Real-time simulation of three-dimensional shoulder girdle and arm dynamics

Electrical stimulation is a promising technology for the restoration of arm function in paralyzed individuals. Control of the paralyzed arm under electrical stimulation, however, is a challenging problem that requires advanced controllers and command interfaces for the user. A real-time model describing the complex dynamics of the arm would allow user-in-the-loop type experiments where the command interface and controller could be assessed. Real-time models of the arm previously described have not included the ability to model the independently controlled scapula and clavicle, limiting their utility for clinical applications of this nature. The goal of this study therefore was to evaluate the performance and mechanical behavior of a real-time, dynamic model of the arm and shoulder girdle. The model comprises seven segments linked by eleven degrees of freedom and actuated by 138 muscle elements. Polynomials were generated to describe the muscle lines of action to reduce computation time, and an implicit, first-order Rosenbrock formulation of the equations of motion was used to increase simulation step-size. The model simulated flexion of the arm faster than real time, simulation time being 92% of actual movement time on standard desktop hardware. Modeled maximum isometric torque values agreed well with values from the literature, showing that the model simulates the moment-generating behavior of a real human arm. The speed of the model enables experiments where the user controls the virtual arm and receives visual feedback in real time. The ability to optimize potential solutions in simulation greatly reduces the burden on the user during development

The relationship between transliminality, hypnotic and imaginative suggestibility, and other personality traits

Data availability: We have shared a link to the data within the manuscript.Copyright © 2024 The Authors. To our knowledge, no study has directly examined the link between hypnotic response and the personality trait of transliminality (which is underpinned, for example, by magical ideation, mystical experience, fantasy proneness, absorption, hyperaesthesia). In order to further understand the correlates of suggestibility, the aim of the current project was to investigate whether transliminality is associated with hypnotic and imaginative suggestibility (considering: objective response, subjective response and involuntariness). Another aim was to assess the contribution of transliminality as a predictor of suggestibility when a range of previously studied personality trait measures were considered. Participants completed: the Revised Transliminality Scale, Tellegen Absorption Scale, Creative Experiences Questionnaire, and the Dissociative Experiences Scale II. To avoid context effects, where knowledge or measurement of one trait or ability might influence measurement of another, a separate standalone study was conducted where hypnotic and imaginative (without hypnosis) suggestibility screenings were carried out in-person in small groups using the modified Carleton University Responsiveness to Suggestion Scale. The merging of these two datasets enabled the analyses. Transliminality was weakly correlated with the imaginative suggestibility subjective response measure (r = 0.19). Likewise, weak correlations were found between transliminality and the hypnotic suggestibility response measures (objective, r = 0.21, subjective, r = 0.23, involuntariness, r = 0.24). The multiple regressions (forward selection) reflected the pattern of correlations, with no model for any of the variables, retaining more than a single significant predictor. In summary, this study combination, avoiding context effects, shows transliminality to be a weak predictor of response to suggestion.The Leverhulme Trust (grant number RPG-2017-291) to W McGeown (Principal Investigator), A Venneri, G Mazzoni and I Kirsch, and The BIAL Foundation (grant number 269/18) to W McGeown (Principal Investigator), R Tate, A Venneri, G Mazzoni and I Kirsch

Reactions to treatment debriefing among the participants of a placebo controlled trial

BACKGROUND: A significant proportion of trial participants respond to placebos for a variety of conditions. Despite the common conduct of these trials and the strong emphasis placed on informed consent, very little is known about informing participants about their individual treatment allocation at trial closure. This study aims to address this gap in the literature by exploring treatment beliefs and reactions to feedback about treatment allocation in the participants of a placebo-controlled randomized clinical trial (RCT). METHODS: Survey of trial participants using a semi-structured questionnaire including close and open-ended questions administered as telephone interviews and postal questionnaires. Trial participants were enrolled in a double-blind placebo-controlled RCT evaluating the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had closed and participants remained blind to treatment allocation. We assessed treatment expectations, the percentage of participants who wanted to be informed about their treatment allocation, their ability to guess and reactions to debriefing. RESULTS: Forty-six (73%) contactable participants responded to our survey. Forty-two were eligible (four participants with bilateral disease were excluded as they had received both treatments). Most (79%) participants did not have any expectations prior to receiving treatment, but many 'hoped' that something would help. Reasons for not having high expectations included the experimental nature of their care and possibility that they may get a placebo. Participants were hopeful because their pain was so severe and because they trusted the staff and services. Most (83%) wanted to be informed about their treatment allocation and study results. Over half (55%) said they could not guess which treatment they had been randomized to, and many of those who attempted a guess were incorrect. Reactions to treatment debriefing were generally positive, including in placebo responders. CONCLUSION: Our study suggests that most trial participants want to be informed about their treatment allocation and trial results. Further research is required to develop measure of hope and expectancy and to rigorously evaluate the effects of debriefing prospectively

Consistent superiority of selective serotonin reuptake inhibitors over placebo in reducing depressed mood in patients with major depression.

The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo. Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter. In this study, we examined whether the negative outcomes of many SSRI trials may be partly caused by the use of this frequently questioned measure of response. We undertook patient-level post-hoc analyses of 18 industry-sponsored placebo-controlled trials regarding paroxetine, citalopram, sertraline or fluoxetine, and including in total 6669 adults with major depression, the aim being to assess what the outcome would have been if the single item depressed mood (rated 0-4) had been used as a measure of efficacy. In total, 32 drug-placebo comparisons were reassessed. While 18 out of 32 comparisons (56%) failed to separate active drug from placebo at week 6 with respect to reduction in HDRS-17-sum, only 3 out of 32 comparisons (9%) were negative when depressed mood was used as an effect parameter (

From habits of attrition to modes of inclusion: enhancing the role of private practitioners in routine disease surveillance

Background: Private practitioners are the preferred first point of care in a majority of low and middle-income countries and in this position, best placed for the surveillance of diseases. However their contribution to routine surveillance data is marginal. This systematic review aims to explore evidence with regards to the role, contribution, and involvement of private practitioners in routine disease data notification. We examined the factors that determine the inclusion of, and the participation thereof of private practitioners in disease surveillance activities. Methods: Literature search was conducted using the PubMed, Web of Knowledge, WHOLIS, and WHO-IRIS databases to identify peer reviewed and gray full-text documents in English with no limits for year of publication or study design. Forty manuscripts were reviewed. Results: The current participation of private practitioners in disease surveillance efforts is appalling. The main barriers to their participation are inadequate knowledge leading to unsatisfactory attitudes and misperceptions that influence their practices. Complicated reporting mechanisms with unclear guidelines, along with unsatisfactory attitudes on behalf of the government and surveillance program managers also contribute to the underreporting of cases. Infrastructural barriers especially the availability of computers and skilled human resources are critical to improving private sector participation in routine disease surveillance. Conclusion: The issues identified are similar to those for underreporting within the Integrated infectious Disease Surveillance and Response systems (IDSR) which collects data mainly from public healthcare facilities. We recommend that surveillance program officers should provide periodic training, supportive supervision and offer regular feedback to the practitioners from both public as well as private sectors in order to improve case notification. Governments need to take leadership and foster collaborative partnerships between the public and private sectors and most importantly exercise regulatory authority where needed

Surgical management of vesicoureteral reflux in children

Vesicoureteral reflux (VUR) is the most common uropathy affecting children. Compared to children without VUR, those with VUR have a higher rate of pyelonephritis and renal scarring following urinary tract infection (UTI). Options for treatment include observation with or without antibiotic prophylaxis and surgical repair. Surgical intervention may be necessary in patients with persistent reflux, renal scarring, and recurrent or breakthrough febrile UTI. Both open and endoscopic approaches to reflux correction are successful and reduce the occurrence of febrile UTI. Estimated success rates of open and endoscopic reflux correction are 98.1% (95% CI 95.1, 99.1) and 83.0% (95% CI 69.1, 91.4), respectively. Factors that affect the success of endoscopic injection include pre-operative reflux grade and presence of functional or anatomic bladder abnormalities including voiding dysfunction and duplicated collecting systems. Few studies have evaluated the long-term outcomes of endoscopic injection, and with variable results. In patients treated endoscopically, recurrent febrile UTI occurred in 0–21%, new renal damage in 9–12%, and recurrent reflux in 17–47.6% of treated ureters with at least 1 year follow-up. These studies highlight the need for standardized outcome reporting and longer follow-up after endoscopic treatment

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers