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Methylmercury (MeHg) is a ubiquitous bioaccumulative neurotoxicant present in aquatic ecosystems. It is known to alter behaviors, sensory functions and learning abilities in fish and other vertebrates. Developmental and early-life stages exposure to MeHg can lead to brain damage with immediate consequences on larvae behavior, but may also induce long term effects in adults after a detoxification period. However, very little is known about developmental origin of behavioral impairment in adults due to early exposure to MeHg. The aim of this study is to assess whether early-life MeHg exposure induces immediate and/or delayed effects on behaviors, related genes expression and DNA methylation (one of epigenetic mechanisms). To reach this goal, newly hatched larvae of mangrove rivulus fish, Kryptolebias marmoratus, were exposed to two sub-lethal concentrations of MeHg (90 μg/L and 135 µg/L) for 7 days, and immediate and delayed effects were assessed respectively in 7 dph (days post-hatching) and 90 dph fish. This species naturally produces isogenic lineages due to its self-fertilizing reproduction system, which is unique among vertebrates. It allows to study how environment stressors can influence organism's phenotype while minimizing genetic variability. As results, both MeHg exposures are associated with a decreased foraging efficiency and thigmotaxis, and a dose-dependent reduction in larvae locomotor activity. Regarding molecular analysis in larvae whole bodies, both MeHg exposures induced significant decreased expression of DNMT3a, MAOA, MeCP2 and NIPBL, and significant increase of GSS, but none of those genes underwent methylation changes in targeted CpGs. None of significant behavioral and molecular impairments observed in 7-dph larvae were found in 90-dph adults, which highlight a distinction between immediate and delayed effects of developmental MeHg exposure. Our results suggest implications of aminergic system and its neurotransmitters, redox/methylation trade-off and possibly other epigenetic mechanisms in MeHg neurotoxicity underlying behavioral alterations in rivulus.

BACKGROUND A large number of drugs administered to children have no commercially available formulations. As a result, health care providers and parents manipulate dosage forms designed for adults. Although compounding is essential to increase access to medicines for children, it can result in adverse events or therapeutic failure. There is an urgent need to undertake a mapping of the needs for child-friendly medicines in Canada. OBJECTIVES To determine: 1) the most frequently compounded medicines in Canadian paediatric hospitals; 2) the challenges associated with drug compounding; and 3) medicines most in need of commercialized oral paediatric formulations. DESIGN/METHODS Sixteen Canadian paediatric academic hospitals were contacted to participate in a telephone survey including 12 open-, close-ended or Likert-scale questions. RESULTS Thirteen centers participated in the survey (81.3%). Fifty-three drugs were identified as most in need of a commercialized oral paediatric formulation. Of those, 12 were reported by ≥4 hospitals as a priority (Table). The most frequently reported compounding challenges were: lack of standardization, bad taste, lack of awareness of prescribers, stability of the formulation, and availability of compounding pharmacies. CONCLUSION This study highlights which drugs are most needed for paediatric oral formulations in Canada. For compounded medicines with paediatric formulations available in other countries we are currently assessing their adequacy and partnering with pharmaceutical industry to bring them to the Canadian market. As for those medicines without paediatric formulations in Canada or abroad we are looking for partners interested in developing such formulations. Furthermore, harmonized regulations and data-sharing should be pursued to facilitate access to child-friendly medicines.

Both magnetic relaxometry and magnetic resonance imaging (MRI) can be used to detect and locate targeted magnetic nanoparticles, noninvasively and without ionizing radiation. Magnetic relaxometry offers advantages in terms of its specificity (only nanoparticles are detected) and the linear dependence of the relaxometry signal on the number of nanoparticles present. In this study, detection of single-core iron oxide nanoparticles by superconducting quantum interference device (SQUID)-detected magnetic relaxometry and standard 4.7 T MRI are compared. The nanoparticles were conjugated to a Her2 monoclonal antibody and targeted to Her2-expressing MCF7/Her2-18 (breast cancer cells); binding of the nanoparticles to the cells was assessed by magnetic relaxometry and iron assay. The same nanoparticle-labeled cells, serially diluted, were used to assess the detection limits and MR relaxivities. The detection limit of magnetic relaxometry was 125 000 nanoparticle-labeled cells at 3 cm from the SQUID sensors. T(2)-weighted MRI yielded a detection limit of 15 600 cells in a 150 µl volume, with r(1) = 1.1 mm(-1) s(-1) and r(2) = 166 mm(-1) s(-1). Her2-targeted nanoparticles were directly injected into xenograft MCF7/Her2-18 tumors in nude mice, and magnetic relaxometry imaging and 4.7 T MRI were performed, enabling direct comparison of the two techniques. Co-registration of relaxometry images and MRI of mice resulted in good agreement. A method for obtaining accurate quantification of microgram quantities of iron in the tumors and liver by relaxometry was also demonstrated. These results demonstrate the potential of SQUID-detected magnetic relaxometry imaging for the specific detection of breast cancer and the monitoring of magnetic nanoparticle-based therapies.

Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable locally advanced stage III non-small cell lung cancer. However, the optimal combination remains unclear. The aim of this study was to evaluate the efficacy of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m2 and cisplatin 75 mg/m2 followed by concurrent chemotherapy (weekly docetaxel-cisplatin, 20 mg/m2) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5 fractions per week/2 Gy per fraction). The primary endpoint was the response rate. Secondary objectives were toxicity, time to progression, and overall survival. Forty-four patients were included and 40 were eligible. The mean age was 60.5 years (range 40.7–72.1), and 75% had stage IIIB disease. Six patients underwent complete R0 resection including 2 pathologic complete responses after a planned intermediate evaluation. Thirty-three patients completed CHRT. The objective response rate was 65% (95% CI 50.2–79.8). Grade 3–4 hematologic and digestive toxicities were observed mainly during the induction phase. Grade 3 esophagitis (5%) was experienced during CHRT. With a median follow-up of 38.7 months, the median progression-free survival was 28.3 months (95% CI 11.0–35.0) and the median survival rate was 31.4 months. Cisplatin-docetaxel induction followed by concurrent 3-D conformal radiotherapy and weekly chemotherapy is a feasible protocol associated with a promising response rate and acceptable toxicity.

Resume Objectif de l’etude La chirurgie est le traitement de reference des sarcomes uterins localises. Nous avons mene une etude retrospective pour definir les facteurs pronostiques dans cette pathologie. Patientes et methodes Nous avons etudie 111 dossiers de patientes traitees par irradiation postoperatoire pour un sarcome uterin dans sept centres. Le recul median etait de 31 mois. Nous avons effectue une analyse unifactorielle afin d’identifier les facteurs de recidive locale. Les facteurs statistiquement significatifs ont ete etudies en analyse multifactorielle selon le modele de Cox. Resultats L’âge moyen des patientes etait de 60 ans et la dose mediane de radiotherapie externe de 45 Gy. Quarante-trois pour cent des patientes ont eu une curietherapie du fond vaginal et 21 % une chimiotherapie. Seulement 6,3 % des patientes ont souffert de complications aigues de grade III et 8,1 % de sequelles a long terme de la radiotherapie. Le taux de survie a cinq ans etait de 74,6 %. On notait 12,6 % de recidives locoregionales isolees, 29,7 % de recidives a distance. Les facteurs correles avec le risque de rechute locoregionale etaient le statut menopausique (p = 0,045) et les tranches de section chirurgicales non saines (p = 0,0095). La chimiotherapie n’ameliorait pas la probabilite de survie globale, ni celle de survie sans recidive. Conclusion La radiotherapie postoperatoire permet un bon taux de controle local dans cette pathologie. La curietherapie n’ameliore pas le taux de controle local. La chimiotherapie n’est pas un standard au stade de tumeur localisee mais le taux de recidive metastatique plaide en faveur du developpement de strategies associant un traitement systemique a la radiotherapie.

We use dynamic susceptometry measurements to extract semiempirical temperature-dependent, 255–400 K, magnetic parameters that determine the behavior of single-core nanoparticles useful for SQUID relaxometry in biomedical applications. Volume susceptibility measurements were made in 5 K degree steps at nine frequencies in the 0.1–1000 Hz range, with a 0.2 mT amplitude probe field. The saturation magnetization (Ms) and anisotropy energy density (K) derived from the fitting of theoretical susceptibility to the measurements both increase with decreasing temperature; good agreement between the parameter values derived separately from the real and imaginary components is obtained. Characterization of the Neel relaxation time indicates that the conventional prefactor, 0.1 ns, is an upper limit, strongly correlated with the anisotropy energy density. This prefactor decreases substantially for lower temperatures as K increases. We find, using the values of the parameters determined from the real part of the susceptibility measurements at 300 K, that SQUID relaxometry measurements of relaxation and excitation curves on the same sample are well described.

Optimizing the sensitivity of SQUID (superconducting quantum interference device)-relaxometry for detecting cell-targeted magnetic nanoparticles for in vivo diagnostics requires nanoparticles with a narrow particle size distribution to ensure that the Néel relaxation times fall within the measurement timescale (50 ms - 2 s, in this work). To determine the optimum particle size, single-core magnetite nanoparticles (with nominal average diameters 20, 25, 30, and 35 nm) were characterized by SQUID-relaxometry, transmission electron microscopy (TEM), SQUID-susceptometry, dynamic light scattering, and zeta potential analysis. The SQUID-relaxometry signal (detected magnetic moment/kg) from both the 25 nm and 30 nm particles was an improvement over previously-studied multi-core particles. However, the detected moments were an order of magnitude lower than predicted based on a simple model that takes into account the measured size distributions (but neglects dipolar interactions and polydispersity of the anisotropy energy density), indicating that improved control of several different nanoparticle properties (size, shape, coating thickness) will be required to achieve the highest detection sensitivity. Antibody conjugation and cell incubation experiments show that single-core particles enable a higher detected moment per cell, but also demonstrate the need for improved surface treatments to mitigate aggregation and improve specificity.

Introduction L’angiostrongylose humaine est une zoonose transmise par un nematode du genre Angiostrongylus. Les 2 principales especes pathogenes identifiees chez l’Homme sont Angiostrongylus cantonensis ( A. cantonensis ) et Angiostrongylus costaricensis ( A. costaricensis ) responsables respectivement d‘angiostrongylose nerveuse (meningo-encephalite a eosinophiles) et d’angiostrongylose intestinale (pseudo-appendicite aigue avec hypereosinophilie). Cette pathologie est endemique sur le continent asiatique et en ocean pacifique mais reste peu decrite dans la Caraibe. La presence conjointe de ces 2 especes d’ Angiostrongylus dans un meme ecosysteme est exceptionnelle et n’a jamais ete rapportee, a notre connaissance, dans les petites Antilles. L’objectif de cette etude etait donc de decrire les donnees epidemiologiques sur l’angiostrongylose humaine en Martinique. Materiels et methodes Une etude observationnelle retrospective monocentrique a ete menee dans notre centre hospitalier entre le 01/01/2000 et le 31/12/2017. Tout patient ayant un diagnostic parasitologique (serologie ou PCR) ou anatomo-pathologique confirme d’angiostrongylose nerveuse ou intestinale etait inclus. Resultats Douze cas de d’angiostrongylose humaine ont ete identifies dans notre etude, incluant 8 cas d’angiostrongylose nerveuse a A. cantonensis et 4 cas d’angiostrongylose intestinale a A. costaricensis . L’âge median etait de 14 ans (IQR : 1–27) avec un sex-ratio homme/femme de 2. Une fievre (> 38 °C) etait observee dans 92 % des cas (11/12). Tous les patients presentaient une hypereosinophilie (> 0,5 G/L) avec une duree mediane de persistance de l’eosinophilie de 23,5 jours (IQR : 14,5–34,5). Tous les patients avaient une confirmation diagnostique serologique (sang ou LCR) ou anatomopathologique pour les cas d’ A. costaricensis . Le mode de transmission probable etait l’ingestion ou un contact etroit dans l’environnement avec Achatina fulica (hote intermediaire) dans 83 % des cas (10/12). Onze patients ont recu un traitement par albendazole (10/12) ou ivermectine (1/12). L’evolution etait favorable dans 11 cas sur 12. Un deces d’angiostrongylose neurologique a ete observe. Conclusion Nous decrivons la plus grande serie de cas d’angiostrongylose humaine dans la Caraibe. L’angiostrongylose, pathologie negligee, doit cependant etre evoquee devant toute hypereosinophilie avec atteinte neurologique ou abdominale en Martinique. Une meilleure connaissance de son hote intermediaire, Achatina fulica , devrait permettre d’ameliorer les strategies de prevention primaire et secondaire.

Acute leukemia is a hematopoietic malignancy for which the accurate measurement of minimal residual disease is critical to determining prognosis and treatment. Although bone marrow aspiration and light microscopy remain the current standard of care for detecting residual disease, these approaches cannot reliably discriminate less than 5% lymphoblast cells. To improve the detection of leukemia cells in the marrow, we developed a novel apparatus that utilizes antibodies conjugated to superparamagnetic iron oxide nanoparticles (SPION) and directed against the acute leukemia antigen CD34, coupled with a “magnetic needle” biopsy. Leukemia cell lines expressing high or minimal CD34 were incubated with anti-CD34–conjugated SPIONs. Three separate approaches including microscopy, superconducting quantum interference device magnetometry, and in vitro magnetic needle extraction were then used to assess cell sampling. We found that CD34-conjugated nanoparticles preferentially bind high CD34-expressing cell lines. Furthermore, the magnetic needle enabled identification of both cell line and patient leukemia cells diluted into normal blood at concentrations below those normally found in remission marrow samples. Finally, the magnetic needle enhanced the percentage of lymphoblasts detectable by light microscopy by 10-fold in samples of fresh bone marrow aspirate approximating minimal residual disease. These data suggest that bone marrow biopsy using antigen-targeted magnetic nanoparticles and a magnetic needle for the evaluation of minimal residual disease in CD34-positive acute leukemias can significantly enhance sensitivity compared with the current standard of care. [Cancer Res 2009;69(21):8310–6]

Magnetite nanoparticles (Chemicell SiMAG-TCL) were characterized by SQUID-relaxometry, susceptometry, and TEM. The magnetization detected by SQUID-relaxometry was 0.33% of that detected by susceptometry, indicating that the sensitivity of SQUID-relaxometry could be significantly increased through improved control of nanoparticle size. The relaxometry data were analyzed by the moment superposition model (MSM) to determine the distribution of nanoparticle moments. Analysis of the binding of CD34-conjugated nanoparticles to U937 leukemia cells revealed 60,000 nanoparticles per cell, which were collected from whole blood using a prototype magnetic biopsy needle, with a capture efficiency of >65% from a 750 µl sample volume in 1 minute.

There is a pronounced need for a sustainable care model for total joint arthroplasty in the United States. Total hip and knee arthroplasty is expected to increase 673% by 2030, and Medicare is the payor for a majority of these episodes. Our objective was to compare orthopedic cohort groups with and without defined postacute care pathways and the effects of the care pathways on service utilization and cost for Medicare patients in the Bundled Payments for Care Improvement program.Claims data for elective hip and knee arthroplasty episodes from a national bundled payments for care improvement database were the source of our study data. Independent reviewers were used to determine which groups had defined clinical pathways. The 2 cohort groups were then compared between those with defined clinical pathways and those without. Outcomes measures included postacute care costs, utilization rates (both frequency and length of time) for inpatient rehabilitation facilities, skilled nursing facilities, home health, and readmissions.Orthopedic physicians with defined postacute care pathways showed consistent decreases in cost and utilization as compared to physicians without defined postacute care pathways. Elective hip arthroplasty per episode cost differential was $3189 per episode between physicians with care pathways ($19,005) and those without ($22,195; P.001). Elective knee arthroplasty per episode cost difference was $2466 per episode between physicians with care pathways ($18,866) and those without ($21,332; P .001). Incident rates of utilization for postacute care services displayed significant differences between physicians with and without postacute care pathways. Physicians with defined postacute pathways demonstrated utilization reductions ranging from 7% to 79% with incident rate reductions ranging from 44% to 79%.The results suggest that orthopedic physicians with defined postacute care pathways affect discharge disposition. The findings show significant cost and utilization reductions for physicians with defined postacute care pathways.

Purpose The objective of this randomised phase II study was to evaluate the impact in terms of response and toxicities of induction or consolidation chemotherapy respectively before or after concurrent chemoradiotherapy in unresectable stage III non-small-cell lung cancer. Patients and methods In the induction arm, patients received induction chemotherapy with cisplatin (80 mg/m 2 ) and paclitaxel (200 mg/m 2 ) on days 1 and 29 followed by a concurrent chemoradiotherapy (66 Gy in 33 fractions, cisplatin 80 mg/m 2 days 1, 29 and 57, vinorelbine 15 mg/m 2 days 1, 8, 29, 36, 57 and 64). In consolidation arm, the same concurrent chemoradiotherapy began on day 1 followed by two cycles of cisplatin and paclitaxel. Results One hundred twenty seven patients were randomised. The intent to treat response rates in induction and consolidation arms were 58% and 56% respectively. Median survival was 19.6 months in induction arm and 16.3 months in consolidation arm and 4-year survival rates were 21% and 30% respectively. Haematologic and non-haematologic toxicities were similar in both arms, except grade 3/4 oesophagitis, more frequent in consolidation arm than in induction arm (17% versus 10%). Conclusion Cisplatin-based chemotherapy as induction or consolidation with concurrent chemoradiotherapy can be administrated safely. Response rates were similar in both arms with a trend in favour for consolidation arm for long-term survival.

A novel sensitive high-performance liquid chromatography-electrospray mass spectrometry method has been developed for the determination of ursodeoxycholic acid (UDCA) and its glycine and taurine conjugates, glycoursodeoxycholic acid (GDCA) and tauroursodeoxycholic acid (TDCA). The procedure involved a solid phase extraction of UDCA, GDCA, TDCA and the internal standard, 23-nordeoxycholic acid from human plasma on a C18 Bond Elut cartridge. Chromatography was performed by isocratic reverse phase separation with methanol/25 mM ammonium acetate (40/60, v/v) containing 0.05% acetic acid on a C18 column with embedded polar functional group. Detection was achieved using an LC-MS/MS system. The standard curve was linear over a working range of 10-3000 ng/ml for all analytes and gave an average correlation coefficient of 0.9992 or better during validation. The absolute recovery for UDCA, GDCA, TDCA and the internal standard was 87.3, 83.7, 79.5 and 95.8%, respectively. This method is simple, sensitive and suitable for pharmacokinetics, bioequivalence or clinical studies.

Introduction La resistance bacterienne represente un probleme majeur de sante publique. Beaucoup d’actions de bon usage concernent l’hopital et peu sont destinees a la ville, ou 90 % des antibiotiques sont prescrits. L’infection urinaire represente 20 % des prescriptions d’antibiotiques en ville et cette antibiotherapie devrait etre reevaluee a j3 (sauf traitements minutes). A ce jour, il n’y a pas de donnee concernant cette reevaluation. L’objectif de cette etude est d’evaluer le pourcentage de reevaluation de l’antibiotherapie dans l’infection urinaire de l’adulte en ambulatoire. Materiels et methodes Etude multicentrique, observationnelle, descriptive, transversale avec inclusion prospective consecutive des patients realisant un ECBU dans l’un des laboratoires participants. Un appel telephonique au patient et au medecin generaliste a j3–j4 a permis d’evaluer la reevaluation, la pertinence de l’antibiotherapie initiale et la conformite aux recommandations. L’objectif secondaire etait d’evaluer le taux d’ECBU realises hors recommandations (cystites simples). A ce jour, le recueil a eu lieu sur un seul groupement de laboratoire. Le recueil sur les 2 groupements restants se fera entre fevrier et avril 2017. L’etude a ete soumise a l’approbation de la CNIL, du CCTIRS et d’un CPP. Resultats A ce jour, 39 patients ont ete inclus. 4 patients sont perdus de vue. Sur les 35 patients restants, il y a eu 28 traitements de plus de 3 jours dont 18 ont ete reevalues a J3 (64,3 %). Dix-neuf ECBU ont ete prescrits hors recommandations (cystites simples) soit 54,3 %. En probabiliste, en cas de traitement de plus de 3 jours (12 cystites simples), la principale molecule prescrite est une fluoroquinolone (15/28 ECBU soit 53,6 %). En cas de reevaluation, l’antibiotherapie etait modifiee dans 33,3 % (6/18 reevaluations). Sur les 31 ECBU realises chez des femmes, 14 d’entres elles (41,2 %) ont eu une prescription de fluoroquinolone apres documentation malgre l’existence d’une alternative therapeutique. Cette etude sur 39 patients a permis d’evaluer les prescriptions de 36 medecins generalistes. Conclusion Cette etude, en vie reelle, permet d’evaluer en prospectif, les antibiotherapies prescrites par un large panel de medecins generalistes. Elle met en evidence un defaut de reevaluation de l’antibiotherapie probabiliste dans l’infection urinaire de l’adulte prise en charge en ambulatoire et confirme l’importance de mettre en place des actions de bon usage a destination de la ville. Ces resultats sont provisoires dans l’attente d’un complement de recueil.

From natural guide star adaptive optics data, we study the properties of the on-axis point spread func- tion and discuss the performance of adaptive optics im- ages. A close relation between the full width half maxi- mum and the Strehl ratio is shown. The ultimate exploita- tion of adaptive optics images requires the deconvolution and therefore the calibration of the point spread function. This calibration is commonly made by sequentially ob- serving a point source close to the astronomical target. In the partial correction regime, the calibration mismatch is the main source of noise or bias in the deconvolution process and it is mainly induced by the varying seeing conditions. Complementary techniques like near-sighted deconvolution, speckle and rebinning are briefly reviewed.

Resume But de l'etude L'amelioration spectaculaire de la survie des patients traites pour une maladie de Hodgkin (MH) a permis l'analyse du devenir des patients survivant a long terme. Ces derniers ont eu un certain nombre de complications, dont des neoplasies secondaires constituant le probleme le plus important. Plusieurs travaux recents font etat d'une augmentation de l'incidence des cancers du sein (CS) chez les jeunes femmes et les enfants traites pour une MH. Materiel et methodes Dans une etude retrospective realisee dans 11 centres de lutte contre le cancer, nous avons recense 63 femmes traitees pour MH et ayant ulterieurement developpe un cancer du sein. Nous avons analyse les resultats obtenus chez 13 patientes (21 %) qui ont eu un cancer du sein bilateral soit synchrone (cinq patientes), soit metachrone (huit patientes). L'âge moyen lors du traitement de la MH etait de 19 ans. Sept patientes avaient ete traitees par irradiation exclusive (comprenant une irradiation sus-diaphragmatiquedetype ≪ mantelet ≫ et six par association chimiotherapie-radiotherapie. Resultats Le delai moyen d'apparition du premier cancer du sein a ete de 16 ans. Selon la classification TNM, on notait: neuf tumeurs de stade T0, quatre tumeurs de stade T1, cinq tumeurs de stade T2, une tumeur de stade T3, deux tumeurs de stade T4 et cinq tumeurs de stade Tx; il y avait 17 carcinomes infiltrants, deux fibrosarcomes et sept carcinomes canalaires in situ. Un envahissement ganglionnaire a ete retrouve dans dix des 15 curages realises pour des cancers infiltrants. Globalement, 17 tumeurs ont ete traitees par chirurgie radicale et neuf par association radiochirurgicale conservatrice. Avec un suivi moyen de 70 mois (extremes: 15–125), trois patientes ont eu une recidive locale et/ou regionale et quatre des metastases. Huit patientes etaient en vie sans signe de maladie et une est decedee d'affection intercurrente. Conclusion Dans la litterature, les cancers du sein representent de 6,3 a 9 % des neoplasies secondaires apres traitement pour MH, mais le risque est beaucoup plus eleve chez les jeunes filles traitees avant 20 ans, et plus particulierement avant 15 ans. Les facteurs favorisants sont: l'irradiation, la jeunesse lors du traitement, la chimiotherapie par agents alkylants, et peut-etre des facteurs genetiques. Ces femmes doivent beneficier d'une surveillance senologique tres reguliere et prolongee, cela au minimum des la fin de la 10e annee apres la fin du traitement de la MH. Un traitement conservateur pour ces cancers du sein secondaires est parfois possible.

Organ transplantation is a life-saving procedure and the preferred method of treatment for a growing number of disease states. The advent of new immunosuppressants and improved care has led to great advances in both patient and graft survival. However, acute T-cell-mediated graft rejection occurs in a significant quantity of recipients and remains a life-threatening condition. Acute rejection is associated with decrease in long-term graft survival, demonstrating a need to carefully monitor transplant patients. Current diagnostic criteria for transplant rejection rely on invasive tissue biopsies or relatively nonspecific clinical features. A noninvasive way is needed to detect, localize, and monitor transplant rejection. Capitalizing on advances in targeted contrast agents and magnetic-based detection technology, we developed anti-CD3 antibody-tagged nanoparticles. T cells were found to bind preferentially to antibody-tagged nanoparticles, as identified through light microscopy, transmission electron microscopy, and confocal microscopy. Using mouse skin graft models, we were also able to demonstrate in vivo vascular delivery of T-cell targeted nanoparticles. We conclude that targeting lymphocytes with magnetic nanoparticles is conducive to developing a novel, noninvasive strategy for identifying transplant rejection.

We present a new method for infrared speckle imaging mainly based on the bispectral analysis algorithm applied to extended objects. The eciency of the reconstruction procedure is increased by a relaxation process making use of redundancies in the pupil plane. The method is applied to near- and mid-infrared data sets of the Red Rectangle (CRL 915) inK,L 'a nd M-bands leading to diraction limited maps of the post-AGB (Asymptotic Giant Branch) bipolar nebula. Studying the morphology of the Red Rectangle at sub-second of arc scale allows to decompose the near and mid-infrared broadband spectrum in two parts: the radiated light from the central part of the nebula and the radiated light from the lobes to the north and south. This decomposition indicates that, in addition to scattering of the light from a central source, thermal extended emission from warm dust may also be important at arsecond and subarcsecond scales in this bipolar nebula.

Surgery is the treatment of choice for localized uterine sarcomas. We conducted a retrospective study to define prognostic factors.We studied 111 cases of patients treated by adjuvant radiotherapy for uterine sarcoma in seven French centers. The median decline was 31 months. We conducted a univariate analysis to identify factors correlated with local recurrence. The statistically significant factors were studied in multivariate analysis by Cox model.The median dose of external beam radiotherapy was 45 Gy. Forty-three percent of patients had vaginal vault brachytherapy and 21 % chemotherapy. Only 6.3 % of patients had complications of acute grade III and 8.1 % of long-term sequelae of radiotherapy. The survival rate at 5 years was 74.6 %. They noted 12.6 % of isolated locoregional recurrences, against 29.7 % for distant recurrences, 80 % were pulmonary. Factors correlated with the risk of locoregional relapse were menopausal status (P = 0.045) and surgical margins suspicious or not healthy (P = 0.0095). The chemotherapy did not improve overall survival or disease free survival but the numbers were low.The postoperative radiotherapy provides good local control in this disease. Brachytherapy is sometimes done, but it does not improve local control. Chemotherapy is not a standard localized stage but the rate of metastatic recurrence calls for the development of strategies involving systemic treatment with radiotherapy.

We analyze the entanglement between two modes of a free Dirac field as seen by two relatively accelerated parties. The entanglement is degraded by the Unruh effect and asymptotically reaches a non-vanishing minimum value in the infinite acceleration limit. This means that the state always remains entangled to a degree and can be used in quantum information tasks, such as teleportation, between parties in relative uniform acceleration. We analyze our results from the point of view afforded by the phenomenon of entanglement sharing and in terms of recent results in the area of multi-qubit complementarity., 15 pages, with 8 figures (Mar 2006); accepted to Physical Review A, July 2006 - slightly revised

We present a model, motivated by the criterion of reality put forward by Einstein, Podolsky, and Rosen and supplemented by classical communication, which correctly reproduces the quantum-mechanical predictions for measurements of all products of Pauli operators on an n-qubit GHZ state (or ``cat state''). The n-2 bits employed by our model are shown to be optimal for the allowed set of measurements, demonstrating that the required communication overhead scales linearly with n. We formulate a connection between the generation of the local values utilized by our model and the stabilizer formalism, which leads us to conjecture that a generalization of this method will shed light on the content of the Gottesman-Knill theorem., New version - expanded and revised to address referee comments

We derive two complementarity relations that constrain the individual and bipartite properties that may simultaneously exist in a multi-qubit system. The first expression, valid for an arbitrary pure state of n qubits, demonstrates that the degree to which single particle properties are possessed by an individual member of the system is limited by the bipartite entanglement that exists between that qubit and the remainder of the system. This result implies that the phenomenon of entanglement sharing is one specific consequence of complementarity. The second expression, which holds for an arbitrary state of two qubits, pure or mixed, quantifies a tradeoff between the amounts of entanglement, separable uncertainty, and single particle properties that are encoded in the quantum state. The separable uncertainty is a natural measure of our ignorance about the properties possessed by individual subsystems, and may be used to completely characterize the relationship between entanglement and mixedness in two-qubit systems. The two-qubit complementarity relation yields a useful geometric picture in which the root mean square values of local subsystem properties act like coordinates in the space of density matrices, and suggests possible insights into the problem of interpreting quantum mechanics., Comment: 15 pages, to be published in Foundations of Physics Letters

A rapid and sensitive high performance liquid chromatography (HPLC) method with fluorescence detection has been developed for the determination of sumatriptan in human plasma. The procedure involved a liquid-liquid extraction of sumatriptan and terazosin (internal standard) from human plasma with ethyl acetate. Chromatography was performed by isocratic reverse phase separation on a C18 column. Fluorescence detection was achieved with an excitation wavelength of 225 nm and an emission wavelength of 350 nm. The standard curve was linear over a working range of 1-100 ng/ml and gave an average correlation coefficient of 0.9997 during validation. The limit of quantitation (LOQ) of this method was 1 ng/ml. The absolute recovery was 92.6% for sumatriptan and 95.6% for the internal standard. The inter-day and intra-day precision and accuracy were between 0.8-3.3 and 1.1-6.3%, respectively. This method is simple, sensitive and suitable for pharmacokinetics or bioequivalence studies.

Individual members of an ensemble of identical systems coupled to a common probe can become entangled with one another, even when they do not interact directly. We investigate how this type of multipartite entanglement is generated in the context of a system consisting of an ensemble of N two-level atoms resonantly coupled to a single mode of the electromagnetic field. In the case where N =2, the dynamical evolution is studied in terms of the entanglements in the different bipartite divisions of the system, as quantified by the I-tangle. We also propose a generalization of the so-called residual tangle that quantifies the inherent three-body correlations in this tripartite system. This allows us to give a complete characterization of the phenomenon of entanglement sharing in the case of the two-atom Tavis-Cummings model. We also introduce an entanglement monotone which constitutes a lower bound on the I-tangle of an arbitrary bipartite system. This measure is seen to be useful in quantifying the entanglement in various bipartite partitions of the TCM in the case where N > 2, i.e ., when there is no known analytic form for the I-tangle.

Individual members of an ensemble of identical systems coupled to a common probe can become entangled with one another, even when they do not interact directly. We investigate how this type of multipartite entanglement is generated in the context of a system consisting of two two-level atoms resonantly coupled to a single mode of the electromagnetic field. The dynamical evolution is studied in terms of the entanglements in the different bipartite partitions of the system, as quantified by the I-tangle. We also propose a generalization of the so-called residual tangle that quantifies the inherent three-body correlations in our tripartite system. This enables us to completely characterize the phenomenon of entanglement sharing in the case of the two-atom Tavis-Cummings model, a system of both theoretical and experimental interest., 11 pages, 4 figures, submitted to PRA, v3 contains corrections to small errors

We present a preliminary report on radial–velocity and infrared interferometric observations, with emphasis on the newly resolved nearby sources Gl 609.2 and Gl 804. We briefly discuss their low–mass companions, their luminosities, and their individual masses inferred from the combined solution of their spectroscopic and visual orbits.

A minimal accuracy is required to achieve audio-localisation in order to place the face of one speaker inside the field of a camera and to initialise a face-tracking module. The TDOA (Time Difference Of Arrival) estimation variance corrupts localisation performance when it is based on a limited array of paired microphones [ber1]. We have revisited this problem in order to improve the signal processing technique and to put forward a mobile configuration. We have done a controlled experiment taking into account 8 factors in order to determine which ones ground the TDOA estimation variance in this context.

In a retrospective multicentric analysis, 63 women treated between 1941 to 1988 for Hodgkin's disease (HD) subsequently developed 76 breast cancers (BC). The median age at diagnosis of HD was 26 years (range 7-67), and 22 women (35%) were 20 years old or less. Exclusive radiotherapy (RT) was used in 36 women (57%) and combined modalities with chemotherapy (CT) in 25 (39%). Breast cancer occurred after a median interval of 16 years (range 2-40) and the median age at diagnosis of the first BC was 42 years (range 25-73). TNM classification (UICC, 1978) showed 10 T0 (non-palpable lesions) (13%), 20 T1 (26%), 22 T2 (29%), 8 T3 (11%), 7 T4 (9%) and 9 Tx (12%), giving altogether a total of 76 tumours, including, respectively, 5 and 8 bilateral synchronous and metachronous lesions. Among the 68 tumours initially discovered, 53 ductal infiltrating, one lobular infiltrating and two medullary carcinomas were found. Moreover, two fibrosarcomas and 10 ductal carcinoma in situ (DCIS) were also found. Among 50 axillary dissections for invasive carcinomas, histological involvement was found in 31 cases (62%). 45 tumours were treated by mastectomy, without (n = 35) or with (n = 10) RT. 27 tumours had lumpectomy, without (n = 7) or with RT (n = 20). 2 others received RT only, and one only CT. 7 patients (11%) developed isolated local recurrence. 20 patients (32%) developed metastases and all died; 38 are in complete remission, whereas 5 died of intercurrent disease. The 5-year disease-specific survival rate by the Kaplan-Meier method was 61%. The 5-year disease-specific survival rate for pN0, pN1-3 and pNor = 3 groups were 91%, 66% and 0%, respectively (P0.0001) and 100%, 88%, 64% and 23% for the T0, T1, T2 and T3T4 groups, respectively. These secondary BCs seem to be of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN3 and/or T3T4); and many tumours with a 'slow development' such as DCIS and microinvasive lesions, especially in patients treated exclusively by RT. Moreover, a very unusual rate of bilateral tumours (21%) was observed. These secondary BC could be 'in field', in 'border of field' or 'out of field'. However, a complete analysis of doses delivered by supradiaphragmatic irradiation was often very difficult, due to large variations in several parameters. We conclude that young women and girls treated for HD should be carefully monitored by clinical examination, mammography and ultrasonography.

Though Hodgkin's disease (HD) is one of the malignancies in which considerable progress has been made, long-term side effects have been observed, second primary cancer being the most significant. Several recent reports have indicated an increased risk of breast cancer (BC) in girls and young women among HD patients.In a retrospective multicenter analysis, 63 women treated for HD subsequently developed BC. Results that were obtained in 13 women (21%) who developed either synchronous (five cases) or metachronous (eight cases) BC were analyzed. The median age at diagnosis of HD was 19 years. Seven patients underwent exclusive radiotherapy (RT) (including "mantle" supradiaphragmatic irradiation) and six received concomittant radiation therapy and chemotherapy.The first breast tumor occurred after a median delay of 16 years. According to the TNM classification, we showed nine stage T0 (non palpable lesions), four stage T1, five stage T2, one stage T3, two stage T4 and five stage Tx BC. Seventeen infiltrating carcinomas, two fibrosarcomas and seven ductal carcinomas in situ were observed. Among 15 axillary dissections performed for invasive carcinomas, histological involvement was found in 10 cases. Seventeen tumors were treated by mastectomy and nine patients underwent conservative surgical treatment. With a 70-month median follow-up (range: 15-125), three patients developed locoregional recurrence and four other metastases. At present, eight are alive with no evidence of disease and one died of intercurrent disease.According to previous works, BC represents 6.3 to 9% of all second cancers occurring after HD treatment. The risk is higher in young women treated before 20 years of age, especially before 15 years of age. Factors that favour the development of secondary BC are: supradiaphragmatic irradiation, very young age at treatment, chemotherapy with alkylating agents, and probably genetic factors. We conclude that young women and girls treated for HD should be carefully monitored at least 10 years after the end of the treatment for HD, using clinical examination, mammography and ultrasonography. The optimal rythm of this follow-up is not yet clearly defined. Moreover, after multidisciplinary concertation, we suggest that secondary BC be sometimes treated by conservative radiosurgical approach.

The aim of the present study was to check whether platinum (Pt) concentrations achieved in tumors with a daily low-dose schedule were close to those promoting radiosensitization. Fifteen previously untreated patients with histologically proven advanced uterine cervix tumors were studied. They received a daily irradiation 30 min after a short infusion of 5 mg cisplatin for 5 consecutive days every week. A biopsy was taken from the accessible tumor mass, 4 to 6 hr after the daily injection. Blood samples were obtained once a week, just before the daily injection (H0) and 30 min after (H30). Quantificative analysis of Pt concentrations was performed by atomic absorption spectrophotometry. Plasma and tumoral Pt concentrations exhibited a marked intersubject variability. The median tumoral Pt concentration was 1,710 mg/g. Median total and ultrafiltrable Pt concentrations in plasma taken at H0 and H30 were 231 and 360 ng/ml, and 7 and 90 ng/ml respectively. Tumoral and total plasma Pt concentrations significantly increased during the course of treatment. Present data show that tumoral Pt concentrations achieved with this CDDP schedule are in the range of tumoral Pt concentrations previously shown to promote radiosensitization (2,000 ng/g). These results suggest that this CDDP radiosensitization regimen might be started with higher CDDP doses in order to reach earlier radiosensitizing Pt tumoral concentrations.

Adaptive optics (AO) works in many cases in the partial correction regime, i.e. with a Strehl ratio lower than 0.8. In this regime, seeing variations induce some variations in the correction (see Tessier 95), as shown on Fig. 1 which plots the Strehl ratio for continuous frames taken with the Come-On Plus instrument (see Beuzit et al. 94 for a description of this instrument).

There are few useful clinical data on pharmacokinetics and pharmacodynamics on cisplatin (CP). The purpose of this prospective study was to analyze the relationship between CP pharmacokinetics and treatment-induced renal dysfunction. Seventy cancer patients were monitored for a total of 162 cycles (24 head and neck, 33 digestive tract, 8 lung, 5 bladder, median age (62, range 42–84). CP was administered as a single short IV perfusion every 3–4 weeks (median dose 76 mg/m2, range 16–104). Blood samples were performed at HO, H36 and H84. Free and total CP (FCP and TCP) were measured by spectrophometric atomic absorption (detection limit 5 ng/ml). Creatinine clearance were computed (cockroft method) before CP administration and between day-2 and day-10 (creat.cl.). Biological renal dysfunction (BRD) was defined as creat, cl In conclusion, CP concentration is an indicator of renal dysfunction which could be useful for selecting the patients who may benefit from an intensive therapeutic action for increasing CP elimination.

A random sample of medical students was compared with others who were unable to cope with unanticipated academic frustration. The noncoping students demonstrated higher levels of debilitating anxiety and lower levels of facilitating anxiety while their perceptions of locus of control tended to be more extreme. No difference was found in study habits and attitudes. Techniques of attribution therapy and desensitization in the counseling of these students proved to be effective in improving coping behavior in six of seven cases.

Six fracture dislocations or dislocations of the olecranon associated with radial head fractures were treated with open reduction and internal fixation of the radial head. The olecranon was reduced and if fractured (three cases) was internally fixed. Postoperatively, early active range of motion was achieved in all cases. Twelve to 48 months after surgery, there was an average loss of 18 degrees of elbow extension and 56 degrees of forearm rotation. An average of 132 degrees of flexion was maintained. There was no elbow instability or wrist pain.