The Gathering Storm: Infectious Diseases and Human Rights in Burma

Documents how decades of repressive rule, civil war, and poor governance in Burma have contributed to the spread of HIV/AIDS, tuberculosis, malaria, and other infectious diseases

Optimization of pillar electrodes in subretinal prosthesis for enhanced proximity to target neurons

OBJECTIVE: High-resolution prosthetic vision requires dense stimulating arrays with small electrodes. However, such miniaturization reduces electrode capacitance and penetration of electric field into tissue. We evaluate potential solutions to these problems with subretinal implants based on utilization of pillar electrodes. APPROACH: To study integration of three-dimensional (3D) implants with retinal tissue, we fabricated arrays with varying pillar diameter, pitch, and height, and implanted beneath the degenerate retina in rats (Royal College of Surgeons, RCS). Tissue integration was evaluated six weeks post-op using histology and whole-mount confocal fluorescence imaging. The electric field generated by various electrode configurations was calculated in COMSOL, and stimulation thresholds assessed using a model of network-mediated retinal response. MAIN RESULTS: Retinal tissue migrated into the space between pillars with no visible gliosis in 90% of implanted arrays. Pillars with 10 μm height reached the middle of the inner nuclear layer (INL), while 22 μm pillars reached the upper portion of the INL. Electroplated pillars with dome-shaped caps increase the active electrode surface area. Selective deposition of sputtered iridium oxide onto the cap ensures localization of the current injection to the pillar top, obviating the need to insulate the pillar sidewall. According to computational model, pillars having a cathodic return electrode above the INL and active anodic ring electrode at the surface of the implant would enable six times lower stimulation threshold, compared to planar arrays with circumferential return, but suffer from greater cross-talk between the neighboring pixels. SIGNIFICANCE: 3D electrodes in subretinal prostheses help reduce electrode-tissue separation and decrease stimulation thresholds to enable smaller pixels, and thereby improve visual acuity of prosthetic vision

Characteristics of prosthetic vision in rats with subretinal flat and pillar electrode arrays

Objective. Retinal prostheses aim to restore sight by electrically stimulating the surviving retinal neurons. In clinical trials of the current retinal implants, prosthetic visual acuity does not exceed 20/550. However, to provide meaningful restoration of central vision in patients blinded by age-related macular degeneration (AMD), prosthetic acuity should be at least 20/200, necessitating a pixel pitch of about 50 µm or lower. With such small pixels, stimulation thresholds are high due to limited penetration of electric field into tissue. Here, we address this challenge with our latest photovoltaic arrays and evaluate their performance in-vivo. 
Approach. We fabricated photovoltaic arrays with 55 and 40 µm pixels (a) in flat geometry, and (b) with active electrodes on 10 µm tall pillars. The arrays were implanted subretinally into rats with degenerate retina. Stimulation thresholds and grating acuity were evaluated using measurements of the visually evoked potentials (VEP). 
Main Results. With 55 μm pixels, we measured grating acuity of 48±11 μm, which matches the linear pixel pitch of the hexagonal array. This geometrically corresponds to a visual acuity of 20/192 in a human eye, matching the threshold of legal blindness in the US (20/200). With pillar electrodes, the irradiance threshold was nearly halved, and duration threshold reduced by more than 3-fold, compared to flat pixels. With 40 μm pixels, VEP was too low for reliable measurements of the grating acuity, even with pillar electrodes. 
Significance. While being helpful for treating a complete loss of sight, current prosthetic technologies are insufficient for addressing the leading cause of untreatable visual impairment - AMD. Subretinal photovoltaic arrays may provide sufficient visual acuity for restoration of central vision in patients blinded by AMD.&#13

Honeycomb-shaped electro-neural interface enables cellular-scale pixels in subretinal prosthesis

High-resolution visual prostheses require small, densely packed pixels, but limited penetration depth of the electric field formed by a planar electrode array constrains such miniaturization. We present a novel honeycomb configuration of an electrode array with vertically separated active and return electrodes designed to leverage migration of retinal cells into voids in the subretinal space. Insulating walls surrounding each pixel decouple the field penetration depth from the pixel width by aligning the electric field vertically, enabling a decrease of the pixel size down to cellular dimensions. We demonstrate that inner retinal cells migrate into the 25 μm deep honeycomb wells as narrow as 18 μm, resulting in more than half of these cells residing within the electrode cavities. Immune response to honeycombs is comparable to that with planar arrays. Modeled stimulation threshold current density with honeycombs does not increase substantially with reduced pixel size, unlike quadratic increase with planar arrays. This 3-D electrode configuration may enable functional restoration of central vision with acuity better than 20/100 for millions of patients suffering from age-related macular degeneration

'When you have children, you're obliged to live': Motherhood, Chronic Illness and Biographical Disruption

Recent work on biographical disruption has emphasised the critical importance of timing and context to the understanding of the effects of illness on identity. This paper takes a different approach by examining the inter-relationship between illness and key sources of identity, in this instance HIV infection and motherhood. It is argued that, viewed in this light, biographical disruption remains a powerful analytic framework with which to explore the intense threat which may be posed to key identities by chronic, potentially fatal illnesses, and the fundamental re-working of such identities occasioned by such threats. With reference to the empirical study on which this paper draws, it is shown that, the respondents’ emphasis on their need to survive and to protect their children, represented a fundamental re-formulation of their identities as mothers and, therefore, a type of biographical disruption while paradoxically also containing elements of biographical reinforcement. It is further argued that the incorporation of such key identities into the analysis problematises work that suggests that biographical disruption is less relevant to those who have experienced difficult lives, while also highlighting the need to take greater account of gender and caring responsibilities in further work in this field

Enhanced Recovery after Surgery (ERAS) and its applicability for major spine surgery

This article examines the relevance of applying the Enhanced Recovery after Surgery (ERAS) approach to patients undergoing major spinal surgery. The history of ERAS, details of the components of the approach, and the underlying rationale are explained. Evidence on outcomes achieved by using the ERAS approach in other orthopaedic and complex surgical procedures are then outlined. Data on major spinal surgery rates and current practice are reviewed and the rationale for the use of ERAS in major spinal surgery is discussed, and potential challenges to its adoption acknowledged. A thorough literature search is then undertaken to examine the use of ERAS pathways in major spinal surgery, and the results presented. The article then reviews the evidence to support the application of individual ERAS components such as patient education, multimodal pain management, surgical approach, blood loss, nutrition, and physiotherapy in major spinal surgery, and discusses the need for further robust research to be undertaken. The article concludes that given the rising costs of surgery and levels of patient dissatisfaction, an ERAS pathway that focuses on optimizing clinical procedures by adopting evidence-based practice, and improving logistics, should enable major spinal surgery patients to recover more quickly with lower rates of morbidity and improved longer term outcomes

Genetic diversity of CHC22 clathrin impacts its function in glucose metabolism

CHC22 clathrin plays a key role in intracellular membrane traffic of the insulin-responsive glucose transporter GLUT4 in humans. We performed population genetic and phylogenetic analyses of the CHC22-encoding CLTCL1 gene, revealing independent gene loss in at least two vertebrate lineages, after arising from gene duplication. All vertebrates retained the paralogous CLTC gene encoding CHC17 clathrin, which mediates endocytosis. For vertebrates retaining CLTCL1, strong evidence for purifying selection supports CHC22 functionality. All human populations maintained two high frequency CLTCL1 allelic variants, encoding either methionine or valine at position 1316. Functional studies indicated that CHC22-V1316, which is more frequent in farming populations than in hunter-gatherers, has different cellular dynamics than M1316-CHC22 and is less effective at controlling GLUT4 membrane traffic, altering its insulin-regulated response. These analyses suggest that ancestral human dietary change influenced selection of allotypes that affect CHC22’s role in metabolism and have potential to differentially influence the human insulin response

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy