Publications by authors named "A M James Shapiro"

2,138 Publications

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Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device.

Cell Rep Med 2021 Dec 2;2(12):100466. Epub 2021 Dec 2.

ViaCyte Inc., San Diego, CA 92121, USA.

These preliminary data from an ongoing first-in-human phase 1/2, open-label study provide proof-of-concept that pluripotent stem cell-derived pancreatic endoderm cells (PEC-01) engrafted in type 1 diabetes patients become islet cells releasing insulin in a physiologically regulated fashion. In this study of 17 subjects aged 22-57 with type 1 diabetes, PEC-01 cells were implanted subcutaneously in VC-02 macroencapsulation devices, allowing for direct vascularization of the cells. Engraftment and insulin expression were observed in 63% of VC-02 units explanted from subjects at 3-12 months post-implant. Six of 17 subjects (35.3%) demonstrated positive C-peptide as early as 6 months post-implant. Most reported adverse events were related to surgical implant or explant procedures (27.9%) or to side-effects of immunosuppression (33.7%). Initial data suggest that pluripotent stem cells, which can be propagated to the desired biomass and differentiated into pancreatic islet-like tissue, may offer a scalable, renewable alternative to pancreatic islet transplants.
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http://dx.doi.org/10.1016/j.xcrm.2021.100466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714853PMC
December 2021

Trends in Glycemic Control Among Youth and Young Adults With Diabetes: The SEARCH for Diabetes in Youth Study.

Diabetes Care 2022 Feb;45(2):285-294

Department of Pediatrics, University of Washington, Seattle, WA.

Objective: To describe temporal trends and correlates of glycemic control in youth and young adults (YYA) with youth-onset diabetes.

Research Design And Methods: The study included 6,369 participants with type 1 or type 2 diabetes from the SEARCH for Diabetes in Youth study. Participant visit data were categorized into time periods of 2002-2007, 2008-2013, and 2014-2019, diabetes durations of 1-4, 5-9, and ≥10 years, and age groups of 1-9, 10-14, 15-19, 20-24, and ≥25 years. Participants contributed one randomly selected data point to each duration and age group per time period. Multivariable regression models were used to test differences in hemoglobin A1c (HbA1c) over time by diabetes type. Models were adjusted for site, age, sex, race/ethnicity, household income, health insurance status, insulin regimen, and diabetes duration, overall and stratified for each diabetes duration and age group.

Results: Adjusted mean HbA1c for the 2014-2019 cohort of YYA with type 1 diabetes was 8.8 ± 0.04%. YYA with type 1 diabetes in the 10-14-, 15-19-, and 20-24-year-old age groups from the 2014-2019 cohort had worse glycemic control than the 2002-2007 cohort. Race/ethnicity, household income, and treatment regimen predicted differences in glycemic control in participants with type 1 diabetes from the 2014-2019 cohort. Adjusted mean HbA1c was 8.6 ± 0.12% for 2014-2019 YYA with type 2 diabetes. Participants aged ≥25 years with type 2 diabetes had worse glycemic control relative to the 2008-2013 cohort. Only treatment regimen was associated with differences in glycemic control in participants with type 2 diabetes.

Conclusions: Despite advances in diabetes technologies, medications, and dissemination of more aggressive glycemic targets, many current YYA are less likely to achieve desired glycemic control relative to earlier cohorts.
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http://dx.doi.org/10.2337/dc21-0507DOI Listing
February 2022

Contributing Areas to Domestic Wells in Dipping Sedimentary Rocks under Extreme Recharge Events.

Ground Water 2022 Jan 5. Epub 2022 Jan 5.

U.S. Geological Survey, Water Mission Area, Reston, VA.

We use particle tracking to determine contributing areas (CAs) to wells for transient flow models that simulate cyclic domestic pumping and extreme recharge events in a small synthetic watershed underlain by dipping sedimentary rocks. The CAs consist of strike-oriented bands at locations where the water table intersects high-hydraulic conductivity beds, and from which groundwater flows to the pumping well. Factors that affect the size and location of the CAs include topographic flow directions, rock dip direction, cross-bed fracture density, and position of the well relative to streams. For an effective fracture porosity (n ) of 10 , the fastest advective travel times from CAs to wells are only a few hours. These results indicate that wells in this type of geologic setting can be highly vulnerable to contaminants or pathogens flushed into the subsurface during extreme recharge events. Increasing n to 10 results in modestly smaller CAs and delayed well vulnerability due to slower travel times. CAs determined for steady-state models of the same setting, but with long-term average recharge and pumping rates, are smaller than CAs in the models with extreme recharge. Also, the earliest-arriving particles arrive at the wells later in the steady-state models than in the extreme-recharge models. The results highlight the importance of characterizing geologic structure, simulating plausible effective porosities, and simulating pumping and recharge transience when determining CAs in fractured rock aquifers to assess well vulnerability under extreme precipitation events.
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http://dx.doi.org/10.1111/gwat.13169DOI Listing
January 2022

Preclinical models of acute liver failure: a comprehensive review.

PeerJ 2021 9;9:e12579. Epub 2021 Dec 9.

Division of General Surgery, Department of Surgery, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada.

Acute liver failure is marked by the rapid deterioration of liver function in a previously well patient over period of days to weeks. Though relatively rare, it is associated with high morbidity and mortality. This makes it a challenging disease to study clinically, necessitating reliance on preclinical models as means to explore pathophysiology and novel therapies. Preclinical models of acute liver failure are artificial by nature, and generally fall into one of three categories: surgical, pharmacologic or immunogenic. This article reviews preclinical models of acute liver failure and considers their relevance in modeling clinical disease.
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http://dx.doi.org/10.7717/peerj.12579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667744PMC
December 2021

Time to knock monoclonal antibodies off the platform for patients hospitalised with COVID-19.

Lancet Infect Dis 2021 Dec 23. Epub 2021 Dec 23.

Department of Global Health and Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, WA 98104, USA; Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

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http://dx.doi.org/10.1016/S1473-3099(21)00762-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700277PMC
December 2021
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