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Background: Laboratory networks provide services through onsite testing or through specimen transport to higher-tier laboratories. This decision is based on the interplay of testing characteristics, treatment characteristics, and epidemiological characteristics. Objectives: Our objective was to develop a generalizable model using the threshold approach to medical decision making to inform test placement decisions. Methods: We developed a decision model to compare the incremental utility of onsite versus send-out testing for clinical purposes. We then performed Monte Carlo simulations to identify the settings under which each strategy would be preferred. Tuberculosis was modeled as an exemplar. Results: The most important determinants of the decision to test onsite versus send-out were the clinical utility lost due to send-out testing delays and the accuracy decrement with onsite testing. When the sensitivity decrements of onsite testing were minimal, onsite testing tended to be preferred when send-out delays reduced clinical utility by >20%. By contrast, when onsite testing incurred large reductions in sensitivity, onsite testing tended to be preferred when utility lost due to delays was >50%. The relative cost of onsite versus send-out testing affected these thresholds, particularly when testing costs were >10% of treatment costs. Conclusions: Decision makers can select onsite versus send-out testing in an evidence-based fashion using estimates of the percentage of clinical utility lost due to send-out delays and the relative accuracy of onsite versus send-out testing. This model is designed to be generalizable to a wide variety of use cases. Highlights: The design of laboratory networks, including the decision to place diagnostic instruments at the point-of-care or at higher tiers as accessed through specimen transport, can be informed using the threshold approach to medical decision making. The most important determinants of the decision to test onsite versus send-out were the clinical utility lost due to send-out testing delays and the accuracy decrement with onsite testing. The threshold approach to medical decision making can be used to compare point-of-care testing accuracy decrements with the lost utility of treatment due to send-out testing delays. The relative cost of onsite versus send-out testing affected these thresholds, particularly when testing costs were >10% of treatment costs. [ABSTRACT FROM AUTHOR]

Tools from molecular biology, combined with in vivo optical imaging techniques, provide new mechanisms for noninvasively observing brain processes. Current approaches primarily probe cell-based variables, such as cytosolic calcium or membrane potential, but not cell-to-cell signaling. We devised cell-based neurotransmitter fluorescent engineered reporters (CNiFERs) to address this challenge and monitor in situ neurotransmitter receptor activation. CNiFERs are cultured cells that are engineered to express a chosen metabotropic receptor, use the G(q) protein-coupled receptor cascade to transform receptor activity into a rise in cytosolic [Ca(2+)] and report [Ca(2+)] with a genetically encoded fluorescent Ca(2+) sensor. The initial realization of CNiFERs detected acetylcholine release via activation of M1 muscarinic receptors. We used chronic implantation of M1-CNiFERs in frontal cortex of the adult rat to elucidate the muscarinic action of the atypical neuroleptics clozapine and olanzapine. We found that these drugs potently inhibited in situ muscarinic receptor activity.

Background: Diagnostic sensitivities of point-of-care SARS-CoV-2 assays depend on specimen type and population-specific viral loads. Evaluation of these assays require "direct" specimens from paired-swab studies rather than more accessible residual specimens in viral transport media (VTM). Methods: Residual VTM and limit-of-detection studies were conducted on Abbott ID NOW™ COVID-19, Quidel Sofia 2™ SARS Antigen FIA, and DiaSorin Simplexa™ COVID-19 Direct assays, with cycle threshold (CT) adjustments to approximate direct-specimen testing based on gene-target doubling each PCR cycle. Logistic regression was used to model assay performance by specimen CT. These models were applied to CT distributions of symptomatic and asymptomatic populations presenting to emergency services to predict the percentage of specimens that would be detected by each assay. A 96-sample paired-swab study was conducted to confirm model results. Results: When using direct nasopharyngeal samples and fit with either VTM or limit-of-detection data, percent positivities for ID NOW (symptomatic 94.9%/97.4%; asymptomatic 88.4.0%/89.6%) and Simplexa (symptomatic 97.8%/97.2%; asymptomatic 91.1%/90.8%) were predicted to be similar. Likewise, percent positivities for ID NOW with direct nasal specimens (symptomatic 77.8%; asymptomatic 64.5%) and, fit with VTM data, Sofia 2 with direct nasopharyngeal specimens (symptomatic 76.6%, asymptomatic 60.3%) were similar. The paired-swab study comparing direct nasopharyngeal specimens on ID NOW and nasopharyngeal VTM specimens on Simplexa showed 99% concordance. Conclusions: Assay performance can be modeled as dependent on viral load, fit using laboratory bench study results, and adjusted to account for direct-specimen testing. When using nasopharyngeal specimens, direct testing on Abbott ID NOW and VTM testing on DiaSorin Simplexa have similar performance. [ABSTRACT FROM AUTHOR]

Objectives: Serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has experienced a changing landscape of available assays coupled with uncertainty surrounding performance characteristics. Studies are needed to directly compare multiple commercially available assays.Methods: Residual serum samples were identified based on SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing, clinical test results, and collection dates. Serum samples were analyzed using assays from four different manufacturers: DiaSorin anti-SARS-CoV-2 S1/S2 IgG, EUROIMMUN anti-SARS-CoV-2 IgG ELISA, Roche Elecsys anti-SARS-CoV-2, and Siemens SARS-CoV-2 Total antibody assays.Results: Samples from SARS-CoV-2 RT-PCR-positive patients became increasingly positive as time from symptom onset increased. For patients with latest sample 14 or more days after symptom onset, sensitivities reached 93.1% to 96.6%, 98.3%, and 96.6% for EUROIMMUN, Roche, and Siemens assays, respectively, which were superior to the DiaSorin assay at 87.7%. The specificity of Roche and Siemens assays was 100% and superior to DiaSorin and EUROIMMUN assays, which ranged from 96.1% to 97.0% and 86.3% to 96.4%, respectively.Conclusions: Laboratories should be aware of the advantages and limitations of serology testing options for SARS-CoV-2. The specificity and sensitivity achieved by the Roche and Siemens assays would be acceptable for testing in lower-prevalence regions and have the potential of orthogonal testing advantages if used in combination. [ABSTRACT FROM AUTHOR]

The article focuses on three approaches to creating an essential diagnostics list.