Functional strength training versus movement performance therapy for upper limb motor recovery early after stroke: a RCT

Background: Not all stroke survivors respond to the same form of physical therapy in the same way early after stroke. The response is variable and a detailed understanding of the interaction between specific physical therapies and neural structure and function is needed. Objectives: To determine if upper limb recovery is enhanced more by functional strength training (FST) than by movement performance therapy (MPT), to identify the differences in the neural correlates of response to (1) FST and (2) MPT and to determine whether or not pretreatment neural characteristics can predict recovery in response to (1) FST and (2) MPT. Design: Randomised, controlled, observer-blind, multicentre trial with embedded explanatory investigations. An independent facility used computer-generated randomisation for participants’ group allocation. Setting: In-patient rehabilitation, participants’ homes, university movement analysis facilities and NHS or university neuroimaging departments in the UK. Participants: People who were between 2 and 60 days after stroke in the territory of the anterior cerebral circulation, with some voluntary muscle contraction in the more affected upper limb but not full function. Interventions: Routine rehabilitation [conventional physical therapy (CPT)] plus either MPT or FST in equal doses during a 6-week intervention phase. FST was progressive resistive exercise provided during training of functional tasks. MPT was therapist ‘hands-on’ sensory input and guidance for production of smooth and accurate movement. Main outcomes: Action Research Arm Test (ARAT) score for clinical efficacy. Neural measures were made of corticocortical [fractional anisotropy (FA) from corpus callosum midline], corticospinal connectivity (asymmetry of corticospinal tracts FA) and resting motor threshold of paretic biceps brachii (pBB) and extensor carpi radialis muscles (derived from transcranial magnetic stimulation). Analysis: Change in ARAT scores were analysed using analysis of covariance models adjusted for baseline variables and randomisation strata. Correlation coefficients were calculated between change in neural measures and change in ARAT score per group and for the whole sample. An interaction term was calculated for each baseline neural measure and ARAT score change from baseline to outcome. Results: A total of 288 participants were randomised [mean age 72.2 (standard deviation 12.5) years; mean ARAT score of 25.5 (18.2); n = 283]. For the 240 participants with ARAT measurements at baseline and outcome, the mean change scores were FST + CPT = 9.70 (11.72) and MPT + CPT = 7.90 (9.18). The group difference did not reach statistical significance (least squares mean difference 1.35, 95% confidence interval –1.20 to 3.90; p = 0.298). Correlations between ARAT change scores and baseline neural values ranged from –0.147 (p = 0.385) for whole-sample corticospinal connectivity (n = 37) to 0.199 (p = 0.320) for MPT + CPT resting motor threshold pBB (n = 27). No statistically significant interaction effects were found between baseline neural variables and change in ARAT score. There were no differences between groups in adverse events. Limitations: The number of participants in the embedded explanatory investigation was lower than expected. Conclusions: The small difference in upper limb improvement in response to FST and MPT did not reach statistical significance. Baseline neural measures neither correlated with upper limb recovery nor predicted therapy response. Future work: Needs to continue investigation of the variability of response to specific physical therapies in people early after stroke. Trial registration: Current Controlled Trials ISRCTN19090862 and National Research Ethics Service reference number 11/EE/0524. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership

Study Protocol: ASCRIBED: The impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in Dementia: a study in acute hip fracture patients

Background: Hip fracture represents a substantial acute inflammatory trauma, which may constitute a significant insult to the degenerating brain. Research suggests that an injury of this kind can affect memory and thinking in the future but it is unclear whether, and how, inflammatory trauma injures the brain. The impact of Acute SystematiC inflammation upon cerebRospinal fluId and blood BiomarkErs of brain inflammation and injury in Dementia: a study in acute hip fracture patients (ASCRIBED) explores this relationship, to understand the effect of inflammation on the progression of dementia. Methods: This protocol describes a multi-centre sample collection observational study. The study utilises the unique opportunity provided by hip fracture operations undertaken via spinal anaesthesia to collect cerebrospinal fluid (CSF) and blood, to investigate the impact of acute brain inflammation caused by hip fracture on the exacerbation of dementia. We will recruit 200 hip fracture patients with a diagnosis or evidence of dementia; and 200 hip fracture patients without dementia. We will also recruit ‘Suitable informants’, individuals in regular contact with the patient, to provide further proxy evidence of a patient’s potential cognitive decline. We will compare these 400 samples with existing CSF and blood samples from a cohort of dementia patients who had not experienced a systemic inflammatory response due to injury. This will provide a comparison between patients with and without dementia who are suffering a systemic inflammatory response; with stable patients living with dementia. Discussion: We will test the hypothesis that hip fracture patients living with dementia show elevated markers of brain inflammation, as well as neuronal injury and Alzheimer-related plaque pathology, in comparison to (1) stable patients living with dementia and (2) hip fracture patients without dementia, as measured by biomarkers in CSF and blood. The findings will address the hypothesis that systemic inflammatory events can exacerbate underlying dementia and inform the search for new treatments targeting inflammation in dementia

The Sweet Technology of Beer

George Matthews, Packaging Manager, and Lead Brewer, Nick Burgoyne, at the Sweetwater Brewery in Atlanta, joins us to chat about the technological challenges of making beer at a large scale

Additional file 2: of PERFECTED enhanced recovery (PERFECT-ER) care versus standard acute care for patients admitted to acute settings with hip fracture identified as experiencing confusion: study protocol for a feasibility cluster randomized controlled trial

Additional information on outcome measures. (DOCX 24 kb

Search for intermediate mass black hole binaries in the first observing run of Advanced LIGO

International audienceDuring their first observational run, the two Advanced LIGO detectors attained an unprecedented sensitivity, resulting in the first direct detections of gravitational-wave signals produced by stellar-mass binary black hole systems. This paper reports on an all-sky search for gravitational waves (GWs) from merging intermediate mass black hole binaries (IMBHBs). The combined results from two independent search techniques were used in this study: the first employs a matched-filter algorithm that uses a bank of filters covering the GW signal parameter space, while the second is a generic search for GW transients (bursts). No GWs from IMBHBs were detected; therefore, we constrain the rate of several classes of IMBHB mergers. The most stringent limit is obtained for black holes of individual mass 100  M⊙, with spins aligned with the binary orbital angular momentum. For such systems, the merger rate is constrained to be less than 0.93  Gpc−3 yr−1 in comoving units at the 90% confidence level, an improvement of nearly 2 orders of magnitude over previous upper limits

First low-frequency Einstein@Home all-sky search for continuous gravitational waves in Advanced LIGO data

International audienceWe report results of a deep all-sky search for periodic gravitational waves from isolated neutron stars in data from the first Advanced LIGO observing run. This search investigates the low frequency range of Advanced LIGO data, between 20 and 100 Hz, much of which was not explored in initial LIGO. The search was made possible by the computing power provided by the volunteers of the Einstein@Home project. We find no significant signal candidate and set the most stringent upper limits to date on the amplitude of gravitational wave signals from the target population, corresponding to a sensitivity depth of 48.7  [1/Hz]. At the frequency of best strain sensitivity, near 100 Hz, we set 90% confidence upper limits of 1.8×10-25. At the low end of our frequency range, 20 Hz, we achieve upper limits of 3.9×10-24. At 55 Hz we can exclude sources with ellipticities greater than 10-5 within 100 pc of Earth with fiducial value of the principal moment of inertia of 1038  kg m2

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

International audienceSpinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signal-to-noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far