Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein

Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm(3)g(-1)) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 mu g)/SV-140 (500 mu g) and FD oE2 (100 mu g)/SV-140 (500 mu g) to induce long-term immunity was compared to immunisation with oE2 (100 mu g) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 mu g) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 mu g SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications

Mathematically aggregating experts' predictions of possible futures

Structured protocols offer a transparent and systematic way to elicit and combine/aggregate, probabilistic predictions from multiple experts. These judgements can be aggregated behaviourally or mathematically to derive a final group prediction. Mathematical rules (e.g., weighted linear combinations of judgments) provide an objective approach to aggregation. The quality of this aggregation can be defined in terms of accuracy, calibration and informativeness. These measures can be used to compare different aggregation approaches and help decide on which aggregation produces the “best” final prediction. When experts’ performance can be scored on similar questions ahead of time, these scores can be translated into performance-based weights, and a performance-based weighted aggregation can then be used. When this is not possible though, several other aggregation methods, informed by measurable proxies for good performance, can be formulated and compared. Here, we develop a suite of aggregation methods, informed by previous experience and the available literature. We differentially weight our experts’ estimates by measures of reasoning, engagement, openness to changing their mind, informativeness, prior knowledge, and extremity, asymmetry or granularity of estimates. Next, we investigate the relative performance of these aggregation methods using three datasets. The main goal of this research is to explore how measures of knowledge and behaviour of individuals can be leveraged to produce a better performing combined group judgment. Although the accuracy, calibration, and informativeness of the majority of methods are very similar, a couple of the aggregation methods consistently distinguish themselves as among the best or worst. Moreover, the majority of methods outperform the usual benchmarks provided by the simple average or the median of estimates

The determinants of vulnerability to currency crises: country-specific factors versus regional factors

We investigate the determinants of exchange market pressures (EMP) for some new EU member states at both the national and regional levels, where macroeconomic and financial variables are considered as potential sources. The regional common factors are extracted from these variables by using dynamic factor analysis. The linear empirical analysis, in general, highlights the importance of country-specific factors to defend themselves against vulnerability in their external sectors. Yet, given a significant impact of the common component in credit on EMP, a contagion effect is apparent through the conduit of credit market integration across these countries under investigation

Smoking and health-related quality of life in English general population: Implications for economic evaluations

Copyright @ 2012 Vogl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.Background: Little is known as to how health-related quality of life (HRQoL) when measured by generic instruments such as EQ-5D differ across smokers, ex-smokers and never-smokers in the general population; whether the overall pattern of this difference remain consistent in each domain of HRQoL; and what implications this variation, if any, would have for economic evaluations of tobacco control interventions. Methods: Using the 2006 round of Health Survey for England data (n = 13,241), this paper aims to examine the impact of smoking status on health-related quality of life in English population. Depending upon the nature of the EQ-5D data (i.e. tariff or domains), linear or logistic regression models were fitted to control for biology, clinical conditions, socio-economic background and lifestyle factors that an individual may have regardless of their smoking status. Age- and gender-specific predicted values according to smoking status are offered as the potential 'utility' values to be used in future economic evaluation models. Results: The observed difference of 0.1100 in EQ-5D scores between never-smokers (0.8839) and heavy-smokers (0.7739) reduced to 0.0516 after adjusting for biological, clinical, lifestyle and socioeconomic conditions. Heavy-smokers, when compared with never-smokers, were significantly more likely to report some/severe problems in all five domains - mobility (67%), self-care (70%), usual activity (42%), pain/discomfort (46%) and anxiety/depression (86%) -. 'Utility' values by age and gender for each category of smoking are provided to be used in the future economic evaluations. Conclusion: Smoking is significantly and negatively associated with health-related quality of life in English general population and the magnitude of this association is determined by the number of cigarettes smoked. The varying degree of this association, captured through instruments such as EQ-5D, may need to be fed into the design of future economic evaluations where the intervention being evaluated affects (e.g. tobacco control) or is affected (e.g. treatment for lung cancer) by individual's (or patients') smoking status

The prevalence and functional impact of musculoskeletal conditions amongst clients of a primary health care facility in an under-resourced area of Cape Town

BACKGROUND:The extent of disease burden of musculoskeletal conditions (MSC) not due to injury has not been well determined in sub-Saharan Africa. The 1999 Global Burden of Disease study estimated the prevalence of osteoarthritis and rheumatoid arthritis to be 150/100,000 compared to 1,500/100,000 in Europe. The objective of the study was to determine the prevalence of MSC and the functional implications in a sample of people attending community health centres in Cape Town, South Africa. METHODS: A cross-sectional, descriptive study was conducted in clinics in two resource poor communities. Phase I consisted of screening and those who screened positive for peripheral or spinal joint pain went on to complete Phase II, which included the Stanford Health Assessment Questionnaire. RESULTS: 1005 people were screened in Phase I. Of these, 362 (36%) reported MSC not due to injury in the past three months. Those with MSC had higher rates of co-morbidities in every category than those without. The mean Disability Index for those with MSC was mild to moderate and moderate to severe in those over 55 years. CONCLUSIONS: Although the sample may not be representative of the general community, the prevalence is considerably greater than those reported elsewhere even when the population of the catchment area is used as a denominator, (367/100 000). The common presentation of MSC with co-morbid diabetes and hypertension requires holistic management by appropriately trained health care practitioners. Any new determination of burden of disease due to MSC should recognise that these disorders may be more prevalent in developing countries than previously estimated

Southeast Asia and the Politics of Vulnerability

The economic and political crises that have recently engulfed the countries of Southeast Asia provide a stark reminder of just how difficult the challenge of sustained regional development remains. In retrospect, the hyperbole that surrounded the 'East Asian miracle' looks overblown, and testimony to the manner in which rhetoric can outstrip reality, especially in the minds of international investors. Certainly, some observers had questioned the depth and resilience of capitalist development in Southeast Asia, but in the years immediately prior to 1997 such analyses tended to be in the minority. Now, of course, it is painfully obvious that much of Southeast Asia's economic and political development was extremely fragile. When seen in historical context, this outcome should not have been surprising since the countries of modern Southeast Asia, both as independent nations and as colonies of various imperial powers, have been highly vulnerable to the actions of powerful external political and economic forces. This paper will examine the economic bases and the political consequences of this vulnerablity, both domestically and at a regional level. I argue that the recent crisis has served as an unwelcome reminder of just how constrained, dependent and vulnerable the Southeast Asia region's development prospects remain, a situation that is exacerbated by, and which contributes to, domestic political crises

(Un)becoming women: Indian factory women's counternarratives of gender

This paper portrays the life stories of five factory workers in Delhi whose life trajectories run counter to normative femininity. As daughters and wives, they are neglected, abandoned or rejected by their families; they live alone, with their parents past the age that is their natal right, with siblings, or with families and men who are not related to them. I explore the circulation of their counternarratives and how their gender transgressions go public through ordinary forms of talk, such as gossip and rumor. I argue that their move out of the normative is not produced by, but produces, their gender politics; that their agency emerges cognitively from the telling of their stories in tandem with their interlocutors' credulity and uptake; and that the site of gender politics for working class Indian women lies in the informal subaltern publics that are formed by the circulation of their stories. Contrary to the notion of a stable unitary subject that precedes the political, these women's counternarratives demonstrate the subject‐in‐process as a political effect. Their alterity does not exist outside the heteronormative gender order but demarcates the boundaries of its historicity, hinting at both the internal contradictions of existing gender relations and their future possibilities.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112196/1/j.1467-954X.2011.02026.x.pd

Region-Specific Expression of Mitochondrial Complex I Genes during Murine Brain Development

Mutations in the nuclear encoded subunits of mitochondrial complex I (NADH:ubiquinone oxidoreductase) may cause circumscribed cerebral lesions ranging from degeneration of the striatal and brainstem gray matter (Leigh syndrome) to leukodystrophy. We hypothesized that such pattern of regional pathology might be due to local differences in the dependence on complex I function. Using in situ hybridization we investigated the relative expression of 33 nuclear encoded complex I subunits in different brain regions of the mouse at E11.5, E17.5, P1, P11, P28 and adult (12 weeks). With respect to timing and relative intensity of complex I gene expression we found a highly variant pattern in different regions during development. High average expression levels were detected in periods of intense neurogenesis. In cerebellar Purkinje and in hippocampal CA1/CA3 pyramidal neurons we found a second even higher peak during the period of synaptogenesis and maturation. The extraordinary dependence of these structures on complex I gene expression during synaptogenesis is in accord with our recent findings that gamma oscillations – known to be associated with higher cognitive functions of the mammalian brain – strongly depend on the complex I activity. However, with the exception of the mesencephalon, we detected only average complex I expression levels in the striatum and basal ganglia, which does not explain the exquisite vulnerability of these structures in mitochondrial disorders