RESUMO
INTRODUCTION: The Manchester Driver Behaviour Questionnaire (DBQ) is the most commonly used self-report tool in traffic safety research and applied settings. It has been claimed that the violation factor of this instrument predicts accident involvement, which was supported by a previous meta-analysis. However, that analysis did not test for methodological effects, or include unpublished results. METHOD: The present study re-analysed studies on prediction of accident involvement from DBQ factors, including lapses, and many unpublished effects. Tests of various types of dissemination bias and common method variance were undertaken. RESULTS: Outlier analysis showed that some effects were probably not reliable data, but excluding them did not change the results. For correlations between violations and crashes, tendencies for published effects to be larger than unpublished ones and for effects to decrease over time were observed, but were not significant. Also, using the mean of accidents as proxy for effect indicated that studies where effects for violations are not reported have smaller effect sizes. These differences indicate dissemination bias. Studies using self-reported accidents as dependent variables had much larger effects than those using recorded accident data. Also, zero-order correlations were larger than partial correlations controlled for exposure. Similarly, violations/accidents effects were strong only when there was also a strong correlation between accidents and exposure. Overall, the true effect is probably very close to zero (r<.07) for violations versus traffic accident involvement, depending upon which tendencies are controlled for. CONCLUSIONS: Methodological factors and dissemination bias have inflated the published effect sizes of the DBQ. Strong evidence of various artefactual effects is apparent. PRACTICAL APPLICATIONS: A greater level of care should be taken if the DBQ continues to be used in traffic safety research. Also, validation of self-reports should be more comprehensive in the future, taking into account the possibility of common method variance.
Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/psicologia , Condução de Veículo/estatística & dados numéricos , Autorrelato , Inquéritos e Questionários , Viés , Previsões , Humanos , Projetos de Pesquisa , Assunção de RiscosRESUMO
Roots of 3-d-old pea seedlings (Pisum sativum L.) were mechanically impeded using a sand core apparatus, which allowed mechanical impedance to be varied independently of aeration and water status. Turgor of root cortical cells was then measured using a pressure probe. In seedlings grown in sand cores for 1 d, impedance had little effect on turgor, but in seedlings grown in the sand cores for 2 d, impedance increased turgor by 0.18 MPa in the apical 6 mm.
Assuntos
Pisum sativum/fisiologia , Fenômenos Biomecânicos , Raízes de Plantas/fisiologia , Pressão , Dióxido de SilícioRESUMO
There are many conflicting opinions among health professionals and parents regarding care of the normal foreskin in young boys as well as the highly controversial subject of circumcision. Minor foreskin related complaints are very common in the first few years of life. Most of these can be managed with advice and reassurance, or with medical treatment alone. Circumcision is very rarely indicated in young boys, particularly under the age of 5 years. The issue of circumcision for non medical reasons, that is, religions, ethnic or personal, remains controversial.
Assuntos
Balanite (Inflamação)/terapia , Circuncisão Masculina , Pênis/anatomia & histologia , Fimose/terapia , Antibacterianos/uso terapêutico , Austrália , Balanite (Inflamação)/etiologia , Pré-Escolar , Fibrose , Humanos , Lactente , Recém-Nascido , Masculino , Pênis/patologia , Fimose/etiologiaRESUMO
The rationale for investigating conformationally restricted analogues of BW245C as DP-receptor ligands and the syntheses of three such racemic bicyclic imidazolidinone analogues are described. Compounds 7 (BW587C), 8 (BW480C85), and 9 (BW572C85) were found to be potent inhibitors of human platelet aggregation and selective DP-receptor agonists in washed platelet and jugular vein isolated tissue assays.
Assuntos
Butiratos/síntese química , Butiratos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Receptores de Prostaglandina/agonistas , Animais , Pressão Sanguínea/efeitos dos fármacos , Butiratos/química , Desenho de Fármacos , Humanos , Hidantoínas/química , Hidantoínas/farmacologia , Imidazóis/química , Veias Jugulares/efeitos dos fármacos , Veias Jugulares/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Coelhos , Ratos , Relação Estrutura-AtividadeRESUMO
BW245C analogues which have 15'-keto, -oximino, -sulphinyl, -sulphonyl, -methyl, -1-adamantyl, 14'-hydroxy, 16'-hydroxy, 13'-14'-NH=CH, -NH-CH2, or -NH-CO groups have been synthesized and evaluated for their activity in inhibiting platelet aggregation and for their cardiovascular actions: the 13'-aza analogues 13 and 14 are more potent inhibitors of human platelet aggregation than BW245C (0.3, 0.6 and 0.2 x PGI2, respectively) and these inhibitory activities on platelet aggregation increase on incubation in vitro. The prostaglandin mimetic properties of 13 (BW68C) and 14 (BW361C) were studied in more detail and their platelet inhibitory and vasodilatory effects found to be of longer duration than those of BW245C. All other modifications to the omega-chain of BW245C led to less potent or inactive compounds.
Assuntos
Hidantoínas/síntese química , Hidantoínas/farmacologia , Inibidores da Agregação Plaquetária/síntese química , Agregação Plaquetária/efeitos dos fármacos , Animais , Cães , Hemodinâmica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Inibidores da Agregação Plaquetária/farmacologia , Coelhos , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Vasodilatadores/síntese química , Vasodilatadores/farmacologiaRESUMO
A series of hydantoin prostaglandin analogues, in which the hexamethylene moiety of the acid side chain was replaced by other spacing groups possessing either ether, sulphide and/or olefin functionality, were prepared and evaluated for platelet aggregation inhibiting activity. The 4-thia analogue 13*) proved to be the most potent inhibitor (ca. 22x PGE1) and the 3-thia- and 3-oxa-analogues, 6 and 10 respectively, are approximately equipotent with BW245C (ca. 14x PGE1). Z-olefinic analogues (e.g. 11) were usually more potent than their E-isomers (e.g. 12). Structure-activity relationships are discussed in detail.
Assuntos
Hidantoínas/síntese química , Inibidores da Agregação Plaquetária/síntese química , Prostaglandinas/síntese química , Alprostadil/farmacologia , Animais , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/farmacologia , Humanos , Hidantoínas/farmacologia , Técnicas In Vitro , Masculino , Inibidores da Agregação Plaquetária/farmacologia , Prostaglandinas/farmacologia , Ratos , Ratos WistarRESUMO
Aryl substituted 1H-imidazo[1,2-a]imidazole 8, imidazo[2,1-b]thiazole 9, 1,4-dihydroimidazo[4,5-d]imidazole 11, and 1(2),4-dihydroimidazo[4,5-c]pyrazoles 12-17 have been prepared. An X-ray crystallographic study confirmed the structure of 8 and showed this analogue to exist as the 1H-tautomer. These heterocycles were evaluated as inotropic agents and analogues 12, 15, and 17 found to display inotropic properties which were less potent in vitro, but more potent in vivo, than those of sulmazole. Structure-activity relationships are discussed.
Assuntos
Cardiotônicos/síntese química , Imidazóis/síntese química , Animais , Cardiotônicos/farmacologia , Cães , Cobaias , Imidazóis/farmacologia , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Músculos Papilares/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The 5-desoxy analogue of BW245C, imidazolidin-2-one 3, has been synthesized by reduction of the N-benzyl hydantoin derivative 6. Compound 3 was found to be approximately equipotent with BW245C as an inhibitor of platelet aggregation and this result indicates that the 5-keto group of BW245C is not essential for platelet inhibitory activity.
Assuntos
Cicloexanos/síntese química , Imidazóis/síntese química , Prostaglandinas Sintéticas/síntese química , Cicloexanos/farmacologia , Humanos , Hidantoínas/síntese química , Hidantoínas/química , Hidantoínas/farmacologia , Imidazóis/farmacologia , Técnicas In Vitro , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/síntese química , Prostaglandinas Sintéticas/química , Prostaglandinas Sintéticas/farmacologia , Relação Estrutura-AtividadeRESUMO
A series of "A" ring substituted sulmazole and isomazole analogues have been prepared and evaluated as inotropic agents. pKA's, protonation sites, and log P values were measured for selected compounds and their electronic properties were calculated. No simple correlation between inotropic activity and pKA, protonation site, or log P value was observed. However, in vitro inotropism did correlate with the calculated charge density of the "B" ring imidazo nitrogen atom. The 6-position of sulmazole appeared to be the most tolerant toward substituents, the 6-amino derivative 7 being a more potent inotrope than sulmazole itself. 4-Methoxyisomazole 13 had comparable in vivo inotropic properties to those of isomazole.
Assuntos
Cardiotônicos/farmacologia , Imidazóis/farmacologia , Contração Miocárdica/efeitos dos fármacos , Animais , Cardiotônicos/síntese química , Fenômenos Químicos , Química , Cães , Eletroquímica , Feminino , Cobaias , Imidazóis/síntese química , Cinética , Masculino , Estrutura Molecular , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiologia , Prótons , Estimulação Química , Relação Estrutura-AtividadeRESUMO
A series of 2-substituted 1H-imidazo[4,5-b]pyridines and the isomeric 1H-imidazo[4,5-c]pyridine derivatives has been prepared and evaluated as inotropic agents. The 1H-imidazo-[4,5-b] derivatives were found to be consistently more potent than their isomers in the [4,5-c] series in isolated guinea pig papillary muscle preparations. Structure-activity relationships and the species-dependence of inotropic potencies are discussed.
Assuntos
Cardiotônicos , Imidazóis/farmacologia , Piridinas/farmacologia , Anestesia , Animais , Cardiotônicos/síntese química , Cães , Feminino , Cobaias , Imidazóis/síntese química , Técnicas In Vitro , Masculino , Músculos Papilares/efeitos dos fármacos , Piridinas/síntese química , Relação Estrutura-AtividadeRESUMO
Isomazole analogues which have achiral electron withdrawing substituents at the 4'-position and analogues with heterocyclic 'C' rings have been synthesized and evaluated as inotropic agents. It was found that pyridyl could replace phenyl in the 'C' ring without loss of activity. The 4'-methylsulphonyl, -cyano, -carboxamido, and acetyl analogues had similar inotropic potencies to Isomazole whilst displaying superior cardiovascular profiles in in vivo studies.