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1.
Appl Spectrosc ; : 37028241256978, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38803165

ABSTRACT

We have demonstrated high-speed, super-resolution infrared (IR) spectroscopy and chemical imaging of autofluorescent biomaterials and organisms using camera-based widefield photothermal detection that takes advantage of temperature-dependent modulations of autofluorescent emission. A variety of biological materials and photosynthetic organisms exhibit strong autofluorescence emission under ultraviolet excitation and the autofluorescent emission has a very strong temperature dependence, of order 1%/K. Illuminating a sample with pulses of IR light from a wavelength-tunable laser source causes periodic localized sample temperature increases that result in a corresponding transient decrease in autofluorescent emission. A low-cost light-emitting diode-based fluorescence excitation source was used in combination with a conventional fluorescence microscopy camera to detect localized variations in autofluorescent emission over a wide area as an indicator of localized IR absorption. IR absorption image stacks were acquired over a range of IR wavelengths, including the fingerprint spectral range, enabling extraction of localized IR absorption spectra. We have applied widefield fluorescence detected photothermal IR (FL-PTIR) to an analysis of autofluorescent biological materials including collagen, leaf tissue, and photosynthetic organisms including diatoms and green microalgae cells. We have also demonstrated the FL-PTIR on live microalgae in water, demonstrating the potential for label-free dynamic chemical imaging of autofluorescent cells.

2.
J Intensive Care Soc ; 25(2): 208-209, 2024 May.
Article in English | MEDLINE | ID: mdl-38737311

ABSTRACT

The COVID-19 pandemic profoundly changed anaesthetic and critical care departments across the UK and fulfilled the definition of a major incident for an extended period of time. It is regularly highlighted that individual and organisational readiness for major incident is inconsistent, as is support in the aftermath. Post-pandemic rates of anxiety and PTSD in healthcare staff have significantly increased, but we still have no embedded method of helping to prevent it. Clinical debriefing is an emerging tool with proven improved psychological outcomes for staff following an adverse event. We surveyed 354 anaesthetists of a range of grades and experiences prior to attending a webinar centred on major incident organisation, human factors and clinical debrief. While 73.8% knew where to access their hospital's major incident plan, only 16.8% had been trained in any form of clinical debrief. Only 29% had ever received any formal training in major incident management. It seems that the occurrence of major incidents is no longer a 'once in a career' event. The inconsistencies in training and preparedness shown in our survey highlight opportunities for our workforce to be more agile and subsequently better supported for the future.

3.
Chaos ; 34(3)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38457846

ABSTRACT

We consider the problem of filtering dynamical systems, possibly stochastic, using observations of statistics. Thus, the computational task is to estimate a time-evolving density ρ(v,t) given noisy observations of the true density ρ†; this contrasts with the standard filtering problem based on observations of the state v. The task is naturally formulated as an infinite-dimensional filtering problem in the space of densities ρ. However, for the purposes of tractability, we seek algorithms in state space; specifically, we introduce a mean-field state-space model, and using interacting particle system approximations to this model, we propose an ensemble method. We refer to the resulting methodology as the ensemble Fokker-Planck filter (EnFPF). Under certain restrictive assumptions, we show that the EnFPF approximates the Kalman-Bucy filter for the Fokker-Planck equation, which is the exact solution to the infinite-dimensional filtering problem. Furthermore, our numerical experiments show that the methodology is useful beyond this restrictive setting. Specifically, the experiments show that the EnFPF is able to correct ensemble statistics, to accelerate convergence to the invariant density for autonomous systems, and to accelerate convergence to time-dependent invariant densities for non-autonomous systems. We discuss possible applications of the EnFPF to climate ensembles and to turbulence modeling.

4.
Open Forum Infect Dis ; 11(1): ofae001, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38250201

ABSTRACT

Background: We report clinical, epidemiological, and laboratory features of a large diarrhea outbreak caused by a novel Cryptosporidium hominis subtype during British military training in Kenya between February and April 2022. Methods: Data were collated from diarrhea cases, and fecal samples were analyzed on site using the multiplex polymerase chain reaction (PCR) BioFire FilmArray. Water was tested using Colilert kits (IDEXX, UK). DNA was extracted from feces for molecular characterization of Cryptosporidium A135, Lib13, ssu rRNA, and gp60 genes. Results: One hundred seventy-two of 1200 (14.3%) personnel at risk developed diarrhea over 69 days. One hundred six primary fecal samples were tested, and 63/106 (59.4%; 95% CI, 0.49%-0.69%) were positive for Cryptosporidium spp. Thirty-eight had Cryptosporidium spp. alone, and 25 had Cryptosporidium spp. with ≥1 other pathogen. A further 27/106 (25.5%; 95% CI, 0.18%-0.35%) had non-Cryptosporidium pathogens only, and 16/106 (15.1%; 95% CI, 0.09%-0.23%) were negative. C. hominis was detected in 58/63 (92.1%) Cryptosporidium spp.-positive primary samples, but the others were not genotypable. Twenty-seven C. hominis specimens were subtypable; 1 was gp60 subtype IeA11G3T3, and 26 were an unusual subtype, ImA13G1 (GenBank accession OP699729), supporting epidemiological evidence suggesting a point source outbreak from contaminated swimming water. Diarrhea persisted for a mean (SD) of 7.6 (4.6) days in Cryptosporidium spp. cases compared with 2.3 (0.9) days in non-Cryptosporidium cases (P = .001). Conclusions: Real-time multiplex PCR fecal testing was vital in managing this large cryptosporidiosis outbreak. The etiology of a rare C. hominis gp60 subtype emphasizes the need for more genotypic surveillance to identify widening host and geographic ranges of novel C. hominis subtypes.

5.
bioRxiv ; 2023 Nov 02.
Article in English | MEDLINE | ID: mdl-37961250

ABSTRACT

Many biological signaling pathways employ proteins that competitively dimerize in diverse combinations. These dimerization networks can perform biochemical computations, in which the concentrations of monomers (inputs) determine the concentrations of dimers (outputs). Despite their prevalence, little is known about the range of input-output computations that dimerization networks can perform (their "expressivity") and how it depends on network size and connectivity. Using a systematic computational approach, we demonstrate that even small dimerization networks (3-6 monomers) are expressive, performing diverse multi-input computations. Further, dimerization networks are versatile, performing different computations when their protein components are expressed at different levels, such as in different cell types. Remarkably, individual networks with random interaction affinities, when large enough (≥8 proteins), can perform nearly all (~90%) potential one-input network computations merely by tuning their monomer expression levels. Thus, even the simple process of competitive dimerization provides a powerful architecture for multi-input, cell-type-specific signal processing.

6.
Chaos ; 33(7)2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37486667

ABSTRACT

Forecasting blood glucose (BG) levels with routinely collected data is useful for glycemic management. BG dynamics are nonlinear, complex, and nonstationary, which can be represented by nonlinear models. However, the sparsity of routinely collected data creates parameter identifiability issues when high-fidelity complex models are used, thereby resulting in inaccurate forecasts. One can use models with reduced physiological fidelity for robust and accurate parameter estimation and forecasting with sparse data. For this purpose, we approximate the nonlinear dynamics of BG regulation by a linear stochastic differential equation: we develop a linear stochastic model, which can be specialized to different settings: type 2 diabetes mellitus (T2DM) and intensive care unit (ICU), with different choices of appropriate model functions. The model includes deterministic terms quantifying glucose removal from the bloodstream through the glycemic regulation system and representing the effect of nutrition and externally delivered insulin. The stochastic term encapsulates the BG oscillations. The model output is in the form of an expected value accompanied by a band around this value. The model parameters are estimated patient-specifically, leading to personalized models. The forecasts consist of values for BG mean and variation, quantifying possible high and low BG levels. Such predictions have potential use for glycemic management as part of control systems. We present experimental results on parameter estimation and forecasting in T2DM and ICU settings. We compare the model's predictive capability with two different nonlinear models built for T2DM and ICU contexts to have a sense of the level of prediction achieved by this model.


Subject(s)
Diabetes Mellitus, Type 2 , Glucose , Humans , Blood Glucose , Insulin , Nonlinear Dynamics
7.
PLoS Biol ; 21(4): e3002092, 2023 04.
Article in English | MEDLINE | ID: mdl-37093882

ABSTRACT

In multipartite viruses, the genome is split into multiple segments, each of which is transmitted via a separate capsid. The existence of multipartite viruses poses a problem, because replication is only possible when all segments are present within the same host. Given this clear cost, why is multipartitism so common in viruses? Most previous hypotheses try to explain how multipartitism could provide an advantage. In so doing, they require scenarios that are unrealistic and that cannot explain viruses with more than 2 multipartite segments. We show theoretically that selection for cheats, which avoid producing a shared gene product, but still benefit from gene products produced by other genomes, can drive the evolution of both multipartite and segmented viruses. We find that multipartitism can evolve via cheating under realistic conditions and does not require unreasonably high coinfection rates or any group-level benefit. Furthermore, the cheating hypothesis is consistent with empirical patterns of cheating and multipartitism across viruses. More broadly, our results show how evolutionary conflict can drive new patterns of genome organisation in viruses and elsewhere.


Subject(s)
Biological Evolution , Viruses , Viruses/genetics , Genome, Viral
8.
BMJ Open ; 12(10): e067265, 2022 10 03.
Article in English | MEDLINE | ID: mdl-36192092

ABSTRACT

INTRODUCTION: Crohn's disease (CD) is characterised by discontinuous, relapsing enteric inflammation. Instituting advanced therapies at an early stage to suppress inflammation aims to prevent future complications such as stricturing or penetrating disease, and subsequent surgical resection. Therapeutics are effective but associated with certain side-effects and relatively expensive. There is therefore an urgent need for robust methods to predict which newly diagnosed patients will develop disabling disease, to identify patients who are most likely to benefit from early, advanced therapies. We aim to determine if magnetic resonance enterography (MRE) features at diagnosis improve prediction of disabling CD within 5 years of diagnosis. METHODS AND ANALYSIS: We describe the protocol for a multicentre, non-randomised, single-arm, prospective study of adult patients with newly diagnosed CD. We will use patients already recruited to the METRIC study and extend their clinical follow-up, as well as a separate group of newly diagnosed patients who were not part of the METRIC trial (MRE within 3 months of diagnosis), to ensure an adequate sample size. Follow-up will extend for at least 4 years. The primary outcome is to evaluate the comparative predictive ability of prognostic models incorporating MRE severity scores (Magnetic resonance Enterography Global Score (MEGS), simplified MAgnetic Resonance Index of Activity (sMaRIA) and Lémann Index) versus models using standard characteristics alone to predict disabling CD (modified Beaugerie definition) within 5 years of new diagnosis. ETHICS AND DISSEMINATION: This study protocol achieved National Health Service Research Ethics Committee (NHS REC), London-Hampstead Research Ethics Committee approval (IRAS 217422). Our findings will be disseminated via conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN76899103.


Subject(s)
Crohn Disease , Adult , Crohn Disease/drug therapy , Humans , Inflammation , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy , Multicenter Studies as Topic , Prospective Studies , State Medicine
9.
Elife ; 112022 10 04.
Article in English | MEDLINE | ID: mdl-36193888

ABSTRACT

A social cheat is typically assumed to be an individual that does not perform a cooperative behaviour, or performs less of it, but can still exploit the cooperative behaviour of others. However, empirical data suggests that cheating can be more subtle, involving evolutionary arms races over the ability to both exploit and resist exploitation. These complications have not been captured by evolutionary theory, which lags behind empirical studies in this area. We bridge this gap with a mixture of game-theoretical models and individual-based simulations, examining what conditions favour more elaborate patterns of cheating. We found that as well as adjusting their own behaviour, individuals can be selected to manipulate the behaviour of others, which we term 'manipulative cheating'. Further, we found that manipulative cheating can lead to dynamic oscillations (arms races), between selfishness, manipulation, and suppression of manipulation. Our results can help explain both variation in the level of cheating, and genetic variation in the extent to which individuals can be exploited by cheats.


Subject(s)
Biological Evolution , Cooperative Behavior , Humans
10.
BMJ Open ; 12(5): e053204, 2022 05 02.
Article in English | MEDLINE | ID: mdl-35501093

ABSTRACT

INTRODUCTION: Chronic liver disease is a growing cause of morbidity and mortality in the UK. Acute presentation with advanced disease is common and prioritisation of resources to those at highest risk at earlier disease stages is essential to improving patient outcomes. Existing prognostic tools are of limited accuracy and to date no imaging-based tools are used in clinical practice, despite multiple anatomical imaging features that worsen with disease severity.In this paper, we outline our scoping review protocol that aims to provide an overview of existing prognostic factors and models that link anatomical imaging features with clinical endpoints in chronic liver disease. This will provide a summary of the number, type and methods used by existing imaging feature-based prognostic studies and indicate if there are sufficient studies to justify future systematic reviews. METHODS AND ANALYSIS: The protocol was developed in accordance with existing scoping review guidelines. Searches of MEDLINE and Embase will be conducted using titles, abstracts and Medical Subject Headings restricted to publications after 1980 to ensure imaging method relevance on OvidSP. Initial screening will be undertaken by two independent reviewers. Full-text data extraction will be undertaken by three pretrained reviewers who have participated in a group data extraction session to ensure reviewer consensus and reduce inter-rater variability. Where needed, data extraction queries will be resolved by reviewer team discussion. Reporting of results will be based on grouping of related factors and their cumulative frequencies. Prognostic anatomical imaging features and clinical endpoints will be reported using descriptive statistics to summarise the number of studies, study characteristics and the statistical methods used. ETHICS AND DISSEMINATION: Ethical approval is not required as this study is based on previously published work. Findings will be disseminated by peer-reviewed publication and/or conference presentations.


Subject(s)
Liver Diseases , Research Design , Humans , Liver Diseases/diagnostic imaging , Mass Screening , Review Literature as Topic
11.
Proc Natl Acad Sci U S A ; 119(15): e2121098119, 2022 04 12.
Article in English | MEDLINE | ID: mdl-35377803

ABSTRACT

The pathogenesis of lung fibrosis involves hyperactivation of innate and adaptive immune pathways that release inflammatory cytokines and growth factors such as tumor growth factor (TGF)ß1 and induce aberrant extracellular matrix protein production. During the genesis of pulmonary fibrosis, resident alveolar macrophages are replaced by a population of newly arrived monocyte-derived interstitial macrophages that subsequently transition into alveolar macrophages (Mo-AMs). These transitioning cells initiate fibrosis by releasing profibrotic cytokines and remodeling the matrix. Here, we describe a strategy for leveraging the up-regulation of the mannose receptor CD206 in interstitial macrophages and Mo-AM to treat lung fibrosis. We engineered mannosylated albumin nanoparticles, which were found to be internalized by fibrogenic CD206+ monocyte derived macrophages (Mo-Macs). Mannosylated albumin nanoparticles incorporating TGFß1 small-interfering RNA (siRNA) targeted the profibrotic subpopulation of CD206+ macrophages and prevented lung fibrosis. The findings point to the potential utility of mannosylated albumin nanoparticles in delivering TGFß-siRNA into CD206+ profibrotic macrophages as an antilung fibrosis strategy.


Subject(s)
Lymphotoxin-alpha , Macrophages, Alveolar , Nanoparticles , Pulmonary Fibrosis , RNA, Small Interfering , Animals , Bleomycin/pharmacology , Disease Models, Animal , Lymphotoxin-alpha/genetics , Macrophages, Alveolar/immunology , Mannose Receptor , Mice , Mice, Inbred C57BL , Nanoparticles/administration & dosage , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/therapy , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/genetics
12.
ACS Nano ; 16(3): 4084-4101, 2022 03 22.
Article in English | MEDLINE | ID: mdl-35230826

ABSTRACT

The complex involvement of neutrophils in inflammatory diseases makes them intriguing but challenging targets for therapeutic intervention. Here, we tested the hypothesis that varying endocytosis capacities would delineate functionally distinct neutrophil subpopulations that could be specifically targeted for therapeutic purposes. By using uniformly sized (∼120 nm in diameter) albumin nanoparticles (ANP) to characterize mouse neutrophils in vivo, we found two subsets of neutrophils, one that readily endocytosed ANP (ANPhigh neutrophils) and another that failed to endocytose ANP (ANPlow population). These ANPhigh and ANPlow subsets existed side by side simultaneously in bone marrow, peripheral blood, spleen, and lungs, both under basal conditions and after inflammatory challenge. Human peripheral blood neutrophils showed a similar duality. ANPhigh and ANPlow neutrophils had distinct cell surface marker expression and transcriptomic profiles, both in naive mice and in mice after endotoxemic challenge. ANPhigh and ANPlow neutrophils were functionally distinct in their capacities to kill bacteria and to produce inflammatory mediators. ANPhigh neutrophils produced inordinate amounts of reactive oxygen species and inflammatory chemokines and cytokines. Targeting this subset with ANP loaded with the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, mitigated the effects of polymicrobial sepsis by reducing tissue inflammation while fully preserving neutrophilic host-defense function.


Subject(s)
Nanoparticles , Neutrophils , Albumins/metabolism , Animals , Endocytosis , Inflammation/drug therapy , Inflammation/metabolism , Mice , Neutrophils/metabolism
13.
Nat Commun ; 13(1): 195, 2022 01 25.
Article in English | MEDLINE | ID: mdl-35078994

ABSTRACT

In bacteria and other microorganisms, the cells within a population often show extreme phenotypic variation. Different species use different mechanisms to determine how distinct phenotypes are allocated between individuals, including coordinated, random, and genetic determination. However, it is not clear if this diversity in mechanisms is adaptive-arising because different mechanisms are favoured in different environments-or is merely the result of non-adaptive artifacts of evolution. We use theoretical models to analyse the relative advantages of the two dominant mechanisms to divide labour between reproductives and helpers in microorganisms. We show that coordinated specialisation is more likely to evolve over random specialisation in well-mixed groups when: (i) social groups are small; (ii) helping is more "essential"; and (iii) there is a low metabolic cost to coordination. We find analogous results when we allow for spatial structure with a more detailed model of cellular filaments. More generally, this work shows how diversity in the mechanisms to produce phenotypic heterogeneity could have arisen as adaptations to different environments.


Subject(s)
Adaptation, Physiological/genetics , Biological Variation, Population/genetics , Cyanobacteria/genetics , Microbial Interactions/genetics , Biological Evolution , Computer Simulation , Cyanobacteria/growth & development , Cyanobacteria/metabolism , Genetic Fitness , Models, Genetic , Phenotype , Selection, Genetic
14.
Ecol Evol ; 11(21): 14475-14489, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34765120

ABSTRACT

Division of labor occurs when cooperating individuals specialize to perform different tasks. In bacteria and other microorganisms, some species divide labor by random specialization, where an individual's role is determined by random fluctuations in biochemical reactions within the cell. Other species divide labor by coordinating across individuals to determine which cells will perform which task, using mechanisms such as between-cell signaling. However, previous theory, examining the evolution of mechanisms to divide labor between reproductives and sterile helpers, has only considered clonal populations, where there is no potential for conflict between individuals. We used a mixture of analytical and simulation models to examine nonclonal populations and found that: (a) intermediate levels of coordination can be favored, between the extreme of no coordination (random) and full coordination; (b) as relatedness decreases, coordinated division of labor is less likely to be favored. Our results can help explain why coordinated division of labor is relatively rare in bacteria, where groups may frequently be nonclonal.

15.
Elife ; 102021 10 29.
Article in English | MEDLINE | ID: mdl-34713804

ABSTRACT

Recent theory has overturned the assumption that accelerating returns from individual specialisation are required to favour the evolution of division of labour. Yanni et al., 2020, showed that topologically constrained groups, where cells cooperate with only direct neighbours such as for filaments or branching growths, can evolve a reproductive division of labour even with diminishing returns from individual specialisation. We develop a conceptual framework and specific models to investigate the factors that can favour the initial evolution of reproductive division of labour. We find that selection for division of labour in topologically constrained groups: (1) is not a single mechanism to favour division of labour-depending upon details of the group structure, division of labour can be favoured for different reasons; (2) always involves an efficiency benefit at the level of group fitness; and (3) requires a mechanism of coordination to determine which individuals perform which tasks. Given that such coordination must evolve prior to or concurrently with division of labour, this could limit the extent to which topological constraints favoured the initial evolution of division of labour. We conclude by suggesting experimental designs that could determine why division of labour is favoured in the natural world.


Subject(s)
Adaptation, Physiological , Biological Evolution , Social Behavior , Humans , Models, Theoretical , Reproduction
16.
Cell Rep ; 36(2): 109353, 2021 07 13.
Article in English | MEDLINE | ID: mdl-34237283

ABSTRACT

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects and identify 14 SARS-CoV-2 neutralizing antibodies. One targets the N-terminal domain (NTD), one recognizes an epitope in S2, and 11 bind the receptor-binding domain (RBD). Three anti-RBD neutralizing antibodies cross-neutralize SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency and antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. All four cross-neutralizing antibodies neutralize the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , COVID-19/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/immunology , Animals , Antibodies, Viral/chemistry , Antibodies, Viral/immunology , Binding Sites , Cell Line , Cross Reactions , Epitopes/immunology , Female , HEK293 Cells , Humans , Mice , Neutralization Tests , Protein Binding/immunology , Protein Domains , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry
17.
J Clin Microbiol ; 59(10): e0052721, 2021 09 20.
Article in English | MEDLINE | ID: mdl-34288726

ABSTRACT

Determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories. Five neutralization assays were compared using 40 plasma samples from convalescent individuals with mild to moderate coronavirus disease 2019 (COVID-19): four cell-based systems using either live recombinant SARS-CoV-2 or pseudotyped viral particles created with lentivirus (LV) or vesicular stomatitis virus (VSV) packaging and one surrogate enzyme-linked immunosorbent assay (ELISA)-based test that measures inhibition of the spike protein receptor binding domain (RBD) binding its receptor human angiotensin converting enzyme 2 (hACE2). Vero cells, Vero E6 cells, HEK293T cells expressing hACE2, and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 were tested. All cell-based assays showed 50% neutralizing dilution (ND50) geometric mean titers (GMTs) that were highly correlated (Pearson r = 0.81 to 0.89) and ranged within 3.4-fold. The live virus assay and LV pseudovirus assays with HEK293T/hACE2 cells showed very similar mean titers, 141 and 178, respectively. ND50 titers positively correlated with plasma IgG targeting SARS-CoV-2 spike protein and RBD (r = 0.63 to 0.89), but moderately correlated with nucleoprotein IgG (r = 0.46 to 0.73). ND80 GMTs mirrored ND50 data and showed similar correlation between assays and with IgG concentrations. The VSV pseudovirus assay and LV pseudovirus assay with HEK293T/hACE2 cells in low- and high-throughput versions were calibrated against the WHO SARS-CoV-2 IgG standard. High concordance between the outcomes of cell-based assays with live and pseudotyped virions enables valid cross-study comparison using these platforms.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , Chlorocebus aethiops , HEK293 Cells , Humans , Neutralization Tests , Spike Glycoprotein, Coronavirus/genetics , Vero Cells
18.
J Am Acad Audiol ; 32(4): 229-234, 2021 04.
Article in English | MEDLINE | ID: mdl-34034343

ABSTRACT

BACKGROUND: During audiologic evaluations, an examination of interaural asymmetry is commonly evaluated. To date, however, interaural differences for tympanometric indices have not been reported for adults. Without documented tympanometric right-left differences, one cannot determine if asymmetries are normal or are indicative of significant clinical asymmetries. PURPOSE: The purpose of this study was to investigate interaural asymmetries in peak compensated static acoustic admittance (Ytm), equivalent ear canal volume (Vea), tympanometric peak pressure (TPP), and tympanometric width (TW) in normal adults. RESEARCH DESIGN: Descriptive, correlational, and inferential measures designs were employed. STUDY SAMPLE: Participants were 188 otologically normal Caucasian young adults (i.e., 77 females and 111 males; M = 23.0 years, standard deviation [SD] = 2.7, range = 18-30 years). DATA COLLECTION AND ANALYSES: Ytm, Vea, TPP, and TW measures were obtained bilaterally from an admittance tympanogram using a 226 Hz probe tone. Separate two-factor mixed measures analysis of variance examined the effect of ear and sex for each tympanometric index. Correlation analyses examined the association between right and left ear indices. Interaural differences in tympanometric indices were examined with independent t-tests. Critical differences, for deciding if two tympanometric indices are different between ears, were computed from the standard deviations of the right-left ear difference for statistical confidence levels of 85, 90, 95, and 99%. RESULTS: The effect of ear was not statistically significant (p > 0.05) on any tympanometric index. Females had significantly lower Ytm and smaller Vea measures than males (p < 0.05). Correlations between all right and left tympanometric indices were positive and statistically significant (p < 0.05). There were no statistically significant differences in interaural differences for any of the tympanometric indices as a function of sex (p > 0.05). Critical differences, for confidence levels for 85% to 99% confidence ranged from ± 0.20-0.36 mmhos for Ytm, ± 0.23-0.41 cm3 for Vea, ± 11.1-19.8 daPa for TPP, and ± 27.2-48.7 daPa for TW. CONCLUSION: A clinician can use these critical differences to determine if tympanometric index interaural differences in ears of young normal Caucasian adults are statistically significant.


Subject(s)
Acoustic Impedance Tests , Audiometry , Acoustics , Ear Canal , Ear, Middle , Female , Humans , Male , Reference Values , Young Adult
19.
bioRxiv ; 2021 Mar 24.
Article in English | MEDLINE | ID: mdl-33791692

ABSTRACT

SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier in the past two decades. The development of a universal human coronavirus vaccine could prevent future pandemics. We characterized 198 antibodies isolated from four COVID19+ subjects and identified 14 SARS-CoV-2 neutralizing antibodies. One targeted the NTD, one recognized an epitope in S2 and twelve bound the RBD. Three anti-RBD neutralizing antibodies cross-neutralized SARS-CoV-1 by effectively blocking binding of both the SARS-CoV-1 and SARS-CoV-2 RBDs to the ACE2 receptor. Using the K18-hACE transgenic mouse model, we demonstrate that the neutralization potency rather than the antibody epitope specificity regulates the in vivo protective potential of anti-SARS-CoV-2 antibodies. The anti-S2 antibody also neutralized SARS-CoV-1 and all four cross-neutralizing antibodies neutralized the B.1.351 mutant strain. Thus, our study reveals that epitopes in S2 can serve as blueprints for the design of immunogens capable of eliciting cross-neutralizing coronavirus antibodies.

20.
BJR Open ; 3(1): 20210048, 2021.
Article in English | MEDLINE | ID: mdl-35707759

ABSTRACT

Objectives: To assess body composition in patients with non-small cell lung cancer (NSCLC) and colorectal cancer using whole-body MRI and relate this to clinical outcomes. Methods: 53 patients with NSCLC (28 males, 25 females; mean age 66.9) and 74 patients with colorectal cancer (42 males, 32 females; mean age 62.9) underwent staging whole-body MRI scans, which were post-processed to derive fat mass (FM), fat free mass (FFM) and skeletal muscle (SM) indices and SM fat fraction (FF). These were compared between the two cancer cohorts using two-sided t-tests and the chi-squared test. Measurements of body composition were correlated with outcomes including length of hospital stay, metastatic status and mortality. Results: Patients with NSCLC had significantly lower FFM (p = 0.0071) and SM (p = 0.0084) indices. Mean SM FF was greater in patients with NSCLC (p = 0.0124) and was associated with longer hospital stay (p = 0.035). There was no significant relationship between FM, FFM and SM indices and length of hospital stay, metastatic status or mortality. Conclusions: Patients with NSCLC had lower FFM and SM indices than patients with colorectal cancer and greater SMFF, indicating lower SM mass with fatty infiltration. These findings reflect differences in the phenotype of the two groups and suggest patients with lung cancer are more likely to require additional nutritional support. Advances in knowledge: Body composition differs between NSCLC and colorectal cancer. Patients with NSCLC have both a reduced SM mass and greater SM FF suggesting that they are more nutritionally deplete than patients with colorectal cancer.

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