Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review.

INTRODUCTION: The phase III EORTC 22033-26033/NCIC CE5 intergroup trial compares 50.4 Gy radiotherapy with up-front temozolomide in previously untreated low-grade glioma. We describe the digital EORTC individual case review (ICR) performed to evaluate protocol radiotherapy (RT) compliance. METHODS: Fifty-eight institutions were asked to submit 1-2 randomly selected cases. Digital ICR datasets were uploaded to the EORTC server and accessed by three central reviewers. Twenty-seven parameters were analysed including volume delineation, treatment planning, organ at risk (OAR) dosimetry and verification. Consensus reviews were collated and summary statistics calculated. RESULTS: Fifty-seven of seventy-two requested datasets from forty-eight institutions were technically usable. 31/57 received a major deviation for at least one section. Relocation accuracy was according to protocol in 45. Just over 30% had acceptable target volumes. OAR contours were missing in an average of 25% of cases. Up to one-third of those present were incorrectly drawn while dosimetry was largely protocol compliant. Beam energy was acceptable in 97% and 48 patients had per protocol beam arrangements. CONCLUSIONS: Digital RT plan submission and review within the EORTC 22033-26033 ICR provide a solid foundation for future quality assurance procedures. Strict evaluation resulted in overall grades of minor and major deviation for 37% and 32%, respectively.

Whole-heart coronary vein imaging: a comparison between non-contrast-agent- and contrast-agent-enhanced visualization of the coronary venous system.

The feasibility of three-dimensional (3D) whole-heart imaging of the coronary venous (CV) system was investigated. The hypothesis that coronary magnetic resonance venography (CMRV) can be improved by using an intravascular contrast agent (CA) was tested. A simplified model of the contrast in T(2)-prepared steady-state free precession (SSFP) imaging was applied to calculate optimal T(2)-preparation durations for the various deoxygenation levels expected in venous blood. Non-contrast-agent (nCA)- and CA-enhanced images were compared for the delineation of the coronary sinus (CS) and its main tributaries. A quantitative analysis of the resulting contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) in both approaches was performed. Precontrast visualization of the CV system was limited by the poor CNR between large portions of the venous blood and the surrounding tissue. Postcontrast, a significant increase in CNR between the venous blood and the myocardium (Myo) resulted in a clear delineation of the target vessels. The CNR improvement was 347% (P < 0.05) for the CS, 260% (P < 0.01) for the mid cardiac vein (MCV), and 430% (P < 0.05) for the great cardiac vein (GCV). The improvement in SNR was on average 155%, but was not statistically significant for the CS and the MCV. The signal of the Myo could be significantly reduced to about 25% (P < 0.001).

Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure.

Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.

Segmentació d'imatge de ressonància magnètica de pit utilitzant atlas probabilístic

La localització d'òrgans és un tòpic important en l'àmbit de la imatge mèdica per l'ajuda del tractament i diagnosi del càncer. Un exemple es pot trobar en la cal•libració de models farmacoquinètics. Aquesta pot ésser realitzada utilitzant un teixit de referència, on, per exemple en imatges de ressonància magnètica de pit, una correcta segmentació del múscul pectoral és necessària per a la detecció de signes de malignitat. Els mètodes de segmentació basat en atlas han estat altament avaluats en imatge de ressonància magnètica de cervell, obtenint resultats satisfactoris. En aquest projecte, en col•laboració amb el el Diagnostic Image Analysis Group de la Radboud University Nijmegen Medical Centre i la supervisió del Dr. N.Karssemeijer, es presenta la primera aproximació d'un mètode de segmentació basat en atlas per segmentar els diferents teixits visibles en imatges de ressonància magnètica (T1) del pit femení. L'atlas consisteix en 5 estructures (teixit greixòs, teixit dens, cor, pulmons i múscul pectoral) i ha estat utilitzat en un algorisme de segmentació Bayesià per tal de delinear les esmentades estructures. A més a més, s'ha dut a terme una comparació entre un mètode de registre global i un de local, utilitzats tant en la construcció de l'atlas com en la fase de segmentació, essent el primer el que ha presentat millors resultats en termes d'eficiència i precisió. Per a l'avaluació, s'ha dut a terme una comparació visual i numèrica entre les segmentacions obtingudes i les realitzades manualment pels experts col•laboradors. Pel que fa a la numèrica, s'ha emprat el coeficient de similitud de Dice ( mesura que dóna valors entre 0 i 1, on 0 significa no similitud i 1 similitud màxima) i s'ha obtingut una mitjana general de 0.8. Aquest resultat confirma la validesa del mètode presentat per a la segmentació d'imatges de ressonància magnètica del pit.

Targetting of the ventro-intermediate nucleus using ultra-high field (7T) MRI for gamma knife surgery purposes: A pilot in vivo study on healthy subjects.

INTRODUCTION: Gamma Knife surgery (GKS) is a non-invasive neurosurgical stereotactic procedure, increasingly used as an alternative to open functional procedures. This includes targeting of the ventro-intermediate nucleus of the thalamus (e.g. Vim) for tremor. We currently perform an indirect targeting, as the Vim is not visible on current 3Tesla MRI acquisitions. Our objective was to enhance anatomic imaging (aiming at refining the precision of anatomic target selection by direct visualisation) in patients treated for tremor with Vim GKS, by using high field 7T MRI. MATERIALS AND METHODSH: Five young healthy subjects were scanned on 3 (T1-w and diffusion tensor imaging) and 7T (high-resolution susceptibility weighted images (SWI)) MRI in Lausanne. All images were further integrated for the first time into the Gamma Plan Software(®) (Elekta Instruments, AB, Sweden) and co-registered (with T1 was a reference). A simulation of targeting of the Vim was done using various methods on the 3T images. Furthermore, a correlation with the position of the found target with the 7T SWI was performed. The atlas of Morel et al. (Zurich, CH) was used to confirm the findings on a detailed analysis inside/outside the Gamma Plan. RESULTS: The use of SWI provided us with a superior resolution and an improved image contrast within the basal ganglia. This allowed visualization and direct delineation of some subgroups of thalamic nuclei in vivo, including the Vim. The position of the target, as assessed on 3T, perfectly matched with the supposed one of the Vim on the SWI. Furthermore, a 3-dimensional model of the Vim-target area was created on the basis of the obtained images. CONCLUSION: This is the first report of the integration of SWI high field MRI into the LGP, aiming at the improvement of targeting validation of the Vim in tremor. The anatomical correlation between the direct visualization on 7T and the current targeting methods on 3T (e.g. quadrilatere of Guyot, histological atlases) seems to show a very good anatomical matching. Further studies are needed to validate this technique, both by improving the accuracy of the targeting of the Vim (potentially also other thalamic nuclei) and to perform clinical assessment.

Nosology and classification of genetic skeletal disorders: 2010 revision.

Genetic disorders involving the skeletal system arise through disturbances in the complex processes of skeletal development, growth and homeostasis and remain a diagnostic challenge because of their variety. The Nosology and Classification of Genetic Skeletal Disorders provides an overview of recognized diagnostic entities and groups them by clinical and radiographic features and molecular pathogenesis. The aim is to provide the Genetics, Pediatrics and Radiology community with a list of recognized genetic skeletal disorders that can be of help in the diagnosis of individual cases, in the delineation of novel disorders, and in building bridges between clinicians and scientists interested in skeletal biology. In the 2010 revision, 456 conditions were included and placed in 40 groups defined by molecular, biochemical, and/or radiographic criteria. Of these conditions, 316 were associated with mutations in one or more of 226 different genes, ranging from common, recurrent mutations to "private" found in single families or individuals. Thus, the Nosology is a hybrid between a list of clinically defined disorders, waiting for molecular clarification, and an annotated database documenting the phenotypic spectrum produced by mutations in a given gene. The Nosology should be useful for the diagnosis of patients with genetic skeletal diseases, particularly in view of the information flood expected with the novel sequencing technologies; in the delineation of clinical entities and novel disorders, by providing an overview of established nosologic entities; and for scientists looking for the clinical correlates of genes, proteins and pathways involved in skeletal biology. © 2011 Wiley-Liss, Inc.

Partial eating disorders among adolescents: a review.

PURPOSE: Many adolescents do not fulfill all the DSM-IV criteria's for anorexia nervosa and bulimia, but do nevertheless suffer from partial eating disorders (EDs). This review focuses on the definition, epidemiology and clinical aspects of these disorders. METHODS: Search on Medline & PsycINFO, review of websites, screening of bibliographies of articles and book chapters. RESULTS: There is still no consensus on the definition of these disorders, which cover a wide range of severity. Affected adolescents often suffer from physical and psychological problems owing to co-morbidity or as a consequence of their eating patterns: chronic constipation, dyspeptic symptoms, nausea, abdominal pain, fatigue, headaches, hypotension, menstrual dysfunction as well as dysthymia, depressive and anxiety disorders, or substance misuse and abuse. In comparison with those who are unaffected, adolescents with partial ED are at higher risk of evolving into full ED. However, most of them evolve into spontaneous remission. Adolescents with partial ED engaged, over a period of several months, in potentially unhealthy weight-control practices, suffering from intense fear of gaining weight and a disturbed body weight/image should be offered therapeutic support. CONCLUSION: Future research should focus on the exact delineation of various subtypes of clinical presentations in partial ED and on evidence-based treatment and follow-up of these various situations.

Four years with FALCON - an ESTRO educational project: achievements and perspectives.

Variability in anatomical contouring is one of the important uncertainties in radiotherapy. FALCON (Fellowship in Anatomic deLineation and CONtouring) is an educational ESTRO (European SocieTy for Radiation and Oncology) project devoted to improve interactive teaching, the homogeneity in contouring and to compare individual contours with endorsed guidelines or expert opinions. This report summarizes the experience from the first 4 years using FALCON for educational activities within ESTRO School and presents the perspectives for the future.

Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning.

PURPOSE: Early assessment of radiotherapy (RT) quality in the ongoing EORTC trial comparing primary temozolomide versus RT in low-grade gliomas. MATERIALS AND METHODS: RT plans provided for dummy cases were evaluated and compared against expert plans. We analysed: (1) tumour and organs-at-risk delineation, (2) geometric and dosimetric characteristics, (3) planning parameters, compliance with dose prescription and Dmax for OAR (4) indices: RTOG conformity index (CI), coverage factor (CF), tissue protection factor (PF); conformity number (CN = PF x CF); dose homogeneity in PTV (U). RESULTS: Forty-one RT plans were evaluated. Only two (5%) centres were requested to repeat CTV-PTV delineations. Three (7%) plans had a significant under-dosage and dose homogeneity in one deviated > 10%. Dose distribution was good with mean values of 1.5, 1, 0.68, and 0.68 (ideal values = 1) for CI, CF, PF, and CN, respectively. CI and CN strongly correlated with PF and they correlated with PTV. Planning with more beams seems to increase PTV(Dmin), improving CF. U correlated with PTV(Dmax). CONCLUSION: Preliminary results of the dummy run procedure indicate that most centres conformed to protocol requirements. To quantify plan quality we recommend systematic calculation of U and either CI or CN, both of which measure the amount of irradiated normal brain tissue.

Detailed 3D seismic imaging of a fault zone beneath Lake Geneva, Switzerland

An efficient high-resolution (HR) three-dimensional (3D) seismic reflection system for small-scale targets in lacustrine settings was developed. In Lake Geneva, near the city of Lausanne, Switzerland, the offshore extension of a complex fault zone well mapped on land was chosen for testing our system. A preliminary two-dimensional seismic survey indicated structures that include a thin (<40 m) layer of subhorizontal Quaternary sediments that unconformably overlie south-east-dipping Tertiary Molasse beds and a major fault zone (Paudeze Fault Zone) that separates Plateau and Subalpine Molasse (SM) units. A 3D survey was conducted over this test site using a newly developed three-streamer system. It provided high-quality data with a penetration to depths of 300 m below the water bottom of non-aliased signal for dips up to 30degrees and with a maximum vertical resolution of 1.1 m. The data were subjected to a conventional 3D processing sequence that included post-stack time migration. Tests with 3D pre-stack depth migration showed that such techniques can be applied to HR seismic surveys. Delineation of several horizons and fault surfaces reveals the potential for small-scale geologic and tectonic interpretation in three dimensions. Five major seismic facies and their detailed 3D geometries can be distinguished. Three fault surfaces and the top of a molasse surface were mapped in 3D. Analysis of the geometry of these surfaces and their relative orientation suggests that pre-existing structures within the Plateau Molasse (PM) unit influenced later faulting between the Plateau and SM. In particular, a change in strike of the PM bed dip may indicate a fold formed by a regional stress regime, the orientation of which was different from the one responsible for the creation of the Paudeze Fault Zone. This structure might have later influenced the local stress regime and caused the curved shape of the Paudeze Fault in our surveyed area.

Genetic structure of the genus Leptospira by multilocus enzyme electrophoresis

Thirty strains from the 11 species of the genus Leptospira were studied by multilocus enzyme electrophoresis at 12 enzyme loci, all of which were polymorphic. The mean number of alleles per locus was 6.5. Twenty-five electrophoretic types were distinguished. Grouping of the strains by cluster analysis was in general agreement with species delineation as determined by DNA-DNA hybridization, except for the strains of Leptospira meyeri and Leptospira inadai, which were scattered throughout the genus, reflecting previously recognized taxonomic uncertainties. Analysis of the clonality within Leptospira interrogans sensu stricto indicated that this population was relatively heterogeneous and a lack of gene linkage disequilibrium could not be excluded. There was a genetic discrimination between the pathogenic species and the saprophytic ones. The phenotypically intermediate species (L. inadai and Leptospira fainei) were also genetically separated and were probably closer to the saprophytes than to the pathogens.

Flow-R, a model for susceptibility mapping of debris flows and other gravitational hazards at a regional scale

The development of susceptibility maps for debris flows is of primary importance due to population pressure in hazardous zones. However, hazard assessment by processbased modelling at a regional scale is difficult due to the complex nature of the phenomenon, the variability of local controlling factors, and the uncertainty in modelling parameters. A regional assessment must consider a simplified approach that is not highly parameter dependant and that can provide zonation with minimum data requirements. A distributed empirical model has thus been developed for regional susceptibility assessments using essentially a digital elevation model (DEM). The model is called Flow-R for Flow path assessment of gravitational hazards at a Regional scale (available free of charge under www.flow-r.org) and has been successfully applied to different case studies in various countries with variable data quality. It provides a substantial basis for a preliminary susceptibility assessment at a regional scale. The model was also found relevant to assess other natural hazards such as rockfall, snow avalanches and floods. The model allows for automatic source area delineation, given user criteria, and for the assessment of the propagation extent based on various spreading algorithms and simple frictional laws.We developed a new spreading algorithm, an improved version of Holmgren's direction algorithm, that is less sensitive to small variations of the DEM and that is avoiding over-channelization, and so produces more realistic extents. The choices of the datasets and the algorithms are open to the user, which makes it compliant for various applications and dataset availability. Amongst the possible datasets, the DEM is the only one that is really needed for both the source area delineation and the propagation assessment; its quality is of major importance for the results accuracy. We consider a 10m DEM resolution as a good compromise between processing time and quality of results. However, valuable results have still been obtained on the basis of lower quality DEMs with 25m resolution.

Quality assurance of the EORTC 22043-30041 trial in post-operative radiotherapy in prostate cancer: Results of the Dummy Run procedure.

BACKGROUND AND PURPOSE: The EORTC 22043-30041 trial investigates the role of the addition of androgen suppression to post-operative radiotherapy in patients who have undergone radical prostatectomy. As part of the quality assurance of radiotherapy (QART) a Dummy Run (DR) procedure was performed. MATERIALS AND METHOD: The protocol included detailed and published delineation guidelines. Participating institutions digitally submitted radiotherapy treatment volumes and a treatment plan for a standard clinical case. Submissions were centrally reviewed using the VODCA software platform. RESULTS: Thirty-eight submissions from thirty-one institutions were reviewed. Six were accepted without comments. Twenty-three were accepted with comments on one or more items: target volume delineation (22), OAR delineation (23), planning and dosimetry (3) or treatment verification (1). Nine submissions were rejected requiring resubmission, seven for target volume delineation reasons alone. Intervention to highlight the importance of delineation guidelines was made prior to the entry of the first patient in the trial. After this, a lower percentage of resubmissions was required. CONCLUSIONS: The EORTC 22043-30041 Dummy Run highlights the need for timely and effective QART in clinical trials. The variation in target volume and OAR definition demonstrates that clinical guidelines and radiotherapy protocols are not a substitute for QART procedures. Early intervention in response to the Dummy Run improved protocol understanding.

Avaliação da infestação de insetos-praga associados à batata (Solanum tuberosum L.) sob efeito de nutrientes nitrogenados e potássicos e teores acumulados de aminoácidos livres nas cultivares Achat e Monalisa

Evaluation of insect-pest infestation associated to potato (Solanum tuberosum L.) under effect of nitrogen and potassium fertilizers and the accumulated amount of free aminoacids in Achat and Monalisa cultivars. The objective of this work was to evaluate the occurence of insect-pests on potato plants influenced by dosages of nitrogen and potassium accumulated in plant organs. A total of 169 plants of the Achat and Monalisa cultivars were evaluated to determine the presence-absence of Diabrotica speciosa Germar, 1824 and Agrotis ipsilon Hüfnagel, 1767. The experiment was carried out and executed at the Universidade Federal Fluminense, and the delineation was complete randomized block design, with four replication and nine treatments, using three fertilization level (0; 75 and 150 Kg/ha) with N-urea + KCl. The aminoacid levels were adjusted by the Leucine standard-curve (µg/l), using the Ninhydrin method, at 570 nm. The results showed that the tubercles of Monalisa accumulated high free aminoacid levels with 7,95% in the treatment N1K2 and 7,75% in the N2K1.These treatments, induced the infestation by D. speciosa larvae in 27,03%, when the aminoacid level was 2,01 ± 0,58% (X ± EP), with probability of 0,0196