HbA1c method performance: The great success story of global standardization

Diagnosing and monitoring the treatment of people with diabetes is a global issue and uses considerable resources in laboratories and clinics worldwide. Hemoglobin A1c (HbA1c) has been the mainstay of monitoring glycemic control in people with diabetes for many years and more recently it has been advocated as a diagnostic tool for type 2 diabetes mellitus (T2DM). Good analytical performance is key to the successful use of any laboratory test, but is critical when using the test to diagnose disease, especially when the potential number of diagnoses could exceed 500 million people. Very small variations in bias or increased imprecision could lead to either a missed diagnosis or overdiagnosis of the disease and given the scale of the global disease burden, this could mean erroneous categorization of potentially millions of people. Fundamental to good performance of diagnostic testing is standardization, with defined reference materials and measurement procedures. In this review, we discuss the historical steps to first harmonize HbA1c testing, followed by the global standardization efforts and provide an update on the current situation and future goals for HbA1c testing

Evaluation of Four HbA1c Point-of-Care Devices Using International Quality Targets: Are They Fit for the Purpose?

BACKGROUND: Point-of-care (POC) testing is becoming increasingly valuable in health care delivery, and it is important that the devices used meet the same quality criteria as main laboratory analyzers. While external quality assessment (EQA) provides a great tool for assessing quality, many POC devices are not enrolled in these schemes and standard laboratory evaluations are needed to assess performance. METHODS: The Clinical and Laboratory Standards Institute (CLSI) protocols EP-5 and EP-9 were applied to investigate imprecision, accuracy and bias. We assessed bias using the mean of 4 certified secondary reference measurement procedures (SRMPs). RESULTS: The Afinion2™ and the Quo-Lab had CVs of ≤1.7 and ≤2.4% respectively in IFCC SI units (≤1.2 and ≤1.7% NGSP) and a bias ≤2 mmol/mol (≤0.2% NGSP) at 48 and 75 mmol/mol (6.5 and 9.0% NGSP). Sigma for the Afinion2 was 5.8 and for the Quo-Lab 4.0. Both methods passed the NGSP criteria with 2 instruments when compared with 4 individual SRMPs. The HbA1c 501 had a CV of 3.4% and 2.7% in IFCC SI units (2.1% and 1.7% NGSP) and a bias ≤2.4 mmol/mol (≤0.2% NGSP) and passed the NGSP criteria with 2 instruments compared with 4 individual SRMPs except for instrument 2 compared with the Tosoh G8. Sigma was 2.1. The A1Care had a sigma of 1.4 and failed all criteria mainly due to a high CV (6.2% and 4.1% in IFCC SI units [4.1% and 2.9% NGSP] at 48 and 75 mmol/mol [6.5 and 9.0% NGSP]). CONCLUSIONS: The analytical performance was excellent for the Afinion2 and the Quo-Lab, acceptable for the HbA1c 501 and unacceptable for the A1Care according to different used criteria, demonstrating that whilst performance is improving there are still areas for considerable improvement

An Understanding of Telephony with Uncoil

The autonomous steganography solution to RPCs is defined not only by the emulation of 128 bit architectures, but also by the natural need for IPv6 [18]. After years of unfortunate research into linked lists, we disconfirm the study of e-business [18]. In our research, we propose a novel methodology for the develop- ment of the UNIVAC computer (Uncoil), disproving that the World Wide Web and web browsers can connect to achieve this objective

Dynamic interaction between tectonic plates, subducting slabs, and the mantle

Mantle convection models have been formulated to investigate the relation between plate kinematics and mantle dynamics. The cylindrical geometry models incorporate mobile, faulted plate margins, a phase change at 670 km depth, non-Newtonian rheology, and tectonic plates. Models with a variety of parameters indicate that a relatively stationary trench is more likely to be associated with a subducted slab that penetrates into the lower mantle with a steep dip angle. However, a subducted slab that is deflected above the 670-km phase change with a shallow dip is more likely to be associated with a margin that has undergone rapid retrograde trench migration. This relation between slab morphology and plate kinematics is consistent with seismic tomography and plate reconstruction of western Pacific subduction zones. The efficiency of slab penetration through the 670-km phase change is controlled by both the buoyancy of the subducting plate and the mobility of the overriding plate. While older subducting plates have a greater propensity for slab penetration, trench mobility reduces the propensity for slab penetration. Smaller overriding plates have a greater mobility. When subducted slabs approach the bottom thermal boundary layer, hot fluid is pushed aside, and plumes form on the periphery of slab accumulations. There are sharp temperature contrasts between the subducted slab and the thermal boundary layer at the core mantle boundary (CMB). Old subducted slabs and a thermal boundary layer lead to large-scale lateral structure near the CMB

Collision and Diffusion in Microwave Breakdown of Nitrogen Gas in and around Microgaps

The microwave induced breakdown of N2 gas in microgaps was modeled using the collision frequency between electrons and neutral molecules and the effective electric field concept. Low pressure breakdown at the threshold electric field occurs outside the gap, but at high pressures it is found to occur inside the microgap with a large threshold breakdown electric field corresponding to a very large electron oscillation amplitude. Three distinct pressure regimes are apparent in the microgap breakdown: a low pressure multipactor branch, a mid-pressure Paschen branch, both of which occur in the space outside the microgap, and a high pressure diffusion-drift branch, which occurs inside the microgap. The Paschen and diffusion-drift branches are divided by a sharp transition and each separately fits the collision frequency model. There is evidence that considerable electron loss to the microgap faces accompanies the diffusion-drift branch in microgaps.Comment: 4 figure

Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1 month.

BACKGROUND:Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1 month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups. RESULTS:PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative "high" (> 80th percentile) vs. "low" (< 20th percentile) toxicant exposure in this cohort. Moreover, breast milk toxicants were associated with microbiome functionality, explaining up to 34% of variance in acetic and propionic SCFAs, essential signaling molecules. Per one standard deviation of exposure, PBDE-28 was associated with less propionic acid (- 24% [95% CI - 35% to - 14%] relative to the mean), and PCB-209 with less acetic acid (- 15% [95% CI - 29% to - 0.4%]). Conversely, PFOA and dioxin-like PCB-167 were associated with 61% (95% CI 35% to 87%) and 22% (95% CI 8% to 35%) more propionic and acetic acid, respectively. CONCLUSIONS:Environmental toxicant exposure may influence infant gut microbial function during a critical developmental window. Future studies are needed to replicate these novel findings and investigate whether this has any impact on child health

An Extended Burst Tail from SGR 1900+14 with a Thermal X-ray Spectrum

The Soft Gamma Repeater, SGR 1900+14, entered a new phase of activity in April 2001 initiated by the intermediate flare recorded on April 18. Ten days following this flare, we discovered an abrupt increase in the source flux between consecutive RXTE orbits. This X-ray flux excess decayed over the next several minutes and was subsequently linked to a high fluence burst from SGR 1900+14 recorded by other spacecraft (Ulysses and KONUS) while the SGR was Earth-occulted for RXTE. We present here spectral and temporal analysis of both the burst of 28 April and the long X-ray tail following it. We find strong evidence of an exclusively thermal X-ray tail in this event and bring this evidence to bear on other bursts and flares from SGR 1900+14 which have shown extended X-ray excesses (e.g. 1998 August 29). We include in this comparison a discussion of the physical origins of SGR bursts and extended X-ray tails.Comment: 27 pages, 13 figures, ApJ submissio

On the X-ray emission mechanisms of the persistent source and very low-fluence bursts of SGR J0501+4516

We present here a detailed spectral study of the X-ray emission of the persistent source and the low-fluence bursts of SGR J0501+4516 observed during a deep XMM-Newton observation near the peak of its 2008 outburst. For the persistent emission we employ a physically motivated continuum emission model and spectroscopically determine important source properties; such as, the surface magnetic field strength and the magnetospheric scattering optical depth. We find that the magnetar surface temperature near the peak of its activity is 0.38 keV, corresponding to an emission area of 131 km^2 at a distance of 2 kpc. The surface magnetic field strength determined spectroscopically, B=2.2E14 G, is consistent with the dipole field strength inferred from the source spin and spin down rate. We fit the stacked spectra of 129 very faint bursts with a modified blackbody model and find a temperature of 1.16 keV, corresponding to an emission area of 93 km^2. We also find an evidence for cooling during the burst decay phase

The Dynamic Behavior of Soft Gamma Repeaters

Soft Gamma Repeaters (SGRs) undergo changes in their pulse properties and persistent emission during episodes of intense burst activity. Both SGR 1900+14 and SGR 1806-20 have shown significant changes in their spin-down rates during the last several years, yet the bulk of this variability is not correlated with burst activity. SGR 1900+14 has undergone large changes in flux and a dramatic pulse profile change following burst activity in 1998. The flux level of SGR 1627$-$41 has been decreasing since its only recorded burst activity. Here, we review the global properties of SGRs as well as the observed dynamics of the pulsed and persistent emission properties of SGR 1900+14, SGR 1806-20 and SGR 1627-41 during and following burst active episodes and discuss what implications these results have for the burst emission mechanism, the magnetic field dynamics of magnetars, the nature of the torque variability, and SGRs in general.Comment: Invited review to appear in "High Energy Studies of Supernova Remnants and Neutron Stars" (COSPAR 2002). 12 pages, 7 figure

Five years of SGR 1900+14 observations with BeppoSAX

We present a systematic analysis of all the BeppoSAX data of the soft gamma-ray repeater SGR 1900+14: these observations allowed us to study the long term properties of the source quiescent emission. In the observation carried out before the 1998 giant flare the spectrum in the 0.8-10 keV energy range was harder and there was evidence for a 20-150 keV emission, possibly associated with SGR 1900+14. This possible hard tail, if compared with the recent INTEGRAL detection of SGR 1900+14, has a harder spectrum (power-law photon index ~1.6 versus ~3) and a 20-100 keV flux ~4 times larger. In the last BeppoSAX observation (April 2002), while the source was entering the long quiescent period that lasted until 2006, the 2-10 keV flux was ~25% below the historical level. We also studied in detail the spectral evolution during the 2001 flare afterglow. This was characterized by a softening that can be interpreted in terms of a cooling blackbody-like component.Comment: Accepted for publication on Astronomy and Astrophysics on August 31, 200