To What Extent is Walking Ability Associated with Participation in People after Stroke?

OBJECTIVES: This study aims to 1) identify the relation between walking ability and participation after stroke and 2) explore whether change in walking ability is associated with change in participation over time in community living-people after stroke. MATERIALS AND METHODS: Fifty-two people after stroke were assessed at baseline and after a 6-week gait training intervention. People were included between two weeks and six months after stroke. The Utrecht Scale for Evaluation of Rehabilitation-Participation was used to measure participation. Assessment of walking ability included the six-minute walking test for walking endurance, Timed-up & Go test for functional mobility, Mini Balance Evaluation Systems Test for dynamic balance, and total duration of walking activity per day to measure walking activity. RESULTS: At baseline, six-minute walking test, Timed-up & Go test, and Mini Balance Evaluation Systems Test were univariately associated with participation (P < 0.001). Backward multiple regression analysis showed that the Mini Balance Evaluation Systems Test independently explained 55.7% of the variance in participation at baseline. Over time, only change in the six-minute walking test was positively associated with change in participation (R2 = 0.087, P = 0.040). CONCLUSIONS: Cross-sectional associations showed that walking ability, and especially dynamic balance, contributes to participation after stroke. Dynamic balance, as underlying variable for walking, was an important independently related factor to participation after stroke which needs attention during rehabilitation. Longitudinally, improvement in walking endurance was significantly associated with improvement in participation, which indicates the relevance of training walking endurance to improve participation after stroke.

Gold Nanoparticles as Boron Carriers for Boron Neutron Capture Therapy: Synthesis, Radiolabelling and In vivo Evaluation.

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]-) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of -18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]- could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]-. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

The structure of PbCl2 on the {100} surface of NaCl and its consequences for crystal growth.

The role that additives play in the growth of sodium chloride is a topic which has been widely researched but not always fully understood at an atomic level. Lead chloride (PbCl2) is one such additive which has been reported to have growth inhibition effects on NaCl {100} and {111}; however, no definitive evidence has been reported which details the mechanism of this interaction. In this investigation, we used the technique of surface x-ray diffraction to determine the interaction between PbCl2 and NaCl {100} and the structure at the surface. We find that Pb2+ replaces a surface Na+ ion, while a Cl- ion is located on top of the Pb2+. This leads to a charge mismatch in the bulk crystal, which, as energetically unfavourable, leads to a growth blocking effect. While this is a similar mechanism as in the anticaking agent ferrocyanide, the effect of PbCl2 is much weaker, most likely due to the fact that the Pb2+ ion can more easily desorb. Moreover, PbCl2 has an even stronger effect on NaCl {111}.

Protecting a Diamond Quantum Memory by Charge State Control.

In recent years, solid-state spin systems have emerged as promising candidates for quantum information processing. Prominent examples are the nitrogen-vacancy (NV) center in diamond, phosphorus dopants in silicon (Si:P), rare-earth ions in solids, and VSi-centers in silicon-carbide. The Si:P system has demonstrated that its nuclear spins can yield exceedingly long spin coherence times by eliminating the electron spin of the dopant. For NV centers, however, a proper charge state for storage of nuclear spin qubit coherence has not been identified yet. Here, we identify and characterize the positively charged NV center as an electron-spin-less and optically inactive state by utilizing the nuclear spin qubit as a probe. We control the electronic charge and spin utilizing nanometer scale gate electrodes. We achieve a lengthening of the nuclear spin coherence times by a factor of 4. Surprisingly, the new charge state allows switching of the optical response of single nodes facilitating full individual addressability.

Dosimetric Quantification of Coating-Related Uptake of Silver Nanoparticles.

The elucidation of mechanisms underlying the cellular uptake of nanoparticles (NPs) is an important topic in nanotoxicological research. Most studies dealing with silver NP uptake provide only qualitative data about internalization efficiency and do not consider NP-specific dosimetry. Therefore, we performed a comprehensive comparison of the cellular uptake of differently coated silver NPs of comparable size in different human intestinal Caco-2 cell-derived models to cover also the influence of the intestinal mucus barrier and uptake-specialized M-cells. We used a combination of the Transwell system, transmission electron microscopy, atomic absorption spectroscopy, and ion beam microscopy techniques. The computational in vitro sedimentation, diffusion, and dosimetry (ISDD) model was used to determine the effective dose of the particles in vitro based on their individual physicochemical characteristics. Data indicate that silver NPs with a similar size and shape show coating-dependent differences in their uptake into Caco-2 cells. The internalization of silver NPs was enhanced in uptake-specialized M-cells while the mucus did not provide a substantial barrier for NP internalization. ISDD modeling revealed a fivefold underestimation of dose-response relationships of NPs in in vitro assays. In summary, the present study provides dosimetry-adjusted quantitative data about the influence of NP coating materials in cellular uptake into human intestinal cells. Underestimation of particle effects in vitro might be prevented by using dosimetry models and by considering cell models with greater proximity to the in vivo situation, such as the M-cell model.

Impact of an Artificial Digestion Procedure on Aluminum-Containing Nanomaterials.

Aluminum has gathered toxicological attention based on relevant human exposure and its suspected hazardous potential. Nanoparticles from food supplements or food contact materials may reach the human gastrointestinal tract. Here, we monitored the physicochemical fate of aluminum-containing nanoparticles and aluminum ions when passaging an in vitro model of the human gastrointestinal tract. Small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), ion beam microscopy (IBM), secondary ion beam mass spectrometry (TOF-SIMS), and inductively coupled plasma mass spectrometry (ICP-MS) in the single-particle mode were employed to characterize two aluminum-containing nanomaterials with different particle core materials (Al0, γAl2O3) and soluble AlCl3. Particle size and shape remained unchanged in saliva, whereas strong agglomeration of both aluminum nanoparticle species was observed at low pH in gastric fluid together with an increased ion release. The levels of free aluminum ions decreased in intestinal fluid and the particles deagglomerated, thus liberating primary particles again. Dissolution of nanoparticles was limited and substantial changes of their shape and size were not detected. The amounts of particle-associated phosphorus, chlorine, potassium, and calcium increased in intestinal fluid, as compared to nanoparticles in standard dispersion. Interestingly, nanoparticles were found in the intestinal fluid after addition of ionic aluminum. We provide a comprehensive characterization of the fate of aluminum nanoparticles in simulated gastrointestinal fluids, demonstrating that orally ingested nanoparticles probably reach the intestinal epithelium. The balance between dissolution and de novo complex formation should be considered when evaluating nanotoxicological experiments.

Falls Are Associated With Lower Self-Reported Functional Status in Patients After Stroke.

OBJECTIVE: To evaluate the association between falls and functional status after stroke. DESIGN: Secondary analysis of data from the randomized controlled FIT-Stroke trial. Outcomes were measured at the time of discharge from inpatient rehabilitation (t0) and after 12 weeks (t1). Between t0 and t1, all patients attended an outpatient rehabilitation program that included the FIT-Stroke intervention. SETTING: Nine centers for rehabilitation medicine. PARTICIPANTS: Outpatients after stroke (N=250) with mild cognitive impairments (Mini-Mental State Examination [MMSE] score ≥24), discharged home after inpatient rehabilitation and able to walk 10m independently. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome was the change in Stroke Impact Scale (SIS)-16 score. The independent variable was ≥1 falls after stroke. The outcome was corrected for type of outpatient rehabilitation (group allocation), severity of hemiplegia (Motricity Index [MI]), and cognition (MMSE) at baseline using multiple regression analysis. RESULTS: Complete data were available for 199 patients, with a mean age of 58±10 years, MMSE score of 28.1±2, and MI score of 130±43. Fifty-five patients (28%) reported falls during the 12 weeks after discharge from inpatient rehabilitation. Falls were significantly associated with less improvement in functional status as assessed with the SIS-16 (P=.009). CONCLUSIONS: Almost 30% of this stroke population with minor cognitive deficits and moderate to high mobility scores reported falls during the 12 weeks of outpatient rehabilitation. Falls were negatively associated with self-reported functional status measured by the change in SIS-16 score. Therefore, it is important to identify patients with high risk of falls and implement strategies to reduce falls.

Determining the internal quantum efficiency of shallow-implanted nitrogen-vacancy defects in bulk diamond.

It is generally accepted that nitrogen-vacancy (NV) defects in bulk diamond are bright sources of luminescence. However, the exact value of their internal quantum efficiency (IQE) has not been measured so far. Here we use an implementation of Drexhage's scheme to quantify the IQE of shallow-implanted NV defects in a single-crystal bulk diamond. Using a spherical metallic mirror with a large radius of curvature compared to the optical spot size, we perform calibrated modifications of the local density of states around NV defects and observe the change of their total decay rate, which is further used for IQE quantification. We also show that at the excitation wavelength of 532 nm, photo-induced relaxation cannot be neglected even at moderate excitation powers well below the saturation level. For NV defects shallow implanted 4.5 ± 1 and 8 ± 2 nm below the diamond surface, we determine the quantum efficiency to be 0.70 ± 0.07 and 0.82 ± 0.08, respectively.

Psychopathology in difficult asthma.

OBJECTIVE: Within the asthma population, difficult asthma (DA) is a severe condition in which patients present with frequent exacerbations, hospitalizations and emergency room visits. The identification and treatment of psychopathology is included in the management of DA. Psychopathology is supposed to predispose patients to DA or vice versa; psychopathology may develop as a consequence of DA. We reviewed the available literature on empirical findings regarding psychopathology in adult patients with DA. METHODS: Studies in English language journals using MEDLINE, Cochrane and PsycINFO databases, were retrieved by an electronic search published from 1990 till July 2014. RESULTS: Literature on psychopathology in DA is scarce. The search identified 16 articles of which only 6 articles were specifically about psychopathology in adult patients with DA. Almost half of the patients with DA had evidence of psychopathology at both syndrome and symptom level. Moreover, psychopathology appeared to be related to frequent exacerbations in patients with DA. CONCLUSIONS: This literature review suggests a high prevalence of psychopathology of patients with DA, although it remains unclear whether psychopathology occurs more often in DA compared to "stable asthma". More research is needed on a possible role of psychopathology on clinical signs and symptoms in DA.

A Novel Noninvasive Device to Assess Sympathetic Nervous System Function in Patients With Heart Failure.

BACKGROUND: Heart failure is a complex syndrome associated with sympathetic nervous system and renin-angiotensin-aldosterone system hyperactivity. Sympathoinhibition and downregulation of sympathetic activity using medications and exercise training improve outcomes in patients with heart failure. Impedance cardiography provides data on hemodynamic and autonomic function that may assist with safe medication, exercise monitoring, and titration. PURPOSE: The purpose of this pilot study was to evaluate the sensitivity of the Vrije Universiteit Ambulatory Monitoring System (VU-AMS) version 5fs to detect hemodynamic and sympathetic nervous system changes associated with postural shift in persons with heart failure with reduced ejection fraction. METHODS: In this descriptive study, participants (N = 28) were recruited from an outpatient device clinic at a tertiary care hospital in Ontario, Canada. They completed a sit-to-stand posture protocol wearing an ambulatory blood pressure (ABP) and a noninvasive VU-AMS version 5fs impedance cardiography system. RESULTS: Most (n = 18, 64%) participants were eliminated from the final analyses in this sample because of difficulty in Q-onset and B-point identification in peculiar electrocardiogram and impedance cardiogram waveforms. The remaining participants (n = 10) had a mean age of 69 years (SD = 10 years) and responses to a sit-to-stand posture protocol that included a 5% increase in heart rate (p = .001), an 18% decrease in stroke volume (p = .01), and an 8% decrease in left ventricular ejection time (p = .01). Participants had an increased preejection period (11%, p = .01), a drop in cardiac output of 13% (p = .02), and a reduced mean arterial pressure of approximately 4% (p = .09) with standing. DISCUSSION: Although the VU-AMS version 5fs system detected anticipated hemodynamic and sympathetic nervous system changes to postural shift in participants (n = 10), the elimination of 64% (n = 18) of the sample because of scoring difficulties limits the use of this impedance cardiography device using standard scoring algorithms in persons with heart failure with reduced ejection fraction.

Addressing single nitrogen-vacancy centers in diamond with transparent in-plane gate structures.

For many applications of the nitrogen-vacancy (NV) center in diamond, the understanding and active control of its charge state is highly desired. In this work, we demonstrate the reversible manipulation of the charge state of a single NV center from NV(-) across NV(0) to a nonfluorescent, dark state by using an all-diamond in-plane gate nanostructure. Applying a voltage to the in-plane gate structure can influence the energy band bending sufficiently for charge state conversion of NV centers. These diamond in-plane structures can function as transparent top gates, enabling the distant control of the charge state of NV centers tens of micrometers away from the nanostructure.

Nanoscale detection of a single fundamental charge in ambient conditions using the NV- center in diamond.

Single charge nanoscale detection in ambient conditions is a current frontier in metrology that has diverse interdisciplinary applications. Here, such single charge detection is demonstrated using two nitrogen-vacancy (NV) centers in diamond. One NV center is employed as a sensitive electrometer to detect the change in electric field created by the displacement of a single electron resulting from the optical switching of the other NV center between its neutral (NV(0)) and negative (NV(-)) charge states. As a consequence, our measurements also provide direct insight into the charge dynamics inside the material.

Using Self-Regulation Assessment to Explore Associations between Self-Regulation, Participation and Health-Related Quality of Life in a Rehabilitation Population.

OBJECTIVE: Self-regulation, participation and health-related quality of life are important rehabilitation outcomes. The aim of this study was to explore associations between these outcomes in a multi-diagnostic and heterogenic group of former rehabilitation patients. METHODS: This cross-sectional survey used the Self-Regulation Assessment (SeRA), Utrecht Scale for Evaluation of Rehabilitation-participation (USERParticipation) and the Patient-Reported-Outcome-Measurement-System (PROMIS) ability and PROMIS satisfaction with participation in social roles, and the EuroQol-5L-5D and PROMIS-10 Global Health. Regression analyses, controlling for demographic and condition-related factors, were performed. RESULTS: Respondents (n = 563) had a mean age of 56.5 (standard deviation (SD) 12.7) years. The largest diagnostic groups were chronic pain disorder and brain injury. In addition to demographic and condition-related factors, self-regulation subscales explained 0-15% of the variance in participation outcome scores, and 0-22% of the variance in HRQoL outcome scores. Self-regulation subscales explained up to 22% of the variance in satisfaction subscales of participation (USER-Participation and PROMIS) and the mental health subscale of the PROMIS-10. Self-regulation subscales explained up to 11% of the restriction and frequency subscales of participation (USER-Participation) and the physical health subscale of the PROMIS-10. CONCLUSION: Self-regulation is more strongly associated with outcomes such as satisfaction with participation and mental health compared with outcomes such as restrictions in participation and physical health.

Microscopic-scale magnetic recording of brain neuronal electrical activity using a diamond quantum sensor.

Quantum sensors using solid state qubits have demonstrated outstanding sensitivity, beyond that possible using classical devices. In particular, those based on colour centres in diamond have demonstrated high sensitivity to magnetic field through exploiting the field-dependent emission of fluorescence under coherent control using microwaves. Given the highly biocompatible nature of diamond, sensing from biological samples is a key interdisciplinary application. In particular, the microscopic-scale study of living systems can be possible through recording of temperature and biomagnetic field. In this work, we use such a quantum sensor to demonstrate such microscopic-scale recording of electrical activity from neurons in fragile living brain tissue. By recording weak magnetic field induced by ionic currents in mouse corpus callosum axons, we accurately recover signals from neuronal action potential propagation while demonstrating in situ pharmacology. Our sensor allows recording of the electrical activity in neural circuits, disruption of which can shed light on the mechanisms of disease emergence. Unlike existing techniques for recording activity, which can require potentially damaging direct interaction, our sensing is entirely passive and remote from the sample. Our results open a promising new avenue for the microscopic recording of neuronal signals, offering the eventual prospect of microscopic imaging of electrical activity in the living mammalian brain.

Tuning a spin bath through the quantum-classical transition.

We study decoherence of a single nitrogen-vacancy (NV) center induced by the 13C nuclear spin bath of diamond. By comparing Hahn-Echo experiments on single and double-quantum transitions of the NV triplet ground state we demonstrate that this bath can be tuned into two different regimes. At low magnetic fields, the nuclei behave as a quantum bath which causes decoherence by entangling with the NV central spin. At high magnetic fields, the bath behaves as a source of classical magnetic field noise, which creates decoherence by imprinting a random phase on the NV central spin.

Nanometers-Thick Ferromagnetic Surface Produced by Laser Cutting of Diamond.

In this work, we demonstrate that cutting diamond crystals with a laser (532 nm wavelength, 0.5 mJ energy, 200 ns pulse duration at 15 kHz) produced a ≲20 nm thick surface layer with magnetic order at room temperature. We measured the magnetic moment of five natural and six CVD diamond crystals of different sizes, nitrogen contents and surface orientations with a SQUID magnetometer. A robust ferromagnetic response at 300 K was observed only for crystals that were cut with the laser along the (100) surface orientation. The magnetic signals were much weaker for the (110) and negligible for the (111) orientations. We attribute the magnetic order to the disordered graphite layer produced by the laser at the diamond surface. The ferromagnetic signal vanished after chemical etching or after moderate temperature annealing. The obtained results indicate that laser treatment of diamond may pave the way to create ferromagnetic spots at its surface.

Combinatorial investigation of Fe-B thin-film nanocomposites.

Combinatorial magnetron sputter deposition from elemental targets was used to create Fe-B composition spread type thin film materials libraries on thermally oxidized 4-in. Si wafers. The materials libraries consisting of wedge-type multilayer thin films were annealed at 500 or 700 °C to transform the multilayers into multiphase alloys. The libraries were characterized by nuclear reaction analysis, Rutherford backscattering, nanoindentation, vibrating sample magnetometry, x-ray diffraction (XRD) and transmission electron microscopy (TEM). Young's modulus and hardness values were related to the annealing parameters, structure and composition of the films. The magnetic properties of the films were improved by annealing in a H2 atmosphere, showing a more than tenfold decrease in the coercive field values in comparison to those of the vacuum-annealed films. The hardness values increased from 8 to 18 GPa when the annealing temperature was increased from 500 to 700 °C. The appearance of Fe2B phases, as revealed by XRD and TEM, had a significant effect on the mechanical properties of the films.

Robust all-optical single-shot readout of nitrogen-vacancy centers in diamond.

High-fidelity projective readout of a qubit's state in a single experimental repetition is a prerequisite for various quantum protocols of sensing and computing. Achieving single-shot readout is challenging for solid-state qubits. For Nitrogen-Vacancy (NV) centers in diamond, it has been realized using nuclear memories or resonant excitation at cryogenic temperature. All of these existing approaches have stringent experimental demands. In particular, they require a high efficiency of photon collection, such as immersion optics or all-diamond micro-optics. For some of the most relevant applications, such as shallow implanted NV centers in a cryogenic environment, these tools are unavailable. Here we demonstrate an all-optical spin readout scheme that achieves single-shot fidelity even if photon collection is poor (delivering less than 103 clicks/second). The scheme is based on spin-dependent resonant excitation at cryogenic temperature combined with spin-to-charge conversion, mapping the fragile electron spin states to the stable charge states. We prove this technique to work on shallow implanted NV centers, as they are required for sensing and scalable NV-based quantum registers.

Perceived barriers and facilitators for gait-related participation in people after stroke: From a patients' perspective.

Background: An important focus of post-stroke physical therapy is to improve walking and walking capacity. However, many people after stroke experience difficulties with gait-related participation, which includes more than walking capacity alone. Gait-related participation involves walking with a participation goal and requires to deal with changes in the environment during walking and perform dual tasks, for example.Objective: To explore barriers and facilitators for gait-related participation from the perspective of people after stroke. This knowledge can contribute to the development of effective interventions to improve gait-related participation.Methods: Semi-structured interviews were conducted to investigate how people after stroke experience gait-related participation. Audio-recorded interviews were transcribed, anonymized, and analyzed thematically. Barriers and facilitators were categorized according to the International Classification of Functioning, Disability and Health (ICF) framework.Results: Twenty-one people after stroke participated. Median age was 65 years, median time since stroke 16 weeks. Barriers were reported in movement-related functions, cognitive functions, mobility, personal factors, and environmental factors. Facilitators were found on participation level and in personal and environmental factors, such as motivation and family support.Conclusion: People after stroke who were physically able to walk independently still described multiple barriers to gait-related participation in all components of the ICF framework.

Effect of Virtual Reality Gait Training on Participation in Survivors of Subacute Stroke: A Randomized Controlled Trial.

OBJECTIVE: After stroke, people experience difficulties with walking that lead to restrictions in participation in daily life. The purpose of this study was to examine the effect of virtual reality gait training (VRT) compared to non-virtual reality gait training (non-VRT) on participation in community-living people after stroke. METHODS: In this assessor-blinded, randomized controlled trial with 2 parallel groups, people were included between 2 weeks and 6 months after stroke and randomly assigned to the VRT group or non-VRT group. Participants assigned to the VRT group received training on the Gait Real-time Analysis Interactive Lab (GRAIL), and participants assigned to the non-VRT group received treadmill training and functional gait exercises without virtual reality. Both training interventions consisted of 12 30-minute sessions during 6 weeks. The primary outcome was participation measured with the restrictions subscale of the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) 3 months postintervention. Secondary outcomes included subjective physical functioning, functional mobility, walking ability, dynamic balance, walking activity, fatigue, anxiety and depression, falls efficacy, and quality of life. RESULTS: Twenty-eight participants were randomly assigned to the VRT group and 27 to the non-VRT group, of whom 25 and 22 attended 75% or more of the training sessions, respectively. No significant differences between the groups were found over time for the USER-P restrictions subscale (1.23; 95% CI = -0.76 to 3.23) or secondary outcome measures. Patients' experiences with VRT were positive, and no serious adverse events were related to the interventions. CONCLUSIONS: The effect of VRT was not statistically different from non-VRT in improving participation in community-living people after stroke. IMPACT: Although outcomes were not statistically different, treadmill-based VRT was a safe and well-tolerated intervention that was positively rated by people after stroke. VR training might, therefore, be a valuable addition to stroke rehabilitation. LAY SUMMARY: VRT is feasible and was positively experienced by people after stroke. However, VRT was not more effective than non-VRT for improving walking ability and participation after stroke.