Cardiac q-space trajectory imaging by motion-compensated tensor-valued diffusion encoding in human heart in vivo.

PURPOSE: Tensor-valued diffusion encoding can probe more specific features of tissue microstructure than what is available by conventional diffusion weighting. In this work, we investigate the technical feasibility of tensor-valued diffusion encoding at high b-values with q-space trajectory imaging (QTI) analysis, in the human heart in vivo. METHODS: Ten healthy volunteers were scanned on a 3T scanner. We designed time-optimal gradient waveforms for tensor-valued diffusion encoding (linear and planar) with second-order motion compensation. Data were analyzed with QTI. Normal values and repeatability were investigated for the mean diffusivity (MD), fractional anisotropy (FA), microscopic FA (µFA), isotropic, anisotropic and total mean kurtosis (MKi, MKa, and MKt), and orientation coherence (Cc ). A phantom, consisting of two fiber blocks at adjustable angles, was used to evaluate sensitivity of parameters to orientation dispersion and diffusion time. RESULTS: QTI data in the left ventricular myocardium were MD = 1.62 ± 0.07 µm2 /ms, FA = 0.31 ± 0.03, µFA = 0.43 ± 0.07, MKa = 0.20 ± 0.07, MKi = 0.13 ± 0.03, MKt = 0.33 ± 0.09, and Cc  = 0.56 ± 0.22 (mean ± SD across subjects). Phantom experiments showed that FA depends on orientation dispersion, whereas µFA was insensitive to this effect. CONCLUSION: We demonstrated the first tensor-valued diffusion encoding and QTI analysis in the heart in vivo, along with first measurements of myocardial µFA, MKi, MKa, and Cc . The methodology is technically feasible and provides promising novel biomarkers for myocardial tissue characterization.

Accuracy and Precision of a Novel Photogate System to Measure Toe Clearance on Stairs.

Background: Toe clearance on stairs is typically measured using optoelectronic systems, though these are often constrained to the laboratory, due to their complex setups. Here we measured stair toe clearance through a novel prototype photogate setup and compared this to optoelectronic measurements. Methods: Twelve participants (age 22 ± 3 years) completed 25 stair ascent trials, each on a seven-step staircase. Toe clearance over the fifth step edge was measured using Vicon and the photogates. Twenty-two photogates were created in rows through laser diodes and phototransistors. The height of the lowest photogate broken at step-edge crossing was used to determine photogate toe clearance. A limits of agreement analysis and Pearson's correlation coefficient compared the accuracy, precision and relationship between systems. Results: We found a mean difference of -1.5 mm (accuracy) between the two measurement systems, with upper and lower limits (precision) of 10.7 mm and -13.8 mm, respectively. A strong positive correlation was also found (r = 70, n = 12, p = 0.009) between the systems. Discussion: The results suggest that photogates could be an option for measuring real-world stair toe clearances, where optoelectronic systems are not routinely used. Improvements to the design and measurement factors may help to improve the precision of the photogates.

Affimer proteins inhibit immune complex binding to FcγRIIIa with high specificity through competitive and allosteric modes of action.

Protein-protein interactions are essential for the control of cellular functions and are critical for regulation of the immune system. One example is the binding of Fc regions of IgG to the Fc gamma receptors (FcγRs). High sequence identity (98%) between the genes encoding FcγRIIIa (expressed on macrophages and natural killer cells) and FcγRIIIb (expressed on neutrophils) has prevented the development of monospecific agents against these therapeutic targets. We now report the identification of FcγRIIIa-specific artificial binding proteins called "Affimer" that block IgG binding and abrogate FcγRIIIa-mediated downstream effector functions in macrophages, namely TNF release and phagocytosis. Cocrystal structures and molecular dynamics simulations have revealed the structural basis of this specificity for two Affimer proteins: One binds directly to the Fc binding site, whereas the other acts allosterically.

An in vivo platform for identifying inhibitors of protein aggregation.

Protein aggregation underlies an array of human diseases, yet only one small-molecule therapeutic targeting this process has been successfully developed to date. Here, we introduce an in vivo system, based on a ß-lactamase tripartite fusion construct, that is capable of identifying aggregation-prone sequences in the periplasm of Escherichia coli and inhibitors that prevent their aberrant self-assembly. We demonstrate the power of the system using a range of proteins, from small unstructured peptides (islet amyloid polypeptide and amyloid ß) to larger, folded immunoglobulin domains. Configured in a 48-well format, the split ß-lactamase sensor readily differentiates between aggregation-prone and soluble sequences. Performing the assay in the presence of 109 compounds enabled a rank ordering of inhibition and revealed a new inhibitor of islet amyloid polypeptide aggregation. This platform can be applied to both amyloidogenic and other aggregation-prone systems, independent of sequence or size, and can identify small molecules or other factors able to ameliorate or inhibit protein aggregation.

ESI-IMS-MS: A method for rapid analysis of protein aggregation and its inhibition by small molecules.

Electrospray ionisation-ion mobility spectrometry-mass spectrometry (ESI-IMS-MS) is a powerful method for the study of conformational changes in protein complexes, including oligomeric species populated during protein self-aggregation into amyloid fibrils. Information on the mass, stability, cross-sectional area and ligand binding capability of each transiently populated intermediate, present in the heterogeneous mixture of assembling species, can be determined individually in a single experiment in real-time. Determining the structural characterisation of oligomeric species and alterations in self-assembly pathways observed in the presence of small molecule inhibitors is of great importance, given the urgent demand for effective therapeutics. Recent studies have demonstrated the capability of ESI-IMS-MS to identify small molecule modulators of amyloid assembly and to determine the mechanism by which they interact (positive, negative, non-specific binding, or colloidal) in a high-throughput format. Here, we demonstrate these advances using self-assembly of Aß40 as an example, and reveal two new inhibitors of Aß40 fibrillation.

The addition of stripes (a version of the 'horizontal-vertical illusion') increases foot clearance when crossing low-height obstacles.

Trips over obstacles are one of the main causes of falling in older adults, with vision playing an important role in successful obstacle negotiation. We determined whether a horizontal-vertical illusion, superimposed onto low-height obstacles to create a perceived increase in obstacle height, increased foot clearances during obstacle negotiation thus reducing the likelihood of tripping. Eleven adults (mean ± 1 SD: age 27.3 ± 5.1 years) negotiated obstacles of varying heights (3, 5, 7 cm) with four different appearance conditions; two were obstacles with a horizontal-vertical illusion (vertical stripes of different thickness) superimposed on the front, one was a plain obstacle and the fourth a plain obstacle with a horizontal black line painted on the top edge. Foot clearance parameters were compared across conditions. Both illusions led to a significant increase in foot clearance when crossing the obstacle, compared to the plain condition, irrespective of obstacle height. Superimposing a horizontal-vertical illusion onto low-height obstacles can increase foot clearance, and its use on the floor section of a double-glazing door frame for example may reduce the incidence of tripping in the home. Practitioner Summary: Low-height obstacles such as the floor section of a double-glazing door frame are potential tripping hazards. In a gait lab-based study we found that a horizontal-vertical illusion superimposed onto low-height obstacles led to significantly higher foot clearances; indicating their potential as a useful safety measure.

The effects of virtual reality game training on trunk to pelvis coupling in a child with cerebral palsy.

BACKGROUND: Good control of trunk and pelvic movements is necessary for well controlled leg movements required to perform activities of daily living. The nature of movement coupling between the trunk and pelvis varies and depends on the type of activity. Children with cerebral palsy often have reduced ability to modulate coupling between the trunk and pelvis but movement patterns of the pelvis can be improved by training. The aim of this study was to examine how pelvis to trunk coupling changed while playing a computer game driven by pelvic rotations. METHODS: One boy with cerebral palsy diplegia played the Goblin Post Office game on the CAREN virtual rehabilitation system for six weeks. He navigated a flying dragon in a virtual cave towards randomly appearing targets by rotating the pelvis around a vertical axis. Motion of the pelvis and trunk was captured in real-time by a Vicon 612 optoelectronic system tracking two clusters of three markers attached to the sacrum and thoracic spine. RESULTS: Convex hull areas calculated from angle-angle plots of pelvic and trunk rotations showed that coupling increased over game training (F1,11 = 7.482, p = 0.019). Reaching to targets far from the midline required tighter coupling than reaching near targets (F1,12 = 10.619, p = 0.007). CONCLUSIONS: Increasing coupling appears to be an initial compensation mechanism using the better controlled trunk to drive rotation of the pelvis. Co-contractions causing increased coupling are expected to reduce over longer exposure to training. The control scheme of the training game can be set to facilitate de-coupling of pelvic movements from the trunk. Using large ranges of pelvic rotation required more coupling suggesting that training of selective pelvic movements is likely to be more effective close to a neutral pelvic posture.

The next step in optimising the stair horizontal-vertical illusion: Does a perception-action link exist in older adults?

INTRODUCTION: Tripping on stairs results from insufficient foot to step edge clearance and can often lead to a fall in older adults. A stair horizontal-vertical illusion is suggested to increase the perceived riser height of a step and increase foot clearance when stepping up. However, this perception-action link has not been empirically determined in older adults. Previous findings suggesting a perception-action effect have also been limited to a single step or a three-step staircase. On larger staircases, somatosensory learning of step heights may be greater which could override the illusory effect on the top step. Furthermore, the striped nature of the existing stair horizontal-vertical illusion is associated with visual stress and may not be aesthetically suitable for use on public stairs. These issues need resolving before potential future implementation on public stairs. METHODS: Experiment 1. A series of four computer-based perception tests were conducted in older (N = 14: 70 ± 6 years) and young adults (N = 42: 24 ± 3 years) to test the influence of different illusion designs on stair riser height estimation. Participants compared images of stairs, with horizontal-vertical illusions or arbitrary designs on the bottom step, to a plain stair with different bottom step riser heights and selected the stair they perceived to have the tallest bottom riser. Horizontal-vertical illusions included a previously developed design and versions with modified spatial frequencies and mark space ratios. Perceived riser height differences were assessed between designs and between age groups. Experiment 2. To assess the perception-action link, sixteen older (70 ± 7 years) and fifteen young (24 ± 3 years) adults ascended a seven-step staircase with and without horizontal-vertical illusions tested in experiment 1 placed onto steps one and seven. Foot clearances were measured over each step. To determine whether changes in perception were linked to changes in foot clearance, perceived riser heights for each horizontal-vertical illusion were assessed using the perception test from experiment 1 before and after stair ascent. Additional measures to characterise stair safety included vertical foot clearance, margins of stability, foot overhang, stair speed, and gaze duration, which were assessed over all seven steps. RESULTS: Experiment 1. All horizontal-vertical illusion designs led to significant increases in the perceived riser height in both young and older adults (12-19% increase) with no differences between age groups. Experiment 2. On step 7, each horizontal-vertical illusion led to an increase in vertical foot clearance for young (up to 0.8 cm) and older adults (up to 2.1 cm). On step 1 significant increases in vertical foot clearance were found for a single horizontal-vertical illusion when compared to plain (1.19 cm increase). The horizontal-vertical illusions caused significant increases in the perceived riser height (young; 13% increase, older; 11% increase) with no differences between illusion design, group or before and after stair ascent. No further differences were found for the remaining variables and steps. CONCLUSION: Results indicate a perception-action link between perceived riser height and vertical foot clearance in response to modified versions of the horizontal-vertical illusion in both young and older adults. This was shown with no detriment to additional stair safety measures. Further evaluating these illusions on private/public stairs, especially those with inconsistently taller steps, may be beneficial to help improve stair safety for older adults.

Using a stair horizontal-vertical illusion to increase foot clearance over an inconsistently taller stair-riser.

INTRODUCTION: Stair falls can be caused by inconsistent stair dimensions. During ascent, inconsistently taller stair risers lead to reduced foot clearances as the inconsistency goes unnoticed. A stair horizontal-vertical illusion increases perceived riser heights and foot clearance and could offset reduced foot clearances over inconsistently taller risers, though this might impact other stair safety measures. METHOD: Twelve participants (age: 22 (3) years) ascended a seven-step staircase under three conditions: i) all steps consistent in riser height (consistent), ii) a 1cm increase in step 5 riser height (inconsistent) and iii) a 1cm increase in step 5 riser height, superimposed with a stair horizontal-vertical illusion (illusion). Vertical foot clearance, foot overhang, and margins of stability were assessed over step 4, 5 and 6. Perceived riser height due to the illusion was determined through a computer perception test. A One-Way Repeated Measures ANOVA compared biomechanical variables between conditions. A One Sample t test compared perceived riser height to the true height. RESULTS: Over the inconsistent step 5, foot clearance reduced by 0.8cm compared to consistent. Illusion increased foot clearance by 1.1cm and decreased foot overhang by 4% compared to inconsistent. On step 4 the illusion led to more anterior instability compared to inconsistent. Illusion and inconsistent led to more mediolateral stability compared to consistent. The illusion increased perceived riser height by 12%. DISCUSSION: Foot clearance reductions over inconsistently taller risers can be offset by a stair horizontal-vertical illusion. Additional benefits included a safer foot overhang and unaffected stability over the inconsistent riser. Changes to step 4 stability might have resulted from leaning forward to look at the step 5 illusion. The stair horizontal-vertical illusion could be a practical solution for inconsistently taller stair risers, where a rebuild is usually the only solution.

Influence of step-surface visual properties on confidence, anxiety, dynamic stability, and gaze behaviour in young and older adults.

BACKGROUND: Step-surface visual properties are often associated with stair falls. However, evidence for decorating stairs typically concerns the application of step-edge highlighters rather than the entire step-surface. Here we examine the influence of step-surface visual properties on stair descent safety, with a view to generating preliminary evidence for safe stair décor. METHODS: Fourteen young (YA: 23.1 ± 3.7 years), 13 higher (HAOA: 67 ± 3.5) and 14 lower (LAOA: 73.4 ± 5.7) ability older adults descended a seven-step staircase. Older adults were stratified based on physiological/cognitive function. Step-surface décor patterns assessed were: Black and white (Busy); fine grey (Plain); and striped multicolour (Striped); each implemented with/without black edge-highlighters (5.5 cm width) totalling six conditions. Participants descended three times per condition. Confidence was assessed prior to, and anxiety following, the first descent in each condition. 3D kinematics (Vicon) quantified descent speed, margin of stability, and foot clearances with respect to step-edges. Eye tracking (Pupil-labs) recorded gaze. Data from three phases of descent (entry, middle, exit) were analysed. Linear mixed-effects models assessed within-subject effects of décor (×3) and edge highlighters (×2), between-subject effects of age (×3), and interactions between terms (α = p < .05). RESULTS: Décor: Plain décor reduced anxiety in all ages and abilities (p = .032, effect size: gav = 0.3), and increased foot clearances in YA and HAOA in the middle phase (p < .001, gav = 0.53), thus improving safety. In contrast, LAOA exhibited no change in foot clearance with Plain décor. Patterned décor slowed descent (Busy: p < .001, gav = 0.2), increased margins of stability (Busy: p < .001, gav = 0.41; Striped: p < .001, gav = 0.25) and reduced steps looked ahead (Busy: p = .053, gav = 0.25; Striped: p = .039, gav = 0.28) in all ages and abilities. This reflects cautious descent, likely due to more challenging conditions for visually extracting information about the spatial characteristics of the steps useful to guide descent. Edge highlighters: Step-edge highlighters increased confidence (p < .001, gav = 0.53) and reduced anxiety (p < .001, gav = 0.45) in all ages and abilities and for all décor, whilst removing them slowed descent in HAOA (p = .01, gav = 0.26) and LAOA (p = .003, gav = 0.25). Step-edge highlighters also increased foot clearance in YA and HAOA (p = .003, gav = 0.14), whilst LAOA older adults showed no adaptation. No change in foot clearances with décor or step-edge highlighters in LAOA suggests an inability to adapt to step-surface visual properties. CONCLUSION: Patterned step surfaces can lead to more cautious and demanding stair negotiation from the perspective of visually extracting spatial information about the steps. In contrast, plain décor with step edge highlighters improves safety. We therefore suggest plain décor with edge highlighters is preferable for use on stairs.

Children With Developmental Coordination Disorder Exhibit Greater Stepping Error Despite Similar Gaze Patterns and State Anxiety Levels to Their Typically Developing Peers.

This study examined stepping accuracy, gaze behavior, and state-anxiety in children with (N = 21, age M = 10.81, SD = 1.89) and without (N = 18, age M = 11.39, SD = 2.06) developmental coordination disorder (DCD) during an adaptive locomotion task. Participants walked at a self-selected pace along a pathway, placing their foot into a raised rectangular floor-based target box followed by either no obstacles, one obstacle, or two obstacles. Stepping kinematics and accuracy were determined using three-dimensional motion capture, whilst gaze was determined using mobile eye-tracking equipment. The children with DCD displayed greater foot placement error and variability when placing their foot within the target box and were more likely to make contact with its edges than their typically developing (TD) peers. The DCD group also displayed greater variability in the length and width of their steps in the approach to the target box. No differences were observed between groups in any of the gaze variables measured, in mediolateral velocity of the center of mass during the swing phase into the target box, or in the levels of self-reported state-anxiety experienced prior to facing each task. We therefore provide the first quantifiable evidence that deficits to foot placement accuracy and precision may be partially responsible for the increased incidence of trips and falls in DCD, and that these deficits are likely to occur independently from gaze behavior and state-anxiety.

Children With Developmental Coordination Disorder Show Altered Visuomotor Control During Stair Negotiation Associated With Heightened State Anxiety.

Safe stair negotiation is an everyday task that children with developmental coordination disorder (DCD) are commonly thought to struggle with. Yet, there is currently a paucity of research supporting these claims. We investigated the visuomotor control strategies underpinning stair negotiation in children with (N = 18, age = 10.50 ± 2.04 years) and without (N = 16, age = 10.94 ± 2.08 years) DCD by measuring kinematics, gaze behavior and state anxiety as they ascended and descended a staircase. A questionnaire was administered to determine parents' confidence in their child's ability to safely navigate stairs and their child's fall history (within the last year). Kinematics were measured using three-dimensional motion capture (Vicon), whilst gaze was measured using mobile eye-tracking equipment (Pupil labs). The parents of DCD children reported significantly lower confidence in their child's ability to maintain balance on the stairs and significantly more stair-related falls in the previous year compared to the parents of typically developing (TD) children. During both stair ascent and stair descent, the children with DCD took longer to ascend/descend the staircase and displayed greater handrail use, reflecting a more cautious stair negotiation strategy. No differences were observed between groups in their margin of stability, but the DCD children exhibited significantly greater variability in their foot-clearances over the step edge, which may increase the risk of a fall. For stair descent only, the DCD children reported significantly higher levels of state anxiety than the TD children and looked significantly further along the staircase during the initial entry phase, suggesting an anxiety-related response that may bias gaze toward the planning of future stepping actions over the accurate execution of an ongoing step. Taken together, our findings provide the first quantifiable evidence that (a) safe stair negotiation is a significant challenge for children with DCD, and that (b) this challenge is reflected by marked differences in their visuomotor control strategies and state anxiety levels. Whilst it is currently unclear whether these differences are contributing to the frequency of stair-related falls in children with DCD, our findings pave the way for future research to answer these important questions.

Optimal lighting levels for stair safety: Influence of lightbulb type and brightness on confidence, dynamic balance and stepping characteristics.

INTRODUCTION: Poor lighting has been associated with stair falls in young and older adults. However, current guidelines for illuminating stairs seem arbitrary, differ widely between sources, and are often difficult to interpret. AIMS: Here we examined the influence of real-world bulb illumination properties on stair descent safety in young and older adults, with a view to generating preliminary evidence for appropriate lightbulb use/stair illumination. METHODS: Stair tread illumination (lx) was measured in a standard UK home (2.23 m ceiling) from a low (50 W; 630 lm) and a high (103 W, 1450 lm) power compact fluorescent lamp (CFL) bulb from the time they were turned on until they reached full brightness. This enabled modelling of their illumination characteristics during warm up. Illumination was also measured from a low (40 W, 470 lm) and a high (100 W, 1521 lm) power LED bulb at first turn-on. Computer-controlled custom lighting then replicated these profiles, in addition to a Bright control (350 lx), on an instrumented staircase descended (3 × trials per light condition) by 12 young (25.3 ± 4.4 years; 5 males), 12 higher ability older (HAOA: 69.6 ± 4.7 years; 5 males) and 13 lower ability older (LAOA: 72.4 ± 4.2; 3 males) healthy adults. Older adults were allocated to ability groups based on physiological and cognitive function. Stair-specific confidence was assessed prior to the first descent in each new lighting condition, and whole-body 3D kinematics (Vicon) quantified margins of stability and foot clearances with respect to the step edges. Mixed ANOVAs examined these measures for within-subject effects of lighting (×5), between-subject effects of age (×3) and interactions between lighting and age. RESULTS: Use of CFL bulbs led to lower self-reported confidence in older adults (20.37%, p = .01), and increased margins of stability (12.47%, p = .015) and foot clearances with respect to the step edges (10.36%, p = .003). Importantly, using CFL bulbs increased foot clearance variability with respect to the bottom step (32.74%, p = .046), which is where a high proportion of falls occur. CONCLUSION: Stair-tread illumination from CFL bulbs at first turn on leads to less safe stair negotiation. We suggest high powered LED bulbs may offer a safer alternative.

Centre of mass control is reduced in older people when descending stairs at an increased riser height.

BACKGROUND: Maintaining body centre of mass (CoM) lowering velocity within manageable/safe limits during stair descent can be problematic for older individuals due to reduced ranges of motion at the involved joints (ankle and knee) and a reduced ability to generate adequate joint moments at the extremes in joint ranges of motion. These problems are likely to magnify in circumstances where the distance of lowering increases, or when misjudging the height of lowering. RESEARCH QUESTION: How does a 50% increase in standard stair riser-height affect control of CoM velocity and acceleration of older people during stair descent? METHODS: Fifteen older (75 ±â€¯3 years) and seventeen young (25 ±â€¯4 years) healthy adults descended a 4-step staircase, at two riser-heights: 170 mm, 255 mm. Changes in peak vertical CoM acceleration and velocity, and lower-limb joint kinetics (moments, work) during landing and lowering phases of stair descent were assessed using a mixed-design repeated measures analysis of variance. RESULTS: Peak CoM accelerations and velocities during landing and lowering were lower in older compared to young adults and increased in both groups at 255 mm riser-height. Duration of lowering also increased, particularly for older adults. Peak ankle moments during landing and lowering, which were lower in older compared to young adults, increased when descending from 255 mm riser-height, whilst the peak knee moment reduced. Both groups produced increased landing-limb negative (eccentric) ankle joint work when descending from 255 mm, but increases were greater for older adults (87.8%) compared to young (76.1%). SIGNIFICANCE: Descending stairs became more challenging in both age groups as riser-height increased. Older adults adopted a strategy of reducing CoM velocity to lessen the eccentric landing demands. In both groups, but more so older adults, there was a greater reliance on using leading-limb eccentric plantarflexion at 255 mm riser-height compared to 170 mm, to arrest/control increased downward CoM velocity and acceleration during landing.

Nanoscale mechanics of microgel particles.

Microgel particles are highly tuneable materials that are useful for a wide range of industrial applications, such as drug delivery, sensing, nanoactuation, emulsion stabilisation and use as cell substrates. Microgels have also been used as model systems investigating physical phenomena such as crystallization, glass-formation, jamming, ageing and complex flow behaviour. The responsiveness of microgel systems such as poly(N-isopropylacrylamide) (PNIPAm) to external stimuli has been established in fundamental investigations and in applications and recent work has begun to quantify the mechanics of individual particles. However little focus has been placed on determining their internal mechanical properties, which is likely to relate to their nonuniform internal structure. In this work we combine atomic force microscopy, force spectroscopy and dynamic light scattering to mechanically profile the internal structure of microgel particles in the size range of ∼100 nm, which is commonly used both in practical applications and in fundamental studies. Nanoindentation using thermally stable cantilevers allows us to determine the particle moduli and the deformation profiles during particle compression with increasing force, while peak force nanomechanical mapping (PF-QNM) AFM is used to capture high resolution images of the particles' mechanical response. Combining these approaches with dynamic light scattering allows a quantitative profile of the particles' internal elastic response to be determined. Our results provide clear evidence for a radial distribution in particle mechanical response with a softer outer "corona" and a stiffer particle core. We determine the particle moduli in the core and corona, using different force microscopy approaches, and find them to vary systematically both in the core (∼17-50 kPa) and at the outer periphery of the particles (∼3-40 kPa). Importantly, we find that highly crosslinked particles have equivalent moduli across their radial profile, reflecting their significantly lower radial heterogeneity. This ability to accurately and precisely probe microgel radial profiles has clear implications both for fundamental science and for industrial applications.

A nuclear magnetic resonance study of water in aggrecan solutions.

Aggrecan, a highly charged macromolecule found in articular cartilage, was investigated in aqueous salt solutions with proton nuclear magnetic resonance. The longitudinal and transverse relaxation rates were determined at two different field strengths, 9.4 T and 0.5 T, for a range of temperatures and aggrecan concentrations. The diffusion coefficients of the water molecules were also measured as a function of temperature and aggrecan concentration, using a pulsed field gradient technique at 9.4 T. Assuming an Arrhenius relationship, the activation energies for the various relaxation processes and the translational motion of the water molecules were determined from temperature dependencies as a function of aggrecan concentration in the range 0-5.3% w/w. The longitudinal relaxation rate and inverse diffusion coefficient were approximately equally dependent on concentration and only increased by upto 20% from that of the salt solution. The transverse relaxation rate at high field demonstrated greatest concentration dependence, changing by an order of magnitude across the concentration range examined. We attribute this primarily to chemical exchange. Activation energies appeared to be approximately independent of aggrecan concentration, except for that of the low-field transverse relaxation rate, which decreased with concentration.

What you see is what you step: the horizontal-vertical illusion increases toe clearance in older adults during stair ascent.

PURPOSE: Falls on stairs are a significant cause of morbidity and mortality in elderly people. A simple safety strategy to avoid tripping on stairs is increasing foot clearance. We determined whether a horizontal-vertical illusion superimposed onto stairs to create an illusory perceived increase in stair-riser height would increase stair ascent foot clearance in older participants. METHODS: Preliminary experiments determined the optimum parameters for the horizontal-vertical illusion. Fourteen older adults (mean age ± 1 SD, 68.5 ± 7.4 years) ascended a three-step staircase with the optimized version of the horizontal-vertical illusion (spatial frequency: 12 cycles per stair riser) positioned either on the bottom or top stair only, or on the bottom and top stair simultaneously. These were compared to a control condition, which had a plain stair riser with edge highlighters positioned flush with each stair-tread edge. Foot clearance and measures of postural stability were compared across conditions. RESULTS: The optimized illusion on the bottom and top stair led to a significant increase in foot clearance over the respective stair edge, compared to the control condition. There were no significant decreases in postural stability. CONCLUSIONS: An optimized horizontal-vertical visual illusion led to significant increases in foot clearance in older adults when ascending a staircase, but the effects did not destabilize their postural stability. Inclusion of the horizontal-vertical illusion on raised surfaces (e.g., curbs) or the bottom and top stairs of staircases could improve stair ascent safety in older adults.

Screening and classifying small-molecule inhibitors of amyloid formation using ion mobility spectrometry-mass spectrometry.

The search for therapeutic agents that bind specifically to precursor protein conformations and inhibit amyloid assembly is an important challenge. Identifying such inhibitors is difficult because many protein precursors of aggregation are partially folded or intrinsically disordered, which rules out structure-based design. Furthermore, inhibitors can act by a variety of mechanisms, including specific or nonspecific binding, as well as colloidal inhibition. Here we report a high-throughput method based on ion mobility spectrometry-mass spectrometry (IMS-MS) that is capable of rapidly detecting small molecules that bind to amyloid precursors, identifying the interacting protein species and defining the mode of inhibition. Using this method we have classified a variety of small molecules that are potential inhibitors of human islet amyloid polypeptide (hIAPP) aggregation or amyloid-beta 1-40 aggregation as specific, nonspecific, colloidal or non-interacting. We also demonstrate the ability of IMS-MS to screen for inhibitory small molecules in a 96-well plate format and use this to discover a new inhibitor of hIAPP amyloid assembly.

Safety on stairs: influence of a tread edge highlighter and its position.

BACKGROUND: Falls sustained when descending stairs are the leading cause of accidental death in older adults. Highly visible edge highlighters/friction strips (often set back from the tread edge) are sometimes used to improve stair safety, but there is no evidence for the usefulness of either. OBJECTIVE: To determine whether an edge highlighter and its location relative to the tread edge affect foot placement/clearance and accidental foot contacts when descending stairs. METHOD: Sixteen older adults (mean±1SD age; 71±7years) with normal vision (experiment 1) and eight young adults (mean±1SD age; 24±4years) with visual impairment due to simulated age-related cataract (experiment 2) completed step descent trials during which a high contrast edge highlighter was either not present, placed flush with the tread edge, or set back from the edge by 10mm or 30mm. Foot placement/clearance and the number of accidental foot contacts were compared across conditions. RESULTS: In experiment 1, a highlighter set back by 30mm led to a reduction in final foot placement (p<0.001) and foot clearance (p<0.001) compared to a highlighter placed flush with the tread edge, and the percentage of foot clearances that were less than 5mm increased from 2% (abutting) to 17% (away30). In experiment 2, a highlighter placed flush with the tread edge led to a decrease in within-subject variability in final foot placement (p=0.004) and horizontal foot clearance (p=0.022), a decrease in descent duration (p=0.009), and a decrease in the number of low clearances (<5mm, from 8% to 0%) and the number of accidental foot contacts (15% to 3%) when compared to a tread edge with no highlighter present. CONCLUSIONS: Changes to foot clearance parameters as a result of highlighter presence and position suggest that stairs with high-contrast edge highlighters positioned flush with the tread edge will improve safety on stairs, particularly for those with age-related visual impairment.

Stair-specific algorithms for identification of touch-down and foot-off when descending or ascending a non-instrumented staircase.

The present study introduces four event detection algorithms for defining touch-down and foot-off during stair descent and stair ascent using segmental kinematics. For stair descent, vertical velocity minima of the whole body center-of-mass was used to define touch-down, and foot-off was defined as the instant of trail limb peak knee flexion. For stair ascent, vertical velocity local minima of the lead-limb toe was used to define touch-down, and foot-off was defined as the local maxima in vertical displacement between the toe and pelvis. The performance of these algorithms was determined as the agreement in timings of kinematically derived events to those defined kinetically (ground reaction forces). Data were recorded while 17 young and 15 older adults completed stair descent and ascent trials over a four-step instrumented staircase. Trials were repeated for three stair riser height conditions (85 mm, 170 mm, and 255 mm). Kinematically derived touch-down and foot-off events showed good agreement (small 95% limits of agreement) with kinetically derived events for both young and older adults, across all riser heights, and for both ascent and descent. In addition, agreement metrics were better than those returned using existing kinematically derived event detection algorithms developed for overground gait. These results indicate that touch-down and foot-off during stair ascent and descent of non-instrumented staircases can be determined with acceptable precision using segmental kinematic data.