Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 110
Filtrer
2.
Sci Data ; 11(1): 478, 2024 May 09.
Article de Anglais | MEDLINE | ID: mdl-38724554

RÉSUMÉ

Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics. Commonly measured soil metrics were analysed in five soil increments for 0-1 metre (n = 4550). Less commonly measured soil metrics which were assumed to change across the soil profile were measured on a subset of samples only (n = 3762). Additionally, we developed a simple method for soil organic matter fractionation using density fractionation which is part of the less common metrics. Finally, soil metrics which may impact SOC dynamics, but with less confidence as to their importance across the soil profile were only measured on topsoil (~5-15 cm = mineral soil) and subsoil (below 50 cm) samples (n = 2567).


Sujet(s)
Carbone , Prairie , Sol , Sol/composition chimique , Carbone/analyse , Angleterre , Forêts , Écosystème
3.
J Med Internet Res ; 26: e60444, 2024 May 27.
Article de Anglais | MEDLINE | ID: mdl-38801770

RÉSUMÉ

[This corrects the article DOI: 10.2196/51058.].

5.
Vaccine ; 42(12): 2945-2950, 2024 Apr 30.
Article de Anglais | MEDLINE | ID: mdl-38580516

RÉSUMÉ

The ComFluCOV trial randomized 679 participants to receive an age-appropriate influenza vaccine, or placebo, alongside their second COVID-19 vaccine. Concomitant administration was shown to be safe, and to preserve systemic immune responses to both vaccines. Here we report on a secondary outcome of the trial investigating SARS-CoV-2-specific mucosal antibody responses. Anti-spike IgG and IgA levels in saliva were measured with in-house ELISAs. Concomitant administration of an influenza vaccine did not affect salivary anti-spike IgG positivity rates to Pfizer/BioNTech BNT162b2 (99.1 cf. 95.6%), or AstraZeneca ChAdOx1 (67.8% cf. 64.9%), at 3-weeks post-vaccination relative to placebo. Furthermore, saliva IgG positively correlated with serum titres highlighting the potential utility of saliva for assessing differences in immunogenicity in future vaccine studies. Mucosal IgA was not detected in response to either COVID-19 vaccine, reinforcing the need for novel vaccines capable of inducing sterilising immunity or otherwise reducing transmission. The trial is registered as ISRCTN 14391248.


Sujet(s)
COVID-19 , Vaccins antigrippaux , Grippe humaine , Humains , Anticorps antiviraux , Vaccin BNT162 , COVID-19/prévention et contrôle , Vaccins contre la COVID-19 , Immunoglobuline G , Grippe humaine/prévention et contrôle , Salive , SARS-CoV-2 , Vaccination
6.
J Med Internet Res ; 26: e51058, 2024 03 29.
Article de Anglais | MEDLINE | ID: mdl-38551639

RÉSUMÉ

BACKGROUND: Despite the impact of physical abuse on children, it is often underdiagnosed, especially among children evaluated in emergency departments (EDs). Electronic clinical decision support (CDS) can improve the recognition of child physical abuse. OBJECTIVE: We aimed to develop and test the usability of a natural language processing-based child abuse CDS system, known as the Child Abuse Clinical Decision Support (CA-CDS), to alert ED clinicians about high-risk injuries suggestive of abuse in infants' charts. METHODS: Informed by available evidence, a multidisciplinary team, including an expert in user design, developed the CA-CDS prototype that provided evidence-based recommendations for the evaluation and management of suspected child abuse when triggered by documentation of a high-risk injury. Content was customized for medical versus nursing providers and initial versus subsequent exposure to the alert. To assess the usability of and refine the CA-CDS, we interviewed 24 clinicians from 4 EDs about their interactions with the prototype. Interview transcripts were coded and analyzed using conventional content analysis. RESULTS: Overall, 5 main categories of themes emerged from the study. CA-CDS benefits included providing an extra layer of protection, providing evidence-based recommendations, and alerting the entire clinical ED team. The user-centered, workflow-compatible design included soft-stop alert configuration, editable and automatic documentation, and attention-grabbing formatting. Recommendations for improvement included consolidating content, clearer design elements, and adding a hyperlink with additional resources. Barriers to future implementation included alert fatigue, hesitancy to change, and concerns regarding documentation. Facilitators of future implementation included stakeholder buy-in, provider education, and sharing the test characteristics. On the basis of user feedback, iterative modifications were made to the prototype. CONCLUSIONS: With its user-centered design and evidence-based content, the CA-CDS can aid providers in the real-time recognition and evaluation of infant physical abuse and has the potential to reduce the number of missed cases.


Sujet(s)
Maltraitance des enfants , Systèmes d'aide à la décision clinique , Nourrisson , Humains , Enfant , Ethnies , Dossiers médicaux électroniques , Minorités , Maltraitance des enfants/diagnostic
7.
BMJ Open ; 13(11): e073813, 2023 11 28.
Article de Anglais | MEDLINE | ID: mdl-38016790

RÉSUMÉ

OBJECTIVE: To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes. DESIGN: A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation. SETTING: Three inner-city UK National Health Service hospitals in London. PARTICIPANTS: Pregnant women with gestational diabetes treated with medication. INTERVENTIONS: 2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention. SECONDARY OUTCOME MEASURES: Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs. RESULTS: Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders. CONCLUSIONS: It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention. TRIAL REGISTRATION NUMBER: ISRCTN20930880.


Sujet(s)
Diabète de type 2 , Diabète gestationnel , Metformine , Femelle , Humains , Grossesse , Metformine/usage thérapeutique , Diabète de type 2/prévention et contrôle , Diabète de type 2/traitement médicamenteux , Diabète gestationnel/prévention et contrôle , Diabète gestationnel/traitement médicamenteux , Études de faisabilité , Médecine d'État , Méthode en double aveugle , Royaume-Uni
9.
J Environ Manage ; 346: 118884, 2023 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-37729834

RÉSUMÉ

Land degradation directly affects around 25% of land globally, undermining progress on most of the UN Sustainable Development Goals (SDG), particularly target 15.3. To assess land degradation, SDG indicator 15.3.1 combines sub-indicators of productivity, soil carbon and land cover. Over 100 countries have set Land Degradation Neutrality (LDN) targets. Here, we demonstrate application of the indicator for a well-established agricultural landscape using the case study of Great Britain. We explore detection of degradation in such landscapes by: 1) transparently evaluating land cover transitions; 2) comparing assessments using global and national data; 3) identifying misleading trends; and 4) including extra sub-indicators for additional forms of degradation. Our results demonstrate significant impacts on the indicator both from the land cover transition evaluation and choice or availability of data. Critically, we identify a misleading improvement trend due to a trade-off between improvement detected by the productivity sub-indicator, and 30-year soil carbon loss trends in croplands (11% from 1978 to 2007). This carbon loss trend would not be identified without additional data from Countryside Survey (CS). Thus, without incorporating field survey data we risk overlooking the degradation of regulating and supporting ecosystem services (linked to soil carbon), in favour of signals from improving provisioning services (productivity sub-indicator). Relative importance of these services will vary between socioeconomic contexts. Including extra sub-indicators for erosion or critical load exceedance, as additional forms of degradation, produced a switch from net area improving (9%) to net area degraded (58%). CS data also identified additional degradation for soil health, including 44% arable soils exceeding bulk density thresholds and 35% of CS squares exceeding contamination thresholds for metals.


Sujet(s)
Agriculture , Écosystème , Sol , Développement durable , Carbone , Conservation des ressources naturelles
10.
bioRxiv ; 2023 Aug 29.
Article de Anglais | MEDLINE | ID: mdl-37693379

RÉSUMÉ

Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers. This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies. Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies.

11.
Int J Mol Sci ; 24(18)2023 Sep 18.
Article de Anglais | MEDLINE | ID: mdl-37762540

RÉSUMÉ

Castration resistance poses a significant challenge in the management of advanced prostate cancer (PCa), with androgen deprivation therapy (ADT) or chemotherapy being the primary treatment options. However, these approaches often lead to significant side effects and the development of therapeutic resistance. Therefore, it is crucial to explore novel treatment options that can efficiently target PCa, improve patient survival, and enhance their quality of life. Neferine (Nef), a bioactive compound derived from plants, has emerged as a promising candidate for cancer treatment due to its ability to induce apoptosis, autophagy, and cell cycle arrest. In this study, we investigated the potential anticancer effects of Nef in androgen receptor (AR)-positive LNCaP and VCaP cells, representative models of androgen-dependent PCa. Our findings demonstrate that Nef effectively inhibits cell growth, proliferation, and the tumorigenic potential of androgen-dependent PCa cells. Furthermore, Nef treatment resulted in the excessive production of reactive oxygen species (ROS), leading to the activation of key markers of autophagy and apoptosis. These results suggest that Nef has the potential to target the oncogenic characteristics of androgen-dependent PCa cells by exploiting the potency of ROS and inducing autophagy and apoptosis in AR-positive PCa cells. These findings shed light on the therapeutic potential of Nef as a novel treatment option with reduced side effects for androgen-dependent prostate cancer. Further investigations are warranted to assess its efficacy and safety in preclinical and clinical settings.

12.
Antioxidants (Basel) ; 12(8)2023 Aug 14.
Article de Anglais | MEDLINE | ID: mdl-37627604

RÉSUMÉ

Community-acquired pneumonia (CAP) is characterized by elevated markers of inflammation and oxidative stress and depleted circulating concentrations of the antioxidant nutrient vitamin C. A feasibility trial of intravenous and oral vitamin C supplementation, matched to the timing of intravenous and oral antibiotic formulations, was carried out and changes in vitamin C status were monitored to determine whether saturating status could be achieved throughout the administration period. Patients with moderate and severe CAP (CURB-65 ≥ 2; n = 75) who were receiving intravenous antimicrobial therapy were randomized to placebo (n = 39) or intravenous vitamin C (2.5 g per 8 h; n = 36) before moving to oral vitamin C (1 g three times daily) when prescribed oral antimicrobials. Blood samples were collected at baseline and then daily whilst in the hospital. Vitamin C concentrations were determined by high-performance liquid chromatography. The inflammatory and infection biomarkers C-reactive protein and procalcitonin were elevated at baseline (158 (61, 277) mg/L and 414 (155, 1708) ng/L, respectively), and vitamin C concentrations were depleted (15 (7, 25) µmol/L). There was an inverse association between vitamin C and C-reactive protein concentrations (r = -0.312, p = 0.01). Within one day of intervention initiation, plasma vitamin C concentrations in the vitamin C group reached median concentrations of 227 (109, 422) µmol/L, and circulating concentrations remained at ≥150 µmol/L for the duration of the intervention, whilst median vitamin C concentrations in the placebo group remained low (≤35 µmol/L). There was a trend toward decreased duration of hospital stay (p = 0.07) and time to clinical stability (p = 0.08) in the vitamin C group. In conclusion, patients with moderate to severe CAP have inadequate plasma vitamin C concentrations for the duration of their hospital stay. The administration of intravenous or oral vitamin C, titrated to match the antimicrobial formulation, provided saturating plasma vitamin C concentrations whilst in the hospital. There were trends toward shorter duration of hospital stay and time to clinical stability. Thus, larger trials assessing the impact of intravenous and oral vitamin C intervention on CAP clinical outcomes are indicated.

13.
Sci Rep ; 13(1): 11879, 2023 07 23.
Article de Anglais | MEDLINE | ID: mdl-37482552

RÉSUMÉ

Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting.


Sujet(s)
Acide ascorbique , Pneumopathie infectieuse , Adulte , Humains , Mâle , Sujet âgé , Femelle , Acide ascorbique/usage thérapeutique , Études de faisabilité , Pneumopathie infectieuse/traitement médicamenteux , Vitamines , Perfusions veineuses
14.
Lett Appl Microbiol ; 76(7)2023 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-37403323

RÉSUMÉ

Legionella longbeachae is an important cause of Legionnaires' disease in Australasia and is associated with exposure to potting soils. Our aim was to identify ways to reduce the load of L. longbeachae in potting soils. Inductively-coupled plasma optical emission spectrometry (ICP-OES) of an all-purpose potting mix showed copper (Cu) concentrations (mg/kg) range from 15.8 to 23.6. Zinc (Zn) and manganese (Mn) were significantly higher than Cu ranging from 88.6-106 to 171-203, respectively. Minimal inhibitory and bactericidal concentrations of 10 salts used in the horticultural industry were determined for Legionella species in buffered yeast extract (BYE) broth. For L. longbeachae (n = 9) the median (range) minimum inhibitory concentration (MIC) (mg/L) of copper sulfate was 31.25 (15.6-31.25), zinc sulfate 31.25 (7.81-31.25), and manganese sulfate 31.25 (7.81-62.5). The MIC and minimum bactericidal concentration (MBC) were within one dilution of each other. Susceptibility to Cu and Zn salts increased as the concentration of pyrophosphate iron in the media decreased. The MIC values for these three metals against Legionella pneumophila (n = 3) and Legionella micdadei (n = 4) were similar. Combinations of Cu, Zn, and Mn were additive. Legionella longbeachae has similar susceptibility to Cu and other metal ions in comparison to L. pneumophila.


Sujet(s)
Legionella longbeachae , Legionella , Maladie des légionnaires , Humains , Cuivre/pharmacologie , Manganèse/pharmacologie , Zinc/pharmacologie , Sels , Sol
15.
J Appl Toxicol ; 43(11): 1645-1666, 2023 Nov.
Article de Anglais | MEDLINE | ID: mdl-37340691

RÉSUMÉ

The Japanese medaka (Oryzias latipes) extended one-generation reproduction test (MEOGRT) (Test Guideline 890.2200) is a Tier 2 test within the Endocrine Disruptor Screening Program of the US Environmental Protection Agency (US EPA). A modified MEOGRT was used to evaluate multigenerational effects of 2-ethylhexyl 4-hydroxybenzoate (2-EHHB) under flow-through conditions starting with adults (parent generation, F0) through a 3-week reproductive phase of the second generation (F2). Fish were exposed to one of five 2-EHHB test concentrations or a dechlorinated tap water control. Fecundity was affected at the lowest exposure (5.32 µg/L) and greater sensitivity occurred in the F1 and F2 generations. Percent fertility was also diminished from no effect level observed in the F0 generation to 101 and 48.8 µg/L in the F1 and F2 generations, respectively. Growth indices were decreased for F0 adult females and F1 subadults and adults at 48.8 µg/L 2-EHHB. Histopathologic examination of gonads, liver, kidney, and thyroid yielded possible delayed reproductive tract development in F1 subadult males, masculinization of the renal phenotype in F1 adult females (renal tubular eosinophilia) and reduced hepatic energy storage (liver glycogen vacuoles) in F1 (11.3 and 48.8 µg/L) and F2 (48.8 and 101 µg/L) males and females, respectively. Endocrine-related findings included a decrease in anal fin papillae in F2 adult males at 101 µg/L. Results of this study demonstrate effects on growth, development, and reproduction that may be mediated by endocrine (weak estrogenic) and nonendocrine mechanisms. Duration of the MEOGRT should not be routinely extended beyond the OCSPP 890 guideline study design.

16.
J Pediatr Nurs ; 72: e47-e52, 2023.
Article de Anglais | MEDLINE | ID: mdl-37330276

RÉSUMÉ

BACKGROUND: Transfer of care, moving hospitalized patients between care areas, is a critical point of vulnerability for healthcare organizations. Patient information handoff is an essential activity occurring frequently in hospital environments. Poor communication has been linked with adverse events and poor patient outcomes. This evidence-based quality project aimed to enhance the handoff process between the Emergency Department (ED) and Pediatric Intensive Care Unit (PICU) by standardizing transfer of care steps. This was accomplished through customizing a reporting tool to contain all the information the receiving department deemed necessary for safe patient care. METHODS: A customized situation, background, assessment, recommendation (SBAR) form handoff tool was developed for ED to PICU transfers. This SBAR tool included information that PICU nurses identified as critical to transfer of care. Nurse perceptions were surveyed pre- and post-implementation. Patient safety event reports were tracked to evaluate events related to transfer of care before and after the practice change. FINDINGS: An increased number of PICU nurses agreed the customized handoff tool was complete and organized. Additionally, more nurses agreed that handoff gave all information needed to safely care for critically ill patients transferred from the ED. Lastly, bedside patient checks increased, and patient safety events related to transfer of care decreased. DISCUSSION: This project demonstrated that implementation of a standardized transfer of care process coupled with a customized handoff tool increased PICU nurse perceptions that handoff was organized, and all information needed to safely care for critically ill patients was conveyed. APPLICATION TO PRACTICE: Transfer of care processes between the ED and PICU should be standardized. The use of customized tools may improve information exchange between nurses and ensure that all vital patient information is communicated.


Sujet(s)
Transfert de la prise en charge du patient , Amélioration de la qualité , Humains , Enfant , Maladie grave , Service hospitalier d'urgences , Soins de réanimation , Communication
17.
Crit Care Nurs Q ; 46(3): 271-276, 2023.
Article de Anglais | MEDLINE | ID: mdl-37226918

RÉSUMÉ

In the last 20 years, the occurrences of drug shortages have increased in frequency as well as duration before returning to the mainstream market. This has prompted intensive care unit nurses and medical staff to seek alternate medication infusion options that provide safe yet effective sedation for patients admitted to intensive care units across the country. Dexmedetomidine (PRECEDEX) emerged in 1999 after the Federal Drug Administration approved it for intensive care use but was quickly embraced by anesthesia providers as it rendered patients undergoing procedures or surgery with adequate analgesia and sedation. Dexmedetomidine (PRECEDEX) continued to maintain patients who required short-term intubation and mechanical ventilation with adequate sedation throughout the entire perioperative period. With patients remaining hemodynamically stable in the initial postoperative period, critical care nurses embraced the use of dexmedetomidine (PRECEDEX) in the intensive care unit setting. As dexmedetomidine (PRECEDEX) gained popularity, it has been used to help manage multiple disease processes such as delirium, agitation, alcoholic withdrawal, and anxiety. Dexmedetomidine (PRECEDEX) has been indicated to be a safer alternative to benzodiazepines, narcotics, or propofol (Diprivan), while providing adequate sedation and allowing patients to maintain hemodynamic stability.


Sujet(s)
Anesthésie , Dexmédétomidine , Humains , Dexmédétomidine/usage thérapeutique , Soins de réanimation , Unités de soins intensifs , Anxiété
18.
Toxicol Sci ; 193(2): 131-145, 2023 05 31.
Article de Anglais | MEDLINE | ID: mdl-37071731

RÉSUMÉ

The U.S. Environmental Protection Agency's Endocrine Disruptor Screening Program (EDSP) is tasked with assessing chemicals for their potential to perturb endocrine pathways, including those controlled by androgen receptor (AR). To address challenges associated with traditional testing strategies, EDSP is considering in vitro high-throughput screening assays to screen and prioritize chemicals more efficiently. The ability of these assays to accurately reflect chemical interactions in nonmammalian species remains uncertain. Therefore, a goal of the EDSP is to evaluate how broadly results can be extrapolated across taxa. To assess the cross-species conservation of AR-modulated pathways, computational analyses and systematic literature review approaches were used to conduct a comprehensive analysis of existing in silico, in vitro, and in vivo data. First, molecular target conservation was assessed across 585 diverse species based on the structural similarity of ARs. These results indicate that ARs are conserved across vertebrates and are predicted to share similarly susceptibility to chemicals that interact with the human AR. Systematic analysis of over 5000 published manuscripts was used to compile in vitro and in vivo cross-species toxicity data. Assessment of in vitro data indicates conservation of responses occurs across vertebrate ARs, with potential differences in sensitivity. Similarly, in vivo data indicate strong conservation of the AR signaling pathways across vertebrate species, although sensitivity may vary. Overall, this study demonstrates a framework for utilizing bioinformatics and existing data to build weight of evidence for cross-species extrapolation and provides a technical basis for extrapolating hAR-based data to prioritize hazard in nonmammalian vertebrate species.


Sujet(s)
Perturbateurs endocriniens , Récepteurs aux androgènes , Animaux , États-Unis , Humains , Récepteurs aux androgènes/métabolisme , Environmental Protection Agency (USA) , Système endocrine/composition chimique , Système endocrine/métabolisme , Perturbateurs endocriniens/toxicité , Perturbateurs endocriniens/composition chimique , Tests de criblage à haut débit/méthodes
19.
Commun Med (Lond) ; 3(1): 37, 2023 Mar 15.
Article de Anglais | MEDLINE | ID: mdl-36922542

RÉSUMÉ

BACKGROUND: Saliva is easily obtainable non-invasively and potentially suitable for detecting both current and previous SARS-CoV-2 infection, but there is limited evidence on the utility of salivary antibody testing for community surveillance. METHODS: We established 6 ELISAs detecting IgA and IgG antibodies to whole SARS-CoV-2 spike protein, to its receptor binding domain region and to nucleocapsid protein in saliva. We evaluated diagnostic performance, and using paired saliva and serum samples, correlated mucosal and systemic antibody responses. The best-performing assays were field-tested in 20 household outbreaks. RESULTS: We demonstrate in test accuracy (N = 320), spike IgG (ROC AUC: 95.0%, 92.8-97.3%) and spike IgA (ROC AUC: 89.9%, 86.5-93.2%) assays to discriminate best between pre-pandemic and post COVID-19 saliva samples. Specificity was 100% in younger age groups (0-19 years) for spike IgA and IgG. However, sensitivity was low for the best-performing assay (spike IgG: 50.6%, 39.8-61.4%). Using machine learning, diagnostic performance was improved when a combination of tests was used. As expected, salivary IgA was poorly correlated with serum, indicating an oral mucosal response whereas salivary IgG responses were predictive of those in serum. When deployed to household outbreaks, antibody responses were heterogeneous but remained a reliable indicator of recent infection. Intriguingly, unvaccinated children without confirmed infection showed evidence of exposure almost exclusively through specific IgA responses. CONCLUSIONS: Through robust standardisation, evaluation and field-testing, this work provides a platform for further studies investigating SARS-CoV-2 transmission and mucosal immunity with the potential for expanding salivo-surveillance to other respiratory infections in hard-to-reach settings.


If a person has been previously infected with SARS-CoV-2 they will produce specific proteins, called antibodies. These are present in the saliva and blood. Saliva is easier to obtain than blood, so we developed and evaluated six tests that detect SARS-CoV-2 antibodies in saliva in children and adults. Some tests detected antibodies to a particular protein made by SARS-CoV-2 called the spike protein, and these tests worked best. The most accurate results were obtained by using a combination of tests. Similar tests could also be developed to detect other respiratory infections which will enable easier identification of infected individuals.

20.
medRxiv ; 2023 Feb 14.
Article de Anglais | MEDLINE | ID: mdl-36798376

RÉSUMÉ

The application of machine learning (ML) tools in electronic health records (EHRs) can help reduce the underdiagnosis of dementia, but models that are not designed to reflect minority population may perpetuate that underdiagnosis. To address the underdiagnosis of dementia in both Black Americans (BAs) and white Americans (WAs), we sought to develop and validate ML models that assign race-specific risk scores. These scores were used to identify undiagnosed dementia in BA and WA Veterans in EHRs. More specifically, risk scores were generated separately for BAs (n=10K) and WAs (n=10K) in training samples of cases and controls by performing ML, equivalence mapping, topic modeling, and a support vector-machine (SVM) in structured and unstructured EHR data. Scores were validated via blinded manual chart reviews (n=1.2K) of controls from a separate sample (n=20K). AUCs and negative and positive predictive values (NPVs and PPVs) were calculated to evaluate the models. There was a strong positive relationship between SVM-generated risk scores and undiagnosed dementia. BAs were more likely than WAs to have undiagnosed dementia per chart review, both overall (15.3% vs 9.5%) and among Veterans with >90th percentile cutoff scores (25.6% vs 15.3%). With chart reviews as the reference standard and varied cutoff scores, the BA model performed slightly better than the WA model (AUC=0.86 with NPV=0.98 and PPV=0.26 at >90th percentile cutoff vs AUC=0.77 with NPV=0.98 and PPV=0.15 at >90th). The AUCs, NPVs, and PPVs suggest that race-specific ML models can assist in the identification of undiagnosed dementia, particularly in BAs. Future studies should investigate implementing EHR-based risk scores in clinics that serve both BA and WA Veterans.

SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE