Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

<p><b>Background and Purpose:</b> Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume.</p> <p><b>Methods:</b> Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III.</p> <p><b>Results:</b> The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms.</p> <p><b>Discussion:</b> Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place.</p&gt

Effect of seed phosphorus levels in three wheat varieties and fertilizer P supply on their growth and grain yields.

Trial 89WH74 Location: Wongan Hills Research Station, Field 4W Effect of phosphorus and fertilizer on the growth and grain of wheat yields

Effect of seed phosphorus , seed size and seeding density on the growth of wheat at two soil P levels.

Trial 89SC23 Location: South Carrabin Effect of soil P, seed P and seed rate on plant counts at 5 weeks.Shoot dry matter (DM) at tillering and heading and seed DM at maturity were strongly depressed by low soil P levels

Effects of seed phosphorus concentrations and the source of the seed on growth of lupins.

Trial 89EC31 Location: East Chapman Research Station. The effect of seed phosphorus concentration, source of seed and fertilizer P level on plant counts from six to 20 weeks

Effect of seed origin and seed phosphorus on the growth of lupins.

Trial: 89BA29 Location: Badgingarra Research Station, Paddock 4A2, old block. Lupin cv. Gungurru sieved to uniform size and sown without inoculation. No basal fertilizers were applied as the soil had previously been treated with high rates of superphosphate, micro-nutrients and potassium. Muriate of potash topdressed on 18/8/89 at 100 kg/ha

The effect of seed origin and seed phosphorus on the growth of lupins

Trial: 89SC20 Location: South Carrabin Research Station, Hayden paddock. The effects of superphosphate and fertilizer on seeds planted over a 21 week period

Effects of Reflection and Refraction of Ultrasonic Waves on the Angle Beam Inspection of Anisotropic Composite Material

Nondestructive testing of composite materials by ultrasonic techniques has several specific features resulting from strong material anisotropy and inhomogeneity. This requires reexamination of old testing methodologies and development of new ones. The latest developments in this direction were recently reviewed by Henneke and Duke [1] and by Bar-Cohen [2]

Genetic Modifiers of Systemic Lupus Erythematosus in FcγRIIB−/− Mice

FcγRIIB is a potent lupus susceptibility gene as demonstrated by the observation that mice deficient in this molecule develop spontaneous antinuclear antibodies (ANA) and fatal glomerulonephritis when on the C57BL/6 background. To determine the mechanisms underlying the epistasis displayed by this gene we have constructed hybrids between FcγRIIB−/− and the systemic lupus erythematosus (SLE) modifiers yaa and lpr and the susceptibility locus Sle1. Sle1 and B6.RIIB−/− are both physically and functionally coupled; compound heterozygotes of Sle1 and B6.RIIB−/− develop significant disease, while single heterozygotes display no evidence of autoimmunity or disease, indicating that these genes lie on the same genetic pathway resulting in the loss of tolerance to nuclear antigens. However, the generation of ANA in itself is insufficient to account for the severity of autoimmune disease in this model, as demonstrated by analysis of yaa and lpr hybrids. Thus, B6.RIIB−/−/lpr mice are protected from disease progression, despite equivalent titers of ANA. In contrast, B6.RIIB−/−/yaa mice have significantly enhanced disease despite reduced ANA titers. Yaa modifies the specificity and thus the pathogenicity of the B6. RIIB−/− ANA, by converting them to antinucleolar antibodies. In addition to these known modifier pathways, we have discovered two novel, recessive loci contributed by the C57BL/6 genome that are required for the ANA phenotype, further indicating the epistatic properties of this SLE model