Physiological Demands of Competitive Sprint and Distance Performance in Elite Female Cross-Country Skiing.

Carlsson, M, Carlsson, T, Wedholm, L, Nilsson, M, Malm, C, and Tonkonogi, M. Physiological demands of competitive sprint and distance performance in elite female cross-country skiing. J Strength Cond Res 30(8): 2138-2144, 2016-The purpose was to investigate the relationship between elite females' competitive performance capability in sprint and distance cross-country skiing and the variables of gross efficiency (GE), work rate at the onset of blood-lactate accumulation (OBLA4mmol), maximal oxygen uptake (V[Combining Dot Above]O2max), maximal speed (Vmax), and peak upper-body oxygen uptake (V[Combining Dot Above]O2peak). Ten elite female cross-country skiers (age 24.5 ± 2.8 years) completed treadmill roller-skiing tests to determine GE, OBLA4mmol, and V[Combining Dot Above]O2max using the diagonal-stride technique as well as Vmax and V[Combining Dot Above]O2peak using the double-poling technique. International Ski Federations ranking points for sprint (FISsprint) and distance (FISdist) races were used as competitive performance data. There were correlations between the FISsprint and the V[Combining Dot Above]O2max expressed absolutely (p = 0.0040), Vmax (p = 0.012), and V[Combining Dot Above]O2peak expressed absolutely (p < 0.001) and as a simple ratio-standard (p = 0.049). The FISdist were correlated with OBLA4mmol (p = 0.048), V[Combining Dot Above]O2max expressed absolutely (L·min) (p = 0.015) and as a simple ratio-standard (p = 0.046), and V[Combining Dot Above]O2peak expressed absolutely (p = 0.036) and as a simple ratio-standard (ml·min·kg) (p = 0.040). The results demonstrate that the physiological abilities reflected by V[Combining Dot Above]O2max and V[Combining Dot Above]O2peak are indicators of competitive sprint and distance performance in elite female cross-country skiing. In addition, the ability to generate a high Vmax indicates the performance in sprint races, whereas the skier's OBLA4mmol reflects the performance capability in distance races. Based on the results, when evaluating the performance capacity of elite female cross-country skiers, it is recommended to use physiological variables that reflect competitive performance.

Visual functions, ocular characteristics and visual quality of life in patients with homocystinuria.

BACKGROUND: Homocystinuria (HCU) is a rare metabolic disease that affects many organs, including the eyes. Aims: to assess visual functions, ocular characteristics, visual quality of life and time from the onset of ocular manifestations to HCU-diagnosis in patients with HCU. MATERIAL AND METHODS: Eighteen patients underwent ophthalmological examinations and visual quality of life questionnaires. RESULTS: Best corrected decimal visual acuity was median 1.0 (range amaurosis - 1.3) right eye and 1.0 (range amaurosis -1.3) left eye. Five patients presented with severe myopia as first HCU manifestation, duration to HCU diagnosis was mean 13.6 years (range 2-25). Two patients had suffered ectopia lentis as first HCU manifestation, HCU diagnosis was established mean 8.0 years (range 7-9) later. One patient had suffered both from thrombosis and ectopia lentis prior to diagnosis. Another four patients suffered thromboembolic events before diagnosis. Median VFQ-25 composite score was 93 (68-98). CONCLUSIONS: The prevalence of myopia, ectopia lentis and monocular blindness was high in HCU-patients, which was reflected in their visual quality of life. Diagnosis was often delayed after the first ocular manifestation, increasing the risk of other severe non-ocular complications.

Integration of neuromorphic AI in event-driven distributed digitized systems: Concepts and research directions.

Increasing complexity and data-generation rates in cyber-physical systems and the industrial Internet of things are calling for a corresponding increase in AI capabilities at the resource-constrained edges of the Internet. Meanwhile, the resource requirements of digital computing and deep learning are growing exponentially, in an unsustainable manner. One possible way to bridge this gap is the adoption of resource-efficient brain-inspired "neuromorphic" processing and sensing devices, which use event-driven, asynchronous, dynamic neurosynaptic elements with colocated memory for distributed processing and machine learning. However, since neuromorphic systems are fundamentally different from conventional von Neumann computers and clock-driven sensor systems, several challenges are posed to large-scale adoption and integration of neuromorphic devices into the existing distributed digital-computational infrastructure. Here, we describe the current landscape of neuromorphic computing, focusing on characteristics that pose integration challenges. Based on this analysis, we propose a microservice-based conceptual framework for neuromorphic systems integration, consisting of a neuromorphic-system proxy, which would provide virtualization and communication capabilities required in distributed systems of systems, in combination with a declarative programming approach offering engineering-process abstraction. We also present concepts that could serve as a basis for the realization of this framework, and identify directions for further research required to enable large-scale system integration of neuromorphic devices.

Reading Alterations in Parkinson's Disease Indicate Worse Cognitive Status.

Background: Reading difficulties are commonly reported in Parkinson's disease (PD). So far, only a few studies have assessed reading in PD, most of them confirming a different pattern in patients compared with healthy populations. Impaired oculomotor control is an early feature of PD. Cognitive deficits, on the other hand, may appear early, but they are most prominent at later stages. Although these two factors are thought to be responsible for the alterations in reading performance, it is unclear how each factor contributes to them. Objectives: To evaluate eye movements during reading in PD and healthy controls (HCs). Methods: Data from 42 HCs (36% men) and 48 patients with PD (67% men) at Hoehn and Yahr stages ≤3 were analyzed. PD participants were further divided into 2 groups based on their Montreal Cognitive Assessment (MoCA) score using a cutoff of ≥26. Eye movements were recorded with Tobii Pro Spectrum, a screen-based eye tracker with a sampling rate of 1200 Hz. Results: PD participants performed fewer fixations per second (P = 0.033), with a longer mean (P = 0.037) and standard deviation fixation duration (P = 0.033) than HC, and further analysis showed that only patients with a lower MoCA score performed worse than HCs. Reading parameters were weakly associated with MoCA scores, irrespective of age and education. Conclusion: Changes in the reading pattern of PD patients are probably attributed to cognitive rather than pure oculomotor alterations.

Pupil light reflex dynamics in Parkinson's disease.

Introduction: Visual disturbance is common symptom in Parkinson's disease (PD), and defective pupil light reflex (PLR) is an anticipated contributing factor that may be associated to the presence of autonomic dysfunction, which is a common non-motor feature of PD. Studies investigating the intercorrelation between PLR and dysautonomia in PD are limited. Methods: The aim of this study was to investigate differences of PLR parameters, measured by eye-tracker, between patients with PD, with and without signs of dysautonomia, and healthy controls (HC). In total, 43 HC and 50 patients with PD were recruited and PLR parameters were measured with Tobii Pro Spectrum, during a long (1,000 ms) and a short (100 ms) light stimulus. Presence of orthostatic hypotension (OH) was used as proxy marker of dysautonomia. Linear mixed-effects model and non-parametric comparative statistics were applied to investigate differences among groups. Results: Peak constriction velocity was slower in PD compared with HC, after adjustment for age and sex in the mixed model, and the difference was greater in the subgroup of PD with OH (unadjusted). Dilation amplitude and velocity were also gradually slower in HC vs. PD without OH vs. PD with OH (unadjusted for confounders). In the mixed model, age was significant predictor of dilation response. Discussion: Our results support previous observations on defective PLR in PD, evaluated with eye-tracker, and show a possible association with autonomic dysfunction. Further studies with more patients and rigorous evaluation of autonomic dysfunction are needed to validate these findings.

Nicotinamide Prevents Retinal Vascular Dropout in a Rat Model of Ocular Hypertension and Supports Ocular Blood Supply in Glaucoma Patients.

Purpose: To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma. Methods: This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA. Results: A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment. Conclusions: NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.

Eye Movements during Reading and their Relationship to Reading Assessment Outcomes in Swedish Elementary School Children.

The characteristics of children's eye movements during reading change as they gradually become better readers. However, few eye tracking studies have investigated children's reading and reading development and little is known about the relationship between reading- related eye movement measures and reading assessment outcomes. We recorded and analyzed three basic eye movement measures in an ecologically valid eye-tracking set-up. The participants were Swedish children (n = 2876) who were recorded in their normal school environment. The relationship between eye movements and reading assessment outcomes was analyzed in using linear mixed effects models. We found similar age-related changes in eye movement characteristics as established in previous studies, and that eye movements seem to correlate with reading outcome measures. Additionally, our results show that eye movements predict the results on several tests from a word reading assessment. Hence eye tracking may potentially be a useful tool in assessing reading development.

Anophthalmia and microphthalmia in children: associated ocular, somatic and genetic morbidities and quality of life.

PURPOSE: To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M). METHODS: Thirty-five children (19 boys) with A/M underwent ophthalmological examinations and a review of medical records. Parents of 12/22 cases completed the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Age at examination ranged from 7 months to 18 years (median 2.3 years). Ten cases were totally blind or had light perception. Isolated A/M occurred in 16/35 cases, while somatic, psychomotor, neuroradiological and/or genetic pathology occurred in 19/35 cases both in the bilateral (7/9) and in the unilateral group (12/26). Among 26 unilateral cases, 4/16 with one normal eye had associated problems compared to 9/10 if the contralateral eye was pathological (p < .01). There was an increased risk for heart defects in children with psychomotor delay (p = .04). Pathogenic genetic abnormalities were identified in 10/24 cases. Neuroimaging demonstrated pathology in 14/20 cases with corpus callosum dysgenesis (6/20) being the most common. The median total PedsQL score of parent reports for ages 2-12 was 52.4 (range 22.6-100). CONCLUSIONS: Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.

Optical Coherence Tomography Can Predict Visual Acuity in Children with Optic Nerve Hypoplasia.

Purpose: Optic nerve hypoplasia (ONH) is a common cause of visual impairment in children. Clinical complexity can cause diagnostic delay and difficulties predicting visual outcome. We evaluated whether optical coherence tomography (OCT) can improve the diagnosis and prediction of vision. Methods: Thirty-seven eyes with ONH from 12 girls and 8 boys, median age 10.5 years (range 2.8-18.9 years), were included in this cross-sectional cohort study. The majority, 17/20, had bilateral ONH. Ophthalmological assessments included best corrected visual acuity (BCVA), fundus photography, measurement of the peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (GCC), Bruch's membrane opening (BMO) and visual fields. We compared OCT parameters with comparison data collected on 140 healthy individuals 5 to 25 years old. Pearson's correlation coefficient was used to determine the correlation of OCT parameters and BCVA. Results: OCT demonstrated thinner mean pRNFL (p < 0.001) and mean GCC compared to the reference material (p < 0.001). BCVA displayed a strong or moderate correlation to pRNFL and to all sectors of the GCC except the inferotemporal. BCVA correlated strongly to Bruch's membrane opening (BMO) (0.71, p < 0.001), and moderately to the Zeki ratio (-0.52, p < 0.001). Multivariate analyses showed that BMO explained 48% of the variance in BCVA. Visual fields correlated strongly to pRNFL and GCC thickness. GCC thinning corresponded to visual field defects presence and location. Conclusion: OCT can facilitate the diagnosis of ONH. Parameters such as pRNFL, GCC and BMO can be predictors of visual acuity whereas GCC and pRNFL thinning can indicate location and severity of visual field defects.

Visual outcome, ocular findings, and visual quality of life in patients with Fabry disease.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal disease, in which diagnosis is often established several years after onset of symptoms. Ocular manifestations can occur in childhood and be a clue to earlier diagnosis. The aim was to report ocular outcome and visual quality of life (QoL) in patients with FD. MATERIAL AND METHODS: FD-patients recruited from Karolinska University Hospital underwent ophthalmological examinations including best corrected visual acuity (BCVA), refraction, biomicroscopy, optical coherence tomography, keratometry, review of medical records and QoL Inventories. A total severity score (TSS), as estimated via Fabry Stabilization Index, was calculated. RESULTS: Twenty-six FD-patients (16 men) mean age 36.4 years (range 5.0-63.5 years) were included. BCVA was median 1.0 (range 0.5-1.6). Conjunctival blood vessel tortuosity occurred in 15/26 patients, chemosis in 2/26 patients, cornea verticillata in 23/26 patients, lens opacities in 19/26 patients, and tortuous or dilated retinal vessels in 20/25 patients. Group-wise comparisons of adult patients showed no differences regarding age, TSS, or ocular parameters. Overall, TSS was correlated to age (r = 0.53, p = 0.02). A linear regression model showed that age and sex explained 38% of the variance in TSS. Keratometry did not reveal corneal ectasia in any of the 12 patients examined. VFQ 25 in 15 patients showed a high median composite score, 93.6 (range: 78.1-100). CONCLUSIONS: BCVA in FD-patients was good despite corneal and lens pathology. Ocular variables did not show an association with TSS in adult patients. Corneal or lens opacities should also lead to a suspicion of FD in children.

Synaptic Delays for Insect-Inspired Temporal Feature Detection in Dynamic Neuromorphic Processors.

Spiking neural networks are well-suited for spatiotemporal feature detection and learning, and naturally involve dynamic delay mechanisms in the synapses, dendrites, and axons. Dedicated delay neurons and axonal delay circuits have been considered when implementing such pattern recognition networks in dynamic neuromorphic processors. Inspired by an auditory feature detection circuit in crickets, featuring a delayed excitation by post-inhibitory rebound, we investigate disynaptic delay elements formed by inhibitory-excitatory pairs of dynamic synapses. We configured such disynaptic delay elements in the DYNAP-SE neuromorphic processor and characterized the distribution of delayed excitations resulting from device mismatch. Interestingly, we found that the disynaptic delay elements can be configured such that the timing and magnitude of the delayed excitation depend mainly on the efficacy of the inhibitory and excitatory synapses, respectively, and that a neuron with multiple delay elements can be tuned to respond selectively to a specific pattern. Furthermore, we present a network with one disynaptic delay element that mimics the auditory feature detection circuit of crickets, and we demonstrate how varying synaptic weights, input noise and processor temperature affect the circuit. Dynamic delay elements of this kind open up for synapse level temporal feature tuning with configurable delays of up to 100 ms.

Formation of reactive oxygen species by human and bacterial pyruvate and 2-oxoglutarate dehydrogenase multienzyme complexes reconstituted from recombinant components.

Individual recombinant components of pyruvate and 2-oxoglutarate dehydrogenase multienzyme complexes (PDHc, OGDHc) of human and Escherichia coli (E. coli) origin were expressed and purified from E. coli with optimized protocols. The four multienzyme complexes were each reconstituted under optimal conditions at different stoichiometric ratios. Binding stoichiometries for the highest catalytic efficiency were determined from the rate of NADH generation by the complexes at physiological pH. Since some of these complexes were shown to possess 'moonlighting' activities under pathological conditions often accompanied by acidosis, activities were also determined at pH 6.3. As reactive oxygen species (ROS) generation by the E3 component of hOGDHc is a pathologically relevant feature, superoxide generation by the complexes with optimal stoichiometry was measured by the acetylated cytochrome c reduction method in both the forward and the reverse catalytic directions. Various known affectors of physiological activity and ROS production, including Ca(2+), ADP, lipoylation status or pH, were investigated. The human complexes were also reconstituted with the most prevalent human pathological mutant of the E3 component, G194C and characterized; isolated human E3 with the G194C substitution was previously reported to have an enhanced ROS generating capacity. It is demonstrated that: i. PDHc, similarly to OGDHc, is able to generate ROS and this feature is displayed by both the E. coli and human complexes, ii. Reconstituted hPDHc generates ROS at a significantly higher rate as compared to hOGDHc in both the forward and the reverse reactions when ROS generation is calculated for unit mass of their common E3 component, iii. The E1 component or E1-E2 subcomplex generates significant amount of ROS only in hOGDHc; iv. Incorporation of the G194C variant of hE3, the result of a disease-causing mutation, into reconstituted hOGDHc and hPDHc indeed leads to a decreased activity of both complexes and higher ROS generation by only hOGDHc and only in its reverse reaction.

Proportional hazards modeling of saccadic response times during reading.

In this article we use proportional hazards models to examine how low-level processes affect the probability of making a saccade over time, through the period of fixation, during reading. We apply the Cox proportional hazards model to investigate how launch distance (relative to word beginning), fixation location (relative to word center), and word frequency affect the hazard of a saccadic response. This model requires that covariates have a constant impact on the hazard over time, the assumption of proportional hazards. We show that this assumption is not supported. The impact of the covariates changes with the time passed since fixation onset. To account for the non-proportional hazards we fit step functions of time, resulting in a model with time-varying effects on the hazard. We evaluate the ability to predict the timing of saccades on held-out fixation data. The model with time-varying effects performs better in predicting the timing of saccades for fixations as short as 100 ms and as long as 500 ms, when compared both to a baseline model without covariates and a model which assumes constant covariate effects. This result suggests that the time-varying effects model better recovers the time course of low-level processes that influence the decision to move the eyes.

Long-time-storage mechanism for Tm:YAG in a magnetic field.

We obtained a long-time-storage mechanism for spectral features in thulium ions doped into YAG by applying a magnetic field that splits the electronic ground state. We show experimentally that the storage time can be more than 30 s, which is 3 orders of magnitude longer than that of the metastable state that normally is used for information storage in this material. Level splitting and storage lifetimes for various magnetic field strengths of as much as 5 T were investigated. This storage mechanism will be relevant in the many coherent transient-based signal-processing schemes in which Tm:YAG is being used, and we demonstrate long-time storage in a basic data storage application.