Excessive Running Research Articles

New methodology for identifying sustainable freshwater resources for the production of green hydrogen

ABSTRACT Managing sustainable and digital transformations in the water industry is a challenge. The identification of freshwater resources for green hydrogen production is necessary for the energy transition away from fossil fuels such as oil and gas. This can be achieved through the sustainable flood retention basin (SFRB) concept for identifying optimal locations for the retention of surface water. This unbiased concept helps in conflict resolution between stakeholders with water rights. Moreover, it serves as a simple tool to produce a digital water supply atlas based on dimensionless parameters with the short names’ population density, location advantage, precipitation, groundwater level, water rights, SFRB, excess running water and proximity to networks. While the first five parameters can be determined during a desk study, the last three parameters require site visits for verification purposes. Germany was used as a representative case study country to demonstrate the proposed methodology to obtain a water atlas based on mapped weighted values. The Kaiserstuhl in Germany served as a worked calculation example indicating well above average potential for water storage using existing retention basins. The water atlas can be used to supplement a (green) hydrogen atlas, supporting decision-makers in building hydrogen infrastructure.

Impact of anti-gravity muscle training protocol on plantar pressure, pain threshold and foot posture on chronic painful heel: an RCT study

Abstract Chronic painful heel (CPH) is a symptom of an underlying condition caused due to obesity, excessive foot pronation, tightness of Tendo-Achilles (TA), excessive running, and sedentary life. The antigravity muscles (AGM) atrophy results due to long working hours in sitting, leading to their deteriorating relationship with gravity thereby reduced sensitivity to its force. Hence, need arises to explore training effects of AGM protocol on CPH condition. A randomised controlled trial was conducted on thirty individuals with CPH allocated randomly to two study groups viz. AGMT (n = 15) and Control group (n = 15) who received intervention for twelve sessions over four weeks. Control group received conventional physiotherapy in form of therapeutic ultrasound and exercises while AGMT received conventional physiotherapy using the AGMT protocol. Outcomes assessed were plantar pressure and foot posture assessed using Harris mat, muscle strength by dynamometer, pain threshold with pressure algometer, and foot functions using Foot and Ankle Ability Measure Scale (FAAM) which were taken at pre- and post-training. The between group analysis of data revealed that foot posture, plantar pressure and muscle strength, pain threshold were significantly better in the AGMT group than in the Control group ( 0.0001), while pain intensity (P = 0.3952) and foot functions (P = 0.2372) were equally effective in both the study groups. In conclusion, the AGMT protocol along with conventional physiotherapy proved to be a promising training protocol for individuals with CPH showing positive outcomes in comparison to conventional therapy alone, suggesting to incorporate AGM strengthening alongside conventional therapy to obtain better clinical outcomes. Trial registration: This trial was prospectively registered in the Clinical trial registry of India with registration number CTRI/2022/10/046138.

Spork: Structured Merge for Java With Formatting Preservation

The highly parallel workflows of modern software development have made merging of source code a common activity for developers. The state of the practice is based on line-based merge, which is ubiquitously used with "git merge". Line-based merge is however a generalized technique for any text that cannot leverage the structured nature of source code, making merge conflicts a common occurrence. As a remedy, research has proposed structured merge tools, which typically operate on abstract syntax trees instead of raw text. Structured merging greatly reduces the prevalence of merge conflicts but suffers from important limitations, the main ones being a tendency to alter the formatting of the merged code and being prone to excessive running times. In this paper, we present SPORK, a novel structured merge tool for JAVA. SPORK is unique as it preserves formatting to a significantly greater degree than comparable state-of-the-art tools. SPORK is also overall faster than the state of the art, in particular significantly reducing worst-case running times in practice. We demonstrate these properties by replaying 1740 real-world file merges collected from 119 open-source projects, and further demonstrate several key differences between SPORK and the state of the art with in-depth case studies.

Optimizing Two-Truck Platooning With Deadlines

We study a transportation problem where two heavy-duty trucks travel across the national highway from separate origins to destinations, subject to individual deadline constraints. Our objective is to minimize their total fuel consumption by jointly optimizing path planning, speed planning, and platooning configuration. Such a two-truck platooning problem is pervasive in practice yet challenging to solve due to hard deadline constraints and enormous platooning configurations to consider. We first leverage a unique problem structure to significantly simplify platooning optimization and present a novel formulation. We prove that the two-truck platooning problem is weakly NP-hard and admits a Fully Polynomial Time Approximation Scheme (FPTAS). The FPTAS can achieve a fuel consumption within a ratio of <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$(1+\epsilon)$ </tex-math></inline-formula> to the optimal (for any <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\epsilon &gt;0$ </tex-math></inline-formula> ) with a time complexity polynomial in the size of the transportation network and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$1/\epsilon $ </tex-math></inline-formula> . These results are in sharp contrast to the general multi-truck platooning problem, which is known to be APX-hard and repels any FPTAS. As the FPTAS still incurs excessive running time for large-scale cases, we design an efficient dual-subgradient algorithm for solving large-/national- scale instances. It is an iterative algorithm that always converges. We prove that each iteration only incurs polynomial-time complexity, albeit it requires solving an integer linear programming problem optimally. We characterize a condition under which the algorithm generates an optimal solution and derive a posterior performance bound when the condition is not met. Extensive simulations based on real-world traces show that our joint solution of path planning, speed planning, and platooning saves up to 24% fuel as compared to baseline alternatives.

Sensitivity analysis of nonlinear frequency response of defected structures

The computation of the steady-stateresponse of large finite element discretized systems subject to periodic excitations is unfeasible because of excessive run time and memory requirements. One could in principle resort to reduced order models stemming from the high fidelity counterparts, which typically require a solution time orders of magnitude smaller. However, when many simulations are required, as in the case of parametric studies, the overall effort could be still significant and the analysis process could be severely hindered. In this work, we propose a sensitivity approach to assess the influence of model parameters on the nonlinear dynamic response. As opposed to the costly evaluation of reduced order solutions over a range of excitation frequencies and model parameters, the sensitivities of a nominal response allow one to approximate the dynamic response by a simple evaluation of an expansion in the directions spanning the parameter space. Special care must be taken on the closure equation that needs to be appended to the system of equations stemming from the harmonic balance method. We discuss the limitations of the current constant frequency approach and propose an improvement. We demonstrate the merits of the proposed approach on a micro-electro-mechanical system affected by parameterized manufacturing defects. Leveraging from a previous contribution, the nonlinear response and the sensitivities are obtained from a reduced order model which is analytical in the defect parameters. Our procedure is able to deliver accurate probability density functions of quantities of interest (e.g. nonlinear resonance peaks, triple solution bandwidth, etc) against statistical distributions of manufacturing defects at negligible computational cost.

The Missing Link in Running Injury Research: Nonrunning Physical Activity.

SYNOPSIS: Overuse injuries from running occur when the loading stimulus exceeds the tissue-specific loading capacity. Excessive running exposure (training errors) are important precursors to injury. Despite the intuitive relationship between loading, running volume, and injury, a definitive safe loading exposure that can reliably differentiate between injured and uninjured groups remains elusive. We propose that a singular focus on running-related factors such as gait, running surface change, sudden change in running volume, frequency of running, and acute-to-chronic workload make it difficult to identify reliable mechanisms of loadrelated running injury. Given that the accumulated loading from nonrunning exercise and physical activities of daily living can impose substantial and consequential load on the musculoskeletal system, we make the case for considering loading from all sources of physical activity as a contributor to running injury. J Orthop Sports Phys Ther 2022;52(11):705-708. Epub: 9 September 2022. doi:10.2519/jospt.2022.11288.

Micellar and sub-micellar chromatography with a cocamidopropyl betaine surfactant

We have coated a typical C18 column with the pH cationic charge controllable zwitterionic synthetic surfactant, cocamidopropyl betaine (CAPB), in order to generate a mixed mode reversed phase weak ion exchange column. As determined by the Thomas model, the column has an adsorbed surfactant capacity of 0.557 mmoles. The addition of 8.8 × 10–4 M CAPB to the totally aqueous mobile phase ensured stability of the surfactant on the column and permitted separation of the four component sulfonamide mixture with micellar liquid chromatography (MLC) in under 11 min. Comparatively, with a dilute H2SO4 mobile phase with no CAPB, the separation time for the sulfonamide mixture reached an excessive run time of an hour on the bare C18 chains. With CAPB in the mobile phase (no organic solvent present), a seven component sulfonamide mixture could be separated in less than 45 min. A five component short chain carboxylic acid mixture, separated in 20 min, was used to examine the ion exchange character of the column in pH environments of 2.3 and 4.6. Three phase MLC equilibrium analysis was also done in these pH environments with the sulfa drug and carboxylic acid mixtures to determine partition coefficients. Finally, a quite high molecular weight (70,000) anionic polystyrene sulfonate polymer was characterized by MLC with only CAPB and variable pH mobile phases; the optimal pH was determined to be 5.6. A totally aqueous mobile phase without CAPB was not suitable for profiling this polymer.

Development of a numerical model for braided river morphology and vegetation evolution with application to the Lower Waitaki River (Aotearoa – New Zealand)

In this paper we develop a two-dimensional modelling framework suitable to study the morphological evolution of vegetated braided rivers. The mathematical model features a unisize-sediment morphological model, which includes accounting for bank erosion, and a vegetation model. While these model components had already appeared separately in different contexts, here we improve and tailor them for modelling vegetated braided river dynamics. We implement a numerical solution to this problem in the framework of the pre-existing morphological model GIAMT2D. We devise a hydrograph-splitting technique to avoid excessive run times in the multi-decadal applications needed to appreciate vegetation-driven morphological change. This hydrograph-splitting technique uses the full model to solve for flood periods, while applying a fixed-bed approximation and only updating vegetation density during low-flow periods. Finally, we apply the developed formulation, tools and techniques to simulate an idealised reach of the Lower Waitaki River (Aotearoa – New Zealand), where we reproduce vegetation encroachment and morphological change observed between 1936 and 1964.

Opioids in the medial nucleus of the solitary tract are not involved in feeding disorder in activity-based anorexia in rats

<h2>Summary</h2><h3>Background & aims</h3> Activity-based anorexia (ABA) is an abnormal behavior caused by mealtime restriction and excessive running. A previous study revealed that running causes the secretion of opioids in rats, and excessive opioids are known to decrease food intake. Thus, we hypothesized that the suppression of food intake in ABA rats that experienced mealtime restriction and excessive wheel running was due to an increase in opioids caused by running. Our previous study showed that ABA rats consumed more food than the control group after an intraperitoneal injection of naloxone. This result indicates that opioids are involved in the regulation of food intake in ABA rats. Here, we queried the involvement of the medial nucleus of the solitary tract (mNST) of the brain that mediates satiety information from the internal organs in rats' ABA and also examined whether opioids in the mNST were involved in feeding regulation in them. <h3>Methods</h3> Each ABA rat was given a running wheel and received feeding time restriction, followed by microinjection of naloxone or saline into the mNST. Each control rat was subjected to only feeding time restriction and then microinjection of naloxone or saline into the mNST. <h3>Results</h3> The results showed that food intake of the ABA group was not increased by naloxone injection into the mNST. <h3>Conclusions</h3> Our results suggest that the mNST is not involved in the regulation of food intake by opioids. Regulation of food intake by opioids may occur in other parts of the brain, such as the parabrachial nucleus and/or hypothalamus.

Automatic quadriceps and patellae segmentation of MRI with cascaded U2 -Net and SASSNet deep learning model.

Automatic muscle segmentation is critical for advancing our understanding of human physiology, biomechanics, and musculoskeletal pathologies, as it allows for timely exploration of large multi-dimensional image sets. Segmentation models are rarely developed/validated for the pediatric model. As such, autosegmentation is not available to explore how muscle architectural changes during development and how disease/pathology affects the developing musculoskeletal system. Thus, we aimed to develop and validate an end-to-end, fully automated, deep learning model for accurate segmentation of the rectus femoris and vastus lateral, medialis, and intermedialis using a pediatric database. We developed a two-stage cascaded deep learning model in a coarse-to-fine manner. In the first stage, the U2 -Net roughly detects the muscle subcompartment region. Then, in the second stage, the shape-aware 3D semantic segmentation method SASSNet refines the cropped target regions to generate the more finer and accurate segmentation masks. We utilized multifeature image maps in both stages to stabilize performance and validated their use with an ablation study. The second-stage SASSNet was independently run and evaluated with three different cropped region resolutions: the original image resolution, and images downsampled 2× and 4× (high, mid, and low). The relationship between image resolution and segmentation accuracy was explored. In addition, the patella was included as a comparator to past work. We evaluated segmentation accuracy using leave-one-out testing on a database of 3D MR images (0.43×0.43×2mm) from 40 pediatric participants (age 15.3 ± 1.9 years, 55.8 ± 11.8kg, 164.2 ± 7.9cm, 38F/2M). The mid-resolution second stage produced the best results for the vastus medialis, rectus femoris, and patella (Dice similarity coefficient=95.0%, 95.1%, 93.7%), whereas the low-resolution second stage produced the best results for the vastus lateralis and vastus intermedialis (DSC=94.5% and 93.7%). In comparing the low- to mid-resolution cases, the vasti intermedialis, vastus medialis, rectus femoris, and patella produced significant differences (p=0.0015, p=0.0101, p<0.0001, p=0.0003) and the vasti lateralis did not (p=0.2177). The high-resolution stage 2 had significantly lower accuracy (1.0 to 4.4 dice percentage points) compared to both the mid- and low-resolution routines (p value ranged from<0.001 to 0.04). The one exception was the rectus femoris, where there was no difference between the low- and high-resolution cases. The ablation study demonstrated that the multifeature is more reliable than the single feature. Our successful implementation of this two-stage segmentation pipeline provides a critical tool for expanding pediatric muscle physiology and clinical research. With a relatively small and variable dataset, our fully automatic segmentation technique produces accuracies that matched or exceeded the current state of the art. The two-stage segmentation avoids memory issues and excessive run times by using a first stage focused on cropping out unnecessary data. The excellent Dice similarity coefficients improve upon previous template-based automatic and semiautomatic methodologies targeting the leg musculature. More importantly, with a naturally variable dataset (size, shape, etc.), the proposed model demonstrates slightly improved accuracies, compared to previous neural networks methods.

Water electrification based triboelectric nanogenerator integrated harmonic oscillator for waste mechanical energy harvesting

Harvesting waste mechanical energy in the surroundings, especially from human and transportation activities, has a great potential for the forthcoming sustainable energy development. With the invention of triboelectric nanogenerators and owing to their universal design, lightweight, low cost, and high efficiency, it has given rise to the rapid growth of this research topic. Herein, an impulsive kinetic energy regulator is presented to convert the mechanical energy from impulse collision into electrical energy. A harmonic oscillator is utilized to regulate the interchange of input kinetic energy and stored potential energy during operation and, through the mechanical motion rectifier, engages the rotary solid–liquid TENG with excessive running time. The performance evaluation of the device is realized under two schemes including both a vertical and horizontal direction effort. As a result, the device can produce an output energy of 25.13 nJ with a maximum current density of 2.29nA·cm−2 concerning a single vertical incentive; whilst, the horizontal direction effort obtains an output energy of 25.43 nJ with a maximum current density of 2.41nA·cm−2. Moreover, the device can power up a few LEDs with human footstep excitation and a wireless-based sensor during boom barrier gate operation, which shows a good possibility in waste mechanical energy harvesting.

Mechanical stimulation of chondrocytes regulates HIF-1α under hypoxic conditions

We investigated the effects of hypoxia-inducible factor (HIF)-1α on articular cartilage under mechanical stimulation and the associated mechanisms. Chondrocytes, isolated from articular cartilage from the knee, hip, and shoulder joints of Wistar rats, were subjected to 20 % tensile stress under hypoxic (5% O2) conditions for 24 h. HIF-1α and aggrecan expression was significantly enhanced with mechanical stimulation under hypoxia but not significantly altered with mechanical stimulation under normoxia. The nuclear translocation of HIF-1α was enhanced by mechanical stress under hypoxia. Under both normoxia and hypoxia, a disintegrin and metalloproteinase with thrombospondin motifs (ADAM-TS) 5 expression was significantly reduced with mechanical stimulation compared to that in the group without mechanical stimulation. However, HIF-1α knockdown mitigated changes in aggrecan and ADAM-TS5 expression mediated by mechanical stimulation under hypoxia. The effects of treadmill running on HIF-1α production in the articular cartilage of rat knee joints were also analyzed. HIF-1α production increased in the moderate running group and decreased to the same levels as those in the control group in the excessive running group. This suggests that HIF-1α regulates aggrecan and ADAM-TS5 expression in response to mechanical stimulation under hypoxia and general mechanical stimulation in articular cartilage under hypoxia, while controlling cartilage homeostasis.

Design Abstraction Techniques in Chip Design

Reaching timing closure on multi-million gate VLSI chips using flat flow is infeasible due to hardware capacity limit, and excessive run time overheads. New flows and design implementations and design abstraction techniques need to be introduced to manage the scalability of design sizes by scaling down the memory usage and run time. Traditionally, the flat implementation of designs was used for smaller designs with maximum accuracy. Then the hierarchical approach was introduced to better the run time and handle the millions of gates by partitioning and assembling. Through this paper, we are going to look at the various implementation flows and like flat, traditional hierarchical, models, post assembly ECO, context views, feasibility flows . These models represent various levels of design abstractions used for modeling the chip state. We are also going to look at a advances in the technology of timing graph reduction and physical data reduction that enables new flow implementations and can be applied to both hierarchical and flat methodologies.

Hierarchical Methodology Approach to SOC Design: A Comprehensive Look

With the process node (CMOS transistor size) becoming increasingly smaller, there is an ever-increasing need for the software to handle the large gate count with faster turnaround time and better accuracy. Reaching timing closure on multi-million gate VLSI chips using flat flow is infeasible due to hardware capacity limit, and excessive run time overheads. New flows and design implementations need to be introduced to manage the scalability of design sizes by scaling down the memory usage and run time. Traditionally, the flat implementation of designs was used for smaller designs with maximum accuracy. Then the hierarchical approach was introduced to better the run time and handle the millions of gates by partitioning and assembling. Through this paper, we are going to look at the various implementation flows and its artifacts viz. flat, traditional hierarchical, models, post assembly ECO, context views, feasibility flows . We are also going to look at a advances in the technology of timing graph reduction and physical data reduction that enables new flow implementations and can be applied to both hierarchical and flat methodologies.

Rapid Topology Generation and Core Mapping of Optical Network-on-Chip for Heterogeneous Computing Platform

The explosive growth of deep learning (DL)–based artificial intelligence (AI) applications necessitates extraordinary computing capabilities that cannot be achieved using traditional CPU standalone computing. Therefore, the heavy mission-critical DL kernel computing currently relies on a heterogeneous computing (HGC) platform integrated with CPUs, GPUs, and accelerators, as well as substantial data storage elements. However, the metallic electrical interconnection in the existing manycore platform would not be sustainable for handling the massively increasing bandwidth demand of big data driven AI applications. Incorporating an optical network-on-chip (ONoC) for providing ultrahigh bandwidth, we propose a rapid topology generation and core mapping of ONoC (REGO) for energy-efficient HGC multicore architecture. The genetic algorithm (GA)-based REGO utilizes the structural characteristics of the optical router to the fitness function and thus compromises the trade-off between the required throughput, optical signal-to-noise ratio (OSNR), and total energy consumption. Furthermore, the crossover step accelerates the convergence speed by suppressing randomness in the GA, thus significantly reducing excessive running time owing to the NP-hard property. The generated ONoC through REGO demonstrates, on an average, an increase of 63.29 % and 22.80 % in throughput and a decrease of 50.24 % and 9.56 % in energy per bit, in the VGG-16 and VGG-19 compared with the conventional mesh- and torus-topology-based ONoCs, respectively.

Changes in running habits during the COVID-19 confinement in amateur distance runners

Introduction: In this study, we examined the impact of government measures being imposed to slow down the spread of COVID-19 pandemic on long-distance runners’ sports habits and well-being. Material and methods: Data from a total of 323 runners (mean age 41.72 (8.78), 41.8% male) were analysed using quantitative and qualitative methods. Results: 46.9% of runners changed their running habits during the pandemic, 20.4% partly changed it. The poorest psychological well-being was found in a group that changed previous habits. Only 9 individuals reported no running activity at all, and 10 trained on a treadmill instead of a field. Overall, our respondents ran significantly more during the quarantine than before, which is partly explained by changed working conditions, reduced working hours, or lost jobs. The explanatory variables of excess running were previous mileage and distress. Conclusions: Running is suitable for relieving distress and restoring the feeling of freedom. All of these were confirmed by our subjects in the survey interview.

The relationship between global positioning system variables and injury occurrences in female field hockey

The noncontact and soft-tissue injuries to lower extremities that occur as a result of excessive running loads are largely preventable. This study investigated the relationship between global positioning system variables and noncontact soft-tissue injuries in female field hockey players based on their position on the field. Fifty-two players enrolled in the Korea National Team were monitored using global positioning system units in game-based training and competitions. The measurements obtained were total distance covered, high-intensity running distance, work–rest ratio, meters per minute, repeated high-intensity effort bouts, maximal velocity, and acceleration and deceleration bouts. Noncontact soft-tissue injuries in lower extremities were documented throughout the same period. For measuring the absolute external workload of each global positioning system variable, players’ data were averaged for 1- and 4-week periods before they were injured (injury-related block), averaging values across 1 and 4 weeks before the injury-related block (non-injury block), as well as averaging values from the beginning of the data collection to the point of injury (total average). These blocks were compared to each other and to the corresponding total averages for the 1- and 4-week periods, depending on their position on the field. Of the 52 players, 28 players (8 forwards, 11 midfielders, and 9 defenders) injured their lower extremities for a total of 38 injuries. Of these injuries, 11 occurred in forwards, 17 occurred in midfielders, and 10 occurred in defenders with some players experiencing more than one injury. Different positions on the field have different global positioning system variables related to the occurrence of noncontact soft-tissue injuries in lower extremities, but there was a significant difference in global positioning system variable of injury-related block for only the 4-week period among their position on the field. Especially, increases in high-intensity running distance and repeated high-intensity effort bouts of defenders during the 4-week period were significantly related to the occurrence of injuries. To decrease the risk of injury in female field hockey players, different global positioning system variables should be monitored and modified in planned future training or competitions.

On the assimilation of environmental tracer observations for model-based decision support

Abstract. It has been advocated that history matching numerical models to a diverse range of observation data types, particularly including environmental tracer concentrations and their interpretations and derivatives (e.g., mean age), constitutes an effective and appropriate means to improve model forecast reliability. This study presents two regional-scale modeling case studies that directly and rigorously assess the value of discrete tritium concentration observations and tritium-derived mean residence time (MRT) estimates in two decision-support contexts; “value” is measured herein as both the improvement (or otherwise) in the reliability of forecasts through uncertainty variance reduction and bias minimization as a result of assimilating tritium or tritium-derived MRT observations. The first case study (Heretaunga Plains, New Zealand) utilizes a suite of steady-state and transient flow models and an advection-only particle-tracking model to evaluate the worth of tritium-derived MRT estimates relative to hydraulic potential, spring discharge and river–aquifer exchange flux observations. The worth of MRT observations is quantified in terms of the change in the uncertainty surrounding ecologically sensitive spring discharge forecasts via first-order second-moment (FOSM) analyses. The second case study (Hauraki Plains, New Zealand) employs paired simple–complex transient flow and transport models to evaluate the potential for assimilation-induced bias in simulated surface-water nitrate discharge to an ecologically sensitive estuary system; formal data assimilation of tritium observations is undertaken using an iterative ensemble smoother. The results of these case studies indicate that, for the decision-relevant forecasts considered, tritium observations are of variable benefit and may induce damaging bias in forecasts; these biases are a result of an imperfect model's inability to properly and directly assimilate the rich information content of the tritium observations. The findings of this study challenge the advocacy of the increasing use of tracers, and of diverse data types more generally, whenever environmental model data assimilation is undertaken with imperfect models. This study also highlights the need for improved imperfect-model data assimilation strategies. While these strategies will likely require increased model complexity (including advanced discretization, processes and parameterization) to allow for appropriate assimilation of rich and diverse data types that operate across a range of spatial and temporal scales commensurate with a forecast of management interest, it is critical that increased model complexity does not preclude the application of formal data assimilation and uncertainty quantification techniques due to model instability and excessive run times.

BiAb Mediated Restoration of the Linkage between Dystroglycan and Laminin-211 as a Therapeutic Approach for α-Dystroglycanopathies.

Patients with α-dystroglycanopathies, a subgroup of rare congenital muscular dystrophies, present with a spectrum of clinical manifestations that includes muscular dystrophy as well as CNS and ocular abnormalities. Although patients with α-dystroglycanopathies are genetically heterogeneous, they share a common defect of aberrant post-translational glycosylation modification of the dystroglycan alpha-subunit, which renders it defective in binding to several extracellular ligands such as laminin-211 in skeletal muscles, agrin in neuromuscular junctions, neurexin in the CNS, and pikachurin in the eye, leading to various symptoms. The genetic heterogeneity associated with the development of α-dystroglycanopathies poses significant challenges to developing a generalized treatment to address the spectrum of genetic defects. Here, we propose the development of a bispecific antibody (biAb) that functions as a surrogate molecular linker to reconnect laminin-211 and the dystroglycan beta-subunit to ameliorate sarcolemmal fragility, a primary pathology in patients with α-dystroglycan-related muscular dystrophies. We show that the treatment of LARGEmyd-3J mice, an α-dystroglycanopathy model, with the biAb improved muscle function and protected muscles from exercise-induced damage. These results demonstrate the viability of a biAb that binds to laminin-211 and dystroglycan simultaneously as a potential treatment for patients with α-dystroglycanopathy.

SUPPLEMENTAL VITAMIN D FOR PREVENTION OF BONE STRESS INJURIES IN COLLEGIATE ATHLETES

Purpose: Vitamin D functions to regulate serum calcium concentrations via several cellular pathways. It has also been demonstrated to affect bone mineralization and turnover, thus making it essential for skeletal strength and adaptation to mechanical stress. Stress fractures are common athletic injuries formed by cyclic, repetitive skeletal loading that causes physical breakdown of the bone’s microstructure. Excessive running or jumping, coinciding with additional factors such as malnutrition or decreased sun exposure, may elevate an athlete’s risk for sustaining this overuse injury. Serum 25(OH)D is used as a clinical marker for vitamin D status. Previous research suggests adequate vitamin D status is important for prevention of skeletal injuries. Our hypothesis states that supplemental vitamin D will normalize athletes’ vitamin D status and will reduce stress fracture injury incidence rates for elite division 1 athletes. Methods: Prospective 245 subjects were recruited from 17 sports teams at the university. All subjects were over 18 years of age. No subjects were excluded. Subject 25(OH)D status was determined twice; once in August 2016, and again in February 2017. Following each testing cycle, subjects with 25(OH)D levels below 70 ng/ml were supplemented with cholecalciferol (50,000 IU) once a week for 8 weeks. Subjects were then monitored throughout their respective sporting seasons for stress fractures or other overuse skeletal injuries. Subjects initially completed an anthropometric questionnaire, and two compliance questionnaires were to be completed following each 8-week supplementation period. Retrospective: Athlete injury reports from each of the 17 teams will be used as a control to determine the incidence of stress fractures during the 2011-2015 seasons among non-supplemented athletes. Results: 245 subjects had 25(OH)D levels tested in August (40.4?14.3 ng/ml) with 18% being insufficient or deficient (&lt;30 ng/ml). 191 subjects were tested in February (27.7?8.85 ng/ml) with 65% being insufficient or deficient, a significant decrease. All but three teams had significantly lower 25(OH)D levels in February compared to August. There was no significant difference between male and female athletes, however both groups saw significant declines in February. There was no significant difference between indoor and outdoor sports in August and February. 2 stress injuries were diagnosed in 118 enrolled subjects in our previous arm (1.65%). 2 additional stress injuries were diagnosed in 191 remaining subjects in our current arm (1.0%). 36 stress fractures were diagnosed in 571 subjects retrospectively (6.3%). Conclusion: Several factors have been shown to influence vitamin D status, including nutrition and sun exposure. Serum 25(OH)D status is expected to decline naturally in winter months due to lack of sun exposure. Results indicate a substantial decline in serum 25(OH)D from August to February in our cohort. This supports the notion that continued supplementation may be necessary to maintain appropriate vitamin D levels. The incidence of stress fractures per year as well as the proportion of stress fractures per academic year have consistently declined as more attention is paid toward vitamin D supplementation.