Experimental Treatment of Ebola Virus Disease with TKM-130803: A Single-Arm Phase 2 Clinical Trial

BackgroundTKM-130803, a small interfering RNA lipid nanoparticle product, has been developed for the treatment of Ebola virus disease (EVD), but its efficacy and safety in humans has not been evaluated.ConclusionsAdministration of TKM-130803 at a dose of 0.3 mg/kg/d by intravenous infusion to adult patients with severe EVD was not shown to improve survival when compared to historic controls.

Trial registration

Pan African Clinical Trials Registry PACTR201501000997429     

A model of cerebellum stabilized and scheduled hybrid long-loop control of upright balance

A recurrent integrator proportional integral derivative (PID) model that has been used to account for cerebrocerebellar stabilization and scaling of transcortical proprioceptive feedback in the control of horizontal planar arm movements has been augmented with long-loop force~feedback and gainscheduling to describe the control of human upright balance. The cerebellar component of the controller is represented by two sets of gains that each provide linear scaling of same-joint and interjoint long-loop stretch responses between ankle, knee, and hip. The cerebral component of the model includes a single set of same-joint linear force feedback gains. Responses to platform translations of a three-segment body model operating under this hybrid proprioception and force-based long-loop control were simulated. With low-velocity platform disturbances, ankle-strategy-type postural recovery kinematics and electromyogram (EMG) patterns were generated using the first set of cerebeller control gains. With faster disturbances, balance was maintained by including the second set of gains cerebellar control gains that yielded mixed ankle-hip strategy-type kinematics and EMG patterns. The addition of small amounts of simulated muscular coactivation improved the fit to certain human datasets. It is proposed that the cerebellum switches control gainsets as a function of sensed body kinematic state. Reduction of cerebellar gains with a compensatory increase in muscular stiffness yielded posture recovery with abnormal motions consistent with those found in cerebellar disease. The model demonstrates that stabilized hybrid long-loop feedback with scheduling of linear gains may afford realistic balance control in the absence of explicit internal dynamics models and suggests that the cerebellum and cerebral cortex may contribute to balance control by such a mechanism.     

A model of cerebrocerebello-spinomuscular interaction in the sagittal control of human walking

A computationally developed model of human upright balance control (Jo and Massaquoi on Biol cybern 91:188–202, 2004) has been enhanced to describe biped walking in the sagittal plane. The model incorporates (a) non-linear muscle mechanics having activation level -dependent impedance, (b) scheduled cerebrocerebellar interaction for control of center of mass position and trunk pitch angle, (c) rectangular pulse-like feedforward commands from a brainstem/ spinal pattern generator, and (d) segmental reflex modulation of muscular synergies to refine inter-joint coordination. The model can stand when muscles around the ankle are coactivated. When trigger signals activate, the model transitions from standing still to walking at 1.5 m/s. Simulated natural walking displays none of seven pathological gait features. The model can simulate different walking speeds by tuning the amplitude and frequency in spinal pattern generator. The walking is stable against forward and backward pushes of up to 70 and 75 N, respectively, and with sudden changes in trunk mass of up to 18%. The sensitivity of the model to changes in neural parameters and the predicted behavioral results of simulated neural system lesions are examined. The deficit gait simulations may be useful to support the functional and anatomical correspondences of the model. The model demonstrates that basic human-like walking can be achieved by a hierarchical structure of stabilized-long loop feedback and synergy-mediated feedforward controls. In particular, internal models of body dynamics are not required.     

Diversity of free-living ‘naked’ amoeboid organisms

Amoeboid organisms are phylogenetically diverse, some being more closely related to plants or metazoans than to each other. Amoeboid organisms are ecologically successful, having been isolated on all continents, including Antarctica, as well as being the main predators controlling bacterial populations in soil. The classification of these organisms has historically relied upon morphological characteristics. The application of electron microscopy, comparison of enzymic profiles after electrophoretic separation, and analysis of nucleic acid fractions have provided reliable bases for classifying amoeboid organisms. The extent of diversity of these organisms has been recognized, as methods to detect, culture, characterize and identify them has increased. It is reasonable to anticipate that the current 40 000 species of protists will increase substantially as amoeboid organisms are cultivated from poorly accessible niches and from extreme environs.