Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke.

Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation

Vouchers for scaling up insecticide-treated nets in Tanzania: Methods for monitoring and evaluation of a national health system intervention

BACKGROUND: The Tanzania National Voucher Scheme (TNVS) uses the public health system and the commercial sector to deliver subsidised insecticide-treated nets (ITNs) to pregnant women. The system began operation in October 2004 and by May 2006 was operating in all districts in the country. Evaluating complex public health interventions which operate at national level requires a multidisciplinary approach, novel methods, and collaboration with implementers to support the timely translation of findings into programme changes. This paper describes this novel approach to delivering ITNs and the design of the monitoring and evaluation (M&E). METHODS: A comprehensive and multidisciplinary M&E design was developed collaboratively between researchers and the National Malaria Control Programme. Five main domains of investigation were identified: (1) ITN coverage among target groups, (2) provision and use of reproductive and child health services, (3) "leakage" of vouchers, (4) the commercial ITN market, and (5) cost and cost-effectiveness of the scheme. RESULTS: The evaluation plan combined quantitative (household and facility surveys, voucher tracking, retail census and cost analysis) and qualitative (focus groups and in-depth interviews) methods. This plan was defined in collaboration with implementing partners but undertaken independently. Findings were reported regularly to the national malaria control programme and partners, and used to modify the implementation strategy over time. CONCLUSION: The M&E of the TNVS is a potential model for generating information to guide national and international programmers about options for delivering priority interventions. It is independent, comprehensive, provides timely results, includes information on intermediate processes to allow implementation to be modified, measures leakage as well as coverage, and measures progress over time

Religious Diversity and Conceptual Schemes: Critically Appraising Internalist Pluralism

Is a philosophical theory needed to ‘underwrite’ attitudes of toleration and respect in a multicultural and religiously diverse world? Many philosophers of religion have thought so, including Victoria Harrison. This article interrogates Harrison’s theory of internalist pluralism, which, though offering a welcome alternative to other theories, such as John Hick’s ‘pluralistic hypothesis’, nevertheless faces problems. Questioning the coherence of the theory’s account of how the existence of objects of worship can avoid being fully conceptual-scheme dependent, and raising doubts about its pretensions to promote interreligious harmony, I also critically discuss the common philosophical tendency to work with under-described and insufficiently analysed examples. What philosophy ought to be able to offer in relation to religious diversity, I propose, is attentiveness to nuances and particularities, thereby aiding religious understanding without the need for a general theory

Common Gamma Chain Cytokines Promote Rapid In Vitro Expansion of Allo-Specific Human CD8+ Suppressor T Cells

Human CD8+ regulatory T cells, particularly the CD8+CD28− T suppressor cells, have emerged as an important modulator of alloimmunity. Understanding the conditions under which these cells are induced and/or expanded would greatly facilitate their application in future clinical trials. In the current study, we develop a novel strategy that combines common gamma chain (γc) cytokines IL-2, IL-7 and IL-15 and donor antigen presenting cells (APCs) to stimulate full HLA-mismatched allogeneic human CD8+ T cells which results in significant expansions of donor-specific CD8+CD28− T suppressor cells in vitro. The expanded CD8+CD28− T cells exhibit increased expressions of CTLA-4, FoxP3, and CD25, while down-regulate expressions of CD56, CD57, CD127, and perforin. Furthermore, these cells suppress proliferation of CD4+ T cells in a contact-dependent and cytokine-independent manner. Interestingly, the specificity of suppression is restricted by the donor HLA class I antigens but promiscuous to HLA class II antigens, providing a potential mechanism for linked suppression. Taken together, our results demonstrate a novel role for common γc cytokines in combination with donor APCs in the expansion of donor-specific CD8+CD28− T suppressor cells, and represent a robust strategy for in vitro generation of such cells for adoptive cellular immunotherapy in transplantation