180 resultados para Causal Relationships


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Several studies have shown social differences in alcohol consumption, and social inequalities of harm related to alcohol use and abuse. However, relationships between the position in the socio-economic spectrum, alcohol use, and alcohol-related health problems are not clear cut. While there is some evidence of social gradients or associations between indicators of deprivation and some adolescence outcomes (e.g. externalising behaviour), the evidence regarding associations between socio-economic status and alcohol-related problems in adolescence is more conflicting. A major problem in studying socio-economic inequalities in adolescent health is related to the paucity of measures of socio-economic status in adolescence that are both conceptually and methodologically sound.
The aims of this study were to investigate socio-economic differences in pathways from onset to establishment of drinking patterns in adolescence, assess the consequences of these pathways in terms of alcohol related harm, and to consider the causal mechanisms that may contribute to socio-economic differences in drinking pathways and outcomes

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Objectives. We investigated whether exposure to negative aspects of close relationships was associated with subsequent increase in body mass index (BMI) and waist circumference.
Methods. Data came from a prospective cohort study (Whitehall II) of 9425 civil servants aged 35 to 55 years at baseline (phase 1: 1985-1988). We assessed negative aspects of close relationships with the Close Persons Questionnaire (range 0-12) at phases 1 and 2 (1989-1990). We measured BMI and waist circumference at phases 3 (1991-1994) and 5 (1997-1999). Covariates at phase 1 included gender, age, marital status, ethnicity, BMI, employment grade, smoking, physical activity, fruit and vegetable consumption, and common mental disorder.
Results. After adjustment for sociodemographic characteristics and health behaviors, participants with higher exposure to negative aspects of close relationships had a higher likelihood of a 10% or greater increase in BMI and waist circumference (odds ratios per 1-unit increase 1.08 [95% confidence interval (CI)=1.02, 1.14; P=.007] and 1.09 [CI=1.04, 1.14; P <= .001], respectively) as well as a transition from the overweight (25 <= BMI <30) to the obese (BMI >= 30) category.
Conclusions. Adverse social relationships may contribute to weight gain.

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The gain coefficient of the strongest 3p --> 3s, J = 2 --> 1 lasing transition at 23.6 nm in the Ne-like Ge collisional excitation scheme has been measured, using the fundamental wavelength from a Nd:glass laser (1.06-mu-m), for a range of incident intensities on massive stripe targets up to 2.2 cm in length. From a threshold incident laser intensity of approximately 6 x 10(12) W/cm2, the gain coefficient rises to approximately 4.5 cm-1 for an irradiation intensity of approximately 2.5 x 10(13) W/cm2, tending towards still higher gain coefficients at higher incident intensities. For targets of maximum length, a gain-length product gL almost-equal-to 10 was reached with a resultant output power at 23.6 nm estimated to be at the approximately kW level. The beam divergence decreased with length to a minimum of approximately 7 mrad but no significant trend in beam pointing with plasma length was observed. From the trend in the gain coefficient, it appears that for a fixed energy laser irradiating a approximately 100-mu-m wide slab targets, an incident intensity of I(i) approximately 1.2 x 10(13) W/cm2 represents an optimum working level, assuming that plasma length is not limited by refractive effects. In addition to the usual valence electron excited 3p --> 3s transitions, the gain coefficient for the core excited 1s(2)2s2p(6)3d --> 1s(2)2s2p(6)3p transition at 19.9 nm has been measured to be approximately 1.5 cm-1 for an incident irradiance of approximately 2.5 x 10(13) W/cm2.

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The current morphological classification of the Demospongiae G4 clade was tested using large subunit ribosomal RNA (LSU rRNA) sequences from 119 taxa. Fifty-three mitochondrial cytochrome oxidase 1 (CO1) barcoding sequences were also analysed to test whether the 28S phylogeny could be recovered using an independent gene. This is the largest and most comprehensive study of the Demospongiae G4 clade. The 28S and CO1 genetrees result in congruent clades but conflict with the current morphological classification. The results confirm the polyphyly of Halichondrida, Hadromerida, Dictyonellidae, Axinellidae and Poecilosclerida and show that several of the characters used in morphological classifications are homoplasious. Robust clades are clearly shown and a new hypothesis for relationships of taxa allocated to G4 is proposed. (C) 2011 Elsevier Inc. All rights reserved.

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This study reports the potent myoactivity of flatworm FMRFamide-related peptides (FaRPs) on isolated muscle fibers of the human blood fluke, Schistosoma mansoni. The turbellarian peptides YIRFamide (EC50 4 eta M), GYIRFamide (EC50 1 eta M). and RYIRFamide (EC50 7 eta M), all induced muscle contraction more potently than the cestode FaRP GNFFRFamide (EC50 500 eta M). Using a series of synthetic analogs of the flatworm peptides YIRFamide, GYIRFamide and RYIRFamide, the structure-activity relationships of the muscle FaRP receptor were examined. With a few exceptions, each residue in YIRFamide is important in the maintenance of its myoactivity. Alanine scans resulted in peptides that were inactive (Ala(1), Ala(2), Ala(3) and Ala(4) YIRFamide; Ala(4) and Ala(5) RYIRFamide) or had much reduced potencies (Ala(1), Ala(2) and Ala(3) RYIRFamide). Substitution of the N-terminal (Tyr(1)) residue of YIRFamide with the non-aromatic residues Thr or Arg produced analogs with greatly reduced potency. Replacement of the N-terminal Tyr with aromatic amino acids resulted in myoactive peptides (FIRFamide, EC50 100 eta M; WIRFamide, EC50 0.5 eta M). The activity of YIRFamide analogs which possessed a Leu(2), Phe(2) or Met(2) residue (EC50's 10, 1 and 3 eta M, respectively) instead of Ile(2) was not significantly altered, whereas, YVRFamide had a greatly reduced (EC50 200 eta M) activity. Replacement of the Phe(4) with a Tyr(4) (YIRYamide) also greatly lowered potency. Truncated analogs were either inactive (FRFamide, YRFamide, HRFamide, RFamide, Famide) or had very low potency (IRFamide and MRFamide), with the exception of nLRFamide (EC50 20 eta M). YIRF free acid was inactive. In summary, these data show the general structural requirements of this schistosome muscle FaRP receptor to be similar, but not identical, to those of previously characterized molluscan FaRP receptors. (C) 1997 Elsevier Science Inc.

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Signal Transducers and Activators of Transcription (STAT) proteins are a group of latent cytoplasmic transcription factors involved in cytokine signaling. STAT3 is a member of the STAT family and is expressed at elevated levels in a large number of diverse human cancers and is now a validated target for anticancer drug discovery.. Understanding the dynamics of the STAT3 dimer interface, accounting for both protein-DNA and protein-protein interactions, with respect to the dynamics of the latent unphosphorylated STAT3 monomer, is important for designing potential small-molecule inhibitors of the activated dimer. Molecular dynamics (MD) simulations have been used to study the activated STAT3 homodimer:DNA complex and the latent unphosphorylated STAT3 monomer in an explicit water environment. Analysis of the data obtained from MD simulations over a 50 ns time frame has suggested how the transcription factor interacts with DNA, the nature of the conformational changes, and ways in which function may be affected. Examination of the dimer interface, focusing on the protein-DNA interactions, including involvement of water molecules, has revealed the key residues contributing to the recognition events involved in STAT3 protein-DNA interactions. This has shown that the majority of mutations in the DNA-binding domain are found at the protein-DNA interface. These mutations have been mapped in detail and related to specific protein-DNA contacts. Their structural stability is described, together with an analysis of the model as a starting-point for the discovery of novel small-molecule STAT3 inhibitors.