Multisite Study of Women Living With HIV's Perceived Barriers to, and Interest in, Long-Acting Injectable Antiretroviral Therapy

BACKGROUND: Adherence to antiretroviral therapy (ART) is imperative for viral suppression and reducing HIV transmission, but many people living with HIV report difficultly sustaining long-term adherence. Long-acting injectable (LAI) ART has the potential to transform HIV treatment and prevention. However, little LAI ART-related behavioral research has occurred among women, particularly outside of clinical trials. SETTING: Six Women's Interagency HIV Study sites: New York, Chicago, Washington DC, Atlanta, Chapel Hill, and San Francisco. METHODS: We conducted 59 in-depth interviews with women living with HIV across 6 Women's Interagency HIV Study sites (10 per site; 9 at Washington DC). We interviewed women who were not included in LAI ART clinical trials but who receive care at university settings that will administer LAI ART once it is approved. Interviews were recorded, transcribed, and analyzed using thematic content analysis. RESULTS: Most women enthusiastically endorsed monthly LAI ART and would prefer it over pills. The following 3 reasons emerged for this preference: (1) convenience and confidentiality, (2) avoiding daily reminders about living with HIV, and (3) believing that shots are more effective than pills. Challenges remain, however, specifically around (1) medical mistrust, (2) concerns about safety and effectiveness, (3) pill burden for HIV and other conditions, and (4) barriers to additional medical visits. CONCLUSIONS: Most women preferred LAI ART over daily pills given its benefits, including convenience, privacy, and perceived effectiveness. Future research should incorporate more women into LAI ART trials to better understand and align development with user concerns and preferences to enhance uptake

Determination of Superconducting Gap of SmFeAsFxO1-x Superconductors by Andreev Reflection Spectroscopy

The superconducting gap in FeAs-based superconductor SmFeAs(O1-xFx) (x = 0.15 and 0.30) and the temperature dependence of the sample with x = 0.15 have been measured by Andreev reflection spectroscopy. The intrinsic superconducting gap is independent of contacts while many other "gap-like" features vary appreciably for different contacts. The determined gap value of 2D = 13.34 +/-0.47 meV for SmFeAs(O0.85F0.15) gives 2D/kBTC = 3.68, close to the BCS prediction of 3.53. The superconducting gap decreases with temperature and vanishes at TC, in a manner similar to the BCS behavior but dramatically different from that of the nodal pseudogap behavior in cuprate superconductors.Comment: 13 pages, 9 figures, Special Issue of Physica C on Superconducting Pnictide

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Using minimalist self-assembling peptides as hierarchical scaffolds to stabilise growth factors and promote stem cell integration in the injured brain

Neurotrophic growth factors are effective in slowing progressive degeneration and/or promoting neural repair through the support of residual host and/or transplanted neurons. However, limitations including short half-life and enzyme susceptibility of growth factors highlight the need for alternative strategies to prolong localised delivery at a site of injury. Here, we establish the utility of minimalist N-fluorenylmethyloxycarbonyl (Fmoc) self-assembling peptides (SAPs) as growth factor delivery vehicle, targeted at supporting neural transplants in an animal model of Parkinson's disease. The neural tissue specific SAP, Fmoc-DIKVAV, demonstrated sustained release of glial cell line derived neurotrophic factor (GDNF), up to 172 hours after gel loading. This represents a significant advance in drug delivery, since its lifetime in phosphate buffered saline (PBS) was less than 1 hour. In vivo transplantation of neural progenitor cells, together with our growth factor-loaded material, into the injured brain improved graft survival compared to cell transplants alone. We show for the first time the use of minimalist Fmoc-SAP in an in vivo disease model for sustaining the delivery of neurotrophic growth factors, facilitating their spatial and temporal delivery in vivo, whilst also providing an enhanced niche environment for transplanted cells

Efficient expansion and dopaminergic differentiation of human fetal ventral midbrain neural stem cells by midbrain morphogens

Human fetal midbrain tissue grafting has provided proof-of-concept for dopamine cell replacement therapy (CRT) in Parkinson's disease (PD). However, limited tissue availability has hindered the development and widespread use of this experimental therapy. Here we present a method for generating large numbers of midbrain dopaminergic (DA) neurons based on expanding and differentiating neural stem/progenitor cells present in the human ventral midbrain (hVM) tissue. Our results show that hVM neurospheres (hVMN) with low cell numbers, unlike their rodent counterparts, expand the total number of cells 3-fold, whilst retaining their capacity to differentiate into midbrain DA neurons. Moreover, Wnt5a promoted DA differentiation of expanded cells resulting in improved morphological maturation, midbrain DA marker expression, DA release and electrophysiological properties. This method results in cell preparations that, after expansion and differentiation, can contain 6-fold more midbrain DA neurons than the starting VM preparation. Thus, our results provide evidence that by improving expansion and differentiation of progenitors present in the hVM it is possible to greatly enrich cell preparations for DA neurons. This method could substantially reduce the amount of human fetal midbrain tissue necessary for CRT in patients with PD, which could have major implications for the widespread adoption of this approach

Genome-wide binding and mechanistic analyses of Smchd1-mediated epigenetic regulation

Functional Genomics of Muscle, Nerve and Brain Disorder

SCREENING FOR AND CHARACTERISING MAMMALIAN EPIGENETIC MODIFIERS

Cardiolog