Not all healthcare inequities in diabetes are equal: a comparison of two medically underserved cohorts.

INTRODUCTION: Diabetes disparities exist based on socioeconomic status, race, and ethnicity. The aim of this study is to compare two cohorts with diabetes from California and Florida to better elucidate how health outcomes are stratified within underserved communities according to state location, race, and ethnicity. RESEARCH DESIGN AND METHODS: Two cohorts were recruited for comparison from 20 Federally Qualified Health Centers as part of a larger ECHO Diabetes program. Participant-level data included surveys and HbA1c collection. Center-level data included Healthcare Effectiveness Data and Information Set metrics. Demographic characteristics were summarized overall and stratified by state (frequencies, percentages, means (95% CIs)). Generalized linear mixed models were used to compute and compare model-estimated rates and means. RESULTS: Participant-level cohort: 582 adults with diabetes were recruited (33.0% type 1 diabetes (T1D), 67.0% type 2 diabetes (T2D)). Mean age was 51.1 years (95% CI 49.5, 52.6); 80.7% publicly insured or uninsured; 43.7% non-Hispanic white (NHW), 31.6% Hispanic, 7.9% non-Hispanic black (NHB) and 16.8% other. Center-level cohort: 32 796 adults with diabetes were represented (3.4% with T1D, 96.6% with T2D; 72.7% publicly insured or uninsured). Florida had higher rates of uninsured (p<0.0001), lower continuous glucose monitor (CGM) use (18.3% Florida; 35.9% California, p<0.0001), and pump use (10.2% Florida; 26.5% California, p<0.0001), and higher proportions of people with T1D/T2D>9% HbA1c (p<0.001). Risk was stratified within states with NHB participants having higher HbA1c (mean 9.5 (95% CI 8.9, 10.0) compared with NHW with a mean of 8.4 (95% CI 7.8, 9.0), p=0.0058), lower pump use (p=0.0426) and CGM use (p=0.0192). People who prefer to speak English were more likely to use a CGM (p=0.0386). CONCLUSIONS: Characteristics of medically underserved communities with diabetes vary by state and by race and ethnicity. Florida's lack of Medicaid expansion could be a factor in worsened risks for vulnerable communities with diabetes.

Communicating computational workflows in a regulatory environment.

The volume of nucleic acid sequence data has exploded recently, amplifying the challenge of transforming data into meaningful information. Processing data can require an increasingly complex ecosystem of customized tools, which increases difficulty in communicating analyses in an understandable way yet is of sufficient detail to enable informed decisions or repeats. This can be of particular interest to institutions and companies communicating computations in a regulatory environment. BioCompute Objects (BCOs; an instance of pipeline documentation that conforms to the IEEE 2791-2020 standard) were developed as a standardized mechanism for analysis reporting. A suite of BCOs is presented, representing interconnected elements of a computation modeled after those that might be found in a regulatory submission but are shared publicly - in this case a pipeline designed to identify viral contaminants in biological manufacturing, such as for vaccines.

Transformation of Metallic Ti to TiH2 Phase in the Ti/MgH2 Composite and Its Influence on the Hydrogen Storage Behavior of MgH2.

The current work explores the in-situ formation of TiH2 additive in a Ti/MgH2 nanocomposite system. Mild mechanical milling leaves Ti chemically unchanged, while formation of stable TiH2-x occurs upon strong mechanical milling. TiH2-x further transforms to TiH2 upon recycling the powder (dehydrogenation and subsequent hydrogenation) and lowers the activation energy of MgH2 to 89.4 kJ (mol H2 )-1 [Ea of as-received MgH2 is 153 kJ (mol H2 )-1 ]. This work also reiterates that metallic Ti additive mixed MgH2 requires strong mechanical milling for better H2 ab/de-sorption performance. The current observations support the view that lattice strain may be an important factor in the catalysis of additives incorporated MgH2 hydrogen storage systems.

Considerations for Optimization of High-Throughput Sequencing Bioinformatics Pipelines for Virus Detection.

High-throughput sequencing (HTS) has demonstrated capabilities for broad virus detection based upon discovery of known and novel viruses in a variety of samples, including clinical, environmental, and biological. An important goal for HTS applications in biologics is to establish parameter settings that can afford adequate sensitivity at an acceptable computational cost (computation time, computer memory, storage, expense or/and efficiency), at critical steps in the bioinformatics pipeline, including initial data quality assessment, trimming/cleaning, and assembly (to reduce data volume and increase likelihood of appropriate sequence identification). Additionally, the quality and reliability of the results depend on the availability of a complete and curated viral database for obtaining accurate results; selection of sequence alignment programs and their configuration, that retains specificity for broad virus detection with reduced false-positive signals; removal of host sequences without loss of endogenous viral sequences of interest; and use of a meaningful reporting format, which can retain critical information of the analysis for presentation of readily interpretable data and actionable results. Furthermore, after alignment, both automated and manual evaluation may be needed to verify the results and help assign a potential risk level to residual, unmapped reads. We hope that the collective considerations discussed in this paper aid toward optimization of data analysis pipelines for virus detection by HTS.

Structure and Electrical-Transport Relations in Ba(Zr,Pr)O3-δ Perovskites.

Members of the perovskite solid solution BaZr1-xPrxO3-δ (0.2 ≤ x ≤ 0.8) with potential high-temperature electrochemical applications were synthesized via mechanical activation and high-temperature annealing at 1250 °C. Structural properties were examined by Rietveld analysis of neutron powder diffraction and Raman spectroscopy at room temperature, indicating rhombohedral symmetry (space group R3̅c) for members x = 0.2 and 0.4 and orthorhombic symmetry (Imma) for x = 0.6 and 0.8. The sequence of phase transitions for the complete solid solution from BaZrO3 to BaPrO3 is Pm3̅m → R3̅c → Imma → Pnma. The structural data indicate that Pr principally exists as Pr4+ on the B site and that oxygen content increases with higher Pr content. Electrical-conductivity measurements in the temperature range of 250-900 °C in dry and humidified (pH2O ≈ 0.03 atm) N2 and O2 atmospheres revealed an increase of total conductivity by over 2 orders of magnitude in dry conditions from x = 0.2 to x = 0.8 (σ ≈ 0.08 S cm-1 at 920 °C in dry O2 for x = 0.8). The conductivity for Pr contents x > 0.2 is attributable to positively charged electronic carriers, whereas for x = 0.2 transport in dry conditions is n-type. The change in conduction mechanism with composition is proposed to arise from the compensation regime for minor amounts of BaO loss changing from predominantly partitioning of Pr on the A site to vacancy formation with increasing Pr content. Conductivity is lower in wet conditions for x > 0.2 indicating that the positive defects are, to a large extent, charge compensated by less mobile protonic species. In contrast, the transport mechanism of the Zr-rich composition (x = 0.2), with much lower electronic conductivity, is essentially independent of moisture content.

Site Redistribution, Partial Frozen-in Defect Chemistry, and Electrical Properties of Ba1-x(Zr,Pr)O3-δ.

Changes in nominal composition of the perovskite (ABO3) solid solution Ba1-x(Zr,Pr)O3-δ and adjusted firing conditions at very high temperatures were used to induce structural changes involving site redistribution and frozen-in point defects, as revealed by Raman and photoluminescence spectroscopies. Complementary magnetic measurements allowed quantification of the reduced content of Pr. Weak dependence of oxygen stoichiometry with temperature was obtained by coulometric titration at temperatures below 1000 °C, consistent with a somewhat complex partial frozen-in defect chemistry. Electrical conductivity measurements combined with transport number and Seebeck coefficient measurements showed prevailing electronic transport and also indicated trends expected for partial frozen-in conditions. Nominal Ba deficiency and controlled firing at very high temperatures allows adjustment of structure and partial frozen-in defect chemistry, opening the way to engineer relevant properties for high-temperature electrochemical applications.

Formation of Mgx Nby Ox+y through the Mechanochemical Reaction of MgH2 and Nb2O5, and Its Effect on the Hydrogen-Storage Behavior of MgH2.

The present study aims to understand the catalysis of the MgH2 -Nb2 O5 hydrogen storage system. To clarify the chemical interaction between MgH2 and Nb2 O5 , the mechanochemical reaction products of a composite mixture of MgH2 +0.167 Nb2 O5 was monitored at different time intervals (2, 5, 15, 30, and 45 min, as well as 1, 2, 5, 10, 15, 20, 25, and 30 h). The study confirms the formation of catalytically active Nb-doped MgO nanoparticles (typically Mgx Nby Ox+y , with a crystallite size of 4-8 nm) by transforming reactants through an intermediate phase typified by Mgm-x Nb2n-y O5n-(x+y) . The initially formed Mgx Nby Ox+y product is shown to be Nb rich, with the concentration of Mg increasing upon increasing milling time. The nanoscale end-product Mgx Nby Ox+y closely resembles the crystallographic features of MgO, but with at least a 1-4 % higher unit cell volume. Unlike MgO, which is known to passivate the surfaces in MgH2 system, the Nb-dissolved MgO effectively mediates the Mg-H2 sorption reaction in the system. We believe that this observation will lead to new developments in the area of catalysis for metal-gas interactions.

Summary of the advanced virus detection technologies users group efforts-2013.

An informal consortium of scientists from the biopharmaceutical industry, academia, and government agencies, including regulators, coalesced during 2013 to further explore advanced virus detection technologies or appropriate applications for characterization and evaluation of biologicals. As a Parenteral Drug Association task force, the Users Group came to focus on four key work areas that required better understanding and data generation: (1) evaluation of sample preparation and processing steps for different sample types, (2) determination of method sensitivity by performing spike recovery studies using selected virus stocks, (3) development of a reliable and comprehensive viral sequence database, and (4) evaluation of bioinformatic analysis pipelines, with primary focus on next-generation DNA sequencing platforms. The year of monthly working meetings and additional subgroup discussions culminated in the 2013 PDA/FDA Advanced Technologies for Virus Detection in the Evaluation of Biologicals Conference held November 13-14, 2013 in Bethesda, MD, which provided a forum for group participants and others for data sharing and knowledge exchange. The Users Group has continued its efforts during 2014 as a PDA Interest Group with increased participation from technology developers and contract research organizations.

Modeling an approach to define sensitivity of viral detection in sample matrices-examples with microarray readout.

Advances in viral detection technologies have the potential to increase the safety assurance of medicines produced in biological production systems. However, taking full advantage of these technological advances in the regulated testing environment will require protocols for standardization and performance testing. The most essential performance characteristics of detection methods for these applications include sensitivity, breadth of detection, and consistency. We have evaluated an approach to establishing the suitability of advanced nucleic-acid-based detection systems for characterization of cell substrates and production cultures. This approach is based on selecting relevant challenge viruses, their preparation and characterization, their application to a sample preparation workflow, and quantitation of their recovery by an independent means as well as the advanced detection readout. This approach helps us evaluate the suitability of the workflow for handling diverse sample matrices across manufacturing platforms for vaccines and other biological products, and also suggests a means by which technology users, developers, and regulators may consider the critical performance attributes of novel detection technologies. We have applied this workflow to a novel microarray-based viral detection system in collaboration with Lawrence Livermore National Laboratory. This system is appealing because of the rapid turnaround of results compared to some other advanced detection technologies.

Defining a sample preparation workflow for advanced virus detection and understanding sensitivity by next-generation sequencing.

The application of next-generation sequencing (also known as deep sequencing or massively parallel sequencing) for adventitious agent detection is an evolving field that is steadily gaining acceptance in the biopharmaceutical industry. In order for this technology to be successfully applied, a robust method that can isolate viral nucleic acids from a variety of biological samples (such as host cell substrates, cell-free culture fluids, viral vaccine harvests, and animal-derived raw materials) must be established by demonstrating recovery of model virus spikes. In this report, we implement the sample preparation workflow developed by Feng et. al. and assess the sensitivity of virus detection in a next-generation sequencing readout using the Illumina MiSeq platform. We describe a theoretical model to estimate the detection of a target virus in a cell lysate or viral vaccine harvest sample. We show that nuclease treatment can be used for samples that contain a high background of non-relevant nucleic acids (e.g., host cell DNA) in order to effectively increase the sensitivity of sequencing target viruses and reduce the complexity of data analysis. Finally, we demonstrate that at defined spike levels, nucleic acids from a panel of model viruses spiked into representative cell lysate and viral vaccine harvest samples can be confidently recovered by next-generation sequencing.