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Mycobacterium bovis Bacillus Calmette-Guerin (BCG), the first-line treatment for non-muscle invasive bladder cancer (NMIBC), promotes the production of inflammatory cytokines, particularly interferon (IFN)-γ. Prolonged inflammation and IFN-γ exposure are known to cause an adaptive immune response, enabling immune escape and proliferation by tumor cells. We investigated HLA-E and NKG2A, a novel T and NK cell checkpoint pathway, as a driver of adaptive resistance in BCG unresponsive NMIBC. We observed ubiquitous inflammation in all patients after BCG immunotherapy, regardless of recurrence status. IFN-γ was shown to drive tumor expression of HLA-E and PD-L1. Further, NKG2A-expressing NK and CD8 T cells were enriched in BCG unresponsive tumors and with enhanced capacity for cytolytic functions. Strikingly, in situ spatial analyses revealed that HLA-EHIGH tumors are activated to recruit NK and T cells via chemokine production, potentially sparing HLA-ELOW tumors that would otherwise be susceptible to lysis. Finally, blood-derived NK cells retained anti-tumor functions at the time of tumor recurrence. These data support combined NKG2A and PD-L1 blockade for BCG unresponsive disease.

We report low-temperature magneto-transport measurements of an undoped Si/SiGe asymmetric double quantum well heterostructure. The density in both layers is tuned independently utilizing a top and a bottom gate, allowing the investigation of quantum wells at both imbalanced and matched densities. Integer quantum Hall states at total filling factor $\nu_{\text{T}} = 1$ and $\nu_{\text{T}} = 2$ are observed in both density regimes, and the evolution of their excitation gaps is reported as a function of density. The $\nu_{\text{T}} = 1$ gap evolution departs from the behavior generally observed for valley splitting in the single layer regime. Furthermore, by comparing the $\nu_{\text{T}} = 2$ gap to the single particle tunneling energy, $\Delta_{\text{SAS}}$, obtained from Schr\"{o}dinger-Poisson (SP) simulations, evidence for the onset of spontaneous inter-layer coherence (SIC) is observed for a relative filling fraction imbalance smaller than ${\sim}50\%$, Comment: 6 pages, 3 figures, accepted in APL

Background: Retrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown. Objectives: We investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF. Methods: Through the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HFLT), 4,438 outpatients were identified and classified into: reduced (= 50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components. Results: Median sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11-2.54; 2.46: 95% CI 1.66-3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P

To the Editor, Immediate hypersensitivity reactions are related to mast cell and/or basophil activation. The mediators released such as tryptase and histamine are involved in clinical symptoms and are key parameters that contribute to diagnosis. Serum tryptase concentrations peak between 30 minutes and 4 hours following the reaction. Tryptase release is considered a robust marker of mast cell degranulation but is not informative in mild reactions.1 Histamine is released at the early beginning of the reaction but has a short half-life. The concentration value can be altered by pre-analytic conditions.2 Anaphylactic reactions can occur during night and week-end when laboratories can’t take charge of samples. To our knowledge, no thorough study of the stability in whole blood of these markers in anaphylaxis has been published. The aim of our study was to evaluate the impact of whole blood sample storage conditions (temperature and delay before centrifugation and plasma collection) on the reliability of tryptase and histamine measurements.Blood samples from 14 patients suspected of anaphylactic reactions (grade 2 to 4 of the Ring and Messmer scale)3 and from 10 volunteers were collected on EDTA after signed informed consent (CCPPRB Caen Basse-Normandie protocol 2004-32). The description of the patient anaphylactic episodes appears in Table 1.When received in the lab, an aliquot of whole blood was processed for diagnostic (reference measurement) and the remaining was divided in aliquots stored at room temperature (RT) or at +4°C for 24, 72 hours or 7 days (patients) or 2, 6, 24 or 72 hours for controls before centrifugation and plasma collection.Total tryptase concentrations were measured by an automated fluoroimmunoassay (ThermoFisher, Phadia SAS, ). Increased tryptase is defined as ≥ 1.2 x basal value + 2 µg.L-1.4 In our hands, tryptase uncertainties of measurement for low and high concentrations (9 µg.L-1 and 38.2 µg.L-1) are 17% and 16% respectively, in accordance with published results.5 Plasma histamine concentrations were measured by a radioimmunoassay (Beckman Coulter, Immunotech, France). Increased values defined by the manufacturer are >10 nmol.L-1, in accordance with published data.6 In our hands, histamine uncertainties of measurement for low and moderate concentrations (4.7 nmol.L-1 and 12.9 nmol.L-1) were 22% and 25%, respectively.The differences between the concentrations measured before and after storage were compared by paired two-tailed t-tests using SAS software. Results were considered significant for p < 0.05.As shown in Figure 1A, storage conditions did not modify tryptase concentrations (linear regression: slope=1.079, R²=0.9675). Tryptase concentrations appeared stable in whole blood left at +4°C for 7 days or 72 hours at RT.Histamine concentrations in patient samples were not modified during 72h at +4°C (Figure 1B) or at RT (Figure 1C). In the control group at RT, histamine concentrations were significantly increased at 6 hours (p=0.005) although moderately increased and staying within the limits of uncertainty measurement and never reaching the positivity threshold (Figure 1E). After 24 hours at RT a false positivity was observed for 8 of 10 samples (p

Introduction The Balance Evaluation System Test (BESTest) and the Mini-BESTest were developed to assess the complementary systems that contribute to balance function. These tests include functional tasks involving several high-level exercises to assess the balance function, which may be even more difficult in case of frailty. The Frail’BESTest has been developed to make it possible to include frail older adults in systemic assessment. In this first paper, the objective is to present the Frail’BESTest and to describe the usefulness and complementarity of each system and to test the inter-rater reliability of the score measurements in two health centers. Methods In the first center, 192 frail and non-frail older patients were enrolled to test I) the contribution of each system, II) internal consistency, and III) the threshold and ceiling effects. The scores of 32 patients from center 1 and 32 patients recruited in another center (center 2) were used to measure the inter-rater reliability of the measurements by means of Kendall’s tau coefficients. Results The internal consistency was moderate to good for five systems and limited for “biomechanical constraints”. The distribution of the Frail’BESTest was more centered than that of the Tinetti and Mini-Motor tests. The Kendall’s tau showed strong concordance in center 1 for all systems and only for 4 on 6 systems in center 2. Discussion Completing a systemic evaluation, the therapist may prioritize the patient’s needs identifying the most challenging systems. This paper presents the Frail’BESTest and confirms the psychometric properties at a first step level.

The rate and extent of granule growth and densification during high-shear wet granulation (HSWG) depends on a variety of formulation and process variables, including material attributes of critical formulation excipients, such as binders. The effects of known binder attributes to the rate and extent of granule growth and densification in a wet granulation process could be either specific or agnostic to a particular active pharmaceutical ingredient (API) or drug product formulation. The effect of binder properties and process variables, such as mode of addition, on the HSWG process and product performance can be explored both experimentally as well as through in silico modeling and simulation. Examples and case studies on the effect of material attributes on process performance using both experimental and modeling methodologies are presented. This chapter demonstrates the essential role of combining multiscale models such as the mechanistic, first principles-based particle-level models, and process models with experimental observations to fully understand and characterize the role of binder attributes on the process outcomes.

Key points The diagnosis of a perioperative allergic reaction is based on clinical features associated with a suggestive timeline, the exclusion of other diagnoses, elevated concentrations of degranulation markers (histamine, tryptase), and positive allergy assessments (skin tests, specific IgE). After initiating appropriate treatment, the anesthesiologist should take blood samples to measure histamine and tryptase concentrations just after the reaction and repeat them 1–2 hours later to validate the diagnosis of immediate hypersensitivity. A delayed measurement of basal tryptase is useful to rule out mastocytosis and to interpret moderate tryptase levels. The anesthesiologist must inform the patient of the reaction to obtain adhesion and consent to subsequent investigations and must record the timing of the reaction and of the blood sampling, the possible causal agents, and the treatment administered. These data must be shared with the laboratory and the allergist. An adverse drug reaction report must be filed. The gold standard for allergy assessment is skin testing. These tests should be done in an appropriate facility, with experienced staff and in compliance with current guidelines. Specific IgE assays and cellular assays can help when clinical features and skin tests are discordant. Provocation tests are sometimes required. After allergy assessment, the safest protocol for subsequent anesthesia is determined in collaboration with the anesthesiologist. The patient must be informed and carry an allergy alert card.

International audience; Background:Iodinated and gadolinium-based contrast media (ICM; GBCM) induce immediate hypersensitivity (IH) reactions. Differentiating allergic from non-allergic IH is crucial; allergy contraindicates the culprit agent for life. We studied frequency of allergic IH among ICM or GBCM reactors.Methods:Patients were recruited in 31 hospitals between 2005 and 2009. Clinical symptoms, plasma histamine and tryptase concentrations and skin tests were recorded. Allergic IH was diagnosed by intradermal tests (IDT) with the culprit CM diluted 1:10, "potentially allergic" IH by positive IDT with pure CM, and non-allergic IH by negative IDT.Findings:Among 245 skin-tested patients (ICM = 209; GBCM = 36), allergic IH to ICM was identified in 41 (19.6%) and to GBCM in 10 (27.8%). Skin cross-reactivity was observed in 11 patients with ICM (26.8%) and 5 with GBCM (50%). Allergy frequency increased with clinical severity and histamine and tryptase concentrations (p 50% of life-threatening ones. GBCM and ICM triggered comparable IH reactions in frequency and severity. Cross-reactivity was frequent, especially for GBCM. We propose considering skin testing with pure contrast agent, as it is more sensitive than the usual 1:10 dilution criteria.

Introduction La preeclampsie (PE) et la maladie renale chronique (MRC) sont liees par une relation de cause a effet partiellement connue. Les connaissances portant sur la prevalence de la MRC chez les patientes en PE sont necessaires pour evaluer le rendement diagnostique du bilan nephrologique apres une PE. Le but de notre etude est de determiner la prevalence de la MRC dans les suites d’une PE sur un echantillon de patientes. Methodes L’etude a ete realisee au Centre Hospitalier du Mans, comportant un service d’obstetrique de troisieme niveau. Le diagnostic de PE a ete identifie sur les codes de sortie de l’hopital ; Apres examen, l’etude comprenait 99 patientes, dont 36 etaient evaluees en nephrologie. Une analyse descriptive de la population etait realisee. La regression logistique multiple a teste le resultat « diagnostic de MRC » ; les co-variables considerees significatives ont ete selectionnees ; seules les grossesses uniques ont ete incluses. L’analyse a ete realisee par le logiciel SPSS. Resultats obtenus ou attendus La prevalence de la MRC etait de 14 %. La MRC etait au stade 1 chez 8/14 (57 %) ; 5 patientes etaient au stade 2 (36 %), et une seule au stade 3 (7 %). La MRC etait connue dans 1 cas seulement. Les diagnostics retenus etaient la nephropathie malformative (5 cas), maladie lithiasique (3), Polykystose renale (1), nephropathie interstitielle (2), nephropathie diabetique (1) et presence d’albuminurie dans le cadre d’un syndrome metabolique (2). Lors de l’analyse de regression logistique, l’accouchement premature (OR :7,849 [1,667–36,968]) et un nouveau-ne normal pour son âge gestationnel (> 10e centile ; OR :6,193 [1,400–27,394]) etaient significativement correles au diagnostic de nephropathie chronique. Conclusion Dans les limites d’une etude monocentrique, nos donnees quantifient la MRC comme etant un risque significatif chez les preeclamptiques et identifie un « phenotype MRC » caracterise par un accouchement premature et une croissance adequate, ce qui suggere que la MRC est compatible avec une bonne fonction placentaire au cours de la derniere phase de la grossesse.

Background Immediate hypersensitivity reactions occurring during anesthesia are classified as allergic when skin tests and mast cell tryptase are positive and as nonallergic when negative results are obtained. Cysteinyl leukotrienes (cysLTs) are potent mediators synthesized by mast cell and eosinophil that induce bronchial constriction. They could play a role in hypersensitivity reactions. Methods cysLT C4, D4, and E4 concentrations were measured by a competition immunoassay in serial plasma samples obtained prospectively from 21 anesthetized controls and retrospectively from 34 patients who reacted at induction of anesthesia (24 with allergic and 10 with nonallergic reactions). Results In controls, the median (interquartile range) cysLT concentration was 0.83 (0.69 to 1.02) μg/l before anesthesia and was unchanged 30 min, 6 h, and 24 h afterward. In the patients with allergic reactions, the values were highly increased 30 to 60 min after the reaction (17.9 [7.8 to 36.0] μg/l), while the patients with nonallergic reactions had less increased values (7.3 [3.0 to 11.5] μg/l). The difference between the three groups was significant (P < 0.0001). Increased values persisted during the 24 h of observation. Concentrations were significantly higher in patients with bronchospasm (P = 0.016). Conclusions cysLTs appear to be an important mediator of allergic and nonallergic immediate hypersensitivity reactions. These findings might open a new field for management of patients with hypersensitivity reactions, especially nonallergic ones.

Background: The diagnosis of acute life-threatening allergic reactions during anesthesia relies on clinical signs, histamine and/or tryptase measurements, and allergic testing. In patients who die after the reaction, skin tests cannot be performed, and the effect of resuscitation manoeuvres on mediator concentrations is unknown. The authors compared plasma histamine and tryptase concentrations in patients with severe allergic reactions during anesthesia with those measured in patients with shock due to other causes. Methods: Patients with life-threatening allergic reactions were retrieved from a previous database (Group ALLERGY). All had positive allergy tests to administered agents. Patients with severe septic/cardiogenic shock or cardiac arrest (Group CONTROL) had histamine and tryptase measurements during resuscitation manoeuvres. Receiver operating characteristics curves were built to calculate the optimal mediator thresholds differentiating allergic reactions from others. Results: One hundred patients were included, 75 in Group ALLERGY (cardiovascular collapse, 67; cardiac arrest, 8) and 25 in Group CONTROL (shock, 11; cardiac arrest, 14). Mean histamine and tryptase concentrations remained unchanged throughout resuscitation in Group CONTROL and were significantly higher in Group ALLERGY. The optimal thresholds indicating an allergic mechanism were determined as 6.35 nmol/l for histamine (sensitivity: 90.7% [95% CI, 81.7 to 96.1]; specificity: 91.7% [73.0 to 98.9]) and 7.35 μg/l for tryptase (sensitivity: 92% [83.4 to 97.0]; specificity: 92% [73.9 to 99.0]). Conclusions: Resuscitation manoeuvres by themselves did not modify mediator concentrations. Virtually all life-threatening reactions during anesthesia associated with mediator concentrations exceeding the thresholds were allergic events. These findings have potential forensic interest when a patient dies during anesthesia.

Introduction Les reactions d’hypersensibilite immediate sont liees a la liberation de mediateurs par les mastocytes et/ou basophiles, dont l’histamine et la tryptase, utilises comme marqueurs diagnostiques. Contrairement a l’histamine, la tryptase est un marqueur repute robuste mais non informatif si la reaction est peu grave. Les conditions pre-analytiques peuvent modifier les concentrations mesurees. Nous avons evalue l’impact des conditions d’acheminement des prelevements de sang sur ces dosages. Methodes Les prelevements de sang sur EDTA de 14 patients lors d’une reaction de grade 2 ou 3 et de 10 sujets sans reaction ont ete divises en plusieurs aliquots des reception au laboratoire. L’un a ete immediatement traite selon les conditions usuelles. Les autres ont ete laisses a +4 °C ou temperature ambiante (TA) de 2 h a 72 h avant centrifugation. La tryptase a ete mesuree par technique ImmunoCap (ThermoFisher) et l’histamine par radioimmunologie (Beckman Coulter). Resultats Aucune variation des concentrations de tryptase n’a ete constatee a +4 °C ni a TA. Pour les sujets sans reaction, a +4 °C, les concentrations d’histamine n’ont pas ete modifiees apres 2 h ou 6 h ; une augmentation moyenne de 1,3 nmol/L (SD = 0,61 ; p 10 nmol/L. Pour les patients, les concentrations d’histamine n’ont pas varie significativement apres conservation a +4 °C ou TA pendant 24 h ou 72 h. Conclusion Il n’y a pas d’impact des conditions de conservation du sang pour la tryptase. Pour l’histamine, si les prelevements ne peuvent etre achemines rapidement vers le laboratoire, ils doivent etre conserves a +4 °C. Il y a un risque de faux-positifs a taux faible pour les prelevements non decantes au-dela de 24 h a +4 °C ou 6 h a TA et le biologiste devra interpreter les resultats en fonction des conditions d’acheminement. Mais tous les prelevements doivent etre acceptes par le laboratoire car ils ne sont pas renouvelables.

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3–4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p = 0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3–4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.

Wear of grinding mill liners and lifters plays a major role in the overall efficiency and economics of mineral processing. Change in the shape of lifters as they wear has a significant influence on grinding efficiency, and the annual cost of maintenance and mill down-time depends on the life of both liners and lifters. The Discrete Element Method (DEM) is a computational method for simulating the dynamics of particle processes. This paper presents an analysis of 3D simulation of a grinding mill carried out using the EDEM software package customised to predict the rate of wear of lifter geometry and to enable progressive updating of worn lifter geometry profiles. A simplified breakage rate model is developed as a tool to correlate liner profile to mill performance. The combination of the prediction of liner profile and grinding rate shows promise to provide a powerful tool for advanced mill liner design – providing a means to balance liner life and mill performance over the life of the liner at the liner design stage.

Background Neuromuscular blocking agents (NMBA) are responsible for most immediate hypersensitivity reactions during anesthesia, as a result of the presence of a quaternary ammonium ion. The aim of this study was to evaluate the diagnostic performance of a commercial immunoglobulin E (IgE) test (quaternary ammonium morphine [QAM]) for diagnosing sensitivity to NMBA. Methods We tested 168 patients exposed to NMBAs during anesthesia. Of those patients, 54 had an uneventful procedure and 114 had immediate hypersensitivity reactions, and 57 patients had positive skin tests to the administered NMBA, whereas 57 had negative skin tests. Specific IgE concentrations determined with the QAM method based on a morphine solid phase were compared with those obtained with a recommended experimental method with a choline solid phase. Results For the QAM test, a 0.35 kUA/l positivity cutoff was chosen from the receiver operating characteristics curve. QAM-specific IgE was found in 84.2% of skin test-positive reactors (80.7% with the recommended method; no significant difference), and binding was inhibited by the culprit NMBA in 80% of cases. The frequency of QAM-specific IgE positivity was significantly higher in skin test-negative reactors (24.6%) than in controls (9.3%), suggesting NMBA sensitivity. Conclusion Sensitivity of the QAM test (84.2%), together with its simplicity and suitability for routine laboratory use, makes it a valuable tool, in conjunction with skin tests, for diagnosing NMBA sensitivity in patients who react after NMBA injection. The QAM test is of particular interest when skin tests are not available or not reliable or give results poorly compatible with mediator release or clinical features.

We attempted to collect diet samples using throat ligatures from nestlings of three songbird species in a riparian woodland in southeastern Arizona from May to August 2009. We had success with Song Sparrows (Melospiza melodia), observed adult Yellow-breasted Chats (Icteria virens) reclaim food from nestlings, and discontinued the use of throat ligatures when we observed an adult Abert's Towhee (Pipilo aberti) remove two, 3–4-day-old ligatured nestlings from its nest. Previous studies have reported problems (e.g., aggression toward nestlings by adults) with throat ligatures, but we are the first to document removal (and subsequent nestling mortality) in response to this technique. We urge investigators to exercise caution when using throat ligatures on species for which evidence of the safety and efficacy of this method are lacking, especially when nestlings are small in size relative to adults.

Resume L’incidence et la morbimortalite des reactions allergiques de type immediat apres injection de produits de contraste iodes (PCI) demeurent inconnues. Le diagnostic etiologique d’une reaction d’hypersensibilite immediate apres injection de PCI est fonde sur un tryptique associant la description precise des signes cliniques inauguraux et leur delai de survenue, les resultats du bilan biologique preleve au decours de la reaction (histamine, tryptase) et les resultats des tests cutanes avec le PCI suspecte. La confrontation de ces arguments permet d’identifier le mecanisme physiopathologique de la reaction et l’allergene implique, s’il s’agit d’un mecanisme allergique. Le bilan cutane doit etre realise selon des criteres rigoureux. La recherche d’une reactivite cutanee avec les autres PCI commercialises permet de rechercher une sensibilisation croisee ; seuls les PCI non reactifs pourront etre proposes le cas echeant lors de procedures ulterieures. Le diagnostic d’allergie a un PCI impliquera l’eviction definitive de celui-ci mais non la contre-indication de l’ensemble des medicaments iodes. La sequence allergenique n’a pas ete identifiee mais ne correspond pas a l’atome d’iode lui-meme. L’asthme, la prise de β-bloquants ne constituent pas en tant que tels des facteurs de risque de survenue d’une reaction d’hypersensibilite allergique immediate aux PCI mais peuvent etre des facteurs aggravants. Les differents protocoles de premedication qui ont pu etre proposes ne previennent pas la survenue d’une reaction allergique/anaphylactique aux PCI. Seule l’eviction du PCI responsable permet d’eviter la recidive de la reaction.

Kesume Le choc anaphylactique peranesthesique (reaction d'hypersensibilite immediate IgE-dependante) est du le plus souvent aux myorelaxants. Les tests biologiques immediats ont pour but de prouver l'histaminoliberation, de rechercher une degranulation mastocytaire et eventuellement, des IgE specifiques de l'agent suspecte d'apres la chronologie des evenements. Une concentration d'histamine augmentee peut etre due a un mecanisme allergique ou a une histaminoliberation non specifique. Le prelevement doit etre obtenu precocement (

We detected buff-breasted flycatchers (Empidonax fulvifrons) while conducting surveys in the Rincon Mountains, Arizona, in 2000 (n = 2), 2004 (n = 4), and 2005 (n = 5). Our detections represent the first records of buff-breasted flycatchers in the Rincon Mountains since 1911, suggesting that this rare species has recolonized a portion of its historical breeding range.

En mai 1998, nous avons mesure les profils des concentrations ambiantes et des changements nets de dimethylsulfoniopropionate particulaire (DMSP p ), de dimethylsulfoniopropionate dissous (DMSP d ) et de sulfure de dimethyle (DMS) dans trois provinces biogeographiques du nord-ouest de l'Atlantique, soit le plateau continental (Grands Bancs), la derive nord-atlantique et la gyre subtropicale de l'Atlantique nord (mer des Sargasses). Toutes les stations/profondeurs affichent d'importantes pertes de DMSP p (jusqu'a 18,0 nmol.L - 1 .jour - 1 ). Le recyclage du DMSP et du DMS varie en fonction de la composition des communautes planctoniques et de leur stade de developpement. Les conditions qui suivent l'efflorescence des diatomees sur les Grands Bancs sont associees a une utilisation efficace du DMSP par le microzooplancton et les bacteries. La production bacterienne de DMS contrebalance la consommation bacterienne de DMS, ce qui explique la faible production nette de DMS (0,3 nmol.L - 1 .jour - 1 ). La situation est tres differente dans les stations de la derive nord-atlantique et de la mer des Sargasses ou les flagelles foisonnent et ou la plus grande partie de la perte de DMSP p est recuperee dans le pool de DMSP dissous, ce qui indique que le metabolisme bacterien du DMSP y est moins actif. Dans ces situations, la scission du DMSP d est importante et elle depasse la consommation bacterienne de DMS, ce qui permet une production nette de DMS (jusqu'a 1,8 nmol.L - 1 .jour - 1 ). Ces resultats indiquent que la production nette maximale de DMS se produit dans les systemes d'algues en croissance, dans lesquels la production de DMSP d due au broutage du microzooplancton surpasse les besoins en carbone et en soufre des bacteries.

Hypersensitivity reactions are a classic side effect of cetuximab. We report the cases of three patients who developed life-threatening hypersensitivity to cetuximab, which could have been predicted by assessing the concentration of serum anticetuximab immunoglobulin (Ig)E. The anti-cetuximab IgE concentration could be an interesting test to predict which patients are at risk of experiencing severe hypersensitivity reactions to cetuximab.

Resume Cent cinquante enfants atteints de mucoviscidose ont ete depistes en periode neonatale en Normandie entre 1980 et 1997, 36 enfants etaient porteurs d'un ileus meconial. Au moment de cette etude retrospective, 11 enfants etaient decedes, neuf d'entre eux avaient eu un ileus meconial (huit deces apres intervention chirurgicale et un deces a cinq ans). A partir d'une cohorte de 60 enfants depistes de 1980 a 1993 et suivis regulierement en Basse-Normandie, dans le meme centre de soins, sur une duree moyenne de 80 mois, des facteurs pronostiques precoces de la survenue de la premiere infection a Pseudomonas aeruginosa ( P. aeruginosa ) et du passage a la chronicite ont ete recherches. L'âge moyen au diagnostic des enfants sans ileus ( n = 44) etait de 41 jours (deviation standard egale a 27 jours). L'analyse statistique a ete effectuee selon une approche univariee puis multivariee pour les variables explicatives suivantes : presence d'un ileus meconial ; sexe ; donnees anthropometriques a la naissance et au diagnostic ; anomalies pulmonaires radiologiques (score de Brasfield), insuffisance pancreatique et donnees bacteriologiques au moment du diagnostic ; mutations genetiques. Pour ces 60 enfants, les facteurs pronostiques mis en evidence ont ete pour la precocite de la premiere atteinte a P. aeruginosa : l'insuffisance pancreatique au diagnostic (odds ratio [OR] egal a 2,2 ; p p P. aeruginosa : la presence d'un ileus (OR = 5,3 ; p p p P. aeruginosa , en analyse multivariee, etait un âge au diagnostic excedant 40 jours de vie (respectivement OR = 4,6 ; p p p

Objective: To elucidate the relationships between growth and zinc and iron status in normal infants. Study design: Growth of normal infants (less than 3 y old; n=66) was prospectively assessed with a mean delay of 24±6 weeks between measurements; subjects were free from illness and presented with a normal growth. Growth was compared to serum zinc (s-zinc), IGF-1 and iron status. Setting: Teaching hospital of Caen. Results: No relation was found between linear or weight growth and s-zinc; when taking into account the effect of age, linear growth was significantly associated with ferritin (P

The processability of industrial polymers was experimentally and numerically investigated. The heating temperature of ABS and HIPS sheets was systematically varied in order to determine the minimum sheet temperature required for vacuum forming onto two different cavity moulds with acceptable thickness variations. Finite element simulations of the process using hyperelastic and viscoelastic constitutive equations were also performed in order to analyze the models' ability to predict thermoformability of polymers. Prediction of minimum required sheet temperature as well as the part thickness distribution were compared to experimental measurements.

In the marine environment, phytoplankton are the fundamental producers of dimethylsulfoniopropionate (DMSP), the precursor of the climatically active gas dimethylsulfide (DMS). DMSP is released by exudation, cell autolysis, and zooplankton grazing during phytoplankton blooms. In this study, we developed a model of phytoplankton DMSP and DMS production allowing quantification of the exudation rates of these compounds during different growth phases. The model was tested on published data from axenic cultures of Prorocentrum minimum and Phaeocystis sp.; DMSP exudation rates vary considerably between the 2 species. Model results show that P. minimum exudes around 1% d(-1) of its DMSP quota during the latent, exponential and senescent phases. This is comparable to the average exudation rate estimated from previous laboratory experiments. However, Phaeocystis sp. exudes from 3 to 11% d(-1) of its DMSP quota. For this species, DMSP exudation rates apparently show an inverse relationship with the population growth rate. The maximum DMSP exudation rate in Phaeocystis sp. is 10 times higher than previously reported DMSP or DMS exudation rates. Our results suggest that exudation may be as important as cell autolysis in the release of DMSP during Phaeocystis sp. blooms. We conclude that exudation should be incorporated in models of DMS cycling in the marine environment. Moreover, our results for Phaeocystis sp. suggest that a low and constant exudation rate, as sometimes used in models, is not suitable for all conditions.

To measure and elucidate the mechanisms of presumed mediators of unexpected severe, immediate reactions to iodinated contrast materials.In a multicenter study, 20 patients with mild to severe reactions to iodinated contrast material and 20 control subjects without reactions were evaluated. Ionic contrast material was associated with 18 (90%) of 20 reactions. Concentrations of plasma histamine, tryptase, urinary methylhistamine, specific immunoglobulin E (IgE) against ioxitalamate or ioxaglate, and the anaphylatoxins C3a and C4a were measured with radioimmunoassays; complement C3 and C4 levels were measured with nephelometry.Histamine levels were increased in 14 patients; tryptase levels, in 16; and methylhistamine levels, in six. Histamine and tryptase values correlated with the severity of the reaction (P.02 and P.004, respectively). Significantly higher levels of specific IgE against ioxaglate (P.005) and ioxitalamate (P = .045) were found in patients. No differences were found for complement fractions. Skin test results in two patients with life-threatening reactions were positive for the administered contrast material.Histamine release and mast cell triggering are related to severe reactions. An IgE-related mechanism is strongly suspected. Radiologists should be trained to identify and treat anaphylactic shock in patients who react to iodinated contrast material.

Background Anaphylaxis, mediated by immunoglobulin E, may be clinically indistinguishable but is mechanistically different than chemically mediated anaphylactoid reactions induced by drugs such as morphine, curare, and vancomycin. A test to distinguish anaphylactic from anaphylactoid reactions would clarify therapeutic and medicolegal issues. Tryptase levels identify anaphylactic reactions but have not been evaluated in vivo during anaphylactoid reactions. A prospective, randomized, double-blinded, placebo-controlled trial of antihistamine chemoprophylaxis for rapid vancomycin infusion was performed, and plasma tryptase was measured using a new immunoassay. Histamine release was established by measurement of plasma histamine and the ability of prophylactic H1 and H2 antagonists to prevent common histamine-associated side effects. Tryptase levels were compared with histamine levels and clinical symptoms. Methods Before elective arthroplasty, 40 patients received vancomycin infusion (1 g over 10 min) and pretreatment with either antihistamines (1 mg/kg diphenhydramine and 4 mg/kg cimetidine) or placebo. Changes in tryptase (at peak histamine and 10 min after vancomycin infusion), histamine levels, and histamine-mediated symptoms were assessed using Fisher's exact test, the Student's t test, or the paired t test, as appropriate. Logistic regression models were used to quantify the association of clinical symptoms with antihistamine treatment and serum levels. Results Plasma tryptase levels were unchanged (99% CI, -0.5 to 1.6) independent of increased histamine levels, antihistamine pretreatment, clinical symptoms, or all of these. Histamine levels >1 ng/ml were significantly associated with hypotension, moderate-to-severe rash, and stopped infusion. Antihistamine pretreatment significantly decreased the incidence and severity of the reactions. Conclusion Plasma tryptase levels were not significantly elevated in confirmed anaphylactoid reactions, so they can be used to distinguish chemical from immunologic reactions.

Objective: This prospective study was designed to assess the relationship between variations of serum Aluminium levels and bone mineralization, which is one of its target tissues, in healthy premature (PT) and fullterm (FT) infants. Study design: Lumbar spine bone mineral density (BMD) and content (BMC) studied by dual energy X-ray absorptiometry were compared to serum aluminium (S-Al), Ca (S-Ca), P (S-P), osteocalcin, alkaline phosphatase activity (S-AP), and 25 OH Vitamin D (25 OH D) by simple and multiple regressions in healthy PT (n=44) following their hospital discharge and FT (n=82). PT (gestational age at birth (mean±1 s.d.) 32±2 weeks) and FT were 43±39 and 36±32 weeks old respectively. Results: In PT multiple stepwise regression analysis including gestational age at birth, postconceptional age and postnatal age displayed only a significant correlation between BMD or BMC and postnatal age and a negative one with S-Al. In FT correlations were found between BMD or BMC and age and S-Ca. Conclusions: In PT, variations in blood Al are associated with developmental delays. Care should be taken to lessen Al levels, even in healthy PT babies.

resume Les reactions anaphylactiques aux medicaments peuvent etre explorees au moment meme ou elles se produisent, par des dosages de mediateurs et d'IgE specifiques. Les reactions sous anesthesie sont un excellent modele pour evaluer la fiabilite de cette approche diagnostique. Si la reaction ne met pas la vie en danger, l'histamine plasmatique est le parametre le plus sensible, a condition de faire le prelevement des les premieres minutes et de respecter quelques regles simples lors de la decantation. Si la reaction est tres severe, la tryptase mastocytaire sera preferee lorsque le prelevement est retarde au-dela de 1 heure. La methylhistamine urinaire est moins fiable, en particulier pour les reactions severes. Le dosage des IgE specifiques du medicament chronologiquement suspect complete l'exploration. Ces tests biologiques ne font pas double emploi avec les tests cutanes habituellement pratiques: leurs resultats aident l'allergologue a conclure quand les tests cutanes sont negatifs ou douteux. Ils permettent de choisir un mode d'anesthesie plus sur si une reintervention rapide est necessaire et ils ont une importance medicolegale en cas de deces, a condition de faire le prelevement avant l'arret de la reanimation.

In the last twenty years injection molding and blow molding have seen a rapid growth due to the development of new application areas in the automotive, sports and leisure, electronics, transportation and packaging industries. This success can be traced to the optimization of existing processes and to the development of new processing techniques employing novel concepts such as gas-assisted injection molding, co-injection, and 3D and sequential blow molding. The complexity of these new molding techniques calls for a much better understanding of the material behavior during the basic stages of the process and its relation to the properties and performance of the final part. These characteristics are directly dependent upon die and mold designs and on the operating conditions during extrusion, injection, inflation and cooling in the mold.

Une courte etude prospective de la fonction thyroidienne du nouveau-ne a terme (n = 90) a ete realisee dans une maternite de Marrakech (Maroc), en preliminaire a la validation de l’efficacite du programme national d’iodisation du sel. La TSH etait elevee (> 5 mU/l) chez 89 % des nouveau-nes. L’iodurie mesuree chez 35 des meres etait normale (100-200 μg/l) ou elevee (> 200 μg/l) (n = 27). La concentration de l’iode dans le lait maternel de 315 femmes de la meme region etait inferieure a la valeur normale (41 μg/l) chez 60 % d’entre elles. L’iodurie elevee observee a l’accouchement peut etre associee a l’utilisation habituelle des desinfectants iodes, mais la carence en iode semble rester frequente chez cette population et justifie une enquete a grande echelle, d’autant que le risque lie a une hypothyroidie transitoire du nouveau-ne n’est pas connu.

In order to achieve a correct diagnosis of drug anaphylaxis using a radioimmunoassay devoid of interferences, we have studied factors leading to false positive or false negative values of plasma histamine. Different steps in sample collection were studied systematically in 30 normal volunteers. False positive values were found in haemolysed samples, with histamine concentrations being correlated with haemoglobin concentrations, and where plasma was aspirated from the white-cell layer. There was no significant increase when a tourniquet or vacuum tubes were used, or when blood tubes were left at 4 degrees C overnight. In 12 patients who experienced an anaphylactic reaction, histamine disappeared from blood 10 times more slowly than expected. False negative values were found in two pregnant women and one heparinized patient. Histamine was remarkably stable in vitro in blood or plasma samples, whereas it disappeared rapidly when plasma from a pregnant woman or a heparinized patient was added to the sample. We conclude that false positive and false negative values are rare when using this radioimmunoassay.

Resume Dans le but de proposer des mesures preventives de l'osteoporose, nous avons compare l'evolution de la densite osseuse vertebrale chez 574 jeunes filles normales, d'origine caucasienne, âgees de 11 a 24 ans, avec celle de l'osteocalcine, marqueur de l'activite des osteoblastes et de l'insulin-like growth factor-1 (IGF-1), principal facteur de croissance. L'IGF-1 passait par un maximum entre 13 et 15 ans, l'osteocalcine entre 11 et 12 ans, et la densite vertebrale augmentait tres rapidement de 11 a 14 ans, pour atteindre un plateau apres 16 ans. Entre 11 et 18 ans, l'accroissement de la densite osseuse representait 37% du maximum obtenu (1,055 ± 0,102 g/cm 2 ). Le plateau de densite vertebrale etait observe a 17 ans d'âge osseux, le pic d'osteocalcine entre 11 et 12 ans et celui d'IGF-1 entre 13 et 14 ans. La densite vertebrale augmentait de 30% entre le stade pubertaire P1 et les premieres regles, et n'atteignait un plateau qu'a la cinquieme annee apres celles-ci. Le pic d'osteocalcine se situait au stade P3, et celui d'IGF-1 entre le stade P4 et la premiere annee apres la menarche. Ces donnees montrent l'importance des annees de la puberte et au-dela pour l'optimisation du pic de masse osseuse.

Anode electrical resistance is more and more recognized as a key parameter for pot operation, as the carbon material itself contributes close to 50% of the anode assembly voltage drop. Factors such as raw materials, forming and baking conditions are sources of significant variation in anode properties, including anode resistance. Anode resistance will vary within an anode and between anode batches, causing voltage differences up to several tens of millivolts. The current method for resistivity measurement is based on core sampling of a small number of anodes in limited locations and may not be representative of the global anode resistance. The current study proposes a non destructive method that reproduces the current distribution in service and provides immediate results. Such results could be used to improve anode resistance and help potrooms cope with anode batch variability.

Resume L’auteur fait le point sur les reactions peranesthesiques typiques et presente les recommandations de la Societe francaise d'anesthesie et de reanimation pour la pratique clinique.

These guidelines represent a consensus among experts on hypersensitivity reactions occurring after transfusion of blood components. They cover recognition, investigation, treatment, and prevention of such reactions. Implemented in France under the auspices of the French Medicines and Healthcare Products Regulatory Agency (AFSSAPS) and based on current knowledge, research, and experience, they aim to provide effective and easily teachable means of further improving the quality of hemovigilance databases, promote interest in this field, and help identify possible mechanisms and at-risk patient groups.