Tracheal Burning from Hot Air Inhalation

Burns in the trachea from inhaling hot gases are a common occurrence and threaten the recovery of fire victims. Inhalation injury is also one of the most common causes of death, especially among children and the elderly. The thermal injury to the respiratory tract is usually limited to the upper respiratory tract, mainly the trachea. A better understanding of the interplay between transient temperature and injury distribution over the trachea may help to direct treatments in the future. Our goal is to model burns in tracheal tissue as a function of time, inhalation temperature, and inhalation velocity. The objective is to understand how variations in those variables affect tracheal injury. The velocity of air in the trachea varies as a function of time due to inspiration and expiration. As a result, the air temperature fluctuates in a cyclical manner. Since the burn concentration is a function of temperature, the extent of the burn rises as temperature increases with inspiration and remains constant as temperature decreases during expiration. Our model shows burn concentration is limited to the entrance to the trachea and the surface of the trachea

Optimizing Two-Color Semiconductor Nanocrystal Immunoassays in Single Well Microtiter Plate Formats

The simultaneous detection of two analytes, chicken IgY (IgG) and Staphylococcal enterotoxin B (SEB), in the single well of a 96-well plate is demonstrated using luminescent semiconductor quantum dot nanocrystal (NC) tracers. The NC-labeled antibodies were prepared via sulfhydryl-reactive chemistry using a facile protocol that took <3 h. Dose response curves for each target were evaluated in a single immunoassay format and compared to Cy5, a fluorophore commonly used in fluorescent immunoassays, and found to be equivalent. Immunoassays were then performed in a duplex format, demonstrating multiplex detection in a single well with limits of detection equivalent to the single assay format: 9.8 ng/mL chicken IgG and 7.8 ng/mL SEB

Evaluation of Optical Detection Platforms for Multiplexed Detection of Proteins and the Need for Point-of-Care Biosensors for Clinical Use

This review investigates optical sensor platforms for protein multiplexing, the ability to analyze multiple analytes simultaneously. Multiplexing is becoming increasingly important for clinical needs because disease and therapeutic response often involve the interplay between a variety of complex biological networks encompassing multiple, rather than single, proteins. Multiplexing is generally achieved through one of two routes, either through spatial separation on a surface (different wells or spots) or with the use of unique identifiers/labels (such as spectral separation—different colored dyes, or unique beads—size or color). The strengths and weaknesses of conventional platforms such as immunoassays and new platforms involving protein arrays and lab-on-a-chip technology, including commercially-available devices, are discussed. Three major public health concerns are identified whereby detecting medically-relevant markers using Point-of-Care (POC) multiplex assays could potentially allow for a more efficient diagnosis and treatment of diseases

Evaluation of optical sensor platforms for multiplexed detection of proteins

This work investigated optical sensor platforms for protein multiplexing, the ability to analyze multiple analytes simultaneously. Multiplexing is becoming increasingly important for clinical needs because disease and therapeutic response often involve the interplay between a variety of complex biological networks involving multiple, rather than single, proteins. Moreover, one biomarker may be indicative of more than one disease, similar diseases can manifest with similar physical symptoms, and monitoring a disease requires the ability to detect subtle differences over time. Multiplexing is generally achieved through one of two routes, either through spatial separation on a surface (different wells or spots) or with the use of unique identifiers/labels (such as spectral separation – different colored dyes, or unique beads – size or color). We looked into combining both spatial separation and unique labels to further expand the multiplexing capabilities of surfaces. Our original research resulted in one of the few demonstrations of reactive semiconductor nanocrystal immunoassays for multiplexed analysis within a single well on a microtiter plate. Innovative planar surface fluorescent immunoassays were developed for both spatial and spectral multiplexing using Quantum Dots and prospective incorporation into a Point-of-Care (POC) device involving an evanescent wave scanner. These assays used standard microscope slides combined with flow cells and were designed to markedly reduce the amount of sample and reagents needed as compared to standard 96-well plate assays. The platform was optimized for detecting Chicken IgG and Staphylococcal Enterotoxin B (SEB); SEB is commonly used in the literature to characterize the performance of biosensor platforms. The planar surface fluorescent immunoassays were applied to a real-world public health need to detect renal injury. Two emerging novel biomarkers, Kidney Injury Marker-1 (KIM-1) and Neutrophil Gelatinase Associated Lipocalin (NGAL), were investigated for their potential to detect injury earlier and with more specificity than current methods using serum creatinine (SCr). Detecting these medically-relevant markers using planar surface fluorescence immunoassays could potentially allow for more rapid diagnosis of acute kidney injury (AKI), among other uses

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee