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BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Left-right asymmetries recurrently evolve in animals but the underlying developmental mechanisms are unknown. In mostDrosophilaspecies, the male genitalia is symmetric and undergoes a clockwise 360° rotation during development. InD. melanogaster, this tissue remodeling process is directed by class I myosins: in MyoID mutants the rotation is reversed and the genitalia remains symmetric. Males ofDrosophila pacheahave evolved unique left-right asymmetric genital organs and a characteristic right-sided copulation posture in the past 3-6 million years. To test if these asymmetries in morphology and behavior evolved via the recruitment of pre-existing directional cues controlled by MyoID, we used CRISPR to knockout MyoID inD. pachea. Strikingly, mutant males undergo a reverse genitalia rotation and develop mirror-image asymmetric genitalia, indicating that MyoID controls both the direction of genitalia rotation direction and morphological asymmetry. Although genital asymmetry is reversed, MyoID mutants still adopt a wild-type right-sided copulation posture. Our results show that MyoID and its asymmetry guidance role were recruited for the evolution of a novel left-right asymmetry inD. pacheaand that lateralized copulation behavior is determined by other mechanisms. The evolution of a new left-right organ size asymmetry inD. pacheainvolved recruitment of existing directional cues.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Rearing temperature is correlated with the timing and speed of development in a wide range of poikiloterm animals that do not regulate their body temperature. However, exceptions exist, especially in species that live in environments with high temperature extremes or oscillations. Drosophila pachea is endemic to the Sonoran desert in Mexico, in which temperatures and temperature variations are extreme. We wondered if the developmental timing in D. pachea may be sensitive to differing rearing temperatures or if it remains constant. We determined the overall timing of the Drosophila pachea life-cycle at 25{degrees}C and 29{degrees}C. The duration of pupal development was similar at both temperatures although the relative progress differed at particular stages. Thus, D. pachea may have evolved mechanisms to buffer temperature influence on developmental speed, potentially to ensure proper development and individuals fitness in desert climate conditions. HighlightsO_LIIn poikilotherms, developmental speed usually increases with rearing temperature C_LIO_LIGlobal pupal development of D. pachea is similar at two different rearing temperatures C_LIO_LIDiscrete temperature dependent timing differences at specific pupal stages C_LIO_LID. pachea development is longer compared to other Drosophila species C_LIO_LITemperature-buffering mechanisms may have evolved to ensure a proper development C_LI

For patients with cT1 renal lesions, Partial Nephrectomy (PN) is the gold standard treatment. However, 20% of small renal masses are benign, situation in which the PN is an overtreatment. The percutaneous Renal Tumor Biopsy (RTB) may lower the risk of overtreatment as there is a 90% concordance rate on histotype between the RTB and the final pathology. It has been suggested that the RTB could increase the difficulty of the PN and increase the risk of surgical complications.To compare surgical outcomes and complications of PN with or without previous RTB.monocentric retrospective review of patients who underwent laparoscopic or robotic-assisted PN between January 2012 and December 2019.perioperative complications were recorded using Clavien-Dindo classification, peroperative data included operative time, clamping time and blood loss, and histological outcomes of RTB and PN.In total, 163 patients were included in our study. There were significantly less benign lesions in PN with prior RTB: 7% (4/56) vs. 20% (22/107) without prior RTB (P=0.03). There were no significant differences regarding Clavien-Dindo2 perioperative complications with respectively 7% (4/56) vs. 10% (11/107) (P=0.57). Same goes for peroperative data such as duration of surgery (P=0.81), warm ischemia (P=0.07) and blood loss (P=0.13).RTB does not increase the risk of surgical complications of PN and may reduce the risk of small renal masses overtreatment.

We present the detection and characterisation of mesoscale waves on the lower clouds of Venus using images from the Visible Infrared Thermal Imaging Spectrometer onboard the European Venus Express space mission and from the 2 $\mu$m camera (IR2) instrument onboard the Japanese space mission Akatsuki. We used image navigation and processing techniques based on contrast enhancement and geometrical projections to characterise morphological properties of the detected waves, such as horizontal wavelength and the relative optical thickness drop between crests and troughs. Additionally, we performed phase velocity and trajectory tracking of wave packets. We combined these observations to derive other properties of the waves such as the vertical wavelength of detected packets. Our observations include 13 months of data from August 2007 to October 2008, and the entire available data set of IR2 from January to November 2016.We characterised almost 300 wave packets across more than 5500 images over a broad region of the globe of Venus. Our results show a wide range of properties and are not only consistent with previous observations but also expand upon them, taking advantage of two instruments that target the same cloud layer of Venus across multiple periods. In general, waves observed on the nightside lower cloud are of a larger scale than the gravity waves reported in the upper cloud. This paper is intended to provide a more in-depth view of atmospheric gravity waves on the lower cloud and enable follow-up works on their influence in the general circulation of Venus., Comment: 15 pages, 18 figures, published on Astronomy & Astrophysics

International audience; Presbycusis, or age-related hearing loss (ARHL), is a major public health issue. About half the phenotypic variance has been attributed to genetic factors. Here, we assessed the contribution to presbycusis of ultrarare pathogenic variants, considered indicative of Mendelian forms. We focused on severe presbycusis without environmental or comorbidity risk factors and studied multiplex family age-related hearing loss (mARHL) and simplex/sporadic age-related hearing loss (sARHL) cases and controls with normal hearing by whole-exome sequencing. Ultrarare variants (allele frequency [AF] < 0.0001) of 35 genes responsible for autosomal dominant early-onset forms of deafness, predicted to be pathogenic, were detected in 25.7% of mARHL and 22.7% of sARHL cases vs. 7.5% of controls ( P = 0.001); half were previously unknown (AF < 0.000002). MYO6 , MYO7A , PTPRQ , and TECTA variants were present in 8.9% of ARHL cases but less than 1% of controls. Evidence for a causal role of variants in presbycusis was provided by pathogenicity prediction programs, documented haploinsufficiency, three-dimensional structure/function analyses, cell biology experiments, and reported early effects. We also established Tmc1 N321I/+ mice, carrying the TMC1 :p.(Asn327Ile) variant detected in an mARHL case, as a mouse model for a monogenic form of presbycusis. Deafness gene variants can thus result in a continuum of auditory phenotypes. Our findings demonstrate that the genetics of presbycusis is shaped by not only well-studied polygenic risk factors of small effect size revealed by common variants but also, ultrarare variants likely resulting in monogenic forms, thereby paving the way for treatment with emerging inner ear gene therapy.

Introduction Male genitalia are thought to ensure transfer of sperm through direct physical contact with female during copulation. However, little attention has been given to their pre-copulatory role with respect to sexual selection and sexual conflict. Males of the fruitfly Drosophila pachea have a pair of asymmetric external genital lobes, which are primary sexual structures and stabilize the copulatory complex of female and male genitalia. We wondered if genital lobes in D. pachea may have a role before or at the onset of copulation, before genitalia contacts are made. Results We tested this hypothesis with a D. pachea stock where males have variable lobe lengths. In 92 mate competition trials with a single female and two males, females preferentially engaged into a first copulation with males that had a longer left lobe and that displayed increased courtship vigor. In 53 additional trials with both males having partially amputated left lobes of different lengths, we observed a weaker and non-significant effect of left lobe length on copulation success. Courtship durations significantly increased with female age and when two males courted the female simultaneously, compared to trials with only one courting male. In addition, lobe length did not affect sperm transfer once copulation was established. Conclusion Left lobe length affects the chance of a male to engage into copulation. The morphology of this primary sexual trait may affect reproductive success by mediating courtship signals or by facilitating the establishment of genital contacts at the onset of copulation.

The musculocutaneous tensor fascia latae flap was one of the first free flaps described. It is possible to harvest a flap with the same skin paddle, vascularized by a septo-cutaneous perforator running through the tensor fascia lata muscle septum and coming from the ascending branch of the lateral circumflex femoral artery. The DIEP is currently the workhorse of autologous breast reconstruction, but there are some contraindications. The septo-cutaneous tensor fascia latae perforator flap may be an alternative for women with lateral upper thigh lipodystrophy. Between 2010 and 2014, three flaps have been performed in two patients for delayed breast reconstruction (one case of unilateral reconstruction, and one bilateral). Perforators were identified by preoperative angiography. The intervention was performed in a two-team approach, in only one operative position. Perforators were located in the horizontal axis of the upper rim of the pubis bone. One perforator artery was dissected for each flap. The mean caliber of the pedicle was 2.8mm, and the mean length was 6.4cm. The operative time was 240minutes for unilateral flap, 375minutes for bilateral flap. There was no case of total or partial necrosis, or complications on the donor site. Cosmetic results were considered satisfying by patients and surgeons with the reconstructed breast as well as the donor site. Septo-cutaneous fascia lata perforator flap is an attractive flap for breast reconstruction in patients with DIEP contraindication and lateral upper thigh lipodystrophy. It has many advantages: easy to harvest, length and calibre of the pedicle, double team approach, only one operating position, quality of reconstruction. It is necessary to carry out a larger series of cases to study the complication rate in the donor site.

IntroductionMale genitalia are thought to ensure transfer of sperm through direct physical contact with female during copulation. However, little attention has been given to their pre-copulatory role with respect to sexual selection and sexual conflict. Males of the fruitflyDrosophila pacheahave a pair of asymmetric external genital lobes, which are primary sexual structures and stabilize the copulatory complex of female and male genitalia. We wondered if genital lobes inD. pacheamay have a role before or at the onset of copulation, before genitalia contacts are made.ResultsWe tested this hypothesis with aD. pacheastock where males have variable lobe lengths. In 92 mate competition trials with a single female and two males, females preferentially engaged into a first copulation with males that had a longer left lobe and that displayed increased courtship vigor. In 53 additional trials with both males having partially amputated left lobes of different lengths, we observed a weaker and non-significant effect of left lobe length on copulation success. Courtship durations significantly increased with female age and when two males courted the female simultaneously, compared to trials with only one courting male. In addition, lobe length did not affect sperm transfer once copulation was established.ConclusionLeft lobe length affects the chance of a male to engage into copulation. The morphology of this primary sexual trait may affect reproductive success by mediating courtship signals or by facilitating the establishment of genital contacts at the onset of copulation.

Introduction L’encephalite a tique (TBE) est une infection virale endemique dans plusieurs pays d’Europe centrale et du Nord, mais rare en France, ou la plupart des cas sont recenses en Alsace. En juin 2017 et aout 2018, deux cas de TBE ont ete diagnostiques par serologie specifique chez des patients du CHU de St-Etienne n’ayant pas quitte la Loire ou la Haute-Loire. Materiels et methodes Une enquete epidemiologique a ete menee afin d’identifier des expositions a risque dans le mois precedant l’apparition des premiers signes cliniques. Resultats L’interrogatoire a distance des patients et de l’entourage du premier cas a permis d’exclure tout sejour en zone endemique en France ou a l’etranger, ainsi que toute consommation de produits a base de lait cru. En revanche, ces deux patients vivent en bordure du massif forestier du Livradois-Forez qu’ils frequentent de maniere occasionnelle ou reguliere, les exposant au risque de piqure de tique. Les dates de debut des signes coincident d’ailleurs avec la saison de proliferation des tiques. Une quinzaine de jours avant le debut des signes cliniques, le premier cas a effectue une randonnee au pied du Mont Bar, en Haute-Loire, au cours de laquelle il a ete pique par des animaux, a priori des arthropodes, qu’il n’a pas identifies. Le second cas est une eleveuse de bovins retraitee, ayant l’habitude de se rendre dans les forets aux alentours de sa ferme situee dans la Loire. Elle rapporte de nombreuses piqures de tiques, notamment le mois precedant les premiers signes cliniques. Conclusion La mise en evidence du virus associe a TBE (TBEV) dans le secteur du Livradois-Forez, avec une transmission a l’homme, necessite l’information des cliniciens susceptibles de prendre en charge des patients de retour ou vivant dans cette zone, et presentant des manifestations cliniques evocatrices de TBE. Un 3e cas d’infection acquise dans la region a ete diagnostique ulterieurement chez un touriste residant dans une autre region. Une estimation de la prevalence du TBEV dans les tiques de la region serait interessante. Enfin, ces cas confirment une zone d’extension du virus plus large qu’historiquement connue. Cette extension du TBEV en France necessite d’etre evaluee, pour adapter si besoin les mesures de prevention, et faciliter la detection des cas humains.

Background Active discopathy is associated with a specific phenotype of chronic low back pain (cLBP). Local inflammation has a role in active discopathy-associated symptoms (1). Objectives To assess the efficacy of a single glucocorticoid intradiscal injection (GC IDI) in cLBP patients with active discopathy. Methods We conducted a prospective, parallel-group, double-blind, randomized controlled study in 3 tertiary care centers in France. 135 cLBP patients with active discopathy on MRI were enrolled. They received a single GC IDI (25 mg prednisolone acetate) during discography (n=67) or discography alone (n=68). The primary outcome was the percentage of patients with LBP intensity in the previous 48 hr Results All randomized patients were included in the primary efficacy analysis. At 1 month, the percentage of responders (LBP intensity At 1 month, the percentage of patients reporting an improvement in spine-specific limitations in activities was higher in the GC IDI than control group (55/65 [84.6%] vs 34/63 [54.0%]; absolute risk difference [95% CI] 30.5 [15.7; 45.2], p Conclusions In active discopathy-associated cLBP, a single GC IDI reduces LBP at 1 month post-intervention but not at 12 months. Registration ClinicalTrials.gov number NCT00804531 (First received: December 8, 2008. Last updated: June 23, 2016). References Nguyen C, Poiraudeau S, Rannou F. From Modic 1 vertebral-endplate subchondral bone signal changes detected by MRI to the concept of 9active discopathy9. Ann Rheum Dis. 2015 Aug;74(8):1488–94. Acknowledgements The study was funded by a research grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique, project no. P070157). The authors thank URC-CIC Paris Descartes Necker/Cochin (Christelle Auger and Nellie Moulopo) for implementation, monitoring and data management of the study. Disclosure of Interest None declared

International audience; Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

The musculocutaneous tensor fascia latae flap was one of the first free flaps described. It is possible to harvest a flap with the same skin paddle, vascularized by a septo-cutaneous perforator running through the tensor fascia lata muscle septum and coming from the ascending branch of the lateral circumflex femoral artery. The DIEP is currently the workhorse of autologous breast reconstruction, but there are some contraindications. The septo-cutaneous tensor fascia latae perforator flap may be an alternative for women with lateral upper thigh lipodystrophy. Between 2010 and 2014, three flaps have been performed in two patients for delayed breast reconstruction (one case of unilateral reconstruction, and one bilateral). Perforators were identified by preoperative angiography. The intervention was performed in a two-team approach, in only one operative position. Perforators were located in the horizontal axis of the upper rim of the pubis bone. One perforator artery was dissected for each flap. The mean caliber of the pedicle was 2.8mm, and the mean length was 6.4cm. The operative time was 240minutes for unilateral flap, 375minutes for bilateral flap. There was no case of total or partial necrosis, or complications on the donor site. Cosmetic results were considered satisfying by patients and surgeons with the reconstructed breast as well as the donor site. Septo-cutaneous fascia lata perforator flap is an attractive flap for breast reconstruction in patients with DIEP contraindication and lateral upper thigh lipodystrophy. It has many advantages: easy to harvest, length and calibre of the pedicle, double team approach, only one operating position, quality of reconstruction. It is necessary to carry out a larger series of cases to study the complication rate in the donor site.

Resume L’hibernome est une tumeur benigne rare des parties molles, generalement asymptomatique, survenant habituellement chez l’adulte jeune. Il s’agit d’un lipome de la graisse brune. Son diagnostic est essentiellement anatomopathologique. Ses principaux diagnostics differentiels sont le lipome et le liposarcome. Son aspect en TEP/TDM au FDG n’a ete rapporte que dans un petit nombre de cas. Nous rapportons le cas d’un homme de 68 ans atteint d’un cancer ORL chez qui une tumeur graisseuse axillaire gauche avait ete decouverte fortuitement sur la tomodensitometrie (TDM) de stadification. Le diagnostic d’hibernome a ete suspecte en TEP/TDM au FDG, avec des arguments concordants sur les differents examens d’imagerie realises. En imagerie par resonance magnetique (IRM) la lesion etait atypique pour un simple lipome car elle se rehaussait apres injection de gadolinium. En TEP/TDM, la lesion fixait intensement le FDG (SUVmax = 16), ce qui est l’une caracteristiques de l’hibernome, tumeur developpee aux depens de la graisse brune. Les examens d’imagerie n’ont pas permis de faire la distinction entre hibernome et liposarcome, et le diagnostic d’hibernome–lipome mixte benin a ete obtenu par histologie apres resection complete de la tumeur. Nous retrouvons des elements quantitatifs qui distinguent hibernome et liposarcome : le caractere hautement metabolique de l’hibernome (SUVmax > 10) et la fluctuation de l’intensite de la fixation du FDG d’un examen a l’autre, le SUVmax passant de 16 a 48 en 16 mois dans le cas presente. Devant une tumeur de densite graisseuse en TDM, une valeur elevee de SUVmax au FDG semble plaider davantage en faveur d’une tumeur benigne, l’hibernome, que de la tumeur maligne apparentee, le liposarcome.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 40 - N° 7 - p. 675-681

Die Diskussionen im Rahmen der Novellierung der EU-Richtlinie 91/414/EEC sind oft von unsachlichen Angriffen auf das bestehende Zulassungsverfahren fur Pflanzenschutzmittel und die beteiligten Behorden gepragt. Das hat die Verbraucher verunsichert und den Eindruck in der Offentlichkeit verstarkt, das Zulassungssystem in Europa sei mangelhaft und die Gesundheit der Verbraucher sowie die Umwelt waren durch Pflanzenschutzmittelruckstande gefahrdet. Eine genaue Uberprufung dieser Meldungen bestatigt jedoch, dass das System zuverlassig arbeitet und aktuelle wissenschaftliche Erkenntnisse berucksichtigt. Das fur aquatische und terrestrische Organismen berechnete Risikopotenzial in Deutschland ist seit 1987 kontinuierlich zuruckgegangen. Vor diesem Hintergrund werden die Auswirkungen und der Nutzen der neuen gesetzlichen Regelungen diskutiert, deren Komplexitat ein noch nicht da gewesenes Ausmas erreicht hat.

We assessed the involvement of harmonin-b, a submembranous protein containing PDZ domains, in the mechanoelectrical transduction machinery of inner ear hair cells. Harmonin-b is located in the region of the upper insertion point of the tip link that joins adjacent stereocilia from different rows and that is believed to gate transducer channel(s) located in the region of the tip link's lower insertion point. In Ush1cdfcr-2J/dfcr-2J mutant mice defective for harmonin-b, step deflections of the hair bundle evoked transduction currents with altered speed and extent of adaptation. In utricular hair cells, hair bundle morphology and maximal transduction currents were similar to those observed in wild-type mice, but adaptation was faster and more complete. Cochlear outer hair cells displayed reduced maximal transduction currents, which may be the consequence of moderate structural anomalies of their hair bundles. Their adaptation was slower and displayed a variable extent. The latter was positively correlated with the magnitude of the maximal transduction current, but the cells that showed the largest currents could be either hyperadaptive or hypoadaptive. To interpret our observations, we used a theoretical description of mechanoelectrical transduction based on the gating spring theory and a motor model of adaptation. Simulations could account for the characteristics of transduction currents in wild-type and mutant hair cells, both vestibular and cochlear. They led us to conclude that harmonin-b operates as an intracellular link that limits adaptation and engages adaptation motors, a dual role consistent with the scaffolding property of the protein and its binding to both actin filaments and the tip link component cadherin-23. Electronic supplementary material The online version of this article (doi:10.1007/s00424-009-0711-x) contains supplementary material, which is available to authorized users.

The effect of juvenoids with different modes of action on embryonic and postembryonic development of Piesma quadratum Four juvenoids were tested against eggs and nymphs of the sugar-beet lace bug by topical and foliar application. Three compounds, namely Hydroprene, Methoprene, and CGA 13353 caused lethal disturbances of metamorphosis and embryogenesis after administration to last instar nymphs and young eggs. On the other hand, the application of ZR-777 resulted in a high mortality of all nymphal instars and of eggs of any age. Populations of nymphs consisting of all instars could not be eliminated totally by the substances. Combinations of the “toxic” product ZR-777 with typical insect growth regulators like Methoprene and CGA 13353 gave the best results concerning total mortality. Zusammenfassung Vier Juvenoide wurden auf ihre entwicklungsstorende Wirkung an Eiern und Larven der Rubenblattwanze P. quadratum untersucht. Hydropren, Methopren und CGA 13353 verursachten letale Storungen der Metamorphose und Embryogenese bei Behandlung sensibler 5. Larven und junger Eier. ZR-777 dagegen rief bei allen Larvenstadien eine hohe Mortalitat hervor und zeigte bei Eiern jeden Alters eine ovizide Wirkung. Durch Kombination des “insektizidahnlich” wirkenden ZR-777 mit einem typischen Insektenwachstumsregler konnte eine Larvenpopulation von P. quadratum befriedigend bekampft werden.

Although the cochlea is an amplifier and a remarkably sensitive and finely tuned detector of sounds, it also produces conspicuous mechanical and electrical waveform distortions1. These distortions reflect non-linear mechanical interactions within the cochlea. By allowing one tone to suppress another (masking effect), they contribute to speech intelligibility2. Tones can also combine to produce sounds with frequencies not present in the acoustic stimulus3. These sounds compose the otoacoustic emissions that are extensively used to screen hearing in newborns. As both cochlear amplification and distortion originate from the outer hair cells, one of the two types of sensory receptor cells, it has been speculated that they stem from a common mechanism. Here, the non-linearity underlying cochlear waveform distortions is shown to rely on the presence of stereocilin, a protein defective in a recessive form of human deafness4. Stereocilin was detected in association with horizontal top connectors5-7, lateral links that join adjacent stereocilia within the outer hair cell’s hair bundle, and these links were absent in stereocilin-null mutant mice. These mice become progressively deaf. At the onset of hearing, however, their cochlear sensitivity and frequency tuning were almost normal, although masking was much reduced and both acoustic and electrical waveform distortions were completely lacking. From this unique functional situation, we conclude that the main source of cochlear waveform distortions is a deflection-dependent hair bundle stiffness resulting from constraints imposed by the horizontal top connectors, and not from the intrinsic non-linear behaviour of the mechanoelectrical transducer channel.

The planar polarity and staircase-like pattern of the hair bundle are essential to the mechanoelectrical transduction function of inner ear sensory cells. Mutations in genes encoding myosin VIIa, harmonin, cadherin 23,protocadherin 15 or sans cause Usher syndrome type I (USH1, characterized by congenital deafness, vestibular dysfunction and retinitis pigmentosa leading to blindness) in humans and hair bundle disorganization in mice. Whether the USH1 proteins are involved in common hair bundle morphogenetic processes is unknown. Here, we show that mouse models for the five USH1 genetic forms share hair bundle morphological defects. Hair bundle fragmentation and misorientation (25-52° mean kinociliary deviation, depending on the mutant) were detected as early as embryonic day 17. Abnormal differential elongation of stereocilia rows occurred in the first postnatal days. In the emerging hair bundles, myosin VIIa, the actin-binding submembrane protein harmonin-b, and the interstereocilia-kinocilium lateral link components cadherin 23 and protocadherin 15, all concentrated at stereocilia tips, in accordance with their known in vitro interactions. Soon after birth,harmonin-b switched from the tip of the stereocilia to the upper end of the tip link, which also comprises cadherin 23 and protocadherin 15. This positional change did not occur in mice deficient for cadherin 23 or protocadherin 15. We suggest that tension forces applied to the early lateral links and to the tip link, both of which can be anchored to actin filaments via harmonin-b, play a key role in hair bundle cohesion and proper orientation for the former, and in stereociliary elongation for the latter.

International audience; Several lines of evidence indicate that very large G-protein-coupled receptor 1 (Vlgr1) makes up the ankle links that connect the stereocilia of hair cells at their base. Here, we show that the transmembrane protein usherin, the putative transmembrane protein vezatin, and the PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain-containing submembrane protein whirlin are colocalized with Vlgr1 at the stereocilia base in developing cochlear hair cells and are absent in Vlgr1 Ϫ/Ϫ mice that lack the ankle links. Direct in vitro interactions between these four proteins further support their involvement in a molecular complex associated with the ankle links and scaffolded by whirlin. In addition, the delocalization of these proteins in myosin VIIa defective mutant mice as well as the myosin VIIa tail direct interactions with vezatin, whirlin, and, we show, Vlgr1 and usherin, suggest that myosin VIIa conveys proteins of the ankle-link complex to the stereocilia. Adenylyl cyclase 6, which was found at the base of stereocilia, was both overexpressed and mislocated in Vlgr1 Ϫ/Ϫ mice. In postnatal day 7 Vlgr1 Ϫ/Ϫ mice, mechanoelectrical transduction currents evoked by displacements of the hair bundle toward the tallest stereocilia (i.e., in the excitatory direction) were reduced in outer but not inner hair cells. In both cell types, stimulation of the hair bundle in the opposite direction paradoxically resulted in significant transduction currents. The absence of ankle-linkmediated cohesive forces within hair bundles lacking Vlgr1 may account for the electrophysiological results. However, because some long cadherin-23 isoforms could no longer be detected in Vlgr1 Ϫ/Ϫ mice shortly after birth, the loss of some apical links could be involved too. The premature disappearance of these cadherin isoforms in the Vlgr1 Ϫ/Ϫ mutant argues in favor of a signaling function of the ankle links in hair bundle differentiation.

International audience; Background: More than 70 % of the cases of congenital deafness are of genetic origin, of which approximately 80 % are non-syndromic and show autosomal recessive transmission (DFNB forms). To date, 60 DFNB genes have been identified, most of which cause congenital, severe to profound deafness, whereas a few cause delayed progressive deafness in childhood. We report the study of two Algerian siblings born to consanguineous parents, and affected by progressive hearing loss. Method: After exclusion of GJB2 (the gene most frequently involved in non-syndromic deafness in Mediterranean countries), we performed whole-exome sequencing in one sibling. Results: A frame-shift variant (c.1014delC; p.Ser339Alafs*15) was identified in EPS8L2, encoding Epidermal growth factor receptor Pathway Substrate 8 L2, a protein of hair cells' stereocilia previously implicated in progressive deafness in the mouse. This variant predicts a truncated, inactive protein, or no protein at all owing to nonsense-mediated mRNA decay. It was detected at the homozygous state in the two clinically affected siblings, and at the heterozygous state in the unaffected parents and one unaffected sibling, whereas it was never found in a control population of 150 Algerians with normal hearing or in the Exome Variant Server database. Conclusion: Whole-exome sequencing allowed us to identify a new gene responsible for childhood progressive hearing loss transmitted on the autosomal recessive mode.

Resume L'expert judiciaire est contraint de s'adresser au juge quand lors d'une expertise il n'a pas l'autorisation des ayants droit pour consulter un dossier medical detenu par un etablissement de sante et indispensable pour repondre aux questions de la mission. Le detenteur devait-il fournir le dossier et etre condamne selon les termes de l'article 226-13 du Code penal pour violation du secret professionnel ou invoquer le motif legitime et refuser la communication ? L'arret du 7 decembre 2004 de la Cour de cassation confirme que le secret medical constitue un empechement legitime que l'etablissement de sante peut invoquer lorsqu'il n'a pas l'accord des ayants droit.

OBJECTIVES To identify all available shoulder disability questionnaires designed to measure physical functioning and to examine those with satisfactory clinimetric quality. METHODS We used the Medline database and the "Guide des outils de mesure de l'evaluation en medecine physique et de readaptation" textbook to search for questionnaires. Analysis took into account the development methodology, clinimetric quality of the instruments and frequency of their utilization. We classified the instruments according to the International Classification of Functioning, Disability and Health. RESULTS Thirty-eight instruments have been developed to measure disease-, shoulder- or upper extremity-specific outcome. Four scales assess upper-extremity disability and 3 others shoulder disability. We found 6 scales evaluating disability and shoulder pain, 7 scales measuring the quality of life in patients with various conditions of the shoulder, 14 scales combining objective and subjective measures, 2 pain scales and 2 unclassified scales. Older instruments developed before the advent of modern measurement development methodology usually combine objective and subjective measures. Recent instruments were designed with appropriate methodology. Most are self-administered questionnaires. CONCLUSION Numerous shoulder outcome measure instruments are available. There is no "gold standard" for assessing shoulder function outcome in the general population.

Objectives To identify all available shoulder disability questionnaires and to examine those that could be used for athlete. Methods We systematically reviewed the literature in Medline using the keywords shoulder, function, scale, index, score, questionnaire, disability, quality of life, assessment, and evaluation. We searched for scales used for athletes with the keywords scale name AND (sport OR athlete). Data were completed by using the "Guide des Outils de Mesure et d'Evaluation en Medecine Physique et de Readaptation" textbook. Analysis took into account the clinimetric quality of the instruments and the number of items specifically related to sports. Results A total of 37 instruments have been developed to measure disease-, shoulder-specific or upper extremity specific outcome. Older instruments were developed before the advent of modern measurement methods. They usually combined objective and subjective measures. Recent instruments were designed with use of more advanced methods. Most are self-administered questionnaires. Fourteen scales included items assessing sport activity. Four of these scales have been used to assess shoulder disability in athlete. Six scales have been used to assess such disability but do not have specific items related to sports. Conclusion There is no gold standard for assessing shoulder outcome in the general population and no validated outcome instruments specifically for athletes. We suggest the use of ASES, WOSI and WORC scales for evaluating shoulder function in the recreational athletes. The DASH scale should be evaluated in this population. The principal criterion in evaluating shoulder function in the high level athlete is a return to the same level of sport performance. Further studies are required to identify measurement tools for shoulder disability that have a high predictive value for return to sport.

The genetic heterogeneity of congenital hearing disorders makes molecular diagnosis expensive and time-consuming using conventional techniques such as Sanger sequencing of DNA. In order to design an appropriate strategy of molecular diagnosis in the Algerian population, we explored the diversity of the involved mutations by studying 65 families affected by autosomal recessive forms of nonsyndromic hearing impairment (DFNB forms), which are the most prevalent early onset forms. We first carried out a systematic screening for mutations in GJB2 and the recurrent p.(Arg34*) mutation in TMC1, which were found in 31 (47.7%) families and 1 (1.5%) family, respectively. We then performed whole exome sequencing in nine of the remaining families, and identified the causative mutations in all the patients analyzed, either in the homozygous state (eight families) or in the compound heterozygous state (one family): (c.709C>T: p.(Arg237*)) and (c.2122C>T: p.(Arg708*)) in OTOF, (c.1334T>G: p.(Leu445Trp)) in SLC26A4, (c.764T>A: p.(Met255Lys)) in GIPC3, (c.518T>A: p.(Cys173Ser)) in LHFPL5, (c.5336T>C: p.(Leu1779Pro)) in MYO15A, (c.1807G>T: p.(Val603Phe)) in OTOA, (c.6080dup: p.(Asn2027Lys*9)) in PTPRQ, and (c.6017del: p.(Gly2006Alafs*13); c.7188_7189ins14: p.(Val2397Leufs*2)) in GPR98. Notably, 7 of these 10 mutations affecting 8 different genes had not been reported previously. These results highlight for the first time the genetic heterogeneity of the early onset forms of nonsyndromic deafness in Algerian families.

Persisting spongy myocardium (also known as noncompaction of the ventricular myocardium) is a rare and special form of cardiomyopathy. The few cases reported in the literature were detected postnatally and involved a high rate of cardiovascular complications. This anomaly of endomyocardial morphogenesis, which occurs during the embryonic phase at the stage of cardiac partitioning, is characterised by an excessive number of prominent trabeculae and by intertrabecular recesses within the myocardial wall. Antenatal detection is difficult in the absence of an associated malformation, which is the general situation. We report a case of antenatal cardiomyopathy which led to therapeutic abortion. The diagnosis of persisting spongy myocardium was made during fetopathologic examination.

Our aim was to assess the efficiency of the peak systolic velocity in the middle cerebral artery (PSV-MCA) to predict neonatal anemia at the end of pregnancies after serial intravenous fetal exchange transfusions (IFET) for red-cell fetomaternal immunization.We conducted a retrospective study from 01/01/2004 to 31/12/2009 of 25 pregnancies after IFET for red-cell fetomaternal immunization, in Saint Vincent de Paul Hospital, Paris. The study assessed correlation between the last prenatal PSV-MCA measured and hemoglobin concentration at birth and other neonatal data.Last prenatal PSV-MCA and hemoglobin concentration at birth were significantly correlated (r=-0.39, P0.01).There is a good correlation between last PSV-MCA measured before birth and neonatal haemoglobin and complexity of neonatal care linked to anemia. Cerebral Doppler is useful for the follow-up of pregnancies at risk for anemia even in the end of the pregnancy and after serial intravenous fetal exchange transfusions.

[1] We locate the sources of double-frequency (or secondary) microseisms in western Europe by frequency slowness analysis of array data as well as polarization and amplitude analysis at individual stations. Array analysis uses data recorded by a temporary array of broadband stations that we deployed in the Quercy region (southwest of France) and those from the Grafenberg array, from 2 December 2005 to 30 January 2006. We determine attenuation laws for microseisms generated in the Mediterranean Sea and in the Atlantic Ocean, which allow us to use noise amplitudes to estimate distances from the source. We then combine azimuth and amplitude measurements to obtain precise locations of microseisms and estimate their source dimensions. Most of the time, microseismic noise originates in coastal regions where the swell reaches steep rocky coasts with normal incidence, in good agreement with the Longuet-Higgins model for the generation of secondary microseisms. In addition, we find evidence of occasional pelagic sources, which are closely related to moving storms, suggesting that nonlinear interaction between wave components can also generate secondary microseisms.

Background Active discopathy detected on magnetic resonance imaging (MRI), and also known as Modic 1 signal changes, encompasses clinical, radiological and biological features, enabling to define a specific subset of patients with chronic low back pain (cLBP). Modic 1 changes are largely associated with degenerative disc disease (DDD) features, however we hypothesized that a specific subset of Modic 1 patients may display milder DDD. Objectives To determine Modic 1 MRI-associated structural alterations, and to identify Modic 1 subsets based on MRI findings. Methods MRI computerized database of a tertiary care hospital in France was searched between 01/01/2006 and 01/31/2008. MRI of the lumbar spine were systematically screened by two assessors. When Modic 1 changes were present at a single level on both adjacent endplates, MRI were considered eligible, and demographics and MRI-associated structural changes were assessed. Results Out of 12,840 recorded MRI, 101 MRI were eligible. Patients9 mean age was 56.6 (13.4) years and 41 (40.6%) were males. Modic 1 changes were more frequent at L4/L5 and L5/S1 levels (37[36.6%], respectively). The most frequent MRI-associated structural alterations were >50% intervertebral space narrowing (IVSN) (70[69.3%]), anterior (51[50.5%]) and posterior (56[55.4%]) disc herniations, and anterior (68[67.3%]) and lateral (59[58.4%]) osteophytes. ≤50% IVSN Modic 1 differed from >50% IVSN Modic 1. On bivariable analysis, patients were younger (51.5[14.1] vs 58.8[12.6] years, p =0.019), ≤50% IVSN Modic 1 were more often located at L5/S1 level (19[61.3%] vs 18[25.7%], p =0.001), and anterior and lateral osteophytes were less frequent (13[41.9%] vs 55[78.6%], p vs 48[68.6%], p =0.002, respectively). On multivariable analysis, variables independently associated with >50% IVSN Modic 1 were location at L4/L5 level, anterior disc herniation and lateral osteophyte. Conclusions Modic 1 changes are frequently associated with MRI DDD features. However, we identified a distinct ≤50% IVSN Modic 1 subset that occurs in younger patients, and is associated with less advanced DDD features. Disclosure of Interest None declared

International audience; Usher syndrome type IIa (USH2A) combines moderate to severe congenital hearing impairment and retinitis pigmentosa. It is the most common genetic form of USH. USH2A encodes usherin, which was previously defined as a basement membrane protein. A much larger USH2A transcript predicted to encode a transmembrane (TM) isoform was recently reported. Here, we address the role of TM usherin in the inner ear. Analysis of the usherin alternative transcripts in the murine inner ear revealed the existence of several predicted TM usherin isoforms with modular ectodomains of different lengths. In addition, we identified in the usherin cytoplasmic region a predicted 24 amino acid peptide, derived from a newly defined exon that is predominantly expressed in the inner ear but not in the retina. In mouse and rat inner ears, we show that TM usherin is present at the base of the differentiating stereocilia, which make up the mechanosensitive hair bundles receptive to sound. The usherin immunolabeling is transient in the hair bundles of cochlear hair cells (HCs), but persists in mature hair bundles of vestibular HCs. Several lines of evidence support the involvement of TM usherin in the composition of the ankle links, a subset of filamentous lateral links connecting stereocilia at the base. By co-immunoprecipitation and in vitro binding assays, we establish that the usherin cytodomain can bind to whirlin and harmonin, two PDZ domain-containing proteins that are defective in genetic forms of isolated deafness and USH type I, respectively. These PDZ proteins are suitable to provide the anchoring of interstereocilia lateral links to the F-actin core of stereocilia. Our results strongly suggest that congenital deafness in USH type I and type II shares similar pathogenic mechanisms, i.e. the disruption of hair bundle links-mediated adhesion forces that are essential for the proper organization of growing hair bundles.

Une description phénoménologique précise de la différenciation de la touffe ciliaire des cellules sensorielles de l’oreille interne a été réalisée il y a environ 20 ans chez le poulet. Pourtant, les mécanismes cellulaires concourant à la formation de cette structure remarquablement organisée, qui assure la transformation d’un son ou d’une accélération en un signal électrique (transduction mécano-électrique), demeurent très mal connus. Récemment, par des approches génétiques conjointes chez l’homme et la souris, cinq des protéines directement impliquées dans le syndrome de Usher de type I, un double déficit sensoriel qui concerne à la fois l’audition et la vision, ont pu être caractérisées. Ces découvertes ont d’ores et déjà permis d’identifier les liens interstéréociliaires comme des acteurs essentiels de la différenciation des touffes ciliaires., Defects in myosin VIIa, the PDZ-domain-containing protein harmonin, cadherin 23, protocadherin 15, and the putative scaffolding protein sans, underlie five genetic forms of Usher syndrome type I (USH1), the most frequent cause of hereditary deafness-blindness in humans. Mice mutants defective for any of these proteins have a severe hearing impairment and display similar inner ear phenotypes characterized by the abnormal spreading of the sensory cells’ stereocilia. These are highly specialized mechanoreceptive organelles derived from microvilli, that normally form a well-structured hair bundle at the apex of inner ear sensory cells. All the USH1 proteins, except sans, have been detected in the growing stereocilia. Moreover, biochemical studies have started to unravel the multiple direct molecular interactions between USH1 proteins. In particular, harmonin can bind to the other four USH1 proteins and to F-actin. Finally, cell biology studies have provided the first insights into the functions of these proteins, and revealed that cadherin 23, and probably protocadherin 15 also, are associated with transient lateral links that interconnect growing stereocilia. These connectors play a critical role in the differentiating hair bundle.

In order to improve the wave forecast, the assimilation of directional wave spectra in wave model has been developed at Meteo France. The assimilation scheme is tested for real ENVISAT ASAR wave spectra provided by the European Space Agency. The scheme takes into account the limitation in frequency related to the ASAR instrument. The preliminary results show that the assimilation of wave spectra is efficient and works correctly. The impact of the assimilation on wave parameters is significant and stays effective in the forecast period. In addition, statistical analysis has shown good skill in term of root mean square and assimilation index for the analyzed wave parameters (wave height, direction and frequency).