Measles immune suppression:lessons from the Macaque Model

Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV) infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA - memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA - memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression. © 2012 de Vries et al.

Breast Cancer Risk in Relation to Occupations with Exposure to Carcinogens and Endocrine Disruptors:a Canadian Case-Control Study

Background

Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours.

Methods

1005 breast cancer cases referred by a regional cancer center and 1147 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case?control design, exposure effects were estimated using conditional logistic regression.

Results

Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5).

Conclusions

These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work histories in environmental and occupational epidemiology.

Rice-arsenate interactions in hydroponics: a three-gene model for tolerance

In this study, the genetic mapping of the tolerance of root growth to 13.3 muM arsenate [As(V)] using the BalaxAzucena population is improved, and candidate genes for further study are identified. A remarkable three-gene model of tolerance is advanced, which appears to involve epistatic interaction between three major genes, two on chromosome 6 and one on chromosome 10. Any combination of two of these genes inherited from the tolerant parent leads to the plant having tolerance. Lists of potential positional candidate genes are presented. These are then refined using whole genome transcriptomics data and bioinformatics. Physiological evidence is also provided that genes related to phosphate transport are unlikely to be behind the genetic loci conferring tolerance. These results offer testable hypotheses for genes related to As(V) tolerance that might offer strategies for mitigating arsenic (As) accumulation in consumed rice.

Autonomy and Control of State Agencies:Comparing States and Agencies

Do public organizations with similar tasks or structures differ across states with respect to their autonomy and control? If so, why? By comparing the autonomy, control and internal management of state agencies, this book shows how New Public Management doctrines actually work in three small European states with different politico-administrative regimes. Using a unique set of similar survey data on 226 state agencies in Norway, Ireland and Flanders, this study explains differences in agency autonomy, control and management by referring to international isomorphic pressures, state-specific politico-administrative regimes and characteristics of agencies. Therefore, organization theory and neo-institutional schools are used to formulate four competing theoretical perspectives and hypotheses are tested through simple and advanced statistical techniques. By comparing practices between states and between types of agencies, this study substantially enhances scientific knowledge about why public organizations are granted autonomy, why they are controlled in specific ways, and how autonomy affects internal management.

Autonomy and regulation of state agencies:Reinforcement, indifference or compensation?

This paper analyses the relationships between the autonomy and regulation of state agencies in Norway, Ireland and Flanders (Belgium). The empirical basis is provided by broad surveys of public sector organizations carried out in 2002-2004. Three hypotheses on these relationships are formulated and examined, indicating different patterns. The reinforcement hypothesis, stating a negative relationship does not get any support. On the other hand, the compensation hypothesis, stating a positive relationship gets some support. In general, however, the indifference hypothesis, stating low or no correlations seems to be the most adequate. The hypotheses are also linked to prevalent administrative doctrines, and the empirical findings indicate how relevant they are. © Springer Science+Business Media, LLC 2008.

Explaining Social Class Inequalities in Smoking: The Role of Education, Self-Efficacy, and Deprivation

Rates of smoking have decreased dramatically in most Northern European countries over the last 50 years or so, but manual working class groups are substantially more likely to smoke daily than are the professional and managerial classes. This article examines three hypotheses about the processes producing these inequalities. The first argues that social class inequalities reflect differences across education groups in knowledge of the risks of smoking. The second suggests that the living conditions of lower social class groups leads to the development of lower self-efficacy and a lower propensity to quit smoking. The third states that smoking has a functional use among poorer individuals. This article draws upon data from the Republic of Ireland to assess these hypotheses. Our analysis provides some support for the first hypothesis in that education independently reduces the odds of a manual class person smoking relative to a non-manual by 12 per cent. The second hypothesis is not supported by the data. The third hypothesis gains the most support: measures of disadvantage and deprivation account for almost one-third of the class differential in smoking. The results suggest that smoking cessation policy should reflect the importance of social and economic context in quitting behaviour.

Welfare regimes and household income packaging in the European Union

This paper uses harmonized data for the member states of the European Union to analyse household income packaging from a 'welfare regimes' perspective. Using data from the third wave of the ECHP, it looks at how the role of welfare transfers in the income package varies across countries and welfare regimes, and assesses whether this is consistent with the predictions of welfare regime theory, having first elaborated some specific hypotheses in that regard. It finds that when one focuses on averages across countries categorized into regimes, many of these hypotheses about the role of transfers are in broad terms borne out by the evidence. However, when one focuses on individual countries rather than regime averages the picture is a good deal more complex and consistency with the range of hypotheses more limited. It is essential that this variation across countries is taken into account in interpreting and using welfare regime theory and typologies.

Urban housing and the role of 'underclass' processes: the case of Ireland

Rising levels of urban deprivation and a perception that poverty has become more concentrated in such areas and has taken on a qualitatively different character have provoked a variety of popular and academic responses. The potentially most fruitful set of hypotheses focuses on the unintended of weak labour force attachment and social isolation is perceived to lead to behaviour and orientations that contribute to a vicious circle of deprivation. In examining the value of this conceptual framework in the Irish case we proceed by measuring directly the social-psychological factors which ave hypothesized to mediate the 'underclass' process.

A significantly higher level of poverty is found in urban public-sector tenant households. This finding cannot be accounted for entirely by socio-demographic differences. It is the assessment of this net or residual effect that is crucial to an evaluation of vicious circle explanations. Controlling for the critical social-psychological factors we found that net effect was reduced by less than a quarter and concluded that the remaining effect is more plausibly attributed to the role of selection than to underclass processes. Analysis of the changing relationship between urban public-sector tenancy and poverty provides support for this interpretation.

For the main part the distinctiveness of social housing tenants is a consequence of the disadvantages they stiffer in relation to employment opportunities and living standards. Ultimately it is these problems that policy interventions, whatever the level at which they take place, must address.

FROM ASCRIPTION TO ACHIEVEMENT - ORIGINS, EDUCATION AND ENTRY TO THE LABOR-FORCE IN THE REPUBLIC OF IRELAND DURING THE 20TH-CENTURY

This paper examines the relationship between class of origin, educational attainment, and class of entry to the labour force, in three cohorts of men in the Republic of Ireland using data collected in 1987. The three cohorts comprise men born (i) before 1937; (ii) between 1937 and 1949; and (iii) between 1950 and 1962. The paper assesses the degree of change over the three cohorts in respect of (a) the gross relationship between origins and entry class; (b) the partial effect (controlling for education) of origin class on entry class; (c) the partial effect of education (controlling for origins) on class of entry. In broad terms the liberal theory of industrialism would imply a movement, over the three cohorts, towards (a) increasing social fluidity; (b) a weakening of the partial effect of origin class; (c) a strengthening of the partial effect of education. These latter two trends should be particularly noticeable in the youngest cohort, which would, to some degree, have benefited from the introduction of free post-primary education in Ireland in 1967.

Our results provide almost no support for these hypotheses. We find that patterns of social fluidity in the origin/entry relationship remain unchanged over the cohorts. The partial effect of class remains relatively constant; and, while the partial effect of education on entry class changes over the cohorts, the most striking result in this area is the declining returns to higher levels of education. While the average level of educational attainment increased over the three cohorts, the advantages accruing to the possession of higher levels of education simultaneously diminished. Taken together our results suggest that, in Ireland, those classes that have historically enjoyed advantages in access to more desirable entry positions in the labour market have been remarkably adept at retaining their advantages during the course of industrialization and through the various educational and other labour market changes that have accompanied this process.

A defeasible reasoning model of inductive concept learning from examples and communication

This paper introduces a logical model of inductive generalization, and specifically of the machine learning task of inductive concept learning (ICL). We argue that some inductive processes, like ICL, can be seen as a form of defeasible reasoning. We define a consequence relation characterizing which hypotheses can be induced from given sets of examples, and study its properties, showing they correspond to a rather well-behaved non-monotonic logic. We will also show that with the addition of a preference relation on inductive theories we can characterize the inductive bias of ICL algorithms. The second part of the paper shows how this logical characterization of inductive generalization can be integrated with another form of non-monotonic reasoning (argumentation), to define a model of multiagent ICL. This integration allows two or more agents to learn, in a consistent way, both from induction and from arguments used in the communication between them. We show that the inductive theories achieved by multiagent induction plus argumentation are sound, i.e. they are precisely the same as the inductive theories built by a single agent with all data. © 2012 Elsevier B.V.

Social class, unemployment, and psychological distress

Attempts to explain variation in rates of psychological distress by social class have included reference to social selection, differential exposure to stress, and differential vulnerability arising from inequalities in access to resources. Our analysis draws on data from a national survey of the Republic of Ireland in order to examine these hypotheses. No evidence to support the social selection hypothesis was found. In addressing the issue of differential responsiveness, attention was focused on the interaction between unemployment and social class in their impact on psychological distress. While rather weak support for the hypothesis of differential vulnerability was found among women, our examination of the impact of husband's unemployment provided no evidence leading in this direction. Among men unemployment actually had a stronger impact for men in higher social classes. The major factors leading to social class differences in psychological distress are greater exposure to unemployment and economic deprivation. © 1994 Oxford University Press.

Exploratory Space-Time Analyses of Rift Valley Fever in South Africa in 2008-2011

Background: Rift Valley fever (RVF) is a zoonotic arbovirosis for which the primary hosts are domestic livestock (cattle, sheep and goats). RVF was first described in South Africa in 1950-1951. Mechanisms for short and long distance transmission have been hypothesised, but there is little supporting evidence. Here we describe RVF occurrence and spatial distribution in South Africa in 2008-11, and investigate the presence of a contagious process in order to generate hypotheses on the different mechanisms of transmission. Methodology/Principal Findings: A total of 658 cases were extracted from World Animal Health Information Database. Descriptive statistics, epidemic curves and maps were produced. The space-time K-function was used to test for evidence of space-time interaction. Five RVF outbreak waves (one in 2008, two in 2009, one in 2010 and one in 2011) of varying duration, location and size were reported. About 70% of cases (n = 471) occurred in 2010, when the epidemic was almost country-wide. No strong evidence of space-time interaction was found for 2008 or the second wave in 2009. In the first wave of 2009, a significant space-time interaction was detected for up to one month and over 40 km. In 2010 and 2011 a significant intense, short and localised space-time interaction (up to 3 days and 15 km) was detected, followed by one of lower intensity (up to 2 weeks and 35 to 90 km). Conclusions/Significance: The description of the spatiotemporal patterns of RVF in South Africa between 2008 and 2011 supports the hypothesis that during an epidemic, disease spread may be supported by factors other than active vector dispersal. Limitations of under-reporting and space-time K-function properties are discussed. Further spatial analyses and data are required to explain factors and mechanisms driving RVF spread. © 2012 Métras et al.

Multidimensional modelling of X-ray spectra for AGN accretion disc outflows - II

Highly ionized fast accretion disc winds have been suggested as an explanation for a variety of observed absorption and emission features in the X-ray spectra of active galactic nuclei. Simple estimates have suggested that these flows may be massive enough to carry away a significant fraction of the accretion energy and could be involved in creating the link between supermassive black holes and their host galaxies. However, testing these hypotheses, and quantifying the outflow signatures, requires high-quality theoretical spectra for comparison with observations. Here, we describe extensions of our Monte Carlo radiative transfer code that allow us to generate realistic theoretical spectra for a much wider variety of disc wind models than that was possible in our previous work. In particular, we have expanded the range of atomic physics simulated by the code so that L- and M-shell ions can now be included. We have also substantially improved our treatment of both ionization and radiative heating such that we are now able to compute spectra for outflows containing far more diverse plasma conditions. We present example calculations that illustrate the variety of spectral features predicted by parametrized outflow models and demonstrate their applicability to the interpretation of data by comparison with observations of the bright quasar PG1211+143. We find that the major features in the observed 2-10 keV spectrum of this object can be well reproduced by our spectra, confirming that it likely hosts a massive outflow. © 2010 The Authors. Journal compilation © 2010 RAS.

Automaticity of cognitive biases in addictive behaviours: Further evidence with gamblers

Objectives. The hypotheses that automatic, non-volitional, attentional and memory biases for addiction-related constructs exist is tested with compulsive gamblers.

Design. An independent groups design was employed. Processing of gambling, compared to neutral and drug-related information was examined in 15 gamblers recruited from new members of Gamblers Anonymous. Comparisons were made with the performance of their spouses (N = 15) to help distinguish addiction mechanisms from more non-specific emotional experiences with gambling, and an independent control group (N = 15), recruited from the staff and students of a university department.

Methods. A modified Stroop procedure was first employed. Automative cognitive interference was assessed relatively, by comparing colour-naming times on the gambling, drug and neutral Stroops. A subsequent word-stem completion task of implicit memory was then used to assess selective and automatic priming of the gambling constructs in memory.

Results. Only the gamblers showed selective and automatic interference for gambling-related constructs on the Stroop task. Spouses behaved like the control group on this task. An implicit memory bias for gambling-related words was statistically detected only in the gamblers compared to the control group, although the trend was similar in the comparison with spouses. Further evidence for the specificity of these effects was obtained in subgroup comparisons involving fruit-machine with racing gamblers.

Conclusions. Results are generally consistent with an automaticity in the cognitive biases gamblers show for gambling-related information. implications for cognitive understanding and treatments are highlighted.

Large-scale spatial patterns in the distribution of Collembola (Hexapoda) species in Antarctic terrestrial ecosystems

We tested whether the distribution of three common springtail species (Gressittacantha terranova, Gomphiocephalus hodgsoni and Friesea grisea) in Victoria Land (Antarctica) could be modelled as a function of latitude, longitude, altitude and distance from the sea.

Victoria Land, Ross Dependency, Antarctica.

Generalized linear models were constructed using species presence/absence data relative to geographical features (latitude, longitude, altitude, distance from sea) across the species' entire ranges. Model results were then integrated with the known phylogeography of each species and hypotheses were generated on the role of climate as a major driver of Antarctic springtail distribution.

Based on model selection using Akaike's information criterion, the species' distributions were: hump-shaped relative to longitude and monotonic with altitude for Gressittacantha terranova; hump-shaped relative to latitude and monotonic with altitude for Gomphiocephalus hodgsoni; and hump-shaped relative to longitude and monotonic with latitude, altitude and distance from the sea for Friesea grisea.

No single distributional pattern was shared by the three species. While distributions were partially a response to climatic spatial clines, the patterns observed strongly suggest that past geological events have influenced the observed distributions. Accordingly, present-day spatial patterns are likely to have arisen from the interaction of historical and environmental drivers. Future studies will need to integrate a range of spatial and temporal scales to further quantify their respective roles.