Continuing challenges in influenza Webster, Robert G.; Govorkova, Elena A.
Annals of the New York Academy of Sciences,
September 2014, Letnik:
1323, Številka:
1
Journal Article
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Influenza is an acute respiratory disease in mammals and domestic poultry that emerges from zoonotic reservoirs in aquatic birds and bats. Although influenza viruses are among the most intensively ...studied pathogens, existing control options require further improvement. Influenza vaccines must be regularly updated because of continuous antigenic drift and sporadic antigenic shifts in the viral surface glycoproteins. Currently, influenza therapeutics are limited to neuraminidase inhibitors; novel drugs and vaccine approaches are therefore urgently needed. Advances in vaccinology and structural analysis have revealed common antigenic epitopes on hemagglutinins across all influenza viruses and suggest that a universal influenza vaccine is possible. In addition, various immunomodulatory agents and signaling pathway inhibitors are undergoing preclinical development. Continuing challenges in influenza include the emergence of pandemic H1N1 influenza in 2009, human infections with avian H7N9 influenza in 2013, and sporadic human cases of highly pathogenic avian H5N1 influenza. Here, we review the challenges facing influenza scientists and veterinary and human public health officials; we also discuss the exciting possibility of achieving the ultimate goal of controlling influenza's ability to change its antigenicity.
A Dynamic Model for Concentric Tube Robots Till, John; Aloi, Vincent; Riojas, Katherine E. ...
IEEE transactions on robotics,
12/2020, Letnik:
36, Številka:
6
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Existing static and kinematic models of concentric tube robots are based on the ordinary differential equations of a static Cosserat rod. In this article, we provide the first dynamic model for ...concentric tube continuum robots by adapting the partial differential equations of a dynamic Cosserat rod to describe the coupled inertial dynamics of precurved concentric tubes. This generates an initial-boundary-value problem that can capture robot vibrations over time. We solve this model numerically at high time resolutions using implicit finite differences in time and arc length. This approach is capable of resolving the high-frequency torsional dynamics that occur during unstable "snapping" motions and provides a simulation tool that can track the true robot configuration through such transitions. Furthermore, it can track slower oscillations associated with bending and torsion as a robot interacts with tissue at real-time speeds. Experimental verification of the model shows that this wide range of effects is captured efficiently and accurately.
Continuum robotics has rapidly become a rich and diverse area of research, with many designs and applications demonstrated. Despite this diversity in form and purpose, there exists remarkable ...similarity in the fundamental simplified kinematic models that have been applied to continuum robots. However, this can easily be obscured, especially to a newcomer to the field, by the different applications, coordinate frame choices, and analytical formalisms employed. In this paper we review several modeling approaches in a common frame and notational convention, illustrating that for piecewise constant curvature, they produce identical results. This discussion elucidates what has been articulated in different ways by a number of researchers in the past several years, namely that constant-curvature kinematics can be considered as consisting of two separate submappings: one that is general and applies to all continuum robots, and another that is robot-specific. These mappings are then developed both for the single-section and for the multi-section case. Similarly, we discuss the decomposition of differential kinematics (the robot’s Jacobian) into robot-specific and robot-independent portions. The paper concludes with a perspective on several of the themes of current research that are shaping the future of continuum robotics.
Continuum robots, which are composed of multiple concentric, precurved elastic tubes, can provide dexterity at diameters equivalent to standard surgical needles. Recent mechanics-based models of ...these "active cannulas" are able to accurately describe the curve of the robot in free space, given the preformed tube curves and the linear and angular positions of the tube bases. However, in practical applications, where the active cannula must interact with its environment or apply controlled forces, a model that accounts for deformation under external loading is required. In this paper, we apply geometrically exact rod theory to produce a forward kinematic model that accurately describes large deflections due to a general collection of externally applied point and/or distributed wrench loads. This model accommodates arbitrarily many tubes, with each having a general preshaped curve. It also describes the independent torsional deformation of the individual tubes. Experimental results are provided for both point and distributed loads. Average tip error under load was 2.91 mm (1.5% - 3% of total robot length), which is similar to the accuracy of existing free-space models.
The interaction between respiratory pathogens and their hosts is complex and incompletely understood. This is particularly true when pathogens encounter the mucus layer covering the respiratory ...tract. The mucus layer provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection. Respiratory mucus has numerous functions and interactions, both with the host and with pathogens. This review summarizes the current understanding of respiratory mucus and its interactions with the respiratory pathogens Pseudomonas aeruginosa, respiratory syncytial virus and influenza viruses, with particular focus on influenza virus transmissibility and host-range specificity. Based on current findings we propose that respiratory mucus represents an understudied host-restriction factor for influenza virus.
Respiratory mucus provides an essential first host barrier to inhaled pathogens. Mucus is a complex, incompletely understood, multicomponent secretion that has numerous interactions with the host and with pathogens. Zanin et al. review the current understanding of respiratory mucus and its interactions with important respiratory pathogens, particularly influenza viruses.
Evolution and ecology of influenza A viruses Yoon, Sun-Woo; Webby, Richard J; Webster, Robert G
Current topics in microbiology and immunology,
01/2014, Letnik:
385
Journal Article
Recenzirano
Wild aquatic bird populations have long been considered the natural reservoir for influenza A viruses with virus transmission from these birds seeding other avian and mammalian hosts. While most ...evidence still supports this dogma, recent studies in bats have suggested other reservoir species may also exist. Extensive surveillance studies coupled with an enhanced awareness in response to H5N1 and pandemic 2009 H1N1 outbreaks is also revealing a growing list of animals susceptible to infection with influenza A viruses. Although in a relatively stable host-pathogen interaction in aquatic birds, antigenic, and genetic evolution of influenza A viruses often accompanies interspecies transmission as the virus adapts to a new host. The evolutionary changes in the new hosts result from a number of processes including mutation, reassortment, and recombination. Depending on host and virus these changes can be accompanied by disease outbreaks impacting wildlife, veterinary, and public health.
Tendons are a widely used actuation strategy for continuum robots that enable forces and moments to be transmitted along the robot from base-mounted actuators. Most prior robots have used tendons ...routed in straight paths along the robot. However, routing tendons through general curved paths within the robot offers potential advantages in reshaping the workspace and enabling a single section of the robot to achieve a wider variety of desired shapes. In this paper, we provide a new model for the statics and dynamics of robots with general tendon routing paths that is derived by coupling the classical Cosserat-rod and Cosserat-string models. This model also accounts for general external loading conditions and includes traditional axially routed tendons as a special case. The advantage of the usage of this coupled model for straight-tendon robots is that it accounts for the distributed wrenches that tendons apply along the robot. We show that these are necessary to consider when the robot is subjected to out-of-plane external loads. Our experimental results demonstrate that the coupled model matches experimental tip positions with an error of 1.7% of the robot length, in a set of experiments that include both straight and nonstraight routing cases, with both point and distributed external loads.
The gastrointestinal tract is home to some of the most deadly human diseases. Exacerbating the problem is the difficulty of accessing it for diagnosis or intervention and the concomitant patient ...discomfort. Flexible endoscopy has established itself as the method of choice and its diagnostic accuracy is high, but there remain technical limitations in modern scopes, and the procedure is poorly tolerated by patients, leading to low rates of compliance with screening guidelines. Although advancement in clinical endoscope design has been slow in recent years, a critical mass of enabling technologies is now paving the way for the next generation of gastrointestinal endoscopes. This review describes current endoscopes and provides an overview of innovative flexible scopes and wireless capsules that can enable painless endoscopy and/or enhanced diagnostic and therapeutic capabilities. We provide a perspective on the potential of these new technologies to address the limitations of current endoscopes in mass cancer screening and other contexts and thus to save many lives.
Needle Steering in 3-D Via Rapid Replanning Patil, Sachin; Burgner, Jessica; Webster, Robert J. ...
IEEE transactions on robotics,
08/2014, Letnik:
30, Številka:
4
Journal Article
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Steerable needles have the potential to improve the effectiveness of needle-based clinical procedures such as biopsy and drug delivery by improving targeting accuracy and reaching previously ...inaccessible targets that are behind sensitive or impenetrable anatomical regions. We present a new needle steering system capable of automatically reaching targets in 3-D environments while avoiding obstacles and compensating for real-world uncertainties. Given a specification of anatomical obstacles and a clinical target (e.g., from preoperative medical images), our system plans and controls needle motion in a closed-loop fashion under sensory feedback to optimize a clinical metric. We unify planning and control using a new fast algorithm that continuously replans the needle motion. Our rapid replanning approach is enabled by an efficient sampling-based rapidly exploring random tree (RRT) planner that achieves orders-of-magnitude reduction in computation time compared with prior 3-D approaches by incorporating variable curvature kinematics and a novel distance metric for planning. Our system uses an electromagnetic tracking system to sense the state of the needle tip during the procedure. We experimentally evaluate our needle steering system using tissue phantoms and animal tissue ex vivo. We demonstrate that our rapid replanning strategy successfully guides the needle around obstacles to desired 3-D targets with an average error of less than 3 mm.
Concentric tube robots can enable new clinical interventions if they are able to pass through soft tissue, deploy along desired paths through open cavities, or travel along winding lumens. These ...behaviors require the robot to deploy in such a way that the curved shape of its shaft remains unchanged as the tip progresses forward (i.e., "follow-the-leader" deployment). Follow-the-leader deployment is challenging for concentric tube robots due to elastic (and particularly torsional) coupling between the tubes that form the robot. However, as we show in this paper, follow-the-leader deployment is possible, provided that tube precurvatures and deployment sequences are appropriately selected. We begin by defining follow-the-leader deployment and providing conditions that must be satisfied for a concentric tube robot to achieve it. We then examine several useful special cases of follow-the-leader deployment, showing that both circular and helical precurvatures can be employed, and provide an experimental illustration of the helical case. We also explore approximate follow-the-leader behavior and provide a metric for the similarity of a general deployment to a follow-the-leader deployment. Finally, we consider access to the hippocampus in the brain to treat epilepsy, as a motivating clinical example for follow-the-leader deployment.
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