Observational Study of Early Metabolic and Vascular Changes in Obesity

Obesity Clinical Trial

— STYJOBS  

Official title:

Study for the Investigation of New Individual Risk Profiles and Therapeutic Strategies in Obesity Related Cardiovascular and Metabolic Disorders.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00482924
• Other study ID #: A2720000021
• Status: Recruiting
• Start date: January 2003
• Est. completion date: December 2022

Study information

• Verified date: September 2021
• Source: Medical University of Graz
• Contact: Harald Mangge, Prof., MD
• Phone: +43 316 385
• Email: harald.mangge[@]klinikum-graz.at
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

To work against the increasing burden of obesity, the STYJOBS / EDECTA (STYrian Juvenile OBesity Study / Early DetECtion of Atherosclerosis) project was started at the Medical University of Graz in 2003. STYJOBS / EDECTA is a prospective, observational study to improve the understanding of atherosclerosis, cardiovascular risk, immune mediated low grade Inflammation, metabolic changes, and general disease propensity in obesity. The investigation of the "non-biased" early phase is strongly focused.

Based on this information, new and effective strategies for preclinical diagnostics and early intervention are of main interest. We seek a better understanding of critical lipid profiles, chronic immune-mediated inflammation, disturbed adipokine balance, critical adipose tissue topography, addiction like behaviour, genetics/epigenetics, early vascular pathology, and fatty liver disease. Interventional branches of study tested a holistic strategy comprehending sports, and lifestyle modification for efficiency. The investigative spectrum of STYJOBS / EDECTA comprehends also non-obese body weight extremes i.e. underweight/anorectic people.

Description:

Obesity is dramatically increasing in countries with so called western Lifestyle, whereby juveniles are affected in particular. Atherosclerosis, a major consequence of obesity, starts early in life and results in cardiovascular disease and stroke, the main causes of mortality in industrialized countries. STYJOBS / EDECTA is a prospective, observational study to improve the understanding of obesity associated pathologic conditions by investigation of the "non-biased" early phase.

We aim

To identify "individual metabolic high risk patterns" in obesity by linking lab parameters (adipokines, immune-inflammatory mediators, oxidative "stress" biomarkers, lipoproteins, molecular genetics, epigenetics), individual adipose tissue topography, early vascular damage, life style habits, and clinical data.

The STYJOBS/EDECTA-Database comprehends currently data from 1325 subjects.For each proband 282 variables are available (Clinical, anthropometric, carotis IMT, 82; Laboratory/Biomarkers, 100; Glucose metabolism, liver, kidney function, lipids, oxidative/nitrosative stress, adipokines, gut-brain axis, clotting, Genetic/mitochondrial function/miscellaneous,100), and the results of an early interventional trial by a holistic strategy.

To establish a comprehensive biobank. The STYJOBS/EDECTA-biomaterial resource comprises serum/plasma/DNA left over probes from currently 1256 probands.

EDECTA (Early DEteCTion of Atherosclerosis) extends the STYJOBS Database and Bioresource with normal weight and obese probands aged up to 80 years.

To improve the understanding of craving and addiction like behaviour in obesity (e.g.link insulin resistance - control of hedonic inputs).

Thus, the STYJOBS / EDECTA resource comprises in extendo data and biomaterial specimen from subjects afflicted with the preclinical phase of major sequels of obesity such as insulin resistance, cardiovascular disease, and probably also certain sorts of cancer.

To further improve the understanding of dysbalanced energy expenditure in obesity mitochondrial haplotypes are investigated in cooperation with Dr.Weghuber, Dr.Eder and Prof.Sperl from the Salzburg Paracelsus Private Medical School. All genetic and epigenetic measurements are performed by an anonymous approach (data privacy protection) after careful accreditation by the local ethical committee.

The investigative spectrum of STYJOBS / EDECTA is also extended to underweight/anorectic people. This condition is an attractive biologic "counterpart" to the overweight/obese group. Extremely underweight and anorectic patients are afflicted with profound metabolic abnormalities. Thus, it is interesting to investigate anorexia associated risk profiles in comparison to those found in overweight/obese people. Especially the craving like behaviour and the cardiovascular/"ox"Stress risk will be focused in our investigations.

Further, we investigate the role of tryptophan (TRP) metabolism in context with obesity, immune-mediated inflammation, skewing of T helper cells and mechanisms underlying uncontrolled overeating.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 3 Years to 55 Years

Eligibility

Inclusion Criteria:

• general healthy condition except overweightness/obesity, age below 55 years

Exclusion Criteria:

• thyroid dysfunction, infections, chronic diseases (e.g. autoimmune, inflammatory), neoplasia

Related Conditions & MeSH terms

• Adiponectin Deficiency
• Atherosclerosis
• Fatty Liver
• Inflammation
• Obesity

Intervention

Other:
• Lifestyle intervention
Regular sports and dietary advices. Controlled by analysis of laboratory parameters, BMI change and performance diagnostics. No drugs included so far.

Locations

Country	Name	City	State
Austria	Clinical Institute for Medical and Chemical Laboratory Diagnosis	Graz	Styria

Sponsors (8)

Lead Sponsor	Collaborator
Medical University of Graz	Bundesministerium für Gesundheit, Familie und Jugend, Graz University of Technology, Paracelsus Medical University, Steiermärkische Landesregierung, Technische Universität München, University of Graz, Zukunftsfonds Steiermark

Country where clinical trial is conducted

Austria, 

References & Publications (54)

Almer G, Frascione D, Pali-Schöll I, Vonach C, Lukschal A, Stremnitzer C, Diesner SC, Jensen-Jarolim E, Prassl R, Mangge H. Interleukin-10: an anti-inflammatory marker to target atherosclerotic lesions via PEGylated liposomes. Mol Pharm. 2013 Jan 7;10(1): — View Citation

Almer G, Saba-Lepek M, Haj-Yahya S, Rohde E, Strunk D, Fröhlich E, Prassl R, Mangge H. Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions. Biologics. 2011;5:95-105. doi: 10.2147/BTT.S22863. Epub 2011 Sep 7. — View Citation

Almer G, Wernig K, Saba-Lepek M, Haj-Yahya S, Rattenberger J, Wagner J, Gradauer K, Frascione D, Pabst G, Leitinger G, Mangge H, Zimmer A, Prassl R. Adiponectin-coated nanoparticles for enhanced imaging of atherosclerotic plaques. Int J Nanomedicine. 2011;6:1279-90. doi: 10.2147/IJN.S18739. Epub 2011 Jun 21. — View Citation

Arnold T, Brandlhofer S, Vrtikapa K, Stangl H, Hermann M, Zwiauer K, Mangge H, Karwautz A, Huemer J, Koller D, Schneider WJ, Strobl W. Effect of obesity on plasma clusterin, [corrected] a proposed modulator of leptin action. Pediatr Res. 2011 Mar;69(3):237-42. doi: 10.1203/PDR.0b013e31820930cb. Erratum in: Pediatr Res. 2011 Apr;69(4):358. — View Citation

Bengesser SA, Lackner N, Birner A, Fellendorf FT, Platzer M, Mitteregger A, Unterweger R, Reininghaus B, Mangge H, Wallner-Liebmann SJ, Zelzer S, Fuchs D, McIntyre RS, Kapfhammer HP, Reininghaus EZ. Peripheral markers of oxidative stress and antioxidative defense in euthymia of bipolar disorder--Gender and obesity effects. J Affect Disord. 2015 Feb 1;172:367-74. doi: 10.1016/j.jad.2014.10.014. Epub 2014 Oct 22. — View Citation

Cimenti C, Mangge H, Haidl H, Zach D, Muntean W. Thrombin generation in severely obese children. J Thromb Haemost. 2006 Aug;4(8):1834-6. — View Citation

Ebner S, Mangge H, Langhof H, Halle M, Siegrist M, Aigner E, Paulmichl K, Paulweber B, Datz C, Sperl W, Kofler B, Weghuber D. Mitochondrial Haplogroup T Is Associated with Obesity in Austrian Juveniles and Adults. PLoS One. 2015 Aug 31;10(8):e0135622. doi — View Citation

Fritsch P, Kleber M, Schlagenhauf A, Laschnik B, Fritsch M, Muntean W, Mangge H, Reinehr T. Normalization of haemostatic alterations in overweight children with weight loss due to lifestyle intervention. Atherosclerosis. 2011 May;216(1):170-3. doi: 10.1016/j.atherosclerosis.2011.01.042. Epub 2011 Feb 2. — View Citation

Gradauer K, Barthelmes J, Vonach C, Almer G, Mangge H, Teubl B, Roblegg E, Dünnhaupt S, Fröhlich E, Bernkop-Schnürch A, Prassl R. Liposomes coated with thiolated chitosan enhance oral peptide delivery to rats. J Control Release. 2013 Dec 28;172(3):872-8. doi: 10.1016/j.jconrel.2013.10.011. Epub 2013 Oct 16. — View Citation

Gruber HJ, Mayer C, Mangge H, Fauler G, Grandits N, Wilders-Truschnig M. Obesity reduces the bioavailability of nitric oxide in juveniles. Int J Obes (Lond). 2008 May;32(5):826-31. doi: 10.1038/sj.ijo.0803795. Epub 2008 Jan 15. — View Citation

Gruber HJ, Mayer C, Meinitzer A, Almer G, Horejsi R, Möller R, Pilz S, März W, Gasser R, Truschnig-Wilders M, Mangge H. Asymmetric dimethylarginine (ADMA) is tightly correlated with growth in juveniles without correlations to obesity related disorders. Ex — View Citation

Hasija R, Pistorio A, Ravelli A, Demirkaya E, Khubchandani R, Guseinova D, Malattia C, Canhao H, Harel L, Foell D, Wouters C, De Cunto C, Huemer C, Kimura Y, Mangge H, Minetti C, Nordal EB, Philippet P, Garozzo R, Martini A, Ruperto N; Pediatric Rheumatology International Trials Organization. Therapeutic approaches in the treatment of juvenile dermatomyositis in patients with recent-onset disease and in those experiencing disease flare: an international multicenter PRINTO study. Arthritis Rheum. 2011 Oct;63(10):3142-52. doi: 10.1002/art.30475. — View Citation

Lackner N, Bengesser SA, Birner A, Painold A, Fellendorf FT, Platzer M, Reininghaus B, Weiss EM, Mangge H, McIntyre RS, Fuchs D, Kapfhammer HP, Wallner-Liebmann SJ, Reininghaus EZ. Abdominal obesity is associated with impaired cognitive function in euthymic bipolar individuals. World J Biol Psychiatry. 2016 Oct;17(7):535-46. doi: 10.3109/15622975.2015.1046917. Epub 2015 Jun 12. — View Citation

Lackner N, Mangge H, Reininghaus EZ, McIntyre RS, Bengesser SA, Birner A, Reininghaus B, Kapfhammer HP, Wallner-Liebmann SJ. Body fat distribution and associations with metabolic and clinical characteristics in bipolar individuals. Eur Arch Psychiatry Clin Neurosci. 2015 Jun;265(4):313-9. doi: 10.1007/s00406-014-0559-8. Epub 2014 Nov 8. — View Citation

Landauer F, Huber G, Paulmichl K, O'Malley G, Mangge H, Weghuber D. Timely diagnosis of malalignment of the distal extremities is crucial in morbidly obese juveniles. Obes Facts. 2013;6(6):542-51. doi: 10.1159/000357280. Epub 2013 Dec 6. — View Citation

Mangge H, Almer G, Haj-Yahya S, Grandits N, Gasser R, Pilz S, Möller R, Horejsi R. Nuchal thickness of subcutaneous adipose tissue is tightly associated with an increased LMW/total adiponectin ratio in obese juveniles. Atherosclerosis. 2009 Mar;203(1):277 — View Citation

Mangge H, Almer G, Haj-Yahya S, Pilz S, Gasser R, Möller R, Horejsi R. Preatherosclerosis and adiponectin subfractions in obese adolescents. Obesity (Silver Spring). 2008 Dec;16(12):2578-84. doi: 10.1038/oby.2008.439. Epub 2008 Oct 9. — View Citation

Mangge H, Almer G, Stelzer I, Reininghaus E, Prassl R. Laboratory medicine for molecular imaging of atherosclerosis. Clin Chim Acta. 2014 Nov 1;437:19-24. doi: 10.1016/j.cca.2014.06.029. Epub 2014 Jul 5. Review. — View Citation

Mangge H, Almer G, Truschnig-Wilders M, Schmidt A, Gasser R, Fuchs D. Inflammation, adiponectin, obesity and cardiovascular risk. Curr Med Chem. 2010;17(36):4511-20. Review. — View Citation

Mangge H, Almer G, Zelzer S, Vasan R, Kraigher-Krainer E, Gasser R, Schnedl W, Ille R, Wallner S, Möller R, Horejsi R, Weghuber D. N-terminal pro-B-type natriuretic peptide in early and advanced phases of obesity. Clin Chem Lab Med. 2011 Sep;49(9):1539-45 — View Citation

Mangge H, Baumgartner B, Schnedl W. Letter: PNPLA3, metabolic syndrome and NAFLD status in obese subjects--authors' reply. Aliment Pharmacol Ther. 2015 Sep;42(5):630-1. doi: 10.1111/apt.13318. — View Citation

Mangge H, Baumgartner BG, Zelzer S, Prüller F, Schnedl WJ, Reininghaus EZ, Haybaeck J, Lackner C, Stauber R, Aigner E, Weghuber D. Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents an — View Citation

Mangge H, Becker K, Fuchs D, Gostner JM. Antioxidants, inflammation and cardiovascular disease. World J Cardiol. 2014 Jun 26;6(6):462-77. doi: 10.4330/wjc.v6.i6.462. Review. — View Citation

Mangge H, Ciardi C, Becker K, Strasser B, Fuchs D, Gostner JM. Influence of Antioxidants on Leptin Metabolism and its Role in the Pathogenesis of Obesity. Adv Exp Med Biol. 2017;960:399-413. doi: 10.1007/978-3-319-48382-5_17. Review. — View Citation

Mangge H, Freytag F, Almer G, Weghuber D, Bauer-Denk C, Fuchs D. Serum neopterin is not increased in obese juveniles. J Obes. 2011;2011:946795. doi: 10.1155/2011/946795. Epub 2011 Jan 12. — View Citation

Mangge H, Pilz S, Haj-Yahya S, Almer G. Uric acid indicates a high cardiovascular risk profile but is not closely associated with insulin resistance in obese adolescents. Diabetes Care. 2008 Apr;31(4):e21. doi: 10.2337/dc07-2411. — View Citation

Mangge H, Prüller F, Zelzer S, Ainödhofer H, Pailer S, Kieslinger P, Haybaeck J, Obermayer-Pietsch B, Cvirn G, Gruber HJ. Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet. Int J Mol Sci. 2015 Jul 10;16(7):15776-84. doi: 10.3390/ijms160715776. — View Citation

Mangge H, Renner W, Almer G, Weghuber D, Möller R, Horejsi R. Rs9939609 variant of the fat mass and obesity-associated gene and trunk obesity in adolescents. J Obes. 2011;2011:186368. doi: 10.1155/2011/186368. Epub 2011 Jan 13. — View Citation

Mangge H, Schauenstein K, Stroedter L, Griesl A, Maerz W, Borkenstein M. Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis. Exp Clin Endocrinol Diabetes. 2004 Jul;112(7):378-82. — View Citation

Mangge H, Stelzer I, Reininghaus EZ, Weghuber D, Postolache TT, Fuchs D. Disturbed tryptophan metabolism in cardiovascular disease. Curr Med Chem. 2014 Jun;21(17):1931-7. Review. — View Citation

Mangge H, Summers K, Almer G, Prassl R, Weghuber D, Schnedl W, Fuchs D. Antioxidant food supplements and obesity-related inflammation. Curr Med Chem. 2013;20(18):2330-7. Review. — View Citation

Mangge H, Summers KL, Meinitzer A, Zelzer S, Almer G, Prassl R, Schnedl WJ, Reininghaus E, Paulmichl K, Weghuber D, Fuchs D. Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome. Obesi — View Citation

Mangge H, Weghuber D, Prassl R, Haara A, Schnedl W, Postolache TT, Fuchs D. The Role of Vitamin D in Atherosclerosis Inflammation Revisited: More a Bystander than a Player? Curr Vasc Pharmacol. 2015;13(3):392-8. Review. — View Citation

Mangge H, Zelzer S, Meinitzer A, Stelzer I, Schnedl WJ, Weghuber D, Fuchs D, Postolache TT, Aigner E, Datz C, Reininghaus EZ. 25OH-Vitamin D3 Levels in Obesity and Metabolic Syndrome-Unaltered in Young and not Correlated to Carotid IMT in All Ages. Curr P — View Citation

Mangge H, Zelzer S, Prüller F, Schnedl WJ, Weghuber D, Enko D, Bergsten P, Haybaeck J, Meinitzer A. Branched-chain amino acids are associated with cardiometabolic risk profiles found already in lean, overweight and obese young. J Nutr Biochem. 2016 Jun;32 — View Citation

Mangge H, Zelzer S, Puerstner P, Schnedl WJ, Reeves G, Postolache TT, Weghuber D. Uric acid best predicts metabolically unhealthy obesity with increased cardiovascular risk in youth and adults. Obesity (Silver Spring). 2013 Jan;21(1):E71-7. doi: 10.1002/o — View Citation

Mangge H. Beyond Cholesterol - New Cardiovascular Biomarkers. Nestle Nutr Inst Workshop Ser. 2016;84:81-8. doi: 10.1159/000436990. Epub 2016 Jan 14. — View Citation

Marsche G, Zelzer S, Meinitzer A, Kern S, Meissl S, Pregartner G, Weghuber D, Almer G, Mangge H. Adiponectin Predicts High-Density Lipoprotein Cholesterol Efflux Capacity in Adults Irrespective of Body Mass Index and Fat Distribution. J Clin Endocrinol Me — View Citation

Moeller R, Horejsi R, Pilz S, Lang N, Sargsyan K, Dimitrova R, Tafeit E, Giuliani A, Almer G, Mangge H. Evaluation of risk profiles by subcutaneous adipose tissue topography in obese juveniles. Obesity (Silver Spring). 2007 May;15(5):1319-24. — View Citation

Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Böhm BO, Winkelmann BR, März W, Fuchs D. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis. 2009 Feb;202(2):543-9. doi: 10.1016/j.atherosclerosis.2008.04.047. Epub 2008 May 15. — View Citation

Pachler C, Ikeoka D, Plank J, Weinhandl H, Suppan M, Mader JK, Bodenlenz M, Regittnig W, Mangge H, Pieber TR, Ellmerer M. Subcutaneous adipose tissue exerts proinflammatory cytokines after minimal trauma in humans. Am J Physiol Endocrinol Metab. 2007 Sep;293(3):E690-6. Epub 2007 Jun 19. — View Citation

Pilz S, Horejsi R, Möller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H. Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. J Clin Endocrinol Met — View Citation

Pilz S, Mangge H, Obermayer-Pietsch B, März W. Visfatin/pre-B-cell colony-enhancing factor: a protein with various suggested functions. J Endocrinol Invest. 2007 Feb;30(2):138-44. Review. — View Citation

Pilz S, Mangge H, Wellnitz B, Seelhorst U, Winkelmann BR, Tiran B, Boehm BO, März W. Adiponectin and mortality in patients undergoing coronary angiography. J Clin Endocrinol Metab. 2006 Nov;91(11):4277-86. Epub 2006 Aug 15. — View Citation

Prüller F, Raggam RB, Posch V, Almer G, Truschnig-Wilders M, Horejsi R, Möller R, Weghuber D, Ille R, Schnedl W, Mangge H. Trunk weighted obesity, cholesterol levels and low grade inflammation are main determinants for enhanced thrombin generation. Athero — View Citation

Raheja UK, Fuchs D, Giegling I, Brenner LA, Rovner SF, Mohyuddin I, Weghuber D, Mangge H, Rujescu D, Postolache TT. In psychiatrically healthy individuals, overweight women but not men have lower tryptophan levels. Pteridines. 2015 Jun;26(2):79-84. — View Citation

Reininghaus EZ, McIntyre RS, Reininghaus B, Geisler S, Bengesser SA, Lackner N, Hecht K, Birner A, Kattnig F, Unterweger R, Kapfhammer HP, Zelzer S, Fuchs D, Mangge H. Tryptophan breakdown is increased in euthymic overweight individuals with bipolar disorder: a preliminary report. Bipolar Disord. 2014 Jun;16(4):432-40. doi: 10.1111/bdi.12166. Epub 2013 Dec 12. — View Citation

Stelzer I, Zelzer S, Raggam RB, Prüller F, Truschnig-Wilders M, Meinitzer A, Schnedl WJ, Horejsi R, Möller R, Weghuber D, Reeves G, Postolache TT, Mangge H. Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation. — View Citation

Wallner-Liebmann S, Koschutnig K, Reishofer G, Sorantin E, Blaschitz B, Kruschitz R, Unterrainer HF, Gasser R, Freytag F, Bauer-Denk C, Schienle A, Schäfer A, Mangge H. Insulin and hippocampus activation in response to images of high-calorie food in norma — View Citation

Wallner-Liebmann SJ, Moeller R, Horejsi R, Jürimäe T, Jürimäe J, Mäestu J, Purge P, Saar M, Tafeit E, Kaimbacher P, Kruschitz R, Weghuber D, Schnedl WJ, Mangge H. Normal weight estonian prepubertal boys show a more cardiovascular-risk-associated adipose tissue distribution than austrian counterparts. ISRN Obes. 2013 Jan 14;2013:506751. doi: 10.1155/2013/506751. eCollection 2013. — View Citation

Weghuber D, Zelzer S, Stelzer I, Paulmichl K, Kammerhofer D, Schnedl W, Molnar D, Mangge H. High risk vs. "metabolically healthy" phenotype in juvenile obesity - neck subcutaneous adipose tissue and serum uric acid are clinically relevant. Exp Clin Endocr — View Citation

Wilders-Truschnig M, Mangge H, Lieners C, Gruber H, Mayer C, März W. IgG antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles. Exp Clin Endocrinol Diabetes. 2008 Apr;116(4):241-5. Epub 2007 Dec 10 — View Citation

Zelzer S, Fuchs N, Almer G, Raggam RB, Prüller F, Truschnig-Wilders M, Schnedl W, Horejsi R, Möller R, Weghuber D, Ille R, Mangge H. High density lipoprotein cholesterol level is a robust predictor of lipid peroxidation irrespective of gender, age, obesit — View Citation

Zelzer S, Mangge H, Pailer S, Ainoedhofer H, Kieslinger P, Stojakovic T, Scharnagl H, Prüller F, Weghuber D, Datz C, Haybaeck J, Obermayer-Pietsch B, Trummer C, Gostner J, Gruber HJ. Oxidized LDL Is Strictly Limited to Hyperthyroidism Irrespective of Fat Feeding in Female Sprague Dawley Rats. Int J Mol Sci. 2015 May 21;16(5):11689-98. doi: 10.3390/ijms160511689. — View Citation

* Note: There are 54 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Anthropometric changes(BMI, SAT-Topography, waist/hipCF, waist to height ratio) during intervention		12 months
Secondary	Obesity related biomarkers (fasting glucose, insulin, HOMA-index, HbA1c, liver transaminases, inflammatory markers, adipokines, clotting parameters, lipids, oxidative stress markers, Biomarkers related to tryptophan metabolism), performance diagnostics.		12 months