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In numerous insects, the olfactory receptor family forms a unique class of heteromeric cation channels. Recent progress in resolving the odorant receptor structures offers unprecedented opportunities for deciphering their molecular mechanisms of ligand recognition. Unexpectedly, these structures in apo or ligand-bound states did not reveal the pathway taken by the ligands between the extracellular space and the deep internal cavities. By combining molecular modeling with electrophysiological recordings, we identified amino acids involved in the dynamic entry pathway and the binding of VUAA1 toDrosophila melanogaster’s odorant receptor co-receptor (Orco). Our results provide new evidence for the exact location of the agonist binding site and a detailed and original mechanism of ligand translocation controlled by a network of conserved residues. These findings would explain the particularly high selectivity of Orcos for their ligands.

International audience

In this study, blood and plasma of grey partridges (Perdix perdix) were analyzed to assess their potential contamination by plant protection products (PPP) and especially pesticide compounds. The group of pesticides selected is composed of a huge variety of compounds. Therefore, in this study, two methods were optimized and validated to analyze 104 compounds including herbicides, insecticides, fungicides and photoprotectors or synergists. Various extraction methods found in the literature were compared and adapted for the extraction of pesticides from blood and plasma. After extraction, samples were concentrated then injected for quantification simultaneously in LC-MS/MS and ATD-GC-MS/MS with an automatic thermal desorption step (ATD). Both LC-MS/MS and ATD-GC-MS/MS analyses were performed using the MRM mode with 2 mass transitions for each compound.The two analytical methods achieved a good linearity for the calibration responses in plasma and blood. Methods allowed sensitive detection and quantification in complex biological matrices such as plasma and blood in both LC and GC. For plasma samples and considering all 104 compounds of the study, the average LOD was 0.005 ng mg

The standard management of locally advanced rectal tumors as cT3-T4 and/or N0/N1 is based on preoperative treatment combining radiotherapy of 45 to 50Gy and chemotherapy based on 5-fluorouracil. Intensity-modulated radiotherapy has already shown its interest compared to conformal radiotherapy in other locations, like in pelvic cancer. The role of intensity-modulated radiotherapy in the pre/postoperative treatment of rectal cancers is not a standard of care. Published studies showed its feasibility with the objective of less toxicity with equivalent efficacy.

Cholangiocarcinomas are digestive tumors whose incidence remains low and have poor prognosis. The benefits of adjuvant radiochemotherapy and radiotherapy have never been demonstrated in any phase III randomized controlled trial. Chemotherapy with capecitabine 6 months is the standard of care in adjuvant setting. Radiochemotherapy is validated in R1 patients. It is not recommended in neoadjuvant situations given the lack of evidence. Chemotherapy and radiochemotherapy are validated in adjuvant or locally advanced diseases. Stereotactic radiation therapy offers an interesting perspective, at the cost of significant digestive toxicities, requiring evaluation in randomized trials.

Preoperative radiotherapy boosted by chemotherapy is a recommended treatment in locally advanced rectal cancers. This treatment is delivered by three dimensional conformal irradiation, which is usually well tolerated but can induce potential toxicity such as rectitis, cystitis and hematologic adverse effects. Intensity-modulated radiotherapy, widely available nowadays, allows optimization of volume covering and sparing of organs at risk such as bladder and bone marrow. This review presents relevant clinical situations and requirements for a beneficial and safe preoperative irradiation of rectal cancers by intensity-modulated technique. This technique is compared to three-dimensional conformal radiotherapy.

Objectives It is not uncommon for athletes to be diagnosed with iron deficiency, yet there remains uncertainty whether the prevalence of suboptimal iron status in elite athletes differs from the normal population or warrants routine screening. The purpose of this study is to describe the distribution of serum ferritin (SF) in a cohort of elite athletes. Design Retrospective cohort study. Methods Electronic health records of 1085 elite adult athletes (570 women, 515 men) from 2012–2017 were examined retrospectively. SF values were compared to published normal population data. The proportion of athletes meeting criterion values for iron deficiency or initiation of treatment was examined. Results SF distributions in male athletes were significantly lower than normal males aged 20 to 0.05) or aged 24 to 0.05). Using 35 ng/ml as the criterion value for stage one iron deficiency, 15% of male athletes and 52% of female athletes displayed suboptimal iron status. Conclusions Male athletes have a significantly lower population distribution of SF values as compared to normative data on healthy males, with 15% of male athletes having suboptimal SF status. The distribution of SF values in elite female athletes did not differ from population values, however approximately half women athletes were iron deficient. These data suggest that iron screening should be considered in both male and female athlete populations.

International audience; We report on the complete temporal characterization of femtosecond laser pulses from second-order interferometric autocorrelation and laser spectrum measurements. The method exploits a newly developed autocorrelator based on a two photon-absorption signal produced directly within a camera sensor so as to provide a single-shot interferometric autocorrelation of great reliability and robustness. Interferometric autocorrelation trace and laser spectrum are exploited for a spectral phase retrieval via an evolutionary algorithm. The quality of the reconstruction for highly modulated spectral phases imprinted by a pulse shaper confirms the reliability of the method. The autocorrelator is compact, robust and easy to use. Possible improvements are discussed.

This paper presents an experimental investigation of tip vortex formation noise produced by wall-mounted finite airfoils. Acoustic measurements were taken in the open jet anechoic wind tunn...

This paper presents the results of experimental investigations on the sound absorption of two porous structures and the far-field noise performance of an airfoil employing sound-absorbing p...

This paper is concerned with the flow characteristics and noise generation at the finite wing–wall junction. To characterize junction flow noise, acoustic measurements were taken in the aco...

InEscherichia coli, DNA replication termination is orchestrated by two clusters ofTersites forming a DNA replication fork trap when bound by Tus proteins. The formation of a ‘locked’ Tus-Tercomplex is essential for halting incoming DNA replication forks. However, the absence of replication fork arrest at someTersites raised questions about their significance. In this study, we examined the genome-wide distribution of Tus and found that only the six innermostTersites (TerA-EandG) were significantly bound by Tus. We also found that a single ectopic insertion ofTerBin its non-permissive orientation could not be achieved, advocating against a need for ‘back-up’Tersites. Finally, examination of the genomes of a variety of Enterobacterales revealed a new replication fork trap architecture exclusively found outside the Enterobacteriaceae family. Taken together, our data enabled the delineation of a narrow prototypical Tus-dependent DNA replication fork trap consisting of only twoTersites.Graphical Abstract

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation.. .) and patient-related factors (comorbidities, sequelae of previous irradiation.. .), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques., Malgré les progrès dans la prise en charge des carcinomes épidermoïdes des voies aérodigestives supé-rieures (VADS), de nombreux patients vont développer une récidive en territoire irradié ou un second primitif. Devant la très grande hétérogénéité de ces patients, des facteurs liés à la maladie (localisa-tion, volume, récidive ou second primitif, intervalle depuis la première irradiation, etc.), des facteurs liés au patient (comorbidités, séquelles de la première irradiation.. .), les indications sont posées au cas par cas. Les données historiques de réirradiation, bien que rapportant des données d'efficacité parfois encourageantes, font état de taux de toxicité de grades 4 et 5 importants. Avec la généralisation récente des techniques de radiothérapie plus précises et mieux conformées comme la radiothérapie confor-mationnelle avec modulation d'intensité (RCMI) ou la radiothérapie stéréotaxique (SBRT), le rapport bénéfice/risque de la réirradiation a évolué ces dernières années. L'objectif de cette revue est de faire le point sur les réirradiations des carcinomes épidermoïdes des voies aérodigestives supérieures en termes de sélection de patients, et de techniques modernes de radiothérapie. © 2019 Société franç aise de radiothérapie oncologique (SFRO).

Laparoscopic cholecystectomy might be considered minor surgery, but it may result in severe postoperative pain. Subcostal transversus abdominis plane (TAP) block, which produces long-lasting supra-umbilical parietal analgesia, might improve analgesia after laparoscopic cholecystectomy.We investigated whether subcostal TAP block would reduce opioid consumption and pain after laparoscopic cholecystectomy in patients provided with multimodal analgesia.A randomised, placebo-controlled, double-blind study.The study was conducted at a university teaching hospital from December 2017 to June 2018.Sixty patients scheduled for laparoscopic cholecystectomy were included. Anaesthesia and postoperative analgesia (etoricoxib, paracetamol, ketamine and dexamethasone) were standardised.After induction of anaesthesia, patients were allocated into two groups: ultrasound-guided bilateral subcostal TAP block with 20 ml of levobupivacaine 0.375% and epinephrine 5 μg ml or 0.9% saline with epinephrine 5 μg ml.Opioid consumption in the recovery room and during the first 24 h after surgery were recorded. Postoperative somatic and visceral pain scores, fatigue and nausea were measured. Intra-operative end-tidal concentrations of sevoflurane (FETSEVO) were also recorded.Twenty-four hour postoperative opioid consumption were similar in both groups: 21.2 mg (95% CI 15.3 to 27.1) vs. 25.2 (95% CI 15.1 to 35.5) oral morphine equivalent in the levobupivacaine and 0.9% saline groups, respectively; P = 0.48. No significant between-group differences were observed with regards to parietal (P = 0.56) and visceral (P = 0.50) pain scores, fatigue and nausea. FETSEVO was slightly lower in the levobupivacaine group (P 0.01).Subcostal TAP block does not improve the analgesia provided by multimodal analgesia after laparoscopic cholecystectomy. It allows for a small reduction in intra-operative sevoflurane requirements.NCT0339153.

This paper presents a combined experimental and large-eddy simulation study to characterise the effect of aspect ratio on the near-wake structure of a square finite wall-mounted cylinder (FWMC). The cylinder aspect ratios (span $L$ to width $W$) investigated in the experiments were $1.4\leqslant L/W\leqslant 21.4$ and the oncoming boundary-layer thicknesses were $1.3W$ and $0.9W$ at a Reynolds number based on cylinder width of $1.4\times 10^{4}$ and $1.1\times 10^{4}$, respectively. In complementary simulations, the cylinder aspect ratios investigated were 1.4, 4.3, 10 and 18.6. The cylinder wake structure was visualised in three-dimensional space using a vortex core detection method and decomposed to its oscillation modes using the spectral proper orthogonal decomposition (SPOD) technique. A parametric diagram is proposed to predict whether the time-averaged wake structure is a dipole or a quadrupole pattern, based on oncoming boundary-layer height and aspect ratio. Cellular shedding occurs when the aspect ratio is high with up to three shedding cells occurring across the span for aspect ratios $L/W>18$. Each of these cells sheds at a distinct frequency, as evidenced by the spectral content of the surface pressure measured on the side face and the near-wake velocity. Amplitude modulation is also observed in the vortex shedding, which explains the amplitude modulation of the acoustic pressure emitted by square FWMCs. SPOD is shown to be a viable method to identify the occurrence of cellular shedding in the wake.

Three-dimensional unsteady flow around a finite wall mounted square cylinder subjected to a steady secondary flow (blowing and suction) from the cylinder's front face has been studied with the aid of direct numerical simulations. The aspect ratio (AR) of the cylinder was varied as AR = 2, 4 and 7 while the ratio Г of the secondary flow to the freestream velocity was changed as −4 ≤ Г ≤ 4. All simulations were carried out at a Reynolds number (Re) of 250, based on the cylinder width, to investigate the influence of Г and AR on cylinder forces, vortex shedding frequency, and mean and instantaneous wake structures. The results show that, independent of AR, both blowing and suction have the potential to reduce the time-mean forces (e.g. more than 90% pressure drag reduction), fluctuating forces and vortex shedding frequency. Furthermore, a detailed investigation of vortex evolution reveals that the suction strategy considerably affects the shedding type and wake flow topology. Increasing the suction ratio changes the shedding from symmetric to asymmetric at AR = 4. Conversely, a planar jet attenuates vortical structures in the vicinity of the wall. Jet deflection is observed at Г = 2 and 4, which plays a key role in the success of the control approach and in the determination of the wake flow structure by changing the pressure distribution on the front face. The effect of AR on the shedding of large-scale vortical structures is also examined. Two critical AR values are determined where the flow and the mean wake structure changed from steady to unsteady (2

L’incidence des fistules anales est comprise entre 12 et 28 sur 100 000 habitants en Europe. L’âge moyen de survenue se situe entre 30 et 50 ans. La majorité des fistules anales surviennent sous la forme d’un abcès anorectal et ont pour origine une infection cryptogénétique des glandes d’Hermann et Desfosses. Le diagnostic est principalement clinique. L’abcès est la plupart du temps facile à repérer, car il se présente sous la forme d’une tuméfaction érythémateuse, plus ou moins volumineuse, chaude, tendue, luisante et hyperalgique à la palpation. Lorsqu’il est intramural ou ischioanal profond, l’inspection de la marge anale est alors normale, et le toucher rectal permet de faire le diagnostic en palpant une voussure douloureuse du bas rectum. En cas de fistulisation, l’aspect est variable, l’examen clinique permet de repérer le ou les orifices secondaires, il peut palper un trajet fistuleux superficiel sous la forme d’un cordon roulant sous la peau. Il doit rechercher l’orifice interne palpable sous la forme d’une dépression ou d’une granulation située au niveau pectinéal, plus rarement visible en anuscopie. Plusieurs techniques d’imagerie permettent de caractériser les fistules anales, notamment complexes, en repérant le trajet fistuleux principal et le ou les trajets fistuleux secondaires, les abcès et diverticules. Les techniques de référence sont l’échoendoscopie anale et l’IRM pelvienne. L’IRM s’impose de plus en plus dans la caractérisation préopératoire des fistules notamment complexes. En pratique, dans la plupart des cas, les fistules anales peuvent être opérées sans examen d’imagerie, mais devant la disponibilité de celle-ci et ses performances, elle est de plus en plus utilisée. Il paraît indispensable de réaliser une IRM préopératoire dans la prise en charge des fistules complexes.

Objective The purpose of this study was to determine whether there are differences in reported gross billings and collections between doctors of chiropractic who have obtained a certificate of additional qualification (CAQ) in sports medicine compared with those without a CAQ in sports medicine. Methods A cross-sectional study was conducted. An e-mail invitation to participate in an anonymous survey was sent to doctors of chiropractic who hold active certifications with the American Chiropractic Board of Sports Physicians. The respondents were provided a link to a web-based survey that was constructed with similar questions to a national chiropractic survey issued by Chiropractic Economics (CE) for the same year (2015). Results Three hundred forty-nine sports medicine CAQ doctors of chiropractic responded (23.8% response rate) in comparison to 719 CE respondents. The CAQ respondents averaged $722 983 in gross billings (9.8% response rate) compared with $539 046 by CE respondents. Sports medicine CAQ doctors of chiropractic averaged $452 376 in gross collections (10.4% response rate) compared with $348 773 by CE respondents. Conclusion An analysis of these 2 surveys illustrates that CAQ respondents report higher total annual gross billings and collections than the CE respondents. Improving study methodology may improve response rates and garner a more accurate representation of any differences between doctors of chiropractic with and without CAQs.

Abstract One known method to reduce vortex shedding from the tip of a blade is the use of end plates or winglets. Although the aerodynamic impact of such end plates has been investigated in the past, no studies exist on the effect of such end plates on the far-field noise. The aeroacoustic noise reduction of three different end-plate geometries is experimentally investigated. The end plates are applied to the free end of a wall-mounted symmetric NACA 0012 airfoil and a cambered NACA 4412 airfoil with an aspect ratio of 2 and natural boundary layer transition. Microphone array measurements are taken in the aeroacoustic open-jet wind tunnel at BTU Cottbus-Senftenberg for chord-based Reynolds numbers between 75,000 and 225,000 and angles of attack from 0$$^\circ$$ ∘ to 30$$^\circ$$ ∘ . The obtained acoustic spectra show a broad frequency hump for the airfoil base configurations at higher angles of attack that is attributed to tip noise. Hot-wire measurements taken for one configuration show that the application of an end plate diffuses the vorticity at the tip. The aeroacoustic noise contribution of the tip can be reduced when the endplates are applied. This reduction is most effective for higher angles of attack, when the tip vortex is the dominant sound source. Graphic abstract

BackgroundThe rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC).MethodsBetween June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities.ResultsEighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response (p = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) (p = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03).ConclusionsTPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

Some over-etch (OE) related defects in semiconductor device processing are only obvious after vias or trenches are already filled. Such defects are usually buried and often discovered after failure analysis from failed devices. Inline detection by physical means using optical inspection tools is not possible. e-Beam inspection has the ability to detect this type of defect electrically. OE related defects create shorts or leakage paths and their ability to cause device failure depends on the level or extent of this leakage. Hard OE fail impacts yield while marginal OE is relatively harmless. e-Beam inspection detects both hard OE fail and marginal OE as bright voltage contrast (BVC) and it has always been a challenge to discern yield impacting hard OE fail from the relatively harmless OE based only on the defect images. TEM analysis is often necessary to distinguish between the two. In this paper attempt is made to relate the extent of OE to e-Beam defect detection parameters, Threshold (TH) and Grey Level (GLV). Correlation between the amount of OE and each of the two parameters is established. Also a correlation is found among the two parameters themselves. With these relationships established, the e-Beam defect detection parameters alone can be used to predict OE’s potential impact on yield without TEM analysis.

International audience; Background: Stereotactic radiotherapy (SRT) should be applied with a biologically effective dose with an α/β of 12 (BED12) ≥ 40 Gy to reach a 1-year local control (LC) ≥ 70%. The aims of this retrospective study were to report a series of 81 unresected large brain metastases treated with Linac-based multifraction SRT according to the ICRU 91 and to identify predictive factors associated with LC.Methods: Included in this study were the first 81 brain metastases (BM) consecutively treated with Linac-based volumetric modulated arc therapy (VMAT) multifraction SRT from 2017 to 2019. The prescribed dose was 33 Gy for the GTV and 23.1 Gy (70% isodose line) for the PTV in 3 fractions (3f). Mean BM largest diameter and GTV were 25.1 mm and 7.2 cc respectively. Mean follow-up was 10.2 months.Results: LC was 79.7% and 69.7% at 1 and 2 years respectively. Significant predictive factors of LC were GTV D98% (HR = 0.84, CI 95% = 0.75-0.95, p = 0.004) and adenocarcinoma as the histological type (HR = 0.29, CI 95% = 0.09-0.96, p = 0.042) in univariate and multivariate analysis. A threshold of 29 Gy for GTV D98% was significantly correlated to LC (1-year LC = 91.9% for GTV D98% ≥ 29 Gy vs 69.6% for GTV D98% < 29 Gy (p = 0.030)), corresponding to a BED12 = 52.4 Gy. No tumor progression was observed for a BED12 ≥ 53.4 Gy, corresponding to a GTV D98% ≥ 20 Gy /1f and GTV D98% ≥ 29.4 Gy 3f. Median OS was 15 months. Symptomatic radionecrosis occurred in 4.9% of cases.Conclusion: The GTV D98% is a strong reproducible significant predictive factor of LC for brain SRT. Dose prescription should lead to a GTV BED12 98% ≥ 52.4-53.4 Gy to significantly improve LC, corresponding to respectively a GTV D98% ≥ 19.7-20 Gy/1f and 29-29.4 Gy/3f.

Drone propeller noise under static and steady inflow conditions has been studied. A numerical model that couples a blade element momentum theory model with a frequency-domain acoustic model is presented. Experimental acoustic data for a 12-inch drone propeller under static and steady inflow are compared with the model. The model compares well against the experimental data for the fundamental tone and first 2–3 harmonics under steady inflow. Discrepancies at the higher harmonics are likely due to the point-loading assumption used to apply the aerodynamic loads in the acoustic model. Comparisons under static conditions are poor and this is thought to be caused by the limited nature of the aerodynamic model used. The results suggest that an accurate and versatile aerodynamics model is most important for accurate prediction of drone propeller noise over a wide range of operating conditions.

The Golo River drains a steep catchment (average gradient of 30 m km−1, surface of 1214 km2) in the northeast part of Corsica Island, delivering sediments to the Ligurian Sea. In this study, we review and revise the geologic map and constrain the extent of the Golo coastal alluvial plain formations and their relative and absolute chronology. To update the surface extent of each formation, we performed a geomorphologic analysis with DEMs and satellite imagery data coupled with an extensive pedogenic and sedimentary field observations database, including a new borehole of 117,4 m depth. Additionally, we performed in-situ cosmogenic 10Be analysis from a depth-profile in the well-preserved alluvial terrace Fy2, yielding a minimum age of 70 ka for its emplacement. Our new chronology, based on cosmogenic 10Be and soil chronosequences, implies older ages than those previously obtained with luminescence methods. Soil mixing by bioturbation is proposed as a possibility to explain differences between luminescence and 10Be ages. In this scenario, 10Be dates the original deposition of the alluvial terrace, while luminescence dates a later soil development. We highlighted at least five outcropping alluvial terraces in the Golo coastal plain, which are controlled by sea-level fluctuations and were most likely deposited during past sea-level highstands (close to present-day sea-level). Moreover, we identified from a borehole more than 117 m of coarse fluvial sediments in the plain, that do not outcrop at the surface. New cosmogenic 26Al/10Be burial ages suggest that this sedimentary unit results from a thick accumulation of fluvial material filling a zone significantly affected by subsidence, probably accommodated by a normal fault during the Early Quaternary.