Empirical study of correlated survival times for recurrent events with proportional hazards margins and the effect of correlation and censoring.

Background: In longitudinal studies where subjects experience recurrent incidents over a period of time, such as respiratory infections, fever or diarrhea, statistical methods are required to take into account the within-subject correlation. Methods: For repeated events data with censored failure, the independent increment (AG), marginal (WLW) and conditional (PWP) models are three multiple failure models that generalize Cox"s proportional hazard model. In this paper, we revise the efficiency, accuracy and robustness of all three models under simulated scenarios with varying degrees of within-subject correlation, censoring levels, maximum number of possible recurrences and sample size. We also study the methods performance on a real dataset from a cohort study with bronchial obstruction. Results: We find substantial differences between methods and there is not an optimal method. AG and PWP seem to be preferable to WLW for low correlation levels but the situation reverts for high correlations. Conclusions: All methods are stable in front of censoring, worsen with increasing recurrence levels and share a bias problem which, among other consequences, makes asymptotic normal confidence intervals not fully reliable, although they are well developed theoretically.

Continental faunal exchange and the asymmetrical radiation of carnivores.

Lineages arriving on islands may undergo explosive evolutionary radiations owing to the wealth of ecological opportunities. Although studies on insular taxa have improved our understanding of macroevolutionary phenomena, we know little about the macroevolutionary dynamics of continental exchanges. Here we study the evolution of eight Carnivora families that have migrated across the Northern Hemisphere to investigate if continental invasions also result in explosive diversification dynamics. We used a Bayesian approach to estimate speciation and extinction rates from a substantial dataset of fossil occurrences while accounting for the incompleteness of the fossil record. Our analyses revealed a strongly asymmetrical pattern in which North American lineages invading Eurasia underwent explosive radiations, whereas lineages invading North America maintained uniform diversification dynamics. These invasions into Eurasia were characterized by high rates of speciation and extinction. The radiation of the arriving lineages in Eurasia coincide with the decline of established lineages or phases of climate change, suggesting differences in the ecological settings between the continents may be responsible for the disparity in diversification dynamics. These results reveal long-term outcomes of biological invasions and show that the importance of explosive radiations in shaping diversity extends beyond insular systems and have significant impact at continental scales.

Stereotactic body radiation therapy with helical tomotherapy for medical inoperable early-stage primary and second-primary non-small cell lung neoplasm : one-year outcome and toxicity analysis

Le cancer du poumon est la première cause de mortalité associée au cancer dans le monde. Le traitement curatif des tumeurs pulmonaires non-à-petites-cellules (NSCLC) diagnostiquées à un stade précoce se base sur une approche chirurgicale. Cependant, étant donné les comorbidités liées à la consommation de tabac, dont la bronchopneumopathie chronique occupe la première place, l'éligibilité chirurgicale pour ce type de cancer se trouve fréquemment limitée. Dans ce contexte, l'emploi de la radiothérapie stéréotaxique (SBRT) est une alternative valable chez les patients atteints d'un NSCLC primaire de stade précoce, et qui sont considérés inopérables à cause de leurs comorbidités. Depuis peu seulemement, le spectre de la SBRT a été élargi aux patients atteints d'un deuxième NSCLC primaire (SPLC), faisant suite à un premier NSCLC, traité avec un but curatif. Ils concernent donc des patients ayant déjà subits une intervention chirurgicale au préalable et qui présentent une réserve fonctionnelle pulmonaire extrêmement réduite. Le succès croissant de la SBRT résulte soit d'une efficacité thérapeutique comparables à la chirurgie, soit de sa toxicité qui semble limitée. À notre connaissance, seulement une étude a reporté des issues cliniques de patients affectés par des NSCLC primaires traités par SBRT. Cette dernière a utilisé la tomothérapie comme système d'irradiation (T-SBRT), sur un faible échantillon de patients (n = 27). Concernant l'irradiation des patients présentant des SPLC, la littérature disponible est pauvre et aucune publication a décrit l'utilisation de la T-SBRT. Ces éléments innovants ont donc motivé la rédaction d'un travail de thèse concernant les premières données cliniques de l'expérience faite au CHUV. Du point de vue des effets secondaires, si la pneumonie actinique précoce et tardive survenant au niveau du champ d'irradiation est désormais une complication iatrogène bien connue de la SBRT, une seule étude s'est intéressée à ce sujet dans le cadre de la T-SBRT. De plus, une entité bénigne et transitoire de pneumonie ( ?) a été reconnue depuis peu : la pneumonie organisée radio-induite (OP). Celle-ci semble se chevaucher comme un autre effet iatrogène à l'extérieur du champ d'irradiation. Originellement, cette dernière avait été rapportée dans les suites de la radiothérapie pour les cancer du sein. Elle a été décrite comme étant initialement limitée au champ d'irradiation et successivement pouvant s'étendre dynamiquement en dehors de celui-ci. Nous avons donc supposé que des infiltrats de OP peuvent être présents chez des patients asymptomatiques, et que ce dynamisme pourrait être identifié déjà au sein du champ d'irradiation. Notre étude a démontré que le traitement par T-SBRT garde des issues cliniques très encourageantes, aussi bien pour les tumeurs primaires que pour les SPLC. Entre autre, ce traitement semble avoir une toxicité limitée, et l'existence vraisemblable de la OP, déjà au sein du champ d'irradiation, peut aider les radiologues à différencier les infiltrats radio-induits d'une une récidive tumorale.

Prototype of a web-based participative decision support platform in natural hazards and risk management

This paper presents the current state and development of a prototype web-GIS (Geographic Information System) decision support platform intended for application in natural hazards and risk management, mainly for floods and landslides. This web platform uses open-source geospatial software and technologies, particularly the Boundless (formerly OpenGeo) framework and its client side software development kit (SDK). The main purpose of the platform is to assist the experts and stakeholders in the decision-making process for evaluation and selection of different risk management strategies through an interactive participation approach, integrating web-GIS interface with decision support tool based on a compromise programming approach. The access rights and functionality of the platform are varied depending on the roles and responsibilities of stakeholders in managing the risk. The application of the prototype platform is demonstrated based on an example case study site: Malborghetto Valbruna municipality of North-Eastern Italy where flash floods and landslides are frequent with major events having occurred in 2003. The preliminary feedback collected from the stakeholders in the region is discussed to understand the perspectives of stakeholders on the proposed prototype platform.

Optimization of Radiation Dose and Image Quality in Musculoskeletal CT: Emphasis on Iterative Reconstruction Techniques (Part 1).

Computed tomography (CT) is a modality of choice for the study of the musculoskeletal system for various indications including the study of bone, calcifications, internal derangements of joints (with CT arthrography), as well as periprosthetic complications. However, CT remains intrinsically limited by the fact that it exposes patients to ionizing radiation. Scanning protocols need to be optimized to achieve diagnostic image quality at the lowest radiation dose possible. In this optimization process, the radiologist needs to be familiar with the parameters used to quantify radiation dose and image quality. CT imaging of the musculoskeletal system has certain specificities including the focus on high-contrast objects (i.e., in CT of bone or CT arthrography). These characteristics need to be taken into account when defining a strategy to optimize dose and when choosing the best combination of scanning parameters. In the first part of this review, we present the parameters used for the evaluation and quantification of radiation dose and image quality. In the second part, we discuss different strategies to optimize radiation dose and image quality at CT, with a focus on the musculoskeletal system and the use of novel iterative reconstruction techniques.

Uncertainty associated with Monte Carlo radiation transport in radionuclide metrology

In radionuclide metrology, Monte Carlo (MC) simulation is widely used to compute parameters associated with primary measurements or calibration factors. Although MC methods are used to estimate uncertainties, the uncertainty associated with radiation transport in MC calculations is usually difficult to estimate. Counting statistics is the most obvious component of MC uncertainty and has to be checked carefully, particularly when variance reduction is used. However, in most cases fluctuations associated with counting statistics can be reduced using sufficient computing power. Cross-section data have intrinsic uncertainties that induce correlations when apparently independent codes are compared. Their effect on the uncertainty of the estimated parameter is difficult to determine and varies widely from case to case. Finally, the most significant uncertainty component for radionuclide applications is usually that associated with the detector geometry. Recent 2D and 3D x-ray imaging tools may be utilized, but comparison with experimental data as well as adjustments of parameters are usually inevitable.

Optimization of Radiation Dose and Image Quality in Musculoskeletal CT: Emphasis on Iterative Reconstruction Techniques (Part 2).

Computed tomography (CT) is a modality of choice for the study of the musculoskeletal system for various indications including the study of bone, calcifications, internal derangements of joints (with CT arthrography), as well as periprosthetic complications. However, CT remains intrinsically limited by the fact that it exposes patients to ionizing radiation. Scanning protocols need to be optimized to achieve diagnostic image quality at the lowest radiation dose possible. In this optimization process, the radiologist needs to be familiar with the parameters used to quantify radiation dose and image quality. CT imaging of the musculoskeletal system has certain specificities including the focus on high-contrast objects (i.e., in CT of bone or CT arthrography). These characteristics need to be taken into account when defining a strategy to optimize dose and when choosing the best combination of scanning parameters. In the first part of this review, we present the parameters used for the evaluation and quantification of radiation dose and image quality. In the second part, we discuss different strategies to optimize radiation dose and image quality of CT, with a focus on the musculoskeletal system and the use of novel iterative reconstruction techniques.

Ambient radiation levels in positron emission tomography/computed tomography (PET/CT) imaging center

Objective: To evaluate the level of ambient radiation in a PET/CT center. Materials and Methods: Previously selected and calibrated TLD-100H thermoluminescent dosimeters were utilized to measure room radiation levels. During 32 days, the detectors were placed in several strategically selected points inside the PET/CT center and in adjacent buildings. After the exposure period the dosimeters were collected and processed to determine the radiation level. Results: In none of the points selected for measurements the values exceeded the radiation dose threshold for controlled area (5 mSv/year) or free area (0.5 mSv/year) as recommended by the Brazilian regulations. Conclusion: In the present study the authors demonstrated that the whole shielding system is appropriate and, consequently, the workers are exposed to doses below the threshold established by Brazilian standards, provided the radiation protection standards are followed.

Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

AbstractObjective:In the present study, the authors investigated the in vitrobehavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy.Materials and Methods:The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed.Results:Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation.Conclusion:Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

Readjustment of abdominal computed tomography protocols in a university hospital: impact on radiation dose

AbstractObjective:To assess the reduction of estimated radiation dose in abdominal computed tomography following the implementation of new scan protocols on the basis of clinical suspicion and of adjusted images acquisition parameters.Materials and Methods:Retrospective and prospective review of reports on radiation dose from abdominal CT scans performed three months before (group A – 551 studies) and three months after (group B – 788 studies) implementation of new scan protocols proposed as a function of clinical indications. Also, the images acquisition parameters were adjusted to reduce the radiation dose at each scan phase. The groups were compared for mean number of acquisition phases, mean CTDIvol per phase, mean DLP per phase, and mean DLP per scan.Results:A significant reduction was observed for group B as regards all the analyzed aspects, as follows: 33.9%, 25.0%, 27.0% and 52.5%, respectively for number of acquisition phases, CTDIvol per phase, DLP per phase and DLP per scan (p < 0.001).Conclusion:The rational use of abdominal computed tomography scan phases based on the clinical suspicion in conjunction with the adjusted images acquisition parameters allows for a 50% reduction in the radiation dose from abdominal computed tomography scans.

Food Safety Testing: Rapid Molecular Methods for Chemical and Biological Hazards

The central goal of food safety policy in the European Union (EU) is to protect consumer health by guaranteeing a high level of food safety throughout the food chain. This goal can in part be achieved by testing foodstuffs for the presence of various chemical and biological hazards. The aim of this study was to facilitate food safety testing by providing rapid and user-friendly methods for the detection of particular food-related hazards. Heterogeneous competitive time-resolved fluoroimmunoassays were developed for the detection of selected veterinary residues, that is coccidiostat residues, in eggs and chicken liver. After a simplified sample preparation procedure, the immunoassays were performed either in manual format with dissociation-enhanced measurement or in automated format with pre-dried assay reagents and surface measurement. Although the assays were primarily designed for screening purposes providing only qualitative results, they could also be used in a quantitative mode. All the developed assays had good performance characteristics enabling reliable screening of samples at concentration levels required by the authorities. A novel polymerase chain reaction (PCR)-based assay system was developed for the detection of Salmonella spp. in food. The sample preparation included a short non-selective pre-enrichment step, after which the target cells were collected with immunomagnetic beads and applied to PCR reaction vessels containing all the reagents required for the assay in dry form. The homogeneous PCR assay was performed with a novel instrument platform, GenomEra^™, and the qualitative assay results were automatically interpreted based on end-point time-resolved fluorescence measurements and cut-off values. The assay was validated using various food matrices spiked with sub-lethally injured Salmonella cells at levels of 1-10 colony forming units (CFU)/25 g of food. The main advantage of the system was the exceptionally short time to result; the entire process starting from the pre-enrichment and ending with the PCR result could be completed in eight hours. In conclusion, molecular methods using state-of-the-art assay techniques were developed for food safety testing. The combination of time-resolved fluorescence detection and ready-to-use reagents enabled sensitive assays easily amenable to automation. Consequently, together with the simplified sample preparation, these methods could prove to be applicable in routine testing.