Patterns of SARS-CoV-2 circulation revealed by a nationwide sewage surveillance programme, the Netherlands, August 2020 to February 2022

BackgroundSurveillance of SARS-CoV-2 in wastewater offers a near real-time tool to track circulation of SARS-CoV-2 at a local scale. However, individual measurements of SARS-CoV-2 in sewage are noisy, inherently variable and can be left-censored.AimWe aimed to infer latent virus loads in a comprehensive sewage surveillance programme that includes all sewage treatment plants (STPs) in the Netherlands and covers 99.6% of the Dutch population.MethodsWe applied a multilevel Bayesian penalised spline model to estimate time- and STP-specific virus loads based on water flow-adjusted SARS-CoV-2 qRT-PCR data for one to four sewage samples per week for each of the more than 300 STPs.ResultsThe model captured the epidemic upsurges and downturns in the Netherlands, despite substantial day-to-day variation in the measurements. Estimated STP virus loads varied by more than two orders of magnitude, from ca 1012 virus particles per 100,000 persons per day in the epidemic trough in August 2020 to almost 1015 per 100,000 in many STPs in January 2022. The timing of epidemics at the local level was slightly shifted between STPs and municipalities, which resulted in less pronounced peaks and troughs at the national level.ConclusionAlthough substantial day-to-day variation is observed in virus load measurements, wastewater-based surveillance of SARS-CoV-2 that is performed at high sampling frequency can track long-term progression of an epidemic at a local scale in near real time

Integrated MicroRNA-mRNA-Analysis of Human Monocyte Derived Macrophages upon Mycobacterium avium subsp. hominissuis Infection

Many efforts have been made to understand basal mechanisms of mycobacterial infections. Macrophages are the first line of host immune defence to encounter and eradicate mycobacteria. Pathogenic species have evolved different mechanisms to evade host response, e.g. by influencing macrophage apoptotic pathways. However, the underlying molecular regulation is not fully understood. A new layer of eukaryotic regulation of gene expression is constituted by microRNAs. Therefore, we present a comprehensive study for identification of these key regulators and their targets in the context of host macrophage response to mycobacterial infections.We performed microRNA as well as mRNA expression analysis of human monocyte derived macrophages infected with several Mycobacterium avium hominissuis strains by means of microarrays as well as quantitative reverse transcription PCR (qRT-PCR). The data revealed the ability of all strains to inhibit apoptosis by transcriptional regulation of BCL2 family members. Accordingly, at 48 h after infection macrophages infected with all M. avium strains showed significantly decreased caspase 3 and 7 activities compared to the controls. Expression of let-7e, miR-29a and miR-886-5p were increased in response to mycobacterial infection at 48 h. The integrated analysis of microRNA and mRNA expression as well as target prediction pointed out regulative networks identifying caspase 3 and 7 as potential targets of let-7e and miR-29a, respectively. Consecutive reporter assays verified the regulation of caspase 3 and 7 by these microRNAs.We show for the first time that mycobacterial infection of human macrophages causes a specific microRNA response. We furthermore outlined a regulatory network of potential interactions between microRNAs and mRNAs. This study provides a theoretical concept for unveiling how distinct mycobacteria could manipulate host cell response. In addition, functional relevance was confirmed by uncovering the control of major caspases 3 and 7 by let-7e and miR-29a, respectively

Detection of radioactivity of unknown origin: Protective actions based on inverse modelling.

The detection of radioactivity of unknown origin necessitates the use of models that can quantify unknown corresponding source term parameters. In this work, a method for solving this inverse problem is described. The main goal of the method is that it can be used in emergency response. Therefore, the full modelling chain dealing with the collection and pre-processing of measurement data, source term estimation, (forward) dispersion modelling, and consequence assessment are discussed. Firstly, to verify this inverse model SHERLOC, the part of the modelling chain concerning the source term estimation based on measurement data, is applied to the first episode of the European Tracer Experiment (ETEX). Secondly, the complete model chain is applied to a release that is still unaccounted for; the 106Ru measured in the atmosphere of Europe in September and October of 2017. It is estimated that during the night of the 25th to the 26th of September 2017 approximately 1.33 PBq (1.33×1015 Bq) of 106Ru was emitted at a location in the region of the Southern Urals in the Russian Federation. Statistical indicators show that the modelled levels of concentration are in good agreement with the measurements. The radiological consequences of the release are estimated to be minor at distances farther than 22 km from the estimated source. However, in the vicinity of the emission the maximum committed dose received by the public may have exceeded 100 mSv. Since the presented approach can be executed within few hours after the collection of measurement data it can be used in the emergency response following the detection of radioactivity of unknown origin

Accurate Blood Flow Measurements: Are Artificial Tracers Necessary?

Imaging-based blood flow measurement techniques, such as particle image velocimetry, have become an important tool in cardiovascular research. They provide quantitative information about blood flow, which benefits applications ranging from developmental biology to tumor perfusion studies. Studies using these methods can be classified based on whether they use artificial tracers or red blood cells to visualize the fluid motion. We here present the first direct comparison in vivo of both methods. For high magnification cases, the experiments using red blood cells strongly underestimate the flow (up to 50% in the present case), as compared to the tracer results. For medium magnification cases, the results from both methods are indistinguishable as they give the same underestimation of the real velocities (approximately 33%, based on in vitro reference measurements). These results suggest that flow characteristics reported in literature cannot be compared without a careful evaluation of the imaging characteristics. A method to predict the expected flow averaging behavior for a particular facility is presented.Process and EnergyMechanical, Maritime and Materials Engineerin

Schematic diagrams of studied structural parameters are shown for clarity.

<p>These parameters are: the tortuosity , the angle between the vessel segment and the main flow direction , the arterial branching angle , the venous branching angle , and Murray’s law ratio for both arterial and venous branches and .</p

Statistics of the relative flow balance for every embryo.

<p>The statistics of the relative flow balance 100% are presented for every embryo for both measurement series (T1 and T2): mean , standard daviation , and the percentage of outliers holding . These parameters are presented for both the total available data set listed under ‘all diameters’, and the selected data set containing only vessel segments with diameters larger than 5 times the spatial resolution (corresponding to 52 <i>μ</i>m, listed under ‘large diameters’).</p

The variety in time-averaged mean velocities for all vessel segment diameters are shown for two consecutive measurements T1 and T2.

<p>For three vessel segments (I, II, and III, indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096856#pone-0096856-g008" target="_blank">Figure 8</a>), the changes in diameter and time-averaged velocity from T1 tot T2 are indicated by the dashed arrows. The cross-sectional velocity profiles shown for three data points (A, B, and C, indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0096856#pone-0096856-g008" target="_blank">Figure 8</a>) show consistency despite the different time-averaged velocities.</p

Distributions of the characteristic hemodynamic parameters for every embryo.

<p>For every embryo, the distributions of the characteristic diameter <i>D</i>, characteristic time-averaged velocity , and characteristic length <i>L</i> of the vessel segments are respresented by the 25%–50%–75% percentiles for both measurement series T1 and T2.</p