Global survey of genetic variation in CCR5, RANTES, and MIP-1α: Impact on the epidemiology of the HIV-1 pandemic

Expression of CC chemokine receptor 5 (CCR5), the major coreceptor for HIV-1 cell entry, and its ligands (e.g., RANTES and MIP-1α) is widely regarded as central to the pathogenesis of HIV-1 infection. By surveying nearly 3,000 HIV+ and HIV− individuals from worldwide populations for polymorphisms in the genes encoding RANTES, MIP-1α, and CCR5, we show that the evolutionary histories of human populations have had a significant impact on the distribution of variation in these genes, and that this may be responsible, in part, for the heterogeneous nature of the epidemiology of the HIV-1 pandemic. The varied distribution of RANTES haplotypes (AC, GC, and AG) associated with population-specific HIV-1 transmission- and disease-modifying effects is a striking example. Homozygosity for the AC haplotype was associated with an increased risk of acquiring HIV-1 as well as accelerated disease progression in European Americans, but not in African Americans. Yet, the prevalence of the ancestral AC haplotype is high in individuals of African origin, but substantially lower in non-Africans. In a Japanese cohort, AG-containing RANTES haplotype pairs were associated with a delay in disease progression; however, we now show that their contribution to HIV-1 pathogenesis and epidemiology in other parts of the world is negligible because the AG haplotype is infrequent in non-Far East Asians. Thus, the varied distribution of RANTES, MIP-1α, and CCR5 haplotype pairs and their population-specific phenotypic effects on HIV-1 susceptibility and disease progression results in a complex pattern of biological determinants of HIV-1 epidemiology. These findings have important implications for the design, assessment, and implementation of effective HIV-1 intervention and prevention strategies.

Ethnogenesis and Craniofacial Change in Japan from the Perspective of Nonmetric Traits

To examine population affinities in light of the ‘dual structure model’, frequencies of 21 nonmetric cranial traits were analyzed in 17 prehistoric to recent samples from Japan and five from continental northeast Asia. Eight bivariate plots, each representing a different bone or region of the skull, as well as cluster analysis of 21-trait mean measures of divergence using multidimensional scaling and additive tree techniques, revealed good discrimination between the Jomon-Ainu indigenous lineage and that of the immigrants who arrived from continental Asia after 300 BC. In Hokkaido, in agreement with historical records, Ainu villages of Hidaka province were least, and those close to the Japan Sea coast were most, hybridized with Wajin. In the central islands, clines were identified among Wajin skeletal samples whereby those from Kyushu most resembled continental northeast Asians, while those from the northernmost prefectures of Tohoku apparently retained the strongest indigenous heritage. In the more southerly prefectures of Tohoku, stronger traces of Jomon ancestry prevailed in the cohort born during the latest Edo period than in the one born after 1870. Thus, it seems that increased inter-regional mobility and gene flow following the Meiji Restoration initiated the most recent episode in the long process of demic diffusion that has helped to shape craniofacial change in Japan.

Mutual perceptions of Asia and the EU/Europe. Media, elite and public opinion in Singapore and Germany. EU Centre in Singapore Working Paper No. 12, December 2012

In an increasingly interlinked and interdependent world, Europe and Asia are key players. Free trade agreements (FTAs), such as the ones the EU concluded with South Korea and Singapore, are indicative of strong mutual economic interests. It is therefore timely to take a closer look at the mutual perceptions of Asians and Europeans – not only at the governmental and policymaking levels, but also in terms of public opinion and the media. Drawing on data from an extensive research project led by the National Centre for Research on Europe (NCRE), New Zealand, the empirical study in this paper assesses the mutual perceptions of the EU/Europe and Asia, and their respective actors, focusing on two countries – Germany and Singapore. It seeks to do so through an analysis of the data collected from print and broadcast media, interviews with media practitioners, and the findings from public opinion surveys.

Moya moya disease : literature review and case report

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Fibrose quística : fenótipo e genótipo : descrição de caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

HIV/AIDS work group on health care access issues for Asian and Pacific Islanders, May 9-10, 1994.

Shipping list no.: 96-0070-P.

Mental health issues : Indochinese refugees : an annotated bibliography /

Mode of access: Internet.

Non-major-histocompatibility-complex genetics of ankylosing spondylitis

There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-I gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-IA. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.

Childhood ethnic differences in ametropia and ocular biometry:the Aston Eye Study

Purpose: To describe the methodology, sampling strategy and preliminary results for the Aston Eye Study (AES), a cross-sectional study to determine the prevalence of refractive error and its associated ocular biometry in a large multi-racial sample of school children from the metropolitan area of Birmingham, England. Methods: A target sample of 1700 children aged 6–7 years and 1200 aged 12–13 years is being selected from Birmingham schools selected randomly with stratification by area deprivation index (a measure of socio-economic status). Schools with pupils predominantly (>70%) from a single race are excluded. Sample size calculations account for the likely participation rate and the clustering of individuals within schools. Procedures involve standardised protocols to allow for comparison with international population-based data. Visual acuity, non-contact ocular biometry (axial length, corneal radius of curvature and anterior chamber depth) and cycloplegic autorefraction are measured in both eyes. Distance and near oculomotor balance, height and weight are also assessed. Questionnaires for parents and older children will allow the influence of environmental factors on refractive error to be examined. Results: Recruitment and data collection are ongoing (currently N = 655). Preliminary cross-sectional data on 213 South Asian, 44 black African Caribbean and 70 white European children aged 6–7 years and 114 South Asian, 40 black African Caribbean and 115 white European children aged 12–13 years found myopia prevalence of 9.4% and 29.4% for the two age groups respectively. A more negative mean spherical equivalent refraction (SER) was observed in older children (-0.21 D vs +0.87 D). Ethnic differences in myopia prevalence are emerging with South Asian children having higher levels than white European children 36.8% vs 18.6% (for the older children). Axial length, corneal radius of curvature and anterior chamber depth were normally distributed, while SER was leptokurtic (p < 0.001) with a slight negative skew. Conclusions: The AES will allow ethnic differences in the ocular characteristics of children from a large metropolitan area of the UK to be examined. The findings to date indicate the emergence of higher levels of myopia by early adolescence in second and third generation British South Asians, compared to white European children. The continuation of the AES will allow the early determinants of these ethnic differences to be studied.

Ocular and systemic markers for vascular function in those at risk of type 2 diabetes mellitus and cardiovascular disease

The devastating impact of Type 2 Diabetes Mellitus (T2DM) -related morbidity and mortality on global healthcare is escalating with higher prevalences of obesity, poor diet, and sedentary lifestyles. Therefore, the clinical need for early diagnosis and prevention in groups of high-risk individuals is necessary. The purpose of this thesis was to investigate the use of surrogate markers, namely retinal vascular function, to determine future vascular endothelial dysfunction, atherosclerosis, large vessel disease and cardiovascular risk in certain groups. This namely covered normoglycaemic and normotensive South Asians (SAs), those with Impaired-Glucose Tolerance (IGT) and individuals with a familial history (FH) of T2DM. Additionally the effect of overweight and obesity was studied. The techniques and modified protocols adopted for this thesis involved the investigation of endothelial function by means of vascular reactivity at the ocular and systemic level. Furthermore, the relationships between retinal and systemic function with circulating markers for endothelial cell function and cardiovascular risk markers were explored. The principal studies and findings of the research were: Vascular Function in Normoglycaemic Individuals with and without a FH of T2DM WE FH individuals exhibited higher levels of total cholesterol levels that correlated well with the retinal arterial dilation amplitude to flicker light stimulus. However this did not extend to noticeable differences in markers for endothelial cell damage and impaired retinal and systemic function. Vascular Function in Normoglycaemic South-Asians vs. White-Europeans without a FH and Vascular Disturbances Compared to healthy WEs (normo -glycaemic and -tensive), SA participants exhibited levels of dyslipidaemia and a state of oxidative stress that extended to impaired vascular function as detected by reduced brachial artery flow-mediated dilation, slower retinal arterial vessel dilation reaction times (Appendix 3) and steeper constriction profiles. Furthermore, gender sub-group analysis presented in a sub-chapter shows that SA males demonstrated 24-hour systemic blood pressure (BP) and heart rate variability (HRV) abnormalities and heightened cardiovascular disease (CVD) risk. Vascular Function in Individuals Newly Diagnosed with IGT as compared to Normoglycaemic Healthy Controls Newly-diagnosed WE and SA IGT patients showed a greater risk for CVD and T2DM progression by means of 24-hour BP abnormalities, dyslipidaemia, increased carotid artery intimal-media thickness (c-IMT), Framingham scores and cholesterol ratios. Additionally, pre-clinical markers for oxidative stress and endothelial dysfunction, as evident by significantly lower levels of plasma glutathione and increased levels of von-Willebrand factor in IGT individuals, extended to impaired vascular systemic and retinal function compared to normal controls. This originally shows retinal, systemic and biochemical disturbances in newly-diagnosed IGT not previously reported before. Vascular Function in Normal, Overweight and Obese Individuals of SA and WE Ethnicity In addition to the intended study chapters, the thesis also investigated the influence of obesity and overweight on vascular function. Most importantly, it was found for the first time that compared to lean individuals it was overweight and not obese individuals that exhibited signs of vascular systemic and ocular dysfunction that was evident alongside markers of atherosclerosis, CVD risk and endothelial damage.

Non-invasive phakometric measurement of corneal and crystalline lens alignment in human eyes

We describe a non-invasive phakometric method for determining corneal axis rotation relative to the visual axis (β) together with crystalline lens axis tilt (α) and decentration (d) relative to the corneal axis. This does not require corneal contact A-scan ultrasonography for the measurement of intraocular surface separations. Theoretical inherent errors of the method, evaluated by ray tracing through schematic eyes incorporating the full range of human ocular component variations, were found to be larger than the measurement errors (β < 0.67°, α < 0.72° and d < 0.08 mm) observed in nine human eyes with known ocular component dimensions. Intersubject variations (mean ± S.D.: β = 6.2 ± 3.4° temporal, α = 0.2 ± 1.8° temporal and d = 0.1 ± 0.1 mm temporal) and repeatability (1.96 × S.D. of difference between repeat readings: β ± 2.0°, α ± 1.8° and d ± 0.2 mm) were studied by measuring the left eyes of 45 subjects (aged 18-42 years, 29 females and 16 males, 15 Caucasians, 29 Indian Asians, one African, refractive error range -7.25 to +1.25 D mean spherical equivalent) on two occasions. © 2005 The College of Optometrists.

How SME owners’ characteristics influences external advice and access to finance

This paper aims to investigate the linkage between the use of external advice and access to finance for small and medium-sized enterprises (SMEs) in the UK, with particular consideration of differences in personal characteristics: gender, ethnicity and education. The approach adopted for the research is a telephone survey conducted by the Barclays small business research team in late 2005 on behalf of the authors. These data are quantitative in nature and involve a large sample of 400 SMEs with specific questions analysed by gender, ethnicity and education level. The approach adopted is robust and empirically sound and is a long established research methodology. We find that there appears to be a correlation between the provision of external advice and the ability to raise bank finance. Furthermore, there are clear gender, ethnic and educational differentials in the use of particular sources of advice, for example: Gender • men and women are equally likely to use accountants as sources of advice. • men are more likely to use family and friends and solicitors. • women, however, are around twice as likely to access external advice from Business Link and Enterprise Agencies. Ethnicity • family and friends is predominant amongst Asians or black respondents and the other ethnic group, which is also slightly true of accountants and solicitors. • ethnic minority respondents were considerably less likely to use Business Link/ Enterprise Agencies. Education • graduates are most likely to use solicitors and accountants, whilst they are very low users of advice from family and friends and Business Links/Enterprise Agencies. • O level and A level educated respondents predominate in family and friends and Business Link/ Enterprise Agencies.

Fair testing in employment selection

This project represents the collaboration of Charta Mede Ltd and the Interdisciplinary Higher Degrees Scheme at the University of Aston. The aim of the project was to monitor the effects of the Civil Service's Executive Officer Qualifying Test Battery on minority group applicants. Prior to monitoring the EO Test Battery, however, an ethnic classification had to be developed which was reliable, acceptable to respondents and appropriate for monitoring. Three pilot studies were conducted to examine these issues, during which different classifications and different ways of asking the question were trialled. The results indicated that by providing more precise instructions as to the meanings of categories, it was possible to obtain classifications which were acceptable and reliable. However, there were also certain terms and expressions which should be avoided such as those referring to colour and anthropological racial groups. Two classifications were used in the Executive Officer Study - one derived from an Office of Population Censuses and Surveys classification and one developed for this project - the MultiCultural British Classification. The results indicated that some minority groups (Asians, West Indians and Africans in particular) pass the tests in significantly lower proportions than the majority group and also score significantly less well on the tests. Factors which were significantly related to pass/fail and test scores included educational qualifications and age on entering the UK (the latter being negatively correlated). Using variables in this study, however, it was only possible to account for 5% of the variance in pass/fail rates and 11% of the variance in test scores. Analyses of covariance carried out indicated that the differences in test scores still remained even though the effects of significantly correlated variables were removed. Although indirect discrimination could not be inferred from the data, further research into differential validity and fairer methods of select ion is needed.

The experiences of South Asian university students in the British education system and in their search for work

This research aimed to provide a comparative analysis of South Asian and White British students in their academic attainment at school and university and in their search for employment. Data were gathered by using a variety of methodological techniques. Completed postal questionnaires were received from 301 South Asian and White British undergraduates from 12 British universities, who were in their final year of study in 1985. In depth interviews were also conducted with 49 graduates who were a self selected group from the original sample. Additional information was also collected by using diary report forms and by administering a second postal questionnaire to selected South Asian and White British participants. It was found that while the pre-university qualifications of the White British and South Asian undergraduates did not differ considerably, many members in the latter group had travelled a more arduous path to academic success. For some South Asians, school experiences included the confrontation of racist attitudes and behaviour, both from teachers and peers. The South Asian respondents in this study were more likely than their White British counterparts, to have attempted some C.S.E. examinations, obtained some of their `O' levels in the Sixth Form and retaken their `A' levels. As a result the South Asians were on average older than their White British peers when entering university. A small sample of South Asians also found that the effects of racism were perpetuated in higher education where they faced difficulty both academically and socially. Overall, however, since going to university most South Asians felt further drawn towards their `cultural background', this often being their own unique view of `Asianess'. Regarding their plans after graduation, it was found that South Asians were more likely to opt for further study, believing that they needed to be better qualified than their White British counterparts. For those South Asians who were searching for work, it was noted that they were better qualified, willing to accept a lower minimum salary, had made more job applications and had started searching for work earlier than the comparable White British participants. Also, although generally they were not having difficulty in obtaining interviews, South Asian applicants were less likely to receive an offer of employment. In the final analysis examining their future plans, it was found that a large proportion of South Asian graduates were aspiring towards self employment.

Telomere length attrition, a marker of biological senescence, is inversely correlated with triglycerides and cholesterol in South Asian males with type 2 diabetes mellitus

South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol (r = -0.419, P <0.01; r = -0.443, P <0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing.