométries 3-D détaillées sur des sections verticales et horizontales: les sédiments lacustres (Holocène), les sédiments glacio-lacustres (Pléistocène), la Molasse du Plateau, la Molasse Subalpine de la zone de faille (chevauchement) et la Molasse Subalpine au sud de cette zone. Les couches de la Molasse du Plateau et de la Molasse Subalpine ont respectivement un pendage de ~8° et ~20°. La zone de faille comprend de nombreuses structures très déformées de pendage d?environ 30°. Des tests préliminaires avec un algorithme de migration 3-D en profondeur avant sommation et à amplitudes préservées démontrent que la qualité excellente des données de la campagne II permet l?application de telles techniques à des campagnes haute-résolution. La méthode de sismique marine 3-D était utilisée jusqu?à présent quasi-exclusivement par l?industrie pétrolière. Son adaptation à une échelle plus petite géographiquement mais aussi financièrement a ouvert la voie d?appliquer cette technique à des objectifs d?environnement et du génie civil.<br/><br/>An efficient high-resolution three-dimensional (3-D) seismic reflection system for small-scale targets in lacustrine settings was developed. In Lake Geneva, near the city of Lausanne, Switzerland, past high-resolution two-dimensional (2-D) investigations revealed a complex fault zone (the Paudèze thrust zone), which was subsequently chosen for testing our system. Observed structures include a thin (<40 m) layer of subhorizontal Quaternary sediments that unconformably overlie southeast-dipping Tertiary Molasse beds and the Paudèze thrust zone, which separates Plateau and Subalpine Molasse units. Two complete 3-D surveys have been conducted over this same test site, covering an area of about 1 km2. In 1999, a pilot survey (Survey I), comprising 80 profiles, was carried out in 8 days with a single-streamer configuration. In 2001, a second survey (Survey II) used a newly developed three-streamer system with optimized design parameters, which provided an exceptionally high-quality data set of 180 common midpoint (CMP) lines in 9 days. The main improvements include a navigation and shot-triggering system with in-house navigation software that automatically fires the gun in combination with real-time control on navigation quality using differential GPS (dGPS) onboard and a reference base near the lake shore. Shots were triggered at 5-m intervals with a maximum non-cumulative error of 25 cm. Whereas the single 48-channel streamer system of Survey I requires extrapolation of receiver positions from the boat position, for Survey II they could be accurately calculated (error <20 cm) with the aid of three additional dGPS antennas mounted on rafts attached to the end of each of the 24- channel streamers. Towed at a distance of 75 m behind the vessel, they allow the determination of feathering due to cross-line currents or small course variations. Furthermore, two retractable booms hold the three streamers at a distance of 7.5 m from each other, which is the same distance as the sail line interval for Survey I. With a receiver spacing of 2.5 m, the bin dimension of the 3-D data of Survey II is 1.25 m in in-line direction and 3.75 m in cross-line direction. The greater cross-line versus in-line spacing is justified by the known structural trend of the fault zone perpendicular to the in-line direction. The data from Survey I showed some reflection discontinuity as a result of insufficiently accurate navigation and positioning and subsequent binning errors. Observed aliasing in the 3-D migration was due to insufficient lateral sampling combined with the relatively high frequency (<2000 Hz) content of the water gun source (operated at 140 bars and 0.3 m depth). These results motivated the use of a double-chamber bubble-canceling air gun for Survey II. A 15 / 15 Mini G.I air gun operated at 80 bars and 1 m depth, proved to be better adapted for imaging the complexly faulted target area, which has reflectors dipping up to 30°. Although its frequencies do not exceed 650 Hz, this air gun combines a penetration of non-aliased signal to depths of 300 m below the water bottom (versus 145 m for the water gun) with a maximum vertical resolution of 1.1 m. While Survey I was shot in patches of alternating directions, the optimized surveying time of the new threestreamer system allowed acquisition in parallel geometry, which is preferable when using an asymmetric configuration (single source and receiver array). Otherwise, resulting stacks are different for the opposite directions. However, the shorter streamer configuration of Survey II reduced the nominal fold from 12 to 6. A 3-D conventional processing flow was adapted to the high sampling rates and was complemented by two computer programs that format the unconventional navigation data to industry standards. Processing included trace editing, geometry assignment, bin harmonization (to compensate for uneven fold due to boat/streamer drift), spherical divergence correction, bandpass filtering, velocity analysis, 3-D DMO correction, stack and 3-D time migration. A detailed semblance velocity analysis was performed on the 12-fold data set for every second in-line and every 50th CMP, i.e. on a total of 600 spectra. According to this velocity analysis, interval velocities range from 1450-1650 m/s for the unconsolidated sediments and from 1650-3000 m/s for the consolidated sediments. Delineation of several horizons and fault surfaces reveal the potential for small-scale geologic and tectonic interpretation in three dimensions. Five major seismic facies and their detailed 3-D geometries can be distinguished in vertical and horizontal sections: lacustrine sediments (Holocene) , glaciolacustrine sediments (Pleistocene), Plateau Molasse, Subalpine Molasse and its thrust fault zone. Dips of beds within Plateau and Subalpine Molasse are ~8° and ~20°, respectively. Within the fault zone, many highly deformed structures with dips around 30° are visible. Preliminary tests with 3-D preserved-amplitude prestack depth migration demonstrate that the excellent data quality of Survey II allows application of such sophisticated techniques even to high-resolution seismic surveys. In general, the adaptation of the 3-D marine seismic reflection method, which to date has almost exclusively been used by the oil exploration industry, to a smaller geographical as well as financial scale has helped pave the way for applying this technique to environmental and engineering purposes.<br/><br/>La sismique réflexion est une méthode d?investigation du sous-sol avec un très grand pouvoir de résolution. Elle consiste à envoyer des vibrations dans le sol et à recueillir les ondes qui se réfléchissent sur les discontinuités géologiques à différentes profondeurs et remontent ensuite à la surface où elles sont enregistrées. Les signaux ainsi recueillis donnent non seulement des informations sur la nature des couches en présence et leur géométrie, mais ils permettent aussi de faire une interprétation géologique du sous-sol. Par exemple, dans le cas de roches sédimentaires, les profils de sismique réflexion permettent de déterminer leur mode de dépôt, leurs éventuelles déformations ou cassures et donc leur histoire tectonique. La sismique réflexion est la méthode principale de l?exploration pétrolière. Pendant longtemps on a réalisé des profils de sismique réflexion le long de profils qui fournissent une image du sous-sol en deux dimensions. Les images ainsi obtenues ne sont que partiellement exactes, puisqu?elles ne tiennent pas compte de l?aspect tridimensionnel des structures géologiques. Depuis quelques dizaines d?années, la sismique en trois dimensions (3-D) a apporté un souffle nouveau à l?étude du sous-sol. Si elle est aujourd?hui parfaitement maîtrisée pour l?imagerie des grandes structures géologiques tant dans le domaine terrestre que le domaine océanique, son adaptation à l?échelle lacustre ou fluviale n?a encore fait l?objet que de rares études. Ce travail de thèse a consisté à développer un système d?acquisition sismique similaire à celui utilisé pour la prospection pétrolière en mer, mais adapté aux lacs. Il est donc de dimension moindre, de mise en oeuvre plus légère et surtout d?une résolution des images finales beaucoup plus élevée. Alors que l?industrie pétrolière se limite souvent à une résolution de l?ordre de la dizaine de mètres, l?instrument qui a été mis au point dans le cadre de ce travail permet de voir des détails de l?ordre du mètre. Le nouveau système repose sur la possibilité d?enregistrer simultanément les réflexions sismiques sur trois câbles sismiques (ou flûtes) de 24 traces chacun. Pour obtenir des données 3-D, il est essentiel de positionner les instruments sur l?eau (source et récepteurs des ondes sismiques) avec une grande précision. Un logiciel a été spécialement développé pour le contrôle de la navigation et le déclenchement des tirs de la source sismique en utilisant des récepteurs GPS différentiel (dGPS) sur le bateau et à l?extrémité de chaque flûte. Ceci permet de positionner les instruments avec une précision de l?ordre de 20 cm. Pour tester notre système, nous avons choisi une zone sur le Lac Léman, près de la ville de Lausanne, où passe la faille de « La Paudèze » qui sépare les unités de la Molasse du Plateau et de la Molasse Subalpine. Deux campagnes de mesures de sismique 3-D y ont été réalisées sur une zone d?environ 1 km2. Les enregistrements sismiques ont ensuite été traités pour les transformer en images interprétables. Nous avons appliqué une séquence de traitement 3-D spécialement adaptée à nos données, notamment en ce qui concerne le positionnement. Après traitement, les données font apparaître différents faciès sismiques principaux correspondant notamment aux sédiments lacustres (Holocène), aux sédiments glacio-lacustres (Pléistocène), à la Molasse du Plateau, à la Molasse Subalpine de la zone de faille et la Molasse Subalpine au sud de cette zone. La géométrie 3-D détaillée des failles est visible sur les sections sismiques verticales et horizontales. L?excellente qualité des données et l?interprétation de plusieurs horizons et surfaces de faille montrent le potentiel de cette technique pour les investigations à petite échelle en trois dimensions ce qui ouvre des voies à son application dans les domaines de l?environnement et du génie civil.

Prospective motion correction of 3D echo-planar imaging data for functional MRI using optical tracking.

We evaluated the performance of an optical camera based prospective motion correction (PMC) system in improving the quality of 3D echo-planar imaging functional MRI data. An optical camera and external marker were used to dynamically track the head movement of subjects during fMRI scanning. PMC was performed by using the motion information to dynamically update the sequence's RF excitation and gradient waveforms such that the field-of-view was realigned to match the subject's head movement. Task-free fMRI experiments on five healthy volunteers followed a 2×2×3 factorial design with the following factors: PMC on or off; 3.0mm or 1.5mm isotropic resolution; and no, slow, or fast head movements. Visual and motor fMRI experiments were additionally performed on one of the volunteers at 1.5mm resolution comparing PMC on vs PMC off for no and slow head movements. Metrics were developed to quantify the amount of motion as it occurred relative to k-space data acquisition. The motion quantification metric collapsed the very rich camera tracking data into one scalar value for each image volume that was strongly predictive of motion-induced artifacts. The PMC system did not introduce extraneous artifacts for the no motion conditions and improved the time series temporal signal-to-noise by 30% to 40% for all combinations of low/high resolution and slow/fast head movement relative to the standard acquisition with no prospective correction. The numbers of activated voxels (p<0.001, uncorrected) in both task-based experiments were comparable for the no motion cases and increased by 78% and 330%, respectively, for PMC on versus PMC off in the slow motion cases. The PMC system is a robust solution to decrease the motion sensitivity of multi-shot 3D EPI sequences and thereby overcome one of the main roadblocks to their widespread use in fMRI studies.

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.

Structure-Based, Rational Design of T Cell Receptors.

Adoptive cell transfer using engineered T cells is emerging as a promising treatment for metastatic melanoma. Such an approach allows one to introduce T cell receptor (TCR) modifications that, while maintaining the specificity for the targeted antigen, can enhance the binding and kinetic parameters for the interaction with peptides (p) bound to major histocompatibility complexes (MHC). Using the well-characterized 2C TCR/SIYR/H-2K(b) structure as a model system, we demonstrated that a binding free energy decomposition based on the MM-GBSA approach provides a detailed and reliable description of the TCR/pMHC interactions at the structural and thermodynamic levels. Starting from this result, we developed a new structure-based approach, to rationally design new TCR sequences, and applied it to the BC1 TCR targeting the HLA-A2 restricted NY-ESO-1157-165 cancer-testis epitope. Fifty-four percent of the designed sequence replacements exhibited improved pMHC binding as compared to the native TCR, with up to 150-fold increase in affinity, while preserving specificity. Genetically engineered CD8(+) T cells expressing these modified TCRs showed an improved functional activity compared to those expressing BC1 TCR. We measured maximum levels of activities for TCRs within the upper limit of natural affinity, K D = ∼1 - 5 μM. Beyond the affinity threshold at K D < 1 μM we observed an attenuation in cellular function, in line with the "half-life" model of T cell activation. Our computer-aided protein-engineering approach requires the 3D-structure of the TCR-pMHC complex of interest, which can be obtained from X-ray crystallography. We have also developed a homology modeling-based approach, TCRep 3D, to obtain accurate structural models of any TCR-pMHC complexes when experimental data is not available. Since the accuracy of the models depends on the prediction of the TCR orientation over pMHC, we have complemented the approach with a simplified rigid method to predict this orientation and successfully assessed it using all non-redundant TCR-pMHC crystal structures available. These methods potentially extend the use of our TCR engineering method to entire TCR repertoires for which no X-ray structure is available. We have also performed a steered molecular dynamics study of the unbinding of the TCR-pMHC complex to get a better understanding of how TCRs interact with pMHCs. This entire rational TCR design pipeline is now being used to produce rationally optimized TCRs for adoptive cell therapies of stage IV melanoma.

Does abdominoplasty with liposuction of the love handles yield a shorter scar? An analysis with abdominal 3D laser scanning.

The aim of this study was to evaluate the combination of abdominoplasty with liposuction of both flanks with regards to length of scar, complications, and patient's satisfaction. A retrospective analysis of 35 patients who underwent esthetic abdominoplasty at our institution between 2002 and 2004 was performed. Thirteen patients underwent abdominoplasty with liposuction of both flanks, 22 patients underwent conventional abdominoplasty. Liposuction of the flanks did not increase the rate of complications of the abdominoplasty procedures. We found a tendency toward shorter scars in patients who underwent abdominoplasty combined with liposuction of the flanks. Implementation of 3-dimensional laser surface scanning to objectify the postoperative outcomes, documented a comparable degree of flatness of the achieved body contouring in both procedures. 3-dimensional laser surface scanning can be a valuable tool to objectify assessment of postoperative results.

Rational design of an organometallic glutathione transferase inhibitor.

Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor (see picture). The mechanism of inhibition was studied using a range of biophysical and biochemical methods.

Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: dummy run and individual case review.

INTRODUCTION: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

Using active learning for monitoring networks design: The example of wind power plants sites evaluation

Locating new wind farms is of crucial importance for energy policies of the next decade. To select the new location, an accurate picture of the wind fields is necessary. However, characterizing wind fields is a difficult task, since the phenomenon is highly nonlinear and related to complex topographical features. In this paper, we propose both a nonparametric model to estimate wind speed at different time instants and a procedure to discover underrepresented topographic conditions, where new measuring stations could be added. Compared to space filling techniques, this last approach privileges optimization of the output space, thus locating new potential measuring sites through the uncertainty of the model itself.