bluuebunny/crossref_metadata_2025_split huggingface dataset:
228-OR: Decoding Human Postprandial Responses to Food and Their Potential for Precision Nutrition: The PREDICT 1 Study
Authors: FRANKS PAUL W. , BERRY SARAH , VALDES ANA M. , DREW DAVID A. , DAVIES RICHARD J. , MERINO JORDI , CHAN ANDREW T. , SEGATA NICOLA , SPECTOR TIM D. 
Published: June 2020

Metabolic responses to food influence diabetes risk, but data suitable for determining personalized nutritional advice are lacking. PREDICT 1 (n=1102 twins and unrelated healthy UK/U.S. adults) examined genetic, metabolic, microbiome, and meal composition/context contributions to postprandial metabolic responses in clinic and at home. This 2-week interventional trial included the administration of standardized meals/beverages and monitored of ad libitum food intake. Objective assessments of sleep and physical activity were made. Blood glucose was continuously assessed and triglycerides and C-peptide were measured repeatedly. Large and consistent differences between individuals in blood triglyceride, glucose, and insulin responses to identical meals were observed. Person-specific factors, including variation in the gut microbiome, had a greater influence than meal macronutrients; genetic variants had a modest impact on predictions. Modifiable factors such as meal timing had large effects, highlighting avenues to improve postprandial responses. As predictors of CVD risk, postprandial triglyceride and glucose improved on traditional fasting markers. Machine learning was utilized to derive personalized predictions for both triglyceride (r=0.47) and glycemic (r=0.77) responses.

Disclosure
P.W. Franks: Advisory Panel; Self; Zoe Global Ltd. Consultant; Self; Eli Lilly and Company, Novo Nordisk A/S. Research Support; Self; Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk A/S, Sanofi, Servier. S. Berry: Consultant; Self; Zoe Global. A.M. Valdes: None. D.A. Drew: None. R.J. Davies: Employee; Self; Zoe Global Ltd. J. Merino: None. A.T. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Pfizer Inc. N. Segata: Consultant; Self; Zoe Global Ltd. T.D. Spector: Stock/Shareholder; Self; Zoe Global Ltd.

Funding
Zoe Global Ltd.; UK Wellcome Trust (212904/Z/18/Z); Medical Research Council/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (M016560/1); European Research Council (CoG-2015_681742_NASCENT to P.W.F.); UK Wellcome Trust; Medical Research Council; European Union; Chronic Disease Research Foundation; Zoe Global Ltd.; National Institute for Health Research-funded BioResource, Clinical Research Facility and Biomedical 511 Research Centre based at Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London
2282-PUB: Impact of Demographic and Socioeconomic Factors on Glycemic Control
Authors: FOLAWEWO KEHINDE M. , HODGE MAKENZIE U. , NUNLEE-BLAND GAIL , OSMAN NADA , ZENEBE ANTENEH , ODONKOR WOLALI , GANTA VIJAYA , OGUNTI RICHARD 
Published: June 2020

Objective: Evaluate the impact of demographic and socio-economic factors on diabetic control (Hba1c) among patients in an outpatient setting.
Methods: A prospective study from January 2015 to May 2017 involving 211 patients with diabetes mellitus managed at an outpatient endocrinology clinic. Serial measurements of HbA1c were collected at baseline, 3 and 6 months. HbA1c was treated as a continuous variable and presented as mean ± standard deviation. Baseline HbA1c level was compared among dichotomized socio-economic variables (married vs. not married; employed vs. unemployed; health literacy (using the REALM survey) and educational level using t-test. A multivariable linear regression model was used to examine the association between Hb1Ac control and patient demographic and socio-economic characteristics.
Results: Among study participants, 96% were African American, 63.5% female, with mean age of 53 ± 14.7) and baseline mean Hb1Ac of 8.80 ± 2.30. In univariate analysis, higher baseline Hb1Ac was observed in patients with REALM score below 7 vs. above 7, (9.30%±2.36 vs. 8.49% ± 2.27, p-value = 0.01), unemployed vs. unemployed (9.17%± 2.46 vs. 8.56%± 2.23, p-value = 0.08), and high school or lower vs. college and above (9.08% ± 2.36 vs. 8.7%± 2.28, p-value = 0.10). Single and divorced patients had higher baseline HbA1C (8.94 ± 2.4 and 8.90 ± 2.4 respectively) compared to their married counterpart (8.65%±2.4)Adjusting for baseline Hb1Ac level, gender, race marital status, employment status and educational level, multivariable regression analysis showed that higher educational level was significantly associated with change in HbA1c values. Patients with college education and above showed significant reduction in HbA1C (regression coefficient -0.75, 95% CI -1.27 to -0.230, p=0.005) compared to those with high school attainment and lower.
Conclusion: In this prospective study involving predominantly African Americans, higher educational attainment was independently associated with better glycemic control.

Disclosure
K.M. Folawewo: None. M.U. Hodge: None. G. Nunlee-Bland: None. N. Osman: None. A. Zenebe: None. W. Odonkor: None. V. Ganta: None. R. Ogunti: None.
2284-PUB: Overweight/Obesity in Young T1D Patients Is Differently Associated to First Degree Relatives’ History or Features According to Their Gender
Authors: VALENTE FERNANDO , VALENTE TATIANA , DIB SERGIO A. 
Published: June 2020

Introduction: Obesity is increasing in T1D patients worldwide and is related to cardiovascular (CV) disease.
Objective: To identify the background characteristics linked to overweight/obesity and CV risk factors during insulin treatment in T1D patients.
Methods: We performed anthropometric, laboratory and genetic analysis - FTO rs9939609 and visfatin rs9770242 of young Brazilian T1D. This study was approved by the Ethic Committee.
Results: From 181 T1D patients (age 23.6±5.5 y, diabetes duration 12.1±7.2 y, A1c 8.9±1.9%), 87 were female - 64.4% normal weight (NW), 26.4% overweight (OW) and 9.2% obese (OB) - and 94 male (77.7% NW, 14.9% OW and 7.4% OB).
Male: OB were older (OB: 29.4±3.7 y vs. OW: 23.2±5.8 vs. NW: 22.5±5.3, p=0.01), had higher prevalence of blacks (57.1% vs. 7.1 vs. 7, p=0.01), higher triglycerides levels (180.3±140.2 mg/dL vs. 74.4±34.4 vs. 87±57.1, p=0.03), diastolic BP (85±8.4 mmHg vs. 78.9±9.2 vs. 73.4±9.6, p=0.009) and lower eGDR (5.4±1.9 mg/Kg/min vs. 6.8±1.9 vs. 7.9±1.7, p=0.003). Higher prevalence of AH (100% vs. 57.1 vs. 50.7, p=0.03) and early CV disease (28.6% vs. 7.1 vs. 2.7, p=0.02) in their first-degree relatives (FDR) were also found in OB. A1c, insulin dose (U/kg/day), diabetes duration, physical activity, high molecular weight (HMW) adiponectin, visfatin, FTO and visfatin genes polymorphisms were not different in NW and OW/OB.
Female: We found no difference between groups in A1c, insulin dose, diabetes duration, physical activity, HMW adiponectin, visfatin or FTO and visfatin genes polymorphisms. OW and OB had lower eGDR (5.4±2.4 mg/Kg/min vs. 6.1±2.1 vs. 8±2.1, p=0.0002). OB women had FDR with obesity more frequently (62.5% vs. 47.8 vs. 25.5, p=0.03).
Conclusion: FDR with obesity is a risk factor to OW/OB in female T1D as well as FDR with early CV disease or AH in male T1D. These specifics familiar background must be considered for early prevention of CV risk factors during natural history of T1D.

Disclosure
F. Valente: Consultant; Spouse/Partner; Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca, Novo Nordisk Inc. T. Valente: None. S.A. Dib: None.
2293-PUB: Epigenomic Analysis of AgRP Neurons Reveals That Leptin Induces Satiety via IRF3
Authors: HEYWARD FRANKIE D. , IVISON RACHAEL , TSAI LINUS T.Y. , ROSEN EVAN 
Published: June 2020

AgRP neurons in the arcuate nucleus (ARC) of the hypothalamus play a dominant role in maintaining energy balance and are dysregulated in obesity, but prior studies examining their transcriptional regulation have been confounded by the rich cellular diversity of the ARC and the low abundance of these neurons. We have employed AgRP neuron-specific Translating Ribosomal Affinity Purification followed by RNA-sequencing (TRAP-seq) and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) to determine the transcriptomic and epigenomic landscape of these neurons during the fed, fasted and leptin-treated states. These rich datasets were computationally integrated to identify candidate transcription factors (TFs) potentially mediating the homeostatic control of food intake, of which the Interferon Regulatory Factor (IRF) family of TFs were enriched during the leptin-treated state. Cell-type specific functional studies have revealed that IRF3 plays a key role in mediating the satiety-inducing effects of leptin. Thus, we have identified a novel role for AgRP-neuron expressed IRF3 in regulating the satiety-evoking effects of leptin.

Disclosure
F.D. Heyward: None. R. Ivison: None. L.T.Y. Tsai: None. E. Rosen: None.

Funding
American Diabetes Association (1-19-PMF-008 to F.D.H.); Burroughs Wellcome Fund; American Heart Association
2306-PUB: Serum CXCL14 Levels Are Associated with Plasma C-Peptide and Fatty Liver Index in T2DM Patients: A Retrospective Analysis
Authors: MATSUSHITA YURIKO , HASEGAWA YUTAKA , TAKEBE NORIKO , ISHIGAKI YASUSHI 
Published: June 2020

Objective: Recent studies have shown that Chemokine (C-X-C motif) ligand 14 (CXCL14), a newly secreted by brown adipose tissue, plays an important role in the pathogenesis of metabolic syndrome. However, clinical significance has not been elucidated in human. The aim of this study is to assess correlations between serum CXCL14 levels and clinical parameters among the patients with type 2 diabetes mellitus (T2DM).
Method: A total of 176 subjects with T2DM were recruited. Serum CXCL14 concentration was determined by ELISA. We examined the association of serum CXCL14 levels with the anthropometric parameters and laboratory values, abdominal CT image information, surrogate markers used for evaluating the pathological state of DM, obesity and atherosclerosis.
Result: Serum CXCL14 levels correlated positively with body mass index and waist circumference, subcutaneous and visceral fat area, estimated glomerular filtration rate, serum levels of ALT, UA, TC, LDL-C, TG, FT3, C-peptide (CPR), neuregulin 4, fibroblast growth factor 21, urine levels of CPR, 8-hydroxy-2’-deoxyguanosine. In contrast, those were inversely correlated with age and pulse wave velocity, plasma levels of adiponectin. Multiple linear regression analysis revealed plasma levels of CPR (β=0.227, p=0.038) and fatty liver index (FLI; β=0.205, p=0.049) to be the only parameters showing independent statistically significant association with serum CXCL14 levels.
Conclusion: Serum CXCL14 levels were independently associated with plasma CPR and FLI in patients with T2DM. In this case, high concentration of plasma CPR might reflect insulin resistance rather than β-cell function, because CXCL14 showed simple correlations with obesity-related parameters. Collectively, these data suggested serum CXCL14 levels in type 2 DM might be useful predictors of insulin resistance and abdominal fat accumulation.

Disclosure
Y. Matsushita: None. Y. Hasegawa: None. N. Takebe: None. Y. Ishigaki: None.
2311-PUB: Metformin Improves Hepatic Inflammation in Diet-Induced Obese Mice through Downregulating CYP7B1
Authors: GUO WANRONG , WANG WEI , ZHENG XIAOBIN , XU FEN 
Published: June 2020

Metformin is an antidiabetic drug widely used to treat type 2 diabetes. Although it has been found for a very long time, its mechanism remains to be discovered. Recently, metformin has been reported to be effective in other disease, such as obesity and tumor. However, whether metformin is beneficial in nonalcoholic fatty liver disease remains controversial. CYP7B1, a cholesterol hydroxylase, has been reported to be upregulated in the inflammatory diseases. We investigated whether CYP7B1 plays an important role in the effect of metformin on the hepatic inflammation in diet-induced obese mice. In this study, eight-week-old C57BL/6 mice were subjected to a chow diet or a high fat diet (HFD) for 12 weeks. After the diet intervention, mice on an HFD were randomly divided into HFD group and HFD+Metformin group (HFDM group) for 4 weeks. The results showed that the body weight, fasting blood glucose, body fat mass, glucose metabolism and insulin sensitivity were remarkably improved by metformin. The histological results including H&E staining and oil red O staining showed that metformin significantly ameliorated fatty liver induced by HFD. And the quantification of liver triglyceride also proved that. The histological results also revealed that adipocytes of epididymal adipose tissue and subcutaneous adipose tissue were smaller after metformin treatment. Meanwhile, metformin also ameliorated the whitening of brown adipose tissue according to the H&E staining. Compared to HFD group, the mRNA levels of CYP7B1 and pro-inflammatory markers (TNFα, IL-1, F4/80 and MCP1) in liver were downregulated in HFDM group. How CYP7B1 functions in the beneficial effect of metformin on improving hepatic inflammation is going to be further studied.

Disclosure
W. Guo: None. W. Wang: None. X. Zheng: None. F. Xu: None.
2312-PUB: Orthostatic Instability in a Patient with Type 1 Diabetes Mellitus after Bariatric Surgery
Authors: CARDONA ZULMA , HAIDER YASSER 
Published: June 2020

Orthostatic Intolerance (OI) refers to a heterogeneous group of disorders of hemodynamic regulation characterized by insufficient cerebral perfusion resulting in symptoms during upright posture relieved by recumbency. To our knowledge this would be the first case to describe a patient with type 1 diabetes mellitus (T1DM) who underwent bariatric surgery and developed debilitating OI. We describe the case of a 46 year old with class III obesity (BMI 42.9), T1DM, complicated by microalbuminuria, diabetic retinopathy, carpal tunnel syndrome, and HTN status post gastric sleeve surgery who presented to the emergency department 10 days after surgery for a syncopal episode, which resulted in head trauma. He endorsed multiple episodes of lightheadedness and falling after surgery. He lost 20 lbs in the first 10 days. His systolic blood pressure was 70 mmHg, however no other physical exam, laboratory, or imaging abnormalities were found. Thereafter he continued to have similar episodes and was only found to have a positive Tilt Test after extensive outpatient workup. He was started on midodrine 5 mg three times a day, fludrocortisone acetate 0.1 mg daily, and Pyridostigmine 60 mg three times a day with resolution of symptoms. There is a relationship between obesity and hypertension, possibly associated to its effect on the renin angiotensin aldosterone system, up regulation of sympathetic nervous system and simultaneous down regulation of parasympathetic nervous system. Bariatric surgery increases the risk of developing OI through the effects of weight loss itself, the type of procedure chosen and ultimately, vitamin deficiencies. Patients with diabetes are also at risk of developing OI following these procedures due to underlying Diabetic Autonomic Neuropathy (DAN) that had been masked by obesity related HTN. Physicians should be mindful of the risk of OI after bariatric surgery, especially in patients with possible underlying DAN. Close follow up is advised for these patients to avoid falls and trauma.

Disclosure
Z. Cardona: None. Y. Haider: None.
232-OR: Long-Term Safety and Efficacy of Ultra-Rapid Lispro (URLi) in PRONTO-T1D
Authors: KLAFF LESLIE J. , CHO JANG IK , DELLVA MARY A. , SCHLOOT NANETTE C. , TOBIAN JANET , MIURA JUNNOSUKE , DAHL DOMINIK , BUE-VALLESKEY JULIANA M. 
Published: June 2020

PRONTO T1D was a phase 3 study evaluating ultra rapid lispro (URLi) in adults with type 1 diabetes (T1D) for 52 weeks. Subjects were randomized to double-blind mealtime URLi, Humalog, or open-label postmeal URLi with insulin degludec or glargine for the first 26 weeks. Subjects on URLi (n=451) and Humalog (n=442) given 0-2 minutes before meals continued for another 26-weeks to assess long-term safety and efficacy. Mean HbA1c at 52 weeks (7.47% URLi; 7.54% Humalog) increased significantly (p&lt;.001) from baseline in both groups (+0.13% [URLi] vs. +0.20% [Humalog]) and showed an estimated treatment difference (ETD) [95% confidence interval (CI)] (ETD: -0.06 [-0.16, 0.03]) that was similar to that previously reported at 26-weeks. Proportions of patients with HbA1c &lt;7% at Week 52 were similar (URLi, 26.8%; Humalog, 24.5%). At Week 52, self-monitored blood glucose profiles (mg/dL) showed that 1-hour (ETD: -13.5 [-19.4, -7.5]) and 2- hour (ETD: -8.4 [-14.1, -2.7]) postmeal daily mean glucose (and corresponding excursions) as well as the daily mean glucose (ETD: -6.1 [-10.6, -1.6]) were statistically significantly (p&lt;.01) lower during treatment with URLi than Humalog. Mean total insulin dose was 0.80 U/kg (URLi) vs. 0.78 U/kg (Humalog). No difference was observed for body weight change (+0.8 kg [URLi] vs. +0.9 kg [Humalog]; ETD: -0.1 kg [−0.5; 0.4]). Adverse events were similar between URLi and Humalog. No difference was observed for severe hypoglycemia (12.28 events/patient-100yr [URLi] vs. 15.96 [Humalog]) or documented symptomatic hypoglycemia rates (glucose &lt;54 mg/dL) with URLi (4.84 events/patient-year) vs. Humalog (5.18) with a relative rate: 0.93 [95% CI: 0.75;1.16]). No long-term safety issues were identified with URLi. Overall glycemic control and improved postprandial glucose via self-monitoring was maintained after 52 weeks with URLi vs. Humalog suggesting that the efficacy and rapid onset of action of URLi is preserved during long-term treatment in patients with T1D.

Disclosure
L.J. Klaff: Research Support; Self; Abbott, Ascensia Diabetes Care, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, REMD Biotherapeutics, Roche Diabetes Care, Sanofi-Aventis, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. J. Cho: None. M.A. Dellva: Employee; Self; Eli Lilly and Company. N.C. Schloot: Employee; Self; Lilly Diabetes. J. Tobian: Employee; Self; Eli Lilly and Company. J. Miura: None. D. Dahl: Advisory Panel; Self; Berlin-Chemie AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novartis AG, Novo Nordisk A/S. J.M. Bue-Valleskey: Employee; Self; Eli Lilly and Company.

Funding
Eli Lilly and Company
233-LB: Spinal Cord Injury Inhibited-FGF21 Signaling Is Associated with Dysregulation of Metabolic Gene Expression in Mouse Liver and Adipose Tissue
Authors: LIU XIN-HUA , HARLOW LAUREN , GRAHAM ZACHARY , YARROW JOSHUA F. , CUSI KENNETH , BAUMAN WILLIAM A. , CARDOZO CHRISTOPHER P. 
Published: June 2020

Spinal cord injury (SCI) causes deleterious changes in the metabolic profile due to muscle atrophy and sedentary lifestyle. SCI is associated with increased risk for cardiovascular disease, liver disorders and type 2 diabetes mellitus (T2DM). Understanding of the mechanisms for these disorders in those with SCI is poor. Fibroblast growth factor 21 (FGF-21), a hepatic hormone, is reported to have beneficial effects on glucose/lipid metabolism in animal models and human subjects with T2DM. However, the expression levels and the potential effect of FGF-21 on SCI related metabolic dysfunction have not been studied. To address this issue, we compared FGF-21 serum and hepatic mRNA levels in sham and SCI mice fed control or high fat diet (HFD) at 84d after SCI. SCI reduced serum FGF-21 levels by 60% and hepatic FGF-21 mRNA levels by 50% compared to sham mice; levels were further suppressed by HFD. These changes were associated with elevated serum levels of alanine aminotransferase, a liver damage marker. In adipose tissue (AT), SCI decreased mRNA expression of FGF-21 receptor (FGFR1), β-Klotho, adiponectin, PPARγ, and leptin. In addition, SCI reduced IRS1 and Glut4 mRNA levels in AT, indicating impaired insulin signaling. Moreover, elevated levels of TNFα in AT and CD11b (a macrophage marker) in the liver were observed, implying a proinflammatory state after SCI. Finally, post-SCI mice fed a HFD had elevated free fatty acid (FFA) levels in serum and liver compared to sham-mice fed a HFD, suggesting defective FFA uptake and metabolism. These data suggest that reduced FGF-21 signaling after SCI may, at least in part, be contributing to the metabolic dysfunction after SCI, and that FGF-21 may be a candidate for the treatment of SCI-related metabolic dysfunction.

Disclosure
X. Liu: None. L. Harlow: None. Z. Graham: None. J.F. Yarrow: None. K. Cusi: Consultant; Self; Allergan plc., AstraZeneca, Bristol-Myers Squibb, Genentech, Inc., Gilead Sciences, Inc., Merck & Co., Inc. Research Support; Self; Cirius Therapeutics, Echosens, Eli Lilly and Company, Inventiva Pharma, Janssen Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Poxel SA, Zydus Pharmaceuticals, Inc. W.A. Bauman: None. C.P. Cardozo: None.

Funding
U.S. Department of Veterans Affairs (B9212C, B2020C)
234-OR: Postprandial Glucose Control Using the Medtronic Advanced Hybrid Closed-Loop System: Faster-Acting Insulin Aspart vs. Insulin Aspart
Authors: LEE MELISSA H. , VOGRIN SARA , PALDUS BARBORA , MORRISON DALE , ZAHARIEVA DESSI , LU JEAN , JONES HANNAH , WYATT SUE A. , NETZER EMMA , SIMS CATRIONA M. , MACISAAC RICHARD , GROSMAN BENYAMIN , ROY ANIRBAN , KURTZ NATALIE , JENKINS ALICIA , ONEAL DAVID N. 
Published: June 2020

Background: Faster-acting insulin aspart (FiAsp) may improve responsiveness of closed-loop (CL) systems and provide better postprandial glucose (PPG) management due to its more rapid onset and offset compared to insulin aspart (Asp). The Medtronic Advanced Hybrid Closed Loop (AHCL) System features auto-basal and auto-bolus functions.
Aim: To compare PPG control using FiAsp vs. Asp delivered using AHCL.
Methods: Twelve adults with T1D (median HbA1c 7.1% [IQR 6.8, 7.2]; 54mmol/mol [51, 55]) were assigned to FiAsp or Asp (unblinded) in random-order over two-stages (6-weeks duration each) using AHCL. Postprandial periods were defined using set time-blocks for breakfast (06:00-10:00); lunch (11:00-15:00); and dinner (17:00-21:00), based on conventional meal-times and meal distribution. CGM data was analyzed using signed-rank test.
Results: With all postprandial time-block data aggregated, FiAsp demonstrated greater overall time-in-range (TIR) (70-180mg/dL) (p=0.028) and less hyperglycaemia (p=0.041) compared with Asp (Table). TIR was greater during lunch (p=0.034) for FiAsp vs. Asp, with no difference during breakfast or dinner. Over the 6-week duration, FiAsp use trended towards greater TIR vs. Asp (82.7% vs. 80.4%, p=0.07).
Conclusions: FiAsp appears to confer an advantage compared with Asp for PPG control whilst using AHCL even in subjects with high overall TIR.

Disclosure
M.H. Lee: Research Support; Self; Medtronic. Speaker’s Bureau; Self; AstraZeneca, Medtronic. S. Vogrin: None. B. Paldus: Research Support; Self; JDRF. Speaker’s Bureau; Self; Australian Diabetes Society, Medtronic. D. Morrison: None. D. Zaharieva: Speaker’s Bureau; Self; Ascensia Diabetes Care, Insulet Corporation, Medtronic. J. Lu: None. H. Jones: None. S.A. Wyatt: Other Relationship; Self; Medtronic, Ypsomed AG. E. Netzer: None. C.M. Sims: Stock/Shareholder; Self; Medtronic. R. MacIsaac: None. B. Grosman: Employee; Self; Medtronic. A. Roy: Employee; Self; Medtronic. N. Kurtz: Employee; Self; Medtronic. A. Jenkins: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Abbott, GlySens Incorporated, Medtronic, Sanofi-Aventis. D.N. ONeal: None.