Glycation and oxidation:a role in the pathogenesis of atherosclerosis

Reactions involving glycation and oxidation of proteins and lipids are believed to contribute to atherogenesis. Glycation, the nonenzymatic binding of glucose to protein molecules, can increase the atherogenic potential of certain plasma constituents, including low-density lipoprotein (LDL). Glycation of LDL is significantly increased in diabetic patients compared with normal subjects, even in the presence of good glycemic control. Metabolic abnormalities associated with glycation of LDL include diminished recognition of LDL by the classic LDL receptor; increased covalent binding of LDL in vessel walls; enhanced uptake of LDL by macrophages, thus stimulating foam cell formation; increased platelet aggregation; formation of LDL-immune complexes; and generation of oxygen free radicals, resulting in oxidative damage to both the lipid and protein components of LDL and to any nearby macromolecules. Oxidized lipoproteins are characterized by cytotoxicity, potent stimulation of foam cell formation by macrophages, and procoagulant effects. Combined glycation and oxidation, "glycoxidation," occurs when oxidative reactions affect the initial products of glycation, and results in irreversible structural alterations of proteins. Glycoxidation is of greatest significance in long-lived proteins such as collagen. In these proteins, glycoxidation products, believed to be atherogenic, accumulate with advancing age: in diabetes, their rate of accumulation is accelerated. Inhibition of glycation, oxidation, and glycoxidation may form the basis of future antiatherogenic strategies in both diabetic and nondiabetic individuals.

Student teachers' experiences of initial teacher preparation in England:Core themes and variation

Drawing on data generated via large-scale survey and in-depth interview methods, this article reports findings which show that being a student teacher in early-twenty-first-century England is a demanding personal experience which requires considerable engagement and commitment in the face of built-in challenges and risks, and which engenders, for many, highly charged affective responses. Student teachers are centrally concerned during this time with their (changing) identities, their relationships with others and the relevance of course provision. Findings also indicate that, in some respects, student teachers’ accounts of their experiences are systematically differentiated according to a number of factors, notably the initial teacher preparation route being followed, their age, and their prior conceptions and expectations of teaching and of learning to teach. These findings are situated in the broader literature on teacher development and some implications for teacher educators are discussed. © 2008 Taylor & Francis

Student Teachers’ Perceptions of the Effectiveness of their Initial Preparation

What influences how well-prepared student teachers feel towards working in schools upon completion of their initial teacher preparation (ITP)? In order to investigate this question, we used a path analysis using data from a longitudinal study investigating the experiences of trainee and early career phase teachers in England. The data were generated via self-complete questionnaires and follow-up telephone interviews with 1,322 trainees. Those on undergraduate or school-based programmes felt better prepared to work as teachers than one-year postgraduate trainees, perhaps because the former give higher ratings of the quality of assessment of, and feedback received on, teaching practice, and because of the clarity of theory-practice links in programmes. Across different kinds of ITP programme, good relationships with school-based mentors significantly boosted trainees' confidence that their ITP had effectively prepared them for teaching. Trainees' motives for entering the profession and their initial concerns about and expectations of ITP also affected their perceptions of its effectiveness, by shaping the way they experienced aspects of their courses. Implications of these findings for policy and practice in teacher preparation are discussed. © 2011 Blackwell Publishing Ltd.

The marginal willingness-to-pay for attributes of a hypothetical HIV vaccine

This paper estimates the marginal willingness-to-pay for attributes of a hypothetical HIV vaccine using discrete choice modeling. We use primary data from 326 respondents from Bangkok and Chiang Mai, Thailand, in 2008–2009, selected using purposive, venue-based sampling across two strata. Participants completed a structured questionnaire and full rank discrete choice modeling task administered using computer-assisted personal interviewing. The choice experiment was used to rank eight hypothetical HIV vaccine scenarios, with each scenario comprising seven attributes (including cost) each of which had two levels. The data were analyzed in two alternative specifications: (1) best-worst; and (2) full-rank, using logit likelihood functions estimated with custom routines in Gauss matrix programming language. In the full-rank specification, all vaccine attributes are significant predictors of probability of vaccine choice. The biomedical attributes of the hypothetical HIV vaccine (efficacy, absence of VISP, absence of side effects, and duration of effect) are the most important attributes for HIV vaccine choice. On average respondents are more than twice as likely to accept a vaccine with 99% efficacy, than a vaccine with 50% efficacy. This translates to a willingness to pay US$383 more for a high efficacy vaccine compared with the low efficacy vaccine. Knowledge of the relative importance of determinants of HIV vaccine acceptability is important to ensure the success of future vaccination programs. Future acceptability studies of hypothetical HIV vaccines should use more finely grained biomedical attributes, and could also improve the external validity of results by including more levels of the cost attribute.

Prevalence of human papillomavirus in women attending cervical screening in the UK and Ireland:New data from northern Ireland and a systematic review and meta-analysis

There is substantial international variation in human papillomavirus (HPV) prevalence; this study details the first report from Northern Ireland and additionally provides a systematic review and meta-analysis pooling the prevalence of high-risk (HR-HPV) subtypes among women with normal cytology in the UK and Ireland. Between February and December 2009, routine liquid based cytology (LBC) samples were collected for HPV detection (Roche Cobas® 4800 [PCR]) among unselected women attending for cervical cytology testing. Four electronic databases, including MEDLINE, were then searched from their inception till April 2011. A random effects meta-analysis was used to calculate a pooled HR-HPV prevalence and associated 95% confidence intervals (CI). 5,712 women, mean age 39 years (±SD 11.9 years; range 20-64 years), were included in the analysis, of which 5,068 (88.7%), 417 (7.3%) and 72 (1.3%) had normal, low, and high-grade cytological findings, respectively. Crude HR-HPV prevalence was 13.2% (95% CI, 12.7-13.7) among women with normal cytology and increased with cytological grade. In meta-analysis the pooled HR-HPV prevalence among those with normal cytology was 0.12 (95% CIs, 0.10-0.14; 21 studies) with the highest prevalence in younger women. HPV 16 and HPV 18 specific estimates were 0.03 (95% CI, 0.02-0.05) and 0.01 (95% CI, 0.01-0.02), respectively. The findings of this Northern Ireland study and meta-analysis verify the prevalent nature of HPV infection among younger women. Reporting of the type-specific prevalence of HPV infection is relevant for evaluating the impact of future HPV immunization initiatives, particularly against HR-HPV types other than HPV 16 and 18. J. Med. Virol. 85:295-308, 2013. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

Care and Management of Ancient Stone Monuments During Environmental Change

Ancient stone monuments (ASMs), such as standing stones and rock art panels, are powerful and iconic expressions of Britain’s rich prehistoric past that have major economic and tourism value. However, ASMs are under pressure due to increasing anthropogenic exposure and changing climatic conditions, which accelerate their rates of disrepair. Although scientific data exists on the integrity of stone monuments, most applies to “built” systems; therefore, additional work specific to ASMs in the countryside is needed to develop better-informed safeguarding strategies. Here, we use Neolithic and Bronze Age rock art panels across Northern England as a case study for delineating ASM management actions required to enhance monument preservation. The state of the rock art is described first, including factors that led to current conditions. Rock art management approaches then are described within the context of future environments, which models suggest to be more dynamic and locally variable. Finally, a Condition Assessment and Risk Evaluation (CARE) scheme is proposed to help prioritise interventions; an example of which is provided based on stone deterioration at Petra in Jordon. We conclude that more focused scientific and behavioural data, specific to deterioration mechanisms, are required for an ASM CARE scheme to be successful.

Extremely Complex Populations of Small RNAs in the Mouse Retina and RPE/Choroid

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs of ~18-22 nucleotides in length that regulate gene expression. They are widely expressed in the retina, being both required for its normal development and perturbed in disease. The aim of this study was to apply new high-throughput sequencing techniques to more fully characterise the microRNAs and other small RNAs expressed in the retina and retinal pigment epithelium (RPE)/choroid of the mouse.

Methods: Retina and RPE/choroid were dissected from eyes of 3 month-old C57BL/6J mice. Small RNA libraries were prepared and deep sequencing performed on a Genome Analyzer (Illumina). Reads were annotated by alignment to miRBase, other non-coding RNA databases and the mouse genome.

Results: Annotation of 9 million reads to 320 microRNAs in retina and 340 in RPE/choroid provides the most comprehensive profiling of microRNAs to date. Two novel microRNAs were identified in retina. Members of the sensory organ specific miR-183,-182,-96 cluster were amongst the most highly expressed, retina-enriched microRNAs. Remarkably, microRNA 'isomiRs', which vary slightly in length and are differentially detected by Taqman RT-PCR assays, existed for all the microRNAs identified in both tissues. More variation occurred at the 3' ends, including non-templated additions of T and A. Drosha-independent mirtron microRNAs and other small RNAs derived from snoRNAs were also detected.

Conclusions: Deep sequencing has revealed the complexity of small RNA expression in the mouse retina and RPE/choroid. This knowledge will improve the design and interpretation of future functional studies of the role of microRNAs and other small RNAs in retinal disease.

Finding Your Feet in the Field: Critical Reflections of Early Career Researchers on Field Research in Transitional Societies

Fieldwork that takes place in conflict or transitional regions is becoming increasingly popular amongst early-career and more seasoned researchers, but is an area that retains an air of mystery and remains an exotic form of knowledge gathering. There exists a paucity of personal reflection on the challenges associated with conducting fieldwork in conflicted or transitional regions and a limited amount of insight into the practical steps taken in advance of and when immersed in the field. Such reticence to share honest fieldwork experiences, particularly the more challenging research that takes place in conflict or transitional settings aids in creating a culture of silence. This paper attempts to counteract this silence by drawing on the challenges experienced by two early career researchers conducting fieldwork in Uganda and Palestine, focusing on the practical steps taken in advance of entering the field, and the challenges faced whilst engaged in fieldwork. Specific challenges are highlighted throughout, including: physical access to areas in conflict; engaging with reluctant research participants; the emotional impact of fieldwork on the researcher; maintaining confidentiality; researching with vulnerable victims; and ensuring appropriate knowledge exchange between researchers and participants. The paper concludes by emphasising the requirement for greater reflection on the inherently personal challenges associated with conducting fieldwork in conflicted or transitional settings and highlights the view that fieldwork is a privileged position that carries great responsibilities which must be upheld to ensure the sustainability of future research. This paper hopes to contribute to the wider debate on conducting fieldwork and the challenges associated with working in conflicted or transitional regions.

Who Feels Inferior? A Test of the Status Anxiety Hypothesis of Social Inequalities in Health

The empirical association between income inequality, population health and other social problems is now well established and the research literature suggests that the relationship is not artefactual. Debate is still ongoing as to the cause of this association. Wilkinson, Marmot and colleagues have argued for some time that the relationship stems from the psycho-social effects of status comparisons. Here, income inequality is a marker of a wider status hierarchy that provokes an emotional stress response in individuals that is harmful to health and well-being. We label this the ‘status anxiety hypothesis’. If true, this would imply a structured relationship between income inequality at the societal level, individual income rank and anxiety relating to social status. This paper sets out strong and weak forms of the hypothesis and then presents three predictions concerning the structuring of ‘status anxiety’ at the individual level given different levels of national income inequality and varying individual income. We then test these predictions using data from a cross-national survey of over 34,000 individuals carried out in 2007 in 31 European countries. Respondents from low inequality countries reported less status anxiety than those in higher inequality countries at all points on the income rank curve. This is an important precondition of support for the status anxiety hypothesis and may be seen as providing support for the weaker version of the hypothesis. However, we do not find evidence to support the stronger version of the hypothesis which requires the negative effect of income rank on status anxiety to be exacerbated by increasing income inequality.

An Excess of Risk-Increasing Low-Frequency Variants Can Be a Signal of Polygenic Inheritance in Complex Diseases

In most complex diseases, much of the heritability remains unaccounted for by common variants. It has been postulated that lower-frequency variants contribute to the remaining heritability. Here, we describe a method to test for polygenic inheritance from lower-frequency variants by using GWAS summary association statistics. We explored scenarios with many causal low-frequency variants and showed that there is more power to detect risk variants than to detect protective variants, resulting in an increase in the ratio of detected risk to protective variants (R/P ratio). Such an excess can also occur if risk variants are present and kept at lower frequencies because of negative selection. The R/P ratio can be falsely elevated because of reasons unrelated to polygenic inheritance, such as uneven sample sizes or asymmetric population stratification, so precautions to correct for these confounders are essential. We tested our method on published GWAS results and observed a strong signal in some diseases (schizophrenia and type 2 diabetes) but not others. We also explored the shared genetic component in overlapping phenotypes related to inflammatory bowel disease (Crohn disease [CD] and ulcerative colitis [UC]) and diabetic nephropathy (macroalbuminuria and end-stage renal disease [ESRD]). Although the signal was still present when both CD and UC were jointly analyzed, the signal was lost when macroalbuminuria and ESRD were jointly analyzed, suggesting that these phenotypes should best be studied separately. Thus, our method may also help guide the design of future genetic studies of various traits and diseases.

The Changing Worlds and Workplaces of Capitalism

How do the large scale structures of capitalism and the local social relations of workplaces and organisations shape each other? Through a series of European studies of capital and labour's shifting struggles and compromises; of the politics of welfare, industrial relations and labour markets; and the transformation of post-industrial networked workplaces, this edited collection shows how capitalist workplaces and economies are changing today. The first section explores how European capitalism developed and the different national forms of the struggle between capital and labour for a bigger share of national income. In the second part of the volume, the contributors investigate the institutions that are the building blocks of these different national forms, and how they are changing as labour markets are increasingly shaped by globalisation, feminisation and liberalisation. The final chapters examine how these institutions of capitalism play out in the contemporary workplace – where the most dynamic sectors are based on loose networks and external labour markets and a shifting, uncertain alliance between employers and workers. The authors argue for a new integration of political economy and the sociology of work and organisations.

Empirical testing of genuine savings as an indicator of weak sustainability: a three-country analysis of long run trends

Genuine Savings has emerged as a widely-used indicator of sustainable development. In this paper, we use long-term data stretching back to 1870 to undertake empirical tests of the relationship between Genuine Savings (GS) and future well-being for three countries: Britain, the USA and Germany. Our tests are based on an underlying theoretical relationship between GS and changes in the present value of future consumption. Based on both single country and panel results, we find evidence supporting the existence of a cointegrating (long run equilibrium) relationship between GS and future well-being, and fail to reject the basic theoretical result on the relationship between these two macroeconomic variables. This provides some support for the GS measure of weak sustainability. We also show the effects of modelling shocks, such as World War Two and the Great Depression.

A statistical analysis of person–to–vehicle communications channels in an urban environment at 5.8 GHz

In recent years, the embracement of smart devices carried or worn by people have transformed how society interact with one another. This trend has also been observed in the advancement of vehicular networks. Here, developments in wireless technologies for vehicle-to-vehicle (V2V) and vehicle-to-roadside (V2R) communications are leading to a new generation of vehicular networks. A natural extension of both types of networks will be their eventual wireless integration. Both people and vehicles will undoubtedly form integral parts of future mobile networks of people and things. Central to this will be the person-to-vehicle (P2V) communications channel. As the P2V channel will be subject to different signal propagation characteristics than either type of communication system considered in isolation, it is imperative the characteristics of the wireless channel must first be fully understood. To the best of the author's knowledge, this is a topic which has not yet been addressed in the open literature. In this paper we will present our most recent research on the statistical characterization of the 5.8 GHz person-to-vehicle channel in an urban environment.

Regulating Services Trade Agreements - A Comparative Analysis of Regulatory Disciplines Included in EU and US Free Trade Agreements

Developed countries, led by the EU and the US, have consistently called for ‘deeper integration’ over the course of the past three decades i.e., the convergence of ‘behind-the-border’ or domestic polices and rules such as services, competition, public procurement, intellectual property (“IP”) and so forth. Following the collapse of the Doha Development Round, the EU and the US have pursued this push for deeper integration by entering into deep and comprehensive free trade agreements (“DCFTAs”) that are comprehensive insofar as they are not limited to tariffs but extend to regulatory trade barriers. More recently, the EU and the US launched negotiations on a Transatlantic Trade and Investment Partnership (“TTIP”) and a Trade in Services Agreement (“TISA”), which put tackling barriers resulting from divergences in domestic regulation in the area of services at the very top of the agenda. Should these agreements come to pass, they may well set the template for the rules of international trade and define the core features of domestic services market regulation. This article examines the regulatory disciplines in the area of services included in existing EU and US DCFTAs from a comparative perspective in order to delineate possible similarities and divergences and assess the extent to which these DCFTAs can shed some light into the possible outcome and limitations of future trade negotiations in services. It also discusses the potential impact of such negotiations on developing countries and, more generally, on the multilateral process.