bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consistent Accuracy over 10 Days with a Factory-Calibrated Continuous Glucose Monitoring System in Children and Adults
Authors: ZHANG XIAOHE , JOHNSON TERRI , PRICE DAVID A. , BALO ANDREW 
Published: June 2018

The burden of calibrating continuous glucose monitoring (CGM) systems may be addressed by factory calibration (FC). We evaluated the accuracy of the "G6 FC" CGM System (Dexcom, Inc.) in adults ages 18+ and children ages 6-17 with type 1 diabetes. This was a prospective, non-randomized, multi-center, single-arm study that enrolled 76 subjects at 4 U.S. sites. Subjects participated in either 1 or 2 clinic sessions of varying duration, depending on age. System performance was evaluated in terms of percent accuracy with respect to YSI. Accuracy was characterized as the proportion of CGM values that were within ± 15%, ± 20% of their paired YSI values for glucose levels &gt; 100 mg/dL or within ± 15 mg/dL, ± 20 mg/dL of YSI for glucose levels ≤ 100 mg/dL. The two-sided 95% bootstrapped confidence interval (CI) was calculated for its statistical significance. Accuracy was also measured by comparing the difference, absolute difference, relative difference and absolute relative difference of the G6 FC System with respect to YSI. The G6 FC System showed an overall percent % 20/20 accuracy of 93.9% (95% CI: 89.8, 97.1%) based on 3,532 matched pairs from 62 subjects (25 adults and 37 children). Similarly, the overall percent % 15/15 accuracy was 83.3% (95% CI: 76.7, 89.4%). The Day-1 and Day 10 percent % 20/20 accuracies were 92.2% and 92.5%, respectively; Day-1 and Day 10 mean absolute relative difference (MARD) values were 9.3% and 9.0%, respectively. The percent % 20/20 accuracy was 92.5% for adults and 96.2% for children. The MARD was 9.0% overall, 9.8% for adults, and 7.7% for children. Mean bias and mean relative difference were -8.3 mg/dL and -5.0%, respectively for overall; -10.9 mg/dL and -6.9% for adults; and -4.3 mg/dL and -2.1% for children. The G6 FC System showed high accuracy using multiple metrics for pediatric and adult subjects across days of wear, including Day 1. Elimination of the requirement for calibrations should improve the acceptability and utility of this novel CGM system.

Disclosure
X. Zhang: Employee; Self; Dexcom, Inc. T. Johnson: Employee; Self; Dexcom, Inc. D.A. Price: Employee; Self; Dexcom, Inc. A. Balo: Employee; Self; Dexcom, Inc..
Linagliptin Reduced Renal Injury and Proteinuria in a Rat Model of Crescentic Nephritis
Authors: MAYER ANNA-LENA , AMANN KERSTIN U. , KLEIN THOMAS , DANIEL CHRISTOPH 
Published: June 2018

Dipeptidyl peptidase 4 (DPP-4) inhibitors are used in the treatment of type 2 diabetes. In human kidney biopsies we observed high DPP-4 expression in early crescent formation. This glomerular lesion occurs in different kidney diseases and is a hallmark in the pathogenesis of renal dysfunction. Thus, we investigated the potential involvement of DPP-4 in the pathogenesis of anti-GBM (glomerular basement membrane antibody) induced nephritis in Wistar rats. Linagliptin (3 mg/kg, n=11) and vehicle (n=11) were used to treat anti-GBM nephritis in an 8 weeks preventional and therapeutical (treatment started 4 weeks after model induction) regimen. Kidney function, morphologic changes, inflammation and fibrosis was monitored. Disease prevention with linagliptin in anti-GBM nephritic rats significantly (p&lt;0.01) reduced the number of crescents (51±3% vs. 65±3%), glomerulosclerosis (score 1.2±0.07 vs. 1.6±0.1), tubule-interstitial injury (score 1.2±0.1 vs. 1.8±0.2), renal fibrosis (score 1.3±0.13 vs. 1.9±0.14) and proteinuria (265±29 vs. 363±22 mg/24h) compared to untreated nephritic rats. Also, preventional linagliptin therapy significantly reduced the number of Pax8+ cells on the glomerular tuft by 17±5% on day 14 (p&lt;0.05) and 60±5% on week 8 (p&lt;0.001), indicating accelerated resolution of the cellular crescents. Disease intervention with linagliptin resulted in weaker amelioration of renal disease on week 8 but also significantly (p&lt;0.05) reduced renal fibrosis (score 1.4±0.13 vs. 1.9±0.14), crescent formation (52±4% vs. 65±3%) and Pax8-positive cells on glomerular tuft (65±5.2% reduction) compared to vehicle. Proteinuria was also reduced but did not reach significance.
In conclusion, DPP-4 inhibition by linagliptin ameliorates renal injury in a severe rat model with anti-GBM induced nephritis as shown by reduced crescents, proteinuria and fibrosis, and resolution of crescents. Therapeutic intervention with linagliptin showed weaker effects compared to a preventional mode.

Disclosure
A. Mayer: Research Support; Spouse/Partner; Boehringer Ingelheim Pharmaceuticals, Inc.. K.U. Amann: None. T. Klein: Employee; Self; Boehringer Ingelheim GmbH. C. Daniel: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc..
(R)-ND-336 as a Therapeutic Agent for Diabetic Wound Healing
Authors: CHANG MAYLAND 
Published: June 2018

Approximately 25% of diabetics develop diabetic foot ulcers (DFUs), resulting in 73,000 lower-limb amputations annually in the United States, with one-year prognosis of 50% mortality. While the involvement of matrix metalloproteinases (MMPs) in wound healing has been known, the challenge remained as to which MMP(s) among the 24 known human variants plays a role in the ailment, compounded by the fact that MMPs exist in three forms, the latent, the activated in complex with protein inhibitors TIMPs, and the activated uninhibited form. The first two are catalytically incompetent. With the use of an affinity resin that fishes out only the catalytically competent MMPs from the complex proteome, we identified active MMP-8 and MMP-9 in wounds of db/db mice and determined that MMP-9 is detrimental and that MMP-8 plays a beneficial role in wound healing. To demonstrate parallels in expression profiles in humans, we studied the debridement tissue from diabetic patients using the affinity resin coupled with proteomics. We identified the very same active MMP-8 and -9 in diabetic human wounds, indicating that the mechanisms of pathology and repair are similar in humans and in mice. Twenty-fold higher levels of the detrimental active MMP-9 were found in Wagner grade 1-4 wounds compared to control. These increased levels for MMP-9 are indeed significant, considering that active MMP-9 is a catalyst that contributes to the recalcitrance of wounds to heal. This observation makes MMP-9 an important target for inhibition with translational potential. We report herein that (R)-ND-336, a novel potent and selective inhibitor of MMP-9, accelerates healing of diabetic wounds and holds promise as recourse in treatment of DFUs. We note that NF-κB levels correlate with that of active MMP-9, hence it is a useful biomarker in identification of candidates for the treatment option.

Disclosure
M. Chang: None.
Combined Treatment with Exendin-4 and Metformin Attenuates Breast Cancer Growth
Authors: IWAYA CHIKAYO , NOMIYAMA TAKASHI , KAWANAMI TAKAKO , HAMAGUCHI YURIKO , TANAKA TOMOKO , YANASE TOSHIHIKO 
Published: June 2018

Cancer is a major cause of death in patients with diabetes. Incretin therapy has received much attention, because of its tissue protective effects beyond glycemic control. We have previously reported anti-prostate cancer effect of Ex-4 and metformin (Diabetes 2014, PLOS ONE 2015). In addition, we have recently reported that Ex-4 attenuates breast cancer growth (Endocrinology 2017). Then, we next examined the effect of combined treatment of Ex-4 with Metformin in breast cancer cells. In human breast cancer cell lines, MCF-7, MDA-MB-231 and KPL-1 cell, Ex-4 or metformin reduced cell number in a dose-dependent manner. Further, combined treatment of 0.1mM Metformin and 10nM Ex-4 additively attenuated the growth curve progression of breast cancer cells. In BrdU assay, Ex-4 or Metformin significantly decreased breast cancer cell proliferation, and further reduction of BrdU incorporation was observed by combined treatment of Ex-4 and Metformin, suggesting that Ex-4 and Metformin additively decreased DNA synthesis in breast cancer cells. Although apoptotic cells were not observed in Ex-4 treated breast cancer cells similar to our previous study, apoptotic cells were clearly detected in metformin treated breast cancer cells using TUNEL assay. These data suggest that Ex-4 and metformin attenuates breast cancer cell proliferation and metformin induces apoptosis in breast cancer cells. Combined treatment of Ex-4 and Metformin could be an optional therapy to inhibit breast cancer progression.

Disclosure
C. Iwaya: None. T. Nomiyama: Research Support; Self; MSD K.K., Sanofi-Aventis, Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceuticals, Japan. T. Kawanami: None. Y. Hamaguchi: None. T. Tanaka: None. T. Yanase: Research Support; Self; MSD K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceuticals, Japan.
Identification of Glucosepane Cross-Link Breaking Enzymes
Authors: STREETER MATTHEW , GODDARD TYLER N. , CRAWFORD JASON M. , SPIEGEL DAVID A. 
Published: June 2018

Glucosepane is a member of the class of advanced glycation end-products (AGEs), which form non-enzymatically in the human body. Glucosepane, is the most abundant AGE found in human collagen and has been implicated in the pathophysiology of various conditions ranging from diabetes to normal human aging. Glucosepane crosslinks impact the structural and mechanical properties of collagen and contribute to stiffening of collagenous tissues and vascular dysfunction. We have previously demonstrated the total synthesis of glucosepane, enabling methods for detecting and targeting glucosepane. The present study seeks to identify enzymes that are capable of catalyzing the decomposition of synthetic glucosepane crosslinks. To identify glucosepane crosslink breaking enzymes, we developed a novel screening technology based on metagenomics. Using this strategy, four enzymes were identified for in vitro validation of glucosepane degradation activity. Thus far, our efforts have focused on identifying metabolites of one class I-like enzyme in particular, since it is heterologously expressed at high levels and does not require any unusual cofactors. In vitro enzymatic assays showed that incubation of glucosepane with the class I-like enzyme led to a product consistent with citrulline. We are currently in the process of evaluating the enzyme’s mechanisms of action and identifying other metabolites generated. This is the first demonstration that glucosepane can be broken down enzymatically. Our findings may provide new insight into the role of glucosepane in aging and disease and aid in the development of novel therapeutic strategies for targeting glucosepane.

Disclosure
M. Streeter: None. T.N. Goddard: None. J.M. Crawford: None. D.A. Spiegel: None.
Embryonic Cell Extracts Ameliorate Wound Healing in Diabetic Mice
Authors: LORETELLI CRISTIAN , NASR MOUFIDA BEN , HAJ GHINA AL , ROCCHIO FRANCESCA , FARAVELLI SILVIA , MALVANDI AMIR MOHAMMAD , D'ADDIO FRANCESCA , MAESTRONI ANNA , LETIZIA TERESA , ASSI EMMA , USUELLI VERA , LEON EDUARDO CASTILLO , MERONI ROBERTA , ZUCCOTTI GIANVINCENZO , FIORINA PAOLO 
Published: June 2018

Wound healing (WH) is a physiological function in which a balanced inflammatory response is required for tissue regeneration and successful wound closure. In diabetic patients WH is impaired and negatively impacts diabetic individuals in terms of morbidity, mortality and social disability, while the lack of an effective wound care highlights the need for novel therapeutic strategies. Extracts obtained from embryonic stem cells (EXTs) exhibited immunomodulatory properties and we hypothesize that EXTs may improve WH in diabetes. Here we explored the in vitro and in vivo effect of EXTs on WH using the diabetic db/db mouse model. Our data show that in vivo EXT topical administration ameliorates wound closure, contraction and re-epithelization by significantly reducing local inflammation and enhancing angiogenesis as compared to acellular protein extracts from 3T3 fibroblast cells (3T3xt) or no treatment. EXTs increased the percentage of regulatory T cells in the wound in vivo and inhibited T cell activation and IFNγ production in vitro. Db/db-derived dendritic cells exposed to EXTs showed decreased maturation, with downregulation of the costimulatory molecules CD80, CD86 and CD40. On the other hand, in vivo 3T3xt administration caused poorer wound closure with enhanced leucocyte infiltration of wounds and CD80, CD86 and CD40 upregulation on activated dendritic cells both in vivo and in vitro. Finally, proteomic analysis revealed 82 molecular entities differentially segregating in the EXT and 3T3xt group. Following unbiased selection, 10 proteins were filtered and assayed for their immune activity. Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) revealed strong immunomodulatory properties at ELISpot analysis by inhibiting IFNγ secretion of human PBMCs. APEX1 may result as the key factor mediating the beneficial effect of EXT on WH. EXTs or acellular extracts with upregulated APEX1 is a tool of remarkable translational potential for a safe, innovative and cost-effective application in the clinic.

Disclosure
C. Loretelli: None. M. Ben Nasr: None. G. Al Haj: None. F. Rocchio: None. S. Faravelli: None. A. Malvandi: None. F. D'Addio: None. A. Maestroni: None. T. Letizia: None. E. Assi: None. V. Usuelli: None. E. Castillo Leon: None. R. Meroni: None. G. Zuccotti: None. P. Fiorina: None.
Glucokinase-MODY Frequently Misdiagnosed and Inappropriately Treated
Authors: BOYD SEAN , BYRNE MARIA M. 
Published: June 2018

Background: GCK-MODY is an autosomal dominant form of diabetes. Heterozygous inactivating mutations in GCK result in mild, persistent asymptomatic hyperglycemia due to a glucose sensing defect. It is reported that GCK-MODY is not associated with significant diabetic complications and that pharmacological therapy does not alter glycemia.
Aim: We aimed to establish the percentage of GCK-MODY patients on pharmacological therapy and its impact on their glycemic control, along with the incidence of diabetic complications.
Methods: 32 patients were identified. Glycemic tolerance was established using an OGTT. Treatment details were recorded. Diabetic complications were identified. Following genetic diagnosis of GCK-MODY pharmacological therapy with Metformin was discontinued in 7 of 11 patients. HbA1c before and 6 months after discontinuing therapy was compared. Data was analysed in Microsoft Excel and Stata 4.2.
Results: Treatment at diagnosis included, insulin (4), sulfonylurea (2), DPP-4 (5), Metformin only (11), and diet alone (15). Mean HbA1c at MODY diagnosis in all patients was 45.7+/-4.4 mmol/mol. 7/11 patients discontinued metformin only and had no change in glycemic control HbA1c(46.8+/-3.5mmol/mol pre vs. 47.9+/-3.0 mmol/mol post; p=0.38). 40.6% of those screened had background diabetic retinopathy not requiring treatment; 0.03% had Microalbuminuria and 0.125% had CAD.
Conclusion: Prior to genetic diagnosis of GCK-MODY, patients were frequently misdiagnosed, with 50% on pharmacological therapy. Discontinuation of metformin resulted in no deterioration of glycemic control indicating that metformin therapy had no impact on the glucose sensing defect. Background diabetic retinopathy was the commonest complication, but did not require treatment.

Disclosure
S. Boyd: None. M.M. Byrne: None.
The Effect of Lixisenatide and Dapagliflozin in Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus Compared with Sitagliptin and Pioglitazone
Authors: KOUTSOVASILIS ANASTASIOS , SOTIROPOULOS ALEXIOS , PAPPA MARIA , PAPADAKI DESPINA , KORDINAS VASILIS , TAMVAKOS CHARALAMPOS , BOURIKOU MARIA , BOUSBOULAS STAVROS , PEPPAS THEODOROS 
Published: June 2018

Introduction: Medications currently taken by patients with NAFLD target concomitant metabolic diseases such as hypertension, dyslipidemia and diabetes.
Aim: The aim of the study was to examine the effectiveness of lixisenatide and dapagliflozin in NAFLD patients with type 2 diabetes mellitus (T2DM) compared with sitagliptin and pioglitazone.
Methods: T2DM patients with NAFLD (n=306) were included in the study. Patients were divided in 4 groups according to their treatment with lixisenatide (n=62), dapagliflozin (n=85), pioglitazone (n=67) and sitagliptin (n=92). All patients also received metformin. Mean follow-up period was 76 weeks ± 2 weeks. The evaluation of liver fibrosis depended on calculation of aspartase aminotransferase (AST) to platelet counts ratio (APRI) index. All patients went through an ultrasonography before being included in the study and after the end of the study.
Results: There were no differences between groups in patient age (p=0.256), duration of T2DM (p=0.283), Body Mass Index (BMI) (p=0.337) and HbA1c (p=0.156). There was a greater improvement of APRI index for the lixisenatide group (1.07 (0.46-1.23) vs. 0.74 (0.38-0.90) p&lt;0.001) compared to dapagliflozin (1.12 (0.59-1.22) vs. 0.83 (0.32-1.01) p=0.010) to pioglitazone (1.10 (0.49-1.27) vs. 0.90 (0.41-1.04), p=0.014), and sitagliptin (1.01 (0.39-1.14) vs. 0.99 (0.38-1.15) vs. 0.98 (0.36-1.14) p=0.366). APRI index’s improvement was accompanied by a significant change of fatty liver in ultrasonography. The decrease of body weight in the lixisenatide (p&lt;0.001) and in the dapagliflozin group (p=0.028) was statistically significant.
Conclusions: Administration of lixisenatide and dapagliflozin led not only to good control of T2DM but also improvement of liver inflammation, alteration of liver fibrosis, and reduction of body weight, which are particularly important factors in patients with T2DM.

Disclosure
A. Koutsovasilis: None. A. Sotiropoulos: None. M. Pappa: None. D. Papadaki: None. V. Kordinas: None. C. Tamvakos: None. M. Bourikou: None. S. Bousboulas: None. T. Peppas: None.
Comparing Treatment Strategies for Patients with Very Elevated HbA1c—A Randomized Trial
Authors: ABREU MARCONI , TUMYAN ANNA , ELHASSAN AHMED , PAPACOSTEA OLIVIA , PEICHER KATHERINE , DIMACHKIE PERIHAN , SIDDIQUI MUHAMMAD S. , ADAMS-HUET BEVERLEY , LI XILONG , POP LAURENTIU , LINGVAY ILDIKO 
Published: June 2018

Basal-bolus insulin (BBI) is the most established treatment strategy for patients with very elevated HbA1c (&gt;10%), especially if symptomatic. The combination of metformin (Met), GLP-1 receptor agonist (GLP-1RA) and basal insulin (BI) is a very effective glucose lowering strategy, but it has not been evaluated in patients with very elevated HbA1c. This is the first randomized trial comparing a GLP-1RA+BI treatment regimen to a BBI treatment regimen in patients with very uncontrolled (HbA1c&gt;10%) T2D. Basal insulin detemir was either continued at the prior dose or initiated at 0.3 units/kg and self-titrated. GLP-1RA liraglutide was titrated according to label to 1.8 mg/day. Meal-time insulin aspart was initiated at 0.1 units/kg/meal and self-titrated. Metformin was continued or (re)initiated if tolerated, all other hypoglycemic agents were discontinued. The primary outcome was change in HbA1c at 6 months, analyzed using a mixed model repeated measures analysis. We randomized 120 patients with a mean age (SD) 47.4 (9.5) years, Hispanic 48%, diabetes duration of 10.54 (7.19) years, 76% were already treated with insulin, HbA1c 12.1 (1.4) %, BMI 37.2 (10.3) kg/m2, 86% had one or more symptoms of hyperglycemia.
Both treatment strategies lead to dramatic improvements in HbA1c, treatment with GLP-1RA+BI, compared with BBI, resulted in significantly better glycemic control, weight, insulin dosage, and hypoglycemia (Table).Table. Effects of treatment with GLP-1RA + basal insulin (GLP1RA+BI) compared with basal-bolus insulin (BBI) on primary & secondary outcomes.VariableGLP1RA+BI GroupBBI GroupEstimated Treatment DifferenceP value between groupsBaseline6 monthsBaseline6 monthsHbA1c(%)12.2 (11.8 to 12.6)8.1 (7.4 to 8.7)11.8 (11.5 to 12.2)8.8 (6.0 to 9.1)1.1 (0.1 to 2.0)0.03Weight (kg)98.2 (89.7 to 106.6)97.5 (89.1 to 106.0)104.5 (96.2 to 112.8)107.6 (99.3 to 115.9)3.7 (1.53 to 5.9)&lt;0.01TDD Insulin (U/day) (median, 25th to 75th percentile)25.0 (22.0 to 36.0)64.0 (39.5 to 80.0)60.0 (43.0 to 72.0)100.0 (66.0 to 155.0)0.3* (0.1 to 0.5)0.01HbA1c ≤7% N (%)NA20 (44.4)NA9 (20.5)Odds Ratio 0.32 (0.13 to 0.82)0.02Patients with any hypoglycemia (glucose &lt;70 mg/dL) N (%)NA19 (35.2)NA37 (66.1)NA&lt;0.01Data represents Least Squares Means (95% confidence intervals) unless otherwise noted.*ETD for the log transformed value

Disclosure
M. Abreu: None. A. Tumyan: None. A. Elhassan: None. O. Papacostea: None. K. Peicher: None. P. Dimachkie: None. M.S. Siddiqui: None. B. Adams-Huet: None. X. Li: None. L. Pop: None. I. Lingvay: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, AstraZeneca, Intarcia Therapeutics, Inc., Sanofi-Aventis. Research Support; Self; Novo Nordisk A/S, Merck Sharp & Dohme Corp., Pfizer Inc., GI Dynamics Inc., Novartis AG. Other Relationship; Self; Sanofi, AstraZeneca, Boehringer Ingelheim GmbH, Novo Nordisk A/S.
Liquid Room Temperature Stable Glucagon—Glucose Response in Pediatric Type 1 Diabetes Patients
Authors: BUCKINGHAM BRUCE , CUMMINS MARTIN J. , PRESTRELSKI STEVEN J. , STRANGE POUL 
Published: June 2018

Objective: The International Society for Pediatric and Adolescent Diabetes recommends age-specific dosing of glucagon for the rescue of severe hypoglycemia. A novel ready-to-use stable liquid glucagon auto-injector (GAI; Xeris Pharmaceuticals) was evaluated for the treatment of hypoglycemia in pediatric subjects with two age-specific doses.
Research Design and Methods: A sequential efficacy and safety study was conducted involving 31 children with T1D (ages 2-17 years) to evaluate two subcutaneous doses of GAI (0.5 mg or 1 mg) for treatment of hypoglycemia (PG &lt; 80 mg/dL), induced via IV insulin or insulin pump. The primary efficacy endpoint was increase in mean plasma glucose from baseline at 30 minutes following administration of an age-appropriate glucagon dose. As secondary endpoints, subjects were assessed for time from dosing to achieve a 25 mg/dl increase in plasma glucose and other PD and PK parameters.
Results: Statistically significant increases in mean plasma glucose from baseline to 30 minutes post administration of glucagon were observed across the 3 pediatric age groups (81.4±18.3 mg/dL, 84.2±25.3 mg/dL, and 54.0±27.3 mg/dL in the 2 to &lt; 6 years [n=7, 0.5 mg dose], 6 to &lt; 12 years [n=13, 0.5 mg dose], and 12 to &lt; 18 years [n=11, 1 mg dose] age groups, respectively). All evaluable subjects achieved the target glucose elevation of ≥25 mg/dL from baseline. Across age groups there were no notable differences with regards to mean glucose AUC0-90m, Cmax, and Tmax or median time to achieve a 25 mg/dl glucose increase. Plasma glucagon AUC0-240m, Cmax, and Tmax were similar across the age groups. Nausea (36.4%) and vomiting (18.2%) were the most commonly reported AEs.
Conclusions: To prevent medical complications and their sequalae, prompt management of severe hypoglycemia emergencies is critically important. These results demonstrate that age-appropriate doses of GAI were effective in treating hypoglycemia, safe, and well tolerated in pediatric subjects ages 2 through 17 years old.

Disclosure
B. Buckingham: Advisory Panel; Self; Novo Nordisk Inc., ConvaTec Inc.. Research Support; Self; Medtronic, Insulet Corporation, Dexcom, Inc., Tandem Diabetes Care, Inc.. Consultant; Self; Tandem Diabetes Care, Inc., Becton, Dickinson and Company. M.J. Cummins: Employee; Self; Xeris Pharmaceuticals, Inc. S.J. Prestrelski: Employee; Self; Xeris Pharmaceuticals, Inc. P. Strange: Other Relationship; Self; AstraZeneca. Consultant; Self; Valeritas, Inc.. Stock/Shareholder; Self; Valeritas, Inc..