Ph.D Durand Fabienne

Ph.D Gaston Anne-Fleur

MD Vicenzi Marco

Ph.D Deboeck Gael

MD Subirats Enric

Ph.D Faoro Vitalie

Pr Fabienne

NON-INVASIVE PULMONARY HEMODYNAMIC EVALUATION IN ATHLETES WITH EXERCISE-INDUCED HYPOXEMIA

Background: Pulmonary capillary stress failure is potentially involved in exercise-induced hypoxemia i.e., a significant fall in hemoglobin O2 saturation (SpO2) during sea level exercise in endurance-trained athletes. Whether there may be specific properties of the pulmonary vascular function in athletes exhibiting O2 desaturation is unknown.

Methods: 10 endurance trained athletes with exercise induced O2 desaturation (EIH), 9 endurance trained athletes without (NEIH) and 10 untrained controls underwent an incremental exercise stress echocardiography coupled with lung diffusion capacity for CO (DLCO) and NO (DLNO). Functional adaptation of the pulmonary circulation was evaluated with measurements of mean pulmonary arterial pressure (mPAP), pulmonary capillary pressure (Pcap), pulmonary vascular resistance (PVR), cardiac output (Qc) and pulmonary vascular distensibility (α) mathematically determined from the curvilinearity of the multipoint mPAP-Qc relationship.

Results: EIH exhibited lower exercise induced PVR decrease compared to untrained and NEIH groups (p<0.001). EIH athletes showed higher maximal mPAP as compared to NEIH (45.4±0.9 mmHg vs 41.6±0.9 mmHg, p=0.003, respectively) while no difference appeared between NEIH and untrained. Alpha was lower in EIH compared to NEIH (p<0.05). Maximal mPAP, Pcap and alpha were correlated with the fall of SpO2 during exercise (p<0.01, p<0.01 and p<0.05 respectively). DLNO and DLCO increased with exercise in all groups without difference between groups while DLNO/Qc was correlated to the exercise induced SpO2 changes (p<0.05).

Conclusions: EIH athletes exhibit higher maximal pulmonary vascular pressures, lower vascular distensibility or exercise induced changes in PVR compared to NEIH subjects, in keeping with pulmonary capillary stress failure or intra-pulmonary shunting hypotheses.

INTRODUCTION

Performance in endurance trained athletes is dependent on the functional interdependence of the physiological components of the convectional and diffusional oxygen (O2) transport system from ambient air to the mitochondria. While cardiac and skeletal muscle can easily adapt to endurance training, the healthy pulmonary system has no structural adaptability to physical training [START_REF] Dempsey | Adaptations and limitations in the pulmonary system during exercise[END_REF] . Recently, research interest on pulmonary system limitations to endurance exercise performance has intensified [START_REF] Amann | Pulmonary system limitations to endurance exercise performance in humans[END_REF][START_REF] Mckenzie | Respiratory physiology: adaptations to high-level exercise[END_REF] . It is well accepted that the capacity of the pulmonary system exceeds the demands required for ventilation and gas exchange during endurance and intensive exercise in normal conditions. However, it must be emphasized that, in specific conditions, the healthy pulmonary system can be a limiting factor of whole-body endurance exercise performance. Accordingly, endurance-trained athletes may develop respiratory muscle fatigue, intrathoracic and extrathoracic obstruction, expiratory flow limitation and O2 arterial desaturation during exercise [START_REF] Amann | Pulmonary system limitations to endurance exercise performance in humans[END_REF][START_REF] Mckenzie | Respiratory physiology: adaptations to high-level exercise[END_REF] . Oxygen arterial desaturation during exercise in highly-trained athletes is called exercise-induced hypoxemia (EIH) and is described according to the level of desaturation. This phenomenon occurs in ∼50% of endurance male trained athletes [START_REF] Prefaut | Exercise-induced arterial hypoxaemia in athletes: a review[END_REF] . Physiopathology of the phenomenon is still debated but major explanations are relative hypoventilation, ventilation/perfusion (VA/Q) inequality and diffusion limitation [START_REF] Hopkins | Effect of prolonged, heavy exercise on pulmonary gas exchange in athletes[END_REF] . It seems that diffusion limitation is responsible for gas exchange abnormalities occurring from exercise intensities of 75 to 100% of maximal oxygen uptake (VO2max) in athletes exhibiting EIH [START_REF] Prefaut | Exercise-induced arterial hypoxaemia in athletes: a review[END_REF][START_REF] Durand | Evidence for an inadequate hyperventilation inducing arterial hypoxemia at submaximal exercise in all highly trained endurance athletes[END_REF] .

Exercising at sea level is associated with an increase in pulmonary diffusing capacity for CO (DLCO) and NO (DLNO) attributed to increased pulmonary capillary blood volume (Vc) and better matching between tissue and erythrocyte surfaces, and to a lesser extent the expansion of the alveolar-capillary membrane surface area [START_REF] Zavorsky | Standardisation and application of the single-breath determination of nitric oxide uptake in the lung[END_REF] . Previous measurements of Vc showed linear increase with exercise intensity without ceiling effect, suggesting unlimited recruitment or distention of pulmonary capillaries. Indeed, recruitment and distention of pulmonary capillaries are known to appear during conditions that raise pulmonary blood flow and pulmonary vascular pressure and are crucial to maintain capillary pressure low during intense exercise [START_REF] Hanson | Site of recruitment in the pulmonary microcirculation[END_REF] . In numerous studies, West et al. highlighted that an abnormal increase in capillary pressure at exercise above a 20-25 mmHg threshold could possibly lead to a capillary stress failure known to elicit interstitial lung edema and altered ventilation/perfusion relationships leading to hypoxemia [START_REF] West | Invited Review: Pulmonary capillary stress failure[END_REF] .

We therefore hypothesized that athletes exhibiting O2 desaturation at exercise have a distinctive pulmonary vascular response to exercise, namely elevated pulmonary vascular pressures which could consequently alter the normal lung diffusion capacity response. We therefore compared the pulmonary vascular response to exercise using non-invasive echocardiographic and lung diffusing capacity measurements, in athletes exhibiting EIH, in athletes without EIH and in a control group of untrained subjects.

MATERIALS AND METHODS

Study Population

Twenty-nine healthy non-smoking males volunteered to participate were recruited for this study. Nineteen subjects were endurance trained athletes in running or cycling, performing at least 5 training sessions per week. The other ten subjects were sedentary or active in recreational sports but had never been engaged in systematic endurance training.

Characteristics of all participants are reported in Table 1 (values of VO2max were obtained from an incremental cardio-pulmonary exercise testing realized in a preliminary visit). Each subject was informed about the procedures to be followed and the potential risks inherent with the experiments and signed a written informed consent form. All procedures were approved by the ethics committee of Consell General de l'Esport, Catalunya (0099S/2046/2013).

Design of the study

All subjects underwent a clinical examination with measurements of systemic blood pressure (sphygmomanometry), hemoglobin concentration (EKF diagnostics, Penarth, Cardiff), heart rate (HR) and hemoglobin O2 saturation (SpO2) with a finger pulse oximeter (Nonin, Minnesota, USA). This examination was successively followed by an echocardiographic examination at rest and an incremental exercise test with echocardiography coupled with lung diffusion capacity measurements.

Stress echocardiography and diffusion capacity measurements

After resting measurements, subjects performed an incremental exercise test on a semi recumbent braked cycle ergometer (Ergoline, model 900 EL, Bilz, Germany) laterally tilted by 20 to 30 degrees to the left. The work rate was increased by 30 to 50 Watts every 2 minutes, according to the previously measured physical capacity of the subject.

Echocardiography and lung diffusion measurements were made at each exercise step using a repeated sequence of measurement. This protocol allowed us to have: 1) at least 5 levels of exercise with echocardiographic measurements, and 2) a time of exercise between 12-14 minutes to reach optimal exercise capacity.

Echocardiography measurements:

The echocardiographic measurements were performed with a portable ultrasound system (CX50 Compact Xtreme Ultrasound System Philips, Amsterdam, Netherlands). Stroke volume (SV) was calculated with the following equation: SV = 3.14 x (LVOT diameter/2) 2 x TVI where LVOT is the left ventricular outflow tract cross sectional area measured at rest and TVI the pulsed Doppler time-velocity integral measurements [START_REF] Christie | Determination of stroke volume and cardiac output during exercise: comparison of two-dimensional and Doppler echocardiography, Fick oximetry, and thermodilution[END_REF] . Cardiac output (Qc) was calculated as the product of SV and HR. Systolic pulmonary arterial pressure (sPAP) was calculated from the maximum velocity of the continuous-Doppler tricuspid regurgitation jet (TRV) and corrected for right atrial pressure as sPAP = 4 TRV 2 + RAP, where RAP is the right atrial pressure estimated from the dimension and the collapsibility of the inferior vena cava. Subjects have been selected according to the TRV to obtain a good quality signal in all subjects. Mean pulmonary arterial pressure (mPAP) was calculated as mPAP = 0.61 * sPAP + 2, as previously reported [START_REF] Naeije | Pulmonary artery pressure limits exercise capacity at high altitude[END_REF] . Pulmonary vascular resistance (PVR) was defined as the ratio of the difference between mPAP and left atrial pressure (LAP) divided by Qc [START_REF] Naeije | Exercise-induced Pulmonary Hypertension: Physiological Basis and Methodological Concerns[END_REF] . LAP was estimated from the ratio of Doppler mitral early flow-velocity wave (E) and tissue Doppler mitral annulus early diastolic velocity (E') with the following equation: LAP = 1.9 + 1.24 E/E' [START_REF] Nagueh | Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures[END_REF] . Pulmonary capillary pressure (Pcap) was calculated as 0.4 x (mPAP-LAP) + LAP [START_REF] Cope | Pulmonary capillary pressure: a review[END_REF] . This non-invasive evaluation of the pulmonary circulation at exercise has been validated i.a. in athletes and untrained healthy subjects but also in patients, and present reasonable accuracy compared to exercise cardiac magnetic resonance imaging with simultaneous invasive pressure records [START_REF] Claessen | Accuracy of Echocardiography to Evaluate Pulmonary Vascular and RV Function During Exercise[END_REF][START_REF] Caravita | Noninvasive versus invasive pressure-flow relationship of the pulmonary circulation: bias and error[END_REF] .

Each point of the mPAP -Qc relationship was fitted to the equation: mPAP = [((1 + αLAP) 5 + 5α.R0.Qc) 1/5 -1] /α where R0 is total PVR at rest, to calculate a distensibility α index expressing the percentage of diameter change in resistive pulmonary vessel per mmHg increase in transmural pressure during exercise [START_REF] Naeije | Exercise-induced Pulmonary Hypertension: Physiological Basis and Methodological Concerns[END_REF] .

Recordings were stored on optical disks and analyzed twice blindly by a cardiologist experienced in stress echocardiography with a reliability above 80%.

Lung diffusion measurements:

The Roughton and Forster equation states that 1/DL = 1/Dm+ 1/θVc, where DL is the diffusing capacity of the lung, Dm its membrane component, θ bloodgas affinity and Vc capillary blood volume [START_REF] Zavorsky | Standardisation and application of the single-breath determination of nitric oxide uptake in the lung[END_REF] . The transposition of the equation to two different gas tracers (NO and CO) after the measurement of their respective diffusion capacity (DLNO and DLCO) allows for the calculation of Dm, and hence Vc. Single breath measurements of DLCO and DLNO were performed at rest and every other exercise level in the echocardiographic position. An automated device, including automated calibrations, mixing of gases and online calculations, and corrections for hemoglobin and inspired partial pressure of oxygen was used (Hyp'Air compact, Medisoft, Dinant, Belgium) in agreement with recent recommendations of an expert Task Force of the European Respiratory Society [START_REF] Zavorsky | Standardisation and application of the single-breath determination of nitric oxide uptake in the lung[END_REF] .

The concentrations of inspired gases were 40 ppm of NO, 1600 ppm of CO, 8% of helium and 19% of O2 in nitrogen. The breath holding time was 4 sec. The first 0.8 L of expired gas was discarded. The coefficient relating DLNO and Dm was set at 1.97 according to the solubility and molecular weights of both gases [START_REF] Aguilaniu | European reference equations for CO and NO lung transfer[END_REF] . Measurements were repeated two to three times at rest, with the aim to obtain DLCO values within 5% and DLNO values within 10% of each other.

SpO2 measurement and O2 desaturation: SpO2 was measured continuously during tests using a finger pulse oximeter (Nonin, Minnesota, USA). This method has been reported to deliver high precision, reproducibility and validity for O2 saturation above 85% when compared to O2 saturation measured from arterial blood gases in highly trained athletes [START_REF] Martin | Validity of pulse oximetry during exercise in elite endurance athletes[END_REF] . The instrument's conducting cable was secured to prevent movement artefacts and before the probe was placed, the finger was warmed up by massage to active arterialized circulation. SpO2 fall ≥ 4% observed between rest and maximal condition during at least 3 minutes of the test was defined as a significant O2 desaturation [START_REF] Prefaut | Exercise-induced arterial hypoxaemia in athletes: a review[END_REF] .

Statistical analysis

Results are expressed as mean ± standard error of mean (SEM). The data were screened for normality of the distribution and homogeneity of variances using the Shapiro-Wilk normality and Levene tests, respectively. Differences between the three groups with unrepeated measures (anthropometric data, VO2max, FEV1, training volume, workload, ΔPVR, mPAP/Qc slope, mPAP/CI slope) were analysed using one-way analysis of variance (Anova). Kruskal-Wallis test has been used when normality of the distribution and homogeneity of variances failed (SpO2max and ΔSpO2 variables). Other hemodynamic and diffusion parameters were analysed using Anova for repeated measures during exercise (rest vs max) as the withinsubject factor and groups (EIH vs. NEIH vs. untrained) as the between-subject factor. When overall significance was obtained, differences between means were identified using a Student-Newman-Keuls post-hoc analysis. Correlation analysis (Pearson's coefficient for normal distribution variables or Spearman's coefficient for non-normal distribution variables) were performed to test the linear relationships between data, especially to identify the specific variables associated to SpO2 at maximal exercise or exercise-induced ΔSpO2. For all statistical tests, the level of significance was set at p < 0.05 and analyses were conducted using SigmaStat software (Ver 3.5).

RESULTS

Incremental exercise test on the semi recumbent braked cycle allowed us to identify two different groups of endurance-trained athletes: one exhibiting O2 exercise desaturation (EIH group) and another without O2 exercise desaturation (NEIH group). Figure 1 reports the fall of SpO2 measured during exercise in the three groups. SpO2 values at the end of exercise were significantly lower in EIH group than in NEIH or untrained groups (94.2 ± 0.3%; 96.1 ± 0.3%; 96.2 ± 0.5%; p = 0.001, respectively). Delta SpO2 (difference of SpO2 between rest and maximal exercise) level measured in EIH signed a physiological desaturation which is not found in NEIH or untrained groups. Semi recumbent braked cycle test was performed at 95 ± 1.8% of HRmax achieved during the incremental cardio-pulmonary exercise test realized during the preliminary visit.

Hemodynamic parameters were reported in Table 2. No between group difference was observed at rest except in PVR: NEIH presented a slightly higher PVR compared to EIH and untrained (Anova interaction p = 0.004, post hoc analyses p = 0.029 and p = 0.005, respectively). PVR decreased with exercise in NEIH only (p = 0.001) while maximal LAP did not change. Delta PVR reflecting the fall of PVR during exercise was significantly higher in NEIH group than in EIH and in untrained subjects (Anova interaction p = 0.002, post hoc analyses p = 0.025 and p = 0.003 respectively). The same effect between EIH and NEIH was observed for the coefficient of arteriolar distensibility alpha (p = 0.045). Qc, cardiac index (CI), HR, SV, mPAP and Pcap increased with exercise in all groups (Anova exercise effect p < 0.001). Qc and CI at maximal exercise were significantly higher in endurance trained athletes (EIH and NEIH) compared to untrained subjects (Anova interaction p = 0.041 and p = 0.010, post hoc analyses p = 0.016 and p = 0.003, respectively). EIH reported significant greater values of maximal mPAP and maximal Pcap compared to NEIH and untrained groups (Anova interaction p = 0.033, post hoc analyses p = 0.003 and p = 0.002, respectively) without difference between NEIH and untrained subjects. Alpha and the increase in mPAP from rest to maximal exercise were correlated with delta PVR (r = -0.79, p < 0.001 and r = 0.45, p = 0.022 respectively).

None of the subjects exhibited mPAP/Qc or maximal TPR above 3 WU. No between groups differences were observed for the mPAP/Qc or mPAP/CI slopes. Delta SpO2 and SpO2 at maximal exercise were significantly correlated with maximal mPAP (r = -0.60, p = 0.002 and r = -0.58, p = 0.002, respectively). The significant correlation between mPAP and delta SpO2 was reported in Figure 2. Maximal Pcap was significantly correlated with the delta of SpO2 (r = -0.55, p = 0.005) and with SpO2max (r = -0.44, p = 0.027). In athletes, the alpha coefficient of pulmonary arteriolar distensibility was also correlated to delta SpO2 (r = 0.43, p < 0.05).

Dm and Vc calculated with θNO assumed to be finite as 4.5 mL.min -1 .mL -1 are shown in Table 3. Maximal exercise was associated with increase in VA, DLCO, DLNO, KCO, KNO, Dm, Vc corrected for Hb, in all groups (Anova exercise effect p < 0.05). The ratio DLNO/DLCO did not change. No group effect was observed at any time. However, DLCO and preponderantly DLNO corrected for Qc at rest or maximal exercise were correlated to delta SpO2 in athletes. Figure 3 shows that DLNO/Qc at maximal exercise decreases with exercise induced SpO2 changes (r = 0.41, p = 0.032).

DISCUSSION

To our knowledge, this study is the first to highlight specific pulmonary vascular adaptations to exercise consisting in higher maximal pulmonary arterial and capillary pressures with concomitantly lower vascular distensibility and decreased PVR reduction at exercise in athletes exhibiting O2 desaturation compared with athletes without O2 desaturation and control group, i.e. untrained subjects.

Methodological consideration

For ethical reasons this study used pulse oximetry, a non-invasive method for estimation of SpO2 rather than blood arterial gases. Pulse oximetry method has been reported to deliver high precision, reproducibility and validity for O2 saturation above 75% when compared to O2 saturation measured from arterial blood gases at rest and exercise [START_REF] Martin | Validity of pulse oximetry during exercise in elite endurance athletes[END_REF][START_REF] Trivedi | Pulse oximeter performance during desaturation and resaturation: a comparison of seven models[END_REF][START_REF] Mollard | Validity of arterialized earlobe blood gases at rest and exercise in normoxia and hypoxia[END_REF] . All the quoted references define exercise induced O2 desaturation in athletes, i.e. EIH during an upright exercise [START_REF] Prefaut | Exercise-induced arterial hypoxaemia in athletes: a review[END_REF][START_REF] Dempsey | Exercise-induced arterial hypoxemia[END_REF] . In our study, subjects performed a stress echocardiography in semi supine position laterally tilted by 20 to 30 degrees to the left for optimal echocardiographic acquisition. Pedersen et al. [START_REF] Pedersen | Reduced arterial O2 saturation during supine exercise in highly trained cyclists[END_REF] reported that despite a lower VO2max and a suggested improvement in VA/Q distribution, there was no difference in O2 desaturation during exercise between upright and supine position. This reference allowed us to use the Prefaut's team definition to determine a significant physiological O2 desaturation [START_REF] Prefaut | Exercise-induced arterial hypoxaemia in athletes: a review[END_REF] .

Invasive studies in the recumbent position previously reported a lower resting PVR compared with upright position explained by a better vascular recruitment when venous return is increased with gravity [START_REF] Reeves | Pulmonary Hemodynamics and Fluid Exchange in the Lungs During Exercise[END_REF] . However, the differences disappeared with exercise because of vascular recruitment/dilation with pulmonary blood flow elevation. Accordingly, Forton et al. compared stress echocardiography in the upright-seated position vs the same semi-recumbent position as used in the present study and showed no body position effect on pulmonary hemodynamic parameters such as maximal PVR, PAP/Qc relationships and no alteration of exercise capacity (identical maximal Qc and VO2max) [START_REF] Forton | Effects of body position on exercise capacity and pulmonary vascular pressure-flow relationships[END_REF] . In the present study, end-exercise HR in a semi recumbent position reached 95% of maximal upright HR as suggested by Forton et al [START_REF] Reeves | Pulmonary Hemodynamics and Fluid Exchange in the Lungs During Exercise[END_REF] .

While echocardiographic evaluation of E/e' was found sensitive to LAP during exercise [START_REF] Nagueh | Doppler tissue imaging: a noninvasive technique for evaluation of left ventricular relaxation and estimation of filling pressures[END_REF] , insufficient accuracy at high levels of exercise has previously been addressed [START_REF] Gerche | Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise[END_REF][START_REF] Olsen | Maximal exercise capacity is related to cardiovascular structure in patients with longstanding hypertension. A LIFE substudy[END_REF] . In the present study and in agreement with previous echocardiographic studies, LAP did not increase significantly during exercise [START_REF] Vriz | Increased pulmonary vascular resistance in early stage systemic hypertension: a resting and exercise stress echocardiography study[END_REF][START_REF] Groepenhoff | Exercise pathophysiology in patients with chronic mountain sickness exercise in chronic mountain sickness[END_REF][START_REF] Lalande | Pulmonary vascular distensibility predicts aerobic capacity in healthy individuals[END_REF][START_REF] Argiento | Exercise Stress Echocardiography for the Study of the Pulmonary Circulation[END_REF] . Accordingly, an invasive study in 5 athletes achieving a maximal VO2 similar to the present study reported no or limited RAP or LAP elevation for exercise intensities under a Qc of 20 L.min -1 31 . At higher Qc, exercise induced LAP elevation was delayed and smoothened in athletes compared to sedentary subjects reaching a moderate value around 15 mmHg [START_REF] Stickland | Does fitness level modulate the cardiovascular hemodynamic response to exercise?[END_REF] . This may be explained by a right shifting of the hyperbolic relationship between LV diastolic pressure and volume in athletes. In the present study, the LAP/Qc ratio, quantifying the post-capillary pressure elevation throughout exercise with less imprecisions than maximal LAP, was very low in all groups suggesting no or little influence of LAP on the exercise induced PAP increase [START_REF] Eisman | Pulmonary Capillary Wedge Pressure Patterns During Exercise Predict Exercise Capacity and Incident Heart Failure[END_REF] . It is therefore reasonable to think that insufficient accuracy of LAP estimations may not account for the presently observed Pcap and mPAP elevation in EIH athletes.

Results discussion

The present results show that athletes with EIH present distinctive pulmonary vascular adaptations to exercise. Even if it is not known whether it is a cause or a consequence, these results are in keeping with the hypothesis that some pathophysiological explanations of EIH may be in relation with pulmonary hemodynamic adaptations to exercise.

Echocardiographic estimations of pulmonary vascular pressures and Qc are advantageous because being noninvasive, flexible and validated [START_REF] Caravita | Noninvasive versus invasive pressure-flow relationship of the pulmonary circulation: bias and error[END_REF][START_REF] Argiento | Exercise Stress Echocardiography for the Study of the Pulmonary Circulation[END_REF] . However, those estimations rely on a series of assumptions in the calculations of pressures and flows. The physiologic range of pulmonary pressures is affected by different hemodynamic, clinical and anthropometrics factors: cardiac output, age, gender, race, body dimensions, body mass index, type and level of exercise training, posture and/or exercise. Kovacs et al. [START_REF] Kovacs | Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review[END_REF] reported in a systematic review that normal mPAP resting values in healthy subjects were not more than about 20.6 mmHg. A study of D'Andrea et al. [START_REF] Riegler | Range of right heart measurements in top-level athletes: the training impact[END_REF] showed that 1) training status should be taken into account and 2) the upper physiologic limit of resting sPAP in endurance athletes may reach 40 mmHg in line with the increased SV. In the present study, resting mPAP values are in good agreement with previous invasive and noninvasive studies. Substantial increase in mPAP occurs during intense exercise as a result of marked increase in cardiac output and pulmonary blood flow along with increase in left ventricular filling pressure [START_REF] Bossone | Range of tricuspid regurgitation velocity at rest and during exercise in normal adult men: implications for the diagnosis of pulmonary hypertension[END_REF] . Argiento et al. [START_REF] Argiento | Exercise Stress Echocardiography for the Study of the Pulmonary Circulation[END_REF] have estimated that for a 10 L•min -1 increase in Qc, from 10 to 20 L•min -1 , pulmonary hypertension is defined by mPAP exceeding an absolute value of 45 mmHg. However invasive or echocardiographic studies reported on considerable variations in pulmonary vascular response to exercise from one subject to another [START_REF] Argiento | Exercise Stress Echocardiography for the Study of the Pulmonary Circulation[END_REF] . In the present study, EIH athletes reached significantly higher values of maximal mPAP and Pcap than NEIH and untrained groups. As the maximal mPAP value depends on the achieved exercise level or Qcmax [START_REF] Argiento | Exercise Stress Echocardiography for the Study of the Pulmonary Circulation[END_REF] , our results could suggest that EIH group exhibit a higher Qc at the end of exercise. However, this observation cannot be attributed to higher maximal Qc or maximal LAP as identical values were reached in both athletes groups.

If the measured maximal Qc may seem low for endurance athletes, we must not forget that i) the mean age of the present athletes is around 40 years old and ii) it is well reported that exercise echocardiography underestimates Qc at exercise in comparison with the exercise cardiac magnetic resonance imaging with simultaneous invasive pressure registration [START_REF] Claessen | Accuracy of Echocardiography to Evaluate Pulmonary Vascular and RV Function During Exercise[END_REF] . This bias is due to underestimation of SV, particularly at maximal exercise in a stress echocardiographic position when peak HR is lower [START_REF] Reeves | Pulmonary Hemodynamics and Fluid Exchange in the Lungs During Exercise[END_REF] . However, the reported maximal values of Qc are higher as compared to previous stress echocardiography in athletes [START_REF] Gerche | Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise[END_REF] . Moreover, the present maximal Qc coincide with predicted values calculated from previous Qc vs workload relationships established during stress echocardiography in heathy subjects [START_REF] Reeves | Pulmonary Hemodynamics and Fluid Exchange in the Lungs During Exercise[END_REF] . As identical maximal Qc was reached in EIH and NEIH groups with identical Vc, the hypothesis that a reduction in capillary transit time altering the O2 saturation of the passing red blood cells can be excluded.

The present study highlights elevated pulmonary vascular pressures during exercise in EIH compared with NEIH and untrained groups suggesting a specific hemodynamic response linked to O2 desaturation during exercise, as illustrated in Figure 2. Indeed, all EIH athletes present mPAP above 42 mmHg and are all included in a clustering. The significant correlation found between the exercise induced mPAP increase and changes in PVR suggests that high pulmonary pressure increase occurs when reduction of PVR with exercise is low. Moreover, the present study also shows impaired exercise induced pulmonary arteriolar distensibility in EIH correlated to ∆SpO2. The reason why this intrinsically particular pulmonary circulation difference exists remains unknown, but it may be hypothesized that it contributes to the excessive exercise-induced PAP elevation and lower exercise-induced PVR reduction in EIH.

During maximal exercise, Durand et al. [START_REF] Durand | Attenuated ANF response to exercise in athletes with exercise-induced hypoxemia[END_REF] have observed an attenuated release of atrial natriuretic factor (pulmonary vasodilator) in athletes with EIH compared to athletes without. Moreover, Verges et al. [START_REF] Verges | Exhaled nitric oxide during normoxic and hypoxic exercise in endurance athletes[END_REF] reported reduced nitric oxide (NO) concentrations in EIH athletes. Indeed, pulmonary vascular tone is in part mediated by NO response to exercise. However, controversial results have been reported on NO production and O2 exercise desaturation in endurance-trained athletes [START_REF] Sheel | Relationship between decreased oxyhaemoglobin saturation and exhaled nitric oxide during exercise[END_REF][START_REF] Kippelen | Exhaled nitric oxide level during and after heavy exercise in athletes with exercise-induced hypoxaemia[END_REF] . In fact, NO response has been reported to be increased by endurance training but also limited by intensive endurance training susceptible to induce vascular remodeling [START_REF] Petersen | Functional and structural vascular remodeling in elite rowers assessed by cardiovascular magnetic resonance[END_REF] , vascular smooth muscle desensitization for NO [START_REF] Yamashita | Functional consequences of mutations in the smooth muscle myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy[END_REF] and/or elevate reactive oxygen species production [START_REF] Sato | Effects of acute endurance exercise and 8 week training on the production of reactive oxygen species from neutrophils in untrained men[END_REF] . These references are in keeping with the present observation of a lower decrease of PVR in EIH athletes compared to NEIH. In numerous studies, West et al. pointed out the fact that EIH could be due to increase in PAP and then Pcap, leading to interstitial pulmonary edema via stress failure process [START_REF] West | Invited Review: Pulmonary capillary stress failure[END_REF][START_REF] West | Stress failure of pulmonary capillaries as a limiting factor for maximal exercise[END_REF] . Indeed, it is well described that during intense exercise, capillary transmural pressure at the base of the lung can exceed 25 mmHg [START_REF] West | Stress failure in pulmonary capillaries[END_REF] . Such pressures may cause very high hoop stress in the thin-walled capillaries. In the present study, Pcap increased during exercise in all groups but with higher values reached in the EIH group compared with NEIH while no inter-group difference was reported between the EIH and the untrained group. Furthermore, it has been previously suggested that during exercise, the opening of small intra-pulmonary arteriovenous anastomoses could allow blood to bypass the air-exchange zone of the lung in relation to exercise induced PAP elevation [START_REF] Yamashita | Functional consequences of mutations in the smooth muscle myosin heavy chain at sites implicated in familial hypertrophic cardiomyopathy[END_REF] . Even if a correlation between intra-pulmonary shunts and the increase of D(A-a)O2 in exercise in healthy humans has been reported [START_REF] Stickland | Intra-pulmonary shunt and pulmonary gas exchange during exercise in humans[END_REF] , Vogiatzis et al.

suggested that pulmonary shunts were not significantly involved in the PaO2 drop in trained athletes during maximal exercise [START_REF] Mckenzie | The effect of repeat exercise on pulmonary diffusing capacity and EIH in trained athletes[END_REF] . However, the present results cannot exclude the presence of intra-pulmonary shunts and its role in the observed exercise hypoxemia.

Our results are thus in agreement with the literature on the topic and confirm the implication of a high pulmonary pressure in EIH physiopathology, as it was often previously suggested but never measured in humans. However, it is to acknowledge that, due to small sample size, a type I error cannot be excluded and could possibly influence the present results.

In the present study and in keeping with previous studies, lung diffusion capacity increased linearly with exercise intensity without ceiling effect and with no or minor changes in the DLNO/DLCO ratio, suggesting no limitation of recruitment and distention of pulmonary capillaries even at high exercise intensities. However, the membrane and the capillary component of the diffusive response to exercise were similar between groups. As physiopathology of EIH suspects abnormalities in gas exchange diffusion from 75% to 100% of VO2max 6 , we hypothesized that some diffusion abnormalities could occur during maximal exercise in EIH athletes. Indeed, previous studies reported a post-exercise decrease in DLCO in endurance-trained athletes associated with O2 desaturation during exercise [START_REF] Mckenzie | The effect of repeat exercise on pulmonary diffusing capacity and EIH in trained athletes[END_REF][START_REF] Hanel | Restricted postexercise pulmonary diffusion capacity does not impair maximal transport for O2[END_REF] . This exercise-induced diffusion limitation has been attributed to changes in the membrane diffusion properties such as interstitial extra-vascular water accumulation. Despite those evidences, the present study did not show any obvious diffusion capacity alteration in EIH athletes compared to NEIH or untrained subjects. However, a type II error could not be excluded in this small sample size study and in the presence of an end-exercise desaturation that could be qualified as "mild" [START_REF] Mollard | Validity of arterialized earlobe blood gases at rest and exercise in normoxia and hypoxia[END_REF] . It is also possible that some occurred changes are not detectable during our short exercise protocol or by the measure of DLCO and DLNO.

Mechanisms such as pulmonary blood flow redistribution and/or lymphatic fluid reabsorption could act and hid some diffusion limitation despite nascent pulmonary interstitial edema.

Notwithstanding, even if the present study could not highlight a specific diffusion alteration in EIH subjects at exercise, the DLNO corrected for Qc was found to be correlated to the exercise induced O2 desaturation (Figure 3). As DLNO is mainly dependent on the membrane component of diffusion, it indicates that subjects desaturating the most at maximal exercise have a less diffusible alveolo-capillary membrane regarding the maximal exercise level reached. This could possibly be explained by extra-capillary fluid accumulation impairing the membrane component of the diffusion limitation. However, further studies need to be established to increase the power of the present observations and confirm the possible pulmonary capillary stress failure or intra-pulmonary shunting hypotheses in EIH endurance athletes.

CONCLUSION

This study is the first to demonstrate that athletes exhibiting O2 arterial desaturation during exercise present distinctive pulmonary vascular response to exercise. Indeed, decreased pulmonary vascular distensibility and smoothened reduction of PVR at high levels of exercise seems to induce higher levels of maximal PAP and Pcap. Although it could not be demonstrated directly and no causality can be proven, the present results are in favor of the pulmonary capillary stress failure theory to explain O2 arterial desaturation of athletes during exercise, while intra-pulmonary shunting cannot be excluded.

Table 1 :

 1 Participant's baseline characteristics

	EIH	NEIH	Untrained
	(n = 10)	(n = 9)	(n = 10)

Table 2 :

 2 Resting and exercise echocardiography parameters for EIH, NEIH and untrained groups.Values are means ± SEM. EIH: athletes exhibiting O2 desaturation; NEIH: athletes without O2 desaturation; untrained subjects; SV: stroke volume; Qc: cardiac output; CI: cardiac index; HR: heart rate; mPAP: mean pulmonary arterial pressure; Pcap: pulmonary capillary pressure; LAP: left atrial pressure; TPR: total pulmonary vascular resistance; PVR: pulmonary vascular resistance; ∆ PVR: changes of PVR from rest to maximal exercise; Alpha: coefficient of pulmonary arteriolar distensibility *, significant difference between rest and maximal exercise within group (p <0.05) †, significantly different from NEIH (p < 0.05) Ψ, significantly different from untrained (p < 0.05)

			EIH	NEIH	Untrained
			(n= 10)	(n = 9)	(n = 10)
	Workload (W)	Max	270 ± 10 Ψ	264 ± 8 Ψ	208 ± 11
	SV (ml)	Rest Max	93 ± 6 146 ± 5*	90 ± 5 149 ± 9*	83 ± 5 124 ± 5*
	Qc (l•min -1 )	Rest Max	5.9 ± 0.3 23.4 ± 1.1 * Ψ	5.2 ± 0.2 22.7 ± 1.2 * Ψ	5.6 ± 0.2 19.6 ± 0.9 *
	CI (l•min -1 •m -2 )	Rest Max	3.2 ± 0.2 12.6 ± 0.5 * Ψ	2.8 ± 0.2 12.1 ± 0.6 * Ψ	2.9 ± 0.1 10.2 ± 0.5 *
	HR (bpm)	Rest Max	63 ± 3 Ψ 168 ± 4 *	61 ± 4 Ψ 162 ± 5 *	78 ± 5 169 ± 5 *
	mPAP (mmHg)	Rest Max	18.7 ± 0.4 45.4 ± 0.9 * † Ψ	18.7 ± 0.9 41.6 ± 0.9 *	18.1 ± 0.7 41.9 ± 0.6 *
	Pcap (mmHg)	Rest Max	12.8 ± 0.4 24.8 ± 0.4 * † Ψ	12.2 ± 0.6 23.3 ± 0.5 *	12.7 ± 0.4 23.4 ± 0.3 *
	LAP (mmHg)	Rest	8.9 ± 0.5	7.9 ± 0.4	9.2 ± 0.5
		Max	11.1 ± 0.5*	11.3 ± 0.3*	11.1 ± 0.3*
	TPR (mmHg)	Rest	3.3 ± 0.2	3.6 ± 0.2	3.3 ± 0.2
		Max	2.0 ± 0.1*	1.9 ± 0.1*	2.2 ± 0.1*
	PVR (WU)	Rest Max	1.7 ± 0.1 † 1.5 ± 0.1	2.1 ± 0.1 1.4 ± 0.1 *	1.7 ± 0.1 † 1.6 ± 0.1
	∆PVR (WU)		-0.2 ± 0.1 †	-0.7 ± 0.2	0.03 ± 0.1 †
	LAP/Qc slope		0.01±0.002	0.01±0.002	0.02±0.009
	(mmHg•m -2 •min -1 )
	mPAP/Qc slope		1.6 ± 0.1	1.5 ± 0.1	1.8 ± 0.1
	(mmHg•m -2 •min -1 )
	mPAP/CI slope		3.0 ± 0.2	2.8 ± 0.2	3.5 ± 0.2
	(mmHg•m -2 •min -1 )
	Alpha (%)		0.8 ± 0.07 †	1.0 ± 0.07	0.8 ± 0.06

Table 3 :

 3 Resting and maximal exercise pulmonary diffusing capacity parameters for EIH, NEIH and untrained groups.Values are means ± SEM. EIH: athletes exhibiting O2 desaturation; NEIH: athletes without O2 desaturation; VA: alveolar volume; DLCO: pulmonary diffusing capacity for CO; DLNO: pulmonary diffusing capacity for NO; KCO: transfert coefficient for CO; KNO: transfert coefficient for NO; Dm: alveolar-capillary membrane conductance; Vc: pulmonary capillary blood volume; DLNO/DLCO: DLNO/DLCO ratio.

	EIH	NEIH	Untrained
	(n= 10)	(n = 9)	(n = 10)

*, significant difference between rest and maximal exercise within group (p < 0.05) †, significantly different from NEIH (p < 0.05) Ψ, significantly different from untrained (p < 0.05)

ACKNOWLEDGEMENTS

We thank all subjects who volunteered to participate in this study. Moreover, we are grateful to Masella ski resort and the Medicine Faculty of Gerona.

Author's Contributions:

• Significant manuscript writer: FD/AFG/VF


Céline Meslier
email: celine.meslier@unilim.fr

Tastaftiyan Risfandy

Amine Tarazi
email: amine.tarazi@unilim.fr

J P Zhao

W Y Hernández

W J Zhou

Y Yang

E I Vovk

M Wu

N Naghavi

M Capron

V Ordomsky

Islamic banks' equity financing, Shariah supervisory board, and banking environments

Keywords: Profit and loss sharing, equity financing, governance, Shariah supervisory board, environment, Islamic banks JEL Classifications: G21, G34, Z12

Although equity financing is a core value in Islamic finance, it is rarely used by Islamic banks which prefer other instruments such as markup or leasing contracts. The purpose of this paper is to investigate the potential determinants of equity financing. Shariah supervisory board (SSB) is regarded as crucial in promoting equity financing. We use hand-collected data on equity financing and governance structure of 88 Islamic banks in 16 countries between 2009 and 2014. Our findings reveal that Islamic banks' equity financing is influenced by the characteristics of SSB. Specifically, the duality of SSB members positively affects equity financing whereas the existence of a Shariah department within banks has a negative impact. We also find that the role of SSB in Islamic banks is influenced by the characteristics of the board of directors (BOD) and the banking environments. The impact of SSB on equity financing is reduced in the better banking environment, possibly suggesting substitution role between SSB and institutional and Islamic environment.

Introduction

The selective oxidation of alcohols to versatile intermediates for the production of chemicals such as aldehydes and ketones remains a challenging task in the industry. It is of special interest the utilization of molecular oxygen as the green oxidant in the presence of a heterogeneous catalyst, thus favoring the atom economy in contrast to the use of toxic and expensive stoichiometric oxidants [START_REF] Steven | Activation through impregnation. Permanganate-coated solid supports[END_REF][START_REF] Muzart | Chromium-Catalyzed Oxidations in Organic Synthesis[END_REF][START_REF] Perree | Manganese Porphyrin-catalysed Oxidation of Olefins to Ketones by Molecular Oxygen[END_REF][START_REF] Uyanik | Hypervalent Iodine-mediated Oxidation of Alcohols[END_REF][START_REF] Satoshi | A New and Facile Method for the Direct Preparation of α-Hydroxycarboxylic Acid Esters from α,β-Unsaturated Carboxylic Acid Esters with Molecular Oxygen and Phenylsilane[END_REF].

Different heterogeneous catalytic systems based on Pt [START_REF] Zhai | Plasmon-Driven Selective Oxidation of Aromatic Alcohols to Aldehydes in Water with Recyclable Pt/TiO2 Nanocomposites[END_REF][START_REF] Ilyas | Liquid-Phase Aerobic Oxidation of Benzyl Alcohol Catalyzed by Pt/ZrO2[END_REF][START_REF] Xie | Influence of Dioxygen on the Promotional Effect of Bi during Pt-Catalyzed Oxidation of 1,6-Hexanediol[END_REF], Pd [START_REF] Hackett | Highactivity, single-site mesoporous Pd/Al2O3 catalysts for selective aerobic oxidation of allylic alcohols[END_REF][START_REF] Parlett | Support-Enhanced Selective Aerobic Alcohol Oxidation over Pd/Mesoporous Silicas[END_REF], Au [START_REF] Zhao | An excellent Au/meso-γ-Al2O3 catalyst for the aerobic selective oxidation of alcohols[END_REF][START_REF] Tanaka | Preparation of Au/CeO2 exhibiting strong surface plasmon resonance effective for selective or chemoselective oxidation of alcohols to aldehydes or ketones in aqueous suspensions under irradiation by green light[END_REF] have been reported for oxidation of alcohols. Among metallic catalysts, Ru has shown to be quite efficient in oxidation reactions [START_REF] Nie | Efficient aerobic oxidation of 5-hydroxymethylfurfural to 2,5diformylfuran on supported Ru catalysts[END_REF][START_REF] Wang | Aerobic oxidation of secondary alcohols via ruthenium-catalysed hydrogen transfer involving a new triple catalytic system[END_REF][START_REF] Zhao | Selective oxidation of alcohols to carbonyl compounds over small size colloidal Ru nanoparticles[END_REF]. However, low selectivity to aldehydes or ketones over heterogeneous catalysts is still a challenging problem due to formation of corresponding acids and esters [START_REF] Schmidt | TPAP-Catalyzed Direct Oxidation of Primary Alcohols to Carboxylic Acids through Stabilized Aldehyde Hydrates[END_REF]. The oxidation mechanism for metallic catalysts usually follows an oxidative dehydrogenation pathway, where both abstraction of hydrogen from alcohols and oxygen reduction processes (regeneration of the active site) simultaneously occur on the metal surface [START_REF] Hernandez | Electrochemically-assisted NOx storage-reduction catalysts[END_REF]. The aldehydes can be further oxidized over the same active sites to acids with decrease of the selectivity and generation of waste products. In general, these catalysts are very efficient in the selective oxidation of activated alcohols (e.g. benzyl and allyl alcohols) but less active and selective for oxidation of aliphatic primary alcohols [START_REF] Adair | Oxidant-free oxidation: ruthenium catalysed dehydrogenation of alcohols[END_REF][START_REF] Deffernez | Bimetallic Bi-Pt, Ru-Pt and Ru-Pd and trimetallic catalysts for the selective oxidation of glyoxal into glyoxalic acid in aqueous phase[END_REF][START_REF] Mori | Hydroxyapatite-Supported Palladium Nanoclusters: A Highly Active Heterogeneous Catalyst for Selective Oxidation of Alcohols by Use of Molecular Oxygen[END_REF][START_REF] Hosokawa | Effect of the Preparation Conditions of Ru/CeO2 Catalysts for the Liquid Phase Oxidation of Benzyl Alcohol[END_REF].

Recently, it has been found that metal-free electron deficient organic compounds like TEMPO (2,2,6,6-Tetramethylpiperidinyloxy) and DDQ (2,3-Dichloro-5,6-Dicyanobenzoquinone) can be used for dehydrogenation of alcohols in stoichiometric way, producing aldehydes and ketones together with the hydrogenated form of TEMPO and DDQ [START_REF] Ryland | Practical Aerobic Oxidations of Alcohols and Amines with Homogeneous Copper/TEMPO and Related Catalyst Systems[END_REF][START_REF] Ma | Development of a General and Practical Iron Nitrate/TEMPO-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes/Ketones: Catalysis with Table Salt[END_REF][START_REF] Walsh | Solar photochemical oxidations of benzylic and allylic alcohols using catalytic organo-oxidation with DDQ: Application to lignin models[END_REF][START_REF] Hu | Fe (NO3)3/2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ): An efficient catalyst system for selective oxidation of alcohols under aerobic conditions[END_REF]. However, the use of large amounts of organic oxidants and difficulties related to their separation and regeneration strongly hinders the viability of this oxidation approach. To solve this drawback, the in-situ regeneration of these type of organic oxidants has been proposed, involving their combination with additional electron transfer mediators (ETM) and the utilization of a different terminal oxidant (e.g. oxygen). For example, Hu et al. explored an aerobic metal-free alcohol oxidation with a catalytic system consisting of TEMPO/Br2/NaNO2, where the Br2/HBr redox pair oxidizes TEMPOH with subsequent regeneration by NO2 [START_REF] Liu | Transition-metal-free: A highly efficient catalytic aerobic alcohol oxidation process[END_REF]. In 1977, the DDQcatalyzed reaction has been reported for the transformation of allylic alcohols to α,βunsaturated ketones using 10 mol% DDQ in the presence of 30 mol% periodic acid under biphasic conditions at room temperature [START_REF] Scott | A Rapid and Mild Process for the Oxidation of 2, 3-Dichloro-5, 6-dicyanobenzoquinone (DDQ) from 2, 3-Dichloro-5, 6-dicyanohydroquinone (DDHQ)[END_REF]. Helquist et al. illustrated similar reactivity using Mn(OAc)3 and DDQ for oxidation of allylic alcohols and benzylic alcohols to the corresponding aldehydes and ketones at mild reaction conditions [START_REF] Cosner | Selective Oxidation of Benzylic and Allylic Alcohols Using Mn(OAc)3/Catalytic 2, 3-Dichloro-5, 6-dicyano-1, 4benzoquinone[END_REF].

Despite this selective oxidation methodology favors the regeneration of the organic oxidant, it still requires the presence of metal salts in the final liquid product. Earlier, we have proposed application of anthraquinones as a catalyst for non-metallic oxidation of alcohols, however, the reaction proceed at relatively high temperature with oxidation of activated alcohols [START_REF] Zhao | Non-metallic Aerobic Oxidation of Alcohols over Anthraquinone Based Compounds[END_REF].

Hereby, we propose the preparation and application of hybrid heterogeneous catalyst characterized by the presence of an organic shell in charge of the abstraction of hydrogen during the selective oxidation of alcohols to carbonyl compounds and a metallic core able to regenerate organic shell of the catalyst (Scheme 1). We have found that deposition of sulfonated anthraquinone over Ru nanoparticles in core-shell catalyst results in selective oxidation of alcohols to aldehydes. The alcohols are selectively oxidized (oxidatively dehydrogenated) over the non-metallic anthraquinone, whereas the production of water takes place on the metallic core, in presence of oxygen. This system mimics the behavior of an electrochemical cell with oxidizing nano-anode in the form of the shell and reducing nano-cathode in the form of the core.

Experimental Section

Reagents

The chemicals RuCl3•H2O (99.9 wt%, CAS: 14898-67-0), γ-Al2O3 (99 wt%, CAS: 1344-28-1), CTAB (99 wt%, CAS: 57-09-0), NaBH4 (96 wt%, CAS: 16940-66-2), biphenyl (99.

Synthesis of Catalysts

Reverse micellar microemulsions of CTAB/1-hexanol/water (as shown in

Catalyst Characterization

The morphologies and particle size distribution of the catalysts and elemental mapping analysis has been performed using JEOL 2100 high-resolution transmission electron microscope (HRTEM) with an accelerating voltage of 200 kV. The 1 H NMR spectra were measured using a Bruker ARX 400 or ARX 100 spectrometer at 400 MHz ( 1 H) and 100 MHz ( 13 C).

Catalysis

The catalytic tests were conducted in a 30 mL autoclave. For a typical test of 1octanol oxidation, 50 mg catalysts and 3 g of 1-octanol have been added in the reactor, which was pressurized with 10 bar of O2 and heated to 100 ⁰C for 1~48 h under continuous stirring. The reference experiments with Ru NPs, pure SQ and the mixture of Ru and SQ were carried out under the same reaction conditions. Other alcohols have been oxidized in a similar way.

The catalytic oxidation of aldehyde has been performed in the same autoclave. The catalysts containing 5 mg of Ru and 0.3 g of octanal were placed in the reactor with air as oxidant at atmospheric pressure and solvent-free conditions. The mixture was stirred at 60 °C for 20 min.

The products of the reaction were analyzed using Agilent 7820A gas chromatography (GC) equipped with a HP-5 column and biphenyl as internal standard.

Cyclic voltammetry

Cyclic voltammetry (CV) was performed with a three-electrode setup controlled by a potentiostat (Reference 3000, Gamry Instruments Inc.). The synthesized catalysts containing Ru NPs or SQ were dispersed in ethanol to form a well-dispersed ink (10 mg/ml) using Nafion 117 solution (5 wt%) as a binder. 100 μL of the ink was deposited onto a polished and pre-cleaned glassy-carbon electrode with a working area of 0.1256 cm 2 . For Ru@SQ-80%, the working electrode was prepared by coating of electrode surface by 20 μL Ru NPs and subsequently 80 μL SQ ink. Ag/Ag + was used as a reference electrode in all measurements while Pt wire as a counter electrode. CVs were carried out at 25 °C in 8 mL solution of 0.1 M LiClO4 in DMSO saturated with Ar at a constant sweep rate of 100 mV/s.

Results and Discussion

Catalytic performances

Water-in-oil microemulsions built of water, hexanol and surfactant cetyltrimethylammonium bromide (CTAB) with RuCl3 and sodium borohydride have been used for the synthesis of metal nanoparticles. Ru nanoparticles form aggregates and the size of Ru nanoparticles measured by TEM varies in the range 2-3 nm (Figure 1).

Ru@quinone catalysts with core-shell structure have been prepared using rotary evaporator for deposition of quinone over Ru nanoparticles by removal of solvent. The prepared samples are denoted as Ru@quinone-X % (X=10, 25, 50, 80), where X is the weight percentage of quinone in the samples. Figure 1 demonstrates TEM images of Ru nanoparticles coated by different amount of disodium anthraquinone-2,6disulfonate (SQ) in Ru@SQ catalysts. There is a clear contrast between the heavier atom of Ru in the core and the lighter SQ shell. Increase of the content of SQ phase leads to increase of the thickness of the shell from 1 to 3 nm.

The catalytic performance of core-shell catalysts with different content of SQ has been compared with the reference Ru nanoparticles and pure SQ in selective oxidation of 1-octanol. Besides aldehyde as the main product of the reaction, there is an octanoic acid as the product of deeper oxidation of aldehyde and octyl octanoate as the product of further esterification (Scheme 2). 1-Octanol in the presence of acid also undergoes etherification reaction to dioctyl ether.

The catalytic activity of 1-octanol oxidation is the highest over Ru NPs with decrease of the activity after deposition of SQ (Figure 2). Increase of SQ loading leads to decrease of the catalytic activity. Almost no activity has been observed for pure SQ.

Thus, presence of Ru NPs in the core of the catalyst affects the catalytic activity in alcohol oxidation. Comparison of the catalytic activity of core-shell Ru@SQ-80% with mechanical mixture Ru+SQ-80% indicates on SQ coating as the reason of low activity (Figure 2). It is interesting to note that activity normalized by Ru is comparable in a series of core-shell Ru@SQ catalysts (Figure 2). It means that the thickness of SQ coating does not affect the catalytic activity and the rate limiting step could be in Ru-SQ interface zone. Non-coated Ru NPs provide significantly higher activity indicating on different mechanism of oxidation with and without SQ coating.

The parent Ru NPs demonstrate (Figure S1, SI) strong decrease of the selectivity to octanal with increase of the conversion of 1-octanol with formation of acid and ester as side products. Figure 3 shows comparison of the selectivities over Ru NPs with coreshell Ru@SQ catalysts at the similar conversions about 60 %. At this conversion, the selectivity to octanal is only about 20 % over Ru NPs. Pure SQ provided even lower selectivity due to intensive over-oxidation to acid and ester. It is interesting to note that the selectivity to octanal was gradually increasing with increase of the content of SQ in the core-shell catalysts from 30 % for Ru@SQ-10% to 74 % for Ru@SQ-80%. Thus, the selectivity increases up to 3 times in comparison with pure Ru NPs and SQ. The catalysts with low loading of SQ still could contain accessible Ru surface, which explains lower selectivity. High selectivity at high SQ loading could be explained by full coverage of Ru surface by SQ.

Usually the aldehyde formation during 1-octanol oxidation is accompanied by subsequent non-catalytic and catalytic oxidation, which results in the formation of acid and esters. In our previous study of alcohols oxidation over Ru NPs we have demonstrated protective role of RuOx species from adsorption and deeper oxidation of aldehydes to acids [START_REF] Zhao | Selective oxidation of alcohols to carbonyl compounds over small size colloidal Ru nanoparticles[END_REF]. Similarly, the presence of SQ coating markedly reduces the exposure of active Ru NPs, which is likely to suppress the deep catalytic oxidation reaction. In order to verify this concept, we have conducted oxidation of 1-octanol using mechanical mixture of Ru NPs with 80 % of SQ (Ru+SQ-80%). It is interesting to note that the selectivity to aldehyde was significantly lower than in the case of coreshell system and comparable with Ru NPs.

SQ is almost insoluble in 1-octanol, however, it could be soluble during the catalytic reaction in the presence of water. The catalytic stability has been studied by separation of the catalyst Ru@SQ-80% after the first cycle with subsequent test using fresh 1-octanol for different reaction time to provide comparable conversions. Figure S2, SI demonstrates decrease of the selectivity to octanal from 75 to 37 % for the second cycle at the selectivity 23 % for pure Ru NPs. It means partial dissolution of SQ during the catalytic reaction, which makes catalytic performance similar to Ru NPs. It is interesting to note that the catalytic performance of Ru@SQ-80% after two cycles could be recovered by recoating of SQ shell (Figure S2, SI). It confirms solubility issue during the catalytic reaction for this composite material, however, provides simple way to recover the catalytic performance.

Characterization of Catalysts

Powder X-ray diffraction (XRD) has been used to study the crystallinity of the 210), ( 201) and (301), respectively, of orthorhombic phase of crystalline SQ [START_REF] Zhao | Sodium sulfonate groups substituted anthraquinone as an organic cathode for potassium batteries[END_REF][START_REF] Peake | X-Ray crystal structure determination of some sodium anthraquinone sulfonate derivatives[END_REF].

The composition and thermal stability of the Ru NPs and Ru@SQ catalysts has been examined by TGA (Figure S4, SI). The curves show weight losses in two steps.

At low temperature (25~300 o C) the weight loss is the result of removal of water, 1hexanol and CTAB used for the catalyst preparation. Subsequently, the weight losses of about 45 wt%, 23 wt%, 14 wt% and 9 wt% for Ru@SQ-X% samples (X=80, 50, 25, 10), respectively, have been observed between 400 °C and 600 °C, which could be ascribed to the combustion of SQ layer. The lower weight loss in comparison with the theoretical content of SQ should be ascribed to the generation of sodium sulfate as a product of oxidation.

XPS analysis of Ru nanoparticles covered by SQ (monolayer and 80%) in comparison with Ru nanoparticles and pure SQ has been performed to investigate the electronic state of the ruthenium species (Figure 4). According to the XPS analysis (Table S2, SI), the ratios of S/Ru in both Ru@SQ-monolayer and Ru@SQ-80% samples are 0. This peak is attenuated as well as Ru 3p doublet with the increase of SQ loading.

Structure-catalytic performances relationship

In order to understand the role of Ru in the core-shell catalyst for oxidation of alcohols, we have varied the metal core. We have used Pd and Pt nanoparticles prepared in the same way for subsequent deposition of SQ to check the effect of metal of the core on the catalytic performance during oxidation of 1-octanol. loading. Thus, one can conclude that there is no interaction between Pt or Pd and SQ in contrast to Ru nanoparticles.

Thus, strong interaction of Ru with SQ could be the key factor of high selectivity during oxidation of alcohols to carbonyl compounds. The mechanism of the reaction has been further studied using FTIR and electrochemical methods.

Mechanism

According to our earlier studies, oxidation of alcohols over Ru nanoparticles proceed according to Mars-van Krevelen mechanism by interaction of surface RuOx species over Ru nanoparticles with alcohol leading to the aldehyde formation and subsequent re-oxidation of Ru nanoparticles [START_REF] Zhao | Selective oxidation of alcohols to carbonyl compounds over small size colloidal Ru nanoparticles[END_REF]. In order to verify if SQ could be involved in this mechanism of oxidation of alcohols, we have performed the 1-octanol oxidation reaction in inert atmosphere. The only product of the reaction is octanal. The key question in this case is how Ru@SQ catalyst provides oxidative dehydrogenation of alcohols. In-situ FTIR has been used to study the state of SQ during interaction with alcohol. FTIR spectrum of parent SQ (Figure 7) shows the peak at 1277 cm -1 attributed to the sulfonate group [START_REF] Zhao | Sodium sulfonate groups substituted anthraquinone as an organic cathode for potassium batteries[END_REF]. The peak at 1514 cm -1 can be assigned to the stretching vibration of aromatic conjugate C=C band [START_REF] Wang | Fast and efficient oil-water separation under harsh conditions of the flexible polyimide aerogel containing benzimidazole structure[END_REF]. The strong characteristic peaks at 1695 cm -1 and 1624 cm -1 can be assigned to the stretching C=O vibrations in non-chelated and a chelated quinone carbonyl group, respectively [START_REF] Demagos | New anthraquinones and anthraquinone glycosides from Morinda lucida[END_REF].

The non-chelated quinone group disappears after core-shell structure fabrication, which could be explained by strong interaction between C=O and Ru NPs in accordance with XPS results (Figure 4). It is interesting to note that the spectrum of mechanical mixture of SQ with Ru is similar to pure SQ and confirms specific interaction of SQ with Ru only in core-shell material (Figure S8, SI).

Presence of hydrogen in IR cell leads to decrease of the intensity of the C=O group at 1624 cm -1 , which could be recovered after the heating treatment at 100 °C in vacuum.

It indicates on easy reduction of C=O to C-OH and subsequent decomposition in the absence of hydrogen.

Pure SQ and mechanical mixture of SQ with Ru does not show any interaction with hydrogen (Figure S8, SI). Hydrogenation of SQ could be initiated by hydrogen dissociation over Ru [START_REF] Rose | Nature of the dissociation sites of hydrogen molecules on Ru (001)[END_REF] with subsequent hydrogen transfer to SQ through Ru-O-SQ linkers. In order to study hydrogen transfer from alcohol molecule, we have introduced furfuryl alcohol vapors in the cell with subsequent heating from 25 to 100 °C (Figure 7). The carbonyl group characterized by the peak located at 1624 cm -1 started to decrease in intensity at 80 °C in comparison with no effect for pure SQ or mechanical mixture Ru+SQ-80% (Figure S8 to the two consecutive one-electron reversible transfer process of the oxydo-reduction of anthraquinones to hydroquinone (Figure 8, Table 1). However, when 0.1 M of furfuryl alcohol (FA) is added a 3 rd anodic wave occurs at -0.14 V for SQ-FA and at -0.21 V for Ru@SQ-80%-FA corresponding to the oxidation of FA.

At the same time, blank Ru NPs/GC and bare GC electrodes have no CVs responses (Figure S9, SI). For the Ru@SQ-80%-FA, the lowest oxydo-reduction peak around -1.62 V shifts to higher voltage -1.25 V, which shows that only one electron transfer is involved in the oxidation of FA. This leads to increase of the current density of FA oxidation at -0.21 V. Moreover, the resulting current density for FA oxidation over Ru@SQ-80% is much higher in comparison with pure SQ. The negative shift and higher current density of this peak for Ru@SQ-80% combined with the shift of the peak of SQ to higher voltages indicates increase of the catalytic activity of Ru@SQ-80% in comparison to pure SQ for the oxidation of FA. The improved electrocatalytic activity in oxidation of FA could be due to the presence of Ru in the core, which accelerates the electron transfer via improved conductivity and change of the electronic state of SQ in the core-shell catalyst observed by FTIR and XPS.

Substrate Scope

The selective oxidation of a wide range of alcohols has been studied over Ru@SQ-80% catalyst in the presence of O2. For benzyl alcohol, methyl-substituted and chlorinated benzylic alcohol conversions of 92 %, 95 % and 95 % have been achieved within 6 h, respectively (Table 2). The selectivity to the target products was higher than 95 %. Similarly, unsaturated cinnamyl alcohol was converted to cinnamaldehyde with 95 % selectivity. In the case of oxidation of furfuryl alcohol and 2,5hydroxymethylfurfural (HMF) the selectivity about 90 % was achieved to furfural and 2,5-diformylfuran (DFF), respectively, at high conversion. Non-activated aliphatic alcohol (i.e., 1-octanol) and cyclic alcohol (i.e., cyclohexanol) over Ru@SQ-80% have been converted to carbonyl compounds with a moderate activity and excellent selectivity. Secondary 2-octanol, can be oxidized with a conversion of >90 % and selectivity of 95 % to corresponding ketone, which is comparable to the selectivity achieved using TEMPO [START_REF] Cecchetto | Efficient Mn-Cu and Mn-Co-TEMPOcatalysed oxidation of alcohols into aldehydes and ketones by oxygen under mild conditions[END_REF].

The excellent catalytic activity towards various oxygenate substrates demonstrates that the uniform organic shell around the metal nanoparticles suppressed over-oxidation of aldehydes toward acids and esters. Nanocell Ru@SQ exhibits much better catalytic behavior than conventional Ru catalysts [START_REF] Corberán | Green oxidation of fatty alcohols: Challenges and opportunities[END_REF]. Isolation of metal nanoparticles from direct contact with alcohols decreases activity, however, results in significant increase of the selectivity toward carbonyl compounds. The catalytic system can be further optimized by variation of the shell type for more efficient alcohols dehydrogenation and hydrogen transfer to combine high activity and selectivity of the catalyst.

Conclusion

In conclusion, we have demonstrated that it is possible to build nanocell with coreshell structure containing Ru nanoparticles in the core and electro-deficient anthraquinones in the shell for selective oxidation of alcohols to carbonyl compounds.

XPS analysis shows strong interaction between quinone species and Ru nanoparticles leading to transfer of the electronic density to Ru and easy activation of alcohols over the shell. In-situ mechanism study confirms transfer of hydrogen to carbonyl groups of quinone species from alcohol with subsequent transfer to the core. This concept can be used for other applications, where contact of the target product of the reaction with metal results in decrease of the selectivity. 1277 cm -1 1374 cm -1 1514 cm -1 1624 cm -1 1695 cm -1 Ru@SQ-80% Ru@SQ-80%-FA SQ SQ-FA b Reaction conditions: catalyst 50.0 mg, toluene 1.0 g + ethanol 1.0 g as solvent.

E pa3 E pa2 E pa1 E pc1 E pc2
c Reaction conditions: catalyst 50.0 mg, solvent-free. 0.14 0.12 0.12 0.10 0.12 0.07 0.08 0.10 0.06 Note: This table is robustness test results from equation (1) using fixed-effect method for column (1)-(3) and random-effect method for column (4)- [START_REF] Hackett | Highactivity, single-site mesoporous Pd/Al2O3 catalysts for selective aerobic oxidation of allylic alcohols[END_REF]. Please see Table 1 for the description of variables. Robust t-statistics are in parentheses. ***, **, and * denotes significance in 1%, 5%, and 10% levels respectively. 29 3)) and Hausman test fixed-effects vs. random effects (column (4)-( 9)). Please see Table 1 for the description of variables. Robust t-statistics are in parentheses. ***, **, and * denotes significance at 1%, 5%, and 10% levels respectively.

X

  -ray diffraction (XRD) was used to characterize the lattice structure. XRD patterns were recorded on a Rigaku D/max-2200/PC diffractometer using Cu Kα radiation (λ = 1.5418 Å) operating at 20 kV. X-ray photoelectron spectroscopy (XPS) spectra were acquired using a Thermo Scientific ESCALAB 250Xi X-ray Photoelectron Spectrometer incorporating a 165 mm hemispherical electron energy analyzer. The incident radiation is Monochromatic Al Kα X-rays (1486.6 eV) at 225 W (15 kV, 15 ma). The deconvolution was performed on Thermo Scientific Avantage Software.Thermogravimetric analysis (TGA) measurements were performed using a SDT 2960 analyzer from TA instrument under air flow (50 mL/min) with a ramping rate of temperature of 10 °C/min.In-situ FTIR spectra were recorded using a Thermo Fisher Scientific Nicolet 6700 FTIR (16 scans at a resolution of 4 cm -1 ) equipped with MCT detector, high-vacuum system and heating zone. The catalyst pellet has been pretreated at 150 o C for 1 h in vacuum at 10 -5 Torr and cooled down to room temperature. The catalyst has been treated by 20 Torr hydrogen or furfuryl alcohol vapors at 25 o C~100 o C for 20 min.

  Figure S5, SI demonstrates selectivity-conversion curves for Pd@SQ and Pt@SQ catalysts with different content of SQ in comparison with Pd and Pt nanoparticles. In comparison with Ru catalysts, the deposition of SQ over Pt and Pd leads either to low effect in selectivity or significant decrease of the selectivity to aldehyde with increase of the contribution of acid and ester. Pt and Pd are well-known catalysts for hydrogenation/dehydrogenation reactions in comparison with Ru, which is used for hydrogenolysis reactions. Pt and Pd nanoparticles do not demonstrate strong interaction with SQ as demonstrated by XPS analysis of the samples before and after SQ impregnation (Figure S6, SI). The reason could be in strong oxophiliticy of Ru leading to easy adsorption of oxygen on the surface with formation of Ru-O species. In order to confirm it, we have examined O 1s XPS spectra. SQ covered Pt and Pd nanoparticles in O 1s spectra do not show peak around 530 eV, which has been assigned to Me-O species (Figure S7, SI). Pd 3d and Pt 4f spectra demonstrate the metallic state of the elements with no changes after SQ

Figure 5

 5 Figure5demonstrates the conversion of 1-octanol depending on the content of SQ in the catalyst. The yield of octanal was gradually decreasing from 9 to 1 % with increase of the content of SQ up to 80 %. It indicates on different mechanism of alcohol oxidation in this case and absence of direct contact of 1-octanol with Ru core.In addition, considering alcohols oxidation to acids as consecutive reaction with intermediate aldehydes formation, the higher selectivity to octanal could be explained by suppression of further aldehyde oxidation over core-shell catalysts. In order to support this assumption, we have performed model reaction of octanal oxidation at mild reaction conditions to avoid autoxidation (Figure6). Blank experiments without Ru species show almost no conversion of octanal at 60 o C and air instead of oxygen. Ru NPs provide conversion of octanal 26 % to acid. Increase of the amount of coated SQ leads to suppression of octanal oxidation and correlates with the results of 1-octanol accessibility to Ru core. It proves that SQ shell protects Ru core from interaction with aldehydes and suppresses over-oxidation, which could be the reason of high selectivity.

  , SI). Thus, carbonyl group of SQ in core-shell catalyst can be involved in hydrogen transfer from alcohol with generation of aldehyde and hydrogenated carbonyl group in the shell. Subsequent transfer of hydrogen through carbonyl group of SQ to Ru and decomposition with regeneration of C=O in SQ could be proposed as mechanism of oxidation of alcohols without direct contact of metal with alcohol (Scheme 1).The advantage of SQ in comparison with the strong electrophilic organic scavengers like TEMPO or DDQ is its intermediate reduction potential leading to lower stability of hydrogenated form, which results in efficient hydrogen transfer and regeneration of SQ over Ru surface.Electrochemical experiments have been used to further evaluate the state of SQ in the core-shell catalyst. Cyclic voltammograms (CVs) of the bare glassy carbon (GC) electrode, Ru NPs/GC, SQ/GC, and Ru@SQ-80%/GC electrodes in Ar-saturated DMSO solution with 0.1 M LiClO4 as electrolyte were studied in the presence/absence of 0.1 M furfuryl alcohol (FA). The cyclic voltammetry data for SQ are characterized by two anodic and cathodic waves between -1.6 V and -1 V vs Ag/Ag + corresponding

Figure 1 .

 1 Figure 1. TEM images of (a) Ru NPs; (b) SQ; (c~f) Ru@SQ-X% catalysts, X=10, 25, 50, 80.

Figure 6 .

 6 Figure 6. Oxidation of 1-octanal with different catalysts. Reaction conditions: amount of catalyst equivalent to 5 mg of Ru, 0.3 g octanal, solvent-free, air atmospheric pressure, T=60 o C, 20 min.

Figure 7 .

 7 Figure 7. In-situ IR spectra of Ru@SQ-80% by H2 and furfuryl alcohol (FA) treatment at different temperatures

Figure 8 .Scheme 1 .Scheme 2 .Scheme 3 .

 8123 Figure 8. Cyclic voltammograms of the studied catalysts on a glassy carbon electrode in 0.1 M LiClO4 in the DMSO solution with/without 0.1 M furfuryl alcohol (FA) inside in the range of -2.0 to 0.8 V at 100 mV/s scan rate.

a

  Reaction conditions: catalyst 50.0 mg, toluene 2.0 g as solvent.

Table S1 ,

 S1 SI) have been prepared[15, ]. Briefly, 10 g of microemulsion B containing 0.14 g

	NaBH4 has been dropwise added to 10 g of microemulsion A containing 0.2 g RuCl3
	during 1 h under vigorous stirring. Ru nanoparticles with uniform size distribution have
	been formed inside the micelles. The catalyst Ru NPs has been separated by
	centrifugation, washed with hot water for 5 times and dried at 60 °C in vacuum oven
	for 12 h.
	The catalysts Ru@SQ with varied shell thickness have been prepared by
	deposition of SQ over Ru NPs. Briefly, different amounts of SQ have been
	ultrasonically dissolved in 3 mL of water and subsequently mixed with 100 mg of Ru
	NPs. The water has been removed from resulting slurry by rotary evaporator and

consequently dried at 60 °C in a vacuum oven overnight. A series of samples Ru@SQ-X% (X = 10, 25, 50 and 80) have been prepared, where X is the theoretical weight percentage of SQ. The sample with monolayer coating Ru@SQ-monolayer has been prepared by deposition of 2 wt. % of SQ over Ru NPs.

  ] groups in SQ. Ru NPs demonstrate a similar O 1s peak with 531.8 eV BE, which is associated with RuO2 or surface Ru(OH)3[START_REF] Ananth | A dielectric barrier discharge (DBD) plasma reactor: an efficient tool to prepare novel RuO2 nanorods[END_REF]. SQ coating over Ru NPs leads to appearance of two additional peaks: the broad peak at 534.1 eV, which can be assigned to oxygen in sulfo groups[START_REF] Lim | Potentiostatically deposited polypyrrole/graphene decorated nano-manganese oxide ternary film for supercapacitors[END_REF], and well defined peak at 530.2 eV (529.8 eV after 80% SQ loading). The 530.2 eV peak we associate with the bridge Ru-O-SQ species, which appearance indicates strong interaction between SQ and Ru (Scheme 3).

1:1.0 and 2.3:1.0, respectively, which correlates well with the difference in SQ loading. Ru 3p core level spectra show the presence of ruthenium in two oxidation states: metallic Ru 0 (Ru 3p3/2 BE 462.0-463.3 eV) and lower contribution of oxidized Ru species with lower electronic density (Ru 3p3/2 BE 464.6-465.5 eV). This assignment was made according to earlier studies of various Ru compounds including metallic Ru, RuO2 and Ru(OH)3 demonstrating different Ru 3p3/2 BEs [32]. After SQ deposition over the surface of Ru NPs, the metallic Ru 3p doublet shifts to lower binding energy values. Additionally, the oxidized Ru peak appears demonstrating partial oxidation of Ru. Increase of SQ deposition leads to decrease of the intensity of Ru peaks due to the attenuation of Ru signal by SQ shell. It should be noted that with the increase of SQ coating the metal Ru 3p doublet shifts to lower binding energy values from 462.7 eV to 462 eV. This shift can be associated with the effect of electron transfer from SQ to Ru leading to increase of the electronic density over Ru.

Pure SQ sample demonstrates only one O 1s peak at 531.8 eV although it is expected to have two types of oxygen in SO3 2-and C=O. Most probably it is due to the strong interaction and electron transfer between oxygen in SO3 2-

[START_REF] Zhao | Sodium sulfonate groups substituted anthraquinone as an organic cathode for potassium batteries[END_REF]

and oxygen in C=O

[START_REF] Peake | X-Ray crystal structure determination of some sodium anthraquinone sulfonate derivatives[END_REF]

Table 1 .

 1 The values of cathodic Epc and anodic Epa peak potentials in DMSO solution.

		Anodic potential (V vs. Ag/Ag + ) Cathodic potential (V vs Ag/Ag + )
		Epa1	Epa2	Epa3	Epc1	Epc2
	SQ	-1.54	-1.13		-1.62	-1.19
	SQ-FA	-1.51	-1.08	-0.14	-1.61	-1.18
	Ru@SQ-80%	-1.56	-1.11		-1.71	-1.22
	Ru@SQ-80%-FA	-1.12		-0.21	-1.25	-1.05

Table 2 .

 2 Substrate scope oxidation by Ru@SQ-80%

	Alcohols	Alcohols

Table 1 .

 1 Descriptive statistics and variable explanations

	Variable	Explanation

Table 2 .

 2 Percentage of Islamic financing (scaled by total financing) across countries

			Equity (PLS) financing		Mark-up and other (Non-PLS) financing
	Country	# Banks	Mudaraba	Musharaka	Murabaha	Ijara Diminishing Musharaka	Qard	Others
			(1)

  mudaraba = profit-sharing; musharaka = partnership; murabaha = cost-plus financing; ijara = leasing; diminishing musharaka = partnership with gradual ownership process; qard = benevolent loan.

	Bahrain	9	4.76	6.43	64.54	22.74	0.00	0.00	1.54
	Bangladesh	6	1.01	0.11	62.20	4.46	13.65	2.18	52.14
	Brunei Darussalam	1	0.00	0.46	83.80	10.49	0.00	0.04	78.03
	Indonesia	8	9.46	30.09	56.00	0.30	0.00	3.67	0.47
	Islamic Republic of Iran 4	23.01	25.82	15.32	1.16	9.11	2.27	11.95
	Jordan	3	0.28	0.54	68.90	28.12	0.00	0.27	1.90
	Kuwait	5	0.00	0.00	86.96	12.95	0.00	0.00	0.09
	Malaysia	17	0.11	3.90	48.05	24.20	0.00	0.04	56.19
	Pakistan	10	0.56	0.74	34.88	25.15	22.90	0.01	15.75
	Qatar	4	1.08	0.47	68.53	19.87	0.04	0.00	10.01
	Saudi Arabia	3	0.00	2.39	94.66	0.87	0.00	0.00	20.86
	Sudan	6	2.69	6.23	74.24	2.72	0.00	0.00	14.12
	Tunisia	1	0.00	0.00	70.56	1.59	0.00	0.17	27.68
	United Arab Emirates	6	5.13	3.06	54.29	24.34	0.00	0.89	12.30
	United Kingdom	4	0.44	0.66	87.79	1.26	0.00	0.00	9.85
	Yemen	1	24.25	8.04	57.64	1.38	0.00	0.00	8.69
	Total	88
	Average		2.77	4.88	57.99	17.29	3.78	0.43	23.38
	Note:

Table 3 .

 3 Impact of SSB on equity financing

	EqFinTL	EqFinTA	EqFinNon
	(1)

  This table is estimation results from equation (1) using fixed-effect method. Please see Table1for the description of variables. Robust t-statistics are in parentheses. ***, **, and * denotes significance in 1%, 5%, and 10% levels respectively.

										)
	INFL	0.0891***	0.0799**	0.0734**	0.0493*	0.0432*	0.0403	0.222*	0.214*	0.194
		(2.66)	(2.38)	(2.26)	(1.94)	(1.68)	(1.60)	(1.81)	(1.73)	(1.61)
	GGDP	-0.102	-0.0855	-0.0960	-0.0999	-0.0894	-0.0939	-0.277	-0.260	-0.295
		(-0.93)	(-0.79)	(-0.85)	(-1.03)	(-0.92)	(-0.95)	(-0.99)	(-0.93)	(-1.05)
	HHI	-0.0356	0.0131	0.0148	0.0293	0.0610	0.0619	-0.297	-0.250	-0.249
		(-0.30)	(0.10)	(0.11)	(0.37)	(0.69)	(0.70)	(-0.62)	(-0.50)	(-0.50)
	GDP	0.0129	-0.0195	0.00360	0.0566	0.0385	0.0498	-0.0700	-0.114	-0.0699
		(0.19)	(-0.26)	(0.04)	(1.13)	(0.69)	(0.81)	(-0.37)	(-0.60)	(-0.36)
	Constant	-0.771	-0.0217	-0.582	-1.746	-1.329	-1.604	0.729	1.750	0.680
		(-0.41)	(-0.01)	(-0.26)	(-1.30)	(-0.88)	(-0.99)	(0.15)	(0.37)	(0.14)
	Year FE	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	N	381	381	381	381	381	381	381	381	381
	R-squared	0.09	0.11	0.07	0.09	0.09	0.07	0.05	0.06	0.06
	Note:

Table 4 .

 4 The interaction of SSB and BOD This table is estimation results from equation (2) using fixed-effect method. Please see Table1for the description of variables. Bank-level and country level controls are not shown to save space. Robust t-statistics are in parentheses. ***, **, and * denotes significance in 1%, 5%, and 10% levels respectively.

	'BOD' =

Table 5 .

 5 The SSB and institutional environments This table is estimation results from equation (2) using fixed-effect method. Please see Table1for the description of variables. Bank-level and country level controls are not shown to save space. Robust t-statistics are in parentheses. ***, **, and * denotes significance in 1%, 5%, and 10% levels respectively.

	'InstEnv' =

Table 6 .

 6 The SSB and Islamic environments This table is estimation results from equation (3) using random-effect method. Please see Table1for the description of variables. Robust t-statistics are in parentheses. ***, **, and * denotes significance in 1%, 5%, and 10% levels respectively.

				'IslamicEnv' =
		ShareIB	MPOP	ShareIB	MPOP	ShareIB	MPOP
		(1)	(2)	(3)	(4)	(5)	(6)
	Size_SSB (β1)	0.0389** 0.0473**
		(2.23)	(2.37)
	Duality_SSB (β1)			0.0643*	0.0704*
				(1.66)	(1.80)
	ShariahDept_SSB (β1)					-0.0299* 0.0462
						(-1.71)	(1.37)
	'IslamicEnv' (β2)	0.280*** 0.167*** 0.0867	0.139***	0.100	0.166***
		(3.72)	(3.34)	(1.33)	(3.16)	(1.16)	(3.29)
	Size_SSB * 'IslamicEnv' (β1*β2)	-0.344*** -0.112**
		(-8.14)	(-2.08)
	Duality_SSB * 'IslamicEnv'' (β1*β2)			-0.150**	-0.199***
				(-2.01)	(-3.09)
	ShariahDept_SSB * 'IslamicEnv'' (β1*β2)					-0.0821	-0.132***
						(-0.75)	(-2.74)
	Lag ROA	-0.0488	-0.104		0.0381	0.0385	0.00848
		(-0.17)	(-0.37)	(0.43)	(0.17)	(0.13)	(0.03)
	Lag EQTA	-0.0698	-0.0778	-0.0558	-0.0354	-0.0565	-0.0306
		(-1.10)	(-1.24)	(-0.90)	(-0.59)	(-0.90)	(-0.51)
	Lag LLP	0.000851 0.0449	0.0485	0.0680	0.0236	0.0538
		(0.01)	(0.47)	(0.60)	(0.82)	(0.25)	(0.54)
	Size	0.000362 0.0136	0.00632	0.0159	0.00870	0.0179
		(0.03)	(1.03)	(0.45)	(1.06)	(0.62)	(1.22)
	INFL	0.0762** 0.0796** 0.0720**	0.0684**	0.0702** 0.0587*
		(2.46)	(2.42)	(2.31)	(2.19)	(2.28)	(1.95)
	GGDP	-0.134	-0.114	-0.104	-0.105	-0.105	-0.112
		(-1.25)	(-1.05)	(-0.97)	(-0.98)	(-0.95)	(-1.02)
	HHI	-0.0371	0.00716	-0.0187	0.00895	-0.0338	0.0295
		(-0.42)	(0.08)	(-0.17)	(0.09)	(-0.31)	(0.28)
	GDP	0.0242	0.0214	0.0237	0.0227	0.0204	0.0265
		(1.53)	(1.34)	(1.43)	(1.48)	(1.23)	(1.54)
	Constant	-0.548	-0.712	-0.612	-0.770	-0.543	-0.910*
		(-1.25)	(-1.47)	(-1.34)	(-1.55)	(-1.16)	(-1.69)
	Wald test
	1. β1 + (β1*β2)	-0.305*** -0.0643	-0.0852	-0.128*** -0.112	-0.087***
		(-8.03)	(-1.30)	(-1.40)	(-2.99)	(-1.07)	(-2.94)
	2. β2 + (β1*β2)	-0.0638	0.0552	-0.0628***	-0.0602*	0.0181	0.0343
		(-1.54)	(1.19)	(-1.02)	(-0.97)	(0.27)	(0.77)
	Year FE	Yes	Yes	Yes	Yes	Yes	Yes
	N obs.	381	381	381	381	381	381
	N banks	83	83	83	83	83	83
	R-sq.	0.21	0.07	0.02	0.03	0.03	0.05
	Note:

Table 7 .

 7 Robustness: Changing bank-fundamental control variables This table is robustness test results from equation (1) using fixed-effect method. Please see Table1for the description of variables. Robust t-statistics are in parentheses. ***, **, and * denotes significance in 1%, 5%, and 10% levels respectively.

	EqFinTL

Table 8 .

 8 Robustness: Islamic banking market competition, country fixed effect, and random effect technique

	EqFinTL

Table 9 .

 9 Robustness: Arellano and Bond's (1991) GMM estimation This table displays robustness test results from equation (1) transformation using Arellano and Bond's (1991) GMM estimation method. Please see Table1for the description of variables. Robust t-statistics are in parentheses. ***, **, and * denotes significance at 1%, 5%, and 10% levels respectively.

		EqFinTL			EqFinTA			EqFinNon
		(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)	(9)
	NumberSSB	-0.00431			-0.00536			-0.0537
		(-0.228)			(-0.408)			(-0.763)
	DualitySSB		0.0150			0.0193*			0.0598
			(1.037)			(1.860)			(1.261)
	ShariaDeptSSB			-0.0652***			0.0138			-0.286***
				(-3.720)			(0.924)			(-5.388)
	Lag EqFinTL	0.717***	0.692***	0.702***
		(10.51)	(10.15)	(10.72)
	Lag EqFinTA				0.703***	0.679***	0.699***
					(4.588)	(4.282)	(4.301)
	Lag EqFinNon							0.541***	0.517**	0.510**
								(2.674)	(2.446)	(2.467)
	Constant	-0.718	-0.689	-0.841	-0.285	-0.281	-0.322	2.410	2.210	1.114
		(-0.466)	(-0.463)	(-0.575)	(-0.216)	(-0.223)	(-0.258)	(0.681)	(0.660)	(0.356)
	Sargan (p-value)	0.296	0.272	0.289	0.441	0.354	0.419	0.045	0.015	0.018
	AR(2) (p-value)	0.187	0.159	0.217	0.909	0.927	0.853	0.191	0.133	0.135
	Year FE	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	Bank-level controls	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	Country-level controls	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	N obs.	269	269	269	269	269	269	269	269	269
	N banks	74	74	74	74	74	74	74	74	74
	Note:

Table A1 .

 A1 Specification test results This table displays specification test results, containing the Breusch Pagan LM test (column (1)-(

		RE	RE	RE	FE	RE	FE	RE	FE	RE
		(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)	(9)
	NumberSSB	0.0244			0.0303***	0.0244**
		(1.257)			(3.160)	(2.576)
	DualitySSB		0.0617				0.0747***	0.0617***
			(1.611)				(4.049)	(3.431)
	ShariaDeptSSB			-0.0437**					-0.0890*	-0.0437
				(-2.405)					(-1.790)	(-1.402)
	Constant	-0.523	-0.564	-0.422	-0.788	-0.523	-0.0438	-0.564	-0.604	-0.422
		(-1.138)	(-1.249)	(-0.937)	(-0.453)	(-1.255)	(-0.0254)	(-1.345)	(-0.343)	(-0.996)
	Breusch Pagan LM Test (p-value)	0.0000	0.0000	0.0000
	Hausman Test FE vs. RE (p-value)				0.0000		0.0000		0.0468
	Year FE	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	Bank-level controls	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	Country-level controls	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
	N obs.	381	381	381	381	381	381	381	381	381
	N banks	83	83	83	83	83	83	83	83	83
	R-sq.	0.01	0.01	0.01	0.094	0.01	0.113	0.01	0.073	0.01
	Note:

Acknowledgments

J.P. Zhao thanks Solvay and CIFRE (2016-1082) for providing him a stipend for PhD study