Anodal cerebellar t-DCS impacts skill learning and transfer on a robotic surgery training task.

The cerebellum has demonstrated a critical role during adaptation in motor learning. However, the extent to which it can contribute to the skill acquisition of complex real-world tasks remains unclear. One particularly challenging application in terms of motor activities is robotic surgery, which requires surgeons to complete complex multidimensional visuomotor tasks through a remotely operated robot. Given the need for high skill proficiency and the lack of haptic feedback, there is a pressing need for understanding and improving skill development. We investigated the effect of cerebellar transcranial direct current stimulation applied during the execution of a robotic surgery training task. Study participants received either real or sham stimulation while performing a needle driving task in a virtual (simulated) and a real-world (actual surgical robot) setting. We found that cerebellar stimulation significantly improved performance compared to sham stimulation at fast (more demanding) execution speeds in both virtual and real-world training settings. Furthermore, participants that received cerebellar stimulation more effectively transferred the skills they acquired during virtual training to the real world. Our findings underline the potential of non-invasive brain stimulation to enhance skill learning and transfer in real-world relevant tasks and, more broadly, its potential for improving complex motor learning.

Dual-Modality Haptic Feedback Improves Dexterous Task Execution With Virtual EMG-Controlled Gripper.

Individuals with upper-extremity limb difference who use myoelectric prostheses currently lack the haptic sensory information needed to perform dexterous activities of daily living. While considerable research has focused on restoring this haptic information, these approaches often rely on single-modality feedback schemes which are necessary but insufficient for the feedforward and feedback control strategies employed by the central nervous system. Multi-modality feedback approaches have been gaining attention in several application domains, however, the utility for myoelectric prosthesis use remains unclear. In this study, we investigated the utility of dual-modality haptic feedback in a virtual EMG-controlled grasp-and-hold task with a brittle object and variable load force. We recruited N = 20 participants without limb difference to perform the task in four conditions: no feedback, vibration feedback of incipient slip, squeezing feedback of grip force, and dual (vibration + squeezing) feedback of incipient slip and grip force. Results suggest that receiving any haptic feedback is better than receiving none, however, dual-modality feedback is far superior to either single-modality feedback approach in terms of preventing the object from breaking or dropping. Control with dual-modality feedback was also seen as more intuitive than with either of the single-modality feedback approaches.

Mirror-Brush Illusion: Creating Phantom Tactile Percepts on Intact Limbs.

Haptic illusions provide unique insights into how we model our bodies separate from our environment. Popular illusions like the rubber-hand illusion and mirror-box illusion have demonstrated that we can adapt the internal representations of our limbs in response to visuo-haptic conflicts. In this manuscript, we extend this knowledge by investigating to what extent, if any, we also augment our external representations of the environment and its action on our bodies in response to visuo-haptic conflicts. Utilizing a mirror and a robotic brushstroking platform, we create a novel illusory paradigm that presents a visuo-haptic conflict using congruent and incongruent tactile stimuli applied to participants' fingers. Overall, we observed that participants perceived an illusory tactile sensation on their visually occluded finger when seeing a visual stimulus that was inconsistent with the actual tactile stimulus provided. We also found residual effects of the illusion after the conflict was removed. These findings highlight how our need to maintain a coherent internal representation of our body extends to our model of our environment.

Haptic shared control improves neural efficiency during myoelectric prosthesis use.

Clinical myoelectric prostheses lack the sensory feedback and sufficient dexterity required to complete activities of daily living efficiently and accurately. Providing haptic feedback of relevant environmental cues to the user or imbuing the prosthesis with autonomous control authority have been separately shown to improve prosthesis utility. Few studies, however, have investigated the effect of combining these two approaches in a shared control paradigm, and none have evaluated such an approach from the perspective of neural efficiency (the relationship between task performance and mental effort measured directly from the brain). In this work, we analyzed the neural efficiency of 30 non-amputee participants in a grasp-and-lift task of a brittle object. Here, a myoelectric prosthesis featuring vibrotactile feedback of grip force and autonomous control of grasping was compared with a standard myoelectric prosthesis with and without vibrotactile feedback. As a measure of mental effort, we captured the prefrontal cortex activity changes using functional near infrared spectroscopy during the experiment. It was expected that the prosthesis with haptic shared control would improve both task performance and mental effort compared to the standard prosthesis. Results showed that only the haptic shared control system enabled users to achieve high neural efficiency, and that vibrotactile feedback was important for grasping with the appropriate grip force. These results indicate that the haptic shared control system synergistically combines the benefits of haptic feedback and autonomous controllers, and is well-poised to inform such hybrid advancements in myoelectric prosthesis technology.

Effects of automated skill assessment on robotic surgery training.

BACKGROUND: Several automated skill-assessment approaches have been proposed for robotic surgery, but their utility is not well understood. This article investigates the effects of one machine-learning-based skill-assessment approach on psychomotor skill development in robotic surgery training. METHODS: N = 29 trainees (medical students and residents) with no robotic surgery experience performed five trials of inanimate peg transfer with an Intuitive Surgical da Vinci Standard robot. Half of the participants received no post-trial feedback. The other half received automatically calculated scores from five Global Evaluative Assessment of Robotic Skill domains post-trial. RESULTS: There were no significant differences between the groups regarding overall improvement or skill improvement rate. However, participants who received post-trial feedback rated their overall performance improvement significantly lower than participants who did not receive feedback. CONCLUSIONS: These findings indicate that automated skill evaluation systems might improve trainee self-awareness but not accelerate early stage psychomotor skill development in robotic surgery training.

The Utility of Synthetic Reflexes and Haptic Feedback for Upper-Limb Prostheses in a Dexterous Task Without Direct Vision.

Individuals who use myoelectric upper-limb prostheses often rely heavily on vision to complete their daily activities. They thus struggle in situations where vision is overloaded, such as multitasking, or unavailable, such as poor lighting conditions. Non-disabled individuals can easily accomplish such tasks due to tactile reflexes and haptic sensation guiding their upper-limb motor coordination. Based on these principles, we developed and tested two novel prosthesis systems that incorporate autonomous controllers and provide the user with touch-location feedback through either vibration or distributed pressure. These capabilities were made possible by installing a custom contact-location sensor on the fingers of a commercial prosthetic hand, along with a custom pressure sensor on the thumb. We compared the performance of the two systems against a standard myoelectric prosthesis and a myoelectric prosthesis with only autonomous controllers in a difficult reach-to-pick-and-place task conducted without direct vision. Results from 40 non-disabled participants in this between-subjects study indicated that vibrotactile feedback combined with synthetic reflexes proved significantly more advantageous than the standard prosthesis in several of the task milestones. In addition, vibrotactile feedback and synthetic reflexes improved grasp placement compared to only synthetic reflexes or pressure feedback combined with synthetic reflexes. These results indicate that autonomous controllers and haptic feedback together facilitate success in dexterous tasks without vision, and that the type of haptic display matters.

Novel Planar Strain Sensor Design for Capturing 3-Dimensional Fingertip Forces from Patients Affected by Hand Paralysis.

Assessment and therapy for individuals who have hand paresis requires force sensing approaches that can measure a wide range of finger forces in multiple dimensions. Here we present a novel strain-gauge force sensor with 3 degrees of freedom (DOF) designed for use in a hand assessment and rehabilitation device. The sensor features a fiberglass printed circuit board substrate to which eight strain gauges are bonded. All circuity for the sensor is routed directly through the board, which is secured to a larger rehabilitative device via an aluminum frame. After design, the sensing package was characterized for weight, capacity, and resolution requirements. Furthermore, a test sensor was calibrated in a three-axis configuration and validated in the larger spherical workspace to understand how accurate and precise the sensor is, while the sensor has slight shortcomings with validation error, it does satisfy the precision, calibration accuracy, and fine sensing requirements in orthogonal loading, and all structural specifications are met. The sensor is therefore a great candidate for sensing technology in rehabilitation devices that assess dexterity in patients with impaired hand function.

Hydroxychloroquine Alternatives for Chronic Disease: Response to a Growing Shortage Amid the Global COVID-19 Pandemic.

With the emergence of a novel severe acute respiratory syndrome coronavirus, investigators worldwide are scrambling to identify appropriate treatment modalities, develop accurate testing, and produce a vaccine. To date, effective treatment remains elusive. Chloroquine phosphate and hydroxychloroquine sulfate (HCQ), well-known antimalarial drugs effective in the treatment of systemic lupus erythematosus, rheumatoid arthritis, porphyria cutanea tarda, and chronic Q fever, are currently under investigation. The United States Food and Drug Administration recently issued an Emergency Use Authorization for CQ and HCQ use in the treatment of coronavirus disease 2019 (COVID-19). With spikes in HCQ use and demand, ethical considerations encompassing appropriate use, patient autonomy, nonmaleficence, and distributive justice abound. As drug experts, pharmacists are uniquely positioned to advocate for patients with chronic conditions necessitating HCQ use, assist in the appropriate prescribing of HCQ for COVID-19, and ensure patients and health care professionals are continually educated during this public health crisis. This review highlights the worldwide pandemic, describes appropriate HCQ use for chronic conditions, highlights available alternatives, and deliberates evolving ethical questions. With assistance from colleagues, state boards of pharmacy, and national organizations, pharmacists ensure the just distribution of valuable pharmaceuticals to patients having COVID-19 while supporting the needs of patients requiring HCQ for chronic conditions.

Comparison of vibrotactile and joint-torque feedback in a myoelectric upper-limb prosthesis.

BACKGROUND: Despite the technological advancements in myoelectric prostheses, body-powered prostheses remain a popular choice for amputees, in part due to the natural sensory advantage they provide. Research on haptic feedback in myoelectric prostheses has delivered mixed results. Furthermore, there is limited research comparing various haptic feedback modalities in myoelectric prostheses. In this paper, we present a comparison of the feedback intrinsically present in body-powered prostheses (joint-torque feedback) to a commonly proposed feedback modality for myoelectric prostheses (vibrotactile feedback). In so doing, we seek to understand whether the advantages of kinesthetic feedback present in body-powered prostheses translate to myoelectric prostheses, and whether there are differences between kinesthetic and cutaneous feedback in prosthetic applications. METHODS: We developed an experimental testbed that features a cable-driven, voluntary-closing 1-DoF prosthesis, a capstan-driven elbow exoskeleton, and a vibrotactile actuation unit. The system can present grip force to users as either a flexion moment about the elbow or vibration on the wrist. To provide an equal comparison of joint-torque and vibrotactile feedback, a stimulus intensity matching scheme was utilized. Non-amputee participants (n=12) were asked to discriminate objects of varying stiffness with the prosthesis in three conditions: no haptic feedback, vibrotactile feedback, and joint-torque feedback. RESULTS: Results indicate that haptic feedback increased discrimination accuracy over no haptic feedback, but the difference between joint-torque feedback and vibrotactile feedback was not significant. In addition, our results highlight nuanced differences in performance depending on the objects' stiffness, and suggest that participants likely pay less attention to incidental cues with the addition of haptic feedback. CONCLUSION: Even when haptic feedback is not modality matched to the task, such as in the case of vibrotactile feedback, performance with a myoelectric prosthesis can improve significantly. This implies it is possible to achieve the same benefits with vibrotactile feedback, which is cheaper and easier to implement than other forms of feedback.

A description of 'Australian Lyme disease' epidemiology and impact: an analysis of submissions to an Australian senate inquiry.

BACKGROUND: Many Australian patients are diagnosed and treated for the scientifically and politically controversial diagnosis of an endemic form of 'Australian Lyme Disease'. Patient advocacy led Senator John Madigan to propose an Australian Senate Inquiry into this illness. AIM: To describe the symptomology and outcomes of patients diagnosed and treated with Lyme disease in Australia. METHODS: All public, first-person submissions (n = 698) to the inquiry were reviewed and responses analysed for epidemiology, symptoms and impact against structured criteria. RESULTS: The most common symptoms described were fatigue (62.6%), disordered thinking (51.9%) and sensory disturbance (46.1%). Respondents reported experiencing symptoms for a median of 10 years and spent a median of $30 000 on diagnosis and treatment. Almost 10% of respondents self-diagnosed after being exposed to a media report of Australian Lyme disease. CONCLUSIONS: Patients diagnosed with Lyme disease in Australia display a symptomology similar to 'medically unexplained physical symptoms' syndromes, experience social and financial harms, and are at risk of nosocomial harms. Negative medical interactions and the media may contribute to patients seeking alternative and potentially non-evidence-based diagnoses and treatments.

Shigella species epidemiology and antimicrobial susceptibility: the implications of emerging azithromycin resistance for guiding treatment, guidelines and breakpoints.

OBJECTIVES: To examine antimicrobial susceptibility patterns and predictors of resistance among Shigella isolates in New South Wales (NSW), Australia during 2013-14 with emphasis on azithromycin. METHODS: Cross-sectional analysis of all shigellosis cases (160) notified to public health authorities in NSW, Australia was performed. RESULTS: Among 160 Shigella isolates tested, 139 (86.9%) were susceptible to azithromycin, 104 (65.0%) to ciprofloxacin and 38 (23.7%) to co-trimoxazole. Ciprofloxacin resistance was 1.9 times more common in infections acquired in Australia compared with those acquired overseas, while azithromycin resistance was 8.5 times more common in males. CONCLUSIONS: We recommend ongoing reconsideration of guidelines for the treatment of shigellosis based on emerging resistance patterns. First-line therapy may need to be reconsidered based on local resistance rates due to common resistance to co-trimoxazole and ciprofloxacin. We recommend culture and susceptibility testing for suspected and proven shigellosis. Azithromycin susceptibility breakpoints for Shigella species may need to be species specific.

Using Contact Forces and Robot Arm Accelerations to Automatically Rate Surgeon Skill at Peg Transfer.

OBJECTIVE: Most trainees begin learning robotic minimally invasive surgery by performing inanimate practice tasks with clinical robots such as the Intuitive Surgical da Vinci. Expert surgeons are commonly asked to evaluate these performances using standardized five-point rating scales, but doing such ratings is time consuming, tedious, and somewhat subjective. This paper presents an automatic skill evaluation system that analyzes only the contact force with the task materials, the broad-bandwidth accelerations of the robotic instruments and camera, and the task completion time. METHODS: We recruited N = 38 participants of varying skill in robotic surgery to perform three trials of peg transfer with a da Vinci Standard robot instrumented with our Smart Task Board. After calibration, three individuals rated these trials on five domains of the Global Evaluative Assessment of Robotic Skill (GEARS) structured assessment tool, providing ground-truth labels for regression and classification machine learning algorithms that predict GEARS scores based on the recorded force, acceleration, and time signals. RESULTS: Both machine learning approaches produced scores on the reserved testing sets that were in good to excellent agreement with the human raters, even when the force information was not considered. Furthermore, regression predicted GEARS scores more accurately and efficiently than classification. CONCLUSION: A surgeon's skill at robotic peg transfer can be reliably rated via regression using features gathered from force, acceleration, and time sensors external to the robot. SIGNIFICANCE: We expect improved trainee learning as a result of providing these automatic skill ratings during inanimate task practice on a surgical robot.

Blood cultures and bacteraemia in an Australian emergency department: Evaluating a predictive rule to guide collection and their clinical impact.

OBJECTIVE: The objective of the present study is to determine whether a predictive rule could safely reduce the number of negative blood cultures collected in an Australian ED and to assess the clinical impact of positive results from blood cultures taken in the ED. METHODS: All positive blood cultures taken in the ED at a single facility were retrospectively identified for the calendar year 2012. Clinically significant bacteraemia episodes were assessed against a predictive rule using major and minor clinical and laboratory criteria gathered from medical records and pathology databases, and compared with a randomly generated sample of ED patient episode with negative blood cultures. The ED and final diagnoses and blood culture impact on clinical management were also collected. RESULTS: The predictive rule has a high sensitivity (98.8%) and modest specificity (48.7%), and if applied stringently would have prevented almost half of all blood cultures in our ED but missed two positives. Blood cultures altered the clinical management of 94.3% bacteraemic patients, representing 3.4% of all ED patients with blood cultures performed. High discordance (54%) between ED diagnosis and discharge diagnosis of bacteraemic patients was noted. CONCLUSIONS: Bacteraemia detected in the ED alters subsequent patient management. The predictive rule can be safely applied in the ED to determine need for blood culture collection. Blood cultures should not be omitted in the ED based entirely on preliminary diagnosis given the high discordance seen between ED and discharge diagnosis.

An Empirical Evaluation of Force Feedback in Body-Powered Prostheses.

Myoelectric prostheses have many advantages over body-powered prostheses, yet the absence of sensory feedback in myoelectric devices is one reason body-powered devices are often preferred by amputees. While considerable progress has been made in the mechanical design and control of myoelectric prostheses, research on haptic feedback has not had a similar impact. In this study, we seek to develop a fundamental understanding of the utility of force feedback and vision in the functional operation of a body-powered upper-limb prosthesis. Using a custom body-powered prosthesis in which force feedback can be conditionally removed, we asked N=10 non-amputee participants to identify objects based on stiffness in four separate conditions with and without visual and/or force feedback. Results indicate that the combination of visual and force feedback allows for the best accuracy, followed by force feedback only, then visual feedback only. In addition, combining force feedback with visual feedback does not significantly affect identification timing compared to visual feedback alone. These findings suggest that consideration should be given to the development of force feedback displays for myoelectric prostheses that function like a Bowden cable, coupling the amputee's control input to the resulting feedback.

Non-Colocated Kinesthetic Display Limits Compliance Discrimination in the Absence of Terminal Force Cues.

An important goal of haptic display is to make available the action/reaction relationships that define interactions between the body and the physical world. While in physical world interactions reaction cues invariably impinge on the same part of the body involved in action (reaction and action are colocated), a haptic interface is quite capable of rendering feedback to a separate body part than that used for producing exploratory actions (non-colocated action and reaction). This most commonly occurs with the use of vibrotactile display, in which a cutaneous cue has been substituted for a kinesthetic cue (a kind of sensory substitution). In this paper, we investigate whether non-colocated force and displacement cues degrade the perception of compliance. Using a custom non-colocated kinesthetic display in which one hand controls displacement and the other senses force, we ask participants to discriminate between two virtual springs with matched terminal force and adjustable non-linearity. An additional condition includes one hand controlling displacement while the other senses force encoded in a vibrotactile cue. Results show that when the terminal force cue is unavailable, and even when sensory substitution is not involved, non-colocated kinesthetic displays degrade compliance discrimination relative to colocated kinesthetic displays. Compliance discrimination is also degraded with vibrotactile display of force. These findings suggest that non-colocated kinesthetic displays and, likewise, cutaneous sensory substitution displays should be avoided when discrimination of compliance is necessary for task success.

An exploration of grip force regulation with a low-impedance myoelectric prosthesis featuring referred haptic feedback.

BACKGROUND: Haptic display technologies are well suited to relay proprioceptive, force, and contact cues from a prosthetic terminal device back to the residual limb and thereby reduce reliance on visual feedback. The ease with which an amputee interprets these haptic cues, however, likely depends on whether their dynamic signal behavior corresponds to expected behaviors-behaviors consonant with a natural limb coupled to the environment. A highly geared motor in a terminal device along with the associated high back-drive impedance influences dynamic interactions with the environment, creating effects not encountered with a natural limb. Here we explore grasp and lift performance with a backdrivable (low backdrive impedance) terminal device placed under proportional myoelectric position control that features referred haptic feedback. METHODS: We fabricated a back-drivable terminal device that could be used by amputees and non-amputees alike and drove aperture (or grip force, when a stiff object was in its grasp) in proportion to a myoelectric signal drawn from a single muscle site in the forearm. In randomly ordered trials, we assessed the performance of N=10 participants (7 non-amputee, 3 amputee) attempting to grasp and lift an object using the terminal device under three feedback conditions (no feedback, vibrotactile feedback, and joint torque feedback), and two object weights that were indiscernible by vision. RESULTS: Both non-amputee and amputee participants scaled their grip force according to the object weight. Our results showed only minor differences in grip force, grip/load force coordination, and slip as a function of sensory feedback condition, though the grip force at the point of lift-off for the heavier object was significantly greater for amputee participants in the presence of joint torque feedback. An examination of grip/load force phase plots revealed that our amputee participants used larger safety margins and demonstrated less coordination than our non-amputee participants. CONCLUSIONS: Our results suggest that a backdrivable terminal device may hold advantages over non-backdrivable devices by allowing grip/load force coordination consistent with behaviors observed in the natural limb. Likewise, the inconclusive effect of referred haptic feedback on grasp and lift performance suggests the need for additional testing that includes adequate training for participants.

Intercontinental dissemination of azithromycin-resistant shigellosis through sexual transmission: a cross-sectional study.

BACKGROUND: Shigellosis is an acute, severe bacterial colitis that, in high-income countries, is typically associated with travel to high-risk regions (Africa, Asia, and Latin America). Since the 1970s, shigellosis has also been reported as a sexually transmitted infection in men who have sex with men (MSM), in whom transmission is an important component of shigellosis epidemiology in high-income nations. We aimed to use sophisticated subtyping and international sampling to determine factors driving shigellosis emergence in MSM linked to an outbreak in the UK. METHODS: We did a large-scale, cross-sectional genomic epidemiological study of shigellosis cases collected from 29 countries between December, 1995, and June 8, 2014. Focusing on an ongoing epidemic in the UK, we collected and whole-genome sequenced clinical isolates of Shigella flexneri serotype 3a from high-risk and low-risk regions, including cases associated with travel and sex between men. We examined relationships between geographical, demographic, and clinical patient data with the isolate antimicrobial susceptibility, genetic data, and inferred evolutionary relationships. FINDINGS: We obtained 331 clinical isolates of S flexneri serotype 3a, including 275 from low-risk regions (44 from individuals who travelled to high-risk regions), 52 from high-risk regions, and four outgroup samples (ie, closely related, but genetically distinct isolates used to determine the root of the phylogenetic tree). We identified a recently emerged lineage of S flexneri 3a that has spread intercontinentally in less than 20 years throughout regions traditionally at low risk for shigellosis via sexual transmission in MSM. The lineage had acquired multiple antimicrobial resistance determinants, and prevailing sublineages were strongly associated with resistance to the macrolide azithromycin. Eight (4%) of 206 isolates from the MSM-associated lineage were obtained from patients who had previously provided an isolate; these serial isolations indicated atypical infection patterns (eg, reinfection). INTERPRETATION: We identified transmission-facilitating behaviours and atypical course(s) of infection as precipitating factors in shigellosis-affected MSM. The intercontinental spread of antimicrobial-resistant shigella through established transmission routes emphasises the need for new approaches to tackle the public health challenge of sexually transmitted infections in MSM. FUNDING: Wellcome Trust (grant number 098051).

Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery.

The RNA component of signal recognition particle (SRP) is transcribed by RNA polymerase III, and most steps in SRP biogenesis occur in the nucleolus. Here, we examine processing and quality control of the yeast SRP RNA (scR1). In common with other pol III transcripts, scR1 terminates in a U-tract, and mature scR1 retains a U4-5 sequence at its 3' end. In cells lacking the exonuclease Rex1, scR1 terminates in a longer U5-6 tail that presumably represents the primary transcript. The 3' U-tract of scR1 is protected from aberrant processing by the La homologue, Lhp1 and overexpressed Lhp1 apparently competes with both the RNA surveillance system and SRP assembly factors. Unexpectedly, the TRAMP and exosome nuclear RNA surveillance complexes are also implicated in protecting the 3' end of scR1, which accumulates in the nucleolus of cells lacking the activities of these complexes. Misassembled scR1 has a primary degradation pathway in which Rrp6 acts early, followed by TRAMP-stimulated exonuclease degradation by the exosome. We conclude that the RNA surveillance machinery has key roles in both SRP biogenesis and quality control of the RNA, potentially facilitating the decision between these alternative fates.