Emergence of functionally aberrant and subsequent reduction of neuromuscular connectivity and improved motor performance after cervical spinal cord injury in Rhesus.

Introduction: The paralysis that occurs after a spinal cord injury, particularly during the early stages of post-lesion recovery (∼6 weeks), appears to be attributable to the inability to activate motor pools well beyond their motor threshold. In the later stages of recovery, however, the inability to perform a motor task effectively can be attributed to abnormal activation patterns among motor pools, resulting in poor coordination. Method: We have tested this hypothesis on four adult male Rhesus monkeys (Macaca mulatta), ages 6-10 years, by recording the EMG activity levels and patterns of multiple proximal and distal muscles controlling the upper limb of the Rhesus when performing three tasks requiring different levels of skill before and up to 24 weeks after a lateral hemisection at C7. During the recovery period the animals were provided routine daily care, including access to a large exercise cage (5' × 7' × 10') and tested every 3-4 weeks for each of the three motor tasks. Results: At approximately 6-8 weeks the animals were able to begin to step on a treadmill, perform a spring-loaded task with the upper limb, and reaching, grasping, and eating a grape placed on a vertical stick. The predominant changes that occurred, beginning at ∼6-8 weeks of the recovery of these tasks was an elevated level of activation of most motor pools well beyond the pre-lesion level. Discussion: As the chronic phase progressed there was a slight reduction in the EMG burst amplitudes of some muscles and less incidence of co-contraction of agonists and antagonists, probably contributing to an improved ability to selectively activate motor pools in a more effective temporal pattern. Relative to pre-lesion, however, the EMG patterns even at the initial stages of recovery of successfully performing the different motor tasks, the level of activity of most muscle remained higher. Perhaps the most important concept that emerges from these data is the large combinations of adaptive strategies in the relative level of recruitment and the timing of the peak levels of activation of different motor pools can progressively provide different stages to regain a motor skill.

Reducing MRI-guided radiotherapy planning and delivery times via efficient leaf sequencing and segment shape optimization algorithms.

Objective.Extended treatment session times are an operational limitation in magnetic resonance imaging guided adaptive radiotherapy (MRIgRT). In this study a novel leaf sequencing algorithm called optimal fluence levels (OFL) and an optimization algorithm called pseudo gradient descent (PGD) are evaluated with respect to plan quality, beam complexity, and the ability to reduce treatment session times on the Elekta Unity MRIgRT system.Approach.Ten total patients were evaluated on this Institutional Review Board approved study: three with prostate cancer, three with oligometastases, two with pancreatic cancer, and two with liver cancer. Plans were generated using the clinical Monaco Hyperion optimizer and leaf sequencer and then re-optimized using OFL and PGD (OFL + PGD) while holding all IMRT constraints and planning parameters constant. All plans were normalized to ensure 95% of the PTV received the prescription dose. A paired t-test was used to evaluate statistical significance.Main Results.Plan quality in terms of dosimetric OAR sparing was found to be equivalent between the OFL + PGD and conventional Monaco Hyperion optimizer plans. The OFL + PGD plans had a reduction in optimization time of 51.4% ± 5.0% (p = 0.002) and reduction in treatment delivery time of 10.6% ± 7.5% (p = 0.005). OFL + PGD generated plans had on average 13.2% ± 12.6% fewer multi-leaf collimator (MLC) segments (p = 0.009) and 0.1 ± 0.1 lower plan averaged beam modulation (PM) (p = 0.004) relative to the Monaco Hyperion plans.Significance.The OFL + PGD algorithms more quickly generate Unity treatment plans that are faster to deliver than with the conventional approach and without compromising dosimetric plan quality. This is likely due to a delivery complexity reduction enabled by OFL + PGD relative to the Monaco Hyperion plans.

Implementation of a real-time, ultrasound-guided prostate HDR brachytherapy program.

This work presents a comprehensive commissioning and workflow development process of a real-time, ultrasound (US) image-guided treatment planning system (TPS), a stepper and a US unit. To adequately benchmark the system, commissioning tasks were separated into (1) US imaging, (2) stepper mechanical, and (3) treatment planning aspects. Quality assurance US imaging measurements were performed following the AAPM TG-128 and GEC-ESTRO recommendations and consisted of benchmarking the spatial resolution, accuracy, and low-contrast detectability. Mechanical tests were first used to benchmark the electronic encoders within the stepper and were later expanded to evaluate the needle free length calculation accuracy. Needle reconstruction accuracy was rigorously evaluated at the treatment planning level. The calibration length of each probe was redundantly checked between the calculated and measured needle free length, which was found to be within 1 mm for a variety of scenarios. Needle placement relative to a reference fiducial and coincidence of imaging coordinate origins were verified to within 1 mm in both sagittal and transverse imaging planes. The source strength was also calibrated within the interstitial needle and was found to be 1.14% lower than when measured in a plastic needle. Dose calculations in the TPS and secondary dose calculation software were benchmarked against manual TG-43 calculations. Calculations among the three calculation methods agreed within 1% for all calculated points. Source positioning and dummy coincidence was tested following the recommendations of the TG-40 report. Finally, the development of the clinical workflow, checklists, and planning objectives are discussed and included within this report. The commissioning of real-time, US-guided HDR prostate systems requires careful consideration among several facets including the image quality, dosimetric, and mechanical accuracy. The TPS relies on each of these components to develop and administer a treatment plan, and as such, should be carefully examined.

Analysis of patient-specific quality assurance for Elekta Unity adaptive plans using statistical process control methodology.

The Elekta Unity MR-linac utilizes daily magnetic resonance imaging (MRI) for online plan adaptation. In the Unity workflow, adapt to position (ATP) and adapt to shape (ATS) treatment planning options are available which represent a virtual shift or full re-plan with contour adjustments respectively. Both techniques generate a new intensity modulated radiation therapy (IMRT) treatment plan while the patient lies on the treatment table and thus adapted plans cannot be measured prior to treatment delivery. A statistical process control methodology was used to analyze 512 patient-specific IMRT QA measurements performed on the MR-compatible SunNuclear ArcCheck with a gamma criterion of 3%/2 mm using global normalization and a 10% low dose threshold. The lower control limit (LCL) was determined from 68 IMRT reference plan measurements, and a one-sided process capability ratio ( C p , l ) was used to assess the pass rates from 432 measured ATP and 80 measured ATS plans. Further analysis was performed to assess differences between SBRT or conventional fractionation pass rates and to determine whether there was any correlation between the pass rates and plan complexity. The LCL of the reference plans was determined to be a gamma pass rate of 0.958, and the C p , l of the measured ATP plans and measured ATS plans were determined to be 1.403 and 0.940 for ATP and ATS plans, respectively, while a C p , l of 0.902 and 1.383 was found for SBRT and conventional fractionations respectively. For plan complexity, no correlation was found between modulation degree and gamma pass rate, but a statistically significant correlation was observed between the beam-averaged aperture area and gamma pass rate. All adaptive plans passed the TG-218 guidelines, but the ATS and SBRT plans tended to have a smaller beam-averaged aperture area with slightly lower gamma pass rates.

Absorbed dose distributions from beta-decaying radionuclides: Experimental validation of Monte Carlo tools for radiopharmaceutical dosimetry.

PURPOSE: This study aims to experimentally validate the Monte Carlo generated absorbed doses from the beta particles emitted by 90 Y and 177 Lu using radiochromic EBT3 film-based dosimetry. METHODS: Line sources of 90 Y and 177 Lu were inserted longitudinally through blocks of low-density polyethylene and tissue-equivalent slabs of cortical bone and lung equivalent plastics. Radiochromic film (Gafchromic EBT3) was laser cut to accommodate orthogonal line sources of radioactivity, and the film was sandwiched intimately between the rectangular blocks to achieve charged particle equilibrium. Line sources consisted of plastic capillary tube of length (13 ± 0.1) cm, with 0.42-mm inner diameter and a wall thickness of 0.21 mm. 90 Y line sources were prepared from a solution of dissolved 90 Y resin microspheres. 177 Lu line sources were prepared from an aliquot of 177 Lu-DOTATATE. Film exposures were conducted for durations ranging from 10 min to 38 h. Radiochromic film calibration was performed by irradiation with 6-MV-bremsstrahlung x rays from a calibrated linear accelerator, in accordance with literature recommendations. Experimental geometries were precisely simulated within the GATE Monte Carlo toolkit, which has previously been used for the generation of dose point kernels. RESULTS: The mean percentage difference between measured and simulated absorbed doses were 5.04% and 7.21% for 90 Y and 177 Lu beta absorbed dose in the range of (0.1-10) Gy. Additionally, 1D gamma analysis using a local 10%/1 mm gamma criterion was performed to compare the absorbed dose distributions. The percentage of measurement points passing the gamma criterion, averaged over all tests, was 93.5%. CONCLUSIONS: We report the experimental validation of Monte Carlo derived beta absorbed dose distributions for 90 Y and 177 Lu, solidifying the validity of using Monte Carlo-based methods for estimating absorbed dose from beta emitters. Overall, excellent agreement was observed between the experimental beta absorbed doses in the linear region of the radiochromic film and the GATE Monte Carlo simulations demonstrating that radiochromic film dosimetry has sufficient sensitivity and spatial resolution to be used as a tool for measuring beta decay absorbed dose distributions.

Dynamics of the use of magnetocardiography in the study of the cardiac conduction system of the chick embryo.

INTRODUCTION: Human fetal magnetocardiography (fMCG) has been done for several decades to evaluate fetal arrhythmias using a superconducting quantum interference device (SQUID) magnetometer, but there is little work in embryonic/fetal animal models. This study uses an optically-pumped magnetometer (OPM) to obtain an fMCG in the chick embryo. METHODS: White Leghorn chick embryos were examined from incubation Day #10-19. Different examination chambers were tested to optimize embryonic thermal stability and magnetic signal acquisition. All examinations were done with magnetic shielding. The OPM sensors were placed next to the egg shell. The embryo's position was localized by transilluminating the intact egg or ultrasound imaging the egg with an open air cell to optimize sensor placement. The raw data for each embryo was postprocessed to obtain a fMCG composite waveform. RESULTS: fMCG's were obtained in embryos from Day #12 to 19. The best success with intact eggs was obtained using five sensors; one at the bottom and four around the lower perimeter of the egg at 90° intervals with the egg oriented vertically and the air cell up. Using ultrasound imaging with the air cell open only two sensors were necessary, one at the bottom and one laterally next to the embryo. fMCGs were analyzed for heart rate and rhythm, each portion of the PQRST waveform, and the PR interval, QRS complex, RR interval, and QT interval. CONCLUSIONS: This study validates the chick embryo as an animal model to study in a longitudinal and noninvasive fashion the fetal cardiac conduction system by using OPM magnetocardiography.

Complex and Novel Arrhythmias Precede Stillbirth in Fetuses With De Novo Long QT Syndrome.

BACKGROUND: Long QT syndrome (LQTS) is a leading cause of sudden cardiac death in early life and has been implicated in ≈10% of sudden infant deaths and unexplained stillbirths. The purpose of our study was to use fetal magnetocardiography to characterize the electrophysiology and rhythm phenotypes of fetuses with de novo and inherited LQTS variants and identify risk factors for sudden death before birth. METHODS: We reviewed the fetal magnetocardiography database from the University of Wisconsin Biomagnetism Laboratory for fetuses with confirmed LQTS. We assessed waveform intervals, heart rate, and rhythm, including the signature LQTS rhythms: functional 2° atrioventricular block, T-wave alternans, and torsade de pointes (TdP). RESULTS: Thirty-nine fetuses had pathogenic variants in LQTS genes: 27 carried the family variant, 11 had de novo variants, and 1 was indeterminate. De novo variants, especially de novo SCN5A variants, were strongly associated with a severe rhythm phenotype and perinatal death: 9 (82%) showed signature LQTS rhythms, 6 (55%) showed TdP, 5 (45%) were stillborn, and 1 (9%) died in infancy. Those that died exhibited novel fetal rhythms, including atrioventricular block with 3:1 conduction ratio, QRS alternans in 2:1 atrioventricular block, long-cycle length TdP, and slow monomorphic ventricular tachycardia. Premature ventricular contractions were also strongly associated with TdP and perinatal death. Fetuses with familial variants showed a lower incidence of signature LQTS rhythm (6/27=22%), including TdP (3/27=11%). All were live born. CONCLUSIONS: The malignancy of de novo LQTS variants was remarkably high and demonstrate that these mutations are a significant cause of stillbirth. Their ability to manifest rhythms not known to be associated with LQTS increases the difficulty of echocardiographic diagnosis and decreases the likelihood that a resultant fetal loss is attributed to LQTS. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03047161.

Repolarization Predictors of Fetal Long QT Syndrome.

BACKGROUND: Diagnosis of fetal long QT syndrome (LQTS) using fetal magnetocardiography (fMCG) is straightforward in cases of overt QTc prolongation accompanied by LQTS rhythms; however, cases of isolated QTc prolongation can be challenging. OBJECTIVE: To characterize repolarization in normal and phenotype-positive LQTS fetuses with the goal of utilizing additional parameters of repolarization to improve the accuracy of fMCG diagnosis of LQTS. METHODS: FMCG recordings were taken from 37 phenotype-positive fetuses with confirmed LQTS and 132 normal controls. The normal fetuses were grouped into those with T-and U-waves and those with only T-waves. We compared the repolarization characteristics of normal fetuses with only T-waves with those of LQTS fetuses. We also compared the repolarization characteristics of normal fetuses with T-and U-waves with those of LQTS fetuses with two-component T-waves. RESULTS: Late-peaking T-waves were strongly associated (35/37= 95%) with LQTS. No normal fetuses showed both QTc prolongation (QTc> 500 ms) and a late-peaking T-wave. U-waves were seen in 11 normal fetuses (8%) and resulted in waveforms that often mimicked those of the 19 LQTS fetuses with two-component T-waves; however, in normal fetuses the polarities of the T-and U-waves were the same, whereas in LQTS fetuses with two-component T-waves the polarity of the components was usually opposite. CONCLUSION: A late-peaking T-wave in association with QTc prolongation is a distinctive, reliable indicator of fetal LQTS. U-waves confound assessment of QTc; however, normal U-waves can usually be distinguished from LQTS T-waves based on polarity.

Low-Cost Fetal Magnetocardiography: A Comparison of Superconducting Quantum Interference Device and Optically Pumped Magnetometers.

Background Fetal magnetocardiography (fMCG) is a highly effective technique for evaluation of fetuses with life-threatening arrhythmia, but its dissemination has been constrained by the high cost and complexity of Superconducting Quantum Interference Device (SQUID) instrumentation. Optically pumped magnetometers (OPMs) are a promising new technology that can replace SQUIDs for many applications. This study compares the performance of an fMCG system, utilizing OPMs operating in a person-sized magnetic shield, to that of a conventional fMCG system, utilizing SQUID magnetometers operating in a magnetically shielded room. Methods and Results fMCG recordings were made in 24 subjects using the SQUID system with the mother lying supine in a magnetically shielded room and the OPM system with the mother lying prone in a person-sized, cylindrical shield. Signal-to-noise ratios of the OPM and SQUID recordings were not statistically different and were adequate for diagnostic purposes with both technologies. Although the environmental noise was higher using the small open-ended shield, this was offset by the higher signal amplitude achieved with prone positioning, which reduced the distance between the fetus and sensors and improved patient comfort. In several subjects, fMCG provided a differential diagnosis that was more precise and/or definitive than was possible with echocardiography alone. Conclusions The OPM-based system was portable, improved patient comfort, and performed as well as the SQUID-based system at a small fraction of the cost. Electrophysiological assessment of fetal rhythm is now practical and will have a major impact on management of fetuses with long QT syndrome and other life-threatening arrhythmias.

Fetal magnetocardiogram waveform characteristics.

BACKGROUND: Fetal magnetocardiography (fMCG) is the most direct and precise method of assessing fetal rhythm and conduction. Although the utility of fMCG for evaluation of fetuses with serious arrhythmia is generally acknowledged, many aspects of fetal rhythm and conduction are relatively unstudied. OBJECTIVE: To record fMCG in a large group of normal fetuses in order to provide a more comprehensive evaluation of fMCG waveform characteristics, including waveform intervals, amplitudes, and morphology. METHODS: The subjects were 132 healthy women with uncomplicated singleton pregnancies, studied at 15.7-39.9 (mean 28.9) weeks' gestation in 259 sessions. The P, PR, QRS, QT, QTc, and RR intervals and the P/QRS and T/QRS amplitude ratios were measured. MAIN RESULTS: The P, PR, QRS, and RR intervals increased with gestational age, but QT and QTc did not. U-waves were seen in 11% of fetuses. The T-waves were often flat with low T/QRS amplitude ratios. Equiphasic QRS complexes were associated with tall P-waves. The PR, QRS, and QT intervals showed a power law dependence on RR interval with power law exponents 0.445, 0.363, and 0.381, respectively. SIGNIFICANCE: The data establish prediction intervals for fMCG waveform intervals and amplitudes in normal fetuses. This is critical for identification of fetuses with abnormal rhythm. Our study is the first to document the incidence of U-waves and flat T-waves in the fetus, both of which are uncommon postnatally. The association of tall P-waves with equiphasic QRS complexes provides a useful means of improving the resolution of fetal P-waves.

A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta).

The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies.

Combined aerobic and resistance training improves bone health of female cancer survivors.

INTRODUCTION: Cancer pathogenesis and resulting treatment may lead to bone loss and poor skeletal health in survivorship. The purpose of this investigation was to evaluate the influence of 26 weeks of combined aerobic and resistance-training (CART) exercise on bone mineral density (BMD) in a multi-racial sample of female cancer survivors. METHODS: Twenty-six female cancer survivors volunteered to undergo CART for 1 h/day, 3 days/week, for 26 weeks. The Improving Physical Activity After Cancer Treatment (IMPAACT) Program involves supervised group exercise sessions including 20 min of cardiorespiratory training, 25 min of circuit-style resistance-training, and 15 min of abdominal exercises and stretching. BMD at the spine, hip, and whole body was assessed using dual-energy X-ray absorptiometry (DXA) before and after the intervention. Serum markers of bone metabolism (procollagen-type I N-terminal propeptide, P1NP, and C-terminal telopeptides, CTX) were measured at baseline, 13 weeks, and at study completion. RESULTS: Eighteen participants, with the average age of 63.0 ± 10.3 years, completed the program. Mean duration since completion of cancer treatment was 6.2 ± 10.6 years. Paired t-tests revealed significant improvements in BMD of the spine (0.971 ± 0.218 g/cm2 vs. 0.995 ± 0.218 g/cm2, p = 0.012), hip (0.860 ± 0.184 g/cm2 vs. 0.875 ± 0.191 g/cm2, p = 0.048), and whole body (1.002 ± 0.153 g/cm2 vs. 1.022 ± 0.159 g/cm2, p = 0.002). P1NP declined 22% at 13 weeks and 28% at 26 weeks in comparison to baseline (p < 0.01) while CTX showed a non-significant decrease of 8% and 18% respectively. CONCLUSIONS: We report significant improvements in BMD at the spine, hip, and whole body for female cancer survivors who completed 26 weeks of CART. This investigation demonstrates the possible effectiveness of CART at improving bone health and reducing risk of osteoporosis for women who have completed cancer treatment. The IMPAACT Program appears to be a safe and feasible way for women to improve health after cancer treatment.

Pronounced species divergence in corticospinal tract reorganization and functional recovery after lateralized spinal cord injury favors primates.

Experimental and clinical studies suggest that primate species exhibit greater recovery after lateralized compared to symmetrical spinal cord injuries. Although this observation has major implications for designing clinical trials and translational therapies, advantages in recovery of nonhuman primates over other species have not been shown statistically to date, nor have the associated repair mechanisms been identified. We monitored recovery in more than 400 quadriplegic patients and found that functional gains increased with the laterality of spinal cord damage. Electrophysiological analyses suggested that corticospinal tract reorganization contributes to the greater recovery after lateralized compared with symmetrical injuries. To investigate underlying mechanisms, we modeled lateralized injuries in rats and monkeys using a lateral hemisection, and compared anatomical and functional outcomes with patients who suffered similar lesions. Standardized assessments revealed that monkeys and humans showed greater recovery of locomotion and hand function than did rats. Recovery correlated with the formation of corticospinal detour circuits below the injury, which were extensive in monkeys but nearly absent in rats. Our results uncover pronounced interspecies differences in the nature and extent of spinal cord repair mechanisms, likely resulting from fundamental differences in the anatomical and functional characteristics of the motor systems in primates versus rodents. Although rodents remain essential for advancing regenerative therapies, the unique response of the primate corticospinal tract after injury reemphasizes the importance of primate models for designing clinically relevant treatments.

Leveraging biomedical informatics for assessing plasticity and repair in primate spinal cord injury.

Recent preclinical advances highlight the therapeutic potential of treatments aimed at boosting regeneration and plasticity of spinal circuitry damaged by spinal cord injury (SCI). With several promising candidates being considered for translation into clinical trials, the SCI community has called for a non-human primate model as a crucial validation step to test efficacy and validity of these therapies prior to human testing. The present paper reviews the previous and ongoing efforts of the California Spinal Cord Consortium (CSCC), a multidisciplinary team of experts from 5 University of California medical and research centers, to develop this crucial translational SCI model. We focus on the growing volumes of high resolution data collected by the CSCC, and our efforts to develop a biomedical informatics framework aimed at leveraging multidimensional data to monitor plasticity and repair targeting recovery of hand and arm function. Although the main focus of many researchers is the restoration of voluntary motor control, we also describe our ongoing efforts to add assessments of sensory function, including pain, vital signs during surgery, and recovery of bladder and bowel function. By pooling our multidimensional data resources and building a unified database infrastructure for this clinically relevant translational model of SCI, we are now in a unique position to test promising therapeutic strategies' efficacy on the entire syndrome of SCI. We review analyses highlighting the intersection between motor, sensory, autonomic and pathological contributions to the overall restoration of function. This article is part of a Special Issue entitled SI: Spinal cord injury.

Relative risk for concussions in young female soccer players.

The objective of this study was to determine the relative risk and reported symptoms of concussions in 11- to 13-year-old, female soccer players. For this, a survey to compare the reported incidence of concussion in age-matched female soccer players to nonsoccer players was performed. The survey included 342 girls between the ages of 11 and 13: 195 were involved in an organized soccer team and 147 were not involved in organized soccer but were allowed to participate in any other sport or activity. A total of 94 of the 195 soccer players, or 48%, reported at least one symptom consistent with a concussion. The most prevalent symptom for these girls was headache (84%). A total of 34 of the 147 nonsoccer players, or 23%, reported at least one symptom consistent with a concussion in the previous six months. These results determined that the relative risk of probable concussions among 11- to 13-year-old, female soccer players is 2.09 (p < .001, α = .05, CI = 95%). This demonstrates that the relative risk of probable concussions in young female soccer players is significantly higher than in a control group of nonsoccer players of the same sex and age.

Development of a database for translational spinal cord injury research.

Efforts to understand spinal cord injury (SCI) and other complex neurotrauma disorders at the pre-clinical level have shown progress in recent years. However, successful translation of basic research into clinical practice has been slow, partly because of the large, heterogeneous data sets involved. In this sense, translational neurological research represents a "big data" problem. In an effort to expedite translation of pre-clinical knowledge into standards of patient care for SCI, we describe the development of a novel database for translational neurotrauma research known as Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI). We present demographics, descriptive statistics, and translational syndromic outcomes derived from our ongoing efforts to build a multi-center, multi-species pre-clinical database for SCI models. We leveraged archived surgical records, postoperative care logs, behavioral outcome measures, and histopathology from approximately 3000 mice, rats, and monkeys from pre-clinical SCI studies published between 1993 and 2013. The majority of animals in the database have measures collected for health monitoring, such as weight loss/gain, heart rate, blood pressure, postoperative monitoring of bladder function and drug/fluid administration, behavioral outcome measures of locomotion, and tissue sparing postmortem. Attempts to align these variables with currently accepted common data elements highlighted the need for more translational outcomes to be identified as clinical endpoints for therapeutic testing. Last, we use syndromic analysis to identify conserved biological mechanisms of recovery after cervical SCI between rats and monkeys that will allow for more-efficient testing of therapeutics that will need to be translated toward future clinical trials.

Norms for an isometric muscle endurance test.

Musculoskeletal performance assessment is critical in the analysis of physical training programs in order to prioritize goals for decreasing injury risk and focusing performance goals. Abdominal endurance as part of this analysis is often assessed with techniques that have validity that has been debated in literature. The purpose of this study was to develop normative sex- and athlete-specific percentiles for a trunk stabilization and muscular endurance by using a prone forearm plank test in college-aged students. A second purpose of this study was to investigate the effect of habitual physical activity and the reason for test termination. There were 471 participants (means ± SE; males: n = 194, age 20.4 ± 0.2 years, body height 179.4 ± 0.5 cm, body mass 81.1 ± 1.2 kg; females: n = 277, age 20.2 ± 0.2 years, body height 165.7 ± 0.4 cm, body mass 63.9 ± 0.7 kg) who performed this test to volitional or technique failure. Males produced significantly higher test durations than females (means ± SD; 124 ± 72 seconds vs. 83 ± 63 seconds) and athletes produced significantly longer test durations than non-athletes (123 ± 69 s vs. 83 ± 63 s) but no interaction effects were seen in the variables of sex and athletic status. The activity level was found to have a threshold of influence (>3 times/week) on abdominal endurance that is dose-specific where greater than 5 times/week showed the greatest influence. The fatigue of the abdominals was the termination reason producing the lowest test duration and there was no sex effect on reason for test termination. These normative percentiles for abdominal endurance suggest that the abdominal plank test can now be used as an alternative to other abdominal assessments in college students, but further investigation is warranted prior to confirmation and generalization to other populations.

Post-concussive syndrome in a female basketball player: a case study.

The objective of this case study was to identify the signs and symptoms of concussion and post-concussive syndrome in a collegiate, female basketball player, as well as her progress to becoming symptom free. The patient, a previously healthy, 21-year-old with no previous head injuries, experienced a concussion and continued to participate in her sport. Even though the athlete knew the risks of playing while symptomatic, she did not report her symptoms, and continued playing until the season ended. This case highlights that even when patients know the risks, they may be willing to overlook them to continue playing and it emphasizes the importance of further education. In addition, it shows that even when following recommended guidelines, and with normal neurocognitive testing, symptoms may come back upon return to play.

Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury.

Primates are an important and unique animal resource. We have developed a nonhuman primate model of spinal cord injury (SCI) to expand our knowledge of normal primate motor function, to assess the impact of disease and injury on sensory and motor function, and to test candidate therapies before they are applied to human patients. The lesion model consists of a lateral spinal cord hemisection at the C7 spinal level with subsequent examination of behavioral, electrophysiological, and anatomical outcomes. Results to date have revealed significant neuroanatomical and functional differences between rodents and primates that impact the development of candidate therapies. Moreover, these findings suggest the importance of testing some therapeutic approaches in nonhuman primates prior to the use of invasive approaches in human clinical trials. Our primate model is intended to: 1) lend greater positive predictive value to human translatable therapies, 2) develop appropriate methods for human translation, 3) lead to basic discoveries that might not be identified in rodent models and are relevant to human translation, and 4) identify new avenues of basic research to "reverse-translate" important questions back to rodent models.