Smaller spared subcortical nuclei are associated with worse post-stroke sensorimotor outcomes in 28 cohorts worldwide

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T1-weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early (n = 179; d = 0.68) and subacute (n = 274, d = 0.46) stroke. In chronic stroke (n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen (d = 0.52) and nucleus accumbens (d = 0.39) volumes, and a larger ipsilesional lateral ventricle (d = -0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen (d = 0.72) and larger lateral ventricle (d = -0.41) volumes, while several measures of activity limitations (n = 116) showed no significant relationships. In the full cohort across all time (n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens (d = 0.23), putamen (d = 0.33), thalamus (d = 0.33) and lateral ventricle (d = -0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes

How to improve walking, balance and social participation following stroke: a comparison of the long term effects of two walking aids--canes and an orthosis TheraTogs--on the recovery of gait following acute stroke. A study protocol for a multi-centre, single blind, randomised control trial

<p>Abstract</p> <p>Background</p> <p>Annually, some 9000 people in Switzerland suffer a first time stroke. Of these 60% are left with moderate to severe walking disability. Evidence shows that rehabilitation techniques which emphasise activity of the hemiplegic side increase ipsilesional cortical plasticity and improve functional outcomes. Canes are commonly used in gait rehabilitation although they significantly reduce hemiplegic muscle activity. We have shown that an orthosis "TheraTogs" (a corset with elasticated strapping) significantly increases hemiplegic muscle activity during gait. The aim of the present study is to investigate the long term effects on the recovery of gait, balance and social participation of gait rehabilitation with TheraTogs compared to gait rehabilitation with a cane following first time acute stroke.</p> <p>Methods/Design</p> <p>Multi-centre, single blind, randomised trial with 120 patients after first stroke. When subjects have reached Functional Ambulation Category 3 they will be randomly allocated into TheraTogs or cane group. TheraTogs will be applied to support hip extensor and abductor musculature according to a standardised procedure. Cane walking held at the level of the radial styloid of the sound wrist. Subjects will walk throughout the day with only the assigned walking aid. Standard therapy treatments and usual care will remain unchanged and documented. The intervention will continue for five weeks or until patients have reached Functional Ambulation category 5. Outcome measures will be assessed the day before begin of intervention, the day after completion, 3 months, 6 months and 2 years. Primary outcome: Timed "up and go" test, secondary outcomes: peak surface EMG of gluteus maximus and gluteus medius, activation patterns of hemiplegic leg musculature, temporo-spatial gait parameters, hemiplegic hip kinematics in the frontal and sagittal planes, dynamic balance, daily activity measured by accelerometry, Stroke Impact Scale. Significance levels will be 5% with 95% CI's. IntentionToTreat analyses will be performed. Descriptive statistics will be presented.</p> <p>Discussion</p> <p>This study could have significant implications for the clinical practice of gait rehabilitation after stroke, particularly the effect and appropriate use of walking aids.</p> <p>The results could be important for the development of clinical guidelines and for the socio-economic costs of post-stroke care</p> <p>Trial registration number</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01366729">NCT01366729</a>.</p

Optimization of Muscle Activity for Task-Level Goals Predicts Complex Changes in Limb Forces across Biomechanical Contexts

Optimality principles have been proposed as a general framework for understanding motor control in animals and humans largely based on their ability to predict general features movement in idealized motor tasks. However, generalizing these concepts past proof-of-principle to understand the neuromechanical transformation from task-level control to detailed execution-level muscle activity and forces during behaviorally-relevant motor tasks has proved difficult. In an unrestrained balance task in cats, we demonstrate that achieving task-level constraints center of mass forces and moments while minimizing control effort predicts detailed patterns of muscle activity and ground reaction forces in an anatomically-realistic musculoskeletal model. Whereas optimization is typically used to resolve redundancy at a single level of the motor hierarchy, we simultaneously resolved redundancy across both muscles and limbs and directly compared predictions to experimental measures across multiple perturbation directions that elicit different intra- and interlimb coordination patterns. Further, although some candidate task-level variables and cost functions generated indistinguishable predictions in a single biomechanical context, we identified a common optimization framework that could predict up to 48 experimental conditions per animal (n = 3) across both perturbation directions and different biomechanical contexts created by altering animals' postural configuration. Predictions were further improved by imposing experimentally-derived muscle synergy constraints, suggesting additional task variables or costs that may be relevant to the neural control of balance. These results suggested that reduced-dimension neural control mechanisms such as muscle synergies can achieve similar kinetics to the optimal solution, but with increased control effort (≈2×) compared to individual muscle control. Our results are consistent with the idea that hierarchical, task-level neural control mechanisms previously associated with voluntary tasks may also be used in automatic brainstem-mediated pathways for balance

The effects of integrated care: a systematic review of UK and international evidence

BACKGROUND: Healthcare systems around the world have been responding to the demand for better integrated models of service delivery. However, there is a need for further clarity regarding the effects of these new models of integration, and exploration regarding whether models introduced in other care systems may achieve similar outcomes in a UK national health service context. METHODS: The study aimed to carry out a systematic review of the effects of integration or co-ordination between healthcare services, or between health and social care on service delivery outcomes including effectiveness, efficiency and quality of care. Electronic databases including MEDLINE; Embase; PsycINFO; CINAHL; Science and Social Science Citation Indices; and the Cochrane Library were searched for relevant literature published between 2006 to March 2017. Online sources were searched for UK grey literature, and citation searching, and manual reference list screening were also carried out. Quantitative primary studies and systematic reviews, reporting actual or perceived effects on service delivery following the introduction of models of integration or co-ordination, in healthcare or health and social care settings in developed countries were eligible for inclusion. Strength of evidence for each outcome reported was analysed and synthesised using a four point comparative rating system of stronger, weaker, inconsistent or limited evidence. RESULTS: One hundred sixty seven studies were eligible for inclusion. Analysis indicated evidence of perceived improved quality of care, evidence of increased patient satisfaction, and evidence of improved access to care. Evidence was rated as either inconsistent or limited regarding all other outcomes reported, including system-wide impacts on primary care, secondary care, and health care costs. There were limited differences between outcomes reported by UK and international studies, and overall the literature had a limited consideration of effects on service users. CONCLUSIONS: Models of integrated care may enhance patient satisfaction, increase perceived quality of care, and enable access to services, although the evidence for other outcomes including service costs remains unclear. Indications of improved access may have important implications for services struggling to cope with increasing demand. TRIAL REGISTRATION: Prospero registration number: 42016037725

Chronic stroke sensorimotor impairment is related to smaller hippocampal volumes: an ENIGMA analysis

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women

Searches for rare B-s(0) and B-0 decays into four muons

Searches for rare $B_s^0$ and $B^0$ decays into four muons are performed using proton-proton collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 9 $\text{fb}^{-1}$. Direct decays and decays via light scalar and $J/\psi$ resonances are considered. No evidence for the six decays searched for is found and upper limits at the 95% confidence level on their branching fractions ranging between $1.8\times10^{-10}$ and $2.6\times10^{-9}$ are set

First measurement of the Z→μ+μ− angular coefficients in the forward region of pp collisions at √s = 13 TeV

The first study of the angular distribution of μ + μ − pairs produced in the forward rapidity region via the Drell-Yan reaction p p → γ ∗ / Z + X → ℓ + ℓ − + X is presented, using data collected with the LHCb detector at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 5.1     fb − 1 . The coefficients of the five leading terms in the angular distribution are determined as a function of the dimuon transverse momentum and rapidity. The results are compared to various theoretical predictions of the Z -boson production mechanism and can also be used to probe transverse-momentum-dependent parton distributions within the proton

Proline isomerism in staphylococcal nuclease characterized by NMR and site-directed mutagenesis

Nuclear magnetic resonance (NMR) studies have shown that two distinct folded conformations of staphylococcal nuclease coexist in solution1 and that these two states can interconvert directly without passing through an unfolded state. These experiments have also revealed that the two forms have very different folding kinetics, although the possibility that one component is an obligatory intermediate for the folding of the other form could be discounted1. Here we report NMR data which show that alternative unfolded states are also distinguishable. These observations led us to hypothesize that cis/trans isomerism at a single peptide bond between a proline and its preceding residue might be the origin of the conformational multiplicity. Proline 117 was identified as a likely candidate for the site concerned and a mutant protein, in which Pro 117 was replaced by Gly, was constructed in order to test this. Alternative conformations are not observed in the spectrum of this mutant, lending powerful support to this hypothesis. © 1987 Nature Publishing Group