Zhoushun Zheng

Helena Zapolsky
email: helena.zapolsky@univ-rouen.fr

Gilles Demange

Zhanpeng Jin

Yingbiao Peng

Han Li

Yong Du
email: yong-du@csu.edu.cn

Jianzhan Long

Zhijian Ye

3D phase field modeling of the morphology of WC grains in WC-Co alloys: The role of interface anisotropy

Keywords: Phase-field model, facetted grain morphology, tungsten carbide, cemented carbides

de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

Tungsten carbides with a cobalt rich binder phase are among the most widespread cemented carbides [START_REF] Exner | Physical and chemical nature of cemented carbides[END_REF] . This class of materials is characterized by a remarkable combination of hardness, toughness and stability at elevated temperatures [START_REF] García | Cemented carbide microstructures: a review[END_REF] , whence their privileged use for drilling and cutting components [START_REF] Norgren | Trends in the P/M hard metal industry[END_REF] . The properties of cemented carbides are determined by their microstructural features, starting with the volume fraction and size distribution of hard phases [START_REF] Milman | Influence of temperature, grain size and cobalt content on the hardness of WC-Co alloys[END_REF] . Non-spherical shapes of solid grains such as the truncated trigonal or triangular prisms were observed in WC-Co alloys.

The basal and prismatic facets of WC grains correspond to different crystal orientations, equipped with specific micro-mechanical properties [START_REF] Csanádi | Deformation characteristics of WC micropillars[END_REF] . In turn, the finest features of 3D faceted morphologies of WC grains such as their truncation and elongation factors [START_REF] Delanoë | Evolution of the WC grain shape in WC-Co alloys during sintering: Effect of C content[END_REF] also influence the macroscopic mechanical performance of the material. [START_REF] Roa | Intrinsic hardness of constitutive phases in WC-Co composites: Nanoindentation testing, statistical analysis, WC crystal orientation effects and flow stress for the constrained metallic binder[END_REF][START_REF] Nam | Microstructure of (W,Ti)C-Co system containing platelet WC[END_REF][START_REF] Yang | Fabrication and mechanical properties of WC-10Co cemented carbides with plate-like WC grains[END_REF] Therefore, understanding and predicting the detailed 3D morphology evolution of WC grains during material preparation is a strict prerequisite to upgrade mechanical properties of WC-Co alloys through optimized fabrication routes.

Cemented carbides are mostly manufactured by liquid phase sintering (LPS). During this process, solid faceted grains grow in the liquid binder phase. In WC-Co alloys, this growth was suggested to proceed by 2D nucleation/growth mechanism. [START_REF] Bonvalet | Modelling of prismatic grain growth in cemented carbides[END_REF][START_REF] Mannesson | Carbide grain growth in cemented carbides[END_REF][START_REF] Park | Abnormal growth of faceted (WC) grains in a (Co) liquid matrix[END_REF][START_REF] Zhong | Growth mechanisms of WC in WC-5.75wt% Co[END_REF] And yet, apart from a pioneering study of the anisotropic growth of WC grains in WC-25 wt. % Co alloy by Ryoo et al [START_REF] Ryoo | Anisotropic grain growth based on the atomic adsorption model in WC-25 pct Co alloy[END_REF] using the 2D pseudo-Monte-Carlo method, quantitative numerical models connecting the dots between anisotropic interface energy and the development of specific faceted morphologies of tungsten carbides hitherto remain scarce. Moreover, as far as we know, the experimentally observed prismatic shape of WC grains has not been simulated in three dimensions yet. In this work, we address the influence of the anisotropy of the interfacial energy on the morphology development of faceted tungsten carbides grains in WC-Co cemented carbides, from both numerical and experimental perspectives.

A numerically efficient way to reproduce faceted morphologies at mesoscopic scale and connect it to the anisotropic surface energy is provided by the Phase-Field model (PFM). [START_REF] Chen | Phase-Field Models for Microstructure Evolution[END_REF] This approach was notably used to study the formation of facets in Nickel thin films [START_REF] Nagashio | Growth mechanism of twin-related and twin-free facet Si dendrites[END_REF] , ice dendrites [START_REF] Demange | A phase field model for snow crystal growth in three dimensions[END_REF][START_REF] Demange | Growth kinetics and morphology of snowflakes in supersaturated atmosphere using a three-dimensional phase-field model[END_REF] and equilibrium voids under irradiation [START_REF] Han | Phase-field modeling of void anisotropic growth behavior in irradiated zirconium[END_REF] . Now, most PFM rely upon regularization procedures to circumvent the numerical instability induced by faceting (seeing for instance in refs. [START_REF] Carlo | A regularized equation for anisotropic motion-by-curvature[END_REF][START_REF] Debierre | Phase-field approach for faceted solidification[END_REF][START_REF] Kobayashi | A continuum model of grain boundaries[END_REF][START_REF] Torabi | A New Phase-Field Model for Strongly Anisotropic Systems[END_REF][START_REF] Moelans | Quantitative phase-field approach for simulating grain growth in anisotropic systems with arbitrary inclination and misorientation dependence[END_REF][START_REF] Ribot | A new approach for phase field modeling of grain boundaries with strongly nonconvex energy[END_REF] ) resulting in the increase of the complexity and a potential loss of transferability for the implemented algorithms. We thus opted for an alternative faceting approach proposed in refs. [START_REF] Zhu | Investigation of faceted void morphologies in UO 2 by phase field modelling[END_REF] and [START_REF] Wendler | A phase-field model for polycrystalline thin film growth[END_REF] , where the anisotropy function is defined directly from the equilibrium crystal shape (ECS). Not only this approach was proved to be stable without need for any regularization procedure, but also it directly connects the energy of facets to the anisotropy function in the PFM in a convenient way.

In this study, a 3-D phase field model for highly anisotropic interfacial energy is presented and the anisotropy functions are derived for WC grains. The model parameters are evaluated based on available data extracted from the ab-initio calculations. In parallel, WC-Co cemented carbides with different carbon contents were manufactured by LPS and the microstructure were observed by scanning electron microscopy. The simulation results are compared to the Wullf construction and our own experimental observations. The validity of the model is then discussed.

Results

The phase-field model

The shape relaxation of tungsten carbide grains is modeled under constant volume constraint. Based on the volume conservation of carbides, we assume that mass transport can be neglected. For this reason, it is not explicitly included in the model.

Then only one variable φ referring to the phase matrix ( =0) and solid phase particle ( =1) is necessary to describe the kinetics of the shape relaxation of grains. The relaxation kinetics of the shape of the WC grain is governed by the Allen-Cahn (nonconserved) phase-field equation:

= - (1)
where L is the kinetic coefficient and F is the total free energy of the system, defined as the integral of the free energy density f over the total volume of system. The energy density f for a heterogeneous system can be expressed in terms of and its gradient as:

, = + + ℎ + 1 -ℎ , (2)
Here is the double-well function guaranteeing local minima at =0 and =1 [START_REF] Kobayashi | Modeling and numerical simulations of dendritic crystal growth[END_REF] .

= -- ! + - ! , (3)
In ref. [START_REF] Kobayashi | Modeling and numerical simulations of dendritic crystal growth[END_REF] , the parameter m is used to introduce the driving force for grain growth and is set to 0 in our simulation.

The coefficient in Eq.( 2) controls the height of energy barrier between two minima at a given temperature. The coefficient " is the gradient energy coefficient. Following the procedure proposed by Fleck et al [START_REF] Fleck | On phasefield modeling with a highly anisotropic interfacial energy[END_REF] , the term ℎ + 1 -ℎ imposes the conservation of the solid grain volume. Here, and are energy densities for bulk particle and matrix, respectively, and ℎ = 6 -15 + 10 is an interpolation function. Then, the evolution equation ( 1) can be further developed as:

= - & -• & ( + ℎ ) * ! (4)
where the parameter * = is set by the constraint of constant volume for the particle + ,-= 0 / with respect to the following formula:

* = + (• 01 0 23 4 01 03 !5/ 6 + 7 8 5/ 6 (5)
The value of * is evaluated dynamically at each time step.

The parameters of the phase-field model, namely , ", and L in Eqs. ( 2) and ( 4) can be linked to the interface properties of the system, such as the interface thickness 9 , the interfacial energy : and the interface mobility M:

9 = ; < =" (6)
: = √< ?√ (7)
@ = A √ < (8)
Note that M is defined as the interface velocity driven by a unit of driving force, so its value is independent of the parameter m.

The modelling of the faceted morphology of WC grains is performed via the specification of the anisotropic interfacial energy. For that purpose, we posit that the gradient coefficient ε depends on crystal orientation:

" = " * BCDEF (9)
Here, " * is the gradient coefficient in the isotropic case and BCDEF is the anisotropy function. Typically, BCDEF depends on the normal vector G HI = ( |( | to the interface.

From Eq.( 7), the interfacial energy thus becomes:

: = K √< ?√ BCDEF = : * BCDEF (10)
where : * can be regarded as the average interfacial energy of the system.

The salient ingredient for the reproduction of carbides faceted morphology is the expression of the anisotropy function BCDEF , introduced in Eqs. ( 9) and (10). In most PFM, the anisotropy function is chosen to account for the crystalline symmetry, using combinations of trigonometric [START_REF] Demange | A phase field model for snow crystal growth in three dimensions[END_REF][START_REF] Demange | Growth kinetics and morphology of snowflakes in supersaturated atmosphere using a three-dimensional phase-field model[END_REF][START_REF] Karma | Phase-field formulation for quantitative modeling of alloy solidification[END_REF][START_REF] Toropova | Theoretical modeling of crystalline symmetry order with dendritic morphology[END_REF] or spherical harmonic [START_REF] Han | Phase-field modeling of void anisotropic growth behavior in irradiated zirconium[END_REF] functions, weighted by anisotropy parameters. Above a certain threshold value for the anisotropy parameters, a range of crystal orientations become unstable and faceting can be achieved, at the price of the instability of the numerical scheme. This problem is then solved by adding higher order terms to the surface energy [START_REF] Carlo | A regularized equation for anisotropic motion-by-curvature[END_REF][START_REF] Torabi | A New Phase-Field Model for Strongly Anisotropic Systems[END_REF][START_REF] Ribot | A new approach for phase field modeling of grain boundaries with strongly nonconvex energy[END_REF] , by convexifying the inverse polar plot of the anisotropy function [START_REF] Eggleston | A phase-field model for highly anisotropic interfacial energy[END_REF] , or by just-so removing the cusps in the anisotropy function [START_REF] Debierre | Phase-field approach for faceted solidification[END_REF] . The first approach involves the addition of a curvature-

dependent

Assessment of the material properties

According to Su et al's work [START_REF] Su | Investigation on morphology evolution of coarse grained WC-6Co cemented carbides fabricated by ball milling route and hydrogen reduction route[END_REF] , the WC grains appear as irregular laminar structure after ball milling, and change to multi-faceted shape during subsequent sintering.

Therefore, the WC/Co interfacial energy should be considered. Interfacial energy for each facet of WC is difficult to measure experimentally. In this work, 3 simulation cases (listed in Tab.1) were set based on the ab-initio calculations from Christensen et al's work [START_REF] Christensen | Quantitative analysis of WC grain shape in sintered WC-Co cemented carbides[END_REF][START_REF] Christensen | Morphology of WC grains in WC-Co alloys: Theoretical determination of grain shape[END_REF] . Case 1 and Case 2 correspond to C-poor and C-rich conditions in the ab-initio calculations, respectively. In both cases, the ECS for WC grains is the truncated trigonal prism (see next section) and type I anisotropy function was used. In Case 1 1.52 [START_REF] Christensen | Morphology of WC grains in WC-Co alloys: Theoretical determination of grain shape[END_REF] 1.80 [START_REF] Christensen | Quantitative analysis of WC grain shape in sintered WC-Co cemented carbides[END_REF] 2.85 34 I Case 2 1.73 [START_REF] Christensen | Morphology of WC grains in WC-Co alloys: Theoretical determination of grain shape[END_REF] 1.94 [START_REF] Christensen | Quantitative analysis of WC grain shape in sintered WC-Co cemented carbides[END_REF] 3.14 [START_REF] Christensen | Quantitative analysis of WC grain shape in sintered WC-Co cemented carbides[END_REF] I Case 3 1.52 [START_REF] Christensen | Morphology of WC grains in WC-Co alloys: Theoretical determination of grain shape[END_REF] 1.80 [START_REF] Christensen | Quantitative analysis of WC grain shape in sintered WC-Co cemented carbides[END_REF]

this work II

The expressions of : are determined from Tab.1. The interface width 9=5×10 -7 m was adopted from ref. [START_REF] Cheng | Phase-field simulation of liquid phase migration in the WC-Co system during liquid phase sintering[END_REF] and the value of α in eq.7 was chosen to be 2.2. The value for L was set to 5 × 10 4 * U • V ⁄ , so that the mobility of (0001) interfaces @ *** was ).

Shape relaxation for single WC grain

The interfacial anisotropy model is first checked against theoretical prediction of equilibrium shape (ECS). Generally speaking, the Wulff construction allows to determine the equilibrium shape of an isolated crystal from the polar plot of its interfacial energy. [START_REF] Wulff | Zur Frage der Geschwindigkeit des Wachsthums und der Auflösung der Krystallflächen[END_REF] An alternative way to assess the equilibrium morphology of a crystal in 3-D case involves the 9-vector formalism proposed by Hoffman and Cahn [START_REF] Hoffman | A Vector Thermodynamics for Anisotropic Surfaces I. Fundamentals and Application to Plane Surface Junctions[END_REF] .

The 9-plot is similar in shape to the Wulff construction, albeit scaled by a factor. According to the 9-plots, the equilibrium shapes of WC grains for Cases 1 and 2 are both truncated trigonal prisms but slightly different in their shape factors. Fig. 3 compares the simulated and the theoretically predicted morphologies for cases 1 and 2. The simulation accuracy is satisfactory given that no extra treatment is used to reduce numerical errors from discretization. previously discussed, upon using the available interfacial energy obtained by ab-initio calculation, phase-field simulations only generate truncated trigonal prisms as the equilibrium grain shape. To reproduce triangular prism, the energy gap between the 2 types of prismatic interfaces should be significant. This prerequisite matches Case 3 and the equilibrium shape of WC grain displayed in Fig. 4(e).

Figure 5 shows the simulated shape relaxation process of a WC grain for Case 1. As the system minimizes its total energy, facets developed swiftly from the spherical grain. Then, a truncated prism consisting in facets with relatively low interfacial energy is formed. Finally, shape factors draw near their equilibrium values.

Discussion

The comparison between experimental observations and simulation results suggest that the shape of a fraction of grains presented in C-poor alloy relates to the middle stage of grain evolution. However, it should be noted that the simulated grain forms facets corresponding to {0001} and {10-10} planes of the WC crystal, while an extra type of facets is often observed in the prepared C-poor alloy . These facets are supposed to be {10-11} planes according to measurements of Kim et al and Sugiyama et al's [START_REF] Kim | Variation of WC grain shape with carbon content in the WC-Co alloys during liquid-phase sintering[END_REF][START_REF] Sugiyama | Blunt corners of WC grains induced by lowering carbon content in WC-12mass%Co cemented carbides[END_REF] . In our simulations, only 3 types of interfaces have been considered. In order to account for more complex grain morphologies, the energy of {10-11} interfaces should also be evaluated and included in the model.

In real alloys, a large grain size distribution is observed, reflecting the process of grains growth phenomenon [START_REF] Mannesson | Carbide grain growth in cemented carbides[END_REF] . For example, the step morphology envisioned in some grains in the C-poor alloy provide a circumstantial piece evidence of this growth regime. The addition of this mechanism to the present model therefore appears as a necessary refinement to further unravel the host of WC grains' morphologies observed during growth. The shape relaxation process obtained numerically is in a good agreement with experimental data and reproduces well the non-equilibrium shape of grains. We believe that the incorporation of an exhaustive dataset of interfacial energies spanning the different types of WC grains' interfaces in the phase field model opens a way to highly tunable models that could provide deep physical insights on grain morphology and growth in cemented carbides. The present simulation work provides insights on how interfacial energy may affect the evolution process of WC grains in WC-Co alloys and lays basis for more realistic models where the growth phenomena will be also taken into account.

Method

Modeling Method

The kinetic Eq. ( 4) was solved in dimensionless form

\ = -] ^ ) -BCDEF ∇ ` + 2 BCDEF ∇ ` BCDEF • ∇ ` + a b c ∇ ` BCDEF & defgh i j k + l b m ∇ ` BCDEF & defgh n j o + p b c ∇ ` BCDEF & defgh q b
kr.

The volume conservation term is ommited here for simplicity. For a detailed evaluation of model parameters, please refer to the supplementary information.

The phase-field equation was solved using forward Euler time integration and central finite difference space discretization in a simulation box with uniform grid spacing and periodic boundary conditions.

Experiment method

An experimental study of WC grains growth under a host of carbon contents was conducted. The 25 wt.% binder content was selected for WC-Co alloys so as to reduce the influence of mutual contact between WC grains [START_REF] Lay | Morphology of WC grains in WC-Co alloys[END_REF] . The raw materials used were coarse WC powder with a Fischer particle size of 10 μm and Co powder with a In order to study the morphology of WC grains under different carbon contents, the as-sintered sample were re-sintered in a carbon-poor and carbon-rich atmosphere, respectively. One as-sintered sample was buried in the carbon black powders and the other was buried in the alumina powders. These samples were sintered at 1500℃ for 6 h again at the same time. Two different samples were obtained, namely carbon-rich sample and carbon-poor sample. In order to observe the morphology of WC grains, the binder phase of the re-sintered sample were removed by immersing in saturation hydrochloric and Fe3Cl mixed solution. Then, the WC grain morphology was observed by scanning electron microscopy (FE-SEM, JSM-6701F, JEOL, Japan).

  regularization term to the energy density expression. Hence extra calculation of mean curvature and evaluation of the regularization parameter are needed. The last two approaches involves the replacement of the anisotropy function near the cusps by regularized or smoothed functions. Such treatment may become complex for a 3D problem. Due to their substantial computational cost and complexity, we suggest that the referred procedures are not best indicated for the dynamics of faceted particles relaxation. The class of anisotropy functions introduced in ref. 26 and 27 was then used in this work. These functions are defined piecewise by: BCDEF G HI, L I M = NO PMP QG HI • L I M R , where L I M is the kth vertex vector of the shape of the crystal grain, itself connected to the interface energy. For the typical shapes of a WC grain, the vertex vectors L I M are shown in fig.1a and fig.1b. The construction of the anisotropy function from the vertex vectors is sketched in two dimensions for a truncated triangle in Fig. 1c. In the present work, the anisotropy functions constructed from Fig.1a and Fig.1b are referred to as types I and II respectively.

Fig. 1

 1 Fig.1 Schematic illustration of η vectors for (a) truncated trigonal prism, (b) triangular

case 3 ,

 3 we aimed at reproducing the triangular prism, often observed experimentally in C-rich alloys. Then type II anisotropy function was used. The input values of : *** and : * S * were the same as Case 1 while : * S * was fixed to 2: * S * to make this orientation energetically unfavorable. Tab.1 Interfacial energy data used in simulation Interfacial energy (J/m 2

  value in ref. 10 (which is 1.0 × 10 4 Y U • V ⁄

Fig. 2 Fig. 2

 22 Fig.2displays the polar plots of :, 1/: and the corresponding 9-plots. The minima on the plots of : correspond to vertices on the 1/ : plots, indicating the stable interface orientations. As for other part of the : plot, it should be regarded as an interpolation, so that the : function as a whole still generates the equilibrium shape while concurrently keeping the 1/ : plot convex. In a nutshell, the present model is a compromise between real properties of the grain and numerical stability of the

Fig. 3

 3 Fig.3 2D slices showing comparison between simulation (solid lines) and theoretical

Figure 4

 4 Figure4shows the experimental observation versus the grain shapes simulated by the

Fig. 4 3 Fig. 5

 435 Fig.4 Experimentally observed WC grains in WC-Co hard metals: (a) C-poor alloy;

Fischer particle size of 1 . 5

 15 μm, both produced by Zhuzhou Cemented Carbide Group Corp. Ltd of China. All samples were prepared by powder technology. According to the set ratio, these powders are wet milled mechanically. The carbon content was fixed to 4.60 wt.% by adding C or W powder. The powder mixtures were milled for 24 h at the ball to powder ratio of 5:1 in ethyl alcohol and dried and granulated. A bars of 25×8×6.7 mm were uniaxially cold pressed under pressure of 100 MPa. The bar samples were sintered at 1410℃ under the 6 MPa pressure for 1 h.

Acknowledgements

The financial supports from Key R&D program of Science and Technology Department of Jiangxi Province in China (Grant No. S2019ZPYFB1240), National Natural Science Foundation of China (Grant No. 51820105001) and the Special Funds for the Construction of Hunan Innovation Province (Grant no. 2019GK2052) are acknowledged.


Coralli

MD Antonio Perciaccante
email: antonioperciaccante@libero.it

Which Saint to pray for fighting against a Covid infection? A short survey

Keywords: Health, Medical anthropology, Parallel medicine, Religion, Survey

Background: In the absence of a treatment still considered universally effective, and of a vaccine validated by the health authorities, we wanted to know which Catholic saint the European Christian community turned to in the event of infection with Covid-19 to request a miraculous healing.

Methodology: An online survey was carried out on a sample of 1,158 adults using social media tools.

Results: All results are presented in this research, with a few saints in the majority, and some dictated by the symptomatology of the Covid-19 infection or the personalities of certain « doctor guru ».

Conclusion:

This medico-anthropological study is revealing the psychology of Western patients vis-à-vis the magic-religious means used in the fight against diseases, particularly in the epidemic/ pandemic context.

BACKGROUND

The relationship between religion and medicine is well known in human communities since antiquity. Medieval medicine was based on Hippocratic and Galenic doctrines, but it was also characterized by spiritual and divine influences. So, in European countries, in Middle Ages, Saints ' invocation for the curing of diseases was an usual practice.

Despite, the spiritual and religious dimensions have deviated from medicine after the Renaissance and the Late Enlightenment, the intercession to the Saints is today again a doctrine spread both in Catholic and Orthodox Churches [START_REF] Torosian | Spirituality and Healing[END_REF]. In particular, the Roman Catholic religion is rich in saints playing the role of intercessor between the omnipotence of the divinity and the demand for divine healing emanating from a mortal.

Since the start of 2020, the Covid-19 pandemic has affected the entire planet. All territories, and therefore all human cultures, are directly implanted by this infectious agent [START_REF] Kickbusch | Covid-10: how a virus is turning the world upside down[END_REF]. In addition to and / or substitute for medical and medicinal care, it remains possible for any people to turn to religion [START_REF] Hart | Religion and health during the Covid-19 pandemic[END_REF].

We therefore wanted to know, in the community targeted by this religious context, who were the saints and / or saints specialized in the Covid-19 pandemic.

METHODOLOGY

We conducted a survey on two of the most used social networks : Twitter and Facebook. The survey was conducted between August 21 and 25, 2020. Each author posted on his Twitter and Facebook page, the following question: "Which saint you would pray for fighting against a Covid infection?". The total number of followers targeted by the question was 15,840 people (92% from Europe).

RESULTS

A total of 1,158 adult anonymous participants (mainly from France and Italy) answered to our question. For obvious ethical reason, no sex, age or cultural background are available. All results are summarized in Table I.

DISCUSSION

Analyzing the results in more detail, from the survey it emerges that the majority saint is St. Rita (figure 1). From a young age, Rita of Cascia (Italy, 1381-1457) dreamed of consecrating herself to God, but she was destined to marry a violent man. Rita's patience and love changed her husband's character. After the violent death of her husband and two children from illness, Rita decided to follow the youthful desire by entering the monastery of the Order of Sant'Agostino in Cascia (Italy) [START_REF] Cavallucci | Vita della Beata Rita da Cascia[END_REF]. Due to the difficult situations that she herself faced in her life as wife, mother and nun, today she is considered patron saint of lost causes, and she is invoked in the most difficult situations. Therefore, Saint Rita's first place clearly reflects the pessimistic and fatalistic nature of the current situation, and the lack of credit given to the therapeutic offer in the face of Covid-19.

We have also to consider that when we conducted the study, the vaccination campaign was far from starting.

In second and third place, we find respectively St Roch and Saint Sebastian, who, based on Catholic tradition, are the two principal Saints considered protectors against the plague, whose epidemic pattern has been compared to that of Covid-19.

Saint Roch and Sebastian were associated to the plague in the different ways, and their cult spread during Late middle Ages and Renaissance, when frequent plague epidemics occurred in several European Countries.

After his parents' death, Saint Roch of Montpellier (France, ca. 1350-1378) distributed his family wealth among the poor people, and started a pilgrimage to Rome (Italy). At that time, a plague's outbreak was spreading in Italy, and he stopped in Acquapendente, a little town sited about 150 km from Rome, where he helped the sick, and healed miraculously some people by the prayer and the sign of the cross. He next visited other neighbouring cities and Rome, and everywhere the plague disappeared by his miraculous power. On the way back, Roch stopped to the city of Piacenza to assist the patients in the local hospital, but he himself contracted the plague, and was forced to leave the hospital and the city. Roch took refuge into a wood, outside the city, avoiding any contact with other people. A dog discovered his refuge and brought him a bread every day to feed him. A day, following the dog, a nobleman (who will became his acolyte) reached Roch's refuge and took care of him until his recovery [START_REF] Voragine | The Golden Legend[END_REF].

Whereas it is believed that Saint Roch had actual contact with the plague, Saint Sebastian is associated with the plague only symbolically. Saint Sebastian (ca. 256-288) was one of the first Christian martyrs. Born in the actual French province of Languedoc (at that time known as Gallia Narbonensis) he went in Rome, where he started his military, becoming captain of the Praetorian Guards under the emperor Diocletian (244-312). Due to his subsequent conversion to Christianity, Saint Sebastian was persecuted and sentenced to death by the emperor Diocletian. Based on the Catholic tradition, he was riddled with arrows but survived miraculously. [START_REF] Voragine | The Golden Legend[END_REF] Later, Sebastian presented himself before Diocletian and he was again condemned to death by beating. He is the patron saint of archers and athletes, and was also venerated as a protector from the bubonic plague. Indeed, since the time of western classical mythology, arrows have symbolised the divine punishment for various transgressions. During the Middle Ages, when the cult of Saint Sebastian started to spreading, epidemics were often considered divine punishments, and the wounds of Saint Sebastian were symbolically viewed as the bubos of the plague [START_REF] Gelpi | Saint Sebastian and the Black Death[END_REF].

Moreover, Sebastian's martyrdom was one of the favourite subjects of depiction by famous, such as Pietro Perugino, Sandro Botticelli, Gian Lorenzo Bernini, and Andrea Mantegna, contributing to the rise in the spread of his cult, especially during plague epidemics.

The results about the first three places suggest that the choice of the saint to invoke seems to be influenced mainly from the awareness about the difficulty of the current pandemic situation, and from a good knowledge of Catholic tradition by the people participating to the survey. As an Egyptian ascetic monk, St Anthony the Great (251-356) is invoked against infectious diseases, mainly ergotism, erysipelas, and shingles, usually referred as "Saint Anthony's fire". Moreover, Catholic hagiography and art contributed to spread Saint Anthony's resistance to supernatural temptation during his stay in Egyptian desert [8].

Saint Adrian (ca. 278-306) was a soldier under the Roman emperor Maximilian. After his conversion to Christianity, he was martyred together his wife. His cult is spread mainly in Northern France and Flanders [START_REF] Marini | Adriano martire protettore di Matelica[END_REF]. Saint Agricole (630-700) was a bishop of Avignon (France), venerated as patron of storks because he prevented an invasion of these birds. Moreover, he is the patron of the city of Avignon, and he is invoked also against the bubonic plague and misfortune of all kinds [START_REF] Ab | La Vie de saint Agricol : évêque et patron de la ville d'Avignon[END_REF].

Saint Edmund the martyr (also known as Saint Edmund of East Anglia) (855-870), king of East Anglia, was killed during the invasion by the coalition of Scandinavian warriors known as the Viking Great Army or the Great Heathen Army. Catholic hagiography affirms that he was beaten, arrowed, and then beheaded by Danish warriors because he refused to renounce to his Christianity [START_REF] Phillips | Edmund the Martyr, Saint[END_REF]. The tradition claimed that, in 1217, his body was moved in the French city of Toulouse, and that, in 1628-1631, this city was saved from a plague's epidemic by Saint Edmund's intercession [START_REF] Gem | A Scientific Examination of the Relics of St Edmund at Arundel Castle[END_REF].

Based on the legend, Saint Quirinus of Neuss (???-116) was a Roman tribune, who converted to Christianity, and was then decapitated [START_REF] Kirsch | Sts. Quirinus[END_REF].

Interestingly, we note the presence of some saints whose choice may have been dictated by linguistic proximity with charismatic personalities linked to the fight against disease (St Didier, St Raoul: in reference to now famous Professor Didier Raoult, from Marseille), with the name linked to the taxonomy of the infectious agent (Ste Corona for Coronaviridae sp.), with the place of emergence of the viral strain (St Jean-Gabriel Perboyre, a lazarist martyred in Wuhan, China, where the virus was firstly described in December 2019), or even with the possibility of an ultimate pleasure before death (St Emilion, named after a famous Bordeaux vineyard producing a prodigious nectar…).

CONCLUSIONS

This short medico-anthropological study is revealing the psychology of Western patients vis-à-vis the magic-religious means used in the fight against diseases, particularly in an epidemic / pandemic context. The survey confirms that Catholic people continue to entrust their sorrows, their anxieties and their hopes to the divinity, especially in time of global stress, mainly if it is a suddenlypresented difficulty that have changed the people's lifestyle. Moreover, the choice of the Saints to invoke is dictated by many factors such as a good knowledge of Catholic tradition, linguistic association, and personal behaviours.

  In addition, five other holy miracle workers are then invoked (St. Anthony the Great, St Adrian of Nicomedia, St Agricola of Avignon, St Edmond the martyr, St Quirinus of Neuss).

Figure 1 .

 1 Figure 1. Image of Saint Rita depicted on her solemn coffin (1457). Monastery of Saint Rita,


Alexandra Monti

Mohamed Doulazmi

Vi-Huong Nguyen-Michel

Eric Pautas

Jean Mariani

Kiyoka Kinugawa
email: kiyoka.kinugawa@aphp.fr

Clinical characteristics of sleep apnea in middle-old and oldest-old inpatients: symptoms and comorbidities

Keywords: sleep disordered breathing, obstructive sleep apnea, oldest-old patients, symptoms, comorbidity

Background: Obstructive sleep apnea (OSA) is prevalent in older adults but still underdiagnosed for many reasons, such as underreported symptoms, non-specific ones because of the comorbidities and polypharmacy, or the social belief of sleep problems as normal with aging.

Objectives: To identify salient symptoms and comorbidities associated with OSA, diagnosed by nocturnal respiratory polygraphy in geriatric inpatients.

Method:

We conducted a retrospective, cross-sectional study in a sample of 102 geriatric inpatients from a French Geriatric University Hospital. We reviewed medical records to collect demographic, medical information including comorbidities, the geriatric cumulative illness rating scale (CIRS-G), subjective sleep-related symptoms and data of overnight level 3 portable sleep polygraphy recording.

Results: Among classic OSA symptoms, only excessive daytime sleepiness (p=0.02) and nocturnal choking (p=0.03) were more prevalent in older inpatients with OSA (n=64) than in those without (n=38). The prevalence of comorbidities and mean CIRS-G scores were not different between groups except for the lower prevalence of chronic obstructive pulmonary disease and the higher level of creatinine clearance in OSA patients. Multivariate analysis showed OSA was associated with excessive daytime sleepiness (OR=2.83, p=0.02) in symptoms-related model and with composite CIRS-G score (OR 1.26, p=0.04) in comorbidities-related model.

Conclusions

Only excessive daytime sleepiness and comorbidity severity (composite CIRS-G score) were associated with the objective diagnosis of OSA, while other usual clinical OSA symptoms and comorbidities in geriatric inpatients were not. These findings emphasize the importance

of excessive daytime sleepiness symptom, when reported in comorbid older patients, strongly suggesting OSA and requiring adequate nocturnal exploration.

INTRODUCTION

Recognizing obstructive sleep apnea (OSA) is important in older patients, because of serious health consequences and available therapy. Sleep-disordered breathing is frequent: the prevalence of moderate to severe sleep-disordered breathing is 23.4% in women and 49.7% in men in a general population and is more important in participants aged 60 years or older [START_REF] Heinzer | Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study[END_REF].

In community-dwelling older adults, it is occurring in up to 56% of women and 70% of men.

OSA is associated with greater risk of cardiovascular and metabolic disorders, cognitive impairment, functional decline, and frailty in older patients [START_REF] Osorio | Sleep-disordered breathing advances cognitive decline in the elderly[END_REF][START_REF] Spira | Sleepdisordered breathing and functional decline in older women[END_REF][START_REF] Ensrud | Sleep disturbances and risk of frailty and mortality in older men[END_REF]. Severe OSA is associated with severity of multimorbidity [START_REF] Robichaud-Hallé | Obstructive sleep apnea and multimorbidity[END_REF]. Consequently, they need greater healthcare resources than those without OSA, and than middle-aged patients with OSA [START_REF] Diaz | Obstructive sleep apnea is associated with higher healthcare utilization in elderly patients[END_REF][START_REF] Tarasiuk | The effect of obstructive sleep apnea on morbidity and health care utilization of middle-aged and older adults[END_REF]. In addition, OSA is treatable by continuous positive airway pressure therapy, which decreases the sleepiness, fatigue, depressive symptoms, and improves quality of life, even in older patients, resulting in functional outcomes comparable to that of younger adults [START_REF] Pallansch | Patient-Reported Outcomes in Older Adults With Obstructive Sleep Apnea Treated With Continuous Positive Airway Pressure Therapy[END_REF].

However, OSA remains under-diagnosed in the older patients. This may be explained by the difficulties to recognize the OSA symptoms for many reasons. Indeed the typical clinical presentation exists in aged individuals, but symptoms are often underreported, nonspecific because of the comorbidities and polypharmacy, underdiagnosed by clinicians, or the social belief of sleep problems as normal with aging. Older patients sleeping alone could not report if they snore and/or have breathing pauses during the night. Snoring, high body mass index (BMI), and breathing pauses were found to be less associated with OSA in older persons [START_REF] Endeshaw | Clinical characteristics of obstructive sleep apnea in communitydwelling older adults[END_REF]. With respect to excessive daytime sleepiness (EDS), a key symptom for OSA, there are substantial difficulties in establishing its existence in older people for various reasons: the high prevalence of sleepiness unrelated to OSA and generally multifactorial in older adults, in particular due to comorbidities and pharmacological treatments; a different perception of this symptom by the older patient; and the social perception of sleepiness as a normal symptom in the older population, even by clinicians [START_REF] Bixler | Excessive Daytime Sleepiness in a General Population Sample: The Role of Sleep Apnea, Age, Obesity, Diabetes, and Depression[END_REF][START_REF] Whitney | Correlates of Daytime Sleepiness in 4578 Elderly Persons: The Cardiovascular Health Study[END_REF][START_REF] Nguyen-Michel | Prevalence and determinants of subjective sleepiness in healthy elderly with unrecognized obstructive sleep apnea[END_REF]. The Epworth Sleepiness Scale (ESS) is the most used tool to detect the subjective sleepiness but underestimates it in older patients [13][14][START_REF] Onen | Limits of the Epworth Sleepiness Scale in older adults[END_REF]. Among some existing screening tools for OSA, the Berlin questionnaire has been widely used [START_REF] Netzer | Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome[END_REF]. It is based on self-reported major symptoms (snoring, stopped breathing, fatigue, sleepiness) and hypertension. However, a study did not validate its use in older people, showing a very low specificity of the Berlin questionnaire for the OSA diagnosis, at only 39% [START_REF] Sforza | Is the Berlin questionnaire a useful tool to diagnose obstructive sleep apnea in the elderly?[END_REF]. The another screening OSA questionnaire, STOP-BANG, based on symptoms, age or BMI is not also sufficiently accurate in the older population [START_REF] Martins | Exploring the STOP-BANG questionnaire for obstructive sleep apnea screening in seniors[END_REF]. And these studies were conducted in independent community-dwelling seniors, and not in comorbid older patients [START_REF] Sforza | Is the Berlin questionnaire a useful tool to diagnose obstructive sleep apnea in the elderly?[END_REF][START_REF] Martins | Exploring the STOP-BANG questionnaire for obstructive sleep apnea screening in seniors[END_REF]. Other symptoms such as nocturia, fatigue, insomnia, memory and mood disorders are quite frequent and non-specific in geriatric patients because of the coexisting multiple comorbidities. These comorbidities will certainly impacts the clinical presentation of OSA in older individuals, and some authors have even suggested sleep apnea in geriatric patients as a unique syndrome [START_REF] Morley | Sleep Apnea: A Geriatric Syndrome[END_REF]. Moreover, a symptom of OSA as fatigue/tiredness is included in the frail phenotype, considering that frailty is a geriatric condition characterized by an increased vulnerability to external stressors, and is one of the leading cause of morbidity and premature mortality in older people [START_REF] Clegg | Frailty in elderly people[END_REF][START_REF] Fried | Frailty in Older Adults: Evidence for a Phenotype[END_REF][START_REF] Morley | Frailty consensus: a call to action[END_REF].

Finally, studies on older people focus on a population over 65 years of age, mostly the youngest-old population aged 65 to 74 years, but the older population is very heterogeneous.

The heterogeneity comes not only from the different age groups (youngest-old, aged 65 to 74 years; middle-old, 75 to 84 years; and oldest-old, ≥85 years), but also from their variable health status marked by comorbidities, various functional status and clinical setting such as community dwelling or hospital setting [START_REF] Nguyen | Health Heterogeneity in Older Adults: Exploration in the Canadian Longitudinal Study on Aging[END_REF]. Most of the existing studies were conducted among community dwelling older adults who are often younger, fitter and independent than geriatric inpatients [START_REF] Endeshaw | Clinical characteristics of obstructive sleep apnea in communitydwelling older adults[END_REF][START_REF] Sforza | Is the Berlin questionnaire a useful tool to diagnose obstructive sleep apnea in the elderly?[END_REF][START_REF] Martins | Exploring the STOP-BANG questionnaire for obstructive sleep apnea screening in seniors[END_REF]. Given the heterogeneity of the older people, it is important to study this latter population. Gamaldo et al. have used a large national healthcare database to comprehensively examine trends in sleep disturbance diagnoses such as OSA among hospitalized older adults in the United States from 2002 to 2012, and whether co-morbidities and outcomes are related to disturbance status [START_REF] Gamaldo | Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide Inpatient Rates, Predictors, and Outcomes[END_REF]. Using clinical diagnostic codes (the International Classification of Diseases Ninth revision, Clinical Modification ICD-9-CM), this previous study observed that while rates of sleep disturbances such as OSA were increasing within hospital settings, the relatively low rates, especially in middle old and oldest old subgroups, might reflect that many older adults' sleep disorders remained underdiagnosed.

To date, very few studies on OSA have been conducted in old inpatients [START_REF] Gamaldo | Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide Inpatient Rates, Predictors, and Outcomes[END_REF][START_REF] Shear | A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients[END_REF][26]. To our knowledge, no study has been done in the very old inpatients with detailed comorbidities and objective diagnosis of OSA. Improving the diagnosis of OSA, a highly prevalent but underdiagnosed sleep disorder, is important in this population. Therefore, the aim of this study is to identify symptoms and comorbidities associated with the diagnosis of OSA established using a level 3 portable sleep testing in geriatric inpatients aged 75 and over. We hypothesized that usual OSA-related symptoms (snoring, EDS, observed apnea or nocturnal choking, morning headache, nocturia, insomnia symptoms including difficulty of initiating and/or maintaining sleep overnight, dissatisfaction with sleep) might not be associated with the diagnosis of OSA in geriatric inpatients. Furthermore, we hypothesized that geriatric inpatients with more severe comorbidity will be more likely to be diagnosed with OSA.

METHODS

We retrospectively analyzed the medical records of inpatients aged 75 and over, who

Clinical data

A geriatrician collected retrospectively information about demographics and medical conditions with systematic review of medical record and hospitalization report for each patient. The comprehensive geriatric assessment performed routinely during their geriatric hospitalization included BMI, as well as the patients' living situation (alone and where (home, nursing home), the score of autonomy in daily living (ADL) Katz scale, cognitive status (including Mini Mental State Examination MMSE score), as well as cardiovascular, respiratory, psychiatric and ophthalmic comorbidities, and prostate disease for men, and the cumulative illness rating scale for geriatrics (CIRS-G) scores. Daily alcohol consumption of more than 30 g in men or 20 g in women defined chronic alcoholism. The cumulative illness rating scale for geriatrics (CIRS-G) score was used to quantify burden of comorbidities in older patients in 14 organ categories, with a 0 to 4 grading scale of impairment in each organ category: the "total" CIRS-G score was the sum of each of the 14 individual system scores and the "composite" CIRS-G score was calculated as the number of categories with a score of 2 or greater [27]. We also collected for each patient biological data including hemoglobin (g/dL), albumin (g/L) and creatinine clearance (CrCl -mL/min -calculated with the Cockcroft and Gault method). At the time of nocturnal polygraphy, physicians had asked patients for subjective symptoms suggesting sleep apnea (snoring, EDS, observed apnea or nocturnal choking, morning headache, nocturia, insomnia symptoms including difficulty of initiating and/or maintaining sleep overnight, dissatisfaction with sleep) that were usually present at their home. These symptoms were asked once the clinical condition had stabilized, and extracted from the request file for nocturnal recording. EDS was reported either by the patient or the primary caregiver but not assessed by the Epworth sleepiness scale (ESS) considering its limitations in the older population [START_REF] Onen | Limits of the Epworth Sleepiness Scale in older adults[END_REF].

Overnight respiratory recording

One-night respiratory recordings were performed during the hospitalization using an ambulatory respiratory polygraphic system (CIDELEC CID 102) with the following recorded parameters: nasal airflow, snoring, thoraco-abdominal respiratory movements, pulse oximetry (SpO2), position, and electrocardiography. All recordings were visually analyzed, and manually scored by 2 physicians specialized in sleep disorders. Hypopnea was defined as a ≥ 30% reduction in airflow lasting for ≥ 10s and associated with ≥ 3% oxygen desaturation [START_REF] Berry | Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine[END_REF].

Apnea was defined as the absence of airflow lasting ≥ 10s. Number of hypopneas and apneas per hour defined the apnea-hypopnea index (AHI). The oxygen desaturation index (ODI) was defined as the number of ≥ 4% arterial oxygen desaturations per hour of recording. OSA patients were defined according to the International Classification of Sleep Disorders (ICSD-3) with an apnea-hypopnea index (AHI) ≥ 15/h even in the absence of associated symptoms or disorders, predominantly obstructive respiratory events.

Statistical analysis

Statistical analyses were performed with SPSS 24 (IBM, Armonk, New York). Categorical variables were compared using Pearson's χ2 test or Fisher's exact test. Quantitative variables were analyzed using Student's t-test or the Mann-Whitney's test, depending on whether the distribution was normal or not. Results are presented as the mean ± standard deviation (SD) or medians, unless otherwise stated. Independent variables (factors/comorbidities or relevant clinical symptoms) were examined for their association with OSA using two multivariate logistic forward stepwise regressions to calculate odds ratios (ORs) and corresponding 95% confidence intervals (95%CI). ORs with a p value < 0.23 on univariate analysis were used to define which covariates should be incorporated into a multivariate analysis. A first multivariate logistic regression for associations between OSA (dependent variable) and factors/comorbidities (gender, chronic obstructive pulmonary disorder, history of stroke, atrial fibrillation, weight, CIRS composite and creatinine clearance CrCl: OSA-associated comorbidities model analysis) was performed. A second multivariate logistic regression for associations was performed between OSA and relevant clinical symptoms (gender, EDS, observed apnea or nocturnal choking, snoring, nocturia, insomnia, dissatisfaction with sleep, morning headache, memory complaint, mood disorders: OSA-related symptoms model analysis). A P-value of < 0.05 was used as a cut-off for statistical significance.

RESULTS

Participants' characteristics

Among 102 patients, 62.7% were diagnosed OSA and 37.3% were not (table 1). These patients were 62.7% females with a mean age 85.5 ± 4.9 years. Between The model was significant (χ2 = 5.14, p = 0.02, Nagelkerke R 2 = 0.067).

β: partial regression coefficient; OR: (EXP (β), Odds Ratio value of the corresponding variable with 95% Confidence Interval.

Concerning the potential gender differences in OSA related symptoms, the forward step-wise logistic regression model including gender in the OSA-related symptoms model analysis showed that gender was not associated with OSA (p=0.12). Moreover, in the univariate analysis among OSA patients, there was no difference in OSA related symptoms between women and men, except for insomnia complaint and mood disorders (table 4). We have used CIRS-G, a comorbidity scale for geriatrics patients registering all coexisting diseases and assessing the severity of diseases according to their impact of disability. Interestingly, OSA was associated with the CIRS-G "composite" score, reflecting the comorbidity severity [27]. A previous study has shown a dose-response relationship between the comorbidities "number" and a high risk for OSA screened by questionnaire, not confirmed by recordings [START_REF] Kleisiaris | Assessing the risk of obstructive sleep apnoea-hypopnoea syndrome in elderly home care patients with chronic multimorbidity: a cross-sectional screening study[END_REF]. Moreover, severe OSA diagnosed by polysomnography was associated with the morbidity severity assessed by a self-report questionnaire, the Disease Burden Morbidity Assessment, in middle-aged patients [START_REF] Robichaud-Hallé | Obstructive sleep apnea and multimorbidity[END_REF], while the CIRS-G is from objective data collected by physicians. Our finding that the comorbidity burden was independently associated with OSA is important, considering a report that comorbidities do not mask the effect of OSA on mortality for inpatients ≥ 50 years old, but OSA possibly worsens the prognosis of comorbid subjects [START_REF] Marrone | Comorbidities and survival in obstructive sleep apnoea beyond the age of 50[END_REF].

Concerning the comorbidities associated with OSA, limited data are available in older inpatients. The United States' nationwide study among older inpatients (aged over 65 years old), examined trends over time, and assessed whether comorbidities and other individuallevel and hospital-level characteristics were related to a sleep disturbance diagnosis (i.e., insomnia, OSA, or other sleep disturbance) and hospitalization outcomes [START_REF] Gamaldo | Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide Inpatient Rates, Predictors, and Outcomes[END_REF]. In this study, many comorbidities had independent positive associations with OSA: rheumatoid arthritis, congestive heart failure, depression, diabetes, hypertension, hypothyroidism, neurological disorders, pulmonary circulation disorders, renal failure, and most importantly obesity [START_REF] Gamaldo | Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide Inpatient Rates, Predictors, and Outcomes[END_REF].

However, the clinical diagnostic codes using ICD-9-CM, given by a health provider, were used to estimate OSA; it is unclear what diagnostic tests were given to assess the symptoms/signs common to OSA. In our study, there were no clinically relevant comorbidities associated with the objective diagnosis of OSA. Indeed, we found no association between OSA and cardiovascular comorbidities, in contrast to the literature [START_REF] Dredla | Cardiovascular Consequences of Obstructive Sleep Apnea[END_REF][START_REF] Salman | Hypertension, and Cardiovascular Risk: Epidemiology, Pathophysiology, and Management[END_REF]. Our result concerning CrCl should be interpreted carefully because the odds ratio is low, although a previous meta-analysis showed that OSA is significantly associated with poorer renal function [START_REF] Hwu | The association of obstructive sleep apnea and renal outcomes-a systematic review and meta-analysis[END_REF]. OSA was negatively associated with COPD in our study, and there are conflicting results in older patients in the literature [START_REF] Shawon | Current evidence on prevalence and clinical outcomes of co-morbid obstructive sleep apnea and chronic obstructive pulmonary disease: A systematic review[END_REF], reflecting the different investigated populations and the possible survival bias against the association COPD-OSA.

Moreover, in our study COPD was a reported medical history and not severe without oxygen dependency and considering that the limit of normal SpO2 in older patients was reported to be 91%. Thus, our finding on COPD is less clinically significant. These comorbidities common in geriatric patients may overshadow the association between comorbidity types and OSA.

These results underline the importance of the global comorbidity burden to be considered in OSA.

The usual symptoms were not associated with the diagnosis of OSA in our geriatric population, except for EDS. It was reported that traditional symptoms suggesting OSA (snoring, high BMI) were not significantly associated with OSA, while the sensation of not feeling well-rested, nocturia, and EDS were independently associated with OSA in community-dwelling independent older adults [START_REF] Endeshaw | Clinical characteristics of obstructive sleep apnea in communitydwelling older adults[END_REF]. Our study was different from Endeshaw's, with very old inpatients (mean age 85.5 years old) from acute geriatric ward, dependant in ADL, and the comorbidities may be more prevalent than in the community-dwelling setting and may overshadow the OSA symptoms. To date, no study has investigated in very old inpatients aged over 75 years including clinical symptoms and comorbidities (using a validated comorbidity scale) associated with an objective diagnosis of OSA. Few studies on OSA with older inpatients have been reported. Shear et al. have reported that two of every 5 general medicine inpatients older than 50 years were screened at "high risk" for OSA using the Berlin questionnaire, without confirming the diagnosis of OSA [START_REF] Shear | A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients[END_REF]. Moreover, they have considered as eligible "older patients", ambulatory, community-dwelling adults aged 50 [START_REF] Gamaldo | Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide Inpatient Rates, Predictors, and Outcomes[END_REF].

In this study, many comorbidities had independent positive associations with OSA: rheumatoid arthritis, congestive heart failure, depression, diabetes, hypertension, hypothyroidism, neurological disorders, pulmonary circulation disorders, renal failure, and most importantly obesity [START_REF] Gamaldo | Sleep Disturbances among Older Adults in the United States, 2002-2012: Nationwide Inpatient Rates, Predictors, and Outcomes[END_REF]. However, the clinical diagnostic codes (ICD-9-CM), given by a health provider, were used to estimate OSA; it is unclear what diagnostic tests were given to assess the symptoms/signs common to OSA, unlike to our study.

Screening OSA questionnaires (e.g Berlin or STOP-BANG) based on symptoms, age or BMI are not sufficiently accurate in the older population [START_REF] Sforza | Is the Berlin questionnaire a useful tool to diagnose obstructive sleep apnea in the elderly?[END_REF][START_REF] Martins | Exploring the STOP-BANG questionnaire for obstructive sleep apnea screening in seniors[END_REF]. These studies were conducted in independent community-dwelling seniors. The existing OSA screening tool for older patients, the "Observation-based nocturnal sleep inventory", is based on nighttime observation of apneic episodes [START_REF] Onen | Limits of the Epworth Sleepiness Scale in older adults[END_REF]. These results show how it is difficult to suggest OSA from only clinical symptoms in older population. Despite the fact that sleepiness was not assessed by the ESS considering its limitations in older population [START_REF] Onen | Limits of the Epworth Sleepiness Scale in older adults[END_REF], the EDS reported by the patient or caregiver was the only symptom statistically associated with OSA in our very old geriatric inpatients. Although there are many other causes of EDS in older people, these results emphasize its importance and encourage us to suspect OSA in co-morbid older patients. Studies performed specifically in older patients have reported that severe OSA not treated with CPAP is associated with mortality, and adequate CPAP treatment may reduce this risk [START_REF] Posadas | Sex differences in obstructive sleep apnoea in an elderly French population[END_REF]. The general view is to treat if OSA patients are symptomatic, whether they are young or old adults, but for example, the question of whether non-sleepy OSA should be routinely treated or not is controversial. It should be emphasized that the clinical picture of OSA in older is different; our study confirmed that only EDS and comorbidity severity were associated with the objective OSA. Diurnal dysfunction secondary to recurrent sympathetic arousals and hypoxemia during sleep are not universal findings in OSA. The evidence for successful treatment of asymptomatic OSA is not strong. However, the evidence for a direct link between untreated OSA and cardio-metabolic consequences is important, even though treatment does not always fully reverse the abnormalities. How to apply these data on a daily basis on older patients remains difficult [START_REF] Posadas | Sex differences in obstructive sleep apnoea in an elderly French population[END_REF]. And treatment is also challenging in older patients; among 64 OSA patients of our study, CPAP was not prescribed in 18.7% (n=12;

severe dementia, moderate OSA without significant symptoms and without severe cardiorespiratory comorbidity, positional moderate OSA), 50% of patients refused or discontinued CPAP in the days following CPAP (n=32), and finally CPAP was prescribed and accepted in 31.3% (n=20) of the patients. Among the 20 patients treated by CPAP, 75% (n=15) were under CPAP at 3 months, with a mean adherence of 3hrs 34min per night. Ten patients had an adherence of more than 4h/night with >80% of days, out of the 15 patients still treated at 3 months (66,7%). In the future, studies on CPAP use in very old patients (≥75 years old) are needed to have an extensive view on this important point.

Prior studies showed gender differences in OSA related symptoms. In our study, there was no difference in OSA related symptoms between women and men in the univariate analysis among OSA patients, except for insomnia complaint and mood disorders, that are less specific of OSA. Moreover, the forward step-wise logistic regression model including gender in the OSA-related symptoms model analysis showed that gender was not associated with OSA. It was also reported that in a general community healthy youngest old population, females reported the cardinal symptoms of OSA less frequently and had a higher risk of having had, or being treated for, mood and anxiety disorders as in middle-aged studies [36].

Although depression and anxiety scores were higher in females with OSA, comparison of females with and without OSA showed that there were no significant differences between groups for anxiety and depression scores, as well as for previous psychiatric treatment.

Therefore, sex differences in personality characteristics, more than the presence of OSA, contribute to clinical spectrum in females with OSA.

Strengths and limitations of the study

In this study, data were obtained from inpatients with very old age and wellcharacterized comorbidities who were representative of geriatric inpatients. Furthermore, OSA was diagnosed using nocturnal recording, more reliable than screening questionnaires.

Some limitations need to be addressed. Monocentric hospital setting, retrospective method with lack of data about ethnicity, cross-sectional design with a relatively small sample size of our study limit its generalization. Of note, Hnin et al. have highlighted that anatomical traits (i.e., obesity, fat distribution, and craniofacial structure) underlie differences in OSA prevalence and severity between ethnic groups; but obesity appears to be the most important factor [START_REF] Hnin | The impact of ethnicity on the prevalence and severity of obstructive sleep apnea[END_REF]. However, our patient population was not obese and the mean BMI was 27. scores and also in the percentage of cognitive impairment between OSA and non-OSA patients in our study. As older population is very heterogeneous, with differences, not only in living situation, but also in comorbidity burden and dependency, the aim of our study was to describe comorbidities and symptoms related to OSA in geriatric older inpatients with complex health problems, including dementia. Therefore we have detailed clinical characteristics to have a global view of these aged geriatric inpatients, and we have kept the representability of a geriatric unit, with patients with their comorbidities, including cognitive impairments. In our study, we have focused on usual symptoms, thus representing another limitation. Other symptoms (e.g., fatigue, palpitation, depression) were not asked. The EDS was not evaluated by the Epworth questionnaire in our study considering its limitations in the older population [START_REF] Robichaud-Hallé | Obstructive sleep apnea and multimorbidity[END_REF], but was reported either by the patient or the primary caregiver.

  had undergone a level 3 portable sleep testing, the nocturnal polygraphy (NP) in a French University geriatric hospital, between April 2009 and June 2014. All patients who have undergone nocturnal recording for OSA diagnosis were eligible. Of 160 patients with NP recording, we excluded 49 because of missing clinical data, recording failure, or insufficient recording time <5 hours, and 9 central sleep apnea. A total of 102 patients were included. The ethics Institutional Review board (IRB00003888, IORG0003254, FWA00005831) of the French Institute of Medical Research and Health (Inserm) has approved the study protocol (approval N° 18-487). An information letter with possibility of opposing medical data collection was previously sent to the patients, informed consent was thus waived in this context. The database was declared to the French National Commission on Informatics and Liberty (CNIL, Paris, France). Data were collected anonymously by a team of medical doctors.

Table 1 : Patients' characteristics

 1 OSA and non-OSA patients, no difference was found regarding age, BMI, ADL, living situation, total and composite CIRS-G score, reason for hospitalization (respiratory, heart failure, confusion, cognitive impairment, infection, stroke, falls, weight loss, seizure), and comorbidities excepted for COPD being more prevalent in non-OSA patients. Biological data showed a lower CrCl in non-OSA patients, but both groups showed moderate renal failure (> 45 mL/min).Examination; ODI: oxygen desaturation index (number of decrease in the oxygen saturation ≥ 4%) ¶ Student's t-test; † Pearson's χ 2 test; § Fisher exact; ‡ Mann-Whitney test; in bold: p<.05OSA-related comorbiditiesTo identify which comorbidities are associated with the diagnosis of OSA, we performed an OSA associated comorbidities model analysis, as covariates: gender, chronic obstructive pulmonary disorder, history of stroke, atrial fibrillation, weight, CIRS composite and creatinine clearance CrCl (Table2). OSA was positively associated with composite CIRS-G score (OR 1.26, 95% CI 1.01-1.57, p=0.04) and CrCl (OR 1.03, 95%CI 1.01-1.06,

		All patients	OSA	non-OSA	p value
		N = 102	N = 64	N= 38
	Clinical characteristics
	Females (%)	62.7	56.3	73.7	0.07 †
	Age, yrs (Mean ± SD)	85.5 ± 4.9 85.4 ± 4.8 85.9 ± 5.2	0.61 ¶
	Weight, kg (Mean ± SD)	71.6 ± 13.1 73.5 ±12.4 68.5 ± 14	0.06 ¶
	BMI, kg/m 2 (Mean ± SD)	26.7 ± 5.1 27.3 ± 4.9 25.7 ± 5.2	0.13 ¶
	ADL (Mean ± SD)	4.7 ± 1.4	4.6 ± 1.5	4.8 ± 1.4	0.52 ‡
	Nursing home (%)	12.7	9.3	18.4	0.18 †
	Living alone at home (%)	63.7	64.1	63.2	0.92
	CIRS-G scores (Mean ± SD)
	• Total CIRS-G	12.3 ± 4.9	12.9 ± 5.2	11.2 ± 4.2	0.21 ‡
	• Composite CIRS-G	4.4 ± 2.1	4.7 ± 2.2	3.9 ± 1.8	0.15 ‡
	Hypertension (%)	85.3	87.5	81.6	0.41 †
	Dyslipidemia (%)	47.0	48.4	44.7	0.71 †
	Diabetes mellitus (%)	32.4	37.5	23.7	0.15 †
	Actual Smoking (%)	9.8	7.8	13.2	0.38 §
	Chronic alcohol addiction (%)	13.7	14.1	13.2	0.89 §
	Heart failure (%)	41.2	40.6	42.1	0.88 †
	Ischemic heart disease (%)	34.3	39.1	26.3	0.19 †
	Atrial fibrillation (%)	38.7	43.8	29.0	0.13 †

CIRS: cumulative Illness Rating Scale; COPD: Chronic obstructive pulmonary disease; CrCl: creatinine clearance; EDS: excessive daytime sleepiness; MMSE: Mini Mental State p=0,02), and negatively with COPD (OR 0.31, 95%CI 0.11-0.85, p=0.02) while no association to other comorbidities was found (p > 0.05). To explore the variables that mediate associations between COPD and OSA, we checked the role of these interaction variables (atrial fibrillation, stroke, ischemic heart disease) for potential confounding effects. The pvalue for the two interactions was not statistically significant. Others interacting variables (depression, insomnia, actual smoking, heart failure, hypertension) were also checked (based on the univariate analysis between COPD vs no COPD) and the p-values were not significant.

Table 2 : Multivariate forward logistic analysis results for the OSA associated comorbidities model analysis.

 2 : partial regression coefficient; CIRS: Cumulative Illness Rating Scale; COPD: Chronic obstructive pulmonary disease; CrCl: Creatinine clearance; OR: (EXP (β), Odds Ratio value of the corresponding variable with 95% Confidence Interval. In bold: p<.05

	OSA-related symptoms
	Subjective clinical symptoms of OSA and objective polygraphy parameters are
	presented in table 1. OSA patients reported significantly more EDS and more observed apnea
	or nocturnal choking than non-OSA patients; the other usual OSA symptoms were not
	statistically different between groups. EDS was not different between severe OSA patients
	(n=46, mean AHI = 46±16 /h, 80% EDS) and moderate OSA (n=18, mean AHI=23±4.7/h,
	83% EDS; p=1).

The model was significant (χ2 = 14.99, p = 0.002, Nagelkerke R 2 = 0.175).

β

To identify which symptoms are associated with the OSA diagnosis, we performed an OSA-related symptoms model analysis, including as covariates: gender, EDS, observed apnea or nocturnal choking, snoring, nocturia, insomnia, dissatisfaction with sleep, morning headache, memory complaint, mood disorders (

Table 3

 3

	). OSA was statistically associated

Table 3 : Multivariate forward logistic analysis results for the OSA-related symptoms model.

 3

Table 4 : OSA Patients' symptoms between women and men.

 4

	Symptoms suggesting sleep apnea (%)	OSA	OSA	p-value
		Women	Men
	EDS	70	79	0.34 †
	Snoring	41	50	0.36 †
	Observed apnea, nocturnal choking	17	21	0.63 †
	Nocturia	27	45	0.06 †
	Insomnia symptoms	41	21	0.04 †
	Dissatisfaction with sleep	20	16	0.57 †
	Morning headache	14	2.6	0.09 §
	Memory loss complaint	28	32	0.71 †
	Mood disorders	61	39	0.04 †

† Pearson's χ 2 test; § Fisher exact;

DISCUSSION/CONCLUSION

This study focused on the symptoms and comorbidities associated with OSA in geriatric inpatients. To our knowledge, our study is the first one performed in wellcharacterized very old inpatients with an objective OSA diagnosis by polygraphy.

  years or older (mean age 65 years old) who were cognitively intact; all these characteristics are far from the geriatric setting. Another study done in hospitalized adults (general medicine ward, n=66, mean age 53 years old) and older adults (geriatric ward, n=36, mean age 82 years old), reported that nearly 80% of hospitalized adults are at risk of sleep apnea, using the prospectively administered STOP-BANG and ISNORED questionnaires [26]. There was no confirmation of OSA, no clinical characteristics described, and individuals with cognitive impairment were excluded, a condition associated with OSA diagnosis, thus limiting comparison with our study. Concerning the comorbidities associated with OSA, limited data are available in older inpatients. The United States' nationwide study among older inpatients (aged over 65 years old), examine trends over time, and assess whether co-morbidities and other individual-level and hospital-level characteristics are related to a sleep disturbance

diagnosis (i.e., insomnia, OSA, or other sleep disturbance) and hospitalization outcomes

  3 ± 4.9kg/m 2 in OSA group, and most of them came from European descent.Although a polysomnography including EEG recording with sleep study was not performed, the diagnosis of OSA was confirmed by an overnight respiratory recording. One overnight recording may have limitation, but it allowed an objective diagnosis of OSA and not estimated by a questionnaire[START_REF] Kleisiaris | Assessing the risk of obstructive sleep apnoea-hypopnoea syndrome in elderly home care patients with chronic multimorbidity: a cross-sectional screening study[END_REF]. Endeshaw et al. had published clinical characteristic of OSA in older adults, using an overnight ambulatory sleep recording as our study, but they had studied in community-dwelling older participants who were independent in their instrumental activities of dialing living[START_REF] Endeshaw | Clinical characteristics of obstructive sleep apnea in communitydwelling older adults[END_REF]. Because older population is heterogeneous, our study provided new information on clinical characteristic of OSA in geriatric inpatients.Symptoms suggesting sleep apnea are often underreported or non-specific among older patients, and maybe not reliable in case of cognitive impairment. To limit this bias, symptoms suggesting sleep apnea were asked from both patients and caregivers if possible to be complete. Moreover, MMSE scores of the participants are around 21.5±5.6 /30, considered as mild to moderate cognitive impairment (mild -MMSE score of between 21 and 24, and moderate -MMSE score of between 10 and 20). Finally, there was no difference in MMSE

  Onen et al. have reported that among all non demented older subjects complaining EDS, only 24% of them had an abnormal ESS score (>10). Almost 60 % of subjects and close relatives were not able to answer at least one question on the ESS[START_REF] Robichaud-Hallé | Obstructive sleep apnea and multimorbidity[END_REF]. The ESS may underestimate sleepiness severity in older subjects. The EDS was also not evaluated by Multiple Sleep Latency Test because while the test is a valuable and widely used diagnostic tool for narcolepsy and idiopathic hypersomnia, the use of Multiple Sleep Latency Test in other sleep disorders, including OSA is not well established[START_REF] Arand | The multiple sleep latency test[END_REF]. This test measures how long it takes the patient to fall asleep during the day in a quiet environment, comprising 5 scheduled naps, separated by a two-hour break, in one day. In the absence of a questionnaire or tool evaluating EDS, suitable for older patients, EDS reported either by the patient or the primary caregiver can be considered sufficiently indicative to suspect sleep apnea in comorbid geriatric patients.Lastly, other data such as duration of hospitalization, sleep duration, history of OSA and CPAP or other treatment in the past, were not collected in this study.Despite these limitations, our study has clinical implications. OSA is highly prevalent in geriatric inpatients and we have shown that most of the usual OSA-related symptoms and comorbidities were not associated with the diagnosis of OSA. EDS, either self-reported or reported by caregiver, was the only OSA-related symptoms associated with OSA in this population. Usual OSA-related comorbidities were not associated with OSA in geriatric inpatients, probably because comorbidities may overshadow the association between comorbidity types and OSA. The severity of global comorbidity burden was indeed associated with the diagnosis of OSA, thus this aspect has to be considered in OSA. Multiple comorbidities may overshadow the usual OSA-related symptoms and comorbidities. These results emphasize the importance of suspecting OSA in comorbid sleepy older patients. Future Challenges in OSA in older patients include, among others, identification of other signs and uncommon symptoms that could be more specific to OSA in older patients with a validation of specific questionnaires, and treatment with CPAP in very old age (over 75 years).

CONCLUSION

Very few parameters were found to be associated with the diagnosis if OSA in geriatric inpatients: only EDS and comorbidity severity (CIRS-G "composite" score) were associated with OSA.

Pickens AW, Forest DJ, Wyderski RJ, Williams JA, Huang KE, Hazzard WR, et al. Identifying Risk of Sleep Apnea and Major Hospital Events in an Older Inpatient Population. J Am Geriatr Soc. 2018 Sep;66(9):1847-8.

Acknowledgements

We thank all the staff members of the Geriatric Acute care and Functional Explorations Units.

We also deeply thank Pr Rachel Sherrard and Pr Ann Lohof for their correction of English. et al. Risk of Sleep Apnea in Hospitalized Older Patients. J Clin Sleep Med. 2014 Oct;10(10):1061-6.

Funding sources

This research did not receive any funding.

Conflict of interest

The authors have no conflict of interest to declare.

Author contributions

AM and KK participated in study concept and design, acquisition of subjects and/or data, analysis and interpretation of data, and wrote the manuscript. MD conducted statistical analysis and participated in the interpretation of data. CL participated in the data collection. KK and VNM participated in acquisition of subjects and/or data. JM and EP participated in the preparation of the manuscript.

Ethical statement

The ethics Institutional Review board (IRB00003888) has approved the study protocol.

Patients were informed of the possibility of objecting medical data collection, and informed consent was thus waived in this context.


Vincent G Chapin

Nicolas Boulanger

Patrick Chassaing

Keywords: flow-vectoring, thrust vectoring, flow control, global instability, rectangular jet, rotating cylinder

The behaviour of the near-field region of a vertical rectangular jet of aspect ratio 4:1 controlled by a rotating cylinder placed on the jet major-axis is investigated experimentally using a new design facility. The objective is to investigate flow control strategies of a rectangular jet based on instability manipulation. It is found experimentally that the controlled jet exhibits similar behaviour to the one described theoretically and numerically by Hammond & Redekopp (1997a, b) on bluff-body wakes with higher control efficiency when the global instability mode is suppressed.

Improvement of the Jet-Vectoring through the Suppression of a Global Instability 1 Introduction

We present experimental results about jet-vectoring using a rotating cylinder placed on the jet major-axis near the exit plane (z/h=1.3, y/h=0) as shown in Figure 1. An interpretation of these results is proposed, within the theoretical framework of Hammond & Redekopp (1997a, b) concerning the relationship between the control efficiency and the presence of global instability modes. Finally, it is concluded that a highly efficient rectangular-jet vectoring can be obtained when the global instability mode present in the controlled flow is suppressed by using a supercritical rotating speed.

Results

The control methodology proposed by [START_REF] Hammond | Global Dynamics and Aerodynamic flow vectoring of wakes[END_REF] will be tested here. Briefly speaking, they show that when a global instability mode is present in the flow, it is necessary to suppress it to be able to develop an efficient control.

In our experiment, the rectangular jet is known to be convectively instable, according to the theoretical concepts reviewed by [START_REF] Huerre | Local and Global Instabilities in Spatially Developing Flows[END_REF]. By introducing a cylinder on the jet centreline, an absolute instability region of critical size develops behind the cylinder, which results in the von Karman vortex shedding (a well known global mode). Also, following the theoretical scenario, it should be necessary to suppress this global mode to enhance the flow control effectiveness.

Numerical simulations of a rotating cylinder in a uniform flow, by [START_REF] Mittal | Flow past a rotating cylinder[END_REF], have shown that the von Karman street disappears for supercritical rotating speed (

Ω * =Ω.d/2.U ∞ > 2).
Since, in the present situation, the cylinder is located in a jet of centreline velocity U j , various rotating speed have been applied to investigate the existence of a threshold Ω * c specific to our flow. The response of the controlled jet to the rotating speed Given this result, we have investigated the flow in greater detail to see whether this critical behaviour could be associated with the disappearance of the von Karman global mode behind the cylinder when its rotating speed is increased. Flow visualizations given in Figure 3, obtained with a high speed CCD camera by illuminating an oil droplets seeded flow with a thin laser sheet, clearly illustrate this point. In the left view, the von Karman antisymmetric vortex shedding is clearly seen. In the right view, it has disappeared being replaced by a chaotic flow. Spectral analyses of the hot-wire measurements of the longitudinal component of the instantaneous velocity in the jet flow behind the cylinder, located along the jet centreline at z/h=0.33, are given in Figure 4. Below the critical speed, a unique sharp peak dominates the spectrum, a typical feature of a self-exited oscillator [START_REF] Monkewitz | Self-excited oscillations and mixing in a hot jet[END_REF]. Above the critical speed, the spectrum is typical of a noise amplifier with broadband and lower peaks at a dominant frequency close to the one found in the free jet shear layers and identified as a jet cavity resonance.

Ω * =Ω.d/2.U j is given in

Conclusion

In a rectangular jet of aspect ratio 4:1 controlled by a rotating cylinder, it is shown experimentally that the suppression of the global instability mode is correlated to an increase of the jetvectoring efficiency. This first experimental evidence supports the theoretical scenario proposed by [START_REF] Hammond | Global Dynamics and Aerodynamic flow vectoring of wakes[END_REF]

Fig. 1 .

 1 Fig. 1. : Jet flow configuration

Figure 2 ,Fig. 2 .

 22 Fig. 2. : Mean deviation angle of the jet versus rotating speed of the cylinder Ω * . Linear regression equations and correlation coefficient are given below and above the critical speed Ω * c .

Fig. 3 .

 3 Fig. 3. : Visualizations of the flow at Ω * = 1.4 (left) and Ω * = 1.64 (right).

Fig. 3 .

 3 Fig. 3. : Velocity Spectra (a) Ω * = 0, (b) Ω * = 0.14, (c) Ω * = 0.8, (d) Ω * = 3.1 The conjunction of theses observations about flow deviation angle, flow visualization and velocity spectra indicates that the suppression of the global instability results in a more efficient jet vectoring for supercritical values of Ω * .

  on wakes and Lim & Redekopp (2002) on jets.

Acknowledgments. Authors thank G. Toulouse for his fine actuator system design.


Emmanuel Conchon
email: econchon@ensica.fr.

Johan Garcia
email: johan.garcia@kau.se.

Increasing the Determinism of Network Emulation to Evaluate Communication Protocols

Keywords: C.2.1 [Computer Systems Organization]: Computer-Communication Networks-Network Architecture and Design Design, Experimentation Emulation, Wireless, Performance Evaluation, Multicast

In this paper, we propose an emulation solution whose purpose is to deal with the need of reproducibility that is encountered in communication protocols evaluation and transport protocols in particular.

INTRODUCTION

Network emulation offers a compromise between live test and simulation and is widely used for communication protocols evaluation. For transport protocols evaluation in particular, researchers need a fully controlable environment that can exactly repeat an experiment to evaluate the behavior of their protocol. Several propositions have been made for wireless network emulation. Some of them, based on realtime simulation such as in [START_REF] Fall | Network Emulation in the VINT/NS Simulator[END_REF] provide such an environment but have scalability problems when the complexity of the network or models increase. Others are based on traffic shapers such as Dummynet [START_REF] Rizzo | Dummynet: A Simple Approach to the Evaluation of Network Protocols[END_REF] which constrains the traffic according to precomputed conditions. In a prior work [START_REF] Pérennou | Two-stage Wireless Network Emulation[END_REF] we have presented W-NINE, a two-stage solution using Dummynet. An offline simulation stage is used prior to the emulation to compute emulation scenarios, followed by an IP level emulation stage that reproduces these scenarios in soft real-time. Another particularity is its ability to deal with traffic based behaviors such as hidden terminals by observing in real time the experimental traffic and reacting accordingly. This solution has been developed for application evaluation and can repeat the same experiment several times. The behavior of a repeated emulation experiment is the same on average but, due to the use of Dummynet it is not possible to affirm that a same packet will be constrained exactly on the same way from an experiment to another. A solution dealing with this need of repeatability is to enhance Dummynet by extending its abilities to control losses and delays. For this purpose, an extension of Dummynet has been developed at the Karlstad University to deal with losses aspects. This paper will provide a brief overview of W-NINE, the two-stage wireless emulation platform, then focusing on the need of repeatability for transport protocol evaluation and on a Dummynet extension providing repeatability of loss patterns.

W-NINE

The W-NINE platform (see Figure 1), developed at EN-SICA and LAAS-CNRS, is designed to emulate a large spectrum of mobile wireless networks based on high-level experiment descriptions written by developers for tests. A high-level experiment description allows the combination of accurate simulation models (e.g. node movements or propagation conditions) by the user, so that tested situations can approximate real conditions. W-NINE consists of a wired network emulation platform, called NINE (Nine Is a Network Emulator) and a Simulator for Wireless Networks Emulation, called SWINE.

Figure 1: The W-NINE Platform Architecture

SWINE is an offline discrete events simulator that precomputes an emulation scenario composed of IP traffic constraints corresponding to a high-level experiment description. NINE provides a physical network interconnecting real nodes with Ethernet, where the IP traffic is shaped in soft real-time by the Dummynet-based router-emulator, according to this scenario (i.e. evolution of available IP data throughput, losses and delays on each end-to-end link), as if the underlying network was a mobile wireless network. The emulation scenario is played in soft real time by NINE's emulation manager, a special host in charge of scheduling the Dummynet instructions.

Moreover, SWINE can produce several possibilities in an emulation scenario to deal with traffic based behaviors that can occur in a wireless network. A classical example of traffic based behavior in ad-hoc networks is the hidden terminals problem that occurs only if two nodes are mutually hidden and try to contact a same third node at the same time. To deal with these behaviors the traffic that crosses the experimentation network is observed in real time by observers hosted on the emulator. When a traffic-based situation occurs, observers warn the emulation manager using feedback mechanisms. The emulation manager can then react accordingly by switching among emulation possibilities.

THE NEED FOR REPEATABILITY

In 802.11b networks, the MAC layer does not work in the same way for unicast or multicast communications. So, effects encountered by a transport protocol or an application under evaluation will depend on the kind of the communication. Due to the lack of retransmission mechanisms in multicast communications, losses can occur at the IP level contrary to unicast transmissions where the reliability of a transmission is almost perfect. The current version of W-NINE supports only unicast communications and effects of retransmission mechanisms are taken into account by SWINE during the computation of the IP throughput.

This solution gives good results on average but is suitable neither for multicast communications where real losses must occur at the IP level nor for protocol evaluation where repeatability is essential. Dummynet provides losses using a uniform packet loss rate. Results found with these random losses give an average behavior of the emulated network. This average behavior is satisfactory for applications evaluation but not for transport protocols evaluation because the position of a loss in a flow can have different consequences on the behavior of transport protocols. For example, the behavior will not be the same for a SYN packet loss in a TCP flow or for a simple data packet loss. The exact repeatability of losses at emulation time is a critical tool that allows the protocol developer to tune his protocol parameters and to evaluate his modifications under the same conditions. This repeatability issue is not always useful for applications evaluation: for instance, the traffic of multimedia applications is not predictable, especially for interactive applications. With this kind of applications, it is sufficient to reproduce an averaged behavior from an experiment to another.

Similarly, it will be suitable to provide a support for delays which can be repeatable from an experiment to another. At the current time, delays due to retransmission mechanisms in unicast communications are taken into account during the IP throughput computation. With this solution the behavior of the emulated network is the same on average. But as for the losses aspect, delays have a direct impact on the behavior of the network, for example they have an impact on the RTO in a TCP flow. A solution introducing a packet by packet delay control would provide a more realistic and more repeatable behavior. For example, packet-controlled delays could be used to reproduce effects due to the backoff and auto-rate fallback mechanisms or even roaming effects in cellular networks with more realism and to finely tune transport-level parameters.

A DUMMYNET EXTENSION DEALING WITH REPEATABILITY

An extension of Dummynet has been developed at the Karlstad University to improve Dummynet's control of losses. This extension presented in [START_REF] Garcia | An Experimental Study on the Performance and Fairness of Loss Differentiation for TCP[END_REF] allows the insertion of bit errors in packets as well as deterministic packet losses. To sum up, a flow notion has been added to the classical loss mechanism of Dummynet in order to be able to lose or corrupt a particular packet in a flow. With this extension it is now possible to lose packets number 10, 20 and 54 in a flow which is very useful for the repeatability and the accuracy of an emulated experiment. Positions are controlled by pattern files for packet losses and for bit-errors.

Integrating this extension into the W-NINE platform will be a first step to deal with reproducibility. With this extension it will be possible to use classical loss models characterizing a wireless channel such as a two-state Markov model to make SWINE computes the loss pattern that might then be reproduced by NINE during the emulation stage. Moreover, several patterns should be produced to deal with traffic based behaviors such as hidden or exposed terminals. Dynamic pattern switching is not supported yet but its development is planned.

CONCLUSION AND FUTURE WORKS

Repeatability is a key point for performance evaluation of communications protocols, in particular at the transport level. We plan to integrate Karlstad's Dummynet extension into the W-NINE emulation platform, in the framework of the NEWCOM NoE, in order to have a network emulator supporting both high-level experiment descriptions and repeatability. With this integration we will have a fully controllable emulation environment that should be used for applications and transport protocols evaluations both for unicast and multicast communications. In a second time it is planned to extend the Dummynet extension pattern notion to delays to deal more precisely with MAC-level retransmission mechanisms or roaming effects.

Acknowledgements

We want to thank the NEWCOM NoE for funding this research and Tanguy Pérennou, Michel Diaz and Anna Brunstrom for their supervision.


Plotine Jardat

Ludovic Calandreau

Vitor Hugo

Bessa Ferreira

Chloé Gouyet

Céline Parias

Fabrice Reigner

Léa Lansade

Pet-directed speech attracts horses' attention more than adult-directed speech on video-projections

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

•

  ., Calandreau, L., Ferreira, V., Gouyet, C., Parias, C., Reigner, F., Lansade, L. Pet-directed speech improves horses' attention toward humans. Sci Rep 12, 4297 (2022). https://doi.org/10.1038/s41598-022-08109-z Plotine Jardat -UMR Physiology of Reproduction and Behaviour, INRAE Centre Val-de-Loire, Nouzilly, , emotional state ? High pitch Wide pitch range Slow rate of speech Methods Pre-registered videos of women speaking in PDS and ADS Behaviour Heart rate HR end -attract horses' attention and has an arousing effect on them No differences in emotional indicators between PDS and ADS DS+ADS Jardat, P., Calandreau, L., Ferreira, V. et al. Pet-directed speech improves horses' attention toward humans. Sci Rep 12, 4297 (2022). https://doi.org/10.1038/s41598-022-08109-z PDS is arousing and attention-drawing for horses → can be used during human-horse interactions  Broadcasting pre-registered videos of humans allows to study horses' perception of us


Christian Chervin

Arak Tira-Umphon

Jean-Paul Roustan

Julien Lamon

Alain Latché

Mondher Bouzayen

Ashraf El-Kereamy

Angelos Kanellis

Ethylene is required for the ripening of grape

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