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 pilot randomised, open, uncontrolled, clinical study of two dosages of St John's wort (Hypericum perforatum) herb extract (LI-160) as an aid to motivational/behavioural support in smoking cessation

There is an association between smoking and depression, yet the herbal antidepressant St John's wort (Hypericum perforatum L.: SJW) herb extract has not previously been investigated as an aid in smoking cessation. In this open, uncontrolled, pilot study, 28 smokers of 10 or more cigarettes per day for at least one year were randomised to receive SJW herb extract (LI-160) 300mg once or twice daily taken for one week before and continued for 3 months after a target quit date. In addition, all participants received motivational/behavioural support from a trained pharmacist. At 3 months, the point prevalence and continuous abstinence rates were both 18%, and at 12 months were 0%. Fifteen participants (54%) reported 23 adverse events up to the end of the 3-month follow-up period. There was no statistically significant difference in the frequency of adverse events for participants taking SJW once or twice daily (p > 0.05). Most adverse events were mild, transient and non-serious. This preliminary study has not provided convincing evidence that a SJW herb extract plus individual motivational/behavioural support is likely to be effective as an aid in smoking cessation. However, it may be premature to rule out a possible effect on the basis of a single, uncontrolled pilot study, and other approaches involving SJW extract may warrant investigation.

Interações medicamentosas de fitoterápicos e fármacos: Hypericum perforatum e Piper methysticum

A utilização de produtos naturais na medicina popular é milenar e persiste até os dias atuais. Entretanto, a idéia de que estes produtos são isentos de toxicidade torna o uso de medicamentos fitoterápicos cada vez maior e indiscriminado. Este trabalho trata de uma revisão sobre as interações que podem ocorrer com a utilização concomitante de Hypericum perforatum L. (erva de são joão) e Piper methysticum F. (kava-kava) com fármacos, podendo levar a sérios efeitos tóxicos, incluindo a fatalidade.

Chemical Composition and Antimicrobial Activities of the Essential Oil of Hypericum cordatum (Vell. Conc.) N. Robson (Hypericaceae)

The volatile Constituents of the fresh materials of Hypericum cordatum were isolated by hydrodistillation kind analyzed by CC and GC/MS. The leaves produced 0.04% of a yellowish essential oil and the flowers did not. The main components of the oil were myrcene (40.18%), alpha-pinene (16.40%), and limonene (12%). The antibacterial activities of the oil against Saccharomyces aureus and Escherichia coli and the anti-fungal activities of the oil against the fungi Cladosporium cladosporioides and C. sphaerospemum were evaluated. The oil showed an antibacterial activity against the bacteria S. aureus and anti-fungal activity against the two fungi.

Estudo da qualidade da informação constante nas bulas dos principais medicamentos fitoterápicos registrados no Brasil

Os objetivos deste trabalho foram: fazer um levantamento das dez espécies vegetais que compõem o maior número de apresentações farmacêuticas de fitoterápicos simples registradas na ANVISA; realizar o diagnóstico da oferta e da qualidade das informações contidas nas bulas das apresentações contendo as cinco espécies vegetais mais utilizadas; e definir as informações técnicas que devem estar contidas na bula de especialidades farmacêuticas que contenham como ingredientes ativos unicamente extratos preparados a partir destas espécies. O levantamento das dez espécies vegetais abrangeu o período de 01/01/1998 a 30/06/2003 e foi realizado através de consulta ao OPTLINE (www.i-helps.com). Os medicamentos fitoterápicos representam 7,76% (1888) das apresentações de registro de medicamentos no Brasil, sendo 1311 (5,38 %) apresentações de medicamentos fitoterápicos simples. Cinqüenta e oito espécies vegetais constituíam os registros de medicamentos fitoterápicos simples, sendo as dez com maior número de apresentações Ginkgo biloba L.: 302 (23,04%); Hypericum perforatum L.: 126 (9,61%); Piper methysticum F.: 87 (6,64%); Cimicifuga racemosa Nutt: 79 (6,03%); Valeriana officinalis L.: 76 (5,80%); Vitis vinifera L.: 69 (5,26%); Echinacea purpurea L.: 58 (4,42%); Aesculus hippocastanum L.: 53 (4,04%); Panax ginseng C. A Mayer: 48 (3,66%) e Cynara scolymus L.: 31 (2,36%). O diagnóstico da oferta e da qualidade das informações contidas nos textos das bulas foi realizado comparando-se estas informações com aquelas apresentadas na base de dados Medline (PubMed - www.ncbi.nhm.nhi.gov) dos últimos 5 anos e em obras bibliográficas de referência aceitas pela ANVISA, além de outras, clássicas na área de farmacognosia e fitoterapia . Foram avaliadas vinte e oito bulas. As informações de todas as bulas apresentavam incompatibilidades com as informações da literatura consultada. Os problemas mais freqüentemente encontrados foram relativos à sinonímia popular, eficácia, via de administração, contra-indicações, uso em idosos, crianças e grupos de risco, reações adversas e interações medicamentosas. Para cada uma das cinco espécies mais citadas, as informações científicas e técnicas compiladas foram organizadas como uma proposta de bula para o Profissional de Saúde a ser incluída no Compêndio de Bulas de Medicamentos (CBM), conforme previsto na Resolução-RDC nº 140/03, o qual consiste em um conjunto de bulas de medicamentos comercializados, editado pelo órgão regulador e com conteúdo da bula para o paciente e da bula para o profissional de saúde.

Towards executable specification : combining i* and AgentSpeak(L).

Agent-oriented conceptual modelling (AoCM) approaches in Requirements Engineering (RE) have received considerable attention recently. Semi-formal modeling frameworks such as i* assist analysts in requirements elicitation and reasoning of early-phase RE. AgentSpeak(L) is a widely accepted agent programming language. The Strategic Rationale (SR) model of the i* framework naturally lends itself to AgentSpeak(L) programs. Furthermore, the Strategic Dependency (SD) component of the i* framework prescribes the interaction between the agents in a multi-agent environment. This paper proposes a formal methodology for transforming a SR model to an AgentS- peak(L) agent. The constructed AgentSpeak(L) agents will then form the essential components of a multi-agent system, MAS.

Enhanced human bone marrow stromal cell affinity for modified poly(L-lactide) surfaces by the upregulation of adhesion molecular genes

To enhance and regulate cell affinity for poly (l-lactic acid) (PLLA) based materials, two hydrophilic ligands, poly (ethylene glycol) (PEG) and poly (l-lysine) (PLL), were used to develop triblock copolymers: methoxy-terminated poly (ethylene glycol)-block-poly (l-lactide)-block-poly (l-lysine) (MPEG-b-PLLA-b-PLL) in order to regulate protein absorption and cell adhesion. Bone marrow stromal cells (BMSCs) were cultured on different composition of MPEG-b-PLLA-b-PLL copolymer films to determine the effect of modified polymer surfaces on BMSC attachment. To understand the molecular mechanism governing the initial cell adhesion on difference polymer surfaces, the mRNA expression of 84 human extracellular matrix (ECM) and adhesion molecules was analysed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). It was found that down regulation of adhesion molecules was responsible for the impaired BMSC attachment on PLLA surface. MPEG-b-PLLA-b-PLL copolymer films improved significantly the cell adhesion and cytoskeleton expression by upregulation of relevant molecule genes significantly. Six adhesion genes (CDH1, ITGL, NCAM1, SGCE, COL16A1, and LAMA3) were most significantly influenced by the modified PLLA surfaces. In summary, polymer surfaces altered adhesion molecule gene expression of BMSCs, which consequently regulated cell initial attachment on modified PLLA surfaces.

Synthesis of 4-arm star poly(L-Lactide) oligomers using an in situ-generated calcium-based initiator

Using an in situ-generated calcium-based initiating species derived from pentaerythritol, the bulk synthesis of well-defined 4-arm star poly(L-lactide) oligomers has been studied in detail. The substitution of the traditional initiator, stannous octoate with calcium hydride allowed the synthesis of oligomers that had both low PDIs and a comparable number of polymeric arms (3.7 – 3.9) to oligomers of similar molecular weight. Investigations into the degree of control observed during the course of the polymerization found that the insolubility of pentaerythritol in molten L-lactide resulted in an uncontrolled polymerization only when the feed mole ratio of L-lactide to pentaerythritol was 13. At feed ratios of 40 and greater, a pseudo-living polymerization was observed. As part of this study, in situ FT-Raman spectroscopy was demonstrated to be a suitable method to monitor the kinetics of the ring-opening polymerization (ROP) of lactide. The advantages of using this technique rather than FT-IR-ATR and 1H NMR for monitoring L-lactide consumption during polymerization are discussed.

L'étendue internationale des nouvelles firmes de hautes technologies: le rôle du capital humain et de l'intention stratégique des fondateurs

De récentes recherches ont mis l’accent sur l’importance pour les nouvelles entreprises internationales de l’existence de ressources et de compétences spécifiques. La présente recherche, qui s’inscrit dans ce courant, montre en particulier l’importance du capital humain acquis par les entrepreneurs sur base de leur expérience internationale passée. Mais nous montrons en même temps que ces organisations sont soutenues par une intention délibérée d’internationalisation dès l’origine. Notre recherche empirique est basée sur l’analyse d’un échantillon de 466 nouvelles entreprises de hautes technologies anglaises et allemandes. Nous montrons que ce capital humain est un actif qui facilite la pénétration rapide des marchés étrangers, et plus encore quand l’entreprise nouvelle est accompagnée d’une intention stratégique délibérée d’internationalisation. Des conclusions similaires peuvent être étendues au niveau des ressources que l’entrepreneur consacre à la start-up : plus ces ressources sont importantes, plus le processus d’internationalisation tend à se faire à grande échelle ; et là aussi, l’influence de ces ressources est augmenté par l’intention stratégique d’internationalisation. Dans le cadre des études empiriques sur les born-globals (entreprises qui démarrent sur un marché globalisé), cette recherche fournit une des premières études empiriques reliant l’influence des conditions initiales de création aux probabilités de croissance internationale rapide.