Accuracy of out-of-field dose calculation of tomotherapy and cyberknife treatment planning systems: A dosimetric study.

PURPOSE: Late toxicities such as second cancer induction become more important as treatment outcome improves. Often the dose distribution calculated with a commercial treatment planning system (TPS) is used to estimate radiation carcinogenesis for the radiotherapy patient. However, for locations beyond the treatment field borders, the accuracy is not well known. The aim of this study was to perform detailed out-of-field-measurements for a typical radiotherapy treatment plan administered with a Cyberknife and a Tomotherapy machine and to compare the measurements to the predictions of the TPS. MATERIALS AND METHODS: Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The measured dose distributions from 6 MV intensity-modulated treatment beams for CyberKnife and TomoTherapy machines were compared to the dose calculations from the TPS. RESULTS: The TPS are underestimating the dose far away from the target volume. Quantitatively the Cyberknife underestimates the dose at 40cm from the PTV border by a factor of 60, the Tomotherapy TPS by a factor of two. If a 50% dose uncertainty is accepted, the Cyberknife TPS can predict doses down to approximately 10 mGy/treatment Gy, the Tomotherapy-TPS down to 0.75 mGy/treatment Gy. The Cyberknife TPS can then be used up to 10cm from the PTV border the Tomotherapy up to 35cm. CONCLUSIONS: We determined that the Cyberknife and Tomotherapy TPS underestimate substantially the doses far away from the treated volume. It is recommended not to use out-of-field doses from the Cyberknife TPS for applications like modeling of second cancer induction. The Tomotherapy TPS can be used up to 35cm from the PTV border (for a 390 cm(3) large PTV).

Croire ensemble. Analyse institutionnelle du paysage religieux en Suisse

L'étude présentée dans cet ouvrage offre pour la première fois en Suisse une perspective sociologique empirique et générale sur les organisations religieuses locales. Vu sous cet angle, le fait religieux se manifeste d'abord, comme le précisaient déjà Weber ou Durkheim, par l'existence de communautés de tailles et de profils divers, tant dans l'espace rural qu'urbain. En Suisse, 5'734 paroisses et groupes religieux ont pu être dénombrés en 2008. Ce recensement permet de souligner la prégnance institutionnelle des Eglises historiques, mais également l'émergence d'une plus forte pluralité religieuse, particulièrement en milieu urbain. La sociologie des organisations que propose cette étude permet de jeter un éclairage nouveau sur les effets de la sécularisation (baisse des membres et de la pratique) et de la pluralisation (diversification des confessions et traditions religieuses). L'analyse des différences et des similitudes organisationnelles selon les traditions religieuses fait apparaître un positionnement social des groupes en fonction de statuts acquis au cours de l'histoire. Les théories classiques - par exemple à pro- pos des relations entre statuts sociaux des membres et groupes d'appartenance, des types d'autorités religieuses ou encore des différences entre Eglise et Secte - sont revisitées, précisées ou reformulées grâce à des données quantitatives originales et représentatives du champ religieux suisse. -- The study presented in this book for the first time in Switzerland offers a broad empirical and sociological perspective on local religious organizations. From this perspective, religion appears first, as already observed by Weber and Durkheim, through communities regardless of their various profiles. In Switzerland, 5,734 parishes and religious groups have been identified by a national census in 2008. The book underlines the institutional salience of historical churches (Reformed and Roman Catholic) but also the emerging religious plurality, particularly in urban areas. This study sheds a new light upon the effects of secularization (lower limbs and practice) and pluralisation (diversification of religious denominations and traditions) in the organizational field. The analysis of differences and similarities between religious traditions shows a social positioning of the local groups according to the statutes acquired in history. The classical theories − e.g. about the relationship between social status of members and membership groups, types of religious authorities or differences between Church and Sect − are revisited, clarified or reformulated based on an original and representative quantitative data of the Swiss religious field.

The social disembedding of business theory and practice. A (neo-)institutional analysis of the homo economicus and corporate social responsibility, and the inherent responsibility of business scholars

Aim Structure of the Thesis In the first article, I focus on the context in which the Homo Economicus was constructed - i.e., the conception of economic actors as fully rational, informed, egocentric, and profit-maximizing. I argue that the Homo Economicus theory was developed in a specific societal context with specific (partly tacit) values and norms. These norms have implicitly influenced the behavior of economic actors and have framed the interpretation of the Homo Economicus. Different factors however have weakened this implicit influence of the broader societal values and norms on economic actors. The result is an unbridled interpretation and application of the values and norms of the Homo Economicus in the business environment, and perhaps also in the broader society. In the second article, I show that the morality of many economic actors relies on isomorphism, i.e., the attempt to fit into the group by adopting the moral norms surrounding them. In consequence, if the norms prevailing in a specific group or context (such as a specific region or a specific industry) change, it can be expected that actors with an 'isomorphism morality' will also adapt their ethical thinking and their behavior -for the 'better' or for the 'worse'. The article further describes the process through which corporations could emancipate from the ethical norms prevailing in the broader society, and therefore develop an institution with specific norms and values. These norms mainly rely on mainstream business theories praising the economic actor's self-interest and neglecting moral reasoning. Moreover, because of isomorphism morality, many economic actors have changed their perception of ethics, and have abandoned the values prevailing in the broader society in order to adopt those of the economic theory. Finally, isomorphism morality also implies that these economic actors will change their morality again if the institutional context changes. The third article highlights the role and responsibility of business scholars in promoting a systematic reflection and self-critique of the business system and develops alternative models to fill the moral void of the business institution and its inherent legitimacy crisis. Indeed, the current business institution relies on assumptions such as scientific neutrality and specialization, which seem at least partly challenged by two factors. First, self-fulfilling prophecy provides scholars with an important (even if sometimes undesired) normative influence over practical life. Second, the increasing complexity of today's (socio-political) world and interactions between the different elements constituting our society question the strong specialization of science. For instance, economic theories are not unrelated to psychology or sociology, and economic actors influence socio-political structures and processes, e.g., through lobbying (Dobbs, 2006; Rondinelli, 2002), or through marketing which changes not only the way we consume, but more generally tries to instill a specific lifestyle (Cova, 2004; M. K. Hogg & Michell, 1996; McCracken, 1988; Muniz & O'Guinn, 2001). In consequence, business scholars are key actors in shaping both tomorrow's economic world and its broader context. A greater awareness of this influence might be a first step toward an increased feeling of civic responsibility and accountability for the models and theories developed or taught in business schools.

The data treatment dependent variability of U-Pb zircon ages obtained using mono-collector, sector field, laser ablation ICP-MS

U-Pb dating of zircons by laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) is a widely used analytical technique in Earth Sciences. For U-Pb ages below 1 billion years (1 Ga), Pb-206/U-238 dates are usually used, showing the least bias by external parameters such as the presence of initial lead and its isotopic composition in the analysed mineral. Precision and accuracy of the Pb/U ratio are thus of highest importance in LA-ICPMS geochronology. We consider the evaluation of the statistical distribution of the sweep intensities based on goodness-of-fit tests in order to find a model probability distribution fitting the data to apply an appropriate formulation for the standard deviation. We then discuss three main methods to calculate the Pb/U intensity ratio and its uncertainty in the LA-ICPMS: (1) ratio-of-the-mean intensities method, (2) mean-of-the-intensity-ratios method and (3) intercept method. These methods apply different functions to the same raw intensity vs. time data to calculate the mean Pb/U intensity ratio. Thus, the calculated intensity ratio and its uncertainty depend on the method applied. We demonstrate that the accuracy and, conditionally, the precision of the ratio-of-the-mean intensities method are invariant to the intensity fluctuations and averaging related to the dwell time selection and off-line data transformation (averaging of several sweeps); we present a statistical approach how to calculate the uncertainty of this method for transient signals. We also show that the accuracy of methods (2) and (3) is influenced by the intensity fluctuations and averaging, and the extent of this influence can amount to tens of percentage points; we show that the uncertainty of these methods also depends on how the signal is averaged. Each of the above methods imposes requirements to the instrumentation. The ratio-of-the-mean intensities method is sufficiently accurate provided the laser induced fractionation between the beginning and the end of the signal is kept low and linear. We show, based on a comprehensive series of analyses with different ablation pit sizes, energy densities and repetition rates for a 193 nm ns-ablation system that such a fractionation behaviour requires using a low ablation speed (low energy density and low repetition rate). Overall, we conclude that the ratio-of-the-mean intensities method combined with low sampling rates is the most mathematically accurate among the existing data treatment methods for U-Pb zircon dating by sensitive sector field ICPMS.

Intraoperative adverse events during laparoscopic colorectal resection-better laparoscopic treatment but unchanged incidence. Lessons learnt from a Swiss multi-institutional analysis of 3,928 patients.

PURPOSE: Intraoperative adverse events significantly influence morbidity and mortality of laparoscopic colorectal resections. Over an 11-year period, the changes of occurrence of such intraoperative adverse events were assessed in this study. METHODS: Analysis of 3,928 patients undergoing elective laparoscopic colorectal resection based on the prospective database of the Swiss Association of Laparoscopic and Thoracoscopic Surgery was performed. RESULTS: Overall, 377 intraoperative adverse events occurred in 329 patients (overall incidence of 8.4 %). Of 377 events, 163 (43 %) were surgical complications and 214 (57 %) were nonsurgical adverse events. Surgical complications were iatrogenic injury to solid organs (n = 63; incidence of 1.6 %), bleeding (n = 62; 1.6 %), lesion by puncture (n = 25; 0.6 %), and intraoperative anastomotic leakage (n = 13; 0.3 %). Of note, 11 % of intraoperative organ/puncture lesions requiring re-intervention were missed intraoperatively. Nonsurgical adverse events were problems with equipment (n = 127; 3.2 %), anesthetic problems (n = 30; 0.8 %), and various (n = 57; 1.5 %). Over time, the rate of intraoperative adverse events decreased, but not significantly. Bleeding complications significantly decreased (p = 0.015), and equipment problems increased (p = 0.036). However, the rate of adverse events requiring conversion significantly decreased with time (p < 0.001). Patients with an intraoperative adverse event had a significantly higher rate of postoperative local and general morbidity (41.2 and 32.9 % vs. 18.0 and 17.2 %, p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Intraoperative surgical complications and adverse events in laparoscopic colorectal resections did not change significantly over time and are associated with an increased postoperative morbidity.

Active deformation fields: dense deformation field estimation for atlas-based segmentation using the active contour framework.

This paper presents a new and original variational framework for atlas-based segmentation. The proposed framework integrates both the active contour framework, and the dense deformation fields of optical flow framework. This framework is quite general and encompasses many of the state-of-the-art atlas-based segmentation methods. It also allows to perform the registration of atlas and target images based on only selected structures of interest. The versatility and potentiality of the proposed framework are demonstrated by presenting three diverse applications: In the first application, we show how the proposed framework can be used to simulate the growth of inconsistent structures like a tumor in an atlas. In the second application, we estimate the position of nonvisible brain structures based on the surrounding structures and validate the results by comparing with other methods. In the final application, we present the segmentation of lymph nodes in the Head and Neck CT images, and demonstrate how multiple registration forces can be used in this framework in an hierarchical manner.

The interplay between radiation and the immune system in the field of post-radical pneumonitis and fibrosis and why it is important to understand it.

A discussion on the importance and pathogenesis of radiation-induced pneumonitis and fibrosis is provided, with a special focus on the role of the immune system. The need to understand this interaction is highlighted in view of emerging therapeutic potential.

Population pharmacokinetics in chronic myeloid leukaemia patients: observations under field-conditions

Introduction: Therapeutic drug monitoring (TDM) of imatinib has been increasingly proposed for chronic myeloid leukaemia (CML) patients, as several studies have found a correlation between trough concentrations (Cmin) >=1000ng/ml and improved response. The pharmacological monitoring project of EUTOS (European Treatment and Outcome Study) was launched to increase the availability of imatinib TDM, standardize labs, and validate proposed Cmin thresholds. Using the collected data, the objective of this analysis was to characterize imatinib Population pharmacokinetics (Pop-PK) in a large cohort of European patients, to quantify its variability and the influence of demographic factors and comedications, and to derive individual exposure variables suitable for further concentration-effect analyses.¦Methods: 4095 PK samples from 2478 adult patients were analyzed between 2006 and 2010 by LC-MS-MS and considered for Pop-PK analysis by NONMEM®. Model building used data from 973 patients with >=2 samples available (2590 samples). A sensitivity analysis was performed using all data. Available comedications (27%) were classified into inducers or inhibitors of P-glycoprotein, CYP3A4/5 and organic-cation-transporter-1 (hOCT-1).¦Results: A one-compartment model with linear elimination, zero-order absorption fitted the data best. Estimated Pop-PK parameters (interindividual variability, IIV %CV) for a 40-year old male patient were: clearance CL = 17.3 L/h (37.7%), volume V = 429L (51.1%), duration of absorption D1 = 3.2h. Outliers, reflecting potential compliance and time recording errors, were taken into account by estimating an IIV on the residual error (35.4%). Intra-individual residuals were 29.1% (proportional) plus ± 84.6 ng/mL (additive). Female patients had a 15.2% lower CL (14.6 L/h). A piece-wise linear effect of age estimated a CL of 18.7 L/h at 20 years, 17.3 L/h at 40 and 13.8 L/h at 60 years. These covariates explained 2% (CL) and 4.5% (V) of IIV variability. No effect of comedication was found. The sensitivity analysis expectedly estimated increased IIV, but similar fixed effect parameters.¦Conclusion: Imatinib PK was well described in a large cohort of CML patients under field conditions and results were concordant with previous studies. Patient characteristics explain only little IIV, confirming limited utility of prior dosage adjustment. As intra-variability is smaller than inter-patient variability, dose adjustment guided by TDM could however be beneficial in order to bring Cmin into a given therapeutic target.

Indeterminate test results of T-SPOT.TB performed under routine field conditions

Interferon-gamma release assays for the diagnosis of tuberculosis (TB) can give indeterminate results. The prevalence of indeterminate test results (ITRs) among T-SPOT.TB tests was assessed. A retrospective analysis of samples processed in 2005 was performed. ITRs were assessed by age, sex, immunosuppression, distance to the laboratory and season. A subgroup of tests performed for specific indications (contact tracing, migrants with positive tuberculin skin test, TB suspects and immunosuppression) were analysed separately. Of a total of 1,429 tests, 49 (3.4%) were indeterminate. ITRs were significantly associated with old age (>75 versus 5-75 yrs; odds ratio (OR) 7.97, 95% confidence interval (CI) 3.968-15.438) and the season during which samples were transported (autumn and winter versus spring and summer; OR 3.47, 95% CI 1.753-7.514). The incidence of ITR was 302 (2.0%) among TB contacts, 75 (1.6%) among immigrants, 156 (3.0%) in TB suspects and 32 (3.0%) among immunosuppressed patients. Sex, young age and distance to the laboratory were not associated with the rate of ITR. Of the 13 tests with ITR that were repeated, 10 gave a clear positive or negative result. Indeterminate test results with T-SPOT.TB under routine conditions were infrequent and more common in individuals aged >75 yrs than in children and younger adults. The incidence of indeterminate test results was low and similar among healthy tuberculosis contacts, immigrants with a positive tuberculin skin test, tuberculosis suspects and the immunosuppressed. The conditions of transportation may influence the incidence of indeterminate test results.

Improving T2 -weighted imaging at high field through the use of kT -points.

PURPOSE: At high magnetic field strengths (B0 ≥ 3 T), the shorter radiofrequency wavelength produces an inhomogeneous distribution of the transmit magnetic field. This can lead to variable contrast across the brain which is particularly pronounced in T2 -weighted imaging that requires multiple radiofrequency pulses. To obtain T2 -weighted images with uniform contrast throughout the whole brain at 7 T, short (2-3 ms) 3D tailored radiofrequency pulses (kT -points) were integrated into a 3D variable flip angle turbo spin echo sequence. METHODS: The excitation and refocusing "hard" pulses of a variable flip angle turbo spin echo sequence were replaced with kT -point pulses. Spatially resolved extended phase graph simulations and in vivo acquisitions at 7 T, utilizing both single channel and parallel-transmit systems, were used to test different kT -point configurations. RESULTS: Simulations indicated that an extended optimized k-space trajectory ensured a more homogeneous signal throughout images. In vivo experiments showed that high quality T2 -weighted brain images with uniform signal and contrast were obtained at 7 T by using the proposed methodology. CONCLUSION: This work demonstrates that T2 -weighted images devoid of artifacts resulting from B1 (+) inhomogeneity can be obtained at high field through the optimization of extended kT -point pulses. Magn Reson Med 71:1478-1488, 2014. © 2013 Wiley Periodicals, Inc.

Real-time full field laser Doppler imaging.

We present a full field laser Doppler imaging instrument, which enables real-time in vivo assessment of blood flow in dermal tissue and skin. This instrument monitors the blood perfusion in an area of about 50 cm(2) with 480 × 480 pixels per frame at a rate of 12-14 frames per second. Smaller frames can be monitored at much higher frame rates. We recorded the microcirculation in healthy skin before, during and after arterial occlusion. In initial clinical case studies, we imaged the microcirculation in burned skin and monitored the recovery of blood flow in a skin flap during reconstructive surgery indicating the high potential of LDI for clinical applications. Small animal imaging in mouse ears clearly revealed the network of blood vessels and the corresponding blood perfusion.