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Record W2808199070 · doi:10.1177/2058739218784820

The dose response of inhaled LPS challenge in healthy subjects

2018· article· en· W2808199070 on OpenAlexaff
Alex Mulvanny, Natalie Jackson, Caroline Pattwell, Sophie Wolosianka, Thomas Southworth, Dave Singh

Bibliographic record

VenueEuropean Journal of Inflammation · 2018
Typearticle
Languageen
FieldMedicine
TopicNeonatal Respiratory Health Research
Canadian institutionsInstitute of Infection and Immunity
FundersJohnson and JohnsonTeva Pharmaceutical IndustriesGlaxoSmithKline
KeywordsMyeloperoxidaseMedicineSputumLipopolysaccharideInhalationTumor necrosis factor alphaImmunologyInflammationCytokinePharmacologyInternal medicineAnesthesiaPathologyTuberculosis

Abstract

fetched live from OpenAlex

Lipopolysaccharide (LPS) inhalation causes neutrophilic airway inflammation. We used LPS produced to Good Manufacturing Practice (GMP) standards to characterise the dose response. A total of 15 healthy non-smoking subjects inhaled 5-, 15- and 50-µg LPS. Whole blood cell counts and serum C-reactive protein (CRP) were measured at baseline and up to 24 h post challenge. Sputum was induced at baseline and 6 h post challenge for cell counts and quantification of myeloperoxidase (MPO), interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor α (TNF-α) in supernatants. LPS inhalation was well tolerated. Blood neutrophil counts increased at 6 h post LPS with all doses. Serum CRP significantly increased with 15- and 50-µg LPS. All LPS doses significantly increased sputum neutrophil percentage ( P < 0.001). IL-1β, IL-6 and TNF-α were significantly increased in sputum supernatant following challenge with 50-µg LPS, there was no change in MPO or IL-8. The 50-µg LPS was well tolerated and produced a robust inflammatory response. This study supports the use of 50-µg GMP-grade LPS as a suitable challenge agent in clinical trials.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0010.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.053
GPT teacher head0.361
Teacher spread0.307 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2018
Admission routes1
Has abstractyes

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