The discursive construction of childhood and youth in AIDS interventions in Lesotho's education sector: Beyond global-local dichotomies

This is the post-print version of this article. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning D,Society and Space 28(5) 791 – 810, 2010, available from the link below. Copyright @ 2010 Pion.In southern Africa interventions to halt the spread of AIDS and address its social impacts are commonly targeted at young people, in many cases through the education sector. In Lesotho, education-sector responses to AIDS are the product of negotiation between a range of ‘local’ and ‘global’ actors. Although many interventions are put forward as government policy and implemented by teachers in schools, funding is often provided by bilateral and multilateral donors, and the international ‘AIDS industry’—in the form of UN agencies and international NGOs—sets agendas and makes prescriptions. This paper analyses interviews conducted with policy makers and practitioners in Lesotho and a variety of documents, critically examining the discourses of childhood and youth that are mobilised in producing changes in education policy and practice to address AIDS. Focusing on bursary schemes, life-skills education, and rights-based approaches, the paper concludes that, although dominant ‘global’ discourses are readily identified, they are not simply imported wholesale from the West, but rather are transformed through the organisations and personnel involved in designing and implementing interventions. Nonetheless, the connections through which these discourses are made, and children are subjectified, are central to the power dynamics of neoliberal globalisation. Although the representations of childhood and youth produced through the interventions are hybrid products of local and global discourses, the power relations underlying them are such that they, often unintentionally, serve a neoliberal agenda by depicting young people as individuals in need of saving, of developing personal autonomy, or of exercising individual rights.RGS-IB

A High-Light Sensitivity Optical Neural Silencer: Development and Application to Optogenetic Control of Non-Human Primate Cortex

Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1–10 mW/mm2, equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications

Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy

3D functional imaging of neuronal activity in entire organisms at single cell level and physiologically relevant time scales faces major obstacles due to trade-offs between the size of the imaged volumes, and spatial and temporal resolution. Here, using light-field microscopy in combination with 3D deconvolution, we demonstrate intrinsically simultaneous volumetric functional imaging of neuronal population activity at single neuron resolution for an entire organism, the nematode Caenorhabditis elegans. The simplicity of our technique and possibility of the integration into epi-fluoresence microscopes makes it an attractive tool for high-speed volumetric calcium imaging.Comment: 25 pages, 7 figures, incl. supplementary informatio

Ethical and methodological issues in engaging young people living in poverty with participatory research methods

This paper discusses the methodological and ethical issues arising from a project that focused on conducting a qualitative study using participatory techniques with children and young people living in disadvantage. The main aim of the study was to explore the impact of poverty on children and young people's access to public and private services. The paper is based on the author's perspective of the first stage of the fieldwork from the project. It discusses the ethical implications of involving children and young people in the research process, in particular issues relating to access and recruitment, the role of young people's advisory groups, use of visual data and collection of data in young people's homes. The paper also identifies some strategies for addressing the difficulties encountered in relation to each of these aspects and it considers the benefits of adopting participatory methods when conducting research with children and young people

Memory consolidation in the cerebellar cortex

Several forms of learning, including classical conditioning of the eyeblink, depend upon the cerebellum. In examining mechanisms of eyeblink conditioning in rabbits, reversible inactivations of the control circuitry have begun to dissociate aspects of cerebellar cortical and nuclear function in memory consolidation. It was previously shown that post-training cerebellar cortical, but not nuclear, inactivations with the GABA(A) agonist muscimol prevented consolidation but these findings left open the question as to how final memory storage was partitioned across cortical and nuclear levels. Memory consolidation might be essentially cortical and directly disturbed by actions of the muscimol, or it might be nuclear, and sensitive to the raised excitability of the nuclear neurons following the loss of cortical inhibition. To resolve this question, we simultaneously inactivated cerebellar cortical lobule HVI and the anterior interpositus nucleus of rabbits during the post-training period, so protecting the nuclei from disinhibitory effects of cortical inactivation. Consolidation was impaired by these simultaneous inactivations. Because direct application of muscimol to the nuclei alone has no impact upon consolidation, we can conclude that post-training, consolidation processes and memory storage for eyeblink conditioning have critical cerebellar cortical components. The findings are consistent with a recent model that suggests the distribution of learning-related plasticity across cortical and nuclear levels is task-dependent. There can be transfer to nuclear or brainstem levels for control of high-frequency responses but learning with lower frequency response components, such as in eyeblink conditioning, remains mainly dependent upon cortical memory storage

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Tuning the sensitivity of genetically encoded fluorescent potassium indicators through structure-guided and genome mining strategies

Genetically encoded potassium indicators lack optimal binding affinity for monitoring intracellular dynamics in mammalian cells. Through structure-guided design and genome mining of potassium binding proteins, we developed green fluorescent potassium indicators with a broad range of binding affinities. KRaION1 (K+ ratiometric indicator for optical imaging based on mNeonGreen 1), based on the insertion of a potassium binding protein, Kbp, from E. coli (Ec-Kbp) into the fluorescent protein mNeonGreen, exhibits an isotonically measured Kd of 69 ± 10 mM (mean ± standard deviation used throughout). We identified Ec-Kbp’s binding site using NMR spectroscopy to detect protein–thallium scalar couplings and refined the structure of Ec-Kbp in its potassium-bound state. Guided by this structure, we modified KRaION1, yielding KRaION1/D9N and KRaION2, which exhibit isotonically measured Kd’s of 138 ± 21 and 96 ± 9 mM. We identified four Ec-Kbp homologues as potassium binding proteins, which yielded indicators with isotonically measured binding affinities in the 39–112 mM range. KRaIONs functioned in HeLa cells, but the Kd values differed from the isotonically measured case. We found that, by tuning the experimental conditions, Kd values could be obtained that were consistent in vitro and in vivo. We thus recommend characterizing potassium indicator Kd in the physiological context of interest before application

Incentive payments to general practitioners aimed at increasing opportunistic testing of young women for chlamydia: a pilot cluster randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Financial incentives have been used for many years internationally to improve quality of care in general practice. The aim of this pilot study was to determine if offering general practitioners (GP) a small incentive payment per test would increase chlamydia testing in women aged 16 to 24 years, attending general practice.</p> <p>Methods</p> <p>General practice clinics (n = 12) across Victoria, Australia, were cluster randomized to receive either a $AUD5 payment per chlamydia test or no payment for testing 16 to 24 year old women for chlamydia. Data were collected on the number of chlamydia tests and patient consultations undertaken by each GP over two time periods: 12 month pre-trial and 6 month trial period. The impact of the intervention was assessed using a mixed effects logistic regression model, accommodating for clustering at GP level.</p> <p>Results</p> <p>Testing increased from 6.2% (95% CI: 4.2, 8.4) to 8.8% (95% CI: 4.8, 13.0) (p = 0.1) in the control group and from 11.5% (95% CI: 4.6, 18.5) to 13.4% (95% CI: 9.5, 17.5) (p = 0.4) in the intervention group. Overall, the intervention did not result in a significant increase in chlamydia testing in general practice. The odds ratio for an increase in testing in the intervention group compared to the control group was 0.9 (95% CI: 0.6, 1.2). Major barriers to increased chlamydia testing reported by GPs included a lack of time, difficulty in remembering to offer testing and a lack of patient awareness around testing.</p> <p>Conclusions</p> <p>A small financial incentive alone did not increase chlamydia testing among young women attending general practice. It is possible small incentive payments in conjunction with reminder and feedback systems may be effective, as may higher financial incentive payments. Further research is required to determine if financial incentives can increase testing in Australian general practice, the type and level of financial scheme required and whether incentives needs to be part of a multi-faceted package.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trial Registry ACTRN12608000499381.</p

Polyene Macrolide Antifungal Drugs Trigger Interleukin-1β Secretion by Activating the NLRP3 Inflammasome

The use of antimycotic drugs in fungal infections is based on the concept that they suppress fungal growth by a direct killing effect. However, amphotericin and nystatin have been reported to also trigger interleukin-1β (IL-1β) secretion in monocytes but the molecular mechanism is unknown. Here we report that only the polyene macrolides amphotericin B, nystatin, and natamycin but none of the tested azole antimycotic drugs induce significant IL-1β secretion in-vitro in dendritic cells isolated from C57BL/6 mouse bone marrow. IL-1β release depended on Toll-like receptor-mediated induction of pro-IL-1β as well as the NLRP3 inflammasome, its adaptor ASC, and caspase-1 for enzymatic cleavage of pro-IL-1β into its mature form. All three drugs induced potassium efflux from the cells as a known mechanism for NLRP3 activation but the P2X7 receptor was not required for this process. Natamycin-induced IL-1β secretion also involved phagocytosis, as cathepsin activation as described for crystal-induced IL-1β release. Together, the polyene macrolides amphotericin B, nystatin, and natamycin trigger IL-1β secretion by causing potassium efflux from which activates the NLRP3-ASC-caspase-1. We conclude that beyond their effects on fungal growth, these antifungal drugs directly activate the host's innate immunity