•An Eulerian sectional aerosol model is applied to simulation of aerosol deposition.•Arbitrary polydispersity is accounted for by the sectional formulation.•Both diffusional and inertial aerosol ...deposition are modeled.•Good agreement with literature is found for deposition inside a bent pipe.•Dependence of deposition on the Reynolds number and curvature ratio is shown.
This paper presents a sectional Eulerian aerosol model for size-dependent droplet deposition at walls of the domain, driven by both diffusion and inertia. The model is based on the internally mixed assumption and employs the formulation for compressible aerosols. It is validated in a bent pipe geometry against models and experimental and numerical data from literature. Good agreement is found in both the diffusion and inertial deposition regimes. To improve the overprediction of inertial deposition by a boundary treatment that adopts zero-gradient droplet wall velocity, we use a corrected wall velocity, based on an analytical solution of the droplet motion near the wall. In the bent pipe setting the corrected wall velocity is found to reduce the overprediction of deposition and is less sensitive to grid refinement. We also show that refining the computational mesh near the pipe wall improves the predicted deposition efficiency, significantly. Finally, we present a parameter study varying the Reynolds number and the bend curvature. The deposition efficiency curve is recorded for droplet diameters ranging from the nanometer scale to beyond the micrometer scale, which is a unique contribution of this paper. The complete size range is simulated in only one simulation, due to the sectional approach. In the diffusion-dominated regime an increase in Reynolds number leads to a gradual enhancement of deposition. In the inertial regime, where droplet drift dominates deposition, a much stronger dependence on the Reynolds number is found. The dependence of the deposition on the bend curvature is less pronounced. The results shown in this paper establish the role of Eulerian simulation in predicting deposition of aerosol droplets and are useful for understanding size-dependent aerosol deposition in other more complex confined geometries.
The serotonin 1B (5-HT1B) receptor has lately received considerable interest in relation to psychiatric and neurological diseases, partly due to findings based on quantification using Positron ...Emission Tomography (PET). Although the brainstem is an important structure in this regard, PET radioligand binding quantification in brainstem areas often shows poor reliability. This study aims to improve PET quantification of 5-HT1B receptor binding in the brainstem.
Volumes of interest (VOIs) were selected based on a 3D 3HAZ10419369 Autoradiography brainstem model, which visualized 5-HT1B receptor distribution in high resolution. Two previously developed VOI delineation methods were tested and compared to a conventional manual method. For a method based on template data, a 11CAZ10419369 PET template was created by averaging parametric binding potential (BPND) images of 52 healthy subjects. VOIs were generated based on a predefined volume and BPND thresholding and subsequently applied to test-retest 11CAZ10419369 parametric BPND images of 8 healthy subjects. For a method based on individual subject data, VOIs were generated directly on each individual parametric image.
Both methods showed improved reliability compared to a conventional manual VOI. The VOIs created with 11CAZ10419369 template data can be automatically applied to future PET studies measuring 5-HT1B receptor binding in the brainstem.
Abstract
Background
The serotonin system has been implicated in several psychiatric disorders. All major psychiatric disorders are associated with cognitive impairment, but treatment improving ...cognitive deficits is lacking, partly due to limited understanding of the neurobiology of cognitive functioning. Several markers for the serotonin system have been associated with cognitive functions. Our research group previously has reported a positive correlation between serotonin (5-HT1B) receptor availability in the dorsal brainstem and visuospatial memory in a pilot study of healthy individuals. Here, we aim to replicate our previous finding in a larger group of healthy volunteers as well as to investigate putative associations between 5-HT1B receptor availability and other cognitive domains.
Methods
Forty-three healthy individuals were examined with positron emission tomography using the 5-HT1B receptor radioligand 11CAZ10419369 and a visuospatial memory test to replicate our previous finding as well as tests of verbal fluency, cognitive flexibility, reaction time, and planning ability to explore other domains potentially associated with the serotonin system.
Results
Replication analysis revealed no statistically significant association between 5-HT1B receptor availability in the dorsal brainstem and visuospatial memory performance. Exploratory analyses showed age-adjusted correlations between 5-HT1B receptor availability in whole brain gray matter and specific brain regions, and number of commission errors, reaction time, and planning ability.
Conclusions
Higher 5-HT1B receptor availability was associated with more false-positive responses and faster reaction time but lower performance in planning and problem-solving. These results corroborate previous research supporting an important role of the serotonin system in impulsive behavior and planning ability.
In radiotherapy, respiratory-induced tumor motion is typically measured using a single four-dimensional computed tomography acquisition (4DCT). Irregular breathing leads to inaccurate motion ...estimates, potentially resulting in undertreatment of the tumor and unnecessary dose to healthy tissue. The aim of the research was to determine if a daily pre-treatment 4DMRI-strategy led to a significantly improved motion estimate compared to single planning 4DMRI (with or without outlier rejection).
4DMRI data sets from 10 healthy volunteers were acquired. The first acquisition simulated a planning MRI, the respiratory motion estimate (constructed from the respiratory signal, i.e. the 1D navigator) was compared to the respiratory signal in the subsequent scans (simulating 5-29 treatment fractions). The same procedure was performed using the first acquisition of each day as an estimate for the subsequent acquisitions that day (2 per day, 4-20 per volunteer), simulating a daily MRI strategy. This was done for three outlier strategies: no outlier rejection (NoOR); excluding 5% of the respiratory signal whilst minimizing the range (Min95) and excluding the datapoints outside the mean end-inhalation and end-exhalation positions (MeanIE).
The planning MRI median motion estimates were 27 mm for NoOR, 18 mm for Min95, and 13 mm for MeanIE. The daily MRI median motion estimates were 29 mm for NoOR, 19 mm for Min95 and 15 mm for MeanIE. The percentage of time outside the motion estimate were for the planning MRI: 2%, 10% and 32% for NoOR, Min95 and MeanIE respectively. These values were reduced with the daily MRI strategy: 0%, 6% and 17%. Applying Min95 accounted for a 30% decrease in motion estimate compared to NoOR.
A daily MRI improved the estimation of respiratory motion as compared to a single 4D (planning) MRI significantly. Combining the Min95 technique with a daily 4DMRI resulted in a decrease of inclusion time of 6% with a 30% decrease of motion. Outlier rejection alone on a planning MRI often led to underestimation of the movement and could potentially lead to an underdosage.
protocol W15_373#16.007.
Acute respiratory infections caused by bacterial or viral pathogens are among the most common reasons for seeking medical care. Despite improvements in pathogen-based diagnostics, most patients ...receive inappropriate antibiotics. Host response biomarkers offer an alternative diagnostic approach to direct antimicrobial use. This observational cohort study determined whether host gene expression patterns discriminate noninfectious from infectious illness and bacterial from viral causes of acute respiratory infection in the acute care setting. Peripheral whole blood gene expression from 273 subjects with community-onset acute respiratory infection (ARI) or noninfectious illness, as well as 44 healthy controls, was measured using microarrays. Sparse logistic regression was used to develop classifiers for bacterial ARI (71 probes), viral ARI (33 probes), or a noninfectious cause of illness (26 probes). Overall accuracy was 87% (238 of 273 concordant with clinical adjudication), which was more accurate than procalcitonin (78%, P < 0.03) and three published classifiers of bacterial versus viral infection (78 to 83%). The classifiers developed here externally validated in five publicly available data sets (AUC, 0.90 to 0.99). A sixth publicly available data set included 25 patients with co-identification of bacterial and viral pathogens. Applying the ARI classifiers defined four distinct groups: a host response to bacterial ARI, viral ARI, coinfection, and neither a bacterial nor a viral response. These findings create an opportunity to develop and use host gene expression classifiers as diagnostic platforms to combat inappropriate antibiotic use and emerging antibiotic resistance.
To investigate the occurrence and characteristics of extended-spectrum β-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae isolates in clinical samples of companion animals and horses and ...compare the results with ESBL/AmpC-producing isolates described in humans. Between October 2007 and August 2009, 2700 Enterobacteriaceae derived from clinical infections in companion animals and horses were collected. Isolates displaying inhibition zones of ≤25 mm for ceftiofur and/or cefquinome by disc diffusion were included. ESBL/AmpC production was confirmed by combination disc tests. The presence of resistance genes was identified by microarray, PCR and sequencing, Escherichia coli genotypes by multilocus sequence typing and antimicrobial susceptibility by broth microdilution. Sixty-five isolates from dogs (n = 38), cats (n = 14), horses (n = 12) and a turtle were included. Six Enterobacteriaceae species were observed, mostly derived from urinary tract infections (n = 32). All except 10 isolates tested resistant to cefotaxime and ceftazidime by broth microdilution using clinical breakpoints. ESBL/AmpC genes observed were blaCTX-M-1, -2, -9, -14, -15, blaTEM-52, blaCMY-2 and blaCMY-39. blaCTX-M-1 was predominant (n = 17). blaCTX-M-9 occurred in combination with qnrA1 in 3 of the 11 Enterobacter cloacae isolates. Twenty-eight different E. coli sequence types (STs) were found. E. coli carrying blaCTX-M-1 belonged to 13 STs of which 3 were previously described in Dutch poultry and patients. This is the first study among a large collection of Dutch companion animals and horses characterizing ESBL/AmpC-producing isolates. A similarity in resistance genes and E. coli STs among these isolates and isolates from Dutch poultry and humans may suggest exchange of resistance between different reservoirs.
Non-typhoid Salmonella (NTS) may invade beyond the intestine, causing bacteraemia, sepsis, and infection of normally sterile sites. The epidemiology of invasive NTS (iNTS) infection is ...under-researched. We determined trends, risk factors, serotype distribution, antimicrobial resistance (AMR), and attributable sources of iNTS infection in a high-income setting.
22,837 records of culture-confirmed human salmonellosis cases and 10,008 serotyped Salmonella isolates from five putative animal reservoirs (pigs, cattle, broilers, layers, reptiles) in the Netherlands during 2005–2018 were retrieved from national surveillance registries. Risk factors for iNTS infection were identified using logistic regression analysis. Source attribution modelling was based on serotyping, prevalence, and exposure data.
The average annual percentage of iNTS infections was 4.6% (range 3.5–5.7%). An increase in iNTS infections was observed since 2012 (odds ratio (OR) 1.09, 95% confidence interval (95% CI) 1.04–1.14). Increased iNTS infection risk was associated with wintertime (OR 1.37, 95% CI 1.12–1.66), male sex (OR 1.73, 95% CI 1.51–1.99), older age (ORs: 3.27 to 16.33, depending on age groups), and living in rural areas (OR 1.54, 95% CI 1.23–1.93). While 52% of iNTS infections (n = 950) were caused by serotypes Enteritidis and Typhimurium, those displaying the highest invasiveness relative to their occurrence were Dublin (32.9%, n = 163), Panama (21.6%, n = 106), and Poona (14.1%, n = 71). Cattle were a larger source of iNTS than non-iNTS infections (12.2% vs. 7.6%). Lower AMR and multi-resistance rates were observed among iNTS (37.9%) than non-iNTS isolates (48.6%).
The increase in iNTS infections, which is reported also in other countries, is of public health and clinical concern. The underlying reasons seem to be multi-factorial in nature. iNTS infection risk depends more on the infecting serotypes and patient demographics, and less on the attributable reservoirs and AMR profiles.
To investigate the occurrence and characteristics of extended-spectrum β-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae isolates in clinical samples of companion animals and horses and ...compare the results with ESBL/AmpC-producing isolates described in humans.
Between October 2007 and August 2009, 2700 Enterobacteriaceae derived from clinical infections in companion animals and horses were collected. Isolates displaying inhibition zones of ≤ 25 mm for ceftiofur and/or cefquinome by disc diffusion were included. ESBL/AmpC production was confirmed by combination disc tests. The presence of resistance genes was identified by microarray, PCR and sequencing, Escherichia coli genotypes by multilocus sequence typing and antimicrobial susceptibility by broth microdilution.
Sixty-five isolates from dogs (n = 38), cats (n = 14), horses (n = 12) and a turtle were included. Six Enterobacteriaceae species were observed, mostly derived from urinary tract infections (n = 32). All except 10 isolates tested resistant to cefotaxime and ceftazidime by broth microdilution using clinical breakpoints. ESBL/AmpC genes observed were bla(CTX-M-1, -2, -9, -14, -15,) bla(TEM-52), bla(CMY-2) and bla(CMY-)(39). bla(CTX-M-1) was predominant (n = 17). bla(CTX-M-9) occurred in combination with qnrA1 in 3 of the 11 Enterobacter cloacae isolates. Twenty-eight different E. coli sequence types (STs) were found. E. coli carrying bla(CTX-M-1) belonged to 13 STs of which 3 were previously described in Dutch poultry and patients.
This is the first study among a large collection of Dutch companion animals and horses characterizing ESBL/AmpC-producing isolates. A similarity in resistance genes and E. coli STs among these isolates and isolates from Dutch poultry and humans may suggest exchange of resistance between different reservoirs.
Essentials
AFSTYLA exhibits ≈50% underestimation in activity when the one‐stage (OS) assay is utilized.
A field study compared the performance of AFSTYLA with Advate in factor VIII activity assays.
...AFSTYLA activity can be monitored with both the chromogenic substrate and the OS assay.
The consistent OS underestimation allows for a conversion factor to be applied to OS results.
Summary
Introduction
AFSTYLA (antihemophilic factor recombinant single chain) is a novel B‐domain truncated recombinant factor VIII (rFVIII). For AFSTYLA, an approximate 50% discrepancy was observed between results of the one‐stage (OS) and chromogenic substrate (ChS) FVIII activity assays. An investigation was undertaken to test whether there is a linear relationship between ChS and OS assay results that would allow reliable clinical interpretation of results independent of the assay method used.
Aims
To provide confidence in future clinical monitoring, this field study investigated the performance of AFSTYLA and a full‐length rFVIII (Advate®) in FVIII activity assays routinely performed in clinical laboratories.
Methods
The comparison of AFSTYLA and Advate was performed in an international, multicenter and blinded field study of simulated post‐infusion samples. The study documented the extent of variability between methods and laboratories and characterized the relationship between the ChS and OS assays.
Results
Results from 23 laboratories demonstrate that intra and interlaboratory variability in OS assays were similar for both products. When comparing within the OS assay format, there was a similar and reagent‐correlated variability in response to different activators for both AFSTYLA and Advate. The OS underestimation was highly predictable and consistent across the complete range of FVIII plasma concentrations.
Conclusion
Post‐infusion plasma AFSTYLA levels can be monitored in patients by the OS and ChS assays. The consistent and predictable difference between the two assay formats provides clinicians with adequate guidance on how to interpret the results of the OS assay using a single conversion factor.
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