The Mark 3 Haploscope

A computer-operated binocular vision testing device was developed as one part of a system designed for NASA to evaluate the visual function of astronauts during spaceflight. This particular device, called the Mark 3 Haploscope, employs semi-automated psychophysical test procedures to measure visual acuity, stereopsis, phoria, fixation disparity, refractive state and accommodation/convergence relationships. Test procedures are self-administered and can be used repeatedly without subject memorization. The Haploscope was designed as one module of the complete NASA Vision Testing System. However, it is capable of stand-alone operation. Moreover, the compactness and portability of the Haploscope make possible its use in a broad variety of testing environments

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

Fitzpatrick\u27s color atlas & synopsis of clinical dermatology

In the present paper, the observation and characterization of isolated response curves (IRCs) are experimentally reported in the case of a nonlinear system consisting of two masses sliding on an horizontal guide. Transverse springs are attached to one mass to provide the nonlinear restoring force, and a harmonic motion of the complete system is imposed by prescribing the displacement of their supports. The existence of an IRC is related to a 3:1 internal resonance between the two modes of the system. The observed IRC is studied in detached and merged conditions using swept-sine excitations and system perturbations

Prediction of isolated resonance curves using nonlinear normal modes

Isolated resonance curves are separate from the main nonlinear forced-response branch, so they can easily be missed by a continuation algorithm and the resonant response might be underpredicted. The present work explores the connection between these isolated resonances and the nonlinear normal modes of the system and adapts an energy balance criterion to connect the two. This approach provides new insights into the occurrence of isolated resonances as well as a method to find an initial guess to compute the isolated resonance curve using numerical continuation. The concepts are illustrated on a finite element model of a cantilever beam with a nonlinear spring at its tip. This system presents jumps in both frequency and amplitude in its response to a swept sinusoidal excitation. The jumps are found to be the result of a modal interaction that creates an isolated resonance curve that eventually merges with the main resonance branch as the excitation force increases. Excellent insight into the observed dynamics is provided with the NNM theory, which supports that NNMs can also be a useful tool for predicting isolated resonance curves and other behaviors in the damped, forced response.</jats:p

Model reduction concepts and substructuring approaches for nonlinear systems

This chapter reviews common nonlinearities that are encountered in engineering structures, with a particular emphasis on geometric nonlinearity. Popular ways to construct reduced order models for geometrically nonlinear problems are discussed. The concept of nonlinear normal modes is presented to help understand the dynamics of these structures, and some recently presented substructuring methods are reviewed

Rotational vertebral artery syndrome: 3D kinematics of nystagmus suggest bilateral labyrinthine dysfunction

Whether the rotational vertebral artery syndrome (RVAS), consisting of attacks of vertigo, nystagmus and tinnitus elicited by head-rotation induced compression of the dominant vertebral artery (VA), reflects ischemic dysfunction of uni- or bilateral peripheral or central vestibular structures, is still debated. We report on a patient with bilateral high-grade carotid stenoses, in whom rightward headrotation led to RVAS symptoms including a prominent nystagmus. Three-dimensional kinematic analysis of the nystagmus pattern, recorded with search coils, revealed major downbeat nystagmus with minor horizontal and torsional components. Magnetic resonance angiography demonstrated a hypoplastic right VA terminating in the posterior inferior cerebellar artery, a dominant left VA, and a hypoplastic P1-segment of the left posterior cerebral artery (PCA) that was supplied by the left posterior communicating artery (PCoA). The right PCA and both anterior inferior cerebellar arteries were supplied by the basilar artery. The right PCoA originated from the right internal carotid artery. Color duplex sonography showed severe reduction of diastolic blood flow velocities in the left VA during RVAS attacks. The nystagmus pattern can be best explained by vectorial addition of 3D sensitivity vectors of stimulated right and left anterior and horizontal semicircular canals with slightly stronger stimulation on the left side. We hypothesize that in RVAS, compression of dominant VA leads to acute vertebrobasilar insufficiency with bilateral, but asymmetric ischemia of the superior labyrinth. With regard to RVAS etiology, our case illustrates a type of pure vascular RVAS. Severity of attacks markedly decreased after successful bilateral carotid endarterectomy

Cobalt Release from a Nanoscale Multiphase Lithiated Cobalt Phosphate Dominates Interaction with Shewanella oneidensis MR-1 and Bacillus subtilis SB491

Cobalt phosphate engineered nanomaterials (ENMs) are an important class of materials that are used as lithium ion battery cathodes, catalysts, and potentially as super capacitors. As production of these nanomaterials increases, so does the likelihood of their environmental release; however, to date, there are relatively few investigations of the impact of nanoscale metal phosphates on biological systems. Furthermore, nanomaterials used in commercial applications are often multiphase materials, and analysis of the toxic potential of mixtures of nanomaterials has been rare. In this work, we studied the interactions of two model environmental bacteria, Shewanella oneidensis MR-1 and Bacillus subtilis, with a multiphase lithiated cobalt phosphate (mLCP) nanomaterial. Using a growth-based viability assay, we found that mLCP was toxic to both bacteria used in this study. To understand the observed toxicity, we screened for production of reactive oxygen species (ROS) and release of Co2+ from mLCP using three abiotic fluorophores. We also used Newport Green DCF dye to show that cobalt was taken up by the bacteria after mLCP exposure. Using transmission electron microscopy, we noted that the mLCP was not associated with the bacterial cell surface. In order for us to further probe the mechanism of interaction of mLCP, the bacteria were exposed to an equivalent dose of cobalt ions that dissolved from mLCP, which recapitulated the changes in viability when the bacteria were exposed to mLCP, and it also recapitulated the observed bacterial uptake of cobalt. Taken together, this implicates the release of cobalt ions and their subsequent uptake by the bacteria as the major toxicity mechanism of mLCP. The properties of the ENM govern the release rate of cobalt, but the toxicity does not arise from nanospecific effects—and importantly, the chemical composition of the ENM may dictate the oxidation state of the metal centers and thus limit ROS production