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.

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.

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.

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.

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.

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.

Detection of biological signals from a live mammalian muscle using an early stage diamond quantum sensor.

The ability to perform noninvasive and non-contact measurements of electric signals produced by action potentials is essential in biomedicine. A key method to do this is to remotely sense signals by the magnetic field they induce. Existing methods for magnetic field sensing of mammalian tissue, used in techniques such as magnetoencephalography of the brain, require cryogenically cooled superconducting detectors. These have many disadvantages in terms of high cost, flexibility and limited portability as well as poor spatial and temporal resolution. In this work we demonstrate an alternative technique for detecting magnetic fields generated by the current from action potentials in living tissue using nitrogen vacancy centres in diamond. With 50 pT/[Formula: see text] sensitivity, we show the first measurements of magnetic sensing from mammalian tissue with a diamond sensor using mouse muscle optogenetically activated with blue light. We show these proof of principle measurements can be performed in an ordinary, unshielded lab environment and that the signal can be easily recovered by digital signal processing techniques. Although as yet uncompetitive with probe electrophysiology in terms of sensitivity, we demonstrate the feasibility of sensing action potentials via magnetic field in mammals using a diamond quantum sensor, as a step towards microscopic imaging of electrical activity in a biological sample using nitrogen vacancy centres in diamond.

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.

Organ burden of inhaled nanoceria in a 2-year low-dose exposure study: dump or depot?

No detailed information on in vivo biokinetics of CeO2 nanoparticles (NPs) following chronic low-dose inhalation is available. The CeO2 burden for lung, lung-associated lymph nodes, and major non-pulmonary organs, blood, and feces, was determined in a chronic whole-body inhalation study in female Wistar rats undertaken according to OECD TG453 (6 h per day for 5 days per week for a 104 weeks with the following concentrations: 0, 0.1, 0.3, 1.0, and 3.0 mg/m3, animals were sacrificed after 3, 12, 24 months). Different spectroscopy methods (ICP-MS, ion-beam-microscopy) were used for the quantification of organ burden and for visualization of NP distribution patterns in tissues. After 24 months of exposure, the highest CeO2 lung burden (4.41 mg per lung) was associated with the highest aerosol concentration and was proportionally lower for the other groups in a dose-dependent manner. Imaging techniques confirmed the presence of CeO2 agglomerates of different size categories within lung tissue with a non-homogenous distribution. For the highest exposure group, after 24 months in total 1.2% of the dose retained in the lung was found in the organs and tissues analyzed in this study, excluding lymph nodes and skeleton. The CeO2 burden per tissue decreased from lungs > lymph nodes > hard bone > liver > bone marrow. For two dosage groups, the liver organ burden showed a low accumulation rate. Here, the liver can be regarded as depot, whereas kidneys, the skeleton, and bone marrow seem to be dumps due to steadily increasing NP burden over time.

Walking activity and its determinants in free-living ambulatory people in a chronic phase after stroke: a cross-sectional study.

Background: Free-living walking activity and its contributing factors in ambulatory people with stroke is poorly investigated.Objective: Evaluating free-living walking activity and identifying factors associated with free-living walking activity.Methods: In this cross-sectional study, participants wore an accelerometer to measure their level of walking activity. They also completed the Berg Balance Scale (BBS) and the Timed Up and Go test for functional balance, the Falls Efficacy Scale, the 10-Metre Walk Test and the Geriatric Depression Scale to investigate the relation between the performance tests and walking activity.Results: The 38 analyzed participants were on average 62 (±11.4) years old and 66 (IQR 64.8) months post stroke. They took an average of 3048.3 ± 1983.1 steps, had 123.3 ± 61.3 walking bouts a day and walked for 32.5 ± 18.2 min a day. Their average speed was 90.3 ± 13.8 steps a minute. The multivariate linear analysis showed that the BBS was the only determinant that was significantly related to all outcomes, except walking bouts.Conclusion: Free-living walking activity levels in ambulatory people with chronic stroke are low. The BBS is an independent significant predictor of free-living walking activity.Implications for rehabilitationFree-living walking activity can be expressed in different outcomes measured by accelerometry.Free-living walking activity levels in ambulatory people with chronic stroke are low, therefore support to sustain walking in the own environment should be part of the rehabilitation program after stroke.Balance is an important related factor to free-living walking activity which needs attention during rehabilitation after stroke.

Coulomb-driven single defect engineering for scalable qubits and spin sensors in diamond.

Qubits based on colour centres in diamond became a prominent system for solid-state quantum information processing and sensing. But the deterministic creation of qubits and the control of their environment are still critical issues, preventing the development of a room-temperature quantum computer. We report on the high creation yield of NV centres of 75% (a tenfold enhancement) by charge-assisted defect engineering, together with an improvement of their spin coherence. The method strongly favours the formation and negative charge state of the NV centres with respect to intrinsic diamond, while it hinders the formation of competing and perturbing defects such as di-vacancies or NVH complexes. We evidence spectrally the charge state tuning of the implantation-induced vacancies from V0 to V-, key element of this Coulomb-driven engineering. The generality of the method is demonstrated using several donors (phosphorous, oxygen and sulphur) and applying it to other centres (SnV and MgV) in diamond.

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.

Virtual reality gait training versus non-virtual reality gait training for improving participation in subacute stroke survivors: study protocol of the ViRTAS randomized controlled trial.

BACKGROUND: A stroke often results in gait impairments, activity limitations and restricted participation in daily life. Virtual reality (VR) has shown to be beneficial for improving gait ability after stroke. Previous studies regarding VR focused mainly on improvements in functional outcomes. As participation in daily life is an important goal for rehabilitation after stroke, it is of importance to investigate if VR gait training improves participation. The primary aim of this study is to examine the effect of VR gait training on participation in community-living people after stroke. METHODS/DESIGN: The ViRTAS study comprises a single-blinded, randomized controlled trial with two parallel groups. Fifty people between 2 weeks and 6 months after stroke, who experience constraints with walking in daily life, are randomly assigned to the virtual reality gait training (VRT) group or the non-virtual reality gait training (non-VRT) group. Both training interventions consist of 12 30-min sessions in an outpatient rehabilitation clinic during 6 weeks. Assessments are performed at baseline, post intervention and 3 months post intervention. The primary outcome is participation measured with the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). Secondary outcomes are subjective physical functioning, functional mobility, walking ability, walking activity, fatigue, anxiety and depression, falls efficacy and quality of life. DISCUSSION: The results of the study provide insight into the effect of VR gait training on participation after stroke. TRIAL REGISTRATION: Netherlands National Trial Register, Identifier NTR6215 . Registered on 3 February 2017.

Controlling the fluorescence properties of nitrogen vacancy centers in nanodiamonds.

Control over the formation and fluorescence properties of nitrogen vacancy (NV) centers in nanodiamonds (NDs) is an important factor for their use in medical and sensor applications. However, reports providing a deep understanding of the potential factors influencing these properties are rare and focus only on a few influencing factors. The current contribution targets this issue and we report a comprehensive study of the fluorescence properties of NVs in nanodiamonds as a function of electron irradiation fluence and surface termination. Here we show that process parameters such as defect center interactions, in particular, different nitrogen defects and radiation induced lattice defects, as well as surface functionalities have a strong influence on the fluorescence intensity, fluorescence lifetime and the charge state ratio of the NV centers. By employing a time-correlated single photon counting approach we also established a method for fast macroscopic monitoring of the fluorescence properties of ND samples. We found that the fluorescence properties of NV centers may be controlled or even tuned depending upon the radiation treatment, annealing, and surface termination.

Implantation of defined activities of phosphorus 32 with reduced target damage.

Materials doped with the unstable isotope phosphorus 32 are promising candidates for use in brachytherapeutic applications. One way to dope a material with 32P is by ion implantation. However, the bombardment of the target with ions other than 32P due to impurities of the ion beam leads to unnecessary damages of the target, which might reduce its potential for medical applications. Furthermore, implanting a pre-selected activity of an unstable isotope into a target requires the repeated determination of the target's activity, which requires removing the target from the implantation chamber. This prolongs the total implantation time and requires handling the radioactive target multiple times, which in turn increases the risk of accidental exposure. We have incorporated an online-detector system into the implantation chamber of a 60 kV ion implanter that allowed us to determine the activity of the target without removing the target from the implantation chamber. We then used this system to investigate the implantation of ions with m = 38 u-instead of ions with m = 32 u-to reduce the fraction of other ions than 32P implanted into the target to reduce the induced damages.

Uptake and molecular impact of aluminum-containing nanomaterials on human intestinal caco-2 cells.

Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al2O3 nanoparticles, while AlCl3 showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 µg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related.

Investigation of room temperature multispin-assisted bulk diamond 13C hyperpolarization at low magnetic fields.

In this work we investigated the time behavior of the polarization of bulk 13C nuclei in diamond above the thermal equilibrium. This nonthermal nuclear hyperpolarization is achieved by cross relaxation between two nitrogen related paramagnetic defect species in diamond in combination with optical pumping. The decay of the hyperpolarization at four different magnetic fields is measured. Furthermore, we use the comparison with conventional nuclear resonance measurements to identify the involved distances of the nuclear spin with respect to the defects and therefore the coupling strengths. Also, a careful look at the linewidth of the signal give valuable information to piece together the puzzle of the hyperpolarization mechanism.

Additive Induced Formation of Ultrathin Sodium Chloride Needle Crystals.

A multitude of ultrathin crystal needles are formed during the evaporation of saturated aqueous NaCl solution droplets in the presence of amide containing additives. The needles are as small as 300 nm wide and 100-1000 µm in length. Heating experiments, X-ray diffraction, and energy dispersive X-ray spectroscopy showed that the needles are cubic sodium chloride crystals with the needle length direction pointing toward [100]. This shape, not expected for the 43̅m point group symmetry of NaCl, has been explained using a model, based on tip formation by initial morphological instability followed by time dependent adsorption of additive molecules blocking the growth of the needle side faces. The latter also suppresses side branch formation, which normally occurs for dendrite growth.

Detection of small bunches of ions using image charges.

A concept for detection of charged particles in a single fly-by, e.g. within an ion optical system for deterministic implantation, is presented. It is based on recording the image charge signal of ions moving through a detector, comprising a set of cylindrical electrodes. This work describes theoretical and practical aspects of image charge detection (ICD) and detector design and its application in the context of real time ion detection. It is shown how false positive detections are excluded reliably, although the signal-to-noise ratio is far too low for time-domain analysis. This is achieved by applying a signal threshold detection scheme in the frequency domain, which - complemented by the development of specialised low-noise preamplifier electronics - will be the key to developing single ion image charge detection for deterministic implantation.