Antituberculosis BCG vaccination: more reasons for varying innate and adaptive immune responses.

Bacillus Calmette-Guérin (BCG) vaccination induces variable protection against pulmonary tuberculosis (TB), and a more effective TB vaccine is needed. The potential for BCG to provide protection against heterologous infections, by induction of innate immune memory, is increasingly recognized. These nonspecific responses may substantially benefit public health, but are also variable. In this issue of the JCI, Koeken and de Bree et al. report that BCG reduces circulating inflammatory markers in males but not in females, while de Bree and Mouritis et al. describe how diurnal rhythms affect the degree of BCG-induced innate memory. These studies further delineate factors that influence the magnitude of responses to BCG and may be crucial to harnessing its potential benefits.

Posttraumatic stress following spinal cord injury: a systematic review of risk and vulnerability factors.

OBJECTIVES: To summarise quantitatively the available evidence relating to pretraumatic, peritraumatic and posttraumatic characteristics that may increase or decrease the risk of developing posttraumatic stress disorder (PTSD) following spinal cord injury (SCI). STUDY DESIGN: Systematic review. METHODS: Seventeen studies were identified from the PubMed, PsycInfo, Embase, Scopus, CINAHL, Web of Science and PILOTS databases. Effect size estimates (r) with associated 95% confidence intervals (CIs), P-values and fail-safe Ns were calculated. RESULTS: Individual studies reported medium-to-large associations between factors that occurred before (psychiatric history r=0.48 (95% CI, 0.23-0.79) P=0.01) or at the time of injury (tetraplegia r=-0.36 (95% CI, -0.50 to -0.19) P<0.01). Postinjury factors had the strongest pooled effects: depressed mood (rw=0.64, (95% CI, 0.54-0.72)), negative appraisals (rw=0.63 (95% CI, 0.52-0.72)), distress (rw=0.57 (95% CI, 0.50-0.62)), anxiety (rw=0.56 (95% CI, 0.49-0.61)) and pain severity (rw=0.35 (95% CI, 0.27-0.43)) were consistently related to worsening PTSD symptoms (P<0.01). Level of injury significantly correlated with current PTSD severity for veteran populations (QB (1)=18.25, P<0.001), although this was based on limited data. CONCLUSION: Combinations of peri- and post-injury factors appear to be influential in the development of PTSD among persons with SCI. Further studies are needed to extrapolate these findings to the broader spinal cord-injured population. More longitudinal research, driven by multicausal models of causation such as the diathesis-stress model, is also needed to determine the temporality of PTSD risk factors.

Artificial neural network model for the generation of muscle activation patterns for human locomotion.

Skilled locomotor behaviour requires information from various levels within the central nervous system (CNS). Mathematical models have permitted researchers to simulate various mechanisms in order to understand the organization of the locomotor control system. While it is difficult to adequately characterize the numerous inputs to the locomotor control system, an alternative strategy may be to use a kinematic movement plan to represent the complex inputs to the locomotor control system based on the possibility that the CNS may plan movements at a kinematic level. We propose the use of artificial neural network (ANN) models to represent the transformation of a kinematic plan into the necessary motor patterns. Essentially, kinematic representation of the actual limb movement was used as the input to an ANN model which generated the EMG activity of 8 muscles of the lower limb and trunk. Data from a wide variety of gait conditions was necessary to develop a robust model that could accommodate various environmental conditions encountered during everyday activity. A total of 120 walking strides representing normal walking and ten conditions where the normal gait was modified in terms of cadence, stride length, stance width or required foot clearance. The final network was assessed on its ability to predict the EMG activity on individual walking trials as well as its ability to represent the general activation pattern of a particular gait condition. The predicted EMG patterns closely matched those recorded experimentally, exhibiting the appropriate magnitude and temporal phasing required for each modification. Only 2 of the 96 muscle/gait conditions had RMS errors above 0.10, only 5 muscle/gait conditions exhibited correlations below 0.80 (most were above 0.90) and only 25 muscle/gait conditions deviated outside the normal range of muscle activity for more than 25% of the gait cycle. These results indicate the ability of single network ANNs to represent the transformation between a kinematic movement plan and the necessary muscle activations for normal steady state locomotion but they were also able to generate muscle activation patterns for conditions requiring changes in walking speed, foot placement and foot clearance. The abilities of this type of network have implications towards both the fundamental understanding of the control of locomotion and practical realizations of artificial control systems for use in rehabilitation medicine.

Contributions of the reticulospinal system to the postural adjustments occurring during voluntary gait modifications.

To test the hypothesis that reticulospinal neurons (RSNs) are involved in the formation of the dynamic postural adjustments that accompany visually triggered, voluntary modifications of limb trajectory during locomotion, we recorded the activity of 400 cells (183 RSNs; 217 unidentified reticular cells) in the pontomedullary reticular formation (PMRF) during a locomotor task in which intact cats were required to step over an obstacle attached to a moving treadmill belt. Approximately one half of the RSNs (97/183, 53%) showed significant changes in cell activity as the cat stepped over the obstacle; most of these cells exhibited either single (26/97, 26.8%) or multiple (63/97, 65.0%) increases of activity. There was a range of discharge patterns that varied in the number, timing, and sequencing of the bursts of modified activity, although individual bursts in different cells tended to occur at similar phases of the gait cycle. Most modified cells, regardless of the number of bursts of increased discharge, or of the discharge activity of the cell during unobstructed, control, locomotion, discharged during the passage of the lead forelimb over the obstacle. Thus, 86.9% of the modified cells increased their discharge when the forelimb ipsilateral to the recording site was the first to pass over the obstacle, and 72.2% when the contralateral limb was the first. Approximately one quarter of the RSNs increased their discharge during the passage of each of the four limbs over the obstacle in both the lead (27.1%) and trail (27.9%) conditions. In general, in any one cell, the number and relative sequencing of the subsequent bursts (with respect to the lead forelimb) was maintained during both lead and trail conditions. Patterns of activity observed in unidentified cells were very similar to the RSN activity despite the diverse population of cells this unidentified group may represent. We suggest that the increased discharge that we observed in these reticular neurons reflects the integration of afferent activity from several sources, including the motor cortex, and that this increased discharge signals the timing and the relative magnitude of the postural patterns that accompany the voluntary gait modification. However, based on the characteristics of the patterns of neuronal activity in these cells, we further suggest that while individual RSNs probably contribute to the selection of different patterns of postural activity, the ultimate expression of the postural response may be determined by the excitability of the locomotor circuits within the spinal cord.

What guides the selection of alternate foot placement during locomotion in humans.

Our goal was to understand the bases for selection of alternate foot placement during locomotion when the normal landing area is undesirable. In this study, a light spot of different shapes and sizes simulated an undesirable landing area. Participants were required to avoid stepping on this spot under different time constraints. Alternate chosen foot placements were categorised into one of eight choices. Results showed that selection of alternate foot placement is systematic. There is a single dominant choice for each combination of light spot and normal landing spot. The dominant choice minimises the displacement of the foot from its normal landing spot (less than half a foot length). If several response choices satisfy this criterion, three selection strategies are used to guide foot placement: placing the foot in the plane of progression, choosing to take a longer step over a shorter step and selecting a medial rather than lateral foot placement. All these alternate foot-placement choices require minimal changes to the ongoing locomotor muscle activity, pose minimal threat to dynamic stability, allow for quick initiation of change in ongoing movement and ensure that the locomotor task runs without interruption. Thus, alternate foot-placement choices are dependent not only on visual input about the location, size and shape of the undesirable surface, but also on the relationship between the characteristics of the undesirable surface and the normal landing area.

Simple artificial neural network models can generate basic muscle activity patterns for human locomotion at different speeds.

A neural network model has been developed to represent the shaping function of a central pattern generator (CPG) for human locomotion. The model was based on cadence and electromyographic data obtained from a single human subject who walked on a treadmill. The only input to the model was the fundamental timing of the gait cycle (stride rate) in the form of sine and cosine waveforms whose period was equal to the stride duration. These simple signals were then shaped into the respective muscle activation patterns of eight muscles of the lower limb and trunk. A network with a relatively small number of hidden units trained with back-propagation was able to produce an excellent representation of both the amplitude and timing characteristics of the EMGs over a range of walking speeds. The results are further discussed with respect to the dependence of some muscles upon sensory feedback and other inputs not explicitly presented to the model.

Characteristics of voluntary visual sampling of the environment for safe locomotion over different terrains.

The characteristics of visual sampling required for successful locomotion over various terrains is the focus of this work. In the first experiment we directly address the role of continuous visual monitoring of the environment in guiding locomotion by allowing the subjects to choose when and where to take a visual sample of the terrain and examine the effects of different terrains on characteristics of visual sampling. Young subjects walked over travel paths of varying difficulties while wearing opaque liquid crystal eyeglasses and pressed a hand-held switch to make the glasses transparent when they needed to sample the environment. Travel time and visual sampling characteristics were recorded. Results show that intermittent sampling (less than 50%) of the environment is adequate for safe locomotion, even over a novel travel path. The frequency, duration and timing of visual samples are dependent on terrain characteristics. Visual sampling of the environment is unaffected by preview restriction of the travel path and is increased when specific foot placement is required and there is a potential hazard in the travel path. In the second experiment we dissociated steering control and obstacle avoidance from specific foot placement and examined visual sampling demands prior to the initiation of the swing phase and during the swing phase. The results show that steering control and obstacle avoidance do influence the visual sampling time, which is scaled to the magnitude of change. Vision was used in a feedforward control mode to plan for and initiate appropriate changes in the swing limb trajectory: its use during the swing phase to provide on-line control was minimal.

Locomotor Patterns of the Leading and the Trailing Limbs as Solid and Fragile Obstacles Are Stepped Over: Some Insights Into the Role of Vision During Locomotion.

The issues explored in this article are the role of exproprioceptive input and the nature of exteroceptive input provided by the visual system in the control of limb elevation as obstacles are stepped over during locomotion. In the first experiment, the differences in limb trajectory of movements over solid and fragile obstacles of similar dimensions were examined. Subjects increased their toe clearance, vertical position of the hip, and the hip vertical velocity when going over a fragile obstacle with the leading limb. This suggests that in addition to visually observable properties of obstacles such as height or width, other properties, such as rigidity or fragility, which may be classified as visually inferred, also influence the limb trajectory. Part of the first and the second experiment was focused on understanding differences in leading limb and trailing limb trajectory over obstacles. The toe clearance of the trailing limb was lower for smaller obstacles. There was no consistent correlation between the toe clearance values of the leading and trailing limbs. The variability in toe clearance was higher for the trailing limb, which is attributable to lack of visual exproprioceptive input about trailing limb movements and to the shorter time available following toe-off to fine-tune the trailing limb trajectory. Because the body center of mass is moving toward the supporting foot when the trailing limb goes over obstacles and the trailing limb foot is moving up, the chances of a trip are minimized and recovery from an unexpected trip are more likely. These results highlight the role of exproprioceptive input provided by the visual system and possible cognitive influences on the limb trajectory as one travels over uneven terrains.

Modelling the time-keeping function of the central pattern generator for locomotion using artificial sequential neural network.

The paper investigates the ability of a sequential neural network to model the time-keeping function (fundamental frequency oscillation) of a central pattern generator for locomotion. The intention is not to strive for biological fidelity, but rather to ensure that the network obeys the organisational and operational principles of central pattern generators developed through empirical research. The timing function serves to produce the underlying locomotor rhythm which can be transformed by nonlinear static shaping functions to construct the necessary locomotor activation patterns. Using two levels of tonic activations in the form of a step increase, a network consisting of nine processing units was successfully trained to output both sine and cosine waveforms, whose frequencies were modified in response to the level of input activation. The network's ability to generalise was demonstrated by appropriately scaling the frequency of oscillation in response to a range of input amplitudes, both within and outside the values on which it was trained. A notable and fortunate result was the model's failure to oscillate in the absence of input activation, which is a necessary property of the CPG model. It was further demonstrated that the oscillation frequency of the output waveforms exhibited both a high temporal stability and a very low sensitivity to input noise. The results indicate that the sequential neural network is a suitable candidate to model the time-keeping functions of the central pattern generator for locomotion.

The role of active forces and intersegmental dynamics in the control of limb trajectory over obstacles during locomotion in humans.

The focus of this paper is to examine the contributions of active and passive forces in the control of limb trajectory over obstacles during locomotion. Kintetic analyses of the swing phase of locomotion were carried out to determine the power profiles at various joints and to parcel the joint moments into moments due to muscle action, gravitational force and motion-dependent terms. The analyses revealed that toe elevation over the obstacles was achieved primarily by flexing at the hip, knee and ankle joint. Power analyses showed that translational energy applied at the hip joint and rotational energy applied at the knee joint were modulated as functions of obstacle height. This demonstrates that increased hip and ankle joint flexion are achieved not through active muscle action but rather through passive forces induced by translational action at the hip (representing contribution by the stance limb muscles) and rotational action at the knee joint. Parcelling the joint moment terms into various components clearly shows how the nervous system exploits intersegmental dynamics to simplify control of limb elevation over obstacles and minimize energy costs.

A history of subspecialization in forensic psychiatry.

Forensic psychiatry became officially recognized as a subspecialty by the American Board of Medical Specialties on September 17, 1992, under the designation of "Added Qualification in Forensic Psychiatry." The historical roots wind through extended time in the complicated interplay of psychiatry and the law. A recognized need for special education, training, and experience, with the assurance of competence, became clearly defined in the mid-20th century. This was brought into perspective in a joint effort by the American Academy of Forensic Sciences and the American Academy of Psychiatry and the Law. At the present time there are 38 fellowship programs with approximately 50 positions available. Within a short time (two to three years), fellowship experience will be a requirement to sit for the examination.

Age-related changes in balance control system: initiation of stepping.

The balance control system of a group of healthy and fit, young and elderly subjects was studied during the initiation of stepping in one of three directions: forward, sideways, and backwards in response to a light cue. The performance of these movements requires shifting support from two to one foot, moving the centre of mass outside the initial base of support and creating a new support configuration. By recording and analysing the vertical ground reaction force beneath the subject's stepping foot, we were able to examine the two phases prior to limb lift-off for stepping: reaction time and weight transfer time. Both reaction time and weight transfer time increased with age: The elderly subjects had a proportionately larger increase in weight transfer time compared to the reaction time. The peak force generated showed an age by stepping direction effect: the elderly had a significantly lower peak force for the forwards stepping compared to the younger subjects. The larger increase in weight transfer results in a slower stepping response. Since a stepping task is often recruited to avoid a fall, the increase in response execution time can have undesirable consequences.

Visual control of locomotion: strategies for changing direction and for going over obstacles.

Dynamics of gait adjustments required to go over obstacles and to alter direction of locomotion when cued visually were assessed through the measurement of ground reaction forces, muscle activity, and kinematics. The time of appearance of obstacles of varying heights, their position within the step cycle, and cue lights for direction change were varied. Direction change must be planned in the previous step to reduce the acceleration of the body center of mass toward the landing foot to 0. The inability of steering within the step cycle is due to the incapacity of muscles to rotate the body and translate it along the mediolateral axes. For obstacle avoidance, Ss systematically manipulated the gait patterns as a function of obstacle height and position and the time available within the ongoing step. Greater supraspinal involvement in control of locomotion is found.