Time In Compartments Research Articles

315. Standardized Measurement of SARS-CoV-2 Viral Load Over Time in Respiratory Compartments and in Response to Remdesivir Treatment

Abstract Background Two years into the pandemic, clinicians do not have access to a standardized measurement of SARS-CoV-2 viral load (VL) that allows for VL comparison across clinical specimens and different assays. Reliable VL measurement in diverse respiratory specimens, over time, and in response to treatments such as remdesivir (RDV), could better inform treatment and prevention. Methods To investigate the use of a standardized VL assay in respiratory specimens, we enrolled patients hospitalized with COVID-19 in Providence, RI, with/without RDV exposure; collected serial samples from 4 compartments (nasopharyngeal-NP, nasal-NA, oropharyngeal-OP, saliva-SA) in 3 visits during the 1st week of hospitalization; and characterized SARS-CoV-2 VL using a ChromaCode HDPCR™ quantitative research use only assay, calibrated to the first World Health Organization (WHO) International Standard (IS). Linear mixed effects models and associated regression coefficients were used to analyze inter-compartmental VL differences at enrollment, over time, and with/without RDV. Results Of 35 participants (60% male; 70% White, 14% Hispanic/Latino, 49% RDV exposure), all had visit 1 samples (median hospital day 1, IQR 0-2; pre-RDV for those exposed); 80% visit 2 samples (median hospital day 2, IQR 1-8); and 37% visit 3 samples (median hospital day 4, IQR 3-7). Overall, 38 NP, 67 NA, 57 OP, and 67 SA samples were collected. Mean log VLs (Log10IU/mL) differed by compartment at visit 1 (NP 6.3, NA 4.9, OP 4.1, SA 5.6, p=0.0001) and significantly decreased over time in all compartments (p< 0.04 for all comparisons). Log VL change over time was not significantly different between compartments or between people treated/not treated with RDV. Conclusion We successfully measured respiratory intercompartmental SARS-CoV-2 VL differences among hospitalized patients using a standardized assay calibrated to the WHO IS. Dissemination of standardized VL measurement methods will allow accurate VL comparisons across assay types quantified in IU/mL and improve assessment of the impact of COVID-19 treatments. Inter-compartmental VL differences at baseline may indicate sampling variability or different viral burden. RDV did not appear to accelerate viral decay. Disclosures Curt Beckwith, MD, Gilead Sciences, Inc: Grant/Research Support Jon Steingrimsson, PhD, Gilead: Grant/Research Support Angela Caliendo, MD, PhD, ChromaCode: Advisor/Consultant|Danaher/Cepheid: Advisor/Consultant|First Light: Advisor/Consultant|Hologic: Grant/Research Support|ID Connect: Advisor/Consultant|Quidel: Advisor/Consultant|Visby: Advisor/Consultant Rami Kantor, MD, Gilead Sciences: Grant/Research Support.

MRI T2 and T1\u03c1 relaxation in patients at risk for knee osteoarthritis: a systematic review and meta-analysis

BackgroundMagnetic resonance imaging (MRI) T2 and T1ρ relaxation are increasingly being proposed as imaging biomarkers potentially capable of detecting biochemical changes in articular cartilage before structural changes are evident. We aimed to: 1) summarize MRI methods of published studies investigating T2 and T1ρ relaxation time in participants at risk for but without radiographic knee OA; and 2) compare T2 and T1ρ relaxation between participants at-risk for knee OA and healthy controls.MethodsWe conducted a systematic review of studies reporting T2 and T1ρ relaxation data that included both participants at risk for knee OA and healthy controls. Participant characteristics, MRI methodology, and T1ρ and T2 relaxation data were extracted. Standardized mean differences (SMDs) were calculated within each study. Pooled effect sizes were then calculated for six commonly segmented knee compartments.Results55 articles met eligibility criteria. There was considerable variability between scanners, coils, software, scanning protocols, pulse sequences, and post-processing. Moderate risk of bias due to lack of blinding was common. Pooled effect sizes indicated participants at risk for knee OA had lengthened T2 relaxation time in all compartments (SMDs from 0.33 to 0.74; p < 0.01) and lengthened T1ρ relaxation time in the femoral compartments (SMD from 0.35 to 0.40; p < 0.001).ConclusionsT2 and T1ρ relaxation distinguish participants at risk for knee OA from healthy controls. Greater standardization of MRI methods is both warranted and required for progress towards biomarker validation.

Effect of a range of microbial polysaccharides on the diffusion of manganese ions using spatially resolved NMR relaxometry.

In accordance with the theory of contact exchange, it is hypothesized that the presence of negative charge in microbial exopolysaccharides increases the rate of cation transport. These typically acidic materials may provide a fast-track for the diffusion of nutrient cations through the polymer layer for uptake at the organism cell surface. We have measured the diffusion coefficient of a model cation, Mn(2+,) through xanthan, de-acetylated xanthan, scleroglucan and chitosan using spatially resolved NMR relaxometry. The concentration of Mn(2+) in solution was measured by recording the change in the spin-spin (T(2)) relaxation time of water (1)H over time in compartments either side of a polymer layer. This approach provides a sensitive, in situ, non-invasive method of measuring the rate of diffusion of paramagnetic cations through hydrophilic polysaccharides. The negatively-charged polysaccharides, xanthan and de-acetylated xanthan, permitted a significantly faster rate (2-2.5x) of cation transport compared to the uncharged polymer, scleroglucan. The positively-charged polysaccharide chitosan reduced the rate of Mn(2+) diffusion to around half the value obtained for scleroglucan. These results suggest that the presence and nature of fixed charges on the polysaccharide molecule affects the rate of cation transport in accordance with the theory of contact exchange. The presence of negative charge on microbial exopolysaccharides may thus improve the availability of nutrient cations at the organism cell surface.

Subversion of a young phagosome: the survival strategies of intracellular pathogens. Microreview

Subversion of a young phagosome: the survival strategies of intracellular pathogens. Microreview

Comparison of methods, markers, sampling sites and models for estimating digesta passage kinetics in cattle fed at two levels of intake

Six ruminally and duodenally cannulated Friesian bulls were used in a switch-back experiment to compare passage models, markers and sampling sites, and duodenal or faecal marker excretion curves and rumen evacuation technique for estimating kinetics of digesta passage. Cr-mordanted and Yb-labelled hay were used as particulate markers and CoEDTA as a liquid-phase marker. The cattle were fed on a dry matter (DM) basis (g kg −1) a diet of hay (600), barley (396) and urea (4) at either low or high DM intake (40 and 80 g DM (kg 0.75 live weight) −1). Post-duodenal digesta kinetics were estimated by administering the markers (CoEDTA, Cr-mordanted and Yb-labelled duodenal digesta particles) into the duodenum and collecting faecal samples. Digesta kinetic parameters were calculated by linear regression of natural log transformed marker concentrations in ruminal fluid, duodenal digesta or faeces, and by non-linear models with either two age-independent compartments (G1G1) or gamma time dependency in the first compartment (GnG1, n = 2–4). Using the models with gamma age dependency improved the curve fitting which suggested an age-dependent flow. In most cases the error mean squares were smallest with the G3G1 model. Total compartmental retention time (CMRT), transit time (TT) and total mean retention time (TMRT) of the markers decreased as DM intake increased. Regardless of marker, sampling site or model, the relative differences in digesta kinetics between the diets' kinetics were similar. Shorter post-duodenal retention time of markers at high compared to low DM intake resulted from both shorter CMRT and TT. Similar post-duodenal kinetics of Co, Cr and Yb indicate that there was no differential passage of liquid and solid digesta in the caecum and proximal colon. Average CMRT was shorter for Yb than for Cr when derived either from duodenal (57.4 vs. 66.8 h) or faecal sampling (61.1 vs. 73.5 h). Faecal sampling resulted in 3.7 h (Yb) and 6.6 h (Cr) longer CMRT than duodenal sampling. Post-duodenal CMRT was only 0.223 (Yb) and 0.146 (Cr) of the retention time in the fast age-dependent compartment derived from faecal sampling. This suggests that preduodenal sites accounted for the major proportion of the retention time in this compartment. The passage rate estimates derived from rumen evacuation were much slower than those calculated from the exponential decline in duodenal and faecal Cr and Yb concentrations, mainly because rumen evacuation derived passage rate includes the retention time in both ruminal compartments. However, when a simple first-order passage rate was calculated from the passage rate from the two ruminal compartments and rate of neutral detergent fibre (NDF) digestion, the values for indigestible NDF, NDF and digestible NDF obtained from the two methods were fairly similar; rumen evacuation: 0.0165, 0.0126 and 0.0095 h −1; Cr: 0.0159, 0.0111 and 0.0085 h −1; Yb: 0.0179, 0.0123 and 0.0099 h −1.

Calculating sprinkler actuation time in compartments

A generalized method is presented for determining the response time for thermally actuated sprinklers installed near the ceiling of both large and small compartments. A substitute source for the actual fire is calculated to account for the effects of a warm gas layer in the upper portion of the enclosure on ceiling-layer flow temperatures. Illustrative examples are given for the change in response time for sprinklers with RTI values of 25, 100, and 400 m 1 2 , s 1 2 , to a given fire in a series of compartments ranging in floor area from 23.8 m 2 (256 ft 2) to 24 300 m 2 (262 000 ft 2). For comparative purposes sprinkler response is also calculated for the limiting case of an unconfined ceiling.