982 resultados para non-responders
Resumo:
Ankylosing spondylitis (AS) has been associated with human leukocyte antigen (HLA)-B27 for over 30 years; however, the mechanism of action has remained elusive. Although many studies have reported associations between AS and other genes in the major histocompatibility complex (MHC) in AS, no conclusive results have emerged. To investigate the contribution of non-B27 MHC genes to AS, a large cohort of AS families and controls were B27 typed and genotyped across the region. Interrogation of the data identified a region of 270kb, lying from 31952649 to 32221738 base pairs from the p-telomere of chromosome 6 and containing 23 genes, which is likely to include genes involved with susceptibility to AS.
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Constrained topography and complex road geometry along rural mountainous roads often represent a demanding driving situation. As a result, traffic crashes along mountainous roads are likely to have different characteristics to crashes on roads in flatter areas; however, there is little research on this topic. The objective of this study is to examine the characteristics of road traffic crashes on rural mountainous roads and to compare these with the characteristics of crashes on non-mountainous roads. This paper explores and compares general crash characteristics including crash type, crash severity, roadway geometric features and environmental factors, and road user/vehicle characteristics. Five years of road traffic crash data (2008-2012) for Sabah were obtained from the Malaysian Institute of Road Safety Research. During this period, a total of 25,439 crashes occurred along federal roads in Sabah, of which 4,875 crashes occurred in mountainous areas. Categorical data analysis techniques were used to examine the differences between mountainous and non-mountainous crashes. Results show that the odds ratio of ‘out-of-control’ crashes and the crash involvement due to speeding are respectively about 4.2 times and 2.8 times higher on mountainous than non-mountainous roads. Other factors and crash characteristics that increase the odds of crashes along mountainous roads compared with non-mountainous roads include horizontal curved sections compared with straight sections, single-vehicle crashes compared with multi-vehicle crashes and weekend crashes compared with weekday crashes. This paper identifies some of the basic characteristics of crashes along rural mountainous roads to aid future research on traffic safety along mountainous roads.
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Evidence increasingly suggests that our behaviour on the road mirrors our behaviour across other aspects of our life. The idea that we drive as we live, described by Tillman and Hobbs more than 65 years ago when examining off-road behaviours of taxi drivers (1949), is the focus of the current paper. As part of a larger study examining the impact of penalty changes on a large cohort of Queensland speeding offenders, criminal (lifetime) and crash history (10 year period) data for a sub-sample of 1000 offenders were obtained. Based on the ‘drive as we live’ maxim, it was hypothesised that crash-involved speeding offenders would be more likely to have a criminal history than non-crash involved offenders. Overall, only 30% of speeding offenders had a criminal history. However, crash-involved offenders were significantly more likely to have a criminal history (49.4%) than non-crash involved offenders (28.6%), supporting the hypothesis. Furthermore, those deemed ‘most at fault’ in a crash were the group most likely to have at least one criminal offence (52.2%). When compared to the non-crash involved offenders, those deemed ‘not most at fault’ in a crash were also more likely to have had at least one criminal offence (46.5%). Therefore, when compared to non-crash involved speeding offenders, those offenders involved in a crash were more likely to have been convicted of at least one criminal offence, irrespective of whether they were deemed ‘most at fault’ in that crash. Implications for traffic offender management and policing are discussed.
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Background. Rheumatoid arthritis (RA) is strongly associated with a series of HLA-DRB1 alleles that encode a conserved sequence of amino acids (70Q/R K/R R A A74) in the DRβ1 chain, known as the shared epitope (SE). However 30% of patients are negative for DRB1*04 and 15% are SE-negative. Exposure to these alleles as non-inherited maternal antigens (NIMA) might explain this discrepancy. We undertook a family study to investigate the role of NIMA in RA. Methods. One hundred families, including the RA proband and both parents, were recruited. HLA-DRB1 genotyping was performed using an allele-specific polymerase chain reaction by standard methods. The frequencies of NIMA and non-inherited paternal antigens (NIPA) were compared using contingency tables and a two-tailed P test. We then reviewed four previously published studies of NIMA in RA and conducted an analysis of the combined data Results. We identified 36 families in which the proband was DRB1*04-negative and 13 in which the proband lacked the SE. There was an excess of DRB1*04 and SE NIMA (P=0.05) compared with NIPA. Combined analysis with previous studies showed that 53/231 mothers (23%) versus 25/205 fathers (12%) had a non-inherited DRB1*04 (P=0.003) and 30/99 mothers versus 18/101 fathers had a non-inherited SE allele (P=0.03). Conclusion. A role for HLA NIMA in RA is suggested by these results.
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Constrained topography and complex road geometry along rural mountainous roads often represent a demanding driving situation. As a result, traffic crashes along mountainous roads are likely to have different characteristics to crashes on roads in flatter areas; however, there is little research on this topic. The objective of this study is to examine the characteristics of road traffic crashes on rural mountainous roads and to compare these with the characteristics of crashes on non-mountainous roads. This paper explores and compares general crash characteristics including crash type, crash severity, roadway geometric features and environmental factors, and road user/vehicle characteristics. Five years of road traffic crash data (2008-2012) for Sabah were obtained from the Malaysian Institute of Road Safety Research. During this period, a total of 25,439 crashes occurred along federal roads in Sabah, of which 4,875 crashes occurred in mountainous areas. Categorical data analysis techniques were used to examine the differences between mountainous and non-mountainous crashes. Results show that the odds ratio of ‘out-of-control’ crashes and the crash involvement due to speeding are respectively about 4.2 times and 2.8 times higher on mountainous than non-mountainous roads. Other factors and crash characteristics that increase the odds of crashes along mountainous roads compared with non-mountainous roads include horizontal curved sections compared with straight sections, single-vehicle crashes compared with multi-vehicle crashes and weekend crashes compared with weekday crashes. This paper identifies some of the basic characteristics of crashes along rural mountainous roads to aid future research on traffic safety along mountainous roads.
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Purpose The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch® method. Method Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch® method. Results The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age. Conclusion This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.
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Dieting and non-dieting are two contrasting approaches to the management of overweight/obesity, but less is known about why people follow non-dieting approaches and how these approaches are associated with health and nutrition status indicators. This thesis enables a greater understanding of why dieting and non-dieting approaches are adopted and provides insight into whether one approach is more favourably associated with nutrition and health status indicators. The findings of this thesis will be useful for clinicians who wish to encourage dieting or non-dieting approaches in their clients and for researchers wishing to understand how best to address overweight and obesity.
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The problem of mixed convection from vertical surfaces in a porous medium saturated with a power-law type non-Newtonian fluid is investigated. The transformed conservation laws are solved numerically for the case of variable wall temperature conditions. Results for the details of the velocity and temperature fields as well as the Nusselt number have been presented. The viscosity index ranged from 0.5-2.0.
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Chemical composition of rainwater changes from sea to inland under the influence of several major factors - topographic location of area, its distance from sea, annual rainfall. A model is developed here to quantify the variation in precipitation chemistry under the influence of inland distance and rainfall amount. Various sites in India categorized as 'urban', 'suburban' and 'rural' have been considered for model development. pH, HCO3, NO3 and Mg do not change much from coast to inland while, SO4 and Ca change is subjected to local emissions. Cl and Na originate solely from sea salinity and are the chemistry parameters in the model. Non-linear multiple regressions performed for the various categories revealed that both rainfall amount and precipitation chemistry obeyed a power law reduction with distance from sea. Cl and Na decrease rapidly for the first 100 km distance from sea, then decrease marginally for the next 100 km, and later stabilize. Regression parameters estimated for different cases were found to be consistent (R-2 similar to 0.8). Variation in one of the parameters accounted for urbanization. Model was validated using data points from the southern peninsular region of the country. Estimates are found to be within 99.9% confidence interval. Finally, this relationship between the three parameters - rainfall amount, coastline distance, and concentration (in terms of Cl and Na) was validated with experiments conducted in a small experimental watershed in the south-west India. Chemistry estimated using the model was in good correlation with observed values with a relative error of similar to 5%. Monthly variation in the chemistry is predicted from a downscaling model and then compared with the observed data. Hence, the model developed for rain chemistry is useful in estimating the concentrations at different spatio-temporal scales and is especially applicable for south-west region of India. (C) 2008 Elsevier Ltd. All rights reserved.
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This article addresses the need of an implementation mechanism for the protection of refugees’ rights. However, it is contended that the principle forms part of Customary International Law, under which it is binding on all states irrespective of whether or not they are parties to the Convention Relating to the Status of Refugees 1951 or its Protocol 1967. Since last decade, U.S and its allies have been fighting to curve terrorism which has raised many issues such as human rights violation, deportation, expulsion, extradition, rendition and many more. Pakistan has played a very critical role in War against Terrorism, particularly in reference of war in Afghanistan. Particular concern of this article is the violation of refugees’ rights in Pakistan in 2008 and 2010. This article would highlight the legislation regarding non-expulsion of Afghan refugees from Pakistan to a territory where they have well founded fear of persecution. Article is divided into three parts, the first one deals with “Principle of Non-Refoulement”, the second one deals with “exceptions to the principle” whereas the last one discusses the violation of the very principle in Pakistan with reference to Afghan refugees.
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Adult male bonnet monkeys exhibit nychthemeral rhythms in testosterone (T) secretion but the precise role of this heightened level of T secretion in regulating spermatogenesis is not known. Intranasal administration of microdoses (500 mu g or 250 mu g/day) of Norethisterone (IN-NET) to adult monkeys (n = 6) at 1600 h each day selectively and completely suppressed the nocturnal surge levels of serum T. Concomitant with this was a significant reduction (P<0.01) in serum LH but not FSH levels. DNA flow cytometric analysis of testicular biopsy tissue showed by week 10 of IN-NET treatment an arrest in meiotic transformation of primary spermatocytes (4C) to round/elongate (1C/HC) spermatids and by week 20 there was a complete absence of 4C, 1C and HC cells (with a relative accumulation in 2C cells). The accumulated meiotic (4C) cells at week 10 showed an increase (>80%, P<0.01) in coefficient of variation and a decrease in intensity of DNA-bound ethidium bromide fluorescence, parameters characteristic of degenerating 'apoptotic' subpopulation of germ cells. While two monkeys exhibited acute oligozoospermia 4 became azoospermic by 20 weeks of IN-NET treatment. A complete, qualitative reversal in the regressive changes in spermatogenesis and near-normal sperm output were apparent at the end of a 20-week recovery phase. These data demonstrate that prolonged, selective suppression of nocturnal surge levels of serum T secretion exerts a primary effect on meiosis in spermatogenesis leading to oligo/azoospermic status in adult bonnet monkeys.
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In the present study a two dimensional model is first developed to show the behaviour of dense non-aqueous phase liquids (DNAPL) within a rough fracture. To consider the rough fracture, the fracture is imposed with variable apertures along its plane. It is found that DNAPL follows preferential pathways. In next part of the study the above model is further extended for non-isothermal DNAPL flow and DNAPL-water interphase mass transfer phenomenon. These two models are then coupled with joint deformation due to normal stresses. The primary focus of these models is specifically to elucidate the influence of joint alteration due to external stress and fluid pressures on flow driven energy transport and interphase mass transfer. For this, it is assumed that the critical value for joint alteration is associated with external stress and average of water and DNAPL pressures in multiphase system and the temporal and spatial evolution of joint alteration are determined for its further influence on energy transport and miscible phase transfer. The developed model has been studied to show the influence of deformation on DNAPL flow. Further this preliminary study demonstrates the influence of joint deformation on heat transport and phase miscibility via multiphase flow velocities. It is seen that the temperature profile changes and shows higher diffusivity due to deformation and although the interphase miscibility value decreases but the lateral dispersion increases to a considerably higher extent.
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We consider some non-autonomous second order Cauchy problems of the form u + B(t)(u) over dot + A(t)u = f (t is an element of [0, T]), u(0) = (u) over dot(0) = 0. We assume that the first order problem (u) over dot + B(t)u = f (t is an element of [0, T]), u(0) = 0, has L-p-maximal regularity. Then we establish L-p-maximal regularity of the second order problem in situations when the domains of B(t(1)) and A(t(2)) always coincide, or when A(t) = kappa B(t).
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Non-Abelian quantum Hall states are characterized by the simultaneous appearance of charge and neutral gapless edge modes, with the structure of the latter being intricately related to the existence of bulk quasiparticle excitations obeying non-Abelian statistics. Here we propose a scenario for detecting the neutral modes by having two point contacts in series separated by a distance set by the thermal equilibration length of the charge mode. We show that by using the first point contact as a heating device, the excess charge noise measured at the second point contact carries a nontrivial signature of the presence of the neutral mode. We also obtain explicit expressions for the thermal conductance and corresponding Lorentz number for transport across a quantum point contact between two edges held at different temperatures and chemical potentials.
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Background: Biomechanical stress analysis has been used for plaque vulnerability assessment. The presence of plaque hemorrhage (PH) is a feature of plaque vulnerability and is associated with thromboembolic ischemic events. The purpose of the present study was to use finite element analysis (FEA) to compare the stress profiles of hemorrhagic and non-hemorrhagic profiles. Methods and Results: Forty-five consecutive patients who had suffered a cerebrovascular ischemic event with an underlying carotid artery disease underwent high-resolution magnetic resonance imaging (MRI) of their symptomatic carotid artery in a 1.5-T MRI system. Axial images were manually segmented for various plaque components and used for FEA. Maximum critical stress (M-CstressSL) for each slice was determined. Within a plaque, the maximum M-CstressSL for each slice of a plaque was selected to represent the maximum critical stress of that plaque (M-CstressPL) and used to compare hemorrhagic and non-hemorrhagic plaques. A total of 62% of plaques had hemorrhage. It was observed that plaques with hemorrhage had significantly higher stress (M-CstressPL) than plaques without PH (median [interquartile range]: 315 kPa [247-434] vs. 200 kPa [171-282], P=0.003). Conclusions: Hemorrhagic plaques have higher biomechanical stresses than non-hemorrhagic plaques. MRI-based FEA seems to have the potential to assess plaque vulnerability.