Whole-body MRI: comprehensive evaluation on a 48-channel 3T MRI system in less than 40 minutes. Preliminary results

OBJECTIVE: To evaluate a comprehensive MRI protocol that investigates for cancer, vascular disease, and degenerative/inflammatory disease from the head to the pelvis in less than 40 minutes on a new generation 48-channel 3T system. MATERIALS AND METHODS: All MR studies were performed on a 48-channel 3T MR scanner. A 20-channel head/neck coil, two 18-channel body arrays, and a 32-channel spine array were employed. A total of 4 healthy individuals were studied. The designed protocol included a combination of single-shot T2-weighted sequences, T1-weighted 3D gradient-echo pre- and post-gadolinium. All images were retrospectively evaluated by two radiologists independently for overall image quality. RESULTS: The image quality for cancer was rated as excellent in the liver, pancreas, kidneys, lungs, pelvic organs, and brain, and rated as fair in the colon and breast. For vascular diseases ratings were excellent in the aorta, major branch vessel origins, inferior vena cava, portal and hepatic veins, rated as good in pulmonary arteries, and as poor in the coronary arteries. For degenerative/inflammatory diseases ratings were excellent in the brain, liver and pancreas. The inter-observer agreement was excellent. CONCLUSION: A comprehensive and time efficient screening for important categories of disease processes may be achieved with high quality imaging in a new generation 48-channel 3T system.

Pair approximation for a model of vertical and horizontal transmission of parasites.

We apply Stochastic Dynamics method for a differential equations model, proposed by Marc Lipsitch and collaborators (Proc. R. Soc. Lond. B 260, 321, 1995), for which the transmission dynamics of parasites occurs from a parent to its offspring (vertical transmission), and by contact with infected host (horizontal transmission). Herpes, Hepatitis and AIDS are examples of diseases for which both horizontal and vertical transmission occur simultaneously during the virus spreading. Understanding the role of each type of transmission in the infection prevalence on a susceptible host population may provide some information about the factors that contribute for the eradication and/or control of those diseases. We present a pair mean-field approximation obtained from the master equation of the model. The pair approximation is formed by the differential equations of the susceptible and infected population densities and the differential equations of pairs that contribute to the former ones. In terms of the model parameters, we obtain the conditions that lead to the disease eradication, and set up the phase diagram based on the local stability analysis of fixed points. We also perform Monte Carlo simulations of the model on complete graphs and Erdös-Rényi graphs in order to investigate the influence of population size and neighborhood on the previous mean-field results; by this way, we also expect to evaluate the contribution of vertical and horizontal transmission on the elimination of parasite. Pair Approximation for a Model of Vertical and Horizontal Transmission of Parasites.

Relationship between body image disturbance and incidence of depression: the SUN prospective cohort

[EN] Background: Body image disturbance is an increasing problem in Western societies and is associated with a number of mental health outcomes including anorexia, bulimia, body dysmorphia, and depression. The aim of this study was to assess the association between body image disturbance and the incidence of depression. Methods: This study included 10,286 participants from a dynamic prospective cohort of Spanish university graduates, who were followed-up for a median period of 4.2 years (Seguimiento Universidad de Navarra – the SUN study). The key characteristic of the study is the permanently open recruitment that started in 1999. The baseline questionnaire included information about body mass index (BMI) and the nine figure schemes that were used to assess body size perception. These variables were grouped according to recommended classifications and the difference between BMI and body size perception was considered as a proxy of body image disturbance. A subject was classified as an incident case of depression if he/she was initially free of depression and reported a physician-made diagnosis of depression and/or the use of antidepressant medication in at least one of the follow-up questionnaires. The association between body image disturbance and the incidence of depression was estimated by calculating the multivariable adjusted Odds Ratio (OR) and its 95% Confidence Interval (95% CI), using logistic regression models. Results: The cumulative incidence of depression during follow-up in the cohort was 4.8%. Men who underestimated their body size had a high percentage of overweight and obesity (50.1% and 12.6%, respectively), whereas women who overestimated their body size had a high percentage of underweight (87.6%). The underestimation exhibited a negative association with the incidence of depression among women (OR: 0.72, 95% CI: 0.54 – 0.95), but this effect disappeared after adjusting for possible confounding variables. The proportion of participants who correctly perceived their body size was high (53.3%) and gross misperception was seldom found, with most cases selecting only one silhouette below (42.7%) or above (2.6%) their actual BMI. Conclusion: We found no association between body image disturbance and subsequent depression in a cohort of university graduates in Spain.

Models and methods for power monolithic microwave integrated circuits

Computer aided design of Monolithic Microwave Integrated Circuits (MMICs) depends critically on active device models that are accurate, computationally efficient, and easily extracted from measurements or device simulators. Empirical models of active electron devices, which are based on actual device measurements, do not provide a detailed description of the electron device physics. However they are numerically efficient and quite accurate. These characteristics make them very suitable for MMIC design in the framework of commercially available CAD tools. In the empirical model formulation it is very important to separate linear memory effects (parasitic effects) from the nonlinear effects (intrinsic effects). Thus an empirical active device model is generally described by an extrinsic linear part which accounts for the parasitic passive structures connecting the nonlinear intrinsic electron device to the external world. An important task circuit designers deal with is evaluating the ultimate potential of a device for specific applications. In fact once the technology has been selected, the designer would choose the best device for the particular application and the best device for the different blocks composing the overall MMIC. Thus in order to accurately reproducing the behaviour of different-in-size devices, good scalability properties of the model are necessarily required. Another important aspect of empirical modelling of electron devices is the mathematical (or equivalent circuit) description of the nonlinearities inherently associated with the intrinsic device. Once the model has been defined, the proper measurements for the characterization of the device are performed in order to identify the model. Hence, the correct measurement of the device nonlinear characteristics (in the device characterization phase) and their reconstruction (in the identification or even simulation phase) are two of the more important aspects of empirical modelling. This thesis presents an original contribution to nonlinear electron device empirical modelling treating the issues of model scalability and reconstruction of the device nonlinear characteristics. The scalability of an empirical model strictly depends on the scalability of the linear extrinsic parasitic network, which should possibly maintain the link between technological process parameters and the corresponding device electrical response. Since lumped parasitic networks, together with simple linear scaling rules, cannot provide accurate scalable models, either complicate technology-dependent scaling rules or computationally inefficient distributed models are available in literature. This thesis shows how the above mentioned problems can be avoided through the use of commercially available electromagnetic (EM) simulators. They enable the actual device geometry and material stratification, as well as losses in the dielectrics and electrodes, to be taken into account for any given device structure and size, providing an accurate description of the parasitic effects which occur in the device passive structure. It is shown how the electron device behaviour can be described as an equivalent two-port intrinsic nonlinear block connected to a linear distributed four-port passive parasitic network, which is identified by means of the EM simulation of the device layout, allowing for better frequency extrapolation and scalability properties than conventional empirical models. Concerning the issue of the reconstruction of the nonlinear electron device characteristics, a data approximation algorithm has been developed for the exploitation in the framework of empirical table look-up nonlinear models. Such an approach is based on the strong analogy between timedomain signal reconstruction from a set of samples and the continuous approximation of device nonlinear characteristics on the basis of a finite grid of measurements. According to this criterion, nonlinear empirical device modelling can be carried out by using, in the sampled voltage domain, typical methods of the time-domain sampling theory.

Stereotactict body radiotherapy (SBRT)

Purpose: evaluation and comparison of volumetric modulated RapidarcTM radiotherapy (RA-IMRT) vs linac based Stereotactic body radiotherapy (SBRT) in the salvage treatment of isolated lymph node recurrences in patients affected by gynaecological cancer. Materials and Methods From January 2010 to September 2011, 15 patients affected by isolated lymph nodes recurrence of gynaecological cancer underwent salvage radiotherapy after conventional imaging staging with CT and 18-FDG-PET/CT. Two different radiotherapy techniques were used in this study: RA-IMRT (RapidarcTM implemented radiotherapy Varian Medical System, Palo Alto, CA, USA) or SBRT (BrainLAB, Feldkirchen, Germany). Five patients underwent CT scan and all patients underwent 18FDG-PET/CT for pre-treatment evaluation and staging. The mean total dose delivered was 54.3 Gy (range 50-60 Gy with conventional fractionation and 27.4 Gy (range 12-40 Gy hypofractionation) for RA-IMRT and SBRT respectively. The mean number of fractions was 27.6 fractions (range 25-31) and 3-4 fractions , the mean overall treatment duration was 40.5 days (range 36-45) and 6.5 days (range 5-8 days) for RA-IMRT and SBRT respectively. Results: At the time of the analysis, October 2011, the overall survival was 92.3 % (80% for RA-IMRT and 100% for SBRT). Six patients are alive with no evidence of disease and also six patients are alive with clinically evident disease in other sites (40% and 50% patients RA-IMRT vs SBRT respectively, one patient died for systemic progression of disease and two patient were not evaluable at this time. Conclusions: Our preliminary results showed that, the use of RA-IMRT and SBRT are an excellent local therapy for isolated lymph nodes recurrences of gynaecological cancer with a good toxicity profile and local control rate, even if any long term survivors would be expected. New treatment modalities like Cyberknife are also being implemented.

Plasticity in body and peripersonal space representations

A successful interaction with objects in the environment requires integrating information concerning object-location with the shape, dimension and position of body parts in space. The former information is coded in a multisensory representation of the space around the body, i.e. peripersonal space (PPS), whereas the latter is enabled by an online, constantly updated, action-orientated multisensory representation of the body (BR) that is critical for action. One of the critical features of these representations is that both PPS and BR are not fixed, but they dynamically change depending on different types of experience. In a series of experiment, I studied plastic properties of PPS and BR in humans. I have developed a series of methods to measure the boundaries of PPS representation (Chapter 4), to study its neural correlates (Chapter 3) and to assess BRs. These tasks have been used to study changes in PPS and BR following tool-use (Chapter 5), multisensory stimulation (Chapter 6), amputation and prosthesis implantation (Chapter 7) or social interaction (Chapter 8). I found that changes in the function (tool-use) and the structure (amputation and prosthesis implantation) of the physical body elongate or shrink both PPS and BR. Social context and social interaction also shape PPS representation. Such high degree of plasticity suggests that our sense of body in space is not given at once, but it is constantly constructed and adapted through experience.

Boron determination in biological samples - Intercomparison of three analytical methods to assist development of a treatment protocol for neoplastic diseases of the liver with Boron Neutron Capture Therapy

Die Bor-Neuroneneinfang-Therapie (engl.: Boron Neutron Capture Therapy, BNCT) ist eine indirekte Strahlentherapie, welche durch die gezielte Freisetzung von dicht ionisierender Strahlung Tumorzellen zerstört. Die freigesetzten Ionen sind Spaltfragmente einer Kernreaktion, bei welcher das Isotop 10B ein niederenergetisches (thermisches) Neutron einfängt. Das 10B wird durch ein spezielles Borpräparat in den Tumorzellen angereichert, welches selbst nicht radioaktiv ist. rnAn der Johannes Gutenberg-Universität Mainz wurde die Forschung für die Anwendung eines klinischen Behandlungsprotokolls durch zwei Heilversuche bei Patienten mit kolorektalen Lebermetastasen an der Universität Pavia, Italien, angeregt, bei denen die Leber außerhalb des Körpers in einem Forschungsreaktor bestrahlt wurde. Als erster Schritt wurde in Kooperation verschiedener universitärer Institute eine klinische Studie zur Bestimmung klinisch relevanter Parameter wie der Borverteilung in verschiedenen Geweben und dem pharmakokinetischen Aufnahmeverhalten des Borpräparates initiiert.rnDie Borkonzentration in den Gewebeproben wurde hinsichtlich ihrer räumlichen Verteilung in verschiedenen Zellarealen bestimmt, um mehr über das Aufnahmeverhalten der Zellen für das BPA im Hinblick auf ihre biologischen Charakteristika zu erfahren. Die Borbestimung wurde per Quantitative Neutron Capture Radiography, Prompt Gamma Activation Analysis und Inductively Coupled Plasma Mass Spectroscopy parallel zur histologischen Analyse des Gewebes durchgeführt. Es war möglich zu zeigen, dass in Proben aus Tumorgewebe und aus tumorfreiem Gewebe mit unterschiedlichen morphologischen Eigenschaften eine sehr heterogene Borverteilung vorliegt. Die Ergebnisse der Blutproben werden für die Erstellung eines pharmakokinetischen Modells verwendet und sind in Übereinstimmung mit existierenden pharmakokinetische Modellen. Zusätzlich wurden die Methoden zur Borbestimmung über speziell hergestellte Referenzstandards untereinander verglichen. Dabei wurde eine gute Übereinstimmung der Ergebnisse festgestellt, ferner wurde für alle biologischen Proben Standardanalyseprotokolle erstellt.rnDie bisher erhaltenen Ergebnisse der klinischen Studie sind vielversprechend, lassen aber noch keine endgültigen Schlussfolgerungen hinsichtlich der Wirksamkeit von BNCT für maligne Lebererkrankungen zu. rn

Towards the 3D attenuation imaging of active volcanoes: methods and tests on real and simulated data

The purpose of my PhD thesis has been to face the issue of retrieving a three dimensional attenuation model in volcanic areas. To this purpose, I first elaborated a robust strategy for the analysis of seismic data. This was done by performing several synthetic tests to assess the applicability of spectral ratio method to our purposes. The results of the tests allowed us to conclude that: 1) spectral ratio method gives reliable differential attenuation (dt*) measurements in smooth velocity models; 2) short signal time window has to be chosen to perform spectral analysis; 3) the frequency range over which to compute spectral ratios greatly affects dt* measurements. Furthermore, a refined approach for the application of spectral ratio method has been developed and tested. Through this procedure, the effects caused by heterogeneities of propagation medium on the seismic signals may be removed. The tested data analysis technique was applied to the real active seismic SERAPIS database. It provided a dataset of dt* measurements which was used to obtain a three dimensional attenuation model of the shallowest part of Campi Flegrei caldera. Then, a linearized, iterative, damped attenuation tomography technique has been tested and applied to the selected dataset. The tomography, with a resolution of 0.5 km in the horizontal directions and 0.25 km in the vertical direction, allowed to image important features in the off-shore part of Campi Flegrei caldera. High QP bodies are immersed in a high attenuation body (Qp=30). The latter is well correlated with low Vp and high Vp/Vs values and it is interpreted as a saturated marine and volcanic sediments layer. High Qp anomalies, instead, are interpreted as the effects either of cooled lava bodies or of a CO2 reservoir. A pseudo-circular high Qp anomaly was detected and interpreted as the buried rim of NYT caldera.

IMEX finite volume methods for the shallow water equations

Die Flachwassergleichungen (SWE) sind ein hyperbolisches System von Bilanzgleichungen, die adäquate Approximationen an groß-skalige Strömungen der Ozeane, Flüsse und der Atmosphäre liefern. Dabei werden Masse und Impuls erhalten. Wir unterscheiden zwei charakteristische Geschwindigkeiten: die Advektionsgeschwindigkeit, d.h. die Geschwindigkeit des Massentransports, und die Geschwindigkeit von Schwerewellen, d.h. die Geschwindigkeit der Oberflächenwellen, die Energie und Impuls tragen. Die Froude-Zahl ist eine Kennzahl und ist durch das Verhältnis der Referenzadvektionsgeschwindigkeit zu der Referenzgeschwindigkeit der Schwerewellen gegeben. Für die oben genannten Anwendungen ist sie typischerweise sehr klein, z.B. 0.01. Zeit-explizite Finite-Volume-Verfahren werden am öftersten zur numerischen Berechnung hyperbolischer Bilanzgleichungen benutzt. Daher muss die CFL-Stabilitätsbedingung eingehalten werden und das Zeitinkrement ist ungefähr proportional zu der Froude-Zahl. Deswegen entsteht bei kleinen Froude-Zahlen, etwa kleiner als 0.2, ein hoher Rechenaufwand. Ferner sind die numerischen Lösungen dissipativ. Es ist allgemein bekannt, dass die Lösungen der SWE gegen die Lösungen der Seegleichungen/ Froude-Zahl Null SWE für Froude-Zahl gegen Null konvergieren, falls adäquate Bedingungen erfüllt sind. In diesem Grenzwertprozess ändern die Gleichungen ihren Typ von hyperbolisch zu hyperbolisch.-elliptisch. Ferner kann bei kleinen Froude-Zahlen die Konvergenzordnung sinken oder das numerische Verfahren zusammenbrechen. Insbesondere wurde bei zeit-expliziten Verfahren falsches asymptotisches Verhalten (bzgl. der Froude-Zahl) beobachtet, das diese Effekte verursachen könnte.Ozeanographische und atmosphärische Strömungen sind typischerweise kleine Störungen eines unterliegenden Equilibriumzustandes. Wir möchten, dass numerische Verfahren für Bilanzgleichungen gewisse Equilibriumzustände exakt erhalten, sonst können künstliche Strömungen vom Verfahren erzeugt werden. Daher ist die Quelltermapproximation essentiell. Numerische Verfahren die Equilibriumzustände erhalten heißen ausbalanciert.rnrnIn der vorliegenden Arbeit spalten wir die SWE in einen steifen, linearen und einen nicht-steifen Teil, um die starke Einschränkung der Zeitschritte durch die CFL-Bedingung zu umgehen. Der steife Teil wird implizit und der nicht-steife explizit approximiert. Dazu verwenden wir IMEX (implicit-explicit) Runge-Kutta und IMEX Mehrschritt-Zeitdiskretisierungen. Die Raumdiskretisierung erfolgt mittels der Finite-Volumen-Methode. Der steife Teil wird mit Hilfe von finiter Differenzen oder au eine acht mehrdimensional Art und Weise approximniert. Zur mehrdimensionalen Approximation verwenden wir approximative Evolutionsoperatoren, die alle unendlich viele Informationsausbreitungsrichtungen berücksichtigen. Die expliziten Terme werden mit gewöhnlichen numerischen Flüssen approximiert. Daher erhalten wir eine Stabilitätsbedingung analog zu einer rein advektiven Strömung, d.h. das Zeitinkrement vergrößert um den Faktor Kehrwert der Froude-Zahl. Die in dieser Arbeit hergeleiteten Verfahren sind asymptotisch erhaltend und ausbalanciert. Die asymptotischer Erhaltung stellt sicher, dass numerische Lösung das "korrekte" asymptotische Verhalten bezüglich kleiner Froude-Zahlen besitzt. Wir präsentieren Verfahren erster und zweiter Ordnung. Numerische Resultate bestätigen die Konvergenzordnung, so wie Stabilität, Ausbalanciertheit und die asymptotische Erhaltung. Insbesondere beobachten wir bei machen Verfahren, dass die Konvergenzordnung fast unabhängig von der Froude-Zahl ist.

Exact quantum Monte Carlo methods for correlated electron systems

Thema dieser Arbeit ist die Entwicklung und Kombination verschiedener numerischer Methoden, sowie deren Anwendung auf Probleme stark korrelierter Elektronensysteme. Solche Materialien zeigen viele interessante physikalische Eigenschaften, wie z.B. Supraleitung und magnetische Ordnung und spielen eine bedeutende Rolle in technischen Anwendungen. Es werden zwei verschiedene Modelle behandelt: das Hubbard-Modell und das Kondo-Gitter-Modell (KLM). In den letzten Jahrzehnten konnten bereits viele Erkenntnisse durch die numerische Lösung dieser Modelle gewonnen werden. Dennoch bleibt der physikalische Ursprung vieler Effekte verborgen. Grund dafür ist die Beschränkung aktueller Methoden auf bestimmte Parameterbereiche. Eine der stärksten Einschränkungen ist das Fehlen effizienter Algorithmen für tiefe Temperaturen.rnrnBasierend auf dem Blankenbecler-Scalapino-Sugar Quanten-Monte-Carlo (BSS-QMC) Algorithmus präsentieren wir eine numerisch exakte Methode, die das Hubbard-Modell und das KLM effizient bei sehr tiefen Temperaturen löst. Diese Methode wird auf den Mott-Übergang im zweidimensionalen Hubbard-Modell angewendet. Im Gegensatz zu früheren Studien können wir einen Mott-Übergang bei endlichen Temperaturen und endlichen Wechselwirkungen klar ausschließen.rnrnAuf der Basis dieses exakten BSS-QMC Algorithmus, haben wir einen Störstellenlöser für die dynamische Molekularfeld Theorie (DMFT) sowie ihre Cluster Erweiterungen (CDMFT) entwickelt. Die DMFT ist die vorherrschende Theorie stark korrelierter Systeme, bei denen übliche Bandstrukturrechnungen versagen. Eine Hauptlimitation ist dabei die Verfügbarkeit effizienter Störstellenlöser für das intrinsische Quantenproblem. Der in dieser Arbeit entwickelte Algorithmus hat das gleiche überlegene Skalierungsverhalten mit der inversen Temperatur wie BSS-QMC. Wir untersuchen den Mott-Übergang im Rahmen der DMFT und analysieren den Einfluss von systematischen Fehlern auf diesen Übergang.rnrnEin weiteres prominentes Thema ist die Vernachlässigung von nicht-lokalen Wechselwirkungen in der DMFT. Hierzu kombinieren wir direkte BSS-QMC Gitterrechnungen mit CDMFT für das halb gefüllte zweidimensionale anisotrope Hubbard Modell, das dotierte Hubbard Modell und das KLM. Die Ergebnisse für die verschiedenen Modelle unterscheiden sich stark: während nicht-lokale Korrelationen eine wichtige Rolle im zweidimensionalen (anisotropen) Modell spielen, ist in der paramagnetischen Phase die Impulsabhängigkeit der Selbstenergie für stark dotierte Systeme und für das KLM deutlich schwächer. Eine bemerkenswerte Erkenntnis ist, dass die Selbstenergie sich durch die nicht-wechselwirkende Dispersion parametrisieren lässt. Die spezielle Struktur der Selbstenergie im Impulsraum kann sehr nützlich für die Klassifizierung von elektronischen Korrelationseffekten sein und öffnet den Weg für die Entwicklung neuer Schemata über die Grenzen der DMFT hinaus.

Lamellar body ultrastructure revisited: high-pressure freezing and cryo-electron microscopy of vitreous sections

Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure-function models of lamellar bodies are based on microscopic analyses of chemically fixed tissue. Despite available alternative fixation methods that are less prone to artifacts, such as cryofixation by high-pressure freezing, the nature of the lung, being mostly air filled, makes it difficult to take advantage of these improved methods. In this paper, we propose a new approach and show for the first time the ultrastructure of intracellular lamellar bodies based on cryo-electron microscopy of vitreous sections in the range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration and contrasting agents, a close to native structure is revealed. Our approach uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron microscope. The lamellar bodies clearly show a tight lamellar morphology. The periodicity of these lamellae was 7.3 nm. Lamellar bifurcations were observed in our cryosections. The technical approach described in this paper allows the examination of the native cellular ultrastructure of the surfactant system under near in vivo conditions, and therefore opens up prospectives for scrutinizing various theories of lamellar body biogenesis, exocytosis and recycling.

Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis

Background: Body mass index (BMI) is a risk factor for endometrial cancer. We quantified the risk and investigated whether the association differed by use of hormone replacement therapy (HRT), menopausal status, and histologic type. Methods: We searched MEDLINE and EMBASE (1966 to December 2009) to identify prospective studies of BMI and incident endometrial cancer. We did random-effects meta-analyses, meta-regressions, and generalized least square regressions for trend estimations assuming linear, and piecewise linear, relationships. Results: Twenty-four studies (17,710 cases) were analyzed; 9 studies contributed to analyses by HRT, menopausal status, or histologic type, all published since 2003. In the linear model, the overall risk ratio (RR) per 5 kg/m2 increase in BMI was 1.60 (95% CI, 1.52–1.68), P < 0.0001. In the piecewise model, RRs compared with a normal BMI were 1.22 (1.19–1.24), 2.09 (1.94–2.26), 4.36 (3.75–5.10), and 9.11 (7.26–11.51) for BMIs of 27, 32, 37, and 42 kg/m2, respectively. The association was stronger in never HRT users than in ever users: RRs were 1.90 (1.57–2.31) and 1.18 (95% CI, 1.06–1.31) with P for interaction ¼ 0.003. In the piecewise model, the RR in never users was 20.70 (8.28–51.84) at BMI 42 kg/m2, compared with never users at normal BMI. The association was not affected by menopausal status (P ¼ 0.34) or histologic type (P ¼ 0.26). Conclusions: HRT use modifies the BMI-endometrial cancer risk association. Impact: These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association, whilst the presence of residual risk in HRT users points to the role of additional systems. Cancer Epidemiol Biomarkers Prev; 19(12); 3119–30.

Body Mass Index and Cancer Risk: The Evidence for Causal Association

Increased body mass index (BMI), as an approximation of body adiposity, is a risk factor for developing several adult malignancies. To quantify these risks, we reported a comprehensive systematic review (Lancet 2008; 371: 569-78) of prospective observational studies determining associations between BMI and risk of incident cancer for 20 cancer types. We demonstrated that associations are: (i) sex-specific; (ii) exist for a wider range of malignancies than previously thought; and (iii) are broadly consistent across geographic populations. In the present paper, we tested these data against the Bradford-Hill criteria of causal association, and argue that the available data support strength of association, consistency, specificity, temporality, biological gradient, plausibility, coherence and probably analogy. However, the experimental evidence supporting reversibility is currently lacking, though indirect evidence from longitudinal data in cohort studies and long-term follow-up post-bariatric surgery is emerging. We additionally assessed these data against appropriate adjustment for available confounding factors; measurement error and study design; and residual confounding; and found lack of alternative explanations. We conclude that there is considerable evidence to support a causal association between BMI and risk for many cancer types, but in order to establish the role of weight control in cancer prevention, there is a need to develop trial frameworks in which to better test reversibility.

A multifactorial analysis of obesity as CVD risk factor: use of neural network based methods in a nutrigenetics context

Obesity is a multifactorial trait, which comprises an independent risk factor for cardiovascular disease (CVD). The aim of the current work is to study the complex etiology beneath obesity and identify genetic variations and/or factors related to nutrition that contribute to its variability. To this end, a set of more than 2300 white subjects who participated in a nutrigenetics study was used. For each subject a total of 63 factors describing genetic variants related to CVD (24 in total), gender, and nutrition (38 in total), e.g. average daily intake in calories and cholesterol, were measured. Each subject was categorized according to body mass index (BMI) as normal (BMI ≤ 25) or overweight (BMI > 25). Two artificial neural network (ANN) based methods were designed and used towards the analysis of the available data. These corresponded to i) a multi-layer feed-forward ANN combined with a parameter decreasing method (PDM-ANN), and ii) a multi-layer feed-forward ANN trained by a hybrid method (GA-ANN) which combines genetic algorithms and the popular back-propagation training algorithm.

"Drug mules" as a radiological challenge: Sensitivity and specificity in identifying internal cocaine in body packers, body pushers and body stuffers by computed tomography, plain radiography and Lodox

PURPOSE: The purpose of our study was to retrospectively evaluate the specificity, sensitivity and accuracy of computed tomography (CT), digital radiography (DR) and low-dose linear slit digital radiography (LSDR, Lodox(®)) in the detection of internal cocaine containers. METHODS: Institutional review board approval was obtained. The study collectively consisted of 83 patients (76 males, 7 females, 16-45 years) suspected of having incorporated cocaine drug containers. All underwent radiological imaging; a total of 135 exams were performed: nCT=35, nDR=70, nLSDR=30. An overall calculation of all "drug mules" and a specific evaluation of body packers, pushers and stuffers were performed. The gold standard was stool examination in a dedicated holding cell equipped with a drug toilet. RESULTS: There were 54 drug mules identified in this study. CT of all drug carriers showed the highest diagnostic accuracy 97.1%, sensitivity 100% and specificity 94.1%. DR in all cases was 71.4% accurate, 58.3% sensitive and 85.3% specific. LSDR of all patients with internal cocaine was 60% accurate, 57.9% sensitive and 63.4% specific. CONCLUSIONS: CT was the most accurate test studied. Therefore, the detection of internal cocaine drug packs should be performed by CT, rather than by conventional X-ray, in order to apply the most sensitive exam in the medico-legal investigation of suspected drug carriers. Nevertheless, the higher radiation applied by CT than by DR or LSDR needs to be considered. Future studies should include evaluation of low dose CT protocols in order to address germane issues and to reduce dosage.