Neurological sequelae of mild traumatic brain injury are associated with the damage to white matter myelinated axons. In vitro models of axonal injury suggest that the progression to pathological ruin is initiated by the mechanical damage to tetrodotoxin-sensitive voltage-gated sodium channels that breaches the ion balance through alteration in kinetic properties of these channels. In myelinated axons, sodium channels are concentrated at nodes of Ranvier, making these sites vulnerable to mechanical injury. Nodal damage can also be inflicted by injury-induced partial demyelination of paranode/juxtaparanode compartments that flank the nodes and contain high density of voltage-gated potassium channels. Demyelination-induced potassium deregulation can further aggravate axonal damage; however, the role of paranode/juxtaparanode demyelination in immediate impairment of axonal function, and its contribution to the development of axonal depolarization remain elusive. A biophysically realistic computational model of myelinated axon that incorporates ion exchange mechanisms and nodal/paranodal/juxtaparanodal organization was developed and used to study the impact of injury-induced demyelination on axonal signal transmission. Injured axons showed alterations in signal propagation that were consistent with the experimental findings and with the notion of reduced axonal excitability immediately post trauma. Injury-induced demyelination strongly modulated the rate of axonal depolarization, suggesting that trauma-induced damage to paranode myelin can affect axonal transition to degradation. Results of these studies clarify the contribution of paranode demyelination to immediate post trauma alterations in axonal function and suggest that partial paranode demyelination should be considered as another "injury parameter" that is likely to determine the stability of axonal function.

In January 2013, the Department of Defense lifted a ban that had prevented women from holding combat positions in the military. However, innate differences in physical traits and physiology between men and women likely will result in differences in physical performance. Sex differences in thermoregulation is a key area that needs to be examined due to the potential impact on physical performance. Therefore, we expanded our previously developed thermoregulation model (TRM) to include the effects of gender. Women have been found to have a lower sweat output in heat stress and lesser shivering in cold stress than men; therefore, the equations for sweat mass loss rate and shivering heat generation were modified for women accordingly. The updated TRM showed good agreement with female data collected from exercise in cool to hot conditions, cold air exposure, and cold water immersion. Gender differences in sweat evaporation appear minimal except for sufficiently high exercise-heat combinations. Gender differences in core temperature and heat generation during cold stress are significant. The expanded TRM can be used to assess gender-specific thermal response with future application to predicting performance differences and optimizing warfighter effectiveness for a wide range of military relevant tasks.

Diffusion imaging and postmortem studies of patients with mild traumatic brain injury (mTBI) of the concussive type are consistent with the observations of diffuse axonal injury to the white matter axons. Mechanical trauma to axons affects the properties of tetrodotoxin-sensitive sodium channels at the nodes of Ranvier, leading to axonal degeneration through intra-axonal accumulation of calcium ions and activation of calcium proteases; however, the immediate implications of axonal trauma regarding axonal functionality and their relevance to transient impairment of function as observed in concussion remain elusive. A biophysically realistic computational model of a myelinated axon was developed to investigate how mTBI could immediately affect axonal function. Traumatized axons showed alterations in signal propagation properties that nonlinearly depended on the level of trauma; subthreshold traumatized axons had decreased spike propagation time, whereas suprathreshold traumatized axons exhibited a slowdown of spike propagation and spike propagation failure. Trauma had consistently reduced axonal spike amplitude. The susceptibility of an axon to trauma could be modulated by the function of an ATP-dependent sodium-potassium pump. The results suggest a mechanism by which concussive mTBI could lead to the immediate impairment of signal propagation through the axon and the emerging dysfunctional neuronal information exchange.

To address the limitations of regression-based performance models, the literature describes a fatigue model that reduces the complexities of motor unit activation into a set of first-order differential equations requiring only a few parameters to capture the global effects of activation physiology (M0: maximal force-generating capacity, F: fatigue rate, R: recovery rate). However, there are no solutions to the general form of the equations, which limits its applicability. We formulate an algorithm that allows the equations to be solved if an arbitrary force profile is specified. Furthermore, we support the validity of the model, applying it to exercises found in the literature including quadriceps contractions (M0=954±326 N, F=2.5±0.4%·s(-1), R=0.3±0.3%·s(-1)), cycling (M0=1095±486 W, F=3.5±0.3%·s(-1), R=1.1±0.3%·s(-1)) and running (M0=9.2±1.2 m·s(-1), F=0.9±0.4%·s(-1), R=1.0±0.3%·s(-1)), where effective muscle forces are converted to cycling power and running speed. The model predicts muscle output for 10 maximum efforts and 32 endurance tests, where the coefficient of determination (R2) ranged from 0.81 to 1.00. These results support the hypothesis found in the literature that motor unit activation and fatigue mechanisms lead to a cumulative muscle fatigue effect that can be observed in exercise performance.

The performance dynamic physiology model (DPM-PE) integrates a modified muscle fatigue model with an exercise physiology model that calculates the transport and delivery of oxygen to working muscles during exposures of oxygen-limiting environments. This mathematical model implements a number of physiologic processes (respiration, circulation, tissue metabolism, diffusion-limited gas transfer at the blood/gas lung interface, and ventilatory control with afferent feedback, central command and humoral chemoreceptor feedback) to replicate the three phases of ventilatory response to a variety of exertion patterns, predict the delivery and transport of oxygen and carbon dioxide from the lungs to tissues, and calculate the amount of aerobic and anaerobic work performed. The ventilatory patterns from passive leg movement, unloaded work, and stepped and ramping loaded work compare well against data. The model also compares well against steady-state ventilation, cardiac output, blood oxygen levels, oxygen consumption, and carbon dioxide generation against a range of exertion levels at sea level and at altitude, thus demonstrating the range of applicability of the exercise model. With the ability to understand and predict gas transport and delivery of oxygen to working muscle tissue for different workloads and environments, the correlation between blood oxygen measures and the recovery factor of the muscle fatigue model was explored. Endurance data sets in normoxia and hypoxia were best replicated using arterial oxygen saturation as the correlate with the recovery factor. This model provides a physiologically based method for predicting physical performance decrement due to oxygen-limiting environments.