PhD Alice Bellicha

MD Muriel Coupaye

MSc Léonore Hocquaux

MSc Fanny Speter

MD Jean-Michel Oppert

MD, PhD Christine Poitou
email: christine.poitou-bernert@aphp.fr

Prof Christine Poitou

Increasing physical activity in adult women with Prader-Willi syndrome: a transferability study

Keywords: Obesity, Prader-Willi syndrome, Physical activity, Exercise training, Accelerometers

Background:

We aimed 1) to objectively quantify spontaneous physical activity (PA) in adult patients with Prader-Willi syndrome (PWS) and 2) to evaluate the transferability of a home-based exercise training program in these patients.

Method: Physical activity was compared between 10 adult women with PWS (PWS group) and 20 adult women with non-syndromic obesity (CON group, for cross-sectional comparison). In the PWS group, PA, body composition, walking capacity, quality of life and eating behavior were then compared before and after a 16-week supervised exercise program.

Results:

The PWS group displayed lower PA and higher sedentary time compared to the CON group. Median attendance to exercise sessions reached 100% (Q1-Q3: 97-100%) sessions. Moderate-to-vigorous PA and walking capacity increased after the program without significant effect on body composition.

Conclusion:

Supervised home-based exercise sessions are an effective strategy to improve PA in women with PWS who are less active than women matched for adiposity.

Introduction

Prader-Willi syndrome (PWS) is the most frequent genetic syndrome causing marked obesity [START_REF] Driscoll | [END_REF] with a prevalence between one in 20,000 to one in 30,000 births [START_REF] Bar | Early diagnosis and care is achieved but should be improved in infants with Prader-Willi syndrome[END_REF][START_REF] Lionti | A population-based profile of 160 Australians with Prader-Willi syndrome: trends in diagnosis, birth prevalence and birth characteristics[END_REF]. PWS is a complex genetic neurodevelopmental disorder caused by an absence of expression of paternal-origin imprinted alleles on chromosome 15 [START_REF] Driscoll | [END_REF]. PWS is characterized by hyperphagia, hypotonia and early fat mass gain as well as decreased motor competencies and physical fitness [START_REF] Capodaglio | Strength characterization of knee flexor and extensor muscles in Prader-Willi and obese patients[END_REF][START_REF] Gross | Physical activity and maximal oxygen uptake in adults with Prader-Willi syndrome[END_REF][START_REF] Lloret-Linares | Comparison of body composition, basal metabolic rate and metabolic outcomes of adults with Prader Willi syndrome or lesional hypothalamic disease, with primary obesity[END_REF].

Subsequently, patients with PWS are prone to develop obesity with severe complications, such as cardiac or respiratory failure as well as physical disabilities [START_REF] Cassidy | Prader-Willi syndrome[END_REF].

Behavioral approaches for the management of PWS include the promotion of physical activity (PA) [START_REF] Goldstone | speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with[END_REF]; however, day-to-day management of these patients with cognitive, and sometimes psychiatric disorders, is particularly challenging and little is known about PA interventions in this population.

In line with current PA guidelines for the general population [START_REF] Pagac | Physical Activity Guidelines Advisory Comittee Report[END_REF], adult patients with obesity are advised to progressively reach a minimum of 150 min of moderate-intensity PA (MVPA) per week consisting of bouts of at least 10 min [START_REF] Garvey | American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity[END_REF][START_REF] Jensen | AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society[END_REF]. In a recent study using accelerometers for the objective assessment of PA, only 15% of adult women with PWS met these recommendations [START_REF] Nordstrom | Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome[END_REF]. This is in agreement with studies that reported a high prevalence of physical inactivity in women with non-syndromic obesity [START_REF] Tudor-Locke | Accelerometer profiles of physical activity and inactivity in normal weight, overweight, and obese U.S. men and women[END_REF]. However, given that no comparison was made with a control group of subjects without intellectual disability in the study by Nordstrom et al., it is unclear whether PA is lower in women with PWS compared to women with non-syndromic obesity.

Studies conducted in children and adolescents with PWS reported 30% to 55% lower levels of objectively-measured PA compared to both normal-weight and non-syndromic obese controls [START_REF] Castner | Patterns of habitual physical activity in youth with and without Prader-Willi Syndrome[END_REF][START_REF] Eiholzer | Improving body composition and physical activity in Prader-Willi Syndrome[END_REF][START_REF] Van Den Berg-Emons | Everyday physical activity and adiposity in Prader-Willi syndrome[END_REF], suggesting that the low level of PA observed in patients with PWS might be related to obesity per se as well as the physical and intellectual disabilities associated with PWS. Additionally, patterns of MVPA and sedentary behavior (i.e. performed in short or longer bouts), which have received growing attention in recent years [START_REF] Saint-Maurice | Moderate-to-Vigorous Physical Activity and All-Cause Mortality: Do Bouts Matter[END_REF][START_REF] Shiroma | Patterns of accelerometerassessed sedentary behavior in older women[END_REF], are not known in adult patients with PWS. Accelerometers are currently the monitoring method of choice for assessing habitual PA and sedentary (sitting) time, especially considering that PA selfreporting is a complex cognitive task that is particularly challenging in patients with PWS [START_REF] Shephard | Limits to the measurement of habitual physical activity by questionnaires[END_REF].

Exercise training programs have been found either to increase [START_REF] Eiholzer | Improving body composition and physical activity in Prader-Willi Syndrome[END_REF][START_REF] Schlumpf | A daily comprehensive muscle training programme increases lean mass and spontaneous activity in children with Prader-Willi syndrome after 6 months[END_REF] or maintain (Rubin, 2019b) habitual PA (i.e. spontaneous PA performed independently of exercise training) in children with PWS but this has not been assessed in adults. As recently reviewed, different types of exercise programs have been conducted in adults with PWS [START_REF] Morales | Physical exercise and Prader-Willi syndrome: A systematic review[END_REF] and most programs were supervised and performed in a residential or community setting [START_REF] Cimolin | Gait strategy in genetically obese patients: a 7-year follow up[END_REF][START_REF] Grolla | Specific treatment of Prader-Willi syndrome through cyclical rehabilitation programmes[END_REF][START_REF] Kaufman | Prader-Willi syndrome: effect of group home placement on obese patients with diabetes[END_REF][START_REF] Shields | Is strength training feasible for young people with Prader-Willi syndrome? A phase I randomised controlled trial[END_REF][START_REF] Silverthorne | Beneficial effects of exercise on aerobic capacity and body composition in adults with Prader-Willi syndrome[END_REF]. This literature review found that residential programs that are organized several times per year and include dietary restriction, a high daily amount of supervised PA and a structured environment substantially reduced body mass over a long-term period [START_REF] Cimolin | Gait strategy in genetically obese patients: a 7-year follow up[END_REF][START_REF] Grolla | Specific treatment of Prader-Willi syndrome through cyclical rehabilitation programmes[END_REF][START_REF] Kaufman | Prader-Willi syndrome: effect of group home placement on obese patients with diabetes[END_REF]. A walking program with two weekly sessions for six months was also effective to reduce body mass and body fat and to improve cardiorespiratory fitness [START_REF] Silverthorne | Beneficial effects of exercise on aerobic capacity and body composition in adults with Prader-Willi syndrome[END_REF]. Finally, a strength training program including two weekly sessions increased muscle strength [START_REF] Shields | Is strength training feasible for young people with Prader-Willi syndrome? A phase I randomised controlled trial[END_REF]. Other programs that were conducted at home for six months without any supervision led to improvements in gait patterns but not muscle strength or balance control [START_REF] Capodaglio | Postural adaptations to long-term training in Prader-Willi patients[END_REF][START_REF] Vismara | Effectiveness of a 6-month home-based training program in Prader-Willi patients[END_REF]. So far, no study has assessed the effectiveness and transferability of a home-based individually supervised exercise training program in adult patients with PWS. Due to the specific impairment of executive functions and psychopathological features in this syndrome, integration of an exercise program as part of daily routine along with individual interaction with health professionals might be especially important [START_REF] Chevalere | Executive functions and Prader-Willi syndrome: global deficit linked with intellectual level and syndrome-specific associations[END_REF]. Two case reports suggested that a home-based exercise training program supervised by a PA instructor was feasible and well-accepted by children with PWS, although mixed findings were reported on changes in body mass and body composition, habitual PA and physical fitness [START_REF] Amaro | Physiological adaptation after a 12-week physical activity program for patients with Prader-Willi syndrome: two case reports[END_REF]. A recent controlled study conducted in youth with PWS reported that a home-based exercise training program facilitated by parents improved muscle strength and gross motor skill proficiency and decreased body mass in subjects who experienced an increase in objectively-measured MVPA (Rubin, 2019a;Rubin, 2019b).

Given the lack of data on objective PA in adults with PWS vs non-syndromic obesity and on the effectiveness of home-based supervised exercise training program in adults with PWS, we aimed 1) to quantify habitual PA using accelerometers, including an analysis of MVPA and sedentary bouts, in adults with PWS and in a control group of patients with non-syndromic obesity matched on age and adiposity; 2) to evaluate the transferability and effectiveness of a home-based supervised exercise training program on habitual PA, physical fitness, and body composition.

Methods

Study design and participants

The current observational study was conducted in a standard care setting and included 10 women with PWS (PWS group) and 20 women with non-syndromic obesity (CON group) to serve as a cross-sectional comparison. Only the women from the PWS group took part in the intervention.

Participants in the PWS group were recruited from June 2016 to January 2018 among patients with PWS and referred to a reference university clinic for patients with PWS. Inclusion criteria were: genetically confirmed PWS, age between 18 and 60 years, BMI ≥ 30 kg.m -2 or body fat ≥ 40%, no treatment modifications in the previous two months, enrollment in a social security program (patient or beneficiary). Considering the low prevalence of PWS and the low number of patients meeting inclusion criteria, all available patients willing to participate were included in the study. No published data allowed sample size calculations relevant to our hypotheses. Approval was obtained from the Ethics Committee of our institution and the study was registered in the ClinicalTrials.gov Web site (Identifier: NCT03673813). Informed written consent was obtained from all subjects and caregivers prior to study inclusion. Participants in the CON group were recruited among bariatric surgery patients with non-syndromic obesity and had been included in a previous clinical trial (ClinicalTrials.gov Web site: NCT01113996). Data were collected from this group presurgery, and details of this study, which was entirely performed at our university medical center, can be found elsewhere [START_REF] Oppert | Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial[END_REF]. Each participant of the PWS group was individually matched with two control participants for gender, age and percent body fat.

Participants from the control group did not participate in the exercise program and their data were used only for cross-sectional comparison of a given set of variables (PA, body composition, handgrip strength).

To address aim 1, we performed a cross-sectional comparison between PWS and CON groups for habitual PA, body composition and handgrip strength, which were measured using similar procedures in participants from the PWS and CON groups. To address aim 2, we compared pre-and post-interventional habitual PA, walking capacity, postural stability, health-related quality of life and eating behavior in the PWS group. The primary outcomes was changes in accelerometry-assessed habitual PA after the intervention. Secondary outcomes included the changes in body composition, physical function, health-related quality of life and eating behavior following the intervention.

Habitual physical activity measurement

PA and sedentary time were measured using a tri-axial GT3x Actigraph accelerometer (Manufacturing Technology, Inc., FL, USA), as previously described [START_REF] Oppert | Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial[END_REF].

Participants were asked to wear the accelerometers at the hip using an elastic belt for seven consecutive days during all waking hours except during water-based activities. To assess habitual PA, accelerometers were worn before and after the end of the intervention, outside of the exercise training program. Therefore, exercise sessions were not included in the measurement of habitual PA. Data were considered valid when the accelerometer was worn for at least three days for at least eight hours each day. Freedson cutpoints were used to quantify sedentary behavior (<100 counts.min -1 ), light-intensity PA (100 to 1951 counts.min - 1 ) and moderate-to-vigorous PA (MVPA, ≥ 1952 counts.min -1 ) [START_REF] Freedson | Calibration of the Computer Science and Applications, Inc. accelerometer[END_REF]. Because wear time differed between PWS and CON groups, the time spent in each intensity category was expressed as the percentage of total wear time. Thus, the sum of sedentary time, lightintensity PA and MVPA equal to 100% of total wear time.

MVPA and sedentary bouts were defined as follows: MVPA bouts of one to 4 four min (MVPA1-4 min), five to nine min (MVPA5-9 min) and at least 10 min (MVPA≥ 10 min); and sedentary bouts of one to nine min (SED1-9 min), 10 to 29 min (SED10-29 min) and of at least 30 min (SED≥ 30 min). MVPA≥ 10 min bouts were defined as a minimum of 10 consecutive min above 1952 counts.min -1 with allowance of two min below this threshold (Saint-Maurice, 2018; Tudor-Locke, 2012). SED≥ 30 min bouts were defined as a minimum of 30 consecutive min below 100 counts.min -1 [START_REF] Tremblay | Sedentary Behavior Research Network (SBRN) -Terminology Consensus Project process and outcome[END_REF]. Participants reaching 150 min per week of MVPA in ≥ 10-min bouts were considered compliant with PA guidelines [START_REF] Pagac | Physical Activity Guidelines Advisory Comittee Report[END_REF].

Anthropometry and body composition measurement

Body composition was estimated by whole-body fan-beam DXA scanning (Hologic QDR 2000, Hologic, France), as previously described [START_REF] Oppert | Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial[END_REF]. Fat mass index and fat-free mass index were calculated as fat mass and lean body mass, respectively, divided by height squared (kg.m -2 ) [START_REF] Schutz | Fat-free mass index and fat mass index percentiles in Caucasians aged 18-98[END_REF].

Physical function measurement

Walking capacity was assessed with the six-min walk-test. The test was performed according to the American Thoracic Society recommendations (American Thoracic Society, 2003), with the exception of more frequent encouragements, as previously described in patients with PWS [START_REF] Nordstrom | Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome[END_REF]. Participants were asked to walk for six min and to cover as much ground as possible between two cones positioned 30 m apart. Handgrip strength was measured with a handgrip dynamometer (Jamar, Sammons Preston Rolyan, Bolingbrook, Canada). Participants sat in a chair with arms close to their sides and elbow flexed at 90° and were asked to provide 5 maximal attempts with each hand [START_REF] Roberts | A review of the measurement of grip strength in clinical and epidemiological studies: towards a standardised approach[END_REF]. The highest value obtained was kept for analyses. Static balance control was assessed using an unipedal stance test. Participants were asked to stand barefoot on one leg for as long as possible, with the eyes open and the other limb raised [START_REF] Springer | Normative values for the unipedal stance test with eyes open and closed[END_REF]. Participants performed 3 trials on each leg and the best trial was recorded. For consistency, all tests were undertaken by the same investigator (AB) for participants in the PWS group.

Quality of life, eating behavior assessment in patients with PWS

Health-related quality of life was assessed with the 12-item short-form (SF-12) questionnaire and was summarized in a physical and mental component score ranging from zero (poor) to 100 (good) [START_REF] Gandek | Cross-validation of item selection and scoring for the SF-12 Health Survey in nine countries: results from the IQOLA Project. International Quality of Life Assessment[END_REF]. Eating behavior was assessed with the Hyperphagia questionnaire, a tool specifically designed for assessing eating behavior in patients with PWS [START_REF] Dykens | Assessment of hyperphagia in Prader-Willi syndrome[END_REF]. (badminton, tennis table). To supervise intensity, PA instructors regularly asked patients to rate their level of effort and verified that patients were able to talk while performing the activity (PAGAC, 2018). Strength exercises targeting major muscle groups were performed with training equipment such as free weights or elastic bands (sit-to-stand transitions, squats, biceps and triceps curls with free weights, or rowing with an elastic band). Exercises were performed either indoors or outdoors close to home, depending on weather conditions. In addition to the training program, patients and their families were encouraged to increase habitual PA. The program was provided free of charge to the participants.

Exercise training program in patients with

Transferability of the exercise training program

Transferability was assessed using the RE-AIM framework [START_REF] Glasgow | Evaluating the public health impact of health promotion interventions: the RE-AIM framework[END_REF], as used previously by our research group in a French setting [START_REF] Bellicha | A multistage controlled intervention to increase stair climbing at work: effectiveness and process evaluation[END_REF]. The following dimensions were described: Reach (participation to exercise sessions), Effectiveness (patient and family satisfaction assessed with a five-point scale and potential adverse consequences, e.g. injuries, temper outbursts, behavioral changes), Adoption (perception of PA instructors involved in the study), Implementation (the extent to which the program was delivered as intended), and Maintenance (the number of participants who maintained the exercise sessions after the end of the study).

Procedures

For the women from the PWS group, all the measures were implemented prior to the intervention and within 2 weeks following the intervention. For the control group, data were collected at a single time point, during the pre-operative visit at our university clinic, as part of standard care.

Statistical analysis

Given the limited sample size and the non-normality of most variables, data are presented as median (25 th -75 th percentile) and non-parametric tests were used. To address aim 1, characteristics of participants in the PWS and CON groups were compared with Mann-Whitney test for continuous variables and with Chi-Square test for categorical variables. To address aim 2, characteristics of participants in the PWS group before and after the exercise training program were compared with Wilcoxon test (continuous variables) and with

McNemar test (categorical variables). Pre-to post-intervention changes were expressed as mean (SD). The null hypothesis was rejected at p<0.05. Analyses were performed using R version 3.4.3 (R Core Team, 2017).

Results

Aim 1: Comparing clinical characteristics, physical activity and sedentary behavior between women with PWS and women with non-syndromic obesity

As expected, patients with PWS were comparable to patients from the CON group in terms of age and percentage body fat but were shorter and had lower BMI, lean body mass and handgrip strength (all P < 0.05) (Table 1). Nine participants were given replacement therapy for gonadotropin deficiency and 3 participants for thyrotropin deficiency. Four participants had received growth hormone (GH) treatment during childhood, however, and none had received GH treatment in adulthood.

The accelerometer was worn during seven days in both groups for a median duration of 12.1 hours.d -1 in the PWS group and 13.5 hours.d -1 in the CON group (P<0.001) (Table 2).

Median activity counts were 37% lower in the PWS group compared to CON group (P<0.05).

Sedentary time was higher in the PWS group while light-intensity PA was lower in patients with PWS (both P < 0.001). Duration of MVPA was not significantly different between groups, although it tended to be lower in the PWS group (P = 0.11). MVPA≥ 10 min was low in both groups, with no significant difference between groups. Only two participants in the PWS group and one participant in the CON group were compliant with PA guidelines (P = 0.52).

MVPA patterns did not differ between PWS and CON groups (Fig. 1). In the PWS group, MVPA1-4 min represented on average 61% of total MVPA, MVPA5-9 min represented 21% of total MVPA and MVPA≥10 min represented 18% of total MVPA (vs. 60%, 27% and 14% in the CON group, respectively). Sedentary patterns differed between groups Fig. 2): SED1-9 min bouts were lower in the PWS group (31% of total sedentary time vs. 44% in the CON group, P < 0.001) and SED≥30 min were higher (41% of total sedentary time vs. 18% in the CON group, P < 0.001).

Aim 2: Assessing the effectiveness and transferability of the exercise training program in women with PWS

After the exercise training program, walking capacity increased by mean (SD) 29 (37) m (P = 0.02) and stance time increased by 4 (6) s (P = 0.02) (Table 2) although no effect was found on body weight and composition (Table 1). Total MVPA increased by 11 (13) min.d -1 (P < 0.05) and MVPA≥10 min by 86 (97) min.week -1 (P = 0.03). After the program, three participants (43%) were compliant with PA guidelines. The percentage of MVPA accumulated in MVPA≥10 min increased to 36% of total MVPA (P = 0.03) while MVPA accumulated in MVPA5-9 min tended to decrease (P = 0.05) (Fig. 1). The physical component of quality of life tended to increase after the program but no effect was found on, sedentary patterns or eating behaviour.

Patient participation in exercise sessions was very good, with a median (25 th -75 th percentile) number of exercise sessions attended of 32 (31-32) sessions. Participants and their families were very satisfied with the program as participants scored their satisfaction 4.4 (4.0-5.0) on a five-point scale and their relatives scored their's 4.8 (4.1-5.0). No adverse events occurred during the program. All of the five PA instructors who participated in the program had at least two years of experience with the management of patients with chronic diseases and physical and/or intellectual disability, and all received a specific training on PWS before the program. The main difficulties reported by instructors were related to psychological disorders associated with PWS (emotional lability and immaturity, mental rigidity), physical disorders (increased fatigability, balance disorders and reduced motor skills), and a lack of motivation.

One-to-one sessions were seen as an important aspect to personalize exercises and general advice about PA and to improve the patient-care provider relationship. All instructors declared that they sometimes had to adapt the exercise sessions according to the patient's motivation, mood, or fatigue. Mainly, the type of endurance-based activities performed was chosen by the instructor in agreement with the patient to make the sessions more enjoyable and to increase motivation. The most frequently performed activities were walking (66% sessions), Nordic walking (19% sessions), ball games (12% sessions), racket games (6% sessions), step or stair climbing (4%), orienteering (3% sessions), cycling (3% sessions), and running (2% sessions). Finally, three participants continued exercise sessions (two to two weekly sessions) at their own expense with the same organization after the end of the study, i.e. from 4 four months after the end of the program.

Discussion

This study provides a detailed analysis of habitual PA and sedentary patterns in adult women with PWS. Compared to control women matched for age and adiposity, total PA assessed with accelerometers was lower and sedentary time was higher in patients with PWS. Our data also demonstrate the effectiveness and feasibility of an exercise program including one-onone sessions of endurance and strength exercises for patients with PWS, when conducted at the participant's home or community setting and supervised by the same PA instructor throughout the program.

In our sample of participants with PWS, the amount of PA assessed as accelerometer counts per min was found to be 37% lower in patients with PWS compared to the CON group.

Sedentary time accounted for almost two-quarters of accelerometer wear time, which was comparable to values previously reported in adult women with PWS [START_REF] Nordstrom | Accelerometer-determined physical activity and walking capacity in persons with Down syndrome, Williams syndrome and Prader-Willi syndrome[END_REF]. This was, however, higher than values obtained in our CON group or previously reported in subjects with severe obesity [START_REF] King | Objective assessment of changes in physical activity and sedentary behavior: Pre-through 3 years post-bariatric surgery[END_REF]. Participants in the PWS group were also characterized by more prolonged, uninterrupted sedentary bouts. Prolonged bouts of 30 min or longer accounted for more than 40% of total sedentary time, more than two-fold the values obtained in the CON group. We found no other study examining PA in PWS to compare these data to. The increase in sedentary time in the PWS group was mainly explained by a decrease in light-intensity PA, and to a lesser extent, by a decrease in MVPA. Previous studies have reported a lower duration of light-intensity PA in youth with PWS and a trend for a lower duration of MVPA [START_REF] Castner | Patterns of habitual physical activity in youth with and without Prader-Willi Syndrome[END_REF][START_REF] Rubin | Changes in cardiometabolic markers in children with Prader-Willi syndrome and nonsyndromic obesity following participation in a home-based physical activity intervention[END_REF].

After the exercise training program, total MVPA increased by more than two-fold and MVPA spent in bouts of ≥ 10 min increased from five to 90 min per week. Despite this substantial increase in MVPA, more than half of the participants remained insufficiently active.

Sedentary time and patterns, as well as light-intensity PA, did not change after the program.

Growing evidence suggests that breaking prolonged sedentary bouts with short bouts of lightintensity PA elicits cardiometabolic benefits [START_REF] Duvivier | Reducing sitting time versus adding exercise: differential effects on biomarkers of endothelial dysfunction and metabolic risk[END_REF]. Interestingly, the cardiometabolic risks associated with an increase in sedentary time might be higher in subjects with lower levels of MVPA [START_REF] Biswas | Sedentary time and its association with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis[END_REF]. Improvements in cardiometabolic factors have been reported after a PA intervention in patients with PWS [START_REF] Kaufman | Prader-Willi syndrome: effect of group home placement on obese patients with diabetes[END_REF][START_REF] Rubin | Changes in cardiometabolic markers in children with Prader-Willi syndrome and nonsyndromic obesity following participation in a home-based physical activity intervention[END_REF]. It should be noted, however, that the study by [START_REF] Kaufman | Prader-Willi syndrome: effect of group home placement on obese patients with diabetes[END_REF] also included a nutritional intervention, and the study by [START_REF] Rubin | Changes in cardiometabolic markers in children with Prader-Willi syndrome and nonsyndromic obesity following participation in a home-based physical activity intervention[END_REF] reported higher metabolic benefits in patients who experienced no gain or a decrease in body fat. Thus, the cardiometabolic benefits described cannot be attributed solely to the PA program. More studies are needed to better understand the contribution of PA to the cardiometabolic health of patients with PWS.

Another important objective of this study was to assess the transferability of a four-month exercise training program in participants with PWS. Participation in exercise sessions was excellent, as well as the satisfaction from both participants and their families. Studies that implemented home-based exercise training programs, either supervised or non-supervised, usually reported high participation in exercise sessions compared to programs based outside the home [START_REF] Amaro | Physiological adaptation after a 12-week physical activity program for patients with Prader-Willi syndrome: two case reports[END_REF][START_REF] Capodaglio | Postural adaptations to long-term training in Prader-Willi patients[END_REF]Rubin, 2019b). Instructors involved in this program reported they had to adapt to the participants' psychological and cognitive disorders and physical limitations associated with PWS, and sometimes to patients' fatigue and lack of motivation. Individual interaction was found to be very important to build-up confidence, improve the patient-health professional relationship, and promote self-esteem in these very sensitive patients. This study showed the potential of transferability of a home-based supervised exercise training program in patients with PWS, even though the sample size was rather small. The data also suggest the need to involve experienced PA instructors with a well-developed capacity to adapt exercise programs and make the sessions enjoyable with these patients.

The program was effective to improve physical function although no change in body weight or body composition was found. Previous studies that reported significant weight loss after a PA intervention in adult patients with PWS also included a dietary intervention [START_REF] Cimolin | Gait strategy in genetically obese patients: a 7-year follow up[END_REF][START_REF] Grolla | Specific treatment of Prader-Willi syndrome through cyclical rehabilitation programmes[END_REF]. Given the major importance of restricting food intake for obtaining negative energy balance, the expected benefit of PA alone should not be to lose weight but rather to focus on improving physical function or metabolic outcomes. A significant 30-m improvement in walking distance was observed after the program, which is consistent with studies that previously examined a three-to four-month exercise training programs in subjects with severe obesity [START_REF] Baillot | Impact of physical activity and fitness in class II and III obese individuals: a systematic review[END_REF][START_REF] Marcon | What Is the Best Treatment before Bariatric Surgery? Exercise, Exercise and Group Therapy, or Conventional Waiting: a Randomized Controlled Trial[END_REF]. This suggests that exercise training could be equally effective to increase walking capacity in patients with PWS or with common obesity. To increase the generalizability of such findings, future research should investigate whether this type of home-based supervised exercise training program is effective in adult patients with other forms of genetic (e.g. Bardet-Biedl) or hypothalamic lesional (e.g. craniopharyngioma) obesity, who represent up to five percent of obesity cases [START_REF] Huvenne | Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016[END_REF], and more broadly in individuals with intellectual disabilities, who often present with overweight or obesity [START_REF] Wallen | High prevalence of diabetes mellitus, hypertension and obesity among persons with a recorded diagnosis of intellectual disability or autism spectrum disorder[END_REF].

Study strengths and limitations

The strengths of this study include the objective monitoring of habitual PA by accelerometers over a relatively long (more than six days) period in a group of adult women with PWS and in a control group of subjects with non-syndromic obesity carefully matched on gender, age and adiposity. Accelerometer data processing was performed using the same procedures, increasing the comparability of data between groups. The min-by-min analysis of accelerometer data provided new insights about MVPA and sedentary patterns in patients with PWS, highlighting the added value of objective measure of PA for improving our understanding of PA patterns and guiding patient management. However, the cutpoints used to define sedentary time and light-, moderate-and vigorous-intensity PA were initially validated in young and non-obese individuals [START_REF] Freedson | Calibration of the Computer Science and Applications, Inc. accelerometer[END_REF], and have not been validated in patients with PWS. According to previous reports [START_REF] Agiovlasitis | Metabolic rate and accelerometer output during walking in people with Down syndrome[END_REF], the relation between counts per min and oxygen consumption differs in patients with intellectual disabilities, suggesting that traditional cutpoints might not be adapted to these subjects. More research is needed to validate specific intensity cutpoints in patients with PWS, and more broadly in patients with intellectual disabilities [START_REF] Leung | Measuring physical activity with accelerometers for individuals with intellectual disability: A systematic review[END_REF]. In addition, the sample size was limited and only women were included in the analyses, which prevents us from extrapolating results to all patients with PWS. Finally, the control group did not receive the intervention and was not used as a control group to compare the effectiveness of the exercise program in PWS vs non syndromic obesity. Hence, although unlikely, we cannot exclude that the improvements observed in the PWS group after the intervention might have been due to other factors.

Conclusion

This study shows substantially lower objectively-measured total PA and higher sedentary time, especially in uninterrupted bouts of 30 min or longer, in women with PWS compared to control subjects with common obesity. Participation in the home-based supervised exercise training program was very high, showing the feasibility and transferability potential of such programs in patients with PWS. The 16-week program was found to be effective to in increasing habitual MVPA and improving walking capacity, although body weight and body composition were not changed. This increase in PA is likely to have beneficial health effects over time, showing the adjunct value of including a specifically-designed PA program in the clinical management and rehabilitation of patients with PWS.

Figures legend

  PWS Patients with PWS participated in a 16-week exercise training program. The program was conceived and implemented in partnership with Siel Bleu, a non-profit organization specialized in delivering PA intervention to patients with chronic diseases and older adults (El-Khoury, 2015). The program included two exercise sessions per week, conducted at home on an individual basis and supervised by a specifically trained PA instructor. Patients were supervised by the same instructor throughout the program. As recommended in PA guidelines for adults with disabilities available at the time the study was designed, exercise sessions were based on a combination of endurance-based and muscle-strengthening activities of moderate intensity (Department of Health and Human Services, 2008). Each training session lasted one hour and included 10 min of a light endurance warm-up, 30 min of moderateintensity endurance training, 15 min of strength training, and five min of stretching and cooling down. To make training sessions more enjoyable and improve adherence, endurance activities varied along the program and included walking, Nordic walking, orienteering, running, step or stair climbing, ball games (football, basketball, volleyball) and racket games

Title:Figure 2 Title:

 2 Abbreviations: PWS group, patients with Prader-Willi syndrome; CON group, control group;

Acknowledgements

The authors thank Valentine Lemoine and Thomas Maurel for their help in clinical investigation. We also sincerely thank the physical instructors and Siel Bleu association, PWS patients, their caregivers and families for their participation in this study and Prader-Willi France association for financial support.

Funding

This study was supported by a research grant from Association Prader-Willi France. The funding source was not involved in the study design, the collection, analysis and interpretation of data, the writing of the report or the decision to submit the article for publication.

Competing interest statement:

The authors declare that they have no conflict of interest.


Alice Bellicha
email: alice.bellicha@u-pec.fr

Caroline Giroux

Cécile Ciangura

Diane Menoux

Philippe Thoumie

Jean-Michel Oppert

Pierre Portero

Vertical Jump on a Force Plate for Assessing Muscle Strength and Power in Women With Severe

Keywords: muscular fitness, vertical jump, force plate, isokinetic testing, obesity

INTRODUCTION

The worldwide prevalence of obesity (defined as body mass index, BMI, ≥ 30 kg.m -2 ) and severe obesity (i.e. BMI ≥ 40 kg.m -2 ) has markedly increased over the last decades and reached up to 39% and 7.6% of the US adult population in 2016, respectively [START_REF] Hales | Differences in Obesity Prevalence by Demographic Characteristics and Urbanization Level Among Adults in the United States, 2013-2016[END_REF]. Obesity is associated with an increased risk of type 2 diabetes, cardiovascular disease, certain forms of cancer, and premature mortality [START_REF] Heymsfield | Mechanisms, Pathophysiology, and Management of Obesity[END_REF], but also with lower muscular fitness and physical function [START_REF] Bollinger | Potential contributions of skeletal muscle contractile dysfunction to altered biomechanics in obesity[END_REF]. In aging subjects with obesity, low muscle mass, strength and function lead to so-called "sarcopenic obesity", which is associated with deleterious health effects [START_REF] Lee | Physical activity and sarcopenic obesity: definition, assessment, prevalence and mechanism[END_REF].

Growing evidence suggests that such deterioration of muscle properties can occur earlier in life [START_REF] Lee | Physical activity and sarcopenic obesity: definition, assessment, prevalence and mechanism[END_REF]. As recently reviewed, middle-aged subjects with obesity have lower muscle strength and power when normalized to body mass, lean body mass or muscle cross sectional area [START_REF] Bollinger | Potential contributions of skeletal muscle contractile dysfunction to altered biomechanics in obesity[END_REF]. Low relative strength and power may be an important factor explaining the lower physical function usually described in this population [START_REF] Carvalho | Prediction of Cardiorespiratory Fitness by the Six-Minute Step Test and Its Association with Muscle Strength and Power in Sedentary Obese and Lean Young Women: A Cross-Sectional Study[END_REF][START_REF] De | Correlation between Body Composition and Walking Capacity in Severe Obesity[END_REF][START_REF] Hulens | Predictors of 6-minute walk test results in lean, obese and morbidly obese women[END_REF].

Lean body mass and knee extension strength have been identified as predictors of walking capacity in subjects with obesity [START_REF] Carvalho | Prediction of Cardiorespiratory Fitness by the Six-Minute Step Test and Its Association with Muscle Strength and Power in Sedentary Obese and Lean Young Women: A Cross-Sectional Study[END_REF][START_REF] De | Correlation between Body Composition and Walking Capacity in Severe Obesity[END_REF][START_REF] Hulens | Predictors of 6-minute walk test results in lean, obese and morbidly obese women[END_REF]. Muscle power assessed during 5 consecutive jumps was also found to be associated with physical performance (i.e. stair climbing and running speed) in this population [START_REF] Lafortuna | Lower limb alactic anaerobic power output assessed with different techniques in morbid obesity[END_REF]. Muscle power has long been recognized as a critical determinant of athletic performance [START_REF] Kraemer | Training for muscular power[END_REF], and growing evidence also suggests the importance of muscle power for carrying out daily living activities in aging individuals [START_REF] Byrne | Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions[END_REF]. Powertraining, also called high-velocity resistance training, has recently emerged as potentially more effective than traditional strength training for improving physical function in older adults, including those with sarcopenic obesity [START_REF] Balachandran | High-speed circuit training vs hypertrophy training to improve physical function in sarcopenic obese adults: a randomized controlled trial[END_REF]. To further document the relations of muscle strength and power with physical function in subjects with obesity, there is a need to identify methods that can be performed in this population with sufficient precision and safety, and that would be feasible in routine clinical care.

In clinical settings, handgrip strength is the most widely used measure of muscle strength.

Although predictive of health status [START_REF] Celis-Morales | Associations of grip strength with cardiovascular, respiratory, and cancer outcomes and all cause mortality: prospective cohort study of half a million UK Biobank participants[END_REF], handgrip strength cannot be used as a surrogate of lower-limb strength [START_REF] Bohannon | Grip and knee extension muscle strength reflect a common construct among adults[END_REF]. Inversely, isokinetic testing, recognized as the gold-standard method for assessing lower-limb strength (1), is not easily accessible in all settings, is timeconsuming and requires trained personnel, limiting its use in a clinical context. Vertical jump is another test frequently used for the assessment of lower-limb strength and power (40) but so far, its use has mainly been limited to athletes. However, several studies have shown good reliability and validity of vertical jump parameters in other populations such as untrained [START_REF] Paasuke | Knee extension strength and vertical jumping performance in nordic combined athletes[END_REF] and older adults [START_REF] Ditroilo | Intra-and intersession reliability of vertical jump performance in healthy middle-aged and older men and women[END_REF][START_REF] Larsen | Reproducibility and relationship of single-joint strength vs multi-joint strength and power in aging individuals[END_REF]. A previous study by Lafortuna et al. (28) had also shown the feasibility of performing 5 consecutive jumps in adults with severe obesity, despite a higher prevalence of orthopedic disorders (i.e. joint pain, osteoarthritis) in this population [START_REF] Allen | Epidemiology of osteoarthritis: state of the evidence[END_REF].

Vertical jump might therefore be adapted to adults with obesity but its reliability and validity have not been assessed.

Therefore, the aims of this study were to investigate in subjects with severe obesity: 1) the intra-session reliability of vertical jump parameters assessed with a force plate, 2) the validity of this method compared to the gold-standard assessment of knee extension strength with an isokinetic ergometer, 3) the relations of vertical jump parameters and knee extension strength with body composition.

METHODS

Experimental approach to the problem

A cross-sectional study was conducted in subjects with severe obesity. The description of participants included age, anthropometrics, body composition assessed by dual x ray absorptiometry (DXA, Hologic Discovery W, software v12.9; Hologic, Bedford, MA), physical function assessed with a 6-min walk test and habitual physical activity assessed by accelerometers (Actigraph GT3x accelerometer, Manufacturing Technology, Inc., FL, USA).

To answer the first study aim, the intraclass correlation coefficients (ICC) and r 2 from r correlation coefficients were calculated for six vertical jump parameters (absolute peak force and power, relative peak force and power, peak velocity and jump height) assessed on a force plate (Kistler, Winterthur, Switzerland; type 9286BA, dimensions 60 x 40 cm). To answer the second study aim, correlation coefficients between vertical jump parameters and knee extension strength assessed with an isokinetic ergometer (Con-Trex, CMV AG, Dübendorf, Switzerland) were analyzed. Finally, to answer the third study aim, the relations of vertical jump parameters and knee extension strength with body mass, body fat and lean body mass by were analyzed.

Subjects

Participants for this study were recruited among patients with severe obesity followed at a single academic center and who were candidates to bariatric surgery (sleeve gastrectomy).

Recruitment took place between October 2017 and July 2018. Inclusion criteria were female gender, age between 18 and 65 years, place of residence in Paris or its region, BMI of 40 kg.m -2 or higher or BMI of 35 kg.m -2 or higher with at least one obesity comorbidity.

Following national [START_REF]Recommandations de bonne pratique -Obésité : prise en charge chirurgicale chez l'adulte[END_REF] and international (33) guidelines for the management of patients seeking this type of surgery, exclusion criteria were: abnormal cardiac stress test, recent coronary event, orthopedic disorders or neuropathy that would limit physical activity, on-going or planned pregnancy. All patients were informed about the benefits and risks of the investigation and signed an informed written consent to join the study. The study was approved by the Ethics Committee of Bron Hospital (Comite de Protection des Personnes Sud-Est III, Bron, France) (clinicaltrials.gov NCT03325764).

Twenty subjects aged from 21 to 63 years were included in the study. Parameters related to age, anthropometrics and body composition are shown in Table 1.

Physical function and objective physical activity data are presented in Table 2. The mean (SD) 6-min walk test distance was 513 (41) m. Participants wore the accelerometers over a mean (SD) of 6.8 (0.5) days and 15 (75%) participants reached the recommended PA level.

Procedures

Body composition (DXA), vertical jump parameters, knee extension strength and physical function were assessed during two consecutive visits within 4 weeks. The second visit took place at our laboratory equipped with a force plate and an isokinetic ergometer. Habitual PA was assessed during 7 days between the two visits.

Description of participants

BMI was calculated as body mass (kg) divided by height squared (m 2 ). Body composition (fat mass, lean body mass) was measured by DXA scanning, as previously described [START_REF] Oppert | Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial[END_REF].

Physical function was assessed with a 6-min walk-test performed in an indoor 30-m corridor according to the recommendations of the American Thoracic Society (3). Participants were asked to walk for 6 min between two cones, covering as much distance as possible. Heart rate (HR) was recorded throughout the test with a Polar M200 Sports optical HR sensor (Polar Electro Oy, Kempele, Finland) [START_REF] Horton | Comparison of Polar M600 Optical Heart Rate and ECG Heart Rate during Exercise[END_REF].

Participants were asked to wear the Actigraph accelerometer at the hip for seven consecutive days during all waking hours except during water-based activities. Data were considered valid when the accelerometer was worn for at least 4 days during at least 8 h each day [START_REF] Oppert | Resistance training and protein supplementation increase strength after bariatric surgery: a randomized controlled trial[END_REF].

Based on previous literature, cut-points below 100 counts.min -1 , between 100 and 1,951 counts.min -1 , between 1,952 and 5,723 counts.min -1 and over 5,724 counts.min -1 were used to quantify sedentary behaviour, light, moderate and vigorous intensity PA, respectively [START_REF] Freedson | Calibration of the Computer Science and Applications, Inc. accelerometer[END_REF].

Patients were considered compliant to the 2018 US PA guidelines when total MVPA was ≥ 150 min.week -1 (37).

Vertical jump

Vertical jump ability was assessed using counter-movement jump (CMJ) performed on a force plate. Participants performed several practice trials of sub-maximal CMJ under the supervision of the research staff to ensure correct execution. After the practice jumps, participants completed two maximal CMJ, with at least 3 min rest between trials. At the beginning of each trial, participants were asked to stand still on the force plate to register body weight. From the initial standing position (with feet shoulder-width apart and hands on hips), participants were asked to initiate a downward movement immediately followed by an upward movement leading to take-off, and to maintain a standing position during at least 3 s [START_REF] Van Hooren | The Difference Between Countermovement and Squat Jump Performances: A Review of Underlying Mechanisms With Practical Applications[END_REF]. Participants self-selected a degree of knee flexion that they felt comfortable with [START_REF] Ditroilo | Intra-and intersession reliability of vertical jump performance in healthy middle-aged and older men and women[END_REF]. Vertical ground reaction force (Fz) was recorded at a sampling frequency of 1000 Hz. Peak force (in N), peak velocity (in cm.s -1 ) and peak power (in W) in the vertical axis, defined as the maximum values obtained between the start of the jump and take-off, were obtained using the Kistler software. Peak power and peak force were also expressed relative to body mass (in W.kg -1 and N.kg -1 , respectively).

Fz component was used to calculate the vertical instantaneous acceleration of the centre of mass (az, expressed in m.s -2 ) as follows:

𝑎 𝑧 = 𝐹 𝑧 𝑚 -𝑔 (1)
where m is the body mass (in kg) and g the acceleration due to gravity. 𝑎 𝑧 was then integrated once to provide instantaneous vertical velocity (𝑣 𝑧 , expressed in m.s -1 ).

𝑣 𝑧 = ∫ 𝑎 𝑑𝑡 + 𝑣 𝑧0 (2)
As the jump begins with a period of immobility, at 𝑡 0 , 𝑣 𝑧0 = 0.

Power output was then calculated as the product of force and velocity (𝑃 𝑧 = 𝐹 𝑧 . 𝑣 𝑧 , in W).

Time in the air (identified as the period between take-off and contact after flight), was used to calculate height jump, as follows:

ℎ𝑒𝑖𝑔ℎ𝑡 = 1 8 𝑔 (𝑇𝐼𝐴)² (3)
where TIA is the time in the air (cm).

Knee extension strength

Isometric and isokinetic concentric quadriceps muscle strength was assessed using a Con-Trex isokinetic ergometer. Only the right lower limb was tested. Positioning of the subjects was standardized, with subjects seated on the ergometer so that the hip was flexed at 85° (0°: full hip extension). Participants performed several practice trials of sub-maximal isometric and isokinetic contractions. Isometric concentric torque was assessed with the knee angle set at 70° (0°: full leg extension). Two trials were performed with 90-s rest between trials.

Isokinetic concentric torque was assessed at angular velocities of 60 and 240°.s -1 . The range of motion was fixed from 10° to 90°. One trial was performed at each angular velocity.

During the isometric and isokinetic tests, participants were strongly encouraged to produce their maximal force during 3 s and throughout the range of motion, respectively.

Statistical analyses

Descriptive data are presented as mean (SD) and min-max values to characterize interindividual variability. Intraclass correlation coefficients (ICC) with 95% confidence intervals and r 2 from Pearson correlation coefficients were used to assess intra-session reliability of vertical jump parameters. Pearson correlations were also used to assess the validity of vertical jump parameters against isokinetic and isometric knee extension torques, and to analyze the relations of vertical jump parameters and knee extension torques with body composition parameters. P-values < 0.05 were considered significant. ICC values and correlation coefficients less than 0.5, between 0.5 and 0.74, between 0.75 and 0.89 and ≥ 0.90 were considered indicative of poor, moderate, good and excellent reliability or validity, respectively [START_REF] Mentiplay | Assessment of Lower Limb Muscle Strength and Power Using Hand-Held and Fixed Dynamometry: A Reliability and Validity Study[END_REF]. Analyses were performed using R version 3.4.3 (R Core Team: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2017).

RESULTS

Vertical jump parameters and knee extension torque are presented in Table 3. Mean (SD) peak power, peak force and jump height were 2604 (560) W, 2034 (289) N and 8.8 (2.9) cm, respectively. Mean isometric torque was 167.4 (34.9) Nm.

Intra-session reliability of vertical jump parameters

Reliability parameters (coefficient correlation r 2 , ICC) are presented in Table 4 for six CMJ variables (absolute and relative peak power and peak force, peak velocity and jump height).

Findings revealed excellent reliability for absolute and relative peak power and for absolute peak force, as documented by ICC ≥ 0.90 and r 2 correlation coefficients > 0.80. Reliability was good for peak velocity and jump height and moderate for relative peak force. The variable with the highest index of reliability was absolute peak power (ICC [95% CI] = 0.95 [0.88-0.98] and r 2 =0.90, P<0.001).

Validity of vertical jump parameters compared to knee extension strength

Relations of peak power, peak force and jump height with isometric and isokinetic knee extension torque are presented in Figure 1. Peak power in vertical jump was positively correlated to all measures of isokinetic and isometric torque (Figure 1 a-c). Peak force in vertical jump was significantly correlated to isokinetic torque (Figure 1 d-e) but was not significantly correlated to isometric torque (Figure 1f). Jump height was significantly correlated to isokinetic torque at 60°.s -1 and isometric torque (Figure 1 h-i) but was not significantly correlated to isokinetic torque at 240°.s -1 (Figure 1g). The highest correlations were obtained between peak power and isokinetic torque at 60°.s -1 (r=0.79, P<0.001) and between jump height and isokinetic torque at 60°.s -1 (r=0.72, P<0.001).

Relations between vertical jump parameters and body composition

As shown in Table 5, age and height were significantly correlated to most vertical jump parameters. Therefore, adjustment on age and height was performed when examining the relations of these parameters with body mass, lean body mass and body fat. Body mass was significantly correlated to peak force, negatively correlated to jump height and tended to be negatively correlated to peak velocity (P=0.06). No relation was observed between body mass and peak power. Similarly, fat mass was positively correlated to peak force and negatively correlated to jump height and peak velocity, and was not significantly correlated to peak power. Lean body mass was positively correlated to peak power and peak force but was not significantly correlated to jump height and peak velocity. The strongest relation was between lean body mass and peak force (r=0.89, P<0.001).

Relations between knee extension strength and body composition

After adjustment on age and height (Table 3), isokinetic torque at 240°.s -1 was significantly correlated to lean body mass and tended to be correlated to body mass (P=0.06). No other significant relation was found between isometric or isokinetic torque at 60°.s -1 and body composition.

DISCUSSION

In this study, we measured lower-limb strength and power in women with severe obesity during vertical jump using a force plate and compared these data with lower-limb strength assessed on an isokinetic dynamometer. As expected, the mean absolute values of knee extension torque and peak force and power during vertical jump appeared higher than values described in adult lean women [START_REF] Ditroilo | Intra-and intersession reliability of vertical jump performance in healthy middle-aged and older men and women[END_REF][START_REF] Mckay | Normative reference values for strength and flexibility of 1,000 children and adults[END_REF], but were similar to values usually reported in women with severe excess body weight [START_REF] Hulens | Study of differences in peripheral muscle strength of lean versus obese women: an allometric approach[END_REF][START_REF] Hulens | Assessment of isokinetic muscle strength in women who are obese[END_REF]. In contrast, jump height was more than twice lower than values described in adult lean women [START_REF] Ditroilo | Intra-and intersession reliability of vertical jump performance in healthy middle-aged and older men and women[END_REF]. There is, however, no other study to compare our data of vertical jump parameters in women with obesity or severe obesity.

The first aim of this study was to assess the intra-session reliability of vertical jump parameters on a force plate in women with severe obesity. Excellent reliability for peak power and peak force during vertical jump were found. ICC values were ≥ 0.90 and similar to that previously reported in young to middle-aged healthy adults [START_REF] Ditroilo | Intra-and intersession reliability of vertical jump performance in healthy middle-aged and older men and women[END_REF][START_REF] Hori | Reliability of performance measurements derived from ground reaction force data during countermovement jump and the influence of sampling frequency[END_REF]. Lower, although good reliability was also found for jump height. These findings suggest that vertical jump, which is widely used to assess lower-limb strength and power in populations from athletes to older adults is also a reliable test in women with severe obesity in the age range 20 to 60 years. It should be acknowledged, however, that only women free of severe orthopedic disorders were included in our study. Given the higher prevalence of joint pain [START_REF] Kraemer | Training for muscular power[END_REF] or osteoarthritis (2) in subjects with obesity, careful medical check-up should be performed before proposing vertical jump testing.

The second aim of this study was to assess the validity of vertical jump parameters compared to the gold-standard assessment of knee extension torque with an isokinetic ergometer.

Strong significant relations were found between peak power in vertical jump or jump height and isokinetic torque at 60°.s -1 . The correlation coefficients observed here, between 0.72 and 0.79, were similar to that previously reported in athletes (r=0.77) [START_REF] Riera | Comparison of two methods for the measurement of the extensor muscle dynamic force of the inferior limb: Isokinetic dynamometry and vertical jump tests[END_REF], untrained adults (r=0.70) [START_REF] Paasuke | Knee extension strength and vertical jumping performance in nordic combined athletes[END_REF], or older adults (r=0.78) [START_REF] Larsen | Reproducibility and relationship of single-joint strength vs multi-joint strength and power in aging individuals[END_REF]. A significant although lower relation was also found between peak power in vertical jump or jump height and isometric torque. Overall, these findings suggest moderate to good validity of vertical jump parameters compared to isokinetic strength, and poor validity compared to isometric strength in women with severe obesity. They also are in agreement with the notion, previously described in athletes that isometric contractions are very different from the actions involved in vertical jump and, consequently, that isometric strength is not a good predictor of vertical jump (4).

Another important aspect of this study was to analyze the relations of vertical jump parameters and knee extension torque with body composition. Peak force in vertical jump was positively correlated to body mass, lean body mass and fat mass, and the strongest relation was with lean body mass (r=0.89). Peak power in vertical jump was positively correlated to lean body mass but peak velocity and height jump were negatively correlated to body fat. Therefore, as previously described in athletes [START_REF] Esco | Field-Based Performance Tests Are Related to Body Fat Percentage and Fat-Free Mass, But Not Body Mass Index[END_REF], body composition appears to be a better predictor of vertical jump performance than body mass alone in subjects with obesity.

Interestingly, only isokinetic torque at high angular velocity was significantly correlated to lean body mass. The correlation coefficient (r=0.49) was similar to that previously described in obese women (r=0.47) [START_REF] Hulens | Assessment of isokinetic muscle strength in women who are obese[END_REF], although very few studies have analyzed relations between knee extension torque and body composition in this population. In our study, vertical jump parameters were more positively correlated to body composition than isokinetic or isometric torque, which suggests that multi-joint weight-bearing movements might better reflect body composition than isolated single-joint movements [START_REF] Larsen | Reproducibility and relationship of single-joint strength vs multi-joint strength and power in aging individuals[END_REF].

The relations observed here between vertical jump parameters and body composition strengthen the notion that absolute values of lower-limb strength increase with body mass.

Several studies have reported higher absolute strength in obese vs. normal-weight subjects [START_REF] Bollinger | Potential contributions of skeletal muscle contractile dysfunction to altered biomechanics in obesity[END_REF] without describing the relation between muscle strength and body mass in subjects with severe obesity. Given the major contribution of muscle strength in performing daily-living activities in subjects with obesity (5, 8, 30), higher muscle strength is likely to have beneficial effects regarding physical function. In contrast, our data showed that peak velocity in vertical jump and jump height decreased with body fat and that peak power was not significantly correlated to body mass. This is in line with previous studies that reported lower velocity and lower relative power during either 5 consecutive jumps or 5 sit-to-stand transitions in obese subjects [START_REF] Lafortuna | Lower limb alactic anaerobic power output assessed with different techniques in morbid obesity[END_REF][START_REF] Schmid | The relationship between different body mass index categories and chair rise performance in adult women[END_REF]. In older adults, muscle power is recognized as a critical determinant of physical function [START_REF] Byrne | Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions[END_REF]. Moreover, power training has been proven to be more effective than traditional resistance training to improve physical function [START_REF] Byrne | Ageing, Muscle Power and Physical Function: A Systematic Review and Implications for Pragmatic Training Interventions[END_REF]. Although data on muscle power in subjects with obesity are scarce, there is some evidence that muscle power is an important contributor to stair climbing and sprinting performance in this population [START_REF] Lafortuna | Lower limb alactic anaerobic power output assessed with different techniques in morbid obesity[END_REF].

More data from large-scale studies are needed to better understand how muscle power affects physical function and activities of daily living (e.g. walking velocity) in subjects with obesity.

Strengths and limitations

Strengths of this study include the use of gold-standard methods for the assessment of knee extension strength (isokinetic ergometer), lower-limb power (force plate) and body composition (DXA absorptiometry). Data were obtained in a homogeneous group of women with severe obesity candidates to the same bariatric surgery procedure. We were able to show good reliability and validity of vertical jump parameters, as well as significant relations of these parameters with body composition. Some limitations should be mentioned. We assessed only the intra-session reliability of vertical jump parameters, and did not assess the intersession reliability. The sample size was relatively small and only women free of severe orthopedic disorders were included, which prevents us from extrapolating results to all obese subjects. It has been shown that relations between body composition and muscle power differed by sex in subjects with obesity [START_REF] Lafortuna | The relationship between body composition and muscle power output in men and women with obesity[END_REF]. Validity of vertical jump parameters and relations with body composition should also be explored in men with obesity.

Conclusion

This study showed excellent intra-session reliability of vertical jump parameters in women with severe obesity and moderate to good validity compared to isokinetic testing.

Interestingly, vertical jump parameters were more positively correlated to body composition than isokinetic or isometric strength. This emphasizes the importance of measures of muscle strength during multi-joints movements, known to better predict physical function compared to muscle strength assessed during single-joint movements. Peak force in vertical jump was strongly and positively correlated to lean body mass, whereas jump height and peak velocity were negatively correlated to fat mass. Peak power, a critical determinant of physical function, was not correlated to body mass, suggesting a potential deficit in muscle power with increasing BMI.

PRACTICAL APPLICATIONS

Vertical jump testing is easy and rapid to implement, whereas isokinetic testing is more challenging, especially because of time constraints (about half an hour vs. a few minutes for vertical jump) and difficulties for positioning subjects with severe obesity on the ergometer.

Vertical jump might therefore be used more broadly in both clinical and research setting with the aim to better describe muscular fitness in adults with and to assess the effect of an intervention. Although the reliability of jump height and its validity compared to isokinetic testing were lower than that of peak power, good and moderate reliability and validity were found, respectively. Contrary to peak power, jump height has the advantage of being easily understandable by patients. In addition, jump height can be assessed accurately with less expensive methods than the force plate such as smartphone applications [START_REF] Balsalobre-Fernandez | The validity and reliability of an iPhone app for measuring vertical jump performance[END_REF], which might facilitate its measure in routine. It is important to note that obesity is often associated with joint pain. We therefore recommend to carefully examine the medical record and to obtain medical authorization before proposing vertical jump testing to these subjects. To generalize vertical jump testing in this population, there is a need to confirm the feasibility of vertical jump in a larger sample of subjects and to establish normative values of vertical jump parameters in this population.

Figure title

Figure 1-Relations between vertical jump parameters and knee extension torque (N=18) between peak force in CMJ and peak isokinetic torque at 240°.s -1 (d), peak isokinetic torque at 60°.s -1 (e), peak isometric torque (f) and between jump height and peak isokinetic torque at 240°.s -1 (g), peak isokinetic torque at 60°.s -1 (h), peak isometric torque (i)

Figure 1 -

 1 Figure 1-Pearson correlations (unadjusted) between peak power in CMJ and peak isokinetic torque at 240°.s -1 (a), peak isokinetic torque at 60°.s -1 (b), peak isometric torque (c), and

  Figure 1

Table 1 -Participants characteristics (N=20)

 1

	Mean (SD)

Abbreviations: BMI, body mass index

Table 2 -Physical function and accelerometry-assessed physical activity data (N=20)

 2

	Mean (SD)

Abbreviations: HR, heart rate; PA, physical activity

Table 3 -Vertical jump parameters and knee extension torque (N=20) Mean (SD) VERTICAL JUMP

 3

	Peak power
	Absolute, W	2604 (560.1)
	Relative, W.kg -1	22.2 (3.5)
	Peak force
	Absolute, N	2034 (288.7)
	Relative, N.kg -1	17.3 (1.1)
	Peak velocity, m.s -1	1.55 (0.18)
	Jump height, cm	8.8 (2.9)
	KNEE	EXTENSION	STRENGTH
	(N=18)*
	Peak isometric torque
	Absolute, Nm	167.4 (34.9)
	Relative, Nm.kg -1	1.41 (0.32)
	Peak isokinetic torque at 60°.s -1
	Absolute, Nm	133.6 (29.2)
	Relative, Nm.kg -1	1.12 (0.23)
	Peak isokinetic torque at 240°.s -1
	Absolute, Nm	88.9 (18.3)
	Relative, Nm.kg -1	0.74 (0.12)

* Because of technical issues with the isokinetic ergometer encountered during the study, isokinetic data were obtained in 18 participants.

Table 4 -Intra-session reliability of vertical jump parameters in women with severe obesity (N=20)

 4

		Mean (SD)	Intra-session reliability
		Test 1	Test 2	r 2 (P-value)	ICC (95% CI)
	Peak power, W	2,412.0 (540.5) 2,597.0 (562.4) 0.90 (P<0.001) 0.95 (0.88-0.98)
	Relative peak power,	20.5 (3.4)	22.1 (3.5)	0.83 (P<0.001) 0.91 (0.79-0.97)
	W.kg -1
	Peak force, N	2,020.0 (291.3) 2,039.0 (286.2) 0.81 (P<0.001) 0.90 (0.77-0.96)
	Relative peak force,	17.2 (1.6)	17.4 (1.1)	0.49 (P<0.001) 0.65 (0.31-0.85)
	N.kg -1
	Peak velocity, m.s -1	1.46 (0.17)	1.55 (0.18)	0.72 (P<0.001) 0.85 (0.65-0.94)
	Jump height, cm	7.2 (2.6)	8.5 (2.9)	0.58 (P<0.001) 0.75 (0.48-0.90)

r are Pearson correlation coefficients (unadjusted); ICC (95% CI): intraclass correlation coefficient (95% confidence interval)

Acknowledgements

This work was supported by the Institute of Cardiometabolism and Nutrition.

We recognize the contribution of the Clinical Research Unit (Unité de Recherche Clinique URC), Pitie-Salpetriere Hospital (AP-HP), Paris, France, in data acquisition and management.

We express our thanks to the patients for their participation in this study.