Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-/- mice

AIM: To investigate the influence of Trichuris muris (T. muris ) infection in a mouse model of genetic susceptibility to inflammatory bowel disease, Mdr1a-/-. METHODS: Mdr1a-/- mice were housed under specific pathogen free conditions to slow the development of colitis and compared to congenic FVB controls. Mice were infected with approximately 200 embryonated ova from T. muris and assessed for worm burden and histological and functional markers of gut inflammation on day 19 post infection. RESULTS: Mdr1a-/- mice exhibited a marked increase in susceptibility to T. muris infection with a 10-fold increase in colonic worm count by day 19 pi compared to FVB controls. Prior to infection, Mdr1a-/- exhibited low-level mucosal inflammation with evidence of an enhanced Th1 environment. T. muris infection accelerated the progression of colitis in Mdr1a-/- as evidenced by marked increases in several indicators including histological damage score, mucosal CD4+ T-cell and DC infiltration and dramatically increased production of proinflammatory cytokines. CONCLUSION: These data provide further evidence of the complex interaction between T. muris and an inflammatory bowel disease (IBD)-susceptible host which may have relevance to the application of helminth therapy in the treatment of human IBD

Labour supply and skills demands in fashion retailing

If, as Adam Smith once famously suggested, Britain was a nation of shopkeepers then it is now a nation of shopworkers. Retail is now a significant part of the UK economy, accounting for £256 billion in sales and one-third of all consumer spending (Skillsmart, 2007). It is the largest private sector employer in the UK, employing 3m workers, or 1 in 10 of the working population. For future job creation in the UK economy retail is also similarly prominent and the sector is expected to create a further 250,000 jobs to 2014 (Skillsmart, 2007). The centrality of retail to economic success and job creation is apparent in other advanced economies. For example, within the US, retail sales is the occupation with the largest projected job growth in the period 2004-2014 (Gatta et al., 2009) and in Australia retail accounts for 1 in 6 workers (Buchanan et al., 2003). Within the UK these workers are employed in approximately 290,000 businesses, encompassing large and small organizations and also a number of sub-sectors. This variance suggests that retail should not be regarded as homogenous in its labour demands. Hart et al. (2007) note how skill requirements and the types of workers employed may differ across the sector. This chapter further opens up this point, providing an analysis of the labour supply and skills demands for the sub-sectors of clothing, footwear and leather goods, which are described by Skillsmart (2007: 48) as being 'significant categories in UK retailing'

Influence of LAR and VAR on Para-Aminopyridine Antimalarials Targetting Haematin in Chloroquine-Resistance

Antimalarial chloroquine (CQ) prevents haematin detoxication when CQ-base concentrates in the acidic digestive vacuole through protonation of its p-aminopyridine (pAP) basic aro- matic nitrogen and sidechain diethyl-N. CQ export through the variant vacuolar membrane export channel, PFCRT, causes CQ-resistance in Plasmodium falciparum but 3-methyl CQ (sontochin SC), des-ethyl amodiaquine (DAQ) and bis 4-aminoquinoline piperaquine (PQ) are still active. This is determined by changes in drug accumulation ratios in parasite lipid (LAR) and in vacuolar water (VAR). Higher LAR may facilitate drug binding to and blocking PFCRT and also aid haematin in lipid to bind drug. LAR for CQ is only 8.3; VAR is 143,482. More hydrophobic SC has LAR 143; VAR remains 68,523. Similarly DAQ with a phenol sub- stituent has LAR of 40.8, with VAR 89,366. In PQ, basicity of each pAP is reduced by distal piperazine N, allowing very high LAR of 973,492, retaining VAR of 104,378. In another bis quinoline, dichlorquinazine (DCQ), also active but clinically unsatisfactory, each pAP retains basicity, being insulated by a 2-carbon chain from a proximal nitrogen of the single linking piperazine. While LAR of 15,488 is still high, the lowest estimate of VAR approaches 4.9 million. DCQ may be expected to be very highly lysosomotropic and therefore potentially hepatotoxic. In 11 pAP antimalarials a quadratic relationship between logLAR and logRe- sistance Index (RI) was confirmed, while log (LAR/VAR) vs logRI for 12 was linear. Both might be used to predict the utility of structural modifications

Using MCDA to generate and interpret evidence to inform local government investment in public health

Smoking is the single biggest cause of preventable death in the Uited Kingdom (UK) and is a major cause of coronary heart disease, some cancers, and respiratory disease, including chronic obstructive pulmonary disease. At the time of initiating the project, smoking prevalence had not changed across four local government areas in South Yorkshire for some years. Most spending had been focussed on helping people quit, an intervention where there was clear evidence of effectiveness. A number of changes occurred in public health structures and targets, requiring a reappraisal of the range of interventions offered. This was challenging due to a lack of clear evidence for some of the areas’ alternative interventions. The aim of this paper is to describe the use of a multi-criteria decision analysis (MCDA) approach to support the health priority setting in local authorities to reduce smoking prevalence. There were three phases to this process: (1) problem structuring; (2) the multiple criteria decision analysis; (3) and using the MCDA results to influence decision making at the local government level. The MCDA approach was used to collate information in a consistent and transparent manner, using expert, stakeholder and public opinion to fill known gaps in evidence. Fifteen interventions (such as stop smoking support services, smoke-free spaces, communication and marketing exercises, and increased investment in enforcement) were ranked across eight criteria (relating to reductions in prevalence across relevant groups, as well as aspects relating to equity and feasibility), allowing a range of relevant concerns to be incorporated. Subsequent steps were taken to translate the results of this stage into workable policy options. The results differed significantly from current practice. Sensitivity analysis showed that the findings were robust to changes in preference weights. These results informed subsequent changes to the interventions offered across the four boroughs. The ability of MCDA techniques to incorporate data and both qualitative and quantitative judgements in a formal manner mean that they are well suited to support public health decision making, where evidence is often only partially available and many policies are value driven. MCDA methods, if used, should be chosen carefully based on their resource/time constraints, scientific validity, and the significance and broader context of the decision problem.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s40070-016-0059-

Giving Miss Marple a makeover : graduate recruitment, systems failure and the Scottish voluntary sector

The voluntary sector in Scotland, as across the globe, is becoming increasingly business like. Resultantly, there is an increasing demand for graduates to work in business and support functions. In Scotland, however, despite an oversupply of graduates in the labor market, the voluntary sector reports skills shortages for graduate-level positions; a leadership deficit was also reported in countries such as the United States. Through exploratory, mainly qualitative, case study and stakeholder research, this article proposes that one reason for this mismatch between the supply of and demand for graduates is a systems failure within the sector. Many graduates and university students remain unaware of potentially suitable paid job opportunities, in part because of the sector's voluntary label. To rectify this systems failure, thought needs to be given to the sector's nomenclature and the manner in which voluntary sector organizations attract graduate recruits, for example, through levering value congruence in potential recruits

Foundation and empire : a critique of Hardt and Negri

In this article, Thompson complements recent critiques of Hardt and Negri's Empire (see Finn Bowring in Capital and Class, no. 83) using the tools of labour process theory to critique the political economy of Empire, and to note its unfortunate similarities to conventional theories of the knowledge economy

Older workers in the hospitality industry: valuing experience and informal learning

The research sets out to identify the learning processes adopted by older workers in the hospitality and visitor attraction industry in Scotland, with a view to determining how employers may better support their education and training within enterprises. The study was undertaken as part of the ESRC project on ‘sustaining the employability of older workers in the hospitality sector: personal learning strategies and cultures of learning. The data collection period was from 2008-2010 and focused on six case studies; three in hospitality and three visitor attraction centres. The conceptual framework of the research is based upon the simple yet important notion of experience and how this enhances the learning lives of older employees. It will be argued that the learning processes used by older employees are primarily recognisable as social practices, based upon the utilisation of existing knowledge and skills. The analysis suggests that organisations should be encouraged to avoid using a ‘one size fits all’ approach to education and training and, in the case of older workers, to make more use of their past work and life experiences in order to facilitate their own and others’ learning

Protecting the malaria drug arsenal: halting the rise and spread of amodiaquine resistance by monitoring the PfCRT SVMNT type

The loss of chloroquine due to selection and spread of drug resistant Plasmodium falciparum parasites has greatly impacted malaria control, especially in highly endemic areas of Africa. Since chloroquine removal a decade ago, the guidelines to treat falciparum malaria suggest combination therapies, preferentially with an artemisinin derivative. One of the recommended partner drugs is amodiaquine, a pro-drug that relies on its active metabolite monodesethylamodiaquine, and is still effective in areas of Africa, but not in regions of South America. Genetic studies on P. falciparum parasites have shown that different pfcrt mutant haplotypes are linked to distinct levels of chloroquine and amodiaquine responses. The pfcrt haplotype SVMNT (termed after the amino acids from codon positions 72-76) is stably present in several areas where amodiaquine was introduced and widely used. Parasites with this haplotype are highly resistant to monodesethylamodiaquine and also resistant to chloroquine. The presence of this haplotype in Africa was found for the first time in 2004 in Tanzania and a role for amodiaquine in the selection of this haplotype was suggested. This commentary discusses the finding of a second site in Africa with high incidence of this haplotype. The >50% SVMNT haplotype prevalence in Angola represents a threat to the rise and spread of amodiaquine resistance. It is paramount to monitor pfcrt haplotypes in every country currently using amodiaquine and to re-evaluate current combination therapies in areas where SVMNT type parasites are prevalent

The New ‘Hidden Abode’: Reflections on Value and Labour in the New Economy

In a pivotal section of Capital, volume 1, Marx (1976: 279) notes that, in order to understand the capitalist production of value, we must descend into the ‘hidden abode of production’: the site of the labour process conducted within an employment relationship. In this paper we argue that by remaining wedded to an analysis of labour that is confined to the employment relationship, Labour Process Theory (LPT) has missed a fundamental shift in the location of value production in contemporary capitalism. We examine this shift through the work of Autonomist Marxists like Hardt and Negri, Lazaratto and Arvidsson, who offer theoretical leverage to prize open a new ‘hidden abode’ outside employment, for example in the ‘production of organization’ and in consumption. Although they can open up this new ‘hidden abode’, without LPT's fine-grained analysis of control/resistance, indeterminacy and structured antagonism, these theorists risk succumbing to empirically naive claims about the ‘new economy’. Through developing an expanded conception of a ‘new hidden abode’ of production, the paper demarcates an analytical space in which both LPT and Autonomist Marxism can expand and develop their understanding of labour and value production in today's economy. </jats:p