An Accurate and Rapidly Calibrating Speech Neuroprosthesis.

BACKGROUND: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy. METHODS: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice. RESULTS: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours. CONCLUSIONS: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.).

Radiofrequency Ablation of the Infrapatellar Branch of the Saphenous Nerve for the Treatment of Chronic Anterior Inferomedial Knee Pain.

INTRO: Genicular nerve radiofrequency ablation (GNRFA) is an effective treatment for chronic knee pain related to osteoarthritis. It is often utilized when conservative management has failed and patients wish to avoid arthroplasty, are poor surgical candidates due to comorbid medical conditions, or in those suffering from persistent pain after arthroplasty. The classic targets for GNRFA include the superior lateral genicular nerve, superior medial genicular nerve, and inferior medial genicular nerve but multiple anatomic studies have demonstrated additional sensory innervation to the knee. OBJECTIVE: In this research article, we propose an image-guided technique that can safely target the infrapatellar branch of the saphenous nerve which also provides sensory innervation to the anterior capsule. PROPOSAL: The proposed technique includes variations for conventional bipolar radiofrequency ablation, cooled radiofrequency ablation, dual-tined bipolar radiofrequency ablation, and monopolar radiofrequency ablation using a long axis approach. The described technique is based on updated anatomic studies and takes into account safety concerns such as thermal risk to the skin and/or pes anserine tendons and breaching of the synovial cavity. CONCLUSION: Future clinical research should be performed to confirm the safety and effectiveness of this specific approach.

Evaluating unintended consequences of intentional species introductions and eradications for improved conservation management.

Increasingly intensive strategies to maintain biodiversity and ecosystem function are being deployed in response to global anthropogenic threats, including intentionally introducing and eradicating species via assisted migration, rewilding, biological control, invasive species eradications, and gene drives. These actions are highly contentious because of their potential for unintended consequences. We conducted a global literature review of these conservation actions to quantify how often unintended outcomes occur and to elucidate their underlying causes. To evaluate conservation outcomes, we developed a community assessment framework for systematically mapping the range of possible interaction types for 111 case studies. Applying this tool, we quantified the number of interaction types considered in each study and documented the nature and strength of intended and unintended outcomes. Intended outcomes were reported in 51% of cases, a combination of intended outcomes and unintended outcomes in 26%, and strictly unintended outcomes in 10%. Hence, unintended outcomes were reported in 36% of all cases evaluated. In evaluating overall conservations outcomes (weighing intended vs. unintended effects), some unintended effects were fairly innocuous relative to the conservation objective, whereas others resulted in serious unintended consequences in recipient communities. Studies that assessed a greater number of community interactions with the target species reported unintended outcomes more often, suggesting that unintended consequences may be underreported due to insufficient vetting. Most reported unintended outcomes arose from direct effects (68%) or simple density-mediated or indirect effects (25%) linked to the target species. Only a few documented cases arose from more complex interaction pathways (7%). Therefore, most unintended outcomes involved simple interactions that could be predicted and mitigated through more formal vetting. Our community assessment framework provides a tool for screening future conservation actions by mapping the recipient community interaction web to identify and mitigate unintended outcomes from intentional species introductions and eradications for conservation.

Evaluación de las Consecuencias Involuntarias de las Introducciones y Erradicaciones Intencionales de Especies para el Manejo Mejorado de la Conservación Resumen Actualmente se despliegan estrategias cada vez más intensas para mantener la biodiversidad y la función del ecosistema como respuesta a las amenazas antropogénicas mundiales, incluyendo la introducción y erradicación intencionales de especies por medio de la migración asistida, el retorno a la vida silvestre, el control biológico, la erradicación de especies invasoras y la genética dirigida. Estas acciones son muy polémicas por el potencial que tienen para generar consecuencias involuntarias. Realizamos una revisión de la literatura mundial sobre estas acciones de conservación para cuantificar cuán seguido ocurren las consecuencias involuntarias y cuáles son sus causas subyacentes. Para evaluar los resultados de conservación, desarrollamos un marco de trabajo de evaluación comunitaria para mapear sistemáticamente el rango de posibles interacciones para 111 estudios de caso. Con la aplicación de esta herramienta cuantificamos el número de tipos de interacción consideradas en cada estudio y documentamos la naturaleza y la fuerza de los resultados involuntarios. Se reportaron los resultados voluntarios en 51% de los casos, una combinación de resultados voluntarios e involuntarios en 26% de los casos y estrictamente los resultados involuntarios en el 10% de los casos. Por lo tanto, los resultados involuntarios fueron reportados en el 36% de todos los casos evaluados. En la evaluación general de los resultados de conservación (sopesando los efectos voluntarios y. los involuntarios), algunos efectos involuntarios fueron bastante inocuos en relación con el objetivo de conservación, mientras que otros resultaron en consecuencias involuntarias severas para las comunidades receptoras. Los estudios que evaluaron un mayor número de interacciones comunitarias con la especie objetivo reportaron resultados involuntarios con mayor frecuencia, lo que sugiere que las consecuencias involuntarias pueden estar subvaloradas debido al escrutinio insuficiente. La mayoría de los resultados involuntarios reportados surgieron de los efectos directos (68%) o de los efectos indirectos o mediados por la densidad (25%) vinculados con la especie diana. Solamente unos cuantos casos documentados surgieron de interacciones más complejas (7%). Por lo tanto, la mayoría de los resultados involuntarios involucran interacciones simples que podrían ser pronosticadas y mitigadas por medio de un escrutinio más formal. Nuestro marco de trabajo de evaluación comunitaria proporciona una herramienta para la revisión de las acciones de conservación en el futuro mediante el mapeo de la red de interacciones entre comunidades receptoras y para la mitigación de los resultados involuntarios surgidos de las introducciones y erradicaciones intencionales de especies a favor de la conservación.

The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Ablation for the Treatment of Vertebrogenic Low Back Pain: An Updated Systematic Review with Single-Arm Meta-analysis.

OBJECTIVE: To provide an estimate of the effectiveness of basivertebral nerve (BVN) radiofrequency ablation (RFA) to treat vertebrogenic low back pain (LBP). DESIGN: Systematic review with single-arm meta-analysis. POPULATION: Persons ≥18 years of age with chronic LBP associated with type 1 or 2 Modic changes. INTERVENTION: Intraosseous BVN RFA. COMPARISON: Sham, placebo procedure, active standard care treatment, or none. OUTCOMES: The proportion of patients treated with BVN RFA who reported ≥50% pain score improvement on a visual analog scale or numeric rating scale. The main secondary outcome was ≥15-point improvement in Oswestry Disability Index score. METHODS: Three reviewers independently assessed articles published before December 6, 2021, in MEDLINE and Embase. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to evaluate the overall quality of evidence. RESULTS: Of the 856 unique records screened, 12 publications met the inclusion criteria, representing six unique study populations, with 414 participants allocated to receive BVN RFA. Single-arm meta-analysis showed a success rate of 65% (95% confidence interval [CI] 51-78%) and 64% (95% CI 43-82%) for ≥50% pain relief at 6 and 12 months, respectively. Rates of ≥15-point Oswestry Disability Index score improvement were 75% (95% CI 63-86%) and 75% (95% CI 63-85%) at 6 and 12 months, respectively. CONCLUSION: According to GRADE, there is moderate-quality evidence that BVN RFA effectively reduces pain and disability in most patients with vertebrogenic LBP. Further high-quality studies will likely improve our understanding of the effectiveness of this procedure.

Innervation of the Posterior Hip Capsule: A Cadaveric Study.

OBJECTIVE: Recent studies of hip anatomy have turned to the posterior hip capsule to better understand the anatomic location of the posterior capsular sensory branches and identify nerves with potential for neural blockade. Current literature has shown the posterior hip capsule is primarily supplied by branches from the sciatic nerve, nerve to quadratus femoris, and superior gluteal nerve (1, 2). This cadaveric study investigated the gross anatomy of the posterior hip, while also identifying potential targets for hip analgesia, with emphasis on the superior gluteal nerve and nerve to quadratus femoris. DESIGN: Cadaveric study. SETTING: UT Health San Antonio Anatomy Lab. METHODS: In total, 10 total cadavers (18 hips total), were posteriorly dissected identifying nerve to quadratus femoris, superior gluteal nerve, and sciatic nerve. Nerves were labeled with radio-opaque markers. Following the dissections, fluoroscopic images were obtained at sequential angles to identify neural anatomy and help expand anatomic knowledge for interventional pain procedures. RESULTS: The posterior hip capsule was supplied by the sciatic nerve in 1/16 hips, the nerve to quadratus femoris in 15/18 hips, and the superior gluteal nerve in 6/18 hips. CONCLUSIONS: The nerve to quadratus femoris reliably innervates the posterior hip joint. Both the sciatic nerve and superior gluteal nerve have small articular branches that may be involved in posterior hip innervation, but this is not seen commonly. The results of this study may elucidate novel therapeutic targets for treatment of chronic refractory hip pain (i.e., the nerve to quadratus femoris).

Peer review in team-based learning: influencing feedback literacy.

BACKGROUND: Peer review in Team-based learning (TBL) exists for three key reasons: to promote reflection on individual behaviours; provide opportunities to develop professional skills; and prevent 'free riders' who fail to contribute effectively to team discussions. A well-developed process that engages students is needed. However, evidence suggests it remains a difficult task to effectively incorporate into TBL. The purpose of this study was to assess medical students' ability to provide written feedback to their peers in TBL, and to explore students' perception of the process, using the conceptual framework of Biggs '3P model'. METHODS: Year 2 students (n = 255) participated in peer review twice during 2019. We evaluated the quality of feedback using a theoretically derived rubric, and undertook a qualitative analysis of focus group data to seek explanations for feedback behaviors. RESULTS: Students demonstrated reasonable ability to provide positive feedback, but were less prepared to identify areas for improvement. Their ability did not improve over time, and was influenced by the perceived task difficulty; social discomfort; and sense of responsibility in providing written feedback. CONCLUSIONS: To increase student engagement, we require a transparent process that incorporates verbal feedback and team discussion, with monitoring of outcomes by faculty and adequate training.

Factors related to doctors' choice of rural pathway in general practice specialty training.

OBJECTIVE: To investigate the factors eligible applicants consider in electing for a rural pathway into specialty training. DESIGN: Cohort study. SETTING: Australia. PARTICIPANTS: Applicants to the Australian General Practice Training program. MAIN OUTCOME MEASURES: Applicants' initial preference of either a general or rural pathway to undertake specialty training. RESULTS: Of the 2,221 applicants, 45% were Australian Medical Graduates (AMGs), 27% Foreign Graduates of Accredited Medical Schools (FGAMS) and 29% International Medical Graduates (IMGs). Through government regulation, two thirds (70%) were eligible to train on both general and rural pathways and a third (30%) were required to train rurally. For applicants eligible for general pathway (n = 1552), those with rural background [Odds Ratio (OR) = 3.7, 95% CI 2.7-5.2] and rural clinical school experience (OR = 2.0, 95% CI 1.5-2.8) were more likely to choose the rural pathway. In addition, FGAMS who were eligible for the general pathway were less likely to choose a rural pathway when compared with IMGs (OR = 0.33, 95%CI 0.1 = 0.7). In applicants who changed their training pathway from their initial to revised preference, lower Multiple-Mini-Interview (OR = 0.54, 95% CI 0.43-0.66) and Situational Judgement Test z-scores (OR = 0.68, 95% CI 0.56-0.83) were associated with a higher probability of changing from a general to rural pathway preference. CONCLUSION: For those eligible for a general or rural pathway, rural background and rural clinical school experience are associated with the decision to elect for rural training. Targeted support for international and foreign graduates of Australia/New Zealand schools may influence them to train rurally.

Intramembrane congestion effects on lysenin channel voltage-induced gating.

All cell membranes are packed with proteins. The ability to investigate the regulatory mechanisms of protein channels in experimental conditions mimicking their congested native environment is crucial for understanding the environmental physicochemical cues that may fundamentally contribute to their functionality in natural membranes. Here we report on investigations of the voltage-induced gating of lysenin channels in congested conditions experimentally achieved by increasing the number of channels inserted into planar lipid membranes. Typical electrophysiology measurements reveal congestion-induced changes to the voltage-induced gating, manifested as a significant reduction of the response to external voltage stimuli. Furthermore, we demonstrate a similar diminished voltage sensitivity for smaller populations of channels by reducing the amount of sphingomyelin in the membrane. Given lysenin's preference for targeting lipid rafts, this result indicates the potential role of the heterogeneous organization of the membrane in modulating channel functionality. Our work indicates that local congestion within membranes may alter the energy landscape and the kinetics of conformational changes of lysenin channels in response to voltage stimuli. This level of understanding may be extended to better characterize the role of the specific membrane environment in modulating the biological functionality of protein channels in health and disease.

Reduced Sleep Acutely Influences Sedentary Behavior and Mood But Not Total Energy Intake in Normal-Weight and Obese Women.

Using a crossover design, 22 normal-weight and 22 obese women completed two free-living sleep conditions: (a) Normal Sleep: night of ~8 hr time in bed; and (b) Reduced Sleep: night of < 5 hr time in bed). Outcome measures were energy intake, physical activity and sedentary time, and mood. Sleep time was 7.7 ± 0.3 and 4.8 ± 0.2 hrs during the Normal Sleep and Reduced Sleep conditions, respectively (F = 1791.94; p < 0.0001). Energy intake did not differ between groups or as a function of sleep condition (F = 2.46; p = 0.1244). Sedentary time was ~ 30 min higher after the Reduced Sleep condition (F = 4.98; p = 0.0318); other physical activity outcomes were not different by condition (p > 0.05). Total mood score, depression, anger, vigor, fatigue, and confusion were worse after Reduced Sleep (p < 0.05). Reducing sleep acutely and negatively influenced sedentary time and mood in normal-weight and obese women.

The social validity of a national assessment centre for selection into general practice training.

BACKGROUND: Internationally, recruiting the best candidates is central to the success of postgraduate training programs and the quality of the medical workforce. So far there has been little theoretically informed research considering selection systems from the perspective of the candidates. We explored candidates' perception of the fairness of a National Assessment Centre (NAC) approach for selection into Australian general practice training, where candidates were assessed by a Multiple Mini Interview (MMI) and a written Situational Judgment Test (SJT), for suitability to undertake general practice (GP) training. METHODS: In 2013, 1,930 medical practitioners, who were eligible to work in Australia attended one of 14 NACs in each of 5 states and 2 territories. A survey was distributed to each candidate at the conclusion of their assessment, which included open-ended questions aimed at eliciting candidates' perceived benefits and challenges of the selection process. A framework analysis was informed by the theoretical lens of Social Validity Theory. RESULTS: Qualitative data was available from 46% (n = 886/1,930) of candidates, who found the NAC experience fair and informative for their training and career goals, but wanted to be provided with more information in preparation. Candidates valued being able to communicate their skills during the MMI, but found some difficulty in interpreting the questions. A significant minority had concerns that a lack of relevant GP experience may inhibit their performance. Candidates also expressed concerns about the time limits within the written paper, particularly if English was not their first language. They also expressed a desire for formative feedback during the interview process. CONCLUSION: During any job selection process, not only is the organisation assessing the candidates, but the candidates are also assessing the organisation. However, a focus on the candidate experience throughout an organisation's selection process may provide benefits to both candidates and the organisation, regardless of whether or not candidates secured the job. Social Validity Theory is a useful addition to the methods for demonstrating the reasonableness of any selection system.

The reliability and validity of a portfolio designed as a programmatic assessment of performance in an integrated clinical placement.

BACKGROUND: Little is known about the technical adequacy of portfolios in reporting multiple complex academic and performance-based assessments. We explored, first, the influencing factors on the precision of scoring within a programmatic assessment of student learning outcomes within an integrated clinical placement. Second, the degree to which validity evidence supported interpretation of student scores. METHODS: Within generalisability theory, we estimated the contribution that each wanted factor (i.e. student capability) and unwanted factors (e.g. the impact of assessors) made to the variation in portfolio task scores. Relative and absolute standard errors of measurement provided a confidence interval around a pre-determined pass/fail standard for all six tasks. Validity evidence was sought through demonstrating the internal consistency of the portfolio and exploring the relationship of student scores with clinical experience. RESULTS: The mean portfolio mark for 257 students, across 372 raters, based on six tasks, was 75.56 (SD, 6.68). For a single student on one assessment task, 11% of the variance in scores was due to true differences in student capability. The most significant interaction was context specificity (49%), the tendency for one student to engage with one task and not engage with another task. Rater subjectivity was 29%. An absolute standard error of measurement of 4.74%, gave a 95% CI of +/- 9.30%, and a 68% CI of +/- 4.74% around a pass/fail score of 57%. Construct validity was supported by demonstration of an assessment framework, the internal consistency of the portfolio tasks, and higher scores for students who did the clinical placement later in the academic year. CONCLUSION: A portfolio designed as a programmatic assessment of an integrated clinical placement has sufficient evidence of validity to support a specific interpretation of student scores around passing a clinical placement. It has modest precision in assessing students' achievement of a competency standard. There were identifiable areas for reducing measurement error and providing more certainty around decision-making. Reducing the measurement error would require engaging with the student body on the value of the tasks, more focussed academic and clinical supervisor training, and revisiting the rubric of the assessment in the light of feedback.

The validity of a behavioural multiple-mini-interview within an assessment centre for selection into specialty training.

BACKGROUND: Entry into specialty training was determined by a National Assessment Centre (NAC) approach using a combination of a behavioural Multiple-Mini-Interview (MMI) and a written Situational Judgement Test (SJT). We wanted to know if interviewers could make reliable and valid decisions about the non-cognitive characteristics of candidates with the purpose of selecting them into general practice specialty training using the MMI. Second, we explored the concurrent validity of the MMI with the SJT. METHODS: A variance components analysis estimated the reliability and sources of measurement error. Further modelling estimated the optimal configurations for future MMI iterations. We calculated the relationship of the MMI with the SJT. RESULTS: Data were available from 1382 candidates, 254 interviewers, six MMI questions, five alternate forms of a 50-item SJT, and 11 assessment centres. For a single MMI question and one assessor, 28% of the variance between scores was due to candidate-to-candidate variation. Interviewer subjectivity, in particular the varying views that interviewer had for particular candidates accounted for 40% of the variance in scores. The generalisability co-efficient for a six question MMI was 0.7; to achieve 0.8 would require ten questions. A disattenuated correlation with the SJT (r = 0.35), and in particular a raw score correlation with the subdomain related to clinical knowledge (r = 0.25) demonstrated evidence for construct and concurrent validity. Less than two per cent of candidates would have failed the MMI. CONCLUSION: The MMI is a moderately reliable method of assessment in the context of a National Assessment Centre approach. The largest source of error relates to aspects of interviewer subjectivity, suggesting enhanced interviewer training would be beneficial. MMIs need to be sufficiently long for precise comparison for ranking purposes. In order to justify long term sustainable use of the MMI in a postgraduate assessment centre approach, more theoretical work is required to understand how written and performance based test of non-cognitive attributes can be combined, in a way that achieves acceptable generalizability, and has validity.

The effect of lumbar medial branch radiofrequency neurotomy on cobb angle progression in individuals with adult scoliosis compared to natural history: A cross-sectional study.

Background: Lumbar radiofrequency neurotomy (LRFN) effectively alleviates zygapophyseal joint-mediated pain by coagulating medial branch nerves to disrupt nociceptive signaling pathways. The concomitant denervation of multifidus fibers has led to concern that LRFN may increase segmental instability and accelerate degenerative changes in patients with certain pre-existing spinal pathologies. There is a paucity of literature evaluating whether LRFN increases the progression of spinal curvature in patients with adult scoliosis. Objective: Compare the lumbosacral Cobb angle progression rate in patients with adult scoliosis who underwent LRFN to the annual progression rate of 0.83 ± 1.1° expected by natural history. Design: Cross-sectional study. Methods: Consecutive patients diagnosed with adult scoliosis who underwent LRFN to treat zygapophyseal joint-related low back pain were identified. Patient demographics, LRFN procedure details, and radiographs confirming scoliosis were collected from electronic medical records. Pre- and post-LRFN radiographs were used to calculate the average annual rate of Cobb angle progression. Data were analyzed using a Wilcoxon signed-rank test and a linear regression model. Results: Sixty patients (mean age 69.2 ± 11.6 years; 70.0 % female) met the criteria and were included in the analyses. The mean time to radiographic follow-up was 35.0 ± 22.7 months post-LRFN. The average Cobb angle progression was 0.54 ± 3.03° per year and did not differ significantly from the known natural progression rate of 0.83 ± 1.1° per year. None of the included covariates (body mass index, LRFN laterality, and number of levels denervated) were significantly associated with the average annual Cobb angle progression rate. Conclusions: Our results suggest that LRFN has no appreciable effect on the rate of Cobb angle progression in patients with adult scoliosis.

An instantaneous voice synthesis neuroprosthesis.

Brain computer interfaces (BCIs) have the potential to restore communication to people who have lost the ability to speak due to neurological disease or injury. BCIs have been used to translate the neural correlates of attempted speech into text 1-3 . However, text communication fails to capture the nuances of human speech such as prosody, intonation and immediately hearing one's own voice. Here, we demonstrate a "brain-to-voice" neuroprosthesis that instantaneously synthesizes voice with closed-loop audio feedback by decoding neural activity from 256 microelectrodes implanted into the ventral precentral gyrus of a man with amyotrophic lateral sclerosis and severe dysarthria. We overcame the challenge of lacking ground-truth speech for training the neural decoder and were able to accurately synthesize his voice. Along with phonemic content, we were also able to decode paralinguistic features from intracortical activity, enabling the participant to modulate his BCI-synthesized voice in real-time to change intonation, emphasize words, and sing short melodies. These results demonstrate the feasibility of enabling people with paralysis to speak intelligibly and expressively through a BCI.

Gesture encoding in human left precentral gyrus neuronal ensembles.

Understanding the cortical activity patterns driving dexterous upper limb motion has the potential to benefit a broad clinical population living with limited mobility through the development of novel brain-computer interface (BCI) technology. The present study examines the activity of ensembles of motor cortical neurons recorded using microelectrode arrays in the dominant hemisphere of two BrainGate clinical trial participants with cervical spinal cord injury as they attempted to perform a set of 48 different hand gestures. Although each participant displayed a unique organization of their respective neural latent spaces, it was possible to achieve classification accuracies of ~70% for all 48 gestures (and ~90% for sets of 10). Our results show that single unit ensemble activity recorded in a single hemisphere of human precentral gyrus has the potential to generate a wide range of gesture-related signals across both hands, providing an intuitive and diverse set of potential command signals for intracortical BCI use.

An accurate and rapidly calibrating speech neuroprosthesis.

Brain-computer interfaces can enable rapid, intuitive communication for people with paralysis by transforming the cortical activity associated with attempted speech into text on a computer screen. Despite recent advances, communication with brain-computer interfaces has been restricted by extensive training data requirements and inaccurate word output. A man in his 40's with ALS with tetraparesis and severe dysarthria (ALSFRS-R = 23) was enrolled into the BrainGate2 clinical trial. He underwent surgical implantation of four microelectrode arrays into his left precentral gyrus, which recorded neural activity from 256 intracortical electrodes. We report a speech neuroprosthesis that decoded his neural activity as he attempted to speak in both prompted and unstructured conversational settings. Decoded words were displayed on a screen, then vocalized using text-to-speech software designed to sound like his pre-ALS voice. On the first day of system use, following 30 minutes of attempted speech training data, the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. On the second day, the size of the possible output vocabulary increased to 125,000 words, and, after 1.4 additional hours of training data, the neuroprosthesis achieved 90.2% accuracy. With further training data, the neuroprosthesis sustained 97.5% accuracy beyond eight months after surgical implantation. The participant has used the neuroprosthesis to communicate in self-paced conversations for over 248 hours. In an individual with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore naturalistic communication after a brief training period.

Medical graduates becoming rural doctors: rural background versus extended rural placement.

OBJECTIVES: To determine whether recruitment of rural students and uptake of extended rural placements are associated with students' expressed intentions to undertake rural internships and students' acceptance of rural internships after finishing medical school, and to compare any associations. DESIGN, SETTING AND PARTICIPANTS: Longitudinal study of three successive cohorts (commencing 2005, 2006, 2007) of medical students in the Sydney Medical Program (SMP), University of Sydney, New South Wales, using responses to self-administered questionnaires upon entry to and exit from the Sydney Medical School and data recorded in rolls. MAIN OUTCOME MEASURES: Students' expressed intentions to undertake rural internships, and their acceptance of rural internships after finishing medical school. RESULTS: Data from 448 students were included. The proportion of students preferring a rural career dropped from 20.7% (79/382) to 12.5% (54/433) between entry into and exit from the SMP. A total of 98 students took extended rural placements. Ultimately, 8.1% (35/434) accepted a rural internship, although 14.5% (60/415) had indicated a first preference for a rural post. Students who had undertaken an extended rural placement were more than three times as likely as those with rural backgrounds to express a first preference for a rural internship (23.9% v 7.7%; χ(2) = 7.04; P = 0.008) and more than twice as likely to accept a rural internship (21.3% v 9.9%; χ(2) = 3.85; P = 0.05). CONCLUSION: For the three cohorts studied, rural clinical training through extended placements in rural clinical schools had a stronger association than rural background with a preference for, and acceptance of, rural internship.

Senior medical students as peer examiners in an OSCE.

BACKGROUND: At Sydney Medical School, we have recently introduced a practice objective structured clinical examination (OSCE) where our junior medical students are assessed by the senior peers. AIM: We sought to evaluate the efficacy of the programme. METHODS: The study took place in 2010 and 2011, with two cohorts of final-year students participating. A total of 40/98 (41%) of final-year students chose to participate as examiners. Following the completion of standardised marking sheets by the student examiners, the marking sheets were reviewed by a senior academic examiner, and the 'global' mark was adjusted in accordance with the marking criteria. Student examiners also completed an open and closed-ended questionnaire regarding their experience as an examiner. A total of 105/115 (91%) of year 2 medical students were examined in the OSCE over the two-year period. RESULTS: The senior academic changed a total of 94 'global' marks, reducing the majority (55%) from 'satisfactory' to 'borderline'; 12% were reduced from 'satisfactory' to 'not satisfactory' and 33% from 'borderline' to 'not satisfactory'. Student questionnaire results showed a high level of engagement with their examiner experience overall, and it was regarded as a useful learning experience. CONCLUSION: Student examiners found peer assessment to be a very useful learning activity. However, our students need further training in how to globally assess a fellow student's overall performance objectively and to provide accurate feedback.

Cationic polymers inhibit the conductance of lysenin channels.

The pore-forming toxin lysenin self-assembles large and stable conductance channels in natural and artificial lipid membranes. The lysenin channels exhibit unique regulation capabilities, which open unexplored possibilities to control the transport of ions and molecules through artificial and natural lipid membranes. Our investigations demonstrate that the positively charged polymers polyethyleneimine and chitosan inhibit the conducting properties of lysenin channels inserted into planar lipid membranes. The preservation of the inhibitory effect following addition of charged polymers on either side of the supporting membrane suggests the presence of multiple binding sites within the channel's structure and a multistep inhibition mechanism that involves binding and trapping. Complete blockage of the binding sites with divalent cations prevents further inhibition in conductance induced by the addition of cationic polymers and supports the hypothesis that the binding sites are identical for both multivalent metal cations and charged polymers. The investigation at the single-channel level has shown distinct complete blockages of each of the inserted channels. These findings reveal key structural characteristics which may provide insight into lysenin's functionality while opening innovative approaches for the development of applications such as transient cell permeabilization and advanced drug delivery systems.

Associations between item characteristics and statistical performance for paediatric medical student multiple choice assessments.

Background: Multiple choice questions (MCQs) are commonly used in medical student assessments but often prepared by clinicians without formal education qualifications. This study aimed to inform the question writing process by investigating the association between MCQ characteristics and commonly used statistical measures of individual item quality for a paediatric medical term. Methods: Item characteristics and statistics for five consecutive annual barrier paediatric medical student assessments (each n=60 items) were examined retrospectively. Items were characterised according to format (single best answer vs. extended matching); stem and option length; vignette presence and whether required to answer the question, inclusion of images/tables; clinical skill assessed; paediatric speciality; clinical relevance/applicability; Bloom's taxonomy domain and item flaws. For each item, we recorded the facility (proportion of students answering correctly) and point biserial (discrimination). Results: Item characteristics significantly positively correlated (p<0.05) with facility were relevant vignette, diagnosis or application items, longer stem length and higher clinical relevance. Recall items (e.g., epidemiology items) were associated with lower facility. Characteristics significantly correlated with higher discrimination were extended matching question (EMQ) format, longer options, diagnostic and subspeciality items. Variation in item characteristics did not predict variation in the facility or point biserial (less than 10% variation explained). Conclusions: Our research supports the use of longer items, relevant vignettes, clinically-relevant content, EMQs and diagnostic items for optimising paediatric MCQ assessment quality. Variation in item characteristics explains a small amount of the observed variation in statistical measures of MCQ quality, highlighting the importance of clinical expertise in writing high quality assessments.