Bibliographic record
Abstract
Cardiovascular disease is the largest cause of morbidity and mortality in the industrialised world. Many patients with a longstanding history of coronary artery disease, multiple coronary interventions and a number of prior coronary events are no longer suitable for conventional revascularisation strategies and are often referred to as "no-option" patients. Despite intensive medical treatment, many present with clinical signs of heart failure and/or angina in the presence of underperfused, viable myocardium. I investigated two new strategies proposed to treat this patient population; angiogenesis induced by gene therapy in a pre-clinical model of myocardial ischaemia and regenerative therapy with autologous bone marrow derived putative stem cells in a Phase IIA pilot clinical trial. After establishing the ameroid porcine model of myocardial ischaemia, the efficacy of epicardially delivered Hypoxia Inducible Factor-1 alpha (HIF-1) was assessed with adenovirus (AdHIF-1α) and two plasmid constructs. AdHIF-1α was found to significantly increase myocardial blood flow and left ventricular function in this model. In a further study electromechanical mapping of ischaemic territory and endocardial delivery with AdHIF-1α demonstrated similar trends. I present the first clinical trial to demonstrate the feasibility of retrograde coronary venous delivery of putative stem cells to the heart. The inclusion of 111-In oxide labelled cells demonstrated a sustained myocardial signal up to 21 days. Retention of cells within the myocardium is likely to be critical in allowing a biologically important paracrine function or stem cell differentiation. In the six-month follow-up, there were no major safety concerns, although only hypothesis generating efficacy endpoints were included, significant improvements were seen in Quality of life, New York Heart Association (NYHA) class and myocardial oxygen consumption (MVO2). A positive correlation was seen with the number of CD34+ cells delivered and change in MVO2. Further randomised placebo controlled trials are required to elucidate further any perceived improvements in efficacy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".