Indication and perspectives of radiation therapy in the setting of de-novo metastatic prostate cancer.

Prostate cancer is the most common cancer and the third leading cause of cancer mortality in men. Each year, approximately 10% of prostate cancers are diagnosed metastatic at initial presentation. The standard treatment option for de-novo metastatic prostate cancer is androgen deprivation therapy with novel hormonal agent or with chemotherapy. Recently, PEACE-1 trial highlighted the benefit of triplet therapy resulting in the combination of androgen deprivation therapy combined with docetaxel and abiraterone. Radiotherapy can be proposed in a curative intent or to treat local symptomatic disease. Nowadays, radiotherapy of the primary disease is only recommended for de novo low-burden/low-volume metastatic prostate cancer, as defined in the CHAARTED criteria. However, studies on stereotactic radiotherapy on oligometastases have shown that this therapeutic approach is feasible and well tolerated. Prospective research currently focuses on the benefit of intensification by combining treatment of the metastatic sites and the primary all together. The contribution of metabolic imaging to better define the target volumes and specify the oligometastatic character allows a better selection of patients. This article aims to define indications of radiotherapy and perspectives of this therapeutic option for de-novo metastatic prostate cancer.

Quantum Vacuum Excitation of a Quasinormal Mode in an Analog Model of Black Hole Spacetime.

Vacuum quantum fluctuations near horizons are known to yield correlated emission by the Hawking effect. We use a driven-dissipative quantum fluid of microcavity polaritons as an analog model of a quantum field theory on a black-hole spacetime and numerically calculate correlated emission. We show that, in addition to the Hawking effect at the sonic horizon, quantum fluctuations may result in a sizable stationary excitation of a quasinormal mode of the field theory. Observable signatures of the excitation of the quasinormal mode are found in the spatial density fluctuations as well as in the spectrum of Hawking emission. This suggests an intrinsic fluctuation-driven mechanism leading to the quantum excitation of quasinormal modes on black hole spacetimes.

A compact-rigid multi-analyser for energy and angle filtering of high-resolution X-ray experiments. Part 2. Efficiency of a single-crystal-comb.

Diffraction instruments using filtering by one or several analyser crystals exist since the 1980s and 1990s at synchrotron radiation sources, but, due to its low efficiency, this filtering is little used on laboratory sources. In order to overcome this limitation, the efficiency of a small diffraction filtering multi-analyzer block (MAD block) realized with a `single-crystal-comb' curved on a rigid support is demonstrated here. The geometry of this curved surface is logarithmic spiral and is optimized to allow multi-filtering over a relatively important diffraction angular range and to be also applicable over an X-ray spectral range. The efficiency of such a small rigid-compact MAD block consisting of this single-crystal-comb generating 20-50 Si(111) single-crystal blades, associated with a block of Soller collimators, is demonstrated. The angle between each crystal is 0.1°, so the measurement range of the comb is 2-5°. The geometry of this system has been optimized for operation with a synchrotron X-ray source over an energy range of 22 keV to 46 keV and could be used with laboratory X-ray sources (Ag Kα1, 22.1 keV). This MAD block complements and exploits the qualities of the `photon-counting' detectors which have very low intrinsic noise. Their joint efficacy is supported by powder pattern measurements of a LaB6 reference sample and of several heterogeneous samples of cultural heritage materials, carried out at 22 keV on the D2AM beamline at the ESRF. Their signal-to-noise ratio is excellent (1000/1) and allows the detection thresholds of the measurements (from 3-1% to 0.1%) to detect minor phases in the studies of `real' heterogeneous materials to be drastically improved.

High-Resolution Coherent Probe Spectroscopy of a Polariton Quantum Fluid.

Characterizing elementary excitations in quantum fluids is essential to study their collective effects. We present an original angle-resolved coherent probe spectroscopy technique to study the dispersion of these excitation modes in a fluid of polaritons under resonant pumping. Thanks to the unprecedented spectral and spatial resolution, we observe directly the low-energy phononic behavior and detect the negative-energy modes, i.e., the ghost branch, of the dispersion relation. In addition, we reveal narrow spectral features precursory of dynamical instabilities due to the intrinsic out-of-equilibrium nature of the system. This technique provides the missing tool for the quantitative study of quantum hydrodynamics in polariton fluids.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

Polariton fluids for analogue gravity physics.

Analogue gravity enables the study of fields on curved space-times in the laboratory. There are numerous experimental platforms in which amplification at the event horizon or the ergoregion has been observed. Here, we demonstrate how optically generating a defect in a polariton microcavity enables the creation of one- and two-dimensional, transsonic fluid flows. We show that this highly tuneable method permits the creation of horizons. Furthermore, we present a rotating geometry akin to the water-wave bathtub vortex. These experiments usher in the possibility of observing stimulated as well as spontaneous amplification by the Hawking, Penrose and Zeld'ovich effects in fluids of light. This article is part of a discussion meeting issue 'The next generation of analogue gravity experiments'.

[Treatment of oligometastatic or oligoprogression cancer]. / Traitement des oligometastases et oligoprogression.

We propose in this short review to report the impact of stereotactic body radiation therapy (SBRT) in oligometastatic or oligoprogressive cancer patients in terms of metastatic progression-free and global survival, and to identify the place of SBRT in patient's pathway.

[Predictive assays for responses of tumors and normal tissues in radiation oncology]. / Outils pour la prédiction de la réponse tumorale et des tissus sains en oncologie radiothérapie.

The impact of curative radiotherapy depends mainly on the total dose delivered homogenously in the target volume. Tumor sensitivity to radiotherapy may be particularly inconstant depending on location, histology, somatic genetic parameters and the capacity of the immune system to infiltrate the tumor. In addition, the dose delivered to the surrounding healthy tissues may reduce the therapeutic ratio of many radiation treatments. In a same population treated in one center with the same technique, it appears that individual radiosensitivity clearly exists, namely in terms of late side effects that are in principle non-reversible. This review details the different radiobiological approaches that have been developed to better predict the tumor response but also the radiation-induced late effects.

[Individual modification of the dose, volume and fractionation of breast radiotherapy]. / Personnalisation de la dose, du volume et du fractionnement de la radiothérapie du sein.

Randomized trials demonstrated similar overall survival between mastectomy and breast-conservative surgery followed by adjuvant radiation therapy. Breast-conservative surgery, with adjuvant radiation therapy, with or without neoadjuvant systemic therapy has become the standard of care for women with early or locally advanced breast cancer. Nevertheless, certain cardiac, lung or cutaneous toxicities may alter the long-term body image and the quality of life of a limited number of patients who consider having had "overtreatment" or treatment outside the best knowledge of science. In case of low-risk breast cancer, several trials have evaluated the carcinologic outcome in absence of radiation therapy after breast-conservative surgery. Local recurrences increased in case of breast-conservative surgery alone but without impact on overall survival. Multiple debates have emerged in order to select the most appropriate evaluation criteria. Finally, a large consensus has considered that reducing local recurrences is important but with modern technologies and after identifying patients of individual radiosensitivity. Indeed, in case of a low absolute risk of local recurrence, radiation therapy techniques have been developed to allow a focal treatment especially for patients with high risk of developing late effects. This kind of compromise takes into account the reduction risk of local recurrences but also the probability of developing radiation-induced cutaneous sequelae. In the same way, for patients considered at high risk of recurrence, the huge volumes need specific techniques to better cover the targets while protecting the surrounding critic organs such as heart and lung. Intensity-modulated radiation therapy and the local high boost may help to decrease local recurrences of these more extended and aggressive diseases while considering the individual radiosensitivity that paves the way of long-term sequelae. In this article, we detail a personalized approach of breast radiation therapy considering the absolute risk of local recurrences and the probability of radiation-induced toxicity appearance.

Analytic expressions for the angular and the spectral fluxes at Compton X-ray sources.

The goal of this paper is to express simply the number of photons impinging on a target in the framework of accelerator-based Compton X-ray sources. From the basic kinematics of Compton sources, analytic formulas for the angular and the spectral fluxes are established as functions of the energy spread or/and the angular divergence of the electron and the laser beams. Their detailed predictions are compared with Monte Carlo simulations. These analytic expressions allow one to compute in a simple and precise way the X-ray flux in a given angular acceptance and a given energy bandwidth, knowing the characteristics of the incoming beams.

Dorsolateral striatum and dorsal hippocampus: a serial contribution to acquisition of cue-reward associations in rats.

In laboratory rodents, procedural and declarative-like memory processes are often considered operating in dual, sometimes even competing with each other. There is evidence that the initial approach of a repetitive task first engages a hippocampus-dependent declarative-like memory system acquiring knowledge. Over repetition, there is a gradual shift towards a striatum-dependent response memory system. In the current experiment, Long-Evans male rats with bilateral, fiber-sparing ibotenic acid-induced lesions of the dorsolateral striatum or the dorsal hippocampus were trained in an olfactory associative task requiring the acquisition of both a procedural and a declarative-like memory. Rats with dorsolateral striatum lesions, and thus an intact hippocampus, were impaired on both sub-categories of memory performance. Rats with dorsal hippocampal lesions exhibited a substantial deficit in learning the declarative-like cue-reward associations, while the acquisition of the procedural memory component of the task was not affected. These data suggest that the dorsolateral striatum is required to acquire the task rule while the dorsal hippocampus is required to acquire the association between a given stimulus and its associated outcome. The finding is that the dorsolateral striatum and the dorsal hippocampus most probably contribute to successful learning of cue-reward associations in a sequential (from procedural to declarative-like memory) order using this olfactory associative learning task.

Differential localization to cytoplasm, nucleus or P-bodies of yeast PKA subunits under different growth conditions.

Our aim in this work was to further characterize the complexity and specificity of the three different isoforms (Tpk1, Tpk2 and Tpk3) of the catalytic and regulatory (Bcy1) subunits of PKA in Saccharomyces cerevisiae. We thus analyzed the subcellular localization of the PKA subunits in living cells by using strains carrying GFP (green fluorescent protein) fused to each PKA subunit. During exponential growth on glucose, both Bcy1 and Tpk2 localized in the nucleus, whereas Tpk1 and Tpk3 showed a mixed pattern of nucleo-cytoplasmic localization. During exponential growth on glycerol and during stationary phase, the PKA subunits showed mostly cytoplasmic localization, with the peculiarity that Tpk2 and Tpk3 but not Bcy1, were found associated to P-bodies and EGP bodies. Tpk3 was accumulated into P-bodies during glucose deprivation and hyper osmotic stress. Deletion of Tpk3 altered the kinetics of P-body formation. Analysis of protein expression showed that the relative expression pattern of each Tpk changes from low levels under fermentative metabolism to higher levels during stationary phase. The increase in Tpk levels produced an imbalance with Bcy1 levels. Our data suggest that the signaling specificity through PKA in yeast could be mediated by a particular subcellular localization of each isoform of Tpk.

[Documentation management: from theory to practice]. / La gestion documentaire: de la théorie à la pratique.

The management of the documentation is one of the key points regarding the efficacy and the performance of the quality management of health centres. It offers to all professionals the possibility to be informed on the procedures in use, leading to a pool of documents for improvement of organisations and for securing the critical steps of the patient management. In this paper, we will describe the optimal organisation of the documentation according to Haute autorité de santé (HAS) and ISO recommendations, then we will discuss in concrete terms the potential methods usable for the production of a tool well adapted to our routine practice, in order to achieve the objectives for security.

Complete recovery of olfactory associative learning by activation of 5-HT4 receptors after dentate granule cell damage in rats.

Bilateral intradentate injections of 3.0microg of colchicine induced a substantial loss of granule cells and damage to the overlying pyramidal cell layer in region CA1 in adult male Long-Evans rats. All rats with such lesions showed a significant associative learning deficit in an olfactory discrimination task, while being unimpaired in the procedural component of this task. Injection of a partial selective 5-HT(4) agonist (SL65.0155; 0.01mg/kg, i.p., vs. saline) before the third of six training sessions enabled complete recovery of associative learning performance in the lesioned rats. Activation of 5-HT(4) receptors by a selective agonist such as SL65.0155 might therefore provide an opportunity to reduce learning and memory deficits associated with temporal lobe damage, and could be useful for the symptomatic treatment of memory dysfunctions related to pathological aging such as Alzheimer's disease.

An active haemovigilance programme characterizing the safety profile of 7437 platelet transfusions prepared with amotosalen photochemical treatment.

BACKGROUND: An active haemovigilance programme was implemented to survey adverse events (AE) associated with transfusion of platelets photochemically treated with amotosalen and ultraviolet A (PCT-PLT). The results of 5106 transfusions have already been reported. Here we report the results of an additional 7437 PCT-PLT transfusions. METHODS: The focus of this ongoing haemovigilance programme is to document all AEs associated with PCT-PLT transfusion. Data collected for AEs include: time of event after starting transfusion, clinical descriptions, vital signs, results from radiographs and bacterial cultures, event severity (Grade 0-4) and causal relationship to PCT-PLT transfusion. RESULTS: One thousand four hundred patients (mean 60 years, range 1-96) received PCT-PLT transfusions. The majority of the patients (53.4%) had haematology-oncology diseases and required conventional chemotherapy (44.8%) or stem cell transplantation (8.6%). Sixty-eight PCT-PLT transfusions were associated with AE. Acute transfusion reactions (ATR), classified as an AE possibly related, probably related, or related to PCT-PLT transfusions were infrequent (n = 55, 55/7437 = 0.7%) and most were of Grade 1 severity. Thirty-nine patients (39/1400 = 2.8%) experienced one or more ATRs. The most frequently reported signs/symptoms were chills, fever, urticaria, dyspnoea, nausea and vomiting. Five AEs were considered severe (> or = Grade 2); however, no causal relationship to PCT-PLT transfusion was found. Repeated exposure to PCT-PLT did not increase the likelihood of an ATR. No cases of transfusion-related acute lung injury and no deaths due to PCT-PLT transfusions were reported. CONCLUSIONS: Routine transfusion of PCT-PLT is well-tolerated in a wide range of patients. ATRs related to PCT-PLT transfusion were infrequent and most were of mild severity.

[Anesthesia for cesarean section in a patient with Lobstein's syndrome]. / Anästhesie zur Sectio caesarea bei einer Patientin mit Osteogenesis imperfecta.

We report on a 21-year-old woman with a severe form of Lobstein's syndrome, who underwent a Cesarean section. The following issues are discussed: the risk of sustaining fractures during positioning, fractures by automatic blood pressure measurement, an almost always existing latex allergy, a susceptibility for malignant hyperthermia, potential cardiac defect, difficult endotracheal intubation, lowering of the conus medullaris to an area usually used for spinal puncture, severe spinal deformities resulting in difficult puncture, hemorrhagic diathesis, and unpredictability of the expansion of local anesthetics in the vertebral canal. In this case the procedure could be carried out in spinal anesthesia without encountering major problems.

Heat shock-induced degradation of Msn2p, a Saccharomyces cerevisiae transcription factor, occurs in the nucleus.

In the yeast Saccharomyces cerevisiae, the zinc finger transcription factor Msn2p is a central component of the general stress response. It is activated in response to a wide variety of environmental changes, including physicochemical stresses as well as nutritional starvation, and induces the expression of a large set of genes required for cellular adaptation. The transcriptional activity of Msn2p in response to stresses is transient, and must therefore be strictly controlled. It is mainly regulated by reversible translocation from the cytoplasm to the nucleus upon the onset of stress, under the control of the cAMP-APK and the TOR pathways. In this report, we describe a new level of control: heat shock-induced degradation of Msn2p by the 26S proteasome. This degradation occurs in the nucleus and is further enhanced when Msn2p is fully active. Moreover, we show that the cyclin-dependent protein kinase Srb10p, a component of the transcription machinery, plays a role in the enhanced degradation of Msn2p upon heat shock. These findings provide new insights into the mechanisms by which Msn2p is transiently activated in response to stress.

Patient perspective on zanamivir in the treatment of influenza.

Placebo-controlled clinical studies have shown zanamivir to be an effective treatment of influenza A and influenza B illness. This survey, conducted in France, was done to evaluate patients' perception of zanamivir in clinical practice. Between January and mid-April 2000, 271 retail pharmacists gave questionnaires to patients with a prescription for zanamivir to be completed on a voluntary basis. A total of 514 patients returned completed questionnaires, of whom 97 (19%) were considered at high risk of developing influenza complications. Fifty-one (10%) patients, mainly those over 65 years, were vaccinated against influenza. Fever or feverishness was reported by 93% of patients, and cough, myalgia and headache by 72%. Most (58%) patients consulted their doctor within 24 hours of the onset of symptoms, and 96% within 48 hours. Eighty-five per cent of patients overall and 82% of high-risk individuals (82/97) reported being satisfied with their zanamivir treatment. Treatment compliance was high with 75% of patients completing the whole course of treatment. Symptom relief was reported by 45% of patients within 24 hours and by 74% of patients within 48 hours; 66% of patients resumed normal activities within 72 hours. These results suggest that patient satisfaction is high and compliance with zanamivir is highly satisfactory. In addition, the use of zanamivir was reported to be associated with rapidsymptom relief and return to normal activity