A novel upper limb rehabilitation system with self-driven virtual arm illusion.

PubMed

Aung, Yee Mon; Al-Jumaily, Adel; Anam, Khairul

2014-01-01

This paper proposes a novel upper extremity rehabilitation system with virtual arm illusion. It aims for fast recovery from lost functions of the upper limb as a result of stroke to provide a novel rehabilitation system for paralyzed patients. The system is integrated with a number of technologies that include Augmented Reality (AR) technology to develop game like exercise, computer vision technology to create the illusion scene, 3D modeling and model simulation, and signal processing to detect user intention via EMG signal. The effectiveness of the developed system has evaluated via usability study and questionnaires which is represented by graphical and analytical methods. The evaluation provides with positive results and this indicates the developed system has potential as an effective rehabilitation system for upper limb impairment.

Effect of limb regeneration on size increase at molt of the shore crabs Hemigrapsus oregonensis and Pachygrapsus crassipes.

PubMed

Kuris, A M; Mager, M

1975-09-01

Size increase at molt is reduced following multiple limb regeneration in the shore crabs, Hemigrapsus oregonensis and Pachygrapsus crassipes. Limb loss per se does not influence postmolt size. Effect of increasing number of regenerating limbs is additive. Postmolt size is programmed early in the premolt period of the preceding instar and is probably not readily influenced by water uptake mechanics at ecdysis. A simple model for growth, molting, and regeneration in heavily calcified Crustacea is developed from the viewpoint of adaptive strategies and energetic considerations.

Exogenous retinoic acid induces digit reduction in opossums (Monodelphis domestica) by disrupting cell death and proliferation, and apical ectodermal ridge and zone of polarizing activity function.

PubMed

Molineaux, Anna C; Maier, Jennifer A; Schecker, Teresa; Sears, Karen E

2015-03-01

Retinoic acid (RA) is a vitamin A derivative. Exposure to exogenous RA generates congenital limb malformations (CLMs) in species from frogs to humans. These CLMs include but are not limited to oligodactyly and long-bone hypoplasia. The processes by which exogenous RA induces CLMs in mammals have been best studied in mouse, but as of yet remain unresolved. We investigated the impact of exogenous RA on the cellular and molecular development of the limbs of a nonrodent model mammal, the opossum Monodelphis domestica. Opossums exposed to exogenous retinoic acid display CLMs including oligodactly, and results are consistent with opossum development being more susceptible to RA-induced disruptions than mouse development. Exposure of developing opossums to exogenous RA leads to an increase in cell death in the limb mesenchyme that is most pronounced in the zone of polarizing activity, and a reduction in cell proliferation throughout the limb mesenchyme. Exogenous RA also disrupts the expression of Shh in the zone of polarizing activity, and Fgf8 in the apical ectodermal ridge, and other genes with roles in the regulation of limb development and cell death. Results are consistent with RA inducing CLMs in opossum limbs by disrupting the functions of the apical ectodermal ridge and zone of polarizing activity, and driving an increase in cell death and reduction of cell proliferation in the mesenchyme of the developing limb. © 2015 Wiley Periodicals, Inc.

The Prx1 limb enhancers: targeted gene expression in developing zebrafish pectoral fins.

PubMed

Hernández-Vega, Amayra; Minguillón, Carolina

2011-08-01

Limbs represent an excellent model to study the induction, growth, and patterning of several organs. A breakthrough to study gene function in various tissues has been the characterization of regulatory elements that allow tissue-specific interference of gene function. The mouse Prx1 promoter has been used to generate limb-specific mutants and overexpress genes in tetrapod limbs. Although zebrafish possess advantages that favor their use to study limb morphogenesis, there is no driver described suitable for specifically interfering with gene function in developing fins. We report the generation of zebrafish lines that express enhanced green fluorescent protein (EGFP) driven by the mouse Prx1 enhancer in developing pectoral fins. We also describe the expression pattern of the zebrafish prrx1 genes and identify three conserved non-coding elements (CNEs) that we use to generate fin-specific EGFP reporter lines. Finally, we show that the mouse and zebrafish regulatory elements may be used to modify gene function in pectoral fins. Copyright © 2011 Wiley-Liss, Inc.

Upper limb function in persons with long term paraplegia and implications for independence: Part II.

PubMed

Pentland, W E; Twomey, L T

1994-04-01

Research has shown that wheelchair use in long term paraplegia is associated with upper limb pain and degeneration that interferes with the independent performance of activities of daily living. This paper proposes a model to explain the development of upper limb problems in persons with long term paraplegia, and one that will guide in the prevention and management of this type of long term complication.

Formation of an internal model of environment dynamics during upper limb reaching movements: a fuzzy approach.

PubMed

MacDonald, Chad; Moussavi, Zahra; Sarkodie-Gyan, Thompson

2007-01-01

This paper presents the development and simulation of a fuzzy logic based learning mechanism to emulate human motor learning. In particular, fuzzy inference was used to develop an internal model of a novel dynamic environment experienced during planar reaching movements with the upper limb. A dynamic model of the human arm was developed and a fuzzy if-then rule base was created to relate trajectory movement and velocity errors to internal model update parameters. An experimental simulation was performed to compare the fuzzy system's performance with that of human subjects. It was found that the dynamic model behaved as expected, and the fuzzy learning mechanism created an internal model that was capable of opposing the environmental force field to regain a trajectory closely resembling the desired ideal.

An animal model to evaluate skin-implant-bone integration and gait with a prosthesis directly attached to the residual limb

PubMed Central

Farrell, Brad J; Prilutsky, Boris I; Kistenberg, Robert S; Dalton, John F; Pitkin, Mark

2014-01-01

Background Despite the number of advantages of bone-anchored prostheses, their use in patients is limited due to the lack of complete skin-implant integration. The objective of the present study was to develop an animal model that would permit both detailed investigations of gait with a bone-anchored limb prosthesis and histological analysis of the skin-implant-bone interface after physiological loading of the implant during standing and walking. Methods Full-body mechanics of walking in two cats was recorded and analyzed before and after implantation of a percutaneous porous titanium pylon into the right tibia and attachment of a prosthesis. The rehabilitation procedures included initial limb casting, progressively increasing loading of implant, and standing and locomotor training. Detailed histological analysis of bone and skin ingrowth into implant was performed at the end of the study. Findings The two animals adopted the bone-anchored prosthesis for standing and locomotion, although loads on the prosthetic limb during walking decreased by 22% and 62%, respectively, 4 months after implantation. The animals shifted body weight to the contralateral side and increased propulsion forces by the contralateral hindlimb. Histological analysis of the limb implants demonstrated bone and skin ingrowth. Interpretation The developed animal model to study prosthetic gait and tissue integration with the implant demonstrated that porous titanium implants may permit bone and skin integration and prosthetic gait with a prosthesis. Future studies with this model will help optimize the implant and prosthesis properties. PMID:24405567

Analysis of the expression and function of Wnt-5a and Wnt-5b in developing and regenerating axolotl (Ambystoma mexicanum) limbs.

PubMed

Ghosh, Sukla; Roy, Stéphane; Séguin, Carl; Bryant, Susan V; Gardiner, David M

2008-05-01

Urodele amphibians are unique adult vertebrates because they are able to regenerate body parts after amputation. Studies of urodele limb regeneration, the key model system for vertebrate regeneration, have led to an understanding of the origin of blastema cells and the importance of positional interactions between blastema cells in the control of growth and pattern formation. Progress is now being made in the identification of the signaling pathways that regulate dedifferentiation, blastema morphogenesis, growth and pattern formation. Members of the Wnt family of secreted proteins are expressed in developing and regenerating limbs, and have the potential to control growth, pattern formation and differentiation. We have studied the expression of two non-canonical Wnt genes, Wnt-5a and Wnt-5b. We report that they are expressed in equivalent patterns during limb development and limb regeneration in the axolotl (Ambystoma mexicanum), and during limb development in other tetrapods, implying conservation of function. Our analysis of the effects of ectopic Wnt-5a expression is consistent with the hypothesis that canonical Wnt signaling functions during the early stages of regeneration to control the dedifferentiation of stump cells giving rise to the regeneration-competent cells of the blastema.

Imparting regenerative capacity to limbs by progenitor cell transplantation

PubMed Central

Lin, Gufa; Chen, Ying; Slack, Jonathan M.W.

2012-01-01

Summary The frog Xenopus can normally regenerate its limbs at early developmental stages but loses the ability during metamorphosis. This behavior provides a potential gain-of-function model for measures that can enhance limb regeneration. Here we show that frog limbs can be caused to form multidigit regenerates after receiving transplants of larval limb progenitor cells. It is necessary to activate Wnt/β -catenin signaling in the cells, and to add Sonic hedgehog, FGF10 and thymosin β4. These factors promote survival and growth of the grafted cells and also provide pattern information. The eventual regenerates are not composed solely of donor tissue; the host cells also make a substantial contribution despite their lack of regeneration-competence. Cells from adult frog legs or from regenerating tadpole tails do not promote limb regeneration, demonstrating the necessity for limb progenitor cells. These findings have obvious implications for the development of a technology to promote limb regeneration in mammals. PMID:23273877

Neurotrophic regulation of epidermal dedifferentiation during wound healing and limb regeneration in the axolotl (Ambystoma mexicanum).

PubMed

Satoh, A; Graham, G M C; Bryant, S V; Gardiner, D M

2008-07-15

Adult urodeles (salamanders) are unique in their ability to regenerate complex organs perfectly. The recently developed Accessory Limb Model (ALM) in the axolotl provides an opportunity to identify and characterize the essential signaling events that control the early steps in limb regeneration. The ALM demonstrates that limb regeneration progresses in a stepwise fashion that is dependent on signals from the wound epidermis, nerves and dermal fibroblasts from opposite sides of the limb. When all the signals are present, a limb is formed de novo. The ALM thus provides an opportunity to identify and characterize the signaling pathways that control blastema morphogenesis and limb regeneration. In the present study, we have utilized the ALM to identity the buttonhead-like zinc-finger transcription factor, Sp9, as being involved in the formation of the regeneration epithelium. Sp9 expression is induced in basal keratinocytes of the apical blastema epithelium in a pattern that is comparable to its expression in developing limb buds, and it thus is an important marker for dedifferentiation of the epidermis. Induction of Sp9 expression is nerve-dependent, and we have identified KGF as an endogenous nerve factor that induces expression of Sp9 in the regeneration epithelium.

Multivariate prediction of upper limb prosthesis acceptance or rejection.

PubMed

Biddiss, Elaine A; Chau, Tom T

2008-07-01

To develop a model for prediction of upper limb prosthesis use or rejection. A questionnaire exploring factors in prosthesis acceptance was distributed internationally to individuals with upper limb absence through community-based support groups and rehabilitation hospitals. A total of 191 participants (59 prosthesis rejecters and 132 prosthesis wearers) were included in this study. A logistic regression model, a C5.0 decision tree, and a radial basis function neural network were developed and compared in terms of sensitivity (prediction of prosthesis rejecters), specificity (prediction of prosthesis wearers), and overall cross-validation accuracy. The logistic regression and neural network provided comparable overall accuracies of approximately 84 +/- 3%, specificity of 93%, and sensitivity of 61%. Fitting time-frame emerged as the predominant predictor. Individuals fitted within two years of birth (congenital) or six months of amputation (acquired) were 16 times more likely to continue prosthesis use. To increase rates of prosthesis acceptance, clinical directives should focus on timely, client-centred fitting strategies and the development of improved prostheses and healthcare for individuals with high-level or bilateral limb absence. Multivariate analyses are useful in determining the relative importance of the many factors involved in prosthesis acceptance and rejection.

The Differential Effect of Arm Movements during Gait on the Forward Acceleration of the Centre of Mass in Children with Cerebral Palsy and Typically Developing Children.

PubMed

Meyns, Pieter; Molenaers, Guy; Duysens, Jacques; Jonkers, Ilse

2017-01-01

Background: We aimed to study the contribution of upper limb movements to propulsion during walking in typically developing (TD) children ( n = 5) and children with hemiplegic and diplegic cerebral palsy (CP; n = 5 and n = 4, respectively). Methods: Using integrated three-dimensional motion capture data and a scaled generic musculoskeletal model that included upper limbs, we generated torque driven simulations of gait in OpenSim. Induced acceleration analyses were then used to determine the contributions of the individual actuators located at the relevant degrees of freedoms of the upper and lower limb joints to the forward acceleration of the COM at each time point of the gait simulation. The mean values of the contribution of the actuators of upper limbs, lower limbs, and gravity in different phases of the gait cycle were compared between the three groups. Findings: The results indicated a limited contribution of the upper limb actuators to COM forward acceleration compared to the contribution of lower limbs and gravity, in the three groups. In diplegic CP, the contribution of the upper limbs seemed larger compared to TD during the preswing and swing phases of gait. In hemiplegic CP, the unaffected arm seemed to contribute more to COM deceleration during (pre)swing, while the affected side contributed to COM acceleration. Interpretation: These findings suggest that in the presence of lower limb dysfunction, the contribution of the upper limbs to forward propulsion is altered, although they remain negligible compared to the lower limbs and gravity.

Limb-state information encoded by peripheral and central somatosensory neurons: Implications for an afferent interface

PubMed Central

Weber, Douglas J.; London, Brian M.; Hokanson, James A.; Ayers, Christopher A.; Gaunt, Robert A.; Torres, Ricardo R.; Zaaimi, Boubker; Miller, Lee E.

2013-01-01

A major issue to be addressed in the development of neural interfaces for prosthetic control is the need for somatosensory feedback. Here, we investigate two possible strategies: electrical stimulation of either dorsal root ganglia (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a model that reflects the representation of limb state in terms of neural discharge. This model can then be used to design stimuli that artificially activate the nervous system to convey information about limb state to the subject. Electrically activating DRG neurons using naturalistic stimulus patterns, modeled on recordings made during passive limb movement, evoked activity in S1 that was similar to that of the original movement. We also found that S1 neural populations could accurately discriminate different patterns of DRG stimulation across a wide range of stimulus pulse-rates. In studying the neural coding of limb-state in S1, we also decoded the kinematics of active limb movement using multi-electrode recordings in the monkey. Neurons having both proprioceptive and cutaneous receptive fields contributed equally to this decoding. Some neurons were most informative of limb state in the recent past, but many others appeared to signal upcoming movements suggesting that they also were modulated by an efference copy signal. Finally, we show that a monkey was able to detect stimulation through a large percentage of electrodes implanted in area 2. We discuss the design of appropriate stimulus paradigms for conveying time-varying limb state information, and the relative merits and limitations of central and peripheral approaches. PMID:21878419

Real-time inverse kinematics for the upper limb: a model-based algorithm using segment orientations.

PubMed

Borbély, Bence J; Szolgay, Péter

2017-01-17

Model based analysis of human upper limb movements has key importance in understanding the motor control processes of our nervous system. Various simulation software packages have been developed over the years to perform model based analysis. These packages provide computationally intensive-and therefore off-line-solutions to calculate the anatomical joint angles from motion captured raw measurement data (also referred as inverse kinematics). In addition, recent developments in inertial motion sensing technology show that it may replace large, immobile and expensive optical systems with small, mobile and cheaper solutions in cases when a laboratory-free measurement setup is needed. The objective of the presented work is to extend the workflow of measurement and analysis of human arm movements with an algorithm that allows accurate and real-time estimation of anatomical joint angles for a widely used OpenSim upper limb kinematic model when inertial sensors are used for movement recording. The internal structure of the selected upper limb model is analyzed and used as the underlying platform for the development of the proposed algorithm. Based on this structure, a prototype marker set is constructed that facilitates the reconstruction of model-based joint angles using orientation data directly available from inertial measurement systems. The mathematical formulation of the reconstruction algorithm is presented along with the validation of the algorithm on various platforms, including embedded environments. Execution performance tables of the proposed algorithm show significant improvement on all tested platforms. Compared to OpenSim's Inverse Kinematics tool 50-15,000x speedup is achieved while maintaining numerical accuracy. The proposed algorithm is capable of real-time reconstruction of standardized anatomical joint angles even in embedded environments, establishing a new way for complex applications to take advantage of accurate and fast model-based inverse kinematics calculations.

Effects of varying inter-limb spacing to limb length ratio in metachronal swimming

NASA Astrophysics Data System (ADS)

Lai, Hong Kuan; Merkel, Rachael; Santhanakrishnan, Arvind

2016-11-01

Crustaceans such as shrimp, krill and crayfish swim by rhythmic paddling of four to five pairs of closely spaced limbs. Each pair is phase-shifted in time relative to the neighboring pair, resulting in a metachronal wave that travels in the direction of animal motion. The broad goal of this study is to investigate how the mechanical design of the swimming limbs affect scalability of metachronal swimming in terms of limb-based Reynolds number (Re). A scaled robotic model of metachronal paddling was developed, consisting of four pairs of hinged acrylic plates actuated using stepper motors that were immersed in a rectangular tank containing water-glycerin fluid medium. 2D PIV measurements show that the propulsive jets transition from being primarily horizontal (thrust-producing direction) at Re of order 10 to angled vertically at Re of order 100. The ratio of inter-limb spacing to limb length among metachronal swimming organisms ranges between 0.2 to 0.65. 2D PIV will be used to examine the jets generated between adjacent limbs for varying inter-limb spacing to limb length ratios. The effect of increasing this ratio to beyond the biologically observed range will be discussed.

Proximity to pollution sources and risk of amphibian limb malformation.

PubMed

Taylor, Brynn; Skelly, David; Demarchis, Livia K; Slade, Martin D; Galusha, Deron; Rabinowitz, Peter M

2005-11-01

The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42-3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem.

Finite element analysis of pedestrian lower limb fractures by direct force: the result of being run over or impact?

PubMed

Li, Zhengdong; Zou, Donghua; Liu, Ningguo; Zhong, Liangwei; Shao, Yu; Wan, Lei; Huang, Ping; Chen, Yijiu

2013-06-10

The elucidation and prediction of the biomechanics of lower limb fractures could serve as a useful tool in forensic practices. Finite element (FE) analysis could potentially help in the understanding of the fracture mechanisms of lower limb fractures frequently caused by car-pedestrian accidents. Our aim was (1) to develop and validate a FE model of the human lower limb, (2) to assess the biomechanics of specific injuries concerning run-over and impact loading conditions, and (3) to reconstruct one real car-pedestrian collision case using the model created in this study. We developed a novel lower limb FE model and simulated three different loading scenarios. The geometry of the model was reconstructed using Mimics 13.0 based on computed tomography (CT) scans from an actual traffic accident. The material properties were based upon a synthesis of data found in published literature. The FE model validation and injury reconstruction were conducted using the LS-DYNA code. The FE model was validated by a comparison of the simulation results of three-point bending, overall lateral impact tests and published postmortem human surrogate (PMHS) results. Simulated loading scenarios of running-over the thigh with a wheel, the impact on the upper leg, and impact on the lower thigh were conducted with velocities of 10 m/s, 20 m/s, and 40 m/s, respectively. We compared the injuries resulting from one actual case with the simulated results in order to explore the possible fracture bio-mechanism. The peak fracture forces, maximum bending moments, and energy lost ratio exhibited no significant differences between the FE simulations and the literature data. Under simulated run-over conditions, the segmental fracture pattern was formed and the femur fracture patterns and mechanisms were consistent with the actual injury features of the case. Our study demonstrated that this simulation method could potentially be effective in identifying forensic cases and exploring of the injury mechanisms of lower limb fractures encountered due to inflicted lesions. This model can also help to distinguish between possible and impossible scenarios. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Calcium Balance in Mature Rats Exposed to a Space Flight Model

NASA Technical Reports Server (NTRS)

Wolinsky, Ira

1996-01-01

Negative calcium balances are seen in humans during spaceflight and bed rest, an analog of space flight. Due to the infrequency and costliness of space flight and the difficulties, cost, and restraints in using invasive procedures in bed rest studies, several ground based animal models of space flight have been employed. The most useful and well developed of these models is hind limb unloading in the rat. In this model the hind limbs are non-weight bearing (unloaded) but still mobile; there is a cephalad fluid shift similar to that seen in astronauts in flight; the animals are able to feed, groom and locomote using their front limbs; the procedure is reversible; and, importantly, the model has been validated by comparison to space flight. Several laboratories have studied calcium balance using rats in hind limb unweighting. Roer and Dillaman used young male rats to study calcium balance in this model for 25 days. They found no differences in dietary calcium intake, percent calcium absorption, urinary and fecal excretion, hence indicating no differences in calcium balance between control and unloaded rats. In another study, employing 120 day old females, rats' hind limbs were unloaded for 28 days. While negative calcium balances were observed during a 25 day recovery period no balance measurements were possible during unweighting since the researchers did not employ appropriate metabolic cages. In a recent study from this laboratory, using 200 g rats in the space flight model for two weeks, we found depressed intestinal calcium absorption and increased fecal calcium excretion (indicating less positive calcium balances) and lower circulating 1,25-dihydroxyvitamin D. The above studies indicate that there remains a dearth of information on calcium balance during the hind limb unloading rat space flight model, especially in mature rats, whose use is a better model for planned manned space flight than juvenile or growing animals. With the aid of a newly designed metabolic cage developed in our laboratory it is now possible to accurately measure urinary and fecal calcium excretions in this space flight model. The purpose of this study, then, was to extend and enlarge our previous findings viz: to measure calcium balances in mature rats exposed to a space flight model.

Development of a lameness model in sheep for assessing efficacy of analgesics.

PubMed

Colditz, I G; Paull, D R; Hervault, G; Aubriot, D; Lee, C

2011-08-01

To develop a lameness model to assess the efficacy of analgesics for alleviating pain, swelling and systemic signs of inflammation in sheep. The response to subcutaneous injection of 0.1 or 0.2 mL turpentine in a forelimb pastern (n = 4 ewes per dose) was examined at 0, 3, 6, 24, 48 and 72 h. In a second experiment, responses were measured at 0, 2, 4, 6, 8, 10, 12 and 24 h in ewes receiving 0.1 mL turpentine ± meloxicam 1 mg/kg IV at 0 h (n = 6 per group). Responses measured included forceplate pressure, skin temperature, limb circumference, nociception, leucocyte count, neutrophil : lymphocyte ratio, haptoglobin and daily feed intake. Turpentine injection caused a decrease in weight borne on the treated limb, increased skin temperature, increased sensitivity at the injection site and leucocytosis by 2 h and increased limb circumference by 4 h. Weight borne and sensitivity of the injected limb returned to control levels after around 24 h, whereas tissue swelling, elevated skin temperature and elevated haptoglobin levels persisted for at least 72 h. Treatment with meloxicam improved weight borne by and tolerance to pressure exerted on the turpentine-injected limb. The local and systemic signs of inflammation and pain, temporary reduction in function of the affected limb and partial amelioration of some of these changes by the dose of meloxicam used here suggest that injection of turpentine in the lower forelimb provides a suitable model for examining the efficacy of analgesics for alleviation of pain and inflammation in sheep. © 2011 The Authors. Australian Veterinary Journal © 2011 Australian Veterinary Association.

Ubiquitous human upper-limb motion estimation using wearable sensors.

PubMed

Zhang, Zhi-Qiang; Wong, Wai-Choong; Wu, Jian-Kang

2011-07-01

Human motion capture technologies have been widely used in a wide spectrum of applications, including interactive game and learning, animation, film special effects, health care, navigation, and so on. The existing human motion capture techniques, which use structured multiple high-resolution cameras in a dedicated studio, are complicated and expensive. With the rapid development of microsensors-on-chip, human motion capture using wearable microsensors has become an active research topic. Because of the agility in movement, upper-limb motion estimation has been regarded as the most difficult problem in human motion capture. In this paper, we take the upper limb as our research subject and propose a novel ubiquitous upper-limb motion estimation algorithm, which concentrates on modeling the relationship between upper-arm movement and forearm movement. A link structure with 5 degrees of freedom (DOF) is proposed to model the human upper-limb skeleton structure. Parameters are defined according to Denavit-Hartenberg convention, forward kinematics equations are derived, and an unscented Kalman filter is deployed to estimate the defined parameters. The experimental results have shown that the proposed upper-limb motion capture and analysis algorithm outperforms other fusion methods and provides accurate results in comparison to the BTS optical motion tracker.

Ectopic Fgf signaling induces the intercalary response in developing chicken limb buds.

PubMed

Makanae, Aki; Satoh, Akira

2018-01-01

Intercalary pattern formation is an important regulatory step in amphibian limb regeneration. Amphibian limb regeneration is composed of multiple steps, including wounding, blastema formation, and intercalary pattern formation. Attempts have been made to transfer insights from regeneration-competent animals to regeneration-incompetent animalsat each step in the regeneration process. In the present study, we focused on the intercalary mechanism in chick limb buds. In amphibian limb regeneration, a proximodistal axis is organized as soon as a regenerating blastema is induced. Intermediate structures are subsequently induced (intercalated) between the established proximal and distal identities. Intercalary tissues are derived from proximal tissues. Fgf signaling mediates the intercalary response in amphibian limb regeneration. We attempted to transfer insights into intercalary regeneration from amphibian models to the chick limb bud. The zeugopodial part was dissected out, and the distal and proximal parts were conjunct at st. 24. Delivering ectopic Fgf2 + Fgf8 between the distal and proximal parts resulted in induction of zeugopodial elements. Examination of HoxA11 expression, apoptosis, and cell proliferation provides insights to compare with those in the intercalary mechanism of amphibian limb regeneration. Furthermore, the cellular contribution was investigated in both the chicken intercalary response and that of axolotl limb regeneration. We developed new insights into cellular contribution in amphibian intercalary regeneration, and found consistency between axolotl and chicken intercalary responses. Our findings demonstrate that the same principal of limb regeneration functions between regeneration-competent and -incompetent animals. In this context, we propose the feasibility of the induction of the regeneration response in amniotes.

The Role of Spatially Controlled Cell Proliferation in Limb Bud Morphogenesis

PubMed Central

Boehm, Bernd; Westerberg, Henrik; Lesnicar-Pucko, Gaja; Raja, Sahdia; Rautschka, Michael; Cotterell, James; Swoger, Jim; Sharpe, James

2010-01-01

Although the vertebrate limb bud has been studied for decades as a model system for spatial pattern formation and cell specification, the cellular basis of its distally oriented elongation has been a relatively neglected topic by comparison. The conventional view is that a gradient of isotropic proliferation exists along the limb, with high proliferation rates at the distal tip and lower rates towards the body, and that this gradient is the driving force behind outgrowth. Here we test this hypothesis by combining quantitative empirical data sets with computer modelling to assess the potential role of spatially controlled proliferation rates in the process of directional limb bud outgrowth. In particular, we generate two new empirical data sets for the mouse hind limb—a numerical description of shape change and a quantitative 3D map of cell cycle times—and combine these with a new 3D finite element model of tissue growth. By developing a parameter optimization approach (which explores spatial patterns of tissue growth) our computer simulations reveal that the observed distribution of proliferation rates plays no significant role in controlling the distally extending limb shape, and suggests that directional cell activities are likely to be the driving force behind limb bud outgrowth. This theoretical prediction prompted us to search for evidence of directional cell orientations in the limb bud mesenchyme, and we thus discovered a striking highly branched and extended cell shape composed of dynamically extending and retracting filopodia, a distally oriented bias in Golgi position, and also a bias in the orientation of cell division. We therefore provide both theoretical and empirical evidence that limb bud elongation is achieved by directional cell activities, rather than a PD gradient of proliferation rates. PMID:20644711

Spatial Heterodyne Observations of Water (SHOW) vapour in the upper troposphere and lower stratosphere from a high altitude aircraft: Modelling and sensitivity analysis

NASA Astrophysics Data System (ADS)

Langille, J. A.; Letros, D.; Zawada, D.; Bourassa, A.; Degenstein, D.; Solheim, B.

2018-04-01

A spatial heterodyne spectrometer (SHS) has been developed to measure the vertical distribution of water vapour in the upper troposphere and the lower stratosphere with a high vertical resolution (∼500 m). The Spatial Heterodyne Observations of Water (SHOW) instrument combines an imaging system with a monolithic field-widened SHS to observe limb scattered sunlight in a vibrational band of water (1363 nm-1366 nm). The instrument has been optimized for observations from NASA's ER-2 aircraft as a proof-of-concept for a future low earth orbit satellite deployment. A robust model has been developed to simulate SHOW ER-2 limb measurements and retrievals. This paper presents the simulation of the SHOW ER-2 limb measurements along a hypothetical flight track and examines the sensitivity of the measurement and retrieval approach. Water vapour fields from an Environment and Climate Change Canada forecast model are used to represent realistic spatial variability along the flight path. High spectral resolution limb scattered radiances are simulated using the SASKTRAN radiative transfer model. It is shown that the SHOW instrument onboard the ER-2 is capable of resolving the water vapour variability in the UTLS from approximately 12 km - 18 km with ±1 ppm accuracy. Vertical resolutions between 500 m and 1 km are feasible. The along track sampling capability of the instrument is also discussed.

Deciphering skeletal patterning: clues from the limb.

PubMed

Mariani, Francesca V; Martin, Gail R

2003-05-15

Even young children can distinguish a Tyrannosaurus rex from a Brontosaurus by observing differences in bone size, shape, number and arrangement, that is, skeletal pattern. But despite our extensive knowledge about cartilage and bone formation per se, it is still largely a mystery how skeletal pattern is established. Much of what we do know has been learned from studying limb development in chicken and mouse embryos. Based on the data from such studies, models for how limb skeletal pattern is established have been proposed and continue to be hotly debated.

Proximity to Pollution Sources and Risk of Amphibian Limb Malformation

PubMed Central

Taylor, Brynn; Skelly, David; Demarchis, Livia K.; Slade, Martin D.; Galusha, Deron; Rabinowitz, Peter M.

2005-01-01

The cause of limb deformities in wild amphibian populations remains unclear, even though the apparent increase in prevalence of this condition may have implications for human health. Few studies have simultaneously assessed the effect of multiple exposures on the risk of limb deformities. In a cross-sectional survey of 5,264 hylid and ranid metamorphs in 42 Vermont wetlands, we assessed independent risk factors for nontraumatic limb malformation. The rate of nontraumatic limb malformation varied by location from 0 to 10.2%. Analysis of a subsample did not demonstrate any evidence of infection with the parasite Ribeiroia. We used geographic information system (GIS) land-use/land-cover data to validate field observations of land use in the proximity of study wetlands. In a multiple logistic regression model that included land use as well as developmental stage, genus, and water-quality measures, proximity to agricultural land use was associated with an increased risk of limb malformation (odds ratio = 2.26; 95% confidence interval, 1.42–3.58; p < 0.001). The overall discriminant power of the statistical model was high (C = 0.79). These findings from one of the largest systematic surveys to date provide support for the role of chemical toxicants in the development of amphibian limb malformation and demonstrate the value of an epidemiologic approach to this problem. PMID:16263502

Contribution of limb momentum to power transfer in athletic wheelchair pushing.

PubMed

Masson, G; Bégin, M-A; Lopez Poncelas, M; Pelletier, S-K; Lessard, J-L; Laroche, J; Berrigan, F; Langelier, E; Smeesters, C; Rancourt, D

2016-09-06

Pushing capacity is a key parameter in athletic racing wheelchair performance. This study estimated the potential contribution of upper limb momentum to pushing. The question is relevant since it may affect the training strategy adopted by an athlete. A muscle-free Lagrangian dynamic model of the upper limb segments was developed and theoretical predictions of power transfer to the wheelchair were computed during the push phase. Results show that limb momentum capacity for pushing can be in the order of 40J per push cycle at 10m/s, but it varies with the specific pushing range chosen by the athlete. Although use of momentum could certainly help an athlete improve performance, quantifying the actual contribution of limb momentum to pushing is not trivial. A preliminary experimental investigation on an ergometer, along with a simplified model of the upper limb, suggests that momentum is not the sole contributor to power transfer to a wheelchair. Muscles substantially contribute to pushing, even at high speeds. Moreover, an optimal pushing range is challenging to find since it most likely differs if an athlete chooses a limb momentum pushing strategy versus a muscular exertion pushing strategy, or both at the same time. The study emphasizes the importance of controlling pushing range, although one should optimize it while also taking the dynamics of the recovery period into account. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spotted star light curve numerical modeling technique and its application to HII 1883 surface imaging

NASA Astrophysics Data System (ADS)

Kolbin, A. I.; Shimansky, V. V.

2014-04-01

We developed a code for imaging the surfaces of spotted stars by a set of circular spots with a uniform temperature distribution. The flux from the spotted surface is computed by partitioning the spots into elementary areas. The code takes into account the passing of spots behind the visible stellar limb, limb darkening, and overlapping of spots. Modeling of light curves includes the use of recent results of the theory of stellar atmospheres needed to take into account the temperature dependence of flux intensity and limb darkening coefficients. The search for spot parameters is based on the analysis of several light curves obtained in different photometric bands. We test our technique by applying it to HII 1883.

The relationship between buccofacial and limb apraxia.

PubMed

Raade, A S; Rothi, L J; Heilman, K M

1991-07-01

There are at least two possible models depicting the relationship between buccofacial and limb apraxia. First, apraxia can be viewed as a unitary motor disorder which transcends the output modalities of both buccofacial and limb output. A high degree of similarity between the two types of apraxia would support this model. Alternatively, the relationship between buccofacial and limb apraxia may not include a unitary mechanism. The presence of quantitative and qualitative differences between buccofacial and limb performance would support this nonunitary model. The results of the present study support the nonunitary model.

Assessing the role of dopamine in limb and cranial-oromotor control in a rat model of Parkinson’s disease

PubMed Central

Kane, Jacqueline R.; Ciucci, Michelle R.; Jacobs, Amber N.; Tews, Nathan; Russell, John A.; Ahrens, Allison M.; Ma, Sean T.; Britt, Joshua M.; Cormack, Lawrence K.; Schallert, Timothy

2012-01-01

Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by sensorimotor dysfunction. The neuropathology of PD includes a loss of dopamine (DA) neurons of the nigrostriatal pathway. Classic signs of the disease include rigidity, bradykinesia, and postural instability. However, as many as 90% of patients also experience significant deficits in speech, swallowing (including mastication), and respiratory control. Oromotor deficits such as these are underappreciated, frequently emerging during the early, often hemi-Parkinson, stage of the disease. In this paper, we review tests commonly used in our labs to model early and hemi-Parkinson deficits in rodents. We have recently expanded our tests to include sensitive models of oromotor deficits. This paper discusses the most commonly used tests in our lab to model both limb and oromotor deficits, including tests of forelimb-use asymmetry, postural instability, vibrissae-evoked forelimb placing, single limb akinesia, dry pasta handling, sunflower seed shelling, and acoustic analyses of ultrasonic vocalizations and pasta biting strength. In particular, we lay new groundwork for developing methods for measuring abnormalities in the acoustic patterns during eating that indicate decreased biting strength and irregular intervals between bites in the hemi-Parkinson rat. Similar to limb motor deficits, oromotor deficits, at least to some degree, appear to be modulated by nigrostriatal DA. Finally, we briefly review the literature on targeted motor rehabilitation effects in PD models. Learning outcomes Readers will: (a) understand how a unilateral lesion to the nigrostriatal pathway affects limb use, (b) understand how a unilateral lesion to the nigrostriatal pathway affects oromotor function, and (c) gain an understanding of how limb motor deficits and oromotor deficits appear to involve dopamine and are modulated by training. PMID:21820129

Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation

PubMed Central

Furlan, Leonardo; Conforto, Adriana Bastos; Cohen, Leonardo G.; Sterr, Annette

2016-01-01

Advances in our understanding of the neural plasticity that occurs after hemiparetic stroke have contributed to the formulation of theories of poststroke motor recovery. These theories, in turn, have underpinned contemporary motor rehabilitation strategies for treating motor deficits after stroke, such as upper limb hemiparesis. However, a relative drawback has been that, in general, these strategies are most compatible with the recovery profiles of relatively high-functioning stroke survivors and therefore do not easily translate into benefit to those individuals sustaining low-functioning upper limb hemiparesis, who otherwise have poorer residual function. For these individuals, alternative motor rehabilitation strategies are currently needed. In this paper, we will review upper limb immobilisation studies that have been conducted with healthy adult humans and animals. Then, we will discuss how the findings from these studies could inspire the creation of a neural plasticity model that is likely to be of particular relevance to the context of motor rehabilitation after stroke. For instance, as will be elaborated, such model could contribute to the development of alternative motor rehabilitation strategies for treating poststroke upper limb hemiparesis. The implications of the findings from those immobilisation studies for contemporary motor rehabilitation strategies will also be discussed and perspectives for future research in this arena will be provided as well. PMID:26843992

Limb regeneration is impaired in an adult zebrafish model of diabetes mellitus.

PubMed

Olsen, Ansgar S; Sarras, Michael P; Intine, Robert V

2010-01-01

The zebrafish (Danio rerio) is an established model organism for the study of developmental processes, human disease, and tissue regeneration. We report that limb regeneration is severely impaired in our newly developed adult zebrafish model of type I diabetes mellitus. Intraperitoneal streptozocin injection of adult, wild-type zebrafish results in a sustained hyperglycemic state as determined by elevated fasting blood glucose values and increased glycation of serum protein. Serum insulin levels are also decreased and pancreas immunohistochemisty revealed a decreased amount of insulin signal in hyperglycemic fish. Additionally, the diabetic complications of retinal thinning and glomerular basement membrane thickening (early signs of retinopathy and nephropathy) resulting from the hyperglycemic state were evident in streptozocin-injected fish at 3 weeks. Most significantly, limb regeneration, following caudal fin amputation, is severely impaired in diabetic zebrafish and nonspecific toxic effects outside the pancreas were not found to contribute to impaired limb regeneration. This experimental system using adult zebrafish facilitates a broad spectrum of genetic and molecular approaches to study regeneration in the diabetic background. © 2010 by the Wound Healing Society.

Computer simulations of neural mechanisms explaining upper and lower limb excitatory neural coupling

PubMed Central

2010-01-01

Background When humans perform rhythmic upper and lower limb locomotor-like movements, there is an excitatory effect of upper limb exertion on lower limb muscle recruitment. To investigate potential neural mechanisms for this behavioral observation, we developed computer simulations modeling interlimb neural pathways among central pattern generators. We hypothesized that enhancement of muscle recruitment from interlimb spinal mechanisms was not sufficient to explain muscle enhancement levels observed in experimental data. Methods We used Matsuoka oscillators for the central pattern generators (CPG) and determined parameters that enhanced amplitudes of rhythmic steady state bursts. Potential mechanisms for output enhancement were excitatory and inhibitory sensory feedback gains, excitatory and inhibitory interlimb coupling gains, and coupling geometry. We first simulated the simplest case, a single CPG, and then expanded the model to have two CPGs and lastly four CPGs. In the two and four CPG models, the lower limb CPGs did not receive supraspinal input such that the only mechanisms available for enhancing output were interlimb coupling gains and sensory feedback gains. Results In a two-CPG model with inhibitory sensory feedback gains, only excitatory gains of ipsilateral flexor-extensor/extensor-flexor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 26%. In a two-CPG model with excitatory sensory feedback gains, excitatory gains of contralateral flexor-flexor/extensor-extensor coupling produced reciprocal upper-lower limb bursts and enhanced output up to 100%. However, within a given excitatory sensory feedback gain, enhancement due to excitatory interlimb gains could only reach levels up to 20%. Interconnecting four CPGs to have ipsilateral flexor-extensor/extensor-flexor coupling, contralateral flexor-flexor/extensor-extensor coupling, and bilateral flexor-extensor/extensor-flexor coupling could enhance motor output up to 32%. Enhancement observed in experimental data exceeded 32%. Enhancement within this symmetrical four-CPG neural architecture was more sensitive to relatively small interlimb coupling gains. Excitatory sensory feedback gains could produce greater output amplitudes, but larger gains were required for entrainment compared to inhibitory sensory feedback gains. Conclusions Based on these simulations, symmetrical interlimb coupling can account for much, but not all of the excitatory neural coupling between upper and lower limbs during rhythmic locomotor-like movements. PMID:21143960

Fundamental Principles of Tremor Propagation in the Upper Limb.

PubMed

Davidson, Andrew D; Charles, Steven K

2017-04-01

Although tremor is the most common movement disorder, there exist few effective tremor-suppressing devices, in part because the characteristics of tremor throughout the upper limb are unknown. To clarify, optimally suppressing tremor requires a knowledge of the mechanical origin, propagation, and distribution of tremor throughout the upper limb. Here we present the first systematic investigation of how tremor propagates between the shoulder, elbow, forearm, and wrist. We simulated tremor propagation using a linear, time-invariant, lumped-parameter model relating joint torques and the resulting joint displacements. The model focused on the seven main degrees of freedom from the shoulder to the wrist and included coupled joint inertia, damping, and stiffness. We deliberately implemented a simple model to focus first on the most basic effects. Simulating tremorogenic joint torque as a sinusoidal input, we used the model to establish fundamental principles describing how input parameters (torque location and frequency) and joint impedance (inertia, damping, and stiffness) affect tremor propagation. We expect that the methods and principles presented here will serve as the groundwork for future refining studies to understand the origin, propagation, and distribution of tremor throughout the upper limb in order to enable the future development of optimal tremor-suppressing devices.

Fundamental Principles of Tremor Propagation in the Upper Limb

PubMed Central

Davidson, Andrew D.; Charles, Steven K.

2017-01-01

Although tremor is the most common movement disorder, there exist few effective tremor-suppressing devices, in part because the characteristics of tremor throughout the upper limb are unknown. To clarify, optimally suppressing tremor requires a knowledge of the mechanical origin, propagation, and distribution of tremor throughout the upper limb. Here we present the first systematic investigation of how tremor propagates between the shoulder, elbow, forearm, and wrist. We simulated tremor propagation using a linear, time-invariant, lumped-parameter model relating joint torques and the resulting joint displacements. The model focused on the seven main degrees of freedom from the shoulder to the wrist and included coupled joint inertia, damping, and stiffness. We deliberately implemented a simple model to focus first on the most basic effects. Simulating tremorogenic joint torque as a sinusoidal input, we used the model to establish fundamental principles describing how input parameters (torque location and frequency) and joint impedance (inertia, damping, and stiffness) affect tremor propagation. We expect that the methods and principles presented here will serve as the groundwork for future refining studies to understand the origin, propagation, and distribution of tremor throughout the upper limb in order to enable the future development of optimal tremor-suppressing devices. PMID:27957608

Limb-Enhancer Genie: An accessible resource of accurate enhancer predictions in the developing limb

DOE PAGES

Monti, Remo; Barozzi, Iros; Osterwalder, Marco; ...

2017-08-21

Epigenomic mapping of enhancer-associated chromatin modifications facilitates the genome-wide discovery of tissue-specific enhancers in vivo. However, reliance on single chromatin marks leads to high rates of false-positive predictions. More sophisticated, integrative methods have been described, but commonly suffer from limited accessibility to the resulting predictions and reduced biological interpretability. Here we present the Limb-Enhancer Genie (LEG), a collection of highly accurate, genome-wide predictions of enhancers in the developing limb, available through a user-friendly online interface. We predict limb enhancers using a combination of > 50 published limb-specific datasets and clusters of evolutionarily conserved transcription factor binding sites, taking advantage ofmore » the patterns observed at previously in vivo validated elements. By combining different statistical models, our approach outperforms current state-of-the-art methods and provides interpretable measures of feature importance. Our results indicate that including a previously unappreciated score that quantifies tissue-specific nuclease accessibility significantly improves prediction performance. We demonstrate the utility of our approach through in vivo validation of newly predicted elements. Moreover, we describe general features that can guide the type of datasets to include when predicting tissue-specific enhancers genome-wide, while providing an accessible resource to the general biological community and facilitating the functional interpretation of genetic studies of limb malformations.« less

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter

PubMed Central

Dantzler, William H.; Pannabecker, Thomas L.

2012-01-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na+ or urea-Cl− cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na+ or urea- Cl− cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data. PMID:22088433

Urine concentrating mechanism: impact of vascular and tubular architecture and a proposed descending limb urea-Na+ cotransporter.

PubMed

Layton, Anita T; Dantzler, William H; Pannabecker, Thomas L

2012-03-01

We extended a region-based mathematical model of the renal medulla of the rat kidney, previously developed by us, to represent new anatomic findings on the vascular architecture in the rat inner medulla (IM). In the outer medulla (OM), tubules and vessels are organized around tightly packed vascular bundles; in the IM, the organization is centered around collecting duct clusters. In particular, the model represents the separation of descending vasa recta from the descending limbs of loops of Henle, and the model represents a papillary segment of the descending thin limb that is water impermeable and highly urea permeable. Model results suggest that, despite the compartmentalization of IM blood flow, IM interstitial fluid composition is substantially more homogeneous compared with OM. We used the model to study medullary blood flow in antidiuresis and the effects of vascular countercurrent exchange. We also hypothesize that the terminal aquaporin-1 null segment of the long descending thin limbs may express a urea-Na(+) or urea-Cl(-) cotransporter. As urea diffuses from the urea-rich papillary interstitium into the descending thin limb luminal fluid, NaCl is secreted via the cotransporter against its concentration gradient. That NaCl is then reabsorbed near the loop bend, raising the interstitial fluid osmolality and promoting water reabsorption from the IM collecting ducts. Indeed, the model predicts that the presence of the urea-Na(+) or urea- Cl(-) cotransporter facilitates the cycling of NaCl within the IM and yields a loop-bend fluid composition consistent with experimental data.

Hysteretic behavior of stage-discharge relationships in urban streams

NASA Astrophysics Data System (ADS)

Miller, A. J.; Lindner, G. A.

2009-12-01

Reliable stage-discharge relationships or rating curves are of critical importance for accurate calculation of streamflow and maintenance of long-term flow records. Urban streams offer particular challenges for the maintenance of accurate rating curves. It is often difficult or impossible to collect direct discharge measurements at high flows, many of which are generated by short-duration high-intensity summer thunderstorms, both because of dangerous conditions in the channel and also because the stream rises and falls so rapidly that field crews cannot reach sites in time and sometimes cannot make measurements rapidly enough to keep pace with changing water levels even when they are on site during a storm. Work in urban streams in the Baltimore metropolitan area has shown that projection of rating curves beyond the range of measured flows can lead to overestimation of flood peaks by as much as 100%, and these can only be corrected when adequate field data are available to support modeling efforts. Even moderate flows that are above safe wading depth and velocity may best be estimated using hydraulic models. Current research for NSF CNH project 0709659 includes the application of 2-d depth-averaged hydraulic models to match existing rating curves over a range of low to moderate flows and to extend rating curves for higher flows, based on field collection of high-water marks. Although it is generally assumed that stage-discharge relationships are single-valued, we find that modeling results in small urban streams often generate hysteretic relationships, with higher discharges on the rising limb of the hydrograph than on the falling limb. The difference between discharges for the same stage on the rising and falling limb can be on the order of 20-30% even for in-channel flows that are less than 1 m deep. As safety considerations dictate that it is preferable to make direct discharge measurements on the falling limb of the hydrograph, the higher direct measurements used in many rating curves probably have been collected on the falling limb and therefore may not capture the correct stage-discharge relationship for the rising limb. In some cases model results selected only from the falling limb are able to match the existing rating curve very closely. Although hysteresis may be explained with reference to the innate properties of the flood wave, other factors also lead to hysteretic behavior. Downstream constrictions and obstructions associated with urban infrastructure may cause substantial backwater effects, particularly during flood flows. Flood conditions at tributary confluences also can exert a controlling influence upstream. Based on our results we recommend that at some sites it is advisable to develop separate rating curves for the rising and falling limbs, and to develop a range of modeling scenarios for predicting the range of potential uncertainty.

[Venous thrombosis of atypical location in patients with cancer].

PubMed

Campos Balea, Begoña; Sáenz de Miera Rodríguez, Andrea; Antolín Novoa, Silvia; Quindós Varela, María; Barón Duarte, Francisco; López López, Rafael

2015-01-01

Venous thromboembolism (VTE) is a complication that frequently occurs in patients with neoplastic diseases. Several models have therefore been developed to identify patient subgroups diagnosed with cancer who are at increased risk of developing VTE. The most common forms of thromboembolic episodes are deep vein thrombosis in the lower limbs and pulmonary thromboembolism. However, venous thrombosis is also diagnosed in atypical locations. There are few revisions of unusual cases of venous thrombosis. In most cases, VTE occurs in the upper limbs and in the presence of central venous catheters, pacemakers and defibrillators. We present the case of a patient diagnosed with breast cancer and treated with surgery, chemotherapy and radiation therapy who developed a thrombosis in the upper limbs (brachial and axillary). Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

A piezoelectric six-DOF vibration energy harvester based on parallel mechanism: dynamic modeling, simulation, and experiment

NASA Astrophysics Data System (ADS)

Yuan, G.; Wang, D. H.

2017-03-01

Multi-directional and multi-degree-of-freedom (multi-DOF) vibration energy harvesting are attracting more and more research interest in recent years. In this paper, the principle of a piezoelectric six-DOF vibration energy harvester based on parallel mechanism is proposed to convert the energy of the six-DOF vibration to single-DOF vibrations of the limbs on the energy harvester and output voltages. The dynamic model of the piezoelectric six-DOF vibration energy harvester is established to estimate the vibrations of the limbs. On this basis, a Stewart-type piezoelectric six-DOF vibration energy harvester is developed and explored. In order to validate the established dynamic model and the analysis results, the simulation model of the Stewart-type piezoelectric six-DOF vibration energy harvester is built and tested with different vibration excitations by SimMechanics, and some preliminary experiments are carried out. The results show that the vibration of the limbs on the piezoelectric six-DOF vibration energy harvester can be estimated by the established dynamic model. The developed Stewart-type piezoelectric six-DOF vibration energy harvester can harvest the energy of multi-directional linear vibration and multi-axis rotating vibration with resonance frequencies of 17 Hz, 25 Hz, and 47 Hz. Moreover, the resonance frequencies of the developed piezoelectric six-DOF vibration energy harvester are not affected by the direction changing of the vibration excitation.

Analysis of temporal dynamics in imagery during acute limb ischemia and reperfusion

NASA Astrophysics Data System (ADS)

Irvine, John M.; Regan, John; Spain, Tammy A.; Caruso, Joseph D.; Rodriquez, Maricela; Luthra, Rajiv; Forsberg, Jonathon; Crane, Nicole J.; Elster, Eric

2014-03-01

Ischemia and reperfusion injuries present major challenges for both military and civilian medicine. Improved methods for assessing the effects and predicting outcome could guide treatment decisions. Specific issues related to ischemia and reperfusion injury can include complications arising from tourniquet use, such as microvascular leakage in the limb, loss of muscle strength and systemic failures leading to hypotension and cardiac failure. Better methods for assessing the viability of limbs/tissues during ischemia and reducing complications arising from reperfusion are critical to improving clinical outcomes for at-risk patients. The purpose of this research is to develop and assess possible prediction models of outcome for acute limb ischemia using a pre-clinical model. Our model relies only on non-invasive imaging data acquired from an animal study. Outcome is measured by pathology and functional scores. We explore color, texture, and temporal features derived from both color and thermal motion imagery acquired during ischemia and reperfusion. The imagery features form the explanatory variables in a model for predicting outcome. Comparing model performance to outcome prediction based on direct observation of blood chemistry, blood gas, urinalysis, and physiological measurements provides a reference standard. Initial results show excellent performance for the imagery-base model, compared to predictions based direct measurements. This paper will present the models and supporting analysis, followed by recommendations for future investigations.

Mechanical Impedance Modeling of Human Arm: A survey

NASA Astrophysics Data System (ADS)

Puzi, A. Ahmad; Sidek, S. N.; Sado, F.

2017-03-01

Human arm mechanical impedance plays a vital role in describing motion ability of the upper limb. One of the impedance parameters is stiffness which is defined as the ratio of an applied force to the measured deformation of the muscle. The arm mechanical impedance modeling is useful in order to develop a better controller for system that interacts with human as such an automated robot-assisted platform for automated rehabilitation training. The aim of the survey is to summarize the existing mechanical impedance models of human upper limb so to justify the need to have an improved version of the arm model in order to facilitate the development of better controller of such systems with ever increase in complexity. In particular, the paper will address the following issue: Human motor control and motor learning, constant and variable impedance models, methods for measuring mechanical impedance and mechanical impedance modeling techniques.

A Bioimpedance Analysis Platform for Amputee Residual Limb Assessment.

PubMed

Sanders, Joan E; Moehring, Mark A; Rothlisberger, Travis M; Phillips, Reid H; Hartley, Tyler; Dietrich, Colin R; Redd, Christian B; Gardner, David W; Cagle, John C

2016-08-01

The objective of this research was to develop a bioimpedance platform for monitoring fluid volume in residual limbs of people with trans-tibial limb loss using prostheses. A customized multifrequency current stimulus profile was sent to thin flat electrodes positioned on the thigh and distal residual limb. The applied current signal and sensed voltage signals from four pairs of electrodes located on the anterior and posterior surfaces were demodulated into resistive and reactive components. An established electrical model (Cole) and segmental limb geometry model were used to convert results to extracellular and intracellular fluid volumes. Bench tests and testing on amputee participants were conducted to optimize the stimulus profile and electrode design and layout. The proximal current injection electrode needed to be at least 25 cm from the proximal voltage sensing electrode. A thin layer of hydrogel needed to be present during testing to ensure good electrical coupling. Using a burst duration of 2.0 ms, intermission interval of 100 μs, and sampling delay of 10 μs at each of 24 frequencies except 5 kHz, which required a 200-μs sampling delay, the system achieved a sampling rate of 19.7 Hz. The designed bioimpedance platform allowed system settings and electrode layouts and positions to be optimized for amputee limb fluid volume measurement. The system will be useful toward identifying and ranking prosthetic design features and participant characteristics that impact residual limb fluid volume.

Load transfer mechanics between trans-tibial prosthetic socket and residual limb--dynamic effects.

PubMed

Jia, Xiaohong; Zhang, Ming; Lee, Winson C C

2004-09-01

The effects of inertial loads on the interface stresses between trans-tibial residual limb and prosthetic socket were investigated. The motion of the limb and prosthesis was monitored using a Vicon motion analysis system and the ground reaction force was measured by a force platform. Equivalent loads at the knee joint during walking were calculated in two cases with and without consideration of the material inertia. A 3D nonlinear finite element (FE) model based on the actual geometry of residual limb, internal bones and socket liner was developed to study the mechanical interaction between socket and residual limb during walking. To simulate the friction/slip boundary conditions between the skin and liner, automated surface-to-surface contact was used. The prediction results indicated that interface pressure and shear stress had the similar double-peaked waveform shape in stance phase. The average difference in interface stresses between the two cases with and without consideration of inertial forces was 8.4% in stance phase and 20.1% in swing phase. The maximum difference during stance phase is up to 19%. This suggests that it is preferable to consider the material inertia effect in a fully dynamic FE model.

Vertebrate limb development: moving from classical morphogen gradients to an integrated 4-dimensional patterning system.

PubMed

Bénazet, Jean-Denis; Zeller, Rolf

2009-10-01

A wealth of classical embryological manipulation experiments taking mainly advantage of the chicken limb buds identified the apical ectodermal ridge (AER) and the zone of polarizing activity (ZPA) as the respective ectodermal and mesenchymal key signaling centers coordinating proximodistal (PD) and anteroposterior (AP) limb axis development. These experiments inspired Wolpert's French flag model, which is a classic among morphogen gradient models. Subsequent molecular and genetic analysis in the mouse identified retinoic acid as proximal signal, and fibroblast growth factors (FGFs) and sonic hedgehog (SHH) as the essential instructive signals produced by AER and ZPA, respectively. Recent studies provide good evidence that progenitors are specified early with respect to their PD and AP fates and that morpho-regulatory signaling is also required for subsequent proliferative expansion of the specified progenitor pools. The determination of particular fates seems to occur rather late and depends on additional signals such as bone morphogenetic proteins (BMPs), which indicates that cells integrate signaling inputs over time and space. The coordinate regulation of PD and AP axis patterning is controlled by an epithelial-mesenchymal feedback signaling system, in which transcriptional regulation of the BMP antagonist Gremlin1 integrates inputs from the BMP, SHH, and FGF pathways. Vertebrate limb-bud development is controlled by a 4-dimensional (4D) patterning system integrating positive and negative regulatory feedback loops, rather than thresholds set by morphogen gradients.

Marker-based method to measure movement between the residual limb and a transtibial prosthetic socket.

PubMed

Childers, Walter Lee; Siebert, Steven

2016-12-01

Limb movement between the residuum and socket continues to be an underlying factor in limb health, prosthetic comfort, and gait performance yet techniques to measure this have been underdeveloped. Develop a method to measure motion between the residual limb and a transtibial prosthetic socket. Single subject, repeated measures with mathematical modeling. The gait of a participant with transtibial amputation was recorded using a motion capture system using a marker set that included arrays on the anterior distal tibia and the lateral epicondyle of the femur. The proximal or distal translation, anterior or posterior translation, and angular movements were quantified. A random Monte Carlo simulation based on the precision of the motion capture system and a model of the bone moving under the skin explored the technique's accuracy. Residual limb tissue stiffness was modeled as a linear spring based on data from Papaioannou et al. Residuum movement relative to the socket went through ~30 mm, 18 mm, and 15° range of motion. Root mean squared errors were 5.47 mm, 1.86 mm, and 0.75° when considering the modeled bone-skin movement in the proximal or distal, anterior or posterior, and angular directions, respectively. The measured movement was greater than the root mean squared error, indicating that this method can measure motion between the residuum and socket. The ability to quantify movement between the residual limb and the prosthetic socket will improve prosthetic treatment through the evaluation of different prosthetic suspensions, socket designs, and motor control of the prosthetic interface. © The International Society for Prosthetics and Orthotics 2015.

Prediction Equation for Lower Limbs Lean Soft Tissue in Circumpubertal Boys Using Anthropometry and Biological Maturation

PubMed Central

Valente-dos-Santos, João; Coelho-e-Silva, Manuel J.; Machado-Rodrigues, Aristides M.; Elferink-Gemser, Marije T.; Malina, Robert M.; Petroski, Édio L.; Minderico, Cláudia S.; Silva, Analiza M.; Baptista, Fátima; Sardinha, Luís B.

2014-01-01

Lean soft tissue (LST), a surrogate of skeletal muscle mass, is largely limited to appendicular body regions. Simple and accurate methods to estimate lower limbs LST are often used in attempts to partition out the influence of body size on performance outputs. The aim of the current study was to develop and cross-validate a new model to predict lower limbs LST in boys aged 10–13 years, using dual-energy X-ray absorptiometry (DXA) as the reference method. Total body and segmental (lower limbs) composition were assessed with a Hologic Explorer-W QDR DXA scanner in a cross-sectional sample of 75 Portuguese boys (144.8±6.4 cm; 40.2±9.0 kg). Skinfolds were measured at the anterior and posterior mid-thigh, and medial calf. Circumferences were measured at the proximal, mid and distal thigh. Leg length was estimated as stature minus sitting height. Current stature expressed as a percentage of attained predicted mature stature (PMS) was used as an estimate of biological maturity status. Backward proportional allometric models were used to identify the model with the best statistical fit: ln (lower limbs LST)  = 0.838× ln (body mass) +0.476× ln (leg length) – 0.135× ln (mid-thigh circumference) – 0.053× ln (anterior mid-thigh skinfold) – 0.098× ln (medial calf skinfold) – 2.680+0.010× (percentage of attained PMS) (R = 0.95). The obtained equation was cross-validated using the predicted residuals sum of squares statistics (PRESS) method (R 2 PRESS = 0.90). Deming repression analysis between predicted and current lower limbs LST showed a standard error of estimation of 0.52 kg (95% limits of agreement: 0.77 to −1.27 kg). The new model accurately predicts lower limbs LST in circumpubertal boys. PMID:25229472

A review of supernumerary and absent limbs and digits of the upper limb.

PubMed

Klaassen, Zachary; Choi, Monica; Musselman, Ruth; Eapen, Deborah; Tubbs, R Shane; Loukas, Marios

2012-03-01

For years people have been enamored by anomalies of the human limbs, particularly supernumerary and absent limbs and digits. Historically, there are a number of examples of such anomalies, including royal families of ancient Chaldea, tribes from Arabia, and examples from across nineteenth century Europe. The development of the upper limbs in a growing embryo is still being elucidated with the recent advent of homeobox genes, but researchers agree that upper limbs develop between stages 12-23 through a complex embryological process. Maternal thalidomide intake during limb development is known to cause limb reduction and subsequent amelia or phocomelia. Additionally, a number of clinical reports have illustrated different limb anomaly cases, with each situation unique in phenotype and developmental abnormality. Supernumerary and absent limbs and digits are not unique to humans, and a number of animal cases have also been reported. This review of the literature illustrates the historical, anatomical, and clinical aspects of supernumerary and absent limbs and digits for the upper limb.

Limb movements during embryonic development in the chick: evidence for a continuum in limb motor control antecedent to locomotion.

PubMed

Bradley, Nina S; Solanki, Dhara; Zhao, Dawn

2005-12-01

New imaging technologies are revealing ever-greater details of motor behavior in fetuses for clinical diagnosis and treatment. Understanding the form, mechanisms, and significance of fetal behavior will maximize imaging applications. The chick is readily available for experimentation throughout embryogenesis, making it an excellent model for this purpose. Yet in 40 yr since Hamburger and colleagues described chick embryonic behavior, we have not determined if motility belongs to a developmental continuum fundamental to posthatching behavior. This study examined kinematics and synchronized electromyography (EMG) during spontaneous limb movements in chicks at four time points between embryonic days (E) 9-18. We report that coordinated kinematic and/or EMG patterns were expressed at each time point. Variability observed in knee and ankle excursions at E15-E18 sorted into distinct in-phase and out-of-phase patterns. EMG patterns did not directly account for out-of-phase patterns, indicating study of movement biomechanics will be critical to fully understand motor control in the embryo. We also provide the first descriptions of 2- to 10-Hz limb movements emerging E15-E18 and a shift from in-phase to out-of-phase interlimb coordination E9-E18. Our findings revealed that coordinated limb movements persist across development and suggest they belong to a developmental continuum for locomotion. Limb patterns were consistent with the half center model for a locomotor pattern generator. Achievement of these patterns by E9 may thus indicate the embryo has completed a critical phase beyond which developmental progression may be less vulnerable to experimental perturbations or prenatal events.

Evaluation of Limb Load Asymmetry Using Two New Mathematical Models

PubMed Central

Kumar, Senthil NS; Omar, Baharudin; Joseph, Leonard H.; Htwe, Ohnmar; Jagannathan, K.; Hamdan, Nor M Y; Rajalakshmi, D.

2015-01-01

Quantitative measurement of limb loading is important in orthopedic and neurological rehabilitation. In current practice, mathematical models such as Symmetry index (SI), Symmetry ratio (SR), and Symmetry angle (SA) are used to quantify limb loading asymmetry. Literatures have identified certain limitations with the above mathematical models. Hence this study presents two new mathematical models Modified symmetry index (MSI) and Limb loading error (LLE) that would address these limitations. Furthermore, the current mathematical models were compared against the new model with the goal of achieving a better model. This study uses hypothetical data to simulate an algorithmic preliminary computational measure to perform with all numerical possibilities of even and uneven limb loading that can occur in human legs. Descriptive statistics are used to interpret the limb loading patterns: symmetry, asymmetry and maximum asymmetry. The five mathematical models were similar in analyzing symmetry between limbs. However, for asymmetry and maximum asymmetry data, the SA and SR values do not give any meaningful interpretation, and SI gives an inflated value. The MSI and LLE are direct, easy to interpret and identify the loading patterns with the side of asymmetry. The new models are notable as they quantify the amount and side of asymmetry under different loading patterns. PMID:25716372

Gait Phase Recognition for Lower-Limb Exoskeleton with Only Joint Angular Sensors

PubMed Central

Liu, Du-Xin; Wu, Xinyu; Du, Wenbin; Wang, Can; Xu, Tiantian

2016-01-01

Gait phase is widely used for gait trajectory generation, gait control and gait evaluation on lower-limb exoskeletons. So far, a variety of methods have been developed to identify the gait phase for lower-limb exoskeletons. Angular sensors on lower-limb exoskeletons are essential for joint closed-loop controlling; however, other types of sensors, such as plantar pressure, attitude or inertial measurement unit, are not indispensable.Therefore, to make full use of existing sensors, we propose a novel gait phase recognition method for lower-limb exoskeletons using only joint angular sensors. The method consists of two procedures. Firstly, the gait deviation distances during walking are calculated and classified by Fisher’s linear discriminant method, and one gait cycle is divided into eight gait phases. The validity of the classification results is also verified based on large gait samples. Secondly, we build a gait phase recognition model based on multilayer perceptron and train it with the phase-labeled gait data. The experimental result of cross-validation shows that the model has a 94.45% average correct rate of set (CRS) and an 87.22% average correct rate of phase (CRP) on the testing set, and it can predict the gait phase accurately. The novel method avoids installing additional sensors on the exoskeleton or human body and simplifies the sensory system of the lower-limb exoskeleton. PMID:27690023

A new model for the determination of limb segment mass in children.

PubMed

Kuemmerle-Deschner, J B; Hansmann, S; Rapp, H; Dannecker, G E

2007-04-01

The knowledge of limb segment masses is critical for the calculation of joint torques. Several methods for segment mass estimation have been described in the literature. They are either inaccurate or not applicable to the limb segments of children. Therefore, we developed a new cylinder brick model (CBM) to estimate segment mass in children. The aim of this study was to compare CBM and a model based on a polynomial regression equation (PRE) to volume measurement obtained by the water displacement method (WDM). We examined forearms, hands, lower legs, and feet of 121 children using CBM, PRE, and WDM. The differences between CBM and WDM or PRE and WDM were calculated and compared using a Bland-Altman plot of differences. Absolute limb segment mass measured by WDM ranged from 0.16+/-0.04 kg for hands in girls 5-6 years old, up to 2.72+/-1.03 kg for legs in girls 11-12 years old. The differences of normalised segment masses ranged from 0.0002+/-0.0021 to 0.0011+/-0.0036 for CBM-WDM and from 0.0023+/-0.0041 to 0.0127+/-0.036 for PRE-WDM (values are mean+/-2 S.D.). The CBM showed better agreement with WDM than PRE for all limb segments in girls and boys. CBM is accurate and superior to PRE for the estimation of individual limb segment mass of children. Therefore, CBM is a practical and useful tool for the analysis of kinetic parameters and the calculation of resulting forces to assess joint functionality in children.

Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo

PubMed Central

2010-01-01

Background Pattern formation of the limb skeleton is regulated by a complex interplay of signaling centers located in the ectodermal sheath and mesenchymal core of the limb anlagen, which results, in the forelimb, in the coordinate array of humerus, radius, ulna, carpals, metacarpals and digits. Much less understood is why skeletal elements form only in the central mesenchyme of the limb, whereas muscle anlagen develop in the peripheral mesenchyme ensheathing the chondrogenic center. Classical studies have suggested a role of the limb ectoderm as a negative regulator of limb chondrogenesis. Results In this paper, we investigated the molecular nature of the inhibitory influence of the ectoderm on limb chondrogenesis in the avian embryo in vivo. We show that ectoderm ablation in the early limb bud leads to increased and ectopic expression of early chondrogenic marker genes like Sox9 and Collagen II, indicating that the limb ectoderm inhibits limb chondrogenesis at an early stage of the chondrogenic cascade. To investigate the molecular nature of the inhibitory influence of the ectoderm, we ectopically expressed Wnt6, which is presently the only known Wnt expressed throughout the avian limb ectoderm, and found that Wnt6 overexpression leads to reduced expression of the early chondrogenic marker genes Sox9 and Collagen II. Conclusion Our results suggest that the inhibitory influence of the ectoderm on limb chondrogenesis acts on an early stage of chondrogenesis upsteam of Sox9 and Collagen II. We identify Wnt6 as a candidate mediator of ectodermal chondrogenic inhibition in vivo. We propose a model of Wnt-mediated centripetal patterning of the limb by the surface ectoderm. PMID:20334703

Temperature-salinity structure of the AMOC in high-resolution ocean simulations and in CMIP5 models

NASA Astrophysics Data System (ADS)

Wang, F.; Xu, X.; Chassignet, E.

2017-12-01

On average, the CMIP5 models represent the AMOC structure, water properties, Heat transport and Freshwater transport reasonably well. For temperature, CMIP5 models exhibit a colder northward upper limb and a warmer southward lower limb. the temperature contrast induces weaker heat transport than observation. For salinity, CMIP5 models exhibit saltier southward lower limb, thus contributes to weaker column freshwater transport. Models have large spread, among them, AMOC strength contributes to Heat transport but not freshwater transport. AMOC structure (the overturning depth) contributes to transport-weighted temperature not transport-weighted salinity in southward lower limb. The salinity contrast in upper and lower limb contributes to freshwater transport, but temperature contrast do not contribute to heat transport.

Development of a Clinical Framework for Mirror Therapy in Patients with Phantom Limb Pain: An Evidence-based Practice Approach.

PubMed

Rothgangel, Andreas; Braun, Susy; de Witte, Luc; Beurskens, Anna; Smeets, Rob

2016-04-01

To describe the development and content of a clinical framework for mirror therapy (MT) in patients with phantom limb pain (PLP) following amputation. Based on an a priori formulated theoretical model, 3 sources of data collection were used to develop the clinical framework. First, a review of the literature took place on important clinical aspects and the evidence on the effectiveness of MT in patients with phantom limb pain. In addition, questionnaires and semi-structured interviews were used to analyze clinical experiences and preferences of physical and occupational therapists and patients suffering from PLP regarding the application of MT. All data were finally clustered into main and subcategories and were used to complement and refine the theoretical model. For every main category of the a priori formulated theoretical model, several subcategories emerged from the literature search, patient, and therapist interviews. Based on these categories, we developed a clinical flowchart that incorporates the main and subcategories in a logical way according to the phases in methodical intervention defined by the Royal Dutch Society for Physical Therapy. In addition, we developed a comprehensive booklet that illustrates the individual steps of the clinical flowchart. In this study, a structured clinical framework for the application of MT in patients with PLP was developed. This framework is currently being tested for its effectiveness in a multicenter randomized controlled trial. © 2015 World Institute of Pain.

Blastema induction in aneurogenic state and Prrx-1 regulation by MMPs and FGFs in Ambystoma mexicanum limb regeneration.

PubMed

Satoh, Akira; makanae, Aki; Hirata, Ayako; Satou, Yutaka

2011-07-15

Urodele amphibians can regenerate amputated limbs. It has been considered that differentiated dermal tissues generate multipotent and undifferentiated cells called blastema cells during limb regeneration. In early phases of limb regeneration, blastema cells are induced by nerves and the apical epithelial cap (AEC). We had previously investigated the role of neurotrophic factors in blastema or blastema-like formation consisting of Prrx-1 positive cells. A new system suitable for investigating early phases of limb regeneration, called the accessory limb model (ALM), was recently developed. In this study, we performed a comparative transcriptome analysis between a blastema and wound using ALM. Matrix metalloproteinase (MMP) and fibroblast growth factor (FGF) signaling components were observed to be predominantly expressed in ALM blastema cells. Furthermore, we found that MMP activity induced a blastema marker gene, Prrx-1, in vitro, and FGF signaling pathways worked in coordination to maintain Prrx-1 expression and ALM blastema formation. Furthermore, we demonstrated that these two activities were sufficient to induce an ALM blastema in the absence of a nerve in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

Developmental origin of limb size variation in lizards.

PubMed

Andrews, Robin M; Skewes, Sable A

2017-05-01

In many respects, reptile hatchlings are fully functional, albeit miniature, adults. This means that the adult morphology must emerge during embryonic development. This insight emphasizes the connection between the mechanisms that generate phenotypic variation during embryonic development and the action of selection on post-hatching individuals. To determine when species-specific differences in limb and tail lengths emerge during embryonic development, we compared allometric patterns of early limb growth of four distantly related species of lizards. The major questions addressed were whether early embryonic limb and tail growth is characterized by the gradual (continuous allometry) or by the abrupt emergence (transpositional allometry) of size differences among species. Our observations supported transpositional allometry of both limbs and tails. Species-specific differences in limb and tail length were exhibited when limb and tail buds first protruded from the body wall. Genes known to be associated with early limb development of tetrapods are obvious targets for studies on the genetic mechanisms that determine interspecific differences in relative limb length. Broadly comparative studies of gene regulation would facilitate understanding of the mechanisms underlying adaptive variation in limb size, including limb reduction and loss, of squamate reptiles. © 2017 Wiley Periodicals, Inc.

Impact of renal medullary three-dimensional architecture on oxygen transport.

PubMed

Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis; Layton, Anita T

2014-08-01

We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial PO2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal PO2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the high metabolic requirements of the thick limbs and raises NaCl reabsorption. Copyright © 2014 the American Physiological Society.

Real-time patient-specific finite element analysis of internal stresses in the soft tissues of a residual limb: a new tool for prosthetic fitting.

PubMed

Portnoy, S; Yarnitzky, G; Yizhar, Z; Kristal, A; Oppenheim, U; Siev-Ner, I; Gefen, A

2007-01-01

Fitting of a prosthetic socket is a critical stage in the process of rehabilitation of a trans-tibial amputation (TTA) patient, since a misfit may cause pressure ulcers or a deep tissue injury (DTI: necrosis of the muscle flap under intact skin) in the residual limb. To date, prosthetic fitting typically depends on the subjective skills of the prosthetist, and is not supported by biomedical instrumentation that allows evaluation of the quality of fitting. Specifically, no technology is presently available to provide real-time continuous information on the internal distribution of mechanical stresses in the residual limb during fitting of the prosthesis, or while using it and this severely limits patient evaluations. In this study, a simplified yet clinically oriented patient-specific finite element (FE) model of the residual limb was developed for real-time stress analysis. For this purpose we employed a custom-made FE code that continuously calculates internal stresses in the residual limb, based on boundary conditions acquired in real-time from force sensors, located at the limb-prosthesis interface. Validation of the modeling system was accomplished by means of a synthetic phantom of the residual limb, which allowed simultaneous measurements of interface pressures and internal stresses. Human studies were conducted subsequently in five TTA patients. The dimensions of bones and soft tissues were obtained from X-rays of the residual limb of each patient. An indentation test was performed in order to obtain the effective elastic modulus of the soft tissues of the residual limb. Seven force sensors were placed between the residual limb and the prosthetic liner, and subjects walked on a treadmill during analysis. Generally, stresses under the shinbones were approximately threefold higher than stresses at the soft tissues behind the bones. Usage of a thigh corset decreased the stresses in the residual limb during gait by approximately 80%. Also, the stresses calculated during the trial of a subject who complained about pain and discomfort were the highest, confirming that his socket was not adequately fitted. We conclude that real-time patient-specific FE analysis of internal stresses in deep soft tissues of the residual limb in TTA patients is feasible. This method is promising for improving the fitting of prostheses in the clinical setting and for protecting the residual limb from pressure ulcers and DTI.

Nipbl and mediator cooperatively regulate gene expression to control limb development.

PubMed

Muto, Akihiko; Ikeda, Shingo; Lopez-Burks, Martha E; Kikuchi, Yutaka; Calof, Anne L; Lander, Arthur D; Schilling, Thomas F

2014-09-01

Haploinsufficiency for Nipbl, a cohesin loading protein, causes Cornelia de Lange Syndrome (CdLS), the most common "cohesinopathy". It has been proposed that the effects of Nipbl-haploinsufficiency result from disruption of long-range communication between DNA elements. Here we use zebrafish and mouse models of CdLS to examine how transcriptional changes caused by Nipbl deficiency give rise to limb defects, a common condition in individuals with CdLS. In the zebrafish pectoral fin (forelimb), knockdown of Nipbl expression led to size reductions and patterning defects that were preceded by dysregulated expression of key early limb development genes, including fgfs, shha, hand2 and multiple hox genes. In limb buds of Nipbl-haploinsufficient mice, transcriptome analysis revealed many similar gene expression changes, as well as altered expression of additional classes of genes that play roles in limb development. In both species, the pattern of dysregulation of hox-gene expression depended on genomic location within the Hox clusters. In view of studies suggesting that Nipbl colocalizes with the mediator complex, which facilitates enhancer-promoter communication, we also examined zebrafish deficient for the Med12 Mediator subunit, and found they resembled Nipbl-deficient fish in both morphology and gene expression. Moreover, combined partial reduction of both Nipbl and Med12 had a strongly synergistic effect, consistent with both molecules acting in a common pathway. In addition, three-dimensional fluorescent in situ hybridization revealed that Nipbl and Med12 are required to bring regions containing long-range enhancers into close proximity with the zebrafish hoxda cluster. These data demonstrate a crucial role for Nipbl in limb development, and support the view that its actions on multiple gene pathways result from its influence, together with Mediator, on regulation of long-range chromosomal interactions.

The Effect of Prosthetic Foot Push-off on Mechanical Loading Associated with Knee Osteoarthritis in Lower Extremity Amputees

PubMed Central

Morgenroth, David C.; Segal, Ava D.; Zelik, Karl E.; Czerniecki, Joseph M.; Klute, Glenn K.; Adamczyk, Peter G.; Orendurff, Michael S.; Hahn, Michael E.; Collins, Steven H.; Kuo, Art D.

2011-01-01

Lower extremity amputation not only limits mobility, but also increases the risk of knee osteoarthritis of the intact limb. Dynamic walking models of non-amputees suggest that pushing-off from the trailing limb can reduce collision forces on the leading limb. These collision forces may determine the peak knee external adduction moment (EAM), which has been linked to the development of knee OA in the general population. We therefore hypothesized that greater prosthetic push-off would lead to reduced loading and knee EAM of the intact limb in unilateral transtibial amputees. Seven unilateral transtibial amputees were studied during gait under three prosthetic foot conditions that were intended to vary push-off. Prosthetic foot-ankle push-off work, intact limb knee EAM and ground reaction impulses for both limbs during step-to-step transition were measured. Overall, trailing limb prosthetic push-off work was negatively correlated with leading intact limb 1st peak knee EAM (slope = −0.72 +/− 0.22; p=0.011). Prosthetic push-off work and 1st peak intact knee EAM varied significantly with foot type. The prosthetic foot condition with the least push-off demonstrated the largest knee EAM, which was reduced by 26% with the prosthetic foot producing the most push-off. Trailing prosthetic limb push-off impulse was negatively correlated with leading intact limb loading impulse (slope = −0.34 +/− 0.14; p=.001), which may help explain how prosthetic limb push-off can affect intact limb loading. Prosthetic feet that perform more prosthetic push-off appear to be associated with a reduction in 1st peak intact knee EAM, and their use could potentially reduce the risk and burden of knee osteoarthritis in this population. PMID:21803584

The effect of prosthetic foot push-off on mechanical loading associated with knee osteoarthritis in lower extremity amputees.

PubMed

Morgenroth, David C; Segal, Ava D; Zelik, Karl E; Czerniecki, Joseph M; Klute, Glenn K; Adamczyk, Peter G; Orendurff, Michael S; Hahn, Michael E; Collins, Steven H; Kuo, Art D

2011-10-01

Lower extremity amputation not only limits mobility, but also increases the risk of knee osteoarthritis of the intact limb. Dynamic walking models of non-amputees suggest that pushing-off from the trailing limb can reduce collision forces on the leading limb. These collision forces may determine the peak knee external adduction moment (EAM), which has been linked to the development of knee OA in the general population. We therefore hypothesized that greater prosthetic push-off would lead to reduced loading and knee EAM of the intact limb in unilateral transtibial amputees. Seven unilateral transtibial amputees were studied during gait under three prosthetic foot conditions that were intended to vary push-off. Prosthetic foot-ankle push-off work, intact limb knee EAM and ground reaction impulses for both limbs during step-to-step transition were measured. Overall, trailing limb prosthetic push-off work was negatively correlated with leading intact limb 1st peak knee EAM (slope=-.72±.22; p=.011). Prosthetic push-off work and 1st peak intact knee EAM varied significantly with foot type. The prosthetic foot condition with the least push-off demonstrated the largest knee EAM, which was reduced by 26% with the prosthetic foot producing the most push-off. Trailing prosthetic limb push-off impulse was negatively correlated with leading intact limb loading impulse (slope=-.34±.14; p=.001), which may help explain how prosthetic limb push-off can affect intact limb loading. Prosthetic feet that perform more prosthetic push-off appear to be associated with a reduction in 1st peak intact knee EAM, and their use could potentially reduce the risk and burden of knee osteoarthritis in this population. Published by Elsevier B.V.

Attenuation of bone morphogenetic protein signaling during amphibian limb development results in the generation of stage-specific defects.

PubMed

Jones, Tamsin E M; Day, Robert C; Beck, Caroline W

2013-11-01

The vertebrate limb is one of the most intensively studied organs in the field of developmental biology. Limb development in tetrapod vertebrates is highly conserved and dependent on the interaction of several important molecular pathways. The bone morphogenetic protein (BMP) signaling cascade is one of these pathways and has been shown to be crucial for several aspects of limb development. Here, we have used a Xenopus laevis transgenic line, in which expression of the inhibitor Noggin is under the control of the heat-shock promoter hsp70 to examine the effects of attenuation of BMP signaling at different stages of limb development. Remarkably different phenotypes were produced at different stages, illustrating the varied roles of BMP in development of the limb. Very early limb buds appeared to be refractory to the effects of BMP attenuation, developing normally in most cases. Ectopic limbs were produced by overexpression of Noggin corresponding to a brief window of limb development at about stage 49/50, as recently described by Christen et al. (2012). Attenuation of BMP signaling in stage 51 or 52 tadpoles lead to a reduction in the number of digits formed, resulting in hypodactyly or ectrodactyly, as well as occasional defects in the more proximal tibia-fibula. Finally, inhibition at stage 54 (paddle stage) led to the formation of dramatically shortened digits resulting from loss of distal phalanges. Transcriptome analysis has revealed the possibility that more Noggin-sensitive members of the BMP family could be involved in limb development than previously suspected. Our analysis demonstrates the usefulness of heat-shock-driven gene expression as an effective method for inhibiting a developmental pathway at different times during limb development. © 2013 Anatomical Society.

The versatility of limb scattered sunlight measurements

NASA Astrophysics Data System (ADS)

Bourassa, A. E.; Degenstein, D. A.; Sioris, C.; Rieger, L. A.; Zawada, D.

2017-12-01

Vertically resolved measurements of limb scattered sunlight spectra in the UV-Vis-NIR spectral range have been made from several satellite instruments in low earth orbit for many years, and there has been much success in using these measurements for retrievals of trace gas and aerosol from the upper troposphere to the mesosphere. Due in a large part to improvements in radiative transfer modelling, the versatility of the limb scatter measurement has continued to grow over the last several years. Using OSIRIS and OMPS instruments as primary examples, this talk will review the current capability of limb scatter measurements, and highlight recent results on ozone variability and trends in the UTLS, the continuation of the aerosol extinction record, NO2 distributions in the upper troposphere, and a new tomographic retrieval of ozone from the OMPS measurements. The future of limb scatter observations will also be discussed, including the development of two new Canadian suborbital instrument concepts that are targeted at high spatial resolution UTLS water vapor and cloud/aerosol measurements.

Transcriptomic insights into the genetic basis of mammalian limb diversity.

PubMed

Maier, Jennifer A; Rivas-Astroza, Marcelo; Deng, Jenny; Dowling, Anna; Oboikovitz, Paige; Cao, Xiaoyi; Behringer, Richard R; Cretekos, Chris J; Rasweiler, John J; Zhong, Sheng; Sears, Karen E

2017-03-23

From bat wings to whale flippers, limb diversification has been crucial to the evolutionary success of mammals. We performed the first transcriptome-wide study of limb development in multiple species to explore the hypothesis that mammalian limb diversification has proceeded through the differential expression of conserved shared genes, rather than by major changes to limb patterning. Specifically, we investigated the manner in which the expression of shared genes has evolved within and among mammalian species. We assembled and compared transcriptomes of bat, mouse, opossum, and pig fore- and hind limbs at the ridge, bud, and paddle stages of development. Results suggest that gene expression patterns exhibit larger variation among species during later than earlier stages of limb development, while within species results are more mixed. Consistent with the former, results also suggest that genes expressed at later developmental stages tend to have a younger evolutionary age than genes expressed at earlier stages. A suite of key limb-patterning genes was identified as being differentially expressed among the homologous limbs of all species. However, only a small subset of shared genes is differentially expressed in the fore- and hind limbs of all examined species. Similarly, a small subset of shared genes is differentially expressed within the fore- and hind limb of a single species and among the forelimbs of different species. Taken together, results of this study do not support the existence of a phylotypic period of limb development ending at chondrogenesis, but do support the hypothesis that the hierarchical nature of development translates into increasing variation among species as development progresses.

Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development.

PubMed

Fröbisch, Nadia B; Bickelmann, Constanze; Olori, Jennifer C; Witzmann, Florian

2015-11-12

Among extant tetrapods, salamanders are unique in showing a reversed preaxial polarity in patterning of the skeletal elements of the limbs, and in displaying the highest capacity for regeneration, including full limb and tail regeneration. These features are particularly striking as tetrapod limb development has otherwise been shown to be a highly conserved process. It remains elusive whether the capacity to regenerate limbs in salamanders is mechanistically and evolutionarily linked to the aberrant pattern of limb development; both are features classically regarded as unique to urodeles. New molecular data suggest that salamander-specific orphan genes play a central role in limb regeneration and may also be involved in the preaxial patterning during limb development. Here we show that preaxial polarity in limb development was present in various groups of temnospondyl amphibians of the Carboniferous and Permian periods, including the dissorophoids Apateon and Micromelerpeton, as well as the stereospondylomorph Sclerocephalus. Limb regeneration has also been reported in Micromelerpeton, demonstrating that both features were already present together in antecedents of modern salamanders 290 million years ago. Furthermore, data from lepospondyl 'microsaurs' on the amniote stem indicate that these taxa may have shown some capacity for limb regeneration and were capable of tail regeneration, including re-patterning of the caudal vertebral column that is otherwise only seen in salamander tail regeneration. The data from fossils suggest that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes. Salamanders are the only modern tetrapods that retained regenerative capacities as well as preaxial polarity in limb development.

A Heart-Hand Syndrome Gene: Tfap2b Plays a Critical Role in the Development and Remodeling of Mouse Ductus Arteriosus and Limb Patterning

PubMed Central

Zhao, Feng; Bosserhoff, Anja-Katrin; Buettner, Reinhard; Moser, Markus

2011-01-01

Background Patent ductus arteriosus (PDA) is one of the most common forms of congenital heart disease. Mutations in transcription factor TFAP2B cause Char syndrome, a human disorder characterized by PDA, facial dysmorphysm and hand anomalies. Animal research data are needed to understand the mechanisms. The aim of our study was to elucidate the pathogenesis of Char syndrome at the molecular level. Methodology/Principal Findings Gene expression of Tfap2b during mouse development was studied, and newborns of Tfap2b-deficient mice were examined to identify phenotypes. Gel shift assays had been carried out to search for Tfap2 downstream genes. Promoters of candidate genes were cloned into a reporter construct and used to demonstrate their regulation by Tfap2b in cell transfection. In situ hybridizations showed that the murine transcription factor Tfap2b was expressed during the entire development of mouse ductus arteriosus. Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. Consequently, the lungs of Tfap2b −/− mice demonstrated progressive congestion of the pulmonary capillaries, which was postulated to result secondarily from PDA. In addition, Tfap2b was expressed in the limb buds, particularly in the posterior limb field during development. Lack of Tfap2b resulted in bilateral postaxial accessory digits. Further study indicated that expressions of bone morphogenetic protein (Bmp) genes, which are reported to be involved in the limb patterning and ductal development, were altered in limb buds of Tfap2b-deficient embryos, due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b. Conclusions/Significance Tfap2b plays important roles in the development of mouse ductus arteriosus and limb patterning. Loss of Tfap2b results in altered Bmp expression that may cause the heart-limb defects observed in Tfap2b mouse mutants and Char syndrome patients. The Tfap2b knockout mouse may add to the very limited available animal models of PDA. PMID:21829553

Discharge destination following lower limb fracture: development of a prediction model to assist with decision making.

PubMed

Kimmel, Lara A; Holland, Anne E; Edwards, Elton R; Cameron, Peter A; De Steiger, Richard; Page, Richard S; Gabbe, Belinda

2012-06-01

Accurate prediction of the likelihood of discharge to inpatient rehabilitation following lower limb fracture made on admission to hospital may assist patient discharge planning and decrease the burden on the hospital system caused by delays in decision making. To develop a prognostic model for discharge to inpatient rehabilitation. Isolated lower extremity fracture cases (excluding fractured neck of femur), captured by the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), were extracted for analysis. A training data set was created for model development and validation data set for evaluation. A multivariable logistic regression model was developed based on patient and injury characteristics. Models were assessed using measures of discrimination (C-statistic) and calibration (Hosmer-Lemeshow (H-L) statistic). A total of 1429 patients met the inclusion criteria and were randomly split into training and test data sets. Increasing age, more proximal fracture type, compensation or private fund source for the admission, metropolitan location of residence, not working prior to injury and having a self-reported pre-injury disability were included in the final prediction model. The C-statistic for the model was 0.92 (95% confidence interval (CI) 0.88, 0.95) with an H-L statistic of χ(2)=11.62, p=0.17. For the test data set, the C-statistic was 0.86 (95% CI 0.83, 0.90) with an H-L statistic of χ(2)=37.98, p<0.001. A model to predict discharge to inpatient rehabilitation following lower limb fracture was developed with excellent discrimination although the calibration was reduced in the test data set. This model requires prospective testing but could form an integral part of decision making in regards to discharge disposition to facilitate timely and accurate referral to rehabilitation and optimise resource allocation. Copyright © 2011 Elsevier Ltd. All rights reserved.

A three-dimensional thermal and electromagnetic model of whole limb heating with a MAPA.

PubMed

Charny, C K; Levin, R L

1991-10-01

Previous studies by the authors have shown that if properly implemented, the Pennes assumptions can be applied to quantify bioheat transfer during extremity heating. Given its relative numerical simplicity and its ability to predict temperatures in thermoregulated tissue, the Pennes model of bioheat transfer was utilized in a three-dimensional thermal model of limb heating. While the arterial blood temperature was assumed to be radially uniform within a cross section of the limb, axial gradients in the arterial and venous blood temperatures were computed with this three-dimensional model. A realistically shaped, three-dimensional finite element model of a tumor-bearing human lower leg was constructed and was "attached" mathematically to the whole body thermal model of man described in previous studies by the authors. The central as well as local thermoregulatory feedback control mechanisms which determine blood perfusion to the various tissues and rate of evaporation by sweating were input into the limb model. In addition, the temperature of the arterial blood which feeds into the most proximal section of the lower leg was computed by the whole body thermal model. The variations in the shape of the tissues which comprise the limb were obtained from computerized tomography scans. Axial variations in the energy deposition patterns along the length of the limb exposed to a miniannular phased array (MAPA) applicator were also input into this model of limb heating. Results indicate that proper positioning of the limb relative to the MAPA is a significant factor in determining the effectiveness of the treatment. A patient-specific hyperthermia protocol can be designed using this coupled electromagnetic and thermal model.

A Lower Limb-Pelvis Finite Element Model with 3D Active Muscles.

PubMed

Mo, Fuhao; Li, Fan; Behr, Michel; Xiao, Zhi; Zhang, Guanjun; Du, Xianping

2018-01-01

A lower limb-pelvis finite element (FE) model with active three-dimensional (3D) muscles was developed in this study for biomechanical analysis of human body. The model geometry was mainly reconstructed from a male volunteer close to the anthropometry of a 50th percentile Chinese male. Tissue materials and structural features were established based on the literature and new implemented experimental tests. In particular, the muscle was modeled with a combination of truss and hexahedral elements to define its passive and active properties as well as to follow the detailed anatomy structure. Both passive and active properties of the model were validated against the experiments of Post-Mortem Human Surrogate (PMHS) and volunteers, respectively. The model was then used to simulate driver's emergency braking during frontal crashes and investigate Knee-Thigh-Hip (KTH) injury mechanisms and tolerances of the human body. A significant force and bending moment variance was noted for the driver's femur due to the effects of active muscle forces during emergency braking. In summary, the present lower limb-pelvis model can be applied in various research fields to support expensive and complex physical tests or corresponding device design.

PyLDTk: Python toolkit for calculating stellar limb darkening profiles and model-specific coefficients for arbitrary filters

NASA Astrophysics Data System (ADS)

Parviainen, Hannu

2015-10-01

PyLDTk automates the calculation of custom stellar limb darkening (LD) profiles and model-specific limb darkening coefficients (LDC) using the library of PHOENIX-generated specific intensity spectra by Husser et al. (2013). It facilitates exoplanet transit light curve modeling, especially transmission spectroscopy where the modeling is carried out for custom narrow passbands. PyLDTk construct model-specific priors on the limb darkening coefficients prior to the transit light curve modeling. It can also be directly integrated into the log posterior computation of any pre-existing transit modeling code with minimal modifications to constrain the LD model parameter space directly by the LD profile, allowing for the marginalization over the whole parameter space that can explain the profile without the need to approximate this constraint by a prior distribution. This is useful when using a high-order limb darkening model where the coefficients are often correlated, and the priors estimated from the tabulated values usually fail to include these correlations.

Initial evaluation of a canine stifle arthrotomy post-operative pain model.

PubMed

Tomas, A; Bledsoe, D; Wall, S; Davidson, G; Lascelles, B D X

2015-06-01

Most models of acute post-operative orthopedic pain involve the injection of a clinically irrelevant pro-inflammatory agent. The ideal model should, however, be clinically relevant and allow full functional recovery of enrolled animals after research is completed. This study explored the validity of a model employing arthrotomy and objectively measured limb use. Six purpose-bred Beagles underwent arthrotomies on each stifle with a washout period in between. Using a randomized crossover design, each dog received placebo and an extended-release buprenorphine (ER-Bup) preparation. Static and dynamic ground reaction forces (GRFs) were measured prior to and for 72 h following surgery using a pressure sensitive walkway (PSW). GRFs for each hind limb were compared using difference (delta), and symmetry indices (SI). The effects of surgery and of treatment were analyzed using repeated measures ANCOVA. The results indicated significantly decreased limb use compared to baseline for placebo, and significantly increased limb use in the ER-Bup group over placebo at all times for % bodyweight distribution (%BWdistrib), peak vertical force (PVF) and vertical impulse (VI). There was a significant treatment by time interaction for velocity (P = 0.03) and %BWdistrib (P = 0.01, 0.003). Overall, the data show that reduced limb use was present for at least 72 h following arthrotomy. In addition, the use of the ER-Bup analgesic decreased lameness, confirming the validity of this approach as a model of post-operative pain. Subjective assessments did not detect the pain-inducing effects of arthrotomy or pain-alleviating effects of treatment, and subjective measures of procedural pain in research dogs need to be developed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of step length and step frequency on lower-limb muscle function in human gait.

PubMed

Lim, Yoong Ping; Lin, Yi-Chung; Pandy, Marcus G

2017-05-24

The aim of this study was to quantify the effects of step length and step frequency on lower-limb muscle function in walking. Three-dimensional gait data were used in conjunction with musculoskeletal modeling techniques to evaluate muscle function over a range of walking speeds using prescribed combinations of step length and step frequency. The body was modeled as a 10-segment, 21-degree-of-freedom skeleton actuated by 54 muscle-tendon units. Lower-limb muscle forces were calculated using inverse dynamics and static optimization. We found that five muscles - GMAX, GMED, VAS, GAS, and SOL - dominated vertical support and forward progression independent of changes made to either step length or step frequency, and that, overall, changes in step length had a greater influence on lower-limb joint motion, net joint moments and muscle function than step frequency. Peak forces developed by the uniarticular hip and knee extensors, as well as the normalized fiber lengths at which these muscles developed their peak forces, correlated more closely with changes in step length than step frequency. Increasing step length resulted in larger contributions from the hip and knee extensors and smaller contributions from gravitational forces (limb posture) to vertical support. These results provide insight into why older people with weak hip and knee extensors walk more slowly by reducing step length rather than step frequency and also help to identify the key muscle groups that ought to be targeted in exercise programs designed to improve gait biomechanics in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modulating tibiofemoral contact force in the sheep hind limb via treadmill walking: Predictions from an opensim musculoskeletal model.

PubMed

Lerner, Zachary F; Gadomski, Benjamin C; Ipson, Allison K; Haussler, Kevin K; Puttlitz, Christian M; Browning, Raymond C

2015-08-01

Sheep are a predominant animal model used to study a variety of orthopedic conditions. Understanding and controlling the in-vivo loading environment in the sheep hind limb is often necessary for investigations relating to bone and joint mechanics. The purpose of this study was to develop a musculoskeletal model of an adult sheep hind limb and investigate the effects of treadmill walking speed on muscle and joint contact forces. We constructed the skeletal geometry of the model from computed topography images. Dual-energy x-ray absorptiometry was utilized to establish the inertial properties of each model segment. Detailed dissection and tendon excursion experiments established the requisite muscle lines of actions. We used OpenSim and experimentally-collected marker trajectories and ground reaction forces to quantify muscle and joint contact forces during treadmill walking at 0.25 m• s(-1) and 0.75 m• s(-1) . Peak compressive and anterior-posterior tibiofemoral contact forces were 20% (0.38 BW, p = 0.008) and 37% (0.17 BW, p = 0.040) larger, respectively, at the moderate gait speed relative to the slower speed. Medial-lateral tibiofemoral contact forces were not significantly different. Adjusting treadmill speed appears to be a viable method to modulate compressive and anterior-posterior tibiofemoral contact forces in the sheep hind limb. The musculoskeletal model is freely-available at www.SimTK.org. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Model tests of gliding with different hindwing configurations in the four-winged dromaeosaurid Microraptor gui

PubMed Central

Alexander, David E.; Gong, Enpu; Martin, Larry D.; Burnham, David A.; Falk, Amanda R.

2010-01-01

Fossils of the remarkable dromaeosaurid Microraptor gui and relatives clearly show well-developed flight feathers on the hind limbs as well as the front limbs. No modern vertebrate has hind limbs functioning as independent, fully developed wings; so, lacking a living example, little agreement exists on the functional morphology or likely flight configuration of the hindwing. Using a detailed reconstruction based on the actual skeleton of one individual, cast in the round, we developed light-weight, three-dimensional physical models and performed glide tests with anatomically reasonable hindwing configurations. Models were tested with hindwings abducted and extended laterally, as well as with a previously described biplane configuration. Although the hip joint requires the hindwing to have at least 20° of negative dihedral (anhedral), all configurations were quite stable gliders. Glide angles ranged from 3° to 21° with a mean estimated equilibrium angle of 13.7°, giving a lift to drag ratio of 4.1:1 and a lift coefficient of 0.64. The abducted hindwing model’s equilibrium glide speed corresponds to a glide speed in the living animal of 10.6 m·s−1. Although the biplane model glided almost as well as the other models, it was structurally deficient and required an unlikely weight distribution (very heavy head) for stable gliding. Our model with laterally abducted hindwings represents a biologically and aerodynamically reasonable configuration for this four-winged gliding animal. M. gui’s feathered hindwings, although effective for gliding, would have seriously hampered terrestrial locomotion. PMID:20133792

Nevus density and melanoma risk in women: a pooled analysis to test the divergent pathway hypothesis

PubMed Central

Olsen, Catherine M.; Zens, Michael S.; Stukel, Therese A.; Sacerdote, Carlotta; Chang, Yu-mei; Armstrong, Bruce K.; Bataille, Veronique; Berwick, Marianne; Elwood, J. Mark; Holly, Elizabeth A.; Kirkpatrick, Connie; Mack, Thomas; Bishop, Julia Newton; Østerlind, Anne; Swerdlow, Anthony J.; Zanetti, Roberto; Green, Adèle C.; Karagas, Margaret R.; Whiteman, David C

2009-01-01

A “divergent pathway” model for the development of cutaneous melanoma has been proposed. The model hypothesizes that melanomas occurring in people with a low tendency to develop nevi will, on average, arise more commonly on habitually sun-exposed body sites such as the head and neck. In contrast, people with an inherent propensity to develop nevi will tend to develop melanomas most often on body sites with large melanocyte populations, such as on the back. We conducted a collaborative analysis to test this hypothesis using the original data from ten case-control studies of melanoma in women (2406 cases and 3119 controls), with assessment of the potential confounding effects of socioeconomic, pigmentary, and sun exposure-related factors. Higher nevus count on the arm was associated specifically with an increased risk of melanoma of the trunk (p for trend=0.0004) and limbs (both upper and lower limb p for trends=0.01), but not of the head and neck (p for trend=0.25). The pooled odds ratios for the highest quartile of non-zero nevus count versus none were 4.6 (95% confidence interval (CI) 2.7–7.6) for melanoma of the trunk, 2.0 (95% CI 0.9–4.5) for the head and neck, 4.2 (95% CI 2.3–7.5) for the upper limbs and 3.4 (95% CI 1.5–7.9) for the lower limbs. Aggregate data from these studies suggest that high nevus counts are strongly associated with melanoma of the trunk but less so if at all of the head and neck. This finding supports different etiologic pathways of melanoma development by anatomic site. PMID:19035450

Musculoskeletal modelling of an ostrich (Struthio camelus) pelvic limb: influence of limb orientation on muscular capacity during locomotion

PubMed Central

Rankin, Jeffery W.; Rubenson, Jonas; Rosenbluth, Kate H.; Siston, Robert A.; Delp, Scott L.

2015-01-01

We developed a three-dimensional, biomechanical computer model of the 36 major pelvic limb muscle groups in an ostrich (Struthio camelus) to investigate muscle function in this, the largest of extant birds and model organism for many studies of locomotor mechanics, body size, anatomy and evolution. Combined with experimental data, we use this model to test two main hypotheses. We first query whether ostriches use limb orientations (joint angles) that optimize the moment-generating capacities of their muscles during walking or running. Next, we test whether ostriches use limb orientations at mid-stance that keep their extensor muscles near maximal, and flexor muscles near minimal, moment arms. Our two hypotheses relate to the control priorities that a large bipedal animal might evolve under biomechanical constraints to achieve more effective static weight support. We find that ostriches do not use limb orientations to optimize the moment-generating capacities or moment arms of their muscles. We infer that dynamic properties of muscles or tendons might be better candidates for locomotor optimization. Regardless, general principles explaining why species choose particular joint orientations during locomotion are lacking, raising the question of whether such general principles exist or if clades evolve different patterns (e.g., weighting of muscle force–length or force–velocity properties in selecting postures). This leaves theoretical studies of muscle moment arms estimated for extinct animals at an impasse until studies of extant taxa answer these questions. Finally, we compare our model’s results against those of two prior studies of ostrich limb muscle moment arms, finding general agreement for many muscles. Some flexor and extensor muscles exhibit self-stabilization patterns (posture-dependent switches between flexor/extensor action) that ostriches may use to coordinate their locomotion. However, some conspicuous areas of disagreement in our results illustrate some cautionary principles. Importantly, tendon-travel empirical measurements of muscle moment arms must be carefully designed to preserve 3D muscle geometry lest their accuracy suffer relative to that of anatomically realistic models. The dearth of accurate experimental measurements of 3D moment arms of muscles in birds leaves uncertainty regarding the relative accuracy of different modelling or experimental datasets such as in ostriches. Our model, however, provides a comprehensive set of 3D estimates of muscle actions in ostriches for the first time, emphasizing that avian limb mechanics are highly three-dimensional and complex, and how no muscles act purely in the sagittal plane. A comparative synthesis of experiments and models such as ours could provide powerful synthesis into how anatomy, mechanics and control interact during locomotion and how these interactions evolve. Such a framework could remove obstacles impeding the analysis of muscle function in extinct taxa. PMID:26082859

The axolotl limb blastema: cellular and molecular mechanisms driving blastema formation and limb regeneration in tetrapods

PubMed Central

McCusker, Catherine; Bryant, Susan V.

2015-01-01

Abstract The axolotl is one of the few tetrapods that are capable of regenerating complicated biological structures, such as complete limbs, throughout adulthood. Upon injury the axolotl generates a population of regeneration‐competent limb progenitor cells known as the blastema, which will grow, establish pattern, and differentiate into the missing limb structures. In this review we focus on the crucial early events that occur during wound healing, the neural−epithelial interactions that drive the formation of the early blastema, and how these mechanisms differ from those of other species that have restricted regenerative potential, such as humans. We also discuss how the presence of cells from the different axes of the limb is required for the continued growth and establishment of pattern in the blastema as described in the polar coordinate model, and how this positional information is reprogrammed in blastema cells during regeneration. Multiple cell types from the mature limb stump contribute to the blastema at different stages of regeneration, and we discuss the contribution of these types to the regenerate with reference to whether they are “pattern‐forming” or “pattern‐following” cells. Lastly, we explain how an engineering approach will help resolve unanswered questions in limb regeneration, with the goal of translating these concepts to developing better human regenerative therapies. PMID:27499868

Expression of Msx-2 during development, regeneration, and wound healing in axolotl limbs.

PubMed

Carlson, M R; Bryant, S V; Gardiner, D M

1998-12-15

Msx genes are transcription factors that are expressed during embryogenesis of developing appendages in regions of epithelial-mesenchymal interactions. Various lines of evidence indicate that these genes function to maintain embryonic tissues in an undifferentiated, proliferative state. We have identified the axolotl homolog of Msx-2, and investigated its expression during limb development, limb regeneration, and wound healing. As in limb buds of higher vertebrates, axolotl Msx-2 is expressed in the apical epidermis and mesenchyme; however, its expression domain is more extensive, reflecting the broader region of the apical epidermal cap in amphibians. Msx-2 expression is downregulated at late stages of limb development, but is reexpressed within one hour after limb amputation. Msx-2 is also reexpressed during wound healing, and may be essential in the early stages of initiation of the limb regeneration cascade.

Can We Achieve Intuitive Prosthetic Elbow Control Based on Healthy Upper Limb Motor Strategies?

PubMed Central

Merad, Manelle; de Montalivet, Étienne; Touillet, Amélie; Martinet, Noël; Roby-Brami, Agnès; Jarrassé, Nathanaël

2018-01-01

Most transhumeral amputees report that their prosthetic device lacks functionality, citing the control strategy as a major limitation. Indeed, they are required to control several degrees of freedom with muscle groups primarily used for elbow actuation. As a result, most of them choose to have a one-degree-of-freedom myoelectric hand for grasping objects, a myoelectric wrist for pronation/supination, and a body-powered elbow. Unlike healthy upper limb movements, the prosthetic elbow joint angle, adjusted prior to the motion, is not involved in the overall upper limb movements, causing the rest of the body to compensate for the lack of mobility of the prosthesis. A promising solution to improve upper limb prosthesis control exploits the residual limb mobility: like in healthy movements, shoulder and prosthetic elbow motions are coupled using inter-joint coordination models. The present study aims to test this approach. A transhumeral amputated individual used a prosthesis with a residual limb motion-driven elbow to point at targets. The prosthetic elbow motion was derived from IMU-based shoulder measurements and a generic model of inter-joint coordinations built from healthy individuals data. For comparison, the participant also performed the task while the prosthetic elbow was implemented with his own myoelectric control strategy. The results show that although the transhumeral amputated participant achieved the pointing task with a better precision when the elbow was myoelectrically-controlled, he had to develop large compensatory trunk movements. Automatic elbow control reduced trunk displacements, and enabled a more natural body behavior with synchronous shoulder and elbow motions. However, due to socket impairments, the residual limb amplitudes were not as large as those of healthy shoulder movements. Therefore, this work also investigates if a control strategy whereby prosthetic joints are automatized according to healthy individuals' coordination models can lead to an intuitive and natural prosthetic control. PMID:29456499

Sonic Hedgehog Signaling in Limb Development

PubMed Central

Tickle, Cheryll; Towers, Matthew

2017-01-01

The gene encoding the secreted protein Sonic hedgehog (Shh) is expressed in the polarizing region (or zone of polarizing activity), a small group of mesenchyme cells at the posterior margin of the vertebrate limb bud. Detailed analyses have revealed that Shh has the properties of the long sought after polarizing region morphogen that specifies positional values across the antero-posterior axis (e.g., thumb to little finger axis) of the limb. Shh has also been shown to control the width of the limb bud by stimulating mesenchyme cell proliferation and by regulating the antero-posterior length of the apical ectodermal ridge, the signaling region required for limb bud outgrowth and the laying down of structures along the proximo-distal axis (e.g., shoulder to digits axis) of the limb. It has been shown that Shh signaling can specify antero-posterior positional values in limb buds in both a concentration- (paracrine) and time-dependent (autocrine) fashion. Currently there are several models for how Shh specifies positional values over time in the limb buds of chick and mouse embryos and how this is integrated with growth. Extensive work has elucidated downstream transcriptional targets of Shh signaling. Nevertheless, it remains unclear how antero-posterior positional values are encoded and then interpreted to give the particular structure appropriate to that position, for example, the type of digit. A distant cis-regulatory enhancer controls limb-bud-specific expression of Shh and the discovery of increasing numbers of interacting transcription factors indicate complex spatiotemporal regulation. Altered Shh signaling is implicated in clinical conditions with congenital limb defects and in the evolution of the morphological diversity of vertebrate limbs. PMID:28293554

Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity

NASA Technical Reports Server (NTRS)

Duke, Jackie C.

1983-01-01

The effect of excess gravity on in vitro mammalian limb chondrogenesis is studied. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured, and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen-sensitive period of chondrogenesis.

ENGINEERING APPLICATION AND ECONOMICS OF LIMB (LIMESTONE INJECTION/MULTISTAGE BURNERS)

EPA Science Inventory

The paper describes the use of an EPA LIMB cost model, in conjunction with cost and performance models for flue gas desulfurization (FGD), to compare these two technologies under similar premises. (NOTE: The performance goals of LIMB, EPA's acronym for Limestone Injection/Multist...

Developing bones are differentially affected by compromised skeletal muscle formation

PubMed Central

Nowlan, Niamh C.; Bourdon, Céline; Dumas, Gérard; Tajbakhsh, Shahragim; Prendergast, Patrick J.; Murphy, Paula

2010-01-01

Mechanical forces are essential for normal adult bone function and repair, but the impact of prenatal muscle contractions on bone development remains to be explored in depth in mammalian model systems. In this study, we analyze skeletogenesis in two ‘muscleless’ mouse mutant models in which the formation of skeletal muscle development is disrupted; Myf5nlacZ/nlacZ:MyoD−/− and Pax3Sp/Sp (Splotch). Ossification centers were found to be differentially affected in the muscleless limbs, with significant decreases in bone formation in the scapula, humerus, ulna and femur, but not in the tibia. In the scapula and humerus, the morphologies of ossification centers were abnormal in muscleless limbs. Histology of the humerus revealed a decreased extent of the hypertrophic zone in mutant limbs but no change in the shape of this region. The elbow joint was also found to be clearly affected with a dramatic reduction in the joint line, while no abnormalities were evident in the knee. The humeral deltoid tuberosity was significantly reduced in size in the Myf5nlacZ/nlacZ:MyoD−/− mutants while a change in shape but not in size was found in the humeral tuberosities of the Pax3Sp/Sp mutants. We also examined skeletal development in a ‘reduced muscle’ model, the Myf5nlacZ/+:MyoD−/− mutant, in which skeletal muscle forms but with reduced muscle mass. The reduced muscle phenotype appeared to have an intermediate effect on skeletal development, with reduced bone formation in the scapula and humerus compared to controls, but not in other rudiments. In summary, we have demonstrated that skeletal development is differentially affected by the lack of skeletal muscle, with certain rudiments and joints being more severely affected than others. These findings indicate that the response of skeletal progenitor cells to biophysical stimuli may depend upon their location in the embryonic limb, implying a complex interaction between mechanical forces and location-specific regulatory factors affecting bone and joint development. PMID:19948261

Detection of genes regulated by Lmx1b during limb dorsalization.

PubMed

Feenstra, Jennifer M; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E; Eppey, Richard J; Oberg, Kerby C

2012-05-01

Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wild type mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes that were differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism that includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. © 2012 The Authors. Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Skin temperature during cutaneous wound healing in an equine model of cutaneous fibroproliferative disorder: kinetics and anatomic-site differences.

PubMed

Celeste, Christophe J; Deschesne, Karine; Riley, Christopher B; Theoret, Christine L

2013-02-01

To map skin temperature kinetics, and by extension skin blood flow throughout normal or abnormal repair of full-thickness cutaneous wounds created on the horse body and limb, using infrared thermography. Experimental. Standardbreds (n = 6), aged 3-4 years. Three cutaneous wounds were created on the dorsolateral surface of each metacarpus and on the lateral thoracic wall. Thoracic skin wounds and those on 1 randomly chosen forelimb healed by second intention without a bandage, whereas contralateral limb wounds were bandaged to induce formation of exuberant granulation tissue (EGT). Thermal data were collected from all planned wound sites before the surgical procedure (baseline), and at 24, 48, 96 hours, 1, 2, and 4 weeks after wounding. Data were analyzed using repeated measures ANOVA and a priori contrasts submitted to Bonferroni sequential correction. Level of significance was P < .05. Cutaneous wound temperature (CWT) increased temporally from preoperative period to week 1 postwounding, independently of anatomic location (P < .0001). CWT of limb wounds was significantly less than that of body wounds throughout healing (P < .01). CWT of limb wounds managed with bandages and developing EGT was significantly less than that of unbandaged limb wounds, which did not develop EGT (P ≤ .01). CWT varied with anatomic location and throughout healing. CWT of wounds developing EGT was significantly less than that of wounds without EGT. © Copyright 2012 by The American College of Veterinary Surgeons.

Detection of Genes Regulated by Lmx1b During Limb Dorsalization

PubMed Central

Feenstra, Jennifer M.; Kanaya, Kohei; Pira, Charmaine U; Hoffman, Sarah E.; Eppey, Richard J.; Oberg, Kerby C.

2012-01-01

Lmx1b is a homeodomain transcription factor that regulates dorsal identity during limb development. Lmx1b knockout (KO) mice develop distal ventral-ventral limbs. Although induction of Lmx1b is linked to Wnt7a expression in the dorsal limb ectoderm, the downstream targets of Lmx1b that accomplish limb dorsalization are unknown. To identify genes targeted by Lmx1b, we compared gene arrays from Lmx1b KO and wildtype mouse limbs during limb dorsalization, i.e., 11.5, 12.5, and 13.5 days post coitum. We identified 54 target genes differentially expressed in all three stages. Several skeletal targets, including Emx2, Matrilin1 and Matrilin4, demonstrated a loss of scapular expression in the Lmx1b KO mice, supporting a role for Lmx1b in scapula development. Furthermore, the relative abundance of extracellular matrix-related soft tissue targets regulated by Lmx1b, such as collagens and proteoglycans, suggests a mechanism which includes changes in the extracellular matrix composition to accomplish limb dorsalization. Our study provides the most comprehensive characterization of genes regulated by Lmx1b during limb development to-date and provides targets for further investigation. PMID:22417325

Modeling rate sensitivity of exercise transient responses to limb motion.

PubMed

Yamashiro, Stanley M; Kato, Takahide

2014-10-01

Transient responses of ventilation (V̇e) to limb motion can exhibit predictive characteristics. In response to a change in limb motion, a rapid change in V̇e is commonly observed with characteristics different than during a change in workload. This rapid change has been attributed to a feed-forward or adaptive response. Rate sensitivity was explored as a specific hypothesis to explain predictive V̇e responses to limb motion. A simple model assuming an additive feed-forward summation of V̇e proportional to the rate of change of limb motion was studied. This model was able to successfully account for the adaptive phase correction observed during human sinusoidal changes in limb motion. Adaptation of rate sensitivity might also explain the reduction of the fast component of V̇e responses previously reported following sudden exercise termination. Adaptation of the fast component of V̇e response could occur by reduction of rate sensitivity. Rate sensitivity of limb motion was predicted by the model to reduce the phase delay between limb motion and V̇e response without changing the steady-state response to exercise load. In this way, V̇e can respond more quickly to an exercise change without interfering with overall feedback control. The asymmetry between responses to an incremental and decremental ramp change in exercise can also be accounted for by the proposed model. Rate sensitivity leads to predicted behavior, which resembles responses observed in exercise tied to expiratory reserve volume. Copyright © 2014 the American Physiological Society.

Development of esMOCA RULA, Motion Capture Instrumentation for RULA Assessment

NASA Astrophysics Data System (ADS)

Akhmad, S.; Arendra, A.

2018-01-01

The purpose of this research is to build motion capture instrumentation using sensors fusion accelerometer and gyroscope to assist in RULA assessment. Data processing of sensor orientation is done in every sensor node by digital motion processor. Nine sensors are placed in the upper limb of operator subject. Development of kinematics model is done with Simmechanic Simulink. This kinematics model receives streaming data from sensors via wireless sensors network. The output of the kinematics model is the relative angular angle between upper limb members and visualized on the monitor. This angular information is compared to the look-up table of the RULA worksheet and gives the RULA score. The assessment result of the instrument is compared with the result of the assessment by rula assessors. To sum up, there is no significant difference of assessment by the instrument with an assessment by an assessor.

Evaluation by medical students of the educational value of multi-material and multi-colored three-dimensional printed models of the upper limb for anatomical education.

PubMed

Mogali, Sreenivasulu Reddy; Yeong, Wai Yee; Tan, Heang Kuan Joel; Tan, Gerald Jit Shen; Abrahams, Peter H; Zary, Nabil; Low-Beer, Naomi; Ferenczi, Michael Alan

2018-01-01

For centuries, cadaveric material has been the cornerstone of anatomical education. For reasons of changes in curriculum emphasis, cost, availability, expertise, and ethical concerns, several medical schools have replaced wet cadaveric specimens with plastinated prosections, plastic models, imaging, and digital models. Discussions about the qualities and limitations of these alternative teaching resources are on-going. We hypothesize that three-dimensional printed (3DP) models can replace or indeed enhance existing resources for anatomical education. A novel multi-colored and multi-material 3DP model of the upper limb was developed based on a plastinated upper limb prosection, capturing muscles, nerves, arteries and bones with a spatial resolution of ∼1 mm. This study aims to examine the educational value of the 3DP model from the learner's point of view. Students (n = 15) compared the developed 3DP models with the plastinated prosections, and provided their views on their learning experience using 3DP models using a survey and focus group discussion. Anatomical features in 3DP models were rated as accurate by all students. Several positive aspects of 3DP models were highlighted, such as the color coding by tissue type, flexibility and that less care was needed in the handling and examination of the specimen than plastinated specimens which facilitated the appreciation of relations between the anatomical structures. However, students reported that anatomical features in 3DP models are less realistic compared to the plastinated specimens. Multi-colored, multi-material 3DP models are a valuable resource for anatomical education and an excellent adjunct to wet cadaveric or plastinated prosections. Anat Sci Educ 11: 54-64. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Air pollution and limb defects: a matched-pairs case-control study in Taiwan.

PubMed

Lin, Yu-Ting; Lee, Yungling Leo; Jung, Chau-Ren; Jaakkola, Jouni J K; Hwang, Bing-Fang

2014-07-01

Air pollution influences the development of limb defects in animals. There is little epidemiologic evidence on the effect of prenatal air pollution exposure on the risk of limb defects. To assess the relations between exposure to ambient air pollutants and the risk of limb defects. We conducted a matched-pairs case-control study in Taiwan from 2001 through 2007. The case group consisted of 1687 limb defects and the control group was density-sampling matched one to ten based on the month and year of conception from 1510,064 live singleton newborns in 2001-2007. Adjusted conditional logistic regression models were used to estimate odds ratios per 10 ppb change for O3, NO2, 1 ppb change for SO2, 10 µg/m(3) change for PM10, and 100 ppb change for CO during the first trimester and first three gestational months. Of the specific limb defects, reduction deformities of limbs (adjusted OR=1.024, 95% CI: 1.000, 1.048) was associated with a 1 ppb increase in SO2 during weeks of 9-12 of gestation as well as the first trimester. Reduction deformities of limbs was also associated with a 10 ppb increase in O3 during weeks of 1-4 of gestation (adjusted OR=1.391, 95% CI: 1.064, 1.818) among preterm births. The present study provides evidence that exposure to outdoor air SO2 during the first trimester of pregnancy may increase the risk of limb defects. Exposure to O3 was associated with reduction deformities of limbs among preterm births. Similar levels of SO2 and O3 are encountered globally by large numbers of pregnant women. Copyright © 2014 Elsevier Inc. All rights reserved.

Multi-view light-sheet imaging and tracking with the MaMuT software reveals the cell lineage of a direct developing arthropod limb

PubMed Central

Stamataki, Evangelia; Harich, Benjamin; Guignard, Léo; Preibisch, Stephan; Shorte, Spencer; Keller, Philipp J

2018-01-01

During development, coordinated cell behaviors orchestrate tissue and organ morphogenesis. Detailed descriptions of cell lineages and behaviors provide a powerful framework to elucidate the mechanisms of morphogenesis. To study the cellular basis of limb development, we imaged transgenic fluorescently-labeled embryos from the crustacean Parhyale hawaiensis with multi-view light-sheet microscopy at high spatiotemporal resolution over several days of embryogenesis. The cell lineage of outgrowing thoracic limbs was reconstructed at single-cell resolution with new software called Massive Multi-view Tracker (MaMuT). In silico clonal analyses suggested that the early limb primordium becomes subdivided into anterior-posterior and dorsal-ventral compartments whose boundaries intersect at the distal tip of the growing limb. Limb-bud formation is associated with spatial modulation of cell proliferation, while limb elongation is also driven by preferential orientation of cell divisions along the proximal-distal growth axis. Cellular reconstructions were predictive of the expression patterns of limb development genes including the BMP morphogen Decapentaplegic. PMID:29595475

Approach for gait analysis in persons with limb loss including residuum and prosthesis socket dynamics.

PubMed

LaPrè, A K; Price, M A; Wedge, R D; Umberger, B R; Sup, Frank C

2018-04-01

Musculoskeletal modeling and marker-based motion capture techniques are commonly used to quantify the motions of body segments, and the forces acting on them during human gait. However, when these techniques are applied to analyze the gait of people with lower limb loss, the clinically relevant interaction between the residual limb and prosthesis socket is typically overlooked. It is known that there is considerable motion and loading at the residuum-socket interface, yet traditional gait analysis techniques do not account for these factors due to the inability to place tracking markers on the residual limb inside of the socket. In the present work, we used a global optimization technique and anatomical constraints to estimate the motion and loading at the residuum-socket interface as part of standard gait analysis procedures. We systematically evaluated a range of parameters related to the residuum-socket interface, such as the number of degrees of freedom, and determined the configuration that yields the best compromise between faithfully tracking experimental marker positions while yielding anatomically realistic residuum-socket kinematics and loads that agree with data from the literature. Application of the present model to gait analysis for people with lower limb loss will deepen our understanding of the biomechanics of walking with a prosthesis, which should facilitate the development of enhanced rehabilitation protocols and improved assistive devices. Copyright © 2017 John Wiley & Sons, Ltd.

3D optical imagery for motion compensation in a limb ultrasound system

NASA Astrophysics Data System (ADS)

Ranger, Bryan J.; Feigin, Micha; Zhang, Xiang; Mireault, Al; Raskar, Ramesh; Herr, Hugh M.; Anthony, Brian W.

2016-04-01

Conventional processes for prosthetic socket fabrication are heavily subjective, often resulting in an interface to the human body that is neither comfortable nor completely functional. With nearly 100% of amputees reporting that they experience discomfort with the wearing of their prosthetic limb, designing an effective interface to the body can significantly affect quality of life and future health outcomes. Active research in medical imaging and biomechanical tissue modeling of residual limbs has led to significant advances in computer aided prosthetic socket design, demonstrating an interest in moving toward more quantifiable processes that are still patient-specific. In our work, medical ultrasonography is being pursued to acquire data that may quantify and improve the design process and fabrication of prosthetic sockets while greatly reducing cost compared to an MRI-based framework. This paper presents a prototype limb imaging system that uses a medical ultrasound probe, mounted to a mechanical positioning system and submerged in a water bath. The limb imaging is combined with three-dimensional optical imaging for motion compensation. Images are collected circumferentially around the limb and combined into cross-sectional axial image slices, resulting in a compound image that shows tissue distributions and anatomical boundaries similar to magnetic resonance imaging. In this paper we provide a progress update on our system development, along with preliminary results as we move toward full volumetric imaging of residual limbs for prosthetic socket design. This demonstrates a novel multi-modal approach to residual limb imaging.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs.

PubMed

Loeffler, I K; Stocum, D L; Fallon, J F; Meteyer, C U

2001-10-15

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs

USGS Publications Warehouse

Loeffler, I.K.; Stocum, D.L.; Fallon, J.F.; Meteyer, C.U.

2001-01-01

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Shared Enhancer Activity in the Limbs and Phallus and Functional Divergence of a Limb-Genital cis-Regulatory Element in Snakes.

PubMed

Infante, Carlos R; Mihala, Alexandra G; Park, Sungdae; Wang, Jialiang S; Johnson, Kenji K; Lauderdale, James D; Menke, Douglas B

2015-10-12

The amniote phallus and limbs differ dramatically in their morphologies but share patterns of signaling and gene expression in early development. Thus far, the extent to which genital and limb transcriptional networks also share cis-regulatory elements has remained unexplored. We show that many limb enhancers are retained in snake genomes, suggesting that these elements may function in non-limb tissues. Consistent with this, our analysis of cis-regulatory activity in mice and Anolis lizards reveals that patterns of enhancer activity in embryonic limbs and genitalia overlap heavily. In mice, deletion of HLEB, an enhancer of Tbx4, produces defects in hindlimbs and genitalia, establishing the importance of this limb-genital enhancer for development of these different appendages. Further analyses demonstrate that the HLEB of snakes has lost hindlimb enhancer function while retaining genital activity. Our findings identify roles for Tbx4 in genital development and highlight deep similarities in cis-regulatory activity between limbs and genitalia. Copyright © 2015 Elsevier Inc. All rights reserved.

Multilayer limb quasi-static electromagnetic modeling with experiments for Galvanic coupling type IBC.

PubMed

Pun, S H; Gao, Y M; Mou, P A; Mak, P U; Vai, M I; Du, M

2010-01-01

Intra-body communication (IBC) is a new, emerging, short-range and human body based communication methodology. It is a technique to network various devices on human body, by utilizing the conducting properties of human tissues. For currently fast developed Body area network(BAN)/Body sensor network(BSN), IBC is believed to have advantages in power consumption, electromagnetic radiation, interference from external electromagnetic noise, security, and restriction in spectrum resource. In this article, the authors propose an improved mathematical model, which includes both electrical properties and proportion of human tissues, for IBC on a human limb. By solving the mathematical model analytically on four-layer system (skin, fat, muscle, and bone) and conducting in-vivo experiment, a comparison has been conducted.

Proximal—distal pattern formation in Drosophila: cell autonomous requirement for Distal-less gene activity in limb development

PubMed Central

Cohen, Stephen M.; Jürgens, Gerd

1989-01-01

Limb development in the Drosophila embryo requires a pattern-forming system to organize positional information along the proximal–distal axis of the limb. This system must function in the context of the well characterized anterior–posterior and dorsal–ventral pattern-forming systems that are required to organize the body plan of the embryo. By genetic criteria the Distal-less gene appears to play a central role in limb development. Lack-of-function Distal-less mutations cause the deletion of a specific subset of embryonic peripheral sense organs that represent the evolutionary remnants of larval limbs. Distal-less activity is also required in the imaginal discs for the development of adult limbs. This requirement is cell autonomous and region specific within the developing limb primordium. Production of genetically mosaic imaginal discs, in which clones of cells lack Distal-less activity, indicates the existence of an organized proximal–distal positional information in very young imaginal disc primordia. We suggest that this graded positional information may depend on the activity of the Distal-less gene. Images PMID:16453891

DLX5, FGF8 and the Pin1 isomerase control ΔNp63α protein stability during limb development: a regulatory loop at the basis of the SHFM and EEC congenital malformations

PubMed Central

Restelli, Michela; Lopardo, Teresa; Lo Iacono, Nadia; Garaffo, Giulia; Conte, Daniele; Rustighi, Alessandra; Napoli, Marco; Del Sal, Giannino; Perez-Morga, David; Costanzo, Antonio; Merlo, Giorgio Roberto; Guerrini, Luisa

2014-01-01

Ectrodactyly, or Split-Hand/Foot Malformation (SHFM), is a congenital condition characterized by the loss of central rays of hands and feet. The p63 and the DLX5;DLX6 transcription factors, expressed in the embryonic limb buds and ectoderm, are disease genes for these conditions. Mutations of p63 also cause the ectodermal dysplasia–ectrodactyly–cleft lip/palate (EEC) syndrome, comprising SHFM. Ectrodactyly is linked to defects of the apical ectodermal ridge (AER) of the developing limb buds. FGF8 is the key signaling molecule in this process, able to direct proximo-distal growth and patterning of the skeletal primordial of the limbs. In the limb buds of both p63 and Dlx5;Dlx6 murine models of SHFM, the AER is poorly stratified and FGF8 expression is severely reduced. We show here that the FGF8 locus is a downstream target of DLX5 and that FGF8 counteracts Pin1–ΔNp63α interaction. In vivo, lack of Pin1 leads to accumulation of the p63 protein in the embryonic limbs and ectoderm. We show also that ΔNp63α protein stability is negatively regulated by the interaction with the prolyl-isomerase Pin1, via proteasome-mediated degradation; p63 mutant proteins associated with SHFM or EEC syndromes are resistant to Pin1 action. Thus, DLX5, p63, Pin1 and FGF8 participate to the same time- and location-restricted regulatory loop essential for AER stratification, hence for normal patterning and skeletal morphogenesis of the limb buds. These results shed new light on the molecular mechanisms at the basis of the SHFM and EEC limb malformations. PMID:24569166

Expression of Msx genes in regenerating and developing limbs of axolotl.

PubMed

Koshiba, K; Kuroiwa, A; Yamamoto, H; Tamura, K; Ide, H

1998-12-15

Msx genes, homeobox-containing genes, have been isolated as homologues of the Drosophila msh gene and are thought to play important roles in the development of chick or mouse limb buds. We isolated two Msx genes, Msx1 and Msx2, from regenerating blastemas of axolotl limbs and examined their expression patterns using Northern blot and whole mount in situ hybridization during regeneration and development. Northern blot analysis revealed that the expression level of both Msx genes increased during limb regeneration. The Msx2 expression level increased in the blastema at the early bud stage, and Msx1 expression level increased at the late bud stage. Whole mount in situ hybridization revealed that Msx2 was expressed in the distal mesenchyme and Msx1 in the entire mesenchyme of the blastema at the late bud stage. In the developing limb bud, Msx1 was expressed in the entire mesenchyme, while Msx2 was expressed in the distal and peripheral mesenchyme. The expression patterns of Msx genes in the blastemas and limb buds of the axolotl were different from those reported for chick or mouse limb buds. These expression patterns of axolotl Msx genes are discussed in relation to the blastema or limb bud morphology and their possible roles in limb patterning.

Ex vivo generation of a functional and regenerative wound epithelium from axolotl (Ambystoma mexicanum) skin.

PubMed

Ferris, Donald R; Satoh, Akira; Mandefro, Berhan; Cummings, Gillian M; Gardiner, David M; Rugg, Elizabeth L

2010-10-01

Urodele amphibians (salamanders) are unique among adult vertebrates in their ability to regenerate structurally complete and fully functional limbs. Regeneration is a stepwise process that requires interactions between keratinocytes, nerves and fibroblasts. The formation of a wound epithelium covering the amputation site is an early and necessary event in the process but the molecular mechanisms that underlie the role of the wound epithelium in regeneration remain unclear. We have developed an ex vivo model that recapitulates many features of in vivo wound healing. The model comprises a circular explant of axolotl (Ambystoma mexicanum) limb skin with a central circular, full thickness wound. Re-epithelialization of the wound area is rapid (typically <11 h) and is dependent on metalloproteinase activity. The ex vivo wound epithelium is viable, responds to neuronal signals and is able to participate in ectopic blastema formation and limb regeneration. This ex vivo model provides a reproducible and tractable system in which to study the cellular and molecular events that underlie wound healing and regeneration. © 2010 The Authors. Journal compilation © 2010 Japanese Society of Developmental Biologists.

Genetic Interactions Between Shox2 and Hox Genes During the Regional Growth and Development of the Mouse Limb

PubMed Central

Neufeld, Stanley J.; Wang, Fan; Cobb, John

2014-01-01

The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb. PMID:25217052

Genetic interactions between Shox2 and Hox genes during the regional growth and development of the mouse limb.

PubMed

Neufeld, Stanley J; Wang, Fan; Cobb, John

2014-11-01

The growth and development of the vertebrate limb relies on homeobox genes of the Hox and Shox families, with their independent mutation often giving dose-dependent effects. Here we investigate whether Shox2 and Hox genes function together during mouse limb development by modulating their relative dosage and examining the limb for nonadditive effects on growth. Using double mRNA fluorescence in situ hybridization (FISH) in single embryos, we first show that Shox2 and Hox genes have associated spatial expression dynamics, with Shox2 expression restricted to the proximal limb along with Hoxd9 and Hoxa11 expression, juxtaposing the distal expression of Hoxa13 and Hoxd13. By generating mice with all possible dosage combinations of mutant Shox2 alleles and HoxA/D cluster deletions, we then show that their coordinated proximal limb expression is critical to generate normally proportioned limb segments. These epistatic interactions tune limb length, where Shox2 underexpression enhances, and Shox2 overexpression suppresses, Hox-mutant phenotypes. Disruption of either Shox2 or Hox genes leads to a similar reduction in Runx2 expression in the developing humerus, suggesting their concerted action drives cartilage maturation during normal development. While we furthermore provide evidence that Hox gene function influences Shox2 expression, this regulation is limited in extent and is unlikely on its own to be a major explanation for their genetic interaction. Given the similar effect of human SHOX mutations on regional limb growth, Shox and Hox genes may generally function as genetic interaction partners during the growth and development of the proximal vertebrate limb. Copyright © 2014 by the Genetics Society of America.

Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms

PubMed Central

Spieker, Janine; Ackermann, Anica; Salfelder, Anika; Vogel-Höpker, Astrid; Layer, Paul G.

2016-01-01

Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS). Here, we first analyzed the expression of acetylcholinesterase (AChE) by IHC and of choline acetyltransferase (ChAT) by ISH in developing embryonic chicken limbs (stages HH17-37). AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER) and zone of polarizing activity (ZPA), respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB) and Alizarin red (AR) stainings, respectively. Both acetylcholine (ACh)- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein. PMID:27574787

Acetylcholinesterase Regulates Skeletal In Ovo Development of Chicken Limbs by ACh-Dependent and -Independent Mechanisms.

PubMed

Spieker, Janine; Ackermann, Anica; Salfelder, Anika; Vogel-Höpker, Astrid; Layer, Paul G

2016-01-01

Formation of the vertebrate limb presents an excellent model to analyze a non-neuronal cholinergic system (NNCS). Here, we first analyzed the expression of acetylcholinesterase (AChE) by IHC and of choline acetyltransferase (ChAT) by ISH in developing embryonic chicken limbs (stages HH17-37). AChE outlined formation of bones, being strongest at their distal tips, and later also marked areas of cell death. At onset, AChE and ChAT were elevated in two organizing centers of the limb anlage, the apical ectodermal ridge (AER) and zone of polarizing activity (ZPA), respectively. Thereby ChAT was expressed shortly after AChE, thus strongly supporting a leading role of AChE in limb formation. Then, we conducted loss-of-function studies via unilateral implantation of beads into chicken limb anlagen, which were soaked in cholinergic components. After varying periods, the formation of cartilage matrix and of mineralizing bones was followed by Alcian blue (AB) and Alizarin red (AR) stainings, respectively. Both acetylcholine (ACh)- and ChAT-soaked beads accelerated bone formation in ovo. Notably, inhibition of AChE by BW284c51, or by the monoclonal antibody MAB304 delayed cartilage formation. Since bead inhibition of BChE was mostly ineffective, an ACh-independent action during BW284c51 and MAB304 inhibition was indicated, which possibly could be due to an enzymatic side activity of AChE. In conclusion, skeletogenesis in chick is regulated by an ACh-dependent cholinergic system, but to some extent also by an ACh-independent aspect of the AChE protein.

Accelerated high-yield generation of limb-innervating motor neurons from human stem cells

PubMed Central

Amoroso, Mackenzie W.; Croft, Gist F.; Williams, Damian J.; O’Keeffe, Sean; Carrasco, Monica A.; Davis, Anne R.; Roybon, Laurent; Oakley, Derek H.; Maniatis, Tom; Henderson, Christopher E.; Wichterle, Hynek

2013-01-01

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3−). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. PMID:23303937

The Effect of Sliding Humeral Osteotomy (SHO) on Frontal Plane Thoracic Limb Alignment: An Ex Vivo Canine Cadaveric Study.

PubMed

Breiteneicher, Adam H; Norby, Bo; Schulz, Kurt S; Kerwin, Sharon C; Hulse, Don A; Fox, Derek B; Saunders, W Brian

2016-11-01

To determine the effect of sliding humeral osteotomy (SHO) on frontal plane thoracic limb alignment in standing and recumbent limb positions. Canine cadaveric study. Canine thoracic limbs (n=15 limb pairs). Limbs acquired from healthy Labrador Retrievers euthanatized for reasons unrelated to this study were mounted in a limb press and aligned in a standing position followed by axial loading at 30% body weight. Frontal plane radiography was performed in standing and recumbent positions pre- and post-SHO. In the standing position, lateralization of the foot was measured pre- and post-SHO using a textured grid secured to the limb press base plate. Twelve thoracic limb alignment values (mean ± SD and 95% CI) were determined using the center of rotation of angulation (CORA) method were compared using linear mixed models to determine if significant differences existed between limb alignment values pre- or post-SHO, controlling for dog, limb, and limb position. Six of 12 standing or recumbent alignment values were significantly different pre- and post-SHO. SHO resulted in decreased mechanical lateral distal humeral angle and movement of the mechanical humeral radio-ulnar angle, radio-ulnar metacarpal angle, thoracic humeral angle, and elbow mechanical axis deviation toward coaxial limb alignment. In the standing position, the foot underwent significant lateralization post-SHO. SHO resulted in significant alteration in frontal plane thoracic limb alignment. Additional studies are necessary to determine if the changes reported using our ex vivo model occur following SHO in vivo. © Copyright 2016 by The American College of Veterinary Surgeons.

Differentiation of cartilaginous anlagen in entire embryonic mouse limbs cultured in a rotating bioreactor

NASA Astrophysics Data System (ADS)

Montufar-Solis, D.; Oakley, C. R.; Jefferson, Y.; Duke, P. J.

2003-10-01

Mechanisms involved in development of the embryonic limb have remained the same throughout eons of genetic and environmental evolution under Earth gravity (lg). During the spaceflight era it has been of interest to explore the ancient theory that form of the skeleton develops in response to gravity, and that changes in gravitational forces can change the developmental pattern of the limb. This has been shown in vivo and in vitro, allowing the hypergravity of centrifugation and microgravity of space to be used as tools to increase our knowledge of limb development. In recapitulations of spaceflight experiments, premetatarsals were cultured in suspension in a bioreactor, and found to be shorter and less differentiated than those cultured in standard culture dishes. This study only measured length of the metatarsals, and did not account for possible changes due to the skeletal elements having a more in vivo 3D shape while in suspension vs. flattened tissues compressed by their own weight. A culture system with an outcome closer to in vivo and that supports growth of younger limb buds than traditional systems will allow studies of early Hox gene expression, and contribute to the understanding of very early stages of development. The purpose of the current experiment was to determine if entire limb buds could be cultured in the bioreactor, and to compare the growth and differentiation with that of culturing in a culture dish system. Fore and hind limbs from E11-E13 ICR mouse embryos were cultured for six days, either in the bioreactor or in center-well organ culture dishes, fixed, and embedded for histology. E13 specimens grown in culture dishes were flat, while bioreactor culture specimens had a more in vivo-like 3D limb shape. Sections showed excellent cartilage differentiation in both culture systems, with more cell maturation, and hypertrophy in the specimens cultured in the bioreactor. Younger limb buds fused together during culture, so an additional set of El 1.5 limb buds was cultured with and without encapsulation in alginate prior to culturing in the bioreactor. Encapsulated limbs grown in the bioreactor did not fuse together, but developed only the more proximal elements while limbs grown in culture dishes formed proximal and distal elements. Alginate encapsulation may have reduced oxygenation to the progress zone of the developing limb bud resulting in lack of development of the more distal elements. These results show that the bioreactor supports growth and differentiation of skeletal elements in entire E13 limb buds, and that a method to culture younger limb buds without fusing together needs to be developed if any morphometric analysis is to be performed.

Limb Darkening and Planetary Transits: Testing Center-to-limb Intensity Variations and Limb-darkening Directly from Model Stellar Atmospheres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neilson, Hilding R.; Lester, John B.; McNeil, Joseph T.

The transit method, employed by Microvariability and Oscillation of Stars ( MOST ), Kepler , and various ground-based surveys has enabled the characterization of extrasolar planets to unprecedented precision. These results are precise enough to begin to measure planet atmosphere composition, planetary oblateness, starspots, and other phenomena at the level of a few hundred parts per million. However, these results depend on our understanding of stellar limb darkening, that is, the intensity distribution across the stellar disk that is sequentially blocked as the planet transits. Typically, stellar limb darkening is assumed to be a simple parameterization with two coefficients thatmore » are derived from stellar atmosphere models or fit directly. In this work, we revisit this assumption and compute synthetic planetary-transit light curves directly from model stellar atmosphere center-to-limb intensity variations (CLIVs) using the plane-parallel Atlas and spherically symmetric SAtlas codes. We compare these light curves to those constructed using best-fit limb-darkening parameterizations. We find that adopting parametric stellar limb-darkening laws leads to systematic differences from the more geometrically realistic model stellar atmosphere CLIV of about 50–100 ppm at the transit center and up to 300 ppm at ingress/egress. While these errors are small, they are systematic, and they appear to limit the precision necessary to measure secondary effects. Our results may also have a significant impact on transit spectra.« less

Angular radiation models for earth-atmosphere system. Volume 2: Longwave radiation

NASA Technical Reports Server (NTRS)

Suttles, J. T.; Green, R. N.; Smith, G. L.; Wielicki, B. A.; Walker, I. J.; Taylor, V. R.; Stowe, L. L.

1989-01-01

The longwave angular radiation models that are required for analysis of satellite measurements of Earth radiation, such as those from the Earth Radiation Budget Experiment (ERBE) are presented. The models contain limb-darkening characteristics and mean fluxes. Limb-darkening characteristics are the longwave anisotropic factor and the standard deviation of the longwave radiance. Derivation of these models from the Nimbus 7 ERB (Earth Radiation Budget) data set is described. Tabulated values and computer-generated plots are included for the limb-darkening and mean-flux models.

LTE modeling of inhomogeneous chromospheric structure using high-resolution limb observations

NASA Technical Reports Server (NTRS)

Lindsey, C.

1987-01-01

The paper discusses considerations relevant to LTE modeling of rough atmospheres. Particular attention is given to the application of recent high-resolution observations of the solar limb in the far-infrared and radio continuum to the modeling of chromospheric spicules. It is explained how the continuum limb observations can be combined with morphological knowledge of spicule structure to model the physical conditions in chromospheric spicules. This discussion forms the basis for a chromospheric model presented in a parallel publication based on observations ranging from 100 microns to 2.6 mm.

Growth factors FGF8 and FGF2 and their receptor FGFR1, transcriptional factors Msx-1 and MSX-2, and apoptotic factors p19 and RIP5 participate in the early human limb development.

PubMed

Becic, Tina; Kero, Darko; Vukojevic, Katarina; Mardesic, Snjezana; Saraga-Babic, Mirna

2018-04-01

The expression pattern of fibroblast growth factors FGF8 and FGF2 and their receptor FGFR1, transcription factors MSX-1 and MSX-2, as well as cell proliferation (Ki-67) and cell death associated caspase-3, p19 and RIP5 factors were analyzed in histological sections of eight 4th-9th-weeks developing human limbs by immunohistochemistry and semi-thin sectioning. Increasing expression of all analyzed factors (except FGF8) characterized both the multilayered human apical ectodermal ridge (AER), sub-ridge mesenchyme (progress zone) and chondrocytes in developing human limbs. While cytoplasmic co-expression of MSX-1 and MSX-2 was observed in both limb epithelium and mesenchyme, p19 displayed strong cytoplasmic expression in non-proliferating cells. Nuclear expression of Ki-67 proliferating cells, and partly of MSX-1 and MSX-2 was detected in the whole limb primordium. Strong expression of factors p19 and RIP5, both in the AER and mesenchyme of human developing limbs indicates their possible involvement in control of cell senescence and cell death. In contrast to animal studies, expression of FGFR1 in the surface ectoderm and p19 in the whole limb primordium might reflect interspecies differences in limb morphology. Expression of FGF2 and downstream RIP5 gene, and transcription factors Msx-1 and MSX-2 did not show human-specific changes in expression pattern. Based on their spatio-temporal expression during human limb development, our study indicates role of FGFs and Msx genes in stimulation of cell proliferation, limb outgrowth, digit elongation and separation, and additionally MSX-2 in control of vasculogenesis. The cascade of orchestrated gene expressions, including the analyzed developmental factors, jointly contribute to the complex human limb development. Copyright © 2018 Elsevier GmbH. All rights reserved.

Influence of temperature fluctuations on infrared limb radiance: a new simulation code

NASA Astrophysics Data System (ADS)

Rialland, Valérie; Chervet, Patrick

2006-08-01

Airborne infrared limb-viewing detectors may be used as surveillance sensors in order to detect dim military targets. These systems' performances are limited by the inhomogeneous background in the sensor field of view which impacts strongly on target detection probability. This background clutter, which results from small-scale fluctuations of temperature, density or pressure must therefore be analyzed and modeled. Few existing codes are able to model atmospheric structures and their impact on limb-observed radiance. SAMM-2 (SHARC-4 and MODTRAN4 Merged), the Air Force Research Laboratory (AFRL) background radiance code can be used to in order to predict the radiance fluctuation as a result of a normalized temperature fluctuation, as a function of the line-of-sight. Various realizations of cluttered backgrounds can then be computed, based on these transfer functions and on a stochastic temperature field. The existing SIG (SHARC Image Generator) code was designed to compute the cluttered background which would be observed from a space-based sensor. Unfortunately, this code was not able to compute accurate scenes as seen by an airborne sensor especially for lines-of-sight close to the horizon. Recently, we developed a new code called BRUTE3D and adapted to our configuration. This approach is based on a method originally developed in the SIG model. This BRUTE3D code makes use of a three-dimensional grid of temperature fluctuations and of the SAMM-2 transfer functions to synthesize an image of radiance fluctuations according to sensor characteristics. This paper details the working principles of the code and presents some output results. The effects of the small-scale temperature fluctuations on infrared limb radiance as seen by an airborne sensor are highlighted.

Investigation of growth fault bend folding using discrete element modeling: Implications for signatures of active folding above blind thrust faults

NASA Astrophysics Data System (ADS)

Benesh, N. P.; Plesch, A.; Shaw, J. H.; Frost, E. K.

2007-03-01

Using the discrete element modeling method, we examine the two-dimensional nature of fold development above an anticlinal bend in a blind thrust fault. Our models were composed of numerical disks bonded together to form pregrowth strata overlying a fixed fault surface. This pregrowth package was then driven along the fault surface at a fixed velocity using a vertical backstop. Additionally, new particles were generated and deposited onto the pregrowth strata at a fixed rate to produce sequential growth layers. Models with and without mechanical layering were used, and the process of folding was analyzed in comparison with fold geometries predicted by kinematic fault bend folding as well as those observed in natural settings. Our results show that parallel fault bend folding behavior holds to first order in these models; however, a significant decrease in limb dip is noted for younger growth layers in all models. On the basis of comparisons to natural examples, we believe this deviation from kinematic fault bend folding to be a realistic feature of fold development resulting from an axial zone of finite width produced by materials with inherent mechanical strength. These results have important implications for how growth fold structures are used to constrain slip and paleoearthquake ages above blind thrust faults. Most notably, deformation localized about axial surfaces and structural relief across the fold limb seem to be the most robust observations that can readily constrain fault activity and slip. In contrast, fold limb width and shallow growth layer dips appear more variable and dependent on mechanical properties of the strata.

Standardized Approach to Quantitatively Measure Residual Limb Skin Health in Individuals with Lower Limb Amputation.

PubMed

Rink, Cameron L; Wernke, Matthew M; Powell, Heather M; Tornero, Mark; Gnyawali, Surya C; Schroeder, Ryan M; Kim, Jayne Y; Denune, Jeffrey A; Albury, Alexander W; Gordillo, Gayle M; Colvin, James M; Sen, Chandan K

2017-07-01

Objective: (1) Develop a standardized approach to quantitatively measure residual limb skin health. (2) Report reference residual limb skin health values in people with transtibial and transfemoral amputation. Approach: Residual limb health outcomes in individuals with transtibial ( n  = 5) and transfemoral ( n  = 5) amputation were compared to able-limb controls ( n  = 4) using noninvasive imaging (hyperspectral imaging and laser speckle flowmetry) and probe-based approaches (laser doppler flowmetry, transcutaneous oxygen, transepidermal water loss, surface electrical capacitance). Results: A standardized methodology that employs noninvasive imaging and probe-based approaches to measure residual limb skin health are described. Compared to able-limb controls, individuals with transtibial and transfemoral amputation have significantly lower transcutaneous oxygen tension, higher transepidermal water loss, and higher surface electrical capacitance in the residual limb. Innovation: Residual limb health as a critical component of prosthesis rehabilitation for individuals with lower limb amputation is understudied in part due to a lack of clinical measures. Here, we present a standardized approach to measure residual limb health in people with transtibial and transfemoral amputation. Conclusion: Technology advances in noninvasive imaging and probe-based measures are leveraged to develop a standardized approach to quantitatively measure residual limb health in individuals with lower limb loss. Compared to able-limb controls, resting residual limb physiology in people that have had transfemoral or transtibial amputation is characterized by lower transcutaneous oxygen tension and poorer skin barrier function.

A Reevaluation of X-Irradiation Induced Phocomelia and Proximodistal Limb Patterning

PubMed Central

Galloway, Jenna L.; Delgado, Irene; Ros, Maria A.; Tabin, Clifford J.

2009-01-01

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a dramatic increase in incidence in the early 1960’s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative1, 2. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation3-5. Both X-irradiation5 and thalidomide-induced phocomelia5, 6 have been interpreted as patterning defects in the context of the Progress Zone Model, which states that a cell’s proximodistal (PD) identity is determined by the length of time spent in a distal limb region termed the “Progress Zone” 7. Indeed, studies of X-irradiation induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the Progress Zone Model. Here, using a combination of molecular analysis and lineage tracing, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. As skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the etiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that PD patterning is unaffected following X-irradiation does not support the predictions of the Progress Zone Model. PMID:19553938

A reevaluation of X-irradiation-induced phocomelia and proximodistal limb patterning.

PubMed

Galloway, Jenna L; Delgado, Irene; Ros, Maria A; Tabin, Clifford J

2009-07-16

Phocomelia is a devastating, rare congenital limb malformation in which the long bones are shorter than normal, with the upper portion of the limb being most severely affected. In extreme cases, the hands or fingers are attached directly to the shoulder and the most proximal elements (those closest to the shoulder) are entirely missing. This disorder, previously known in both autosomal recessive and sporadic forms, showed a marked increase in incidence in the early 1960s due to the tragic toxicological effects of the drug thalidomide, which had been prescribed as a mild sedative. This human birth defect is mimicked in developing chick limb buds exposed to X-irradiation. Both X-irradiation and thalidomide-induced phocomelia have been interpreted as patterning defects in the context of the progress zone model, which states that a cell's proximodistal identity is determined by the length of time spent in a distal limb region termed the 'progress zone'. Indeed, studies of X-irradiation-induced phocomelia have served as one of the two major experimental lines of evidence supporting the validity of the progress zone model. Here, using a combination of molecular analysis and lineage tracing in chick, we show that X-irradiation-induced phocomelia is fundamentally not a patterning defect, but rather results from a time-dependent loss of skeletal progenitors. Because skeletal condensation proceeds from the shoulder to fingers (in a proximal to distal direction), the proximal elements are differentially affected in limb buds exposed to radiation at early stages. This conclusion changes the framework for considering the effect of thalidomide and other forms of phocomelia, suggesting the possibility that the aetiology lies not in a defect in the patterning process, but rather in progenitor cell survival and differentiation. Moreover, molecular evidence that proximodistal patterning is unaffected after X-irradiation does not support the predictions of the progress zone model.

CRISM Limb Observations of Aerosols and Water Vapor

NASA Technical Reports Server (NTRS)

Smith, Michael D.; Wolff, M.J.; Clancy, R.T.; Seelos, F.; Murchie, S.L.

2009-01-01

Near-infrared spectra taken in a limb-viewing geometry by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on-board the Mars Reconnaissance Orbiter (MRO) provide a useful tool for probing atmospheric structure. Here we describe preliminary work on the retrieval of vertical profiles of aerosols and water vapor from the CRISM limb observations. The first full set of CRISM limb observations was taken in July 2009, with subsequent limb observations planned once every two months. Each set of limb observations contains about four dozen scans across the limb giving pole-to-pole coverage for two orbits at roughly 100 and 290 W longitude. Radiative transfer modeling taking account of aerosol scattering in the limb-viewing geometry is used to model the observations. The retrievals show the height to which dust and water vapor extend and the location and height of water ice clouds. Results from the First set of CRISM limb observations (July 2009, Ls=300) show dust aerosol well-mixed to about three scale heights above the surface with thin water ice clouds above the dust near the equator and at mid-northern latitudes. Water vapor is concentrated at high southern latitudes.

Neuroprosthetic limb control with electrocorticography: approaches and challenges.

PubMed

Thakor, Nitish V; Fifer, Matthew S; Hotson, Guy; Benz, Heather L; Newman, Geoffrey I; Milsap, Griffin W; Crone, Nathan E

2014-01-01

Advanced upper limb prosthetics, such as the Johns Hopkins Applied Physics Lab Modular Prosthetic Limb (MPL), are now available for research and preliminary clinical applications. Research attention has shifted to developing means of controlling these prostheses. Penetrating microelectrode arrays are often used in animal and human models to decode action potentials for cortical control. These arrays may suffer signal loss over the long-term and therefore should not be the only implant type investigated for chronic BMI use. Electrocorticographic (ECoG) signals from electrodes on the cortical surface may provide more stable long-term recordings. Several studies have demonstrated ECoG's potential for decoding cortical activity. As a result, clinical studies are investigating ECoG encoding of limb movement, as well as its use for interfacing with and controlling advanced prosthetic arms. This overview presents the technical state of the art in the use of ECoG in controlling prostheses. Technical limitations of the current approach and future directions are also presented.

Can Video Self-Modeling Improve Affected Limb Reach and Grasp Ability in Stroke Patients?

PubMed

Steel, Kylie Ann; Mudie, Kurt; Sandoval, Remi; Anderson, David; Dogramaci, Sera; Rehmanjan, Mohammad; Birznieks, Ingvars

2018-01-01

The authors examined whether feedforward video self-modeling (FF VSM) would improve control over the affected limb, movement self-confidence, movement self-consciousness, and well-being in 18 stroke survivors. Participants completed a cup transport task and 2 questionnaires related to psychological processes pre- and postintervention. Pretest video footage of the unaffected limb performing the task was edited to create a best-of or mirror-reversed training DVD, creating the illusion that patients were performing proficiently with the affected limb. The training yielded significant improvements for the forward movement of the affected limb compared to the unaffected limb. Significant improvements were also seen in movement self-confidence, movement self-consciousness, and well-being. FF VSM appears to be a viable way to improve motor ability in populations with movement disorders.

Changes in expression of the lysosomal membrane glycoprotein, LAMP-1 in interdigital regions during embryonic mouse limb development, in vivo and in vitro.

PubMed

Stewart, S; Yi, S; Kassabian, G; Mayo, M; Sank, A; Shuler, C

2000-06-01

Syndactyly, a failure of the digits to separate into individual units, affects about 8 to 9 per 1000 newborns and results from an aberration of the normal development of the interdigital tissues. Limb digit separation is the result of programmed cell death (apoptosis). Lysosomes play a role in the process of cell self-destruction. Our experiment was designed to test the hypothesis that the intensity of interdigital lysosomes increases during the separation of digits in vivo and in vitro. The primary mouse monoclonal antibody, 1D4B, detects the presence of lysosomes by identifying the LAMP-1 glycoprotein on the lysosome cell membrane. In our experiment this antibody immunodetected interdigital lysosome proteins in serial sections of limbs from Swiss-Webster mouse embryos, gestational ages E12.5 through E15, key developmental stages for digit separation. Digit separation was associated with an increase in intensity of lysosomal protein staining. In E12.5 limbs, the presence of lysosomes was enriched in the distal aspect of the interdigital tissue. However, the number of lysosomes markedly increased in the E13 and E14 limbs, including the entire length and width of the interdigital tissue in the E14 limbs. This lysosomal protein presence in E14 limbs was significant compared to E12.5, E13, and E15 limbs. By day 12.5, the mouse embryo limb is committed to digit separation. Addition of retinoic acid to the culture medium of limbs earlier in development, such as E12, results in induction of the process of digit separation. Cultured E12 limbs that did not receive an addition of retinoic acid, did not show digit separation. We conclude that in the limb development process, the enrichment in interdigit LAMP-1 proteins, may indicate a relationship between lysosomes, apoptosis, and digit separation. We also conclude that retinoic acid has an important role in digit separation in vivo, as shown in limb development, and demonstrated through the addition of retinoic acid to media of cultured tissues.

Fibroblast growth factor receptors in in vitro and in vivo chondrogenesis: relating tissue engineering using adult mesenchymal stem cells to embryonic development.

PubMed

Hellingman, Catharine A; Koevoet, Wendy; Kops, Nicole; Farrell, Eric; Jahr, Holger; Liu, Wei; Baatenburg de Jong, Robert J; Frenz, Dorothy A; van Osch, Gerjo J V M

2010-02-01

Adult mesenchymal stem cells (MSCs) are considered promising candidate cells for therapeutic cartilage and bone regeneration. Because tissue regeneration and embryonic development may involve similar pathways, understanding common pathways may lead to advances in regenerative medicine. In embryonic limb development, fibroblast growth factor receptors (FGFRs) play a role in chondrogenic differentiation. The aim of this study was to investigate and compare FGFR expression in in vivo embryonic limb development and in vitro chondrogenesis of MSCs. Our study showed that in in vitro chondrogenesis of MSCs three sequential stages can be found, as in embryonic limb development. A mesenchymal condensation (indicated by N-cadherin) is followed by chondrogenic differentiation (indicated by collagen II), and hypertrophy (indicated by collagen X). FGFR1-3 are expressed in a stage-dependent pattern during in vitro differentiation and in vivo embryonic limb development. In both models FGFR2 is clearly expressed by cells in the condensation phase. No FGFR expression was observed in differentiating and mature hyaline chondrocytes, whereas hypertrophic chondrocytes stained strongly for all FGFRs. To evaluate whether stage-specific modulation of chondrogenic differentiation in MSCs is possible with different subtypes of FGF, FGF2 and FGF9 were added to the chondrogenic medium during different stages in the culture process (early or late). FGF2 and FGF9 differentially affected the amount of cartilage formed by MSCs depending on the stage in which they were added. These results will help us understand the role of FGF signaling in chondrogenesis and find new tools to monitor and control chondrogenic differentiation.

Suppression of morphogenesis in embryonic mouse limbs exposed in vitro to excess gravity.

PubMed

Duke, J C

1983-06-01

This paper is a report of the first investigation of the effect of excess gravity on in vitro mammalian limb chondrogenesis. Limb buds from mice of various gestational stages were exposed to excess gravity (2.6G) using a culture centrifuge. Both forelimbs and hind limbs were cultured and the development of various limb elements was scored after four to six days. The 2.6G force significantly depressed the development of limb elements when applied during the teratogen-sensitive period of chondrogenesis. There was a proximodistal gradient of sensitivity to excess gravity in the limb with proximal structures being less susceptible than distal ones. In some cases, proximal limb elements present prior to explantation disappeared upon exposure to excess gravity. Hypergravity's teratogenic effect is assumed to operate via changes in tension and/or pressure on the cells, accompanied by alterations in cell morphometry and membrane properties.

Probability of Regenerating a Normal Limb After Bite Injury in the Mexican Axolotl (Ambystoma mexicanum).

PubMed

Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher; Niemiller, Matthew L; Voss, S Randal

2014-06-01

Multiple factors are thought to cause limb abnormalities in amphibian populations by altering processes of limb development and regeneration. We examined adult and juvenile axolotls ( Ambystoma mexicanum ) in the Ambystoma Genetic Stock Center (AGSC) for limb and digit abnormalities to investigate the probability of normal regeneration after bite injury. We observed that 80% of larval salamanders show evidence of bite injury at the time of transition from group housing to solitary housing. Among 717 adult axolotls that were surveyed, which included solitary-housed males and group-housed females, approximately half presented abnormalities, including examples of extra or missing digits and limbs, fused digits, and digits growing from atypical anatomical positions. Bite injury likely explains these limb defects, and not abnormal development, because limbs with normal anatomy regenerated after performing rostral amputations. We infer that only 43% of AGSC larvae will present four anatomically normal looking adult limbs after incurring a bite injury. Our results show regeneration of normal limb anatomy to be less than perfect after bite injury.

New Uses for Sensitivity Analysis: How Different Movement Tasks Effect Limb Model Parameter Sensitivity

NASA Technical Reports Server (NTRS)

Winters, J. M.; Stark, L.

1984-01-01

Original results for a newly developed eight-order nonlinear limb antagonistic muscle model of elbow flexion and extension are presented. A wider variety of sensitivity analysis techniques are used and a systematic protocol is established that shows how the different methods can be used efficiently to complement one another for maximum insight into model sensitivity. It is explicitly shown how the sensitivity of output behaviors to model parameters is a function of the controller input sequence, i.e., of the movement task. When the task is changed (for instance, from an input sequence that results in the usual fast movement task to a slower movement that may also involve external loading, etc.) the set of parameters with high sensitivity will in general also change. Such task-specific use of sensitivity analysis techniques identifies the set of parameters most important for a given task, and even suggests task-specific model reduction possibilities.

Development of force adaptation during childhood.

PubMed

Konczak, Jürgen; Jansen-Osmann, Petra; Kalveram, Karl-Theodor

2003-03-01

Humans learn to make reaching movements in novel dynamic environments by acquiring an internal motor model of their limb dynamics. Here, the authors investigated how 4- to 11-year-old children (N = 39) and adults (N = 7) adapted to changes in arm dynamics, and they examined whether those data support the view that the human brain acquires inverse dynamics models (IDM) during development. While external damping forces were applied, the children learned to perform goal-directed forearm flexion movements. After changes in damping, all children showed kinematic aftereffects indicative of a neural controller that still attempted to compensate the no longer existing damping force. With increasing age, the number of trials toward complete adaptation decreased. When damping was present, forearm paths were most perturbed and most variable in the youngest children but were improved in the older children. The findings indicate that the neural representations of limb dynamics are less precise in children and less stable in time than those of adults. Such controller instability might be a primary cause of the high kinematic variability observed in many motor tasks during childhood. Finally, the young children were not able to update those models at the same rate as the older children, who, in turn, adapted more slowly than adults. In conclusion, the ability to adapt to unknown forces is a developmental achievement. The present results are consistent with the view that the acquisition and modification of internal models of the limb dynamics form the basis of that adaptive process.

Msx genes are important apoptosis effectors downstream of the Shh/Gli3 pathway in the limb.

PubMed

Lallemand, Yvan; Bensoussan, Vardina; Cloment, Cécile Saint; Robert, Benoît

2009-07-15

In tetrapods, the anteroposterior (AP) patterning of the limb is under the control of the antagonistic activities of the secreted factor Sonic hedgehog (Shh) and Gli3R, the truncated repressor form of the transcription factor Gli3. In this report, we show that Msx1 and Msx2 are targets and downstream effectors of Gli3R. Consequently, in Shh null mutants, Msx genes are overexpressed and, furthermore, partially responsible for the limb phenotype. This is exemplified by the fact that reducing Msx activity in Shh mutants partially restores a normal limb development. Finally, we show that the main action of the Msx genes, in both normal and Shh(-/-) limb development, is to control cell death in the mesenchyme. We propose that, in the limb, Msx genes act downstream of the Shh/Gli3 pathway by transducing BMP signaling and that, in the absence of Shh signaling, their deregulation contributes to the extensive apoptosis that impairs limb development.

New limb-darkening coefficients for modeling binary star light curves

NASA Technical Reports Server (NTRS)

Van Hamme, W.

1993-01-01

We present monochromatic, passband-specific, and bolometric limb-darkening coefficients for a linear as well as nonlinear logarithmic and square root limb-darkening laws. These coefficients, including the bolometric ones, are needed when modeling binary star light curves with the latest version of the Wilson-Devinney light curve progam. We base our calculations on the most recent ATLAS stellar atmosphere models for solar chemical composition stars with a wide range of effective temperatures and surface gravitites. We examine how well various limb-darkening approximations represent the variation of the emerging specific intensity across a stellar surface as computed according to the model. For binary star light curve modeling purposes, we propose the use of a logarithmic or a square root law. We design our tables in such a manner that the relative quality of either law with respect to another can be easily compared. Since the computation of bolometric limb-darkening coefficients first requires monochromatic coefficients, we also offer tables of these coefficients (at 1221 wavelength values between 9.09 nm and 160 micrometer) and tables of passband-specific coefficients for commonly used photometric filters.

Development of a 3-D Rehabilitation System for Upper Limbs Using ER Actuators in a Nedo Project

NASA Astrophysics Data System (ADS)

Furusho, Junji; Koyanagi, Ken'ichi; Nakanishi, Kazuhiko; Ryu, Ushio; Takenaka, Shigekazu; Inoue, Akio; Domen, Kazuhisa; Miyakoshi, Koichi

New training methods and exercises for upper limbs rehabilitation are made possible by application of robotics and virtual reality technology. The technologies can also make quantitative evaluations and enhance the qualitative effect of training. We have joined a project managed by NEDO (New Energy and Industrial Technology Development Organization as a semi-governmental organization under the Ministry of Economy, Trade and Industry of Japan) 5-year Project, "Rehabilitation System for the Upper Limbs and Lower Limbs", and developed a 3-DOF exercise machine for upper limbs (EMUL) using ER actuators. In this paper, we also present the development of software for motion exercise trainings and some results of clinical evaluation. Moreover, it is discussed how ER actuators ensure the mechanical safety.

Loading, electromyograph, and motion during exercise

NASA Technical Reports Server (NTRS)

Figueroa, Fernando

1993-01-01

A system is being developed to gather kineto-dynamic data for a study to determine the load vectors applied to bone during exercise on equipment similar to that used in space. This information will quantify bone loading for exercise countermeasures development. Decreased muscle loading and external loading of bone during weightlessness results in cancellous bone loss of 1 percent per month in the lower extremities and 2 percent per month in the calcaneous. It is hypothesized that loading bone appropriately during exercise may prevent the bone loss. The system consists of an ergometer instrumented to provide position of the pedal (foot), pedaling forces on the foot (on the sagittal plane), and force on the seat. Accelerometers attached to the limbs will provide acceleration. These data will be used as input to an analytical model of the limb to determine forces on the bones and on groups of muscles. EMG signals from activity in the muscles will also be used in conjunction with the equations of mechanics of motion to be able to discern forces exerted by specific muscles. The tasks to be carried out include: design of various mechanical components to mount transducers, specification of mechanical components, specification of position transducers, development of a scheme to control the data acquisition instruments (TEAC recorder and optical encoder board), development of a dynamic model of the limbs in motion, and development of an overall scheme for data collection analysis and presentation. At the present time, all the hardware components of the system are operational, except for a computer board to gather position data from the pedals and crank. This board, however, may be put to use by anyone with background in computer based instrumentation. The software components are not all done. Software to transfer data recorded from the EMG measurements is operational, software to drive the optical encoder card is mostly done. The equations to model the kinematics and dynamics of motion of the limbs have been developed, but they have not yet been implemented in software. Aside from the development of the hardware and software components of the system, the methodology to use accelerometers and encoders and the formulation of the appropriate equations are an important contribution to the area of biomechanics, particularly in space applications.

Design of a biologically inspired lower limb exoskeleton for human gait rehabilitation.

PubMed

Lyu, Mingxing; Chen, Weihai; Ding, Xilun; Wang, Jianhua; Bai, Shaoping; Ren, Huichao

2016-10-01

This paper proposes a novel bionic model of the human leg according to the theory of physiology. Based on this model, we present a biologically inspired 3-degree of freedom (DOF) lower limb exoskeleton for human gait rehabilitation, showing that the lower limb exoskeleton is fully compatible with the human knee joint. The exoskeleton has a hybrid serial-parallel kinematic structure consisting of a 1-DOF hip joint module and a 2-DOF knee joint module in the sagittal plane. A planar 2-DOF parallel mechanism is introduced in the design to fully accommodate the motion of the human knee joint, which features not only rotation but also relative sliding. Therefore, the design is consistent with the requirements of bionics. The forward and inverse kinematic analysis is studied and the workspace of the exoskeleton is analyzed. The structural parameters are optimized to obtain a larger workspace. The results using MATLAB-ADAMS co-simulation are shown in this paper to demonstrate the feasibility of our design. A prototype of the exoskeleton is also developed and an experiment performed to verify the kinematic analysis. Compared with existing lower limb exoskeletons, the designed mechanism has a large workspace, while allowing knee joint rotation and small amount of sliding.

Design of a biologically inspired lower limb exoskeleton for human gait rehabilitation

NASA Astrophysics Data System (ADS)

Lyu, Mingxing; Chen, Weihai; Ding, Xilun; Wang, Jianhua; Bai, Shaoping; Ren, Huichao

2016-10-01

This paper proposes a novel bionic model of the human leg according to the theory of physiology. Based on this model, we present a biologically inspired 3-degree of freedom (DOF) lower limb exoskeleton for human gait rehabilitation, showing that the lower limb exoskeleton is fully compatible with the human knee joint. The exoskeleton has a hybrid serial-parallel kinematic structure consisting of a 1-DOF hip joint module and a 2-DOF knee joint module in the sagittal plane. A planar 2-DOF parallel mechanism is introduced in the design to fully accommodate the motion of the human knee joint, which features not only rotation but also relative sliding. Therefore, the design is consistent with the requirements of bionics. The forward and inverse kinematic analysis is studied and the workspace of the exoskeleton is analyzed. The structural parameters are optimized to obtain a larger workspace. The results using MATLAB-ADAMS co-simulation are shown in this paper to demonstrate the feasibility of our design. A prototype of the exoskeleton is also developed and an experiment performed to verify the kinematic analysis. Compared with existing lower limb exoskeletons, the designed mechanism has a large workspace, while allowing knee joint rotation and small amount of sliding.

Modelling of the Human Knee Joint Supported by Active Orthosis

NASA Astrophysics Data System (ADS)

Musalimov, V.; Monahov, Y.; Tamre, M.; Rõbak, D.; Sivitski, A.; Aryassov, G.; Penkov, I.

2018-02-01

The article discusses motion of a healthy knee joint in the sagittal plane and motion of an injured knee joint supported by an active orthosis. A kinematic scheme of a mechanism for the simulation of a knee joint motion is developed and motion of healthy and injured knee joints are modelled in Matlab. Angles between links, which simulate the femur and tibia are controlled by Simulink block of Model predictive control (MPC). The results of simulation have been compared with several samples of real motion of the human knee joint obtained from motion capture systems. On the basis of these analyses and also of the analysis of the forces in human lower limbs created at motion, an active smart orthosis is developed. The orthosis design was optimized to achieve an energy saving system with sufficient anatomy, necessary reliability, easy exploitation and low cost. With the orthosis it is possible to unload the knee joint, and also partially or fully compensate muscle forces required for the bending of the lower limb.

On the dynamics of a human body model.

NASA Technical Reports Server (NTRS)

Huston, R. L.; Passerello, C. E.

1971-01-01

Equations of motion for a model of the human body are developed. Basically, the model consists of an elliptical cylinder representing the torso, together with a system of frustrums of elliptical cones representing the limbs. They are connected to the main body and each other by hinges and ball and socket joints. Vector, tensor, and matrix methods provide a systematic organization of the geometry. The equations of motion are developed from the principles of classical mechanics. The solution of these equations then provide the displacement and rotation of the main body when the external forces and relative limb motions are specified. Three simple example motions are studied to illustrate the method. The first is an analysis and comparison of simple lifting on the earth and the moon. The second is an elementary approach to underwater swimming, including both viscous and inertia effects. The third is an analysis of kicking motion and its effect upon a vertically suspended man such as a parachutist.

Open framework for management and processing of multi-modality and multidimensional imaging data for analysis and modelling muscular function

NASA Astrophysics Data System (ADS)

García Juan, David; Delattre, Bénédicte M. A.; Trombella, Sara; Lynch, Sean; Becker, Matthias; Choi, Hon Fai; Ratib, Osman

2014-03-01

Musculoskeletal disorders (MSD) are becoming a big healthcare economical burden in developed countries with aging population. Classical methods like biopsy or EMG used in clinical practice for muscle assessment are invasive and not accurately sufficient for measurement of impairments of muscular performance. Non-invasive imaging techniques can nowadays provide effective alternatives for static and dynamic assessment of muscle function. In this paper we present work aimed toward the development of a generic data structure for handling n-dimensional metabolic and anatomical data acquired from hybrid PET/MR scanners. Special static and dynamic protocols were developed for assessment of physical and functional images of individual muscles of the lower limb. In an initial stage of the project a manual segmentation of selected muscles was performed on high-resolution 3D static images and subsequently interpolated to full dynamic set of contours from selected 2D dynamic images across different levels of the leg. This results in a full set of 4D data of lower limb muscles at rest and during exercise. These data can further be extended to a 5D data by adding metabolic data obtained from PET images. Our data structure and corresponding image processing extension allows for better evaluation of large volumes of multidimensional imaging data that are acquired and processed to generate dynamic models of the moving lower limb and its muscular function.

Geometric Morphometrics on Gene Expression Patterns Within Phenotypes: A Case Example on Limb Development

PubMed Central

Martínez-Abadías, Neus; Mateu, Roger; Niksic, Martina; Russo, Lucia; Sharpe, James

2016-01-01

How the genotype translates into the phenotype through development is critical to fully understand the evolution of phenotypes. We propose a novel approach to directly assess how changes in gene expression patterns are associated with changes in morphology using the limb as a case example. Our method combines molecular biology techniques, such as whole-mount in situ hybridization, with image and shape analysis, extending the use of Geometric Morphometrics to the analysis of nonanatomical shapes, such as gene expression domains. Elliptical Fourier and Procrustes-based semilandmark analyses were used to analyze the variation and covariation patterns of the limb bud shape with the expression patterns of two relevant genes for limb morphogenesis, Hoxa11 and Hoxa13. We devised a multiple thresholding method to semiautomatically segment gene domains at several expression levels in large samples of limb buds from C57Bl6 mouse embryos between 10 and 12 postfertilization days. Besides providing an accurate phenotyping tool to quantify the spatiotemporal dynamics of gene expression patterns within developing structures, our morphometric analyses revealed high, non-random, and gene-specific variation undergoing canalization during limb development. Our results demonstrate that Hoxa11 and Hoxa13, despite being paralogs with analogous functions in limb patterning, show clearly distinct dynamic patterns, both in shape and size, and are associated differently with the limb bud shape. The correspondence between our results and already well-established molecular processes underlying limb development confirms that this morphometric approach is a powerful tool to extract features of development regulating morphogenesis. Such multilevel analyses are promising in systems where not so much molecular information is available and will advance our understanding of the genotype–phenotype map. In systematics, this knowledge will increase our ability to infer how evolution modified a common developmental pattern to generate a wide diversity of morphologies, as in the vertebrate limb. PMID:26377442

Modeling digits. Digit patterning is controlled by a Bmp-Sox9-Wnt Turing network modulated by morphogen gradients.

PubMed

Raspopovic, J; Marcon, L; Russo, L; Sharpe, J

2014-08-01

During limb development, digits emerge from the undifferentiated mesenchymal tissue that constitutes the limb bud. It has been proposed that this process is controlled by a self-organizing Turing mechanism, whereby diffusible molecules interact to produce a periodic pattern of digital and interdigital fates. However, the identities of the molecules remain unknown. By combining experiments and modeling, we reveal evidence that a Turing network implemented by Bmp, Sox9, and Wnt drives digit specification. We develop a realistic two-dimensional simulation of digit patterning and show that this network, when modulated by morphogen gradients, recapitulates the expression patterns of Sox9 in the wild type and in perturbation experiments. Our systems biology approach reveals how a combination of growth, morphogen gradients, and a self-organizing Turing network can achieve robust and reproducible pattern formation. Copyright © 2014, American Association for the Advancement of Science.

Limb-darkening and the structure of the Jovian atmosphere

NASA Technical Reports Server (NTRS)

Newman, W. I.; Sagan, C.

1978-01-01

By observing the transit of various cloud features across the Jovian disk, limb-darkening curves were constructed for three regions in the 4.6 to 5.1 mu cm band. Several models currently employed in describing the radiative or dynamical properties of planetary atmospheres are here examined to understand their implications for limb-darkening. The statistical problem of fitting these models to the observed data is reviewed and methods for applying multiple regression analysis are discussed. Analysis of variance techniques are introduced to test the viability of a given physical process as a cause of the observed limb-darkening.

Lower limb estimation from sparse landmarks using an articulated shape model.

PubMed

Zhang, Ju; Fernandez, Justin; Hislop-Jambrich, Jacqui; Besier, Thor F

2016-12-08

Rapid generation of lower limb musculoskeletal models is essential for clinically applicable patient-specific gait modeling. Estimation of muscle and joint contact forces requires accurate representation of bone geometry and pose, as well as their muscle attachment sites, which define muscle moment arms. Motion-capture is a routine part of gait assessment but contains relatively sparse geometric information. Standard methods for creating customized models from motion-capture data scale a reference model without considering natural shape variations. We present an articulated statistical shape model of the left lower limb with embedded anatomical landmarks and muscle attachment regions. This model is used in an automatic workflow, implemented in an easy-to-use software application, that robustly and accurately estimates realistic lower limb bone geometry, pose, and muscle attachment regions from seven commonly used motion-capture landmarks. Estimated bone models were validated on noise-free marker positions to have a lower (p=0.001) surface-to-surface root-mean-squared error of 4.28mm, compared to 5.22mm using standard isotropic scaling. Errors at a variety of anatomical landmarks were also lower (8.6mm versus 10.8mm, p=0.001). We improve upon standard lower limb model scaling methods with shape model-constrained realistic bone geometries, regional muscle attachment sites, and higher accuracy. Copyright © 2016 Elsevier Ltd. All rights reserved.

A bioinformatics expert system linking functional data to anatomical outcomes in limb regeneration

PubMed Central

Lobo, Daniel; Feldman, Erica B.; Shah, Michelle; Malone, Taylor J.

2014-01-01

Abstract Amphibians and molting arthropods have the remarkable capacity to regenerate amputated limbs, as described by an extensive literature of experimental cuts, amputations, grafts, and molecular techniques. Despite a rich history of experimental effort, no comprehensive mechanistic model exists that can account for the pattern regulation observed in these experiments. While bioinformatics algorithms have revolutionized the study of signaling pathways, no such tools have heretofore been available to assist scientists in formulating testable models of large‐scale morphogenesis that match published data in the limb regeneration field. Major barriers to preventing an algorithmic approach are the lack of formal descriptions for experimental regenerative information and a repository to centralize storage and mining of functional data on limb regeneration. Establishing a new bioinformatics of shape would significantly accelerate the discovery of key insights into the mechanisms that implement complex regeneration. Here, we describe a novel mathematical ontology for limb regeneration to unambiguously encode phenotype, manipulation, and experiment data. Based on this formalism, we present the first centralized formal database of published limb regeneration experiments together with a user‐friendly expert system tool to facilitate its access and mining. These resources are freely available for the community and will assist both human biologists and artificial intelligence systems to discover testable, mechanistic models of limb regeneration. PMID:25729585

Comparative Transcriptional Profiling of the Axolotl Limb Identifies a Tripartite Regeneration-Specific Gene Program

PubMed Central

Knapp, Dunja; Schulz, Herbert; Rascon, Cynthia Alexander; Volkmer, Michael; Scholz, Juliane; Nacu, Eugen; Le, Mu; Novozhilov, Sergey; Tazaki, Akira; Protze, Stephanie; Jacob, Tina; Hubner, Norbert; Habermann, Bianca; Tanaka, Elly M.

2013-01-01

Understanding how the limb blastema is established after the initial wound healing response is an important aspect of regeneration research. Here we performed parallel expression profile time courses of healing lateral wounds versus amputated limbs in axolotl. This comparison between wound healing and regeneration allowed us to identify amputation-specific genes. By clustering the expression profiles of these samples, we could detect three distinguishable phases of gene expression – early wound healing followed by a transition-phase leading to establishment of the limb development program, which correspond to the three phases of limb regeneration that had been defined by morphological criteria. By focusing on the transition-phase, we identified 93 strictly amputation-associated genes many of which are implicated in oxidative-stress response, chromatin modification, epithelial development or limb development. We further classified the genes based on whether they were or were not significantly expressed in the developing limb bud. The specific localization of 53 selected candidates within the blastema was investigated by in situ hybridization. In summary, we identified a set of genes that are expressed specifically during regeneration and are therefore, likely candidates for the regulation of blastema formation. PMID:23658691

A new method to quantify liner deformation within a prosthetic socket for below knee amputees.

PubMed

Lenz, Amy L; Johnson, Katie A; Bush, Tamara Reid

2018-06-06

Many amputees who wear a leg prosthesis develop significant skin wounds on their residual limb. The exact cause of these wounds is unclear as little work has studied the interface between the prosthetic device and user. Our research objective was to develop a quantitative method for assessing displacement patterns of the gel liner during walking for patients with transtibial amputation. Using a reflective marker system and a custom clear socket, evaluations were conducted with a clear transparent test socket mounted over a plaster limb model and a deformable limb model. Distances between markers placed on the limb were measured with a digital caliper and then compared with data from the motion capture system. Additionally, the rigid plaster set-up was moved in the capture volume to simulate walking and evaluate if inter-marker distances changed in comparison to static data. Dynamic displacement trials were then collected to measure changes in inter-marker distance due to vertical elongation of the gel liner. Static and dynamic inter-marker distances within day and across days confirmed the ability to accurately capture displacements using this new approach. These results encourage this novel method to be applied to a sample of amputee patients during walking to assess displacements and the distribution of the liner deformation within the socket. The ability to capture changes in deformation of the gel liner will provide new data that will enable clinicians and researchers to improve design and fit of the prosthesis so the incidence of pressure ulcers can be reduced. Copyright © 2018 Elsevier Ltd. All rights reserved.

Establishing Multiscale Models for Simulating Whole Limb Estimates of Electric Fields for Osseointegrated Implants

PubMed Central

Isaacson, Brad M.; Stinstra, Jeroen G.; Bloebaum, Roy D.; Pasquina, COL Paul F.; MacLeod, Rob S.

2011-01-01

Although the survival rates of warfighters in recent conflicts are among the highest in military history, those who have sustained proximal limb amputations, may pose additional rehabilitation concerns. In some of these cases, traditional prosthetic limbs may not provide adequate function for returning to an active lifestyle. Osseointegration has emerged as a potential prosthetic alternative for those with limited residual limb length. Using this technology, direct skeletal attachment occurs between a transcutaneous osseointegrated implant (TOI) and the host bone, thereby eliminating the need for a socket. While reports from the first 100 patients with a TOI have been promising, some rehabilitation regimens require 12–18 months of restricted weight bearing to prevent overloading at the bone implant-interface. Electrically induced osseointegration has been proposed as an option for expediting periprosthetic fixation and preliminary studies have demonstrated the feasibility of adapting the TOI into a functional cathode. To assure safe and effective electrical fields that are conducive for osseoinduction and osseointegration, we have developed multiscale modeling approaches to simulate the expected electric metrics at the bone-implant interface. We have used computed tomography scans and volume segmentation tools to create anatomically accurate models that clearly distinguish tissue parameters and serve as the basis for finite element analysis. This translational computational biological process has supported biomedical electrode design, implant placement, and experiments to date have demonstrated the clinical feasibility of electrically induced osseointegration. PMID:21712151

The computer-aided parallel external fixator for complex lower limb deformity correction.

PubMed

Wei, Mengting; Chen, Jianwen; Guo, Yue; Sun, Hao

2017-12-01

Since parameters of the parallel external fixator are difficult to measure and calculate in real applications, this study developed computer software that can help the doctor measure parameters using digital technology and generate an electronic prescription for deformity correction. According to Paley's deformity measurement method, we provided digital measurement techniques. In addition, we proposed an deformity correction algorithm to calculate the elongations of the six struts and developed a electronic prescription software. At the same time, a three-dimensional simulation of the parallel external fixator and deformed fragment was made using virtual reality modeling language technology. From 2013 to 2015, fifteen patients with complex lower limb deformity were treated with parallel external fixators and the self-developed computer software. All of the cases had unilateral limb deformity. The deformities were caused by old osteomyelitis in nine cases and traumatic sequelae in six cases. A doctor measured the related angulation, displacement and rotation on postoperative radiographs using the digital measurement techniques. Measurement data were input into the electronic prescription software to calculate the daily adjustment elongations of the struts. Daily strut adjustments were conducted according to the data calculated. The frame was removed when expected results were achieved. Patients lived independently during the adjustment. The mean follow-up was 15 months (range 10-22 months). The duration of frame fixation from the time of application to the time of removal averaged 8.4 months (range 2.5-13.1 months). All patients were satisfied with the corrected limb alignment. No cases of wound infections or complications occurred. Using the computer-aided parallel external fixator for the correction of lower limb deformities can achieve satisfactory outcomes. The correction process can be simplified and is precise and digitized, which will greatly improve the treatment in a clinical application.

Probability of regenerating a normal limb after bite injury in the Mexican axolotl (Ambystoma mexicanum)

PubMed Central

Thompson, Sierra; Muzinic, Laura; Muzinic, Christopher; Niemiller, Matthew L.

2014-01-01

Abstract Multiple factors are thought to cause limb abnormalities in amphibian populations by altering processes of limb development and regeneration. We examined adult and juvenile axolotls (Ambystoma mexicanum) in the Ambystoma Genetic Stock Center (AGSC) for limb and digit abnormalities to investigate the probability of normal regeneration after bite injury. We observed that 80% of larval salamanders show evidence of bite injury at the time of transition from group housing to solitary housing. Among 717 adult axolotls that were surveyed, which included solitary‐housed males and group‐housed females, approximately half presented abnormalities, including examples of extra or missing digits and limbs, fused digits, and digits growing from atypical anatomical positions. Bite injury probably explains these limb defects, and not abnormal development, because limbs with normal anatomy regenerated after performing rostral amputations. We infer that only 43% of AGSC larvae will present four anatomically normal looking adult limbs after incurring a bite injury. Our results show regeneration of normal limb anatomy to be less than perfect after bite injury. PMID:25745564

Pediatric post-thrombotic syndrome in children: Toward the development of a new diagnostic and evaluative measurement tool.

PubMed

Avila, M L; Brandão, L R; Williams, S; Ward, L C; Montoya, M I; Stinson, J; Kiss, A; Lara-Corrales, I; Feldman, B M

2016-08-01

Our goal was to conduct the item generation and piloting phases of a new discriminative and evaluative tool for pediatric post-thrombotic syndrome. We followed a formative model for the development of the tool, focusing on the signs/symptoms (items) that define post-thrombotic syndrome. For item generation, pediatric thrombosis experts and subjects diagnosed with extremity post-thrombotic syndrome during childhood nominated items. In the piloting phase, items were cross-sectionally measured in children with limb deep vein thrombosis to examine item performance. Twenty-three experts and 16 subjects listed 34 items, which were then measured in 140 subjects with previous diagnosis of limb deep vein thrombosis (70 upper extremity and 70 lower extremity). The items with strongest correlation with post-thrombotic syndrome severity and largest area under the curve were pain (in older children), paresthesia, and swollen limb for the upper extremity group, and pain (in older children), tired limb, heaviness, tightness and paresthesia for the lower extremity group. The diagnostic properties of the items and their correlations with post-thrombotic syndrome severity varied according to the assessed venous territory. The information gathered in this study will help experts decide which item should be considered for inclusion in the new tool. Copyright © 2016 Elsevier Ltd. All rights reserved.

Heterochrony in the regulation of the developing marsupial limb.

PubMed

Chew, Keng Yih; Shaw, Geoffrey; Yu, Hongshi; Pask, Andrew J; Renfree, Marilyn B

2014-02-01

At birth, marsupial neonates have precociously developed forelimbs. The development of the tammar wallaby (Macropus eugenii) hindlimbs lags significantly behind that of the forelimbs. This differs from the grey short-tailed opossum, Monodelphis domestica, which has relatively similar fore- and hindlimbs at birth. This study examines the expression of the key patterning genes TBX4, TBX5, PITX1, FGF8, and SHH in developing limb buds in the tammar wallaby. All genes examined were highly conserved with orthologues from opossum and mouse. TBX4 expression appeared earlier in development than in the mouse, but later than in the opossum. SHH expression is restricted to the zone of polarising activity, while TBX5 (forelimb) and PITX1 (hindlimb) showed diffuse mRNA expression. FGF8 is specifically localised to the apical ectodermal ridge, which is more prominent than in the opossum. The most marked divergence in limb size in marsupials occurs in the kangaroos and wallabies. The faster development of the fore limb compared to that of the hind limb correlates with the early timing of the expression of the key patterning genes in these limbs. Copyright © 2013 Wiley Periodicals, Inc.

Modeling for intra-body communication with bone effect.

PubMed

Pun, S H; Gao, Y M; Mak, P U; Du, M; Vai, M I

2009-01-01

Intra-body communication (IBC) is a new, different "wireless" communication technique based on the human tissue. This short range "wireless" communication technology provides an alternative solution to wearable sensors, home health system, telemedicine and implanted devices. The development of the IBC enables the possibilities of providing less complexity and convenient communication methodologies for these devices. By regarding human tissue as communication channel, IBC making use of the conductivities properties of human tissue to send electrical signal from transmitter to receiver. In this paper, the authors proposed a new mathematical model for galvanic coupling type IBC based on a human limb. Starting from the electromagnetic theory, the authors treat human tissue as volume conductor, which is in analogous with the bioelectric phenomena analysis. In order to explain the mechanism of galvanic coupling type technique of IBC, applying the quasi-static approximation, the governing equation can be reduced to Laplace Equation. Finally, the analytical model is evaluated with on-body measurement for testing its performance. The comparison result shows that the developed mathematical model can provide good approximation for galvanic coupling type IBC on human limb under low operating frequencies.

Lower-Limb Amputation and Effect of Posttraumatic Stress Disorder on Department of Veterans Affairs Outpatient Cost Trends

DTIC Science & Technology

2015-07-01

JRRD Volume 52, Number 7, 2015Pages 827–838Lower-limb amputation and effect of posttraumatic stress disorder on Department of Veterans Affairs...lower- limb amputations and limb injuries. We evaluated the effect of lower-limb injury, amputation(s), and PTSD on outpatient costs, adjusting for...amputation status and significant parameters were tested (p  0.05) and models stratified by significant effect modi- fiers (p  0.05). For cost categories

Using multimodal imaging techniques to monitor limb ischemia: a rapid noninvasive method for assessing extremity wounds

NASA Astrophysics Data System (ADS)

Luthra, Rajiv; Caruso, Joseph D.; Radowsky, Jason S.; Rodriguez, Maricela; Forsberg, Jonathan; Elster, Eric A.; Crane, Nicole J.

2013-03-01

Over 70% of military casualties resulting from the current conflicts sustain major extremity injuries. Of these the majority are caused by blasts from improvised explosive devices. The resulting injuries include traumatic amputations, open fractures, crush injuries, and acute vascular disruption. Critical tissue ischemia—the point at which ischemic tissues lose the capacity to recover—is therefore a major concern, as lack of blood flow to tissues rapidly leads to tissue deoxygenation and necrosis. If left undetected or unaddressed, a potentially salvageable limb may require more extensive debridement or, more commonly, amputation. Predicting wound outcome during the initial management of blast wounds remains a significant challenge, as wounds continue to "evolve" during the debridement process and our ability to assess wound viability remains subjectively based. Better means of identifying critical ischemia are needed. We developed a swine limb ischemia model in which two imaging modalities were combined to produce an objective and quantitative assessment of wound perfusion and tissue viability. By using 3 Charge-Coupled Device (3CCD) and Infrared (IR) cameras, both surface tissue oxygenation as well as overall limb perfusion could be depicted. We observed a change in mean 3CCD and IR values at peak ischemia and during reperfusion correlate well with clinically observed indicators for limb function and vitality. After correcting for baseline mean R-B values, the 3CCD values correlate with surface tissue oxygenation and the IR values with changes in perfusion. This study aims to not only increase fundamental understanding of the processes involved with limb ischemia and reperfusion, but also to develop tools to monitor overall limb perfusion and tissue oxygenation in a clinical setting. A rapid and objective diagnostic for extent of ischemic damage and overall limb viability could provide surgeons with a more accurate indication of tissue viability. This may help reducing the number of surgical interventions required, by aiding surgeons in identifying and demarcating areas of critical tissue ischemia, so that a more adequate debridement may be performed. This would have obvious benefits of reducing patient distress and decreasing both the overall recovery time and cost of rehabilitation.

Limb darkening laws for two exoplanet host stars derived from 3D stellar model atmospheres. Comparison with 1D models and HST light curve observations

NASA Astrophysics Data System (ADS)

Hayek, W.; Sing, D.; Pont, F.; Asplund, M.

2012-03-01

We compare limb darkening laws derived from 3D hydrodynamical model atmospheres and 1D hydrostatic MARCS models for the host stars of two well-studied transiting exoplanet systems, the late-type dwarfs HD 209458 and HD 189733. The surface brightness distribution of the stellar disks is calculated for a wide spectral range using 3D LTE spectrum formation and opacity sampling⋆. We test our theoretical predictions using least-squares fits of model light curves to wavelength-integrated primary eclipses that were observed with the Hubble Space Telescope (HST). The limb darkening law derived from the 3D model of HD 209458 in the spectral region between 2900 Å and 5700 Å produces significantly better fits to the HST data, removing systematic residuals that were previously observed for model light curves based on 1D limb darkening predictions. This difference arises mainly from the shallower mean temperature structure of the 3D model, which is a consequence of the explicit simulation of stellar surface granulation where 1D models need to rely on simplified recipes. In the case of HD 189733, the model atmospheres produce practically equivalent limb darkening curves between 2900 Å and 5700 Å, partly due to obstruction by spectral lines, and the data are not sufficient to distinguish between the light curves. We also analyze HST observations between 5350 Å and 10 500 Å for this star; the 3D model leads to a better fit compared to 1D limb darkening predictions. The significant improvement of fit quality for the HD 209458 system demonstrates the higher degree of realism of 3D hydrodynamical models and the importance of surface granulation for the formation of the atmospheric radiation field of late-type stars. This result agrees well with recent investigations of limb darkening in the solar continuum and other observational tests of the 3D models. The case of HD 189733 is no contradiction as the model light curves are less sensitive to the temperature stratification of the stellar atmosphere and the observed data in the 2900-5700 Å region are not sufficient to distinguish more clearly between the 3D and 1D limb darkening predictions. Full theoretical spectra for both stars are available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/539/A102, as well as at www.astro.ex.ac.uk/people/sing.

The investigation of advanced remote sensing, radiative transfer and inversion techniques for the measurement of atmospheric constituents

NASA Technical Reports Server (NTRS)

Deepak, Adarsh; Wang, Pi-Huan

1985-01-01

The research program is documented for developing space and ground-based remote sensing techniques performed during the period from December 15, 1977 to March 15, 1985. The program involved the application of sophisticated radiative transfer codes and inversion methods to various advanced remote sensing concepts for determining atmospheric constituents, particularly aerosols. It covers detailed discussions of the solar aureole technique for monitoring columnar aerosol size distribution, and the multispectral limb scattered radiance and limb attenuated radiance (solar occultation) techniques, as well as the upwelling scattered solar radiance method for determining the aerosol and gaseous characteristics. In addition, analytical models of aerosol size distribution and simulation studies of the limb solar aureole radiance technique and the variability of ozone at high altitudes during satellite sunrise/sunset events are also described in detail.

Kinematic and dynamic gait compensations in a rat model of lumbar radiculopathy and the effects of tumor necrosis factor-alpha antagonism

PubMed Central

2011-01-01

Introduction Tumor necrosis factor-α (TNFα) has received significant attention as a mediator of lumbar radiculopathy, with interest in TNF antagonism to treat radiculopathy. Prior studies have demonstrated that TNF antagonists can attenuate heightened nociception resulting from lumbar radiculopathy in the preclinical model. Less is known about the potential impact of TNF antagonism on gait compensations, despite being of clinical relevance. In this study, we expand on previous descriptions of gait compensations resulting from lumbar radiculopathy in the rat and describe the ability of local TNF antagonism to prevent the development of gait compensations, altered weight bearing, and heightened nociception. Methods Eighteen male Sprague-Dawley rats were investigated for mechanical sensitivity, weight-bearing, and gait pre- and post-operatively. For surgery, tail nucleus pulposus (NP) tissue was collected and the right L5 dorsal root ganglion (DRG) was exposed (Day 0). In sham animals, NP tissue was discarded (n = 6); for experimental animals, autologous NP was placed on the DRG with or without 20 μg of soluble TNF receptor type II (sTNFRII, n = 6 per group). Spatiotemporal gait characteristics (open arena) and mechanical sensitivity (von Frey filaments) were assessed on post-operative Day 5; gait dynamics (force plate arena) and weight-bearing (incapacitance meter) were assessed on post-operative Day 6. Results High-speed gait characterization revealed animals with NP alone had a 5% decrease in stance time on their affected limbs on Day 5 (P ≤0.032). Ground reaction force analysis on Day 6 aligned with temporal changes observed on Day 5, with vertical impulse reduced in the affected limb of animals with NP alone (area under the vertical force-time curve, P <0.02). Concordant with gait, animals with NP alone also had some evidence of affected limb mechanical allodynia on Day 5 (P = 0.08) and reduced weight-bearing on the affected limb on Day 6 (P <0.05). Delivery of sTNFRII at the time of NP placement ameliorated signs of mechanical hypersensitivity, imbalanced weight distribution, and gait compensations (P <0.1). Conclusions Our data indicate gait characterization has value for describing early limb dysfunctions in pre-clinical models of lumbar radiculopathy. Furthermore, TNF antagonism prevented the development of gait compensations subsequent to lumbar radiculopathy in our model. PMID:21871102

Bone density in limb-immobilized beagles: An animal model for bone loss in weightlessness

NASA Technical Reports Server (NTRS)

Wolinsky, Ira

1987-01-01

Prolonged weightlessness is man in space flight results in a slow progressive demineralization of bone accompanied by an increased calcium output in the urine resulting in negative calcium balances. This possibly irreversible bone loss may constitute a serious limiting factor to long duration manned space flight. In order to seek and test preventative measures an appropriate ground based animal model simulating weightlessness is necessary. Use of the mature Beagle in limb immobilization has been documented as an excellent model for orthopedic research since this animal most closely simulates the phenomenom of bone loss with regards to growth, remodeling, structure, chemistry and mineralization. The purpose of this project is to develop a research protocol for the study of bone loss in Beagles during and after cast immobilization of a hindleg; research will then be initiated.

Modelling the effect of race surface and racehorse limb parameters on in silico fetlock motion and propensity for injury.

PubMed

Symons, J E; Hawkins, D A; Fyhrie, D P; Upadhyaya, S K; Stover, S M

2017-09-01

The metacarpophalangeal joint (fetlock) is the most commonly affected site of racehorse injury, with multiple observed pathologies consistent with extreme fetlock dorsiflexion. Race surface mechanics affect musculoskeletal structure loading and injury risk because surface forces applied to the hoof affect limb motions. Race surface mechanics are a function of controllable factors. Thus, race surface design has the potential to reduce the incidence of musculoskeletal injury through modulation of limb motions. However, the relationship between race surface mechanics and racehorse limb motions is unknown. To determine the effect of changing race surface and racehorse limb model parameters on distal limb motions. Sensitivity analysis of in silico fetlock motion to changes in race surface and racehorse limb parameters using a validated, integrated racehorse and race surface computational model. Fetlock motions were determined during gallop stance from simulations on virtual surfaces with differing average vertical stiffness, upper layer (e.g. cushion) depth and linear stiffness, horizontal friction, tendon and ligament mechanics, as well as fetlock position at heel strike. Upper layer depth produced the greatest change in fetlock motion, with lesser depths yielding greater fetlock dorsiflexion. Lesser fetlock changes were observed for changes in lower layer (e.g. base or pad) mechanics (nonlinear), as well as palmar ligament and tendon stiffness. Horizontal friction and fetlock position contributed less than 1° change in fetlock motion. Simulated fetlock motions are specific to one horse's anatomy reflected in the computational model. Anatomical differences among horses may affect the magnitude of limb flexion, but will likely have similar limb motion responses to varied surface mechanics. Race surface parameters affected by maintenance produced greater changes in fetlock motion than other parameters studied. Simulations can provide evidence to inform race surface design and management to reduce the incidence of injury. © 2017 EVJ Ltd.

The effect of leg dominance and landing height on ACL loading among female athletes.

PubMed

Mokhtarzadeh, Hossein; Ewing, Katie; Janssen, Ina; Yeow, Chen-Hua; Brown, Nicholas; Lee, Peter Vee Sin

2017-07-26

Female athletes are more prone to anterior cruciate ligament (ACL) injury. A neuromuscular imbalance called leg dominance may provide a biomechanical explanation. Therefore, the purpose of this study was to compare the side-to-side lower limb differences in movement patterns, muscle forces and ACL forces during a single-leg drop-landing task from two different heights. We hypothesized that there will be significant differences in lower limb movement patterns (kinematics), muscle forces and ACL loading between the dominant and non-dominant limbs. Further, we hypothesized that significant differences between limbs will be present when participants land from a greater drop-landing height. Eight recreational female participants performed dominant and non-dominant single-leg drop landings from 30 to 60cm. OpenSim software was used to develop participant-specific musculoskeletal models and to calculate muscle forces. We also predicted ACL loading using our previously established method. There were no significant differences between dominant and non-dominant leg landing except in ankle dorsiflexion and GMED muscle forces at peak GRF. Landing from a greater height resulted in significant differences among most kinetics and kinematics variables and ACL forces. Minimal differences in lower-limb muscle forces and ACL loading between the dominant and non-dominant legs during single-leg landing may suggest similar risk of injury across limbs in this cohort. Further research is required to confirm whether limb dominance may play an important role in the higher incidence of ACL injury in female athletes with larger and sport-specific cohorts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hydrodynamics of metachronal paddling in crustaceans

NASA Astrophysics Data System (ADS)

Santhanakrishnan, A.; Lai, H. K.; Samaee, M.; Lewis, T. J.; Guy, R. D.

2016-02-01

Long-tailed crustaceans such as crayfish and krill swim by rhythmically paddling a set of four to five limbs (swimmerets) originating from their abdomen. Despite variations in limb size and stroke frequency, movements of ipsilateral limbs always maintain a tail-to-head metachronal rhythm with an approximate quarter-period inter-limb phase difference. Relatively few studies have examined the fluid dynamics of metachronal limb stroke for the range of Reynolds numbers at which crustaceans operate. The objective of this study is to investigate metachronal paddling as a function of Reynolds number (Re) for quantifying hydrodynamic scalability of this swimming mechanism, including the effect of hinges on paddles as seen in crustacean swimmerets. Our approach included experiments on a scaled physical model and computational fluid dynamics (CFD) simulations using the immersed boundary (IB) method. The scaled robotic model of metachronal paddling consisted of a rectangular aquarium tank fitted above with four stepper motors coupled to a four-bar linkage that actuated four acrylic paddles immersed in water-glycerin fluid medium. 2D particle image velocimetry (PIV) was used for quantitative flow visualization in the experiments. The swimmerets were modeled in CFD simulations as rigid 1D rods in a 2D fluid. The inter-limb phase difference was varied from 0% (synchronous paddling) through 50% across Re range of O(10-1000). Two types of experimental limb models were tested, including a simple flat plate and a `split-paddle' structure with two flat plates connected halfway with hinges. Our results show that the natural tail-to-head metachronal rhythm with an approximate quarter-period phase difference is the most effective and efficient rhythm across a wide range of Reynolds numbers. Limb models with hinges generated increased horizontal flow compared to the simple flat plate paddles, suggesting that asymmetry between power and return stroke is important to augment thrust.

Design & control of a 3D stroke rehabilitation platform.

PubMed

Cai, Z; Tong, D; Meadmore, K L; Freeman, C T; Hughes, A M; Rogers, E; Burridge, J H

2011-01-01

An upper limb stroke rehabilitation system is developed which combines electrical stimulation with mechanical arm support, to assist patients performing 3D reaching tasks in a virtual reality environment. The Stimulation Assistance through Iterative Learning (SAIL) platform applies electrical stimulation to two muscles in the arm using model-based control schemes which learn from previous trials of the task. This results in accurate movement which maximises the therapeutic effect of treatment. The principal components of the system are described and experimental results confirm its efficacy for clinical use in upper limb stroke rehabilitation. © 2011 IEEE

The role of early development in mammalian limb diversification: a descriptive comparison of early limb development between the Natal long-fingered bat (Miniopterus natalensis) and the mouse (Mus musculus).

PubMed

Hockman, Dorit; Mason, Mandy K; Jacobs, David S; Illing, Nicola

2009-04-01

Comparative embryology expands our understanding of unique limb structures, such as that found in bats. Bat forelimb digits 2 to 5 are differentially elongated and joined by webbing, while the hindlimb digits are of similar length in many species. We compare limb development between the mouse and the Natal long-fingered bat, Miniopterus natalensis, to pinpoint the stage at which their limbs begin to differ. The bat forelimb differs from the mouse at Carollia stage (CS) 14 with the appearance of the wing membrane primordia. This difference is enhanced at CS 15 with the posterior expansion of the hand plate. The bat hindlimb begins to differ from the mouse between CS 15 and 16 when the foot plate undergoes a proximal expansion resulting in digit primordia of very similar length. Our findings support recent gene expression studies, which reveal a role for early patterning in the development of the bat limb. Copyright 2009 Wiley-Liss, Inc.

Upper and Lower Limb Muscle Architecture of a 104 Year-Old Cadaver

PubMed Central

Infantolino, Benjamin

2016-01-01

Muscle architecture is an important component to typical musculoskeletal models. Previous studies of human muscle architecture have focused on a single joint, two adjacent joints, or an entire limb. To date, no study has presented muscle architecture for the upper and lower limbs of a single cadaver. Additionally, muscle architectural parameters from elderly cadavers are lacking, making it difficult to accurately model elderly populations. Therefore, the purpose of this study was to present muscle architecture of the upper and lower limbs of a 104 year old female cadaver. The major muscles of the upper and lower limbs were removed and the musculotendon mass, tendon mass, musculotendon length, tendon length, pennation angle, optimal fascicle length, physiological cross-sectional area, and tendon cross-sectional area were determined for each muscle. Data from this complete cadaver are presented in table format. The data from this study can be used to construct a musculoskeletal model of a specific individual who was ambulatory, something which has not been possible to date. This should increase the accuracy of the model output as the model will be representing a specific individual, not a synthesis of measurements from multiple individuals. Additionally, an elderly individual can be modeled which will provide insight into muscle function as we age. PMID:28033339

Upper and Lower Limb Muscle Architecture of a 104 Year-Old Cadaver.

PubMed

Ruggiero, Marissa; Cless, Daniel; Infantolino, Benjamin

2016-01-01

Muscle architecture is an important component to typical musculoskeletal models. Previous studies of human muscle architecture have focused on a single joint, two adjacent joints, or an entire limb. To date, no study has presented muscle architecture for the upper and lower limbs of a single cadaver. Additionally, muscle architectural parameters from elderly cadavers are lacking, making it difficult to accurately model elderly populations. Therefore, the purpose of this study was to present muscle architecture of the upper and lower limbs of a 104 year old female cadaver. The major muscles of the upper and lower limbs were removed and the musculotendon mass, tendon mass, musculotendon length, tendon length, pennation angle, optimal fascicle length, physiological cross-sectional area, and tendon cross-sectional area were determined for each muscle. Data from this complete cadaver are presented in table format. The data from this study can be used to construct a musculoskeletal model of a specific individual who was ambulatory, something which has not been possible to date. This should increase the accuracy of the model output as the model will be representing a specific individual, not a synthesis of measurements from multiple individuals. Additionally, an elderly individual can be modeled which will provide insight into muscle function as we age.

Sall4-Gli3 system in early limb progenitors is essential for the development of limb skeletal elements.

PubMed

Akiyama, Ryutaro; Kawakami, Hiroko; Wong, Julia; Oishi, Isao; Nishinakamura, Ryuichi; Kawakami, Yasuhiko

2015-04-21

Limb skeletal elements originate from the limb progenitor cells, which undergo expansion and patterning to develop each skeletal element. Posterior-distal skeletal elements, such as the ulna/fibula and posterior digits develop in a Sonic hedgehog (Shh)-dependent manner. However, it is poorly understood how anterior-proximal elements, such as the humerus/femur, the radius/tibia and the anterior digits, are developed. Here we show that the zinc finger factors Sall4 and Gli3 cooperate for proper development of the anterior-proximal skeletal elements and also function upstream of Shh-dependent posterior skeletal element development. Conditional inactivation of Sall4 in the mesoderm before limb outgrowth caused severe defects in the anterior-proximal skeletal elements in the hindlimb. We found that Gli3 expression is reduced in Sall4 mutant hindlimbs, but not in forelimbs. This reduction caused posteriorization of nascent hindlimb buds, which is correlated with a loss of anterior digits. In proximal development, Sall4 integrates Gli3 and the Plzf-Hox system, in addition to proliferative expansion of cells in the mesenchymal core of nascent hindlimb buds. Whereas forelimbs developed normally in Sall4 mutants, further genetic analysis identified that the Sall4-Gli3 system is a common regulator of the early limb progenitor cells in both forelimbs and hindlimbs. The Sall4-Gli3 system also functions upstream of the Shh-expressing ZPA and the Fgf8-expressing AER in fore- and hindlimbs. Therefore, our study identified a critical role of the Sall4-Gli3 system at the early steps of limb development for proper development of the appendicular skeletal elements.

THE CHROMOSPHERIC SOLAR LIMB BRIGHTENING AT RADIO, MILLIMETER, SUB-MILLIMETER, AND INFRARED WAVELENGTHS

DOE Office of Scientific and Technical Information (OSTI.GOV)

De la Luz, V.

2016-07-10

Observations of the emission at radio, millimeter, sub-millimeter, and infrared wavelengths in the center of the solar disk validate the autoconsistence of semi-empirical models of the chromosphere. Theoretically, these models must reproduce the emission at the solar limb. In this work, we tested both the VALC and C7 semi-empirical models by computing their emission spectrum in the frequency range from 2 GHz to 10 THz at solar limb altitudes. We calculate the Sun's theoretical radii as well as their limb brightening. Non-local thermodynamic equilibrium was computed for hydrogen, electron density, and H{sup −}. In order to solve the radiative transfermore » equation, a three-dimensional (3D) geometry was employed to determine the ray paths, and Bremsstrahlung, H{sup −}, and inverse Bremsstrahlung opacity sources were integrated in the optical depth. We compared the computed solar radii with high-resolution observations at the limb obtained by Clark. We found that there are differences between the observed and computed solar radii of 12,000 km at 20 GHz, 5000 km at 100 GHz, and 1000 km at 3 THz for both semi-empirical models. A difference of 8000 km in the solar radii was found when comparing our results against the heights obtained from H α observations of spicules-off at the solar limb. We conclude that the solar radii cannot be reproduced by VALC and C7 semi-empirical models at radio—infrared wavelengths. Therefore, the structures in the high chromosphere provide a better measurement of the solar radii and their limb brightening as shown in previous investigations.« less

Automated hexahedral mesh generation from biomedical image data: applications in limb prosthetics.

PubMed

Zachariah, S G; Sanders, J E; Turkiyyah, G M

1996-06-01

A general method to generate hexahedral meshes for finite element analysis of residual limbs and similar biomedical geometries is presented. The method utilizes skeleton-based subdivision of cross-sectional domains to produce simple subdomains in which structured meshes are easily generated. Application to a below-knee residual limb and external prosthetic socket is described. The residual limb was modeled as consisting of bones, soft tissue, and skin. The prosthetic socket model comprised a socket wall with an inner liner. The geometries of these structures were defined using axial cross-sectional contour data from X-ray computed tomography, optical scanning, and mechanical surface digitization. A tubular surface representation, using B-splines to define the directrix and generator, is shown to be convenient for definition of the structure geometries. Conversion of cross-sectional data to the compact tubular surface representation is direct, and the analytical representation simplifies geometric querying and numerical optimization within the mesh generation algorithms. The element meshes remain geometrically accurate since boundary nodes are constrained to lie on the tubular surfaces. Several element meshes of increasing mesh density were generated for two residual limbs and prosthetic sockets. Convergence testing demonstrated that approximately 19 elements are required along a circumference of the residual limb surface for a simple linear elastic model. A model with the fibula absent compared with the same geometry with the fibula present showed differences suggesting higher distal stresses in the absence of the fibula. Automated hexahedral mesh generation algorithms for sliced data represent an advancement in prosthetic stress analysis since they allow rapid modeling of any given residual limb and optimization of mesh parameters.

Evaluation of the Effects of Sativex (THC BDS: CBD BDS) on Inhibition of Spasticity in a Chronic Relapsing Experimental Allergic Autoimmune Encephalomyelitis: A Model of Multiple Sclerosis

PubMed Central

Hilliard, A.; Stott, C.; Wright, S.; Guy, G.; Pryce, G.; Al-Izki, S.; Bolton, C.; Giovannoni, G.

2012-01-01

This study investigated the antispasticity potential of Sativex in mice. Chronic relapsing experimental allergic encephalomyelitis was induced in adult ABH mice resulting in hind limb spasticity development. Vehicle, Sativex, and baclofen (as a positive control) were injected intravenously and the “stiffness” of limbs assessed by the resistance force against hind limb flexion. Vehicle alone caused no significant change in spasticity. Baclofen (5 mg/kg) induced approximately a 40% peak reduction in spasticity. Sativex dose dependently reduced spasticity; 5 mg/kg THC + 5 mg/kg CBD induced approximately a 20% peak reduction; 10 mg/kg THC + 10 mg/kg CBD produced approximately a 40% peak reduction in spasticity. Sativex has the potential to reduce spasticity in an experimental mouse model of multiple sclerosis (MS). Baclofen reduced spasticity and served as a positive control. Sativex (10 mg/kg) was just as effective as baclofen, providing supportive evidence for Sativex use in the treatment of spasticity in MS. PMID:22928118

Progress Toward Optimizing Prosthetic Socket Fit and Suspension Using Elevated Vacuum to Promote Residual Limb Health.

PubMed

Wernke, Matthew M; Schroeder, Ryan M; Haynes, Michael L; Nolt, Lonnie L; Albury, Alexander W; Colvin, James M

2017-07-01

Objective: Prosthetic sockets are custom made for each amputee, yet there are no quantitative tools to determine the appropriateness of socket fit. Ensuring a proper socket fit can have significant effects on the health of residual limb soft tissues and overall function and acceptance of the prosthetic limb. Previous work found that elevated vacuum pressure data can detect movement between the residual limb and the prosthetic socket; however, the correlation between the two was specific to each user. The overall objective of this work is to determine the relationship between elevated vacuum pressure deviations and prosthetic socket fit. Approach: A tension compression machine was used to apply repeated controlled forces onto a residual limb model with sockets of different internal volume. Results: The vacuum pressure-displacement relationship was dependent on socket fit. The vacuum pressure data were sensitive enough to detect differences of 1.5% global volume and can likely detect differences even smaller. Limb motion was reduced as surface area of contact between the limb model and socket was maximized. Innovation: The results suggest that elevated vacuum pressure data provide information to quantify socket fit. Conclusions: This study provides evidence that the use of elevated vacuum pressure data may provide a method for prosthetists to quantify and monitor socket fit. Future studies should investigate the relationship between socket fit, limb motion, and limb health to define optimal socket fit parameters.

LIMB-DARKENING COEFFICIENTS FOR ECLIPSING WHITE DWARFS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gianninas, A.; Strickland, B. D.; Kilic, Mukremin

2013-03-20

We present extensive calculations of linear and nonlinear limb-darkening coefficients as well as complete intensity profiles appropriate for modeling the light-curves of eclipsing white dwarfs. We compute limb-darkening coefficients in the Johnson-Kron-Cousins UBVRI photometric system as well as the Large Synoptic Survey Telescope (LSST) ugrizy system using the most up to date model atmospheres available. In all, we provide the coefficients for seven different limb-darkening laws. We describe the variations of these coefficients as a function of the atmospheric parameters, including the effects of convection at low effective temperatures. Finally, we discuss the importance of having readily available limb-darkening coefficientsmore » in the context of present and future photometric surveys like the LSST, Palomar Transient Factory, and the Panoramic Survey Telescope and Rapid Response System (Pan-STARRS). The LSST, for example, may find {approx}10{sup 5} eclipsing white dwarfs. The limb-darkening calculations presented here will be an essential part of the detailed analysis of all of these systems.« less

Recent advancements in prosthetic hand technology.

PubMed

Saikia, Angana; Mazumdar, Sushmi; Sahai, Nitin; Paul, Sudip; Bhatia, Dinesh; Verma, Suresh; Rohilla, Punit Kumar

2016-07-01

Recently, significant advances over the past decade have been made in robotics, artificial intelligence and other cognitive related fields, allowing development of highly sophisticated bio-mimetic robotics systems. In addition, enormous number of robots have been designed and assembled by explicitly realising their biological oriented behaviours. To enhance skill behaviours and adequate grasping abilities in these devices, a new phase of dexterous hands has been developed recently with bio-mimetically oriented and bio-inspired functionalities. The aim in writing this review paper is to present a detailed insight towards the development of the bio-mimetic based dexterous robotic multi-fingered artificial hand. An "ideal" upper limb prosthesis should be perceived as a part of their natural body by the amputee and should replicate sensory-motor capabilities of the amputated limb. Upper-limb amputations are most often the result of sudden trauma to the body, although they also can be caused by malignancy, congenital deficiencies and vascular diseases. This paper discusses the different bio-mimetic approaches using a framework that permits for a common description of biological and technical based hand manipulation behaviour. In particular, the review focuses on a number of developments in the inspired robotic systems. In conclusion, the study found that a huge amount of research efforts in terms of kinematics, dynamics, modelling and control methodologies are being put in to improve the present hand technology, thereby providing more functionality to the prosthetic limb of the amputee. This would improve their quality-of-life and help in performing activities of daily living (ADL) tasks with comparative ease in the near future.

A Limb Action Detector Enabling People with Multiple Disabilities to Control Environmental Stimulation through Limb Action with a Nintendo Wii Remote Controller

ERIC Educational Resources Information Center

Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

2010-01-01

This study assessed whether two persons with multiple disabilities would be able to control environmental stimulation using limb action with a Nintendo Wii Remote Controller and a newly developed limb action detection program (LADP, i.e., a new software program that turns a Wii Remote Controller into a precise limb action detector). This study was…

A New Limb Movement Detector Enabling People with Multiple Disabilities to Control Environmental Stimulation through Limb Swing with a Gyration Air Mouse

ERIC Educational Resources Information Center

Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

2010-01-01

This study assessed whether two persons with multiple disabilities would be able to control environmental stimulation using limb swing with a gyration air mouse and a newly developed limb movement detection program (LMDP, i.e., a new software program that turns a gyration air mouse into a precise limb movement detector). The study was performed…

Evolution of antero‐posterior patterning of the limb: Insights from the chick

PubMed Central

2017-01-01

Summary The developing limbs of chicken embryos have served as pioneering models for understanding pattern formation for over a century. The ease with which chick wing and leg buds can be experimentally manipulated, while the embryo is still in the egg, has resulted in the discovery of important developmental organisers, and subsequently, the signals that they produce. Sonic hedgehog (Shh) is produced by mesenchyme cells of the polarizing region at the posterior margin of the limb bud and specifies positional values across the antero‐posterior axis (the axis running from the thumb to the little finger). Detailed experimental embryology has revealed the fundamental parameters required to specify antero‐posterior positional values in response to Shh signaling in chick wing and leg buds. In this review, the evolution of the avian wing and leg will be discussed in the broad context of tetrapod paleontology, and more specifically, ancestral theropod dinosaur paleontology. How the parameters that dictate antero‐posterior patterning could have been modulated to produce the avian wing and leg digit patterns will be considered. Finally, broader speculations will be made regarding what the antero‐posterior patterning of chick limbs can tell us about the evolution of other digit patterns, including those that were found in the limbs of the earliest tetrapods. PMID:28734068

Different regulation of limb development by p63 transcript variants.

PubMed

Kawata, Manabu; Taniguchi, Yuki; Mori, Daisuke; Yano, Fumiko; Ohba, Shinsuke; Chung, Ung-Il; Shimogori, Tomomi; Mills, Alea A; Tanaka, Sakae; Saito, Taku

2017-01-01

The apical ectodermal ridge (AER), located at the distal end of each limb bud, is a key signaling center which controls outgrowth and patterning of the proximal-distal axis of the limb through secretion of various molecules. Fibroblast growth factors (FGFs), particularly Fgf8 and Fgf4, are representative molecules produced by AER cells, and essential to maintain the AER and cell proliferation in the underlying mesenchyme, meanwhile Jag2-Notch pathway negatively regulates the AER and limb development. p63, a transcription factor of the p53 family, is expressed in the AER and indispensable for limb formation. However, the underlying mechanisms and specific roles of p63 variants are unknown. Here, we quantified the expression of p63 variants in mouse limbs from embryonic day (E) 10.5 to E12.5, and found that ΔNp63γ was strongly expressed in limbs at all stages, while TAp63γ expression was rapidly increased in the later stages. Fluorescence-activated cell sorting analysis of limb bud cells from reporter mouse embryos at E11.5 revealed that all variants were abundantly expressed in AER cells, and their expression was very low in mesenchymal cells. We then generated AER-specific p63 knockout mice by mating mice with a null and a flox allele of p63, and Msx2-Cre mice (Msx2-Cre;p63Δ/fl). Msx2-Cre;p63Δ/fl neonates showed limb malformation that was more obvious in distal elements. Expression of various AER-related genes was decreased in Msx2-Cre;p63Δ/fl limb buds and embryoid bodies formed by p63-knockdown induced pluripotent stem cells. Promoter analyses and chromatin immunoprecipitation assays demonstrated Fgf8 and Fgf4 as transcriptional targets of ΔNp63γ, and Jag2 as that of TAp63γ. Furthermore, TAp63γ overexpression exacerbated the phenotype of Msx2-Cre;p63Δ/fl mice. These data indicate that ΔNp63 and TAp63 control limb development through transcriptional regulation of different target molecules with different roles in the AER. Our findings contribute to further understanding of the molecular network of limb development.

The role of canonical Wnt signaling in leg regeneration and metamorphosis in the red flour beetle Tribolium castaneum.

PubMed

Shah, Mita V; Namigai, Erica K O; Suzuki, Yuichiro

2011-01-01

Many organisms across the Metazoa have regenerative abilities with potentially conserved genetic mechanisms that can enlighten both medicine and evolutionary studies. Here, the role of canonical Wnt signaling was examined in the red flour beetle Tribolium castaneum in order to explore its role during metamorphosis and larval leg regeneration. Double-stranded RNA mediated silencing of Wnt-1 signaling resulted in a loss of wings and appendages with a dramatic reduction in width, indicating that the Wnt-1 signaling pathway is necessary for proper post-embryonic appendage development in T. castaneum. Furthermore, disruption of canonical Wnt signaling led to the complete impairment of limb regeneration in T. castaneum. Our findings suggest that Wnt-1 signaling is a conserved mechanism for appendage development across all holometabolous insects and indicate that the role of Wnt-1 signaling in limb regeneration has been retained across all insects as various modes of limb development evolved. Importantly, this study shows that the availability of the genome sequence and the ease of performing leg ablations make Tribolium an excellent holometabolous insect model for studying regeneration. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Carbon dioxide water-bath treatment augments peripheral blood flow through the development of angiogenesis.

PubMed

Xu, Yan-Jun; Elimban, Vijayan; Dhalla, Naranjan S

2017-08-01

In this study, we investigated the effects of CO 2 water-bath therapy on blood flow and angiogenesis in the ischemic hind limb, as well as some plasma angiogenic factors in peripheral ischemic model. The hind limb ischemia was induced by occluding the femoral artery for 2 weeks in rats and treated with or without CO 2 water-bath therapy at 37 °C for 4 weeks (20 min treatment every day for 5 days per week). The peak blood flow and minimal and mean blood flow in the ischemic skeletal muscle were markedly increased by the CO 2 water-bath therapy. This increase in blood flow was associated with development of angiogenesis in the muscle, as well as reduction in the ischemia-induced increase in plasma malondialdehyde levels. Although plasma vascular endothelial growth factor and nitric oxide levels were increased in animals with peripheral ischemia, the changes in these biomarkers were not affected by CO 2 water-bath therapy. These results suggest that augmentation of blood flow in the ischemic hind limb by CO 2 water-bath therapy may be due to the development of angiogenesis and reduction in oxidative stress.

A 3D musculoskeletal model of the western lowland gorilla hind limb: moment arms and torque of the hip, knee and ankle.

PubMed

Goh, Colleen; Blanchard, Mary L; Crompton, Robin H; Gunther, Michael M; Macaulay, Sophie; Bates, Karl T

2017-10-01

Three-dimensional musculoskeletal models have become increasingly common for investigating muscle moment arms in studies of vertebrate locomotion. In this study we present the first musculoskeletal model of a western lowland gorilla hind limb. Moment arms of individual muscles around the hip, knee and ankle were compared with previously published data derived from the experimental tendon travel method. Considerable differences were found which we attribute to the different methodologies in this specific case. In this instance, we argue that our 3D model provides more accurate and reliable moment arm data than previously published data on the gorilla because our model incorporates more detailed consideration of the 3D geometry of muscles and the geometric constraints that exist on their lines-of-action about limb joints. Our new data have led us to revaluate the previous conclusion that muscle moment arms in the gorilla hind limb are optimised for locomotion with crouched or flexed limb postures. Furthermore, we found that bipedalism and terrestrial quadrupedalism coincided more regularly with higher moment arms and torque around the hip, knee and ankle than did vertical climbing. This indicates that the ability of a gorilla to walk bipedally is not restricted by musculoskeletal adaptations for quadrupedalism and vertical climbing, at least in terms of moment arms and torque about hind limb joints. © 2017 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.

Running over rough terrain reveals limb control for intrinsic stability.

PubMed

Daley, Monica A; Biewener, Andrew A

2006-10-17

Legged animals routinely negotiate rough, unpredictable terrain with agility and stability that outmatches any human-built machine. Yet, we know surprisingly little about how animals accomplish this. Current knowledge is largely limited to studies of steady movement. These studies have revealed fundamental mechanisms used by terrestrial animals for steady locomotion. However, it is unclear whether these models provide an appropriate framework for the neuromuscular and mechanical strategies used to achieve dynamic stability over rough terrain. Perturbation experiments shed light on this issue, revealing the interplay between mechanics and neuromuscular control. We measured limb mechanics of helmeted guinea fowl (Numida meleagris) running over an unexpected drop in terrain, comparing their response to predictions of the mass-spring running model. Adjustment of limb contact angle explains 80% of the variation in stance-phase limb loading following the perturbation. Surprisingly, although limb stiffness varies dramatically, it does not influence the response. This result agrees with a mass-spring model, although it differs from previous findings on humans running over surfaces of varying compliance. However, guinea fowl sometimes deviate from mass-spring dynamics through posture-dependent work performance of the limb, leading to substantial energy absorption following the perturbation. This posture-dependent actuation allows the animal to absorb energy and maintain desired velocity on a sudden substrate drop. Thus, posture-dependent work performance of the limb provides inherent velocity control over rough terrain. These findings highlight how simple mechanical models extend to unsteady conditions, providing fundamental insights into neuromuscular control of movement and the design of dynamically stable legged robots and prosthetic devices.

Thoracic limb alignment in healthy labrador retrievers: evaluation of standing versus recumbent frontal plane radiography.

PubMed

Goodrich, Zachary J; Norby, Bo; Eichelberger, Bunita M; Friedeck, Wade O; Callis, Hollye N; Hulse, Don A; Kerwin, Sharon C; Fox, Derek B; Saunders, W Brian

2014-10-01

To report thoracic limb alignment values in healthy dogs; to determine if limb alignment values are significantly different when obtained from standing versus recumbent radiographic projections. Prospective cross-sectional study. Labrador Retrievers (n = 45) >15 months of age. Standing and recumbent radiographs were obtained and limb montages were randomized before analysis by a single investigator blinded to dog, limb, and limb position. Twelve limb alignment values were determined using the CORA methodology. Measurements were performed in triplicate and intra-observer variability was evaluated by intra-class correlation coefficient (ICC). Limb alignment values were reported as mean ± SD and 95% confidence intervals. Linear mixed models were used to determine if significant associations existed between limb alignment values and limb, limb position, gender, age, weight, and body condition score. There were significant differences in standing and recumbent limb alignment values for all values except elbow mechanical axis deviation (eMAD). Limb, gender, age, body weight, and body condition score had no effect. ICC values ranged from 0.522 to 0.758, indicating moderate to substantial agreement for repeated measurements by a single investigator. Limb alignment values are significantly different when determined from standing versus recumbent radiographs in healthy Labrador Retrievers. © Copyright 2014 by The American College of Veterinary Surgeons.

Influence of Ribeiroia ondatrae (Trematoda: Digenea) infection on limb development and survival of northern leopard frogs (Rana pipiens): effects of host stage and parasite-exposure level

USGS Publications Warehouse

Schotthoefer, Anna M.; Koehler, Anson V.; Meteyer, Carol U.; Cole, Rebecca A.

2003-01-01

Recent evidence suggests that infection by larvae of the trematode Ribeiroia ondatrae accounts for a significant proportion of limb malformations currently observed in amphibian populations of North America. However, the effects of R. ondatrae infection on northern leopard frogs (Rana pipiens), one of the species most frequently reported with malformations, have not been adequately explored. Moreover, the risk factors associated with R. ondatrae-induced malformations have not been clearly identified. We examined the effects of timing of infection on tadpole survival and limb development. Rana pipiens tadpoles were individually exposed to R. ondatrae cercariae at the pre-limb-bud (Gosner stages 24 and 25), limb-bud (Gosner stages 27 and 28), or paddle (Gosner stages 31–33) stages of development and monitored through metamorphosis. The effects of infection were stage-specific. Infections acquired at the pre-limb-bud stage resulted in a high mortality rate (47.5–97.5%), whereas tadpoles infected at the limb-bud stage displayed a high malformation rate (16% overall), and the magnitude of effects increased with the level of exposure to cercariae. In contrast, infections acquired at the paddle stage had no effect on limb development or tadpole survival, which suggests that the timing of R. ondatrae infection in relation to the stage structure of tadpole populations in the wild is an important determinant of the degree to which populations are affected by R. ondatrae.

The yeast two hybrid system in a screen for proteins interacting with axolotl (Ambystoma mexicanum) Msx1 during early limb regeneration.

PubMed

Abuqarn, Mehtap; Allmeling, Christina; Amshoff, Inga; Menger, Bjoern; Nasser, Inas; Vogt, Peter M; Reimers, Kerstin

2011-07-01

Urodele amphibians are exceptional in their ability to regenerate complex body structures such as limbs. Limb regeneration depends on a process called dedifferentiation. Under an inductive wound epidermis terminally differentiated cells transform to pluripotent progenitor cells that coordinately proliferate and eventually redifferentiate to form the new appendage. Recent studies have developed molecular models integrating a set of genes that might have important functions in the control of regenerative cellular plasticity. Among them is Msx1, which induced dedifferentiation in mammalian myotubes in vitro. Herein, we screened for interaction partners of axolotl Msx1 using a yeast two hybrid system. A two hybrid cDNA library of 5-day-old wound epidermis and underlying tissue containing more than 2×10⁶ cDNAs was constructed and used in the screen. 34 resulting cDNA clones were isolated and sequenced. We then compared sequences of the isolated clones to annotated EST contigs of the Salamander EST database (BLASTn) to identify presumptive orthologs. We subsequently searched all no-hit clone sequences against non redundant NCBI sequence databases using BLASTx. It is the first time, that the yeast two hybrid system was adapted to the axolotl animal model and successfully used in a screen for proteins interacting with Msx1 in the context of amphibian limb regeneration. 2011 Elsevier B.V. All rights reserved.

Real-time control of walking using recordings from dorsal root ganglia.

PubMed

Holinski, B J; Everaert, D G; Mushahwar, V K; Stein, R B

2013-10-01

The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the DRG. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modelled from recorded neural firing rates. These models were then used for closed-loop feedback. Overall, firing-rate-based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48 ± 13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development.

Effects of Design Variants in Lower-Limb Prostheses on Gait Synergy

PubMed Central

Pitkin, Mark R.

2016-01-01

A lower-limb prosthesis is the mechanical device with which an amputee’s residual limb interacts with the walking surface. The pressure and shear forces that affect the residuum due to prosthesis use are the sources of pain, residual-limb skin problems and gait deviations. Direct approaches to reducing these problems include improving fit, alignment technique and socket design as well as increasing cushioning with socket liners. A summary of typical malalignments and their consequences is presented. The malalignments are considered sources of excessive moments applied to the residuum, which simplifies the analysis of a patient’s gait. A better design of prosthetic joints could improve prosthetic gait. This article addresses the key mechanical parameter of prosthetic joints, namely the dependence “moment of resistance/angle of deflection.” A mathematical model has been developed that links stresses on the residuum in transtibial amputees with the moment of resistance in the prosthetic ankle at the critical gait phases. Analysis of the model yields a substantial decrease in stresses on the residuum during the most demanding, load-bearing phase of stance if the moment of resistance in the ankle is similar to that seen in the biological ankle joint. Gait study shows use of the experimental rolling-joint prosthetic foot more closely simulates normal gait synergy than the SACH foot. PMID:27087763

Internal models for interpreting neural population activity during sensorimotor control

PubMed Central

Golub, Matthew D; Yu, Byron M; Chase, Steven M

2015-01-01

To successfully guide limb movements, the brain takes in sensory information about the limb, internally tracks the state of the limb, and produces appropriate motor commands. It is widely believed that this process uses an internal model, which describes our prior beliefs about how the limb responds to motor commands. Here, we leveraged a brain-machine interface (BMI) paradigm in rhesus monkeys and novel statistical analyses of neural population activity to gain insight into moment-by-moment internal model computations. We discovered that a mismatch between subjects’ internal models and the actual BMI explains roughly 65% of movement errors, as well as long-standing deficiencies in BMI speed control. We then used the internal models to characterize how the neural population activity changes during BMI learning. More broadly, this work provides an approach for interpreting neural population activity in the context of how prior beliefs guide the transformation of sensory input to motor output. DOI: http://dx.doi.org/10.7554/eLife.10015.001 PMID:26646183

Epidemiology of race-day distal limb fracture in flat racing Thoroughbreds in Great Britain (2000 to 2013).

PubMed

Rosanowski, S M; Chang, Y M; Stirk, A J; Verheyen, K L P

2018-05-28

A key focus of the racing industry is to minimise the number of race-day distal limb fractures, although no studies have identified risk factors for both fatal and non-fatal distal limb fractures. To determine risk factors for race-day distal limb fractures experienced by Thoroughbred racehorses participating in flat racing in Great Britain (GB). Retrospective cohort. Information was collected from all flat racing starts occurring on GB racecourses between 2000 and 2013, including horse, race, course, trainer and jockey data for each horse start and race-day injury data as reported by on-course veterinarians. Associations between exposure variables and cases of distal limb fracture were assessed using mixed effects logistic regression analyses using data from all starts, and turf starts only. A total of 806,764 starts and 624 cases of distal limb fracture were included, of which 548,571 starts and 379 cases of distal limb fracture occurred on turf surfaces. In both models, increasing firmness of the going, increasing racing distance and horses in their first year of racing were at a higher risk of distal limb fracture, while increasing number of previous race starts were protective. Trainer performance was associated with distal limb fracture. Generally, the risk of distal limb fracture increased with increasing horse age. Starts in selling or claiming races or Group 1, Group 3 or claiming races were at higher odds of distal limb fracture in the all starts and turf models, respectively. Clinical diagnosis of distal limb fracture and all types of distal limb fracture considered as one outcome. This study confirmed previously identified risk factors for distal limb fracture including going, race distance and number of horse starts. Novel risk factors were related to trainer and horse performance, and race type. Identification of at risk groups will help inform interventions to reduce distal limb fracture occurrence in flat racing horses. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Assessing Forelimb Function after Unilateral Cervical SCI using Novel Tasks: Limb Step-alternation, Postural Instability and Pasta Handling

PubMed Central

Schallert, Timothy; Schmidt, Christine E.

2013-01-01

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI. PMID:24084700

Assessing forelimb function after unilateral cervical SCI using novel tasks: limb step-alternation, postural instability and pasta handling.

PubMed

Khaing, Zin Z; Geissler, Sydney A; Schallert, Timothy; Schmidt, Christine E

2013-09-16

Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. A majority of the spinal cord injuries in humans occur at the cervical levels. Therefore, developing cervical injury models and developing relevant and sensitive behavioral tests is of great importance. Here we describe the use of a newly developed forelimb step-alternation test after cervical spinal cord injury in rats. In addition, we describe two behavioral tests that have not been used after spinal cord injury: a postural instability test (PIT), and a pasta-handling test. All three behavioral tests are highly sensitive to injury and are easy to use. Therefore, we feel that these behavioral tests can be instrumental in investigating therapeutic strategies after cSCI.

Benchmarking of dynamic simulation predictions in two software platforms using an upper limb musculoskeletal model

PubMed Central

Saul, Katherine R.; Hu, Xiao; Goehler, Craig M.; Vidt, Meghan E.; Daly, Melissa; Velisar, Anca; Murray, Wendy M.

2014-01-01

Several opensource or commercially available software platforms are widely used to develop dynamic simulations of movement. While computational approaches are conceptually similar across platforms, technical differences in implementation may influence output. We present a new upper limb dynamic model as a tool to evaluate potential differences in predictive behavior between platforms. We evaluated to what extent differences in technical implementations in popular simulation software environments result in differences in kinematic predictions for single and multijoint movements using EMG- and optimization-based approaches for deriving control signals. We illustrate the benchmarking comparison using SIMM-Dynamics Pipeline-SD/Fast and OpenSim platforms. The most substantial divergence results from differences in muscle model and actuator paths. This model is a valuable resource and is available for download by other researchers. The model, data, and simulation results presented here can be used by future researchers to benchmark other software platforms and software upgrades for these two platforms. PMID:24995410

Benchmarking of dynamic simulation predictions in two software platforms using an upper limb musculoskeletal model.

PubMed

Saul, Katherine R; Hu, Xiao; Goehler, Craig M; Vidt, Meghan E; Daly, Melissa; Velisar, Anca; Murray, Wendy M

2015-01-01

Several opensource or commercially available software platforms are widely used to develop dynamic simulations of movement. While computational approaches are conceptually similar across platforms, technical differences in implementation may influence output. We present a new upper limb dynamic model as a tool to evaluate potential differences in predictive behavior between platforms. We evaluated to what extent differences in technical implementations in popular simulation software environments result in differences in kinematic predictions for single and multijoint movements using EMG- and optimization-based approaches for deriving control signals. We illustrate the benchmarking comparison using SIMM-Dynamics Pipeline-SD/Fast and OpenSim platforms. The most substantial divergence results from differences in muscle model and actuator paths. This model is a valuable resource and is available for download by other researchers. The model, data, and simulation results presented here can be used by future researchers to benchmark other software platforms and software upgrades for these two platforms.

Heterochronic shift in Hox-mediated activation of sonic hedgehog leads to morphological changes during fin development.

PubMed

Sakamoto, Koji; Onimaru, Koh; Munakata, Keijiro; Suda, Natsuno; Tamura, Mika; Ochi, Haruki; Tanaka, Mikiko

2009-01-01

We explored the molecular mechanisms of morphological transformations of vertebrate paired fin/limb evolution by comparative gene expression profiling and functional analyses. In this study, we focused on the temporal differences of the onset of Sonic hedgehog (Shh) expression in paired appendages among different vertebrates. In limb buds of chick and mouse, Shh expression is activated as soon as there is a morphological bud, concomitant with Hoxd10 expression. In dogfish (Scyliorhinus canicula), however, we found that Shh was transcribed late in fin development, concomitant with Hoxd13 expression. We utilized zebrafish as a model to determine whether quantitative changes in hox expression alter the timing of shh expression in pectoral fins of zebrafish embryos. We found that the temporal shift of Shh activity altered the size of endoskeletal elements in paired fins of zebrafish and dogfish. Thus, a threshold level of hox expression determines the onset of shh expression, and the subsequent heterochronic shift of Shh activity can affect the size of the fin endoskeleton. This process may have facilitated major morphological changes in paired appendages during vertebrate limb evolution.

Lower extremity finite element model for crash simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schauer, D.A.; Perfect, S.A.

1996-03-01

A lower extremity model has been developed to study occupant injury mechanisms of the major bones and ligamentous soft tissues resulting from vehicle collisions. The model is based on anatomically correct digitized bone surfaces of the pelvis, femur, patella and the tibia. Many muscles, tendons and ligaments were incrementally added to the basic bone model. We have simulated two types of occupant loading that occur in a crash environment using a non-linear large deformation finite element code. The modeling approach assumed that the leg was passive during its response to the excitation, that is, no active muscular contraction and thereforemore » no active change in limb stiffness. The approach recognized that the most important contributions of the muscles to the lower extremity response are their ability to define and modify the impedance of the limb. When nonlinear material behavior in a component of the leg model was deemed important to response, a nonlinear constitutive model was incorporated. The accuracy of these assumptions can be verified only through a review of analysis results and careful comparison with test data. As currently defined, the model meets the objective for which it was created. Much work remains to be done, both from modeling and analysis perspectives, before the model can be considered complete. The model implements a modeling philosophy that can accurately capture both kinematic and kinetic response of the lower limb. We have demonstrated that the lower extremity model is a valuable tool for understanding the injury processes and mechanisms. We are now in a position to extend the computer simulation to investigate the clinical fracture patterns observed in actual crashes. Additional experience with this model will enable us to make a statement on what measures are needed to significantly reduce lower extremity injuries in vehicle crashes. 6 refs.« less

Predicting translational deformity following opening-wedge osteotomy for lower limb realignment.

PubMed

Barksfield, Richard C; Monsell, Fergal P

2015-11-01

An opening-wedge osteotomy is well recognised for the management of limb deformity and requires an understanding of the principles of geometry. Translation at the osteotomy is needed when the osteotomy is performed away from the centre of rotation of angulation (CORA), but the amount of translation varies with the distance from the CORA. This translation enables proximal and distal axes on either side of the proposed osteotomy to realign. We have developed two experimental models to establish whether the amount of translation required (based on the translation deformity created) can be predicted based upon simple trigonometry. A predictive algorithm was derived where translational deformity was predicted as 2(tan α × d), where α represents 50 % of the desired angular correction, and d is the distance of the desired osteotomy site from the CORA. A simulated model was developed using TraumaCad online digital software suite (Brainlab AG, Germany). Osteotomies were simulated in the distal femur, proximal tibia and distal tibia for nine sets of lower limb scanograms at incremental distances from the CORA and the resulting translational deformity recorded. There was strong correlation between the distance of the osteotomy from the CORA and simulated translation deformity for distal femoral deformities (correlation coefficient 0.99, p < 0.0001), proximal tibial deformities (correlation coefficient 0.93-0.99, p < 0.0001) and distal tibial deformities (correlation coefficient 0.99, p < 0.0001). There was excellent agreement between the predictive algorithm and simulated translational deformity for all nine simulations (correlation coefficient 0.93-0.99, p < 0.0001). Translational deformity following corrective osteotomy for lower limb deformity can be anticipated and predicted based upon the angular correction and the distance between the planned osteotomy site and the CORA.

Attenuated sensing of SHH by Ptch1 underlies evolution of bovine limbs.

PubMed

Lopez-Rios, Javier; Duchesne, Amandine; Speziale, Dario; Andrey, Guillaume; Peterson, Kevin A; Germann, Philipp; Unal, Erkan; Liu, Jing; Floriot, Sandrine; Barbey, Sarah; Gallard, Yves; Müller-Gerbl, Magdalena; Courtney, Andrew D; Klopp, Christophe; Rodriguez, Sabrina; Ivanek, Robert; Beisel, Christian; Wicking, Carol; Iber, Dagmar; Robert, Benoit; McMahon, Andrew P; Duboule, Denis; Zeller, Rolf

2014-07-03

The large spectrum of limb morphologies reflects the wide evolutionary diversification of the basic pentadactyl pattern in tetrapods. In even-toed ungulates (artiodactyls, including cattle), limbs are adapted for running as a consequence of progressive reduction of their distal skeleton to symmetrical and elongated middle digits with hoofed phalanges. Here we analyse bovine embryos to establish that polarized gene expression is progressively lost during limb development in comparison to the mouse. Notably, the transcriptional upregulation of the Ptch1 gene, which encodes a Sonic hedgehog (SHH) receptor, is disrupted specifically in the bovine limb bud mesenchyme. This is due to evolutionary alteration of a Ptch1 cis-regulatory module, which no longer responds to graded SHH signalling during bovine handplate development. Our study provides a molecular explanation for the loss of digit asymmetry in bovine limb buds and suggests that modifications affecting the Ptch1 cis-regulatory landscape have contributed to evolutionary diversification of artiodactyl limbs.

3D reconstruction of the structure of a residual limb for customising the design of a prosthetic socket.

PubMed

Shuxian, Zheng; Wanhua, Zhao; Bingheng, Lu

2005-01-01

Aiming at overcoming the limitations of the plaster-casting method in traditional prosthetic socket fabrication, the idea of reconstructing the 3D models for bones and skin of the residual limb is proposed. Given the two-dimensional obtained image through CT scanning, using image processing and reverse engineering techniques, the 3D solid model of the residual limb can be successfully reconstructed. The new approach can reproduce both the internal and the external structure of the residual limb. It can moreover avoid making a positive mould by the way of manual modifications. In addition to this, it can provide a scientific basis for the individualization of prosthetic socket design.

Modeling equine race surface vertical mechanical behaviors in a musculoskeletal modeling environment.

PubMed

Symons, Jennifer E; Fyhrie, David P; Hawkins, David A; Upadhyaya, Shrinivasa K; Stover, Susan M

2015-02-26

Race surfaces have been associated with the incidence of racehorse musculoskeletal injury, the leading cause of racehorse attrition. Optimal race surface mechanical behaviors that minimize injury risk are unknown. Computational models are an economical method to determine optimal mechanical behaviors. Previously developed equine musculoskeletal models utilized ground reaction floor models designed to simulate a stiff, smooth floor appropriate for a human gait laboratory. Our objective was to develop a computational race surface model (two force-displacement functions, one linear and one nonlinear) that reproduced experimental race surface mechanical behaviors for incorporation in equine musculoskeletal models. Soil impact tests were simulated in a musculoskeletal modeling environment and compared to experimental force and displacement data collected during initial and repeat impacts at two racetracks with differing race surfaces - (i) dirt and (ii) synthetic. Best-fit model coefficients (7 total) were compared between surface types and initial and repeat impacts using a mixed model ANCOVA. Model simulation results closely matched empirical force, displacement and velocity data (Mean R(2)=0.930-0.997). Many model coefficients were statistically different between surface types and impacts. Principal component analysis of model coefficients showed systematic differences based on surface type and impact. In the future, the race surface model may be used in conjunction with previously developed the equine musculoskeletal models to understand the effects of race surface mechanical behaviors on limb dynamics, and determine race surface mechanical behaviors that reduce the incidence of racehorse musculoskeletal injury through modulation of limb dynamics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Propulsive forces of mudskipper fins and salamander limbs during terrestrial locomotion: implications for the invasion of land.

PubMed

Kawano, Sandy M; Blob, Richard W

2013-08-01

The invasion of land was a pivotal event in vertebrate evolution that was associated with major appendicular modifications. Although fossils indicate that the evolution of fundamentally limb-like appendages likely occurred in aquatic environments, the functional consequences of using early digited limbs, rather than fins, for terrestrial propulsion have had little empirical investigation. Paleontological and experimental analyses both have led to the proposal of an early origin of "hind limb-driven" locomotion among tetrapods or their ancestors. However, the retention of a pectoral appendage that had already developed terrestrial adaptations has been proposed for some taxa, and few data are available from extant functional models that can provide a foundation for evaluating the relative contributions of pectoral and pelvic appendages to terrestrial support among early stem tetrapods. To examine these aspects of vertebrate locomotor evolution during the invasion of land, we measured three-dimensional ground reaction forces (GRFs) produced by isolated pectoral fins of mudskipper fishes (Periophthalmus barbarus) during terrestrial crutching, and compared these to isolated walking footfalls by the forelimbs and hind limbs of tiger salamanders (Ambystoma tigrinum), a species with subequally-sized limbs that facilitate comparisons to early tetrapods. Pectoral appendages of salamanders and mudskippers exhibited numerous differences in GRFs. Compared with salamander forelimbs, isolated fins of mudskippers bear lower vertical magnitudes of GRFs (as a proportion of body weight), and had GRFs that were oriented more medially. Comparing the salamanders' forelimbs and hind limbs, although the peak net GRF occurs later in stance for the forelimb, both limbs experience nearly identical mediolateral and vertical components of GRF, suggesting comparable contributions to support. Thus, forelimbs could also have played a significant locomotor role among basal tetrapods that had limbs of sub-equal size. However, the salamander hind limb and mudskipper pectoral fin had a greater acceleratory role than did the salamander forelimb. Together, data from these extant taxa help to clarify how structural change may have influenced locomotor function through the evolutionary invasion of land by vertebrates.

Progress Toward Optimizing Prosthetic Socket Fit and Suspension Using Elevated Vacuum to Promote Residual Limb Health

PubMed Central

Wernke, Matthew M.; Schroeder, Ryan M.; Haynes, Michael L.; Nolt, Lonnie L.; Albury, Alexander W.; Colvin, James M.

2017-01-01

Objective: Prosthetic sockets are custom made for each amputee, yet there are no quantitative tools to determine the appropriateness of socket fit. Ensuring a proper socket fit can have significant effects on the health of residual limb soft tissues and overall function and acceptance of the prosthetic limb. Previous work found that elevated vacuum pressure data can detect movement between the residual limb and the prosthetic socket; however, the correlation between the two was specific to each user. The overall objective of this work is to determine the relationship between elevated vacuum pressure deviations and prosthetic socket fit. Approach: A tension compression machine was used to apply repeated controlled forces onto a residual limb model with sockets of different internal volume. Results: The vacuum pressure–displacement relationship was dependent on socket fit. The vacuum pressure data were sensitive enough to detect differences of 1.5% global volume and can likely detect differences even smaller. Limb motion was reduced as surface area of contact between the limb model and socket was maximized. Innovation: The results suggest that elevated vacuum pressure data provide information to quantify socket fit. Conclusions: This study provides evidence that the use of elevated vacuum pressure data may provide a method for prosthetists to quantify and monitor socket fit. Future studies should investigate the relationship between socket fit, limb motion, and limb health to define optimal socket fit parameters. PMID:28736683

Interferometric radius and limb darkening of the asteroseismic red giant η Serpentis with the CHARA Array

NASA Astrophysics Data System (ADS)

Mérand, A.; Kervella, P.; Barban, C.; Josselin, E.; ten Brummelaar, T. A.; McAlister, H. A.; Coudé du Foresto, V.; Ridgway, S. T.; Turner, N.; Sturmann, J.; Sturmann, L.; Goldfinger, P. J.; Farrington, C.

2010-07-01

Context. The radius of a star is a very important constraint to evolutionary models, particularly when combined with asteroseismology. Diameters can now be measured interferometrically with great precision (better than 1%), but the center-to-limb darkening (CLD) remains a potential source of bias. Measuring this bias is possible by completely resolving the star using long-baseline interferometry, and has only been achieved for a handful of stars. Aims: The red giant η Ser (K0III-IV) is a particularly interesting target, as asteroseismic oscillations have recently been detected in this star by spectroscopy. We aim to measure its radius with high accuracy, debiased from limb darkening, in order to bring new constraints to its models. Methods: We obtained interferometric observations of η Ser in the near-infrared using the CHARA/FLUOR instrument, in particular in the so-called second lobe of visibility in order to constrain the CLD and debias our diameter estimation. Results: The limb darkened angular diameter of η Ser is 2.944 ± 0.010 mas (using spherical photosphere models PHOENIX and MARCS for the limb darkening), that converts into a radius of 5.897 ± 0.028 R_⊙ with the Hipparcos parallax. Thanks to a precise visibility measurement in the second lobe of the visibility function of η Ser and a one-parameter limb-darkened visibility profile, we were able to show that the photosphere models have the best agreement possible. Conclusions: Our limb darkening measurement of η Ser is in agreement with existing atmosphere models of this star, with a slightly better agreement for models using spherical geometry. This is a strong indication that interferometric angular diameter measurements for red giants, corrected for the CLD using models, are unbiased at a very small level (a fraction of 1%). In particular, this strengthens our confidence in the existing catalogues of calibrator stars for interferometry that are based on giant stars similar to η Ser. The high accuracy of our measurement brings a new and strong constraint for the asteroseismic modeling of this star.

Using MERRA-2 analysis fields to simulate limb scattered radiance profiles for inhomogeneous atmospheric lines of sight: Preparation for data assimilation of OMPS LP radiances through 2D single-scattering GSLS radiative transfer model development

NASA Astrophysics Data System (ADS)

Loughman, R. P.; Bhartia, P. K.; Moy, L.; Kramarova, N. A.; Wargan, K.

2016-12-01

Many remote sensing techniques used to monitor the Earth's upper atmosphere fall into the broad category of "limb viewing" (LV) measurements, which includes any method for which the line of sight (LOS) fails to intersect the surface. Occultation, limb emission and limb scattering (LS) measurements are all LV methods that offer strong sensitivity to changes in the atmosphere near the tangent point of the LOS, due to the enhanced geometric path through the tangent layer (where the concentration also typically peaks, for most atmospheric species). But many of the retrieval algorithms used to interpret LV measurements assume that the atmosphere consists of "spherical shells", in which the atmospheric properties vary only with altitude (creating a 1D atmosphere). This assumption simplifies the analysis, but at the possible price of misinterpreting measurements made in the real atmosphere. In this presentation, we focus on the problem of LOS inhomogeneity for LS measurements made by the OMPS Limb Profiler (LP) instrument during the 2015 ozone hole period. The GSLS radiative transfer model (RTM) used in the default OMPS LP algorithms assumes a spherical-shell atmosphere defined at levels spaced 1 km apart, with extinction coefficients assumed to vary linearly with height between levels. Several recent improvements enable an updated single-scattering version of the GSLS RTM to ingest 3D MERRA-2 analysis fields (including temperature, pressure, and ozone concentration) when creating the model atmosphere, by introducing flexible altitude grids, flexible atmospheric specification along the LOS, and improved treatment of the radiative transfer within each atmospheric layer. As a result, the effect of LOS inhomogeneity on the current (1D) OMPS LP retrieval algorithm can now be studied theoretically, using realistic 3D atmospheric profiles. This work also represents a step towards enabling OMPS LP data to be ingested as part of future data assimilation efforts.

Lmx1b-targeted cis-regulatory modules involved in limb dorsalization.

PubMed

Haro, Endika; Watson, Billy A; Feenstra, Jennifer M; Tegeler, Luke; Pira, Charmaine U; Mohan, Subburaman; Oberg, Kerby C

2017-06-01

Lmx1b is a homeodomain transcription factor responsible for limb dorsalization. Despite striking double-ventral (loss-of-function) and double-dorsal (gain-of-function) limb phenotypes, no direct gene targets in the limb have been confirmed. To determine direct targets, we performed a chromatin immunoprecipitation against Lmx1b in mouse limbs at embryonic day 12.5 followed by next-generation sequencing (ChIP-seq). Nearly 84% ( n =617) of the Lmx1b-bound genomic intervals (LBIs) identified overlap with chromatin regulatory marks indicative of potential cis -regulatory modules (PCRMs). In addition, 73 LBIs mapped to CRMs that are known to be active during limb development. We compared Lmx1b-bound PCRMs with genes regulated by Lmx1b and found 292 PCRMs within 1 Mb of 254 Lmx1b-regulated genes. Gene ontological analysis suggests that Lmx1b targets extracellular matrix production, bone/joint formation, axonal guidance, vascular development, cell proliferation and cell movement. We validated the functional activity of a PCRM associated with joint-related Gdf5 that provides a mechanism for Lmx1b-mediated joint modification and a PCRM associated with Lmx1b that suggests a role in autoregulation. This is the first report to describe genome-wide Lmx1b binding during limb development, directly linking Lmx1b to targets that accomplish limb dorsalization. © 2017. Published by The Company of Biologists Ltd.

Limb-darkening functions as derived from along-track operation of the ERBE scanning radiometer for January 1985

NASA Technical Reports Server (NTRS)

Smith, G. Louis; Manalo, Natividad; Suttles, John T.; Walker, Ira

1989-01-01

During January 1985, the scanning radiometer aboard the Earth Radiation Budget Satellite was operated to scan along-track. These data have been analyzed to produce limb-darkening functions for Earth emitted radiation, which relate the radiance in any given direction to the radiant exitance. Limb-darkening functions are presented in tabular form and shown as figures for 10 day cases and 12 night cases, corresponding to various scene types and latitude zones. The scene types were computed using measurements within 10 deg of zenith. The limb-darkening functions have values of 1.03 to 1.09 at zenith, with 1.06 being typical. It is found that latitude causes a variation on the order of 1 percent, except for zenith angles greater than 70 deg. These limb-darkening models are about 2 percent higher at zenith than the models derived from Nimbus 7 data.

Goal-Directed Aiming: Two Components but Multiple Processes

ERIC Educational Resources Information Center

Elliott, Digby; Hansen, Steve; Grierson, Lawrence E. M.; Lyons, James; Bennett, Simon J.; Hayes, Spencer J.

2010-01-01

This article reviews the behavioral literature on the control of goal-directed aiming and presents a multiple-process model of limb control. The model builds on recent variants of Woodworth's (1899) two-component model of speed-accuracy relations in voluntary movement and incorporates ideas about dynamic online limb control based on prior…

The Dependence of Solar Flare Limb Darkening on Emission Peak Formation Temperature

NASA Astrophysics Data System (ADS)

Thiemann, Edward; Epp, Luke; Eparvier, Francis; Chamberlin, Phillip C.

2017-08-01

Solar limb effects are local brightening or darkening of an emission that depend on where in the Sun's atmosphere it forms. Near the solar limb, optically thick (thin) emissions will darken (brighten) as the column of absorbers (emitters) along the line-of-sight increases. Note that in limb brightening, emission sources are re-arranged whereas in limb darkening they are obscured. Thus, only limb darkening is expected to occur in disk integrated observations. Limb darkening also results in center-to-limb variations of disk-integrated solar flare spectra, with important consequences for how planetary atmospheres are affected by flares. Flares are typically characterized by their flux in the optically thin 0.1-0.8 nm band measured by the X-ray Sensor (XRS) on board the Geostationary Operational Environmental Satellite (GOES). On the other hand, Extreme Ultraviolet (EUV) line emissions can limb darken because they are sensitive to resonant scattering, resulting in a flare's location on the solar disk controlling the amount of ionizing radiation that reaches a planet. For example, an X-class flare originating from disk center may significantly heat a planet's thermosphere, whereas the same flare originating near the limb may have no effect because much of the effective emissions are scattered in the solar corona.To advance the relatively poor understanding of flare limb darkening, we use over 300 M-class or larger flares observed by the EUV Variability Experiment (EVE) onboard the Solar Dynamics Observatory (SDO) to characterize limb darkening as a function of emission peak formation temperature, Tf. For hot coronal emissions (Tf>2 MK), these results show a linear relationship between the degree of limb darkening and Tf where lines with Tf=2 MK darken approximately 7 times more than lines with Tf=16 MK. Because the extent of limb darkening is dependent on the height of the source plasma, we use simple Beer-Lambert radiative transfer analysis to interpret these results and characterize the average thermal structure of the flares considered. As such, these results can be used to constrain both empirical flare irradiance models and more sophisticated flare loop hydrodynamic models.

Contribution of tibiofemoral joint contact to net loads at the knee in gait.

PubMed

Walter, Jonathan P; Korkmaz, Nuray; Fregly, Benjamin J; Pandy, Marcus G

2015-07-01

Inverse dynamics analysis is commonly used to estimate the net loads at a joint during human motion. Most lower-limb models of movement represent the knee as a simple hinge joint when calculating muscle forces. This approach is limited because it neglects the contributions from tibiofemoral joint contact forces and may therefore lead to errors in estimated muscle forces. The aim of this study was to quantify the contributions of tibiofemoral joint contact loads to the net knee loads calculated from inverse dynamics for multiple subjects and multiple gait patterns. Tibiofemoral joint contact loads were measured in four subjects with instrumented implants as each subject walked at their preferred speed (normal gait) and performed prescribed gait modifications designed to treat medial knee osteoarthritis. Tibiofemoral contact loads contributed substantially to the net knee extension and knee adduction moments in normal gait with mean values of 16% and 54%, respectively. These findings suggest that knee-contact kinematics and loads should be included in lower-limb models of movement for more accurate determination of muscle forces. The results of this study may be used to guide the development of more realistic lower-limb models that account for the effects of tibiofemoral joint contact at the knee. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Influence of physical fitness on cardio-metabolic risk factors in European children. The IDEFICS study.

PubMed

Zaqout, M; Michels, N; Bammann, K; Ahrens, W; Sprengeler, O; Molnar, D; Hadjigeorgiou, C; Eiben, G; Konstabel, K; Russo, P; Jiménez-Pavón, D; Moreno, L A; De Henauw, S

2016-07-01

The aim of the study was to assess the associations of individual and combined physical fitness components with single and clustering of cardio-metabolic risk factors in children. This 2-year longitudinal study included a total of 1635 European children aged 6-11 years. The test battery included cardio-respiratory fitness (20-m shuttle run test), upper-limb strength (handgrip test), lower-limb strength (standing long jump test), balance (flamingo test), flexibility (back-saver sit-and-reach) and speed (40-m sprint test). Metabolic risk was assessed through z-score standardization using four components: waist circumference, blood pressure (systolic and diastolic), blood lipids (triglycerides and high-density lipoprotein) and insulin resistance (homeostasis model assessment). Mixed model regression analyses were adjusted for sex, age, parental education, sugar and fat intake, and body mass index. Physical fitness was inversely associated with clustered metabolic risk (P<0.001). All coefficients showed a higher clustered metabolic risk with lower physical fitness, except for upper-limb strength (β=0.057; P=0.002) where the opposite association was found. Cardio-respiratory fitness (β=-0.124; P<0.001) and lower-limb strength (β=-0.076; P=0.002) were the most important longitudinal determinants. The effects of cardio-respiratory fitness were even independent of the amount of vigorous-to-moderate activity (β=-0.059; P=0.029). Among all the metabolic risk components, blood pressure seemed not well predicted by physical fitness, while waist circumference, blood lipids and insulin resistance all seemed significantly predicted by physical fitness. Poor physical fitness in children is associated with the development of cardio-metabolic risk factors. Based on our results, this risk might be modified by improving mainly cardio-respiratory fitness and lower-limb muscular strength.

Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome.

PubMed

Woods, C G; Stricker, S; Seemann, P; Stern, R; Cox, J; Sherridan, E; Roberts, E; Springell, K; Scott, S; Karbani, G; Sharif, S M; Toomes, C; Bond, J; Kumar, D; Al-Gazali, L; Mundlos, S

2006-08-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development.

Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome

PubMed Central

Woods, C. G.; Stricker, S.; Seemann, P.; Stern, R.; Cox, J.; Sherridan, E.; Roberts, E.; Springell, K.; Scott, S.; Karbani, G.; Sharif, S. M.; Toomes, C.; Bond, J.; Kumar, D.; Al-Gazali, L.; Mundlos, S.

2006-01-01

Fuhrmann syndrome and the Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome are considered to be distinct limb-malformation disorders characterized by various degrees of limb aplasia/hypoplasia and joint dysplasia in humans. In families with these syndromes, we found homozygous missense mutations in the dorsoventral-patterning gene WNT7A and confirmed their functional significance in retroviral-mediated transfection of chicken mesenchyme cell cultures and developing limbs. The results suggest that a partial loss of WNT7A function causes Fuhrmann syndrome (and a phenotype similar to mouse Wnt7a knockout), whereas the more-severe limb truncation phenotypes observed in Al-Awadi/Raas-Rothschild/Schinzel phocomelia syndrome result from null mutations (and cause a phenotype similar to mouse Shh knockout). These findings illustrate the specific and conserved importance of WNT7A in multiple aspects of vertebrate limb development. PMID:16826533

Analysis of the intermediate size proteoglycans from the developing chick limb buds.

PubMed

Vasan, N

1982-08-01

Limb-bud proteoglycans are heterogeneous molecules which vary in their chemical and physical properties with development. This report describes proteoglycan intermediates (PG-I) that predominate in stage-34 limbs, and compares them with proteoglycan aggregates (PG-A) in stage-38 limbs. We analysed proteoglycans and their components extracted with guanidinium chloride by subjecting them to density gradient centrifugation, molecular sieve chromatography, electrophoretic separation, and selective enzymatic degradation. PG-I and PG-A have similar chondroitin sulphate composition, amino sugars, chondroitin sulphate side-chain length, glycoprotein link factors, and hyaluronic acid binding capacity, and both cross react with antisera prepared against cartilage-specific chick sternal proteoglycans. However, PG-I has lower molecular weight, lower buoyant density, and fewer chondroitin sulphate side chains on the protein core. The PG-I in the developing limb can be considered a mixture of smaller aggregates and cartilage-specific large monomers in which the former predominate.

Prenatal development of the foot and ankle.

PubMed

Bareither, D

1995-12-01

The general development of the lower limb and the specific development of the foot and ankle are discussed for each horizon in the embryonic and fetal periods of development. Lower limb general development is discussed only to the extent necessary for the understanding of foot and ankle development.

Intercomparison of daytime stratospheric NO2 satellite retrievals and model simulations

NASA Astrophysics Data System (ADS)

Belmonte Rivas, M.; Veefkind, P.; Boersma, F.; Levelt, P.; Eskes, H.; Gille, J.

2014-01-01

This paper evaluates the agreement between stratospheric NO2 retrievals from infrared limb sounders (MIPAS and HIRDLS) and solar UV/VIS backscatter sensors (OMI, SCIAMACHY limb and nadir) over the 2005-2007 period and across the seasons. The observational agreement is contrasted with the representation of NO2 profiles in 3-D chemical transport models such as the Whole Atmosphere Community Climate Model (SD-WACCM) and TM4. A conclusion central to this work is that the definition of a reference for stratospheric NO2 columns formed by consistent agreement among SCIAMACHY, MIPAS and HIRDLS limb records (all of which agree to within 0.25 × 1015 molecules cm-2 or better than 10%) allows us to draw attention to relative errors in other datasets, e.g.: (1) the WACCM model overestimates NO2 densities in the extratropical lower stratosphere, particularly over northern latitudes by up to 35% relative to limb observations, and (2) there are remarkable discrepancies between stratospheric NO2 column estimates from limb and nadir techniques, with a characteristic seasonal and latitude dependent pattern. We find that SCIAMACHY nadir and OMI stratospheric columns show overall biases of -0.6 × 1015 molecules cm-2 (-20%) and +0.6 × 10 15 molecules cm-2 (+20%) relative to limb observations. It is highlighted that biases in nadir stratospheric columns are not expected to affect tropospheric retrievals significantly, and that they can be attributed to errors in the total slant column density, either related to algorithmic or instrumental effects. In order to obtain accurate and long time series of stratospheric NO2, a critical evaluation of the currently used Differential Optical Absorption Spectroscopy (DOAS) approaches to nadir retrievals becomes essential, as well as their agreement to limb and ground-based observations, particularly now that limb techniques are giving way to nadir observations as the next generation of climate and air quality monitoring instruments pushes forth.

Ectopic expression of Msx-2 in posterior limb bud mesoderm impairs limb morphogenesis while inducing BMP-4 expression, inhibiting cell proliferation, and promoting apoptosis.

PubMed

Ferrari, D; Lichtler, A C; Pan, Z Z; Dealy, C N; Upholt, W B; Kosher, R A

1998-05-01

During early stages of chick limb development, the homeobox-containing gene Msx-2 is expressed in the mesoderm at the anterior margin of the limb bud and in a discrete group of mesodermal cells at the midproximal posterior margin. These domains of Msx-2 expression roughly demarcate the anterior and posterior boundaries of the progress zone, the highly proliferating posterior mesodermal cells underneath the apical ectodermal ridge (AER) that give rise to the skeletal elements of the limb and associated structures. Later in development as the AER loses its activity, Msx-2 expression expands into the distal mesoderm and subsequently into the interdigital mesenchyme which demarcates the developing digits. The domains of Msx-2 expression exhibit considerably less proliferation than the cells of the progress zone and also encompass several regions of programmed cell death including the anterior and posterior necrotic zones and interdigital mesenchyme. We have thus suggested that Msx-2 may be in a regulatory network that delimits the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed. In the present study we show that ectopic expression of Msx-2 via a retroviral expression vector in the posterior mesoderm of the progress zone from the time of initial formation of the limb bud severely impairs limb morphogenesis. Msx-2-infected limbs are typically very narrow along the anteroposterior axis, are occasionally truncated, and exhibit alterations in the pattern of formation of skeletal elements, indicating that as a consequence of ectopic Msx-2 expression the morphogenesis of large portions of the posterior mesoderm has been suppressed. We further show that Msx-2 impairs limb morphogenesis by reducing cell proliferation and promoting apoptosis in the regions of the posterior mesoderm in which it is ectopically expressed. The domains of ectopic Msx-2 expression in the posterior mesoderm also exhibit ectopic expression of BMP-4, a secreted signaling molecule that is coexpressed with Msx-2 during normal limb development in the anterior limb mesoderm, the posterior necrotic zone, and interdigital mesenchyme. This indicates that Msx-2 regulates BMP-4 expression and that the suppressive effects of Msx-2 on limb morphogenesis might be mediated in part by BMP-4. These studies indicate that during normal limb development Msx-2 is a key component of a regulatory network that delimits the boundaries of the progress zone by suppressing the morphogenesis of the regions of the limb mesoderm in which it is highly expressed, thus restricting the outgrowth and formation of skeletal elements and associated structures to the progress zone. We also report that rather large numbers of apoptotic cells as well as proliferating cells are present throughout the AER during all stages of normal limb development we have examined, indicating that many of the cells of the AER are continuously undergoing programmed cell death at the same time that new AER cells are being generated by cell proliferation. Thus, a balance between cell proliferation and programmed cell death may play a very important role in maintaining the activity of the AER. Copyright 1998 Academic Press.

Decision-Making in Critical Limb Ischemia: A Markov Simulation.

PubMed

Deutsch, Aaron J; Jain, C Charles; Blumenthal, Kimberly G; Dickinson, Mark W; Neilan, Anne M

2017-11-01

Critical limb ischemia (CLI) is a feared complication of peripheral vascular disease that often requires surgical management and may require amputation of the affected limb. We developed a decision model to inform clinical management for a 63-year-old woman with CLI and multiple medical comorbidities, including advanced heart failure and diabetes. We developed a Markov decision model to evaluate 4 strategies: amputation, surgical bypass, endovascular therapy (e.g. stent or revascularization), and medical management. We measured the impact of parameter uncertainty using 1-way, 2-way, and multiway sensitivity analyses. In the base case, endovascular therapy yielded similar discounted quality-adjusted life months (26.50 QALMs) compared with surgical bypass (26.34 QALMs). Both endovascular and surgical therapies were superior to amputation (18.83 QALMs) and medical management (11.08 QALMs). This finding was robust to a wide range of periprocedural mortality weights and was most sensitive to long-term mortality associated with endovascular and surgical therapies. Utility weights were not stratified by patient comorbidities; nonetheless, our conclusion was robust to a range of utility weight values. For a patient with CLI, endovascular therapy and surgical bypass provided comparable clinical outcomes. However, this finding was sensitive to long-term mortality rates associated with each procedure. Both endovascular and surgical therapies were superior to amputation or medical management in a range of scenarios. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of upper limb prostheses: current progress and areas for growth.

PubMed

González-Fernández, Marlís

2014-06-01

Upper extremity prosthetic technology has significantly changed in recent years. The devices available and those under development are more and more able to approximate the function of the lost limb; however, other challenges remain. This article provides a brief perspective on the most advanced upper limb prostheses available and the challenges present for continued development of the technology. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Clinical practice guidelines for the management of acute limb compartment syndrome following trauma.

PubMed

Wall, Christopher J; Lynch, Joan; Harris, Ian A; Richardson, Martin D; Brand, Caroline; Lowe, Adrian J; Sugrue, Michael

2010-03-01

Acute compartment syndrome is a serious and not uncommon complication of limb trauma. The condition is a surgical emergency, and is associated with significant morbidity if not managed appropriately. There is variation in management of acute limb compartment syndrome in Australia. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma were developed in accordance with Australian National Health and Medical Research Council recommendations. The guidelines were based on critically appraised literature evidence and the consensus opinion of a multidisciplinary team involved in trauma management who met in a nominal panel process. Recommendations were developed for key decision nodes in the patient care pathway, including methods of diagnosis in alert and unconscious patients, appropriate assessment of compartment pressure, timing and technique of fasciotomy, fasciotomy wound management, and prevention of compartment syndrome in patients with limb injuries. The recommendations were largely consensus based in the absence of well-designed clinical trial evidence. Clinical practice guidelines for the management of acute limb compartment syndrome following trauma have been developed that will support consistency in management and optimize patient health outcomes.

Behavioral and Neurophysiological Correlates of Striatal Dopamine Depletion: A Rodent Model of Parkinson's Disease

ERIC Educational Resources Information Center

Plowman, Emily K.; Kleim, Jeffrey A.

2011-01-01

Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and…

Appropriateness of advanced upper limb prosthesis prescription for a patient with cognitive impairment: a case report.

PubMed

Barredo, Jennifer; Acluche, Frantzy; Disla, Roxanne; Fantini, Christopher; Fishelis, Leah; Sasson, Nicole; Resnik, Linda

2017-08-01

To describe a participant with scapulo-thoracic amputation and cognitive impairment trained to use the DEKA Arm and discuss factors relevant to the determination that he was not an appropriate candidate for independent home use of the device. The participant underwent 40 h of in-laboratory training with the DEKA Arm Advanced Upper Limb Prosthesis. Pre-training neuropsychological measures of cognition were collected. Qualitative and quantitative data related to functional performance, quality of life and pain were collected after 10 h of training, and at the conclusion of training. Using a constant comparative approach, data were binned into major themes; elements within each theme were identified. Six themes were relevant to the determination that the participant was inappropriate for home use of the DEKA Arm: physical and mental health; learning, memory and cognition; adult role function; functional performance; user safety and judgement and capacity for independent device use. Issues contraindicating unsupervised device use included: uncontrolled health symptoms, poor knowledge application, safety concerns, absenteeism and performance degradation under stress. The findings have implications for training with and prescription of the DEKA Arm and other complex upper limb prostheses. Further research is needed to develop a model to guide prescription of technologically complex upper limb prostheses. Implications for Rehabilitation Advanced upper limb prostheses, like the DEKA Arm, promise greater functionality, but also may be cognitively demanding, raising questions of when, and if, prescription is appropriate for patients with cognitive impairment. At this time, no formal criteria exist to guide prescription of advanced upper limb prostheses. Each clinical team applies their own informal standards in decision-making. In this case report, we described six factors that were considered in determining whether or not a research participant, with scapulo-thoracic amputation and cognitive impairment was appropriate for home use of a complex upper limb prosthesis. The findings have implications for training with and prescription of the DEKA Arm, and highlights the need for further research to develop prescription guidelines for advanced assistive devices.

Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb.

PubMed

Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline; Sugiyama, Yoshinori; Sayo, Tetsuya; Okuno, Misako; Dealy, Caroline N; Toole, Bryan P; Takeda, Junji; Yamaguchi, Yu; Kosher, Robert A

2009-08-01

The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb.

Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation.

PubMed

Kingery, W S; Guo, T; Agashe, G S; Davies, M F; Clark, J D; Maze, M

2001-09-21

Sciatic nerve section in rats evokes chronic limb edema, pain behavior, and hindpaw hyperalgesia, a syndrome resembling the complex regional pain syndrome type II (CRPS II or causalgia) in man. Glucocorticoids such as methylprednisolone (MP) have been used as analgesic and anti-edematous agents in patients suffering from CRPS, and interestingly these therapeutic effects appear to persist in some patients after stopping the medication. Similar to the CRPS clinical response to glucocorticoids, we now demonstrate that chronic hindpaw edema in the sciatic transection CRPS model is reversed by a continuous infusion of MP (3 mg/kg/day over 21 days), and this anti-edematous effect persists for at least 1 week after discontinuing MP. Furthermore, there is a chronic increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous hands of CRPS patients. A 2-week infusion of MP (3 mg/kg/day) reduced spontaneous protein extravasation in the hindpaw skin by 80%. We postulated that increased spontaneous neurogenic extravasation resulted in development of limb edema in both the animal model and the CRPS patient, and that the anti-edematous effects of MP are due to an inhibition of spontaneous extravasation. Additional experiments examined the inhibitory effects of MP infusion on electrically-evoked neurogenic extravasation in the hindpaw skin of normal rats. MP inhibition was dose- and time-dependent, with an ED(50) of 1.2 mg/kg/day for a 14-day continuous infusion of MP, and a maximum inhibitory effect requiring 17 days of MP infusion (3 mg/kg/day). MP (3 mg/kg/day for 14 days) also blocked both capsaicin- and SP-evoked neurogenic extravasation, indicating a post-junctional inhibitory effect. Our interpretation is that increased spontaneous neurogenic extravasation in this CRPS model contributed to the development and maintenance of hindpaw edema, and that chronic MP administration dose- and time-dependently blocked neurogenic extravasation at a post-junctional level, thus reversing spontaneous extravasation and limb edema in this model.

Modeling the interactions between a prosthetic socket, polyurethane liners and the residual limb in transtibial amputees using non-linear finite element analysis.

PubMed

Simpson, G; Fisher, C; Wright, D K

2001-01-01

Continuing earlier studies into the relationship between the residual limb, liner and socket in transtibial amputees, we describe a geometrically accurate non-linear model simulating the donning of a liner and then a socket. The socket is rigid and rectified and the liner is a polyurethane geltype which is accurately described using non-linear (Mooney-Rivlin) material properties. The soft tissue of the residual limb is modelled as homogeneous, non-linear and hyperelastic and the bone structure within the residual limb is taken as rigid. The work gives an indication of how the stress induced by the process of donning the rigid socket is redistributed by the liner. Ultimately we hope to understand how the liner design might be modified to reduce discomfort. The ANSYS finite element code, version 5.6 is used.

The Quest toward limb regeneration: a regenerative engineering approach

PubMed Central

Laurencin, Cato T.; Nair, Lakshmi S.

2016-01-01

The Holy Grail to address the clinical grand challenge of human limb loss is to develop innovative strategies to regrow the amputated limb. The remarkable advances in the scientific understanding of regeneration, stem cell science, material science and engineering, physics and novel surgical approaches in the past few decades have provided a regenerative tool box to face this grand challenge and address the limitations of human wound healing. Here we discuss the convergence approach put forward by the field of Regenerative Engineering to use the regenerative tool box to design and develop novel translational strategies to limb regeneration. PMID:27047679

Factors impacting participation in sports for children with limb absence: a qualitative study.

PubMed

Sayed Ahmed, Batoul; Lamy, Marena; Cameron, Debra; Artero, Lisa; Ramdial, Sandra; Leineweber, Matthew; Andrysek, Jan

2018-06-01

Individuals with limb absence benefit from participating in sports. While barriers and facilitators affecting sport participation are well documented for adults, they have not been explored for children with limb absence. To identify the perceived factors impacting participation in sports according to children with limb absence and their parents. This study uses a descriptive qualitative study design. Nineteen participants, consisting of children and their parents, were recruited from an outpatient hospital clinic for semi-structured interviews. The 11 interviews were audio recorded and transcribed. Transcripts were then coded and analyzed using the DEPICT model. The thematic analysis was guided by the International Classification of Functioning, Disability, and Health framework. Analysis of our participant interviews identified six themes as having an influence on sport participation: "functionality of prosthesis", "plan in advance", "know what I can do" (understanding capabilities), "it's like every stroke, 2 million questions" (stigma and the social environment), "love for the game" (love for sport), and "these things are an investment" (the investment involved). The findings have the potential to inform the development and implementation of strategies to increase levels of participation in sports among children with limb absence. Information from this study may help to deepen the rehabilitation team's understanding of factors that impact engagement in sports among children with limb absence. Implications for Rehabilitation Children with limb absence present with unique barriers and facilitators to participating in sports, thus, what may be a facilitator or barrier for one child may not for another. Strategies to increase a child's participation in sports should consider both person and environmental factors. Rehabilitation professionals can play a crucial role in educating both families and the community on living and coping with a limb difference, services and community supports available, and the use of specialized prosthesis and attachments for sport participation.

Robust Real-Time Musculoskeletal Modeling Driven by Electromyograms.

PubMed

Durandau, Guillaume; Farina, Dario; Sartori, Massimo

2018-03-01

Current clinical biomechanics involves lengthy data acquisition and time-consuming offline analyses with biomechanical models not operating in real-time for man-machine interfacing. We developed a method that enables online analysis of neuromusculoskeletal function in vivo in the intact human. We used electromyography (EMG)-driven musculoskeletal modeling to simulate all transformations from muscle excitation onset (EMGs) to mechanical moment production around multiple lower-limb degrees of freedom (DOFs). We developed a calibration algorithm that enables adjusting musculoskeletal model parameters specifically to an individual's anthropometry and force-generating capacity. We incorporated the modeling paradigm into a computationally efficient, generic framework that can be interfaced in real-time with any movement data collection system. The framework demonstrated the ability of computing forces in 13 lower-limb muscle-tendon units and resulting moments about three joint DOFs simultaneously in real-time. Remarkably, it was capable of extrapolating beyond calibration conditions, i.e., predicting accurate joint moments during six unseen tasks and one unseen DOF. The proposed framework can dramatically reduce evaluation latency in current clinical biomechanics and open up new avenues for establishing prompt and personalized treatments, as well as for establishing natural interfaces between patients and rehabilitation systems. The integration of EMG with numerical modeling will enable simulating realistic neuromuscular strategies in conditions including muscular/orthopedic deficit, which could not be robustly simulated via pure modeling formulations. This will enable translation to clinical settings and development of healthcare technologies including real-time bio-feedback of internal mechanical forces and direct patient-machine interfacing.

Whole limb kinematics are preferentially conserved over individual joint kinematics after peripheral nerve injury

PubMed Central

Chang, Young-Hui; Auyang, Arick G.; Scholz, John P.; Nichols, T. Richard

2009-01-01

Summary Biomechanics and neurophysiology studies suggest whole limb function to be an important locomotor control parameter. Inverted pendulum and mass-spring models greatly reduce the complexity of the legs and predict the dynamics of locomotion, but do not address how numerous limb elements are coordinated to achieve such simple behavior. As a first step, we hypothesized whole limb kinematics were of primary importance and would be preferentially conserved over individual joint kinematics after neuromuscular injury. We used a well-established peripheral nerve injury model of cat ankle extensor muscles to generate two experimental injury groups with a predictable time course of temporary paralysis followed by complete muscle self-reinnervation. Mean trajectories of individual joint kinematics were altered as a result of deficits after injury. By contrast, mean trajectories of limb orientation and limb length remained largely invariant across all animals, even with paralyzed ankle extensor muscles, suggesting changes in mean joint angles were coordinated as part of a long-term compensation strategy to minimize change in whole limb kinematics. Furthermore, at each measurement stage (pre-injury, paralytic and self-reinnervated) step-by-step variance of individual joint kinematics was always significantly greater than that of limb orientation. Our results suggest joint angle combinations are coordinated and selected to stabilize whole limb kinematics against short-term natural step-by-step deviations as well as long-term, pathological deviations created by injury. This may represent a fundamental compensation principle allowing animals to adapt to changing conditions with minimal effect on overall locomotor function. PMID:19837893

Predictive Value of Upper Limb Muscles and Grasp Patterns on Functional Outcome in Cervical Spinal Cord Injury.

PubMed

Velstra, Inge-Marie; Bolliger, Marc; Krebs, Jörg; Rietman, Johan S; Curt, Armin

2016-05-01

To determine which single or combined upper limb muscles as defined by the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI); upper extremity motor score (UEMS) and the Graded Redefined Assessment of Strength, Sensibility, and Prehension (GRASSP), best predict upper limb function and independence in activities of daily living (ADLs) and to assess the predictive value of qualitative grasp movements (QlG) on upper limb function in individuals with acute tetraplegia. As part of a Europe-wide, prospective, longitudinal, multicenter study ISNCSCI, GRASSP, and Spinal Cord Independence Measure (SCIM III) scores were recorded at 1 and 6 months after SCI. For prediction of upper limb function and ADLs, a logistic regression model and unbiased recursive partitioning conditional inference tree (URP-CTREE) were used. Results: Logistic regression and URP-CTREE revealed that a combination of ISNCSCI and GRASSP muscles (to a maximum of 4) demonstrated the best prediction (specificity and sensitivity ranged from 81.8% to 96.0%) of upper limb function and identified homogenous outcome cohorts at 6 months. The URP-CTREE model with the QlG predictors for upper limb function showed similar results. Prediction of upper limb function can be achieved through a combination of defined, specific upper limb muscles assessed in the ISNCSCI and GRASSP. A combination of a limited number of proximal and distal muscles along with an assessment of grasping movements can be applied for clinical decision making for rehabilitation interventions and clinical trials. © The Author(s) 2015.

Large-scale mechanical buckle fold development and the initiation of tensile fractures

NASA Astrophysics Data System (ADS)

Eckert, Andreas; Connolly, Peter; Liu, Xiaolong

2014-11-01

failure associated with buckle folding is commonly associated to the distribution of outer arc extension but has also been observed on fold limbs. This study investigates whether tensile stresses and associated failure can be explained by the process of buckling under realistic in situ stress conditions. A 2-D plane strain finite element modeling approach is used to study single-layer buckle folds with a Maxwell viscoelastic rheology. A variety of material parameters are considered and their influence on the initiation of tensile stresses during the various stages of deformation is analyzed. It is concluded that the buckling process determines the strain distribution within the fold layer but is not solely responsible for the initiation of tensile stresses. The modeling results show that tensile stresses are most dependent on the permeability, viscosity, and overburden thickness. Low permeability (<10-19 m2), high viscosity (≥1021 Pa s), and low overburden pressure can explain tensile failure at the fold hinge. Tensile stresses in the limb of the fold cannot (in general) be explained by buckling. Rather, it develops due to a combination of compression and erosional unloading. The modeling results show that erosion of high permeability rocks can explain the generation of tensile stresses at significant depths (˜2 km) both at the hinge of the fold and throughout the limb of the fold. This study shows that tensile stresses and associated failure within buckle folds is directly dependent on the distribution of material parameters but moreover to the strain history of the geologic system.

Compensatory Limb Use and Behavioral Assessment of Motor Skill Learning Following Sensorimotor Cortex Injury in a Mouse Model of Ischemic Stroke

PubMed Central

Kerr, Abigail L.; Tennant, Kelly A.

2014-01-01

Mouse models have become increasingly popular in the field of behavioral neuroscience, and specifically in studies of experimental stroke. As models advance, it is important to develop sensitive behavioral measures specific to the mouse. The present protocol describes a skilled motor task for use in mouse models of stroke. The Pasta Matrix Reaching Task functions as a versatile and sensitive behavioral assay that permits experimenters to collect accurate outcome data and manipulate limb use to mimic human clinical phenomena including compensatory strategies (i.e., learned non-use) and focused rehabilitative training. When combined with neuroanatomical tools, this task also permits researchers to explore the mechanisms that support behavioral recovery of function (or lack thereof) following stroke. The task is both simple and affordable to set up and conduct, offering a variety of training and testing options for numerous research questions concerning functional outcome following injury. Though the task has been applied to mouse models of stroke, it may also be beneficial in studies of functional outcome in other upper extremity injury models. PMID:25045916

Robust Revascularization in Models of Limb Ischemia Using a Clinically Translatable Human Stem Cell-Derived Endothelial Cell Product.

PubMed

MacAskill, Mark G; Saif, Jaimy; Condie, Alison; Jansen, Maurits A; MacGillivray, Thomas J; Tavares, Adriana A S; Fleisinger, Lucija; Spencer, Helen L; Besnier, Marie; Martin, Ernesto; Biglino, Giovanni; Newby, David E; Hadoke, Patrick W F; Mountford, Joanne C; Emanueli, Costanza; Baker, Andrew H

2018-03-28

Pluripotent stem cell-derived differentiated endothelial cells offer high potential in regenerative medicine in the cardiovascular system. With the aim of translating the use of a human stem cell-derived endothelial cell product (hESC-ECP) for treatment of critical limb ischemia (CLI) in man, we report a good manufacturing practice (GMP)-compatible protocol and detailed cell tracking and efficacy data in multiple preclinical models. The clinical-grade cell line RC11 was used to generate hESC-ECP, which was identified as mostly endothelial (60% CD31 + /CD144 + ), with the remainder of the subset expressing various pericyte/mesenchymal stem cell markers. Cell tracking using MRI, PET, and qPCR in a murine model of limb ischemia demonstrated that hESC-ECP was detectable up to day 7 following injection. Efficacy in several murine models of limb ischemia (immunocompromised/immunocompetent mice and mice with either type I/II diabetes mellitus) demonstrated significantly increased blood perfusion and capillary density. Overall, we demonstrate a GMP-compatible hESC-ECP that improved ischemic limb perfusion and increased local angiogenesis without engraftment, paving the way for translation of this therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Development of a prosthesis shoulder mechanism for upper limb amputees: application of an original design methodology to optimize functionality and wearability.

PubMed

Troncossi, Marco; Borghi, Corrado; Chiossi, Marco; Davalli, Angelo; Parenti-Castelli, Vincenzo

2009-05-01

The application of a design methodology for the determination of the optimal prosthesis architecture for a given upper limb amputee is presented in this paper along with the discussion of its results. In particular, a novel procedure was used to provide the main guidelines for the design of an actuated shoulder articulation for externally powered prostheses. The topology and the geometry of the new articulation were determined as the optimal compromise between wearability (for the ease of use and the patient's comfort) and functionality of the device (in terms of mobility, velocity, payload, etc.). This choice was based on kinematic and kinetostatic analyses of different upper limb prosthesis models and on purpose-built indices that were set up to evaluate the models from different viewpoints. Only 12 of the 31 simulated prostheses proved a sufficient level of functionality: among these, the optimal solution was an articulation having two actuated revolute joints with orthogonal axes for the elevation of the upper arm in any vertical plane and a frictional joint for the passive adjustment of the humeral intra-extra rotation. A prototype of the mechanism is at the clinical test stage.

EEG controlled neuromuscular electrical stimulation of the upper limb for stroke patients

NASA Astrophysics Data System (ADS)

Tan, Hock Guan; Shee, Cheng Yap; Kong, Keng He; Guan, Cuntai; Ang, Wei Tech

2011-03-01

This paper describes the Brain Computer Interface (BCI) system and the experiments to allow post-acute (<3 months) stroke patients to use electroencephalogram (EEG) to trigger neuromuscular electrical stimulation (NMES)-assisted extension of the wrist/fingers, which are essential pre-requisites for useful hand function. EEG was recorded while subjects performed motor imagery of their paretic limb, and then analyzed to determine the optimal frequency range within the mu-rhythm, with the greatest attenuation. Aided by visual feedback, subjects then trained to regulate their mu-rhythm EEG to operate the BCI to trigger NMES of the wrist/finger. 6 post-acute stroke patients successfully completed the training, with 4 able to learn to control and use the BCI to initiate NMES. This result is consistent with the reported BCI literacy rate of healthy subjects. Thereafter, without the loss of generality, the controller of the NMES is developed and is based on a model of the upper limb muscle (biceps/triceps) groups to determine the intensity of NMES required to flex or extend the forearm by a specific angle. The muscle model is based on a phenomenological approach, with parameters that are easily measured and conveniently implemented.

Development of a parent‐reported questionnaire evaluating upper limb activity limitation in children with cerebral palsy

PubMed Central

Preston, N.; Levesley, M.; Mon‐Williams, M.; O'Connor, R.J.

2017-01-01

Abstract Background and purpose Upper limb activity measures for children with cerebral palsy have a number of limitations, for example, lack of validity and poor responsiveness. To overcome these limitations, we developed the Children's Arm Rehabilitation Measure (ChARM), a parent‐reported questionnaire validated for children with cerebral palsy aged 5–16 years. This paper describes both the development of the ChARM items and response categories and its psychometric testing and further refinement using the Rasch measurement model. Methods To generate valid items for the ChARM, we collected goals of therapy specifically developed by therapists, children with cerebral palsy, and their parents for improving activity limitation of the upper limb. The activities, which were the focus of these goals, formed the basis for the items. Therapists typically break an activity into natural stages for the purpose of improving activity performance, and these natural orders of achievement formed each item's response options. Items underwent face validity testing with health care professionals, parents of children with cerebral palsy, academics, and lay persons. A Rasch analysis was performed on ChARM questionnaires completed by the parents of 170 children with cerebral palsy from 12 hospital paediatric services. The ChARM was amended, and the procedure repeated on 148 ChARMs (from children's mean age: 10 years and 1 month; range: 4 years and 8 months to 16 years and 11 months; 85 males; Manual Ability Classification System Levels I = 9, II = 26, III = 48, IV = 45, and V = 18). Results The final 19‐item unidimensional questionnaire displayed fit to the Rasch model (chi‐square p = .18), excellent reliability (person separation index = 0.95, α = 0.95), and no floor or ceiling effects. Items showed no response bias for gender, distribution of impairment, age, or learning disability. Discussion The ChARM is a psychometrically sound measure of upper limb activity validated for children with cerebral palsy aged 5–16 years. The ChARM is freely available for use to clinicians and nonprofit organisations. PMID:28112465

Real-time control of walking using recordings from dorsal root ganglia

NASA Astrophysics Data System (ADS)

Holinski, B. J.; Everaert, D. G.; Mushahwar, V. K.; Stein, R. B.

2013-10-01

Objective. The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach. In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the DRG. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modelled from recorded neural firing rates. These models were then used for closed-loop feedback. Main results. Overall, firing-rate-based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48 ± 13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance. Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development.

Real-time control of walking using recordings from dorsal root ganglia

PubMed Central

Holinski, B J; Everaert, D G; Mushahwar, V K; Stein, R B

2013-01-01

Objective The goal of this study was to decode sensory information from the dorsal root ganglia (DRG) in real time, and to use this information to adapt the control of unilateral stepping with a state-based control algorithm consisting of both feed-forward and feedback components. Approach In five anesthetized cats, hind limb stepping on a walkway or treadmill was produced by patterned electrical stimulation of the spinal cord through implanted microwire arrays, while neuronal activity was recorded from the dorsal root ganglia. Different parameters, including distance and tilt of the vector between hip and limb endpoint, integrated gyroscope and ground reaction force were modeled from recorded neural firing rates. These models were then used for closed-loop feedback. Main Results Overall, firing-rate based predictions of kinematic sensors (limb endpoint, integrated gyroscope) were the most accurate with variance accounted for >60% on average. Force prediction had the lowest prediction accuracy (48±13%) but produced the greatest percentage of successful rule activations (96.3%) for stepping under closed-loop feedback control. The prediction of all sensor modalities degraded over time, with the exception of tilt. Significance Sensory feedback from moving limbs would be a desirable component of any neuroprosthetic device designed to restore walking in people after a spinal cord injury. This study provides a proof-of-principle that real-time feedback from the DRG is possible and could form part of a fully implantable neuroprosthetic device with further development. PMID:23928579

Center-to-limb variation of intensity and polarization in continuum spectra of FGK stars for spherical atmospheres

NASA Astrophysics Data System (ADS)

Kostogryz, N. M.; Milic, I.; Berdyugina, S. V.; Hauschildt, P. H.

2016-02-01

Aims: One of the necessary parameters needed for the interpretation of the light curves of transiting exoplanets or eclipsing binary stars (as well as interferometric measurements of a star or microlensing events) is how the intensity and polarization of light changes from the center to the limb of a star. Scattering and absorption processes in the stellar atmosphere affect both the center-to-limb variation of intensity (CLVI) and polarization (CLVP). In this paper, we present a study of the CLVI and CLVP in continuum spectra, taking into consideration the different contributions of scattering and absorption opacity for a variety of spectral type stars with spherical atmospheres. Methods: We solve the radiative transfer equation for polarized light in the presence of a continuum scattering, taking into consideration the spherical model of a stellar atmosphere. To cross-check our results, we developed two independent codes that are based on Feautrier and short characteristics methods, respectively, Results: We calculate the center-to-limb variation of intensity (CLVI) and polarization (CLVP) in continuum for the Phoenix grid of spherical stellar model atmospheres for a range of effective temperatures (4000-7000 K), gravities (log g = 1.0-5.5), and wavelengths (4000-7000 Å), which are tabulated and available at the CDS. In addition, we present several tests of our codes and compare our calculations for the solar atmosphere with published photometric and polarimetric measurements. We also show that our two codes provide similar results in all considered cases. Conclusions: For sub-giant and dwarf stars (log g = 3.0-4.5), the lower gravity and lower effective temperature of a star lead to higher limb polarization of the star. For giant and supergiant stars (log g = 1.0-2.5), the highest effective temperature yields the largest polarization. By decreasing the effective temperature of a star down to 4500-5500 K (depending on log g), the limb polarization decreases and reaches a local minimum. It increases again with a corresponding decrease in temperature down to 4000 K. For the most compact dwarf stars (log g = 5.0-5.5), the limb polarization degree shows a maximum for models with effective temperatures in the range 4200-4600 K (depending on log g) and decreases toward higher and lower temperatures. The intensity and polarization profiles are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/586/A87

EFFECTS OF RETINOIC ACID AND ULTRAVIOLET RADIATION ON LIMB DEVELOPMENT IN ANURANS

EPA Science Inventory

Several recent studies suggest that the prevalence of limb abnormalities in North American anurans is elevated compared to historical records. These obsrvations have caused concern that environmental conditions are responsible for the increase through perturbation of normal limb ...

Upper Limb Posture Estimation in Robotic and Virtual Reality-Based Rehabilitation

PubMed Central

Cortés, Camilo; Ardanza, Aitor; Molina-Rueda, F.; Cuesta-Gómez, A.; Ruiz, Oscar E.

2014-01-01

New motor rehabilitation therapies include virtual reality (VR) and robotic technologies. In limb rehabilitation, limb posture is required to (1) provide a limb realistic representation in VR games and (2) assess the patient improvement. When exoskeleton devices are used in the therapy, the measurements of their joint angles cannot be directly used to represent the posture of the patient limb, since the human and exoskeleton kinematic models differ. In response to this shortcoming, we propose a method to estimate the posture of the human limb attached to the exoskeleton. We use the exoskeleton joint angles measurements and the constraints of the exoskeleton on the limb to estimate the human limb joints angles. This paper presents (a) the mathematical formulation and solution to the problem, (b) the implementation of the proposed solution on a commercial exoskeleton system for the upper limb rehabilitation, (c) its integration into a rehabilitation VR game platform, and (d) the quantitative assessment of the method during elbow and wrist analytic training. Results show that this method properly estimates the limb posture to (i) animate avatars that represent the patient in VR games and (ii) obtain kinematic data for the patient assessment during elbow and wrist analytic rehabilitation. PMID:25110698

Subcutaneous Crotaline Fab antivenom for the treatment of rattlesnake envenomation in a porcine model.

PubMed

Offerman, Steven R; Barry, J David; Richardson, William H; Tong, Tri; Tanen, Dave; Bush, Sean P; Clark, Richard F

2009-01-01

This study was designed to investigate whether the local, subcutaneous injection of Crotaline Fab antivenom (CroFab) at the rattlesnake envenomation site would result in less extremity edema when compared to intravenous (i.v.) antivenom infusion alone. This is a randomized, three-arm laboratory experiment using a porcine model. Each animal was anesthetized, intubated, and maintained on mechanical ventilation. About 6 mg/kg of Crotalus atrox venom was injected subcutaneously at the hock of the right hind leg. Animals were then randomized to immediately receive subcutaneous and i.v. antivenom (SC/IV), i.v. antivenom only, or saline control. SC/IV animals received two vials of CroFab subcutaneously at the envenomation site and two vials intravenously. IV animals received four vials of CroFab intravenously. Limb edema was tracked by serial circumference and volumetric measurements over an 8-h period. Limb circumference was measured at four pre-determined locations hourly. Limb volume was measured by a water displacement method at baseline, 4, and 8 h. Twenty-six animals were randomized to the three treatment groups. The SC/IV and IV arms included nine animals each. Two animals in the SC/IV group died suddenly during the study, leaving seven animals for data analysis. There were eight controls. Increasing limb edema was observed in all groups. No differences were detected in limb circumferences or limb volumes between control and either treatment arms. In this porcine model of crotaline envenomation, no differences in limb edema were found between animals treated with SC/IV or IV CroFab when compared to saline controls.

Gait and Lower Limb Observation of Paediatrics (GALLOP): development of a consensus based paediatric podiatry and physiotherapy standardised recording proforma.

PubMed

Cranage, Simone; Banwell, Helen; Williams, Cylie M

2016-01-01

Paediatric gait and lower limb assessments are frequently undertaken in podiatry and physiotherapy clinical practice and this is a growing area of expertise within Australia. No concise paediatric standardised recording proforma exists to assist clinicians in clinical practice. The aim of this study was to develop a gait and lower limb standardised recording proforma guided by the literature and consensus, for assessment of the paediatric foot and lower limb in children aged 0-18 years. Expert Australian podiatrists and physiotherapists were invited to participate in a three round Delphi survey panel using the online Qualtrics(©) survey platform. The first round of the survey consisted of open-ended questions on paediatric gait and lower limb assessment developed from existing templates and a literature search of standardised lower limb assessment methods. Rounds two and three consisted of statements developed from the first round responses. Questions and statements were included in the final proforma if 70 % or more of the participants indicated consensus or agreement with the assessment method and if there was support within the literature for paediatric age-specific normative data with acceptable reliability of outcome measures. There were 17 of the 21 (81 %) participants who completed three rounds of the survey. Consensus was achieved for 41 statements in Round one, 54 statements achieved agreement in two subsequent rounds. Participants agreed on 95 statements relating to birth history, developmental history, hip measurement, rotation of the lower limb, ankle range of motion, foot posture, balance and gait. Assessments with acceptable validity and reliability were included within the final Gait and Lower Limb Observation of Paediatrics (GALLOP) proforma. The GALLOP proforma is a consensus based, systematic and standardised way to collect information and outcome measures in paediatric lower limb assessment. This standardised recording proforma will assist professions to collect information in a standardised format based on best evidence assessment methods whilst aiding consistency in communication between health professionals.

Measurement properties and usability of non-contact scanners for measuring transtibial residual limb volume.

PubMed

Kofman, Rianne; Beekman, Anna M; Emmelot, Cornelis H; Geertzen, Jan H B; Dijkstra, Pieter U

2018-06-01

Non-contact scanners may have potential for measurement of residual limb volume. Different non-contact scanners have been introduced during the last decades. Reliability and usability (practicality and user friendliness) should be assessed before introducing these systems in clinical practice. The aim of this study was to analyze the measurement properties and usability of four non-contact scanners (TT Design, Omega Scanner, BioSculptor Bioscanner, and Rodin4D Scanner). Quasi experimental. Nine (geometric and residual limb) models were measured on two occasions, each consisting of two sessions, thus in total 4 sessions. In each session, four observers used the four systems for volume measurement. Mean for each model, repeatability coefficients for each system, variance components, and their two-way interactions of measurement conditions were calculated. User satisfaction was evaluated with the Post-Study System Usability Questionnaire. Systematic differences between the systems were found in volume measurements. Most of the variances were explained by the model (97%), while error variance was 3%. Measurement system and the interaction between system and model explained 44% of the error variance. Repeatability coefficient of the systems ranged from 0.101 (Omega Scanner) to 0.131 L (Rodin4D). Differences in Post-Study System Usability Questionnaire scores between the systems were small and not significant. The systems were reliable in determining residual limb volume. Measurement systems and the interaction between system and residual limb model explained most of the error variances. The differences in repeatability coefficient and usability between the four CAD/CAM systems were small. Clinical relevance If accurate measurements of residual limb volume are required (in case of research), modern non-contact scanners should be taken in consideration nowadays.

Conditional inactivation of Has2 reveals a crucial role for hyaluronan in skeletal growth, patterning, chondrocyte maturation and joint formation in the developing limb

PubMed Central

Matsumoto, Kazu; Li, Yingcui; Jakuba, Caroline; Sugiyama, Yoshinori; Sayo, Tetsuya; Okuno, Misako; Dealy, Caroline N.; Toole, Bryan P.; Takeda, Junji; Yamaguchi, Yu; Kosher, Robert A.

2009-01-01

Summary The glycosaminoglycan hyaluronan (HA) is a structural component of extracellular matrices and also interacts with cell surface receptors to directly influence cell behavior. To explore functions of HA in limb skeletal development, we conditionally inactivated the gene for HA synthase 2, Has2, in limb bud mesoderm using mice that harbor a floxed allele of Has2 and mice carrying a limb mesoderm-specific Prx1-Cre transgene. The skeletal elements of Has2-deficient limbs are severely shortened, indicating that HA is essential for normal longitudinal growth of all limb skeletal elements. Proximal phalanges are duplicated in Has2 mutant limbs indicating an involvement of HA in patterning specific portions of the digits. The growth plates of Has2-deficient skeletal elements are severely abnormal and disorganized, with a decrease in the deposition of aggrecan in the matrix and a disruption in normal columnar cellular relationships. Furthermore, there is a striking reduction in the number of hypertrophic chondrocytes and in the expression domains of markers of hypertrophic differentiation in the mutant growth plates, indicating that HA is necessary for the normal progression of chondrocyte maturation. In addition, secondary ossification centers do not form in the central regions of Has2 mutant growth plates owing to a failure of hypertrophic differentiation. In addition to skeletal defects, the formation of synovial joint cavities is defective in Has2-deficient limbs. Taken together, our results demonstrate that HA has a crucial role in skeletal growth, patterning, chondrocyte maturation and synovial joint formation in the developing limb. PMID:19633173

A novel model to assess lamellar signaling relevant to preferential weight bearing in the horse.

PubMed

Gardner, A K; van Eps, A W; Watts, M R; Burns, T A; Belknap, J K

2017-03-01

Supporting limb laminitis (SLL) is a devastating sequela to severe unilateral lameness in equine patients. The manifestation of SLL, which usually only affects one limb, is unpredictable and the etiology is unknown. A novel, non-painful preferential weight bearing model designed to mimic the effects of severe unilateral forelimb lameness was developed to assess lamellar signaling events in the supporting limb (SL). A custom v-shaped insert was attached to the shoe of one forelimb to prevent normal weight bearing and redistribute weight onto the SL. Testing of the insert using a custom scale platform built into the floor of stocks confirmed increased distribution of weight on the SL compared with the unloaded forelimb (UL) and the contralateral (CH) and ipsilateral (IH) hind limbs in six Standardbred horses. In a second part of the study, eight healthy Standardbred horses were fitted with the insert and tied with consistent monitoring and free access to hay and water for 48 h, after which the lamellae were harvested. Real-time qPCR was performed to assess lamellar mRNA concentrations of inflammatory genes and immunoblotting and immunofluorescence were performed to assess lamellar protein concentration and cellular localization of hypoxia-related proteins, respectively. Lamellar mRNA concentrations of inflammatory signaling proteins did not differ between SL and either CH or IH samples. HIF-1α concentrations were greater (P < 0.05) in the SL compared to the CH. This work establishes an experimental model to study preferential weight bearing and initial results suggest that lamellar hypoxia may occur in the SL. Copyright © 2017. Published by Elsevier Ltd.

batman: BAsic Transit Model cAlculatioN in Python

NASA Astrophysics Data System (ADS)

Kreidberg, Laura

2015-10-01

batman provides fast calculation of exoplanet transit light curves and supports calculation of light curves for any radially symmetric stellar limb darkening law. It uses an integration algorithm for models that cannot be quickly calculated analytically, and in typical use, the batman Python package can calculate a million model light curves in well under ten minutes for any limb darkening profile.

The origin of mean arterial and jugular venous blood pressures in giraffes.

PubMed

Mitchell, Graham; Maloney, Shane K; Mitchell, Duncan; Keegan, D James

2006-07-01

Using a mechanical model of the giraffe neck and head circulation consisting of a rigid, ascending, 'carotid' limb, a 'cranial' circulation that could be rigid or collapsible, and a descending, 'jugular' limb that also could be rigid or collapsible, we have analyzed the origin of the high arterial and venous pressures in giraffe, and whether blood flow is assisted by a siphon. When the tubes were rigid and the 'jugular' limb exit was lower than the 'carotid' limb entrance a siphon operated, 'carotid' hydrostatic pressures became more negative, and flow was 3.3 l min(-1) but ceased when the 'cranial' and 'jugular' limbs were collapsible or when the 'jugular' limb was opened to the atmosphere. Pumping water through the model produced positive pressures in the 'carotid' limb similar to those found in giraffe. Applying an external 'tissue' pressure to the 'jugular' tube during pump flow produced the typical pressures found in the jugular vein in giraffe. Constriction of the lowest, 'jugular cuff', portion of the 'jugular' limb showed that the cuff may augment the orthostatic reflex during head raising. Except when all tubes were rigid, pressures were unaffected by a siphon. We conclude that mean arterial blood pressure in giraffes is a consequence of the hydrostatic pressure generated by the column of blood in the neck, that tissue pressure around the collapsible jugular vein produces the known jugular pressures, and that a siphon does not assist flow through the cranial circulation.

Energetic benefits and adaptations in mammalian limbs: Scale effects and selective pressures.

PubMed

Kilbourne, Brandon M; Hoffman, Louwrens C

2015-06-01

Differences in limb size and shape are fundamental to mammalian morphological diversity; however, their relevance to locomotor costs has long been subject to debate. In particular, it remains unknown if scale effects in whole limb morphology could partially underlie decreasing mass-specific locomotor costs with increasing limb length. Whole fore- and hindlimb inertial properties reflecting limb size and shape-moment of inertia (MOI), mass, mass distribution, and natural frequency-were regressed against limb length for 44 species of quadrupedal mammals. Limb mass, MOI, and center of mass position are negatively allometric, having a strong potential for lowering mass-specific locomotor costs in large terrestrial mammals. Negative allometry of limb MOI results in a 40% reduction in MOI relative to isometry's prediction for our largest sampled taxa. However, fitting regression residuals to adaptive diversification models reveals that codiversification of limb mass, limb length, and body mass likely results from selection for differing locomotor modes of running, climbing, digging, and swimming. The observed allometric scaling does not result from selection for energetically beneficial whole limb morphology with increasing size. Instead, our data suggest that it is a consequence of differing morphological adaptations and body size distributions among quadrupedal mammals, highlighting the role of differing limb functions in mammalian evolution. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

EMG-Based Estimation of Limb Movement Using Deep Learning With Recurrent Convolutional Neural Networks.

PubMed

Xia, Peng; Hu, Jie; Peng, Yinghong

2017-10-25

A novel model based on deep learning is proposed to estimate kinematic information for myoelectric control from multi-channel electromyogram (EMG) signals. The neural information of limb movement is embedded in EMG signals that are influenced by all kinds of factors. In order to overcome the negative effects of variability in signals, the proposed model employs the deep architecture combining convolutional neural networks (CNNs) and recurrent neural networks (RNNs). The EMG signals are transformed to time-frequency frames as the input to the model. The limb movement is estimated by the model that is trained with the gradient descent and backpropagation procedure. We tested the model for simultaneous and proportional estimation of limb movement in eight healthy subjects and compared it with support vector regression (SVR) and CNNs on the same data set. The experimental studies show that the proposed model has higher estimation accuracy and better robustness with respect to time. The combination of CNNs and RNNs can improve the model performance compared with using CNNs alone. The model of deep architecture is promising in EMG decoding and optimization of network structures can increase the accuracy and robustness. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Dimeric combinations of MafB, cFos and cJun control the apoptosis-survival balance in limb morphogenesis.

PubMed

Suda, Natsuno; Itoh, Takehiko; Nakato, Ryuichiro; Shirakawa, Daisuke; Bando, Masashige; Katou, Yuki; Kataoka, Kohsuke; Shirahige, Katsuhiko; Tickle, Cheryll; Tanaka, Mikiko

2014-07-01

Apoptosis is an important mechanism for sculpting morphology. However, the molecular cascades that control apoptosis in developing limb buds remain largely unclear. Here, we show that MafB was specifically expressed in apoptotic regions of chick limb buds, and MafB/cFos heterodimers repressed apoptosis, whereas MafB/cJun heterodimers promoted apoptosis for sculpting the shape of the limbs. Chromatin immunoprecipitation sequencing in chick limb buds identified potential target genes and regulatory elements controlled by Maf and Jun. Functional analyses revealed that expression of p63 and p73, key components known to arrest the cell cycle, was directly activated by MafB and cJun. Our data suggest that dimeric combinations of MafB, cFos and cJun in developing chick limb buds control the number of apoptotic cells, and that MafB/cJun heterodimers lead to apoptosis via activation of p63 and p73. © 2014. Published by The Company of Biologists Ltd.

Revised upper limb module for spinal muscular atrophy: Development of a new module.

PubMed

Mazzone, Elena S; Mayhew, Anna; Montes, Jacqueline; Ramsey, Danielle; Fanelli, Lavinia; Young, Sally Dunaway; Salazar, Rachel; De Sanctis, Roberto; Pasternak, Amy; Glanzman, Allan; Coratti, Giorgia; Civitello, Matthew; Forcina, Nicola; Gee, Richard; Duong, Tina; Pane, Marika; Scoto, Mariacristina; Pera, Maria Carmela; Messina, Sonia; Tennekoon, Gihan; Day, John W; Darras, Basil T; De Vivo, Darryl C; Finkel, Richard; Muntoni, Francesco; Mercuri, Eugenio

2017-06-01

There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients. An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale. Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups. The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. Muscle Nerve 55: 869-874, 2017. © 2016 Wiley Periodicals, Inc.

HAND2 Targets Define a Network of Transcriptional Regulators that Compartmentalize the Early Limb Bud Mesenchyme

DOE PAGES

Osterwalder, Marco; Speziale, Dario; Shoukry, Malak; ...

2014-11-10

The genetic networks that govern vertebrate development are well studied, but how the interactions of trans-acting factors with cis-regulatory modules (CRMs) are integrated into spatiotemporal regulation of gene expression is not clear. The transcriptional regulator HAND2 is required during limb, heart, and branchial arch development. Here, we identify the genomic regions enriched in HAND2 chromatin complexes from mouse embryos and limb buds. Then we analyze the HAND2 target CRMs in the genomic landscapes encoding transcriptional regulators required in early limb buds. HAND2 controls the expression of genes functioning in the proximal limb bud and orchestrates the establishment of anterior andmore » posterior polarity of the nascent limb bud mesenchyme by impacting Gli3 and Tbx3 expression. TBX3 is required downstream of HAND2 to refine the posterior Gli3 expression boundary. In conclusion, our analysis uncovers the transcriptional circuits that function in establishing distinct mesenchymal compartments downstream of HAND2 and upstream of SHH signaling.« less

Inverse biomimetics: how robots can help to verify concepts concerning sensorimotor control of human arm and leg movements.

PubMed

Kalveram, Karl Theodor; Seyfarth, André

2009-01-01

Simulation test, hardware test and behavioral comparison test are proposed to experimentally verify whether a technical control concept for limb movements is logically precise, physically sound, and biologically relevant. Thereby, robot test-beds may play an integral part by mimicking functional limb movements. The procedure is exemplarily demonstrated for human aiming movements with the forearm: when comparing competitive control concepts, these movements are described best by a spring-like operating muscular-skeletal device which is assisted by feedforward control through an inverse internal model of the limb--without regress to a forward model of the limb. In a perspective on hopping, the concept of exploitive control is addressed, and its comparison to concepts derived from classical control theory advised.

Simulating Limb Formation in the U.S. EPA Virtual Embryo - Risk Assessment Project

EPA Science Inventory

The U.S. EPA’s Virtual Embryo project (v-Embryo™) is a computer model simulation of morphogenesis that integrates cell and molecular level data from mechanistic and in vitro assays with knowledge about normal development processes to assess in silico the effects of chemicals on d...

Conserved regulation of mesenchymal gene expression by Fgf-8 in face and limb development.

PubMed

Tucker, A S; Al Khamis, A; Ferguson, C A; Bach, I; Rosenfeld, M G; Sharpe, P T

1999-01-01

Clim-2 (NLI, Lbd1) is one of two related mouse proteins that interact with Lim-domain homeoproteins. In the mouse, embryonic expression of Clim-2 is particularly pronounced in facial ectomesenchyme and limb bud mesenchyme in association with Lim genes, Lhx-6 and Lmx-1 respectively. We show that in common with both these Lim genes, Clim-2 expression is regulated by signals from overlying epithelium. In both the developing face and the limb buds we identify Fgf-8 as the likely candidate signalling molecule that regulates Clim-2 expression. We show that in the mandibular arch, as in the limb, Fgf-8 functions in combination with CD44, a cell surface binding protein, and that blocking CD44 binding results in inhibition of Fgf8-induced expression of Clim-2 and Lhx-6. Regulation of gene expression by Fgf8 in association with CD44 is thus conserved between limb and mandibular arch development.

Phosphorus Export Model Development in a Terminal Lake Basin using Concentration-Streamflow Relationship

NASA Astrophysics Data System (ADS)

Jeannotte, T.; Mahmood, T. H.; Matheney, R.; Hou, X.

2017-12-01

Nutrient export to streams and lakes by anthropogenic activities can lead to eutrophication and degradation of surface water quality. In Devils Lake, ND, the only terminal lake in the Northern Great Plains, the algae boom is of great concern due to the recent increase in streamflow and consequent rise in phosphorus (P) export from prairie agricultural fields. However, to date, very few studies explored the concentration (c) -streamflow (q) relationship in the headwater catchments of the Devils Lake basin. A robust watershed-scale quantitative framework would aid understanding of the c-q relationship, simulating P concentration and load. In this study, we utilize c-q relationships to develop a simple model to estimate phosphorus concentration and export from two headwater catchments of different size (Mauvais Coulee: 1032 km2 and Trib 3: 160 km2) draining to Devils Lake. Our goal is to link the phosphorus export model with a physically based hydrologic model to identify major drivers of phosphorus export. USGS provided the streamflow measurements, and we collected water samples (filtered and unfiltered) three times daily during the spring snowmelt season (March 31, 2017- April 12, 2017) at the outlets of both headwater catchments. Our results indicate that most P is dissolved and very little is particulate, suggesting little export of fine-grained sediment from agricultural fields. Our preliminary analyses in the Mauvais Coulee catchment show a chemostatic c-q relationship in the rising limb of the hydrograph, while the recession limb shows a linear and positive c-q relationship. The poor correlation in the rising limb of the hydrograph suggests intense flushing of P by spring snowmelt runoff. Flushing then continues in the recession limb of the hydrograph, but at a more constant rate. The estimated total P load for the Mauvais Coulee basin is 193 kg/km2, consistent with other catchments of similar size across the Red River of the North basin to the east. We expect our P measurements at Trib 3 basin, a considerably smaller basin compared to Mauvais Coulee, provide an opportunity to investigate the impacts of watershed scales on nutrient exports and c-q relationship. Finally, our study will lay a strong foundation for future nutrient modeling studies in the Devils Lake basin.

Reactivation of larval keratin gene (krt62.L) in blastema epithelium during Xenopus froglet limb regeneration.

PubMed

Satoh, Akira; Mitogawa, Kazumasa; Saito, Nanami; Suzuki, Miyuki; Suzuki, Ken-Ichi T; Ochi, Haruki; Makanae, Aki

2017-12-15

Limb regeneration is considered a form of limb redevelopment because of the molecular and morphological similarities. Forming a regeneration blastema is, in essence, creating a developing limb bud in an adult body. This reactivation of a developmental process in a mature body is worth studying. Xenopus laevis has a biphasic life cycle that involves distinct larval and adult stages. These distinct developmental stages are useful for investigating the reactivation of developmental processes in post-metamorphic frogs (froglets). In this study, we focused on the re-expression of a larval gene (krt62.L) during Xenopus froglet limb regeneration. Recently renamed krt62.L, this gene was known as the larval keratin (xlk) gene, which is specific to larval-tadpole stages. During limb regeneration in a froglet, krt62.L was re-expressed in a basal layer of blastema epithelium, where adult-specific keratin (Krt12.6.S) expression was also observable. Nerves produce important regulatory factors for amphibian limb regeneration, and also play a role in blastema formation and maintenance. The effect of nerve function on krt62.L expression could be seen in the maintenance of krt62.L expression, but not in its induction. When an epidermis-stripped limb bud was grafted in a froglet blastema, the grafted limb bud could reach the digit-forming stage. This suggests that krt62.L-positive froglet blastema epithelium is able to support the limb development process. These findings imply that the developmental process is locally reactivated in an postmetamorphic body during limb regeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

BMP-Mediated Functional Cooperation between Dlx5;Dlx6 and Msx1;Msx2 during Mammalian Limb Development

PubMed Central

Vieux-Rochas, Maxence; Bouhali, Kamal; Mantero, Stefano; Garaffo, Giulia; Provero, Paolo; Astigiano, Simonetta; Barbieri, Ottavia; Caratozzolo, Mariano F.; Tullo, Apollonia; Guerrini, Luisa; Lallemand, Yvan; Robert, Benoît

2013-01-01

The Dlx and Msx homeodomain transcription factors play important roles in the control of limb development. The combined disruption of Msx1 and Msx2, as well as that of Dlx5 and Dlx6, lead to limb patterning defects with anomalies in digit number and shape. Msx1;Msx2 double mutants are characterized by the loss of derivatives of the anterior limb mesoderm which is not observed in either of the simple mutants. Dlx5;Dlx6 double mutants exhibit hindlimb ectrodactyly. While the morphogenetic action of Msx genes seems to involve the BMP molecules, the mode of action of Dlx genes still remains elusive. Here, examining the limb phenotypes of combined Dlx and Msx mutants we reveal a new Dlx-Msx regulatory loop directly involving BMPs. In Msx1;Dlx5;Dlx6 triple mutant mice (TKO), beside the expected ectrodactyly, we also observe the hallmark morphological anomalies of Msx1;Msx2 double mutants suggesting an epistatic role of Dlx5 and Dlx6 over Msx2. In Msx2;Dlx5;Dlx6 TKO mice we only observe an aggravation of the ectrodactyly defect without changes in the number of the individual components of the limb. Using a combination of qPCR, ChIP and bioinformatic analyses, we identify two Dlx/Msx regulatory pathways: 1) in the anterior limb mesoderm a non-cell autonomous Msx-Dlx regulatory loop involves BMP molecules through the AER and 2) in AER cells and, at later stages, in the limb mesoderm the regulation of Msx2 by Dlx5 and Dlx6 occurs also cell autonomously. These data bring new elements to decipher the complex AER-mesoderm dialogue that takes place during limb development and provide clues to understanding the etiology of congenital limb malformations. PMID:23382810

BMP-mediated functional cooperation between Dlx5;Dlx6 and Msx1;Msx2 during mammalian limb development.

PubMed

Vieux-Rochas, Maxence; Bouhali, Kamal; Mantero, Stefano; Garaffo, Giulia; Provero, Paolo; Astigiano, Simonetta; Barbieri, Ottavia; Caratozzolo, Mariano F; Tullo, Apollonia; Guerrini, Luisa; Lallemand, Yvan; Robert, Benoît; Levi, Giovanni; Merlo, Giorgio R

2013-01-01

The Dlx and Msx homeodomain transcription factors play important roles in the control of limb development. The combined disruption of Msx1 and Msx2, as well as that of Dlx5 and Dlx6, lead to limb patterning defects with anomalies in digit number and shape. Msx1;Msx2 double mutants are characterized by the loss of derivatives of the anterior limb mesoderm which is not observed in either of the simple mutants. Dlx5;Dlx6 double mutants exhibit hindlimb ectrodactyly. While the morphogenetic action of Msx genes seems to involve the BMP molecules, the mode of action of Dlx genes still remains elusive. Here, examining the limb phenotypes of combined Dlx and Msx mutants we reveal a new Dlx-Msx regulatory loop directly involving BMPs. In Msx1;Dlx5;Dlx6 triple mutant mice (TKO), beside the expected ectrodactyly, we also observe the hallmark morphological anomalies of Msx1;Msx2 double mutants suggesting an epistatic role of Dlx5 and Dlx6 over Msx2. In Msx2;Dlx5;Dlx6 TKO mice we only observe an aggravation of the ectrodactyly defect without changes in the number of the individual components of the limb. Using a combination of qPCR, ChIP and bioinformatic analyses, we identify two Dlx/Msx regulatory pathways: 1) in the anterior limb mesoderm a non-cell autonomous Msx-Dlx regulatory loop involves BMP molecules through the AER and 2) in AER cells and, at later stages, in the limb mesoderm the regulation of Msx2 by Dlx5 and Dlx6 occurs also cell autonomously. These data bring new elements to decipher the complex AER-mesoderm dialogue that takes place during limb development and provide clues to understanding the etiology of congenital limb malformations.

A kinematic model to assess spinal motion during walking.

PubMed

Konz, Regina J; Fatone, Stefania; Stine, Rebecca L; Ganju, Aruna; Gard, Steven A; Ondra, Stephen L

2006-11-15

A 3-dimensional multi-segment kinematic spine model was developed for noninvasive analysis of spinal motion during walking. Preliminary data from able-bodied ambulators were collected and analyzed using the model. Neither the spine's role during walking nor the effect of surgical spinal stabilization on gait is fully understood. Typically, gait analysis models disregard the spine entirely or regard it as a single rigid structure. Data on regional spinal movements, in conjunction with lower limb data, associated with walking are scarce. KinTrak software (Motion Analysis Corp., Santa Rosa, CA) was used to create a biomechanical model for analysis of 3-dimensional regional spinal movements. Measuring known angles from a mechanical model and comparing them to the calculated angles validated the kinematic model. Spine motion data were collected from 10 able-bodied adults walking at 5 self-selected speeds. These results were compared to data reported in the literature. The uniaxial angles measured on the mechanical model were within 5 degrees of the calculated kinematic model angles, and the coupled angles were within 2 degrees. Regional spine kinematics from able-bodied subjects calculated with this model compared well to data reported by other authors. A multi-segment kinematic spine model has been developed and validated for analysis of spinal motion during walking. By understanding the spine's role during ambulation and the cause-and-effect relationship between spine motion and lower limb motion, preoperative planning may be augmented to restore normal alignment and balance with minimal negative effects on walking.

Do Different Young Plantation-Grown Species Require Different Biomass Models?

Treesearch

Bryce E. Schlaegel; Harvey E. Kennedy

1985-01-01

Sweetgum and water oak trees sampled from a plantation over 7 years were used to test whether primary tree component (bole wood, bole bark, limb wood, limb bark, and leaves) predictions could be summed to estimate total bole, total limb, and total tree values. Estimations by summing primary component predictions were not significantly different from predictions for the...

Relating ranging ecology, limb length, and locomotor economy in terrestrial animals.

PubMed

Pontzer, Herman

2012-03-07

Ecomorphological analyses have identified a number of important evolutionary trends in vertebrate limb design, but the relationships between daily travel distance, locomotor ecology, and limb length in terrestrial animals remain poorly understood. In this paper I model the net rate of energy intake as a function of foraging efficiency, and thus of locomotor economy; improved economy leads to greater net energy intake. However, the relationship between locomotor economy and net intake is highly dependent on foraging efficiency; only species with low foraging efficiencies experience strong selection pressure for improved locomotor economy and increased limb length. Examining 237 terrestrial species, I find that nearly all taxa obtain sufficiently high foraging efficiencies that selection for further increases in economy is weak. Thus selection pressures for increased economy and limb length among living terrestrial animals may be relatively weak and similar in magnitude across ecologically diverse species. The Economy Selection Pressure model for locomotor economy may be useful in investigating the evolution of limb design in early terrestrial taxa and the coevolution of foraging ecology and locomotor anatomy in lineages with low foraging efficiencies. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

PubMed

Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

2017-01-01

Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

Risk factors of the upper limb disorders among cashiers in grocery retail industries: A review

NASA Astrophysics Data System (ADS)

Zuhaidi, Muhammad Fareez Ahmad; Nasrull Abdol Rahman, Mohd

2017-08-01

Cashiers have been appointed as one of top ten occupations in developing musculoskeletal disorders (MSDs) particularly on the upper limb. Many of the workers are still in high risk injury due to incorrect workstations and lack of employee education in basic biomechanical principles. Normally, cashiers are exposed in several risk factors such as awkward and static postures, repetition motion and forceful exertions. Thus, cashiers in supermarket are considered at risk from developing upper limb disorders (ULDs). This review evaluates selected papers that have studied risk factors of the upper limb disorders among cashiers in grocery retail industries. In addition, other studies from related industry were reviewed as applicable. In order to understand risk factors of the upper limb disorders among cashiers, it is recommended that future studies are needed in evaluating these risk factors among cashiers.

EFFECTS OF ETHANOL AND HYDROGEN PEROXIDE ON MOUSE LIMB BUD MESENCHYME DIFFERENTIATION AND CELL DEATH

EPA Science Inventory

Many of the morphological defects associated with embryonic alcohol exposure are a result of cell death. During limb development, ethanol administration produces cell death in the limb and digital defects, including postaxial ectrodactyly. Because an accumulation of reactive oxyg...

Limb replantation with two robots: a feasibility study in a pig model.

PubMed

Taleb, Chihab; Nectoux, Eric; Liverneaux, Philippe

2009-01-01

The aim of this study is to assess the feasibility of limb replantations and transplantations by telesurgery. The material consisted in a large white pig and two surgical robots (DaVinciS telemanipulators). The procedure consisted in a trans-humeral cross-section of the left thoracic limb, which was secondarily replanted. Results showed good vascular permeability, while the operator's physiological tremor was suppressed. Our results seem to demonstrate that telesurgery could improve limb replantation and transplantation management, especially regarding operating gesture precision. (c) 2009 Wiley-Liss, Inc.

Lineage tracing of genome-edited alleles reveals high fidelity axolotl limb regeneration.

PubMed

Flowers, Grant Parker; Sanor, Lucas D; Crews, Craig M

2017-09-16

Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs. This allowed us, for the first time, to assess the contributions of multiple low frequency cell lineages to the regenerating limb at once. Our comparisons reveal that regenerated limbs are high fidelity replicas of the originals even after repeated amputations.

Robotics in Lower-Limb Rehabilitation after Stroke

PubMed Central

2017-01-01

With the increase in the elderly, stroke has become a common disease, often leading to motor dysfunction and even permanent disability. Lower-limb rehabilitation robots can help patients to carry out reasonable and effective training to improve the motor function of paralyzed extremity. In this paper, the developments of lower-limb rehabilitation robots in the past decades are reviewed. Specifically, we provide a classification, a comparison, and a design overview of the driving modes, training paradigm, and control strategy of the lower-limb rehabilitation robots in the reviewed literature. A brief review on the gait detection technology of lower-limb rehabilitation robots is also presented. Finally, we discuss the future directions of the lower-limb rehabilitation robots. PMID:28659660

Robotics in Lower-Limb Rehabilitation after Stroke.

PubMed

Zhang, Xue; Yue, Zan; Wang, Jing

2017-01-01

With the increase in the elderly, stroke has become a common disease, often leading to motor dysfunction and even permanent disability. Lower-limb rehabilitation robots can help patients to carry out reasonable and effective training to improve the motor function of paralyzed extremity. In this paper, the developments of lower-limb rehabilitation robots in the past decades are reviewed. Specifically, we provide a classification, a comparison, and a design overview of the driving modes, training paradigm, and control strategy of the lower-limb rehabilitation robots in the reviewed literature. A brief review on the gait detection technology of lower-limb rehabilitation robots is also presented. Finally, we discuss the future directions of the lower-limb rehabilitation robots.

Two-dimensional radiative transfer for the retrieval of limb emission measurements in the martian atmosphere

NASA Astrophysics Data System (ADS)

Kleinböhl, Armin; Friedson, A. James; Schofield, John T.

2017-01-01

The remote sounding of infrared emission from planetary atmospheres using limb-viewing geometry is a powerful technique for deriving vertical profiles of structure and composition on a global scale. Compared with nadir viewing, limb geometry provides enhanced vertical resolution and greater sensitivity to atmospheric constituents. However, standard limb profile retrieval techniques assume spherical symmetry and are vulnerable to biases produced by horizontal gradients in atmospheric parameters. We present a scheme for the correction of horizontal gradients in profile retrievals from limb observations of the martian atmosphere. It characterizes horizontal gradients in temperature, pressure, and aerosol extinction along the line-of-sight of a limb view through neighboring measurements, and represents these gradients by means of two-dimensional radiative transfer in the forward model of the retrieval. The scheme is applied to limb emission measurements from the Mars Climate Sounder instrument on Mars Reconnaissance Orbiter. Retrieval simulations using data from numerical models indicate that biases of up to 10 K in the winter polar region, obtained with standard retrievals using spherical symmetry, are reduced to about 2 K in most locations by the retrieval with two-dimensional radiative transfer. Retrievals from Mars atmospheric measurements suggest that the two-dimensional radiative transfer greatly reduces biases in temperature and aerosol opacity caused by observational geometry, predominantly in the polar winter regions.

Transient Inhibition of FGFR2b-Ligands Signaling Leads to Irreversible Loss of Cellular β-Catenin Organization and Signaling in AER during Mouse Limb Development

PubMed Central

Tabatabai, Reza; Baptista, Sheryl; Tiozzo, Caterina; Carraro, Gianni; Wheeler, Matthew; Barreto, Guillermo; Braun, Thomas; Li, Xiaokun; Hajihosseini, Mohammad K.; Bellusci, Saverio

2013-01-01

The vertebrate limbs develop through coordinated series of inductive, growth and patterning events. Fibroblast Growth Factor receptor 2b (FGFR2b) signaling controls the induction of the Apical Ectodermal Ridge (AER) but its putative roles in limb outgrowth and patterning, as well as in AER morphology and cell behavior have remained unclear. We have investigated these roles through graded and reversible expression of soluble dominant-negative FGFR2b molecules at various times during mouse limb development, using a doxycycline/transactivator/tet(O)-responsive system. Transient attenuation (≤24 hours) of FGFR2b-ligands signaling at E8.5, prior to limb bud induction, leads mostly to the loss or truncation of proximal skeletal elements with less severe impact on distal elements. Attenuation from E9.5 onwards, however, has an irreversible effect on the stability of the AER, resulting in a progressive loss of distal limb skeletal elements. The primary consequences of FGFR2b-ligands attenuation is a transient loss of cell adhesion and down-regulation of P63, β1-integrin and E-cadherin, and a permanent loss of cellular β-catenin organization and WNT signaling within the AER. Combined, these effects lead to the progressive transformation of the AER cells from pluristratified to squamous epithelial-like cells within 24 hours of doxycycline administration. These findings show that FGFR2b-ligands signaling has critical stage-specific roles in maintaining the AER during limb development. PMID:24167544

Motor control and learning with lower-limb myoelectric control in amputees.

PubMed

Alcaide-Aguirre, Ramses E; Morgenroth, David C; Ferris, Daniel P

2013-01-01

Advances in robotic technology have recently enabled the development of powered lower-limb prosthetic limbs. A major hurdle in developing commercially successful powered prostheses is the control interface. Myoelectric signals are one way for prosthetic users to provide feedforward volitional control of prosthesis mechanics. The goal of this study was to assess motor learning in people with lower-limb amputation using proportional myoelectric control from residual-limb muscles. We examined individuals with transtibial amputation and nondisabled controls performing tracking tasks of a virtual object. We assessed how quickly the individuals with amputation improved their performance and whether years since amputation correlated with performance. At the beginning of training, subjects with amputation performed much worse than control subjects. By the end of a short training period, tracking error did not significantly differ between subjects with amputation and nondisabled subjects. Initial but not final performance correlated significantly with time since amputation. This study demonstrates that although subjects with amputation may initially have poor volitional control of their residual lower-limb muscles, training can substantially improve their volitional control. These findings are encouraging for the future use of proportional myoelectric control of powered lower-limb prostheses.

Dynamic gene expression of Lin-28 during embryonic development in mouse and chicken.

PubMed

Yokoyama, Shigetoshi; Hashimoto, Megumi; Shimizu, Hirohito; Ueno-Kudoh, Hiroe; Uchibe, Kenta; Kimura, Ichiro; Asahara, Hiroshi

2008-02-01

The Caenorhabditis elegans heterochronic gene lin-28 regulates developmental timing in the nematode trunk. We report the dynamic expression patterns of Lin-28 homologues in mouse and chick embryos. Whole mount in situ hybridization revealed specific and intriguing expression patterns of Lin-28 in the developing mouse and chick limb bud. Mouse Lin-28 expression was detected in both the forelimb and hindlimb at E9.5, but disappeared from the forelimb at E10.5, and finally from the forelimb and hindlimb at E11.5. Chicken Lin-28, which was first detected in the limb primordium at stage 15/16, was also downregulated as the stage proceeded. The amino acid sequences of mouse and chicken Lin-28 genes are highly conserved and the similar expression patterns of Lin-28 during limb development in mouse and chicken suggest that this heterochronic gene is also conserved during vertebrate limb development.

Forward and Inverse Predictive Model for the Trajectory Tracking Control of a Lower Limb Exoskeleton for Gait Rehabilitation: Simulation modelling analysis

NASA Astrophysics Data System (ADS)

Zakaria, M. A.; Majeed, A. P. P. A.; Taha, Z.; Alim, M. M.; Baarath, K.

2018-03-01

The movement of a lower limb exoskeleton requires a reasonably accurate control method to allow for an effective gait therapy session to transpire. Trajectory tracking is a nontrivial means of passive rehabilitation technique to correct the motion of the patients’ impaired limb. This paper proposes an inverse predictive model that is coupled together with the forward kinematics of the exoskeleton to estimate the behaviour of the system. A conventional PID control system is used to converge the required joint angles based on the desired input from the inverse predictive model. It was demonstrated through the present study, that the inverse predictive model is capable of meeting the trajectory demand with acceptable error tolerance. The findings further suggest the ability of the predictive model of the exoskeleton to predict a correct joint angle command to the system.

Novel Method to Assess Arterial Insufficiency in Rodent Hindlimb

PubMed Central

Ziegler, Matthew A.; DiStasi, Matthew R.; Miller, Steven J.; Dalsing, Michael C.; Unthank, Joseph L.

2015-01-01

Background Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hindlimb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. Materials and methods VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young healthy rats (Wistar Kyoto, WKY; lean Zucker, LZR) and rats with cardiovascular risk factors (Spontaneously Hypertensive, SHR; Obese Zucker, OZR) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. Results VO measurement in WKY demonstrated the utility of this method to assess hindlimb perfusion at rest and during calf muscle contraction. While application to diseased models (OZR, SHR) demonstrated normal resting perfusion compared to contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. Conclusion The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in pre-clinical rodent models. PMID:26850199

Growth of Fault-Cored Anticlines by Flexural Slip Folding: Analysis by Boundary Element Modeling

NASA Astrophysics Data System (ADS)

Johnson, Kaj M.

2018-03-01

Fault-related folds develop due to a combination of slip on the associated fault and distributed deformation off the fault. Under conditions that are sufficient for sedimentary layering to act as a stack of mechanical layers with contact slip, buckling can dramatically amplify the folding process. We develop boundary element models of fault-related folding of viscoelastic layers embedded with a reverse fault to examine the influence of such layering on fold growth. The strength of bedding contacts, the thickness and stiffness of layering, and fault geometry all contribute significantly to the resulting fold form. Frictional contact strength between layers controls the degree of localization of slip within fold limbs; high contact friction in relatively thin bedding tends to localize bedding slip within narrow kink bands on fold limbs, and low contact friction tends to produce widespread bedding slip and concentric fold form. Straight ramp faults tend to produce symmetric folds, whereas listric faults tend to produce asymmetric folds with short forelimbs and longer backlimbs. Fault-related buckle folds grow exponentially with time under steady loading rates. At early stages of folding, fold growth is largely attributed to slip on the fault, but as the fold increases amplitude, a larger portion of the fold growth is attributed to distributed slip across bedding contacts on the limbs of the fold. An important implication for geologic and earthquake studies is that not all surface deformation associated with blind reverse faults may be attributed to slip on the fault during earthquakes.

High Salt Intake Promotes Urinary Loss of Vitamin D Metabolites by Dahl Salt-Sensitive Rats in a Space Flight Model

NASA Technical Reports Server (NTRS)

Thierry-Palmer, M.; Cephas, S.; Sayavongsa, P.; Clark, T.; Arnaud, S. B.

2004-01-01

Vitamin D metabolism in the Dahl salt-sensitive (S) rat, a model of salt-induced hypertension, differs from that in the Dahl salt-resistant (R) rat. We have demonstrated that female S rats are more vulnerable than female R rats to decreases in plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations during hind limb unloading (a space flight model). We report here on the response of the vitamin D endocrine system of S and R rats to hind limb unloading during high salt intake. Dahl female rats (9.7-week-old) were tail-suspended (hind limb unloaded) for 28 days, while fed a diet containing twice the salt in standard rat chow (2 % sodium chloride). Control rats were fed the same diet, but were not hind limb unloaded. Vitamin D metabolites were analyzed by HPLC and radioimmunoassay kits from Diasorin.

Learning about Vertebrate Limb Development

ERIC Educational Resources Information Center

Liang, Jennifer O.; Noll, Matthew; Olsen, Shayna

2014-01-01

We have developed an upper-level undergraduate laboratory exercise that enables students to replicate a key experiment in developmental biology. In this exercise, students have the opportunity to observe live chick embryos and stain the apical ectodermal ridge, a key tissue required for development of the vertebrate limb. Impressively, every…

Factors associated with interest in novel interfaces for upper limb prosthesis control

PubMed Central

Engdahl, Susannah M.; Chestek, Cynthia A.; Kelly, Brian; Davis, Alicia

2017-01-01

Background Surgically invasive interfaces for upper limb prosthesis control may allow users to operate advanced, multi-articulated devices. Given the potential medical risks of these invasive interfaces, it is important to understand what factors influence an individual’s decision to try one. Methods We conducted an anonymous online survey of individuals with upper limb loss. A total of 232 participants provided personal information (such as age, amputation level, etc.) and rated how likely they would be to try noninvasive (myoelectric) and invasive (targeted muscle reinnervation, peripheral nerve interfaces, cortical interfaces) interfaces for prosthesis control. Bivariate relationships between interest in each interface and 16 personal descriptors were examined. Significant variables from the bivariate analyses were then entered into multiple logistic regression models to predict interest in each interface. Results While many of the bivariate relationships were significant, only a few variables remained significant in the regression models. The regression models showed that participants were more likely to be interested in all interfaces if they had unilateral limb loss (p ≤ 0.001, odds ratio ≥ 2.799). Participants were more likely to be interested in the three invasive interfaces if they were younger (p < 0.001, odds ratio ≤ 0.959) and had acquired limb loss (p ≤ 0.012, odds ratio ≥ 3.287). Participants who used a myoelectric device were more likely to be interested in myoelectric control than those who did not (p = 0.003, odds ratio = 24.958). Conclusions Novel prosthesis control interfaces may be accepted most readily by individuals who are young, have unilateral limb loss, and/or have acquired limb loss However, this analysis did not include all possible factors that may have influenced participant’s opinions on the interfaces, so additional exploration is warranted. PMID:28767716

Intra-articular decorin influences the fibrosis genetic expression profile in a rabbit model of joint contracture.

PubMed

Abdel, M P; Morrey, M E; Barlow, J D; Grill, D E; Kolbert, C P; An, K N; Steinmann, S P; Morrey, B F; Sanchez-Sotelo, J

2014-01-01

The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82-8.

Factors associated with interest in novel interfaces for upper limb prosthesis control.

PubMed

Engdahl, Susannah M; Chestek, Cynthia A; Kelly, Brian; Davis, Alicia; Gates, Deanna H

2017-01-01

Surgically invasive interfaces for upper limb prosthesis control may allow users to operate advanced, multi-articulated devices. Given the potential medical risks of these invasive interfaces, it is important to understand what factors influence an individual's decision to try one. We conducted an anonymous online survey of individuals with upper limb loss. A total of 232 participants provided personal information (such as age, amputation level, etc.) and rated how likely they would be to try noninvasive (myoelectric) and invasive (targeted muscle reinnervation, peripheral nerve interfaces, cortical interfaces) interfaces for prosthesis control. Bivariate relationships between interest in each interface and 16 personal descriptors were examined. Significant variables from the bivariate analyses were then entered into multiple logistic regression models to predict interest in each interface. While many of the bivariate relationships were significant, only a few variables remained significant in the regression models. The regression models showed that participants were more likely to be interested in all interfaces if they had unilateral limb loss (p ≤ 0.001, odds ratio ≥ 2.799). Participants were more likely to be interested in the three invasive interfaces if they were younger (p < 0.001, odds ratio ≤ 0.959) and had acquired limb loss (p ≤ 0.012, odds ratio ≥ 3.287). Participants who used a myoelectric device were more likely to be interested in myoelectric control than those who did not (p = 0.003, odds ratio = 24.958). Novel prosthesis control interfaces may be accepted most readily by individuals who are young, have unilateral limb loss, and/or have acquired limb loss However, this analysis did not include all possible factors that may have influenced participant's opinions on the interfaces, so additional exploration is warranted.

The simplest acquisition protocol is sometimes the best protocol: performing and learning a 1:2 bimanual coordination task.

PubMed

Panzer, Stefan; Kennedy, Deanna; Wang, Chaoyi; Shea, Charles H

2018-02-01

An experiment was conducted to determine if the performance and learning of a multi-frequency (1:2) coordination pattern between the limbs are enhanced when a model is provided prior to each acquisition trial. Research has indicated very effective performance of a wide variety of bimanual coordination tasks when Lissajous plots with goal templates are provided, but this research has also found that participants become dependent on this information and perform quite poorly when it is withdrawn. The present experiment was designed to test three forms of modeling (Lissajous with template, Lissajous without template, and limb model), but in each situations, the model was presented prior to practice and not available during the performance of the task. This was done to decrease dependency on the model and increase the development of an internal reference of correctness that could be applied on test trials. A control condition was also collected, where a metronome was used to guide the movement. Following less than 7 min of practice, participants in the three modeling conditions performed the first test block very effectively; however, performance of the control condition was quite poor. Note that Test 1 was performed under the same conditions as used during acquisition. Test 2 was conducted with no augmented information provided prior to or during the performance of the task. Only participants in the limb model condition were able to maintain performance on Test 2. The findings suggest that a very simple intuitive display can provide the necessary information to form an effective internal representation of the coordination pattern which can be used guide performance when the augmented display is withdrawn.

Cryopreservation and replantation of amputated rat hind limbs

PubMed Central

2014-01-01

Background In spite of the relatively high success rate of limb replantation, many patients cannot undergo replantation surgery because the preservation time of an amputated limb is only about six hours. In addition, although allotransplantation of composite tissues is being performed more commonly with increasingly greater success rates, the shortage of donors limits the number of patients that can be treated. So the purpose of this study is to examine the feasibility of cryopreservation and replantation of limbs in a rat model. Methods Twelve five-month-old Sprague-Dawley rats were divided evenly into group A (above-knee amputation) and group B (Syme’s amputation). One hind limb was amputated from each rat. The limbs were irrigated with cryoprotectant, cooled in a controlled manner to -140°C, and placed in liquid nitrogen. Thawing and replantation were performed 14 days later. Results In group A, the limbs became swollen after restoration of blood flow resulting in blood vessel compression and all replantations failed. In group B, restoration of blood flow was noted in all limbs after replantation. In one case, the rat chewed the replanted limb and replantation failed. The other five rats were followed for three months with no abnormalities noted in the replanted limbs. Conclusions Limbs with a minimal amount of muscle tissue can be successfully cryopreserved and replanted. PMID:24886622

Limb observations of the 12.32 micron solar emission line during the 1991 July total eclipse

NASA Technical Reports Server (NTRS)

Deming, Drake; Jennings, Donald E.; Mccabe, George; Noyes, Robert; Wiedemann, Gunter; Espenak, Fred

1992-01-01

The limb profile of the Mg I 12.32-micron emission line is determined by occultation in the July 11, 1991 total solar eclipse over Mauna Kea. It is shown that the emission peaks are very close to the 12-micron continuum limb, as predicted by recent theory for this line as a non-LTE photospheric emission. The increase in optical depth for this extreme limb-viewing situation indicates that most of the observed emission arises from above the chromospheric temperature minimum, and it is found that this emission is extended to heights well in excess of the model predictions. The line emission can be observed as high as 2000 km above the 12-micron continuum limb, whereas theory predicts it to remain observable no higher than about 500 km above the continuum limb. The substantial limb extension observed in this line is quantitatively consistent with limb extensions seen in the far-IR continuum, and it is concluded that it is indicative of departures from gravitational hydrostatic equilibrium, or spatial inhomogeneities, in the upper solar atmosphere.

Intercomparison of daytime stratospheric NO2 satellite retrievals and model simulations

NASA Astrophysics Data System (ADS)

Belmonte Rivas, M.; Veefkind, P.; Boersma, F.; Levelt, P.; Eskes, H.; Gille, J.

2014-07-01

This paper evaluates the agreement between stratospheric NO2 retrievals from infrared limb sounders (Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) and High Resolution Dynamics Limb Sounder (HIRDLS)) and solar UV/VIS backscatter sensors (Ozone Monitoring Instrument (OMI), Scanning Imaging Absorption Spectrometer for Atmospheric Cartography (SCIAMACHY) limb and nadir) over the 2005-2007 period and across the seasons. The observational agreement is contrasted with the representation of NO2 profiles in 3-D chemical transport models such as the Whole Atmosphere Community Climate Model (WACCM) and TM4. A conclusion central to this work is that the definition of a reference for stratospheric NO2 columns formed by consistent agreement among SCIAMACHY, MIPAS and HIRDLS limb records (all of which agree to within 0.25 × 1015 molecules cm-2 or better than 10%) allows us to draw attention to relative errors in other data sets, e.g., (1) WACCM overestimates NO2 densities in the extratropical lower stratosphere, particularly in the springtime and over northern latitudes by up to 35% relative to limb observations, and (2) there are remarkable discrepancies between stratospheric NO2 column estimates from limb and nadir techniques, with a characteristic seasonally and latitudinally dependent pattern. We find that SCIAMACHY nadir and OMI stratospheric columns show overall biases of -0.5 × 1015 molecules cm-2 (-20%) and +0.6 × 1015 molecules cm-2 (+20%) relative to limb observations, respectively. It is argued that additive biases in nadir stratospheric columns are not expected to affect tropospheric retrievals significantly, and that they can be attributed to errors in the total slant column density, related either to algorithmic or instrumental effects. In order to obtain accurate and long-term time series of stratospheric NO2, an effort towards the harmonization of currently used differential optical absorption spectroscopy (DOAS) approaches to nadir retrievals becomes essential, as well as their agreement to limb and ground-based observations, particularly now that limb techniques are giving way to nadir observations as the next generation of climate and air quality monitoring instruments pushes forth.

Vertical Distribution of Aersols and Water Vapor Using CRISM Limb Observations

NASA Technical Reports Server (NTRS)

Smith, Michael D.; Wolff, Michael J.; Clancy, R. Todd

2011-01-01

Near-infrared spectra taken in a limb-viewing geometry by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on-board the Mars Reconnaissance Orbiter (MRO) provide a useful tool for probing atmospheric structure. Specifically, the observed radiance as a function of wavelength and height above the limb allows the vertical distribution of both dust and ice aerosols to be retrieved. These data serve as an important supplement to the aerosol profiling provided by the MRO/MCS instrument allowing independent validation and giving additional information on particle physical and scattering properties through multi-wavelength studies. A total of at least ten CRISM limb observations have been taken so far covering a full Martian year. Each set of limb observations nominally contains about four dozen scans across the limb giving pole-to-pole coverage for two orbits at roughly 100 and 290 W longitude over the Tharsis and Syrtis/Hellas regions, respectively. At each longitude, limb scans are spaced roughly 10 degrees apart in latitude, with a vertical spatial resolution on the limb of roughly 800 m. Radiative transfer modeling is used to model the observations. We compute synthetic CRISM limb spectra using a discrete-ordinates radiative transfer code that accounts for multiple scattering from aerosols and accounts for spherical geometry of the limb observations by integrating the source functions along curved paths in that coordinate system. Retrieved are 14-point vertical profiles for dust and water ice aerosols with resolution of 0.4 scale heights between one and six scale heights above the surface. After the aerosol retrieval is completed, the abundances of C02 (or surface pressure) and H20 gas are retrieved by matching the depth of absorption bands at 2000 nm for carbon dioxide and at 2600 run for water vapor. In addition to the column abundance of water vapor, limited information on its vertical structure can also be retrieved depending on the signal available from aerosol scattering.

Finite element analysis of the contact interface between trans-femoral stump and prosthetic socket.

PubMed

Zhang, Linlin; Zhu, Ming; Shen, Ling; Zheng, Feng

2013-01-01

Transfemoral amputees need prosthetic devices after amputation surgery, and the interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee's satisfaction and comfort. The purpose of this study was to build a nonlinear finite element model to investigate the interface pressure between the above-knee residual limb and its prosthetic socket. The model was three-dimensional (3D) with consideration of nonlinear boundary conditions. Contact analysis was used to simulate the friction conditions between skin and the socket. The normal stresses up to 80.57 kPa at the distal end of the soft tissue. The longitudinal and circumferential shear stress distributions at the limb-socket interface were also simulated. This study explores the influences of load transfer between trans-femoral residual limb and its prosthetic socket.

Phantom Limbs, Neuroprosthetics, and the Developmental Origins of Embodiment.

PubMed

Blumberg, Mark S; Dooley, James C

2017-10-01

Amputees who wish to rid themselves of a phantom limb must weaken the neural representation of the absent limb. Conversely, amputees who wish to replace a lost limb must assimilate a neuroprosthetic with the existing neural representation. Whether we wish to remove a phantom limb or assimilate a synthetic one, we will benefit from knowing more about the developmental process that enables embodiment. A potentially critical contributor to that process is the spontaneous activity - in the form of limb twitches - that occurs exclusively and abundantly during active (REM) sleep, a particularly prominent state in early development. The sensorimotor circuits activated by twitching limbs, and the developmental context in which activation occurs, could provide a roadmap for creating neuroprosthetics that feel as if they are part of the body. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of genetic variations in platelet glycoproteins and eNOS in the development of arterial ischaemia of lower limbs in type 2 diabetes mellitus patients.

PubMed

Carvalhais, Virginia; Ruivães, Ema; Pina-Cabral, Luis Bernardo; Mesquita, Bárbara; Oliveira, Flávio; Monteiro, Maria Céu; Criado, Maria Begoña

2016-12-01

Endothelial and platelet dysfunction increase the atherothrombotic risk in diabetes mellitus patients. Therefore, arterial ischaemia of lower limbs is an important complication in diabetes mellitus. In the present work, type 2 diabetic patients were classified by a podiatrist into presence or absence of arterial ischaemia of lower limbs. Several polymorphisms in platelet glycoproteins and eNOS genes were evaluated. Our results suggest that the -5CC genotype in Kozak sequence of GPIbα may be associated with a higher risk of developing arterial ischaemia of lower limbs in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling and design of a tendon actuated soft robotic exoskeleton for hemiparetic upper limb rehabilitation.

PubMed

Nycz, Christopher J; Delph, Michael A; Fischer, Gregory S

2015-01-01

Robotic technology has recently been explored as a means to rehabilitate and assist individuals suffering from hemiparesis of their upper limbs. Robotic approaches allow for targeted rehabilitation routines which are more personalized and adaptable while providing quantitative measurements of patient outcomes. Development of these technologies into inherently safe and portable devices has the potential to extend the therapy outside of the clinical setting and into the patient's home with benefits to the cost and accessibility of care. To this end, a soft, cable actuated robotic glove and sleeve was designed, modeled, and constructed to provide assistance of finger and elbow movements in a way that mimics the biological function of the tendons. The resulting design increases safety through greater compliance as well as greater tolerance for misalignment with the user's skeletal frame over traditional rigid exoskeletons. Overall this design provides a platform to expand and study the concepts around soft robotic rehabilitation.

Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia.

PubMed

Kishimoto, Satoko; Inoue, Ken-Ichi; Nakamura, Shingo; Hattori, Hidemi; Ishihara, Masayuki; Sakuma, Masashi; Toyoda, Shigeru; Iwaguro, Hideki; Taguchi, Isao; Inoue, Teruo; Yoshida, Ken-Ichiro

2016-06-01

Heparin/protamine micro/nanoparticles (LH/P-MPs) were recently developed as low-molecular weight, biodegradable carriers for adipose-derived stromal cells (ADSCs). These particles can be used for a locally delivered stem cell therapy that promotes angiogenesis. LH/P-MPs bind to the cell surface of ADSCs and promote cell-to-cell interaction and aggregation of ADSCs. Cultured ADSC/LH/P-MP aggregates remain viable. Here, we examined the ability of these aggregates to rescue limb loss in a mouse model of hindlimb ischemia. Unilateral hindlimb ischemia was induced in adult male BALB/c mice by ligation of the iliac artery and hindlimb vein. For allotransplantation of ADSCs from the same inbred strain, we injected ADSC alone or ADSC/LH/P-MP aggregates or control medium (sham-treated) directly into the ischemic muscles. Ischemic limb blood perfusion, vessel density, and vessel area were recorded. The extent of ischemic limb necrosis or limb loss was assessed on postoperative days 2, 7, and 14. Compared with the sham-treatment control, treatment with ADSCs alone showed modest effects on blood perfusion recovery and increased the number of α-SMA-positive vessels. Response to ADSC/LH/P-MP aggregates was significantly greater than ADSCs alone for every endpoint. ADSC/LH/P-MP aggregates more effectively prevented the loss of ischemic hindlimbs than ADSCs alone or the sham-treatment. The LH/P-MPs augmented the effects of ADSCs on angiogenesis and reversal of limb ischemia. Use of ADSC/LH/P-MP aggregates offers a novel and convenient treatment method and potentially represents a promising new therapeutic approach to inducing angiogenesis in ischemic diseases. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Data Impact of the DMSP F18 SSULI UV Data on the Operational GAIM Model

NASA Astrophysics Data System (ADS)

Dandenault, P. B.; Metzler, C. A.; Nicholas, A. C.; Coker, C.; Budzien, S. A.; Chua, D. H.; Finne, T. T.; Dymond, K.; Walker, P. W.; Schunk, R. W.; Scherliess, L.; Gardner, L. C.

2011-12-01

The Naval Research Laboratory (NRL) has developed five ultraviolet remote sensing instruments for the United States Air Force (USAF) Defense Meteorological Satellite Program (DMSP). The DMSP satellites are launched in a near-polar, sun-synchronous orbit at an altitude of approximately 830 km. Each Special Sensor Ultraviolet Limb Imager (SSULI) instrument measures vertical profiles of the natural airglow radiation from atoms, molecules and ions in the upper atmosphere and ionosphere by viewing the earth's limb within a tangent altitude range of approximately 50 km to 750 km. Limb observations are made from the extreme ultraviolet (EUV) to the far ultraviolet (FUV) over the wavelength range of 80 nm to 170 nm, with 1.8 nm resolution. Data products from SSULI observations include nightglow and dayglow Sensor Data Records (SDRs), as well as Environmental Data Records (EDRs) which contain vertical profiles of electron (Ne) densities, N2, O2, O, O+, and Temperature, hmF2, NmF2 and vertical Total Electron Content (TEC). On October 18, 2009, the third SSULI sensor launched from Vandenberg Air Force Base aboard the DMSP F18 spacecraft. The Calibration and Validation of the F18 instrument has completed and the SSULI program is scheduled to go operational at the Air Force Weather Agency (AFWA) in Fall 2011. The SSULI F18 data are ingested by the Global Assimilation of Ionospheric Measurements (GAIM) space weather model, which was developed by Utah State University and has been used operationally at AFWA since February 2006. A brief overview of the SSULI F18 SDR data assimilation process with GAIM is provided and the impact of the SSULI 1356 Å emission on the GAIM model is examined for spring and summer 2011 nightside data in the low-latitude region.

A Surgical Model of Posttraumatic Osteoarthritis With Histological and Gait Validation.

PubMed

Zahoor, Talal; Mitchell, Reed; Bhasin, Priya; Schon, Lew; Zhang, Zijun

2016-07-01

Posttraumatic osteoarthritis (PTOA) is secondary to an array of joint injuries. Animal models are useful tools for addressing the uniqueness of PTOA progression in each type of joint injury and developing strategies for PTOA prevention and treatment. Intra-articular fracture induces PTOA pathology. Descriptive laboratory study. Through a parapatellar incision, the medial tibial plateau was exposed in the left knees of 8 Sprague-Dawley rats. Osteotomy at the midpoint between the tibial crest and the outermost portion of the medial tibial plateau, including the covering articular cartilage, was performed using a surgical blade. The fractured medial tibial plateau was fixed with 2 needles transversely. The fractured knees were not immobilized. Before and after surgery, rat gait was recorded. Rats were sacrificed at week 8, and their knees were harvested for histology. After intra-articular fracture, the affected limbs altered gait from baseline (week 0). In the first 2 weeks, the gait of the operated limbs featured a reduced paw print intensity and stride length but increased maximal contact and stance time. Reduction of maximal and mean print area and duty cycle (the percentage of stance phase in a step) was present from week 1 to week 5. Only print length was reduced in weeks 7 and 8. At week 8, histology of the operated knees demonstrated osteoarthritic pathology. The severity of the PTOA pathology did not correlate with the changes of print length at week 8. Intra-articular fracture of the medial tibial plateau effectively induced PTOA in rat knees. During PTOA development, the injured limbs demonstrated characteristic gait. Intra-articular fracture represents severe joint injury and associates with a high rate of PTOA. This animal model, with histologic and gait validations, can be useful for future studies of PTOA prevention and early diagnosis.

Prosthesis Prescription Protocol of the Arm (PPP-Arm): The implementation of a national prosthesis prescription protocol.

PubMed

Wijdenes, Paula; Brouwers, Michael; van der Sluis, Corry K

2018-02-01

In order to create more uniformity in the prescription of upper limb prostheses by Dutch rehabilitation teams, the development and implementation of a Prosthesis Prescription Protocol of the upper limb (PPP-Arm) was initiated. The aim was to create a national digital protocol to structure, underpin, and evaluate the prescription of upper limb prostheses for clients with acquired or congenital arm defects. Prosthesis Prescription Protocol of the Arm (PPP-Arm) was developed on the basis of the International Classification of Functioning and consisted of several layers. All stakeholders (rehabilitation teams, orthopedic workshops, patients, and insurance companies) were involved in development and implementation. A national project coordinator and knowledge brokers in each team were essential for the project. PPP-Arm was successfully developed and implemented in nine Dutch rehabilitation teams. The protocol improved team collaboration, structure, and completeness of prosthesis prescriptions and treatment uniformity and might be interesting for other countries as well. Clinical relevance A national protocol to prescribe upper limb prostheses can be helpful to create uniformity in treatment of patients with upper limb defects. Such a protocol improves quality of care for all patients in the country.

Design and Development of a Novel Upper-Limb Cycling Prosthesis

PubMed Central

Soni-Sadar, Shivam; Rowbottom, Jack; Patel, Shilen; Mathewson, Edward; Pearson, Samuel; Hutchins, David; Head, John; Hutchins, Stephen

2017-01-01

The rise in popularity of the Paralympics in recent years has created a need for effective, low-cost sports-prosthetic devices for upper-limb amputees. There are various opportunities for lower-limb amputees to participate in cycling; however, there are only few options for those with upper-limb amputations. If the individual previously participated in cycling, a cycling-specific prosthesis could allow these activities to be integrated into rehabilitation methods. This article describes the processes involved with designing, developing and manufacturing such a prosthesis. The fundamental needs of people with upper-limb amputation were assessed and realised in the prototype of a transradial terminal device with two release mechanisms, including a sliding mechanism (for falls and minor collisions) and clamping mechanism (for head-on collisions). The sliding mechanism requires the rider to exert approximately 200 N, while the clamping mechanism requires about 700 N. The force ranges can be customised to match rider requirements. Experiments were conducted in a controlled environment to demonstrate stability of the device during normal cycling. Moreover, a volunteer test-rider was able to successfully activate the release mechanism during a simulated emergency scenario. The development of this prosthesis has the potential to enable traumatic upper-limb amputees to participate in cycling for rehabilitation or recreation. PMID:29144392

Design and Development of a Novel Upper-Limb Cycling Prosthesis.

PubMed

Tiele, Akira; Soni-Sadar, Shivam; Rowbottom, Jack; Patel, Shilen; Mathewson, Edward; Pearson, Samuel; Hutchins, David; Head, John; Hutchins, Stephen

2017-11-16

The rise in popularity of the Paralympics in recent years has created a need for effective, low-cost sports-prosthetic devices for upper-limb amputees. There are various opportunities for lower-limb amputees to participate in cycling; however, there are only few options for those with upper-limb amputations. If the individual previously participated in cycling, a cycling-specific prosthesis could allow these activities to be integrated into rehabilitation methods. This article describes the processes involved with designing, developing and manufacturing such a prosthesis. The fundamental needs of people with upper-limb amputation were assessed and realised in the prototype of a transradial terminal device with two release mechanisms, including a sliding mechanism (for falls and minor collisions) and clamping mechanism (for head-on collisions). The sliding mechanism requires the rider to exert approximately 200 N, while the clamping mechanism requires about 700 N. The force ranges can be customised to match rider requirements. Experiments were conducted in a controlled environment to demonstrate stability of the device during normal cycling. Moreover, a volunteer test-rider was able to successfully activate the release mechanism during a simulated emergency scenario. The development of this prosthesis has the potential to enable traumatic upper-limb amputees to participate in cycling for rehabilitation or recreation.

Wnt and FGF signals interact to coordinate growth with cell fate specification during limb development.

PubMed

ten Berge, Derk; Brugmann, Samantha A; Helms, Jill A; Nusse, Roel

2008-10-01

A fundamental question in developmental biology is how does an undifferentiated field of cells acquire spatial pattern and undergo coordinated differentiation? The development of the vertebrate limb is an important paradigm for understanding these processes. The skeletal and connective tissues of the developing limb all derive from a population of multipotent progenitor cells located in its distal tip. During limb outgrowth, these progenitors segregate into a chondrogenic lineage, located in the center of the limb bud, and soft connective tissue lineages located in its periphery. We report that the interplay of two families of signaling proteins, fibroblast growth factors (FGFs) and Wnts, coordinate the growth of the multipotent progenitor cells with their simultaneous segregation into these lineages. FGF and Wnt signals act together to synergistically promote proliferation while maintaining the cells in an undifferentiated, multipotent state, but act separately to determine cell lineage specification. Withdrawal of both signals results in cell cycle withdrawal and chondrogenic differentiation. Continued exposure to Wnt, however, maintains proliferation and re-specifies the cells towards the soft connective tissue lineages. We have identified target genes that are synergistically regulated by Wnts and FGFs, and show how these factors actively suppress differentiation and promote growth. Finally, we show how the spatial restriction of Wnt and FGF signals to the limb ectoderm, and to a specialized region of it, the apical ectodermal ridge, controls the distribution of cell behaviors within the growing limb, and guides the proper spatial organization of the differentiating tissues.

An Efficient and Reproducible Protocol for Distraction Osteogenesis in a Rat Model Leading to a Functional Regenerated Femur.

PubMed

Pithioux, Martine; Roseren, Flavy; Jalain, Christian; Launay, Franck; Charpiot, Philippe; Chabrand, Patrick; Roffino, Sandrine; Lamy, Edouard

2017-10-23

This protocol describes the use of a newly developed external fixator for distraction osteogenesis in a rat femoral model. Distraction osteogenesis (DO) is a surgical technique leading to bone regeneration after an osteotomy. The osteotomized extremities are moved away from each other by gradual distraction to reach the desired elongation. This procedure is widely used in humans for lower and upper limb lengthening, treatment after a bone nonunion, or the regeneration of a bone defect following surgery for bone tumor excision, as well as in maxillofacial reconstruction. Only a few studies clearly demonstrate the efficiency of their protocol in obtaining a functional regenerated bone, i.e., bone that will support physiological weight-bearing without fracture after removal of the external fixator. Moreover, protocols for DO vary and reproducibility is limited by lack of information, making comparison between studies difficult. The aim of this study was to develop a reproducible protocol comprising an appropriate external fixator design for rat limb lengthening, with a detailed surgical technique that permits physiological weight-bearing by the animal after removal of the external fixator.

Geometry, kinematics and tectonic models of the Kazakhstan Orocline, Central Asian Orogenic Belt

NASA Astrophysics Data System (ADS)

Li, Pengfei; Sun, Min; Rosenbaum, Gideon; Yuan, Chao; Safonova, Inna; Cai, Keda; Jiang, Yingde; Zhang, Yunying

2018-03-01

The Central Asian Orogenic Belt (CAOB) is one of the largest accretionary orogens on Earth and is characterized by the occurrence of tight oroclines (Kazakhstan and Tuva-Mongolian oroclines). The origin of these large-scale orogenic curvatures is not quite understood, but is fundamentally important for understanding crustal growth and tectonic evolution of the CAOB. Here we provide an outline of available geological and paleomagnetic data around the Kazakhstan Orocline, with an aim of clarifying the geometry, kinematics and geodynamic origin of the orocline. The Kazakhstan Orocline is evident in a total magmatic image, and can be traced by the continuation of high magnetic anomalies associated with the Devonian Volcanic Belt and the Late Devonian to Carboniferous Balkhash-Yili arc. Paleomagnetic data show ∼112-126° clockwise rotation of the northern limb relative to the southern limb in the Late Devonian to Early Carboniferous, as well as ∼15-28° clockwise rotation of the northern limb and ∼39-40° anticlockwise rotation of the southern limb relative to the hinge of the orocline during the Late Carboniferous to Permian. We argue that the Kazakhstan Orocline experienced two-stage bending with the early stage of bending (Late Devonian to Early Carboniferous; ∼112-126°) driven by slab rollback, and the later stage (Late Carboniferous to Permian; 54-68°) possibly associated with the amalgamation of the Siberian, Tarim and Baltic cratons. This new tectonic model is compatible with the occurrence of rift basins, the spatial migration of magmatic arc, and the development of large-scale strike-slip fault systems during oroclinal bending.

A novel method to guide classification of para swimmers with limb deficiency.

PubMed

Hogarth, Luke; Payton, Carl; Van de Vliet, Peter; Connick, Mark; Burkett, Brendan

2018-05-30

The International Paralympic Committee has directed International Federations that govern Para sports to develop evidence-based classification systems. This study defined the impact of limb deficiency impairment on 100 m freestyle performance to guide an evidence-based classification system in Para Swimming, which will be implemented following the 2020 Tokyo Paralympic games. Impairment data and competitive race performances of 90 international swimmers with limb deficiency were collected. Ensemble partial least squares regression established the relationship between relative limb length measures and competitive 100 m freestyle performance. The model explained 80% of the variance in 100 m freestyle performance, and found hand length and forearm length to be the most important predictors of performance. Based on the results of this model, Para swimmers were clustered into four-, five-, six- and seven-class structures using nonparametric kernel density estimations. The validity of these classification structures, and effectiveness against the current classification system, were examined by establishing within-class variations in 100 m freestyle performance and differences between adjacent classes. The derived classification structures were found to be more effective than current classification based on these criteria. This study provides a novel method that can be used to improve the objectivity and transparency of decision-making in Para sport classification. Expert consensus from experienced coaches, Para swimmers, classifiers and sport science and medicine personnel will benefit the translation of these findings into a revised classification system that is accepted by the Para swimming community. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Evidence of a significant rotational non-LTE effect in the CO2 4.3 µm PFS-MEX limb spectra

NASA Astrophysics Data System (ADS)

Kutepov, Alexander A.; Rezac, Ladislav; Feofilov, Artem G.

2017-01-01

Since January 2004, the planetary Fourier spectrometer (PFS) on board the Mars Express satellite has been recording near-infrared limb spectra of high quality up to the tangent altitudes ≈ 150 km, with potential information on density and thermal structure of the upper Martian atmosphere. We present first results of our modeling of the PFS short wavelength channel (SWC) daytime limb spectra for the altitude region above 90 km. We applied a ro-vibrational non-LTE model based on the stellar astrophysics technique of accelerated lambda iteration (ALI) to solve the multi-species and multi-level CO2 problem in the Martian atmosphere. We show that the long-standing discrepancy between observed and calculated spectra in the cores and wings of 4.3 µm region is explained by the non-thermal rotational distribution of molecules in the upper vibrational states 10011 and 10012 of the CO2 main isotope second hot (SH) bands above 90 km altitude. The redistribution of SH band intensities from band branch cores into their wings is caused (a) by intensive production of the CO2 molecules in rotational states with j > 30 due to the absorption of solar radiation in optically thin wings of 2.7 µm bands and (b) by a short radiative lifetime of excited molecules, which is insufficient at altitudes above 90 km for collisions to maintain rotation of excited molecules thermalized. Implications for developing operational algorithms for massive processing of PFS and other instrument limb observations are discussed.

Body size and lower limb posture during walking in humans.

PubMed

Hora, Martin; Soumar, Libor; Pontzer, Herman; Sládek, Vladimír

2017-01-01

We test whether locomotor posture is associated with body mass and lower limb length in humans and explore how body size and posture affect net joint moments during walking. We acquired gait data for 24 females and 25 males using a three-dimensional motion capture system and pressure-measuring insoles. We employed the general linear model and commonality analysis to assess the independent effect of body mass and lower limb length on flexion angles at the hip, knee, and ankle while controlling for sex and velocity. In addition, we used inverse dynamics to model the effect of size and posture on net joint moments. At early stance, body mass has a negative effect on knee flexion (p < 0.01), whereas lower limb length has a negative effect on hip flexion (p < 0.05). Body mass uniquely explains 15.8% of the variance in knee flexion, whereas lower limb length uniquely explains 5.4% of the variance in hip flexion. Both of the detected relationships between body size and posture are consistent with the moment moderating postural adjustments predicted by our model. At late stance, no significant relationship between body size and posture was detected. Humans of greater body size reduce the flexion of the hip and knee at early stance, which results in the moderation of net moments at these joints.

Real-time implementation of biofidelic SA1 model for tactile feedback.

PubMed

Russell, A F; Armiger, R S; Vogelstein, R J; Bensmaia, S J; Etienne-Cummings, R

2009-01-01

In order for the functionality of an upper-limb prosthesis to approach that of a real limb it must be able to, accurately and intuitively, convey sensory feedback to the limb user. This paper presents results of the real-time implementation of a 'biofidelic' model that describes mechanotransduction in Slowly Adapting Type 1 (SA1) afferent fibers. The model accurately predicts the timing of action potentials for arbitrary force or displacement stimuli and its output can be used as stimulation times for peripheral nerve stimulation by a neuroprosthetic device. The model performance was verified by comparing the predicted action potential (or spike) outputs against measured spike outputs for different vibratory stimuli. Furthermore experiments were conducted to show that, like real SA1 fibers, the model's spike rate varies according to input pressure and that a periodic 'tapping' stimulus evokes periodic spike outputs.

A general model for estimating lower extremity inertial properties of individuals with transtibial amputation.

PubMed

Ferris, Abbie E; Smith, Jeremy D; Heise, Gary D; Hinrichs, Richard N; Martin, Philip E

2017-03-21

Lower extremity joint moment magnitudes during swing are dependent on the inertial properties of the prosthesis and residual limb of individuals with transtibial amputation (TTA). Often, intact limb inertial properties (INTACT) are used for prosthetic limb values in an inverse dynamics model even though these values overestimate the amputated limb's inertial properties. The purpose of this study was to use subject-specific (SPECIFIC) measures of prosthesis inertial properties to generate a general model (GENERAL) for estimating TTA prosthesis inertial properties. Subject-specific mass, center of mass, and moment of inertia were determined for the shank and foot segments of the prosthesis (n=11) using an oscillation technique and reaction board. The GENERAL model was derived from the means of the SPECIFIC model. Mass and segment lengths are required GENERAL model inputs. Comparisons of segment inertial properties and joint moments during walking were made using three inertial models (unique sample; n=9): (1) SPECIFIC, (2) GENERAL, and (3) INTACT. Prosthetic shank inertial properties were significantly smaller with the SPECIFIC and GENERAL model than the INTACT model, but the SPECIFIC and GENERAL model did not statistically differ. Peak knee and hip joint moments during swing were significantly smaller for the SPECIFIC and GENERAL model compared with the INTACT model and were not significantly different between SPECIFIC and GENERAL models. When subject-specific measures are unavailable, using the GENERAL model produces a better estimate of prosthetic side inertial properties resulting in more accurate joint moment measurements for individuals with TTA than the INTACT model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prenatal Development of Interlimb Motor Learning in the Rat Fetus

PubMed Central

Robinson, Scott R.; Kleven, Gale A.; Brumley, Michele R.

2010-01-01

The role of sensory feedback in the early ontogeny of motor coordination remains a topic of speculation and debate. On E20 of gestation (the 20th day after conception, 2 days before birth), rat fetuses can alter interlimb coordination after a period of training with an interlimb yoke, which constrains limb movement and promotes synchronized, conjugate movement of the yoked limbs. The aim of this study was to determine how the ability to express this form of motor learning may change during prenatal development. Fetal rats were prepared for in vivo study at 4 ages (E18–21) and tested in a 65-min training-and-testing session examining hind limb motor learning. A significant increase in conjugate hind limb activity was expressed by E19, but not E18 fetuses, with further increases in conjugate hind limb activity on E20 and E21. These findings suggest substantial development of the ability of fetal rats to modify patterns of interlimb coordination in response to kinesthetic feedback during motor training before birth. PMID:20198121

Upper extremity prosthesis user perspectives on unmet needs and innovative technology.

PubMed

Benz, Heather L; Jia Yao; Rose, Laura; Olgac, Okan; Kreutz, Karen; Saha, Anindita; Civillico, Eugene F

2016-08-01

The needs of individuals with upper limb amputation and congenital limb difference are not being fully met by current prostheses, as evidenced by prosthesis rejection, non-wear, and user reports of pain and challenging activities. Emerging technologies such as dexterous sensorized robotic limbs, osseointegrated prostheses, implantable EMG electrodes, and electrical stimulation for sensory feedback have the potential to address unmet needs, but pose additional risks. We plan to assess upper limb prosthesis user needs and perspectives on these new benefits and risks using an extensive quantitative survey. In preparation for this survey, we report here on qualitative interviews with seven individuals with upper limb amputation or congenital limb difference. Unstructured text was mined using topic modeling and the results compared with identified themes. A more complete understanding of how novel technologies could address real user concerns will inform implementation of new technologies and regulatory decision-making.

Upper Extremity Prosthesis User Perspectives on Unmet Needs and Innovative Technology

PubMed Central

Benz, Heather L.; Yao, Jia; Rose, Laura; Olgac, Okan; Kreutz, Karen; Saha, Anindita; Civillico, Eugene F.

2017-01-01

The needs of individuals with upper limb amputation and congenital limb difference are not being fully met by current prostheses, as evidenced by prosthesis rejection, non-wear, and user reports of pain and challenging activities. Emerging technologies such as dexterous sensorized robotic limbs, osseointegrated prostheses, implantable EMG electrodes, and electrical stimulation for sensory feedback have the potential to address unmet needs, but pose additional risks. We plan to assess upper limb prosthesis user needs and perspectives on these new benefits and risks using an extensive quantitative survey. In preparation for this survey, we report here on qualitative interviews with seven individuals with upper limb amputation or congenital limb difference. Unstructured text was mined using topic modeling and the results compared with identified themes. A more complete understanding of how novel technologies could address real user concerns will inform implementation of new technologies and regulatory decision-making. PMID:28268333

Upper limb stroke rehabilitation: the effectiveness of Stimulation Assistance through Iterative Learning (SAIL).

PubMed

Meadmore, Katie L; Cai, Zhonglun; Tong, Daisy; Hughes, Ann-Marie; Freeman, Chris T; Rogers, Eric; Burridge, Jane H

2011-01-01

A novel system has been developed which combines robotic therapy with electrical stimulation (ES) for upper limb stroke rehabilitation. This technology, termed SAIL: Stimulation Assistance through Iterative Learning, employs advanced model-based iterative learning control (ILC) algorithms to precisely assist participant's completion of 3D tracking tasks with their impaired arm. Data is reported from a preliminary study with unimpaired participants, and also from a single hemiparetic stroke participant with reduced upper limb function who has used the system in a clinical trial. All participants completed tasks which involved moving their (impaired) arm to follow an image of a slowing moving sphere along a trajectory. The participants' arm was supported by a robot and ES was applied to the triceps brachii and anterior deltoid muscles. During each task, the same tracking trajectory was repeated 6 times and ILC was used to compute the stimulation signals to be applied on the next iteration. Unimpaired participants took part in a single, one hour training session and the stroke participant undertook 18, 1 hour treatment sessions composed of tracking tasks varying in length, orientation and speed. The results reported describe changes in tracking ability and demonstrate feasibility of the SAIL system for upper limb rehabilitation. © 2011 IEEE

Prosthetic Cost Projections for Servicemembers with Major Limb Loss from Vietnam and OIF/OEF

DTIC Science & Technology

2010-01-01

death rates ), DOD = Department of Defense, DSS = Decision Support Sys- tem, MFCL = Medicare Functional Classification Level, OEF = Operation...age-sex-race-adjusted death rates . Figure 3. Markov model for unilateral upper limb and bilateral upper limbs for Operation Iraqi Freedom...Operation Enduring Freedom (OIF/OEF) group. ASR = age-sex-race-adjusted death rates . 394 JRRD, Volume 47, Number 4, 2010 higher, one level lower, or

Thermal time constant: optimising the skin temperature predictive modelling in lower limb prostheses using Gaussian processes

PubMed Central

Buis, Arjan

2016-01-01

Elevated skin temperature at the body/device interface of lower-limb prostheses is one of the major factors that affect tissue health. The heat dissipation in prosthetic sockets is greatly influenced by the thermal conductive properties of the hard socket and liner material employed. However, monitoring of the interface temperature at skin level in lower-limb prosthesis is notoriously complicated. This is due to the flexible nature of the interface liners used which requires consistent positioning of sensors during donning and doffing. Predicting the residual limb temperature by monitoring the temperature between socket and liner rather than skin and liner could be an important step in alleviating complaints on increased temperature and perspiration in prosthetic sockets. To predict the residual limb temperature, a machine learning algorithm – Gaussian processes is employed, which utilizes the thermal time constant values of commonly used socket and liner materials. This Letter highlights the relevance of thermal time constant of prosthetic materials in Gaussian processes technique which would be useful in addressing the challenge of non-invasively monitoring the residual limb skin temperature. With the introduction of thermal time constant, the model can be optimised and generalised for a given prosthetic setup, thereby making the predictions more reliable. PMID:27695626

Thermal time constant: optimising the skin temperature predictive modelling in lower limb prostheses using Gaussian processes.

PubMed

Mathur, Neha; Glesk, Ivan; Buis, Arjan

2016-06-01

Elevated skin temperature at the body/device interface of lower-limb prostheses is one of the major factors that affect tissue health. The heat dissipation in prosthetic sockets is greatly influenced by the thermal conductive properties of the hard socket and liner material employed. However, monitoring of the interface temperature at skin level in lower-limb prosthesis is notoriously complicated. This is due to the flexible nature of the interface liners used which requires consistent positioning of sensors during donning and doffing. Predicting the residual limb temperature by monitoring the temperature between socket and liner rather than skin and liner could be an important step in alleviating complaints on increased temperature and perspiration in prosthetic sockets. To predict the residual limb temperature, a machine learning algorithm - Gaussian processes is employed, which utilizes the thermal time constant values of commonly used socket and liner materials. This Letter highlights the relevance of thermal time constant of prosthetic materials in Gaussian processes technique which would be useful in addressing the challenge of non-invasively monitoring the residual limb skin temperature. With the introduction of thermal time constant, the model can be optimised and generalised for a given prosthetic setup, thereby making the predictions more reliable.

Models to Tailor Brain Stimulation Therapies in Stroke

PubMed Central

Plow, E. B.; Sankarasubramanian, V.; Cunningham, D. A.; Potter-Baker, K.; Varnerin, N.; Cohen, L. G.; Sterr, A.; Conforto, A. B.; Machado, A. G.

2016-01-01

A great challenge facing stroke rehabilitation is the lack of information on how to derive targeted therapies. As such, techniques once considered promising, such as brain stimulation, have demonstrated mixed efficacy across heterogeneous samples in clinical studies. Here, we explain reasons, citing its one-type-suits-all approach as the primary cause of variable efficacy. We present evidence supporting the role of alternate substrates, which can be targeted instead in patients with greater damage and deficit. Building on this groundwork, this review will also discuss different frameworks on how to tailor brain stimulation therapies. To the best of our knowledge, our report is the first instance that enumerates and compares across theoretical models from upper limb recovery and conditions like aphasia and depression. Here, we explain how different models capture heterogeneity across patients and how they can be used to predict which patients would best respond to what treatments to develop targeted, individualized brain stimulation therapies. Our intent is to weigh pros and cons of testing each type of model so brain stimulation is successfully tailored to maximize upper limb recovery in stroke. PMID:27006833

Analysis of crash parameters and driver characteristics associated with lower limb injury.

PubMed

Ye, Xin; Poplin, Gerald; Bose, Dipan; Forbes, Aaron; Hurwitz, Shepard; Shaw, Greg; Crandall, Jeff

2015-10-01

This study aims to investigate changes in frequency, risk, and patterns of lower limb injuries due to vehicle and occupant parameters as a function of vehicle model year. From the National Automotive Sampling System-Crashworthiness Data System, 10,988 observations were sampled and analyzed, representing 4.7 million belted drivers involved in frontal crashes for the years 1998-2010. A logistic regression model was developed to understand the association of sustaining knee and below knee lower limb injuries of moderate or greater severity with motor vehicle crash characteristics such as vehicle type and model years, toepan and instrument panel intrusions in addition to the occupant's age, gender, height and weight. Toepan intrusion greater than 2cm was significantly associated with an increased likelihood of injury (odds ratio: 9.10, 95% confidence interval 1.82-45.42). Females sustained a higher likelihood of distal lower limb injuries (OR: 6.83, 1.56-29.93) as compared to males. Increased mass of the driver was also found to have a positive association with injury (OR: 1.04, 1.02-1.06), while age and height were not associated with injury likelihood. Relative to passenger cars, vans exhibited a protective effect against sustaining lower limb injury (OR: 0.24, 0.07-0.78), whereas no association was shown for light trucks (OR: 1.31, 0.69-2.49) or SUVs (OR: 0.76, 0.28-2.02). To examine whether current crash testing results are representative of real-world NASS-CDS findings, data from frontal offset crash tests performed by the Insurance Institute for Highway Safety (IIHS) were examined. IIHS data indicated a decreasing trend in vehicle foot well and toepan intrusion, foot accelerations, tibia axial forces and tibia index in relation to increasing vehicle model year between the year 1995 and 2013. Over 90% of vehicles received the highest IIHS rating, with steady improvement from the upper and lower tibia index, tibia axial force and the resultant foot acceleration considering both left and right extremities. Passenger cars received the highest rating followed by SUVs and light trucks, while vans attained the lowest rating. These results demonstrate that while there has been steady improvement in vehicle crash test performance, below-knee lower extremity injuries remain the most common AIS 2+ injury in real-world frontal crashes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Protease-activated receptor (PAR)2, but not PAR1, is involved in collateral formation and anti-inflammatory monocyte polarization in a mouse hind limb ischemia model.

PubMed

van den Hengel, Lisa G; Hellingman, Alwine A; Nossent, Anne Yael; van Oeveren-Rietdijk, Annemarie M; de Vries, Margreet R; Spek, C Arnold; van Zonneveld, Anton Jan; Reitsma, Pieter H; Hamming, Jaap F; de Boer, Hetty C; Versteeg, Henri H; Quax, Paul H A

2013-01-01

In collateral development (i.e. arteriogenesis), mononuclear cells are important and exist as a heterogeneous population consisting of pro-inflammatory and anti-inflammatory/repair-associated cells. Protease-activated receptor (PAR)1 and PAR2 are G-protein-coupled receptors that are both expressed by mononuclear cells and are involved in pro-inflammatory reactions, while PAR2 also plays a role in repair-associated responses. Here, we investigated the physiological role of PAR1 and PAR2 in arteriogenesis in a murine hind limb ischemia model. PAR1-deficient (PAR1-/-), PAR2-deficient (PAR2-/-) and wild-type (WT) mice underwent femoral artery ligation. Laser Doppler measurements revealed reduced post-ischemic blood flow recovery in PAR2-/- hind limbs when compared to WT, while PAR1-/- mice were not affected. Upon ischemia, reduced numbers of smooth muscle actin (SMA)-positive collaterals and CD31-positive capillaries were found in PAR2-/- mice when compared to WT mice, whereas these parameters in PAR1-/- mice did not differ from WT mice. The pool of circulating repair-associated (Ly6C-low) monocytes and the number of repair-associated (CD206-positive) macrophages surrounding collaterals in the hind limbs were increased in WT and PAR1-/- mice, but unaffected in PAR2-/- mice. The number of repair-associated macrophages in PAR2-/- hind limbs correlated with CD11b- and CD115-expression on the circulating monocytes in these animals, suggesting that monocyte extravasation and M-CSF-dependent differentiation into repair-associated cells are hampered. PAR2, but not PAR1, is involved in arteriogenesis and promotes the repair-associated response in ischemic tissues. Therefore, PAR2 potentially forms a new pro-arteriogenic target in coronary artery disease (CAD) patients.

Gain-of-function mutation of a voltage-gated sodium channel NaV1.7 associated with peripheral pain and impaired limb development.

PubMed

Tanaka, Brian S; Nguyen, Phuong T; Zhou, Eray Yihui; Yang, Yong; Yarov-Yarovoy, Vladimir; Dib-Hajj, Sulayman D; Waxman, Stephen G

2017-06-02

Dominant mutations in voltage-gated sodium channel Na V 1.7 cause inherited erythromelalgia, a debilitating pain disorder characterized by severe burning pain and redness of the distal extremities. Na V 1.7 is preferentially expressed within peripheral sensory and sympathetic neurons. Here, we describe a novel Na V 1.7 mutation in an 11-year-old male with underdevelopment of the limbs, recurrent attacks of burning pain with erythema, and swelling in his feet and hands. Frequency and duration of the episodes gradually increased with age, and relief by cooling became less effective. The patient's sister had short stature and reported similar complaints of erythema and burning pain, but with less intensity. Genetic analysis revealed a novel missense mutation in Na V 1.7 (2567G>C; p.Gly856Arg) in both siblings. The G856R mutation, located within the DII/S4-S5 linker of the channel, substitutes a highly conserved non-polar glycine by a positively charged arginine. Voltage-clamp analysis of G856R currents revealed that the mutation hyperpolarized (-11.2 mV) voltage dependence of activation and slowed deactivation but did not affect fast inactivation, compared with wild-type channels. A mutation of Gly-856 to aspartic acid was previously found in a family with limb pain and limb underdevelopment, and its functional assessment showed hyperpolarized activation, depolarized fast inactivation, and increased ramp current. Structural modeling using the Rosetta computational modeling suite provided structural clues to the divergent effects of the substitution of Gly-856 by arginine and aspartic acid. Although the proexcitatory changes in gating properties of G856R contribute to the pathophysiology of inherited erythromelalgia, the link to limb underdevelopment is not well understood. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The healing process of intracorporeally and in situ devitalized distal femur by microwave in a dog model and its mechanical properties in vitro.

PubMed

Ji, Zhenwei; Ma, Yunlei; Li, Wei; Li, Xiaoxiang; Zhao, Guangyi; Yun, Zhe; Qian, Jixian; Fan, Qingyu

2012-01-01

Limb-salvage surgery has been well recognized as a standard treatment and alternative to amputation for patients with malignant bone tumors. Various limb-sparing techniques have been developed including tumor prosthesis, allograft, autograft and graft-prosthesis composite. However, each of these methods has short- and long-term disadvantages such as nonunion, mechanical failures and poor limb function. The technique of intracorporeal devitalization of tumor-bearing bone segment in situ by microwave-induced hyperthermia after separating it from surrounding normal tissues with a safe margin is a promising limb-salvage method, which may avoid some shortcomings encountered by the above-mentioned conventional techniques. The purpose of this study is to assess the healing process and revitalization potential of the devitalized bone segment by this method in a dog model. In addition, the immediate effect of microwave on the biomechanical properties of bone tissue was also explored in an in vitro experiment. We applied the microwave-induced hyperthermia to devitalize the distal femurs of dogs in situ. Using a monopole microwave antenna, we could produce a necrotic bone of nearly 20 mm in length in distal femur. Radiography, bone scintigraphy, microangiography, histology and functional evaluation were performed at 2 weeks and 1, 2, 3, 6, 9 and 12 months postoperatively to assess the healing process. In a biomechanical study, two kinds of bone specimens, 3 and 6 cm in length, were used for compression and three-point bending test respectively immediately after extracorporeally devitalized by microwave. An in vivo study showed that intracorporeally and in situ devitalized bone segment by microwave had great revitalization potential. An in vitro study revealed that the initial mechanical strength of the extracorporeally devitalized bone specimen may not be affected by microwave. Our results suggest that the intracorporeal microwave devitalization of tumor-bearing bone segment in situ may be a promising limb-salvage method.

A fast code for channel limb radiances with gas absorption and scattering in a spherical atmosphere

NASA Astrophysics Data System (ADS)

Eluszkiewicz, Janusz; Uymin, Gennady; Flittner, David; Cady-Pereira, Karen; Mlawer, Eli; Henderson, John; Moncet, Jean-Luc; Nehrkorn, Thomas; Wolff, Michael

2017-05-01

We present a radiative transfer code capable of accurately and rapidly computing channel limb radiances in the presence of gaseous absorption and scattering in a spherical atmosphere. The code has been prototyped for the Mars Climate Sounder measuring limb radiances in the thermal part of the spectrum (200-900 cm-1) where absorption by carbon dioxide and water vapor and absorption and scattering by dust and water ice particles are important. The code relies on three main components: 1) The Gauss Seidel Spherical Radiative Transfer Model (GSSRTM) for scattering, 2) The Planetary Line-By-Line Radiative Transfer Model (P-LBLRTM) for gas opacity, and 3) The Optimal Spectral Sampling (OSS) for selecting a limited number of spectral points to simulate channel radiances and thus achieving a substantial increase in speed. The accuracy of the code has been evaluated against brute-force line-by-line calculations performed on the NASA Pleiades supercomputer, with satisfactory results. Additional improvements in both accuracy and speed are attainable through incremental changes to the basic approach presented in this paper, which would further support the use of this code for real-time retrievals and data assimilation. Both newly developed codes, GSSRTM/OSS for MCS and P-LBLRTM, are available for additional testing and user feedback.

What Explains Patterns of Diversification and Richness among Animal Phyla?

PubMed Central

Jezkova, Tereza; Wiens, John J.

2016-01-01

Animal phyla vary dramatically in species richness (from 1 species to >1.2 million), but the causes of this variation remain largely unknown. Animals have also evolved striking variation in morphology and ecology, including sessile marine taxa lacking heads, eyes, limbs, and complex organs (e.g. sponges), parasitic worms (e.g. nematodes, platyhelminths), and taxa with eyes, skeletons, limbs, and complex organs that dominate terrestrial ecosystems (arthropods, chordates). Relating this remarkable variation in traits to the diversification and richness of animal phyla is a fundamental yet unresolved problem in biology. Here, we test the impacts of 18 traits (including morphology, ecology, reproduction, and development) on diversification and richness of extant animal phyla. Using phylogenetic multiple regression, the best-fitting model includes five traits that explain ~74% of the variation in diversification rates (dioecy, parasitism, eyes/photoreceptors, a skeleton, non-marine habitat). However, a model including just three (skeleton, parasitism, habitat) explains nearly as much variation (~67%). Diversification rates then largely explain richness patterns. Our results also identify many striking traits that have surprisingly little impact on diversification (e.g. head, limbs, and complex circulatory and digestive systems). Overall, our results reveal the key factors that shape large-scale patterns of diversification and richness across >80% of all extant, described species. PMID:28221832

What Explains Patterns of Diversification and Richness among Animal Phyla?

PubMed

Jezkova, Tereza; Wiens, John J

2017-03-01

Animal phyla vary dramatically in species richness (from one species to >1.2 million), but the causes of this variation remain largely unknown. Animals have also evolved striking variation in morphology and ecology, including sessile marine taxa lacking heads, eyes, limbs, and complex organs (e.g., sponges), parasitic worms (e.g., nematodes, platyhelminths), and taxa with eyes, skeletons, limbs, and complex organs that dominate terrestrial ecosystems (arthropods, chordates). Relating this remarkable variation in traits to the diversification and richness of animal phyla is a fundamental yet unresolved problem in biology. Here, we test the impacts of 18 traits (including morphology, ecology, reproduction, and development) on diversification and richness of extant animal phyla. Using phylogenetic multiple regression, the best-fitting model includes five traits that explain ∼74% of the variation in diversification rates (dioecy, parasitism, eyes/photoreceptors, a skeleton, nonmarine habitat). However, a model including just three (skeleton, parasitism, habitat) explains nearly as much variation (∼67%). Diversification rates then largely explain richness patterns. Our results also identify many striking traits that have surprisingly little impact on diversification (e.g., head, limbs, and complex circulatory and digestive systems). Overall, our results reveal the key factors that shape large-scale patterns of diversification and richness across >80% of all extant, described species.

ATHLETE: Lunar Cargo Unloading from a High Deck

NASA Technical Reports Server (NTRS)

Wilcox, Brian H.

2010-01-01

As part of the NASA Exploration Technology Development Program, the Jet Propulsion Laboratory is developing a vehicle called ATHLETE: the All-Terrain Hex-Limbed Extra-Terrestrial Explorer. Each vehicle is based on six wheels at the ends of six multi-degree-of freedom limbs. Because each limb has enough degrees of freedom for use as a general-purpose leg, the wheels can be locked and used as feet to walk out of excessively soft or other extreme terrain. Since the vehicle has this alternative mode of traversing through or at least out of extreme terrain, the wheels and wheel actuators can be sized for nominal terrain. There are substantial mass savings in the wheel and wheel actuators associated with designing for nominal instead of extreme terrain. These mass savings are at least comparable-to or larger-than the extra mass associated with the articulated limbs. As a result, the entire mobility system, including wheels and limbs, can be lighter than a conventional all-terrain mobility chassis. A side benefit of this approach is that each limb has sufficient degrees-of freedom to be used as a general-purpose manipulator (hence the name "limb" instead of "leg"). Our prototype ATHLETE vehicles have quick-disconnect tool adapters on the limbs that allow tools to be drawn out of a "tool belt" and maneuvered by the limb. A power-take-off from the wheel actuates the tools, so that they can take advantage of the 1+ horsepower motor in each wheel to enable drilling, gripping or other power-tool functions.

ATHLETE: a Cargo and Habitat Transporter for the Moon

NASA Technical Reports Server (NTRS)

Wilcox, Brian H.

2009-01-01

As part of the NASA Exploration Technology Development Program, the Jet Propulsion Laboratory is developing a vehicle called ATHLETE: the All-Terrain Hex-Limbed Extra-Terrestrial Explorer. The vehicle concept is based on six wheels at the ends of six multi-degree-of-freedom limbs. Because each limb has enough degrees of freedom for use as a general-purpose leg, the wheels can be locked and used as feet to walk out of excessively soft or other extreme terrain. Since the vehicle has this alternative mode of traversing through (or at least out of) extreme terrain, the wheels and wheel actuators can be sized only for nominal terrain. There are substantial mass savings in the wheels and wheel actuators associated with designing for nominal instead of extreme terrain. These mass savings are comparable-to or larger-than the extra mass associated with the articulated limbs. As a result, the entire mobility system, including wheels and limbs, can be about 25 percent lighter than a conventional mobility chassis for planetary exploration. A side benefit of this approach is that each limb has sufficient degrees-of-freedom for use as a general-purpose manipulator (hence the name "limb" instead of "leg"). Our prototype ATHLETE vehicles have quick-disconnect tool adapters on the limbs that allow tools to be drawn out of a "tool belt" and maneuvered by the limb. A rotating power-take-off from the wheel actuates the tools, so that they can take advantage of the 1-plus-horsepower motor in each wheel to enable drilling, gripping or other power-tool functions.

Exploring the fine structure at the limb in coronal holes

NASA Technical Reports Server (NTRS)

Karovska, Magarita; Blundell, Solon F.; Habbal, Shadia Rifai

1994-01-01

The fine structure of the solar limb in coronal holes is explored at temperatures ranging from 10(exp 4) to 10(exp 6) K. An image enhancement algorithm orignally developed for solar eclipse observations is applied to a number of simultaneous multiwavelength observations made with the Harvard Extreme Ultraviolet Spectrometer experiment on Skylab. The enhanced images reveal the presence of filamentary structures above the limb with a characteristic separation of approximately 10 to 15 sec . Some of the structures extend from the solar limb into the corona to at least 4 min above the solar limb. The brightness of these structures changes as a function of height above the limb. The brightest emission is associated with spiculelike structures in the proximity of the limb. The emission characteristic of high-temperature plasma is not cospatial with the emission at lower temperatures, indicating the presence of different temperature plasmas in the field of view.

batman: BAsic Transit Model cAlculatioN in Python

NASA Astrophysics Data System (ADS)

Kreidberg, Laura

2015-11-01

I introduce batman, a Python package for modeling exoplanet transit light curves. The batman package supports calculation of light curves for any radially symmetric stellar limb darkening law, using a new integration algorithm for models that cannot be quickly calculated analytically. The code uses C extension modules to speed up model calculation and is parallelized with OpenMP. For a typical light curve with 100 data points in transit, batman can calculate one million quadratic limb-darkened models in 30 seconds with a single 1.7 GHz Intel Core i5 processor. The same calculation takes seven minutes using the four-parameter nonlinear limb darkening model (computed to 1 ppm accuracy). Maximum truncation error for integrated models is an input parameter that can be set as low as 0.001 ppm, ensuring that the community is prepared for the precise transit light curves we anticipate measuring with upcoming facilities. The batman package is open source and publicly available at https://github.com/lkreidberg/batman .

An interim prosthesis program for lower limb amputees: comparison of public and private models of service.

PubMed

Gordon, Robert; Magee, Christopher; Frazer, Anna; Evans, Craig; McCosker, Kathryn

2010-06-01

This study compared the outcomes of an interim mechanical prosthesis program for lower limb amputees operated under a public and private model of service. Over a two-year period, 60 transtibial amputees were fitted with an interim prosthesis as part of their early amputee care. Thirty-four patients received early amputee care under a public model of service, whereby a prosthetist was employed to provide the interim mechanical prosthesis service. The remaining 26 patients received early amputee care under a private model of service, where an external company was contracted to provide the interim mechanical prosthesis service. The results suggested comparable clinical outcomes between the two patient groups. However, the public model appeared to be less expensive with the average labour cost per patient being 29.0% lower compared with the private model. The results suggest that a public model of service may provide a more comprehensive and less expensive interim prosthesis program for lower limb amputees.

Northwestern University Flexible Subischial Vacuum Socket for persons with transfemoral amputation-Part 1: Description of technique.

PubMed

Fatone, Stefania; Caldwell, Ryan

2017-06-01

Current transfemoral prosthetic sockets restrict function, lack comfort, and cause residual limb problems. Lower proximal trim lines are an appealing way to address this problem. Development of a more comfortable and possibly functional subischial socket may contribute to improving quality of life of persons with transfemoral amputation. The purpose of this study was to (1) describe the design and fabrication of a new subischial socket and (2) describe efforts to teach this technique. Development project. Socket development involved defining the following: subject and liner selection, residual limb evaluation, casting, positive mold rectification, check socket fitting, definitive socket fabrication, and troubleshooting of socket fit. Three hands-on workshops to teach the socket were piloted and attended by 30 certified prosthetists and their patient models. Patient models responded positively to the comfort, range of motion, and stability of the new socket while prosthetists described the technique as "straight forward, reproducible." To our knowledge, this is the first attempt to create a teachable subischial socket, and while it appears promising, more definitive evaluation is needed. Clinical relevance We developed the Northwestern University Flexible Subischial Vacuum (NU-FlexSIV) Socket as a more comfortable alternative to current transfemoral sockets and demonstrated that it could be taught successfully to prosthetists.

Analysis of Msx1; Msx2 double mutants reveals multiple roles for Msx genes in limb development.

PubMed

Lallemand, Yvan; Nicola, Marie-Anne; Ramos, Casto; Bach, Antoine; Cloment, Cécile Saint; Robert, Benoît

2005-07-01

The homeobox-containing genes Msx1 and Msx2 are highly expressed in the limb field from the earliest stages of limb formation and, subsequently, in both the apical ectodermal ridge and underlying mesenchyme. However, mice homozygous for a null mutation in either Msx1 or Msx2 do not display abnormalities in limb development. By contrast, Msx1; Msx2 double mutants exhibit a severe limb phenotype. Our analysis indicates that these genes play a role in crucial processes during limb morphogenesis along all three axes. Double mutant limbs are shorter and lack anterior skeletal elements (radius/tibia, thumb/hallux). Gene expression analysis confirms that there is no formation of regions with anterior identity. This correlates with the absence of dorsoventral boundary specification in the anterior ectoderm, which precludes apical ectodermal ridge formation anteriorly. As a result, anterior mesenchyme is not maintained, leading to oligodactyly. Paradoxically, polydactyly is also frequent and appears to be associated with extended Fgf activity in the apical ectodermal ridge, which is maintained up to 14.5 dpc. This results in a major outgrowth of the mesenchyme anteriorly, which nevertheless maintains a posterior identity, and leads to formation of extra digits. These defects are interpreted in the context of an impairment of Bmp signalling.

Evaluation of the response of rat skeletal muscle to a model of weightlessness

NASA Technical Reports Server (NTRS)

Templeton, G. H.; Padalino, M.; Glasberg, M.; Manton, J.; Silver, P.; Sutko, J.

1982-01-01

Suspension of rats in a head-down tilt position such that their hind limbs are non-load bearing has been proposed as a model for weightlessness. Changes observed in metabolism, bone formation (Morey et al., 1979), and muscle catabolism (Mussachia et al., 1980) support the validity of the model. To further document this model, the effects of suspension on the mechanical, biochemical and histochemical characteristics of two hind limb skeletal muscles, the gastrocnemius and the soleus, are investigated.

A limb action detector enabling people with multiple disabilities to control environmental stimulation through limb action with a Nintendo Wii Remote Controller.

PubMed

Shih, Ching-Hsiang; Chang, Man-Ling; Shih, Ching-Tien

2010-01-01

This study assessed whether two persons with multiple disabilities would be able to control environmental stimulation using limb action with a Nintendo Wii Remote Controller and a newly developed limb action detection program (LADP, i.e., a new software program that turns a Wii Remote Controller into a precise limb action detector). This study was carried out according to an ABAB sequence in which A represented baseline and B represented intervention phases. Data showed that both participants significantly increased their target response, thus increasing the level of environmental stimulation by activating the control system through limb action, during the intervention phases. Practical and developmental implications of the findings are discussed. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Computation Modeling of Limb-bud Dysmorphogenesis: Predicting Cellular Dynamics and Key Events in Developmental Toxicity with a Multicellular Systems Model (FutureToxII)

EPA Science Inventory

Congenital limb malformations are among the most frequent malformation occurs in humans, with a frequency of about 1 in 500 to 1 in 1000 human live births. ToxCast is profiling the bioactivity of thousands of chemicals based on high-throughput (HTS) and computational methods that...

Update on embryology of the upper limb.

PubMed

Al-Qattan, Mohammad M; Kozin, Scott H

2013-09-01

Current concepts in the steps of upper limb development and the way the limb is patterned along its 3 spatial axes are reviewed. Finally, the embryogenesis of various congenital hand anomalies is delineated with an emphasis on the pathogenetic basis for each anomaly. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

A Standardized Rat Model of Volumetric Muscle Loss Injury for the Development of Tissue Engineering Therapies

PubMed Central

Wu, Xiaowu; Corona, Benjamin T.; Chen, Xiaoyu

2012-01-01

Abstract Soft tissue injuries involving volumetric muscle loss (VML) are defined as the traumatic or surgical loss of skeletal muscle with resultant functional impairment and represent a challenging clinical problem for both military and civilian medicine. In response, a variety of tissue engineering and regenerative medicine treatments are under preclinical development. A wide variety of animal models are being used, all with critical limitations. The objective of this study was to develop a model of VML that was reproducible and technically uncomplicated to provide a standardized platform for the development of tissue engineering and regenerative medicine solutions to VML repair. A rat model of VML involving excision of ∼20% of the muscle's mass from the superficial portion of the middle third of the tibialis anterior (TA) muscle was developed and was functionally characterized. The contralateral TA muscle served as the uninjured control. Additionally, uninjured age-matched control rats were also tested to determine the effect of VML on the contralateral limb. TA muscles were assessed at 2 and 4 months postinjury. VML muscles weighed 22.7% and 19.5% less than contralateral muscles at 2 and 4 months postinjury, respectively. These differences were accompanied by a reduction in peak isometric tetanic force (Po) of 28.4% and 32.5% at 2 and 4 months. Importantly, Po corrected for differences in body weight and muscle wet weights were similar between contralateral and age-matched control muscles, indicating that VML did not have a significant impact on the contralateral limb. Lastly, repair of the injury with a biological scaffold resulted in rapid vascularization and integration with the wound. The technical simplicity, reliability, and clinical relevance of the VML model developed in this study make it ideal as a standard model for the development of tissue engineering solutions for VML. PMID:23515319

Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl

PubMed Central

Zhu, Wei; Pao, Gerald M; Satoh, Akira; Cummings, Gillian; Monaghan, James R; Harkins, Timothy T; Bryant, Susan V; Voss, S Randal; Gardiner, David M; Hunter, Tony

2013-01-01

The capacity for tissue and organ regeneration in humans is dwarfed by comparison to that of salamanders. Emerging evidence suggests that mechanisms learned from the early phase of salamander limb regeneration – wound healing, cellular dedifferentiation and blastemal formation – will reveal therapeutic approaches for tissue regeneration in humans. Here we describe a unique transcriptional fingerprint of regenerating limb tissue in the Mexican axolotl (Ambystoma mexicanum) that is indicative of cellular reprogramming of differentiated cells to a germline-like state. Two genes that are required for self-renewal of germ cells in mice and flies, Piwi-like 1 (PL1) and Piwi-like 2 (PL2), are expressed in limb blastemal cells, the basal layer keratinocytes and the thickened apical epithelial cap in the wound epidermis in the regenerating limb. Depletion of PL1 and PL2 by morpholino oligonucleotides decreased cell proliferation and increased cell death in the blastema leading to a significant retardation of regeneration. Examination of key molecules that are known to be required for limb development or regeneration further revealed that FGF8 is transcriptionally downregulated in the presence of the morpholino oligos, indicating PL1 and PL2 might participate in FGF signaling during limb regeneration. Given the requirement for FGF signaling in limb development and regeneration, the results suggest that PL1 and PL2 function to establish a unique germline-like state that is associated with successful regeneration. PMID:22841627

Chicken homeobox gene Msx-1: structure, expression in limb buds and effect of retinoic acid.

PubMed

Yokouchi, Y; Ohsugi, K; Sasaki, H; Kuroiwa, A

1991-10-01

A chicken gene carrying a homeobox highly homologous to the Drosophila muscle segment homeobox (msh) gene was isolated and designated as Msx-1. Conceptual translation from the longest ORF gave a protein of 259 amino acids lacking the conserved hexapeptide. Northern analysis detected a single 2.6 kb transcript. As early as day 2 of incubation, the transcript was detected but was not found in adult tissue. In situ hybridization analysis revealed that Msx-1 expression is closely related to a particular mesenchymal cell lineage during limb bud formation. In early stage embryos, Msx-1 was expressed in the somatopleure. When primordial mesenchyme cells for limb bud were generated from the Wolffian ridge of the somatopleure, Msx-1 expression began to diminish in the posterior half of the limb bud then in the presumptive cartilage-forming mesenchyme. In developing limb buds, remarkable expression was seen in the apical ectodermal ridge (AER), which is responsible for the sustained outgrowth and development of the limb. The Msx-1 transcripts were found in the limb mesenchymal cells in the region covering the necrotic zone and ectodermal cells overlying such mesenchymal cells. Both ectodermal and mesenchymal expression in limb bud were rapidly suppressed by local treatment of retinoic acid which can generate mirror-image duplication of digits. This indicates that retinoic acid alters the marginal presumptive non-cartilage forming mesenchyme cell lineage through suppression of Msx-1 expression.

A two-model hydrologic ensemble prediction of hydrograph: case study from the upper Nysa Klodzka river basin (SW Poland)

NASA Astrophysics Data System (ADS)

Niedzielski, Tomasz; Mizinski, Bartlomiej

2016-04-01

The HydroProg system has been elaborated in frame of the research project no. 2011/01/D/ST10/04171 of the National Science Centre of Poland and is steadily producing multimodel ensemble predictions of hydrograph in real time. Although there are six ensemble members available at present, the longest record of predictions and their statistics is available for two data-based models (uni- and multivariate autoregressive models). Thus, we consider 3-hour predictions of water levels, with lead times ranging from 15 to 180 minutes, computed every 15 minutes since August 2013 for the Nysa Klodzka basin (SW Poland) using the two approaches and their two-model ensemble. Since the launch of the HydroProg system there have been 12 high flow episodes, and the objective of this work is to present the performance of the two-model ensemble in the process of forecasting these events. For a sake of brevity, we limit our investigation to a single gauge located at the Nysa Klodzka river in the town of Klodzko, which is centrally located in the studied basin. We identified certain regular scenarios of how the models perform in predicting the high flows in Klodzko. At the initial phase of the high flow, well before the rising limb of hydrograph, the two-model ensemble is found to provide the most skilful prognoses of water levels. However, while forecasting the rising limb of hydrograph, either the two-model solution or the vector autoregressive model offers the best predictive performance. In addition, it is hypothesized that along with the development of the rising limb phase, the vector autoregression becomes the most skilful approach amongst the scrutinized ones. Our simple two-model exercise confirms that multimodel hydrologic ensemble predictions cannot be treated as universal solutions suitable for forecasting the entire high flow event, but their superior performance may hold only for certain phases of a high flow.

[Analysis of the effect of detector's operating temperature on SNR in space-based remote sensor].

PubMed

Li, Zhan-feng; Wang, Shu-rong; Huang, Yu

2012-03-01

Limb viewing is a new viewing geometry for space-based atmospheric remote sensing, but the spectral radiance of atmosphere scattering reduces rapidly with limb height. So the signal-noise-ratio (SNR) is a key performance parameter of limb remote sensor. A SNR model varying with detector's temperature is proposed, based on analysis of spectral radiative transfer and noise' source in representative instruments. The SNR at limb height 70 km under space conditions was validated by simulation experiment on limb remote sensing spectrometer prototype. Theoretic analysis and experiment's results indicate congruously that when detector's temperature reduces to some extent, a maximum SNR will be reached. After considering the power consumption, thermal conductivity and other issues, optimal operating temperature of detector can be decided.

Review: Biological and Molecular Differences between Tail Regeneration and Limb Scarring in Lizard: An Inspiring Model Addressing Limb Regeneration in Amniotes.

PubMed

Alibardi, Lorenzo

2017-09-01

Tissue regeneration in lizards represents a unique model of regeneration and scarring in amniotes. The tail and limb contain putative stem cells but also dedifferentiating cells contribute to regeneration. Following tail amputation, inflammation is low and cell proliferation high, leading to regeneration while the intense inflammation in the limb leads to low proliferation and scarring. FGFs stimulate tail and limb regeneration and are present in the wound epidermis and blastema while they disappear in the limb wound epidermis 2-3 weeks postamputation in the scarring outgrowth. FGFs localize in the tail blastema and the apical epidermal peg (AEP), an epidermal microregion that allows tail growth but is absent in the limb. Inflammatory cells invade the limb blastema and wound epidermis, impeding the formation of an AEP. An embryonic program of growth is activated in the tail, dominated by Wnt-positive and -negative regulators of cell proliferation and noncoding RNAs, that represent the key regenerative genes. The balanced actions of these regulators likely impede the formation of a tumor in the tail tip. Genes for FACIT and fibrillar collagens, protease inhibitors, and embryonic keratins are upregulated in the regenerating tail blastema. A strong downregulation of genes for both B and T-lymphocyte activation suggests the regenerating tail blastema is a temporal immune-tolerated organ, whereas a scarring program is activated in the limb. Wnt inhibitors, pro-inflammatory genes, negative regulators of cell proliferation, downregulation of myogenic genes, proteases, and oxidases favoring scarring are upregulated. The evolution of an efficient immune system may be the main limiting barrier for organ regeneration in amniotes, and the poor regeneration of mammals and birds is associated with the efficiency of their mature immune system. This does not tolerate embryonic antigens formed in reprogrammed embryonic cells (as for neoplastic cells) that are consequently eliminated impeding the regeneration of lost organs. © 2017 Wiley Periodicals, Inc.

Obstacle Crossing During Gait in Children With Cerebral Palsy: Cross-Sectional Study With Kinematic Analysis of Dynamic Balance and Trunk Control.

PubMed

Malone, Ailish; Kiernan, Damien; French, Helen; Saunders, Valerie; O'Brien, Timothy

2016-08-01

Balance problems are common in children who have cerebral palsy (CP) but are active and ambulant. Control of the whole-body center of mass is critical in maintaining dynamic stability during challenging mobility tasks, such as clearing an obstacle while walking. The objective of this study was to compare trunk and lower limb kinematics and center-of-mass control in children with CP and those in children with typical development during obstacle crossing. This was a cross-sectional study. Thirty-four children who were 5 to 17 years of age (17 with CP and 17 with typical development) and matched in age and height completed 2 gait trials involving crossing a 10-cm obstacle. Three-dimensional kinematic and kinetic data were captured with a general-purpose 3-dimensional motion tracking system and forceplates. Trunk data were captured with a validated model. All children cleared the obstacle with similar hip and knee kinematics, step length, and single-support duration. In children with CP, step width was increased by 4.81 cm, and center-of-mass velocity was significantly slower at lead limb toe-off (0.31 m/s) and during lead limb clearance (0.2 m/s). Children with CP showed altered trunk and pelvis movement, characterized by significantly greater pelvic obliquity, pelvic tilt, and trunk rotation throughout the task, increased lateral trunk lean during lead limb crossing (3.7°), and greater sagittal trunk movement as the trail limb crossed (5.1°). The study was not powered to analyze differences between children with diplegia and those with hemiplegia. Children with CP required greater adjustments at the trunk and pelvis to achieve successful obstacle crossing. The increase in trunk movement could have been compensatory for reduced stability distally or for a primary problem reflecting poor proximal control. The findings suggest that rehabilitation should focus on both proximal trunk control and distal stability to improve balance. © 2016 American Physical Therapy Association.

Function and position determine relative proportions of different fiber types in limb muscles of the lizard Tropidurus psammonastes.

PubMed

Pereira, Anieli G; Abdala, Virginia; Kohlsdorf, Tiana

2015-02-01

Skeletal muscles can be classified as flexors or extensors according to their function, and as dorsal or ventral according to their position. The latter classification evokes their embryological origin from muscle masses initially divided during limb development, and muscles sharing a given position do not necessarily perform the same function. Here, we compare the relative proportions of different fiber types among six limb muscles in the lizard Tropidurus psammonastes. Individual fibers were classified as slow oxidative (SO), fast glycolytic (FG) or fast oxidative-glycolytic (FOG) based on mitochondrial content; muscles were classified according to position and function. Mixed linear models considering one or both effects were compared using likelihood ratio tests. Variation in the proportion of FG and FOG fibers is mainly explained by function (flexor muscles have on average lower proportions of FG and higher proportions of FOG fibers), while variation in SO fibers is better explained by position (they are less abundant in ventral muscles than in those developed from a dorsal muscle mass). Our results clarify the roles of position and function in determining the relative proportions of the various muscle fibers and provide evidence that these factors may differentially affect distinct fiber types. Copyright © 2014. Published by Elsevier GmbH.

The "waiting period" of sensory and motor axons in early chick hindlimb: its role in axon pathfinding and neuronal maturation.

PubMed

Wang, G; Scott, S A

2000-07-15

During embryonic development motor axons in the chick hindlimb grow out slightly before sensory axons and wait in the plexus region at the base of the limb for approximately 24 hr before invading the limb itself (Tosney and Landmesser, 1985a). We have investigated the role of this waiting period by asking, Is the arrest of growth cones in the plexus region a general property of both sensory and motor axons? Why do axons wait? Does eliminating the waiting period affect the further development of motor and sensory neurons? Here we show that sensory axons, like motor axons, pause in the plexus region and that neither sensory nor motor axons require cues from the other population to wait in or exit from the plexus region. By transplanting older or younger donor limbs to host embryos, we show that host axons innervate donor limbs on a schedule consistent with the age of the grafted limbs. Thus, axons wait in the plexus region for maturational changes to occur in the limb rather than in the neurons themselves. Both sensory and motor axons innervate their appropriate peripheral targets when the waiting period is eliminated by grafting older donor limbs. Therefore, axons do not require a prolonged period in the plexus region to sort out and project appropriately. Eliminating the waiting period does, however, accelerate the onset of naturally occurring cell death, but it does not enhance the development of central projections or the biochemical maturation of sensory neurons.

B4GALNT2 (GALGT2) Gene Therapy Reduces Skeletal Muscle Pathology in the FKRP P448L Mouse Model of Limb Girdle Muscular Dystrophy 2I.

PubMed

Thomas, Paul J; Xu, Rui; Martin, Paul T

2016-09-01

Overexpression of B4GALNT2 (previously GALGT2) inhibits the development of muscle pathology in mouse models of Duchenne muscular dystrophy, congenital muscular dystrophy 1A, and limb girdle muscular dystrophy 2D. In these models, muscle GALGT2 overexpression induces the glycosylation of α dystroglycan with the cytotoxic T cell glycan and increases the overexpression of dystrophin and laminin α2 surrogates known to inhibit disease. Here, we show that GALGT2 gene therapy significantly reduces muscle pathology in FKRP P448Lneo(-) mice, a model for limb girdle muscular dystrophy 2I. rAAVrh74.MCK.GALGT2-treated FKRP P448Lneo(-) muscles showed reduced levels of centrally nucleated myofibers, reduced variance, increased size of myofiber diameters, reduced myofiber immunoglobulin G uptake, and reduced muscle wasting at 3 and 6 months after treatment. GALGT2 overexpression in FKRP P448Lneo(-) muscles did not cause substantial glycosylation of α dystroglycan with the cytotoxic T cell glycan or increased expression of dystrophin and laminin α2 surrogates in mature skeletal myofibers, but it increased the number of embryonic myosin-positive regenerating myofibers. These data demonstrate that GALGT2 overexpression can reduce the extent of muscle pathology in FKRP mutant muscles, but that it may do so via a mechanism that differs from its ability to induce surrogate gene expression. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Morphology of a Coronal Prominence Cavity

NASA Technical Reports Server (NTRS)

Gibson, S. E.; Kucera, T. A.; Rastawicki, D.; Dove, J.; deToma, G.; Hao, J.; Hill, S.; Hudson, H. S.; Marque, C.; McIntosh, P. S.;

Functional testing of space flight induced changes in tonic motor control by using limb-attached excitation and load devices

NASA Astrophysics Data System (ADS)

Gallasch, Eugen; Kozlovskaya, Inessa

2007-02-01

Long term space flights induce atrophy and contractile changes on postural muscles such effecting tonic motor control. Functional testing of tonic motor control structures is a challenge because of the difficulties to deliver appropriate test forces on crew members. In this paper we propose two approaches for functional testing by using limb attached loading devices. The first approach is based on a frequency and amplitude controllable moving magnet exciter to deliver sinusoidal test forces during limb postures. The responding limb deflection is recorded by an embedded accelerometer to obtain limb impedance. The second approach is based on elastic limb loading to evoke self-excited oscillations during arm extensions. Here the contraction force at the oscillation onset provides information about limb stiffness. The rationale for both testing approaches is based on Feldman's λ-model. An arm expander based on the second approach was probed in a 6-month MIR space flight. The results obtained from the load oscillations, confirmed that this device is well suited to capture space flight induced neuromuscular changes.

SPECTRO-POLARIMETRIC SIMULATIONS OF THE SOLAR LIMB: ABSORPTION-EMISSION Fe I 6301.5 Å AND 6302.5 Å LINE PROFILES AND TORSIONAL FLOWS IN THE INTERGRANULAR MAGNETIC FLUX CONCENTRATIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shelyag, S.

2015-03-01

Using radiative magnetohydrodynamic simulations of the magnetized solar photosphere and detailed spectro-polarimetric diagnostics with the Fe I 6301.5 Å and 6302.5 Å photospheric lines in the local thermodynamic equilibrium approximation, we model active solar granulation as if it was observed at the solar limb. We analyze general properties of the radiation across the solar limb, such as the continuum and the line core limb darkening and the granulation contrast. We demonstrate the presence of profiles with both emission and absorption features at the simulated solar limb, and pure emission profiles above the limb. These profiles are associated with the regionsmore » of strong linear polarization of the emergent radiation, indicating the influence of the intergranular magnetic fields on the line formation. We analyze physical origins of the emission wings in the Stokes profiles at the limb, and demonstrate that these features are produced by localized heating and torsional motions in the intergranular magnetic flux concentrations.« less

ATHLETE: A Limbed Vehicle for Solar System Exploration

NASA Technical Reports Server (NTRS)

Wilcox, Brian H.

2012-01-01

As part of the Human-Robot Systems project funded by NASA, the Jet Propulsion Laboratory has developed a vehicle called ATHLETE: the All-Terrain Hex-Limbed Extra-Terrestrial Explorer. Each vehicle is based on six wheels at the ends of six multi-degree-of-freedom limbs. Because each limb has enough degrees of freedom for use as a general-purpose leg, the wheels can be locked and used as feet to walk out of excessively soft or other extreme terrain. Since the vehicle has this alternative mode of traversing through or at least out of extreme terrain, the wheels and wheel actuators can be sized for nominal terrain. There are substantial mass savings in the wheel and wheel actuators associated with designing for nominal instead of extreme terrain. These mass savings are comparable-to or larger-than the extra mass associated with the articulated limbs. As a result, the entire mobility system, including wheels and limbs, can be about 25% lighter than a conventional mobility chassis. A side benefit of this approach is that each limb has sufficient degrees-of-freedom to use as a general-purpose manipulator (hence the name "limb" instead of "leg"). Our prototype ATHLETE vehicles have quick-disconnect tool adapters on the limbs that allow tools to be drawn out of a "tool belt" and maneuvered by the limb.

Development of an EMG-ACC-Based Upper Limb Rehabilitation Training System.

PubMed

Ling Liu; Xiang Chen; Zhiyuan Lu; Shuai Cao; De Wu; Xu Zhang

2017-03-01

This paper focuses on the development of an upper limb rehabilitation training system designed for use by children with cerebral palsy (CP). It attempts to meet the requirements of in-home training by taking advantage of the combination of portable accelerometers (ACC) and surface electromyography (SEMG) sensors worn on the upper limb to capture functional movements. In the proposed system, the EMG-ACC acquisition device works essentially as wireless game controller, and three rehabilitation games were designed for improving upper limb motor function under a clinician's guidance. The games were developed on the Android platform based on a physical engine called Box2D. The results of a system performance test demonstrated that the developed games can respond to the upper limb actions within 210 ms. Positive questionnaire feedbacks from twenty CP subjects who participated in the game test verified both the feasibility and usability of the system. Results of a long-term game training conducted with three CP subjects demonstrated that CP patients could improve in their game performance through repetitive training, and persistent training was needed to improve and enhance the rehabilitation effect. According to our experimental results, the novel multi-feedback SEMG-ACC-based user interface improved the users' initiative and performance in rehabilitation training.

The choice of a constitutive formulation for modeling limb flexion-induced deformations and stresses in the human femoropopliteal arteries of different ages.

PubMed

Desyatova, Anastasia; MacTaggart, Jason; Poulson, William; Deegan, Paul; Lomneth, Carol; Sandip, Anjali; Kamenskiy, Alexey

2017-06-01

Open and endovascular treatments for peripheral arterial disease are notorious for high failure rates. Severe mechanical deformations experienced by the femoropopliteal artery (FPA) during limb flexion and interactions between the artery and repair materials play important roles and may contribute to poor clinical outcomes. Computational modeling can help optimize FPA repair, but these simulations heavily depend on the choice of constitutive model describing the arterial behavior. In this study finite element model of the FPA in the standing (straight) and gardening (acutely bent) postures was built using computed tomography data, longitudinal pre-stretch and biaxially determined mechanical properties. Springs and dashpots were used to represent surrounding tissue forces associated with limb flexion-induced deformations. These forces were then used with age-specific longitudinal pre-stretch and mechanical properties to obtain deformed FPA configurations for seven age groups. Four commonly used invariant-based constitutive models were compared to determine the accuracy of capturing deformations and stresses in each age group. The four-fiber FPA model most accurately portrayed arterial behavior in all ages, but in subjects younger than 40 years, the performance of all constitutive formulations was similar. In older subjects, Demiray (Delfino) and classic two-fiber Holzapfel-Gasser-Ogden formulations were better than the Neo-Hookean model for predicting deformations due to limb flexion, but both significantly overestimated principal stresses compared to the FPA or Neo-Hookean models.

A Neurocognitive Perspective on Developmental Disregard in Children with Hemiplegic Cerebral Palsy

ERIC Educational Resources Information Center

Houwink, Annemieke; Aarts, Pauline B. M.; Geurts, Alexander C. H.; Steenbergen, Bert

2011-01-01

A common problem in children with hemiplegic cerebral palsy (CP) is the asymmetrical development of arm and hand capacity caused by the lack of use of the affected upper limb, or developmental disregard. In this paper, we provide a neuropsychological model that relates developmental disregard to attentional processes and motor learning. From this…

A conditional allele of Rspo3 reveals redundant function of R-spondins during mouse limb development.

PubMed

Neufeld, Stanley; Rosin, Jessica M; Ambasta, Anshula; Hui, Kristen; Shaneman, Venessa; Crowder, Ray; Vickerman, Lori; Cobb, John

2012-10-01

R-spondins are secreted ligands that bind cell surface receptors and activate Wnt/β-catenin signaling. Human mutations and gene inactivation studies in mice have revealed a role for these four proteins (RSPO1-4) in diverse developmental processes ranging from sex determination to limb development. Among the genes coding for R-spondins, only inactivation of Rspo3 shows early embryonic lethality (E10.5 in mice). Therefore, a conditional allele of this gene is necessary to understand the function of R-spondins throughout murine development. To address this need, we have produced an allele in which loxP sites flank exons 2-4 of Rspo3, allowing tissue-specific deletion of these exons in the presence of Cre recombinase. We used these mice to investigate the role of Rspo3 during limb development and found that limbs ultimately developed normally in the absence of Rspo3 function. However, severe hindlimb truncations resulted when Rspo3 and Rspo2 mutations were combined, demonstrating redundant function of these genes. Copyright © 2012 Wiley Periodicals, Inc.

Limb Correction of Polar-Orbiting Imagery for the Improved Interpretation of RGB Composites

NASA Technical Reports Server (NTRS)

Jedlovec, Gary J.; Elmer, Nicholas

2016-01-01

Red-Green-Blue (RGB) composite imagery combines information from several spectral channels into one image to aid in the operational analysis of atmospheric processes. However, infrared channels are adversely affected by the limb effect, the result of an increase in optical path length of the absorbing atmosphere between the satellite and the earth as viewing zenith angle increases. This paper reviews a newly developed technique to quickly correct for limb effects in both clear and cloudy regions using latitudinally and seasonally varying limb correction coefficients for real-time applications. These limb correction coefficients account for the increase in optical path length in order to produce limb-corrected RGB composites. The improved utility of a limb-corrected Air Mass RGB composite from the application of this approach is demonstrated using Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) imagery. However, the limb correction can be applied to any polar-orbiting sensor infrared channels, provided the proper limb correction coefficients are calculated. Corrected RGB composites provide multiple advantages over uncorrected RGB composites, including increased confidence in the interpretation of RGB features, improved situational awareness for operational forecasters, and the ability to use RGB composites from multiple sensors jointly to increase the temporal frequency of observations.

Chemical activation of Wnt/β-catenin signalling inhibits innervation and causes skeletal tissue malformations during axolotl limb regeneration.

PubMed

Wischin, Sabina; Castañeda-Patlán, Cristina; Robles-Flores, Martha; Chimal-Monroy, Jesús

2017-04-01

Limb regeneration involves several interrelated physiological processes in which a particular signalling pathway may play a variety of functions. Blocking the function of Wnt/β-catenin signalling during limb regeneration inhibits regeneration in axolotls (Ambystoma mexicanum). Limb development shares many features with limb regeneration, and Wnt/β-catenin activation has different effects depending on the developmental stage. The aim of this study was to evaluate whether Wnt/β-catenin signalling activation during axolotl limb regeneration has different effects when activated at different stages of regeneration. To evaluate this hypothesis, we treated amputated axolotls with a Wnt agonist chemical at different stages of limb regeneration. The results showed that limb regeneration was inhibited when the treatment began before blastema formation. Under these conditions, blastema formation was hindered, possibly due to the lack of innervation. On the other hand, when axolotls were treated after blastema formation and immediately before the onset of morphogenesis, we observed structural disorganization in skeletal formation. In conclusion, we found that limb regeneration was differentially affected depending on the stage at which the Wnt signalling pathway was activated. Copyright © 2017 Elsevier B.V. All rights reserved.

Neural mechanisms of limb position estimation in the primate brain.

PubMed

Shi, Ying; Buneo, Christopher A

2011-01-01

Understanding the neural mechanisms of limb position estimation is important both for comprehending the neural control of goal directed arm movements and for developing neuroprosthetic systems designed to replace lost limb function. Here we examined the role of area 5 of the posterior parietal cortex in estimating limb position based on visual and somatic (proprioceptive, efference copy) signals. Single unit recordings were obtained as monkeys reached to visual targets presented in a semi-immersive virtual reality environment. On half of the trials animals were required to maintain their limb position at these targets while receiving both visual and non-visual feedback of their arm position, while on the other trials visual feedback was withheld. When examined individually, many area 5 neurons were tuned to the position of the limb in the workspace but very few neurons modulated their firing rates based on the presence/absence of visual feedback. At the population level however decoding of limb position was somewhat more accurate when visual feedback was provided. These findings support a role for area 5 in limb position estimation but also suggest that visual signals regarding limb position are only weakly represented in this area, and only at the population level.

Detailed expression profile of the six Glypicans and their modifying enzyme, Notum during chick limb and feather development.

PubMed

Saad, Kawakeb; Theis, Susanne; Otto, Anthony; Luke, Graham; Patel, Ketan

2017-04-30

The development of vertebrate appendages, especially the limb and feather buds are orchestrated by numerous secreted signalling molecules including Sonic Hedgehog, Bone Morphogenetic Proteins, Fibroblast Growth Factors and Wnts. These proteins coordinate the growth and patterning of ectodermal and mesenchymal cells. The influence of signalling molecules is affected over large distances by their concentration (morphogen activity) but also at local levels by the presence of proteins that either attenuate or promote their activity. Glypicans are cell surface molecules that regulate the activity of the major secreted signalling molecules expressed in the limb and feather bud. Here we investigated the expression of all Glypicans during chick limb and feather development. In addition we profiled the expression of Notum, an enzyme that regulates Glypican activity. We show that five of the six Glypicans and Notum are expressed in a dynamic manner during the development of limbs and feathers. We also investigated the expression of key Glypicans and show that they are controlled by signalling molecules highlighting the presence of feedback loops. Lastly we show that Glypicans and Notum are expressed in a tissue specific manner in adult chicken tissues. Our results strongly suggest that the Glypicans and Notum have many as yet undiscovered roles to play during the development of vertebrate appendages. Copyright © 2017 Elsevier B.V. All rights reserved.

The evolutionary history of the development of the pelvic fin/hindlimb

PubMed Central

Don, Emily K; Currie, Peter D; Cole, Nicholas J

2013-01-01

The arms and legs of man are evolutionarily derived from the paired fins of primitive jawed fish. Few evolutionary changes have attracted as much attention as the origin of tetrapod limbs from the paired fins of ancestral fish. The hindlimbs of tetrapods are derived from the pelvic fins of ancestral fish. These evolutionary origins can be seen in the examination of shared gene and protein expression patterns during the development of pelvic fins and tetrapod hindlimbs. The pelvic fins of fish express key limb positioning, limb bud induction and limb outgrowth genes in a similar manner to that seen in hindlimb development of higher vertebrates. We are now at a point where many of the key players in the development of pelvic fins and vertebrate hindlimbs have been identified and we can now readily examine and compare mechanisms between species. This is yielding fascinating insights into how the developmental programme has altered during evolution and how that relates to anatomical change. The role of pelvic fins has also drastically changed over evolutionary history, from playing a minor role during swimming to developing into robust weight-bearing limbs. In addition, the pelvic fins/hindlimbs have been lost repeatedly in diverse species over evolutionary time. Here we review the evolution of pelvic fins and hindlimbs within the context of the changes in anatomical structure and the molecular mechanisms involved. PMID:22913749

Working conditions at hospital food service and the development of venous disease of lower limbs.

PubMed

da Luz, Clarissa Medeiros; da Costa Proença, Rossana Pacheco; de Salazar, Begoña Rodriguez Ortiz; do Nascimento Galego, Gilberto

2013-12-01

The present study assesses some factors that may influence the development of lower limb venous disease in workers of a hospital food service unit. An Ergonomic analysis of work was carried out at a hospital located in the south of Brazil. As for data collection, the following were used: interviews and body mass index assessment; specific clinical examination to diagnose venous disease, water displacement volumetry of the lower limbs. The activities performed at the workplace were followed by direct observation with image registration, use of pedometers, stopwatches, decibel meter, and digital thermo-hygrometer. It was observed different degrees of venous disease in 78% of the cases investigated. The volumetric variation of the lower limbs was 5.13%, showing the presence of edema. Working in hospital food service is associated with circulatory disorders of lower limbs, such as edema and venous disease. The following risk factors were identified: standing activities at work during a long period of time, high temperature, and humidity and carrying heavy weights.

Golf and upper limb injuries: a summary and review of the literature

PubMed Central

McHardy, Andrew J; Pollard, Henry P

2005-01-01

Background Golf is a popular past time that provides exercise with social interaction. However, as with all sports and activities, injury may occur. Many golf-related injuries occur in the upper limb, yet little research on the potential mechanisms of these injuries has been conducted. Objective To review the current literature on golf-related upper limb injuries and report on potential causes of injury as it relates to the golf swing. Discussion An overview of the golf swing is described in terms of its potential to cause the frequently noted injuries. Most injuries occur at impact when the golf club hits the ball. This paper concludes that more research into golf-related upper limb injuries is required to develop a thorough understanding of how injuries occur. Types of research include epidemiology studies, kinematic swing analysis and electromyographic studies of the upper limb during golf. By conducting such research, preventative measures maybe developed to reduce golf related injury. PMID:15967021

Assessing upper limb function in nonambulant SMA patients: development of a new module.

PubMed

Mazzone, Elena; Bianco, Flaviana; Martinelli, Diego; Glanzman, Allan M; Messina, Sonia; De Sanctis, Roberto; Main, Marion; Eagle, Michelle; Florence, Julaine; Krosschell, Kristin; Vasco, Gessica; Pelliccioni, Marco; Lombardo, Marilena; Pane, Marika; Finkel, Richard; Muntoni, Francesco; Bertini, Enrico; Mercuri, Eugenio

2011-06-01

We report the development of a module specifically designed for assessing upper limb function in nonambulant SMA patients, including young children and those with severe contractures. The application of the module to a preschool cohort of 40 children (age 30-48 months) showed that all the items could be completed by 30 months. The module was also used in 45 nonambulant SMA patients (age 30 months to 27 years). Their scores were more variable than in the preschool cohort, ranging from 0 to 18. The magnitude of scores was not related to age (r=-0.19). The upper limb scores had a good correlation with the Hammersmith Functional Motor Scale, r=0.75, but the upper limb function did not always strictly follow the overall gross motor function. These findings suggest that even some of the very weak nonambulant children possess upper limb skills that can be measured. Copyright © 2011 Elsevier B.V. All rights reserved.

Maximum voluntary joint torque as a function of joint angle and angular velocity: model development and application to the lower limb.

PubMed

Anderson, Dennis E; Madigan, Michael L; Nussbaum, Maury A

2007-01-01

Measurements of human strength can be important during analyses of physical activities. Such measurements have often taken the form of the maximum voluntary torque at a single joint angle and angular velocity. However, the available strength varies substantially with joint position and velocity. When examining dynamic activities, strength measurements should account for these variations. A model is presented of maximum voluntary joint torque as a function of joint angle and angular velocity. The model is based on well-known physiological relationships between muscle force and length and between muscle force and velocity and was tested by fitting it to maximum voluntary joint torque data from six different exertions in the lower limb. Isometric, concentric and eccentric maximum voluntary contractions were collected during hip extension, hip flexion, knee extension, knee flexion, ankle plantar flexion and dorsiflexion. Model parameters are reported for each of these exertion directions by gender and age group. This model provides an efficient method by which strength variations with joint angle and angular velocity may be incorporated into comparisons between joint torques calculated by inverse dynamics and the maximum available joint torques.

Three-dimensional, automated, real-time video system for tracking limb motion in brain-machine interface studies.

PubMed

Peikon, Ian D; Fitzsimmons, Nathan A; Lebedev, Mikhail A; Nicolelis, Miguel A L

2009-06-15

Collection and analysis of limb kinematic data are essential components of the study of biological motion, including research into biomechanics, kinesiology, neurophysiology and brain-machine interfaces (BMIs). In particular, BMI research requires advanced, real-time systems capable of sampling limb kinematics with minimal contact to the subject's body. To answer this demand, we have developed an automated video tracking system for real-time tracking of multiple body parts in freely behaving primates. The system employs high-contrast markers painted on the animal's joints to continuously track the three-dimensional positions of their limbs during activity. Two-dimensional coordinates captured by each video camera are combined and converted to three-dimensional coordinates using a quadratic fitting algorithm. Real-time operation of the system is accomplished using direct memory access (DMA). The system tracks the markers at a rate of 52 frames per second (fps) in real-time and up to 100fps if video recordings are captured to be later analyzed off-line. The system has been tested in several BMI primate experiments, in which limb position was sampled simultaneously with chronic recordings of the extracellular activity of hundreds of cortical cells. During these recordings, multiple computational models were employed to extract a series of kinematic parameters from neuronal ensemble activity in real-time. The system operated reliably under these experimental conditions and was able to compensate for marker occlusions that occurred during natural movements. We propose that this system could also be extended to applications that include other classes of biological motion.

What is the price for the Duchenne gait pattern in patients with cerebral palsy?

PubMed

Salami, Firooz; Niklasch, Mirjam; Krautwurst, Britta K; Dreher, Thomas; Wolf, Sebastian I

2017-10-01

Duchenne gait is characterized by trunk lean towards the affected stance limb with the pelvis stable or elevated on the swinging limb side during single limb stance phase. We assessed the relationship between hip abduction moments and trunk kinetics in patients with cerebral palsy showing excessive lateral trunk motion. Data of 18 subjects with bilateral spastic cerebral palsy (CP) and 20 aged matched typically developing subjects (TD) were collected retrospectively. Criteria for patient selection were barefoot walking without aid presenting with excessive lateral trunk motion. Subjects had been monitored by conventional 3D gait analysis of the lower extremity including four markers for monitoring trunk motion. Post-hoc, a generic musculoskeletal full body model (OpenSim 3.3) assuming a rigid trunk articulated to the pelvis by a single ball joint was applied for analyzing joint kinematics and kinetics of the lower limb joints including this spine joint. Joint angle ranges of motion, maximum joint moments and powers in the frontal plane as well as mechanical work were calculated and averaged within groups showing prominent differences between groups in all parameters. To the best of our knowledge, this is the first work explicitly looking into the kinetics of Duchenne gait in patients with CP, clinically known as compensation for unloading hip abductor muscles. The results show that excessive lateral trunk motion may indeed be an extremely effective compensation mechanism to unload the hip abductors in single limb stance but for the price of a drastic increase in demand on trunk muscle effort and work. Copyright © 2017 Elsevier B.V. All rights reserved.

Can new technologies improve upper limb performance in grown-up diplegic children?

PubMed

Turconi, Anna C; Biffi, Emilia; Maghini, Cristina; Peri, Elisabetta; Servodio Iammarone, Fernanda; Gagliardi, Chiara

2016-10-01

Few systematic studies describe rehabilitation trainings for upper limb in diplegic children with cerebral palsy (CP), who - especially once grown up - are often not considered as a target for rehabilitation interventions. In this pilot study, we describe the details and the effectiveness of an intensive, technology assisted intervention for upper limb. The treatment combines the utilization of Armeo® Spring with a training focused on hand/finger fluency and dexterity in a pre-post treatment experimental design. Participants were ten school-aged children (mean age 11.2) with bilateral CP and diplegia, attending mainstream schools. Participants underwent 40 therapy sessions in four weeks. Armeo® Spring measures, standardized motor and perceptual outcome indexes, as well as everyday life indicators were utilized to assess the effect of the intervention. Upper limb coordination, fluency and quality of movements mainly of hands and fingers significantly improved, with a good transferability to everyday life also in areas not specifically trained, such as self-care abilities and mobility. Probably due to the visual feedback provided by the virtual reality setting (which was all in one the context, the incentive and the product of activities), perceptual abilities significantly improved, too. Our study suggests the importance of intervention on upper limb even in milder CP diplegic forms and in relatively grown-up children. The possibility of modification at least partially relies on learning processes that are active all along development and benefit from stimulation. Though further studies with control groups and follow-up perspective are needed to confirm, new technologies offer interesting possibilities to be integrated into new evidence-based rehabilitation models.

Posttraumatic Oedema in Lower Limbs. Advances in Understanding Etiopathogenesis and Treatment. Review Article.

PubMed

Waśko, Marcin K; Langner, Maciej; Pomianowski, Stanisław

2016-11-30

Mechanical injury to soft tissues and bones of the lower limbs may be complicated by thrombosis and oedema. Treatment of posttraumatic oedema in the lower limbs can be difficult and protracted and rarely leads to complete recovery. The pathogenesis of posttraumatic oedema has not been fully elucidated. This paper presents the aetiopathogenesis of posttraumatic oedema in the lower limbs and a review of relevant literature in English and Polish of the last 5 years, describing therapy outcomes and potential perspectives for develop ment.

Skeletal muscle contractile properties in a novel murine model for limb girdle muscular dystrophy 2i.

PubMed

Rehwaldt, Jordan D; Rodgers, Buel D; Lin, David C

2017-12-01

Limb-girdle muscular dystrophy (LGMD) 2i results from mutations in fukutin-related protein and aberrant α-dystroglycan glycosylation. Although this significantly compromises muscle function and ambulation, the comprehensive characteristics of contractile dysfunction are unknown. Therefore, we quantified the in situ contractile properties of the medial gastrocnemius in young adult P448L mice, an affected muscle of a novel model of LGMD2i. Normalized maximal twitch force, tetanic force, and power were significantly smaller in P448L mice, compared with sex-matched, wild-type mice. These differences were consistent with the replacement of contractile fibers by passive tissue. The shape of the active force-length relationships were similar in both groups, regardless of sex, consistent with an intact sarcomeric structure in P448L mice. Passive force-length curves normalized to maximal isometric force were steeper in P448L mice, and passive elements contribute disproportionately more to total contractile force in P448L mice. Sex differences were mostly noted in the force-velocity curves, as normalized values for maximal and optimal velocities were significantly slower in P448L males, compared with wild-type, but not in P448L females. This suggests that the dystrophic phenotype, which may include possible changes in cross-bridge kinetics and fiber-type proportions, progresses more quickly in P448L males. These results together indicate that active force and power generation are compromised in both sexes of P448L mice, while passive forces increase. More importantly, the results identified several functional markers of disease pathophysiology that could aid in developing and assessment of novel therapeutics for LGMD2i and possibly other dystroglycanopathies as well. NEW & NOTEWORTHY Comprehensive assessments of muscle contractile function have, until now, never been performed in an animal model for any dystroglycanopathy. This study suggests that skeletal muscle contractile properties are significantly compromised in a recently developed model for limb-girdle muscular dystrophy 2i, the P448L mouse. It further identifies novel pathological markers of muscle function that are suitable for developing therapeutics and for better understanding of disease pathogenesis.

Risk of fall-related injury in people with lower limb amputations: A prospective cohort study.

PubMed

Wong, Christopher Kevin; Chihuri, Stanford T; Li, Guohua

2016-01-01

To assess fall-related injury risk and risk factors in people with lower limb amputation. Prospective longitudinal cohort with follow-up every 6 months for up to 41 months. Community-dwelling adults with lower limb amputations of any etiology and level recruited from support groups and prosthetic clinics. Demographic and clinical characteristics were obtained by self-reported questionnaire and telephone or in-person follow-up. Fall-related injury incidence requiring medical care per person-month and adjusted hazard ratio of fall-related injury were calculated using multivariable proportional hazards regression modeling. A total of 41 subjects, with 782 follow-up person-months in total, had 11 fall-related injury incidents (14.1/1,000 person-months). During follow-up, 56.1% of subjects reported falling and 26.8% reported fall-related injury. Multivariable proportional hazard modeling showed that women were nearly 6 times more likely as men to experience fall-related injury and people of non-white race were 13 times more likely than people of white race to experience fall-related injury. The final predictive model also included vascular amputation and age. Risk of fall-related injury requiring medical care in people with lower limb amputation appears to be higher than in older adult inpatients. Intervention programs to prevent fall-related injury in people with lower limb amputation should target women and racial minorities.

Body size and lower limb posture during walking in humans

PubMed Central

Hora, Martin; Soumar, Libor; Pontzer, Herman; Sládek, Vladimír

2017-01-01

We test whether locomotor posture is associated with body mass and lower limb length in humans and explore how body size and posture affect net joint moments during walking. We acquired gait data for 24 females and 25 males using a three-dimensional motion capture system and pressure-measuring insoles. We employed the general linear model and commonality analysis to assess the independent effect of body mass and lower limb length on flexion angles at the hip, knee, and ankle while controlling for sex and velocity. In addition, we used inverse dynamics to model the effect of size and posture on net joint moments. At early stance, body mass has a negative effect on knee flexion (p < 0.01), whereas lower limb length has a negative effect on hip flexion (p < 0.05). Body mass uniquely explains 15.8% of the variance in knee flexion, whereas lower limb length uniquely explains 5.4% of the variance in hip flexion. Both of the detected relationships between body size and posture are consistent with the moment moderating postural adjustments predicted by our model. At late stance, no significant relationship between body size and posture was detected. Humans of greater body size reduce the flexion of the hip and knee at early stance, which results in the moderation of net moments at these joints. PMID:28192522

Functional analysis of limb enhancers in the developing fin

PubMed Central

Booker, Betty M.; Murphy, Karl K.

2013-01-01

Despite diverging ~365 million years ago, tetrapod limbs and pectoral fins express similar genes that could be regulated by shared regulatory elements. In this study, we set out to analyze the ability of enhancers to maintain tissue specificity in these two divergent structures. We tested 22 human sequences that were previously reported as mouse limb enhancers for their enhancer activity in zebrafish (Danio rerio). Using a zebrafish enhancer assay, we found that 10/22 (45 %) were positive for pectoral fin activity. Analysis of the various criteria that correlated with positive fin activity found that both spatial limb activity and evolutionary conservation are not good predictors of fin enhancer activity. These results suggest that zebrafish enhancer assays may be limited in detecting human limb enhancers, and this limitation does not improve by the use of limb spatial expression or evolutionary conservation. PMID:24068387

Slow Movements of Bio-Inspired Limbs

NASA Astrophysics Data System (ADS)

Babikian, Sarine; Valero-Cuevas, Francisco J.; Kanso, Eva

2016-10-01

Slow and accurate finger and limb movements are essential to daily activities, but the underlying mechanics is relatively unexplored. Here, we develop a mathematical framework to examine slow movements of tendon-driven limbs that are produced by modulating the tendons' stiffness parameters. Slow limb movements are driftless in the sense that movement stops when actuations stop. We demonstrate, in the context of a planar tendon-driven system representing a finger, that the control of stiffness suffices to produce stable and accurate limb postures and quasi-static (slow) transitions among them. We prove, however, that stable postures are achievable only when tendons are pretensioned, i.e., they cannot become slack. Our results further indicate that a non-smoothness in slow movements arises because the precision with which individual stiffnesses need to be altered changes substantially throughout the limb's motion.

Growth and differentiation of mammalian embryonic tissues exposed to hypergravity in vivo and in vitro

NASA Technical Reports Server (NTRS)

Duke, J.; Janer, L.; Moore, J.

1985-01-01

Decreased cartilage areas in embryonic limbs developing under excess g in vitro, is reported, as well as delayed skeletal development in embryos and fetuses exposed to excess g in utero. 12.5-day mouse limb buds were cultured at 2.6 g, and fixed at two days and six days of culture. In vivo experiments used alizarin-stained 18-day fetuses exposed to 2.3 g. In all studies, cartilage areas were determined using a digitized tablet. Form factor analysis determined that the main effect of in vitro centrifugation was a reduction in length of the limb elements, probably due to the precocious chondrogenesis seen in the upper regions of centrifuged limbs. Similar reductions in length of ossified areas was seen in the in utero studies.

Vertical Distribution of Aerosols and Water Vapor Using CRISM Limb Observations

NASA Astrophysics Data System (ADS)

Smith, M. D.; Wolff, M. J.; Clancy, R. T.; CRISM Science; Operations Teams

2011-12-01

Near-infrared spectra taken in a limb-viewing geometry by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on-board the Mars Reconnaissance Orbiter (MRO) provide a useful tool for probing atmospheric structure. Specifically, the observed radiance as a function of wavelength and height above the limb allows the vertical distribution of both dust and ice aerosols to be retrieved. These data serve as an important supplement to the aerosol profiling provided by the MRO/MCS instrument allowing independent validation and giving additional information on particle physical and scattering properties through multi-wavelength studies. A total of at least ten CRISM limb observations have been taken so far covering a full Martian year. Each set of limb observations nominally contains about four dozen scans across the limb giving pole-to-pole coverage for two orbits at roughly 100 and 290 W longitude over the Tharsis and Syrtis/Hellas regions, respectively. At each longitude, limb scans are spaced roughly 10 degrees apart in latitude, with a vertical spatial resolution on the limb of roughly 800 m. Radiative transfer modeling is used to model the observations. We compute synthetic CRISM limb spectra using a discrete-ordinates radiative transfer code that accounts for multiple scattering from aerosols and accounts for spherical geometry of the limb observations by integrating the source functions along curved paths in that coordinate system. Retrieved are 14-point vertical profiles for dust and water ice aerosols with resolution of 0.4 scale heights between one and six scale heights above the surface. After the aerosol retrieval is completed, the abundances of CO2 (or surface pressure) and H2O gas are retrieved by matching the depth of absorption bands at 2000 nm for carbon dioxide and at 2600 nm for water vapor. In addition to the column abundance of water vapor, limited information on its vertical structure can also be retrieved depending on the signal available from aerosol scattering. Significant differences are seen in the retrieved vertical profiles of dust and water ice as a function of season. Dust typically extends to higher altitudes during the perihelion season. Ice aerosols are often observed to cap the dust layer during all seasons. Water vapor is observed to be deeply mixed in the perihelion season and confined near the surface in the aphelion season. The CRISM limb-geometry observations support the quantitative retrieval of aerosol and gas vertical profiles. These quantities cannot be retrieved using nadir observations, and they enable the study of important new science questions. The CRISM limbs also serve as a valuable supplement to the MRO/MCS limb profiles, enabling validation and multi-wavelength comparisons. Additional CRISM limb-geometry sets will continue to be taken approximately every two months (~30 degrees of Ls) as operations allow.

Comparative genomic analysis of the false killer whale (Pseudorca crassidens) LMBR1 locus.

PubMed

Kim, Dae-Won; Choi, Sang-Haeng; Kim, Ryong Nam; Kim, Sun-Hong; Paik, Sang-Gi; Nam, Seong-Hyeuk; Kim, Dong-Wook; Kim, Aeri; Kang, Aram; Park, Hong-Seog

2010-09-01

The sequencing and comparative genomic analysis of LMBR1 loci in mammals or other species, including human, would be very important in understanding evolutionary genetic changes underlying the evolution of limb development. In this regard, comparative genomic annotation of the false killer whale LMBR1 locus could shed new light on the evolution of limb development. We sequenced two false killer whale BAC clones, corresponding to 156 kb and 144 kb, respectively, harboring the tightly linked RNF32, LMBR1, and NOM1 genes. Our annotation of the false killer whale LMBR1 gene showed that it consists of 17 exons (1473 bp), in contrast to 18 exons (1596 bp) in human, and it displays 93.1% and 95.6% nucleotide and amino acid sequence similarity, respectively, compared with the human gene. In particular, we discovered that exon 10, deleted in the false killer whale LMBR1 gene, is present only in primates, and this fact strongly implies that exon 10 might be crucial in determining primate-specific limb development. ZRS and TFBS sequences have been well conserved across 11 species, suggesting that these regions could be involved in an important function of limb development and limb patterning. The neighboring gene RNF32 showed several lineage-conserved exons, such as exons 2 through 9 conserved in eutherian mammals, exons 3 through 9 conserved in mammals, and exons 5 through 9 conserved in vertebrates. The other neighboring gene, NOM1, had undergone a substitution (ATG→GTA) at the start codon, giving rise to a 36 bp shorter N-terminal sequence compared with the human sequence. Our comparative analysis of the false killer whale LMBR1 genomic locus provides important clues regarding the genetic regions that may play crucial roles in limb development and patterning.

Phosphorylation of Lbx1 controls lateral myoblast migration into the limb.

PubMed

Masselink, Wouter; Masaki, Megumi; Sieiro, Daniel; Marcelle, Christophe; Currie, Peter D

2017-10-15

The migration of limb myogenic precursors from limb level somites to their ultimate site of differentiation in the limb is a paradigmatic example of a set of dynamic and orchestrated migratory cell behaviours. The homeobox containing transcription factor ladybird homeobox 1 (Lbx1) is a central regulator of limb myoblast migration, null mutations of Lbx1 result in severe disruptions to limb muscle formation, particularly in the distal region of the limb in mice (Gross et al., 2000). As such Lbx1 has been hypothesized to control lateral migration of myoblasts into the distal limb anlage. It acts as a core regulator of the limb myoblast migration machinery, controlled by Pax3. A secondary role for Lbx1 in the differentiation and commitment of limb musculature has also been proposed (Brohmann et al., 2000; Uchiyama et al., 2000). Here we show that lateral migration, but not differentiation or commitment of limb myoblasts, is controlled by the phosphorylation of three adjacent serine residues of LBX1. Electroporation of limb level somites in the chick embryo with a dephosphomimetic form of Lbx1 results in a specific defect in the lateral migration of limb myoblasts. Although the initial delamination and migration of myoblasts is unaffected, migration into the distal limb bud is severely disrupted. Interestingly, myoblasts undergo normal differentiation independent of their migratory status, suggesting that the differentiation potential of hypaxial muscle is not regulated by the phosphorylation state of LBX1. Furthermore, we show that FGF8 and ERK mediated signal transduction, both critical regulators of the developing limb bud, have the capacity to induce the phosphorylation of LBX1 at these residues. Overall, this suggests a mechanism whereby the phosphorylation of LBX1, potentially through FGF8 and ERK signalling, controls the lateral migration of myoblasts into the distal limb bud. Copyright © 2017. Published by Elsevier Inc.

[Study on the center-driven multiple degrees of freedom upper limb rehabilitation training robot].

PubMed

Huang, Xiaohai; Yu, Hongliu; Wang, Jinchao; Dong, Qi; Zhang, Linling; Meng, Qiaoling; Li, Sujiao; Wang, Duojin

2018-03-01

With the aging of the society, the number of stroke patients has been increasing year by year. Compared with the traditional rehabilitation therapy, the application of upper limb rehabilitation robot has higher efficiency and better rehabilitation effect, and has become an important development direction in the field of rehabilitation. In view of the current development status and the deficiency of upper limb rehabilitation robot system, combined with the development trend of all kinds of products of the upper limb rehabilitation robot, this paper designed a center-driven upper limb rehabilitation training robot for cable transmission which can help the patients complete 6 degrees of freedom (3 are driven, 3 are underactuated) training. Combined the structure of robot with more joints rehabilitation training, the paper choosed a cubic polynomial trajectory planning method in the joint space planning to design two trajectories of eating and lifting arm. According to the trajectory equation, the movement trajectory of each joint of the robot was drawn in MATLAB. It laid a foundation for scientific and effective rehabilitation training. Finally, the experimental prototype is built, and the mechanical structure and design trajectories are verified.

COMPARING THE EFFECTS OF RETINOIC ACID ON AMPHIBIAN LIMB DEVELOPMENT AND LETHALITY: CHRONIC EXPOSURE RESULTS IN LETHALITY NOT LIMB MALFORMATIONS

EPA Science Inventory

Recently, high frequencies of malformations have been reported in amphibians across the United States. It has been suggested that the malformations may be the result of xenobiotic disruption of retinoid signaling pathways during embryogenesis and tadpole development. Therefore, a...

Effective Work Procedure design Using Discomfort and Effort Factor in Brick stacking operation-A case study

NASA Astrophysics Data System (ADS)

Rout, Biswaranjan; Dash, R. R.; Dhupal, D.

2018-02-01

In this work a typical planning of movement of limbs and torso of the worker to be well design to reduce fatigue and energy of the worker. A simulation model is generated to suit the procedure and comply with the constraints in the workspace. It requires verifying the capability of human postures and movements in different working conditions for the evaluation of effectiveness of the new design. In this article a simple human performance measure is introduce that enable the mathematical model for evaluation of a cost function. The basic scheme is to evaluate the performance in the form of several cost factors using AI techniques. Here two main cost factors taken in to consideration are discomfort factor and effort factor in limb movements. Discomfort factor measures the level of discomfort from the most neutral position of a given limb to the position of the corresponding limb after movement and effort factor is a measure of the displacement of the corresponding limbs from the original position. The basic aim is to optimize the movement of the limbs with the above mentioned cost functions. The effectiveness of the procedure is tested with an example of working procedure of workers used for stacking of fly ash bricks in a local fly ash bricks manufacturing unit. The objective is to find out the optimised movement of the limbs to reduce discomfort level and effort required of workers. The effectiveness of the procedure in this case study illustrated with the obtained results.

Fasciotomy worsens the amount of myonecrosis in a porcine model of crotaline envenomation.

PubMed

Tanen, David A; Danish, David C; Grice, Guerard A; Riffenburgh, Robert H; Clark, Richard F

2004-08-01

We evaluate the efficacy of fasciotomy or crotaline snake antivenom in reducing myonecrosis. We used a randomized, blinded, controlled acute animal preparation. Twenty anesthetized swine were injected intramuscularly in the anterior tibiales muscle of both hind limbs with 6 mg/kg of Crotalus atrox venom (total of 12 mg/kg of venom per animal). Immediately after venom injection, the right hind limb underwent fasciotomy. Muscle biopsies were obtained from the fasciotomized hind limb at 0, 4, and 8 hours and from the other hind limb at the conclusion of the study (8 hours). In addition, animals received either 8 vials of reconstituted Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) or an equal volume of normal saline solution intravenously 1 hour after venom injection. A pathologist blinded to the study determined the percentage of myonecrotic cells in each biopsy. Statistical analysis was performed using repeated measures analysis of variance for compartment pressure. Rank-order methods were used for comparison of myonecrosis between groups. Biopsies from hind limbs undergoing fasciotomy revealed a progressive increase in the amount of myonecrosis over time (myonecrosis median at 0, 4, or 8 hours [or death]: 0%, 14%, or 14.5%, respectively; P<.001). Comparison of the amount of myonecrosis of biopsies at death or 8 hours revealed that limbs that underwent fasciotomy had significantly more myonecrosis than those that did not (myonecrosis median: 14.5% versus 2.5%, P=.048). No difference was detected in the amount of myonecrosis when FabAV was compared with normal saline solution on final biopsies from either fasciotomy or nonfasciotomy hind limb (myonecrosis median: 10.0% versus 10.0%, P=.64). Fasciotomy significantly worsens the amount of myonecrosis in a porcine model of intramuscular crotaline venom injection. No change in the amount of myonecrosis was detected with the use of FabAV treatment at the dosages used in this animal model.

Transplantation of dedifferentiated fat cell-derived micromass pellets contributed to cartilage repair in the rat osteochondral defect model.

PubMed

Shimizu, Manabu; Matsumoto, Taro; Kikuta, Shinsuke; Ohtaki, Munenori; Kano, Koichiro; Taniguchi, Hiroaki; Saito, Shu; Nagaoka, Masahiro; Tokuhashi, Yasuaki

2018-03-20

Mature adipocyte-derived dedifferentiated fat (DFAT) cells possesses the ability to proliferate effectively and the potential to differentiate into multiple linages of mesenchymal tissue; similar to adipose-derived stem cells (ASCs). The purpose of this study is to examine the effects of DFAT cell transplantation on cartilage repair in a rat model of osteochondral defects. Full-thickness osteochondral defects were created in the knees of Sprague-Dawley rats bilaterally. Cartilage-like micromass pellets were prepared from green fluorescent protein (GFP)-labeled rat DFAT cells and subsequently transplanted into the affected right knee of these rats. Defects in the left knee were used as a control. Macroscopic and microscopic changes of treated and control defects were evaluated up to 12 weeks post-treatment with DFAT cells. To observe the transplanted cells, sectioned femurs were immunostained for GFP and type II collagen. DFAT cells formed micromass pellets expressing characteristics of immature cartilage in vitro. In the DFAT cell-transplanted limbs, the defects were completely filled with white micromass pellets as early as 2 weeks post-treatment. These limbs became smooth at 4 weeks. Conversely, the defects in the control limbs were still not repaired by 4 weeks. Macroscopic ICRS scores at 2 and 4 weeks were significantly higher in the DFAT cells-transplanted limbs compared to those of the control limbs. The modified O'Driscol histological scores for the DFAT cell-transplanted limbs were significantly higher than those of the control limbs at corresponding time points. GFP-positive DAFT cells were detected in the transplanted area at 2 weeks but hardly visible at 12 weeks post-operation. Transplantation of DFAT cell-derived micromass pellets contribute to cartilage repair in a rat osteochondral defect model. DFAT cell transplantation may be a viable therapeutic strategy for the repair of osteochondral injuries. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Development of five digits is controlled by a bipartite long-range cis-regulator.

PubMed

Lettice, Laura A; Williamson, Iain; Devenney, Paul S; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E

2014-04-01

Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs.

Assessment and prediction of inter-joint upper limb movement correlations based on kinematic analysis and statistical regression

NASA Astrophysics Data System (ADS)

Toth-Tascau, Mirela; Balanean, Flavia; Krepelka, Mircea

2013-10-01

Musculoskeletal impairment of the upper limb can cause difficulties in performing basic daily activities. Three dimensional motion analyses can provide valuable data of arm movement in order to precisely determine arm movement and inter-joint coordination. The purpose of this study was to develop a method to evaluate the degree of impairment based on the influence of shoulder movements in the amplitude of elbow flexion and extension based on the assumption that a lack of motion of the elbow joint will be compensated by an increased shoulder activity. In order to develop and validate a statistical model, one healthy young volunteer has been involved in the study. The activity of choice simulated blowing the nose, starting from a slight flexion of the elbow and raising the hand until the middle finger touches the tip of the nose and return to the start position. Inter-joint coordination between the elbow and shoulder movements showed significant correlation. Statistical regression was used to fit an equation model describing the influence of shoulder movements on the elbow mobility. The study provides a brief description of the kinematic analysis protocol and statistical models that may be useful in describing the relation between inter-joint movements of daily activities.

Bioelectric analyses of an osseointegrated intelligent implant design system for amputees.

PubMed

Isaacson, Brad M; Stinstra, Jeroen G; MacLeod, Rob S; Webster, Joseph B; Beck, James P; Bloebaum, Roy D

2009-07-15

The projected number of American amputees is expected to rise to 3.6 million by 2050. Many of these individuals depend on artificial limbs to perform routine activities, but prosthetic suspensions using traditional socket technology can prove to be cumbersome and uncomfortable for a person with limb loss. Moreover, for those with high proximal amputations, limited residual limb length may prevent exoprosthesis attachment all together. Osseointegrated implant technology is a novel operative procedure which allows firm skeletal attachment between the host bone and an implant. Preliminary results in European amputees with osseointegrated implants have shown improved clinical outcomes by allowing direct transfer of loads to the bone-implant interface. Despite the apparent advantages of osseointegration over socket technology, the current rehabilitation procedures require long periods of restrictive load bearing prior which may be reduced with expedited skeletal attachment via electrical stimulation. The goal of the osseointegrated intelligent implant design (OIID) system is to make the implant part of an electrical system to accelerate skeletal attachment and help prevent periprosthetic infection. To determine optimal electrode size and placement, we initiated proof of concept with computational modeling of the electric fields and current densities that arise during electrical stimulation of amputee residual limbs. In order to provide insure patient safety, subjects with retrospective computed tomography scans were selected and three dimensional reconstructions were created using customized software programs to ensure anatomical accuracy (Seg3D and SCIRun) in an IRB and HIPAA approved study. These software packages supported the development of patient specific models and allowed for interactive manipulation of electrode position and size. Preliminary results indicate that electric fields and current densities can be generated at the implant interface to achieve the homogenous electric field distributions required to induce osteoblast migration, enhance skeletal fixation and may help prevent periprosthetic infections. Based on the electrode configurations experimented with in the model, an external two band configuration will be advocated in the future.

A Nonlinear Dynamics-Based Estimator for Functional Electrical Stimulation: Preliminary Results From Lower-Leg Extension Experiments.

PubMed

Allen, Marcus; Zhong, Qiang; Kirsch, Nicholas; Dani, Ashwin; Clark, William W; Sharma, Nitin

2017-12-01

Miniature inertial measurement units (IMUs) are wearable sensors that measure limb segment or joint angles during dynamic movements. However, IMUs are generally prone to drift, external magnetic interference, and measurement noise. This paper presents a new class of nonlinear state estimation technique called state-dependent coefficient (SDC) estimation to accurately predict joint angles from IMU measurements. The SDC estimation method uses limb dynamics, instead of limb kinematics, to estimate the limb state. Importantly, the nonlinear limb dynamic model is formulated into state-dependent matrices that facilitate the estimator design without performing a Jacobian linearization. The estimation method is experimentally demonstrated to predict knee joint angle measurements during functional electrical stimulation of the quadriceps muscle. The nonlinear knee musculoskeletal model was identified through a series of experiments. The SDC estimator was then compared with an extended kalman filter (EKF), which uses a Jacobian linearization and a rotation matrix method, which uses a kinematic model instead of the dynamic model. Each estimator's performance was evaluated against the true value of the joint angle, which was measured through a rotary encoder. The experimental results showed that the SDC estimator, the rotation matrix method, and EKF had root mean square errors of 2.70°, 2.86°, and 4.42°, respectively. Our preliminary experimental results show the new estimator's advantage over the EKF method but a slight advantage over the rotation matrix method. However, the information from the dynamic model allows the SDC method to use only one IMU to measure the knee angle compared with the rotation matrix method that uses two IMUs to estimate the angle.

An official American Thoracic Society/European Respiratory Society statement: update on limb muscle dysfunction in chronic obstructive pulmonary disease.

PubMed

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P N Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N A; Janssens, Wim; Polkey, Micheal I; Roca, Josep; Saey, Didier; Schols, Annemie M W J; Spruit, Martijn A; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D

2014-05-01

Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed.

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

PubMed Central

Maltais, François; Decramer, Marc; Casaburi, Richard; Barreiro, Esther; Burelle, Yan; Debigaré, Richard; Dekhuijzen, P. N. Richard; Franssen, Frits; Gayan-Ramirez, Ghislaine; Gea, Joaquim; Gosker, Harry R.; Gosselink, Rik; Hayot, Maurice; Hussain, Sabah N. A.; Janssens, Wim; Polkey, Micheal I.; Roca, Josep; Saey, Didier; Schols, Annemie M. W. J.; Spruit, Martijn A.; Steiner, Michael; Taivassalo, Tanja; Troosters, Thierry; Vogiatzis, Ioannis; Wagner, Peter D.

2014-01-01

Background: Limb muscle dysfunction is prevalent in chronic obstructive pulmonary disease (COPD) and it has important clinical implications, such as reduced exercise tolerance, quality of life, and even survival. Since the previous American Thoracic Society/European Respiratory Society (ATS/ERS) statement on limb muscle dysfunction, important progress has been made on the characterization of this problem and on our understanding of its pathophysiology and clinical implications. Purpose: The purpose of this document is to update the 1999 ATS/ERS statement on limb muscle dysfunction in COPD. Methods: An interdisciplinary committee of experts from the ATS and ERS Pulmonary Rehabilitation and Clinical Problems assemblies determined that the scope of this document should be limited to limb muscles. Committee members conducted focused reviews of the literature on several topics. A librarian also performed a literature search. An ATS methodologist provided advice to the committee, ensuring that the methodological approach was consistent with ATS standards. Results: We identified important advances in our understanding of the extent and nature of the structural alterations in limb muscles in patients with COPD. Since the last update, landmark studies were published on the mechanisms of development of limb muscle dysfunction in COPD and on the treatment of this condition. We now have a better understanding of the clinical implications of limb muscle dysfunction. Although exercise training is the most potent intervention to address this condition, other therapies, such as neuromuscular electrical stimulation, are emerging. Assessment of limb muscle function can identify patients who are at increased risk of poor clinical outcomes, such as exercise intolerance and premature mortality. Conclusions: Limb muscle dysfunction is a key systemic consequence of COPD. However, there are still important gaps in our knowledge about the mechanisms of development of this problem. Strategies for early detection and specific treatments for this condition are also needed. PMID:24787074

Evidence of asymmetries in the Aldebaran photosphere from multiwavelength lunar occultations

NASA Astrophysics Data System (ADS)

Richichi, A.; Dyachenko, V.; Pandey, A. K.; Sharma, S.; Tasuya, O.; Balega, Y.; Beskakotov, A.; Rastegaev, D.; Dhillon, V. S.

2017-01-01

We have recorded three lunar occultations of Aldebaran (α Tau) at different telescopes and using various band-passes, from the ultraviolet to the far red. The data have been analysed using both model-dependent and model-independent methods. The derived uniform-disc angular diameter values have been converted to limb-darkened values using model atmosphere relations and are found in broad agreement among themselves and with previous literature values. The limb-darkened diameter is about 20.3 mas on average. However, we have found indications that the photospheric brightness profile of Aldebaran may have not been symmetric, a finding already reported by other authors for this and for similar late-type stars. At the sampling scale of our brightness profile, between 1 and 2 mas, the uniform and limb-darkened disc models may not be a good description for Aldebaran. The asymmetries appear to differ with wavelength and over the 137-d time span of our measurements. Surface spots appear as a likely explanation for the differences between observations and the models.

PARTICIPATORY DESIGN OF PEDIATRIC UPPER LIMB PROSTHESES: QUALITATIVE METHODS AND PROTOTYPING.

PubMed

Sims, Tara; Cranny, Andy; Metcalf, Cheryl; Chappell, Paul; Donovan-Hall, Maggie

2017-01-01

The study aims to develop an understanding of the views of children and adolescents, parents, and professionals on upper limb prosthetic devices to develop and improve device design. Previous research has found that children are dissatisfied with prostheses but has relied heavily on parent proxy reports and quantitative measures (such as questionnaires) to explore their views. Thirty-four participants (eight children aged 8-15 years with upper limb difference, nine parents, eight prosthetists, and nine occupational therapists) contributed to the development of new devices through the BRIDGE methodology of participatory design, using focus groups and interviews. The study identified areas for improving prostheses from the perspective of children and adolescents, developed prototypes based on these and gained feedback on the prototypes from the children and other stakeholders (parents and professionals) of paediatric upper limb prostheses. Future device development needs to focus on ease of use, versatility, appearance, and safety. This study has demonstrated that children and adolescents can and should be involved as equal partners in the development of daily living equipment and that rapid prototyping (three-dimensional printing or additive manufacturing), used within a participatory design framework, can be a useful tool for facilitating this.

Development of rehabilitation training support system for occupational therapy of upper limb motor function

NASA Astrophysics Data System (ADS)

Morita, Yoshifumi; Hirose, Akinori; Uno, Takashi; Uchid, Masaki; Ukai, Hiroyuki; Matsui, Nobuyuki

2007-12-01

In this paper we propose a new rehabilitation training support system for upper limbs. The proposed system enables therapists to quantitatively evaluate the therapeutic effect of upper limb motor function during training, to easily change the load of resistance of training and to easily develop a new training program suitable for the subjects. For this purpose we develop control algorithms of training programs in the 3D force display robot. The 3D force display robot has parallel link mechanism with three motors. The control algorithm simulating sanding training is developed for the 3D force display robot. Moreover the teaching/training function algorithm is developed. It enables the therapists to easily make training trajectory suitable for subject's condition. The effectiveness of the developed control algorithms is verified by experiments.

Measures of upper limb function for people with neck pain: a systematic review of measurement and practical properties (protocol).

PubMed

Alreni, Ahmad Salah Eldin; Harrop, Deborah; Gumber, Anil; McLean, Sionnadh

2015-04-07

Upper limb disability is a common musculoskeletal condition frequently associated with neck pain. Recent literature has reported the need to utilise validated upper limb outcome measures in the assessment and management of patients with neck pain. However, there is a lack of clear guidance about the suitability of available measures, which may impede utilisation. This review will identify all available measures of upper limb function developed for use in neck pain patients and evaluate their measurement and practical properties in order to identify those measures that are most appropriate for use in clinical practice and research. This review will be performed in two phases. Phase one will identify all measures used to assess upper limb function for patients with neck pain. Phase two will identify all available studies of the measurement and practical properties of identified instrument. The COnsensus-based Standards for selection of health Measurement INstrument (COSMIN) will be used to evaluate the methodological quality of the included studies. To ensure methodological rigour, the findings of this review will be reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline. Optimal management of patients with neck pain should incorporate upper limb rehabilitation. The findings of this study will assist clinicians who seek to utilise suitable and accurate measures to assess upper limb function for a patient with neck pain. In addition, the findings of this study may suggest new research directions to support the development of upper limb outcome measures for patients with neck pain. PROSPERO CRD42015016624.

Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from Maine, Minnesota, and Vermont suggest multiple etiologies

USGS Publications Warehouse

Meteyer, C.U.; Loeffler, I.K.; Fallon, J.F.; Converse, K.A.; Green, E.; Helgen, J.C.; Kersten, S.; Levey, R.; Eaton-Poole, L.; Burkhart, J.G.

2000-01-01

Background Reports of malformed frogs have increased throughout the North American continent in recent years. Most of the observed malformations have involved the hind limbs. The goal of this study was to accurately characterize the hind limb malformations in wild frogs as an important step toward understanding the possible etiologies. Methods During 1997 and 1998, 182 recently metamorphosed northern leopard frogs (Rana pipiens) were collected from Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of these frogs, which underwent necropsy and radiographic evaluation at the National Wildlife Health Center. These malformations are described in detail and classified into four major categories: (1) no limb (amelia); (2) multiple limbs or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly; and (4) distally complete but malformed limb (bone rotations, bridging, skin webbing, and micromelia). Results Amelia and reduced segments and/or elements were the most common finding. Frogs with bilateral hind limb malformations were not common, and in only eight of these 22 frogs were the malformations symmetrical. Malformations of a given type tended to occur in frogs collected from the same site, but the types of malformations varied widely among all three states, and between study sites within Minnesota. Conclusions Clustering of malformation type suggests that developmental events may produce a variety of phenotypes depending on the timing, sequence, and severity of the environmental insult. Hind limb malformations in free-living frogs transcend current mechanistic explanations of tetrapod limb development.

Kinematic analysis of the gait of adult sheep during treadmill locomotion: Parameter values, allowable total error, and potential for use in evaluating spinal cord injury.

PubMed

Safayi, Sina; Jeffery, Nick D; Shivapour, Sara K; Zamanighomi, Mahdi; Zylstra, Tyler J; Bratsch-Prince, Joshua; Wilson, Saul; Reddy, Chandan G; Fredericks, Douglas C; Gillies, George T; Howard, Matthew A

2015-11-15

We are developing a novel intradural spinal cord (SC) stimulator designed to improve the treatment of intractable pain and the sequelae of SC injury. In-vivo ovine models of neuropathic pain and moderate SC injury are being implemented for pre-clinical evaluations of this device, to be carried out via gait analysis before and after induction of the relevant condition. We extend previous studies on other quadrupeds to extract the three-dimensional kinematics of the limbs over the gait cycle of sheep walking on a treadmill. Quantitative measures of thoracic and pelvic limb movements were obtained from 17 animals. We calculated the total-error values to define the analytical performance of our motion capture system for these kinematic variables. The post- vs. pre-injury time delay between contralateral thoracic and pelvic-limb steps for normal and SC-injured sheep increased by ~24s over 100 steps. The pelvic limb hoof velocity during swing phase decreased, while range of pelvic hoof elevation and distance between lateral pelvic hoof placements increased after SC injury. The kinematics measures in a single SC-injured sheep can be objectively defined as changed from the corresponding pre-injury values, implying utility of this method to assess new neuromodulation strategies for specific deficits exhibited by an individual. Copyright © 2015 Elsevier B.V. All rights reserved.

Can the contralateral limb be used as a control during the growing period in a rodent model?

PubMed

Mustafy, Tanvir; Londono, Irène; Villemure, Isabelle

2018-05-12

The contralateral limb is often used as a control in various clinical, forensic and anthropological studies. However, no studies have been performed to determine if the contra-lateral limb is a suitable control during the bone development period. The aim of this study was to determine the bilateral symmetry of growing rat tibiae in terms of geometric shape, mechanical strength and bone morphological parameters with developmental stages. Left and right tibias of 18 male Sprague-Dawley rats at 4, 8 and 12 weeks of age were scanned with micro-CT for bone-morphometric evaluation and for 3D deviation analysis to quantify the geometric shape variations between left and right tibiae. Overall tibial lengths and curvatures were also measured, and bone mechanical strength was investigated using three-point bending tests. Deviation distributions between bilateral tibiae remained below 0.5 mm for more than 80% of the geometry for all groups. Tibial lengths, longitudinal tibial curvatures, bone-morphometric parameters and mechanical strengths changed significantly during the growing period but kept a strong degree of symmetry between bilateral tibiae. These results suggest that bilateral tibiae can be considered symmetrical in nature and that contralateral limb can be used as a control during the growing period in different experimental scenarios. Copyright © 2018 Elsevier Ltd. All rights reserved.

Apparent motion perception in lower limb amputees with phantom sensations: "obstacle shunning" and "obstacle tolerance".

PubMed

Saetta, Gianluca; Grond, Ilva; Brugger, Peter; Lenggenhager, Bigna; Tsay, Anthony J; Giummarra, Melita J

2018-03-21

Phantom limbs are the phenomenal persistence of postural and sensorimotor features of an amputated limb. Although immaterial, their characteristics can be modulated by the presence of physical matter. For instance, the phantom may disappear when its phenomenal space is invaded by objects ("obstacle shunning"). Alternatively, "obstacle tolerance" occurs when the phantom is not limited by the law of impenetrability and co-exists with physical objects. Here we examined the link between this under-investigated aspect of phantom limbs and apparent motion perception. The illusion of apparent motion of human limbs involves the perception that a limb moves through or around an object, depending on the stimulus onset asynchrony (SOA) for the two images. Participants included 12 unilateral lower limb amputees matched for obstacle shunning (n = 6) and obstacle tolerance (n = 6) experiences, and 14 non-amputees. Using multilevel linear models, we replicated robust biases for short perceived trajectories for short SOA (moving through the object), and long trajectories (circumventing the object) for long SOAs in both groups. Importantly, however, amputees with obstacle shunning perceived leg stimuli to predominantly move through the object, whereas amputees with obstacle tolerance perceived leg stimuli to predominantly move around the object. That is, in people who experience obstacle shunning, apparent motion perception of lower limbs was not constrained to the laws of impenetrability (as the phantom disappears when invaded by objects), and legs can therefore move through physical objects. Amputees who experience obstacle tolerance, however, had stronger solidity constraints for lower limb apparent motion, perhaps because they must avoid co-location of the phantom with physical objects. Phantom limb experience does, therefore, appear to be modulated by intuitive physics, but not in the same way for everyone. This may have important implications for limb experience post-amputation (e.g., improving prosthesis embodiment when limb representation is constrained by the same limits as an intact limb). Copyright © 2018 Elsevier Ltd. All rights reserved.

A Search for Mountain Waves in MLS Stratospheric Limb Radiances from the Winter Northern Hemisphere: Data Analysis and Global Mountain Wave Modeling

DTIC Science & Technology

2004-02-11

the general circulation of the middle atmosphere, Philos. Trans. R. Soc. London, Ser. A, 323, 693–705. Anton , H. (2000), Elementary Linear Algebra ...Because the saturated radiances may depend slightly on tangent height as the limb path length decreases, a linear trend (described by parameters a and b...track days and interpolated onto the same limb-track orbits. The color bar scale for radiance variance is linear . (b) Digital elevations of northern

[A Case of Middle Cerebral Artery Stenosis Presented with Limb-Shaking TIA].

PubMed

Uno, Junji; Mineta, Haruyuki; Ren, Nice; Takagishi, Sou; Nagaoka, Shintarou; Kameda, Katsuharu; Maeda, Kazushi; Ikai, Yoshiaki; Gi, Hidefuku

2016-07-01

Involuntary movement is a rare clinical manifestation of transient ischemic attack (TIA). However, limb-shaking TIA is well described presentation of carotid occlusive disease. We present the case of a patient who developed limb-shaking TIA associated with high-grade stenosis of middle cerebral artery (M1), which was treated with percutaneous transluminal angioplasty (PTA). The procedure was performed successfully without complication and the symptom disappeared immediately after the procedure. The patient remained free of symptoms at the 38-month follow-up. There was no tendency of restenosis of M1. In this case, PTA was technically feasible and beneficial for limb-shaking TIA with M1 stenosis. Limb-shaking TIA can be a symptom of high-grade stenosis of M1.

Hang Them High: A Hands-Free Technique for Upper Extremity Limb Holding During Surgical Preparation.

PubMed

Aneja, Arun; Leung, Patrick; Marquez-Lara, Alejandro

Lifting and holding upper and lower limbs during the "prep and drape" portion of certain orthopaedic procedures exert strong forces on the holder and may lead to musculoskeletal disorders. To address these challenges during upper extremity procedures, this article describes a hand-free elevation and traction technique of the upper limbs during preoperative skin preparation with the use of items readily available within the operating room (OR). This technique is particularly useful for heavy or fractured limbs that may impose a physical challenge to lift and maintain in a stable position. Implementation of this technique reduces the risk to nurses, OR personnel, and caregivers of developing work-related musculoskeletal injuries while lifting and holding limbs in the orthopaedic OR.

Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb.

PubMed

Gamer, L W; Cox, K A; Small, C; Rosen, V

2001-01-15

GDF11, a new member of the TGF-beta gene superfamily, regulates anterior/posterior patterning in the axial skeleton during mouse embryogenesis. Gdf11 null mice display skeletal abnormalities that appear to represent anterior homeotic transformations of vertebrae consistent with high levels of Gdf11 expression in the primitive streak, presomitic mesoderm, and tail bud. However, despite strong Gdf11 expression in the limb throughout development, this structure does not appear to be affected in the knockout mice. In order to understand this dichotomy of Gdf11 expression versus Gdf11 function, we identified the chicken Gdf11 gene and studied its role during limb formation. In the early limb bud, Gdf11 transcripts are detected in the subectodermal mesoderm at the distal tip, in a region overlapping the progress zone. At these stages, Gdf11 is excluded from the central core mesenchyme where precartilaginous condensations will form. Later in development, Gdf11 continues to be expressed in the distal most mesenchyme and can also be detected more proximally, in between the forming skeletal elements. When beads incubated in GDF11 protein were implanted into the early wing bud, GDF11 caused severe truncations of the limb that affected both the cartilage elements and the muscle. Limb shortening appeared to be the result of an inhibition of chondrogenesis and myogenesis and using an in vitro micromass assay, we confirmed the negative effects of GDF11 on both myogenic and chondrogenic cell differentiation. Analysis of molecular markers of skeletal patterning revealed that GDF11 induced ectopic expression of Hoxd-11 and Hoxd-13, but not of Hoxa-11, Hoxa-13, or the Msx genes. These data suggest that GDF11 may be involved in controlling the late distal expression of the Hoxd genes during limb development and that misregulation of these Hox genes by excess GDF11 may cause some of the observed alterations in skeletal element shape. In addition, GDF11 induced the expression of its own antagonist follistatin, indicating that the activity of GFD11 may be limited by a negative feedback mechanism. The data from our studies in the chick suggest that Gdf11 plays a role in the formation and development of the avian limb skeleton.

Polarization from Thomson scattering of the light of a spherical, limb-darkened star

NASA Technical Reports Server (NTRS)

Rudy, R. J.

1979-01-01

The polarized flux produced by the Thomson scattering of the light of a spherical, limb-darkened star by optically thin, extrastellar regions of electrons is calculated and contrasted to previous models which treated the star as a point source. The point-source approximation is found to be valid for scattering by particles more than a stellar radius from the surface of the star but is inappropriate for those lying closer. The specific effect of limb darkening on the fractional polarization of the total light of a system is explored. If the principal source of light is the unpolarized flux of the star, the polarization is nearly independent of limb darkening.

How the embryo makes a limb: determination, polarity and identity

PubMed Central

Tickle, Cheryll

2015-01-01

The vertebrate limb with its complex anatomy develops from a small bud of undifferentiated mesoderm cells encased in ectoderm. The bud has its own intrinsic polarity and can develop autonomously into a limb without reference to the rest of the embryo. In this review, recent advances are integrated with classical embryology, carried out mainly in chick embryos, to present an overview of how the embryo makes a limb bud. We will focus on how mesoderm cells in precise locations in the embryo become determined to form a limb and express the key transcription factors Tbx4 (leg/hindlimb) or Tbx5 (wing/forelimb). These Tbx transcription factors have equivalent functions in the control of bud formation by initiating a signalling cascade involving Wnts and fibroblast growth factors (FGFs) and by regulating recruitment of mesenchymal cells from the coelomic epithelium into the bud. The mesoderm that will form limb buds and the polarity of the buds is determined with respect to both antero-posterior and dorso-ventral axes of the body. The position in which a bud develops along the antero-posterior axis of the body will also determine its identity – wing/forelimb or leg/hindlimb. Hox gene activity, under the influence of retinoic acid signalling, is directly linked with the initiation of Tbx5 gene expression in the region along the antero-posterior axis of the body that will form wings/forelimbs and determines antero-posterior polarity of the buds. In contrast, Tbx4 expression in the regions that will form legs/hindlimbs is regulated by the homeoprotein Pitx1 and there is no evidence that Hox genes determine antero-posterior polarity of the buds. Bone morphogenetic protein (BMP) signalling determines the region along the dorso-ventral axis of the body in which both wings/forelimbs and legs/hindlimbs develop and dorso-ventral polarity of the buds. The polarity of the buds leads to the establishment of signalling regions – the dorsal and ventral ectoderm, producing Wnts and BMPs, respectively, the apical ectodermal ridge producing fibroblast growth factors and the polarizing region, Sonic hedgehog (Shh). These signals are the same in both wings/forelimbs and legs/hindlimbs and control growth and pattern formation by providing the mesoderm cells of the limb bud as it develops with positional information. The precise anatomy of the limb depends on the mesoderm cells in the developing bud interpreting positional information according to their identity – determined by Pitx1 in hindlimbs – and genotype. The competence to form a limb extends along the entire antero-posterior axis of the trunk – with Hox gene activity inhibiting the formation of forelimbs in the interlimb region – and also along the dorso-ventral axis. PMID:26249743

How the embryo makes a limb: determination, polarity and identity.

PubMed

Tickle, Cheryll

2015-10-01

The vertebrate limb with its complex anatomy develops from a small bud of undifferentiated mesoderm cells encased in ectoderm. The bud has its own intrinsic polarity and can develop autonomously into a limb without reference to the rest of the embryo. In this review, recent advances are integrated with classical embryology, carried out mainly in chick embryos, to present an overview of how the embryo makes a limb bud. We will focus on how mesoderm cells in precise locations in the embryo become determined to form a limb and express the key transcription factors Tbx4 (leg/hindlimb) or Tbx5 (wing/forelimb). These Tbx transcription factors have equivalent functions in the control of bud formation by initiating a signalling cascade involving Wnts and fibroblast growth factors (FGFs) and by regulating recruitment of mesenchymal cells from the coelomic epithelium into the bud. The mesoderm that will form limb buds and the polarity of the buds is determined with respect to both antero-posterior and dorso-ventral axes of the body. The position in which a bud develops along the antero-posterior axis of the body will also determine its identity - wing/forelimb or leg/hindlimb. Hox gene activity, under the influence of retinoic acid signalling, is directly linked with the initiation of Tbx5 gene expression in the region along the antero-posterior axis of the body that will form wings/forelimbs and determines antero-posterior polarity of the buds. In contrast, Tbx4 expression in the regions that will form legs/hindlimbs is regulated by the homeoprotein Pitx1 and there is no evidence that Hox genes determine antero-posterior polarity of the buds. Bone morphogenetic protein (BMP) signalling determines the region along the dorso-ventral axis of the body in which both wings/forelimbs and legs/hindlimbs develop and dorso-ventral polarity of the buds. The polarity of the buds leads to the establishment of signalling regions - the dorsal and ventral ectoderm, producing Wnts and BMPs, respectively, the apical ectodermal ridge producing fibroblast growth factors and the polarizing region, Sonic hedgehog (Shh). These signals are the same in both wings/forelimbs and legs/hindlimbs and control growth and pattern formation by providing the mesoderm cells of the limb bud as it develops with positional information. The precise anatomy of the limb depends on the mesoderm cells in the developing bud interpreting positional information according to their identity - determined by Pitx1 in hindlimbs - and genotype. The competence to form a limb extends along the entire antero-posterior axis of the trunk - with Hox gene activity inhibiting the formation of forelimbs in the interlimb region - and also along the dorso-ventral axis. © 2015 Anatomical Society.

Consistency, precision, and accuracy of optical and electromagnetic shape-capturing systems for digital measurement of residual-limb anthropometrics of persons with transtibial amputation.

PubMed

Geil, Mark D

2007-01-01

Computer-aided design (CAD) and computer-aided manufacturing systems have been adapted for specific use in prosthetics, providing practitioners with a means to digitally capture the shape of a patient's limb, modify the socket model using software, and automatically manufacture either a positive model to be used in the fabrication of a socket or the socket itself. The digital shape captured is a three-dimensional (3-D) model from which standard anthropometric measures can be easily obtained. This study recorded six common anthropometric dimensions from CAD shape files of three foam positive models of the residual limbs of persons with transtibial amputations. Two systems were used to obtain 3-D models of the residual limb, a noncontact optical system and a contact-based electromagnetic field system, and both experienced practitioners and prosthetics students conducted measurements. Measurements were consistent; the mean range (difference of maximum and minimum) across all measurements was 0.96 cm. Both systems provided similar results, and both groups used the systems consistently. Students were slightly more consistent than practitioners but not to a clinically significant degree. Results also compared favorably with traditional measurement, with differences versus hand measurements about 5 mm. These results suggest the routine use of digital shape capture for collection of patient volume information.

Earth-from-Luna Limb Imager (ELLI) for Deep Space Gateway

NASA Astrophysics Data System (ADS)

Gorkavyi, N.; DeLand, M.

2018-02-01

The new type of limb imager with a high-frequency imaging proposed for Deep Space Gateway. Each day this CubeSat' scale imager will generate the global 3D model of the aerosol component of the Earth's atmosphere and Polar Mesospheric Clouds.

Review of the socket design and interface pressure measurement for transtibial prosthesis.

PubMed

Pirouzi, Gh; Abu Osman, N A; Eshraghi, A; Ali, S; Gholizadeh, H; Wan Abas, W A B

2014-01-01

Socket is an important part of every prosthetic limb as an interface between the residual limb and prosthetic components. Biomechanics of socket-residual limb interface, especially the pressure and force distribution, have effect on patient satisfaction and function. This paper aimed to review and evaluate studies conducted in the last decades on the design of socket, in-socket interface pressure measurement, and socket biomechanics. Literature was searched to find related keywords with transtibial amputation, socket-residual limb interface, socket measurement, socket design, modeling, computational modeling, and suspension system. In accordance with the selection criteria, 19 articles were selected for further analysis. It was revealed that pressure and stress have been studied in the last decaeds, but quantitative evaluations remain inapplicable in clinical settings. This study also illustrates prevailing systems, which may facilitate improvements in socket design for improved quality of life for individuals ambulating with transtibial prosthesis. It is hoped that the review will better facilitate the understanding and determine the clinical relevance of quantitative evaluations.

Review of the Socket Design and Interface Pressure Measurement for Transtibial Prosthesis

PubMed Central

Pirouzi, Gh.; Abu Osman, N. A.; Eshraghi, A.; Ali, S.; Gholizadeh, H.; Wan Abas, W. A. B.

2014-01-01

Socket is an important part of every prosthetic limb as an interface between the residual limb and prosthetic components. Biomechanics of socket-residual limb interface, especially the pressure and force distribution, have effect on patient satisfaction and function. This paper aimed to review and evaluate studies conducted in the last decades on the design of socket, in-socket interface pressure measurement, and socket biomechanics. Literature was searched to find related keywords with transtibial amputation, socket-residual limb interface, socket measurement, socket design, modeling, computational modeling, and suspension system. In accordance with the selection criteria, 19 articles were selected for further analysis. It was revealed that pressure and stress have been studied in the last decaeds, but quantitative evaluations remain inapplicable in clinical settings. This study also illustrates prevailing systems, which may facilitate improvements in socket design for improved quality of life for individuals ambulating with transtibial prosthesis. It is hoped that the review will better facilitate the understanding and determine the clinical relevance of quantitative evaluations. PMID:25197716

Influence of maturation on instep kick biomechanics in female soccer athletes.

PubMed

Lyle, Mark A; Sigward, Susan M; Tsai, Liang-Ching; Pollard, Christine D; Powers, Christopher M

2011-10-01

The purpose of this study was to compare kicking biomechanics between young female soccer players at two different stages of physical maturation and to identify biomechanical predictors of peak foot velocity. Swing and stance limb kinematics and kinetics were recorded from 20 female soccer players (10 prepubertal, 10 postpubertal) while kicking a soccer ball using an angled two-step approach. Peak foot velocity as well as hip and knee kinematics and kinetics were compared between groups using independent-samples t-tests. Pearson correlation coefficients and stepwise multiple regression were used to identify predictors of peak foot velocity. Peak foot velocity and the peak swing limb net hip flexor moment was significantly greater in the postpubertal group when compared with the prepubertal group (13.4 vs 11.6 m·s(-1), P = 0.003; 1.22 vs 1.07 N·m·kg(-1)·m(-1), P = 0.03). Peak stance limb hip and knee extensor moments were not different between groups. Although the peak swing limb hip and knee flexion angles were similar between groups, the postpubertal group demonstrated significantly less peak stance limb hip and knee flexion angles when compared with the prepubertal group (P < 0.001 and P = 0.045). Using a linear regression model, swing limb peak hip flexor moment and peak swing limb hip extension range of motion combined to explain 65% of the variance in peak foot velocity. Despite a difference in stance limb kinematics, similar swing limb kinematics between groups indicates that the prepubertal female athletes kicked with a mature swing limb kick pattern. The ability to generate a large hip flexor moment of the swing limb seems to be an important factor for improving kicking performance in young female soccer players.

Three-Dimensional Upper Limb Movement Characteristics in Children with Hemiplegic Cerebral Palsy and Typically Developing Children

ERIC Educational Resources Information Center

Jaspers, Ellen; Desloovere, Kaat; Bruyninckx, Herman; Klingels, Katrijn; Molenaers, Guy; Aertbelien, Erwin; Van Gestel, Leen; Feys, Hilde

2011-01-01

The aim of this study was to measure which three-dimensional spatiotemporal and kinematic parameters differentiate upper limb movement characteristics in children with hemiplegic cerebral palsy (HCP) from those in typically developing children (TDC), during various clinically relevant tasks. We used a standardized protocol containing three reach…

A finite element model of the lower limb during stance phase of gait cycle including the muscle forces.

PubMed

Diffo Kaze, Arnaud; Maas, Stefan; Arnoux, Pierre-Jean; Wolf, Claude; Pape, Dietrich

2017-12-07

Results of finite element (FE) analyses can give insight into musculoskeletal diseases if physiological boundary conditions, which include the muscle forces during specific activities of daily life, are considered in the FE modelling. So far, many simplifications of the boundary conditions are currently made. This study presents an approach for FE modelling of the lower limb for which muscle forces were included. The stance phase of normal gait was simulated. Muscle forces were calculated using a musculoskeletal rigid body (RB) model of the human body, and were subsequently applied to a FE model of the lower limb. It was shown that the inertial forces are negligible during the stance phase of normal gait. The contact surfaces between the parts within the knee were modelled as bonded. Weak springs were attached to the distal tibia for numerical reasons. Hip joint reaction forces from the RB model and those from the FE model were similar in magnitude with relative differences less than 16%. The forces of the weak spring were negligible compared to the applied muscle forces. The maximal strain was 0.23% in the proximal region of the femoral diaphysis and 1.7% in the contact zone between the tibia and the fibula. The presented approach based on FE modelling by including muscle forces from inverse dynamic analysis of musculoskeletal RB model can be used to perform analyses of the lower limb with very realistic boundary conditions. In the present form, this model can be used to better understand the loading, stresses and strains of bones in the knee area and hence to analyse osteotomy fixation devices.

Modeling of Prosthetic Limb Rotation Control by Sensing Rotation of Residual Arm Bone

PubMed Central

Kuiken, Todd A.

2011-01-01

We proposed a new approach to improve the control of prosthetic arm rotation in amputees. Arm rotation is sensed by implanting a small permanent magnet into the distal end of the residual bone, which produces a magnetic field. The position of the bone rotation can be derived from magnetic field distribution detected with magnetic sensors on the arm surface, and then conveyed to the prosthesis controller to manipulate the rotation of the prosthesis. Proprioception remains intact for residual limb skeletal structures; thus, this control system should be natural and easy-to-use. In this study, simulations have been conducted in an upper arm model to assess the feasibility and performance of sensing the voluntary rotation of residual humerus with an implanted magnet. A sensitivity analysis of the magnet size and arm size was presented. The influence of relative position of the magnet to the magnetic sensors, orientation of the magnet relative to the limb axis, and displacement of the magnetic sensors on the magnetic field was evaluated. The performance of shielding external magnetostatic interference was also investigated. The simulation results suggest that the direction and angle of rotation of residual humerus could be obtained by decoding the magnetic field signals with magnetic sensors built into a prosthetic socket. This pilot study provides important guidelines for developing a practical interface between the residual bone rotation and the prosthesis for control of prosthetic rotation. PMID:18713682

CO concentration in the upper stratosphere and mesosphere of Titan from VIMS dayside limb observations at 4.7 μm

NASA Astrophysics Data System (ADS)

Fabiano, F.; López Puertas, M.; Adriani, A.; Moriconi, M. L.; D'Aversa, E.; Funke, B.; López-Valverde, M. A.; Ridolfi, M.; Dinelli, B. M.

2017-09-01

During the last 30 years, many works have focused on the determination of the CO abundance in Titan's atmosphere, but no measurement above 300 km has been done yet due to the faint signal of CO. Nevertheless, such measurements are particularly awaited as a confirmation of photochemical models predictions that CO is uniformly mixed in the whole atmosphere. Moreover, since CO is the main atmospheric reservoir of oxygen, its actual abundance has implications on the origins of Titan's atmosphere. In this work, we analyse a set of Cassini VIMS daytime limb observations of Titan at 4.7 μm, which is dominated by solar-pumped non-LTE (non-local thermodynamic equilibrium) emission of CO ro-vibrational bands. In order to retrieve the CO abundance from these observations, we developed a non-LTE model for the CO vibrational levels. The retrieval of the CO concentration is performed following a bayesian approach and using the calculated non-LTE populations. The data set analysed consists of 47 limb scanning sequences -about 1500 spectra- acquired by VIMS in 2006 and 2007. CO relative abundance profiles from 200 to 500 km are obtained, for each set analysed. The mean result shows no significant variations with altitude and is consistent with the prediction of a well-mixed vertical profile. However, if compared with Earth-based mm measurements, a small vertical gradient is plausible.

Contribution of oxidative stress to pathology in diaphragm and limb muscles with Duchenne muscular dystrophy.

PubMed

Kim, Jong-Hee; Kwak, Hyo-Bum; Thompson, LaDora V; Lawler, John M

2013-02-01

Duchenne muscular dystrophy (DMD) is a degenerative skeletal muscle disease that makes walking and breathing difficult. DMD is caused by an X-linked (Xp21) mutation in the dystrophin gene. Dystrophin is a scaffolding protein located in the sarcolemmal cytoskeleton, important in maintaining structural integrity and regulating muscle cell (muscle fiber) growth and repair. Dystrophin deficiency in mouse models (e.g., mdx mouse) destabilizes the interface between muscle fibers and the extracellular matrix, resulting in profound damage, inflammation, and weakness in diaphragm and limb muscles. While the link between dystrophin deficiency with inflammation and pathology is multi-factorial, elevated oxidative stress has been proposed as a central mediator. Unfortunately, the use of non-specific antioxidant scavengers in mouse and human studies has led to inconsistent results, obscuring our understanding of the importance of redox signaling in pathology of muscular dystrophy. However, recent studies with more mechanistic approaches in mdx mice suggest that NAD(P)H oxidase and nuclear factor-kappaB are important in amplifying dystrophin-deficient muscle pathology. Therefore, more targeted antioxidant therapeutics may ameliorate damage and weakness in human population, thus promoting better muscle function and quality of life. This review will focus upon the pathobiology of dystrophin deficiency in diaphragm and limb muscle primarily in mouse models, with a rationale for development of targeted therapeutic antioxidants in DMD patients.

Effects of a multichannel dynamic functional electrical stimulation system on hemiplegic gait and muscle forces

PubMed Central

Qian, Jing-guang; Rong, Ke; Qian, Zhenyun; Wen, Chen; Zhang, Songning

2015-01-01

[Purpose] The purpose of the study was to design and implement a multichannel dynamic functional electrical stimulation system and investigate acute effects of functional electrical stimulation of the tibialis anterior and rectus femoris on ankle and knee sagittal-plane kinematics and related muscle forces of hemiplegic gait. [Subjects and Methods] A multichannel dynamic electrical stimulation system was developed with 8-channel low frequency current generators. Eight male hemiplegic patients were trained for 4 weeks with electric stimulation of the tibia anterior and rectus femoris muscles during walking, which was coupled with active contraction. Kinematic data were collected, and muscle forces of the tibialis anterior and rectus femoris of the affected limbs were analyzed using a musculoskelatal modeling approach before and after training. A paired sample t-test was used to detect the differences between before and after training. [Results] The step length of the affected limb significantly increased after the stimulation was applied. The maximum dorsiflexion angle and maximum knee flexion angle of the affected limb were both increased significantly during stimulation. The maximum muscle forces of both the tibia anterior and rectus femoris increased significantly during stimulation compared with before functional electrical stimulation was applied. [Conclusion] This study established a functional electrical stimulation strategy based on hemiplegic gait analysis and musculoskeletal modeling. The multichannel functional electrical stimulation system successfully corrected foot drop and altered circumduction hemiplegic gait pattern. PMID:26696734

L-alpha intensity in coronal streamers

NASA Technical Reports Server (NTRS)

Noci, G.; Poletto, G.; Suess, S. T.; Wang, A.-H.; Wu, S. T.

1993-01-01

White-light images are presently the primary source of information on physical conditions in the solar corona at distances greater than a few tenths of a solar radius above the limb. As a consequence, we still only have an incomplete description of structures extending beyond the solar limb. In particular, streamers, although observed for decades, represent a poorly known phenomenon. SOHO, to be launched in 1995, will be able to make long-term observations of these features up to heights of a few solar radii, both in white light and UV. In this paper we present simulations of L-alpha intensity in coronal streamers, based on the two-dimensional (2D) model developed by Wang et at. (1992, 1993) via a time-dependent numerical relaxation approach. Because the model is 2D, we make an a priori hypothesis about the extension of streamers in the third dimension. L-alpha data, obtained from a rocket (Kohl et al., 1983), allowed us to identify a shape which fits the observations.

Duplications of BHLHA9 are associated with ectrodactyly and tibia hemimelia inherited in non-Mendelian fashion.

PubMed

Klopocki, Eva; Lohan, Silke; Doelken, Sandra C; Stricker, Sigmar; Ockeloen, Charlotte W; Soares Thiele de Aguiar, Renata; Lezirovitz, Karina; Mingroni Netto, Regina Celia; Jamsheer, Aleksander; Shah, Hitesh; Kurth, Ingo; Habenicht, Rolf; Warman, Matthew; Devriendt, Koenraad; Kordass, Ulrike; Hempel, Maja; Rajab, Anna; Mäkitie, Outi; Naveed, Mohammed; Radhakrishna, Uppala; Antonarakis, Stylianos E; Horn, Denise; Mundlos, Stefan

2012-02-01

Split-hand/foot malformation (SHFM)-also known as ectrodactyly-is a congenital disorder characterised by severe malformations of the distal limbs affecting the central rays of hands and/or feet. A distinct entity termed SHFLD presents with SHFM and long bone deficiency. Mouse models suggest that a defect of the central apical ectodermal ridge leads to the phenotype. Although six different loci/mutations (SHFM1-6) have been associated with SHFM, the underlying cause in a large number of cases is still unresolved. High resolution array comparative genomic hybridisation (CGH) was performed in patients with SHFLD to detect copy number changes. Candidate genes were further evaluated for expression and function during limb development by whole mount in situ hybridisation and morpholino knock-down experiments. Array CGH showed microduplications on chromosome 17p13.3, a locus previously associated with SHFLD. Detailed analysis of 17 families revealed that this copy number variation serves as a susceptibility factor for a highly variable phenotype with reduced penetrance, particularly in females. Compared to other known causes for SHFLD 17p duplications appear to be the most frequent cause of SHFLD. A ~11.8 kb minimal critical region was identified encompassing a single gene, BHLHA9, a putative basic loop helix transcription factor. Whole mount in situ hybridisation showed expression restricted to the limb bud mesenchyme underlying the apical ectodermal ridge in mouse and zebrafish embryos. Knock down of bhlha9 in zebrafish resulted in shortening of the pectoral fins. Genomic duplications encompassing BHLHA9 are associated with SHFLD and non-Mendelian inheritance characterised by a high degree of non-penetrance with sex bias. Knock-down of bhlha9 in zebrafish causes severe reduction defects of the pectoral fin, indicating a role for this gene in limb development.

Digit loss in archosaur evolution and the interplay between selection and constraints.

PubMed

de Bakker, Merijn A G; Fowler, Donald A; den Oude, Kelly; Dondorp, Esther M; Navas, M Carmen Garrido; Horbanczuk, Jaroslaw O; Sire, Jean-Yves; Szczerbińska, Danuta; Richardson, Michael K

2013-08-22

Evolution involves interplay between natural selection and developmental constraints. This is seen, for example, when digits are lost from the limbs during evolution. Extant archosaurs (crocodiles and birds) show several instances of digit loss under different selective regimes, and show limbs with one, two, three, four or the ancestral number of five digits. The 'lost' digits sometimes persist for millions of years as developmental vestiges. Here we examine digit loss in the Nile crocodile and five birds, using markers of three successive stages of digit development. In two independent lineages under different selection, wing digit I and all its markers disappear. In contrast, hindlimb digit V persists in all species sampled, both as cartilage, and as Sox9- expressing precartilage domains, 250 million years after the adult digit disappeared. There is therefore a mismatch between evolution of the embryonic and adult phenotypes. All limbs, regardless of digit number, showed similar expression of sonic hedgehog (Shh). Even in the one-fingered emu wing, expression of posterior genes Hoxd11 and Hoxd12 was conserved, whereas expression of anterior genes Gli3 and Alx4 was not. We suggest that the persistence of digit V in the embryo may reflect constraints, particularly the conserved posterior gene networks associated with the zone of polarizing activity (ZPA). The more rapid and complete disappearance of digit I may reflect its ZPA-independent specification, and hence, weaker developmental constraints. Interacting with these constraints are selection pressures for limb functions such as flying and perching. This model may help to explain the diverse patterns of digit loss in tetrapods. Our study may also help to understand how selection on adults leads to changes in development.

The accuracy and precision of radiostereometric analysis in upper limb arthroplasty.

PubMed

Ten Brinke, Bart; Beumer, Annechien; Koenraadt, Koen L M; Eygendaal, Denise; Kraan, Gerald A; Mathijssen, Nina M C

2017-06-01

Background and purpose - Radiostereometric analysis (RSA) is an accurate method for measurement of early migration of implants. Since a relation has been shown between early migration and future loosening of total knee and hip prostheses, RSA plays an important role in the development and evaluation of prostheses. However, there have been few RSA studies of the upper limb, and the value of RSA of the upper limb is not yet clear. We therefore performed a systematic review to investigate the accuracy and precision of RSA of the upper limb. Patients and methods - PRISMA guidelines were followed and the protocol for this review was published online at PROSPERO under registration number CRD42016042014. A systematic search of the literature was performed in the databases Embase, Medline, Cochrane, Web of Science, Scopus, Cinahl, and Google Scholar on April 25, 2015 based on the keywords radiostereometric analysis, shoulder prosthesis, elbow prosthesis, wrist prosthesis, trapeziometacarpal joint prosthesis, humerus, ulna, radius, carpus. Articles concerning RSA for the analysis of early migration of prostheses of the upper limb were included. Quality assessment was performed using the MINORS score, Downs and Black checklist, and the ISO RSA Results - 23 studies were included. Precision values were in the 0.06-0.88 mm and 0.05-10.7° range for the shoulder, the 0.05-0.34 mm and 0.16-0.76° range for the elbow, and the 0.16-1.83 mm and 11-124° range for the TMC joint. Accuracy data from marker- and model-based RSA were not reported in the studies included. Interpretation - RSA is a highly precise method for measurement of early migration of orthopedic implants in the upper limb. However, the precision of rotation measurement is poor in some components. Challenges with RSA in the upper limb include the symmetrical shape of prostheses and the limited size of surrounding bone, leading to over-projection of the markers by the prosthesis. We recommend higher adherence to RSA guidelines and encourage investigators to publish long-term follow-up RSA studies.

Northwestern University Flexible Subischial Vacuum Socket for persons with transfemoral amputation-Part 1: Description of technique

PubMed Central

Fatone, Stefania; Caldwell, Ryan

2017-01-01

Background: Current transfemoral prosthetic sockets restrict function, lack comfort, and cause residual limb problems. Lower proximal trim lines are an appealing way to address this problem. Development of a more comfortable and possibly functional subischial socket may contribute to improving quality of life of persons with transfemoral amputation. Objectives: The purpose of this study was to (1) describe the design and fabrication of a new subischial socket and (2) describe efforts to teach this technique. Study design: Development project. Methods: Socket development involved defining the following: subject and liner selection, residual limb evaluation, casting, positive mold rectification, check socket fitting, definitive socket fabrication, and troubleshooting of socket fit. Three hands-on workshops to teach the socket were piloted and attended by 30 certified prosthetists and their patient models. Results: Patient models responded positively to the comfort, range of motion, and stability of the new socket while prosthetists described the technique as “straight forward, reproducible.” Conclusion: To our knowledge, this is the first attempt to create a teachable subischial socket, and while it appears promising, more definitive evaluation is needed. Clinical relevance We developed the Northwestern University Flexible Subischial Vacuum (NU-FlexSIV) Socket as a more comfortable alternative to current transfemoral sockets and demonstrated that it could be taught successfully to prosthetists. PMID:28094686

Development of an Equine Groove Model to Induce Metacarpophalangeal Osteoarthritis: A Pilot Study on 6 Horses

PubMed Central

Maninchedda, Ugo; Lepage, Olivier M.; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

2015-01-01

The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or “grooves” were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy. PMID:25680102

Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses.

PubMed

Maninchedda, Ugo; Lepage, Olivier M; Gangl, Monika; Hilairet, Sandrine; Remandet, Bernard; Meot, Francoise; Penarier, Geraldine; Segard, Emilie; Cortez, Pierre; Jorgensen, Christian; Steinberg, Régis

2015-01-01

The aim of this work was to develop an equine metacarpophalangeal joint model that induces osteoarthritis that is not primarily mediated by instability or inflammation. The study involved six Standardbred horses. Standardized cartilage surface damage or "grooves" were created arthroscopically on the distal dorsal aspect of the lateral and medial metacarpal condyles of a randomly chosen limb. The contralateral limb was sham operated. After 2 weeks of stall rest, horses were trotted 30 minutes every other day for 8 weeks, then evaluated for lameness and radiographed. Synovial fluid was analyzed for cytology and biomarkers. At 10 weeks post-surgery, horses were euthanized for macroscopic and histologic joint evaluation. Arthroscopic grooving allowed precise and identical damage to the cartilage of all animals. Under the controlled exercise regime, this osteoarthritis groove model displayed significant radiographic, macroscopic, and microscopic degenerative and reactive changes. Histology demonstrated consistent surgically induced grooves limited to non-calcified cartilage and accompanied by secondary adjacent cartilage lesions, chondrocyte necrosis, chondrocyte clusters, cartilage matrix softening, fissuring, mild subchondral bone inflammation, edema, and osteoblastic margination. Synovial fluid biochemistry and cytology demonstrated significantly elevated total protein without an increase in prostaglandin E2, neutrophils, or chondrocytes. This equine metacarpophalangeal groove model demonstrated that standardized non-calcified cartilage damage accompanied by exercise triggered altered osteochondral morphology and cartilage degeneration with minimal or inefficient repair and little inflammatory response. This model, if validated, would allow for assessment of disease processes and the effects of therapy.

Development of a model osseo-magnetic link for intuitive rotational control of upper-limb prostheses.

PubMed

Rouse, Elliott J; Nahlik, David C; Peshkin, Michael A; Kuiken, Todd A

2011-04-01

The lack of proprioceptive feedback is a serious deficiency of current prosthetic control systems. The Osseo-Magnetic Link (OML) is a novel humeral or wrist rotation control system that could preserve proprioception. It utilizes a magnet implanted within the residual bone and sensors mounted in the prosthetic socket to detect magnetic field vectors and determine the bone's orientation. This allows the use of volitional bone rotation to control a prosthetic rotator. We evaluated the performance of the OML using a physical model of a transhumeral residual limb. A small Neodymium-Iron-Boron magnet was placed in a model humerus, inside a model upper arm. Four three-axis Hall-effect sensors were mounted on a ring 3 cm distal to the magnet. An optimization algorithm based on Newton's method determined the position and orientation of the magnet within the model humerus under various conditions, including bone translations, interference, and magnet misalignment. The orientation of the model humerus was determined within 3° for rotations centered in the arm; an additional 6° error was found for translations 20 mm from center. Adjustments in sensor placement may reduce these errors. The results demonstrate that the OML is a feasible solution for providing prosthesis rotation control while preserving rotational proprioception.

Running in ostriches (Struthio camelus): three-dimensional joint axes alignment and joint kinematics.

PubMed

Rubenson, Jonas; Lloyd, David G; Besier, Thor F; Heliams, Denham B; Fournier, Paul A

2007-07-01

Although locomotor kinematics in walking and running birds have been examined in studies exploring many biological aspects of bipedalism, these studies have been largely limited to two-dimensional analyses. Incorporating a five-segment, 17 degree-of-freedom (d.f.) kinematic model of the ostrich hind limb developed from anatomical specimens, we quantified the three-dimensional (3-D) joint axis alignment and joint kinematics during running (at approximately 3.3 m s(-1)) in the largest avian biped, the ostrich. Our analysis revealed that the majority of the segment motion during running in the ostrich occurs in flexion/extension. Importantly, however, the alignment of the average flexion/extension helical axes of the knee and ankle are rotated externally to the direction of travel (37 degrees and 21 degrees , respectively) so that pure flexion and extension at the knee will act to adduct and adbuct the tibiotarsus relative to the plane of movement, and pure flexion and extension at the ankle will act to abduct and adduct the tarsometatarsus relative to the plane of movement. This feature of the limb anatomy appears to provide the major lateral (non-sagittal) displacement of the lower limb necessary for steering the swinging limb clear of the stance limb and replaces what would otherwise require greater adduction/abduction and/or internal/external rotation, allowing for less complex joints, musculoskeletal geometry and neuromuscular control. Significant rotation about the joints' non-flexion/extension axes nevertheless occurs over the running stride. In particular, hip abduction and knee internal/external and varus/valgus motion may further facilitate limb clearance during the swing phase, and substantial non-flexion/extension movement at the knee is also observed during stance. Measurement of 3-D segment and joint motion in birds will be aided by the use of functionally determined axes of rotation rather than assumed axes, proving important when interpreting the biomechanics and motor control of avian bipedalism.

Titan's Stratospheric Water Vapor profile from Cassini CIRS far-infrared Spectra

NASA Astrophysics Data System (ADS)

Cottini, V.; Nixon, C. A.; Achterberg, R. K.; Gorius, N.; Coustenis, A.; Irwin, P. G. J.; Anderson, C. M.; Bjoraker, G. L.; Jennings, D. E.; Flasar, F. M.; Ansty, T. M.

2017-09-01

In this work we present an update of water vapor abundance in Titan's stratosphere through modeling of its emission lines present in the spectral range (100 - 300 cm-1) observed by the Cassini Composite Infrared Spectrometer (CIRS) far-IR Focal Plane 1 (FP1) detector. We model and analyze high spectral resolution (0.5 cm-1) disk and limb observations acquired from December 2004 to December 2016 to determine the water mixing ratio profile. Nadir data and limb data acquired up to 2011 and pointing at two altitudes in Titan's stratosphere (125 and 225 km) have been previously used in [1] to detect water vapor and retrieve its abundance at two limb altitudes. Few years of more data and improved calibrations are now available to further investigate water vapor. In particular, three far-infrared limb integrations were planned and acquired in 2014 and 2016 with CIRS staring at a single altitude (175 km) for longer time. These new data provided us with one more altitude point to derive the water vapor abundance and improve its retrieved vertical profile, increasing significantly the science results. These results will also be compared to previous results and to the latest photochemical models of Titan's oxygen species.

Limb-darkening coefficients for the purpose of pulsation mode identification for A-F stars. .

NASA Astrophysics Data System (ADS)

Barban, C.; Goupil, M. J.; van't Veer-Menneret, C.; Garrido, R.; Heiter, U.; Kupka, F.

Limb-darkening coefficients are computed from a set of model atmospheres with: a solar chemical composition, 6000 K< Teff < 8500 K (Delta T_eff=250 K), 2.5 < logg < 4.5 (Delta log g=0.1) and a microturbulent velocity of 2 km/s. Convection is included assuming either the turbulent convection approach of \\citet{cm} or the classical mixing length prescription with alpha =0.5 and 1.25. Four limb-darkening laws have been used: quadratic, cubic, square root and the one of \\citet{cl}. We compare the ATLAS 9 intensities and the ones computed from these laws. We find that Claret's law is the best law for almost all the models, independently of the convection prescription used.

Quadrupedal rodent gait compensations in a low dose monoiodoacetate model of osteoarthritis.

PubMed

Lakes, Emily H; Allen, Kyle D

2018-06-01

Rodent gait analysis provides robust, quantitative results for preclinical musculoskeletal and neurological models. In prior work, surgical models of osteoarthritis have been found to result in a hind limb shuffle-stepping gait compensation, while a high dose monoiodoacetate (MIA, 3 mg) model resulted in a hind limb antalgic gait. However, it is unknown whether the antalgic gait caused by MIA is associated with severity of degeneration from the high dosage or the whole-joint degeneration associated with glycolysis inhibition. This study evaluates rodent gait changes resulting from a low dose, 1 mg unilateral intra-articular injection of MIA compared to saline injected and naïve rats. Spatiotemporal and dynamic gait parameters were collected from a total of 42 male Lewis rats spread across 3 time points: 1, 2, and 4 weeks post-injection. To provide a detailed analysis of this low dose MIA model, gait analysis was used to uniquely quantify both fore and hind limb gait parameters. Our data indicate that 1 mg of MIA caused relatively minor degeneration and a shuffle-step gait compensation, similar to the compensation observed in prior surgical models. These data from a 1 mg MIA model show a different gait compensation compared to a previously studied 3 mg model. This 1 mg MIA model resulted in gait compensations more similar to a previously studied surgical model of osteoarthritis. Additionally, this study provides detailed 4 limb analysis of rodent gait that includes spatiotemporal and dynamic data from the same gait trial. These data highlight the importance of measuring dynamic data in combination with spatiotemporal data, since compensatory gait patterns may not be captured by spatial, temporal, or dynamic characterizations alone. Copyright © 2018 Elsevier B.V. All rights reserved.

Modulation of shoulder muscle and joint function using a powered upper-limb exoskeleton.

PubMed

Wu, Wen; Fong, Justin; Crocher, Vincent; Lee, Peter V S; Oetomo, Denny; Tan, Ying; Ackland, David C

2018-04-27

Robotic-assistive exoskeletons can enable frequent repetitive movements without the presence of a full-time therapist; however, human-machine interaction and the capacity of powered exoskeletons to attenuate shoulder muscle and joint loading is poorly understood. This study aimed to quantify shoulder muscle and joint force during assisted activities of daily living using a powered robotic upper limb exoskeleton (ArmeoPower, Hocoma). Six healthy male subjects performed abduction, flexion, horizontal flexion, reaching and nose touching activities. These tasks were repeated under two conditions: (i) the exoskeleton compensating only for its own weight, and (ii) the exoskeleton providing full upper limb gravity compensation (i.e., weightlessness). Muscle EMG, joint kinematics and joint torques were simultaneously recorded, and shoulder muscle and joint forces calculated using personalized musculoskeletal models of each subject's upper limb. The exoskeleton reduced peak joint torques, muscle forces and joint loading by up to 74.8% (0.113 Nm/kg), 88.8% (5.8%BW) and 68.4% (75.6%BW), respectively, with the degree of load attenuation strongly task dependent. The peak compressive, anterior and superior glenohumeral joint force during assisted nose touching was 36.4% (24.6%BW), 72.4% (13.1%BW) and 85.0% (17.2%BW) lower than that during unassisted nose touching, respectively. The present study showed that upper limb weight compensation using an assistive exoskeleton may increase glenohumeral joint stability, since deltoid muscle force, which is the primary contributor to superior glenohumeral joint shear, is attenuated; however, prominent exoskeleton interaction moments are required to position and control the upper limb in space, even under full gravity compensation conditions. The modeling framework and results may be useful in planning targeted upper limb robotic rehabilitation tasks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Center-to-Limb Variability of Hot Coronal EUV Emissions During Solar Flares

NASA Astrophysics Data System (ADS)

Thiemann, E. M. B.; Chamberlin, P. C.; Eparvier, F. G.; Epp, L.

2018-02-01

It is generally accepted that densities of quiet-Sun and active region plasma are sufficiently low to justify the optically thin approximation, and this is commonly used in the analysis of line emissions from plasma in the solar corona. However, the densities of solar flare loops are substantially higher, compromising the optically thin approximation. This study begins with a radiative transfer model that uses typical solar flare densities and geometries to show that hot coronal emission lines are not generally optically thin. Furthermore, the model demonstrates that the observed line intensity should exhibit center-to-limb variability (CTLV), with flares observed near the limb being dimmer than those occurring near disk center. The model predictions are validated with an analysis of over 200 flares observed by the EUV Variability Experiment (EVE) on the Solar Dynamics Observatory (SDO), which uses six lines, with peak formation temperatures between 8.9 and 15.8 MK, to show that limb flares are systematically dimmer than disk-center flares. The data are then used to show that the electron column density along the line of sight typically increases by 1.76 × 10^{19} cm^{-2} for limb flares over the disk-center flare value. It is shown that the CTLV of hot coronal emissions reduces the amount of ionizing radiation propagating into the solar system, and it changes the relative intensities of lines and bands commonly used for spectral analysis.

Vertical Distribution of Dust and Water Ice Aerosols from CRISM Limb-geometry Observations

NASA Technical Reports Server (NTRS)

Smith, Michael Doyle; Wolff, Michael J.; Clancy, Todd; Kleinbohl, Armin; Murchie, Scott L.

2013-01-01

[1] Near-infrared spectra taken in a limb-viewing geometry by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) on board the Mars Reconnaissance Orbiter provide a useful tool for probing atmospheric structure. Specifically, the observed radiance as a function of wavelength and height above the limb enables the vertical distribution of both dust and water ice aerosols to be retrieved. More than a dozen sets of CRISM limb observations have been taken so far providing pole-to-pole cross sections, spanning more than a full Martian year. Radiative transfer modeling is used to model the observations taking into account multiple scattering from aerosols and the spherical geometry of the limb observations. Both dust and water ice vertical profiles often show a significant vertical structure for nearly all seasons and latitudes that is not consistent with the well-mixed or Conrath-v assumptions that have often been used in the past for describing aerosol vertical profiles for retrieval and modeling purposes. Significant variations are seen in the retrieved vertical profiles of dust and water ice aerosol as a function of season. Dust typically extends to higher altitudes (approx. 40-50km) during the perihelion season than during the aphelion season (<20km), and the Hellas region consistently shows more dust mixed to higher altitudes than other locations. Detached water ice clouds are common, and water ice aerosols are observed to cap the dust layer in all seasons.

Males that drop a sexually selected weapon grow larger testes.

PubMed

Joseph, Paul N; Emberts, Zachary; Sasson, Daniel A; Miller, Christine W

2018-01-01

Costly sexually selected weapons are predicted to trade off with postcopulatory traits, such as testes. Although weapons can be important for achieving access to females, individuals of some species can permanently drop (i.e. autotomize) their weapons, without regeneration, to escape danger. We capitalized on this natural behavior to experimentally address whether the loss of a sexually selected weapon leads to increased testes investment in the leaf-footed cactus bug, Narnia femorata Stål (Hemiptera: Coreidae). In a second experiment, we measured offspring production for males that lost a weapon during development. As predicted, males that dropped a hind limb during development grew significantly larger testes than the control treatments. Hind-limb autotomy did not result in the enlargement of other nearby traits. Our results are the first to experimentally demonstrate that males compensate for natural weapon loss by investing more in testes. In a second experiment we found that females paired with males that lost a hind limb had 40% lower egg hatching success than females paired with intact males, perhaps because of lower mating receptivity to males with a lost limb. Importantly, in those cases where viable offspring were produced, males missing a hind limb produced 42% more offspring than males with intact limbs. These results suggest that the loss of a hind-limb weapon can, in some cases, lead to greater fertilization success. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Development of five digits is controlled by a bipartite long-range cis-regulator

PubMed Central

Lettice, Laura A.; Williamson, Iain; Devenney, Paul S.; Kilanowski, Fiona; Dorin, Julia; Hill, Robert E.

2014-01-01

Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs. PMID:24715461

Prior nonhip limb fracture predicts subsequent hip fracture in institutionalized elderly people.

PubMed

Nakamura, K; Takahashi, S; Oyama, M; Oshiki, R; Kobayashi, R; Saito, T; Yoshizawa, Y; Tsuchiya, Y

2010-08-01

This 1-year cohort study of nursing home residents revealed that historical fractures of upper limbs or nonhip lower limbs were associated with hip fracture (hazard ratio = 2.14), independent of activities of daily living (ADL), mobility, dementia, weight, and type of nursing home. Prior nonhip fractures are useful for predicting of hip fracture in institutional settings. The aim of this study was to evaluate the utility of fracture history for the prediction of hip fracture in nursing home residents. This was a cohort study with a 1-year follow-up. Subjects were 8,905 residents of nursing homes in Niigata, Japan (mean age, 84.3 years). Fracture histories were obtained from nursing home medical records. ADL levels were assessed by caregivers. Hip fracture diagnosis was based on hospital medical records. Subjects had fracture histories of upper limbs (5.0%), hip (14.0%), and nonhip lower limbs (4.6%). Among historical single fractures, only prior nonhip lower limbs significantly predicted subsequent fracture (adjusted hazard ratio, 2.43; 95% confidence interval (CI), 1.30-4.57). The stepwise method selected the best model, in which a combined historical fracture at upper limbs or nonhip lower limbs (adjusted hazard ratio, 2.14; 95% CI, 1.30-3.52), dependence, ADL levels, mobility, dementia, weight, and type of nursing home independently predicted subsequent hip fracture. A fracture history at upper or nonhip lower limbs, in combination with other known risk factors, is useful for the prediction of future hip fracture in institutional settings.

A short overview of upper limb rehabilitation devices

NASA Astrophysics Data System (ADS)

Macovei, S.; Doroftei, I.

2016-08-01

As some studies show, the number of people over 65 years old increases constantly, leading to the need of solution to provide services regarding patient mobility. Diseases, accidents and neurologic problems affect hundreds of people every day, causing pain and lost of motor functions. The ability of using the upper limb is indispensable for a human being in everyday activities, making easy tasks like drinking a glass of water a real challenge. We can agree that physiotherapy promotes recovery, but not at an optimal level, due to limited financial and human resources. Hence, the need of robot-assisted rehabilitation emerges. A robot for upper-limb exercises should have a design that can accurately control interaction forces and progressively adapt assistance to the patients’ abilities and also to record the patient's motion and evolution. In this paper a short overview of upper limb rehabilitation devices is presented. Our goal is to find the shortcomings of the current developed devices in terms of utility, ease of use and costs, for future development of a mechatronic system for upper limb rehabilitation.

Development of a residuum/socket interface simulator for lower limb prosthetics.

PubMed

McGrath, Michael Paul; Gao, Jianliang; Tang, Jinghua; Laszczak, Piotr; Jiang, Liudi; Bader, Dan; Moser, David; Zahedi, Saeed

2017-03-01

Mechanical coupling at the interface between lower limb residua and prosthetic sockets plays an important role in assessing socket fitting and tissue health. However, most research lab-based lower limb prosthetic simulators to-date have implemented a rigid socket coupling. This study describes the fabrication and implementation of a lower limb residuum/socket interface simulator, designed to reproduce the forces and moments present during the key loading phases of amputee walking. An artificial residuum made with model bones encased in silicone was used, mimicking the compliant mechanical loading of a real residuum/socket interface. A 6-degree-of-freedom load cell measured the overall kinetics, having previously been incorporated into an amputee's prosthesis to collect reference data. The developed simulator was compared to a setup where a rigid pylon replaced the artificial residuum. A maximum uniaxial load of 850 N was applied, comparable to the peak vertical ground reaction force component during amputee walking. Load cell outputs from both pylon and residuum setups were compared. During weight acceptance, when including the artificial residuum, compression decreased by 10%, while during push off, sagittal bending and anterior-posterior shear showed a 25% increase and 34% decrease, respectively. Such notable difference by including a compliant residuum further highlighted the need for such an interface simulator. Subsequently, the simulator was adjusted to produce key load cell outputs briefly aligning with those from amputee walking. Force sensing resistors were deployed at load bearing anatomic locations on the residuum/socket interface to measure pressures and were compared to those cited in the literature for similar locations. The development of such a novel simulator provides an objective adjunct, using commonly available mechanical test machines. It could potentially be used to provide further insight into socket design, fit and the complex load transfer mechanics at the residuum/socket interface, as well as to evaluate the structural performance of prostheses.

FGFR3 is a target of the homeobox transcription factor SHOX in limb development.

PubMed

Decker, Eva; Durand, Claudia; Bender, Sebastian; Rödelsperger, Christian; Glaser, Anne; Hecht, Jochen; Schneider, Katja U; Rappold, Gudrun

2011-04-15

The short stature homeobox gene SHOX encodes a transcription factor which is important for normal limb development. In humans, SHOX deficiency has been associated with various short stature syndromes including Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia and Turner syndrome as well as non-syndromic idiopathic short stature. A common feature of these syndromes is disproportionate short stature with a particular shortening of the forearms and lower legs. In our studies employing microarray analyses and cell culture experiments, we revealed a strong positive effect of SHOX on the expression of the fibroblast growth factor receptor gene FGFR3, another well-known factor for limb development. Luciferase reporter gene assays show that SHOX activates the extended FGFR3 promoter, and results from chromatin immunoprecipitation (ChIP)-sequencing, ChIP and electrophoretic mobility shift assay experiments suggest a direct binding of SHOX to multiple upstream sequences of FGFR3. To further investigate these regulations in a cellular system for limb development, the effect of viral overexpression of Shox in limb bud derived chicken micromass cultures was tested. We found that Fgfr3 was negatively regulated by Shox, as demonstrated by quantitative real-time polymerase chain reaction and in situ hybridization. This repressive effect might explain the almost mutually exclusive expression patterns of Fgfr3 and Shox in embryonic chicken limbs. A negative regulation that occurs mainly in the mesomelic segments, a region where SHOX is known to be strongly expressed, offers a possible explanation for the phenotypes seen in patients with FGFR3 (e.g. achondroplasia) and SHOX defects (e.g. LWD). In summary, these data present a link between two frequent short stature phenotypes.

Development and reliability of the rating of compensatory movements in upper limb prosthesis wearers during work-related tasks.

PubMed

van der Laan, Tallie M J; Postema, Sietke G; Reneman, Michiel F; Bongers, Raoul M; van der Sluis, Corry K

2018-02-10

Reliability study. Quantifying compensatory movements during work-related tasks may help to prevent musculoskeletal complaints in individuals with upper limb absence. (1) To develop a qualitative scoring system for rating compensatory shoulder and trunk movements in upper limb prosthesis wearers during the performance of functional capacity evaluation tests adjusted for use by 1-handed individuals (functional capacity evaluation-one handed [FCE-OH]); (2) to examine the interrater and intrarater reliability of the scoring system; and (3) to assess its feasibility. Movement patterns of 12 videotaped upper limb prosthesis wearers and 20 controls were analyzed. Compensatory movements were defined for each FCE-OH test, and a scoring system was developed, pilot tested, and adjusted. During reliability testing, 18 raters (12 FCE experts and 6 physiotherapists/gait analysts) scored videotapes of upper limb prosthesis wearers performing 4 FCE-OH tests 2 times (2 weeks apart). Agreement was expressed in % and kappa value. Feasibility (focus area's "acceptability", "demand," and "implementation") was determined by using a questionnaire. After 2 rounds of pilot testing and adjusting, reliability of a third version was tested. The interrater reliability for the first and second rating sessions were к = 0.54 (confidence interval [CI]: 0.52-0.57) and к = 0.64 (CI: 0.61-0.66), respectively. The intrarater reliability was к = 0.77 (CI: 0.72-0.82). The feasibility was good but could be improved by a training program. It seems possible to identify compensatory movements in upper limb prosthesis wearers during the performance of FCE-OH tests reliably by observation using the developed observational scoring system. Interrater reliability was satisfactory in most instances; intrarater reliability was good. Feasibility was established. Copyright © 2018 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Low-Cost Methodology for Skin Strain Measurement of a Flexed Biological Limb.

PubMed

Lin, Bevin; Moerman, Kevin M; McMahan, Connor G; Pasch, Kenneth A; Herr, Hugh M

2017-12-01

The purpose of this manuscript is to compute skin strain data from a flexed biological limb, using portable, inexpensive, and easily available resources. We apply and evaluate this approach on a person with bilateral transtibial amputations, imaging left and right residual limbs in extended and flexed knee postures. We map 3-D deformations to a flexed biological limb using freeware and a simple point-and-shoot camera. Mean principal strain, maximum shear strain, as well as lines of maximum, minimum, and nonextension are computed from 3-D digital models to inform directional mappings of the strain field for an unloaded residual limb. Peak tensile strains are ∼0.3 on the anterior surface of the knee in the proximal region of the patella, whereas peak compressive strains are ∼ -0.5 on the posterior surface of the knee. Peak maximum shear strains are ∼0.3 on the posterior surface of the knee. The accuracy and precision of this methodology are assessed for a ground-truth model. The mean point location distance is found to be 0.08 cm, and the overall standard deviation for point location difference vectors is 0.05 cm. This low-cost and mobile methodology may prove critical for applications such as the prosthetic socket interface where whole-limb skin strain data are required from patients in the field outside of traditional, large-scale clinical centers. Such data may inform the design of wearable technologies that directly interface with human skin.

Requirement for ErbB2/ErbB signaling in developing cartilage and bone.

PubMed

Fisher, Melanie C; Clinton, Gail M; Maihle, Nita J; Dealy, Caroline N

2007-08-01

During endochondral ossification, the skeletal elements of vertebrate limbs form and elongate via coordinated control of chondrocyte and osteoblast differentiation and proliferation. The role of signaling by the ErbB family of receptor tyrosine kinases, which consists of ErbB1 (epidermal growth factor receptor or EGFR), ErbB2, ErbB3 and ErbB4, has been little studied during cartilage and bone development. Signaling by the ErbB network generates a diverse array of cellular responses via formation of ErbB dimers activated by distinct ligands that produce distinct signal outputs. Herstatin is a soluble ErbB2 receptor that acts in a dominant negative fashion to inhibit ErbB signaling by binding to endogenous ErbB receptors, preventing functional dimer formation. Here, we examine the effects of Herstatin on limb skeletal element development in transgenic mice, achieved via Prx1 promoter-driven expression in limb cartilage and bone. The limb skeletal elements of Prx1-Herstatin embryos are shortened, and chondrocyte maturation and osteoblast differentiation are delayed. In addition, proliferation by chondrocytes and periosteal cells of Prx1-Herstatin limb skeletal elements is markedly reduced. Our study identifies requirements for ErbB signaling in the maintenance of chondrocyte and osteoblast proliferation involved in the timely progression of chondrocyte maturation and periosteal osteoblast differentiation.

Loss and Re-emergence of Legs in Snakes by Modular Evolution of Sonic hedgehog and HOXD Enhancers.

PubMed

Leal, Francisca; Cohn, Martin J

2016-11-07

Limb reduction and loss are hallmarks of snake evolution. Although advanced snakes are completely limbless, basal and intermediate snakes retain pelvic girdles and small rudiments of the femur. Moreover, legs may have re-emerged in extinct snake lineages [1-5], suggesting that the mechanisms of limb development were not completely lost in snakes. Here we report that hindlimb development arrests in python embryos as a result of mutations that abolish essential transcription factor binding sites in the limb-specific enhancer of Sonic hedgehog (SHH). Consequently, SHH transcription is weak and transient in python hindlimb buds, leading to early termination of a genetic circuit that drives limb outgrowth. Our results suggest that degenerate evolution of the SHH limb enhancer played a role in reduction of hindlimbs during snake evolution. By contrast, HOXD digit enhancers are conserved in pythons, and HOXD gene expression in the hindlimb buds progresses to the distal phase, forming an autopodial (digit) domain. Python hindlimb buds then develop transitory pre-chondrogenic condensations of the tibia, fibula, and footplate, raising the possibility that re-emergence of hindlimbs during snake evolution did not require de novo re-evolution of lost structures but instead could have resulted from persistence of embryonic legs. VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.

An assessment of postcranial indices, ratios, and body mass versus eco-geographical variables of prehistoric Jomon, Yayoi agriculturalists, and Kumejima Islanders of Japan.

PubMed

Seguchi, Noriko; Quintyn, Conrad B; Yonemoto, Shiori; Takamuku, Hirofumi

2017-09-10

We explore variations in body and limb proportions of the Jomon hunter-gatherers (14,000-2500 BP), the Yayoi agriculturalists (2500-1700 BP) of Japan, and the Kumejima Islanders of the Ryukyus (1600-1800 AD) with 11 geographically diverse skeletal postcranial samples from Africa, Europe, Asia, Australia, and North America using brachial-crural indices, femur head-breadth-to-femur length ratio, femur head-breadth-to-lower-limb-length ratio, and body mass as indicators of phenotypic climatic adaptation. Specifically, we test the hypothesis that variation in limb proportions seen in Jomon, Yayoi, and Kumejima is a complex interaction of genetic adaptation; development and allometric constraints; selection, gene flow and genetic drift with changing cultural factors (i.e., nutrition) and climate. The skeletal data (1127 individuals) were subjected to principle components analysis, Manly's permutation multiple regression tests, and Relethford-Blangero analysis. The results of Manly's tests indicate that body proportions and body mass are significantly correlated with latitude, and minimum and maximum temperatures while limb proportions were not significantly correlated with these climatic variables. Principal components plots separated "climatic zones:" tropical, temperate, and arctic populations. The indigenous Jomon showed cold-adapted body proportions and warm-adapted limb proportions. Kumejima showed cold-adapted body proportions and limbs. The Yayoi adhered to the Allen-Bergmann expectation of cold-adapted body and limb proportions. Relethford-Blangero analysis showed that Kumejima experienced gene flow indicated by high observed variances while Jomon experienced genetic drift indicated by low observed variances. The complex interaction of evolutionary forces and development/nutritional constraints are implicated in the mismatch of limb and body proportions. © 2017 Wiley Periodicals, Inc.

Effects of Ethylene Glycol Monomethyl Ether and Its Metabolite, 2-Methoxyacetic Acid, on Organogenesis Stage Mouse Limbs In Vitro

PubMed Central

Dayan, Caroline; Hales, Barbara F

2014-01-01

Exposure to ethylene glycol monomethyl ether (EGME), a glycol ether compound found in numerous industrial products, or to its active metabolite, 2-methoxyacetic acid (2-MAA), increases the incidence of developmental defects. Using an in vitro limb bud culture system, we tested the hypothesis that the effects of EGME on limb development are mediated by 2-MAA-induced alterations in acetylation programming. Murine gestation day 12 embryonic forelimbs were exposed to 3, 10, or 30 mM EGME or 2-MAA in culture for 6 days to examine effects on limb morphology; limbs were cultured for 1 to 24 hr to monitor effects on the acetylation of histones (H3K9 and H4K12), a nonhistone protein, p53 (p53K379), and markers for cell cycle arrest (p21) and apoptosis (cleaved caspase-3). EGME had little effect on limb morphology and no significant effects on the acetylation of histones or p53 or on biomarkers for cell cycle arrest or apoptosis. In contrast, 2-MAA exposure resulted in a significant concentration-dependent increase in limb abnormalities. 2-MAA induced the hyperacetylation of histones H3K9Ac and H4K12Ac at all concentrations tested (3, 10, and 30 mM). Exposure to 10 or 30 mM 2-MAA significantly increased acetylation of p53 at K379, p21 expression, and caspase-3 cleavage. Thus, 2-MAA, the proximate metabolite of EGME, disrupts limb development in vitro, modifies acetylation programming, and induces biomarkers of cell cycle arrest and apoptosis PMID:24798094

Growth characteristics of fibroblasts isolated from the trunk and distal aspect of the limb of horses and ponies.

PubMed

Miller, C B; Wilson, D A; Keegan, K G; Kreeger, J M; Adelstein, E H; Ganjam, V K

2000-01-01

To determine if there is a difference in in vitro growth of fibroblasts isolated from the trunk and distal aspect of the limb of horses and ponies. To determine the effects of a corticosteroid and monokine on in vitro growth of fibroblasts isolated from the trunk and distal aspect of the limb of horses and ponies. Growth of fibroblasts from tissues harvested from the trunk and limb were compared from horse and pony samples grown in control media and control media with triamcinolone or monokine added. Dermal and subcutaneous tissue from 22 horses and 17 ponies of various ages and breeds. Fibroblast growth was assessed by tritiated thymidine uptake using standard cell culture techniques. The effect of a monokine or triamcinolone plus control media were compared with control media for fibroblast growth. Fibroblast growth from tissues isolated from the horse limb was significantly less than growth from the horse trunk and the limb and trunk of ponies. Monokine was more effective than triamcinolone in suppressing fibroblast growth from tissues isolated from the trunk and limb in both horses and ponies. There are growth differences in fibroblasts isolated from the limb of horses compared with those isolated from the trunk and from the limb and trunk of ponies. The difference in fibroblast growth from tissues isolated from the trunk and limb of horses and ponies may provide evidence for the difference reported in the healing characteristics of limb wounds in horses and ponies. Influencing fibroblast growth may provide a key to controlling the development of exuberant granulation tissue in horses and ponies.

Assisting people with attention deficit hyperactivity disorder by actively reducing limb hyperactive behavior with a gyration air mouse through a controlled environmental stimulation.

PubMed

Shih, Ching-Hsiang

2011-01-01

The latest researches have adopted software technology turning the gyration air mouse into a high performance limb movement detector, and have assessed whether two persons with multiple disabilities would be able to control an environmental stimulation using limb movement. This study extends gyration air mouse functionality by actively reducing limb hyperactive behavior to assess whether two persons with attention deficit hyperactivity disorder (ADHD) would be able to actively reduce their limb hyperactive behavior by controlling their favorite stimulation on/off using a gyration air mouse with a newly developed actively limb hyperactive behavior reducing program (ALHBRP). The study was performed according to an ABAB design, in which A represented the baseline and B represented intervention phases. Data showed that both participants significantly increased their time duration of maintaining a static limb posture (TDMSLP) to activate the control system in order to produce environmental stimulation during the intervention phases. Practical and developmental implications of the findings are discussed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Development of limb volume measuring system

NASA Technical Reports Server (NTRS)

Bhagat, P. K.; Kadaba, P. K.

1983-01-01

The mechanisms underlying the reductions in orthostatic tolerance associated with weightlessness are not well established. Contradictory results from measurements of leg volume changes suggest that altered venomotor tone and reduced blood flow may not be the only contributors to orthostatic intolerance. It is felt that a more accurate limb volume system which is insensitive to environmental factors will aid in better quantification of the hemodynamics of the leg. Of the varous limb volume techniques presently available, the ultrasonic limb volume system has proven to be the best choice. The system as described herein is free from environmental effects, safe, simple to operate and causes negligible radio frequency interference problems. The segmental ultrasonic ultrasonic plethysmograph is expected to provide a better measurement of limb volume change since it is based on cross-sectional area measurements.

Periodic Limb Movements during Sleep and Cardiac Arrhythmia in Older Men (MrOS Sleep)

PubMed Central

Koo, Brian B.; Mehra, Reena; Blackwell, Terri; Ancoli-Israel, Sonia; Stone, Katie L.; Redline, Susan

2014-01-01

Study Objectives: To determine if periodic limb movements during sleep (PLMS) are associated with nocturnal cardiac arrhythmia. Methods: 2,793 community-dwelling older men underwent polysomnography with measurement of limb movements and EKG. Logistic regression assessed association of periodic limb movement index and periodic limb movement arousal index with arrhythmia including atrial fibrillation and non-sustained ventricular tachycardia detected by polysomnography. Models were adjusted for age, race, cardiovascular risk factors, and clinic site. Secondary analyses were subset to men without calcium channel/β-adrenergic medication usage, and stratified by congestive heart failure or myocardial infarction history. Results: In the overall cohort, periodic limb movement index, and periodic limb movement arousal index were not associated with ventricular or atrial arrhythmia after considering potential confounders. In men not taking calcium channel/β-blocking medication, increased adjusted odds of non-sustained ventricular tachycardia were observed for periodic limb movement index (OR = 1.30 per SD increase; 95% CI 1.00, 1.68) and periodic limb movement arousal index (OR = 1.29 per SD increase; 95% CI 1.03, 1.62). In men with CHF or MI, there was a suggested association of atrial fibrillation with periodic limb movement index (OR = 1.29, 95% CI 0.96, 1.73 per SD increase; p = 0.09) or periodic limb movement arousal index (OR = 1.21, 95% CI 0.94, 1.57 per SD increase; p = 0.14), although results were not statistically significant. Conclusions: There is not an association between PLMS and cardiac arrhythmia in all older men but in subsets of men, particularly those with structural heart disease and not on calcium channel or β-adrenergic medication, cardiac arrhythmia does associate with PLMS. Citation: Koo BB; Mehra R; Blackwell T; Ancoli-Israel S; Stone KL; Redline S; for the Osteoporotic Fractures in Men (MrOS) Study Group. Periodic limb movements during sleep and cardiac arrhythmia in older men (MrOS sleep). J Clin Sleep Med 2014;10(1):7-11. PMID:24426814

Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury

PubMed Central

Boyce, Mary K.; Trumble, Troy N.; Carlson, Cathy S.; Groschen, Donna M.; Merritt, Kelly A.; Brown, Murray P.

2013-01-01

Objective Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. Results Osteochondral fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (P=0.0012), while joint circumference (P<0.0001) and effusion scores (P<0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Conclusion Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery. PMID:23467035

Bionic hand exoprosthesis – Perspectives for the future in Romania

PubMed Central

Pogarasteanu, ME; Barbilian, AG

2014-01-01

Prosthetics is a modern area of interest and a challenge in Orthopedics. Over time, there has been a transition from an artisanal method of prosthetics production to modern concepts and materials, including a re-education through virtual reality. The conditions for an efficient fitting of a prosthesis include the necessity that the prosthesis respects the form and function of the lost limb, both anatomically and biomechanically. Prosthetics are made individually, personalized according to sex, age, physiological characteristics, profession and preference. In our country, thoracic limb prosthetics has a relatively short-recorded history of approximately a century, the most preeminent centers being in Iasi, Cluj and Bucharest. Currently, thoracic limb prosthetics, and particularly hand prosthetics, are in a period of development. A technique for amputation and stump reamputation called “circumferential osteoneuromioplasty” (CONM) is currently being used in the Orthopedics and Trauma Clinic of the Central Military University Emergency Hospital in Bucharest. The method was created with the purpose of obtaining distinct myoelectric signals of better quality, following the contraction of each muscle. The CONM method can be used in conjuncture with both the new hand prostheses that are currently available in Romania, and with the model that is being developed by a mixed team from the Polytechnic University in Bucharest, in collaboration with the Central Military University Emergency Hospital in Bucharest. PMID:25713630

EMG-Torque correction on Human Upper extremity using Evolutionary Computation

NASA Astrophysics Data System (ADS)

JL, Veronica; Parasuraman, S.; Khan, M. K. A. Ahamed; Jeba DSingh, Kingsly

2016-09-01

There have been many studies indicating that control system of rehabilitative robot plays an important role in determining the outcome of the therapy process. Existing works have done the prediction of feedback signal in the controller based on the kinematics parameters and EMG readings of upper limb's skeletal system. Kinematics and kinetics based control signal system is developed by reading the output of the sensors such as position sensor, orientation sensor and F/T (Force/Torque) sensor and there readings are to be compared with the preceding measurement to decide on the amount of assistive force. There are also other works that incorporated the kinematics parameters to calculate the kinetics parameters via formulation and pre-defined assumptions. Nevertheless, these types of control signals analyze the movement of the upper limb only based on the movement of the upper joints. They do not anticipate the possibility of muscle plasticity. The focus of the paper is to make use of the kinematics parameters and EMG readings of skeletal system to predict the individual torque of upper extremity's joints. The surface EMG signals are fed into different mathematical models so that these data can be trained through Genetic Algorithm (GA) to find the best correlation between EMG signals and torques acting on the upper limb's joints. The estimated torque attained from the mathematical models is called simulated output. The simulated output will then be compared with the actual individual joint which is calculated based on the real time kinematics parameters of the upper movement of the skeleton when the muscle cells are activated. The findings from this contribution are extended into the development of the active control signal based controller for rehabilitation robot.

Orthopedic surgery and bone fracture pain are both significantly attenuated by sustained blockade of nerve growth factor

PubMed Central

Majuta, Lisa A.; Longo, Geraldine; Fealk, Michelle N.; McCaffrey, Gwen; Mantyh, Patrick W.

2015-01-01

The number of patients suffering from postoperative pain due to orthopedic surgery and bone fracture is projected to dramatically increase because the human life span, weight, and involvement in high-activity sports continue to rise worldwide. Joint replacement or bone fracture frequently results in skeletal pain that needs to be adequately controlled for the patient to fully participate in needed physical rehabilitation. Currently, the 2 major therapies used to control skeletal pain are nonsteroidal anti-inflammatory drugs and opiates, both of which have significant unwanted side effects. To assess the efficacy of novel therapies, mouse models of orthopedic and fracture pain were developed and evaluated here. These models, orthopedic surgery pain and bone fracture pain, resulted in skeletal pain–related behaviors that lasted 3 weeks and 8 to 10 weeks, respectively. These skeletal pain behaviors included spontaneous and palpation-induced nocifensive behaviors, dynamic weight bearing, limb use, and voluntary mechanical loading of the injured hind limb. Administration of anti–nerve growth factor before orthopedic surgery or after bone fracture attenuated skeletal pain behaviors by 40% to 70% depending on the end point being assessed. These data suggest that nerve growth factor is involved in driving pain due to orthopedic surgery or bone fracture. These animal models may be useful in developing an understanding of the mechanisms that drive postoperative orthopedic and bone fracture pain and the development of novel therapies to treat these skeletal pains. PMID:25599311

A Tunable Silk Hydrogel Device for Studying Limb Regeneration in Adult Xenopus Laevis

PubMed Central

Golding, Anne; Levin, Michael; Kaplan, David L.

2016-01-01

In certain amphibian models limb regeneration can be promoted or inhibited by the local wound bed environment. This research introduces a device that can be utilized as an experimental tool to characterize the conditions that promotes limb regeneration in the adult frog (Xenopus laevis) model. In particular, this device was designed to manipulate the local wound environment via a hydrogel insert. Initial characterization of the hydrogel insert revealed that this interaction had a significant influence on mechanical forces to the animal, due to the contraction of the hydrogel. The material and mechanical properties of the hydrogel insert were a factor in the device design in relation to the comfort of the animal and the ability to effectively manipulate the amputation site. The tunable features of the hydrogel were important in determining the pro-regenerative effects in limb regeneration, which was measured by cartilage spike formation and quantified by micro-computed tomography. The hydrogel insert was a factor in the observed morphological outcomes following amputation. Future work will focus on characterizing and optimizing the device’s observed capability to manipulate biological pathways that are essential for limb regeneration. However, the present work provides a framework for the role of a hydrogel in the device and a path forward for more systematic studies. PMID:27257960

Adaptive control based on an on-line parameter estimation of an upper limb exoskeleton.

PubMed

Riani, Akram; Madani, Tarek; Hadri, Abdelhafid El; Benallegue, Abdelaziz

2017-07-01

This paper presents an adaptive control strategy for an upper-limb exoskeleton based on an on-line dynamic parameter estimator. The objective is to improve the control performance of this system that plays a critical role in assisting patients for shoulder, elbow and wrist joint movements. In general, the dynamic parameters of the human limb are unknown and differ from a person to another, which degrade the performances of the exoskeleton-human control system. For this reason, the proposed control scheme contains a supplementary loop based on a new efficient on-line estimator of the dynamic parameters. Indeed, the latter is acting upon the parameter adaptation of the controller to ensure the performances of the system in the presence of parameter uncertainties and perturbations. The exoskeleton used in this work is presented and a physical model of the exoskeleton interacting with a 7 Degree of Freedom (DoF) upper limb model is generated using the SimMechanics library of MatLab/Simulink. To illustrate the effectiveness of the proposed approach, an example of passive rehabilitation movements is performed using multi-body dynamic simulation. The aims is to maneuver the exoskeleton that drive the upper limb to track desired trajectories in the case of the passive arm movements.

A new look at the Dynamic Similarity Hypothesis: the importance of swing phase.

PubMed

Raichlen, David A; Pontzer, Herman; Shapiro, Liza J

2013-01-01

The Dynamic Similarity Hypothesis (DSH) suggests that when animals of different size walk at similar Froude numbers (equal ratios of inertial and gravitational forces) they will use similar size-corrected gaits. This application of similarity theory to animal biomechanics has contributed to fundamental insights in the mechanics and evolution of a diverse set of locomotor systems. However, despite its popularity, many mammals fail to walk with dynamically similar stride lengths, a key element of gait that determines spontaneous speed and energy costs. Here, we show that the applicability of the DSH is dependent on the inertial forces examined. In general, the inertial forces are thought to be the centripetal force of the inverted pendulum model of stance phase, determined by the length of the limb. If instead we model inertial forces as the centripetal force of the limb acting as a suspended pendulum during swing phase (determined by limb center of mass position), the DSH for stride length variation is fully supported. Thus, the DSH shows that inter-specific differences in spatial kinematics are tied to the evolution of limb mass distribution patterns. Selection may act on morphology to produce a given stride length, or alternatively, stride length may be a "spandrel" of selection acting on limb mass distribution.

Delayed amputation following trauma increases residual lower limb infection.

PubMed

Jain, Abhilash; Glass, Graeme E; Ahmadi, Hootan; Mackey, Simon; Simmons, Jon; Hettiaratchy, Shehan; Pearse, Michael; Nanchahal, Jagdeep

2013-04-01

Residual limb infection following amputation is a devastating complication, resulting in delayed rehabilitation, repeat surgery, prolonged hospitalisation and poor functional outcome. The aim of this study was to identify variables predicting residual limb infection following non-salvageable lower limb trauma. All cases of non-salvageable lower limb trauma presenting to a specialist centre over 5 years were evaluated from a prospective database and clinical and management variables correlated with the development of deep infection. Forty patients requiring 42 amputations were identified with a mean age of 49 years (±19.9, 1SD). Amputations were performed for 21 Gustilo IIIB injuries, 12 multi-planar degloving injuries, seven IIIC injuries and one open Schatzker 6 fracture. One limb was traumatically amputated at the scene and surgically revised. Amputation level was transtibial in 32, through-knee in one and transfemoral in nine. Median time from injury to amputation was 4 days (range 0-30 days). Amputation following only one debridement and within 5 days resulted in significantly fewer stump infections (p = 0.026 and p = 0.03, respectively, Fisher's exact test). The cumulative probability of infection-free residual limb closure declined steadily from day 5. Multivariate analyses revealed that neither the nature of the injury nor pre-injury patient morbidity independently influenced residual limb infection. Avoiding residual limb infection is critically dependent on prompt amputation of non-salvageable limbs. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A STUDY OF SOLAR PHOTOSPHERIC TEMPERATURE GRADIENT VARIATION USING LIMB DARKENING MEASUREMENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Criscuoli, Serena; Foukal, Peter

2017-01-20

The variation in area of quiet magnetic network measured over the sunspot cycle should modulate the spatially averaged photospheric temperature gradient, since temperature declines with optical depth more gradually in magnetic flux tube atmospheres. Yet, limb darkening measurements show no dependence upon activity level, even at an rms precision of 0.04%. We study the sensitivity of limb darkening to changes in area filling factor using a 3D MHD model of the magnetized photosphere. The limb darkening change expected from the measured 11-year area variation lies below the level of measured limb darkening variations, for a reasonable range of magnetic fluxmore » in quiet network and internetwork regions. So the remarkably constant limb darkening observed over the solar activity cycle is not inconsistent with the measured 11-year change in area of quiet magnetic network. Our findings offer an independent constraint on photospheric temperature gradient changes reported from measurements of the solar spectral irradiance from the Spectral Irradiance Monitor, and recently, from wavelength-differential spectrophotometry using the Solar Optical Telescope aboard the HINODE spacecraft.« less

Allometric associations between body size, shape, and 100-m butterfly speed performance.

PubMed

Sammoud, Senda; Nevill, Alan M; Negra, Yassine; Bouguezzi, Raja; Chaabene, Helmi; Hachana, Younés

2018-05-01

This study aimed to estimate the optimal body size, limb-segment length, and girth or breadth ratios associated with 100-m butterfly speed performance in swimmers. One-hundred-sixty-seven swimmers as subjects (male: N.=103; female: N.=64). Anthropometric measurements comprised height, body-mass, skinfolds, arm-span, upper-limb-length, upper-arm, forearm, hand-lengths, lower-limb-length, thigh-length, leg-length, foot-length, arm-relaxed-girth, forearm-girth, wrist-girth, thigh-girth, calf-girth, ankle-girth, biacromial and biiliocristal-breadths. To estimate the optimal body size and body composition components associated with 100-m butterfly speed performance, we adopted a multiplicative allometric log-linear regression model, which was refined using backward elimination. Fat-mass was the singularly most important whole-body characteristic. Height and body-mass did not contribute to the model. The allometric model identified that having greater limb segment length-ratio (arm-ratio = [arm-span]/[forearm]) and limb girth-ratio (girth-ratio = [calf-girth]/[ankle-girth]) were key to butterfly speed performance. A greater arm-span to forearm-length ratio and a greater calf to ankle-girth-ratio suggest that a combination of larger arm-span and shorter forearm-length and the combination of larger calves and smaller ankles-girth may benefit butterfly swim speed performance. In addition having greater biacromial and biliocristal breadths is also a major advantage in butterfly swimming speed performance. Finally, the estimation of these ratios was made possible by adopting a multiplicative allometric model that was able to confirm, theoretically, that swim speeds are nearly independent of total body size. The 100-m butterfly speed performance was strongly negatively associated with fat mass and positively associated with the segment length ratio (arm-span/forearm-length) and girth ratio (calf-girth)/(ankle-girth), having controlled for the developmental changes in age.

Limb Amputations in Fixed Dystonia: A Form of Body Integrity Identity Disorder?

PubMed Central

Edwards, Mark J; Alonso-Canovas, Araceli; Schrag, Arnette; Bloem, Bastiaan R; Thompson, Philip D; Bhatia, Kailash

2011-01-01

Fixed dystonia is a disabling disorder mainly affecting young women who develop fixed abnormal limb postures and pain after apparently minor peripheral injury. There is continued debate regarding its pathophysiology and management. We report 5 cases of fixed dystonia in patients who sought amputation of the affected limb. We place these cases in the context of previous reports of patients with healthy limbs and patients with chronic regional pain syndrome who have sought amputation. Our cases, combined with recent data regarding disorders of mental rotation in patients with fixed dystonia, as well as previous data regarding body integrity identity disorder and amputations sought by patients with chronic regional pain syndrome, raise the possibility that patients with fixed dystonia might have a deficit in body schema that predisposes them to developing fixed dystonia and drives some to seek amputation. The outcome of amputation in fixed dystonia is invariably unfavorable. © 2011 Movement Disorder Society PMID:21484872

Limb amputations in fixed dystonia: a form of body integrity identity disorder?

PubMed

Edwards, Mark J; Alonso-Canovas, Araceli; Schrag, Arnette; Bloem, Bastiaan R; Thompson, Philip D; Bhatia, Kailash

2011-07-01

Fixed dystonia is a disabling disorder mainly affecting young women who develop fixed abnormal limb postures and pain after apparently minor peripheral injury. There is continued debate regarding its pathophysiology and management. We report 5 cases of fixed dystonia in patients who sought amputation of the affected limb. We place these cases in the context of previous reports of patients with healthy limbs and patients with chronic regional pain syndrome who have sought amputation. Our cases, combined with recent data regarding disorders of mental rotation in patients with fixed dystonia, as well as previous data regarding body integrity identity disorder and amputations sought by patients with chronic regional pain syndrome, raise the possibility that patients with fixed dystonia might have a deficit in body schema that predisposes them to developing fixed dystonia and drives some to seek amputation. The outcome of amputation in fixed dystonia is invariably unfavorable. Copyright © 2011 Movement Disorder Society.

The influence of nutrients, biliary-pancreatic secretions, and systemic trophic hormones on intestinal adaptation in a Roux-en-Y bypass model.

PubMed

Taqi, Esmaeel; Wallace, Laurie E; de Heuvel, Elaine; Chelikani, Prasanth K; Zheng, Huiyuan; Berthoud, Hans-Rudolph; Holst, Jens J; Sigalet, David L

2010-05-01

The signals that govern the upregulation of nutrient absorption (adaptation) after intestinal resection are not well understood. A Gastric Roux-en-Y bypass (GRYB) model was used to isolate the relative contributions of direct mucosal stimulation by nutrients, biliary-pancreatic secretions, and systemic enteric hormones on intestinal adaptation in short bowel syndrome. Male rats (350-400 g; n = 8/group) underwent sham or GRYB with pair feeding and were observed for 14 days. Weight and serum hormonal levels (glucagon-like peptide-2 [GLP-2], PYY) were quantified. Adaptation was assessed by intestinal morphology and crypt cell kinetics in each intestinal limb of the bypass and the equivalent points in the sham intestine. Mucosal growth factors and expression of transporter proteins were measured in each limb of the model. The GRYB animals lost weight compared to controls and exhibited significant adaptive changes with increased bowel width, villus height, crypt depth, and proliferation indices in the alimentary and common intestinal limbs. Although the biliary limb did not adapt at the mucosa, it did show an increased bowel width and crypt cell proliferation rate. The bypass animals had elevated levels of systemic PYY and GLP-2. At the mucosal level, insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF) increased in all limbs of the bypass animals, whereas keratinocyte growth factor (KGF) and epidermal growth factor (EGF) had variable responses. The expression of the passive transporter of glucose, GLUT-2, expression was increased, whereas GLUT-5 was unchanged in all limbs of the bypass groups. Expression of the active mucosal transporter of glucose, SGLT-1 was decreased in the alimentary limb. Adaptation occurred maximally in intestinal segments stimulated by nutrients. Partial adaptation in the biliary limb may reflect the effects of systemic hormones. Mucosal content of IGF-1, bFGF, and EGF appear to be stimulated by systemic hormones, potentially GLP-2, whereas KGF may be locally regulated. Further studies to examine the relationships between the factors controlling nutrient-induced adaptation are suggested. Direct contact with nutrients appears to be the most potent factor in inducing mucosal adaptation. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Use of the TRPV1 Agonist Capsaicin to Provide Long-Term Analgesia in a Rat Limb Fracture/Open Repair, Internal Fixation Model

DTIC Science & Technology

2012-10-01

W81XWH-10-2-0093 TITLE: Use of the TRPV1 Agonist Capsaicin to Provide Long-Term Analgesia in a Rat Limb Fracture/Open Repair, Internal Fixation Model...2. REPORT TYPE Final 3. DATES COVERED (From - To) 30September2010-29September2012 4. TITLE AND SUBTITLE Use of the TRPV1 Agonist Capsaicin to...capsaicin around the fracture site. 15. SUBJECT TERMS Femur fracture, Rat Model, Pain, Capsaicin, Trauma, TRPV1 16. SECURITY CLASSIFICATION OF

Measurement of Forces and Moments Transmitted to the Residual Limb

DTIC Science & Technology

2008-08-01

leg and residual limb, the condition of your residual limb including touch and pressure sensation, and the type of components used in your prosthesis ...measured by a tri-axial transducer mounted on the pylon of a transtibial prosthesis distal to the socket can be used to estimate the intra-socket...alignment has been developed, and IRB approval has been obtained. 15. SUBJECT TERMS Amputees, prosthesis alignment, socket pressure, gait, force and moment

Development of Device to Evoke Stretch Reflexes by Use of Electromagnetic Force for the Rehabilitation of the Hemiplegic Upper Limb after Stroke

NASA Astrophysics Data System (ADS)

Hayashi, Ryota; Ishimine, Tomoyasu; Kawahira, Kazumi; Yu, Yong; Tsujio, Showzow

In this research, we focus on the method of rehabilitation with stretch reflexes for the hemiplegic upper limb in stroke patients. We propose a new device which utilizes electromagnetic force to evoke stretch reflexes. The device can exert an assisting force safely, because the electromagnetic force is non contact force. In this paper, we develop a support system applying the proposed device for the functional recovery training of the hemiplegic upper limb. The results obtained from several clinical tests with and without our support system are compared. Then we discuss the validity of our support system.

Finite element modeling of a 3D coupled foot-boot model.

PubMed

Qiu, Tian-Xia; Teo, Ee-Chon; Yan, Ya-Bo; Lei, Wei

2011-12-01

Increasingly, musculoskeletal models of the human body are used as powerful tools to study biological structures. The lower limb, and in particular the foot, is of interest because it is the primary physical interaction between the body and the environment during locomotion. The goal of this paper is to adopt the finite element (FE) modeling and analysis approaches to create a state-of-the-art 3D coupled foot-boot model for future studies on biomechanical investigation of stress injury mechanism, foot wear design and parachute landing fall simulation. In the modeling process, the foot-ankle model with lower leg was developed based on Computed Tomography (CT) images using ScanIP, Surfacer and ANSYS. Then, the boot was represented by assembling the FE models of upper, insole, midsole and outsole built based on the FE model of the foot-ankle, and finally the coupled foot-boot model was generated by putting together the models of the lower limb and boot. In this study, the FE model of foot and ankle was validated during balance standing. There was a good agreement in the overall patterns of predicted and measured plantar pressure distribution published in literature. The coupled foot-boot model will be fully validated in the subsequent works under both static and dynamic loading conditions for further studies on injuries investigation in military and sports, foot wear design and characteristics of parachute landing impact in military. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Multibody system of the upper limb including a reverse shoulder prosthesis.

PubMed

Quental, C; Folgado, J; Ambrósio, J; Monteiro, J

2013-11-01

The reverse shoulder replacement, recommended for the treatment of several shoulder pathologies such as cuff tear arthropathy and fractures in elderly people, changes the biomechanics of the shoulder when compared to the normal anatomy. Although several musculoskeletal models of the upper limb have been presented to study the shoulder joint, only a few of them focus on the biomechanics of the reverse shoulder. This work presents a biomechanical model of the upper limb, including a reverse shoulder prosthesis, to evaluate the impact of the variation of the joint geometry and position on the biomechanical function of the shoulder. The biomechanical model of the reverse shoulder is based on a musculoskeletal model of the upper limb, which is modified to account for the properties of the DELTA® reverse prosthesis. Considering two biomechanical models, which simulate the anatomical and reverse shoulder joints, the changes in muscle lengths, muscle moment arms, and muscle and joint reaction forces are evaluated. The muscle force sharing problem is solved for motions of unloaded abduction in the coronal plane and unloaded anterior flexion in the sagittal plane, acquired using video-imaging, through the minimization of an objective function related to muscle metabolic energy consumption. After the replacement of the shoulder joint, significant changes in the length of the pectoralis major, latissimus dorsi, deltoid, teres major, teres minor, coracobrachialis, and biceps brachii muscles are observed for a reference position considered for the upper limb. The shortening of the teres major and teres minor is the most critical since they become unable to produce active force in this position. Substantial changes of muscle moment arms are also observed, which are consistent with the literature. As expected, there is a significant increase of the deltoid moment arms and more fibers are able to elevate the arm. The solutions to the muscle force sharing problem support the biomechanical advantages attributed to the reverse shoulder design and show an increase in activity from the deltoid, teres minor, and coracobrachialis muscles. The glenohumeral joint reaction forces estimated for the reverse shoulder are up to 15% lower than those in the normal shoulder anatomy. The data presented here complements previous publications, which, all together, allow researchers to build a biomechanical model of the upper limb including a reverse shoulder prosthesis.

Acute lower motor neuron tetraparesis.

PubMed

Añor, Sònia

2014-11-01

Flaccid nonambulatory tetraparesis or tetraplegia is an infrequent neurologic presentation; it is characteristic of neuromuscular disease (lower motor neuron [LMN] disease) rather than spinal cord disease. Paresis beginning in the pelvic limbs and progressing to the thoracic limbs resulting in flaccid tetraparesis or tetraplegia within 24 to 72 hours is a common presentation of peripheral nerve or neuromuscular junction disease. Complete body flaccidity develops with severe decrease or complete loss of spinal reflexes in pelvic and thoracic limbs. Animals with acute generalized LMN tetraparesis commonly show severe motor dysfunction in all limbs and severe generalized weakness in all muscles. Copyright © 2014 Elsevier Inc. All rights reserved.

Distal limb cast sores in horses: risk factors and early detection using thermography.

PubMed

Levet, T; Martens, A; Devisscher, L; Duchateau, L; Bogaert, L; Vlaminck, L

2009-01-01

There is a lack of evidence-based data on the prevalence, outcome and risk factors of distal limb cast sores, and no objective tool has been described for the early detection of cast sores. To investigate the prevalence, location, outcome and risk factors of cast sores after application of a distal limb cast and to determine whether static thermography of the cast is a valuable tool for the assessment of sores. A prospective study was conducted on horses treated with a distal limb cast. At each cast removal, cast sores were graded as superficial sores (SS), deep dermal sores (DS) or full thickness skin ulcerations (FS). In several cases, a thermographic evaluation of the cast was performed immediately prior to removal and differences in temperature (AT) between the coolest point of the cast and 2 cast regions predisposed for sore development (dorsoproximal mc/mtIII and palmar/plantar fetlock) were calculated. Mean +/- s.d. total casting time of 70 horses was 31 +/- 18 days. Overall, 57 legs (81%) developed at least SS. Twenty-four legs (34%) ultimately developed DS and one horse had an FS. Multivariable analysis showed that the severity of sores was positively associated with increasing age (OR: 1.111, P = 0.028), a normal (vs. swollen) limb (OR: 3387, P = 0.023) and an increase in total casting time (OR per week: 1.363, P = 0.002). The thermographic evaluation (35 casts) revealed that the severity of sores was positively associated with increasing deltaT (OR: 2.100, P = 0.0005). The optimal cut-off values for the presence of SS and DS were set at, respectively, deltaT = 23 and 43 degrees C. Distal limb cast is a safe coaptation technique with increasing risk of developing sores with time. Thermography is a valuable and rapid clinical tool to monitor the development of cast sores.

Restoring movement representation and alleviating phantom limb pain through short-term neurorehabilitation with a virtual reality system.

PubMed

Osumi, M; Ichinose, A; Sumitani, M; Wake, N; Sano, Y; Yozu, A; Kumagaya, S; Kuniyoshi, Y; Morioka, S

2017-01-01

We developed a quantitative method to measure movement representations of a phantom upper limb using a bimanual circle-line coordination task (BCT). We investigated whether short-term neurorehabilitation with a virtual reality (VR) system would restore voluntary movement representations and alleviate phantom limb pain (PLP). Eight PLP patients were enrolled. In the BCT, they repeatedly drew vertical lines using the intact hand and intended to draw circles using the phantom limb. Drawing circles mentally using the phantom limb led to the emergence of an oval transfiguration of the vertical lines ('bimanual-coupling' effect). We quantitatively measured the degree of this bimanual-coupling effect as movement representations of the phantom limb before and immediately after short-term VR neurorehabilitation. This was achieved using an 11-point numerical rating scale (NRS) for PLP intensity and the Short-Form McGill Pain Questionnaire (SF-MPQ). During VR neurorehabilitation, patients wore a head-mounted display that showed a mirror-reversed computer graphic image of an intact arm (the virtual phantom limb). By intending to move both limbs simultaneously and similarly, the patients perceived voluntary execution of movement in their phantom limb. Short-term VR neurorehabilitation promptly restored voluntary movement representations in the BCT and alleviated PLP (NRS: p = 0.015; 39.1 ± 28.4% relief, SF-MPQ: p = 0.015; 61.5 ± 48.5% relief). Restoration of phantom limb movement representations and reduced PLP intensity were linearly correlated (p < 0.05). VR rehabilitation may encourage patient's motivation and multimodal sensorimotor re-integration of a phantom limb and subsequently have a potent analgesic effect. There was no objective evidence that restoring movement representation by neurorehabilitation with virtual reality alleviated phantom limb pain. This study revealed quantitatively that restoring movement representation with virtual reality rehabilitation using a bimanual coordination task correlated with alleviation of phantom limb pain. © 2016 European Pain Federation - EFIC®.

Comparison of LDPI to SPECT perfusion imaging using (99m)Tc-sestamibi and (99m)Tc-pyrophosphate in a murine ischemic hind limb model of neovascularization.

PubMed

Hendrikx, Geert; Vries, Mark H; Bauwens, Matthias; De Saint-Hubert, Marijke; Wagenaar, Allard; Guillaume, Joël; Boonen, Levinia; Post, Mark J; Mottaghy, Felix M

2016-12-01

We aimed to determine the accuracy of laser Doppler perfusion imaging (LDPI) in an animal model for hind limb ischemia. We used a murine (C57Bl/6 mice) ischemic hind limb model in which we compared LDPI with the clinically used (99m)Tc-sestamibi SPECT perfusion imaging (n = 7). In addition, we used the SPECT tracer (99m)Tc-pyrophosphate ((99m)Tc-PyP) to image muscular damage (n = 6). LDPI indicated a quick and prominent decrease in perfusion immediately after ligation, subsequently recovering to 21.9 and 25.2 % 14 days later in the (99m)Tc-sestamibi and (99m)Tc-PyP group, respectively. (99m)Tc-sestamibi SPECT scans also showed a quick decrease in perfusion. However, nearly full recovery was reached 7 days post ligation. Muscular damage, indicated by the uptake of (99m)Tc-PyP, was highest at day 3 and recovered to baseline levels at day 14 post ligation. Postmortem histology supported these findings, as a significantly increased collateral diameter was found 7 and 14 days after ligation and peak macrophage infiltration and TUNEL positivity was found on day 3 after ligation. Here, we indicate that LDPI strongly underestimates perfusion recovery in a hind limb model for profound ischemia.

Quantitative analysis of tissue deformation dynamics reveals three characteristic growth modes and globally aligned anisotropic tissue deformation during chick limb development.

PubMed

Morishita, Yoshihiro; Kuroiwa, Atsushi; Suzuki, Takayuki

2015-05-01

Tissue-level characterization of deformation dynamics is crucial for understanding organ morphogenetic mechanisms, especially the interhierarchical links among molecular activities, cellular behaviors and tissue/organ morphogenetic processes. Limb development is a well-studied topic in vertebrate organogenesis. Nevertheless, there is still little understanding of tissue-level deformation relative to molecular and cellular dynamics. This is mainly because live recording of detailed cell behaviors in whole tissues is technically difficult. To overcome this limitation, by applying a recently developed Bayesian approach, we here constructed tissue deformation maps for chick limb development with high precision, based on snapshot lineage tracing using dye injection. The precision of the constructed maps was validated with a clear statistical criterion. From the geometrical analysis of the map, we identified three characteristic tissue growth modes in the limb and showed that they are consistent with local growth factor activity and cell cycle length. In particular, we report that SHH signaling activity changes dynamically with developmental stage and strongly correlates with the dynamic shift in the tissue growth mode. We also found anisotropic tissue deformation along the proximal-distal axis. Morphogenetic simulation and experimental studies suggested that this directional tissue elongation, and not local growth, has the greatest impact on limb shaping. This result was supported by the novel finding that anisotropic tissue elongation along the proximal-distal axis occurs independently of cell proliferation. Our study marks a pivotal point for multi-scale system understanding in vertebrate development. © 2015. Published by The Company of Biologists Ltd.

New model for estimating the relationship between surface area and volume in the human body using skeletal remains.

PubMed

Kasabova, Boryana E; Holliday, Trenton W

2015-04-01

A new model for estimating human body surface area and body volume/mass from standard skeletal metrics is presented. This model is then tested against both 1) "independently estimated" body surface areas and "independently estimated" body volume/mass (both derived from anthropometric data) and 2) the cylindrical model of Ruff. The model is found to be more accurate in estimating both body surface area and body volume/mass than the cylindrical model, but it is more accurate in estimating body surface area than it is for estimating body volume/mass (as reflected by the standard error of the estimate when "independently estimated" surface area or volume/mass is regressed on estimates derived from the present model). Two practical applications of the model are tested. In the first test, the relative contribution of the limbs versus the trunk to the body's volume and surface area is compared between "heat-adapted" and "cold-adapted" populations. As expected, the "cold-adapted" group has significantly more of its body surface area and volume in its trunk than does the "heat-adapted" group. In the second test, we evaluate the effect of variation in bi-iliac breadth, elongated or foreshortened limbs, and differences in crural index on the body's surface area to volume ratio (SA:V). Results indicate that the effects of bi-iliac breadth on SA:V are substantial, while those of limb lengths and (especially) the crural index are minor, which suggests that factors other than surface area relative to volume are driving morphological variation and ecogeographical patterning in limb prorportions. © 2014 Wiley Periodicals, Inc.

A cortical-spinal prosthesis for targeted limb movement in paralyzed primate avatars

PubMed Central

Shanechi, Maryam M.; Hu, Rollin C.; Williams, Ziv M.

2014-01-01

Motor paralysis is among the most disabling aspects of injury to the central nervous system. Here we develop and test a target-based cortical-spinal neural prosthesis that employs neural activity recorded from pre-motor neurons to control limb movements in functionally paralyzed primate avatars. Given the complexity by which muscle contractions are naturally controlled, we approach the problem of eliciting goal-directed limb movement in paralyzed animals by focusing on the intended targets of movement rather than their intermediate trajectories. We then match this information in real-time with spinal cord and muscle stimulation parameters that produce free planar limb movements to those intended target locations. We demonstrate that both the decoded activities of pre-motor populations and their adaptive responses can be used, after brief training, to effectively direct an avatar’s limb to distinct targets variably displayed on a screen. These findings advance the future possibility of reconstituting targeted limb movement in paralyzed subjects. PMID:24549394

Movement analysis of upper limb during resistance training using general purpose robot arm "PA10"

NASA Astrophysics Data System (ADS)

Morita, Yoshifumi; Yamamoto, Takashi; Suzuki, Takahiro; Hirose, Akinori; Ukai, Hiroyuki; Matsui, Nobuyuki

2005-12-01

In this paper we perform movement analysis of an upper limb during resistance training. We selected sanding training, which is one type of resistance training for upper limbs widely performed in occupational therapy. Our final aims in the future are to quantitatively evaluate the therapeutic effect of upper limb motor function during training and to develop a new rehabilitation training support system. For these purposes, first of all we perform movement analysis using a conventional training tool. By measuring upper limb motion during the sanding training we perform feature abstraction. Next we perform movement analysis using the simulated sanding training system. This system is constructed using the general purpose robot arm "PA10". This system enables us to measure the force/torque exerted by subjects and to easily change the load of resistance. The control algorithm is based on impedance control. We found these features of the upper limb motion during the sanding training.

Novel and optimized strategies for inducing fibrosis in vivo: focus on Duchenne Muscular Dystrophy

PubMed Central

2014-01-01

Background Fibrosis, an excessive collagen accumulation, results in scar formation, impairing function of vital organs and tissues. Fibrosis is a hallmark of muscular dystrophies, including the lethal Duchenne muscular dystrophy (DMD), which remains incurable. Substitution of muscle by fibrotic tissue also complicates gene/cell therapies for DMD. Yet, no optimal models to study muscle fibrosis are available. In the widely used mdx mouse model for DMD, extensive fibrosis develops in the diaphragm only at advanced adulthood, and at about two years of age in the ‘easy-to-access’ limb muscles, thus precluding fibrosis research and the testing of novel therapies. Methods We developed distinct experimental strategies, ranging from chronic exercise to increasing muscle damage on limb muscles of young mdx mice, by myotoxin injection, surgically induced trauma (laceration or denervation) or intramuscular delivery of profibrotic growth factors (such as TGFβ). We also extended these approaches to muscle of normal non-dystrophic mice. Results These strategies resulted in advanced and enhanced muscle fibrosis in young mdx mice, which persisted over time, and correlated with reduced muscle force, thus mimicking the severe DMD phenotype. Furthermore, increased fibrosis was also obtained by combining these procedures in muscles of normal mice, mirroring aberrant repair after severe trauma. Conclusions We have developed new and improved experimental strategies to accelerate and enhance muscle fibrosis in vivo. These strategies will allow rapidly assessing fibrosis in the easily accessible limb muscles of young mdx mice, without necessarily having to use old animals. The extension of these fibrogenic regimes to the muscle of non-dystrophic wild-type mice will allow fibrosis assessment in a wide array of pre-existing transgenic mouse lines, which in turn will facilitate understanding the mechanisms of fibrogenesis. These strategies should improve our ability to combat fibrosis-driven dystrophy progression and aberrant regeneration. PMID:25157321

Pattern of spread and prognosis in lower limb-onset ALS

PubMed Central

TURNER, MARTIN R.; BROCKINGTON, ALICE; SCABER, JAKUB; HOLLINGER, HANNAH; MARSDEN, RACHAEL; SHAW, PAMELA J.; TALBOT, KEVIN

2011-01-01

Our objective was to establish the pattern of spread in lower limb-onset ALS (contra- versus ipsi-lateral) and its contribution to prognosis within a multivariate model. Pattern of spread was established in 109 sporadic ALS patients with lower limb-onset, prospectively recorded in Oxford and Sheffield tertiary clinics from 2001 to 2008. Survival analysis was by univariate Kaplan-Meier log-rank and multivariate Cox proportional hazards. Variables studied were time to next limb progression, site of next progression, age at symptom onset, gender, diagnostic latency and use of riluzole. Initial progression was either to the contralateral leg (76%) or ipsilateral arm (24%). Factors independently affecting survival were time to next limb progression, age at symptom onset, and diagnostic latency. Time to progression as a prognostic factor was independent of initial direction of spread. In a regression analysis of the deceased, overall survival from symptom onset approximated to two years plus the time interval for initial spread. In conclusion, rate of progression in lower limb-onset ALS is not influenced by whether initial spread is to the contralateral limb or ipsilateral arm. The time interval to this initial spread is a powerful factor in predicting overall survival, and could be used to facilitate decision-making and effective care planning. PMID:20001488

The Relative Contribution of Ankle Moment and Trailing Limb Angle to Propulsive Force during Gait

PubMed Central

Hsiao, HaoYuan; Knarr, Brian A.; Higginson, Jill S.; Binder-Macleod, Stuart A.

2014-01-01

A major factor for increasing walking speed is the ability to increase propulsive force. Although propulsive force has been shown to be related to ankle moment and trailing limb angle, the relative contribution of each factor to propulsive force has never been determined. The primary purpose of this study was to quantify the relative contribution of ankle moment and trailing limb angle to propulsive force for able-bodied individuals walking at different speeds. Twenty able-bodied individuals walked at their self-selected and 120% of self-selected walking speed on the treadmill. Kinematic data were collected using an 8-camera motion-capture system. A model describing the relationship between ankle moment, trailing limb angle and propulsive force was obtained through quasi-static analysis. Our main findings were that ankle moment and trailing limb angle each contributes linearly to propulsive force, and that the change in trailing limb angle contributes almost as twice as much as the change in ankle moment to the increase in propulsive force during speed modulation for able-bodied individuals. Able-bodied individuals preferentially modulate trailing limb angle more than ankle moment to increase propulsive force. Future work will determine if this control strategy can be applied to individuals poststroke. PMID:25498289

Studies of limb-dislodging forces acting on an ejection seat occupant.

PubMed

Schneck, D J

1980-03-01

A mathematical theory is being developed in order to calculate the aerodynamic loading to which a pilot is exposed during high-speed ejections. Neglecting the initial effects of flow separation, results thus far indicate that a pilot's musculoskeletal system is not likely to withstand the tendency for limb-flailing if he is ejecting at Mach numbers in excess of about 0.7. This tendency depends very strongly upon the angle at which the pilot's limbs intercept a high-speed flow; the forces that cause limb dislodgement increase dramatically with speed of ejection. Examining the time-course of limb-dislodging forces after the initial onset of windblast, the theory further predicts the generation of a double vortex street pattern on the downstream side of the limbs of an ejection seat occupant. This results in the corresponding appearance of oscillating forces tending to cause lateral motion (vibration) of the limbs. The amplitude and frequency of these oscillating forces are also very dependent on the Mach number of ejection and the angle at which the pilot's limbs intercept the flow. However, even at moderate Mach numbers, the frequency can be as high as 100 cycles per second, and the amplitude rapidly exceeds a pilot's musculo-skeletal resistive powers for Mach numbers above 0.7.

Development and preliminary evaluation of a new anatomically based prosthetic alignment method for below-knee prosthesis.

PubMed

Tafti, Nahid; Karimlou, Masoud; Mardani, Mohammad Ali; Jafarpisheh, Amir Salar; Aminian, Gholam Reza; Safari, Reza

2018-04-20

The objectives of current study were to a) assess similarities and relationships between anatomical landmark-based angles and distances of lower limbs in unilateral transtibial amputees and b) develop and evaluate a new anatomically based static prosthetic alignment method. First sub-study assessed the anthropometrical differences and relationships between the lower limbs in the photographs taken from amputees. Data were analysed via paired t-test and regression analysis. Results show no significant differences in frontal and transverse planes. In the sagittal plane, the anthropometric parameters of the amputated limb were significantly correlated to the corresponding variables of the sound limb. The results served as bases for the development of a new prosthetic alignment method. The method was evaluated on a single subject study. Prosthetic alignment carried out by an experienced prosthetist was compared with such alignment adjusted by an inexperienced prosthetist but with the use of the developed method. In sagittal and frontal planes, the socket angle was tuned with respect to the shin angle, and the position of the prosthetic foot was tuned in relation to the pelvic landmarks. Further study is needed to assess the proposed method on a larger sample of amputees and prosthetists.

Enhancer elements upstream of the SHOX gene are active in the developing limb.

PubMed

Durand, Claudia; Bangs, Fiona; Signolet, Jason; Decker, Eva; Tickle, Cheryll; Rappold, Gudrun

2010-05-01

Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.

Enhancer elements upstream of the SHOX gene are active in the developing limb

PubMed Central

Durand, Claudia; Bangs, Fiona; Signolet, Jason; Decker, Eva; Tickle, Cheryll; Rappold, Gudrun

2010-01-01

Léri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD. PMID:19997128

Stochastic Estimation of Arm Mechanical Impedance During Robotic Stroke Rehabilitation

PubMed Central

Palazzolo, Jerome J.; Ferraro, Mark; Krebs, Hermano Igo; Lynch, Daniel; Volpe, Bruce T.; Hogan, Neville

2009-01-01

This paper presents a stochastic method to estimate the multijoint mechanical impedance of the human arm suitable for use in a clinical setting, e.g., with persons with stroke undergoing robotic rehabilitation for a paralyzed arm. In this context, special circumstances such as hypertonicity and tissue atrophy due to disuse of the hemiplegic limb must be considered. A low-impedance robot was used to bring the upper limb of a stroke patient to a test location, generate force perturbations, and measure the resulting motion. Methods were developed to compensate for input signal coupling at low frequencies apparently due to human–machine interaction dynamics. Data was analyzed by spectral procedures that make no assumption about model structure. The method was validated by measuring simple mechanical hardware and results from a patient's hemiplegic arm are presented. PMID:17436881

A novel functional electrical stimulation-control system for restoring motor function of post-stroke hemiplegic patients

PubMed Central

Huang, Zonghao; Wang, Zhigong; Lv, Xiaoying; Zhou, Yuxuan; Wang, Haipeng; Zong, Sihao

2014-01-01

Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, multi-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique. PMID:25657728

Skeletal Structural Consequences of Reduced Gravity Environments

NASA Technical Reports Server (NTRS)

Ruff, Christropher B.

1999-01-01

The overall goal of this project is to provide structurally meaningful data on bone loss after exposure to reduced gravity environments so that more precise estimates of fracture risk and the effectiveness of countermeasures in reducing fracture risk can be developed. The project has three major components: (1) measure structural changes in the limb bones of rats subjected to complete and partial nonweightbearing, with and without treatment with ibandronate and periodic full weightbearing; (2) measure structural changes in the limb bones of human bedrest subjects, with and without treatment with alendronate and resistive exercise, and Russian cosmonauts flying on the Mir Space Station; and (3) validate and extend the 2-dimensional structural analyses currently possible in the second project component (bedrest and Mir subjects) using 3-dimensional finite element modeling techniques, and determine actual fracture-producing loads on earth and in space.

Quasi-static modeling of human limb for intra-body communications with experiments.

PubMed

Pun, Sio Hang; Gao, Yue Ming; Mak, PengUn; Vai, Mang I; Du, Min

2011-11-01

In recent years, the increasing number of wearable devices on human has been witnessed as a trend. These devices can serve for many purposes: personal entertainment, communication, emergency mission, health care supervision, delivery, etc. Sharing information among the devices scattered across the human body requires a body area network (BAN) and body sensor network (BSN). However, implementation of the BAN/BSN with the conventional wireless technologies cannot give optimal result. It is mainly because the high requirements of light weight, miniature, energy efficiency, security, and less electromagnetic interference greatly limit the resources available for the communication modules. The newly developed intra-body communication (IBC) can alleviate most of the mentioned problems. This technique, which employs the human body as a communication channel, could be an innovative networking method for sensors and devices on the human body. In order to encourage the research and development of the IBC, the authors are favorable to lay a better and more formal theoretical foundation on IBC. They propose a multilayer mathematical model using volume conductor theory for galvanic coupling IBC on a human limb with consideration on the inhomogeneous properties of human tissue. By introducing and checking with quasi-static approximation criteria, Maxwell's equations are decoupled and capacitance effect is included to the governing equation for further improvement. Finally, the accuracy and potential of the model are examined from both in vitro and in vivo experimental results.

Knee joint transplantation combined with surgical angiogenesis in rabbits – a new experimental model

PubMed Central

Kremer, Thomas; Giusti, Guilherme; Friedrich, Patricia F.; Willems, Wouter; Bishop, Allen T.; Giessler, Goetz A.

2012-01-01

Summary Purpose We have previously described a means to maintain bone allotransplant viability, without long-term immune modulation, replacing allogenic bone vasculature with autogenous vessels. A rabbit model for whole knee joint transplantation was developed and tested using the same methodology, initially as an autotransplant. Materials/Methods Eight New Zealand White rabbit knee joints were elevated on a popliteal vessel pedicle to evaluate limb viability in a non-survival study. Ten additional joints were elevated and replaced orthotopically in a fashion identical to allotransplantation, obviating only microsurgical repairs and immunosuppression. A superficial inferior epigastric facial (SIEF) flap and a saphenous arteriovenous (AV) bundle were introduced into the femur and tibia respectively, generating a neoangiogenic bone circulation. In allogenic transplantation, this step maintains viability after cessation of immunosuppression. Sixteen weeks later, x-rays, microangiography, histology, histomorphometry and biomechanical analysis were performed. Results Limb viability was preserved in the initial 8 animals. Both soft tissue and bone healing occurred in 10 orthotopic transplants. Surgical angiogenesis from the SIEF flap and AV bundle was always present. Bone and joint viability was maintained, with demonstrable new bone formation. Bone strength was less than the opposite side. Arthrosis and joint contractures were frequent. Conclusion We have developed a rabbit knee joint model and evaluation methods suitable for subsequent studies of whole joint allotransplantation. PMID:22113889

Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients

PubMed Central

2014-01-01

Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs—from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns—specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients. PMID:24910602

Evaluation of FNS control systems: software development and sensor characterization.

PubMed

Riess, J; Abbas, J J

1997-01-01

Functional Neuromuscular Stimulation (FNS) systems activate paralyzed limbs by electrically stimulating motor neurons. These systems have been used to restore functions such as standing and stepping in people with thoracic level spinal cord injury. Research in our laboratory is directed at the design and evaluation of the control algorithms for generating posture and movement. This paper describes software developed for implementing FNS control systems and the characterization of a sensor system used to implement and evaluate controllers in the laboratory. In order to assess FNS control algorithms, we have developed a versatile software package using Lab VIEW (National Instruments, Corp). This package provides the ability to interface with sensor systems via serial port or A/D board, implement data processing and real-time control algorithms, and interface with neuromuscular stimulation devices. In our laboratory, we use the Flock of Birds (Ascension Technology Corp.) motion tracking sensor system to monitor limb segment position and orientation (6 degrees of freedom). Errors in the sensor system have been characterized and nonlinear polynomial models have been developed to account for these errors. With this compensation, the error in the distance measurement is reduced by 90 % so that the maximum error is less than 1 cm.

Structure design of lower limb exoskeletons for gait training

NASA Astrophysics Data System (ADS)

Li, Jianfeng; Zhang, Ziqiang; Tao, Chunjing; Ji, Run

2015-09-01

Due to the close physical interaction between human and machine in process of gait training, lower limb exoskeletons should be safe, comfortable and able to smoothly transfer desired driving force/moments to the patients. Correlatively, in kinematics the exoskeletons are required to be compatible with human lower limbs and thereby to avoid the uncontrollable interactional loads at the human-machine interfaces. Such requirement makes the structure design of exoskeletons very difficult because the human-machine closed chains are complicated. In addition, both the axis misalignments and the kinematic character difference between the exoskeleton and human joints should be taken into account. By analyzing the DOF(degree of freedom) of the whole human-machine closed chain, the human-machine kinematic incompatibility of lower limb exoskeletons is studied. An effective method for the structure design of lower limb exoskeletons, which are kinematically compatible with human lower limb, is proposed. Applying this method, the structure synthesis of the lower limb exoskeletons containing only one-DOF revolute and prismatic joints is investigated; the feasible basic structures of exoskeletons are developed and classified into three different categories. With the consideration of quasi-anthropopathic feature, structural simplicity and wearable comfort of lower limb exoskeletons, a joint replacement and structure comparison based approach to select the ideal structures of lower limb exoskeletons is proposed, by which three optimal exoskeleton structures are obtained. This paper indicates that the human-machine closed chain formed by the exoskeleton and human lower limb should be an even-constrained kinematic system in order to avoid the uncontrollable human-machine interactional loads. The presented method for the structure design of lower limb exoskeletons is universal and simple, and hence can be applied to other kinds of wearable exoskeletons.

Cellular anomalies underlying retinoid-induced phocomelia.

PubMed

Zhou, Jian; Kochhar, Devendra M

2004-11-01

The question of how alterations in cell behavior produced by retinoic acid (RA) influenced the development of skeletogenic mesenchyme of the limb bud was examined in this study. Our established model was employed, which involves treatment of pregnant mice with a teratogenic dose of RA (100 mg/kg) on 11 days postcoitum (dpc) resulting in a severe truncation of all long bones of the forelimbs in virtually every exposed fetus. It is shown that RA, administered at a stage to induce phocomelia in virtually all exposed embryos, resulted in immediate appearance of enhanced cell death within the mesenchyme in the central core of the limb bud, an area destined for chondrogenesis. The central core mesenchyme, which in the untreated limb buds experiences a sharp decline in cell proliferation heralding the onset of chondrogenesis, demonstrated a reversal of the process; this mesenchyme maintained a higher rate of cell proliferation upon RA exposure. These events resulted in a truncation and disorganization of the chondrogenic anlage, more pronounced in zeugopodal mesenchyme than in the autopod. We conclude that an inhibition of chondrogenesis was secondary to a disruption in cellular behavior caused by RA, a likely consequence of misregulation in the growth factor signaling cascade.

Characterization of in vitro transcriptional responses of dorsal root ganglia cultured in the presence and absence of blastema cells from regenerating salamander limbs

PubMed Central

Athippozhy, Antony; Lehrberg, Jeffrey; Monaghan, James R.; Gardiner, David M.

2014-01-01

Abstract During salamander limb regeneration, nerves provide signals that induce the formation of a mass of proliferative cells called the blastema. To better understand these signals, we developed a blastema−dorsal root ganglia (DRG) co‐culture model system to test the hypothesis that nerves differentially express genes in response to cues provided by the blastema. DRG with proximal and distal nerve trunks were isolated from axolotls (Ambystoma mexicanum), cultured for 5 days, and subjected to microarray analysis. Relative to freshly isolated DRG, 1541 Affymetrix probe sets were identified as differentially expressed and many of the predicted genes are known to function in injury and neurodevelopmental responses observed for mammalian DRG. We then cultured 5‐day DRG explants for an additional 5 days with or without co‐cultured blastema cells. On day 10, we identified 27 genes whose expression in cultured DRG was significantly affected by the presence or absence of blastema cells. Overall, our study established a DRG−blastema in vitro culture system and identified candidate genes for future investigations of axon regrowth, nerve−blastema signaling, and neural regulation of limb regeneration. PMID:25750744

Development and Reliability Testing of the Comprehensive High-Level Activity Mobility Predictor (CHAMP) in Male Servicemembers with Traumatic Lower-Limb Loss

DTIC Science & Technology

2013-01-01

Levin GT, Ben Abdelkrim N, Laurencelle L, Castagna C. Lower limb maxi- mal dynamic strength and agility determinants in elite basket - ball players . J...IRB = Institutional Review Board, LLL = lower-limb loss, MBP = Medicine Ball Put, MDC = minimal detectable change, NMCSD = Naval Medical Center...consid- ered for the CHAMP. Coordination, power, speed, and agility are important physical components necessary for successful perfor- mance in sports

Optimizing the use of Limb Tourniquets in Tactical Combat Casualty Care: TCCC Guidelines Change 14-02

DTIC Science & Technology

2014-02-01

Sebesta JA, Blackbourne LH, Herbert GS, Kauvar DS, Baer DG, Walters TJ, Mullenix PS, Holcomb JB, 31 st Combat Support Hospital Research Group...K, Dixon P, Cowart J, Spencer J, Rasmussen TE. Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and

The effects of topical oxygen therapy on equine distal limb dermal wound healing.

PubMed

Tracey, Alexandra K; Alcott, Cody J; Schleining, Jennifer A; Safayi, Sina; Zaback, Peter C; Hostetter, Jesse M; Reinertson, Eric L

2014-12-01

Topical oxygen therapy (TOT) has been used in human medicine to promote healing in chronic wounds. To test the efficacy and safety of TOT in horses, an experimental wound model was created by making 1 standardized dermal wound on each limb of 4 healthy horses (n = 16). Each wound was fitted with an oxygen delivery cannula and covered with a bandage. One limb of each front and hind pair was randomly assigned to the treatment group (fitted with an oxygen concentrator device), with the contralateral limb assigned to the control group (no device). Wound area, epithelial area, and contraction were measured every 3 to 4 d. Biopsy samples and culture swabs were taken on days 16 and 32 to evaluate angiogenesis, fibroplasia, epithelial hyperplasia, inflammation and bacterial growth. Mean healing time in treated wounds (45 d, range: 38 to 52 d) was not significantly different from that in the paired control wounds (50 d, range: 38 to 62 d). Topical oxygen therapy had little effect on dermal wound healing in this experimental wound model in healthy horses.

Sleep Is Critical for Remote Preconditioning-Induced Neuroprotection.

PubMed

Brager, Allison J; Yang, Tao; Ehlen, J Christopher; Simon, Roger P; Meller, Robert; Paul, Ketema N

2016-11-01

Episodes of brief limb ischemia (remote preconditioning) in mice induce tolerance to modeled ischemic stroke (focal brain ischemia). Since stroke outcomes are in part dependent on sleep-wake history, we sought to determine if sleep is critical for the neuroprotective effect of limb ischemia. EEG/EMG recording electrodes were implanted in mice. After a 24 h baseline recording, limb ischemia was induced by tightening an elastic band around the left quadriceps for 10 minutes followed by 10 minutes of release for two cycles. Two days following remote preconditioning, a second 24 h EEG/EMG recording was completed and was immediately followed by a 60-minute suture occlusion of the middle cerebral artery (modeled ischemic stroke). This experiment was then repeated in a model of circadian and sleep abnormalities ( Bmal1 knockout [KO] mice sleep 2 h more than wild-type littermates). Brain infarction was determined by vital dye staining, and sleep was assessed by trained identification of EEG/EMG recordings. Two days after limb ischemia, wild-type mice slept an additional 2.4 h. This additional sleep was primarily comprised of non-rapid eye movement (NREM) sleep during the middle of the light-phase (i.e., naps). Repeating the experiment but preventing increases in sleep after limb ischemia abolished tolerance to ischemic stroke. In Bmal1 knockout mice, remote preconditioning did not increase daily sleep nor provide tolerance to subsequent focal ischemia. These results suggest that sleep induced by remote preconditioning is both sufficient and necessary for its neuroprotective effects on stroke outcome. © 2016 Associated Professional Sleep Societies, LLC.

Characterization of interfacial socket pressure in transhumeral prostheses: A case series.

PubMed

Schofield, Jonathon S; Schoepp, Katherine R; Williams, Heather E; Carey, Jason P; Marasco, Paul D; Hebert, Jacqueline S

2017-01-01

One of the most important factors in successful upper limb prostheses is the socket design. Sockets must be individually fabricated to arrive at a geometry that suits the user's morphology and appropriately distributes the pressures associated with prosthetic use across the residual limb. In higher levels of amputation, such as transhumeral, this challenge is amplified as prosthetic weight and the physical demands placed on the residual limb are heightened. Yet, in the upper limb, socket fabrication is largely driven by heuristic practices. An analytical understanding of the interactions between the socket and residual limb is absent in literature. This work describes techniques, adapted from lower limb prosthetic research, to empirically characterize the pressure distribution occurring between the residual limb and well-fit transhumeral prosthetic sockets. A case series analyzing the result of four participants with transhumeral amputation is presented. A Tekscan VersaTek pressure measurement system and FaroArm Edge coordinate measurement machine were employed to capture socket-residual limb interface pressures and geometrically register these values to the anatomy of participants. Participants performed two static poses with their prosthesis under two separate loading conditions. Surface pressure maps were constructed from the data, highlighting pressure distribution patterns, anatomical locations bearing maximum pressure, and the relative pressure magnitudes. Pressure distribution patterns demonstrated unique characteristics across the four participants that could be traced to individual socket design considerations. This work presents a technique that implements commercially available tools to quantitatively characterize upper limb socket-residual limb interactions. This is a fundamental first step toward improved socket designs developed through informed, analytically-based design tools.