445 research outputs found
Alcohol-related expectancies are associated with the D2 dopamine receptor and GABAa receptor B3 subunit genes
Molecular genetic research has identified promising markers of alcohol dependence, including alleles of the D2 dopamine receptor (DRD2) and the GABAA receptor ¬3 subunit (GABRB3) genes. Whether such genetic risk manifests itself in stronger alcohol-related outcome expectancies, or in difficulty resisting alcohol, is unknown. In the present study, A1+ (A1A1 and A1A2 genotypes) and A1- (A2A2 genotype) alleles of the DRD2 and G1+ (G1G1 and G1 non-G1 genotypes) and G1- (non-G1 non-G1 genotype) alleles of the GABRB3 were determined in a group of 56 medically-ill patients diagnosed with alcohol dependence. Mood-related Alcohol Expectancy (AE) and Drinking Refusal Self-Efficacy (DRSE) were assessed using the Drinking Expectancy Profile (Young and Oei, 1996). Patients with the DRD2 A1+ allele, compared to those with the DRD2 A1- allele, reported lower DRSE in situations of social pressure (p=. 009). Similarly, lower DRSE was reported under social pressure by patients with the GABRB3 G1+ allele when compared to those with the GABRB3 G1- allele (p=.027). Patients with the GABRB3 G1+ allele also revealed reduced DRSE in situations characterized by negative affect than patients with the GABRB3 G1- alleles (p=. 037). Patients carrying the GABRB3 G1+ allele showed stronger AE relating to negative affective change (for example, increased depression) than their GABRB3 G1- counterparts (p=. 006). Biological influence in the development of some classes of cognitions is hypothesized. The clinical implications, particularly with regard to patient-treatment matching and the development of an integrated psychological and pharmacogenetic approach are discussed
Core transcriptional regulatory circuitry in human hepatocytes
We mapped the transcriptional regulatory circuitry for six master regulators in human hepatocytes using chromatin immunoprecipitation and high-resolution promoter microarrays. The results show that these regulators form a highly interconnected core circuitry, and reveal the local regulatory network motifs created by regulator–gene interactions. Autoregulation was a prominent theme among these regulators. We found that hepatocyte master regulators tend to bind promoter regions combinatorially and that the number of transcription factors bound to a promoter corresponds with observed gene expression. Our studies reveal portions of the core circuitry of human hepatocytes
Core transcriptional regulatory circuitry in human hepatocytes
We mapped the transcriptional regulatory circuitry for six master regulators in human hepatocytes using chromatin immunoprecipitation and high-resolution promoter microarrays. The results show that these regulators form a highly interconnected core circuitry, and reveal the local regulatory network motifs created by regulator–gene interactions. Autoregulation was a prominent theme among these regulators. We found that hepatocyte master regulators tend to bind promoter regions combinatorially and that the number of transcription factors bound to a promoter corresponds with observed gene expression. Our studies reveal portions of the core circuitry of human hepatocytes
Engaging with issues of emotionality in mathematics teacher education for social justice
This article focuses on the relationship between social justice, emotionality and mathematics teaching in the context of the education of prospective teachers of mathematics. A relational approach to social justice calls for giving attention to enacting socially-just relationships in mathematics classrooms. Emotionality and social justice in teaching mathematics variously intersect, interrelate or interweave. An intervention, usng creative action methods, with a cohort of prospective teachers addressing these issues is described to illustrate the connection between emotionality and social justice in the context of mathematics teacher education. Creative action methods involve a variety of dramatic, interactive and experiential tools that can promote personal and group engagement and embodied reflection. The intervention aimed to engage the prospective teachers with some key issues for social justice in mathematics education through dialogue about the emotionality of teaching and learning mathematics. Some of the possibilities and limits of using such methods are considered
Impulsivity-related cognition in alcohol dependence: is it moderated by DRD2/ANKK1 gene status and executive dysfunction?
Perceived impaired control over alcohol use is a key cognitive construct in alcohol dependence that has been related prospectively to treatment outcome and may mediate the risk for problem drinking conveyed by impulsivity in non-dependent drinkers. The aim of the current study was to investigate whether perceived impaired control may mediate the association between impulsivity-related measures (derived from the Short-form Eysenck Personality Questionnaire Revised) and alcohol-dependence severity in alcohol-dependent drinkers. Furthermore, the extent to which this hypothesized relationship was moderated by genetic risk (Taq1A polymorphism in the DRD2/ANKK1 gene cluster) and verbal fluency as an indicator of executive cognitive ability (Controlled Oral Word Association Test) was also examined. A sample of 143 alcohol-dependent inpatients provided an extensive clinical history of their alcohol use, gave 10 ml of blood for DNA analysis, and completed self-report measures relating to impulsivity, impaired control and severity of dependence. As hypothesized, perceived impaired control (partially) mediated the association between impulsivity-related measures and alcohol-dependence severity. This relationship was not moderated by the DRD2/ANICK1 polymorphism or verbal fluency. These results suggest that, in alcohol dependence, perceived impaired control is a cognitive mediator of impulsivity-related constructs that may be unaffected by DRD2/ANKK1 and neurocognitive processes underlying the retrieval of verbal information. (C) 2014 Elsevier Ltd. All rights reserved
‘Dominant ethnicity’ and the ‘ethnic-civic’ dichotomy in the work of A. D. Smith
This article considers the way in which the work of Anthony Smith has helped to structure debates surrounding the role of ethnicity in present-day nations. Two major lines of enquiry are evident here. First, the contemporary role of dominant ethnic groups within 'their' nations and second, the interplay between ethnic and civic elements in nationalist argument. The two processes are related, but maintain elements of distinctiveness. Smith's major contribution to the dominant ethnicity debate has been to disembed ethnicity from the ideologically-charged and/or anglo-centric discourse of ethnic relations and to place it in historical context, thereby opening up space for dominant group ethnicity to be considered as a distinct phenomenon. This said, Smith's work does not adequately account for the vicissitudes of dominant ethnicity in the contemporary West. Building on the classical works of Hans Kohn and Friedrich Meinecke, Anthony Smith has also made a seminal contribution to the debate on civic and ethnic forms of national identity and nationalist ideology. As well as freeing this debate from the strong normative overtones which it has often carried, he has continued to insist that the terms civic and ethnic should be treated as an ideal-typical distinction rather than a scheme of classification
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Adjuvant bevacizumab in patients with melanoma at high risk of recurrence (AVAST-M): preplanned interim results from a multicentre, open-label, randomised controlled phase 3 study
Background Bevacizumab, a monoclonal antibody that targets VEGF, has shown restricted activity in patients with
advanced melanoma. We aimed to assess the role of bevacizumab as adjuvant treatment for patients with resected
melanoma at high risk of recurrence. We report results from the preplanned interim analysis.
Methods We did a multicentre, open-label, randomised controlled phase 3 trial at 48 centres in the UK between
July 18, 2007, and March 29, 2012. Patients aged 16 years or older with American Joint Committee on Cancer stage
(AJCC) stage IIB, IIC, and III cutaneous melanoma were randomly allocated (1:1), via a central, computer-based
minimisation procedure, to receive intravenous bevacizumab 7·5 mg/kg, every 3 weeks for 1 year, or to observation.
Randomisation was stratifi ed by Breslow thickness of the primary tumour, N stage according to AJCC staging criteria,
ulceration of the primary tumour, and patient sex. The primary endpoint was overall survival; secondary endpoints
included disease-free interval, distant-metastases interval and quality of life. Analysis was by intention-to-treat. This
trial is registered as an International Standardised Randomised Controlled Trial, number ISRCTN81261306.
Findings 1343 patients were randomised to either the bevacizumab group (n=671) or the observation group (n=672).
Median follow-up was 25 months (IQR 16ñ37) in the bevacizumab group and 25 months (17ñ37) in the observation
group. At the time of interim analysis, 286 (21%) of 1343 enrolled patients had died: 140 (21%) of 671 patients in the
bevacizumab group, and 146 (22%) of 672 patients in the observation group. 134 (96%) of patients in the bevacizumab
group died because of melanoma versus 139 (95%) in the observation group. We noted no signifi cant di┎ erence in
overall survival between treatment groups (hazard ratio [HR] 0·97, 95% CI 0·78ñ1·22; p=0·76); this fi nding persisted
after adjustment for stratifi cation variables (HR 1·03; 95% CI 0·81ñ1·29; p=0·83). Median duration of treatment with
bevacizumab was 51 weeks (IQR 21ñ52) and dose intensity was 86% (41ñ96), showing good tolerability. 180 grade 3 or 4
adverse events were recorded in 101 (15%) of 671 patients in the bevacizumab group, and 36 (5%) of 672 patients in
the observation group. Bevacizumab resulted in a higher incidence of grade 3 hypertension than did observation
(41 [6%] vs one [<1%]). There was an improvement in disease-free interval for patients in the bevacizumab group
compared with those in the observation group (HR 0·83, 95% CI 0·70ñ0·98, p=0·03), but no signifi cant di┎ erence
between groups for distant-metastasis-free interval (HR 0·88, 95% CI 0·73ñ1·06, p=0·18). No signifi cant di┎ erences
were noted between treatment groups in the standardised area under the curve for any of the quality-of-life scales over
36 months. Three adverse drug reactions were regarded as both serious and unexpected: one patient had optic neuritis
after the fi rst bevacizumab infusion, a second patient had persistent erectile dysfunction, and a third patient died of a
haemopericardium after receiving two bevacizumab infusions and was later identifi ed to have had signifi cant
predisposing cardiovascular risk factors.
Interpretation Bevacizumab has promising tolerability. Longer follow-up is needed to identify an e┎ect on the primary
endpoint of overall survival at 5 years.
Funding Cancer Research U
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