The SLEEEP Study Protocol - ANZCTR



-49530-41719500The SLEEEP Study ProtocolScientific TitleSleep, Lifestyle, Energy, Eating, Exercise Program for the management of sleep apnea patients indicated for weight loss treatment: A randomised controlled pilot studySimplified TitleSLEEEP StudyInvestigatorsPrincipal Investigator:Prof Ron GrunsteinAssociate Investigators:A/Prof Amanda Sainsbury-SalisA/Prof Brendon YeeDr Keith WongDr Kishani KannangaraDr Christopher GordonDr Camilla HoyosDr Nathaniel MarshallPhD Student/Study Coordinator: Miss Elizabeth Machan Sleep and Circadian GroupWoolcock Institute of Medical Research Address: The Woolcock Institute of Medical ResearchPO Box M77, Missenden Road NSW 2050This study will be conducted in compliance with the protocol, Good Clinical Practice and all other applicable regulatory requirements, including the archiving of essential documents.Part or all of the information in this protocol may be unpublished material.Accordingly, this protocol is to be treated as confidential and restricted to its intended use.Table of Contents TOC \o "1-2" \u The SLEEEP Study Protocol PAGEREF _Toc338798039 \h 1Scientific Title PAGEREF _Toc338798040 \h 1Simplified Title PAGEREF _Toc338798041 \h 1Investigators PAGEREF _Toc338798042 \h 1Table of Contents PAGEREF _Toc338798043 \h 2Aim PAGEREF _Toc338798044 \h 3Hypotheses PAGEREF _Toc338798045 \h 3Background PAGEREF _Toc338798046 \h 4Research Plan PAGEREF _Toc338798047 \h 6Methods PAGEREF _Toc338798048 \h 6Recruitment PAGEREF _Toc338798049 \h 8Inclusion and exclusion criteria PAGEREF _Toc338798050 \h 9Randomisation PAGEREF _Toc338798059 \h 10Statistical Analysis PAGEREF _Toc338798060 \h 11Follow up /Assessments PAGEREF _Toc338798061 \h 11Interventions PAGEREF _Toc338798068 \h 15Participant Withdrawal PAGEREF _Toc338798069 \h 18Exit Points PAGEREF _Toc338798071 \h 18Risks and Discomforts PAGEREF _Toc338798072 \h 19Participant Visits PAGEREF _Toc338798073 \h 20Data Analysis PAGEREF _Toc338798074 \h 22References PAGEREF _Toc338798075 \h 23AIMIn this phase 2A study we will not statistically compare the effectiveness of these two tailored isocaloric dietary interventions of “low GI/high protein” (LGHP) or a “standard hypocaloric diet based on the Australian guide to healthy eating” (AGHE) each preceded by an identical three month very low energy diet (VLED) and lifestyle modification program. We are studying the prognosis of patients given these diets while using randomisation to ensure the groups of patients are comparable. We suspect that these two treatments will have equivalent effects. Any statement of relative effectiveness of these diets will need to be tested in a larger more adequately powered trial. The difference in sympathetic activity will predict success of weight loss maintenance and be correlated with improvement in cardiovascular risk and obstructive sleep apnea profiles with the additive benefit of mechanical treatment of obstructive sleep apnea. Phenotyping the sympathetic activity response to weight loss following these two different dietary programs will allow better tailored treatment and more realistic treatment outcome prediction amongst obese patients with OSA.HypothesesPatients randomised to the low GI/high protein diet will maintain weight loss achieved through a very low energy diet and demonstrate a reduction in clinical symptoms associated with sleep apnea. Patients randomised to the standard hypocaloric diet will maintain weight loss achieved through a very low energy diet and demonstrate a reduction in clinical symptoms associated with sleep apnea.N.b. we are not statistically testing the relative effectiveness of these two diets Patients with obstructive sleep apnea have lower sympathetic activity following weight loss.Patients with higher sympathetic activity at baseline are more resistant to weight loss across diets Patients with higher sympathetic activity at the point of randomisation following a very low energy diet will be more resistant to weight loss maintenance. Smaller reductions in sympathetic activity following a very low energy diet will be predictive of weight regain.In addition, part of the secondary aim of this study will determine whether the magnitude of weight loss will be influenced by levels of self-efficacy whereby patients with higher self-efficacy will also have a higher quality of life as assessed through questionnaires.BackgroundObstructive Sleep Apnea (OSA) affects over 3.5 million Australians with approximately 25% complaining of marked sleepiness and is one of the most common health complications of obesity and central adiposity. OSA is a disorder which is characterised by repetitive episodes of partial (hypopnea) or complete (apnea) upper airway obstruction occurring during sleep. These episodes often result in snoring and oxyhaemoglobin desaturations that are usually terminated by brief arousals from sleep. OSA is associated with hypertension, cardiovascular disease, depression, impaired quality of life, excessive daytime sleepiness (EDS) and impaired neurobehavioral functioning. Continuous positive airway pressure (CPAP) is considered to be the ‘gold standard’ treatment for OSA. CPAP effectively alleviates obstructive episodes during sleep and has been found to improve parameters of sleepiness, cognitive performance and functional status in patients with severe OSA, however, compliance with this treatment as well as other mechanical alternatives is problematic. The only major modifiable risk factor for sleep apnea is obesity but the efficacy of weight loss in reducing OSA in individual patients is extremely variable. We know that weight loss is effective for reducing the clinical problems associated with sleep apnea such as daytime sleepiness, cardiovascular risk etc. As gradual weight loss is the recommended treatment approach in OSA, many patients will not immediately improve the disturbing daytime sleepiness that is often the chief clinical complaint and one of the factors accountable for the lack of weight loss. Furthermore, mechanical treatment compliance often limits the potential for improvement in symptoms of daytime sleepiness.Most weight loss studies in this clinical population are of limited duration and there is little insight into the diets that are effective for long term weight maintenance in this population. Current evidence regarding dietary prescription in the OSA population is limited and usually incorporates exclusive use of very low energy diets (VLED) rather than coupling such diets with a maintenance phase for long term sustained with loss ADDIN EN.CITE <EndNote><Cite><Author>Anandam</Author><Year>2012</Year><IDText>Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis</IDText><DisplayText>(Anandam et al. 2012)</DisplayText><record><foreign-keys><key app="EN" db-id="zsswwdp2d0zsfmeeawx50xdrrx2esrz2wa5p">2296</key></foreign-keys><dates><pub-dates><date>Feb 29</date></pub-dates><year>2012</year></dates><urls><related-urls><url> (Electronic)&#xD;1520-9512 (Linking)</isbn><titles><title>Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis</title><secondary-title>Sleep &amp; breathing = Schlaf &amp; Atmung</secondary-title><alt-title>Sleep Breath</alt-title></titles><contributors><authors><author>Anandam, A.</author><author>Akinnusi, M.</author><author>Kufel, T.</author><author>Porhomayon, J.</author><author>El-Solh, A. A.</author></authors></contributors><edition>2012/03/01</edition><language>Eng</language><added-date format="utc">1347420181</added-date><ref-type name="Journal Article">17</ref-type><auth-address>Western New York Respiratory Research Center, Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions, Buffalo, NY, USA.</auth-address><rec-number>402</rec-number><last-updated-date format="utc">1347420181</last-updated-date><accession-num>22374151</accession-num><electronic-resource-num>10.1007/s11325-012-0677-3</electronic-resource-num></record></Cite></EndNote>(Anandam et al. 2012). Recent studies have alluded that the macronutrient composition of diets during weight loss can influence energy expenditure during weight loss and maintenance phases PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FYmJlbGluZzwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

PElEVGV4dD5FZmZlY3RzIG9mIERpZXRhcnkgQ29tcG9zaXRpb24gb24gRW5lcmd5IEV4cGVuZGl0

dXJlIER1cmluZyBXZWlnaHQtTG9zcyBNYWludGVuYW5jZTwvSURUZXh0PjxEaXNwbGF5VGV4dD4o

RWJiZWxpbmcgZXQgYWwuIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+

PGtleSBhcHA9IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVw

Ij4yMjk0PC9rZXk+PC9mb3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+SnVuIDI3

PC9kYXRlPjwvcHViLWRhdGVzPjx5ZWFyPjIwMTI8L3llYXI+PC9kYXRlcz48a2V5d29yZHM+PGtl

eXdvcmQ+bXVzY2xlIHdvcmsgZWZmaWNpZW5jeTwva2V5d29yZD48a2V5d29yZD5sb3ctZ2x5Y2Vt

aWMgbG9hZDwva2V5d29yZD48a2V5d29yZD5sb3ctZmF0IGRpZXQ8L2tleXdvcmQ+PGtleXdvcmQ+

c2tlbGV0YWwtbXVzY2xlPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW4gc2Vuc2l0aXZpdHk8L2tl

eXdvcmQ+PGtleXdvcmQ+cmFuZG9taXplZC10cmlhbDwva2V5d29yZD48a2V5d29yZD5sb3ctY2Fy

Ym9oeWRyYXRlPC9rZXl3b3JkPjxrZXl3b3JkPm9iZXNlIGFkdWx0czwva2V5d29yZD48a2V5d29y

ZD5yaXNrLWZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+Ym9keS13ZWlnaHQ8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8wMDAz

MDU2OTI2MDAwMzE8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDA5OC03NDg0PC9p

c2JuPjx0aXRsZXM+PHRpdGxlPkVmZmVjdHMgb2YgRGlldGFyeSBDb21wb3NpdGlvbiBvbiBFbmVy

Z3kgRXhwZW5kaXR1cmUgRHVyaW5nIFdlaWdodC1Mb3NzIE1haW50ZW5hbmNlPC90aXRsZT48c2Vj

b25kYXJ5LXRpdGxlPkphbWEtSm91cm5hbCBvZiB0aGUgQW1lcmljYW4gTWVkaWNhbCBBc3NvY2lh

dGlvbjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+SmFtYS1KIEFtIE1lZCBBc3NvYzwvYWx0

LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4yNjI3LTI2MzQ8L3BhZ2VzPjxudW1iZXI+MjQ8L251bWJl

cj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RWJiZWxpbmcsIEMuIEIuPC9hdXRob3I+

PGF1dGhvcj5Td2FpbiwgSi4gRi48L2F1dGhvcj48YXV0aG9yPkZlbGRtYW4sIEguIEEuPC9hdXRo

b3I+PGF1dGhvcj5Xb25nLCBXLiBXLjwvYXV0aG9yPjxhdXRob3I+SGFjaGV5LCBELiBMLjwvYXV0

aG9yPjxhdXRob3I+R2FyY2lhLUxhZ28sIEUuPC9hdXRob3I+PGF1dGhvcj5MdWR3aWcsIEQuIFMu

PC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5n

dWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQyMDE4MTwvYWRkZWQtZGF0ZT48cmVm

LXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5M

dWR3aWcsIERTJiN4RDtDaGlsZHJlbnMgSG9zcCBCb3N0b24sIE5ldyBCYWxhbmNlIEZkbiwgT2Jl

cyBQcmV2ZW50IEN0ciwgMzAwIExvbmd3b29kIEF2ZSwgQm9zdG9uLCBNQSAwMjExNSBVU0EmI3hE

O0NoaWxkcmVucyBIb3NwIEJvc3RvbiwgTmV3IEJhbGFuY2UgRmRuLCBPYmVzIFByZXZlbnQgQ3Ry

LCAzMDAgTG9uZ3dvb2QgQXZlLCBCb3N0b24sIE1BIDAyMTE1IFVTQSYjeEQ7Q2hpbGRyZW5zIEhv

c3AgQm9zdG9uLCBOZXcgQmFsYW5jZSBGZG4sIE9iZXMgUHJldmVudCBDdHIsIEJvc3RvbiwgTUEg

MDIxMTUgVVNBJiN4RDtDaGlsZHJlbnMgSG9zcCBCb3N0b24sIENsaW4gUmVzIEN0ciwgQm9zdG9u

LCBNQSAwMjExNSBVU0EmI3hEO0JyaWdoYW0gJmFtcDsgV29tZW5zIEhvc3AsIEJvc3RvbiwgTUEg

MDIxMTUgVVNBJiN4RDtBUlMsIEJheWxvciBDb2xsIE1lZCwgVVNEQSwgQ2hpbGRyZW5zIE51dHIg

UmVzIEN0ciwgSG91c3RvbiwgVFggVVNBJiN4RDtWYW5kZXJiaWx0IFVuaXYsIE5hc2h2aWxsZSwg

VE4gVVNBPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDAwPC9yZWMtbnVtYmVyPjxsYXN0LXVw

ZGF0ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQyMDE4MTwvbGFzdC11cGRhdGVkLWRhdGU+PGFj

Y2Vzc2lvbi1udW0+SVNJOjAwMDMwNTY5MjYwMDAzMTwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjMw

Nzwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5FYmJlbGluZzwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

PElEVGV4dD5FZmZlY3RzIG9mIERpZXRhcnkgQ29tcG9zaXRpb24gb24gRW5lcmd5IEV4cGVuZGl0

dXJlIER1cmluZyBXZWlnaHQtTG9zcyBNYWludGVuYW5jZTwvSURUZXh0PjxEaXNwbGF5VGV4dD4o

RWJiZWxpbmcgZXQgYWwuIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+

PGtleSBhcHA9IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVw

Ij4yMjk0PC9rZXk+PC9mb3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+SnVuIDI3

PC9kYXRlPjwvcHViLWRhdGVzPjx5ZWFyPjIwMTI8L3llYXI+PC9kYXRlcz48a2V5d29yZHM+PGtl

eXdvcmQ+bXVzY2xlIHdvcmsgZWZmaWNpZW5jeTwva2V5d29yZD48a2V5d29yZD5sb3ctZ2x5Y2Vt

aWMgbG9hZDwva2V5d29yZD48a2V5d29yZD5sb3ctZmF0IGRpZXQ8L2tleXdvcmQ+PGtleXdvcmQ+

c2tlbGV0YWwtbXVzY2xlPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW4gc2Vuc2l0aXZpdHk8L2tl

eXdvcmQ+PGtleXdvcmQ+cmFuZG9taXplZC10cmlhbDwva2V5d29yZD48a2V5d29yZD5sb3ctY2Fy

Ym9oeWRyYXRlPC9rZXl3b3JkPjxrZXl3b3JkPm9iZXNlIGFkdWx0czwva2V5d29yZD48a2V5d29y

ZD5yaXNrLWZhY3RvcnM8L2tleXdvcmQ+PGtleXdvcmQ+Ym9keS13ZWlnaHQ8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8wMDAz

MDU2OTI2MDAwMzE8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDA5OC03NDg0PC9p

c2JuPjx0aXRsZXM+PHRpdGxlPkVmZmVjdHMgb2YgRGlldGFyeSBDb21wb3NpdGlvbiBvbiBFbmVy

Z3kgRXhwZW5kaXR1cmUgRHVyaW5nIFdlaWdodC1Mb3NzIE1haW50ZW5hbmNlPC90aXRsZT48c2Vj

b25kYXJ5LXRpdGxlPkphbWEtSm91cm5hbCBvZiB0aGUgQW1lcmljYW4gTWVkaWNhbCBBc3NvY2lh

dGlvbjwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+SmFtYS1KIEFtIE1lZCBBc3NvYzwvYWx0

LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4yNjI3LTI2MzQ8L3BhZ2VzPjxudW1iZXI+MjQ8L251bWJl

cj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+RWJiZWxpbmcsIEMuIEIuPC9hdXRob3I+

PGF1dGhvcj5Td2FpbiwgSi4gRi48L2F1dGhvcj48YXV0aG9yPkZlbGRtYW4sIEguIEEuPC9hdXRo

b3I+PGF1dGhvcj5Xb25nLCBXLiBXLjwvYXV0aG9yPjxhdXRob3I+SGFjaGV5LCBELiBMLjwvYXV0

aG9yPjxhdXRob3I+R2FyY2lhLUxhZ28sIEUuPC9hdXRob3I+PGF1dGhvcj5MdWR3aWcsIEQuIFMu

PC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5n

dWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQyMDE4MTwvYWRkZWQtZGF0ZT48cmVm

LXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5M

dWR3aWcsIERTJiN4RDtDaGlsZHJlbnMgSG9zcCBCb3N0b24sIE5ldyBCYWxhbmNlIEZkbiwgT2Jl

cyBQcmV2ZW50IEN0ciwgMzAwIExvbmd3b29kIEF2ZSwgQm9zdG9uLCBNQSAwMjExNSBVU0EmI3hE

O0NoaWxkcmVucyBIb3NwIEJvc3RvbiwgTmV3IEJhbGFuY2UgRmRuLCBPYmVzIFByZXZlbnQgQ3Ry

LCAzMDAgTG9uZ3dvb2QgQXZlLCBCb3N0b24sIE1BIDAyMTE1IFVTQSYjeEQ7Q2hpbGRyZW5zIEhv

c3AgQm9zdG9uLCBOZXcgQmFsYW5jZSBGZG4sIE9iZXMgUHJldmVudCBDdHIsIEJvc3RvbiwgTUEg

MDIxMTUgVVNBJiN4RDtDaGlsZHJlbnMgSG9zcCBCb3N0b24sIENsaW4gUmVzIEN0ciwgQm9zdG9u

LCBNQSAwMjExNSBVU0EmI3hEO0JyaWdoYW0gJmFtcDsgV29tZW5zIEhvc3AsIEJvc3RvbiwgTUEg

MDIxMTUgVVNBJiN4RDtBUlMsIEJheWxvciBDb2xsIE1lZCwgVVNEQSwgQ2hpbGRyZW5zIE51dHIg

UmVzIEN0ciwgSG91c3RvbiwgVFggVVNBJiN4RDtWYW5kZXJiaWx0IFVuaXYsIE5hc2h2aWxsZSwg

VE4gVVNBPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDAwPC9yZWMtbnVtYmVyPjxsYXN0LXVw

ZGF0ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQyMDE4MTwvbGFzdC11cGRhdGVkLWRhdGU+PGFj

Y2Vzc2lvbi1udW0+SVNJOjAwMDMwNTY5MjYwMDAzMTwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjMw

Nzwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+AG==

ADDIN EN.CITE.DATA (Ebbeling et al. 2012) however this concept has not been specifically investigated in a sleep apnea cohort. Current evidence indicates the use of a low glycemic index high protein diet in individuals seeking weight loss, metabolic and cardiovascular risk reduction for weight loss maintenance PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXJzZW48L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxJ

RFRleHQ+RGlldHMgd2l0aCBIaWdoIG9yIExvdyBQcm90ZWluIENvbnRlbnQgYW5kIEdseWNlbWlj

IEluZGV4IGZvciBXZWlnaHQtTG9zcyBNYWludGVuYW5jZTwvSURUZXh0PjxEaXNwbGF5VGV4dD4o

TGFyc2VuIGV0IGFsLiAyMDEwLCBCcmFuZC1NaWxsZXIgZXQgYWwuIDIwMDIsIE1jTWlsbGFuLVBy

aWNlIGV0IGFsLiAyMDA2KTwvRGlzcGxheVRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkg

YXBwPSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY2

Njwva2V5PjwvZm9yZWlnbi1rZXlzPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3

Lm5lam0ub3JnL2RvaS9mdWxsLzEwLjEwNTYvTkVKTW9hMTAwNzEzNzwvdXJsPjwvcmVsYXRlZC11

cmxzPjwvdXJscz48dGl0bGVzPjx0aXRsZT5EaWV0cyB3aXRoIEhpZ2ggb3IgTG93IFByb3RlaW4g

Q29udGVudCBhbmQgR2x5Y2VtaWMgSW5kZXggZm9yIFdlaWdodC1Mb3NzIE1haW50ZW5hbmNlPC90

aXRsZT48c2Vjb25kYXJ5LXRpdGxlPk5ldyBFbmdsYW5kIEpvdXJuYWwgb2YgTWVkaWNpbmU8L3Nl

Y29uZGFyeS10aXRsZT48L3RpdGxlcz48cGFnZXM+MjEwMi0yMTEzPC9wYWdlcz48bnVtYmVyPjIy

PC9udW1iZXI+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkxhcnNlbiwgVGhvbWFzIE1l

aW5lcnQ8L2F1dGhvcj48YXV0aG9yPkRhbHNrb3YsIFN0aW5lLU1hdGhpbGRlPC9hdXRob3I+PGF1

dGhvcj52YW4gQmFhaywgTWFybGVlbjwvYXV0aG9yPjxhdXRob3I+SmViYiwgU3VzYW4gQS48L2F1

dGhvcj48YXV0aG9yPlBhcGFkYWtpLCBBbmdlbGlraTwvYXV0aG9yPjxhdXRob3I+UGZlaWZmZXIs

IEFuZHJlYXMgRi5ILjwvYXV0aG9yPjxhdXRob3I+TWFydGluZXosIEouIEFsZnJlZG88L2F1dGhv

cj48YXV0aG9yPkhhbmRqaWV2YS1EYXJsZW5za2EsIFRlb2RvcmE8L2F1dGhvcj48YXV0aG9yPkt1

bmXFoW92w6EsIE1hcmllPC9hdXRob3I+PGF1dGhvcj5QaWhsc2fDpXJkLCBNYXRzPC9hdXRob3I+

PGF1dGhvcj5TdGVuZGVyLCBTdGVlbjwvYXV0aG9yPjxhdXRob3I+SG9sc3QsIENsYXVzPC9hdXRo

b3I+PGF1dGhvcj5TYXJpcywgV2ltIEguTS48L2F1dGhvcj48YXV0aG9yPkFzdHJ1cCwgQXJuZTwv

YXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+

MTM0NzU5MDY4NDwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGRhdGVzPjx5ZWFyPjIwMTA8L3llYXI+PC9kYXRlcz48cmVjLW51bWJlcj40

MTE8L3JlYy1udW1iZXI+PGxhc3QtdXBkYXRlZC1kYXRlIGZvcm1hdD0idXRjIj4xMzQ3NTkwNjg0

PC9sYXN0LXVwZGF0ZWQtZGF0ZT48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+ZG9pOjEwLjEwNTYv

TkVKTW9hMTAwNzEzNzwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHZvbHVtZT4zNjM8L3ZvbHVt

ZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5CcmFuZC1NaWxsZXI8L0F1dGhvcj48WWVh

cj4yMDAyPC9ZZWFyPjxJRFRleHQ+R2x5Y2VtaWMgaW5kZXggYW5kIG9iZXNpdHk8L0lEVGV4dD48

cmVjb3JkPjxkYXRlcz48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48eWVh

cj4yMDAyPC95ZWFyPjwvZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPmdseWNlbWljIGluZGV4PC9r

ZXl3b3JkPjxrZXl3b3JkPm9iZXNpdHk8L2tleXdvcmQ+PGtleXdvcmQ+b3ZlcndlaWdodDwva2V5

d29yZD48a2V5d29yZD5pbnN1bGluPC9rZXl3b3JkPjxrZXl3b3JkPmdsdWNvc2UgcmVzcG9uc2Vz

PC9rZXl3b3JkPjxrZXl3b3JkPjwva2V5d29yZD48a2V5d29yZD5jYXJib2h5ZHJhdGU8L2tleXdv

cmQ+PGtleXdvcmQ+RElBQkVUSUMgUkFUUzwva2V5d29yZD48a2V5d29yZD5ESUVUQVJZIEZJQkVS

PC9rZXl3b3JkPjxrZXl3b3JkPkJPRFktV0VJR0hUPC9rZXl3b3JkPjxrZXl3b3JkPkZBVCBPWElE

QVRJT048L2tleXdvcmQ+PGtleXdvcmQ+Q09NTU9OIEZPT0RTPC9rZXl3b3JkPjxrZXl3b3JkPjwv

a2V5d29yZD48a2V5d29yZD5DQVJCT0hZRFJBVEU8L2tleXdvcmQ+PGtleXdvcmQ+SU5TVUxJTjwv

a2V5d29yZD48a2V5d29yZD5TQVRJRVRZPC9rZXl3b3JkPjxrZXl3b3JkPkdMVUNPU0U8L2tleXdv

cmQ+PGtleXdvcmQ+TVVTQ0xFPC9rZXl3b3JkPjwva2V5d29yZHM+PHVybHM+PHJlbGF0ZWQtdXJs

cz48dXJsPiZsdDtHbyB0byBJU0kmZ3Q7Oi8vV09TOjAwMDE3NjM3ODUwMDA0MDwvdXJsPjwvcmVs

YXRlZC11cmxzPjwvdXJscz48aXNibj4wMDAyLTkxNjU8L2lzYm4+PHdvcmstdHlwZT5BcnRpY2xl

OyBQcm9jZWVkaW5ncyBQYXBlcjwvd29yay10eXBlPjx0aXRsZXM+PHRpdGxlPkdseWNlbWljIGlu

ZGV4IGFuZCBvYmVzaXR5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFtZXJpY2FuIEpvdXJuYWwg

b2YgQ2xpbmljYWwgTnV0cml0aW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbS4gSi4g

Q2xpbi4gTnV0ci48L2FsdC10aXRsZT48L3RpdGxlcz48cGFnZXM+MjgxUy0yODVTPC9wYWdlcz48

bnVtYmVyPjE8L251bWJlcj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QnJhbmQtTWls

bGVyLCBKLiBDLjwvYXV0aG9yPjxhdXRob3I+SG9sdCwgUy4gSC4gQS48L2F1dGhvcj48YXV0aG9y

PlBhd2xhaywgRC4gQi48L2F1dGhvcj48YXV0aG9yPk1jTWlsbGFuLCBKLjwvYXV0aG9yPjwvYXV0

aG9ycz48L2NvbnRyaWJ1dG9ycz48bGFuZ3VhZ2U+RW5nbGlzaDwvbGFuZ3VhZ2U+PGFkZGVkLWRh

dGUgZm9ybWF0PSJ1dGMiPjEzNDc1ODk2OTE8L2FkZGVkLWRhdGU+PHJlZi10eXBlIG5hbWU9Ikpv

dXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRoLWFkZHJlc3M+VW5pdiBTeWRuZXksIEh1

bWFuIE51dHIgVW5pdCwgU2NoIE1vbCAmYW1wOyBNaWNyb2JpYWwgQmlvc2NpLCBTeWRuZXksIE5T

VyAyMDA2LCBBdXN0cmFsaWEuJiN4RDtCcmFuZC1NaWxsZXIsIEpDIChyZXByaW50IGF1dGhvciks

IFVuaXYgU3lkbmV5LCBIdW1hbiBOdXRyIFVuaXQsIFNjaCBNb2wgJmFtcDsgTWljcm9iaWFsIEJp

b3NjaSwgU3lkbmV5LCBOU1cgMjAwNiwgQXVzdHJhbGlhLjwvYXV0aC1hZGRyZXNzPjxyZWMtbnVt

YmVyPjQwNzwvcmVjLW51bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDc1

ODk2OTE8L2xhc3QtdXBkYXRlZC1kYXRlPjxhY2Nlc3Npb24tbnVtPldPUzowMDAxNzYzNzg1MDAw

NDA8L2FjY2Vzc2lvbi1udW0+PHZvbHVtZT43Njwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0

ZT48QXV0aG9yPk1jTWlsbGFuLVByaWNlPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48SURUZXh0

PkNvbXBhcmlzb24gb2YgNCBEaWV0cyBvZiBWYXJ5aW5nIEdseWNlbWljIExvYWQgb24gV2VpZ2h0

IExvc3MgYW5kIENhcmRpb3Zhc2N1bGFyIFJpc2sgUmVkdWN0aW9uIGluIE92ZXJ3ZWlnaHQgYW5k

IE9iZXNlIFlvdW5nIEFkdWx0czogQSBSYW5kb21pemVkIENvbnRyb2xsZWQgVHJpYWw8L0lEVGV4

dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpz

Zm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNzE8L2tleT48L2ZvcmVpZ24ta2V5cz48ZGF0ZXM+

PHB1Yi1kYXRlcz48ZGF0ZT5KdWx5IDI0LCAyMDA2PC9kYXRlPjwvcHViLWRhdGVzPjx5ZWFyPjIw

MDY8L3llYXI+PC9kYXRlcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL2FyY2hpbnRl

LmFtYS1hc3NuLm9yZy9jZ2kvY29udGVudC9hYnN0cmFjdC8xNjYvMTQvMTQ2NjwvdXJsPjwvcmVs

YXRlZC11cmxzPjwvdXJscz48dGl0bGVzPjx0aXRsZT5Db21wYXJpc29uIG9mIDQgRGlldHMgb2Yg

VmFyeWluZyBHbHljZW1pYyBMb2FkIG9uIFdlaWdodCBMb3NzIGFuZCBDYXJkaW92YXNjdWxhciBS

aXNrIFJlZHVjdGlvbiBpbiBPdmVyd2VpZ2h0IGFuZCBPYmVzZSBZb3VuZyBBZHVsdHM6IEEgUmFu

ZG9taXplZCBDb250cm9sbGVkIFRyaWFsPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFyY2ggSW50

ZXJuIE1lZDwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4xNDY2LTE0NzU8L3BhZ2Vz

Pjx1cmxzPjxwZGYtdXJscz48dXJsPmludGVybmFsLXBkZjovL0NvbXBhcmlzb24gb2YgNCBkaWV0

cyBvZiB2YXJ5aW5nIGdseWNlbWljIGxvYWQgb24gd2VpZ2h0IGxvc3MgYW5kIENWIHJyaXNrIHJl

ZHVjdGlvbiBvLTM2MzgwNjg3MzYvQ29tcGFyaXNvbiBvZiA0IGRpZXRzIG9mIHZhcnlpbmcgZ2x5

Y2VtaWMgbG9hZCBvbiB3ZWlnaHQgbG9zcyBhbmQgQ1YgcnJpc2sgcmVkdWN0aW9uIG9uIG92ZXJ3

ZWlnaHQgYW5kIG9iZXNlIHlvdW5nIGFkdWx0cy5wZGY8L3VybD48L3BkZi11cmxzPjwvdXJscz48

bnVtYmVyPjE0PC9udW1iZXI+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1jTWlsbGFu

LVByaWNlLCBKb2FubmE8L2F1dGhvcj48YXV0aG9yPlBldG9jeiwgUGV0ZXI8L2F1dGhvcj48YXV0

aG9yPkF0a2luc29uLCBGaW9uYTwvYXV0aG9yPjxhdXRob3I+TyZhcG9zO05laWxsLCBLYXRobGVl

bjwvYXV0aG9yPjxhdXRob3I+U2FtbWFuLCBTYW1pcjwvYXV0aG9yPjxhdXRob3I+U3RlaW5iZWNr

LCBLYXRoZXJpbmU8L2F1dGhvcj48YXV0aG9yPkNhdGVyc29uLCBJYW48L2F1dGhvcj48YXV0aG9y

PkJyYW5kLU1pbGxlciwgSmVubmllPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxh

ZGRlZC1kYXRlIGZvcm1hdD0idXRjIj4xMzQ3NTc2MjQ1PC9hZGRlZC1kYXRlPjxyZWYtdHlwZSBu

YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48cmVjLW51bWJlcj4zNjwvcmVjLW51

bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDc1OTA2NDU8L2xhc3QtdXBk

YXRlZC1kYXRlPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDAxL2FyY2hpbnRlLjE2Ni4x

NC4xNDY2PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48dm9sdW1lPjE2Njwvdm9sdW1lPjwvcmVj

b3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5MYXJzZW48L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxJ

RFRleHQ+RGlldHMgd2l0aCBIaWdoIG9yIExvdyBQcm90ZWluIENvbnRlbnQgYW5kIEdseWNlbWlj

IEluZGV4IGZvciBXZWlnaHQtTG9zcyBNYWludGVuYW5jZTwvSURUZXh0PjxEaXNwbGF5VGV4dD4o

TGFyc2VuIGV0IGFsLiAyMDEwLCBCcmFuZC1NaWxsZXIgZXQgYWwuIDIwMDIsIE1jTWlsbGFuLVBy

aWNlIGV0IGFsLiAyMDA2KTwvRGlzcGxheVRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkg

YXBwPSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY2

Njwva2V5PjwvZm9yZWlnbi1rZXlzPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3

Lm5lam0ub3JnL2RvaS9mdWxsLzEwLjEwNTYvTkVKTW9hMTAwNzEzNzwvdXJsPjwvcmVsYXRlZC11

cmxzPjwvdXJscz48dGl0bGVzPjx0aXRsZT5EaWV0cyB3aXRoIEhpZ2ggb3IgTG93IFByb3RlaW4g

Q29udGVudCBhbmQgR2x5Y2VtaWMgSW5kZXggZm9yIFdlaWdodC1Mb3NzIE1haW50ZW5hbmNlPC90

aXRsZT48c2Vjb25kYXJ5LXRpdGxlPk5ldyBFbmdsYW5kIEpvdXJuYWwgb2YgTWVkaWNpbmU8L3Nl

Y29uZGFyeS10aXRsZT48L3RpdGxlcz48cGFnZXM+MjEwMi0yMTEzPC9wYWdlcz48bnVtYmVyPjIy

PC9udW1iZXI+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPkxhcnNlbiwgVGhvbWFzIE1l

aW5lcnQ8L2F1dGhvcj48YXV0aG9yPkRhbHNrb3YsIFN0aW5lLU1hdGhpbGRlPC9hdXRob3I+PGF1

dGhvcj52YW4gQmFhaywgTWFybGVlbjwvYXV0aG9yPjxhdXRob3I+SmViYiwgU3VzYW4gQS48L2F1

dGhvcj48YXV0aG9yPlBhcGFkYWtpLCBBbmdlbGlraTwvYXV0aG9yPjxhdXRob3I+UGZlaWZmZXIs

IEFuZHJlYXMgRi5ILjwvYXV0aG9yPjxhdXRob3I+TWFydGluZXosIEouIEFsZnJlZG88L2F1dGhv

cj48YXV0aG9yPkhhbmRqaWV2YS1EYXJsZW5za2EsIFRlb2RvcmE8L2F1dGhvcj48YXV0aG9yPkt1

bmXFoW92w6EsIE1hcmllPC9hdXRob3I+PGF1dGhvcj5QaWhsc2fDpXJkLCBNYXRzPC9hdXRob3I+

PGF1dGhvcj5TdGVuZGVyLCBTdGVlbjwvYXV0aG9yPjxhdXRob3I+SG9sc3QsIENsYXVzPC9hdXRo

b3I+PGF1dGhvcj5TYXJpcywgV2ltIEguTS48L2F1dGhvcj48YXV0aG9yPkFzdHJ1cCwgQXJuZTwv

YXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+

MTM0NzU5MDY4NDwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGRhdGVzPjx5ZWFyPjIwMTA8L3llYXI+PC9kYXRlcz48cmVjLW51bWJlcj40

MTE8L3JlYy1udW1iZXI+PGxhc3QtdXBkYXRlZC1kYXRlIGZvcm1hdD0idXRjIj4xMzQ3NTkwNjg0

PC9sYXN0LXVwZGF0ZWQtZGF0ZT48ZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+ZG9pOjEwLjEwNTYv

TkVKTW9hMTAwNzEzNzwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHZvbHVtZT4zNjM8L3ZvbHVt

ZT48L3JlY29yZD48L0NpdGU+PENpdGU+PEF1dGhvcj5CcmFuZC1NaWxsZXI8L0F1dGhvcj48WWVh

cj4yMDAyPC9ZZWFyPjxJRFRleHQ+R2x5Y2VtaWMgaW5kZXggYW5kIG9iZXNpdHk8L0lEVGV4dD48

cmVjb3JkPjxkYXRlcz48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48eWVh

cj4yMDAyPC95ZWFyPjwvZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPmdseWNlbWljIGluZGV4PC9r

ZXl3b3JkPjxrZXl3b3JkPm9iZXNpdHk8L2tleXdvcmQ+PGtleXdvcmQ+b3ZlcndlaWdodDwva2V5

d29yZD48a2V5d29yZD5pbnN1bGluPC9rZXl3b3JkPjxrZXl3b3JkPmdsdWNvc2UgcmVzcG9uc2Vz

PC9rZXl3b3JkPjxrZXl3b3JkPjwva2V5d29yZD48a2V5d29yZD5jYXJib2h5ZHJhdGU8L2tleXdv

cmQ+PGtleXdvcmQ+RElBQkVUSUMgUkFUUzwva2V5d29yZD48a2V5d29yZD5ESUVUQVJZIEZJQkVS

PC9rZXl3b3JkPjxrZXl3b3JkPkJPRFktV0VJR0hUPC9rZXl3b3JkPjxrZXl3b3JkPkZBVCBPWElE

QVRJT048L2tleXdvcmQ+PGtleXdvcmQ+Q09NTU9OIEZPT0RTPC9rZXl3b3JkPjxrZXl3b3JkPjwv

a2V5d29yZD48a2V5d29yZD5DQVJCT0hZRFJBVEU8L2tleXdvcmQ+PGtleXdvcmQ+SU5TVUxJTjwv

a2V5d29yZD48a2V5d29yZD5TQVRJRVRZPC9rZXl3b3JkPjxrZXl3b3JkPkdMVUNPU0U8L2tleXdv

cmQ+PGtleXdvcmQ+TVVTQ0xFPC9rZXl3b3JkPjwva2V5d29yZHM+PHVybHM+PHJlbGF0ZWQtdXJs

cz48dXJsPiZsdDtHbyB0byBJU0kmZ3Q7Oi8vV09TOjAwMDE3NjM3ODUwMDA0MDwvdXJsPjwvcmVs

YXRlZC11cmxzPjwvdXJscz48aXNibj4wMDAyLTkxNjU8L2lzYm4+PHdvcmstdHlwZT5BcnRpY2xl

OyBQcm9jZWVkaW5ncyBQYXBlcjwvd29yay10eXBlPjx0aXRsZXM+PHRpdGxlPkdseWNlbWljIGlu

ZGV4IGFuZCBvYmVzaXR5PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFtZXJpY2FuIEpvdXJuYWwg

b2YgQ2xpbmljYWwgTnV0cml0aW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbS4gSi4g

Q2xpbi4gTnV0ci48L2FsdC10aXRsZT48L3RpdGxlcz48cGFnZXM+MjgxUy0yODVTPC9wYWdlcz48

bnVtYmVyPjE8L251bWJlcj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+QnJhbmQtTWls

bGVyLCBKLiBDLjwvYXV0aG9yPjxhdXRob3I+SG9sdCwgUy4gSC4gQS48L2F1dGhvcj48YXV0aG9y

PlBhd2xhaywgRC4gQi48L2F1dGhvcj48YXV0aG9yPk1jTWlsbGFuLCBKLjwvYXV0aG9yPjwvYXV0

aG9ycz48L2NvbnRyaWJ1dG9ycz48bGFuZ3VhZ2U+RW5nbGlzaDwvbGFuZ3VhZ2U+PGFkZGVkLWRh

dGUgZm9ybWF0PSJ1dGMiPjEzNDc1ODk2OTE8L2FkZGVkLWRhdGU+PHJlZi10eXBlIG5hbWU9Ikpv

dXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRoLWFkZHJlc3M+VW5pdiBTeWRuZXksIEh1

bWFuIE51dHIgVW5pdCwgU2NoIE1vbCAmYW1wOyBNaWNyb2JpYWwgQmlvc2NpLCBTeWRuZXksIE5T

VyAyMDA2LCBBdXN0cmFsaWEuJiN4RDtCcmFuZC1NaWxsZXIsIEpDIChyZXByaW50IGF1dGhvciks

IFVuaXYgU3lkbmV5LCBIdW1hbiBOdXRyIFVuaXQsIFNjaCBNb2wgJmFtcDsgTWljcm9iaWFsIEJp

b3NjaSwgU3lkbmV5LCBOU1cgMjAwNiwgQXVzdHJhbGlhLjwvYXV0aC1hZGRyZXNzPjxyZWMtbnVt

YmVyPjQwNzwvcmVjLW51bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDc1

ODk2OTE8L2xhc3QtdXBkYXRlZC1kYXRlPjxhY2Nlc3Npb24tbnVtPldPUzowMDAxNzYzNzg1MDAw

NDA8L2FjY2Vzc2lvbi1udW0+PHZvbHVtZT43Njwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48Q2l0

ZT48QXV0aG9yPk1jTWlsbGFuLVByaWNlPC9BdXRob3I+PFllYXI+MjAwNjwvWWVhcj48SURUZXh0

PkNvbXBhcmlzb24gb2YgNCBEaWV0cyBvZiBWYXJ5aW5nIEdseWNlbWljIExvYWQgb24gV2VpZ2h0

IExvc3MgYW5kIENhcmRpb3Zhc2N1bGFyIFJpc2sgUmVkdWN0aW9uIGluIE92ZXJ3ZWlnaHQgYW5k

IE9iZXNlIFlvdW5nIEFkdWx0czogQSBSYW5kb21pemVkIENvbnRyb2xsZWQgVHJpYWw8L0lEVGV4

dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpz

Zm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNzE8L2tleT48L2ZvcmVpZ24ta2V5cz48ZGF0ZXM+

PHB1Yi1kYXRlcz48ZGF0ZT5KdWx5IDI0LCAyMDA2PC9kYXRlPjwvcHViLWRhdGVzPjx5ZWFyPjIw

MDY8L3llYXI+PC9kYXRlcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL2FyY2hpbnRl

LmFtYS1hc3NuLm9yZy9jZ2kvY29udGVudC9hYnN0cmFjdC8xNjYvMTQvMTQ2NjwvdXJsPjwvcmVs

YXRlZC11cmxzPjwvdXJscz48dGl0bGVzPjx0aXRsZT5Db21wYXJpc29uIG9mIDQgRGlldHMgb2Yg

VmFyeWluZyBHbHljZW1pYyBMb2FkIG9uIFdlaWdodCBMb3NzIGFuZCBDYXJkaW92YXNjdWxhciBS

aXNrIFJlZHVjdGlvbiBpbiBPdmVyd2VpZ2h0IGFuZCBPYmVzZSBZb3VuZyBBZHVsdHM6IEEgUmFu

ZG9taXplZCBDb250cm9sbGVkIFRyaWFsPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFyY2ggSW50

ZXJuIE1lZDwvc2Vjb25kYXJ5LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4xNDY2LTE0NzU8L3BhZ2Vz

Pjx1cmxzPjxwZGYtdXJscz48dXJsPmludGVybmFsLXBkZjovL0NvbXBhcmlzb24gb2YgNCBkaWV0

cyBvZiB2YXJ5aW5nIGdseWNlbWljIGxvYWQgb24gd2VpZ2h0IGxvc3MgYW5kIENWIHJyaXNrIHJl

ZHVjdGlvbiBvLTM2MzgwNjg3MzYvQ29tcGFyaXNvbiBvZiA0IGRpZXRzIG9mIHZhcnlpbmcgZ2x5

Y2VtaWMgbG9hZCBvbiB3ZWlnaHQgbG9zcyBhbmQgQ1YgcnJpc2sgcmVkdWN0aW9uIG9uIG92ZXJ3

ZWlnaHQgYW5kIG9iZXNlIHlvdW5nIGFkdWx0cy5wZGY8L3VybD48L3BkZi11cmxzPjwvdXJscz48

bnVtYmVyPjE0PC9udW1iZXI+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPk1jTWlsbGFu

LVByaWNlLCBKb2FubmE8L2F1dGhvcj48YXV0aG9yPlBldG9jeiwgUGV0ZXI8L2F1dGhvcj48YXV0

aG9yPkF0a2luc29uLCBGaW9uYTwvYXV0aG9yPjxhdXRob3I+TyZhcG9zO05laWxsLCBLYXRobGVl

bjwvYXV0aG9yPjxhdXRob3I+U2FtbWFuLCBTYW1pcjwvYXV0aG9yPjxhdXRob3I+U3RlaW5iZWNr

LCBLYXRoZXJpbmU8L2F1dGhvcj48YXV0aG9yPkNhdGVyc29uLCBJYW48L2F1dGhvcj48YXV0aG9y

PkJyYW5kLU1pbGxlciwgSmVubmllPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxh

ZGRlZC1kYXRlIGZvcm1hdD0idXRjIj4xMzQ3NTc2MjQ1PC9hZGRlZC1kYXRlPjxyZWYtdHlwZSBu

YW1lPSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48cmVjLW51bWJlcj4zNjwvcmVjLW51

bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDc1OTA2NDU8L2xhc3QtdXBk

YXRlZC1kYXRlPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT4xMC4xMDAxL2FyY2hpbnRlLjE2Ni4x

NC4xNDY2PC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48dm9sdW1lPjE2Njwvdm9sdW1lPjwvcmVj

b3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE.DATA (Larsen et al. 2010, Brand-Miller et al. 2002, McMillan-Price et al. 2006) but this has not been tested in people with OSA. It is vitally important to test weight management interventions specifically in populations with OSA because there is evidence to suggest that this population may be particularly resistant to weight loss. Such weight loss resistance may be related to the symptoms of sleep apnea (such as daytime sleepiness interfering with exercise capacity), which are known to be associated with alterations in sympathetic activity. Furthermore, obstructive sleep apnea is frequently associated with heightened sympathetic nervous activity and there is a complex integration between cardiovascular reflexes and central autonomic influences that control physiological sleep dependent changes in arterial blood pressure and heart rate PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3J0ZWxsaTwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

PElEVGV4dD5CYXJvcmVmbGV4IG1vZHVsYXRpb24gZHVyaW5nIHNsZWVwIGFuZCBpbiBvYnN0cnVj

dGl2ZSBzbGVlcCBhcG5lYSBzeW5kcm9tZTwvSURUZXh0PjxEaXNwbGF5VGV4dD4oQ29ydGVsbGkg

ZXQgYWwuIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9

IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yMzA5PC9r

ZXk+PC9mb3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+SnVsIDI8L2RhdGU+PC9w

dWItZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5hcnRl

cmlhbCBiYXJvcmVmbGV4PC9rZXl3b3JkPjxrZXl3b3JkPmF1dG9ub21pYyBuZXJ2b3VzIHN5c3Rl

bTwva2V5d29yZD48a2V5d29yZD5zeW1wYXRoZXRpYyBhY3Rpdml0eTwva2V5d29yZD48a2V5d29y

ZD5ibG9vZCBwcmVzc3VyZSB2YXJpYWJpbGl0eTwva2V5d29yZD48a2V5d29yZD5oZWFydCByYXRl

IHZhcmlhYmlsaXR5PC9rZXl3b3JkPjxrZXl3b3JkPmFydGVyaWFsIGh5cGVydGVuc2lvbjwva2V5

d29yZD48a2V5d29yZD5vYnN0cnVjdGl2ZSBzbGVlcCBhcG5lYTwva2V5d29yZD48a2V5d29yZD5k

YXl0aW1lIHNvbW5vbGVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+c2xlZXA8L2tleXdvcmQ+PGtleXdv

cmQ+cG9zaXRpdmUgYWlyd2F5IHByZXNzdXJlPC9rZXl3b3JkPjxrZXl3b3JkPnN5bXBhdGhldGlj

LW5lcnZlIGFjdGl2aXR5PC9rZXl3b3JkPjxrZXl3b3JkPmFydGVyaWFsLWJsb29kLXByZXNzdXJl

PC9rZXl3b3JkPjxrZXl3b3JkPmhlYXJ0LXJhdGU8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fyb3RpZCBi

YXJvcmVmbGV4PC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsYXIgY29ydGV4PC9rZXl3b3JkPjxrZXl3

b3JkPmludGVybWl0dGVudCBoeXBveGlhPC9rZXl3b3JkPjxrZXl3b3JkPmJyZWF0aGluZyBkaXNv

cmRlcnM8L2tleXdvcmQ+PGtleXdvcmQ+ZGF5dGltZSBzbGVlcGluZXNzPC9rZXl3b3JkPjxrZXl3

b3JkPmJyYWluIGFjdGl2YXRpb248L2tleXdvcmQ+PC9rZXl3b3Jkcz48dXJscz48cmVsYXRlZC11

cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8wMDAzMDUzNjI4MDAwMDM8L3VybD48L3JlbGF0

ZWQtdXJscz48L3VybHM+PGlzYm4+MTU2Ni0wNzAyPC9pc2JuPjx0aXRsZXM+PHRpdGxlPkJhcm9y

ZWZsZXggbW9kdWxhdGlvbiBkdXJpbmcgc2xlZXAgYW5kIGluIG9ic3RydWN0aXZlIHNsZWVwIGFw

bmVhIHN5bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkF1dG9ub21pYyBOZXVyb3NjaWVu

Y2UtQmFzaWMgJmFtcDsgQ2xpbmljYWw8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkF1dG9u

IE5ldXJvc2NpLUJhc2ljPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjctMTE8L3BhZ2VzPjxu

dW1iZXI+MTwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Db3J0ZWxsaSwg

UC48L2F1dGhvcj48YXV0aG9yPkxvbWJhcmRpLCBDLjwvYXV0aG9yPjxhdXRob3I+TW9udGFnbmEs

IFAuPC9hdXRob3I+PGF1dGhvcj5QYXJhdGksIEcuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJp

YnV0b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0

YyI+MTM0NzQzMzY3NTwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xl

Ij4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5QYXJhdGksIEcmI3hEO1MgTHVjYSBIb3NwLCBJ

c3QgQXV4b2wgSXRhbGlhbiwgRGVwdCBDYXJkaW9sLCBWaWEgU3BhZ25vbGV0dG8gMywgSS0yMDE1

OSBNaWxhbiwgSXRhbHkmI3hEO1MgTHVjYSBIb3NwLCBJc3QgQXV4b2wgSXRhbGlhbiwgRGVwdCBD

YXJkaW9sLCBWaWEgU3BhZ25vbGV0dG8gMywgSS0yMDE1OSBNaWxhbiwgSXRhbHkmI3hEO1MgTHVj

YSBIb3NwLCBJc3QgQXV4b2wgSXRhbGlhbiwgRGVwdCBDYXJkaW9sLCBJLTIwMTU5IE1pbGFuLCBJ

dGFseSYjeEQ7QWxtYSBNYXRlciBTdHVkaW9ydW0gVW5pdiBCb2xvZ25hLCBJUkNTUyBJc3QgU2Np

IE5ldXJvbCBCb2xvZ25hLCBEaXBhcnRpbWVudG8gU2NpIE5ldXJvbCwgQm9sb2duYSwgSXRhbHkm

I3hEO1VuaXYgQm9sb2duYSwgQ3RyIFNsZWVwIERpc29yZGVycywgRGVwdCBOZXVyb2wgU2NpLCBC

b2xvZ25hLCBJdGFseSYjeEQ7VW5pdiBNaWxhbm8gQmljb2NjYSwgRGVwdCBDbGluIE1lZCAmYW1w

OyBQcmV2ZW50LCBNaWxhbiwgSXRhbHk8L2F1dGgtYWRkcmVzcz48cmVjLW51bWJlcj40MDM8L3Jl

Yy1udW1iZXI+PGxhc3QtdXBkYXRlZC1kYXRlIGZvcm1hdD0idXRjIj4xMzQ3NDMzNjc1PC9sYXN0

LXVwZGF0ZWQtZGF0ZT48YWNjZXNzaW9uLW51bT5JU0k6MDAwMzA1MzYyODAwMDAzPC9hY2Nlc3Np

b24tbnVtPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT5ET0kgMTAuMTAxNi9qLmF1dG5ldS4yMDEy

LjAyLjAwNTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHZvbHVtZT4xNjk8L3ZvbHVtZT48L3Jl

Y29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Db3J0ZWxsaTwvQXV0aG9yPjxZZWFyPjIwMTI8L1llYXI+

PElEVGV4dD5CYXJvcmVmbGV4IG1vZHVsYXRpb24gZHVyaW5nIHNsZWVwIGFuZCBpbiBvYnN0cnVj

dGl2ZSBzbGVlcCBhcG5lYSBzeW5kcm9tZTwvSURUZXh0PjxEaXNwbGF5VGV4dD4oQ29ydGVsbGkg

ZXQgYWwuIDIwMTIpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9

IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yMzA5PC9r

ZXk+PC9mb3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+SnVsIDI8L2RhdGU+PC9w

dWItZGF0ZXM+PHllYXI+MjAxMjwveWVhcj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5hcnRl

cmlhbCBiYXJvcmVmbGV4PC9rZXl3b3JkPjxrZXl3b3JkPmF1dG9ub21pYyBuZXJ2b3VzIHN5c3Rl

bTwva2V5d29yZD48a2V5d29yZD5zeW1wYXRoZXRpYyBhY3Rpdml0eTwva2V5d29yZD48a2V5d29y

ZD5ibG9vZCBwcmVzc3VyZSB2YXJpYWJpbGl0eTwva2V5d29yZD48a2V5d29yZD5oZWFydCByYXRl

IHZhcmlhYmlsaXR5PC9rZXl3b3JkPjxrZXl3b3JkPmFydGVyaWFsIGh5cGVydGVuc2lvbjwva2V5

d29yZD48a2V5d29yZD5vYnN0cnVjdGl2ZSBzbGVlcCBhcG5lYTwva2V5d29yZD48a2V5d29yZD5k

YXl0aW1lIHNvbW5vbGVuY2U8L2tleXdvcmQ+PGtleXdvcmQ+c2xlZXA8L2tleXdvcmQ+PGtleXdv

cmQ+cG9zaXRpdmUgYWlyd2F5IHByZXNzdXJlPC9rZXl3b3JkPjxrZXl3b3JkPnN5bXBhdGhldGlj

LW5lcnZlIGFjdGl2aXR5PC9rZXl3b3JkPjxrZXl3b3JkPmFydGVyaWFsLWJsb29kLXByZXNzdXJl

PC9rZXl3b3JkPjxrZXl3b3JkPmhlYXJ0LXJhdGU8L2tleXdvcmQ+PGtleXdvcmQ+Y2Fyb3RpZCBi

YXJvcmVmbGV4PC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsYXIgY29ydGV4PC9rZXl3b3JkPjxrZXl3

b3JkPmludGVybWl0dGVudCBoeXBveGlhPC9rZXl3b3JkPjxrZXl3b3JkPmJyZWF0aGluZyBkaXNv

cmRlcnM8L2tleXdvcmQ+PGtleXdvcmQ+ZGF5dGltZSBzbGVlcGluZXNzPC9rZXl3b3JkPjxrZXl3

b3JkPmJyYWluIGFjdGl2YXRpb248L2tleXdvcmQ+PC9rZXl3b3Jkcz48dXJscz48cmVsYXRlZC11

cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8wMDAzMDUzNjI4MDAwMDM8L3VybD48L3JlbGF0

ZWQtdXJscz48L3VybHM+PGlzYm4+MTU2Ni0wNzAyPC9pc2JuPjx0aXRsZXM+PHRpdGxlPkJhcm9y

ZWZsZXggbW9kdWxhdGlvbiBkdXJpbmcgc2xlZXAgYW5kIGluIG9ic3RydWN0aXZlIHNsZWVwIGFw

bmVhIHN5bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkF1dG9ub21pYyBOZXVyb3NjaWVu

Y2UtQmFzaWMgJmFtcDsgQ2xpbmljYWw8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkF1dG9u

IE5ldXJvc2NpLUJhc2ljPC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjctMTE8L3BhZ2VzPjxu

dW1iZXI+MTwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Db3J0ZWxsaSwg

UC48L2F1dGhvcj48YXV0aG9yPkxvbWJhcmRpLCBDLjwvYXV0aG9yPjxhdXRob3I+TW9udGFnbmEs

IFAuPC9hdXRob3I+PGF1dGhvcj5QYXJhdGksIEcuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJp

YnV0b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0

YyI+MTM0NzQzMzY3NTwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xl

Ij4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5QYXJhdGksIEcmI3hEO1MgTHVjYSBIb3NwLCBJ

c3QgQXV4b2wgSXRhbGlhbiwgRGVwdCBDYXJkaW9sLCBWaWEgU3BhZ25vbGV0dG8gMywgSS0yMDE1

OSBNaWxhbiwgSXRhbHkmI3hEO1MgTHVjYSBIb3NwLCBJc3QgQXV4b2wgSXRhbGlhbiwgRGVwdCBD

YXJkaW9sLCBWaWEgU3BhZ25vbGV0dG8gMywgSS0yMDE1OSBNaWxhbiwgSXRhbHkmI3hEO1MgTHVj

YSBIb3NwLCBJc3QgQXV4b2wgSXRhbGlhbiwgRGVwdCBDYXJkaW9sLCBJLTIwMTU5IE1pbGFuLCBJ

dGFseSYjeEQ7QWxtYSBNYXRlciBTdHVkaW9ydW0gVW5pdiBCb2xvZ25hLCBJUkNTUyBJc3QgU2Np

IE5ldXJvbCBCb2xvZ25hLCBEaXBhcnRpbWVudG8gU2NpIE5ldXJvbCwgQm9sb2duYSwgSXRhbHkm

I3hEO1VuaXYgQm9sb2duYSwgQ3RyIFNsZWVwIERpc29yZGVycywgRGVwdCBOZXVyb2wgU2NpLCBC

b2xvZ25hLCBJdGFseSYjeEQ7VW5pdiBNaWxhbm8gQmljb2NjYSwgRGVwdCBDbGluIE1lZCAmYW1w

OyBQcmV2ZW50LCBNaWxhbiwgSXRhbHk8L2F1dGgtYWRkcmVzcz48cmVjLW51bWJlcj40MDM8L3Jl

Yy1udW1iZXI+PGxhc3QtdXBkYXRlZC1kYXRlIGZvcm1hdD0idXRjIj4xMzQ3NDMzNjc1PC9sYXN0

LXVwZGF0ZWQtZGF0ZT48YWNjZXNzaW9uLW51bT5JU0k6MDAwMzA1MzYyODAwMDAzPC9hY2Nlc3Np

b24tbnVtPjxlbGVjdHJvbmljLXJlc291cmNlLW51bT5ET0kgMTAuMTAxNi9qLmF1dG5ldS4yMDEy

LjAyLjAwNTwvZWxlY3Ryb25pYy1yZXNvdXJjZS1udW0+PHZvbHVtZT4xNjk8L3ZvbHVtZT48L3Jl

Y29yZD48L0NpdGU+PC9FbmROb3RlPgB=

ADDIN EN.CITE.DATA (Cortelli et al. 2012). Perturbations in neuroadrenergic function play a key role in the genesis and progression of the metabolic syndrome and its related cardiometabolic risk PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5jaWE8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxJ

RFRleHQ+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtIGFuZCB0aGUgbWV0YWJvbGljIHN5

bmRyb21lPC9JRFRleHQ+PERpc3BsYXlUZXh0PihNYW5jaWEgZXQgYWwuIDIwMDcpPC9EaXNwbGF5

VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ienNzd3dkcDJk

MHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNjY5PC9rZXk+PC9mb3JlaWduLWtleXM+PGRh

dGVzPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHViLWRhdGVzPjx5ZWFyPjIwMDc8L3ll

YXI+PC9kYXRlcz48a2V5d29yZHM+PGtleXdvcmQ+Y2VudHJhbCBzeW1wYXRob2x5dGljIGRydWdz

PC9rZXl3b3JkPjxrZXl3b3JkPmh5cGVydGVuc2lvbjwva2V5d29yZD48a2V5d29yZD5pbnN1bGlu

PC9rZXl3b3JkPjxrZXl3b3JkPm1ldGFib2xpYyBzeW5kcm9tZTwva2V5d29yZD48a2V5d29yZD5v

YmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPnNsZWVwIGFwbm9lYTwva2V5d29yZD48a2V5d29yZD5z

eW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbTwva2V5d29yZD48a2V5d29yZD50eXBlLTIgZGlhYmV0

ZXMtbWVsbGl0dXM8L2tleXdvcmQ+PGtleXdvcmQ+b2Jlc2l0eS1yZWxhdGVkIGh5cGVydGVuc2lv

bjwva2V5d29yZD48a2V5d29yZD5vYnN0cnVjdGl2ZSBzbGVlcC1hcG5lYTwva2V5d29yZD48a2V5

d29yZD5jb3JvbmFyeS1oZWFydC1kaXNlYXNlPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW4tcmVz

aXN0YW5jZSBzeW5kcm9tZTwva2V5d29yZD48a2V5d29yZD5sZWZ0LXZlbnRyaWN1bGFyIG1hc3M8

L2tleXdvcmQ+PGtleXdvcmQ+dGFyZ2V0IG9yZ2FuIGRhbWFnZTwva2V5d29yZD48a2V5d29yZD50

cmVhdG1lbnQtcGFuZWwtaWlpPC9rZXl3b3JkPjxrZXl3b3JkPmMtcmVhY3RpdmUgcHJvdGVpbjwv

a2V5d29yZD48a2V5d29yZD5ibG9vZC1wcmVzc3VyZTwva2V5d29yZD48L2tleXdvcmRzPjx1cmxz

PjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0OzovLzAwMDI0NTc0MTIwMDAwMjwv

dXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMjYzLTYzNTI8L2lzYm4+PHRpdGxlcz48

dGl0bGU+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtIGFuZCB0aGUgbWV0YWJvbGljIHN5

bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkpvdXJuYWwgb2YgSHlwZXJ0ZW5zaW9uPC9z

ZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5KIEh5cGVydGVuczwvYWx0LXRpdGxlPjwvdGl0bGVz

PjxwYWdlcz45MDktOTIwPC9wYWdlcz48bnVtYmVyPjU8L251bWJlcj48Y29udHJpYnV0b3JzPjxh

dXRob3JzPjxhdXRob3I+TWFuY2lhLCBHLjwvYXV0aG9yPjxhdXRob3I+Qm91c3F1ZXQsIFAuPC9h

dXRob3I+PGF1dGhvcj5FbGdob3ppLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+RXNsZXIsIE0uPC9h

dXRob3I+PGF1dGhvcj5HcmFzc2ksIEcuPC9hdXRob3I+PGF1dGhvcj5KdWxpdXMsIFMuPC9hdXRo

b3I+PGF1dGhvcj5SZWlkLCBKLjwvYXV0aG9yPjxhdXRob3I+VmFuIFp3aWV0ZW4sIFAuIEEuPC9h

dXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFn

ZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2OTwvYWRkZWQtZGF0ZT48cmVmLXR5

cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5NYW5j

aWEsIEcmI3hEO1VuaXYgTWlsYW5vIEJpY29jY2EsIE9zcGVkIFNhbiBHZXJhbGRvIFRpbnRvcmks

IFZpYSBQZXJnb2xlc2kgMzMsIEktMjAwNTIgTW9uemEsIE1pbGFuLCBJdGFseSYjeEQ7VW5pdiBN

aWxhbm8gQmljb2NjYSwgT3NwZWQgU2FuIEdlcmFsZG8gVGludG9yaSwgVmlhIFBlcmdvbGVzaSAz

MywgSS0yMDA1MiBNb256YSwgTWlsYW4sIEl0YWx5JiN4RDtVbml2IE1pbGFubyBCaWNvY2NhLCBP

c3BlZCBTYW4gR2VyYWxkbyBUaW50b3JpLCBJLTIwMDUyIE1vbnphLCBNaWxhbiwgSXRhbHkmI3hE

O1VuaXYgU3RyYXNib3VyZyAxLCBGYWMgTWVkLCBTdHJhc2JvdXJnLCBGcmFuY2UmI3hEO0hvcCBO

ZWNrZXIgRW5mYW50cyBNYWxhZCwgVUYgUGhhcm1hY29sIENsaW4sIFBhcmlzLCBGcmFuY2UmI3hE

O0Jha2VyIE1lZCBSZXMgSW5zdCwgTWVsYm91cm5lLCBWaWMsIEF1c3RyYWxpYSYjeEQ7VW5pdiBN

aWNoaWdhbiBIbHRoIFN5c3QsIERlcHQgSW50ZXJuYWwgTWVkLCBBbm4gQXJib3IsIE1JIFVTQSYj

eEQ7VW5pdiBHbGFzZ293LCBEZXB0IE1lZCAmYW1wOyBUaGVyYXBldXQsIEdhcmRpbmVyIEluc3Qs

IEdsYXNnb3csIExhbmFyaywgU2NvdGxhbmQmI3hEO1VuaXYgQW1zdGVyZGFtLCBBY2FkIE1lZCBD

dHIsIERlcHQgUGhhcm1hY290aGVyYXB5LCBOTC0xMTA1IEFaIEFtc3RlcmRhbSwgTmV0aGVybGFu

ZHMmI3hEO1VuaXYgQW1zdGVyZGFtLCBBY2FkIE1lZCBDdHIsIERlcHQgQ2FyZGlvbCwgTkwtMTEw

NSBBWiBBbXN0ZXJkYW0sIE5ldGhlcmxhbmRzJiN4RDtVbml2IEFtc3RlcmRhbSwgQWNhZCBNZWQg

Q3RyLCBEZXB0IENhcmRpb3B1bG0gU3VyZywgTkwtMTEwNSBBWiBBbXN0ZXJkYW0sIE5ldGhlcmxh

bmRzPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDEzPC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0

ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2OTwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vz

c2lvbi1udW0+SVNJOjAwMDI0NTc0MTIwMDAwMjwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjI1PC92

b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5jaWE8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxJ

RFRleHQ+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtIGFuZCB0aGUgbWV0YWJvbGljIHN5

bmRyb21lPC9JRFRleHQ+PERpc3BsYXlUZXh0PihNYW5jaWEgZXQgYWwuIDIwMDcpPC9EaXNwbGF5

VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0ienNzd3dkcDJk

MHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNjY5PC9rZXk+PC9mb3JlaWduLWtleXM+PGRh

dGVzPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHViLWRhdGVzPjx5ZWFyPjIwMDc8L3ll

YXI+PC9kYXRlcz48a2V5d29yZHM+PGtleXdvcmQ+Y2VudHJhbCBzeW1wYXRob2x5dGljIGRydWdz

PC9rZXl3b3JkPjxrZXl3b3JkPmh5cGVydGVuc2lvbjwva2V5d29yZD48a2V5d29yZD5pbnN1bGlu

PC9rZXl3b3JkPjxrZXl3b3JkPm1ldGFib2xpYyBzeW5kcm9tZTwva2V5d29yZD48a2V5d29yZD5v

YmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPnNsZWVwIGFwbm9lYTwva2V5d29yZD48a2V5d29yZD5z

eW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbTwva2V5d29yZD48a2V5d29yZD50eXBlLTIgZGlhYmV0

ZXMtbWVsbGl0dXM8L2tleXdvcmQ+PGtleXdvcmQ+b2Jlc2l0eS1yZWxhdGVkIGh5cGVydGVuc2lv

bjwva2V5d29yZD48a2V5d29yZD5vYnN0cnVjdGl2ZSBzbGVlcC1hcG5lYTwva2V5d29yZD48a2V5

d29yZD5jb3JvbmFyeS1oZWFydC1kaXNlYXNlPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW4tcmVz

aXN0YW5jZSBzeW5kcm9tZTwva2V5d29yZD48a2V5d29yZD5sZWZ0LXZlbnRyaWN1bGFyIG1hc3M8

L2tleXdvcmQ+PGtleXdvcmQ+dGFyZ2V0IG9yZ2FuIGRhbWFnZTwva2V5d29yZD48a2V5d29yZD50

cmVhdG1lbnQtcGFuZWwtaWlpPC9rZXl3b3JkPjxrZXl3b3JkPmMtcmVhY3RpdmUgcHJvdGVpbjwv

a2V5d29yZD48a2V5d29yZD5ibG9vZC1wcmVzc3VyZTwva2V5d29yZD48L2tleXdvcmRzPjx1cmxz

PjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0OzovLzAwMDI0NTc0MTIwMDAwMjwv

dXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMjYzLTYzNTI8L2lzYm4+PHRpdGxlcz48

dGl0bGU+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtIGFuZCB0aGUgbWV0YWJvbGljIHN5

bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkpvdXJuYWwgb2YgSHlwZXJ0ZW5zaW9uPC9z

ZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5KIEh5cGVydGVuczwvYWx0LXRpdGxlPjwvdGl0bGVz

PjxwYWdlcz45MDktOTIwPC9wYWdlcz48bnVtYmVyPjU8L251bWJlcj48Y29udHJpYnV0b3JzPjxh

dXRob3JzPjxhdXRob3I+TWFuY2lhLCBHLjwvYXV0aG9yPjxhdXRob3I+Qm91c3F1ZXQsIFAuPC9h

dXRob3I+PGF1dGhvcj5FbGdob3ppLCBKLiBMLjwvYXV0aG9yPjxhdXRob3I+RXNsZXIsIE0uPC9h

dXRob3I+PGF1dGhvcj5HcmFzc2ksIEcuPC9hdXRob3I+PGF1dGhvcj5KdWxpdXMsIFMuPC9hdXRo

b3I+PGF1dGhvcj5SZWlkLCBKLjwvYXV0aG9yPjxhdXRob3I+VmFuIFp3aWV0ZW4sIFAuIEEuPC9h

dXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFn

ZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2OTwvYWRkZWQtZGF0ZT48cmVmLXR5

cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5NYW5j

aWEsIEcmI3hEO1VuaXYgTWlsYW5vIEJpY29jY2EsIE9zcGVkIFNhbiBHZXJhbGRvIFRpbnRvcmks

IFZpYSBQZXJnb2xlc2kgMzMsIEktMjAwNTIgTW9uemEsIE1pbGFuLCBJdGFseSYjeEQ7VW5pdiBN

aWxhbm8gQmljb2NjYSwgT3NwZWQgU2FuIEdlcmFsZG8gVGludG9yaSwgVmlhIFBlcmdvbGVzaSAz

MywgSS0yMDA1MiBNb256YSwgTWlsYW4sIEl0YWx5JiN4RDtVbml2IE1pbGFubyBCaWNvY2NhLCBP

c3BlZCBTYW4gR2VyYWxkbyBUaW50b3JpLCBJLTIwMDUyIE1vbnphLCBNaWxhbiwgSXRhbHkmI3hE

O1VuaXYgU3RyYXNib3VyZyAxLCBGYWMgTWVkLCBTdHJhc2JvdXJnLCBGcmFuY2UmI3hEO0hvcCBO

ZWNrZXIgRW5mYW50cyBNYWxhZCwgVUYgUGhhcm1hY29sIENsaW4sIFBhcmlzLCBGcmFuY2UmI3hE

O0Jha2VyIE1lZCBSZXMgSW5zdCwgTWVsYm91cm5lLCBWaWMsIEF1c3RyYWxpYSYjeEQ7VW5pdiBN

aWNoaWdhbiBIbHRoIFN5c3QsIERlcHQgSW50ZXJuYWwgTWVkLCBBbm4gQXJib3IsIE1JIFVTQSYj

eEQ7VW5pdiBHbGFzZ293LCBEZXB0IE1lZCAmYW1wOyBUaGVyYXBldXQsIEdhcmRpbmVyIEluc3Qs

IEdsYXNnb3csIExhbmFyaywgU2NvdGxhbmQmI3hEO1VuaXYgQW1zdGVyZGFtLCBBY2FkIE1lZCBD

dHIsIERlcHQgUGhhcm1hY290aGVyYXB5LCBOTC0xMTA1IEFaIEFtc3RlcmRhbSwgTmV0aGVybGFu

ZHMmI3hEO1VuaXYgQW1zdGVyZGFtLCBBY2FkIE1lZCBDdHIsIERlcHQgQ2FyZGlvbCwgTkwtMTEw

NSBBWiBBbXN0ZXJkYW0sIE5ldGhlcmxhbmRzJiN4RDtVbml2IEFtc3RlcmRhbSwgQWNhZCBNZWQg

Q3RyLCBEZXB0IENhcmRpb3B1bG0gU3VyZywgTkwtMTEwNSBBWiBBbXN0ZXJkYW0sIE5ldGhlcmxh

bmRzPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDEzPC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0

ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2OTwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vz

c2lvbi1udW0+SVNJOjAwMDI0NTc0MTIwMDAwMjwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjI1PC92

b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA (Mancia et al. 2007). In established obesity, metabolic, hemodynamic and medical (OSA) factors contribute to sustained elevation in sympathetic tone, a long term cycle that in the long term, leads to target organ damage and worse clinical prognosis PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5jaWE8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxJ

RFRleHQ+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtIGFuZCB0aGUgbWV0YWJvbGljIHN5

bmRyb21lPC9JRFRleHQ+PERpc3BsYXlUZXh0PihNYW5jaWEgZXQgYWwuIDIwMDcsIFNlYWxzIGFu

ZCBCZWxsIDIwMDQpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9

IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNjY5PC9r

ZXk+PC9mb3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHVi

LWRhdGVzPjx5ZWFyPjIwMDc8L3llYXI+PC9kYXRlcz48a2V5d29yZHM+PGtleXdvcmQ+Y2VudHJh

bCBzeW1wYXRob2x5dGljIGRydWdzPC9rZXl3b3JkPjxrZXl3b3JkPmh5cGVydGVuc2lvbjwva2V5

d29yZD48a2V5d29yZD5pbnN1bGluPC9rZXl3b3JkPjxrZXl3b3JkPm1ldGFib2xpYyBzeW5kcm9t

ZTwva2V5d29yZD48a2V5d29yZD5vYmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPnNsZWVwIGFwbm9l

YTwva2V5d29yZD48a2V5d29yZD5zeW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbTwva2V5d29yZD48

a2V5d29yZD50eXBlLTIgZGlhYmV0ZXMtbWVsbGl0dXM8L2tleXdvcmQ+PGtleXdvcmQ+b2Jlc2l0

eS1yZWxhdGVkIGh5cGVydGVuc2lvbjwva2V5d29yZD48a2V5d29yZD5vYnN0cnVjdGl2ZSBzbGVl

cC1hcG5lYTwva2V5d29yZD48a2V5d29yZD5jb3JvbmFyeS1oZWFydC1kaXNlYXNlPC9rZXl3b3Jk

PjxrZXl3b3JkPmluc3VsaW4tcmVzaXN0YW5jZSBzeW5kcm9tZTwva2V5d29yZD48a2V5d29yZD5s

ZWZ0LXZlbnRyaWN1bGFyIG1hc3M8L2tleXdvcmQ+PGtleXdvcmQ+dGFyZ2V0IG9yZ2FuIGRhbWFn

ZTwva2V5d29yZD48a2V5d29yZD50cmVhdG1lbnQtcGFuZWwtaWlpPC9rZXl3b3JkPjxrZXl3b3Jk

PmMtcmVhY3RpdmUgcHJvdGVpbjwva2V5d29yZD48a2V5d29yZD5ibG9vZC1wcmVzc3VyZTwva2V5

d29yZD48L2tleXdvcmRzPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0

OzovLzAwMDI0NTc0MTIwMDAwMjwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMjYz

LTYzNTI8L2lzYm4+PHRpdGxlcz48dGl0bGU+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVt

IGFuZCB0aGUgbWV0YWJvbGljIHN5bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkpvdXJu

YWwgb2YgSHlwZXJ0ZW5zaW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5KIEh5cGVydGVu

czwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz45MDktOTIwPC9wYWdlcz48bnVtYmVyPjU8L251

bWJlcj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TWFuY2lhLCBHLjwvYXV0aG9yPjxh

dXRob3I+Qm91c3F1ZXQsIFAuPC9hdXRob3I+PGF1dGhvcj5FbGdob3ppLCBKLiBMLjwvYXV0aG9y

PjxhdXRob3I+RXNsZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5HcmFzc2ksIEcuPC9hdXRob3I+PGF1

dGhvcj5KdWxpdXMsIFMuPC9hdXRob3I+PGF1dGhvcj5SZWlkLCBKLjwvYXV0aG9yPjxhdXRob3I+

VmFuIFp3aWV0ZW4sIFAuIEEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxsYW5n

dWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2

OTwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGF1dGgtYWRkcmVzcz5NYW5jaWEsIEcmI3hEO1VuaXYgTWlsYW5vIEJpY29jY2EsIE9zcGVk

IFNhbiBHZXJhbGRvIFRpbnRvcmksIFZpYSBQZXJnb2xlc2kgMzMsIEktMjAwNTIgTW9uemEsIE1p

bGFuLCBJdGFseSYjeEQ7VW5pdiBNaWxhbm8gQmljb2NjYSwgT3NwZWQgU2FuIEdlcmFsZG8gVGlu

dG9yaSwgVmlhIFBlcmdvbGVzaSAzMywgSS0yMDA1MiBNb256YSwgTWlsYW4sIEl0YWx5JiN4RDtV

bml2IE1pbGFubyBCaWNvY2NhLCBPc3BlZCBTYW4gR2VyYWxkbyBUaW50b3JpLCBJLTIwMDUyIE1v

bnphLCBNaWxhbiwgSXRhbHkmI3hEO1VuaXYgU3RyYXNib3VyZyAxLCBGYWMgTWVkLCBTdHJhc2Jv

dXJnLCBGcmFuY2UmI3hEO0hvcCBOZWNrZXIgRW5mYW50cyBNYWxhZCwgVUYgUGhhcm1hY29sIENs

aW4sIFBhcmlzLCBGcmFuY2UmI3hEO0Jha2VyIE1lZCBSZXMgSW5zdCwgTWVsYm91cm5lLCBWaWMs

IEF1c3RyYWxpYSYjeEQ7VW5pdiBNaWNoaWdhbiBIbHRoIFN5c3QsIERlcHQgSW50ZXJuYWwgTWVk

LCBBbm4gQXJib3IsIE1JIFVTQSYjeEQ7VW5pdiBHbGFzZ293LCBEZXB0IE1lZCAmYW1wOyBUaGVy

YXBldXQsIEdhcmRpbmVyIEluc3QsIEdsYXNnb3csIExhbmFyaywgU2NvdGxhbmQmI3hEO1VuaXYg

QW1zdGVyZGFtLCBBY2FkIE1lZCBDdHIsIERlcHQgUGhhcm1hY290aGVyYXB5LCBOTC0xMTA1IEFa

IEFtc3RlcmRhbSwgTmV0aGVybGFuZHMmI3hEO1VuaXYgQW1zdGVyZGFtLCBBY2FkIE1lZCBDdHIs

IERlcHQgQ2FyZGlvbCwgTkwtMTEwNSBBWiBBbXN0ZXJkYW0sIE5ldGhlcmxhbmRzJiN4RDtVbml2

IEFtc3RlcmRhbSwgQWNhZCBNZWQgQ3RyLCBEZXB0IENhcmRpb3B1bG0gU3VyZywgTkwtMTEwNSBB

WiBBbXN0ZXJkYW0sIE5ldGhlcmxhbmRzPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDEzPC9y

ZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2OTwvbGFz

dC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1udW0+SVNJOjAwMDI0NTc0MTIwMDAwMjwvYWNjZXNz

aW9uLW51bT48dm9sdW1lPjI1PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+

U2VhbHM8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFyPjxJRFRleHQ+Q2hyb25pYyBzeW1wYXRoZXRp

YyBhY3RpdmF0aW9uIC0gQ29uc2VxdWVuY2UgYW5kIGNhdXNlIG9mIGFnZS1hc3NvY2lhdGVkIG9i

ZXNpdHk/PC9JRFRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9

Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY3Mjwva2V5PjwvZm9yZWln

bi1rZXlzPjxkYXRlcz48cHViLWRhdGVzPjxkYXRlPkZlYjwvZGF0ZT48L3B1Yi1kYXRlcz48eWVh

cj4yMDA0PC95ZWFyPjwvZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPm5lcnZvdXMtc3lzdGVtIGFj

dGl2aXR5PC9rZXl3b3JkPjxrZXl3b3JkPnBsYXNtYSBub3JlcGluZXBocmluZTwva2V5d29yZD48

a2V5d29yZD5tZXRhYm9saWMtcmF0ZTwva2V5d29yZD48a2V5d29yZD53ZWlnaHQtZ2Fpbjwva2V5

d29yZD48a2V5d29yZD5ib2R5LWZhdDwva2V5d29yZD48a2V5d29yZD5zeW1wYXRob2FkcmVuYWwg

c3lzdGVtPC9rZXl3b3JkPjxrZXl3b3JkPmNlcmVicm9zcGluYWwtZmx1aWQ8L2tleXdvcmQ+PGtl

eXdvcmQ+YWJkb21pbmFsIGFkaXBvc2l0eTwva2V5d29yZD48a2V5d29yZD5ibG9vZC1wcmVzc3Vy

ZTwva2V5d29yZD48a2V5d29yZD5lbGRlcmx5IG1lbjwva2V5d29yZD48L2tleXdvcmRzPjx1cmxz

PjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0OzovLzAwMDE4ODczOTYwMDAwMjwv

dXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMDEyLTE3OTc8L2lzYm4+PHRpdGxlcz48

dGl0bGU+Q2hyb25pYyBzeW1wYXRoZXRpYyBhY3RpdmF0aW9uIC0gQ29uc2VxdWVuY2UgYW5kIGNh

dXNlIG9mIGFnZS1hc3NvY2lhdGVkIG9iZXNpdHk/PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkRp

YWJldGVzPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5EaWFiZXRlczwvYWx0LXRpdGxlPjwv

dGl0bGVzPjxwYWdlcz4yNzYtMjg0PC9wYWdlcz48bnVtYmVyPjI8L251bWJlcj48Y29udHJpYnV0

b3JzPjxhdXRob3JzPjxhdXRob3I+U2VhbHMsIEQuIFIuPC9hdXRob3I+PGF1dGhvcj5CZWxsLCBD

LjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48bGFuZ3VhZ2U+RW5nbGlzaDwvbGFu

Z3VhZ2U+PGFkZGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDg3OTg4MDc8L2FkZGVkLWRhdGU+PHJl

Zi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRoLWFkZHJlc3M+

U2VhbHMsIERSJiN4RDtVbml2IENvbG9yYWRvLCBEZXB0IEludGVncmF0IFBoeXNpb2wsIFlDQiAz

NTQsIEJvdWxkZXIsIENPIDgwMzA5IFVTQSYjeEQ7VW5pdiBDb2xvcmFkbywgRGVwdCBJbnRlZ3Jh

dCBQaHlzaW9sLCBZQ0IgMzU0LCBCb3VsZGVyLCBDTyA4MDMwOSBVU0EmI3hEO1VuaXYgQ29sb3Jh

ZG8sIERlcHQgSW50ZWdyYXQgUGh5c2lvbCwgQm91bGRlciwgQ08gODAzMDkgVVNBPC9hdXRoLWFk

ZHJlc3M+PHJlYy1udW1iZXI+NDE0PC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0ZSBmb3Jt

YXQ9InV0YyI+MTM0ODc5ODgwNzwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1udW0+SVNJ

OjAwMDE4ODczOTYwMDAwMjwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjUzPC92b2x1bWU+PC9yZWNv

cmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYW5jaWE8L0F1dGhvcj48WWVhcj4yMDA3PC9ZZWFyPjxJ

RFRleHQ+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtIGFuZCB0aGUgbWV0YWJvbGljIHN5

bmRyb21lPC9JRFRleHQ+PERpc3BsYXlUZXh0PihNYW5jaWEgZXQgYWwuIDIwMDcsIFNlYWxzIGFu

ZCBCZWxsIDIwMDQpPC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9

IkVOIiBkYi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNjY5PC9r

ZXk+PC9mb3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHVi

LWRhdGVzPjx5ZWFyPjIwMDc8L3llYXI+PC9kYXRlcz48a2V5d29yZHM+PGtleXdvcmQ+Y2VudHJh

bCBzeW1wYXRob2x5dGljIGRydWdzPC9rZXl3b3JkPjxrZXl3b3JkPmh5cGVydGVuc2lvbjwva2V5

d29yZD48a2V5d29yZD5pbnN1bGluPC9rZXl3b3JkPjxrZXl3b3JkPm1ldGFib2xpYyBzeW5kcm9t

ZTwva2V5d29yZD48a2V5d29yZD5vYmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPnNsZWVwIGFwbm9l

YTwva2V5d29yZD48a2V5d29yZD5zeW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbTwva2V5d29yZD48

a2V5d29yZD50eXBlLTIgZGlhYmV0ZXMtbWVsbGl0dXM8L2tleXdvcmQ+PGtleXdvcmQ+b2Jlc2l0

eS1yZWxhdGVkIGh5cGVydGVuc2lvbjwva2V5d29yZD48a2V5d29yZD5vYnN0cnVjdGl2ZSBzbGVl

cC1hcG5lYTwva2V5d29yZD48a2V5d29yZD5jb3JvbmFyeS1oZWFydC1kaXNlYXNlPC9rZXl3b3Jk

PjxrZXl3b3JkPmluc3VsaW4tcmVzaXN0YW5jZSBzeW5kcm9tZTwva2V5d29yZD48a2V5d29yZD5s

ZWZ0LXZlbnRyaWN1bGFyIG1hc3M8L2tleXdvcmQ+PGtleXdvcmQ+dGFyZ2V0IG9yZ2FuIGRhbWFn

ZTwva2V5d29yZD48a2V5d29yZD50cmVhdG1lbnQtcGFuZWwtaWlpPC9rZXl3b3JkPjxrZXl3b3Jk

PmMtcmVhY3RpdmUgcHJvdGVpbjwva2V5d29yZD48a2V5d29yZD5ibG9vZC1wcmVzc3VyZTwva2V5

d29yZD48L2tleXdvcmRzPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0

OzovLzAwMDI0NTc0MTIwMDAwMjwvdXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMjYz

LTYzNTI8L2lzYm4+PHRpdGxlcz48dGl0bGU+VGhlIHN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVt

IGFuZCB0aGUgbWV0YWJvbGljIHN5bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkpvdXJu

YWwgb2YgSHlwZXJ0ZW5zaW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5KIEh5cGVydGVu

czwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz45MDktOTIwPC9wYWdlcz48bnVtYmVyPjU8L251

bWJlcj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+TWFuY2lhLCBHLjwvYXV0aG9yPjxh

dXRob3I+Qm91c3F1ZXQsIFAuPC9hdXRob3I+PGF1dGhvcj5FbGdob3ppLCBKLiBMLjwvYXV0aG9y

PjxhdXRob3I+RXNsZXIsIE0uPC9hdXRob3I+PGF1dGhvcj5HcmFzc2ksIEcuPC9hdXRob3I+PGF1

dGhvcj5KdWxpdXMsIFMuPC9hdXRob3I+PGF1dGhvcj5SZWlkLCBKLjwvYXV0aG9yPjxhdXRob3I+

VmFuIFp3aWV0ZW4sIFAuIEEuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxsYW5n

dWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2

OTwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5

cGU+PGF1dGgtYWRkcmVzcz5NYW5jaWEsIEcmI3hEO1VuaXYgTWlsYW5vIEJpY29jY2EsIE9zcGVk

IFNhbiBHZXJhbGRvIFRpbnRvcmksIFZpYSBQZXJnb2xlc2kgMzMsIEktMjAwNTIgTW9uemEsIE1p

bGFuLCBJdGFseSYjeEQ7VW5pdiBNaWxhbm8gQmljb2NjYSwgT3NwZWQgU2FuIEdlcmFsZG8gVGlu

dG9yaSwgVmlhIFBlcmdvbGVzaSAzMywgSS0yMDA1MiBNb256YSwgTWlsYW4sIEl0YWx5JiN4RDtV

bml2IE1pbGFubyBCaWNvY2NhLCBPc3BlZCBTYW4gR2VyYWxkbyBUaW50b3JpLCBJLTIwMDUyIE1v

bnphLCBNaWxhbiwgSXRhbHkmI3hEO1VuaXYgU3RyYXNib3VyZyAxLCBGYWMgTWVkLCBTdHJhc2Jv

dXJnLCBGcmFuY2UmI3hEO0hvcCBOZWNrZXIgRW5mYW50cyBNYWxhZCwgVUYgUGhhcm1hY29sIENs

aW4sIFBhcmlzLCBGcmFuY2UmI3hEO0Jha2VyIE1lZCBSZXMgSW5zdCwgTWVsYm91cm5lLCBWaWMs

IEF1c3RyYWxpYSYjeEQ7VW5pdiBNaWNoaWdhbiBIbHRoIFN5c3QsIERlcHQgSW50ZXJuYWwgTWVk

LCBBbm4gQXJib3IsIE1JIFVTQSYjeEQ7VW5pdiBHbGFzZ293LCBEZXB0IE1lZCAmYW1wOyBUaGVy

YXBldXQsIEdhcmRpbmVyIEluc3QsIEdsYXNnb3csIExhbmFyaywgU2NvdGxhbmQmI3hEO1VuaXYg

QW1zdGVyZGFtLCBBY2FkIE1lZCBDdHIsIERlcHQgUGhhcm1hY290aGVyYXB5LCBOTC0xMTA1IEFa

IEFtc3RlcmRhbSwgTmV0aGVybGFuZHMmI3hEO1VuaXYgQW1zdGVyZGFtLCBBY2FkIE1lZCBDdHIs

IERlcHQgQ2FyZGlvbCwgTkwtMTEwNSBBWiBBbXN0ZXJkYW0sIE5ldGhlcmxhbmRzJiN4RDtVbml2

IEFtc3RlcmRhbSwgQWNhZCBNZWQgQ3RyLCBEZXB0IENhcmRpb3B1bG0gU3VyZywgTkwtMTEwNSBB

WiBBbXN0ZXJkYW0sIE5ldGhlcmxhbmRzPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDEzPC9y

ZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0ODc5ODA2OTwvbGFz

dC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1udW0+SVNJOjAwMDI0NTc0MTIwMDAwMjwvYWNjZXNz

aW9uLW51bT48dm9sdW1lPjI1PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjxDaXRlPjxBdXRob3I+

U2VhbHM8L0F1dGhvcj48WWVhcj4yMDA0PC9ZZWFyPjxJRFRleHQ+Q2hyb25pYyBzeW1wYXRoZXRp

YyBhY3RpdmF0aW9uIC0gQ29uc2VxdWVuY2UgYW5kIGNhdXNlIG9mIGFnZS1hc3NvY2lhdGVkIG9i

ZXNpdHk/PC9JRFRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9

Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY3Mjwva2V5PjwvZm9yZWln

bi1rZXlzPjxkYXRlcz48cHViLWRhdGVzPjxkYXRlPkZlYjwvZGF0ZT48L3B1Yi1kYXRlcz48eWVh

cj4yMDA0PC95ZWFyPjwvZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPm5lcnZvdXMtc3lzdGVtIGFj

dGl2aXR5PC9rZXl3b3JkPjxrZXl3b3JkPnBsYXNtYSBub3JlcGluZXBocmluZTwva2V5d29yZD48

a2V5d29yZD5tZXRhYm9saWMtcmF0ZTwva2V5d29yZD48a2V5d29yZD53ZWlnaHQtZ2Fpbjwva2V5

d29yZD48a2V5d29yZD5ib2R5LWZhdDwva2V5d29yZD48a2V5d29yZD5zeW1wYXRob2FkcmVuYWwg

c3lzdGVtPC9rZXl3b3JkPjxrZXl3b3JkPmNlcmVicm9zcGluYWwtZmx1aWQ8L2tleXdvcmQ+PGtl

eXdvcmQ+YWJkb21pbmFsIGFkaXBvc2l0eTwva2V5d29yZD48a2V5d29yZD5ibG9vZC1wcmVzc3Vy

ZTwva2V5d29yZD48a2V5d29yZD5lbGRlcmx5IG1lbjwva2V5d29yZD48L2tleXdvcmRzPjx1cmxz

PjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0OzovLzAwMDE4ODczOTYwMDAwMjwv

dXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMDEyLTE3OTc8L2lzYm4+PHRpdGxlcz48

dGl0bGU+Q2hyb25pYyBzeW1wYXRoZXRpYyBhY3RpdmF0aW9uIC0gQ29uc2VxdWVuY2UgYW5kIGNh

dXNlIG9mIGFnZS1hc3NvY2lhdGVkIG9iZXNpdHk/PC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkRp

YWJldGVzPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5EaWFiZXRlczwvYWx0LXRpdGxlPjwv

dGl0bGVzPjxwYWdlcz4yNzYtMjg0PC9wYWdlcz48bnVtYmVyPjI8L251bWJlcj48Y29udHJpYnV0

b3JzPjxhdXRob3JzPjxhdXRob3I+U2VhbHMsIEQuIFIuPC9hdXRob3I+PGF1dGhvcj5CZWxsLCBD

LjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48bGFuZ3VhZ2U+RW5nbGlzaDwvbGFu

Z3VhZ2U+PGFkZGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDg3OTg4MDc8L2FkZGVkLWRhdGU+PHJl

Zi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRoLWFkZHJlc3M+

U2VhbHMsIERSJiN4RDtVbml2IENvbG9yYWRvLCBEZXB0IEludGVncmF0IFBoeXNpb2wsIFlDQiAz

NTQsIEJvdWxkZXIsIENPIDgwMzA5IFVTQSYjeEQ7VW5pdiBDb2xvcmFkbywgRGVwdCBJbnRlZ3Jh

dCBQaHlzaW9sLCBZQ0IgMzU0LCBCb3VsZGVyLCBDTyA4MDMwOSBVU0EmI3hEO1VuaXYgQ29sb3Jh

ZG8sIERlcHQgSW50ZWdyYXQgUGh5c2lvbCwgQm91bGRlciwgQ08gODAzMDkgVVNBPC9hdXRoLWFk

ZHJlc3M+PHJlYy1udW1iZXI+NDE0PC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0ZSBmb3Jt

YXQ9InV0YyI+MTM0ODc5ODgwNzwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1udW0+SVNJ

OjAwMDE4ODczOTYwMDAwMjwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjUzPC92b2x1bWU+PC9yZWNv

cmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA (Mancia et al. 2007, Seals and Bell 2004). Weight loss and diet induced changes in sympathetic nervous activity have implications in obese patients with OSA PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Zb3VuZzwvQXV0aG9yPjxZZWFyPjE5ODI8L1llYXI+PElE

VGV4dD5EaWV0LWluZHVjZWQgY2hhbmdlcyBpbiBzeW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbSBh

Y3Rpdml0eTogcG9zc2libGUgaW1wbGljYXRpb25zIGZvciBvYmVzaXR5IGFuZCBoeXBlcnRlbnNp

b248L0lEVGV4dD48RGlzcGxheVRleHQ+KFlvdW5nIGFuZCBMYW5kc2JlcmcgMTk4MiwgVHJvaXNp

IGV0IGFsLiAxOTkxKTwvRGlzcGxheVRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBw

PSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjMzODwv

a2V5PjwvZm9yZWlnbi1rZXlzPjxrZXl3b3Jkcz48a2V5d29yZD5BZG9sZXNjZW50PC9rZXl3b3Jk

PjxrZXl3b3JkPkFkcmVuYWwgTWVkdWxsYS9zZWNyZXRpb248L2tleXdvcmQ+PGtleXdvcmQ+QWR1

bHQ8L2tleXdvcmQ+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5BbmltYWxzPC9rZXl3

b3JkPjxrZXl3b3JkPkF1cm90aGlvZ2x1Y29zZS9hZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2U8

L2tleXdvcmQ+PGtleXdvcmQ+RGlldGFyeSBDYXJib2h5ZHJhdGVzL2FkbWluaXN0cmF0aW9uICZh

bXA7IGRvc2FnZTwva2V5d29yZD48a2V5d29yZD5FbmVyZ3kgSW50YWtlL2RydWcgZWZmZWN0czwv

a2V5d29yZD48a2V5d29yZD5FcGluZXBocmluZS9zZWNyZXRpb248L2tleXdvcmQ+PGtleXdvcmQ+

R2x1Y29zZS9hZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2U8L2tleXdvcmQ+PGtleXdvcmQ+SHVt

YW5zPC9rZXl3b3JkPjxrZXl3b3JkPkh5cGVydGVuc2lvbi8qZXRpb2xvZ3k8L2tleXdvcmQ+PGtl

eXdvcmQ+SW5zdWxpbi9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+

PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5Ob3JlcGluZXBocmluZS9ibG9vZC9tZXRh

Ym9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk9iZXNpdHkvKmV0aW9sb2d5PC9rZXl3b3JkPjxrZXl3

b3JkPlJhdHM8L2tleXdvcmQ+PGtleXdvcmQ+UmF0cywgSW5icmVkIFN0cmFpbnM8L2tleXdvcmQ+

PGtleXdvcmQ+U3Vjcm9zZS9hZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2U8L2tleXdvcmQ+PGtl

eXdvcmQ+U3ltcGF0aGV0aWMgTmVydm91cyBTeXN0ZW0vKnBoeXNpb2xvZ3k8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3dy5uY2JpLm5sbS5uaWgu

Z292L3B1Ym1lZC82ODE2ODA5PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxpc2JuPjAwMjEt

OTY4MSAoUHJpbnQpJiN4RDswMDIxLTk2ODEgKExpbmtpbmcpPC9pc2JuPjx3b3JrLXR5cGU+Q29t

cGFyYXRpdmUgU3R1ZHkmI3hEO1Jlc2VhcmNoIFN1cHBvcnQsIFUuUy4gR292JmFwb3M7dCwgUC5I

LlMuPC93b3JrLXR5cGU+PHRpdGxlcz48dGl0bGU+RGlldC1pbmR1Y2VkIGNoYW5nZXMgaW4gc3lt

cGF0aGV0aWMgbmVydm91cyBzeXN0ZW0gYWN0aXZpdHk6IHBvc3NpYmxlIGltcGxpY2F0aW9ucyBm

b3Igb2Jlc2l0eSBhbmQgaHlwZXJ0ZW5zaW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkpvdXJu

YWwgb2YgY2hyb25pYyBkaXNlYXNlczwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+SiBDaHJv

bmljIERpczwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz44NzktODY8L3BhZ2VzPjxudW1iZXI+

MTI8L251bWJlcj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+WW91bmcsIEouIEIuPC9h

dXRob3I+PGF1dGhvcj5MYW5kc2JlcmcsIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxlZGl0aW9uPjE5ODIvMDEvMDE8L2VkaXRpb24+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+

PGFkZGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDc0MzU0Njg8L2FkZGVkLWRhdGU+PHJlZi10eXBl

IG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxkYXRlcz48eWVhcj4xOTgyPC95

ZWFyPjwvZGF0ZXM+PHJlYy1udW1iZXI+NDA0PC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0

ZSBmb3JtYXQ9InV0YyI+MTM0NzQzNTQ2ODwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1u

dW0+NjgxNjgwOTwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjM1PC92b2x1bWU+PC9yZWNvcmQ+PC9D

aXRlPjxDaXRlPjxBdXRob3I+VHJvaXNpPC9BdXRob3I+PFllYXI+MTk5MTwvWWVhcj48SURUZXh0

PlJlbGF0aW9uIG9mIG9iZXNpdHkgYW5kIGRpZXQgdG8gc3ltcGF0aGV0aWMgbmVydm91cyBzeXN0

ZW0gYWN0aXZpdHk8L0lEVGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBk

Yi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yMzMzPC9rZXk+PC9m

b3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHViLWRhdGVz

Pjx5ZWFyPjE5OTE8L3llYXI+PC9kYXRlcz48a2V5d29yZHM+PGtleXdvcmQ+QWRpcG9zZSBUaXNz

dWUvYW5hdG9teSAmYW1wOyBoaXN0b2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QWR1bHQ8L2tleXdv

cmQ+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5CbG9vZCBQcmVzc3VyZTwva2V5d29y

ZD48a2V5d29yZD5Cb2R5IE1hc3MgSW5kZXg8L2tleXdvcmQ+PGtleXdvcmQ+Q3Jvc3MtU2VjdGlv

bmFsIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+KkRpZXQ8L2tleXdvcmQ+PGtleXdvcmQ+RXBp

bmVwaHJpbmUvdXJpbmU8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3Jk

PkxvbmdpdHVkaW5hbCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtl

eXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+Tm9yZXBpbmVwaHJpbmUvdXJpbmU8

L2tleXdvcmQ+PGtleXdvcmQ+T2Jlc2l0eS8qcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3

b3JkPlJlZ3Jlc3Npb24gQW5hbHlzaXM8L2tleXdvcmQ+PGtleXdvcmQ+U3ltcGF0aGV0aWMgTmVy

dm91cyBTeXN0ZW0vKnBoeXNpb3BhdGhvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjx1cmxzPjxy

ZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIwMjI0

MTA8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDE5NC05MTFYIChQcmludCkmI3hE

OzAxOTQtOTExWCAoTGlua2luZyk8L2lzYm4+PHdvcmstdHlwZT5SZXNlYXJjaCBTdXBwb3J0LCBO

b24tVS5TLiBHb3YmYXBvczt0JiN4RDtSZXNlYXJjaCBTdXBwb3J0LCBVLlMuIEdvdiZhcG9zO3Qs

IE5vbi1QLkguUy4mI3hEO1Jlc2VhcmNoIFN1cHBvcnQsIFUuUy4gR292JmFwb3M7dCwgUC5ILlMu

PC93b3JrLXR5cGU+PHRpdGxlcz48dGl0bGU+UmVsYXRpb24gb2Ygb2Jlc2l0eSBhbmQgZGlldCB0

byBzeW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbSBhY3Rpdml0eTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5IeXBlcnRlbnNpb248L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkh5cGVydGVuc2lv

bjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz42NjktNzc8L3BhZ2VzPjxudW1iZXI+NTwvbnVt

YmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Ucm9pc2ksIFIuIEouPC9hdXRob3I+

PGF1dGhvcj5XZWlzcywgUy4gVC48L2F1dGhvcj48YXV0aG9yPlBhcmtlciwgRC4gUi48L2F1dGhv

cj48YXV0aG9yPlNwYXJyb3csIEQuPC9hdXRob3I+PGF1dGhvcj5Zb3VuZywgSi4gQi48L2F1dGhv

cj48YXV0aG9yPkxhbmRzYmVyZywgTC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+

PGVkaXRpb24+MTk5MS8wNS8wMTwvZWRpdGlvbj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48YWRk

ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQzNTg5NzwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFt

ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5Ob3JtYXRpdmUg

QWdpbmcgU3R1ZHksIFZldGVyYW5zIEFkbWluaXN0cmF0aW9uIE91dHBhdGllbnQgQ2xpbmljLCBC

b3N0b24sIE1hc3MuPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDA1PC9yZWMtbnVtYmVyPjxs

YXN0LXVwZGF0ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQzNTg5NzwvbGFzdC11cGRhdGVkLWRh

dGU+PGFjY2Vzc2lvbi1udW0+MjAyMjQxMDwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjE3PC92b2x1

bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Zb3VuZzwvQXV0aG9yPjxZZWFyPjE5ODI8L1llYXI+PElE

VGV4dD5EaWV0LWluZHVjZWQgY2hhbmdlcyBpbiBzeW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbSBh

Y3Rpdml0eTogcG9zc2libGUgaW1wbGljYXRpb25zIGZvciBvYmVzaXR5IGFuZCBoeXBlcnRlbnNp

b248L0lEVGV4dD48RGlzcGxheVRleHQ+KFlvdW5nIGFuZCBMYW5kc2JlcmcgMTk4MiwgVHJvaXNp

IGV0IGFsLiAxOTkxKTwvRGlzcGxheVRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBw

PSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjMzODwv

a2V5PjwvZm9yZWlnbi1rZXlzPjxrZXl3b3Jkcz48a2V5d29yZD5BZG9sZXNjZW50PC9rZXl3b3Jk

PjxrZXl3b3JkPkFkcmVuYWwgTWVkdWxsYS9zZWNyZXRpb248L2tleXdvcmQ+PGtleXdvcmQ+QWR1

bHQ8L2tleXdvcmQ+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5BbmltYWxzPC9rZXl3

b3JkPjxrZXl3b3JkPkF1cm90aGlvZ2x1Y29zZS9hZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2U8

L2tleXdvcmQ+PGtleXdvcmQ+RGlldGFyeSBDYXJib2h5ZHJhdGVzL2FkbWluaXN0cmF0aW9uICZh

bXA7IGRvc2FnZTwva2V5d29yZD48a2V5d29yZD5FbmVyZ3kgSW50YWtlL2RydWcgZWZmZWN0czwv

a2V5d29yZD48a2V5d29yZD5FcGluZXBocmluZS9zZWNyZXRpb248L2tleXdvcmQ+PGtleXdvcmQ+

R2x1Y29zZS9hZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2U8L2tleXdvcmQ+PGtleXdvcmQ+SHVt

YW5zPC9rZXl3b3JkPjxrZXl3b3JkPkh5cGVydGVuc2lvbi8qZXRpb2xvZ3k8L2tleXdvcmQ+PGtl

eXdvcmQ+SW5zdWxpbi9tZXRhYm9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+

PGtleXdvcmQ+TWljZTwva2V5d29yZD48a2V5d29yZD5Ob3JlcGluZXBocmluZS9ibG9vZC9tZXRh

Ym9saXNtPC9rZXl3b3JkPjxrZXl3b3JkPk9iZXNpdHkvKmV0aW9sb2d5PC9rZXl3b3JkPjxrZXl3

b3JkPlJhdHM8L2tleXdvcmQ+PGtleXdvcmQ+UmF0cywgSW5icmVkIFN0cmFpbnM8L2tleXdvcmQ+

PGtleXdvcmQ+U3Vjcm9zZS9hZG1pbmlzdHJhdGlvbiAmYW1wOyBkb3NhZ2U8L2tleXdvcmQ+PGtl

eXdvcmQ+U3ltcGF0aGV0aWMgTmVydm91cyBTeXN0ZW0vKnBoeXNpb2xvZ3k8L2tleXdvcmQ+PC9r

ZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+aHR0cDovL3d3dy5uY2JpLm5sbS5uaWgu

Z292L3B1Ym1lZC82ODE2ODA5PC91cmw+PC9yZWxhdGVkLXVybHM+PC91cmxzPjxpc2JuPjAwMjEt

OTY4MSAoUHJpbnQpJiN4RDswMDIxLTk2ODEgKExpbmtpbmcpPC9pc2JuPjx3b3JrLXR5cGU+Q29t

cGFyYXRpdmUgU3R1ZHkmI3hEO1Jlc2VhcmNoIFN1cHBvcnQsIFUuUy4gR292JmFwb3M7dCwgUC5I

LlMuPC93b3JrLXR5cGU+PHRpdGxlcz48dGl0bGU+RGlldC1pbmR1Y2VkIGNoYW5nZXMgaW4gc3lt

cGF0aGV0aWMgbmVydm91cyBzeXN0ZW0gYWN0aXZpdHk6IHBvc3NpYmxlIGltcGxpY2F0aW9ucyBm

b3Igb2Jlc2l0eSBhbmQgaHlwZXJ0ZW5zaW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkpvdXJu

YWwgb2YgY2hyb25pYyBkaXNlYXNlczwvc2Vjb25kYXJ5LXRpdGxlPjxhbHQtdGl0bGU+SiBDaHJv

bmljIERpczwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz44NzktODY8L3BhZ2VzPjxudW1iZXI+

MTI8L251bWJlcj48Y29udHJpYnV0b3JzPjxhdXRob3JzPjxhdXRob3I+WW91bmcsIEouIEIuPC9h

dXRob3I+PGF1dGhvcj5MYW5kc2JlcmcsIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxlZGl0aW9uPjE5ODIvMDEvMDE8L2VkaXRpb24+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+

PGFkZGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNDc0MzU0Njg8L2FkZGVkLWRhdGU+PHJlZi10eXBl

IG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxkYXRlcz48eWVhcj4xOTgyPC95

ZWFyPjwvZGF0ZXM+PHJlYy1udW1iZXI+NDA0PC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0

ZSBmb3JtYXQ9InV0YyI+MTM0NzQzNTQ2ODwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1u

dW0+NjgxNjgwOTwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjM1PC92b2x1bWU+PC9yZWNvcmQ+PC9D

aXRlPjxDaXRlPjxBdXRob3I+VHJvaXNpPC9BdXRob3I+PFllYXI+MTk5MTwvWWVhcj48SURUZXh0

PlJlbGF0aW9uIG9mIG9iZXNpdHkgYW5kIGRpZXQgdG8gc3ltcGF0aGV0aWMgbmVydm91cyBzeXN0

ZW0gYWN0aXZpdHk8L0lEVGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBk

Yi1pZD0ienNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yMzMzPC9rZXk+PC9m

b3JlaWduLWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+TWF5PC9kYXRlPjwvcHViLWRhdGVz

Pjx5ZWFyPjE5OTE8L3llYXI+PC9kYXRlcz48a2V5d29yZHM+PGtleXdvcmQ+QWRpcG9zZSBUaXNz

dWUvYW5hdG9teSAmYW1wOyBoaXN0b2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QWR1bHQ8L2tleXdv

cmQ+PGtleXdvcmQ+QWdlZDwva2V5d29yZD48a2V5d29yZD5CbG9vZCBQcmVzc3VyZTwva2V5d29y

ZD48a2V5d29yZD5Cb2R5IE1hc3MgSW5kZXg8L2tleXdvcmQ+PGtleXdvcmQ+Q3Jvc3MtU2VjdGlv

bmFsIFN0dWRpZXM8L2tleXdvcmQ+PGtleXdvcmQ+KkRpZXQ8L2tleXdvcmQ+PGtleXdvcmQ+RXBp

bmVwaHJpbmUvdXJpbmU8L2tleXdvcmQ+PGtleXdvcmQ+SHVtYW5zPC9rZXl3b3JkPjxrZXl3b3Jk

PkxvbmdpdHVkaW5hbCBTdHVkaWVzPC9rZXl3b3JkPjxrZXl3b3JkPk1hbGU8L2tleXdvcmQ+PGtl

eXdvcmQ+TWlkZGxlIEFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+Tm9yZXBpbmVwaHJpbmUvdXJpbmU8

L2tleXdvcmQ+PGtleXdvcmQ+T2Jlc2l0eS8qcGh5c2lvcGF0aG9sb2d5PC9rZXl3b3JkPjxrZXl3

b3JkPlJlZ3Jlc3Npb24gQW5hbHlzaXM8L2tleXdvcmQ+PGtleXdvcmQ+U3ltcGF0aGV0aWMgTmVy

dm91cyBTeXN0ZW0vKnBoeXNpb3BhdGhvbG9neTwva2V5d29yZD48L2tleXdvcmRzPjx1cmxzPjxy

ZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5paC5nb3YvcHVibWVkLzIwMjI0

MTA8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDE5NC05MTFYIChQcmludCkmI3hE

OzAxOTQtOTExWCAoTGlua2luZyk8L2lzYm4+PHdvcmstdHlwZT5SZXNlYXJjaCBTdXBwb3J0LCBO

b24tVS5TLiBHb3YmYXBvczt0JiN4RDtSZXNlYXJjaCBTdXBwb3J0LCBVLlMuIEdvdiZhcG9zO3Qs

IE5vbi1QLkguUy4mI3hEO1Jlc2VhcmNoIFN1cHBvcnQsIFUuUy4gR292JmFwb3M7dCwgUC5ILlMu

PC93b3JrLXR5cGU+PHRpdGxlcz48dGl0bGU+UmVsYXRpb24gb2Ygb2Jlc2l0eSBhbmQgZGlldCB0

byBzeW1wYXRoZXRpYyBuZXJ2b3VzIHN5c3RlbSBhY3Rpdml0eTwvdGl0bGU+PHNlY29uZGFyeS10

aXRsZT5IeXBlcnRlbnNpb248L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkh5cGVydGVuc2lv

bjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz42NjktNzc8L3BhZ2VzPjxudW1iZXI+NTwvbnVt

YmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Ucm9pc2ksIFIuIEouPC9hdXRob3I+

PGF1dGhvcj5XZWlzcywgUy4gVC48L2F1dGhvcj48YXV0aG9yPlBhcmtlciwgRC4gUi48L2F1dGhv

cj48YXV0aG9yPlNwYXJyb3csIEQuPC9hdXRob3I+PGF1dGhvcj5Zb3VuZywgSi4gQi48L2F1dGhv

cj48YXV0aG9yPkxhbmRzYmVyZywgTC48L2F1dGhvcj48L2F1dGhvcnM+PC9jb250cmlidXRvcnM+

PGVkaXRpb24+MTk5MS8wNS8wMTwvZWRpdGlvbj48bGFuZ3VhZ2U+ZW5nPC9sYW5ndWFnZT48YWRk

ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQzNTg5NzwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFt

ZT0iSm91cm5hbCBBcnRpY2xlIj4xNzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5Ob3JtYXRpdmUg

QWdpbmcgU3R1ZHksIFZldGVyYW5zIEFkbWluaXN0cmF0aW9uIE91dHBhdGllbnQgQ2xpbmljLCBC

b3N0b24sIE1hc3MuPC9hdXRoLWFkZHJlc3M+PHJlYy1udW1iZXI+NDA1PC9yZWMtbnVtYmVyPjxs

YXN0LXVwZGF0ZWQtZGF0ZSBmb3JtYXQ9InV0YyI+MTM0NzQzNTg5NzwvbGFzdC11cGRhdGVkLWRh

dGU+PGFjY2Vzc2lvbi1udW0+MjAyMjQxMDwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjE3PC92b2x1

bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT4A

ADDIN EN.CITE.DATA (Young and Landsberg 1982, Troisi et al. 1991). While evidence supports that very low calorie diets support improved baroreflex sensitivity PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYW5zYW5lbjwvQXV0aG9yPjxZZWFyPjE5OTg8L1llYXI+

PElEVGV4dD5UaGUgZWZmZWN0IG9mIGEgdmVyeSBsb3ctY2Fsb3JpZSBkaWV0LWluZHVjZWQgd2Vp

Z2h0IGxvc3Mgb24gdGhlIHNldmVyaXR5IG9mIG9ic3RydWN0aXZlIHNsZWVwIGFwbm9lYSBhbmQg

YXV0b25vbWljIG5lcnZvdXMgZnVuY3Rpb24gaW4gb2Jlc2UgcGF0aWVudHMgd2l0aCBvYnN0cnVj

dGl2ZSBzbGVlcCBhcG5vZWEgc3luZHJvbWU8L0lEVGV4dD48RGlzcGxheVRleHQ+KEthbnNhbmVu

IGV0IGFsLiAxOTk4KTwvRGlzcGxheVRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBw

PSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjM0MDwv

a2V5PjwvZm9yZWlnbi1rZXlzPjxkYXRlcz48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1

Yi1kYXRlcz48eWVhcj4xOTk4PC95ZWFyPjwvZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0

PC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+QXV0b25vbWljIE5lcnZv

dXMgU3lzdGVtLypwaHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QmFyb3JlZmxleC9w

aHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkJhc2FsIE1ldGFib2xpc20vcGh5c2lvbG9neTwv

a2V5d29yZD48a2V5d29yZD5CbG9vZCBQcmVzc3VyZS9waHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3

b3JkPipEaWV0LCBSZWR1Y2luZzwva2V5d29yZD48a2V5d29yZD5FbGVjdHJvY2FyZGlvZ3JhcGh5

PC9rZXl3b3JkPjxrZXl3b3JkPkVuZXJneSBJbnRha2U8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxl

PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IFJhdGUvcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29y

ZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUg

QWdlZDwva2V5d29yZD48a2V5d29yZD5PYmVzaXR5LypwaHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+

PGtleXdvcmQ+U2xlZXAgQXBuZWEgU3luZHJvbWVzLypkaWV0IHRoZXJhcHkvKnBoeXNpb3BhdGhv

bG9neTwva2V5d29yZD48a2V5d29yZD5XZWlnaHQgTG9zcy8qcGh5c2lvbG9neTwva2V5d29yZD48

L2tleXdvcmRzPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5p

aC5nb3YvcHVibWVkLzk3MTU3NjU8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDE0

NC01OTc5IChQcmludCkmI3hEOzAxNDQtNTk3OSAoTGlua2luZyk8L2lzYm4+PHRpdGxlcz48dGl0

bGU+VGhlIGVmZmVjdCBvZiBhIHZlcnkgbG93LWNhbG9yaWUgZGlldC1pbmR1Y2VkIHdlaWdodCBs

b3NzIG9uIHRoZSBzZXZlcml0eSBvZiBvYnN0cnVjdGl2ZSBzbGVlcCBhcG5vZWEgYW5kIGF1dG9u

b21pYyBuZXJ2b3VzIGZ1bmN0aW9uIGluIG9iZXNlIHBhdGllbnRzIHdpdGggb2JzdHJ1Y3RpdmUg

c2xlZXAgYXBub2VhIHN5bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNsaW5pY2FsIHBo

eXNpb2xvZ3k8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkNsaW4gUGh5c2lvbDwvYWx0LXRp

dGxlPjwvdGl0bGVzPjxwYWdlcz4zNzctODU8L3BhZ2VzPjxudW1iZXI+NDwvbnVtYmVyPjxjb250

cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5LYW5zYW5lbiwgTS48L2F1dGhvcj48YXV0aG9yPlZh

bm5pbmVuLCBFLjwvYXV0aG9yPjxhdXRob3I+VHV1bmFpbmVuLCBBLjwvYXV0aG9yPjxhdXRob3I+

UGVzb25lbiwgUC48L2F1dGhvcj48YXV0aG9yPlR1b25vbmVuLCBWLjwvYXV0aG9yPjxhdXRob3I+

SGFydGlrYWluZW4sIEouPC9hdXRob3I+PGF1dGhvcj5NdXNzYWxvLCBILjwvYXV0aG9yPjxhdXRo

b3I+VXVzaXR1cGEsIE0uPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxlZGl0aW9u

PjE5OTgvMDgvMjY8L2VkaXRpb24+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PGFkZGVkLWRhdGUg

Zm9ybWF0PSJ1dGMiPjEzNDc0MzU4OTg8L2FkZGVkLWRhdGU+PHJlZi10eXBlIG5hbWU9IkpvdXJu

YWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBPdG9s

YXJ5bmdvbG9neSwgS3VvcGlvIFVuaXZlcnNpdHkgSG9zcGl0YWwsIEZpbmxhbmQuPC9hdXRoLWFk

ZHJlc3M+PHJlYy1udW1iZXI+NDA2PC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0ZSBmb3Jt

YXQ9InV0YyI+MTM0NzQzNTg5ODwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1udW0+OTcx

NTc2NTwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjE4PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT4A

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5LYW5zYW5lbjwvQXV0aG9yPjxZZWFyPjE5OTg8L1llYXI+

PElEVGV4dD5UaGUgZWZmZWN0IG9mIGEgdmVyeSBsb3ctY2Fsb3JpZSBkaWV0LWluZHVjZWQgd2Vp

Z2h0IGxvc3Mgb24gdGhlIHNldmVyaXR5IG9mIG9ic3RydWN0aXZlIHNsZWVwIGFwbm9lYSBhbmQg

YXV0b25vbWljIG5lcnZvdXMgZnVuY3Rpb24gaW4gb2Jlc2UgcGF0aWVudHMgd2l0aCBvYnN0cnVj

dGl2ZSBzbGVlcCBhcG5vZWEgc3luZHJvbWU8L0lEVGV4dD48RGlzcGxheVRleHQ+KEthbnNhbmVu

IGV0IGFsLiAxOTk4KTwvRGlzcGxheVRleHQ+PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBw

PSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2ZtZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjM0MDwv

a2V5PjwvZm9yZWlnbi1rZXlzPjxkYXRlcz48cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1

Yi1kYXRlcz48eWVhcj4xOTk4PC95ZWFyPjwvZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPkFkdWx0

PC9rZXl3b3JkPjxrZXl3b3JkPkFnZWQ8L2tleXdvcmQ+PGtleXdvcmQ+QXV0b25vbWljIE5lcnZv

dXMgU3lzdGVtLypwaHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+PGtleXdvcmQ+QmFyb3JlZmxleC9w

aHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3b3JkPkJhc2FsIE1ldGFib2xpc20vcGh5c2lvbG9neTwv

a2V5d29yZD48a2V5d29yZD5CbG9vZCBQcmVzc3VyZS9waHlzaW9sb2d5PC9rZXl3b3JkPjxrZXl3

b3JkPipEaWV0LCBSZWR1Y2luZzwva2V5d29yZD48a2V5d29yZD5FbGVjdHJvY2FyZGlvZ3JhcGh5

PC9rZXl3b3JkPjxrZXl3b3JkPkVuZXJneSBJbnRha2U8L2tleXdvcmQ+PGtleXdvcmQ+RmVtYWxl

PC9rZXl3b3JkPjxrZXl3b3JkPkhlYXJ0IFJhdGUvcGh5c2lvbG9neTwva2V5d29yZD48a2V5d29y

ZD5IdW1hbnM8L2tleXdvcmQ+PGtleXdvcmQ+TWFsZTwva2V5d29yZD48a2V5d29yZD5NaWRkbGUg

QWdlZDwva2V5d29yZD48a2V5d29yZD5PYmVzaXR5LypwaHlzaW9wYXRob2xvZ3k8L2tleXdvcmQ+

PGtleXdvcmQ+U2xlZXAgQXBuZWEgU3luZHJvbWVzLypkaWV0IHRoZXJhcHkvKnBoeXNpb3BhdGhv

bG9neTwva2V5d29yZD48a2V5d29yZD5XZWlnaHQgTG9zcy8qcGh5c2lvbG9neTwva2V5d29yZD48

L2tleXdvcmRzPjx1cmxzPjxyZWxhdGVkLXVybHM+PHVybD5odHRwOi8vd3d3Lm5jYmkubmxtLm5p

aC5nb3YvcHVibWVkLzk3MTU3NjU8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDE0

NC01OTc5IChQcmludCkmI3hEOzAxNDQtNTk3OSAoTGlua2luZyk8L2lzYm4+PHRpdGxlcz48dGl0

bGU+VGhlIGVmZmVjdCBvZiBhIHZlcnkgbG93LWNhbG9yaWUgZGlldC1pbmR1Y2VkIHdlaWdodCBs

b3NzIG9uIHRoZSBzZXZlcml0eSBvZiBvYnN0cnVjdGl2ZSBzbGVlcCBhcG5vZWEgYW5kIGF1dG9u

b21pYyBuZXJ2b3VzIGZ1bmN0aW9uIGluIG9iZXNlIHBhdGllbnRzIHdpdGggb2JzdHJ1Y3RpdmUg

c2xlZXAgYXBub2VhIHN5bmRyb21lPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNsaW5pY2FsIHBo

eXNpb2xvZ3k8L3NlY29uZGFyeS10aXRsZT48YWx0LXRpdGxlPkNsaW4gUGh5c2lvbDwvYWx0LXRp

dGxlPjwvdGl0bGVzPjxwYWdlcz4zNzctODU8L3BhZ2VzPjxudW1iZXI+NDwvbnVtYmVyPjxjb250

cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5LYW5zYW5lbiwgTS48L2F1dGhvcj48YXV0aG9yPlZh

bm5pbmVuLCBFLjwvYXV0aG9yPjxhdXRob3I+VHV1bmFpbmVuLCBBLjwvYXV0aG9yPjxhdXRob3I+

UGVzb25lbiwgUC48L2F1dGhvcj48YXV0aG9yPlR1b25vbmVuLCBWLjwvYXV0aG9yPjxhdXRob3I+

SGFydGlrYWluZW4sIEouPC9hdXRob3I+PGF1dGhvcj5NdXNzYWxvLCBILjwvYXV0aG9yPjxhdXRo

b3I+VXVzaXR1cGEsIE0uPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0b3JzPjxlZGl0aW9u

PjE5OTgvMDgvMjY8L2VkaXRpb24+PGxhbmd1YWdlPmVuZzwvbGFuZ3VhZ2U+PGFkZGVkLWRhdGUg

Zm9ybWF0PSJ1dGMiPjEzNDc0MzU4OTg8L2FkZGVkLWRhdGU+PHJlZi10eXBlIG5hbWU9IkpvdXJu

YWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRoLWFkZHJlc3M+RGVwYXJ0bWVudCBvZiBPdG9s

YXJ5bmdvbG9neSwgS3VvcGlvIFVuaXZlcnNpdHkgSG9zcGl0YWwsIEZpbmxhbmQuPC9hdXRoLWFk

ZHJlc3M+PHJlYy1udW1iZXI+NDA2PC9yZWMtbnVtYmVyPjxsYXN0LXVwZGF0ZWQtZGF0ZSBmb3Jt

YXQ9InV0YyI+MTM0NzQzNTg5ODwvbGFzdC11cGRhdGVkLWRhdGU+PGFjY2Vzc2lvbi1udW0+OTcx

NTc2NTwvYWNjZXNzaW9uLW51bT48dm9sdW1lPjE4PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwv

RW5kTm90ZT4A

ADDIN EN.CITE.DATA (Kansanen et al. 1998) there is no specific available evidence regarding sustainable, gradual weight loss in OSA populations nor whether macronutrient composition or glycemic index modulates this response. It is unclear how greater levels of sympathetic activity may impact upon people with OSA’s capacity to lose weight and furthermore, their ability to maintain this weight loss. The current study will investigate how weight loss via two different dietary interventions relates to individual differences in baseline sympathetic drive as well as how weight loss may steer subsequent improvement in sympathetic neural activity via different dietary macronutrient compositions and glycemic index with the potential additive effects of non-randomised use of mechanical treatment in a clinical setting.Energy restriction decreases sympathetic reactivity:?VLED reduces sympathetic nervous activity, as indicated by significant reductions in 24-hour urinary norepinephrine excretion PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3NlbmJhdW08L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFy

PjxJRFRleHQ+RWZmZWN0cyBvZiBjaGFuZ2VzIGluIGJvZHkgd2VpZ2h0IG9uIGNhcmJvaHlkcmF0

ZSBtZXRhYm9saXNtLCBjYXRlY2hvbGFtaW5lIGV4Y3JldGlvbiwgYW5kIHRoeXJvaWQgZnVuY3Rp

b248L0lEVGV4dD48RGlzcGxheVRleHQ+KFJvc2VuYmF1bSBldCBhbC4gMjAwMCk8L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ6c3N3d2RwMmQw

enNmbWVlYXd4NTB4ZHJyeDJlc3J6MndhNXAiPjI2OTA8L2tleT48L2ZvcmVpZ24ta2V5cz48ZGF0

ZXM+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PHllYXI+MjAwMDwveWVh

cj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5vYmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPmRp

YWJldGVzPC9rZXl3b3JkPjxrZXl3b3JkPmdsdWNvc2U8L2tleXdvcmQ+PGtleXdvcmQ+Y2F0ZWNo

b2xhbWluZXM8L2tleXdvcmQ+PGtleXdvcmQ+dGh5cm9pZCBob3Jtb25lczwva2V5d29yZD48a2V5

d29yZD53ZWlnaHQgY2hhbmdlPC9rZXl3b3JkPjxrZXl3b3JkPmVuZXJneSBob21lb3N0YXNpczwv

a2V5d29yZD48a2V5d29yZD5ib2R5IHdlaWdodDwva2V5d29yZD48a2V5d29yZD5hZHVsdHM8L2tl

eXdvcmQ+PGtleXdvcmQ+c3ltcGF0aGV0aWMgbmVydm91cy1zeXN0ZW08L2tleXdvcmQ+PGtleXdv

cmQ+aGVwYXRpYyBpbnN1bGluLWNsZWFyYW5jZTwva2V5d29yZD48a2V5d29yZD5lbmVyZ3ktZXhw

ZW5kaXR1cmU8L2tleXdvcmQ+PGtleXdvcmQ+YWRpcG9zZS10aXNzdWU8L2tleXdvcmQ+PGtleXdv

cmQ+aHVtYW4gb2Jlc2l0eTwva2V5d29yZD48a2V5d29yZD5yZXNwb25zZXM8L2tleXdvcmQ+PGtl

eXdvcmQ+c2Vuc2l0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+cmVzaXN0YW5jZTwva2V5d29yZD48

a2V5d29yZD5tZWNoYW5pc21zPC9rZXl3b3JkPjxrZXl3b3JkPmFkaXBvY3l0ZXM8L2tleXdvcmQ+

PC9rZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8w

MDAwODc0MjYzMDAwMDk8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDAwMi05MTY1

PC9pc2JuPjx0aXRsZXM+PHRpdGxlPkVmZmVjdHMgb2YgY2hhbmdlcyBpbiBib2R5IHdlaWdodCBv

biBjYXJib2h5ZHJhdGUgbWV0YWJvbGlzbSwgY2F0ZWNob2xhbWluZSBleGNyZXRpb24sIGFuZCB0

aHlyb2lkIGZ1bmN0aW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFtZXJpY2FuIEpvdXJuYWwg

b2YgQ2xpbmljYWwgTnV0cml0aW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbSBKIENs

aW4gTnV0cjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4xNDIxLTE0MzI8L3BhZ2VzPjxudW1i

ZXI+NjwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Sb3NlbmJhdW0sIE0u

PC9hdXRob3I+PGF1dGhvcj5IaXJzY2gsIEouPC9hdXRob3I+PGF1dGhvcj5NdXJwaHksIEUuPC9h

dXRob3I+PGF1dGhvcj5MZWliZWwsIFIuIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+

MTM1MTU3Mjg5MzwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5Sb3NlbmJhdW0sIE0mI3hEO1J1c3MgQmVycmllIE1l

ZCBTY2ksIFBhdmlsLDZ0aCBGbG9vciwxMTUwIFN0LE5pY2hvbGFzIEF2ZSwgTmV3IFlvcmssIE5Z

IDEwMDMyIFVTQSYjeEQ7UnVzcyBCZXJyaWUgTWVkIFNjaSwgUGF2aWwsNnRoIEZsb29yLDExNTAg

U3QsTmljaG9sYXMgQXZlLCBOZXcgWW9yaywgTlkgMTAwMzIgVVNBJiN4RDtSb2NrZWZlbGxlciBV

bml2LCBIdW1hbiBCZWhhdiAmYW1wOyBNZXRhYiBMYWIsIE5ldyBZb3JrLCBOWSAxMDAyMSBVU0Em

I3hEO0NvbHVtYmlhIFVuaXYsIE5ldyBZb3JrIFByZXNieXRlcmlhbiBNZWQgQ3RyLCBDb2xsIFBo

eXMgJmFtcDsgU3VyZywgRGl2IE1vbCBHZW5ldCxEZXB0IFBlZGlhdCwgTmV3IFlvcmssIE5ZIDEw

MDI3IFVTQTwvYXV0aC1hZGRyZXNzPjxyZWMtbnVtYmVyPjQxNzwvcmVjLW51bWJlcj48bGFzdC11

cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNTE1NzI4OTM8L2xhc3QtdXBkYXRlZC1kYXRlPjxh

Y2Nlc3Npb24tbnVtPklTSTowMDAwODc0MjYzMDAwMDk8L2FjY2Vzc2lvbi1udW0+PHZvbHVtZT43

MTwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3NlbmJhdW08L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFy

PjxJRFRleHQ+RWZmZWN0cyBvZiBjaGFuZ2VzIGluIGJvZHkgd2VpZ2h0IG9uIGNhcmJvaHlkcmF0

ZSBtZXRhYm9saXNtLCBjYXRlY2hvbGFtaW5lIGV4Y3JldGlvbiwgYW5kIHRoeXJvaWQgZnVuY3Rp

b248L0lEVGV4dD48RGlzcGxheVRleHQ+KFJvc2VuYmF1bSBldCBhbC4gMjAwMCk8L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ6c3N3d2RwMmQw

enNmbWVlYXd4NTB4ZHJyeDJlc3J6MndhNXAiPjI2OTA8L2tleT48L2ZvcmVpZ24ta2V5cz48ZGF0

ZXM+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PHllYXI+MjAwMDwveWVh

cj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5vYmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPmRp

YWJldGVzPC9rZXl3b3JkPjxrZXl3b3JkPmdsdWNvc2U8L2tleXdvcmQ+PGtleXdvcmQ+Y2F0ZWNo

b2xhbWluZXM8L2tleXdvcmQ+PGtleXdvcmQ+dGh5cm9pZCBob3Jtb25lczwva2V5d29yZD48a2V5

d29yZD53ZWlnaHQgY2hhbmdlPC9rZXl3b3JkPjxrZXl3b3JkPmVuZXJneSBob21lb3N0YXNpczwv

a2V5d29yZD48a2V5d29yZD5ib2R5IHdlaWdodDwva2V5d29yZD48a2V5d29yZD5hZHVsdHM8L2tl

eXdvcmQ+PGtleXdvcmQ+c3ltcGF0aGV0aWMgbmVydm91cy1zeXN0ZW08L2tleXdvcmQ+PGtleXdv

cmQ+aGVwYXRpYyBpbnN1bGluLWNsZWFyYW5jZTwva2V5d29yZD48a2V5d29yZD5lbmVyZ3ktZXhw

ZW5kaXR1cmU8L2tleXdvcmQ+PGtleXdvcmQ+YWRpcG9zZS10aXNzdWU8L2tleXdvcmQ+PGtleXdv

cmQ+aHVtYW4gb2Jlc2l0eTwva2V5d29yZD48a2V5d29yZD5yZXNwb25zZXM8L2tleXdvcmQ+PGtl

eXdvcmQ+c2Vuc2l0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+cmVzaXN0YW5jZTwva2V5d29yZD48

a2V5d29yZD5tZWNoYW5pc21zPC9rZXl3b3JkPjxrZXl3b3JkPmFkaXBvY3l0ZXM8L2tleXdvcmQ+

PC9rZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8w

MDAwODc0MjYzMDAwMDk8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDAwMi05MTY1

PC9pc2JuPjx0aXRsZXM+PHRpdGxlPkVmZmVjdHMgb2YgY2hhbmdlcyBpbiBib2R5IHdlaWdodCBv

biBjYXJib2h5ZHJhdGUgbWV0YWJvbGlzbSwgY2F0ZWNob2xhbWluZSBleGNyZXRpb24sIGFuZCB0

aHlyb2lkIGZ1bmN0aW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFtZXJpY2FuIEpvdXJuYWwg

b2YgQ2xpbmljYWwgTnV0cml0aW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbSBKIENs

aW4gTnV0cjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4xNDIxLTE0MzI8L3BhZ2VzPjxudW1i

ZXI+NjwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Sb3NlbmJhdW0sIE0u

PC9hdXRob3I+PGF1dGhvcj5IaXJzY2gsIEouPC9hdXRob3I+PGF1dGhvcj5NdXJwaHksIEUuPC9h

dXRob3I+PGF1dGhvcj5MZWliZWwsIFIuIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+

MTM1MTU3Mjg5MzwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5Sb3NlbmJhdW0sIE0mI3hEO1J1c3MgQmVycmllIE1l

ZCBTY2ksIFBhdmlsLDZ0aCBGbG9vciwxMTUwIFN0LE5pY2hvbGFzIEF2ZSwgTmV3IFlvcmssIE5Z

IDEwMDMyIFVTQSYjeEQ7UnVzcyBCZXJyaWUgTWVkIFNjaSwgUGF2aWwsNnRoIEZsb29yLDExNTAg

U3QsTmljaG9sYXMgQXZlLCBOZXcgWW9yaywgTlkgMTAwMzIgVVNBJiN4RDtSb2NrZWZlbGxlciBV

bml2LCBIdW1hbiBCZWhhdiAmYW1wOyBNZXRhYiBMYWIsIE5ldyBZb3JrLCBOWSAxMDAyMSBVU0Em

I3hEO0NvbHVtYmlhIFVuaXYsIE5ldyBZb3JrIFByZXNieXRlcmlhbiBNZWQgQ3RyLCBDb2xsIFBo

eXMgJmFtcDsgU3VyZywgRGl2IE1vbCBHZW5ldCxEZXB0IFBlZGlhdCwgTmV3IFlvcmssIE5ZIDEw

MDI3IFVTQTwvYXV0aC1hZGRyZXNzPjxyZWMtbnVtYmVyPjQxNzwvcmVjLW51bWJlcj48bGFzdC11

cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNTE1NzI4OTM8L2xhc3QtdXBkYXRlZC1kYXRlPjxh

Y2Nlc3Npb24tbnVtPklTSTowMDAwODc0MjYzMDAwMDk8L2FjY2Vzc2lvbi1udW0+PHZvbHVtZT43

MTwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE.DATA (Rosenbaum et al. 2000). Since sympathetic activity is an important regulator of metabolic rate, substrate oxidation PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3NlbmJhdW08L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFy

PjxJRFRleHQ+RWZmZWN0cyBvZiBjaGFuZ2VzIGluIGJvZHkgd2VpZ2h0IG9uIGNhcmJvaHlkcmF0

ZSBtZXRhYm9saXNtLCBjYXRlY2hvbGFtaW5lIGV4Y3JldGlvbiwgYW5kIHRoeXJvaWQgZnVuY3Rp

b248L0lEVGV4dD48RGlzcGxheVRleHQ+KFJvc2VuYmF1bSBldCBhbC4gMjAwMCk8L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ6c3N3d2RwMmQw

enNmbWVlYXd4NTB4ZHJyeDJlc3J6MndhNXAiPjI2OTA8L2tleT48L2ZvcmVpZ24ta2V5cz48ZGF0

ZXM+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PHllYXI+MjAwMDwveWVh

cj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5vYmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPmRp

YWJldGVzPC9rZXl3b3JkPjxrZXl3b3JkPmdsdWNvc2U8L2tleXdvcmQ+PGtleXdvcmQ+Y2F0ZWNo

b2xhbWluZXM8L2tleXdvcmQ+PGtleXdvcmQ+dGh5cm9pZCBob3Jtb25lczwva2V5d29yZD48a2V5

d29yZD53ZWlnaHQgY2hhbmdlPC9rZXl3b3JkPjxrZXl3b3JkPmVuZXJneSBob21lb3N0YXNpczwv

a2V5d29yZD48a2V5d29yZD5ib2R5IHdlaWdodDwva2V5d29yZD48a2V5d29yZD5hZHVsdHM8L2tl

eXdvcmQ+PGtleXdvcmQ+c3ltcGF0aGV0aWMgbmVydm91cy1zeXN0ZW08L2tleXdvcmQ+PGtleXdv

cmQ+aGVwYXRpYyBpbnN1bGluLWNsZWFyYW5jZTwva2V5d29yZD48a2V5d29yZD5lbmVyZ3ktZXhw

ZW5kaXR1cmU8L2tleXdvcmQ+PGtleXdvcmQ+YWRpcG9zZS10aXNzdWU8L2tleXdvcmQ+PGtleXdv

cmQ+aHVtYW4gb2Jlc2l0eTwva2V5d29yZD48a2V5d29yZD5yZXNwb25zZXM8L2tleXdvcmQ+PGtl

eXdvcmQ+c2Vuc2l0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+cmVzaXN0YW5jZTwva2V5d29yZD48

a2V5d29yZD5tZWNoYW5pc21zPC9rZXl3b3JkPjxrZXl3b3JkPmFkaXBvY3l0ZXM8L2tleXdvcmQ+

PC9rZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8w

MDAwODc0MjYzMDAwMDk8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDAwMi05MTY1

PC9pc2JuPjx0aXRsZXM+PHRpdGxlPkVmZmVjdHMgb2YgY2hhbmdlcyBpbiBib2R5IHdlaWdodCBv

biBjYXJib2h5ZHJhdGUgbWV0YWJvbGlzbSwgY2F0ZWNob2xhbWluZSBleGNyZXRpb24sIGFuZCB0

aHlyb2lkIGZ1bmN0aW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFtZXJpY2FuIEpvdXJuYWwg

b2YgQ2xpbmljYWwgTnV0cml0aW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbSBKIENs

aW4gTnV0cjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4xNDIxLTE0MzI8L3BhZ2VzPjxudW1i

ZXI+NjwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Sb3NlbmJhdW0sIE0u

PC9hdXRob3I+PGF1dGhvcj5IaXJzY2gsIEouPC9hdXRob3I+PGF1dGhvcj5NdXJwaHksIEUuPC9h

dXRob3I+PGF1dGhvcj5MZWliZWwsIFIuIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+

MTM1MTU3Mjg5MzwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5Sb3NlbmJhdW0sIE0mI3hEO1J1c3MgQmVycmllIE1l

ZCBTY2ksIFBhdmlsLDZ0aCBGbG9vciwxMTUwIFN0LE5pY2hvbGFzIEF2ZSwgTmV3IFlvcmssIE5Z

IDEwMDMyIFVTQSYjeEQ7UnVzcyBCZXJyaWUgTWVkIFNjaSwgUGF2aWwsNnRoIEZsb29yLDExNTAg

U3QsTmljaG9sYXMgQXZlLCBOZXcgWW9yaywgTlkgMTAwMzIgVVNBJiN4RDtSb2NrZWZlbGxlciBV

bml2LCBIdW1hbiBCZWhhdiAmYW1wOyBNZXRhYiBMYWIsIE5ldyBZb3JrLCBOWSAxMDAyMSBVU0Em

I3hEO0NvbHVtYmlhIFVuaXYsIE5ldyBZb3JrIFByZXNieXRlcmlhbiBNZWQgQ3RyLCBDb2xsIFBo

eXMgJmFtcDsgU3VyZywgRGl2IE1vbCBHZW5ldCxEZXB0IFBlZGlhdCwgTmV3IFlvcmssIE5ZIDEw

MDI3IFVTQTwvYXV0aC1hZGRyZXNzPjxyZWMtbnVtYmVyPjQxNzwvcmVjLW51bWJlcj48bGFzdC11

cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNTE1NzI4OTM8L2xhc3QtdXBkYXRlZC1kYXRlPjxh

Y2Nlc3Npb24tbnVtPklTSTowMDAwODc0MjYzMDAwMDk8L2FjY2Vzc2lvbi1udW0+PHZvbHVtZT43

MTwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Sb3NlbmJhdW08L0F1dGhvcj48WWVhcj4yMDAwPC9ZZWFy

PjxJRFRleHQ+RWZmZWN0cyBvZiBjaGFuZ2VzIGluIGJvZHkgd2VpZ2h0IG9uIGNhcmJvaHlkcmF0

ZSBtZXRhYm9saXNtLCBjYXRlY2hvbGFtaW5lIGV4Y3JldGlvbiwgYW5kIHRoeXJvaWQgZnVuY3Rp

b248L0lEVGV4dD48RGlzcGxheVRleHQ+KFJvc2VuYmF1bSBldCBhbC4gMjAwMCk8L0Rpc3BsYXlU

ZXh0PjxyZWNvcmQ+PGZvcmVpZ24ta2V5cz48a2V5IGFwcD0iRU4iIGRiLWlkPSJ6c3N3d2RwMmQw

enNmbWVlYXd4NTB4ZHJyeDJlc3J6MndhNXAiPjI2OTA8L2tleT48L2ZvcmVpZ24ta2V5cz48ZGF0

ZXM+PHB1Yi1kYXRlcz48ZGF0ZT5KdW48L2RhdGU+PC9wdWItZGF0ZXM+PHllYXI+MjAwMDwveWVh

cj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5vYmVzaXR5PC9rZXl3b3JkPjxrZXl3b3JkPmRp

YWJldGVzPC9rZXl3b3JkPjxrZXl3b3JkPmdsdWNvc2U8L2tleXdvcmQ+PGtleXdvcmQ+Y2F0ZWNo

b2xhbWluZXM8L2tleXdvcmQ+PGtleXdvcmQ+dGh5cm9pZCBob3Jtb25lczwva2V5d29yZD48a2V5

d29yZD53ZWlnaHQgY2hhbmdlPC9rZXl3b3JkPjxrZXl3b3JkPmVuZXJneSBob21lb3N0YXNpczwv

a2V5d29yZD48a2V5d29yZD5ib2R5IHdlaWdodDwva2V5d29yZD48a2V5d29yZD5hZHVsdHM8L2tl

eXdvcmQ+PGtleXdvcmQ+c3ltcGF0aGV0aWMgbmVydm91cy1zeXN0ZW08L2tleXdvcmQ+PGtleXdv

cmQ+aGVwYXRpYyBpbnN1bGluLWNsZWFyYW5jZTwva2V5d29yZD48a2V5d29yZD5lbmVyZ3ktZXhw

ZW5kaXR1cmU8L2tleXdvcmQ+PGtleXdvcmQ+YWRpcG9zZS10aXNzdWU8L2tleXdvcmQ+PGtleXdv

cmQ+aHVtYW4gb2Jlc2l0eTwva2V5d29yZD48a2V5d29yZD5yZXNwb25zZXM8L2tleXdvcmQ+PGtl

eXdvcmQ+c2Vuc2l0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+cmVzaXN0YW5jZTwva2V5d29yZD48

a2V5d29yZD5tZWNoYW5pc21zPC9rZXl3b3JkPjxrZXl3b3JkPmFkaXBvY3l0ZXM8L2tleXdvcmQ+

PC9rZXl3b3Jkcz48dXJscz48cmVsYXRlZC11cmxzPjx1cmw+Jmx0O0dvIHRvIElTSSZndDs6Ly8w

MDAwODc0MjYzMDAwMDk8L3VybD48L3JlbGF0ZWQtdXJscz48L3VybHM+PGlzYm4+MDAwMi05MTY1

PC9pc2JuPjx0aXRsZXM+PHRpdGxlPkVmZmVjdHMgb2YgY2hhbmdlcyBpbiBib2R5IHdlaWdodCBv

biBjYXJib2h5ZHJhdGUgbWV0YWJvbGlzbSwgY2F0ZWNob2xhbWluZSBleGNyZXRpb24sIGFuZCB0

aHlyb2lkIGZ1bmN0aW9uPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkFtZXJpY2FuIEpvdXJuYWwg

b2YgQ2xpbmljYWwgTnV0cml0aW9uPC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRsZT5BbSBKIENs

aW4gTnV0cjwvYWx0LXRpdGxlPjwvdGl0bGVzPjxwYWdlcz4xNDIxLTE0MzI8L3BhZ2VzPjxudW1i

ZXI+NjwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Sb3NlbmJhdW0sIE0u

PC9hdXRob3I+PGF1dGhvcj5IaXJzY2gsIEouPC9hdXRob3I+PGF1dGhvcj5NdXJwaHksIEUuPC9h

dXRob3I+PGF1dGhvcj5MZWliZWwsIFIuIEwuPC9hdXRob3I+PC9hdXRob3JzPjwvY29udHJpYnV0

b3JzPjxsYW5ndWFnZT5FbmdsaXNoPC9sYW5ndWFnZT48YWRkZWQtZGF0ZSBmb3JtYXQ9InV0YyI+

MTM1MTU3Mjg5MzwvYWRkZWQtZGF0ZT48cmVmLXR5cGUgbmFtZT0iSm91cm5hbCBBcnRpY2xlIj4x

NzwvcmVmLXR5cGU+PGF1dGgtYWRkcmVzcz5Sb3NlbmJhdW0sIE0mI3hEO1J1c3MgQmVycmllIE1l

ZCBTY2ksIFBhdmlsLDZ0aCBGbG9vciwxMTUwIFN0LE5pY2hvbGFzIEF2ZSwgTmV3IFlvcmssIE5Z

IDEwMDMyIFVTQSYjeEQ7UnVzcyBCZXJyaWUgTWVkIFNjaSwgUGF2aWwsNnRoIEZsb29yLDExNTAg

U3QsTmljaG9sYXMgQXZlLCBOZXcgWW9yaywgTlkgMTAwMzIgVVNBJiN4RDtSb2NrZWZlbGxlciBV

bml2LCBIdW1hbiBCZWhhdiAmYW1wOyBNZXRhYiBMYWIsIE5ldyBZb3JrLCBOWSAxMDAyMSBVU0Em

I3hEO0NvbHVtYmlhIFVuaXYsIE5ldyBZb3JrIFByZXNieXRlcmlhbiBNZWQgQ3RyLCBDb2xsIFBo

eXMgJmFtcDsgU3VyZywgRGl2IE1vbCBHZW5ldCxEZXB0IFBlZGlhdCwgTmV3IFlvcmssIE5ZIDEw

MDI3IFVTQTwvYXV0aC1hZGRyZXNzPjxyZWMtbnVtYmVyPjQxNzwvcmVjLW51bWJlcj48bGFzdC11

cGRhdGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNTE1NzI4OTM8L2xhc3QtdXBkYXRlZC1kYXRlPjxh

Y2Nlc3Npb24tbnVtPklTSTowMDAwODc0MjYzMDAwMDk8L2FjY2Vzc2lvbi1udW0+PHZvbHVtZT43

MTwvdm9sdW1lPjwvcmVjb3JkPjwvQ2l0ZT48L0VuZE5vdGU+

ADDIN EN.CITE.DATA (Rosenbaum et al. 2000), and bone mass PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWtlZGE8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFyPjxJ

RFRleHQ+TGVwdGluIHJlZ3VsYXRlcyBib25lIGZvcm1hdGlvbiB2aWEgdGhlIHN5bXBhdGhldGlj

IG5lcnZvdXMgc3lzdGVtPC9JRFRleHQ+PERpc3BsYXlUZXh0PihUYWtlZGEgZXQgYWwuIDIwMDIp

PC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0i

enNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNjkxPC9rZXk+PC9mb3JlaWdu

LWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+Tm92IDE8L2RhdGU+PC9wdWItZGF0ZXM+PHll

YXI+MjAwMjwveWVhcj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5kb3BhbWluZS1iZXRhLWh5

ZHJveHlsYXNlPC9rZXl3b3JkPjxrZXl3b3JkPnZlbnRyb21lZGlhbCBoeXBvdGhhbGFtdXM8L2tl

eXdvcmQ+PGtleXdvcmQ+Z2x1Y29jb3J0aWNvaWQgcmVjZXB0b3I8L2tleXdvcmQ+PGtleXdvcmQ+

cG9zdG1lbm9wYXVzYWwgd29tZW48L2tleXdvcmQ+PGtleXdvcmQ+ZnJhbWVzaGlmdCBtdXRhdGlv

bjwva2V5d29yZD48a2V5d29yZD50cmFuc2dlbmljIG1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+cG9t

YyBuZXVyb25zPC9rZXl3b3JkPjxrZXl3b3JkPkROQS1iaW5kaW5nPC9rZXl3b3JkPjxrZXl3b3Jk

Pm9iLXI8L2tleXdvcmQ+PGtleXdvcmQ+b2Jlc2l0eTwva2V5d29yZD48L2tleXdvcmRzPjx1cmxz

PjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0OzovLzAwMDE3OTAxMDEwMDAwNDwv

dXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMDkyLTg2NzQ8L2lzYm4+PHRpdGxlcz48

dGl0bGU+TGVwdGluIHJlZ3VsYXRlcyBib25lIGZvcm1hdGlvbiB2aWEgdGhlIHN5bXBhdGhldGlj

IG5lcnZvdXMgc3lzdGVtPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNlbGw8L3NlY29uZGFyeS10

aXRsZT48YWx0LXRpdGxlPkNlbGw8L2FsdC10aXRsZT48L3RpdGxlcz48cGFnZXM+MzA1LTMxNzwv

cGFnZXM+PG51bWJlcj4zPC9udW1iZXI+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRh

a2VkYSwgUy48L2F1dGhvcj48YXV0aG9yPkVsZWZ0ZXJpb3UsIEYuPC9hdXRob3I+PGF1dGhvcj5M

ZXZhc3NldXIsIFIuPC9hdXRob3I+PGF1dGhvcj5MaXUsIFguIFkuPC9hdXRob3I+PGF1dGhvcj5a

aGFvLCBMLiBQLjwvYXV0aG9yPjxhdXRob3I+UGFya2VyLCBLLiBMLjwvYXV0aG9yPjxhdXRob3I+

QXJtc3Ryb25nLCBELjwvYXV0aG9yPjxhdXRob3I+RHVjeSwgUC48L2F1dGhvcj48YXV0aG9yPkth

cnNlbnR5LCBHLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48bGFuZ3VhZ2U+RW5n

bGlzaDwvbGFuZ3VhZ2U+PGFkZGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNTE1NzI4OTQ8L2FkZGVk

LWRhdGU+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRo

LWFkZHJlc3M+S2Fyc2VudHksIEcmI3hEO0JheWxvciBDb2xsIE1lZCwgRGVwdCBNb2wgJmFtcDsg

SHVtYW4gR2VuZXQsIDEgQmF5bG9yIFBsYXphLCBIb3VzdG9uLCBUWCA3NzAzMCBVU0EmI3hEO0Jh

eWxvciBDb2xsIE1lZCwgRGVwdCBNb2wgJmFtcDsgSHVtYW4gR2VuZXQsIDEgQmF5bG9yIFBsYXph

LCBIb3VzdG9uLCBUWCA3NzAzMCBVU0EmI3hEO0JheWxvciBDb2xsIE1lZCwgRGVwdCBNb2wgJmFt

cDsgSHVtYW4gR2VuZXQsIEhvdXN0b24sIFRYIDc3MDMwIFVTQSYjeEQ7QmF5bG9yIENvbGwgTWVk

LCBCb25lIERpcyBQcm9ncmFtIFRleGFzLCBIb3VzdG9uLCBUWCA3NzAzMCBVU0EmI3hEO0JheWxv

ciBDb2xsIE1lZCwgRGVwdCBQYXRob2wsIEhvdXN0b24sIFRYIDc3MDMwIFVTQSYjeEQ7QmF5bG9y

IENvbGwgTWVkLCBEZXB0IE1lZCwgSG91c3RvbiwgVFggNzcwMzAgVVNBJiN4RDtVbml2IFRleGFz

LCBTVyBNZWQgQ3RyLCBEZXB0IEludGVybmFsIE1lZCwgRGFsbGFzLCBUWCA3NTM5MCBVU0E8L2F1

dGgtYWRkcmVzcz48cmVjLW51bWJlcj40MTg8L3JlYy1udW1iZXI+PGxhc3QtdXBkYXRlZC1kYXRl

IGZvcm1hdD0idXRjIj4xMzUxNTcyODk0PC9sYXN0LXVwZGF0ZWQtZGF0ZT48YWNjZXNzaW9uLW51

bT5JU0k6MDAwMTc5MDEwMTAwMDA0PC9hY2Nlc3Npb24tbnVtPjxlbGVjdHJvbmljLXJlc291cmNl

LW51bT5Eb2kgMTAuMTAxNi9TMDA5Mi04Njc0KDAyKTAxMDQ5LTg8L2VsZWN0cm9uaWMtcmVzb3Vy

Y2UtbnVtPjx2b2x1bWU+MTExPC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5UYWtlZGE8L0F1dGhvcj48WWVhcj4yMDAyPC9ZZWFyPjxJ

RFRleHQ+TGVwdGluIHJlZ3VsYXRlcyBib25lIGZvcm1hdGlvbiB2aWEgdGhlIHN5bXBhdGhldGlj

IG5lcnZvdXMgc3lzdGVtPC9JRFRleHQ+PERpc3BsYXlUZXh0PihUYWtlZGEgZXQgYWwuIDIwMDIp

PC9EaXNwbGF5VGV4dD48cmVjb3JkPjxmb3JlaWduLWtleXM+PGtleSBhcHA9IkVOIiBkYi1pZD0i

enNzd3dkcDJkMHpzZm1lZWF3eDUweGRycngyZXNyejJ3YTVwIj4yNjkxPC9rZXk+PC9mb3JlaWdu

LWtleXM+PGRhdGVzPjxwdWItZGF0ZXM+PGRhdGU+Tm92IDE8L2RhdGU+PC9wdWItZGF0ZXM+PHll

YXI+MjAwMjwveWVhcj48L2RhdGVzPjxrZXl3b3Jkcz48a2V5d29yZD5kb3BhbWluZS1iZXRhLWh5

ZHJveHlsYXNlPC9rZXl3b3JkPjxrZXl3b3JkPnZlbnRyb21lZGlhbCBoeXBvdGhhbGFtdXM8L2tl

eXdvcmQ+PGtleXdvcmQ+Z2x1Y29jb3J0aWNvaWQgcmVjZXB0b3I8L2tleXdvcmQ+PGtleXdvcmQ+

cG9zdG1lbm9wYXVzYWwgd29tZW48L2tleXdvcmQ+PGtleXdvcmQ+ZnJhbWVzaGlmdCBtdXRhdGlv

bjwva2V5d29yZD48a2V5d29yZD50cmFuc2dlbmljIG1pY2U8L2tleXdvcmQ+PGtleXdvcmQ+cG9t

YyBuZXVyb25zPC9rZXl3b3JkPjxrZXl3b3JkPkROQS1iaW5kaW5nPC9rZXl3b3JkPjxrZXl3b3Jk

Pm9iLXI8L2tleXdvcmQ+PGtleXdvcmQ+b2Jlc2l0eTwva2V5d29yZD48L2tleXdvcmRzPjx1cmxz

PjxyZWxhdGVkLXVybHM+PHVybD4mbHQ7R28gdG8gSVNJJmd0OzovLzAwMDE3OTAxMDEwMDAwNDwv

dXJsPjwvcmVsYXRlZC11cmxzPjwvdXJscz48aXNibj4wMDkyLTg2NzQ8L2lzYm4+PHRpdGxlcz48

dGl0bGU+TGVwdGluIHJlZ3VsYXRlcyBib25lIGZvcm1hdGlvbiB2aWEgdGhlIHN5bXBhdGhldGlj

IG5lcnZvdXMgc3lzdGVtPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPkNlbGw8L3NlY29uZGFyeS10

aXRsZT48YWx0LXRpdGxlPkNlbGw8L2FsdC10aXRsZT48L3RpdGxlcz48cGFnZXM+MzA1LTMxNzwv

cGFnZXM+PG51bWJlcj4zPC9udW1iZXI+PGNvbnRyaWJ1dG9ycz48YXV0aG9ycz48YXV0aG9yPlRh

a2VkYSwgUy48L2F1dGhvcj48YXV0aG9yPkVsZWZ0ZXJpb3UsIEYuPC9hdXRob3I+PGF1dGhvcj5M

ZXZhc3NldXIsIFIuPC9hdXRob3I+PGF1dGhvcj5MaXUsIFguIFkuPC9hdXRob3I+PGF1dGhvcj5a

aGFvLCBMLiBQLjwvYXV0aG9yPjxhdXRob3I+UGFya2VyLCBLLiBMLjwvYXV0aG9yPjxhdXRob3I+

QXJtc3Ryb25nLCBELjwvYXV0aG9yPjxhdXRob3I+RHVjeSwgUC48L2F1dGhvcj48YXV0aG9yPkth

cnNlbnR5LCBHLjwvYXV0aG9yPjwvYXV0aG9ycz48L2NvbnRyaWJ1dG9ycz48bGFuZ3VhZ2U+RW5n

bGlzaDwvbGFuZ3VhZ2U+PGFkZGVkLWRhdGUgZm9ybWF0PSJ1dGMiPjEzNTE1NzI4OTQ8L2FkZGVk

LWRhdGU+PHJlZi10eXBlIG5hbWU9IkpvdXJuYWwgQXJ0aWNsZSI+MTc8L3JlZi10eXBlPjxhdXRo

LWFkZHJlc3M+S2Fyc2VudHksIEcmI3hEO0JheWxvciBDb2xsIE1lZCwgRGVwdCBNb2wgJmFtcDsg

SHVtYW4gR2VuZXQsIDEgQmF5bG9yIFBsYXphLCBIb3VzdG9uLCBUWCA3NzAzMCBVU0EmI3hEO0Jh

eWxvciBDb2xsIE1lZCwgRGVwdCBNb2wgJmFtcDsgSHVtYW4gR2VuZXQsIDEgQmF5bG9yIFBsYXph

LCBIb3VzdG9uLCBUWCA3NzAzMCBVU0EmI3hEO0JheWxvciBDb2xsIE1lZCwgRGVwdCBNb2wgJmFt

cDsgSHVtYW4gR2VuZXQsIEhvdXN0b24sIFRYIDc3MDMwIFVTQSYjeEQ7QmF5bG9yIENvbGwgTWVk

LCBCb25lIERpcyBQcm9ncmFtIFRleGFzLCBIb3VzdG9uLCBUWCA3NzAzMCBVU0EmI3hEO0JheWxv

ciBDb2xsIE1lZCwgRGVwdCBQYXRob2wsIEhvdXN0b24sIFRYIDc3MDMwIFVTQSYjeEQ7QmF5bG9y

IENvbGwgTWVkLCBEZXB0IE1lZCwgSG91c3RvbiwgVFggNzcwMzAgVVNBJiN4RDtVbml2IFRleGFz

LCBTVyBNZWQgQ3RyLCBEZXB0IEludGVybmFsIE1lZCwgRGFsbGFzLCBUWCA3NTM5MCBVU0E8L2F1

dGgtYWRkcmVzcz48cmVjLW51bWJlcj40MTg8L3JlYy1udW1iZXI+PGxhc3QtdXBkYXRlZC1kYXRl

IGZvcm1hdD0idXRjIj4xMzUxNTcyODk0PC9sYXN0LXVwZGF0ZWQtZGF0ZT48YWNjZXNzaW9uLW51

bT5JU0k6MDAwMTc5MDEwMTAwMDA0PC9hY2Nlc3Npb24tbnVtPjxlbGVjdHJvbmljLXJlc291cmNl

LW51bT5Eb2kgMTAuMTAxNi9TMDA5Mi04Njc0KDAyKTAxMDQ5LTg8L2VsZWN0cm9uaWMtcmVzb3Vy

Y2UtbnVtPjx2b2x1bWU+MTExPC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE.DATA (Takeda et al. 2002), and since reduced capacity to activate the sympathetic nervous system is associated with decreased weight loss in obesity PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb2JiaW9uaS1IYXJzY2g8L0F1dGhvcj48WWVhcj4yMDA0

PC9ZZWFyPjxJRFRleHQ+UmVsYXRpb25zaGlwIGJldHdlZW4gc3ltcGF0aGV0aWMgcmVhY3Rpdml0

eSBhbmQgYm9keSB3ZWlnaHQgbG9zcyBpbiBtb3JiaWRseSBvYmVzZSBzdWJqZWN0czwvSURUZXh0

PjxEaXNwbGF5VGV4dD4oQm9iYmlvbmktSGFyc2NoIGV0IGFsLiAyMDA0KTwvRGlzcGxheVRleHQ+

PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2Zt

ZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY5Mjwva2V5PjwvZm9yZWlnbi1rZXlzPjxkYXRlcz48

cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48eWVhcj4yMDA0PC95ZWFyPjwv

ZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPnN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtPC9rZXl3

b3JkPjxrZXl3b3JkPmJvZHkgd2VpZ2h0IGxvc3M8L2tleXdvcmQ+PGtleXdvcmQ+bGFzZXIgZG9w

cGxlciBmbHV4aW1ldHJ5PC9rZXl3b3JkPjxrZXl3b3JkPmdhc3RyaWMgYnlwYXNzPC9rZXl3b3Jk

PjxrZXl3b3JkPnN1YmN1dGFuZW91cyBhZGlwb3NlLXRpc3N1ZTwva2V5d29yZD48a2V5d29yZD5n

YXN0cmljIGJ5cGFzczwva2V5d29yZD48a2V5d29yZD5ub3JlcGluZXBocmluZSBzcGlsbG92ZXI8

L2tleXdvcmQ+PGtleXdvcmQ+bmVydmUgYWN0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+d29tZW48

L2tleXdvcmQ+PGtleXdvcmQ+bGlwb2x5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW48L2tl

eXdvcmQ+PGtleXdvcmQ+ZGlldDwva2V5d29yZD48a2V5d29yZD5zZW5zaXRpdml0eTwva2V5d29y

ZD48a2V5d29yZD5yZXNpc3RhbmNlPC9rZXl3b3JkPjwva2V5d29yZHM+PHVybHM+PHJlbGF0ZWQt

dXJscz48dXJsPiZsdDtHbyB0byBJU0kmZ3Q7Oi8vMDAwMjIyMTM2NTAwMDExPC91cmw+PC9yZWxh

dGVkLXVybHM+PC91cmxzPjxpc2JuPjAzMDctMDU2NTwvaXNibj48dGl0bGVzPjx0aXRsZT5SZWxh

dGlvbnNoaXAgYmV0d2VlbiBzeW1wYXRoZXRpYyByZWFjdGl2aXR5IGFuZCBib2R5IHdlaWdodCBs

b3NzIGluIG1vcmJpZGx5IG9iZXNlIHN1YmplY3RzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPklu

dGVybmF0aW9uYWwgSm91cm5hbCBvZiBPYmVzaXR5PC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRs

ZT5JbnQgSiBPYmVzaXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjkwNi05MTE8L3BhZ2Vz

PjxudW1iZXI+NzwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Cb2JiaW9u

aS1IYXJzY2gsIEUuPC9hdXRob3I+PGF1dGhvcj5Cb25nYXJkLCBPLjwvYXV0aG9yPjxhdXRob3I+

SGFiaWNodCwgRi48L2F1dGhvcj48YXV0aG9yPldlaW1lciwgRC48L2F1dGhvcj48YXV0aG9yPkJv

dW5hbWVhdXgsIEguPC9hdXRob3I+PGF1dGhvcj5IdWJlciwgTy48L2F1dGhvcj48YXV0aG9yPkNo

YXNzb3QsIEcuPC9hdXRob3I+PGF1dGhvcj5Nb3JlbCwgUC48L2F1dGhvcj48YXV0aG9yPkFzc2lt

YWNvcG91bG9zLUplYW5uZXQsIEYuPC9hdXRob3I+PGF1dGhvcj5Hb2xheSwgQS48L2F1dGhvcj48

L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGxhbmd1YWdlPkVuZ2xpc2g8L2xhbmd1YWdlPjxhZGRl

ZC1kYXRlIGZvcm1hdD0idXRjIj4xMzUxNTcyODk0PC9hZGRlZC1kYXRlPjxyZWYtdHlwZSBuYW1l

PSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48YXV0aC1hZGRyZXNzPkJvYmJpb25pLUhh

cnNjaCwgRSYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERp

cywgMjQgUnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFu

ZCYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgMjQg

UnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFuZCYjeEQ7

VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgQ0gtMTIxMSBH

ZW5ldmEgMTQsIFN3aXR6ZXJsYW5kJiN4RDtHZW5ldmEgU2NoIE1lZCwgRGl2IFRoZXJhcGV1dCBF

ZHVjIENocm9uIERpcywgR2VuZXZhLCBTd2l0emVybGFuZCYjeEQ7R2VuZXZhIFNjaCBNZWQsIERp

diBBbmdpb2wgJmFtcDsgSGFlbW9zdGFzaXMsIEdlbmV2YSwgU3dpdHplcmxhbmQmI3hEO0dlbmV2

YSBTY2ggTWVkLCBDbGluIERpZ2VzdCBTdXJnLCBHZW5ldmEsIFN3aXR6ZXJsYW5kJiN4RDtHZW5l

dmEgU2NoIE1lZCwgRGVwdCBNZWQgQmlvY2hlbSwgR2VuZXZhLCBTd2l0emVybGFuZDwvYXV0aC1h

ZGRyZXNzPjxyZWMtbnVtYmVyPjQxOTwvcmVjLW51bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9y

bWF0PSJ1dGMiPjEzNTE1NzI4OTQ8L2xhc3QtdXBkYXRlZC1kYXRlPjxhY2Nlc3Npb24tbnVtPklT

STowMDAyMjIxMzY1MDAwMTE8L2FjY2Vzc2lvbi1udW0+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt

PkRPSSAxMC4xMDM4L3NqLmlqby4wODAyNjIwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48dm9s

dW1lPjI4PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb2JiaW9uaS1IYXJzY2g8L0F1dGhvcj48WWVhcj4yMDA0

PC9ZZWFyPjxJRFRleHQ+UmVsYXRpb25zaGlwIGJldHdlZW4gc3ltcGF0aGV0aWMgcmVhY3Rpdml0

eSBhbmQgYm9keSB3ZWlnaHQgbG9zcyBpbiBtb3JiaWRseSBvYmVzZSBzdWJqZWN0czwvSURUZXh0

PjxEaXNwbGF5VGV4dD4oQm9iYmlvbmktSGFyc2NoIGV0IGFsLiAyMDA0KTwvRGlzcGxheVRleHQ+

PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2Zt

ZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY5Mjwva2V5PjwvZm9yZWlnbi1rZXlzPjxkYXRlcz48

cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48eWVhcj4yMDA0PC95ZWFyPjwv

ZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPnN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtPC9rZXl3

b3JkPjxrZXl3b3JkPmJvZHkgd2VpZ2h0IGxvc3M8L2tleXdvcmQ+PGtleXdvcmQ+bGFzZXIgZG9w

cGxlciBmbHV4aW1ldHJ5PC9rZXl3b3JkPjxrZXl3b3JkPmdhc3RyaWMgYnlwYXNzPC9rZXl3b3Jk

PjxrZXl3b3JkPnN1YmN1dGFuZW91cyBhZGlwb3NlLXRpc3N1ZTwva2V5d29yZD48a2V5d29yZD5n

YXN0cmljIGJ5cGFzczwva2V5d29yZD48a2V5d29yZD5ub3JlcGluZXBocmluZSBzcGlsbG92ZXI8

L2tleXdvcmQ+PGtleXdvcmQ+bmVydmUgYWN0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+d29tZW48

L2tleXdvcmQ+PGtleXdvcmQ+bGlwb2x5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW48L2tl

eXdvcmQ+PGtleXdvcmQ+ZGlldDwva2V5d29yZD48a2V5d29yZD5zZW5zaXRpdml0eTwva2V5d29y

ZD48a2V5d29yZD5yZXNpc3RhbmNlPC9rZXl3b3JkPjwva2V5d29yZHM+PHVybHM+PHJlbGF0ZWQt

dXJscz48dXJsPiZsdDtHbyB0byBJU0kmZ3Q7Oi8vMDAwMjIyMTM2NTAwMDExPC91cmw+PC9yZWxh

dGVkLXVybHM+PC91cmxzPjxpc2JuPjAzMDctMDU2NTwvaXNibj48dGl0bGVzPjx0aXRsZT5SZWxh

dGlvbnNoaXAgYmV0d2VlbiBzeW1wYXRoZXRpYyByZWFjdGl2aXR5IGFuZCBib2R5IHdlaWdodCBs

b3NzIGluIG1vcmJpZGx5IG9iZXNlIHN1YmplY3RzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPklu

dGVybmF0aW9uYWwgSm91cm5hbCBvZiBPYmVzaXR5PC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRs

ZT5JbnQgSiBPYmVzaXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjkwNi05MTE8L3BhZ2Vz

PjxudW1iZXI+NzwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Cb2JiaW9u

aS1IYXJzY2gsIEUuPC9hdXRob3I+PGF1dGhvcj5Cb25nYXJkLCBPLjwvYXV0aG9yPjxhdXRob3I+

SGFiaWNodCwgRi48L2F1dGhvcj48YXV0aG9yPldlaW1lciwgRC48L2F1dGhvcj48YXV0aG9yPkJv

dW5hbWVhdXgsIEguPC9hdXRob3I+PGF1dGhvcj5IdWJlciwgTy48L2F1dGhvcj48YXV0aG9yPkNo

YXNzb3QsIEcuPC9hdXRob3I+PGF1dGhvcj5Nb3JlbCwgUC48L2F1dGhvcj48YXV0aG9yPkFzc2lt

YWNvcG91bG9zLUplYW5uZXQsIEYuPC9hdXRob3I+PGF1dGhvcj5Hb2xheSwgQS48L2F1dGhvcj48

L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGxhbmd1YWdlPkVuZ2xpc2g8L2xhbmd1YWdlPjxhZGRl

ZC1kYXRlIGZvcm1hdD0idXRjIj4xMzUxNTcyODk0PC9hZGRlZC1kYXRlPjxyZWYtdHlwZSBuYW1l

PSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48YXV0aC1hZGRyZXNzPkJvYmJpb25pLUhh

cnNjaCwgRSYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERp

cywgMjQgUnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFu

ZCYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgMjQg

UnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFuZCYjeEQ7

VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgQ0gtMTIxMSBH

ZW5ldmEgMTQsIFN3aXR6ZXJsYW5kJiN4RDtHZW5ldmEgU2NoIE1lZCwgRGl2IFRoZXJhcGV1dCBF

ZHVjIENocm9uIERpcywgR2VuZXZhLCBTd2l0emVybGFuZCYjeEQ7R2VuZXZhIFNjaCBNZWQsIERp

diBBbmdpb2wgJmFtcDsgSGFlbW9zdGFzaXMsIEdlbmV2YSwgU3dpdHplcmxhbmQmI3hEO0dlbmV2

YSBTY2ggTWVkLCBDbGluIERpZ2VzdCBTdXJnLCBHZW5ldmEsIFN3aXR6ZXJsYW5kJiN4RDtHZW5l

dmEgU2NoIE1lZCwgRGVwdCBNZWQgQmlvY2hlbSwgR2VuZXZhLCBTd2l0emVybGFuZDwvYXV0aC1h

ZGRyZXNzPjxyZWMtbnVtYmVyPjQxOTwvcmVjLW51bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9y

bWF0PSJ1dGMiPjEzNTE1NzI4OTQ8L2xhc3QtdXBkYXRlZC1kYXRlPjxhY2Nlc3Npb24tbnVtPklT

STowMDAyMjIxMzY1MDAwMTE8L2FjY2Vzc2lvbi1udW0+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt

PkRPSSAxMC4xMDM4L3NqLmlqby4wODAyNjIwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48dm9s

dW1lPjI4PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE.DATA (Bobbioni-Harsch et al. 2004), it is important to determine whether VLED and followed by conventional maintenance diets may have differential effects on sympathetic reactivity. Additionally, as the changes in sympathetic reactivity with weight loss may be mediated by the same hypothalamic ‘master switch’ that initiates other adaptive responses to weight loss.Deep inspiration induces vasoconstriction in skin capillaries via sympathetic activation, and dynamic weight loss has been shown to inhibit this response PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb2JiaW9uaS1IYXJzY2g8L0F1dGhvcj48WWVhcj4yMDA0

PC9ZZWFyPjxJRFRleHQ+UmVsYXRpb25zaGlwIGJldHdlZW4gc3ltcGF0aGV0aWMgcmVhY3Rpdml0

eSBhbmQgYm9keSB3ZWlnaHQgbG9zcyBpbiBtb3JiaWRseSBvYmVzZSBzdWJqZWN0czwvSURUZXh0

PjxEaXNwbGF5VGV4dD4oQm9iYmlvbmktSGFyc2NoIGV0IGFsLiAyMDA0KTwvRGlzcGxheVRleHQ+

PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2Zt

ZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY5Mjwva2V5PjwvZm9yZWlnbi1rZXlzPjxkYXRlcz48

cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48eWVhcj4yMDA0PC95ZWFyPjwv

ZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPnN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtPC9rZXl3

b3JkPjxrZXl3b3JkPmJvZHkgd2VpZ2h0IGxvc3M8L2tleXdvcmQ+PGtleXdvcmQ+bGFzZXIgZG9w

cGxlciBmbHV4aW1ldHJ5PC9rZXl3b3JkPjxrZXl3b3JkPmdhc3RyaWMgYnlwYXNzPC9rZXl3b3Jk

PjxrZXl3b3JkPnN1YmN1dGFuZW91cyBhZGlwb3NlLXRpc3N1ZTwva2V5d29yZD48a2V5d29yZD5n

YXN0cmljIGJ5cGFzczwva2V5d29yZD48a2V5d29yZD5ub3JlcGluZXBocmluZSBzcGlsbG92ZXI8

L2tleXdvcmQ+PGtleXdvcmQ+bmVydmUgYWN0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+d29tZW48

L2tleXdvcmQ+PGtleXdvcmQ+bGlwb2x5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW48L2tl

eXdvcmQ+PGtleXdvcmQ+ZGlldDwva2V5d29yZD48a2V5d29yZD5zZW5zaXRpdml0eTwva2V5d29y

ZD48a2V5d29yZD5yZXNpc3RhbmNlPC9rZXl3b3JkPjwva2V5d29yZHM+PHVybHM+PHJlbGF0ZWQt

dXJscz48dXJsPiZsdDtHbyB0byBJU0kmZ3Q7Oi8vMDAwMjIyMTM2NTAwMDExPC91cmw+PC9yZWxh

dGVkLXVybHM+PC91cmxzPjxpc2JuPjAzMDctMDU2NTwvaXNibj48dGl0bGVzPjx0aXRsZT5SZWxh

dGlvbnNoaXAgYmV0d2VlbiBzeW1wYXRoZXRpYyByZWFjdGl2aXR5IGFuZCBib2R5IHdlaWdodCBs

b3NzIGluIG1vcmJpZGx5IG9iZXNlIHN1YmplY3RzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPklu

dGVybmF0aW9uYWwgSm91cm5hbCBvZiBPYmVzaXR5PC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRs

ZT5JbnQgSiBPYmVzaXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjkwNi05MTE8L3BhZ2Vz

PjxudW1iZXI+NzwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Cb2JiaW9u

aS1IYXJzY2gsIEUuPC9hdXRob3I+PGF1dGhvcj5Cb25nYXJkLCBPLjwvYXV0aG9yPjxhdXRob3I+

SGFiaWNodCwgRi48L2F1dGhvcj48YXV0aG9yPldlaW1lciwgRC48L2F1dGhvcj48YXV0aG9yPkJv

dW5hbWVhdXgsIEguPC9hdXRob3I+PGF1dGhvcj5IdWJlciwgTy48L2F1dGhvcj48YXV0aG9yPkNo

YXNzb3QsIEcuPC9hdXRob3I+PGF1dGhvcj5Nb3JlbCwgUC48L2F1dGhvcj48YXV0aG9yPkFzc2lt

YWNvcG91bG9zLUplYW5uZXQsIEYuPC9hdXRob3I+PGF1dGhvcj5Hb2xheSwgQS48L2F1dGhvcj48

L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGxhbmd1YWdlPkVuZ2xpc2g8L2xhbmd1YWdlPjxhZGRl

ZC1kYXRlIGZvcm1hdD0idXRjIj4xMzUxNTcyODk0PC9hZGRlZC1kYXRlPjxyZWYtdHlwZSBuYW1l

PSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48YXV0aC1hZGRyZXNzPkJvYmJpb25pLUhh

cnNjaCwgRSYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERp

cywgMjQgUnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFu

ZCYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgMjQg

UnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFuZCYjeEQ7

VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgQ0gtMTIxMSBH

ZW5ldmEgMTQsIFN3aXR6ZXJsYW5kJiN4RDtHZW5ldmEgU2NoIE1lZCwgRGl2IFRoZXJhcGV1dCBF

ZHVjIENocm9uIERpcywgR2VuZXZhLCBTd2l0emVybGFuZCYjeEQ7R2VuZXZhIFNjaCBNZWQsIERp

diBBbmdpb2wgJmFtcDsgSGFlbW9zdGFzaXMsIEdlbmV2YSwgU3dpdHplcmxhbmQmI3hEO0dlbmV2

YSBTY2ggTWVkLCBDbGluIERpZ2VzdCBTdXJnLCBHZW5ldmEsIFN3aXR6ZXJsYW5kJiN4RDtHZW5l

dmEgU2NoIE1lZCwgRGVwdCBNZWQgQmlvY2hlbSwgR2VuZXZhLCBTd2l0emVybGFuZDwvYXV0aC1h

ZGRyZXNzPjxyZWMtbnVtYmVyPjQxOTwvcmVjLW51bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9y

bWF0PSJ1dGMiPjEzNTE1NzI4OTQ8L2xhc3QtdXBkYXRlZC1kYXRlPjxhY2Nlc3Npb24tbnVtPklT

STowMDAyMjIxMzY1MDAwMTE8L2FjY2Vzc2lvbi1udW0+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt

PkRPSSAxMC4xMDM4L3NqLmlqby4wODAyNjIwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48dm9s

dW1lPjI4PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb2JiaW9uaS1IYXJzY2g8L0F1dGhvcj48WWVhcj4yMDA0

PC9ZZWFyPjxJRFRleHQ+UmVsYXRpb25zaGlwIGJldHdlZW4gc3ltcGF0aGV0aWMgcmVhY3Rpdml0

eSBhbmQgYm9keSB3ZWlnaHQgbG9zcyBpbiBtb3JiaWRseSBvYmVzZSBzdWJqZWN0czwvSURUZXh0

PjxEaXNwbGF5VGV4dD4oQm9iYmlvbmktSGFyc2NoIGV0IGFsLiAyMDA0KTwvRGlzcGxheVRleHQ+

PHJlY29yZD48Zm9yZWlnbi1rZXlzPjxrZXkgYXBwPSJFTiIgZGItaWQ9Inpzc3d3ZHAyZDB6c2Zt

ZWVhd3g1MHhkcnJ4MmVzcnoyd2E1cCI+MjY5Mjwva2V5PjwvZm9yZWlnbi1rZXlzPjxkYXRlcz48

cHViLWRhdGVzPjxkYXRlPkp1bDwvZGF0ZT48L3B1Yi1kYXRlcz48eWVhcj4yMDA0PC95ZWFyPjwv

ZGF0ZXM+PGtleXdvcmRzPjxrZXl3b3JkPnN5bXBhdGhldGljIG5lcnZvdXMgc3lzdGVtPC9rZXl3

b3JkPjxrZXl3b3JkPmJvZHkgd2VpZ2h0IGxvc3M8L2tleXdvcmQ+PGtleXdvcmQ+bGFzZXIgZG9w

cGxlciBmbHV4aW1ldHJ5PC9rZXl3b3JkPjxrZXl3b3JkPmdhc3RyaWMgYnlwYXNzPC9rZXl3b3Jk

PjxrZXl3b3JkPnN1YmN1dGFuZW91cyBhZGlwb3NlLXRpc3N1ZTwva2V5d29yZD48a2V5d29yZD5n

YXN0cmljIGJ5cGFzczwva2V5d29yZD48a2V5d29yZD5ub3JlcGluZXBocmluZSBzcGlsbG92ZXI8

L2tleXdvcmQ+PGtleXdvcmQ+bmVydmUgYWN0aXZpdHk8L2tleXdvcmQ+PGtleXdvcmQ+d29tZW48

L2tleXdvcmQ+PGtleXdvcmQ+bGlwb2x5c2lzPC9rZXl3b3JkPjxrZXl3b3JkPmluc3VsaW48L2tl

eXdvcmQ+PGtleXdvcmQ+ZGlldDwva2V5d29yZD48a2V5d29yZD5zZW5zaXRpdml0eTwva2V5d29y

ZD48a2V5d29yZD5yZXNpc3RhbmNlPC9rZXl3b3JkPjwva2V5d29yZHM+PHVybHM+PHJlbGF0ZWQt

dXJscz48dXJsPiZsdDtHbyB0byBJU0kmZ3Q7Oi8vMDAwMjIyMTM2NTAwMDExPC91cmw+PC9yZWxh

dGVkLXVybHM+PC91cmxzPjxpc2JuPjAzMDctMDU2NTwvaXNibj48dGl0bGVzPjx0aXRsZT5SZWxh

dGlvbnNoaXAgYmV0d2VlbiBzeW1wYXRoZXRpYyByZWFjdGl2aXR5IGFuZCBib2R5IHdlaWdodCBs

b3NzIGluIG1vcmJpZGx5IG9iZXNlIHN1YmplY3RzPC90aXRsZT48c2Vjb25kYXJ5LXRpdGxlPklu

dGVybmF0aW9uYWwgSm91cm5hbCBvZiBPYmVzaXR5PC9zZWNvbmRhcnktdGl0bGU+PGFsdC10aXRs

ZT5JbnQgSiBPYmVzaXR5PC9hbHQtdGl0bGU+PC90aXRsZXM+PHBhZ2VzPjkwNi05MTE8L3BhZ2Vz

PjxudW1iZXI+NzwvbnVtYmVyPjxjb250cmlidXRvcnM+PGF1dGhvcnM+PGF1dGhvcj5Cb2JiaW9u

aS1IYXJzY2gsIEUuPC9hdXRob3I+PGF1dGhvcj5Cb25nYXJkLCBPLjwvYXV0aG9yPjxhdXRob3I+

SGFiaWNodCwgRi48L2F1dGhvcj48YXV0aG9yPldlaW1lciwgRC48L2F1dGhvcj48YXV0aG9yPkJv

dW5hbWVhdXgsIEguPC9hdXRob3I+PGF1dGhvcj5IdWJlciwgTy48L2F1dGhvcj48YXV0aG9yPkNo

YXNzb3QsIEcuPC9hdXRob3I+PGF1dGhvcj5Nb3JlbCwgUC48L2F1dGhvcj48YXV0aG9yPkFzc2lt

YWNvcG91bG9zLUplYW5uZXQsIEYuPC9hdXRob3I+PGF1dGhvcj5Hb2xheSwgQS48L2F1dGhvcj48

L2F1dGhvcnM+PC9jb250cmlidXRvcnM+PGxhbmd1YWdlPkVuZ2xpc2g8L2xhbmd1YWdlPjxhZGRl

ZC1kYXRlIGZvcm1hdD0idXRjIj4xMzUxNTcyODk0PC9hZGRlZC1kYXRlPjxyZWYtdHlwZSBuYW1l

PSJKb3VybmFsIEFydGljbGUiPjE3PC9yZWYtdHlwZT48YXV0aC1hZGRyZXNzPkJvYmJpb25pLUhh

cnNjaCwgRSYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERp

cywgMjQgUnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFu

ZCYjeEQ7VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgMjQg

UnVlIE1pY2hlbGwgZHUgQ3Jlc3QsIENILTEyMTEgR2VuZXZhIDE0LCBTd2l0emVybGFuZCYjeEQ7

VW5pdiBIb3NwIEdlbmV2YSwgRGl2IFRoZXJhcGV1dCBFZHVjIENocm9uIERpcywgQ0gtMTIxMSBH

ZW5ldmEgMTQsIFN3aXR6ZXJsYW5kJiN4RDtHZW5ldmEgU2NoIE1lZCwgRGl2IFRoZXJhcGV1dCBF

ZHVjIENocm9uIERpcywgR2VuZXZhLCBTd2l0emVybGFuZCYjeEQ7R2VuZXZhIFNjaCBNZWQsIERp

diBBbmdpb2wgJmFtcDsgSGFlbW9zdGFzaXMsIEdlbmV2YSwgU3dpdHplcmxhbmQmI3hEO0dlbmV2

YSBTY2ggTWVkLCBDbGluIERpZ2VzdCBTdXJnLCBHZW5ldmEsIFN3aXR6ZXJsYW5kJiN4RDtHZW5l

dmEgU2NoIE1lZCwgRGVwdCBNZWQgQmlvY2hlbSwgR2VuZXZhLCBTd2l0emVybGFuZDwvYXV0aC1h

ZGRyZXNzPjxyZWMtbnVtYmVyPjQxOTwvcmVjLW51bWJlcj48bGFzdC11cGRhdGVkLWRhdGUgZm9y

bWF0PSJ1dGMiPjEzNTE1NzI4OTQ8L2xhc3QtdXBkYXRlZC1kYXRlPjxhY2Nlc3Npb24tbnVtPklT

STowMDAyMjIxMzY1MDAwMTE8L2FjY2Vzc2lvbi1udW0+PGVsZWN0cm9uaWMtcmVzb3VyY2UtbnVt

PkRPSSAxMC4xMDM4L3NqLmlqby4wODAyNjIwPC9lbGVjdHJvbmljLXJlc291cmNlLW51bT48dm9s

dW1lPjI4PC92b2x1bWU+PC9yZWNvcmQ+PC9DaXRlPjwvRW5kTm90ZT5=

ADDIN EN.CITE.DATA (Bobbioni-Harsch et al. 2004), possibly by the same hypothalamic alterations that induce the various adaptive responses to weight loss.A standard “public health” lifestyle prescription of a healthy diet and increased physical activity may be unrealistic in individuals who are obese and experiencing significant daytime sleepiness. The one size fits all approach is not adequate for the majority of individuals trying to lose weight. A theoretically grounded lifestyle modification program that addresses the aetiology of disease onset and progression of OSA combined with health coaching behavioural interventions focused on solution focused therapy holds potential for more effective weight loss and long term maintenance. Therefore we have designed a completely novel lifestyle intervention specific for obstructive sleep apnea comparing combinations of mechanical treatment versus no active treatment and low glycemic index/high protein diet or standard hypocaloric diet (Australian Guide to healthy eating) and weight loss program. The results from this study will not only provide insights of immediate benefit to the clinical management of patients with OSA in our clinic and others around the world, they will also provide insights into potential predictors of who will respond to the different weight loss regimes available.Research PlanSTUDY TYPE: This unblinded, randomised controlled trial will incorporate two intervention arms in two separate groups stratified by treatment use. The intervention arms for the SLEEEP study include: SETTING/LOCATION: The Woolcock Institute of Medical ResearchRoyal Prince Alfred Hospital (recruitment only)Potential for home visits/internet contact via email and SkypeDURATION OF THE STUDY: The SLEEEP study will recruit for a minimum of 6 months. Participants will be enrolled for a total of 12 months consisting of 3 overnight visits, 2 clinic visits lasting between 2-3 hours and 6 Skype/Phone sessions. In addition, patients will be contacted to attend a 3 year follow up visit to track progress.TREATMENT STABILITY: Patient recently diagnosed with OSA and instructed to use mechanical treatment must demonstrate consistent compliance for a three month period prior being entered to the study. They will remain on hold during this period. This will reduce the likelihood of a treatment user moving to a no active treatment group should they reject mechanical therapy soon after a new prescription.MethodsSTUDY POPULATIONThis pilot study will recruit the maximum number of participants possible in a minimum period of six months. Potential participants must fulfil the following criteria: Patients with Obstructive sleep apnea Significant adiposity: BMI>30 kg/m2 and/or waist circumferences > 88cm for women and >102cm for men.Patients will be aged > 18 and < 65 and will be excluded if they are actively involved in a structured weight loss program for the last 3 months, have any contraindications to exercise (e.g. known aneurism, severe aortic stenosis, unstable angina etc) or if in the study physician’s opinion would not be a suitable candidate for a weight loss program. Diagnostic polysomnography will be required to confirm presence of OSA if no recent overnight sleep study has been conducted.STRATIFICATION: for treatment versus non treatment usersRecruitmentRecruitment will primarily be conducted through the physicians at the Sleep Clinics of:The Woolcock InstituteRoyal Prince Alfred HospitalPotentially eligible participants will be given an information sheet detailing the aims of the study, basic eligibility criteria and the study staff coordinator contact number to call if they are interested in participating. Participants who are recruited from one of the Sleep Clinics listed may fill in a form requesting to be contacted by a study investigator if they prefer. Other sources of potential volunteers include:The Woolcock Clinic: Treating physicians, all Woolcock affiliated, will be alerted to the study and asked to inform candidate patients of the trial. Patients will be assured that an unwillingness to participate in the trial will in no way affect their ongoing treatment and level of care.Local print media including newspaper advertisements, local newsletters, university mail and newsletters etc.Specialist/GP Referral and potential advertisements in GP wait roomsSleep Disorders Australia websiteAustralasian Sleep Trials Network websiteAustralasian Sleep Association websiteDatabases from previous studies where individuals have consented to be contacted for future studiesAdvertisements may also be displayed in health magazines, websites or papers that are targeted at similar patients. Sleep Disorders Australia and larger general practices will also be advised of the trial to advertise the trial for potential participants.To assess the eligibility for the SLEEEP Study, interested volunteers will undergo a telephone screening. The questions on the form were designed to address all inclusion and exclusion criteria. A 15-30 minute phone call from the interviewer will allow all volunteers to answer the questions and ask any that they may have about the study. A confidential study database will maintain a record of all screens conducted and indicate potential participants and note those who wish not to be contacted in the future.Participants will be informed about their eligibility or be placed on hold for further medical information and/or investigation(s). An information package will be sent via email or post to the potentially eligible subjects and will include an appointment to see the study physician, information regarding the location of the screening, testing venue, a permission slip for access of medical records, a study information sheet including a brief outline of the assessment procedures and a brochure outlining the weight loss program and diets. If not eligible, the researcher will ask volunteer’s permission to retain their contact details in case their situation changes over time and they become eligible at a later date. To obtain medical clarification for volunteers, letters will be sent to their relative doctors along with the signed permission slip from the volunteers indicating that the physician may release relevant medical information where this information may be lacking at the discretion of the study physician.Potentially eligible participants will be given the informed consent and will be guided through all aspects of the information sheet and offered the opportunity to ask any questions related to the study when they attend their screening visit at the Woolcock Institute. Those subjects who agree to participate in the area will be asked to sign the consent form according to the guidelines of the Sydney Local Health District’s Ethics Review Committee. If the patient is willing to participate in the study, they will be requested to also provide written and witnessed informed consent for use of a sample for Pharmacogenetic Research. To determine final eligibility the study physician will examine, consult and review the medical records and telephone screening of each subject. Screening bloods will be collected to check against inclusion/exclusion criteria along with a 12 lead resting ECG. If necessary, a screening overnight PSG will requested to confirm OSA prior to the participant being entered into the study. Eligible subjects will then be asked to attend a baseline visit. Baseline visits will take place overnight at The Woolcock Institute (Glebe). Eligible volunteers will all commence Optifast for the proceeding two month period prior to be randomised to one of the intervention arms as stratified by treatment versus non-treatment use. Inclusion and exclusion criteriaThe following conditions permanently exclude the participant from the SLEEEP Study: Unstable aortic aneurysm Rapidly progressive or terminal illness Severe left ventricular dysfunction/end stage congestive heart failure Severe aortic stenosis Severe psychosis or behavioural disturbance or cognitive impairment Patients known to be involved in illegal activityThe following conditions require medical intervention or re-evaluation prior to participation in the SLEEEP Study:Abnormal resting ECG Alcohol or Caffeine dependence as patients undergo multiple 24 hours periods in our sleep laboratory without access to these.Angina (unstable) Arrhythmias or heart block (uncontrolled) Breathing problem or motion disorder Cardiac surgery (within last 6 months) Cataract extraction (within last month) CHF (uncontrolled) Cognitive impairment (mild-moderate) COPD / CAL (uncontrolled) Current active involvement in another diet/weight loss intervention study or in a weight loss program or drug trial within the preceding three months.Uncontrolled DiabetesDeep venous thrombosis (acute) Endocarditis Fracture (recent or delayed union) Haemorrhoids (severe) Hepatic Impairment Hernia (unrepaired or symptomatic; abdominal or inguinal;) SBP≥180 and/or DBP≥110.Inability to exerciseKnee joint injury within the past 6 months More than 20% of AHI with central apneas.Myocardial infarction (acute; within last 6 months) Neurological disease (rapidly progressive or unstable) Pericarditis (acute) Pregnant or breastfeeding or planning to fall pregnant in the next 12 monthsPulmonary embolism or infarction (acute) Retinopathy, recently treated, unstable Renal ImpairmentUnstable medication use in the preceding 3 months or throughout the study (variable dosages) including antidepressant or anxiolytic medicationsSevere functional limitation (unable to walk unaided by a person) INCLUSION CRITERIAThe following inclusion criteria enable the volunteer to participate in the SLEEEP Study:Males & Females aged 18-65 years.General or central obesity: BMI: ≥30kg/m2 (≥26kg/m2 amongst non-Europeans) or waist circumference ≥88cm for women and ≥102cm for men (>90cm in men and >80cm in women who are non-European).Willing and medically able to participate in a supervised very low energy diet (Optifast) and the dietary and lifestyle modification groups for a 12 month period. Mild-severe, symptomatic OSA (degree of symptoms at the treating physician’s discretion based on overnight sleep study report) No history of or current presence of eating disorders , significant/extensive food allergies or significant food intolerances (e.g. coeliac disease)Willing and able to complete all assessments outlined in participant information sheetHold a current driver’s license or have access to transport.Participants will be required to inform the researcher if they commence any new medications or if medication dosage changes. If this will not interfere with their ability to lose weight the medication will be recorded on the concomitant medication form. RandomisationOnly eligible adults providing written informed consent according to the current approved protocol will be enrolled into the trial. OSA volunteers will be enrolled sequentially according to two pre- allocated randomisation lists stratified as the treatment and non-treatment users and randomised in concealed variable blocks of 4-8 into the standard low calorie diet and lifestyle modification program OR a low GI and High protein diet and lifestyle modification program following two months of VLED. The randomisation sequence will be pre-determined by a research assistant not involved in testing/training, using a computer-generated random number sequence. Sequential treatment allocations will be enclosed in numbered, opaque sealed envelopes, and distributed to each participant at their 2 month visit stratified according to treatment to evenly distribute patients between treatment groups and aid generalisability. The dietary intervention is an open label study as participants cannot be blinded to their treatment allocation.Screening Numbers:Prior to commencing the trial and following signing informed consent, each volunteer will be allocated a unique patient screening number in sequential, ascending chronological order. This number will be a two-digit number prefixed by “S” (e.g. S01, S02 etc) and will be used to identify patients during the screening phase prior to randomisation. As patients commence their baseline visit they will be assigned an additional number according to order of intake and this number will be a double digit prefix used to identify patients prior to randomisation following intake after scrrening (e.g. 01S001 or 05S003) whereby Randomisation Numbers:Randomisation will take place at visit 4 (month 2). This will involve assigning a unique patient number in sequential, ascending chronological order. Since the trial is stratified by treatment use this number will be an ‘R’ and then three-digit number prefixed with 1 or 2 as coded for treatment or non-treatment respectively (e.g. for treatment user 1R_001, 1R_002 etc and for non-treatment user, 2R_001, 2R_002 etc) and will be used to identify stratified patients based on pre-existing mechinical treatment use. Intervention assignment will be determined according to a computer generated randomisation list as described earlier.Statistical AnalysisThis is a pilot trial to describe the variability of weight regain in these two different maintenance diets following a very low energy diet. Recruitment will enrol a maximum number of participants within a target period of six months. No power calculations have been conducted as this is a pilot trial however we anticipate that 20 people will be recruited for each study arm for a total of n=40 over the 6 month recruitment phase. Data will be analysed on an intention-to-treat basis. Mixed model analyses of variance will be used to test each diet treatment effect. Treatment will be the fixed effect and individual patients the random effect. Main effects for the trial will be regarded as statistically significant when p < 0.05. 95% confidence intervals will be used to analyse weight rebound in order to measure the variability associated with weight regain. Follow up /AssessmentsThe primary outcome will be assessed at baseline before the start of the lifestyle modification program and immediately after completion of the VLED 2 months, 6 months and at 12 months as a follow up. Participants will also be assessed for various secondary, tertiary and explanatory outcomes at 1, 2, 6 and 12 month visits as defined in the visit schedule later in the protocol. Blinding of participants is not possible due to the nature of the dietary interventions, but they will not be aware of the investigator’s specific hypotheses. Primary OutcomeWaist Circumference: measured using the International Diabetes Federation Guidelines. The unit will be cm loss and this outcome will be assessed at baseline, 1 month, 2 months, 6 months and 12 months.Secondary OutcomesApnea-Hypopnea Index (AHI): measured via polysomnography to define sleep apnea severity. Leads will be attached to the subject’s head in order to measure chest and abdominal movement, airflow at the mouth and lips, blood oxygen level, muscle tone, eye movements, heart rate and electrical activity in the brain. The subject will be required to sleep with these leads attached. The study is scored using standard criteria and this outcome will be assessed at baseline, 2 months and 12 months.For those patients using CPAP this measurement will be via their CPAP machine which is used on the night of their sleep study.The SF-36 questionnaire: as a tool to measure general health related quality of life in the domains of physical and mental health and will be assessed at baseline, 2 months, 6 months and 12 months.Tertiary and Explanatory Outcomes and effect modifiersSympathetic Activity (Effect Modifiers)24 hour urinary catecholamines: Collected over a 24 hour period and split into wake versus sleep period to measure sympathetic activity (specifically dopamine,?norepinephrine, epinephrine and serotonin) These will be measured at baseline, 2 months, 6 months and 12 months.24 hour cardiopulmonary coupling: to assess sleep quality via a sleep spectrogram (a visualisation or image created by CPC analysis that displays the integrated or coupled) biological oscillations of sleep. This will be measured at baseline, 2 months, 6 months and 12 months. CPC uses autonomic and respiration physiological data streams to mathematically capture the common activity strongly modulated by a third physiological stream: electrocorticol activity. The visualisation of sleep created by this interplay can be used to phenotype various sleep and breathing disorders including OSA. Coupling signatures are categorised as high frequency coupling (HFC:0.1-0.4 Hz) or low frequency coupling (LFC: 0.0 to 0.1 Hz). HFC indicated stable sleep and is increased by conditions that improve the effectiveness or efficiency of sleep. LFC is present when sleep is unstable or inefficient and increased by conditions that add disruptive influences in sleep. During the course of a night’s sleep there are spontaneous switches between HFC and LFC that occur within a sleep cycle. In health, more time (more than 50%) is spent in HFC however diseases disrupting sleep can erode HFC periods, reducing their duration and the percentage of sleep in the HFC state while simultaneously increasing LFC. Patients may also be phenotyped as narrow band, broad band or complex according to spectral dispersion of the coupling sprectra.24 hour heart rate variability: heart rate is modulated by the combined effects of the sympathetic and parasympathetic nervous systems. Measurement of heart rate changes over time (i.e. heart rate variability) provide information about autonomic functioning) and can be measured as a domain of cardiopulmonary coupling. Heart rate variability (HRV) is the standard deviation of the R-R interval and we expect will increase with weight loss. This will be measured at baseline, 2 months, 6 months and 12 months. Core temperature, skin temperature and sweating: Measured using ibutton, electrodermal activity (through skin) and via a component of the CPC Embla device. Objective assessment via electro- dermal activity (EDA), a measurement of the activation of the eccrine sweat glands (Bouscein, 1993). EDA correlates highly with an actual sweat measurement, the ventilated capsule method (r = 0.88) (Kobayashi et al., 2003). Electrodermal activity will be measured with NoiseFree single bio-potential silver-silver ? chloride electrodes connected to the Em- blaTM digital recording device. EDA will be recorded using the skin potential method by placing one electrode on the hypothenar eminence as an active site and another on a lightly abraded site on the volar surface of the forearm as an inactive site (two-thirds of the distance from wrist to elbow) on the right arm (Andreassi, 1995; Fowles et al., 1981). A thermoregulatory index will also be calculated based upon the autonomic function questionnaire.Autonomic Functioning Questionnaire: measuring self-reported autonomic regulationClinical Symptoms Associated with Sleep Apnea and Phenotyping of Sleep ApneaAnthropometric measurements: including height (only measured at baseline); change in weight (kg) , neck circumference (cm) and hip circumference (cm). This will be measured at baseline, 1 month, 2 months, 6 months and 12 months. Change in grams of fat mass, fat free mass, total body water, intracellular fluid and extracellular fluid measured by BIA between baseline and 2 months, baseline and 6 months. Polysomnography: Sleep shall be monitored using standard polysomnography at the Woolcock Institute for the purpose of determining sleep apnea severity via RDI, sleep quality and sleep efficiency. Leads will be attached to the subject’s head in order to measure chest and abdominal movement, airflow at the mouth and lips, blood oxygen level, muscle tone, eye movements, heart rate and electrical activity in the brain. The subject will be required to sleep with these leads attached. The study is scored using standard criteria and this outcome will be assessed at baseline, 2 months and 12 months.Laboratory Analyses for metabolic risk, inflammatory markers and hormones: lipoprotein profile, plasma leptin, insulin sensitivity (HOMA), triacylglycerol concentrations, C-reactive protein, inflammatory markers (IL-4, IL-6, TNF-α), liver function tests, cortisol, ghrelin, adiponectin, testosterone, luteinising hormone, follicle stimulating hormone and a genetic marker for the COMT polymorphism. A 20ml blood sample will be collected at baseline, 1 month, 2 month, 6 month and 12 month visits using standard venepuncture to measure the hormonal and cardiovascular markers noted. Serum will be frozen and processed by a central laboratory. If the patient consents, blood will also be taken and stored for genetic testing at a future occasion. Lipids electrolytes and liver function 1 X 7ml (gold top gel tube)Full blood count takes 1 X 4ml EDTA (purple top tube)Hormones and fasting insulin/glucose 1 x 7 mL (gold top)At the baseline visit a 4ml sample will be taken for genetic testing for the COMT polymorphisms that have been reported to predict sleepiness.Vitals (resting blood pressure and heart rate): Blood pressure (BP), and heart rate (HR), are recorded at each contact visit including the termination visit should it occur, following ESH guidelines. The BP and HR are measured using a consistent device and cuff throughout the study on the same arm used at baseline that showed the higher value. At least 2 measurements should be taken (with 1-2 minutes between) after at least 5 minutes of sitting and resting. A third measure should be taken if there is >10 mmHg discrepancy between the first two measurements.Sleepiness related quality of life: as measured by the functional outcomes of sleepiness questionnaire (FOSQ) and Epworth Sleepiness Scale (ESS)Craniofacial Photography: a photograph of the participants face will be taken with appropriate markers attached to determine craniofacial dimensions specific to sleep apnea.Self Efficacy Self Regulation Questionnaire (SRQ): measures the ability to develop, implement, and flexibly maintain planned behaviour in order to achieve one's goals.General Self Efficacy Scale: to assess a general sense of perceived self efficacy.Bandura’s nutrition and physical exercise self efficacy scale The Kentucky Inventory of Mindfulness Skills (KIMS; Baer 2004) will be used to assess the specific mindfulness skills of participants Quality of Life MeasuresDepression and Anxiety and Stress Scale (DASS): ?to measure the three related negative emotional states of depression, anxiety and tension/stress.Impact of Weight on Quality of Life Questionnaire: to assess the effects of the obese condition on the quality of life of persons seeking treatment for this condition.Three Factor Eating Questionnaire: (TFEQ; Stunkard & Messick, 1985) will be used as a measure of eating behaviour, specifically assessing cognitive restraint, disinhibition of eating, and perceived hunger. Qualitative/Habitual OutcomesHabitual physical activity, energy expenditure, sleep and sedentary behaviour: Actigraph accelerometers will be worn during all waking hours for seven days on the non dominant wrist at all times to monitor activity. These wrist activity monitors will be used to estimate sleep and wake periods by using activity measured by wrist accelerometry. We will also be using this device’s raw activity counts as an objective measure of physical activity levels. Sensewear armbands will also be worn for a seven day period on the upper portion of the non-dominant arm to quantify energy expenditure, sleep, body temperature, intensity of physical activity and steps taken. Food and Activity Diary: Minimum 4 day collection period (3 weekdays and 2 weekend days) to assess habitual dietary intake and energy expenditure via the Bouchard Questionnaire.Actiwatch DiaryFood Habits Questionnaire (FHQ95): To assess usual eating habitsInternational Physical Activity Questionnaire (IPAQ): To provide health related physical activity data Screening QuestionnairesEating Disorder Examination Questionnaire: (EDE-Q; Fairburn & Cooper, 1993) will be used to assess the specific psychopathology of eating disorders. The EDE-Q is comprised of four subscales: restraint, weight, shape and eating concerns.InterventionsVery Low Energy Diets (VLED): All participantsVery low energy diets are frequently used as an efficient and rapid means of controlled weight loss prior to patients transitioning to a maintenance diet. There is a strong body of evidence using VLED in overweight/obese sleep apnea patients as a precursor to other treatment options. The VLED program structure has been provided by RPAH Metabolism and Obesity Services and has been utilised in clinical services and other research trials frequently in the past. The state of ketosis is achieved as large amounts of fatty acids are broken down in response to extreme energy restriction. VLEDs also contain the recommended daily requirements for?vitamins,?minerals,?trace elements, fatty acids?and?protein.?Those patients achieving desired body weight prior to completion of the 3 month shake period will be reviewed by the study physician and supervising nutritional staff to determine whether to graduate them to a maintenance diet earlier than projected. The specific VLED program can be found in the standard operating procedures manual. Patients will follow a full VLED program for an 8 week period (3 shakes per day) then an initial transition phase for 2 weeks (2 shakes, one meal) followed by a latter transition phase (1 shake, 2 meals) before initiating their randomised maintenance diet. Safety and Compliance VLED Pathology Measurements:Baseline: Biochemistry (Electrolytes, Liver function tests, Creatinine, Glucose, Total cholesterol, LDL and HDL, Triglycerides) Haematology: (Full blood count, Iron studies) Endocrine: TFTs, glucose, insulin (HOMA)Follow up pathologyElectrolytes, creatinine and LFTs: after completion of first 4 weeks of the diet; if results are normal no need for further blood testing.Urate – second weekly, if the patient had a history of gout or baseline urate level is above the normal range.Endocrine team to decide on the appropriate pathology follow up.High Protein/ Low GI DietParticipants in this group will be coached to adopt a high protein/low GI weight loss diet based on a 500 calorie restriction (as determined by Harris Benedict Equation). The goal of the diet is to maintain a minimum of 5-10 % weight loss over a 12 month period with sustainable changes in eating patterns.The target macronutrient contribution is 45% of energy from carbohydrates, emphasising low glycaemic sources, 30% from fat and 25% from protein. This macronutrient distribution is similar to the Australian average diet but the GI is lower. The diet will aim to be as low in GI as practical as achieved by replacing higher GI carbohydrates (e.g. conventional white bread, breakfast cereals and potatoes) with lower GI carbohydrates (e.g. Burgen? grain breads, oats, pasta, basmati rice). The GI of the low GI/GL diet will be < 50 (glucose = 100) and calculated using published data for Australian foods. The diet will emphasise lean sources of protein and restriction of saturated and transfats (but not total fat).Participants will be provided with The Shoppers Guide to Low GI that outline the carbohydrate choices and the food amounts that constitute one serving. They will also be provided information on the whole diet to ensure energy and overall nutrient balance. Australian Guide to Healthy EatingParticipants in this group will be coached to adopt a variety of healthy foods from all food groups based on a 500 calorie restriction (as determined by Harris Benedict Equation). It will be modelled around the current Australian guide to healthy eating. The goal of the diet is to maintain a minimum of 5-10 % weight loss over a 12 month period with sustainable changes in eating patterns. Patients will be encouraged to choose whole grains, sources of high fibre, reduce sugar intake and decrease fat intake (specifically saturated and trans fats). The target macronutrient contribution is 60% of energy from carbohydrates, 23% from fat and 17% from protein. This macronutrient distribution is within the recommendation ranges provided by the Australian Guide to Healthy Eating.Participants will be provided with The Australian Guide to Healthy Eating that outlines the carbohydrate choices and the food amounts that constitute one serving. They will also be provided information on the whole diet to ensure energy and overall nutrient balance. Lifestyle Modification ProgramIndividual dietary counselling is necessary to identify current dietary patterns, recommend specific changes and identify barriers and target behavioural change strategies to the individual successfully. Participants will be scheduled at the following sessions as well as being provided with a lifestyle modification booklet at baseline to be made available in each session. All patients will receive identical models of counselling for exercise and overall lifestyle modification according to the pre-designed program. The visit scheduling has been designed to minimise patient burden and make use of convenient means of communication/counselling where possible such as Skype or telephone calls. All participants will be weighed at each clinic visit using the same calibrated scale at the laboratory, as frequent weighing has been shown to enhance weight loss significantly. The participants will also be asked to weigh themselves each morning and measure their waist circumference once a week and record this. These measurements are not data points but will be reviewed at each point of contact with the study staff. Logging of behaviour and goals has been shown to significantly enhance compliance and weight loss. At baseline, 2, 6, and 12 months, collection of 4-day food diary will aid assessment of dietary compliance. Participants who have low adherence (<75%) will receive additional individual booster sessions either in person or by telephone if they are not attending sessions or require additional support (this will be at the discretion of the research officers and medical staff) The behavioural change principles that will be utilised to maximise adherence include the theoretically-grounded principles of decisional balance, social cognitive theory and the stages of change model. Participant WithdrawalPatients who are unable to tolerate the VLED will be considered by the medical supervisory staff to determine whether they are able to reduce their VLED prescription while maintaining an acceptable rate of weight loss so as to enable them to remain in the study. These decisions will be considered on a case by case basis. Patients who are unable to be randomised due to inability to lose weight through the VLED will undertake an exit interview prior to exiting the trial and will be offered medical support as required.Booster SessionsPatients presenting with low adherence to dietary program or demonstrating a need for additional support via more frequent anthropometry may be offered to participate in face to face sessions instead of skype/phonecall sessions. This will be at the discretion of the study physicians and study coordinator where a consensus must be met based on weight loss and patient compliance monitoring.Withdrawal:Patients will be informed that they have the right to withdraw from the study at any time without prejudice to their medical care, and are not obliged to state their reasons. The investigator will follow up any withdrawals. Additionally the investigator may withdraw a patient at:Any time for the following reasons:PregnancySevere hypertension (SBP≥180 and/or DBP≥110).Excessive sleepiness with increased risk for driving-related accidents requiring immediate treatment.Serious incident medical or psychiatric diseaseAfter Randomisation for the following reasons:Patients may be withdrawn if in the opinion of the patient, the treating physician and the data safety physician it is in their best interests. Reasonable effort should still be made to collect the outcome data and at the very least the primary outcome measures regardless of whether the patient has been undergoing the weight loss program.Serious Adverse Events that preclude the ability to measure the primary outcomeAdministrative reasons.If a patient fails to return for follow up or discontinues for personal reasons, attempts will be made to determine what the reason for not returning is if not an adverse event (respecting that the patient is not obliged to state his/her reasons). If discontinuation occurs, an early termination visit will be encouraged with an attempt to collect the primary outcome.Additional Visits: in case of early terminationIf in any case whereby the patient is withdrawn before study completion date, an early termination visit should be arranged as soon as possible. The investigator should examine the following;Anthropometry measurements.Office blood pressure and heart rate.Collection of adverse events.Adverse Event Reporting.Exit Points:If a patient wishes to prematurely withdraw from the trial they should be asked whether they wish to continue participation until an exit point is reached. In the event of them wanting to completely withdraw from the lifestyle program, the participant will cease all treatment however be encouraged to attend their next scheduled visit to enable collection of data for the major outcomes. Exit points exist at the following time points (2, 6 or 9 months). Every effort should be made to ensure that the major outcome measures are collected if the patient is happy to offer their time for these assessments. Risks and DiscomfortsMinor side effects such as fatigue, constipation, diarrhoea, nausea, dizziness, headache, irritability and cold intolerance are usually transient and rarely prevent patients from completing the VLED program. Longer term side effects such as dry skin, hair loss and brittle nails usually subside with the re-introduction of a standard weight maintenance diet. In extreme cases vomiting, acute gout, acute gall bladder disease or cardiac disturbances (particularly if electrolyte disturbances) may preclude therapy.Study Discontinuation:The trial as a whole may be discontinued at any time on the advice of the responsible Principal Investigators and the Data safety monitor based on new information regarding safety or efficacy. Additionally, the study may be terminated if progress is unsatisfactory.In case of premature termination or suspension of the trial, the investigator will inform the trial subjects and ensure appropriate medical follow up. In addition, the appropriate regulatory authorities and ethics committee will be informed, where relevant.If the study is discontinued for safety reasons, the investigators must contact all affected patients within a reasonable period to inform them of the termination of their involvement in the study.Participant Visits-95077108585Screening Visit00Screening VisitPrior to conducting the screening visit, in order to determine eligibility, the investigator must:Provide the participant with written information on the study.Discuss study participation including answering questions about procedures, randomisation, potential risks and no guaranteed benefit from participation.Perform the telephone screeningObtain signed consent.If the investigator is satisfied that the person is potentially eligible, understands the nature and purpose of the study and is willing to participate fully in the study, he/she will be asked to sign the consent form. A signed informed consent must be obtained prior to the following procedures and tests being completed.In order to determine eligibility, the following procedures need to be completed:Medical history and examination.Office Blood Pressure and Heart Rate.Venous blood sample, approximately 10mls of blood will be taken if a recent clinical blood test is not available.Current medicationResting ECG to rule out any potential contraindications to exerciseA previously recorded nocturnal polysomnogram (PSG) report is required to confirm patient eligibility. A PSG will be scheduled if it has not already been performed within the last 24 months or the patient has recently lost or gained >5% body mass.Patients who satisfy eligibility criteria will proceed to visit 1 (week 0) baseline. -11430614680Follow up with Study Doctor00Follow up with Study DoctorPatients demonstrating any absolute or relative contraindication to exercise through their resting ECG must be reviewed by the safety officer Dr Keith Wong FRACP for inclusion/exclusion/ referral to a cardiologist.-11430403168Randomisation00RandomisationFor patients who do not pass the screening visit, a follow up visit should be organised with the clinic doctor.Following 2 months optifast completion all participants will be randomized to their dietary groupBaseline o/night0.25 month P/C or Skype0.5 month P/C or Skype1 month clinic2 month o/night3 month P/C or Skype ?4.5 month P/C or Skype6 month clinic9 month P/C or Skype12 month o/night3 years*#??#?* ?#*#*#RandomisationOvernight PSGSympathetic Activity Battery (24hour urinary catecholamines, CPC, HRV, temperature, sweat & Autonomic Questionnaire) PathologyAnthropometry and BIAVitalsQuestionnaires (Self Efficacy & Quality of Life)Diaries, Habitual Questionnaires and monitors (actiwatch and sensewear)Facial Photography*Patients will be required to wear an actiwatch and sensewear armbands for a week prior and fill out a detailed sleep, diet and exercise diary for 4 days prior to each of these visits. Patients should try to have dinner before arriving at the sleep clinic for 7:00 pm. At this point, the patients will follow the standard overnight visit protocol. ? All patients will be required to participate in a lifestyle modification session. These modules will be accompanied by a manual/workbook and all sessions will be conducted by an Accredited Exercise Physiologist (EM) according to methods taught by Health Coaching Australia: Health Coaching for Health Professionals. # Patients will be required to drop off the 24 hour Embla device (to reception at the Woolcock) and to drop off 24 hour urine collection to their most convenient pathology service.References ADDIN EN.REFLIST Anandam, A., M. Akinnusi, T. Kufel, J. Porhomayon & A. A. El-Solh (2012) Effects of dietary weight loss on obstructive sleep apnea: a meta-analysis. Sleep & breathing = Schlaf & Atmung.Bobbioni-Harsch, E., O. Bongard, F. Habicht, D. Weimer, H. Bounameaux, O. Huber, G. Chassot, P. Morel, F. Assimacopoulos-Jeannet & A. Golay (2004) Relationship between sympathetic reactivity and body weight loss in morbidly obese subjects. International Journal of Obesity, 28, 906-911.Brand-Miller, J. C., S. H. A. Holt, D. B. Pawlak & J. McMillan (2002) Glycemic index and obesity. American Journal of Clinical Nutrition, 76, 281S-285S.Cortelli, P., C. Lombardi, P. Montagna & G. Parati (2012) Baroreflex modulation during sleep and in obstructive sleep apnea syndrome. Autonomic Neuroscience-Basic & Clinical, 169, 7-11.Ebbeling, C. B., J. F. Swain, H. A. Feldman, W. W. Wong, D. L. Hachey, E. Garcia-Lago & D. S. Ludwig (2012) Effects of Dietary Composition on Energy Expenditure During Weight-Loss Maintenance. Jama-Journal of the American Medical Association, 307, 2627-2634.Jaffrin, M. Y. (2009) Body composition determination by bioimpedance: an update. Current Opinion in Clinical Nutrition and Metabolic Care, 12, 482-486.Kansanen, M., E. Vanninen, A. Tuunainen, P. Pesonen, V. Tuononen, J. Hartikainen, H. Mussalo & M. Uusitupa (1998) The effect of a very low-calorie diet-induced weight loss on the severity of obstructive sleep apnoea and autonomic nervous function in obese patients with obstructive sleep apnoea syndrome. Clinical physiology, 18, 377-85.Larsen, T. M., S.-M. Dalskov, M. van Baak, S. A. Jebb, A. Papadaki, A. F. H. Pfeiffer, J. A. Martinez, T. Handjieva-Darlenska, M. Kune?ová, M. Pihlsg?rd, S. Stender, C. Holst, W. H. M. Saris & A. Astrup (2010) Diets with High or Low Protein Content and Glycemic Index for Weight-Loss Maintenance. New England Journal of Medicine, 363, 2102-2113.Mancia, G., P. Bousquet, J. L. Elghozi, M. Esler, G. Grassi, S. Julius, J. Reid & P. A. Van Zwieten (2007) The sympathetic nervous system and the metabolic syndrome. Journal of Hypertension, 25, 909-920.McMillan-Price, J., P. Petocz, F. Atkinson, K. O'Neill, S. Samman, K. Steinbeck, I. Caterson & J. Brand-Miller (2006) Comparison of 4 Diets of Varying Glycemic Load on Weight Loss and Cardiovascular Risk Reduction in Overweight and Obese Young Adults: A Randomized Controlled Trial. Arch Intern Med, 166, 1466-1475.Rosenbaum, M., J. Hirsch, E. Murphy & R. L. Leibel (2000) Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. American Journal of Clinical Nutrition, 71, 1421-1432.Seals, D. R. & C. Bell (2004) Chronic sympathetic activation - Consequence and cause of age-associated obesity? Diabetes, 53, 276-284.Takeda, S., F. Elefteriou, R. Levasseur, X. Y. Liu, L. P. Zhao, K. L. Parker, D. Armstrong, P. Ducy & G. Karsenty (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell, 111, 305-317.Troisi, R. J., S. T. Weiss, D. R. Parker, D. Sparrow, J. B. Young & L. Landsberg (1991) Relation of obesity and diet to sympathetic nervous system activity. Hypertension, 17, 669-77.Young, J. B. & L. Landsberg (1982) Diet-induced changes in sympathetic nervous system activity: possible implications for obesity and hypertension. Journal of chronic diseases, 35, 879-86. ................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download