A Novel Role for MAPKAPK2 in Morphogenesis during Zebrafish Development

One of the earliest morphogenetic processes in the development of many animals is epiboly. In the zebrafish, epiboly ensues when the animally localized blastoderm cells spread, thin over, and enclose the vegetally localized yolk. Only a few factors are known to function in this fundamental process. We identified a maternal-effect mutant, betty boop (bbp), which displays a novel defect in epiboly, wherein the blastoderm margin constricts dramatically, precisely when half of the yolk cell is covered by the blastoderm, causing the yolk cell to burst. Whole-blastoderm transplants and mRNA microinjection rescue demonstrate that Bbp functions in the yolk cell to regulate epiboly. We positionally cloned the maternal-effect bbp mutant gene and identified it as the zebrafish homolog of the serine-threonine kinase Mitogen Activated Protein Kinase Activated Protein Kinase 2, or MAPKAPK2, which was not previously known to function in embryonic development. We show that the regulation of MAPKAPK2 is conserved and p38 MAP kinase functions upstream of MAPKAPK2 in regulating epiboly in the zebrafish embryo. Dramatic alterations in calcium dynamics, together with the massive marginal constrictive force observed in bbp mutants, indicate precocious constriction of an F-actin network within the yolk cell, which first forms at 50% epiboly and regulates epiboly progression. We show that MAPKAPK2 activity and its regulator p38 MAPK function in the yolk cell to regulate the process of epiboly, identifying a new pathway regulating this cell movement process. We postulate that a p38 MAPKAPK2 kinase cascade modulates the activity of F-actin at the yolk cell margin circumference allowing the gradual closure of the blastopore as epiboly progresses

Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs

A Data-Driven Approach for Estimating Postural Control Using an Inertial Measurement Unit

In this paper, we propose a probabilistic multi-Gaussian parameter estimation technique which addresses the complex relationship between acceleration and ground force signals used to derive a human’s static center of pressure. The intent of this work is to develop an accurate accelerometer-based method for determining postural control and neuromuscular status which is more portable and cost-effective than force plate-based techniques. Acceleration data was collected using an inertial measurement unit while ground reaction forces were simultaneously measured using a force plate. Various metrics were calculated from both sensors and probabilistic data models were built to characterize the relationships between the two sensors. These models were used to predict force-based postural control metrics corresponding to observed acceleration metrics. Data collected from one participant was used as a training set to which the test data of two individuals were then applied. We conclude that converted acceleration-based metrics on average can accurately predict all the corresponding force-based metrics we studied here. Furthermore, the proposed multi-Gaussian parameter estimation approach outperforms a more basic linear transformation technique for 75% of the metrics studied, as evidenced by an increase in correlation coefficients between true and estimated force plate metrics

Probabilistic Estimation of Posture Metrics using Novel Loadsols

This paper presents an original technique for estimating human posture metrics using Novel Loadsols®. Under the proposed technique, center of pressure (COP) metrics are derived by combining physics- and data-driven estimates to achieve reasonably high accuracy at relatively low cost. To develop a training set upon which the probabilistic data model was constructed, 79 trials were conducted in which participants stood comfortably still for 30 seconds at a time simultaneously on a force plate and a pair of Loadsols, where the force plate is considered to be the gold-standard of COP measurement. These data were then used to generate Gaussian mixture models (GMMs) of pairwise combinations of force plate and Loadsol metrics. The GMMs can then be conditioned on Loadsol measurements and fused using Bayesian inference. When the training set was re-processed by converting 12 Loadsol metrics into estimated force plate metrics, it was found that the converted metrics matched ground-truth more accurately on average than raw Loadsol metrics. Furthermore, there was improvement in the r2 values of the regression lines after conversion for 75% of the metrics. Given some experiment and algorithm refinement, the proposed probabilistic approach has potential to offer the accuracy of force plate COP estimation at a fraction of the cost

A Broader Look at The Role of Andragogy in Engineering Education

The word pedagogy is commonly used to describe teaching techniques and practices; however, the root of the word actually denotes ‘leading’ or teaching children. The assumptions inherent in this description may be incompatible with the desired outcomes and goals in undergraduate engineering education. This work builds on previous effort which explored whether the term andragogy, translated as ‘leading man’ or the education of adults, is a more appropriate term to achieve the outcomes of engineering educators and engineering societies. The previous paper used a case study approach to explore documents related to mechanical engineering and the guiding documents of one mechanical engineering program and its key stakeholders. The work showed that there was a disconnect between the term pedagogy and the attributes required of mechanical engineers and desired of graduates of the program, particularly when it came to assumptions about the nature of the students. The purpose of this paper is to expand upon the previous mechanical engineeringcentered single case study and determine the applicability of andragogical learner assumptions to additional engineering disciplines and programs. This study examines the guiding literature of various engineering disciplines for evidence to support an andragogical orientation toward undergraduate students. In addition, the study examines strategic documents associated with multiple engineering programs to explore whether the findings of the single case study could transfer to other engineering program related contexts. Finally, the study steps beyond engineering programs to examine emerging andragogical literature. This literature survey provides engineering educators a glimpse into the next evolution of how an andragogical approach to undergraduate learners may be applied to the engineering education enterprise and accommodate more than just older, more experienced learners

Andragogical Learning Characteristics in Second-year and Fourth-year Mechanical

According to the ABET, the goal of an undergraduate mechanical engineering program is to prepare students to work professionally in the fields of thermal and mechanical systems. As a part of the accreditation process, ABET requires programs to demonstrate how their students are able to acquire knowledge as life-long learners. Employers are interested in new graduates with the ability to think critically and work independently, which aligns well with adult learner characteristics often referred to as andragogy. Previous work on an examination of stakeholder documents and the purpose statements of undergraduate institutions also portrays a desire to create graduates with an andragogical mindset, despite the relative absence of the use of the term andragogy in engineering education literature. Pembridge developed a pilot instrument to measure andragogical constructs utilizing different instruments directly measuring the theoretical frameworks supporting assumptions of adult learning, while also comparing responses from firstyear and fourth-year engineering students.1 He found significant differences between the two year groups of engineering students, with fourth-year students having improved ability at selfdirected learning and a stronger sense of adulthood. It is unknown how these results apply to a cadet population, where increased structure and additional military training may influence learning characteristics. The purpose of this research is to investigate the learning characteristics of United States Military Academy students enrolled in the mechanical engineering major. We surveyed students in a second year design course and a fourth year capstone design course to better understand the progression from a pedagogical to an andragogical learning orientation. Survey data was collected from n = 58 (out of 85 total enrolled) second-year and n = 62 (out of 99 total enrolled) fourth-year mechanical engineering students. The survey used was a slightly modified version from1, which drew upon previous instruments aligned with assumptions of andragogy. This survey provides insight in Self-Directed Learning Dimensions Scale (SDLAS), Inventory of the Dimensions of Emerging Adulthood (IDEA), Epistemological Beliefs Assessment for Engineering (EBAE), Engineering Expectancy and Value Scale (EV), and Engineering Design Self-Efficacy. The results of this study contrast the andragogical orientations of second- and fourth-year students at the United States Military Academy. The results of this work allow engineering educators to better understand the current learning states of their students by expanding the contexts within which andragogical learning assumptions are applied. As a result, faculty may be more informed in curriculum decisions to fit the preponderant learning orientation. This work also allows engineering educators to identify strategies to better align undergraduate engineering students with the adult learning characteristics required in professional practice

Accuracy of Wireless Sensors for Treadmill Walking and Running in Combat Boots

The purpose of this study was to validate the accuracy of MilestonePod (MSP) wireless running sensors and IMeasureU inertial measurement units with custom algorithms (IMU) for subjects wearing combat boots while walking and running. Results indicate that in general, the IMU demonstrates large inaccuracies for both running and walking, while the MSP demonstrates large inaccuracies for walking, but is reasonably accurate for three of the four variables studied while running

A Novel Method for Evaluating Loading Rate During Running Regardless of Impact Peak

Recently there has been a focus on the relationship between the characteristics of the vertical ground reaction force (vGRF) and running injury occurrence. [1,2] AVLR is defined as the slope of the vGRF-time curve following initial contact. There are several methods for computing AVLR in the literature, however, the 20-80% method can only be calculated in the presence of an impact peak, [3] typically only associated with a rearfoot strike pattern. Additionally, the 3-12% method is unreliable when the impact peak occurs earlier than 12% of stance phase. This presents a problem when computing, interpreting and comparing research findings amongst runners with different foot strike patterns. To our knowledge, no study has described a method that can evaluate AVLR regardless of time or occurrence of the impact peak. The purpose of this study was to introduce the 3-12% auto method for calculating AVLR and compare it to the 3-12% and 20-80% methods

Gait Retraining Improves Loading Asymmetry, Pain, and Running Function after Anterior Cruciate Ligament Reconstruction

Return to sport rates are low following anterior cruciate ligament reconstruction (ACLR), with 63% resuming pre-injury level of activity and only 44% returning to competitive sport.1 The risk of poor outcome may be related to deficits in muscle strength2 and altered limb loading strategies during jumping, running, and landing activ-ities3,4 that are noted following return to high-level activity. Running with a non–rearfoot strike (NRFS) pattern may assist post-ACLR patients by reducing average vertical loading rate (AVLR), reducing braking forces, and reducing negative knee extensor work.5 The purpose of this study was to describe a return to run program that attempted to alter running form in individuals following ACLR and examine several parameters over time that may reduce their risk of poor outcom

A Non-Rearfoot Strike Transition Program Improves Loading, Pain, and Function in Runners Recovering from Lower-Extremity Injury

Rearfoot strike (RFS) runners have demonstrated greater average vertical loading rates (AVLR), reduced cadence, and greater incidence of repetitive stress injuries than runners using a non-rearfoot strike (NRFS) pattern. ADDIN EN.CITE 1-2 Running with a NRFS pattern may assist previously injured patients return to activity with reduced lower-extremity loads and pain during running. Obiective: The purpose of this study was to further investigate the changes in AVLR, cadence, and pain when transitioning previously injured runners from a RFS to a NRFS running style. We hypothesized that following the transition from RFS to NRFS, a decrease in AVLR and pain with running and increase in cadence would be observed. Design: Prospective Cohort. Setting: The study was conducted at West Point, NY at the Arvin Cadet Physical Therapy Clinic and Mahan Hall Chemical and Mechanical Engineering Lab. Patients or Other Participants: A convenience sample of twenty-seven Cadets and active duty Soldiers recovering from running-related injury were recruited to participate in the study (mean age = 25.3 ± 9.9 yrs, mean ht = 1.7 ± 0.1 m, mean wt = 73.0 ± 12.0 kg). Interventions: Initially and at 10 weeks running kinetic data were assessed with an instrumented treadmill sampling at 1,000 Hz. Foot strike pattern (FSP) was assessed from a Casio High Speed EX-ZR200 digital camera sampling at 240Hz. After initial data collection, each participant received a 30-minute training session focused on instruction of a return to run program. Nine of the participants received additional training with a clinician and 18 of the participants received training with an instrumented sock; both training methods encouraged NRFS FSP transition by focusing on landing off the heel and a step rate of 180 steps per minute. Main Outcome Measures: The dependent variables of this study include; FSP, AVLR, and pain measured by the single assessment numeric evaluation (SANE). FSP were investigated via descriptive statistics. AVLR and pain were investigated via paired samples t-tests using SPSS v.19. Results: Mean AVLR of the right leg reduced from 58 ± 12 body weights/second (BW/s) initially to 38 ± 13 BW/s (p \u3c .001). Mean AVLR of the left leg reduced from 55 ± 15 initially to 35 ± 14 BW/s (p \u3c .001). Mean step rate increased from 169 ± 8 to 174 ± 7 steps/minute (p \u3c .001). Mean SANE scores increased from 79 ± 18 to 93 ± 10 out of 100 (p \u3c .001). Conclusions: All runners demonstrated significant improvement in all outcomes after participating in a NRFS return to run program. The results of this study suggest that individuals recovering from lower-extremity injury may benefit from changes in running form