Transcription profiling of a recently colonised pyrethroid resistant Anopheles gambiae strain from Ghana

BACKGROUND: Mosquito resistance to the pyrethroid insecticides used to treat bednets threatens the sustainability of malaria control in sub-Saharan Africa. While the impact of target site insensitivity alleles is being widely discussed the implications of insecticide detoxification – though equally important – remains elusive. The successful development of new tools for malaria intervention and management requires a comprehensive understanding of insecticide resistance, including metabolic resistance mechanisms. Although three enzyme families (cytochrome P450s, glutathione S-transferases and carboxylesterases) have been widely associated with insecticide detoxification the role of individual enzymes is largely unknown. RESULTS: Here, constitutive expression patterns of genes putatively involved in conferring pyrethroid resistance was investigated in a recently colonised pyrethroid resistant Anopheles gambiae strain from Odumasy, Southern Ghana. RNA from the resistant strain and a standard laboratory susceptible strain, of both sexes was extracted, reverse transcribed and labelled with either Cy3- or Cy5-dye. Labelled cDNA was co-hybridised to the detox chip, a custom-made microarray containing over 230 A. gambiae gene fragments predominantly from enzyme families associated with insecticide resistance. After hybridisation, Cy3- and Cy5-signal intensities were measured and compared gene by gene. In both females and males of the resistant strain the cytochrome P450s CYP6Z2 and CYP6M2 are highly over-expressed along with a member of the superoxide dismutase (SOD) gene family. CONCLUSION: These genes differ from those found up-regulated in East African strains of pyrethroid resistant A. gambiae and constitute a novel set of candidate genes implicated in insecticide detoxification. These data suggest that metabolic resistance may have multiple origins in A. gambiae, which has strong implications for the management of resistance

Cognitive dysfunction in patients with cerebral microbleeds on T2*-weighted gradient-echo MRI.

Gradient echo T2*-weighted MRI has high sensitivity in detecting cerebral microbleeds, which appear as small dot-like hypointense lesions. Microbleeds are strongly associated with intracerebral haemorrhage, hypertension, lacunar stroke and ischaemic small vessel disease, and have generated interest as a marker of bleeding-prone microangiopathy. Microbleeds have generally been considered to be clinically silent; however, since they are located in widespread cortical and basal ganglia regions and are histologically characterized by tissue damage, we hypothesized that they would cause cognitive dysfunction. We therefore studied patients with microbleeds (n = 25) and a non-microbleed control group (n = 30) matched for age, gender and intelligence quotient. To avoid the confounding effects of coexisting cerebrovascular disease, the groups were also matched for the extent of MRI-visible white matter changes of presumed ischaemic origin, location of cortical strokes, and for the proportion of patients with different stroke subtypes (including lacunar stroke). A battery of neuropsychological tests was used to assess current intellectual function, verbal and visual memory, naming and perceptual skills, speed and attention and executive function. Microbleeds were most common in the basal ganglia but were also found in frontal, parieto-occipital, temporal and infratentorial regions. There was a striking difference between the groups in the prevalence of executive dysfunction, which was present in 60% of microbleed patients compared with 30% of non-microbleed patients (P = 0.03). Logistic regression confirmed that microbleeds (but not white matter changes) were an independent predictor of executive impairment (adjusted odds ratio = 1.32, 95% confidence interval 1.01-1.70, P = 0.04). Patients with executive dysfunction had more microbleeds in the frontal region (mean count 1.54 versus 0.03; P = 0.002) and in the basal ganglia (mean 1.17 versus 0.32; P = 0.048). There was a modest correlation between the number of microbleeds and the number of cognitive domains impaired (r = 0.44, P = 0.03). This study provides novel evidence that microbleeds are associated with cognitive dysfunction, independent of the extent of white matter changes of presumed ischaemic origin, or the presence of ischaemic stroke. The striking effect of microbleeds on executive dysfunction is likely to result from associated tissue damage in the frontal lobes and basal ganglia. These findings have implications for the diagnosis of stroke patients with cognitive impairment, and for the appropriate use of antihypertensive and antiplatelet treatments in these patients

Rights, responsibilities and redress? : Research on policy and practice for Roma inclusion in ten Member States: Final Report

This report is intended to assist the European Commission, civil society organisations, academics and a variety of key organisations and engaged individuals in furthering understanding of how policy impacts on the lives of Roma in countries across Europe. This report presents the findings from the empirical research in a number of thematic areas. More specifically, Chapter 2 briefly outlines the policy context for this report. In Chapter 3 we consider issues relating to cross-community relations. Employment is the focus of Chapter 4, whilst Chapter 5 focuses on the reporting of antidiscrimination and issues relating to redress mechanisms. Chapter 6 looks at the issues associated with Roma children living in and leaving public care systems. Finally, Chapter 7 discusses a number of cross-cutting issues that permeate the findings across the four main themes, provides some conclusions arising from this research and presents some key recommendations

Ultrashort echo time (UTE) imaging using gradient pre-equalization and compressed sensing.

Ultrashort echo time (UTE) imaging is a well-known technique used in medical MRI, however, the implementation of the sequence remains non-trivial. This paper introduces UTE for non-medical applications and outlines a method for the implementation of UTE to enable accurate slice selection and short acquisition times. Slice selection in UTE requires fast, accurate switching of the gradient and r.f. pulses. Here a gradient "pre-equalization" technique is used to optimize the gradient switching and achieve an effective echo time of 10μs. In order to minimize the echo time, k-space is sampled radially. A compressed sensing approach is used to minimize the total acquisition time. Using the corrections for slice selection and acquisition along with novel image reconstruction techniques, UTE is shown to be a viable method to study samples of cork and rubber with a shorter signal lifetime than can typically be measured. Further, the compressed sensing image reconstruction algorithm is shown to provide accurate images of the samples with as little as 12.5% of the full k-space data set, potentially permitting real time imaging of short T2(*) materials.HTF would like to acknowledge the financial support of the Gates-Cambridge Trust and all authors of the EPSRC (EP/K008218/1). In addition, we would like to thank SoftPoint Industries Inc. for providing samples of rubber.This version is final published version, distributed under a Creative Commons Attribution License 2.0. This can also be viewed on the publisher's website at: http://www.sciencedirect.com/science/article/pii/S1090780714001840

Detecting disordered eating among recreational exercisers; exploring the role of personal trainers

This study aimed to understand how personal trainers identify and manage disordered eating among their clients. Semi-structured interviews were undertaken with eleven UK based personal trainers to document their experiences of working with clients exhibiting symptoms of disordered eating. The interviews were recorded, fully transcribed and subjected to a thematic analysis. The findings suggest that personal trainers rely on external cues to identify disordered eating among clients such as changes to physical appearance, exercise behaviours and performance. The findings also revealed that personal trainers lack knowledge and hold misconceptions about disordered eating. Such misconceptions influenced their ability to identify and manage potential problems among their clients. Participants described the need for further education and guidelines to increase their knowledge and confidence in identifying and managing disordered eating among their clients. The findings from this study will be useful for professional bodies and practitioners in the development of guidelines and educational material for personal trainers

Rights, responsibilities and redress? : Research on policy and practice for Roma inclusion in ten Member States: Summary Report

The overall objective of the research element was to investigate how the national strategies for Roma integration were being operationalised and delivered within the partner states in respect of combating ‘anti-Gypsyism’. Under this broad remit the research was guided by four specific objectives: 1. To map and explore existing policies and practice for combating anti-Gypsyism and promoting social inclusion in relation to the four core areas outlined above; 2. To consider the effectiveness of existing policies and procedures in combating antiGypsyism; 3. To investigate how existing policy and procedural frameworks are operationalised in practice on the ground; and 4. To explore how policies are experienced by organisations supporting and/or representing the interests of Rom