Malcolm R. Macleod

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The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were(More)
The development of stroke drugs has been characterized by success in animal studies and subsequent failure in clinical trials. Animal studies might have overstated efficacy, or clinical trials might have understated efficacy; in either case we need to better understand the reasons for failure. Techniques borrowed from clinical trials have recently allowed(More)
BACKGROUND AND PURPOSE The extensive neuroprotective literature describing the efficacy of candidate drugs in focal ischemia has yet to lead to the development of effective stroke treatments. Ideally, the choice of drugs taken forward to clinical trial should be based on an unbiased assessment of all available data. Such an assessment might include not only(More)
OBJECTIVE To examine concordance between treatment effects in animal experiments and clinical trials. Study design Systematic review. DATA SOURCES Medline, Embase, SIGLE, NTIS, Science Citation Index, CAB, BIOSIS. STUDY SELECTION Animal studies for interventions with unambiguous evidence of a treatment effect (benefit or harm) in clinical trials: head(More)
The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst "experts" and in the public understanding. Where data are collected but remain unpublished, they(More)
OBJECTIVE Preclinical evaluation of neuroprotectants fostered high expectations of clinical efficacy. When not matched, the question arises whether experiments are poor indicators of clinical outcome or whether the best drugs were not taken forward to clinical trial. Therefore, we endeavored to contrast experimental efficacy and scope of testing of drugs(More) Vol 383 January 11, 2014 101 Of 1575 reports about cancer prognostic markers pub lished in 2005, 1509 (96%) detailed at least one signifi cant prognostic variable. However, few identifi ed biomarkers have been confi rmed by subsequent research and few have entered routine clinical practice. This pattern—initially promising fi ndings not(More)
The nuclear mineralocorticoid receptor (MR), a high-affinity receptor for glucocorticoids, is highly expressed in the hippocampus where it underpins cognitive, behavioural and neuroendocrine regulation. Increased neuronal MR expression occurs early in the response to cellular injury in vivo and in vitro and is associated with enhanced neuronal survival. To(More)
Induced hypothermia is proposed as a treatment for acute ischaemic stroke, but there have been too few clinical trials involving too few patients to draw any conclusions about the therapeutic benefit of cooling. Animal studies of induced hypothermia in focal cerebral ischaemia have tested cooling throughout a wide range of target temperatures, durations and(More)