Brain-State Dependent Stimulation boosts functional recovery following stroke

This is the peer reviewed version of the following article: “Brain-State Dependent Stimulation boosts functional recovery following stroke”, which has been published in final form at http://dx.doi.org/10.1002/ana.25375. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived.Objective Adjuvant protocols devised to enhance motor recovery in subacute stroke patients have failed to show benefits with respect to classic therapeutic interventions. Here we evaluate the efficacy of a novel brain-state dependent intervention based on known mechanisms of memory and learning, that is integrated as part of the weekly rehabilitation program in subacute stroke patients. Methods Twenty-four hospitalized subacute stroke patients were randomly assigned to two intervention groups; 1. The associative group received thirty pairings of a peripheral electrical nerve stimulus (ES) such that the generated afferent volley arrived precisely during the most active phase of the motor cortex as patients attempted to perform a movement; 2. In the control group the ES intensity was too low to generate a stimulation of the nerve. Functional (including the lower extremity Fugl-Meyer assessment (LE-FM; primary outcome measure)) and neurophysiological (changes in motor evoked potentials (MEPs)) assessments were performed prior to and following the intervention period. Results The associative group significantly improved functional recovery with respect to the control group (median (interquartile range) LE-FM improvement: 6.5 (3.5-8.25) and 3 (0.75-3), respectively; p=0.029). Significant increases in MEP amplitude were seen following all sessions in the associative group only (p’s≤0.006). Interpretation This is the first evidence of a clinical effect of a neuromodulatory intervention in the subacute phase of stroke. This was evident with relatively few repetitions in comparison to available techniques, making it a clinically-viable approach. The results indicate the potential of the proposed neuromodulation system in daily clinical routine for stroke rehabilitation. This article is protected by copyright. All rights reserved.Kong Christian den Tiendes Fond (39/2016

The conceptual and practical ethical dilemmas of using health discussion board posts as research data.

Increasing numbers of people living with a long-term health condition are putting personal health information online, including on discussion boards. Many discussion boards contain material of potential use to researchers; however, it is unclear how this information can and should be used by researchers. To date there has been no evaluation of the views of those individuals sharing health information online regarding the use of their shared information for research purposes

Effects of treadmill slip and trip perturbation-based balance training on falls in community-dwelling older adults (STABILITY): study protocol for a randomised controlled trial

INTRODUCTION: Falls among older adults are most frequently caused by slips and trips and can have devastating consequences. Perturbation-based balance training (PBT) have recently shown promising fall preventive effects after even small training dosages. However, the fall preventive effects of PBT delivered on a treadmill are still unknown. Therefore, this parallel-group randomised controlled trial aims to quantify the effects of a four-session treadmill-PBT training intervention on falls compared with treadmill walking among community-dwelling older adults aged 65 years or more. METHODS AND ANALYSIS: 140 community-dwelling older adults will be recruited and randomised into either the treadmill-PBT or the treadmill walking group. Each group will undergo three initial training sessions within a week and an additional ‘booster’ session after 26 weeks. Participants in the treadmill-PBT group will receive 40 slip and/or trip perturbations induced by accurately timed treadmill belt accelerations at each training session. The primary outcome of interest is daily life fall rates collected using fall calendars for a follow-up period of 52 weeks. Secondary outcomes include physical, cognitive and social–psychological fall-related risk factors and will be collected at the pre-training and post-training test and the 26-week and 52-week follow-up tests. All outcomes will be analysed using the intention-to-treat approach by an external statistician. A Poisson’s regressions with bootstrapping, to account for overdispersion, will be used to compare group differences in fall rates. ETHICS AND DISSEMINATION: The study protocol has been approved by the North Denmark Region Committee on Health Research Ethics (N-20200089). The results will be disseminated in peer-reviewed journals and at international conferences. TRIAL REGISTRATION NUMBER: NCT04733222

Achimota Pararubulavirus 3: A New Bat-Derived Paramyxovirus of the Genus Pararubulavirus.

Bats are an important source of viral zoonoses, including paramyxoviruses. The paramyxoviral Pararubulavirus genus contains viruses mostly derived from bats that are common, diverse, distributed throughout the Old World, and known to be zoonotic. Here, we describe a new member of the genus Achimota pararubulavirus 3 (AchPV3) and its isolation from the urine of African straw-coloured fruit bats on primary bat kidneys cells. We sequenced and analysed the genome of AchPV3 relative to other Paramyxoviridae, revealing it to be similar to known pararubulaviruses. Phylogenetic analysis of AchPV3 revealed the failure of molecular detection in the urine sample from which AchPV3 was derived and an attachment protein most closely related with AchPV2-a pararubulavirus known to cause cross-species transmission. Together these findings add to the picture of pararubulaviruses, their sources, and variable zoonotic potential, which is key to our understanding of host restriction and spillover of bat-derived paramyxoviruses. AchPV3 represents a novel candidate zoonosis and an important tool for further study

Advancing Tests of Relativistic Gravity via Laser Ranging to Phobos

Phobos Laser Ranging (PLR) is a concept for a space mission designed to advance tests of relativistic gravity in the solar system. PLR's primary objective is to measure the curvature of space around the Sun, represented by the Eddington parameter $\gamma$, with an accuracy of two parts in $10^7$, thereby improving today's best result by two orders of magnitude. Other mission goals include measurements of the time-rate-of-change of the gravitational constant, $G$ and of the gravitational inverse square law at 1.5 AU distances--with up to two orders-of-magnitude improvement for each. The science parameters will be estimated using laser ranging measurements of the distance between an Earth station and an active laser transponder on Phobos capable of reaching mm-level range resolution. A transponder on Phobos sending 0.25 mJ, 10 ps pulses at 1 kHz, and receiving asynchronous 1 kHz pulses from earth via a 12 cm aperture will permit links that even at maximum range will exceed a photon per second. A total measurement precision of 50 ps demands a few hundred photons to average to 1 mm (3.3 ps) range precision. Existing satellite laser ranging (SLR) facilities--with appropriate augmentation--may be able to participate in PLR. Since Phobos' orbital period is about 8 hours, each observatory is guaranteed visibility of the Phobos instrument every Earth day. Given the current technology readiness level, PLR could be started in 2011 for launch in 2016 for 3 years of science operations. We discuss the PLR's science objectives, instrument, and mission design. We also present the details of science simulations performed to support the mission's primary objectives.Comment: 25 pages, 10 figures, 9 table

Complement-Mediated Virus Infectivity Neutralisation by HLA Antibodies Is Associated with Sterilising Immunity to SIV Challenge in the Macaque Model for HIV/AIDS.

Sterilising immunity is a desired outcome for vaccination against human immunodeficiency virus (HIV) and has been observed in the macaque model using inactivated simian immunodeficiency virus (SIV). This protection was attributed to antibodies specific for cell proteins including human leucocyte antigens (HLA) class I and II incorporated into virions during vaccine and challenge virus preparation. We show here, using HLA bead arrays, that vaccinated macaques protected from virus challenge had higher serum antibody reactivity compared with non-protected animals. Moreover, reactivity was shown to be directed against HLA framework determinants. Previous studies failed to correlate serum antibody mediated virus neutralisation with protection and were confounded by cytotoxic effects. Using a virus entry assay based on TZM-bl cells we now report that, in the presence of complement, serum antibody titres that neutralise virus infectivity were higher in protected animals. We propose that complement-augmented virus neutralisation is a key factor in inducing sterilising immunity and may be difficult to achieve with HIV/SIV Env-based vaccines. Understanding how to overcome the apparent block of inactivated SIV vaccines to elicit anti-envelope protein antibodies that effectively engage the complement system could enable novel anti-HIV antibody vaccines that induce potent, virolytic serological response to be developed

Taking tissue seriously means taking communities seriously

<p>Abstract</p> <p>Background</p> <p>Health research is increasingly being conducted on a global scale, particularly in the developing world to address leading causes of morbidity and mortality. While research interest has increased, building scientific capacity in the developing world has not kept pace. This often leads to the export of human tissue (defined broadly) from the developing to the developed world for analysis. These practices raise a number of important ethical issues that require attention.</p> <p>Discussion</p> <p>In the developed world, there is great heterogeneity of regulatory practices regarding human tissues. In this paper, we outline the salient ethical issues raised by tissue exportation, review the current ethical guidelines and norms, review the literature on what is known empirically about perceptions and practices with respect to tissue exportation from the developing to the developed world, set out what needs to be known in terms of a research agenda, and outline what needs to be done immediately in terms of setting best practices. We argue that the current status of tissue exportation is ambiguous and requires clarification lest problems that have plagued the developed world occur in the context of global heath research with attendant worsening of inequities. Central to solutions to current ethical concerns entail moving beyond concern with individual level consent and embracing a robust interaction with communities engaged in research.</p> <p>Conclusion</p> <p>Greater attention to community engagement is required to understand the diverse issues associated with tissue exportation.</p