Virtual reality and consciousness inference in dreaming

This article explores the notion that the brain is genetically endowed with an innate virtual reality generator that – through experience-dependent plasticity – becomes a generative or predictive model of the world. This model, which is most clearly revealed in rapid eye movement (REM) sleep dreaming, may provide the theater for conscious experience. Functional neuroimaging evidence for brain activations that are time-locked to rapid eye movements (REMs) endorses the view that waking consciousness emerges from REM sleep – and dreaming lays the foundations for waking perception. In this view, the brain is equipped with a virtual model of the world that generates predictions of its sensations. This model is continually updated and entrained by sensory prediction errors in wakefulness to ensure veridical perception, but not in dreaming. In contrast, dreaming plays an essential role in maintaining and enhancing the capacity to model the world by minimizing model complexity and thereby maximizing both statistical and thermodynamic efficiency. This perspective suggests that consciousness corresponds to the embodied process of inference, realized through the generation of virtual realities (in both sleep and wakefulness). In short, our premise or hypothesis is that the waking brain engages with the world to predict the causes of sensations, while in sleep the brain’s generative model is actively refined so that it generates more efficient predictions during waking. We review the evidence in support of this hypothesis – evidence that grounds consciousness in biophysical computations whose neuronal and neurochemical infrastructure has been disclosed by sleep research

Teaching MBA Students Teamwork And Team Leadership Skills: An Empirical Evaluation Of A Classroom Educational Program

A comprehensive educational program for teaching behavioral teamwork and team leadership skills was rigorously evaluated with 148 MBA students enrolled at an urban regional campus of a Midwestern public university.  Major program components included (1) videotaped student teams in leaderless group discussion (LGD) exercises at the course beginning and end, (2) behavioral assessment of student teamwork and team leadership in the LGD’s, (3) peer and instructor performance feedback and coaching after each LGD, (4) informational modules on teamwork and team leadership, and (5) multiple opportunities (classroom and field) to practice teamwork and team leadership skills.  Prominent findings indicated (1) a statistically significant increase in overall teamwork and overall team leadership scores of, respectively, 14% and 8%, (2) no demographic differences in student improvements as a function of sex, age, or race/ethnicity, and (3) very favorable student responses to end-of-course questions concerning teamwork and team leadership skills improvement, self-confidence, and attitudes

A Leucyl-tRNA Synthetase Urzyme: Authenticity of tRNA Synthetase Catalytic Activities and Promiscuous Phosphorylation of Leucyl-5′AMP

Aminoacyl-tRNA synthetase (aaRS)/tRNA cognate pairs translate the genetic code by synthesizing specific aminoacyl-tRNAs that are assembled on messenger RNA by the ribosome. Deconstruction of the two distinct aaRS superfamilies (Classes) has provided conceptual and experimental models for their early evolution. Urzymes, containing ~120–130 amino acids excerpted from regions where genetic coding sequence complementarities have been identified, are key experimental models motivated by the proposal of a single bidirectional ancestral gene. Previous reports that Class I and Class II urzymes accelerate both amino acid activation and tRNA aminoacylation have not been extended to other synthetases. We describe a third urzyme (LeuAC) prepared from the Class IA Pyrococcus horikoshii leucyl-tRNA synthetase. We adduce multiple lines of evidence for the authenticity of its catalysis of both canonical reactions, amino acid activation and tRNALeu aminoacylation. Mutation of the three active-site lysine residues to alanine causes significant, but modest reduction in both amino acid activation and aminoacylation. LeuAC also catalyzes production of ADP, a non-canonical enzymatic function that has been overlooked since it first was described for several full-length aaRS in the 1970s. Structural data suggest that the LeuAC active site accommodates two ATP conformations that are prominent in water but rarely seen bound to proteins, accounting for successive, in situ phosphorylation of the bound leucyl-5′AMP phosphate, accounting for ADP production. This unusual ATP consumption regenerates the transition state for amino acid activation and suggests, in turn, that in the absence of the editing and anticodon-binding domains, LeuAC releases leu-5′AMP unusually slowly, relative to the two phosphorylation reactions

The feasibility of conducting a randomised controlled trial comparing arthroscopic hip surgery to conservative care for patients with femoroacetabular impingement syndrome : the FASHIoN feasibility study

BACKGROUND: Femoroacetabular impingement (FAI) is a syndrome of hip or groin pain associated with shape abnormalities of the hip joint. Treatments include arthroscopic surgery and conservative care. This study explored the feasibility of a randomised controlled trial to compare these treatments. OBJECTIVES: The objectives of this study were to estimate the number of patients available for a full randomised controlled trial (RCT); to explore clinician and patient willingness to participate in such a RCT; to develop consensus on eligibility criteria, surgical and best conservative care protocols; to examine possible outcome measures and estimate the sample size for a full RCT; and to develop trial procedures and estimate recruitment and follow-up rates. METHODS: Pre-pilot work: we surveyed all UK NHS hospital trusts (n = 197) to identify all FAI surgeons and to estimate how much arthroscopic FAI surgery they performed. We interviewed a purposive sample of 18 patients, 36 physiotherapists, 18 surgeons and two sports physicians to explore attitudes towards a RCT and used consensus-building methods among them to develop treatment protocols and patient information. Pilot RCT: we performed a pilot RCT in 10 hospital trusts. Patients were randomised to receive either hip arthroscopy or best conservative care and then followed up at 3, 6 and 12 months using patient-reported questionnaires for hip pain and function, activity level, quality of life, and a resource-use questionnaire. Qualitative recruitment intervention: we performed semistructured interviews with all researchers and clinicians involved in the pilot RCT in eight hospital trusts and recorded and analysed diagnostic and recruitment consultations with eligible patients. RESULTS: We identified 120 surgeons who reported treating at least 1908 patients with FAI by hip arthroscopy in the NHS in the financial year 2011/12. There were 34 hospital trusts that performed ≥ 20 arthroscopic FAI operations in the year. We found that clinicians were positive about a RCT: only half reported equipoise, but most said that they would be prepared to randomise patients. Patients strongly supported a RCT, but expressed concerns about its design; these were used to develop patient information for the pilot RCT. We developed a surgical protocol and showed that this could be used in a RCT. We developed a physiotherapy-led exercise-based package of best conservative care called 'personalised hip therapy' and showed that this was practicable. In the pilot RCT, we recruited 42 out of 60 eligible patients (70%) across nine sites. The mean duration and recruitment rate across all sites were 4.5 months and one patient per site per month, respectively. The lead site recruited for the longest period (9.3 months) and accrued the largest number of patients (2.1 patients per month). We recorded and analysed 84 diagnostic and recruitment consultations in 60 patients and used these to develop a model for an optimal recruitment consultation. We identified the International Hip Outcome Tool at 12 months as an appropriate outcome measure and estimated the sample size for a full trial as 344 participants: a number that could be recruited in 25 centres over 18 months. CONCLUSION: We have demonstrated that it is feasible to perform a RCT to establish the clinical effectiveness of hip arthroscopy compared with best conservative care for FAI. We have designed a full trial and developed and tested procedures for it, including an innovative approach to recruitment. We propose that a full trial be implemented

Influence of training status on high-intensity intermittent performance in response to β-alanine supplementation

Recent investigations have suggested that highly trained athletes may be less responsive to the ergogenic effects of β-alanine (BA) supplementation than recreationally active individuals due to their elevated muscle buffering capacity. We investigated whether training status influences the effect of BA on repeated Wingate performance. Forty young males were divided into two groups according to their training status (trained: T, and non-trained: NT cyclists) and were randomly allocated to BA and a dextrose-based placebo (PL) groups, providing four experimental conditions: NTPL, NTBA, TPL, TBA. BA (6.4 g day-1 ) or PL was ingested for 4 weeks, with participants completing four 30-s lower-body Wingate bouts, separated by 3 min, before and after supplementation. Total work done was significantly increased following supplementation in both NTBA (p = 0.03) and TBA (p = 0.002), and it was significantly reduced in NTPL (p = 0.03) with no difference for TPL (p = 0.73). BA supplementation increased mean power output (MPO) in bout 4 for the NTBA group (p = 0.0004) and in bouts 1, 2 and 4 for the TBA group (p ≤ 0.05). No differences were observed in MPO for NTPL and TPL. BA supplementation was effective at improving repeated high-intensity cycling performance in both trained and non-trained individuals, highlighting the efficacy of BA as an ergogenic aid for high-intensity exercise regardless of the training status of the individual

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

Positive relationships between association strength and phenotypic similarity characterize the assembly of mixed-species bird flocks worldwide

Competition theory predicts that local communities should consist of species that are more dissimilar than expected by chance. We find a strikingly different pattern in a multicontinent data set (55 presence-absence matrices from 24 locations) on the composition of mixed-species bird flocks, which are important sub-units of local bird communities the world over. By using null models and randomization tests followed by meta-analysis, we find the association strengths of species in flocks to be strongly related to similarity in body size and foraging behavior and higher for congeneric compared with noncongeneric species pairs. Given the local spatial scales of our individual analyses, differences in the habitat preferences of species are unlikely to have caused these association patterns; the patterns observed are most likely the outcome of species interactions. Extending group-living and social-information-use theory to a heterospecific context, we discuss potential behavioral mechanisms that lead to positive interactions among similar species in flocks, as well as ways in which competition costs are reduced. Our findings highlight the need to consider positive interactions along with competition when seeking to explain community assembly

Preclinical Evaluation of Long-Acting Emtricitabine Semi-Solid Prodrug Nanoparticle Formulations.

Long-acting injectable (LAI) formulations promise to deliver patient benefits by overcoming issues associated with non-adherence. A preclinical assessment of semi-solid prodrug nanoparticle (SSPN) LAI formulations of emtricitabine (FTC) is reported here. Pharmacokinetics over 28 days were assessed in Wistar rats, New Zealand white rabbits, and Balb/C mice following intramuscular injection. Two lead formulations were assessed for the prevention of an HIV infection in NSG-cmah-/- humanised mice to ensure antiviral activities were as anticipated according to the pharmacokinetics. Cmax was reached by 12, 48, and 24 h in rats, rabbits, and mice, respectively. Plasma concentrations were below the limit of detection (2 ng/mL) by 21 days in rats and rabbits, and 28 days in mice. Mice treated with SSPN formulations demonstrated undetectable viral loads (700 copies/mL detection limit), and HIV RNA remained undetectable 28 days post-infection in plasma, spleen, lung, and liver. The in vivo data presented here demonstrate that the combined prodrug/SSPN approach can provide a dramatically extended pharmacokinetic half-life across multiple preclinical species. Species differences in renal clearance of FTC mean that longer exposures are likely to be achievable in humans than in preclinical models

Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation

To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity

Arthroscopic hip surgery compared with personalised hip therapy in people over 16 years old with femoroacetabular impingement syndrome : UK FASHIoN RCT

Background: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery or with physiotherapist-led conservative care. Objective: To compare the clinical effectiveness and cost-effectiveness of hip arthroscopy with best conservative care. Design: The UK FASHIoN (full trial of arthroscopic surgery for hip impingement compared with non-operative care) trial was a pragmatic, multicentre, randomised controlled trial that was carried out at 23 NHS hospitals. Participants: Participants were included if they had femoroacetabular impingement, were aged ≥ 16 years old, had hip pain with radiographic features of cam or pincer morphology (but no osteoarthritis) and were believed to be likely to benefit from hip arthroscopy. Intervention: Participants were randomly allocated (1 : 1) to receive hip arthroscopy followed by postoperative physiotherapy, or personalised hip therapy (i.e. an individualised physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre using a central telephone randomisation service. Outcome assessment and analysis were masked. Main outcome measure: The primary outcome was hip-related quality of life, measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed by intention to treat. Results: Between July 2012 and July 2016, 648 eligible patients were identified and 348 participants were recruited. In total, 171 participants were allocated to receive hip arthroscopy and 177 participants were allocated to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (N = 319; hip arthroscopy, n = 157; personalised hip therapy, n = 162). At 12 months, mean International Hip Outcome Tool (iHOT-33) score had improved from 39.2 (standard deviation 20.9) points to 58.8 (standard deviation 27.2) points for participants in the hip arthroscopy group, and from 35.6 (standard deviation 18.2) points to 49.7 (standard deviation 25.5) points for participants in personalised hip therapy group. In the primary analysis, the mean difference in International Hip Outcome Tool scores, adjusted for impingement type, sex, baseline International Hip Outcome Tool score and centre, was 6.8 (95% confidence interval 1.7 to 12.0) points in favour of hip arthroscopy (p = 0.0093). This estimate of treatment effect exceeded the minimum clinically important difference (6.1 points). Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment and one serious adverse event in the personalised hip therapy group was not. Thirty-eight (24%) personalised hip therapy patients chose to have hip arthroscopy between 1 and 3 years after randomisation. Nineteen (12%) hip arthroscopy patients had a revision arthroscopy. Eleven (7%) personalised hip therapy patients and three (2%) hip arthroscopy patients had a hip replacement within 3 years. Limitations: Study participants and treating clinicians were not blinded to the intervention arm. Delays were encountered in participants accessing treatment, particularly surgery. Follow-up lasted for 3 years. Conclusion: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement in quality of life than personalised hip therapy, and this difference was clinically significant at 12 months. This study does not demonstrate cost-effectiveness of hip arthroscopy compared with personalised hip therapy within the first 12 months. Further follow-up will reveal whether or not the clinical benefits of hip arthroscopy are maintained and whether or not it is cost-effective in the long term. Trial registration: Current Controlled Trials ISRCTN64081839. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 16. See the NIHR Journals Library website for further project information