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• A fast yet reliable framework for the aerodynamic optimization of aircraft wings is developed. • The framework combines Computational Fluid Dynamics (CFD) and Machine Learning (ML). • The ML-based framework is applied to NASA's Common Research Model aircraft. • The ML-based framework is benchmarked against a conventional optimisation approach. • The framework demonstrates a similar accuracy as the conventional one, for half the CPU cost. This study proposes a fast yet reliable optimization framework for the aerodynamic design of transonic aircraft wings. Combining Computational Fluid Dynamics (CFD) and Machine Learning (ML), the framework is successfully applied to the Common Research Model (CRM) benchmark aircraft proposed by NASA. The framework relies on a series of automated CFD simulations, from which no less than 160 planform variations of the CRM wing are assessed from an aerodynamic standpoint. This database is used to educate an ML surrogate model, for which two specific algorithms are explored, namely eXtreme Gradient Boosting (XGB) and Light Gradient Boosting Machine (LGBM). Once trained with 80 % of this database and tested with the remaining 20 %, the ML surrogates are employed to explore a larger design space, their optimum being then inferred using an optimization framework relying on a Multi-Objective Genetic Algorithm (MOGAO). Each ML-based optimal planform is then simulated through CFD to confirm its aerodynamic merits, which are then compared against those of a conventional, fully CFD-based optimization. The comparison is very favourable, the best ML-based optimal planform exhibiting similar performances as its CFD-optimized counterpart (e.g. a 14 % higher lift-to-drag ratio) for only half of the CPU cost. Overall, this study demonstrates the potential of ML-based methods for optimizing aircraft wings, thereby paving the way to the adoption of more disruptive, data-driven aircraft design paradigms. [ABSTRACT FROM AUTHOR]

Focusing on a bio-inspired passive flow control strategy with a potential application to wind turbines, this study consists of an experimental characterization of the aerodynamics of a representative wind turbine blade section to be possibly equipped with leading-edge tubercles. A total of five airfoils are tested in a low-speed wind tunnel, their aerodynamic characteristics being explored over a wide range of flow conditions by the means of load measurements and wall-flow visualizations. Results reveal that the leading-edge tubercles alter differently the airfoil's aerodynamics, depending on their specific design (amplitude and wavelength) as well as on the flow conditions (speed and incidence). The magnitude of these effects is seen to vary with the tubercles' amplitude and/or wavelength, ultimately leading to an optimal trade-off between pre- and post-stall regimes being offered by an intermediate amplitude-to-wavelength ratio. Second, the aerodynamic benefits/penalties induced by the leading-edge tubercles are explored through wall-flow visualizations; The tubercled airfoils exhibit pairs of counter-rotating vortices, whose characteristics are driven by the tubercles' design, the airfoil shape, and/or the flow conditions. Overall, these vortex pairs are more prominent for large-amplitude and/or small-wavelength tubercles, each design altering the near-wall flow and, thus, the aerodynamic performances in a specific fashion. [Display omitted] • A wind turbine blade section with leading-edge tubercles is explored experimentally. • Five tubercle designs are explored over numerous flow conditions (speed, incidence). • The tubercles improve the aerodynamics at post-stall, degrading them at pre-stall. • The tubercles' benefits/penalties depend on their design (amplitude, wavelength). • The tubercles of moderate amplitude-to-wavelength ratio offer the best trade-off. [ABSTRACT FROM AUTHOR]

A two-step approach to address the toolpath planning optimization problem is introduced. The first step divides the surface into zones with similar local geometric properties in order to improve efficiency of tool-path planning algorithms. To do this, an unsupervised clustering algorithm (like K-means) is used on a mesh defined by isoparametric curves. The second step applies a toolpath planning algorithm to each zone, according to its optimal machining direction. This optimal direction is calculated using a blackbox optimization software. The final goal is to enhance gradually the formulation of the optimization problem to obtain better and better results. [ABSTRACT FROM AUTHOR]

As part of a research effort towards greener aviation, this study focuses on the noise impact of aircraft operations around major airports. First, a pre-existing aircraft noise prediction platform based on a simplified (semi-empirical) approach is refined, to account for all refraction effects inherited from realistic (e.g., heterogeneous) atmospheres. To do so, the platform is enhanced with a more advanced noise propagation kernel relying on Ray Tracing, which combines state-of-the-art functionalities and novel refinements (e.g., to account for the three-dimensional nature of winds). This improved prediction platform is then validated against various benchmark cases, delivering outcomes of both phenomenological and methodological natures (e.g., the importance of accounting for 3D wind patterns whilst numerically handling them with care). Finally, the platform is applied to real-life situations involving representative aircraft operations and actual meteorological conditions, revealing how weather variations can significantly alter the propagation − and thus impact − of aircraft noise. [ABSTRACT FROM AUTHOR]

Yttria-stabilised zirconia (YSZ) materials are of great interest due to their mechanical properties, chemical inertness, low thermal conductivity and high ionic conductivity. However, a high temperature is required to consolidate the YSZ, while homogeneity problems may arise. This study proposes a modified wet chemical method for commercial YSZ sintering started from a scalable colloidal solution containing yttrium and lithium in an aqueous medium. This homogeneous mixture, adjusted by pH and Li/Y content, transforms into intermediate phases that play a key role as "cement" linking YSZ particles at low sintering temperatures. The originality consists of the use of the citric acid enabling the formation of either porous or dense microstructure depending on processing conditions. A complete follow-up of the transformation of compounds throughout the process, from liquid phase to cement, is proposed and enables us to propose the consolidation mechanism that will be useful for further optimization. [ABSTRACT FROM AUTHOR]

Summary Although growing evidence indicates that bioenergetic metabolism plays an important role in the progression of tumorigenesis, little information is available on the contribution of reprogramming of energy metabolism in cancer initiation. By applying a quantitative proteomic approach and targeted metabolomics, we find that specific metabolic modifications precede primary skin tumor formation. Using a multistage model of ultraviolet B (UVB) radiation-induced skin cancer, we show that glycolysis, tricarboxylic acid (TCA) cycle, and fatty acid β-oxidation are decreased at a very early stage of photocarcinogenesis, while the distal part of the electron transport chain (ETC) is upregulated. Reductive glutamine metabolism and the activity of dihydroorotate dehydrogenase (DHODH) are both necessary for maintaining high ETC. Mice with decreased DHODH activity or impaired ETC failed to develop pre-malignant and malignant lesions. DHODH activity represents a major link between DNA repair efficiency and bioenergetic patterning during skin carcinogenesis. [ABSTRACT FROM AUTHOR]

L'homocystéine (HCy) est un intermédiaire du métabolisme de la méthionine, et son élévation est corrélée à un risque accru de maladies vasculaires artérielles et veineuses (thrombotiques et athéromateuses). Chez les patients atteints de porphyrie aiguë intermittente (PAI) produisant des taux élevés de porphyrines (précurseurs de l'hème) à long terme, 62,5 % présentent une hyperhomocystéinémie (HHCy) [1]. Nous rapportons un cas d'HHCy majeure sous givosiran (ARN interférant), traitement de fond actuel de la PAI. Une femme âgée de 63 ans est atteinte d'une première poussée de PAI sous la forme d'un syndrome PRES (syndrome d'encéphalopathie postérieure réversible). Après un séjour en rénaimation l'évolution est satisfaisante. Elle est traitée par hémine humaine. Elle rechute 5 ans plus tard avec une cécité transitoire de résolution rapide. En 2021, elle présente une 3e crise aiguë de PAI à la suite d'une pyélonéphrite, résolutive sous hémine humaine. Plusieurs cas de PAI ont été diagnostiqués dans la famille, son frère, sa sœur, sa nièce et ses 2 filles sont porteurs de la mutation du gène HMBS. Biologiquement, un mois après la dernière crise traitée avec de l'hémine humaine, les taux de porphyrines étaient les suivants : ALA/créat : 49 micromol/mmol et PBG/créat : 63 micromol/mmol (similaires aux taux observés durant la crise aiguë un mois avant). L'HCy à jeun a été mesurée à 79 micromol/l (N < 16). Il est alors décidé de débuter un traitement par givosiran (ARNi) sous-cutané tous les mois pendant 2 mois (traitement de fond actuel des PAI). Un mois après la 1ère injection, les taux de porphyrines ont nettement diminué : ALA/créat : 2,8 et PBG/créat : 11,4, mais le taux d'HCy s'est élevé à plus de 30 fois la normale, mesuré à 447. Un traitement par vitamine B6 fortes doses est débuté (250 mg 3 fois/jour et un comprimé de cystine par jour) pendant 60 jours. La 2e injection de givosiran est réalisée. Un mois plus tard l'HCy plasmatique est mesurée à 317 et deux mois plus tard à 13 (N < 16). Au bout de 3 mois sans traitement de fond le taux des porphyrines remonte et une 4e injection de givosiran est décidée. Le traitement par vitamine B6 est poursuivi. Les taux de porphyrines se normalisent et le taux d'HCy reste inférieur à la normale montrant un contrôle satisfaisant des taux d'HCy malgré le traitement par givosiran. Le rythme des injections de givosiran est adapté selon la réponse au traitement et l'évolution des taux de porphyrines urinaires [2]. Au-delà de l'élévation fréquente des taux d'HCy rapportés dans la littérature au cours des PAI, il est désormais démontré que le givosiran peut provoquer une élévation des taux d'HCy [3]. Les principales comorbidités au cours des PAI se résument classiquement à l'insuffisance rénale chronique, l'HTA et au risque très élevé de carcinome hépatocellulaire (38 fois plus élevé au cours des PAI comparé à la population générale). L'HHCy au cours de la PAI est un phénomène connu depuis quelques années. Depuis l'utilisation récente du givosiran, des cas d'augmentation de l'HCy parfois à des taux très élevés ont été rapportés. L'efficacité du traitement par vitamine B6 (connu au cours des hypercystinuries et des HHCY chez des patients déficitaires en cystathionine bêta synthase) n'avait jamais été clairement montrée chez des patients atteints de porphyries et traités par givosiran. Pour la première fois dans la littérature nous montrons qu'une HHCy majeure provoquée par le givosiran peut être totalement contrôlée par un traitement par vitamine B6, comme cela est recommandé dans les HHCy majeures, permettant la poursuite du traitement de fond par givosiran et une diminution du sur-risque vasculaire de la patiente. [ABSTRACT FROM AUTHOR]

Los fármacos inhibidores del factor de necrosis tumoral alfa (anti-TNF alfa) son ampliamente utilizados en diversas especialidades médicas. El principal efecto adverso de estos fármacos es el aumento del riesgo de infecciones. Presentamos el caso de un varón de 30 años con espondilitis anquilosante, en tratamiento desde hacía 2 semanas con golimumab, que consulta por lesiones asalmonadas en tronco, palmas y plantas de 10 días de evolución. Con la sospecha de un secundarismo luético se solicitaron pruebas treponémicas y no treponémicas que confirmaron el diagnóstico. Asimismo se solicitó una punción lumbar, aunque no existía sintomatología neurológica, para descartar neurosífilis. Los casos de sífilis en pacientes en tratamiento con anti-TNF alfa son excepcionales en la literatura y no hay protocolos establecidos que nos guíen sobre cómo actuar ante esta situación. Inhibitors of tumor necrosis factor-alpha (anti-TNF-alpha) are widely used in different medical specialties. The main adverse effect of these agents is the increased risk of infection. We report the case of a 30-year-old man with ankylosing spondylitis who had begun receiving golimumab two weeks earlier. He presented with a 10-day history of salmon-colored lesions on trunk, palms and soles. The clinical suspicion was secondary syphilis. Treponemal and nontreponemal tests confirmed the diagnosis of syphilis. Lumbar puncture was also performed, although there was no neurological involvement, to rule out neurosyphilis. Cases of syphilis in patients in treatment with TNF-alpha inhibitors are uncommon in the literature and there are no established protocols. [ABSTRACT FROM AUTHOR]

The present article proposes an advanced methodology for numerically simulating complex noise problems. More precisely, we consider the so-called multi-stage acoustic hybrid approach, which principle is to couple sound generation and acoustic propagation stages. Under that approach, we propose an advanced hybrid method which acoustic propagation stage relies on Computational AeroAcoustics (CAA) techniques. To this end, first, an innovative weak-coupling technique is developed, which allows an implicit forcing of the CAA stage with a given source signal coming from an a priori evaluation, whether the latter evaluation is of analytical or computational nature. Then, thanks to additional innovative solutions, the resulting CAA-based hybrid approach is optimized so that it can be applied to realistic and complex acoustic problems in an easier and safer way. All these innovative features are then validated on the basis of an academic test case, before the resulting advanced CAA-based hybrid methodology is applied to two problems of flow-induced noise radiation. This demonstrates the ability of the here proposed method to address realistic problems, by offering to handle at the same time both acoustic generation and propagation phenomena, despite their intrinsic multiscale character. [ABSTRACT FROM AUTHOR]

Objective: The etiologic diagnosis of acute dyspnea in the emergency department (ED) remains difficult, especially for elderly patients or those with previous cardiorespiratory medical history. This may lead to inappropriate treatment and potentially a higher mortality rate. Our objective was to evaluate the performance of cardiopulmonary ultrasound compared with usual care for the etiologic diagnosis of acute dyspnea in the ED. Methods: Patients admitted to the ED for acute dyspnea underwent upon arrival a cardiopulmonary ultrasound performed by an emergency physician, in addition to standard care. The performances of the clinical examination, chest x-ray, N-terminal brain natriuretic peptide (NT-proBNP), and cardiopulmonary ultrasound were compared with the final diagnosis made by 2 independent physicians. Results: One hundred thirty patients were analyzed. For the diagnosis of acute left-sided heart failure, cardiopulmonary ultrasound had an accuracy of 90% (95% confidence interval [CI], 84-95) vs 67% (95% CI, 57-75), P = .0001 for clinical examination, and 81% (95% CI, 72-88), P = .04 for the combination "clinical examination-NT-proBNP-x-ray". Cardiopulmonary ultrasound led to the diagnosis of pneumonia or pleural effusion with an accuracy of 86% (95% CI, 80-92) and decompensated chronic obstructive pulmonary disease or asthma with an accuracy of 95% (95% CI, 92-99). Cardiopulmonary ultrasound lasted an average of 12 ± 3 minutes. Conclusions: Cardiopulmonary ultrasounds performed in the ED setting allow one to rapidly establish the etiology of acute dyspnea with an accuracy of 90%. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to assess the potential of bedside lung ultrasound examination by the attending emergency physician in the diagnosis of acute pneumonia. Material and Methods: This observational single-center study was conducted between January 2010 and June 2012 in the emergency unit of a general hospital, and analyzed 144 adult patients. The ultrasound examination was performed by one of five trained emergency physicians, and a chest radiograph interpreted by a radiologist. The primary end point was the diagnosis of hospital discharge. Results: We found a sensitivity of 0.95 for the ultrasound examination against 0.6 for radiography (P < .05). The negative predictive value was 0.67 against 0.25 for radiography (P < .05). Conclusion: These results exhort to promote the use of thoracic ultrasound in the first-line diagnosis of pneumonia. [ABSTRACT FROM AUTHOR]

Abstract: When end milling free-form surfaces using a torus milling cutter, the notion of cutter effective radius is often used to address the procedure for removal of material from a purely geometrical perspective. Using an original analytical approach, the present study establishes a relation enabling the value of this effective radius to be easily computed. The limits of validity of this relation are then discussed and precisely defined. By way of an illustration, an example of how this relation can be used to generate a numerical tool for analysis of the possibilities for machining free-form surfaces on multi-axis machine-tools is also presented. [Copyright &y& Elsevier]

Abstract: Background: Low socioeconomic position predicts risk of substance abuse, yet few studies tested the role of preexisting familial and individual characteristics. Methods: Data come from the TEMPO (Trajectoires Epidémiologiques en Population) study (community sample in France, 1991–2009, n =1103, 22–35 years in 2009) set up among offspring of participants of an epidemiological study (GAZEL). Past 12-month substance use was assessed in 2009 by self-completed mail survey: regular tobacco smoking, alcohol abuse (AUDIT), cannabis use, problematic cannabis use (CAST), other illegal drug use. Socioeconomic position was defined by educational attainment, occupational grade, employment stability and unemployment. Covariates included demographics (age, sex, relationship status, parenthood), family background (parental income, parental tobacco smoking, parental alcohol use), and juvenile characteristics (psychological problems, academic difficulties) measured longitudinally. Results: 35.8% of study participants were regular smokers, 14.3% abused alcohol, 22.6% used cannabis (6.3% had problematic cannabis use) and 4.1% used other illegal drugs. Except for alcohol abuse, substance use rates were systematically higher in individuals with low, rather than intermediate/high, socioeconomic position (age and sex-adjusted ORs from 1.75 for cannabis use to 2.11 for tobacco smoking and 2.44 for problematic cannabis use). In multivariate analyses these socioeconomic disparities were decreased, but remained statistically significant (except for illegal drugs other than cannabis). Conclusions: Tobacco smoking, alcohol, cannabis and polysubstance use are common behaviors among young adults, particularly those experiencing socioeconomic disadvantage. Interventions aiming to decrease substance abuse and reduce socioeconomic inequalities in this area should be implemented early in life. [Copyright &y& Elsevier]

Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Diagnostic and prognostic value of gated single photon emission computed tomography (gated SPECT) has not been documented in this setting. We identified 110 consecutive heart transplant recipients (with transplantation >18 months) who underwent stress–rest gated SPECT and coronary angiography within 1 month, and were clinically monitored in a single heart transplantation center. Visual scoring of perfusion and wall motion images used a 16-segment model. Left ventricular function was automatically calculated. Coronary angiography was normal in 64 patients (58%) and abnormal in 46 (any CAV, 42%), of whom 19 had severe stenoses. Sensitivity and negative predictive (NPV) value were .63 and .75 for identification of any CAV, and .84 and .96 for severe CAV. Cox regression analysis showed that independent predictors of cardiac death and retransplantation were the presence of any angiographic CAV lesions (RR = 8.816, P = .043) and a stress perfusion defect >3 segments (RR = 5.607, P = .0053). A stress perfusion defect >3 segments predicted the need for late coronary revascularization >2 months (RR = 6.11, P = .0002). We conclude that perfusion gated SPECT is a useful noninvasive screening test and may be proposed to help identify heart transplant recipients with a high risk of poor clinical outcome. A normal gated SPECT was associated with a low risk of cardiac hard event and might alleviate the need for coronary angiography. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Conventional antibody induction therapy is currently used in heart transplantation despite safety concerns. This 6-month, prospective, randomized, multicenter, open-label study examined whether basiliximab offers a tolerability benefit compared with anti-thymocyte globulin (ATG) while maintaining similar efficacy in de novo heart transplant recipients. Methods: Adult heart transplant recipients were randomized to receive basiliximab (20 mg on Day 0 and Day 4) or ATG (2.5 mg/kg/day for 3 to 5 days) with cyclosporine, mycophenolate mofetil and steroids. The primary safety end-point was a composite of serum sickness, fever, cutaneous rash, anaphylaxis, infection, thrombocytopenia, leukopenia and post-transplant proliferative disease. Efficacy was assessed by a composite end-point of death, graft loss, acute rejection Grade >1B, acute rejection associated with hemodynamic compromise or treated with antibody therapy, or loss to follow-up, whichever occurred first. Results: Eighty patients were randomized and analyzed. By Month 6, the incidence of the composite safety end-point was significantly lower with basiliximab than with ATG (50.0% vs 78.6%, p = 0.01), and infectious death was less frequent in the basiliximab group (0 of 38 vs 6 of 42, p = 0.027). The composite efficacy end-point occurred in 24 patients (63.2%) in the basiliximab arm vs 28 patients (66.7%, p = not significant [NS]) receiving ATG. Acute rejection episodes of Grade ≥1B were reported with similar frequency (50% with basiliximab vs 45.2% with ATG, p = NS); 7 patients (18.4%) in the basiliximab group and 3 (7.1%) in the ATG group had rejection Grade ≥3A. Conclusions: These results suggest that basiliximab offers improved tolerability with similar efficacy compared with current polyclonal antibody induction therapy in de novo heart transplant patients. [Copyright &y& Elsevier]

Copyright of IBS, Immuno-analyse & Biologie Specialisee is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Résumé: Nous proposons deux cas cliniques d’embolie pulmonaire sévère chez des adultes jeunes. Une hyperhomocystéinémie sévère a été découverte grâce au dosage biologique. Ceci confirme l’intérêt d’évaluer l’homocystéine dans ces circonstances cliniques. [ABSTRACT FROM AUTHOR]

• Acoustic installation effects in a typical open-jet, anechoic wind tunnel are characterized. • An advanced CAA (Computational AeroAcoustics) approach is used. • Various configurations (from very simple to rather complex) are numerically simulated. • Outcomes are both phenomenological (noise physics) and methodological (noise predictions). • The study further aids designing and/or conducting better airframe noise experiments. This study focuses on acoustic installation effects that may occur during airframe noise experiments conducted in a typical open-jet anechoic wind tunnel, exemplified here by the NASA Langley Quiet Flow Facility (QFF). These acoustic installation effects are assessed through numerical simulation, using Computational Aeroacoustics (CAA). CAA calculations involve either elementary or complex noise sources and account for either canonical or representative steady jet mean flows as well as part, or all, of the testing apparatus. The results highlight how far the refraction/convection effects induced by the open jet flow and/or the reflection/diffraction effects coming from the testing apparatus may impact the acoustic measurements. All this further aids the assessment of acoustic installation effects that might be important in the type of testing typically done in anechoic wind tunnels, such as QFF. This also shows how CAA methods can facilitate the characterization of anechoic facilities, thus offering great potential in the advanced design of optimized aeroacoustic wind tunnels. [ABSTRACT FROM AUTHOR]

• The noise impact by aircraft operations around a major airport is assessed, using both experimental and computational means. • An extensive dual campaign (experimental and computational) is conducted, to assess the noise of about 70 flights, either at take-off or approach. • All flights are experimentally measured through field-tests and numerically simulated using a state-of-the-art computational platform. • The experimental and computational results are favourably compared, thereby delivering a cross-validation of the methodological steps followed. • The causes for the possible discrepancies observed between experimental and computational results are investigated in a systematic fashion, through a sensitivity analysis. As part of a more global research effort towards a greener aviation, the present study focuses on the noise impact by aircraft operations around a major airport, namely the Hong Kong International Airport (HKIA). To assess a pre-existing aircraft noise prediction platform vis-à-vis the specificities of the local aviation scene, the ground noise impacts of 70+ aircraft flying in and out of HKIA are live-measured in two locations of Hong Kong city. This is achieved through in-situ audio recordings of aircraft during take-off/landing flight phases, along with a real-time tracking of their characteristics (aircraft and engine types, flightpaths, atmospheric conditions, etc.). Once suitably post-processed, the measurements are analyzed to characterize better the noise impacts by these various flights in regard to their specificities (e.g., aircraft types, flight operations). In a second stage, these noise impacts are compared against their digital twins, which are simulated via the noise prediction platform, using the actual flight characteristics (aircraft types, flightpaths, thrust, airspeed, etc.). This comparative assessment is achieved for a total of 60 flights consisting of 37 departures (resp. 23 arrivals) and involving 6 (resp. 5) aircraft types. Overall, the comparison between the field tests and their digital twins proves to be reasonably good, with both measured and predicted noise levels falling within a range of a few decibels across all flights, on average. Finally, specific analyses are conducted to explore the uncertainties weighing on the predictions, possibly explaining some of the mismatches observed between the experimental and computational results. Overall, the study further demonstrates that aircraft noise prediction methods such as the present one constitute a valuable means to assess the environmental impacts of air traffic operations, including when the latter are highly specific — as in Hong Kong city, owing to its complex airspace and meteorological conditions. [ABSTRACT FROM AUTHOR]

Background Emery-Dreifuss muscular dystrophy (EDMD) is an hereditary syndrome related to mutations in lamin A/C gene (LMNA) and is characterised by severe dilated cardiomyopathy, mostly slight peripheral muscular dystrophy, supra-ventricular arrhythmia and atrio-ventricular (AV) block. Transplantation for EDMD is rarely reported in the ISHLT registry. We aim to study outcomes after heart transplantation (HTx) for end-stage heart failure in twelve EDMD patients. Methods 12 cases of HTx performed for EDMD confirmed by genetic analysis in a single institution between 1997 and 2011 were compared to 12 patients age, sex and year of transplantation matched. Survival curves were analysed by Kaplan-Meier method. Results Before transplantation, EDMD patients had similar age (56 vs 57 yo, p=0,81), sex ratio (42% male), pre-transplantation NYHA functional class III (p=0,207), left ventricular ejection fraction (LVEF=33% vs 32%, p=0,89), higher rate of supra-ventricular arrythmia (100% vs 45%, p=0,002) and AV block (58% vs 12.5%, p=0,042) compared to non-EDMD. After HTx, NYHA functional class was similar (I, p=1,00), LVEF (72+/-5,91% vs 69+/-11,3%, p=0,49), rejection rate (19+/-3,8% vs 40+/-8,2% by year, p=0,45), infection rate (14% vs 6% by year, p=0,087), renal function (eGFR=89+/-49 vs 66+/-37 ml/min, p=0,22) were similar after HTx in EDMD and non-EDMD group. Survival rate at 1 year, 2 years, 5 years were not significantly different (respectively 91.6%, 90.9%, 81.5% versus 100%, 100%, 100% p=0,146). 42% EDMD patients had slight muscular dysfunction, compatible with good quality of life. Conclusion Despite reluctance for heart transplantation in end-stage HF patients with EDMD, long term outcomes are similar to non EDMD patients at 1,2 and 5-year follow-up in our institution. [ABSTRACT FROM AUTHOR]

Summary: Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome are serious maternal illnesses occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. AFLP may result from mitochondrial defects in the beta-oxidation of fatty acids, in particular a deficiency of the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) in the fetus. Clinical findings in AFLP vary and its diagnosis is complicated by a significant overlap in clinical and biochemical features with HELLP syndrome. We report the case of 2 siblings who died, the first one in the neonatal period of asphyxia with multivisceral presentation and the second one from sudden death at 7 months. Autopsy of the latter infant revealed hepatic steatosis associated with cardiomyopathy, which led to suspicion of a fatty acid oxidation deficiency. Mutation analysis demonstrated that both children were homozygous for the common mutation c.1528G>C and the parents were heterozygous for this same mutation. This case demonstrates the importance of screening mothers with acute fatty liver disease of pregnancy and their children at birth for a metabolic disease. This article proposes several metabolic tests for mother and child suspected of having beta-oxidation of a fatty acid disorder. [Copyright &y& Elsevier]

Abstract: Many risk factors of aseptic osteonecrosis (AO) are well-known, even if 40% of events are idiopathic. Intravascular thrombosis is one of the physiopathological mechanisms of AO. The aim of this study is to determine the influence of coagulopathies on AO set-up. We performed a prospective case–control study, with 39 cases and 39 controls matched on age and sex. Cases are defined according to radiological criteria, and controls as non-affected by renal or hepatic insuffiency, and without inflammatory syndrome. Well-known AO risk factors were studied. Assessment of thrombosis was based on anti-phospholipid, anti ß2 Glycoprotein I, antiprothrombin, anti-cardiolipin, antithrombin, protein S and C, factor V Leiden, prothrombin gene and MTHFR mutations. 71% of cases presented a classical AO risk factor, vs. 38% of the controls. A significant association was also found between smoking and risk of AO. No significant difference in coagulopathy frequency was shown between cases and controls (56.4% vs. 48.7% respectively, p >0.05). Only abusive consumption of alcohol and tobacco is associated with risk of AO. Our study did not demonstrate any implication of coagulopathies in AO susceptibility. Further studies are needed to investigate more precisely these features. [Copyright &y& Elsevier]

Résumé: Objectifs: Bien que de nombreux facteurs de risque aient été décrits au cours de l’ostéonécrose aseptique (ON), le bilan étiologique n’identifie aucun de ces facteurs dans environ 40 % des cas qui sont alors considérés comme idiopathique. Depuis quelques années, différentes coagulopathies ont été incriminées dans le risque de thrombose intravasculaire. Ces coagulopathies pourraient-elles intervenir dans la physiopathologie de certaines ON et expliquer une part des formes dites idiopathiques ? Méthodes: Nous avons réalisé une étude prospective comportant 39 cas et 39 témoins. Les cas sont des sujets affectés d’une ON d’après des critères radiologiques. Les témoins sont appariés sur l’âge et le sexe, indemnes d’insuffisance rénale, hépatique et syndrome inflammatoire. Les facteurs de risque classique d’ON ont été recherchés pour chacun des patients. Le bilan de thrombose comprenait : antiphospholipides, anti-2GPI, antiprothrombine, anticoagulant circulant lupique, lipoprotéine (a), protéines S et C, antithrombine, résistance à la protéine C activée, mutation du gène de la prothrombine et de la 5,10 Méthylènetétrahydrofolate reductase (MTHFR). Résultats: Soixante et onze pour cent des cas présentaient un facteur de risque classique d’ON contre 38 % des témoins. Le tabagisme, non identifié comme un facteur de risque traditionnel d’ON, est également plus fréquemment retrouvé chez les cas que chez les témoins. Un pourcentage de 56,4 % des cas présentaient au moins une coagulopathie contre 48,7% des témoins (différence non significative). Conclusion: Les facteurs classiques d’ON qui sont statistiquement significatives sont l’exogénose et le tabagisme. Notre étude ne plaide pas pour une influence des coagulopathies dans la constitution d’une ON. Des études de plus grande envergure sont nécessaires pour confirmer ces conclusions. [Copyright &y& Elsevier]

Abstract: This article covers side milling of ruled surfaces using a milling cutter. Flank milling is useful for machining objects such as impellers, turbine blades, fan vanes and all workpieces defined by non-developable, ruled surfaces. In the present article, the influence of parameters defining improved positioning described in a previous study will be appraised. The general idea with improved positioning is to position the milling cutter at a tangent to the 2 directrices of the ruled surface while keeping a point of contact between the milling cutter and the rule considered. This is obtained by a rotation at a point about an imposed axis. Having defined calculation of error between the milled surface and the nominal surface, the influence of the point and the axis of rotation of improved positioning on error will be studied. From this, optimum improved positioning parameters allowing minimisation of error between the ruled surface and the milling cutter will be deduced. [Copyright &y& Elsevier]

Abstract: This article covers side milling of ruled surfaces using a milling cutter. Flank milling is useful for machining objects such as impellers, turbine blades, fan vanes and all workpieces defined by non-developable, ruled surfaces. In the present article, we first introduce two types of positioning on ruled surfaces developed within the Toulouse Mechanical Engineering Laboratory. The positioning studied is taken from the geometric situation not taking the instantaneous speed of rotation of the milling cutter into account. The swept profile of the tool is then determined based on the tool motion. Having defined the envelope surface, we seek to analyse improved and standard positioning errors comparing envelope surfaces with the ruled surface. We then introduce an example to illustrate positioning developed through a first theoretical study before experimentation including machining and measurement of the test piece. Finally, we give our conclusions as to the validity of improved positioning without taking the instantaneous speed of rotation of the milling cutter into account. [Copyright &y& Elsevier]

A chronic excess of glucocorticoids elicits deleterious effects in the hippocampus. Conversely, retinoic acid plays a major role in aging brain plasticity. As synaptic plasticity depends on mechanisms related to cell morphology, we investigated the involvement of retinoic acid and glucocorticoids in the remodelling of the HT22 neurons actin cytoskeleton. Cells exhibited a significantly more elongated shape with retinoic acid and a rounder shape with dexamethasone; retinoic acid reversed the effects of dexamethasone. Actin expression and abundance were unchanged by retinoic acid or dexamethasone but F-actin organization was dramatically modified. Indeed, retinoic acid and dexamethasone increased (70 ± 7% and 176 ± 5%) cortical actin while retinoic acid suppressed the effect of dexamethasone (90 ± 6%). Retinoic acid decreased (−22 ± 9%) and dexamethasone increased (134 ± 16%) actin stress fibres. Retinoic acid also suppressed the effect of dexamethasone (−21 ± 7%). Spectrin is a key protein in the actin network remodelling. Its abundance was decreased by retinoic acid and increased by dexamethasone (−21 ± 11% and 52 ± 10%). However, retinoic acid did not modify the effect of dexamethasone (48 ± 7%). Calpain activity on spectrin was increased by retinoic acid and decreased by dexamethasone (26 ± 14% and −57 ± 5%); retinoic acid mildly but significantly modified the effect of dexamethasone (−44 ± 7%). The calpain inhibitor calpeptin suppressed the effects of retinoic acid and dexamethasone on cell shape and actin stress fibres remodelling but did not modify the effects on cortical actin. Retinoic acid and dexamethasone have a dramatic but mainly opposite effect on actin cytoskeleton remodelling. These effects originate, at least partly, from calpain activity. [ABSTRACT FROM AUTHOR]

Abstract: This paper investigates stability and dynamic behaviour of torus tool in climb milling on 5 positioned axes. The stability lobes theory is used to enable stable cutting conditions to be chosen. As the adaptation of such a theory to complex milling configurations is a difficult matter, new methods are presented to identify the dynamic parameters. Tool dynamic characteristics (stiffness and natural pulsation) are determined with an original coupled calculations-tests method. Start and exit angles are computed exactly using an original numerical model. A sensitivity analysis highlights the influence of machining parameters on stability of climb milling. This shows that a third region of “potential instability” must be taken into account in plotting stability lobes, due to the uncertainty of prediction due to modelling and identification of parameters. The results were validated experimentally with an innovative approach, especially through the use of high-speed cameras. Analysis of vibrations and the surface roughness allowed the analytical model to be verified so as to optimise the inclination of the tool on the surface. [Copyright &y& Elsevier]

The Papillon–Lefèvre syndrome (PLS) is an autosomal recessive disorder. The gene responsible for the disease, cathepsin C (CTSC), is localized in 11q14.1–q14.21. We performed mutational and functional analyses of CTSC in two patients affected by this condition. Three previously unreported CTSC mutations were identified. The first patient had a compound heterozygous status with a p.G386R missense mutation and an intragenic deletion spanning exons 3–7. Second patient carried a homozygous splice site mutation, p.A253SfsX30. CTSC activity was undetectable in both patients, thus demonstrating the pathological effect of these mutations. We describe early evidence of an original intragenic deletion reported in PLS. Since this mutational mechanism could not be detected by direct sequencing, intragenic deletion has to be specifically investigated using gene dosage analysis techniques such as quantitative multiplex fluorescent polymerase chain reaction. We consider that this technique should be performed in patients with apparently homozygous CTSC mutations when one parent does not carry the expected mutation or is not available for analysis.Journal of Investigative Dermatology (2008) 128, 322–325; doi:10.1038/sj.jid.5700987; published online 18 October 2007 [ABSTRACT FROM AUTHOR]

Continuous renal replacement therapy (CRRT) is associated with micronutrients loss. Current recommendations are to administer 1–1.5 g/kg/day of proteins during CRRT. We aim to evaluate the net effect of CRRT on amino acids (AA), vitamins A and C (Vit A, Vit C) levels. This is a prospective observational study embedded within a randomised controlled trial comparing two CRRT doses in patients with septic shock. CRRT was provided in continuous veno-venous haemofiltration mode at a dose of either 35 ml/kg/h or 70 ml/kg/h. All patients received parenteral nutrition with standard trace elements and vitamins (protein intake 1 g/kg/d). We measured serum levels of glutamine, valine and alanine as well as Vit A and Vit C upon randomisation, study day four and eight. In addition, we measured a larger panel of AA in a subset of 11 patients. We included 30 patients (17 allocated to 70 ml/kg/h and 13 to 35 ml/kg/h CRRT). Before CRRT initiation, mean plasma levels of glutamine and valine, Vit A and Vit C were low. CRRT was not associated with any significant change in AA levels except for a decrease in cystein. It was associated with an increase in Vit A and a decrease in Vit C levels. CRRT dose had no impact on those nutrients blood levels. Irrespective of dose, CRRT was associated with a decrease in cysteine and Vit C and an increase in Vit A with no significant change in other AA. Further studies should focus on lean mass wasting during CRRT. [ABSTRACT FROM AUTHOR]

This paper deals with the effect of the introduction of a central flat zone on the mechanical strength of quasi-isotropic curved composite beams. Composite fittings, a particular kind of curved composite beams, are often used in the aeronautical industry as junction parts. In most cases, and in order to connect parallel or orthogonal panels, they present a C-, T- or L-shaped geometry. Subjected to complex loadings, including bending, they have to face out-of-plane tension in their curved region. This phenomenon, known as unfolding, can lead to unstable delaminations and to a global failure of the assembly. In this study, a central flat zone is introduced in the curved region of a L-shaped laminated composite curved beam. Experimental results demonstrate the strengthening effect of this architecture, with a rise in the mechanical strength of around 15%. A finite element model, based on continuum mechanics and cohesive zones model, is developed. After dealing with the difficulties met with cohesive zones model and mesh size dependency, the proposed model presents results in agreement with experimental observations. It enables the understanding of the differences between the failure scenario of the original and modified curved composite specimens. [ABSTRACT FROM AUTHOR]

Introduction Les syndromes de déficit en créatine regroupent trois maladies héréditaires affectant le métabolisme de la créatine : le déficit en guanidinoacétate méthyltransférase (GAMT), le déficit en arginine : glycine amidinotransférase (AGAT) et le déficit en transporteur membranaire de la créatine (CRTR). Ces pathologies se traduisent par un déficit cérébral en créatine ayant pour conséquence une atteinte neurologique peu spécifique avec retard mental. Le dosage du guanidinoacétate et de la créatine au niveau urinaire et plasmatique par LC-MS/MS permet de poser le diagnostic, et d’orienter vers l’un des trois déficits. À ce jour, l’analyse de ces molécules polaires et basiques s’avère délicate. En effet pour l’étude de ces molécules peu retenues sur colonne standard, la méthode de référence requiert une étape de dérivatisation par butanol/HCl 6 M rendant la technique longue et contraignante. Pour s’affranchir de cette étape, il a été choisi d’utiliser la technique d’appariement d’ions. Le principe consiste en l’ajout, au niveau des deux phases mobiles, d’un ion de charge opposée à la molécules d’intérêt, de telle sorte qu’ils puissent ensemble former un complexe non chargé. Le contre ion, ici l’acide perfluoropentanoique, possédant une chaîne hydrophobe, va interagir via celle-ci avec la phase stationnaire organique permettant ainsi une plus forte rétention du complexe. Matériels et méthode Une gamme d’étalonnage a été choisie pour couvrir les valeurs biologiques et pathologiques. Les points de gamme, les contrôles de qualité interne et les urines des patients sont diluées au 1/20 dans une solution aqueuse d’étalon interne. Après agitation et centrifugation, ils sont analysés directement par LC-MS/MS (Alliance, Quattromicro Waters). L’utilisation de la technique d’appariement d’ions permet d’éliminer une étape de dérivatisation par estérification lente et délicate. Pour valider la méthode, il a été choisi de suivre les recommandations du COFRAC (portée B) tout en les adaptant aux critères spécifiques des dosages réalisés par technique chromatographique. Résultas Les CV intra-jours représentant la répétabilité et les CV inter-jours représentant la reproductibilité sont tous inférieurs à 15 % même pour la LOQ prouvant ainsi la fidélité de notre méthode. La justesse, évaluée par les échantillons externes de qualité, s’est avérée bonne avec des biais < 15 %. Il n’a pas été noté d’effet matrice, ni de phénomène de contamination. Par ailleurs, la comparaison entre notre méthode et la méthode référence a montré des résultats sensiblement identiques. De plus, le temps de préparation des échantillons avant LC-MS/MS est passé de 2 h pour l’ancienne technique à 30 min par cette nouvelle méthode. Ceci correspond à un gain de temps technique de 75 % associé à une très importante simplification technique. Conclusion Dans le dosage du guanidinoacétate et de la créatine par LC MS/MS, l’utilisation de l’appariement d’ions que nous avons développé permet une simplification technique de la méthode ainsi qu’un un gain de temps et apparaît donc comme une optimisation de la méthode actuelle. [ABSTRACT FROM AUTHOR]

Introduction Les déficits du cycle de l’urée (UCD) sont des pathologies touchant principalement les nouveau-nés, caractérisées par un déficit portant sur une des six enzymes ou un des transporteurs impliqués dans le cycle. Ce cycle garantissant l’élimination d’azote sous forme d’urée, une inhibition du cycle provoque une hyperammoniémie pouvant être mortelle. Ce déficit enzymatique est dû à une mutation génétique. Le nouveau-né, après un intervalle libre, présente une anorexie avec des pleurs, puis des nausées avec ou sans vomissement associés à des troubles de conscience pouvant mener au coma, à des crises convulsives, voire au décès. Si la pathologie est moins sévère, la révélation peut être plus tardive, dans l’enfance ou parfois à l’âge adulte [1] . Certains patients peuvent aussi être asymptomatiques sur le plan clinique mais être porteurs d’une mutation qui laisse une activité enzymatique suffisante au fonctionnement physiologique de leur organisme. Ces derniers sont diagnostiqués lors d’une enquête familiale autour d’un cas index. L’objectif de cette étude est de décrire une cohorte de patients adultes afin de mieux caractériser la présentation des déficits du cycle de l’urée diagnostiqués à l’âge adulte. Patients et méthodes Il s’agit d’une étude rétrospective, observationnelle et multicentrique française incluant des patients ayant un UCD diagnostiqué après l’âge de 16 ans. Les pathologies incluses sont un déficit en une des enzymes du cycle (nacétylglutamate synthase NAGS, carbamylphosphate synthétase CPS, ornithine transcarbamylase OTC, arginosuccinate synthétase, arginosuccinate lyase ou arginase), la citrullinémie de type 2 (déficit en transporteur mitochondrial de l’aspartate) et le syndrome hyperammoniémie, hyperornithinémie et homocitrullinurie (HHH) (due à un déficit en un transporteur de l’ornithine). Les données cliniques, biologiques et la prise en charge initiale ont été analysées, ainsi que l’état des patients au moment de l’étude (vivant ou décédé). Résultats Au total, 49 patients ont été inclus, 31 femmes (63 %) et 18 hommes (37 %) avec un âge moyen de 37 ans. Quarante-deux patients étaient atteints de déficit en OTC, 3 de déficit en CPS1, 2 avaient un syndrome HHH, 1 avait une acidurie arginosuccinique et un patient est resté sans diagnostic. Le diagnostic a été fait lors de la première décompensation hyperammoniémique pour 29 patients (59 % de notre cohorte) d’âge moyen 38 ans, (17 femmes et 12 hommes). Parmi ces 29 patients, 23 étaient atteints de déficit en OTC, 3 de déficit en CPS, 1 patient avait un syndrome HHH, 1 un déficit en ASL et 1 UCD non caractérisé. Au diagnostic, 28 patients présentaient de symptômes neurologiques (allant des céphalées au coma avec état de mal épileptique), 17 patients souffraient de troubles digestifs (nausées, vomissements, douleurs abdominales) et 8 patients de symptômes psychiatriques. Dix-huit patients (37 %) ont été diagnostiqués dans le cadre d’un dépistage familial, (14 femmes et 4 hommes, âge moyen 39 ans), tous atteints de déficit en OTC. Au total, 78 % de ces patients étaient déjà symptomatiques, et tous présentaient un hyperammoniémie (avant ou après test de charge en protéines). Les symptômes principaux étaient une éviction spontanée des protéines dans leur régime alimentaire (8 patients), des épisodes de vomissements (7 patients) ou de céphalées récurrentes (6 patients). Deux patients (âge moyen 21 ans), atteints de syndrome HHH et de déficit en OTC ont été diagnostiqués lors d’un bilan de symptômes chroniques. Lors d’une décompensation, tous les patients avaient une hyperammoniémie (pic moyen à 395 μmol/L) et un facteur déclenchant était retrouvé dans 76 % des cas, avec en premier lieu une majoration des apports protéiques. Vingt-quatre patients ont été hospitalisés en réanimation lors de leur première décompensation. Au total, 5 patients sont décédés, dont 3 lors de leur première décompensation. La valeur du pic d’ammoniémie était un facteur de gravité. Les patients qui décèdent durant leur première décompensation sont les patients qui ont les concentrations d’ammoniémie parmi les plus élevées (500, 700 et 1250 μmol/L). Conclusion Notre étude est la plus grosse cohorte de patients ayant une révélation tardive après 16 ans. Elle confirme les résultats déjà publiés sur la triade clinique : signes neurologiques, psychiatriques et digestifs. Les 10 % de mortalité de cette étude démontrent une nouvelle fois la potentielle gravité du diagnostic. Il doit être évoqué devant toute encéphalopathie hyperammoniémique non expliquée, surtout en présence de patients ayant des antécédents de syndrome confusionnel et/ou de vomissements récurrents. [ABSTRACT FROM AUTHOR]