Abstract
Background
The Recipient Epidemiology and Donor Evaluation Study-IV-Pediatric (REDS-IV-P) Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) ...seroprevalence study conducted monthly cross-sectional testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in blood donors in 6 US metropolitan regions to estimate the extent of SARS-CoV-2 infections over time.
Methods
During March–August 2020, approximately ≥1000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences compared with the general population. Seroprevalence was compared with reported coronavirus disease 2019 (COVID-19) case rates over time.
Results
For all regions, seroprevalence was <1.0% in March 2020. New York, New York, experienced the biggest increase (peak seroprevalence, 15.8% in May). All other regions experienced modest increases in seroprevalence (1%–2% in May–June to 2%–4% in July–August). Seroprevalence was higher in younger, non-Hispanic black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3–5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case were reported to the Centers for Disease Control and Prevention.
Conclusions
Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic black and Hispanic than in non-Hispanic white blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.
SARS-CoV-2 serosurveillance of blood donors in 6 US regions enabled population weighted seroprevalence estimates. Seroprevelance rates were higher in younger, non-Hispanic Black, and Hispanic donors and correlated with regional case rates. The study has expanded to a national serosurveillance program.
Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in ...the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB.
To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance.
The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed.
A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; Dl
, 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval CI, 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio OR, 23.4; 95% CI, 6.36-86.1;
< 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR, 1.8; 95% CI, 1.08-3.01;
= 0.03). The predictors of discordance included older age, family history, and radiologic asymmetry.
Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).
Mycobacterium tuberculosis causes pulmonary tuberculosis (TB) and claims ~1.8 million human lives per annum. Host nitric oxide (NO) is important in controlling TB infection. M. tuberculosis WhiB1 is ...a NO-responsive Wbl protein (actinobacterial iron-sulfur proteins first identified in the 1970s). Until now, the structure of a Wbl protein has not been available. Here a NMR structural model of WhiB1 reveals that Wbl proteins are four-helix bundles with a core of three α-helices held together by a 4Fe-4S cluster. The iron-sulfur cluster is required for formation of a complex with the major sigma factor (σ
) and reaction with NO disassembles this complex. The WhiB1 structure suggests that loss of the iron-sulfur cluster (by nitrosylation) permits positively charged residues in the C-terminal helix to engage in DNA binding, triggering a major reprogramming of gene expression that includes components of the virulence-critical ESX-1 secretion system.
Evolution of thermally stratified open channel flow after removal of a volumetric heat source is investigated using direct numerical simulation. The heat source models radiative heating from above ...and varies with height due to progressive absorption. After removal of the heat source the initial stable stratification breaks down and the channel approaches a fully mixed isothermal state. The initial state consists of three distinct regions: a near-wall region where stratification plays only a minor role, a central region where stratification has a significant effect on flow dynamics and a near-surface region where buoyancy effects dominate. We find that a state of local energetic equilibrium observed in the central region of the channel in the initial state persists until the late stages of the destratification process. In this region local turbulence parameters such as eddy diffusivity
$k_{h}$
and flux Richardson number
$R_{f}$
are found to be functions only of the Prandtl number
$Pr$
and a mixed parameter
${\mathcal{Q}}$
, which is equal to the ratio of the local buoyancy Reynolds number
$Re_{b}$
and the friction Reynolds number
$Re_{\unicodeSTIX{x1D70F}}$
. Close to the top and bottom boundaries turbulence is also affected by
$Re_{\unicodeSTIX{x1D70F}}$
and vertical position
$z$
. In the initial heated equilibrium state the laminar surface layer is stabilised by the heat source, which acts as a potential energy sink. Removal of the heat source allows Kelvin–Helmholtz-like shear instabilities to form that lead to a rapid transition to turbulence and significantly enhance the mixing process. The destratifying flow is found to be governed by bulk parameters
$Re_{\unicodeSTIX{x1D70F}}$
,
$Pr$
and the friction Richardson number
$Ri_{\unicodeSTIX{x1D70F}}$
. The overall destratification rate
${\mathcal{D}}$
is found to be a function of
$Ri_{\unicodeSTIX{x1D70F}}$
and
$Pr$
.
AbstractThis study utilizes a detailed analysis of the first direct numerical simulation (DNS) of thermally stratified open-channel flows through idealized sine-generated meanders with varying ...sinuosity to enhance our understanding of the impact of thermal stratification on the mean flow, secondary currents, and boundary shear stresses. Four different channel sinuosities Si=(1.07,1.34,2.12,3.70) at a moderate curvature of Rmin/B=2.5 and channel aspect ratio B/H=10 with friction Reynolds number Reτ=200 in neutral and density stratified flows are presented. The results indicate that thermal stratification has a significant effect on the characteristics of the mean flow, resulting in differences in the separated shear layers and separation zones for different sinuosity, as well as in the bed and sidewall shear stress distributions for both neutral and stratified flows.
Characterisation of the dynamics of Zika virus persistence following acute infection is needed to inform blood donor and diagnostic testing policies and understand the natural history of Zika virus ...infection. We aimed to characterise the natural history, persistence, and clinical outcomes of Zika virus infection through a prospective study in initially asymptomatic Zika virus RNA-positive blood donors.
Zika virus-infected blood donors identified through Zika virus nucleic acid amplification test (NAAT) screening at three blood collection organisations in the USA were enrolled into a 1-year follow-up study, with blood and body fluid samples and detailed symptom data collected at up to seven visits. All samples were tested for Zika virus RNA by real-time PCR (rtPCR); follow-up plasma, whole blood, and urine were also tested by replicate NAAT. Plasma was tested for flavivirus-specific IgM and IgG by ELISA. Zika virus RNA persistence for each assay or sample type and plasma antibody persistence from estimated date of plasma NAAT-detectable infection were calculated from follow-up data using survival statistical methods.
Between July 6, 2016 and March 7, 2017, we enrolled 53 participants. From the estimated date of plasma NAAT-detectable infection, Zika virus RNA was detectable in plasma for 9·9 days (95% CI 8·1–12·0), in red blood cells for 95·4 days (62·8–129·1), and in whole blood for 73·5 days (39·8–107·5). Replicate NAATs (one or more of eight replicates positive) extended detection of Zika virus RNA in plasma to 34·8 days (19·9–56·2) and in whole blood (at least one of two tests positive) to 104·8 days (76·7–129·9). Urine was rtPCR reactive up to 14·5 days (10·5–20·3) and saliva up to 26·4 days (19·7–38·7). Zika virus IgM persisted for 237·7 days (128·7–459·5) from estimated time since plasma NAAT-detectable infection. Zika virus RNA fell below detectable limits more rapidly in the saliva of participants with pre-existing dengue virus IgG than in those without. Of 25 donors identified pre-seroconversion with symptom data at the first or second study visit, 16 (64%) developed multiple Zika virus-related symptoms after asymptomatic index donations, compared with nine (36%) of 25 donors detected after seroconversion.
Determination of viral marker persistence is enhanced by follow-up of blood donors who are pre-symptomatic or asymptomatic, Zika virus RNA-positive, and antibody negative. Zika virus RNA persists in red blood cells for several months following clearance from plasma and body fluids, and replicate, highly sensitive NAATs extend RNA detection in all compartments. Whole blood testing can extend detection of acute infection for diagnostics and monitoring of pregnant women, sexual partners, and travellers.
National Heart, Lung, and Blood Institute, Biomedical Advanced Research and Development Authority.
Many bacteria undergo transitions between environments with differing O₂ availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation ...when bacteria experience changes in O₂ availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process.
Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O₂ sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR.
Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O₂ combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O₂ sensor FNR during transition from anaerobic to micro-aerobic conditions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite adequate correction, the pelvis may fail to readjust, deemed pelvic nonresponse (PNR). To assess alignment outcomes PNR, proximal junctional kyphosis (PJK), postoperative cervical deformity ...(CD) following adult spinal deformity (ASD) surgery utilizing different realignment strategies.
ASD patients with two-year data were included. PNR defined as undercorrected in age-adjusted pelvic tilt (PT) at six weeks and maintained at two years. Patients classified by alignment utilities: (a) improvement in Scoliosis Research Society-Schwab sagittal vertical axis, (b) matching in age-adjusted pelvic incidence-lumbar lordosis, (c) matching in Roussouly, (d) aligning Global Alignment and Proportionality (GAP) score. Multivariable regression analyses, controlling for age, baseline deformity, and surgical factors, assessed rates of PNR, PJK, and CD development following realignment.
A total of 686 patients met the inclusion criteria. Rates of postoperative PJK and CD were not significant in the PNR group (both P >0.15). PNR patients less often met substantial clinical benefit in Oswestry Disability Index by two years odds ratio: 0.6 (0.4-0.98). Patients overcorrected in age-adjusted pelvic incidence-lumbar lordosis, matching Roussouly, or proportioned in GAP at six weeks had lower rates of PNR (all P <0.001). Incremental addition of classifications led to 0% occurrence of PNR, PJK, and CD. Stratifying by baseline PT severity, Low and moderate deformity demonstrated the least incidence of PNR (7.7%) when proportioning in GAP at six weeks, while severe PT benefited most from matching in Roussouly (all P <0.05).
Following ASD corrective surgery, 24.9% of patients showed residual pelvic malalignment. This occurrence was often accompanied by undercorrection of lumbopelvic mismatch and less improvement of pain. However, overcorrection in any strategy incurred higher rates of PJK. We recommend surgeons identify a middle ground using one, or more, of the available classifications to inform correction goals in this regard.
III.
Chikungunya virus (CHIKV) caused large epidemics throughout the Caribbean in 2014. We conducted nucleic acid amplification testing (NAAT) for CHIKV RNA (n = 29,695) and serologic testing for IgG ...against CHIKV (n = 1,232) in archived blood donor samples collected during and after an epidemic in Puerto Rico in 2014. NAAT yields peaked in October with 2.1% of donations positive for CHIKV RNA. A total of 14% of NAAT-reactive donations posed a high risk for virus transmission by transfusion because of high virus RNA copy numbers (10 (4) -10 (9) RNA copies/mL) and a lack of specific IgM and IgG responses. Testing of minipools of 16 donations would not have detected 62.5% of RNA-positive donations detectable by individual donor testing, including individual donations without IgM and IgG. Serosurveys before and after the epidemic demonstrated that nearly 25% of blood donors in Puerto Rico acquired CHIKV infections and seroconverted during the epidemic.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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