Production of Highly Polarized Positrons Using Polarized Electrons at MeV Energies.

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-Z target. Positron polarization up to 82% have been measured for an initial electron beam momentum of 8.19 MeV/c, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.

[Is nocturnal polyuria more frequent among patients with Parkinson's disease?]. / La polyurie nocturne est-elle plus fréquente chez les patients parkinsoniens?

OBJECTIVE: Nocturia is a frequent complaint in the population of idiopathic Parkinson's disease patients (IPD). The consequences of nocturia in the IPD population are at high importance as these patients have motor problems and therefore a risk of nocturnal fall. The aim of the study was to determine the mechanism of nocturia in patients with MPI, by determining the prevalence of nocturnal polyuria (NP) in this population. METHOD: A prospective study by bladder diary was conducted on 70 consecutive IPD patients consulting for regular neurological follow-up at a non-severe stage. Nocturia was defined as 1 or more awakenings to urinate. Two definitions of NP were used: nocturnal diuresis 33% or higher of the total diuresis (NUV33), which is the ICS (International Continence Society) definition, and nocturnal diuresis 90 mL/h or higher (NUP90). RESULTS: The mean patient age was 71 years (45-86, sex ratio 33/30). On average, patients were diagnosed for IPD 6.76 years earlier. The prevalence of NP was 64.5% according to NUV33 definition, and 17.7% according to NUP90 definition. Among patients with nocturia, the prevalence of NP was 66% (NUV33) and 21.5% (NUP90). No association was observed between disease duration of the IPD and the prevalence of nocturia and NP. Patients 70 years and older were more likely to have NP as defined by NUV33 than those less than 70 years (72.7% versus 55.17%, P=0.015). Men had more frequently nocturia (33.3% versus 20.7%, P=0.027). CONCLUSIONS: The prevalence of NP and nocturia was analyzed in patients with IPD at a non-severe stage. This prevalence was not higher than in the general population of the same age. The mechanism of nocturia in patients with IPD is not unambiguous and therefore requires to be explored by a bladder diary.

[Are the patients not carrying protections after radical prostatectomy really continent?]. / Les patients ne portant pas de protection après prostatectomie radicale sont-ils vraiment continents?

AIM: To analyse urinary continence and related quality of life in patients not wearing any pad after robotic assisted radical prostatectomy (RARP). METHOD: Two hundred and sixteen patients operated consecutively by RARP between January 2009 and June 2011 were evaluated by the ICS (International Continence Society) Male Self-questionnaire. The questionnaires were sent by mail and mailed back by patients with a minimum of 14 months following surgery. The ICS questionnaire contains a symptom score (ICS 1) and a quality of life score (ICS 2). RESULTS: Out of 216 sent questionnaires, 145 (67%) were received. The subgroup of 121 patients who replied that they were not wearing any pad was analysed. Fifty-three (43,8%) of them reported not having leakage when coughing or sneezing, 65 (53,7%) reported not having spontaneous leakage, and 102 (84,3%) reported not having leakage when sleeping. The ICS 1 and ICS 2 scores were strongly correlated (Pearson correlation coefficient 0.96). CONCLUSION: Within a group of patients not wearing any pad following RARP, the continence as assessed by self-questionnaires remains altered. This analysis might help counselling patients who are about to choose a surgical treatment for their prostate cancer.

[Limits of dose constraint definition for organs at risk specific to stereotactic radiotherapy]. / Limites de la définition des contraintes de dose pour les organes à risque spécifiques à la radiothérapie stéréotaxique.

Stereotactic radiotherapy is a very hypofractionated radiotherapy (>7.5Gy per fraction), and therefore is more likely to induce late toxicities than conventional normofractionated irradiations. The present study examines four frequent and potentially serious late toxicities: brain radionecrosis, radiation pneumonitis, radiation myelitis, and radiation-induced pelvic toxicities. The critical review focuses on the toxicity scales, the definition of the dose constrained volume, the dosimetric parameters, and the non-dosimetric risk factors. The most commonly used toxicity scales remain: RTOG/EORTC or common terminology criteria for adverse events (CTCAE). The definition of organ-at-risk volume requiring protection is often controversial, which limits the comparability of studies and the possibility of accurate dose constraints. Nevertheless, for the brain, whatever the indication (arteriovenous malformation, benign tumor, metastasis of solid tumors...), the association between the volume of brain receiving 12Gy (V12Gy) and the risk of cerebral radionecrosis is well established for both single and multi-fraction stereotactic irradiation. For the lung, the average dose received by both lungs and the V20 seem to correlate well with the risk of radiation-induced pneumonitis. For the spinal cord, the maximum dose is the most consensual parameter. Clinical trial protocols are useful for nonconsensual dose constraints. Non-dosimetric risk factors should be considered when validating the treatment plan.

[Management of patients with long term indwelling catheter: Survey of Limousin general practitioners]. / Prise en charge des patients avec sonde vesicale à demeure au long cours : enquête auprès des médecins généralistes du Limousin.

OBJECTIVE: To evaluate the management of patients with long-term (>1 month) indwelling catheter by general practitioners (GP). PATIENTS AND METHODS: A self-questionnaire was sent to 603 regional GP, between March and May 2010. It was composed of 12 multiple-choice questions and one open question, about management of their patients with indwelling catheter. RESULTS: Two hundred and twenty-eight self-questionnaires were analyzed: 126 (55%) from urban GP and 102 (45%) from rural GP. On average, each GP managed 1.3 patients with long term indwelling catheter (>1 month). The catheters were changed by the GP, urologists, and nurses in 23.2, 23.7, and 53.1%, respectively. In a majority of cases, catheters were changed every 4 weeks (59%). Nursing cares were prescribed by 64.5% of GP. Prescribed drainage bags were sterile in 42.5%. Most of GP reported to prescribe a daily change of drainage bag (56.1%). Urine analysis as performed only in case of symptomatic urine infection by 58% of respondents. Fifty percent of GP required guidelines for the management of patients with long term indwelling catheter. Rural GP managed significantly more patients with indwelling catheter, prescribed fewer sterile drainage bags, made change the drainage bag less often, and required the help of urologist less frequently. CONCLUSION: Management of long term indwelling catheter was heterogeneous among GP, and varied according to rural or urban practice. Some used significantly differed from available practice guidelines. This survey could be a basis for the preparation of an informative document aimed at GP.

[Magnetic resonance imaging for delineation of prostate in radiotherapy: monocentric experience and review of literature]. / Imagerie par résonance magnétique et délinéation de la prostate en radiothérapie : expérience monocentrique et revue de la littérature.

PURPOSE: To assess the benefits of magnetic resonance imaging (MRI) in the dosimetric treatment planning for prostate radiotherapy. PATIENTS AND METHODS: Ten consecutive patients have been enrolled. They were treated for a low risk prostate adenocarcinoma. A rigid superimposition was performed between MRI and scan slides obtained at time of virtual simulation, then prostate volume was delineated by four to five physicians, on TDM slides and on MRI/TDM superimposition. For each treatment plan, we assessed the impact of MRI in terms of planned treatment volume (PTV) position, individual variability of prostate delineation and doses delivered to the critical organs. The prescribed dose was 74 Gy in 37 fractions to the PTV. RESULTS: PTV delineated on TDM (V(TDM)) were 1.15 (SD 3.71) larger than volumes delineated on MRI. Prostate apex was 4.6 mm (SD 2.87) lower on TDM than on MRI. Posterior limit of the prostate was in mean 4 mm more posterior on TDM. The variability between physicians in terms of prostate delineation was lower using MRI. For apex, these variations were 6.8 mm using TDM, versus 3.3 mm using MRI. Mean rectal dose was 8 % lower with MRI, compared to delineation using TDM. CONCLUSION: Superimposition TDM/MRI improves accuracy, decreases delineation variability, and allows to spare anterior part of the rectum from irradiation. It remains unknown whether this strategy translates into clinical benefit.

Autologous dendritic cells pulsed with allogeneic tumour cell lysate induce tumour-reactive T-cell responses in patients with pancreatic cancer: A phase I study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is notorious for its poor prognosis even after curative resection. Responses to immunotherapy are rare and related to inadequate T-cell priming. We previously demonstrated the potency of allogeneic lysate-dendritic cell (DC) vaccination in a preclinical model. Here we translate this concept to patients. METHODS: In this phase I study, patients with resected PDAC were included when they demonstrated no radiologic signs of recurrence after standard-of-care treatment. Allogeneic tumour lysate-loaded autologous monocyte-derived DCs were injected at weeks 0, 2, 4 and at months 3 and 6. Objectives are feasibility, safety and immunogenicity of allogeneic tumour-DCs. The presence of tumour antigens shared between the vaccine and patient tumours was investigated. Immunological analyses were performed on peripheral blood, skin and tumour. RESULTS: Ten patients were included. DC production and administration were successful. All patients experienced a grade 1 injection-site and infusion-related reaction. Two patients experienced a grade 2 fever and 1 patient experienced a grade 3 dyspnoea. No vaccine-related serious adverse events were observed. Shared tumour antigens were found between the vaccine and patient tumours. All evaluated patients displayed a vaccine-induced response indicated by increased frequencies of Ki67+ and activated PD-1+ circulating T-cells. In addition, treatment-induced T-cell reactivity to autologous tumour of study patients was detected. Seven out of ten patients have not experienced disease recurrence or progression at a median follow-up of 25 months (15-32 months). CONCLUSION: Allogeneic tumour lysate-DC treatment is feasible, safe and induces immune reactivity to PDAC expressed antigens.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

TCT.1, a target molecule for gamma/delta T cells, is encoded by an immunoglobulin superfamily gene (Blast-1) located in the CD1 region of human chromosome 1.

We have recently generated a series of gamma/delta T cell clones able to kill, after in vitro immunization, an Epstein-Barr Virus-transformed B cell line (designated E418) in a non-major histocompatibility complex-requiring fashion. A monoclonal antibody, termed anti-10H3, produced against E418 was selected by its ability to block these cytotoxic interactions. Further analysis indicated that the inhibitory effects of anti-10H3 were highly selective (i.e., no blocking activity with multiple control clones used as effector cells; no alteration of the natural killer-like function mediated by the relevant gamma/delta clones against 10H3+ tumor cells such as Rex). The molecule immunoprecipitated by anti-10H3, termed TCT.1, was characterized as a 43-kD protein broadly distributed in the hematopoietic system. The TCT.1 molecule has been further studied here by protein microsequencing. Results show that the TCT.1-derived peptide sequences are virtually identical to corresponding regions of Blast-1, a previously described surface protein with unknown function. The likely identity of the two molecules has been strengthened by analyzing the susceptibility of TCT.1 to phosphatidylinositol-specific phospholipase C digestion in light of the known anchorage of Blast-1 to the cell membrane through a glycosyl-phosphatidylinositol-containing lipid. The TCT.1/Blast-1-encoding gene is well characterized; it belongs to the immunoglobulin gene superfamily and it is located in the same band of chromosome 1 as the CD1 gene cluster. Together, these data further support the view that proteins distinct from the conventional class I/II histocompatibility molecules are involved in specific T cell recognition.

Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjogren syndrome: a case-control study.

OBJECTIVES: To assess subclinical central nervous system (CNS) involvement in primary Sjögren syndrome (pSS), by comparing standard brain MRI, in-depth neuropsychological testing and (99m)Tc-ECD brain single-photon emission computed tomography (SPECT) of patients with pSS with matched controls. METHODS: 10 women (<55 years old), with pSS defined using European-American criteria, presence of anti-SSA and/or anti-SSB antibodies and no history of neurological involvement were prospectively investigated, and compared with 10 age- and sex-matched controls. All subjects underwent, within 1 month, brain MRI, neuropsychological testing, including overall evaluation and focal cognitive function assessment, and (99m)Tc-ECD brain SPECT. RESULTS: (99m)Tc-ECD brain SPECT abnormalities were significantly more common in patients with pSS (10/10) than controls (2/10; p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial disorders, were also significantly more common in patients with pSS (8/10) than controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant correlation to be established between neuropsychological assessment and (99m)Tc-ECD brain SPECT abnormalities in patients with pSS (r(s) = 0.49, p<0.01). MRI abnormalities in patients and controls did not differ significantly. CONCLUSIONS: Neuropsychological testing and (99m)Tc-ECD brain SPECT seem to be the most sensitive tools to detect subclinical CNS dysfunction in pSS. The strong correlation between cortical hypoperfusion in (99m)Tc-ECD brain SPECT and cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS. These data should be confirmed in a larger study.

[MRI features of spinal neurosarcoidosis associed with cervical spondylosis]. / Myélopathie sarcoïdosique associée à un canal cervical rétréci : aspects IRM.

INTRODUCTION: Spinal neurosarcoidosis is rare and exceptionally inaugural. OBSERVATION: A 49-year-old African woman developed a progressive left Brown-Sequard syndrome. Magnetic resonance imaging (MRI) scans of the cervical spinal cord revealed an intramedullary lesion from C2 to T1 with intense pial enhancement after administration of contrast material associated with cervical spondylosis. The diagnostic of sarcoidosis was confirmed by liver biopsy which demonstrated noncaseating granulomas. CONCLUSIONS: MRI features of spinal neurosarcoidosis were reviewed by the authors with focus on differential diagnosis.

Independent 6D quality assurance of stereotactic radiotherapy repositioning on linacs.

PURPOSE: A high level of accuracy while positioning the patient is mandatory for frameless stereotactic radiotherapy (SRT), as large doses in multiple fractions can be delivered near organs at risk. The objective of this study is to propose an end-to-end quality assurance method to verify that submillimetre alignment can be achieved with stereotactic conventional linacs. METHODS: We used a TrueBeam® linear accelerator equipped with a 6DOF robotic couch. The "ISO Cube" phantom was used with a homemade stand designed to generate known translational and rotational offsets. A reference CT scan was performed with straight alignment of the phantom. The procedure introduced 1.6° angular offset for the couch pitch and roll, at various gantry angles. The couch base was also moved between 0° and 270°. We compared the results with the daily machine performance check tests (MPC, Varian). RESULTS: The mean isocentre size, MV and kV imager offsets were found to agree to within 0.1mm, 0.1mm and 0.3mm respectively, and were in close agreement between the methods. For a total four months data collection period, the mean deviation between requested and measured 6DOF couch shifts was 0.6mm and 0.2°. Errors on field size were smaller than 1mm for 97.7% of the 324 data points. CONCLUSION: Results demonstrate that the linac equipped with a 6DOF robotic positioner and CBCT imaging satisfies requirements for SRT. Our methodology, based on a modified Winston-Lutz quality control, allowed us to quantitatively assess end-to-end accuracy of a linac in order to safely deliver SRT.

Is skeletal muscle mitochondrial dysfunction a cause or an indirect consequence of insulin resistance in humans?

The precise cause of insulin resistance and type 2 diabetes is unknown. However, there is a strong association between insulin resistance and lipid accumulation - and, in particular, lipotoxic fatty acid metabolites - in insulin-target tissues. Such accumulation is known to cause insulin resistance, particularly in skeletal muscle, by reducing insulin-stimulated glucose uptake. Reduced fat-oxidation capacity appears to cause such lipid accumulation and, over the past few years, many studies have concluded that decreased mitochondrial oxidative phosphorylation could be the initiating cause of lipid deposition and the development of insulin resistance. The aim of this review is to summarize the latest findings regarding the link between skeletal muscle mitochondrial dysfunction and insulin resistance in humans. At present, there are too few studies to definitively conclude that, in this context, mitochondria are functionally impaired (dysfunction in the respiratory chain). Indeed, insulin resistance could also be related to a decrease in the number of mitochondria or to a combination of this and mitochondrial dysfunction. Finally, we also consider whether or not these aberrations could be the cause of the development of the disease or whether mitochondrial dysfunction may simply be the consequence of an insulin-resistant state.

Ultrasonic properties near 50 K of the quasi-one-dimensional conductors A(0.30)MoO(3) (A = K, Rb) and Rb(0.30)(Mo(1-x)V(x))O(3).

The charge density wave (CDW) nonlinear conductivity of the blue bronzes A(0.30)MoO(3) (A = K, Rb) shows two different regimes depending on the temperature: a strongly damped CDW motion above ∼50 K and a CDW motion with almost no damping below ∼50 K. In a search for an elastic signature of this CDW behaviour, we performed ultrasonic measurements on A(0.30)MoO(3) single crystals in the temperature range 4-300 K. In Rb(0.30)MoO(3), at T∼50 K, upon cooling, a large increase of the sound velocity for the longitudinal mode measured along the [Formula: see text], [102] and b directions is observed. The ultrasonic attenuation coefficient shows an increase down to 50 K followed by a plateau. Similar results are found in K(0.30)MoO(3). In V-doped samples, Rb(0.30)(Mo(1-x)V(x))O(3) (x = 0.4%) the anomaly broadens and is shifted towards higher temperatures. The results are discussed in relation to the changes in the CDW rigidity, disorder and dielectric response. A scenario based on a glass transition for the CDW superstructure is proposed.

[Dosimetric impact of the 2D motion of a platform simulating breathing during a dynamic mode treatment]. / Impact dosimétrique du mouvement 2D d'une plateforme simulant la respiration lors d'un traitement en mode dynamique.

Breathing-adapted techniques in external radiotherapy lead to the improvement of the taken into account of the tumour motion during the patient treatment. Indeed, this motion involves dosimetric uncertainties, in particular during a dynamic treatment (intensity-modulated radiation therapy, dynamic wedge...). As tumoral movement is complex and is carried out in various directions of space, a dynamic platform moving in one or two plans was conceived. This article approaches the technical aspects of design and functioning of this prototype. A study of the dosimetric effects of the respiratory movement on one and two plans during a dynamic treatment without gating will be presented. Films were irradiated while varying the rates with wedged fields at various speeds. The penumbra of beams were compared with the static case and appeared twice broader in the majority of the cases. The results highlighted the contributions of the longitudinal and the axial components of the motion on the form of the dose distribution. These results were completed with gamma index measurements to determine an internal margin. Moreover, this platform proves to be a promising tool for breathing-adapted treatment, in particularly to test the synchronisation of RPM system in fluoroscopic mode in board imaging system.

[Preoperative factors of misdiagnosis of renal angiomyolipoma]. / Facteurs associés à l'échec du diagnostic préopératoire des angiomyolipomes rénaux.

OBJECTIVES: To explain the high incidence of misdiagnosis of angiomyolipoma (AML) prior to surgery. MATERIALS AND METHODS: Between 1989 and 2007, 2,657 patients were operated for a renal tumor at Dupuytren hospital in Limoges and at Cochin hospital in Paris. In 85 cases (3.2%), tumors were AMLs on pathology. The group of patients in which the diagnosis was done preoperatively was compared to the one in which the diagnosis was missed. RESULTS: Mean age of patients was 57-years-old and the sex-ratio was five women for one man. The mean size of AMLs was 5.4 cm. The patients were symptomatic in 46% of cases (39/85). The diagnosis of AML was ignored preoperatively in 62 patients (73%). In multivariate analysis, the small size of the AML, low proportion of fat and male sex were significantly associated with misdiagnosis of AML (p<0.001, p<0.018 and p<0.008, respectively). CONCLUSIONS: The incidence of misdiagnosis of AML preoperatively is high. The diagnosis seems particularly difficult when the tumor is small or contains a small proportion of fat. In addition, this study highlights that the diagnosis of AML is frequently ignored in men. The increased resolution of CTscan and the use of preoperative biopsies for tumors less than 4 cm could be helpful to decrease the incidence of useless surgery of AMLs.

"The VIHsibilite Project": HIV-positive people in the Quebec press and community responses.

The VIHsibilite Project is a community-based action-research initiative that examines newspaper coverage of HIV/AIDS issues in Quebec from 1988 to 2004. Using standard qualitative research methods, and in consultation with an advisory committee of people directly impacted by HIV/AIDS news coverage, the project discerns trends in reporting on HIV/AIDS and undertakes discursive content analysis of these, aiming to better understand in what normative ways seropositive people are represented in print media, and, ultimately, to reduce the stigma attendant upon HIV infection. Preliminary findings include indications that seropositive women tend to be represented markedly differently from men in the news.

Antitumor activity of sorafenib in FLT3-driven leukemic cells.

Activating internal tandem duplication (ITD) insertions in the juxtamembrane domain of the FLT3 tyrosine kinase are found in about one fourth of patients with acute myeloid leukemia and have been shown to be an independent negative prognostic factor for survival. We show that sorafenib (BAY 43-9006, Nexavar) potently inhibits FLT3 enzymatic and signaling activities. In HEK293 cells stably transfected with FLT3-WT or FLT3-ITD, sorafenib blocked basal and ligand dependent FLT3-mediated tyrosine autophosphorylation as well as extracellular signal-regulated kinase1/2 and Stat5 phosphorylation. In leukemia cell lines MV4-11 and EOL-1, sorafenib treatment resulted in decreased cell proliferation and inhibition of FLT3 signaling. The growth of the FLT3-independent RS4-11 cell line was only weakly inhibited by sorafenib. Cell cycle arrest and induction of apoptosis were observed upon treatment with sorafenib in MV4-11 and EOL-1 cells. The antitumor efficacy of sorafenib was evaluated against the MV4-11 leukemia grown subcutaneously in NCr nu/nu mice. Doses of 3 and 10 mg/kg administered orally for 14 days resulted in six and nine out of 10 animals with complete responses, respectively. The demonstration that sorafenib exhibits potent target inhibition and efficacy in FLT3-driven models suggests that this compound may have a therapeutic benefit for patients with FLT3-driven leukemias.

[MR and CT features of craniocervical junction tuberculosis: a report of 5 cases]. / Caractéristiques IRM et TDM de la tuberculose de la jonction crânio-vertébrale: à propos de 5 cas.

Tuberculosis of the craniocervical junction is rare but may cause significant complications with severe sequelae due to the nearby presence of important neurovascular structures. The CT and MR features of 5 cases are presented with correlation with reports from the literature. The differential diagnosis is reviewed.