Artérite á cellules géantes et vitesse de sédimentation normale: plus qu'une exception [Giant cell arteritis and normal sedimentation rate: more than an exception!]

BACKGROUND: Giant cell arteritis (GCA) is a systemic segmental vasculitis of unknown etiology, typically affecting elderly patients. Elevated erythrocyte-sedimentation rate (ESR) is usually found in such patients. PATIENTS AND METHODS: One hundred and twenty three patients underwent temporal artery biopsy in our institution between 1977 and 1995. Among them, 66 (53.7%) biopsies were positive (i.e. histologic findings were very suggestive of GCA). The clinical charts from all patients with positive biopsies were retrieved and 47 were eligible for our study (inadequate data in 19 cases). RESULTS: Seven of the 47 patients with positive biopsies (15%) had a normal ESR and 70% (33/47 cases) had neuro-ophthalmic complications including anterior ischemic optic neuropathy, central retinal artery occlusion, choroidal ischemia and extraocular muscle and/or cranial nerve palsy (III, IV, VI). No differences were found between the groups with normal or elevated ESR as 87.5% (6/7 cases) of the group with normal ESR exhibited neuro-ophthalmic complications. CONCLUSIONS: ESR was normal in 15% of our GCA patients and these patients had the same frequency of neuro-ophthalmic complications as the GCA patients with elevated ESR. Thus, our study does not support the previous concept that patients with higher ESR are more at risk for neuro-ophthalmic complications. GCA with normal ESR is not rare and such patients should be investigated with other blood studies (C-reactive protein) and with fluorescein angiography.

Faktorenanalytische Untersuchung und Rehabilitätsbestimmung der statischen und dynamischen Pupillometrie bei Normalpersonen und psychopathologischen Gruppen [Factor analytic study and determination of rehabilitation of static and dynamic pupillometry in normal persons and psychopathologic groups]

Variables measured during static and dynamic pupillometry were factor-analyzed. Following factors were obtained regardless whether investigations were carried out in normals or in psychiatric patients: A static factor, a dynamic factor, a stimulus-specific factor and a restitution-dependent factor. Evaluation of reliability in normals demonstrated a high reliability for the static variables of pupillometry.

Increased body fat is independently and negatively related with cardiorespiratory fitness levels in children and adolescents with normal weight.

Body mass index (BMI) is related with cardiorespiratory fitness (CRF), but less is known regarding the combined relationships between BMI and body fat (BF) on CRF. Cross-sectional study included 2361 girls and 2328 boys aged 10–18 years living in the area of Lisbon, Portugal. BMI was calculated by measuring height and weight, and obesity was assessed by international criteria. BF was assessed by bioimpedance. CRF was assessed by the 20-m shuttle run and the participants were classified as normal-to-high or low-CRF level according to Fitness gram criterion-referenced standards. The prevalence of low CRF was 47 and 39% in girls and boys, respectively. The corresponding values for the prevalence of obesity were 4.8 and 5.6% (not significant) and of excess BF of 12.1 and 25.1% (P <0.001), respectively. In both sexes, BMI and BF were inversely related with CRF: r = – 0.53 and – 0.45 for BMI and % BF, respectively, in boys and the corresponding values in girls were – 0.50 and – 0.33 (all P <0.01). When compared with a participant with normal BMI and BF, the odds ratios (95% confidence interval) for low CRF were 1.94 (1.46–2.58) for a participant with normal BMI and high BF, and 6.19 (5.02–7.63) for a participant with high BMI and high BF. The prevalence of low-CRF levels is high in Portuguese youths. BF negatively influences CRF levels among children/adolescents with normal BMI.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study.

BACKGROUND: We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. METHODS: For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. FINDINGS: Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. INTERPRETATION: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Time consistent Pareto solutions in common access resource gameswith asymmetric players

In the analysis of equilibrium policies in a di erential game, if agents have different time preference rates, the cooperative (Pareto optimum) solution obtained by applying the Pontryagin's Maximum Principle becomes time inconsistent. In this work we derive a set of dynamic programming equations (in discrete and continuous time) whose solutions are time consistent equilibrium rules for N-player cooperative di erential games in which agents di er in their instantaneous utility functions and also in their discount rates of time preference. The results are applied to the study of a cake-eating problem describing the management of a common property exhaustible natural resource. The extension of the results to a simple common property renewable natural resource model in in nite horizon is also discussed.

Discrete analysis of dividend payments in a non-life insurance portfolio

The process of free reserves in a non-life insurance portfolio as defined in the classical model of risk theory is modified by the introduction of dividend policies that set maximum levels for the accumulation of reserves. The first part of the work formulates the quantification of the dividend payments via the expectation of their current value under diferent hypotheses. The second part presents a solution based on a system of linear equations for discrete dividend payments in the case of a constant dividend barrier, illustrated by solving a specific case.

On the use of spatially discrete data to compute energy and mass balance

In many practical applications the state of field soils is monitored by recording the evolution of temperature and soil moisture at discrete depths. We theoretically investigate the systematic errors that arise when mass and energy balances are computed directly from these measurements. We show that, even with no measurement or model errors, large residuals might result when finite difference approximations are used to compute fluxes and storage term. To calculate the limits set by the use of spatially discrete measurements on the accuracy of balance closure, we derive an analytical solution to estimate the residual on the basis of the two key parameters: the penetration depth and the distance between the measurements. When the thickness of the control layer for which the balance is computed is comparable to the penetration depth of the forcing (which depends on the thermal diffusivity and on the forcing period) large residuals arise. The residual is also very sensitive to the distance between the measurements, which requires accurately controlling the position of the sensors in field experiments. We also demonstrate that, for the same experimental setup, mass residuals are sensitively larger than the energy residuals due to the nonlinearity of the moisture transport equation. Our analysis suggests that a careful assessment of the systematic mass error introduced by the use of spatially discrete data is required before using fluxes and residuals computed directly from field measurements.

SBML qualitative models: a model representation format and infrastructure to foster interactions between qualitative modelling formalisms and tools.

BACKGROUND: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing. RESULTS: We present the Systems Biology Markup Language (SBML) Qualitative Models Package ("qual"), an extension of the SBML Level 3 standard designed for computer representation of qualitative models of biological networks. We demonstrate the interoperability of models via SBML qual through the analysis of a specific signalling network by three independent software tools. Furthermore, the collective effort to define the SBML qual format paved the way for the development of LogicalModel, an open-source model library, which will facilitate the adoption of the format as well as the collaborative development of algorithms to analyse qualitative models. CONCLUSIONS: SBML qual allows the exchange of qualitative models among a number of complementary software tools. SBML qual has the potential to promote collaborative work on the development of novel computational approaches, as well as on the specification and the analysis of comprehensive qualitative models of regulatory and signalling networks.

Tc-99m-MAA SPECT-derived tumor-to-normal liver ratios for partition model dosimetry in selective internal radiation therapy (SIRT)

Aim: When planning SIRT using 90Y microspheres, the partition model is used to refine the activity calculated by the body surface area (BSA) method to potentially improve the safety and efficacy of treatment. For this partition model dosimetry, accurate determination of mean tumor-to-normal liver ratio (TNR) is critical since it directly impacts absorbed dose estimates. This work aimed at developing and assessing a reliable methodology for the calculation of 99mTc-MAA SPECT/CT-derived TNR ratios based on phantom studies. Materials and methods: IQ NEMA (6 hot spheres) and Kyoto liver phantoms with different hot/background activity concentration ratios were imaged on a SPECT/CT (GE Infinia Hawkeye 4). For each reconstruction with the IQ phantom, TNR quantification was assessed in terms of relative recovery coefficients (RC) and image noise was evaluated in terms of coefficient of variation (COV) in the filled background. RCs were compared using OSEM with Hann, Butterworth and Gaussian filters, as well as FBP reconstruction algorithms. Regarding OSEM, RCs were assessed by varying different parameters independently, such as the number of iterations (i) and subsets (s) and the cut-off frequency of the filter (fc). The influence of the attenuation and diffusion corrections was also investigated. Furthermore, both 2D-ROIs and 3D-VOIs contouring were compared. For this purpose, dedicated Matlab© routines were developed in-house for automatic 2D-ROI/3D-VOI determination to reduce intra-user and intra-slice variability. Best reconstruction parameters and RCs obtained with the IQ phantom were used to recover corrected TNR in case of the Kyoto phantom for arbitrary hot-lesion size. In addition, we computed TNR volume histograms to better assess uptake heterogeneityResults: The highest RCs were obtained with OSEM (i=2, s=10) coupled with the Butterworth filter (fc=0.8). Indeed, we observed a global 20% RC improvement over other OSEM settings and a 50% increase as compared to the best FBP reconstruction. In any case, both attenuation and diffusion corrections must be applied, thus improving RC while preserving good image noise (COV<10%). Both 2D-ROI and 3D-VOI analysis lead to similar results. Nevertheless, we recommend using 3D-VOI since tumor uptake regions are intrinsically 3D. RC-corrected TNR values lie within 17% around the true value, substantially improving the evaluation of small volume (<15 mL) regions. Conclusions: This study reports the multi-parameter optimization of 99mTc MAA SPECT/CT images reconstruction in planning 90Y dosimetry for SIRT. In phantoms, accurate quantification of TNR was obtained using OSEM coupled with Butterworth and RC correction.

Pharmacodynamic and humoral effects of single intravenous doses of captopril in normal subjects.

The blood pressure, heart rate and humoral responses to single intravenous doses of the angiotensin converting enzyme inhibitor captopril were evaluated in 5 volunteers on a free salt intake. Each subject was given at one-week intervals a 1, 5 and 25 mg intravenous dose of captopril as well as the vehicle of captopril. The study was conducted in a single-blind fashion and the order of treatment phases was randomized. Captopril was found to inhibit the renin-angiotensin system in a dose-dependent fashion. A fall in circulating angiotensin II was observed with doses of 1 and 5 mg. Plasma angiotensin II was not detectable 15 min after the 25 mg dose. Acute inhibition of angiotensin converting enzyme with intravenous captopril had no effect on blood pressure and heart rate.

Current-density-functional approach to large quantum dots in intense magnetic fields

Within current-density-functional theory, we have studied a quantum dot made of 210 electrons confined in a disk geometry. The ground state of this large dot exhibits some features as a function of the magnetic field (Beta) that can be attributed in a clear way to the formation of compressible and incompressible states of the system. The orbital and spin angular momenta, the total energy, ionization and electron chemical potentials of the ground state, as well as the frequencies of far-infrared edge modes are calculated as a function of Beta, and compared with available experimental and theoretical results.

Ground-state self-consistent calculation of quantum dots under magnetic fields: Addition spectrum

A density-functional self-consistent calculation of the ground-state electronic density of quantum dots under an arbitrary magnetic field is performed. We consider a parabolic lateral confining potential. The addition energy, E(N+1)-E(N), where N is the number of electrons, is compared with experimental data and the different contributions to the energy are analyzed. The Hamiltonian is modeled by a density functional, which includes the exchange and correlation interactions and the local formation of Landau levels for different equilibrium spin populations. We obtain an analytical expression for the critical density under which spontaneous polarization, induced by the exchange interaction, takes place.

Exchange-correlation effects on quantum wires with spin-orbit interactions under the influence of in-plane magnetic fields.

Within the noncollinear local spin-density approximation, we have studied the ground state structure of a parabolically confined quantum wire submitted to an in-plane magnetic field, including both Rashba and Dresselhaus spin-orbit interactions. We have explored a wide range of linear electronic densities in the weak (strong) coupling regimes that appear when the ratio of spin-orbit to confining energy is small (large). These results are used to obtain the conductance of the wire. In the strong coupling limit, the interplay between the applied magnetic field¿irrespective of the in-plane direction, the exchange-correlation energy, and the spin-orbit energy-produces anomalous plateaus in the conductance vs linear density plots that are otherwise absent, or washes out plateaus that appear when the exchange-correlation energy is not taken into account.