bluuebunny/crossref_metadata_2025_split huggingface dataset:
21-OR: Real-World Treatment Escalation from Metformin Monotherapy in Youth-Onset Type 2 Diabetes Mellitus: A Retrospective Cohort Study
Authors: VAJRAVELU MARY ELLEN , HITT TALIA A. , AMARAL SANDRA , KATZ LORRAINE E. , LEE JOYCE M. , KELLY ANDREA 
Published: June 2021

Background: Due to high rates of comorbidities and rapid progression, youth with type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin.
Objective: To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with type 2 diabetes in clinical practice.
Subjects: Commercially-insured patients with incident youth-onset (10-18 years) type 2 diabetes initially treated with metformin only.
Methods: Retrospective cohort study using a patient-level medical claims database with data from 2000 - 2019. Frequency and order of treatment escalation to insulin and non-insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, and metformin adherence (medication possession ratio ≥0.8).
Results: The cohort included 806 (66% female; median age at diagnosis 15 years; 19% Hispanic, 16% Black) patients, with median 3.0-year follow-up after metformin initiation. One-quarter underwent treatment escalation (n=198; 78 to insulin, 160 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin as the initial or only antihyperglycemic prescribed. Age at diagnosis (HR 1.14, 95% CI 1.07-1.22), medication adherence (HR 3.77, 95% CI 2.71-5.23), and Hispanic ethnicity (HR 1.46, 95% CI 1.05-2.04) were positively associated with treatment escalation, but comorbidities were not associated.
Conclusions: In clinical practice, treatment escalation for pediatric type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs and is most common among older adolescents.

Disclosure
M. Vajravelu: None. T. A. Hitt: None. S. Amaral: None. L. E. Katz: None. J. M. Lee: Advisory Panel; Self; GoodRx. A. Kelly: Consultant; Self; Vertex Pharmaceuticals Incorporated, vTv Therapeutics.

Funding
National Institutes of Health (K23DK125719-01, 5T32DK063688-17, R01DK110749, R01DK120886, R01HD091185, 5U01DK061230, UL1-TR000003, 2P30DK089503-11, R01HD074559-01-A1, UH3HD087979, R01DK115648, DK97830, UL1TR001878); Caswell Diabetes Institute at the University of Michigan
211-LB: Antifibrotic Effect of a Novel Long-Acting GLP-1/GCG/FGF21/Anti-Cytokine Tetra-Specific Liver Microenvironment-Targeting Drug (OGB21502) in CCl4-Induced Liver Fibrosis Mice Model
Authors: KIM MIN SUN 
Published: June 2021

Liver fibrosis is a feature in the majority of chronic liver disease and oxidative stress. If not treated, it may lead to fibrotic liver disease, liver failure and hepatocellular carcinoma (HCC). Since complex biological pathways are involved, therapeutic strategies simultaneously targeting multiple aspects might be required to effectively treat fibrosis as well as NASH. Therefore, we developed a novel long-acting and multi-target drug (GCGR, GLP-1R, FGFR1/KLB, cytokineR), OGB21502 using UniStac technology, which is our proprietary multi-specific platform. OGB21502 prevents inflammation and fibrosis of liver tissue by controlling players in liver microenvironment (LME) such as apoptosis, macrophage activation, and fibroblast activation. Here we evaluate the effect of OGB21502 in liver fibrosis using CCl4 induced mice. Ocaliva was used as comparative control. In CCl4 induced mice (8 weeks induction), OGB21502 treatment led to a significant decrease in blood ALT (-38.1% vs. vehicle); hepatic hydroxyproline (-31.5% vs. vehicle) and total bilirubin in blood. Histopathological analysis indicated that OGB21502 meaningfully reduced fibrosis score (-37.5% vs. vehicle); hepatocyte ballooning score (-50% vs. vehicle) and inflammation score (-16.7% vs. vehicle). While all of the vehicle progressed to cirrhosis, 80% of the population administered OGB21502 at high concentrations had cirrhosis progression inhibition. Also, OGB21502 reduced the level of picosirius red positive area (-32.5% vs. vehicle); collagen I (-23.7% vs. vehicle); TGF-β (-27.2% vs. vehicle) and α-SMA (-32.3% vs. vehicle). Based on these results, OGB21502, a novel long-acting tetra-specific LME-targeting drug offers a therapeutic anti-inflammatory and anti-fibrotic effect.

Disclosure
M. Kim: None.
212-LB: Therapeutic Effect of a Novel Long-Acting GLP-1/GCG/FGF21/Anticytokine Tetra-Specific Liver Microenvironment-Targeting Drug (OGB21502) in MCD-Induced NASH Mice Model
Authors: KIM MIN SUN 
Published: June 2021

Nonalcoholic steatohepatitis (NASH) is liver inflammation and damage caused by a buildup of fat in the liver. It is characterized by varying degrees of hepatic steatosis, cytoskeletal damage, and lobular inflammation which further leads to fibrosis, cirrhosis and even liver failure. Due to the complexity of the occurrence of NASH and fibrosis, a multi-targeting strategy attracts much attention to effectively address the vicious cycle formed in liver microenvironment. In this respect, we developed a novel long-acting and multi-target drug (GCGR, GLP-1R, FGFR1/KLB, cytokineR), OGB21502, using UniStac technology, which is our proprietary multispecific platform. Here we evaluate the effect of OGB21502 in NASH and fibrosis using MCD diet induced mice model. Liraglutide (Saxenda, Eli lilly) and dulaglutide (Trulicity, Eli lilly) was used as comparative control. In MCD diet-fed mice (8 weeks induction), OGB21502 treatment led to a significant decrease in blood ALT (-45.2% vs. vehicle). Histopathological analysis indicated that OGB21502 meaningfully reduced NAS score (NAFLD activity score, -56.5% vs. vehicle); steatosis score (-57.1% vs. vehicle) and inflammation score (-84.6% vs. vehicle). Compared to vehicle, 100% of OGB21502 dramatically showed “Not NASH” histopathological results. Also, the level of TGF-β (-39.9% vs. vehicle) and α-SMA in liver were significantly decreased in the OGB21502 treatment group. Based on these results, OGB21502, a novel long-acting tetra-specific drug, elicited anti-inflammatory and anti-fibrotic effects in MCD-induced mice model.

Disclosure
M. Kim: None.
219-LB: The Changes in Body Composition in Obese Patients with Polycystic Ovary Syndrome after Laparoscopic Sleeve Gastrectomy: A 12-Month Follow-Up
Authors: CAI MEILI , GAO JINGYANG , LEI DU , CHENG XIAOYUN , ZHU JIANGFAN , QU SHEN , ZHANG MANNA 
Published: June 2021

Objectives: To investigate the changes in body fat distribution in obese women with polycystic ovary syndrome (PCOS) after laparoscopic sleeve gastrectomy (LSG), and to explore the factors that may predict changes in body fat distribution in PCOS patients after LSG.
Methods: A total of 83 obese patients with PCOS aged 18-45 years and 70 patients without PCOS were consecutively enrolled in the Hospital, between May 2013 and September 2020. The demographic characteristics, metabolic and sex hormone parameters, and body fat distribution were collected at baseline, and again at 3, 6, and 12 months after LSG in all patients. Dual-energy X-ray absorptiometry (DEXA) was used to assess body fat distribution.
Results: Although the loss of percentage of fat mass in the visceral adipose tissue (VAT) region was more than that in any other body region at 12 months after LSG in all patients, homeostatic model assessment of insulin resistance (HOMA-IR) at baseline and the change of HOMA-IR were only negatively correlated with the variations in VAT mass and volume at 3 months after LSG in PCOS women with obese. Logistic regression analysis showed that HOMA-IR&lt;6.65 was an independent predictive factor for the changes in VAT mass [OR=0.145 (0.024-0.887) P=0.037] and volume at 3 months [OR=0.045 (0.005-0.393) P=0.005] after surgery in patients with PCOS.
Conclusions: Compared with control patients, HOMA-IR at baseline was an independent risk factor for the changes in VAT mass and volume at 3 months after surgery in patients with PCOS.

Disclosure
M. Cai: None. J. Gao: None. D. Lei: None. X. Cheng: None. J. Zhu: None. S. Qu: None. M. Zhang: None.

Funding
National Natural Science Foundation of China (81601269)
220-OR: Comparing Cardiovascular Benefits between GLP-1RA and SGLT2i as an Add-On to Metformin among U.S. Adults with Type 2 Diabetes (T2D)
Authors: DEREMER CHRISTINA E. , GUO JINGCHUAN , VOURI SCOTT M. , HALLER MICHAEL J. , DONAHOO WILLIAM T. , WINTERSTEIN ALMUT G. , SHAO HUI 
Published: June 2021

Head-to-head comparison of clinical benefits between glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) are scarce. In this study, we aimed to compare real world cardiovascular benefits associated with the use of GLP-1RA vs. SGLT2i as add-on therapies to metformin among US adults with T2D.
Methods: This study used data from the IBM® MarketScan® Commercial Claims Databases (2012-2018). We identified metformin users, age ≥ 18 and with T2D, who initiated GLP-1RA or SGLT2i between Mar 29th and Dec 31st, 2013. Patients were followed until the primary endpoint, end of the study period (Dec 31st 2018), study drug discontinuation or initiation of the other study drug, or disenrollment from the health plan (whichever occurred first). The primary endpoint was a major cardiovascular composite (MCC), including acute myocardial infarction (MI), hospitalization for congestive heart failure (CHF), and stroke. The secondary endpoints included individual components of MCC. We constructed Cox proportional hazard regression models to compare the risks of cardiovascular endpoints between GLP-1RA and SGLT2i users, controlling for demographics, clinical characteristics, and the Diabetes Complication Severity Index.
Results: We identified 11,911 adults with T2D who initiated a GLP-1RA or SGLT2i as an add-on therapy to metformin. No difference in the risk of MCC or any secondary endpoints was observed between GLP-1RA users and SGLT2i users who did not have established cardiovascular disease. However, significantly lower risks of MCC (HR:0.67, 95% CI: 0.47-0.97) and CHF (HR:0.47, 95% CI:0.28-0.79) was observed among SGLT2i users compared with GLP-1RA users, among individuals with established cardiovascular complications.
Conclusions: Results suggest a greater cardioprotective benefit from SGLT2i compared to GLP-1RA when used for secondary prevention among adults with T2D.

Disclosure
C. E. Deremer: Research Support; Self; Pfizer Inc., Speaker’s Bureau; Spouse/Partner; Pharmacy Times, Stock/Shareholder; Self; Portola Pharmaceuticals, Inc. J. Guo: None. S. M. Vouri: None. M. J. Haller: Board Member; Self; SAB Biotherapeutics, Inc., Consultant; Self; MannKind Corporation, Other Relationship; Self; Janssen Pharmaceuticals, Inc., Sanofi. W. T. Donahoo: None. A. G. Winterstein: Research Support; Self; Merck Sharp & Dohme Corp. H. Shao: Research Support; Self; Sanofi.
228-LB: ß-arrestin-2 Deletion Influences GLP-1 Receptor Signaling in Pancreatic ß Cells In Vivo
Authors: BITSI STAVROULA , SUBA KINGA , MOHAMED NIMCO , LECLERC ISABELLE , RUTTER GUY A. , SALEM VICTORIA , JONES BEN , TOMAS ALEJANDRA 
Published: June 2021

β-arrestin-2 (Barr2) is typically associated with G protein-coupled receptor desensitization and endocytosis, and reduced Barr2 recruitment is thought to enable prolongation of pharmacodynamic effects of biased glucagon-like peptide-1 receptor (GLP-1R) agonists. However, the precise role of Barr2 in GLP-1R function in β-cells is poorly understood. To study this role, a tamoxifen-inducible β-cell specific Barr2 knockout mouse model was generated (Pdx1CreERT/Barr2 fl/fl, referred to as β-Barr2 KO). β-Barr2 KO animals on high-fat high-sucrose diet were less glucose tolerant and tended to respond worse to acute exendin-4 (Ex4) treatment vs. controls (Barr2 fl/fl). However, Ex4 effects on blood glucose were more pronounced in KO mice 6h post-agonist injection [IPGTT AUC (6h) for Ex4/ vehicle: 0.84 ± 0.04 vs. 1.08 ± 0.05, p&lt;0.001; ΔAUC (6h-0h): -49.8 ± 65.8 vs. 158.2 ± 43.6, p&lt;0.05; KO vs. control]. This effect was not apparent with Ex-phe1, an Ex4 derivative biased away from Barr2 recruitment. Ex4-induced potentiation of insulin secretion in β-Barr2 KO islets was reduced acutely, but tended to increase overnight, resulting in significantly reduced desensitization vs. control islets. On chow diet, acute Ex4-stimulated calcium increases were unaffected, but acute cAMP responses were attenuated in KO islets [Emax (vs. baseline): 1.51 ± 0.17 vs. 1.72 ± 0.07, p&lt;0.05; KO vs. control]. The latter was corroborated in INS1 832/3 Barr2 KO CRISPR cells, as NanoBiT™ functional assays showed reduced Ex4-induced Gs protein activation vs. control. GLP-1R trafficking profiles observed in vivo by imaging of Ex4-TMR uptake into islets implanted in the anterior chamber of the eye, as well as in vitro with GLP-1R-NLuc - KRAS/Rab5 NanoBRET assays were unaltered by Barr2 deletion. Thus, we provide evidence for opposing effects of Barr2 in acute vs. prolonged GLP-1R signaling, supporting a direct role for Barr2 in mediating the anti-hyperglycemic effects of biased GLP-1R agonists, but dispensability for GLP-1R trafficking.

Disclosure
S. Bitsi: None. K. Suba: None. N. Mohamed: None. I. Leclerc: Consultant; Spouse/Partner; Sun Pharmaceutical Industries Ltd. G. A. Rutter: Advisory Panel; Self; Sun Pharmaceutical Industries Ltd. V. Salem: None. B. Jones: Research Support; Self; Sun Pharmaceutical Industries Ltd. A. Tomas: Other Relationship; Self; Sun Pharmaceutical Industries Ltd.

Funding
Medical Research Council (MR/R010676/1)
231-OR: Neighborhood Walkability Is Associated with Prediabetes in a Behavioral Weight Loss Study
Authors: KARIUKI JACOB K. , BIZHANOVA ZHADYRA , ROCKETTE-WAGNER BONNY , GIBBS BETHANY B. , SEREIKA SUSAN M. , KLINE CHRISTOPHER , ERICKSON KIRK , MENDEZ DARA , PULANTARA I. WAYAN , CHENG JESSICA , BURKE LORA E. 
Published: June 2021

Background: Behavioral interventions targeting weight loss may be affected by socio-environmental factors that influence physical activity (PA) and cardiometabolic outcomes.
Purpose: To evaluate the relation of neighborhood walkability on PA levels and glucose control in a sample of adults participating in a weight loss study.
Methods: Secondary analysis of a prospective observational study providing a 12-month behavioral weight loss intervention to examine lapses after intentional weight loss. Neighborhood walkability was assessed via Walk Score (0-100), PA via waist-worn ActiGraph GT3X, and blood glucose via phlebotomy. Study variables included car-dependent and walkable neighborhoods (Walk Score &lt; vs. ≥50), prediabetes (fasting blood glucose from 100-126mg/dL) and recommended PA (moderate-to-vigorous PA [MVPA] &gt;22 minutes/day; steps ≥7500/day). Standard descriptive and group comparative statistics were employed. Regression results are reported as adjusted odds ratios (OR) with 95% confidence intervals (CI).
Results: The sample (N=112) was mostly female (90.2%), white (90.2%), well educated (75.9% with ≥4 years of college) and on average 51.5±9.8 years of age. At baseline, no differences existed between persons from car-dependent vs. walkable neighborhoods across all metrics. At 12 months, PA and glucose control were improved for the entire sample, with no differences across walkability categories. Neighborhood walkability did not predict attainment of recommended MVPA (OR=1.16, 95% CI: 0.97-1.39) or steps (OR=1.08, 95% CI: 0.90-1.30) at 12 months. However, those from walkable neighborhoods had 17% lower odds of having prediabetes compared to those from car-dependent neighborhoods (OR=0.83, 95% CI: 0.72-0.97).
Conclusion: Our findings corroborate previous studies showing an inverse relation between neighborhood walkability and prediabetes. The key drivers of this association warrant further investigation in a study with a larger, more diverse sample.

Disclosure
J. K. Kariuki: None. J. Cheng: None. L. E. Burke: None. Z. Bizhanova: None. B. Rockette-wagner: None. B. B. Gibbs: None. S. M. Sereika: None. C. Kline: None. K. Erickson: None. D. Mendez: None. I. Pulantara: None.

Funding
National Heart, Lung, and Blood Institute (HL107370S to J.K.K.)
238-OR: Treatment with Testosterone Undecanoate Injections (TU) Up to 12 Years Improves Glycemic Control in Patients with Hypogonadism and Type 2 Diabetes (T2DM): Update of Real-World Data with 3,149 Patient-Years
Authors: SAAD FARID , HAIDER KARIM S. , HAIDER AHMAD 
Published: June 2021

Background: Prevalence of hypogonadism has been reported as high as 50% in men with T2DM. ADA Guidelines recommend assessment of hypogonadism in men with T2DM.
Methods: In a registry of 865 men with hypogonadism, 361 men (41.7%) had T2DM. 183 received TU 1000 mg/12 weeks (T-group), 178 opted against treatment (CTRL). Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups.
Results: Mean follow-up 8.7±3.1, baseline age: 60.7±5.5 (T-group) and 63.0±4.9 (CTRL) years. T-group: HbA1c progressively decreased by 3.7±0.2% at 12 years (unadjusted from 9.4±1.4% to 5.6±0.2%). CTRL: HbA1c increased by 3.2±0.2% (from 7.8±0.7% to 10.4±1.2%) (p&lt;0.0001 for both). Fasting glucose (mmol/L) decreased in T-group by 1.9±0.1 (from 7.8±1.3 to 5.4±0.1) and increased in CTRL by 1.8±0.1 (from 6.3±0.7 to 8.0±1.2) (p&lt;0.0001 for both). In the T-group, 89 men (48.6%) received insulin at baseline at a mean dose of 38.0±13.3 U/d. Dose requirement declined by 32.7±1.3 U/d (from 38.0±13.3 to 8.8±9.2) during the observation period. In CTRL, 69 men (38.8%) received insulin at baseline at a mean dose of 31.3±6.2 U/d. Dose requirement increased by 20.0±1.4 U/d (from 31.3±6.2 to 43.8±7.8) (p&lt;0.0001 for both). HOMA-IR decreased by 8.0±0.3 (from 10.1±2.1 to 1.7±0.4) in the T-group and increased by 6.5±0.4 (from 7.3±1.3 to 14.3±2.3) in CTRL (p&lt;0.0001 for both). In CTRL, 22 patients were started on insulin during the observation period. 37 patients had incident T2DM during the observation time.
Conclusions: Long-term testosterone therapy with TU in men with hypogonadism and T2DM progressively improved glycemic control which deteriorated in untreated men.

Disclosure
F. Saad: Consultant; Self; Bayer AG, Stock/Shareholder; Self; AbbVie Inc., Bayer AG, Novo Nordisk. K. S. Haider: Other Relationship; Self; Bayer AG. A. Haider: Other Relationship; Self; Bayer AG.

Funding
Bayer AG
249-OR: Type 2 Diabetes (T2D) Genetic Clusters for Association with Glycemic Responses to Intervention for Diabetes Prevention
Authors: BILLINGS LIANA K. , JABLONSKI KATHLEEN A. , FRANKS PAUL W. , GOLDBERG RONALD B. , HIVERT MARIE-FRANCE , KAHN STEVEN E. , KNOWLER WILLIAM C. , LEE CHRISTINE , MERINO JORDI , RAGHAVAN SRIDHARAN , SRINIVASAN SHYLAJA , XU JIANFENG , FLOREZ JOSE C. , UDLER MIRIAM ,   GROUP DPP RESEARCH
Published: June 2021

Polygenic scores (PS) of T2D genetic variants based on pathophysiologic mechanisms underlying diabetes have been developed. We investigated whether T2D cluster PS influences response to interventions for diabetes prevention. We examined 2,647 DPP participants with impaired glucose tolerance and genetic data randomized to intensive lifestyle, metformin or placebo arms for diabetes prevention. We generated five PS clusters including β-cell related clusters (β-cell, proinsulin) and insulin resistance clusters (liver/lipid, obesity, lipodystrophy).
We examined associations of PS with baseline and 1-year glycemic traits after intervention derived from oral glucose tolerance tests using general linear models, and with diabetes incidence over an average period of 3 years using Cox Regression Models. Models were adjusted for sex, age, and 10 principal components, respective baseline trait, and treatment group.
At one-year follow-up, β-cell PS was associated with reduction in the insulinogenic index and corrected insulin response, in each treatment group and, statistically significant, in all combined (P&lt;0.001), with no statistically significant interaction term between treatment groups, a finding consistent with a slightly increased diabetes incidence (HR 1.02 per weighted allele [CI 95% 1.00, 1.03]). The remaining PS were associated with baseline participant features, but not with diabetes incidence or change in glycemic parameters from baseline.
We conclude that high genetic burden in β-cell cluster PS is associated with greater risk of diabetes and a decrease in insulin secretion, seen across all treatment groups. Despite interventions with intensive lifestyle and metformin, participants with high β-cell cluster genetic burden had an increased risk of diabetes and worsening in insulin secretion similar to placebo group. These data suggest that alternate therapies may be needed to prevent β-cell decline in this subset of prediabetes patients.

Disclosure
L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. S. Raghavan: None. S. Srinivasan: None. J. Xu: None. J. C. Florez: Consultant; Self; Goldfinch Bio, Inc., Other Relationship; Self; Novo Nordisk. M. Udler: None. D. Research group: None. K. A. Jablonski: None. P. W. Franks: Advisory Panel; Self; Zoe Global Limited, Consultant; Self; Eli Lilly and Company, Novo Nordisk. R. B. Goldberg: None. M. Hivert: None. S. E. Kahn: Advisory Panel; Self; Bayer AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk, Pfizer Inc. W. C. Knowler: None. C. Lee: None. J. Merino: None.

Funding
National Institute of Diabetes and Digestive and Kidney Diseases (U01DK048489)
25-LB: Are You a Good Steward of Data?
Authors: BAKER REBECCA , OWEN JOHN M. 
Published: June 2021

The Problem: There is an urgent need for innovative solutions for new and improved treatments and therapies. Often clinical research data is “silo-ed” within an organization, preventing the broader research community from leveraging aggregated information from individuals and studies globally. This isolation of data limits the discoveries possible within a disease preventing the discovery of new scientific links between disease areas. Inconsistent and ambiguous data representation leads to a lack of transparency, traceability and reproducibility, in turn fostering inefficiencies and inaccuracies in research that loses time and increases costs. Simply put Are we being good stewards of our study data?
Data Standards and Data Sharing as part of the solution: Describing data consistently using data standards can bring clarity to data that amplifies its value. The T1D Data Standards Project builds on existing CDISC diabetes standards by describing concepts relevant to T1D in the areas of: • Pediatrics and Devices (Released Sep 2020) • Exercise and Nutrition (Due Q2-2021) • Screening, Staging and Monitoring for Pre-Clinical Type 1 Diabetes (Due Q3-2021). The team of CDISC standards experts, T1D experts from CDISC member organizations and T1D subject matter experts from academia and industry followed a consensus-driven process to ensure the final standards are fit for use within the research community, reinforced by the open community review.
How data standards help overcome some of the challenges: Publicizing the availability and promoting adoption of consistent standards brings clarity to data, reduces data collection, organization and analysis time, and facilitates interoperability that promotes data re-use and operational efficiencies. When researchers speak the same harmonized language, talking and understanding each other is much easier leading to the sharing of common, understandable data within the research community, thereby promoting scientific and therapeutic advances general confidence in the data.

Disclosure
R. Baker: None. J. M. Owen: None.

Funding
The Leona M. and Harry B. Helmsley Charitable Trust (G-2018PG-T1D069)