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Toward Wisdom From Failure

2002· review· en· W2123152434 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueStroke · 2002
Typereview
Languageen
FieldMedicine
TopicAcute Ischemic Stroke Management
Canadian institutionsSunnybrook Health Science CentreOntario Stroke Network
FundersCanadian Institutes of Health ResearchUniversity of TorontoRoyal College of Physicians and Surgeons of CanadaHeart and Stroke Foundation of Canada
KeywordsMedicineNeuroprotectionPenumbraClinical trialTranslational researchStroke (engine)Drug developmentIntensive care medicineStroke recoveryNeuroscienceIschemiaDrugPharmacologyPhysical therapyCardiologyRehabilitationPathologyPsychology

Abstract

fetched live from OpenAlex

BACKGROUND: Neuroprotective drugs for acute stroke have appeared to work in animals, only to fail when tested in humans. With the failure of so many clinical trials, the future of neuroprotective drug development is in jeopardy. Current hypotheses and methodologies must continue to be reevaluated, and new strategies need to be explored. Summary of Review- In part 1, we review key challenges and complexities in translational stroke research by focusing on the "disconnect" in the way that neuroprotective agents have traditionally been assessed in clinical trials compared with animal models. In preclinical studies, determination of neuroprotection has relied heavily on assessment of infarct volume measurements (instead of functional outcomes), short-term (instead of long-term) end points, transient (instead of permanent) ischemia models, short (instead of extended) time windows for drug administration, and protection of cerebral gray matter (instead of both gray and white matter). Clinical trials have often been limited by inappropriately long time windows, insufficient statistical power, insensitive outcome measures, inclusion of protocol violators, failure to target specific stroke subtypes, and failure to target the ischemic penumbra. In part 2, we explore new concepts in ischemic pathophysiology that should encourage us also to think beyond the hyperacute phase of ischemia and consider the design of trials that use multiagent therapy and exploit the capacity of the brain for neuroplasticity and repair. CONCLUSIONS: By recognizing the strengths and limitations of animal models of stroke and the shortcomings of previous clinical trials, we hope to move translational research forward for the development of new therapies for the acute and subacute stages after stroke.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesInsufficient payload (model declined to judge)
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.642
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0020.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0040.003

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 head0.055
GPT teacher head0.306
Teacher spread0.251 · 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