Flometrics (United States)

BackgroundRural communities were disproportionately impacted by the COVID-19 pandemic. Current and future pandemic preparedness in rural areas could be aided by serological (antibody) testing. However, benefits to be gained from serosurveillance are challenged both by the accessibility of serological testing resources in hard-to-reach rural areas, and by likely hesitancy towards their use in many rural communities. Trials are needed to evaluate outreach and health communication strategies that can increase rural receptivity towards serosurveillance.MethodsWe conducted a two-arm randomized controlled trial that recruited N = 194 participants from rural northern Michigan. In a single online session lasting approximately 45 min, participants were randomly assigned to view either a general SARS-CoV-2 antibody testing didactic video, or a rural targeted didactic video co-created with a rural community advisory board and containing unique rural messaging. Primary self-report outcomes included receptivity to antibody testing, as well as activation of medical mistrust and concern for rural-discrimination in future SARS-CoV-2 antibody testing. We also developed and provided an opportunity to participate in a home-based salivary antibody screening program. In addition to assessing the feasibility and fidelity of this program, we assessed interest and full participation in the serosurveillance program as behavioral outcomes.DiscussionFindings from this study can guide the use of home-based screening programs and targeted health communication strategies to promote greater uptake of health resources in rural communities. In doing so, study results can also guide public health strategies to reduce pandemic-related and other rural health disparities.

The high variability in efficacy and safety of antichagasic chemotherapy involving benznidazole (BNZ) may be due to pharmacokinetic-related factors. The study evaluated the impact of experimental acute and chronic infections by the Berenice-78 strain of Trypanosoma cruzi on the pharmacokinetics of BNZ in dogs. Twenty-seven mongrel dogs were divided into the following groups: acute infection state treated with BNZ, chronic infection state treated with BNZ, acute and chronic positive controls (not treated with BNZ), and a healthy group treated with BNZ. They were evaluated at (1) basal state, (2) during infection without treatment, for cytokines panel (IL-6, interferon γ (IFN-γ), IL-10 and tumor necrosis factor α (TNF-α)) evaluation, and (3) during BNZ steady-state levels at 10, 30, 40, and 60 days after start of treatment with oral BNZ 3.5 mg/kg b.i.d. administration, in acute and chronic T. cruzi-infection, for BNZ pharmacokinetics and cytokines panel evaluation, and (4) 30 days after BNZ treatment end for cytokines evaluation. BNZ levels in serum samples were quantified using a curve range of 0.1-100 μg/mL in plasma by high-performance liquid chromatography with diode array detection (HPLC-DAD) analysis. Pharmacokinetic parameters remained stable during treatment phases, indicating no autoinduction or inhibition. Acute infection pharmacokinetics resembled that of healthy controls. Chronic infection significantly increased C max, C ss, and AUC0-12, while decreasing Vd/F and CL/F compared to both healthy and acute groups. Notably, IL-6 levels were elevated ∼7-fold during chronic infection. These data suggest that chronic inflammatory status modulates BNZ disposition, likely via IL-6 mediated P-glycoprotein inhibition. Understanding these pharmacokinetic changes is critical for optimizing BNZ dosing strategies in Chagas disease management.

The Planetary Boundaries framework, published in 2009 and updated in 2015 and 2023, proposes limits for nine environmental processes, which should not be transgressed to maintain the stability and resilience of the Earth system. To operationalize the Planetary Boundaries, these must be translated to lower scales, such as countries, suitable for action. This article reviews the allocation principles and methods enabling the quantification of fair limits and ultimately the assessment of performance at the country level. Based on a literature review, we synthesize six steps and six allocation principles applicable to translating the Planetary Boundaries at a country scale. We conclude that computing national shares based on multiple allocation principles for Planetary Boundaries remains a considerable challenge that does not preclude, however, discussions about the insights gained in terms of possible priorities. In its current status, the quantification of limits can and should support transparent political discussions on concrete and urgent commitments to maintain a well-functioning Earth system for humankind.

Background: In-vivo CRISPR Cas genome editing is a complex therapy involving lipid nanoparticle (LNP), messenger RNA (mRNA), and single guide RNA (sgRNA). This novel modality requires prior modeling to predict dose-exposure-response relationships due to limited information on sgRNA and mRNA biodistribution. This work presents a QSP model to characterize, predict, and translate the Pharmacokinetics/Pharmacodynamics (PK/PD) of CRISPR therapies from preclinical species (mouse, non-human primate (NHP)) to humans using two case studies: transthyretin amyloidosis and LDL-cholesterol reduction. Methods: PK/PD data were sourced from literature. The QSP model incorporates mechanisms post-IV injection: 1) LNP binding to opsonins in liver vasculature; 2) Phagocytosis into the Mononuclear Phagocytotic System (MPS); 3) LNP internalization via endocytosis and LDL receptor-mediated endocytosis in the liver; 4) Cellular internalization and transgene product release; 5) mRNA and sgRNA disposition via exocytosis and clathrin-mediated endocytosis; 6) Renal elimination of LNP and sgRNA; 7) Exonuclease degradation of sgRNA and mRNA; 8) mRNA translation into Cas9 and RNP complex formation for gene editing. Monte-Carlo simulations were performed for 1000 subjects and showed a reduction in serum TTR. Results: The rate of internalization in interstitial layer was 0.039 1/h in NHP and 0.007 1/h in humans. The rate of exocytosis was 6.84 1/h in mouse, 2690 1/h in NHP, and 775 1/h in humans. Pharmacodynamics were modeled using an indirect response model, estimating first-order degradation rate (0.493 1/d) and TTR reduction parameters in NHP. Discussion: The QSP model effectively characterized biodistribution and dose-exposure relationships, aiding the development of these novel therapies. The utility of platform QSP model can be paramount in facilitating the discovery and development of these novel agents.

High‐dimensional single‐cell data has become an important tool in unraveling the complexity of the immune system and its involvement in homeostasis and a large array of pathologies. As technological tools are developed, researchers are adopting them to answer increasingly complex biological questions. Up until recently, mass cytometry (MC) has been the main technology employed in cytometric assays requiring more than 29 markers. Recently, however, with the introduction of full spectrum flow cytometry (FSFC), it has become possible to break the fluorescence barrier and go beyond 29 fluorescent parameters. In this study, in collaboration with the Stanford Human Immune Monitoring Center (HIMC), we compared five patient samples using an established immune panel developed by the HIMC using their MC platform. Using split samples and the same antibody panel, we were able to demonstrate highly comparable results between the two technologies using multiple data analysis approaches. We report here a direct comparison of two technology platforms (MC and FSFC) using a 32‐marker flow cytometric immune monitoring panel that can identify all the previously described and anticipated immune subpopulations defined by this panel.

<p>Nanometrics' Pegasus digitizer is the basis for a scientific grade node and is the latest development in many years of designing and building reliable seismic instruments for the scientific and monitoring community. Coupled in a grab-and-go quick deploy package with a variety of sensors enables responses to many types of events and environmental measurements. These types of systems are not only for hazards, such as earthquakes and volcanoes, but can form the basis of better tools used for critical structure and microzonation studies using ambient noise.  Pegasus takes advantage of a complete ecosystem of software, making planning, deploying and data harvesting very simple and straightforward as well as providing a dataset that includes automatically generated metadata in the form of StationXML and standard miniSEED data files.  Pegasus design criteria was based on optimal SWaP (Size, Weight and Power) and makes it unique in short to long duration deployments without swapping of units in the field, while its broad sensor compatibility enables many types of measurements and is completely compatible with the advantages of Nanometrics smart sensors.</p>

Summary Over the past decades, it can be observed that several development of seismic methods utilizing the ambient noise is made. It is relatively important to have adequate information of the subsurface profile in geotechnical construction activities. A passive surface wave method, ambient noise tomography was used to delineate the geological profile for geotechnical engineering purpose at northern Singapore. Two linear array configuration measurement lines were deployed in geophone-interval spaced 5m, and the measurement was carried out at night time to avoid heavy traffic. Common midpoint spatial autocorrelation (CMP-SPAC) method was used to process ambient noise acquired. With the calibration to several borehole logs nearby, the subsurface stratigraphy along the proposed tunnel alignment was mapped and delineated. The Backfill and Kallang Formation modeled at the lowest S-wave velocity (Vs) ranges from 160m/s to 200m/s, residual soil and Bukit Timah Granite (GIV) ranges from 200m/s to 360m/s while Bukit Timah Granite (GIII) with Vs > 360m/s. The Vs-to-geological layer is almost similar in both measurement lines. This paper summarizes, the site of investigation, data acquisition, processing and investigation results.

PURPOSE AND APPROPRIATE SAMPLE TYPESThis 40‐color flow cytometry‐based panel was developed for in‐depth immunophenotyping of the major cell subsets present in human peripheral blood. Sample availability can often be limited, especially in cases of clinical trial material, when multiple types of testing are required from a single sample or timepoint. Maximizing the amount of information that can be obtained from a single sample not only provides more in‐depth characterization of the immune system but also serves to address the issue of limited sample availability. The panel presented here identifies CD4 T cells, CD8 T cells, regulatory T cells, γδ T cells, NKT‐like cells, B cells, NK cells, monocytes and dendritic cells. For each specific cell type, the panel includes markers for further characterization by including a selection of activation and differentiation markers, as well as chemokine receptors. Moreover, the combination of multiple markers in one tube might lead to the discovery of new immune phenotypes and their relevance in certain diseases. Of note, this panel was designed to include only surface markers to avoid the need for fixation and permeabilization steps. The panel can be used for studies aimed at characterizing the immune response in the context of infectious or autoimmune diseases, monitoring cancer patients on immuno‐ or chemotherapy, and discovery of unique and targetable biomarkers. Different from all previously published OMIPs, this panel was developed using a full spectrum flow cytometer, a technology that has allowed the effective use of 40 fluorescent markers in a single panel. The panel was developed using cryopreserved human peripheral blood mononuclear cells (PBMC) from healthy adults (Table 1). Although we have not tested the panel on fresh PBMCs or whole blood, it is anticipated that the panel could be used in those sample preparations without further optimization. @ 2020 Cytek Biosciences, Inc. Cytometry Part A published by Wiley Periodicals LLC on behalf of International Society for Advancement of Cytometry.