The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

The significance of "nonsignificance" in randomized controlled studies: a discussion inspired by a double-blinded study on St. John's Wort (Hypericum perforatum L.) for premenstrual symptoms

Objectives: This study aimed to investigate the efficacy of St. John's wort extract (SJW) as a treatment for premenstrual symptoms. Design: The study was a randomized, double-blinded, placebo-controlled trial, with two parallel treatment groups. After a no-treatment baseline cycle, volunteers were randomized to either SJW or placebo for a further two menstrual cycles. Settings/location: A postal trial conducted from The University of Reading, Berkshire, England. Subjects: One hundred and sixty-nine (169) normally menstruating women who experienced recurrent premenstrual symptoms were recruited onto the study. One hundred and twenty-five (125) completed the protocol and were included in the analysis. Interventions: Six hundred milligrams (600) mg of SJW (standardized to contain 1800 mug of hypericin) or placebo (containing lactose and cellulose). Outcome measure: A menstrual diary was used to assess changes in premenstrual symptoms. The anxiety-related subgroup of symptoms of this instrument was used as the primary outcome measure. Results: After averaging the effects of treatment over both treatment cycles it was found that there was a trend for SJW to be superior to placebo. However, this finding was not statistically significant. Conclusion: The possibility that this nonsignificant finding resulted from insufficient statistical power in the study, rather than a lack of efficacy of SJW, is discussed. Following this discussion the recommendation is made that, in future, similar studies should be powered to detect a minimum clinically relevant difference between treatments.

A potential lag between the open solar magnetic source flux and solar EUV and X-ray emissions as measured by the Earth's ionosphere during total solar eclipses

Measurements of the ionospheric E-region during total solar eclipses have been used to provide information about the evolution of the solar magnetic field and EUV and X-ray emissions from the solar corona and chromosphere. By measuring levels of ionisation during an eclipse and comparing these measurements with an estimate of the unperturbed ionisation levels (such as those made during a control day, where available) it is possible to estimate the percentage of ionising radiation being emitted by the solar corona and chromosphere. Previously unpublished data from the two eclipses presented here are particularly valuable as they provide information that supplements the data published to date. The eclipse of 23 October 1976 over Australia provides information in a data gap that would otherwise have spanned the years 1966 to 1991. The eclipse of 4 December 2002 over Southern Africa is important as it extends the published sequence of measurements. Comparing measurements from eclipses between 1932 and 2002 with the solar magnetic source flux reveals that changes in the solar EUV and X-ray flux lag the open source flux measurements by approximately 1.5 years. We suggest that this unexpected result comes about from changes to the relative size of the limb corona between eclipses, with the lag representing the time taken to populate the coronal field with plasma hot enough to emit the EUV and X-rays ionising our atmosphere.

Metal cluster expansion by addition of low valent group 14 reagents: III. Reaction of bis[bis(trimethylsilyl)methyl]tin with M3(CO)12 or its derivatives (M = Fe, Ru, or Os): the crystal and molecular structures of M3(μ-SnR2)2(CO)10(R = CH(SiMe3)2; M = Ru or Os)

The stannylene [SnR2] (R = CH(SiMe3)2) reacts in different ways with the three dodecacarbonyls of the iron triad: [Fe3(CO)12] gives [Fe2(CO)8(μ-SnR2)], [Ru3(CO)12] gives the planar pentametallic cluster [Ru3(CO)10(μ-SnR2)2], for which a full structural analysis is reported, while [Os3(CO)12] fails to react. Different products are also obtained from three nitrile derivatives: [Fe3-(CO)11(MeCN)] gives [Fe2(CO)6(μ-SnR2)2], which has a structure significantly different from that of known Fe2Sn2 clusters, [Ru3(CO)10(MeCN)2] gives the pentametallic cluster described above, while [Os3(CO)10(MeCN)2] gives the isostructural osmium analogue, which shows the unusual feature of a CO group bridging two osmium atoms.

Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.