Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.

Anomalous small angle X-ray scattering can in principle be used to determine distances between metal label species on biological molecules. Previous experimental studies in the past were unable to distinguish the label-label scattering contribution from that of the molecule, because of the use of atomic labels; these labels contribute only a small proportion of the total scattering signal. However, with the development of nanocrystal labels (of 50-100 atoms) there is the possibility for a renewed attempt at applying anomalous small angle X-ray scattering for distance measurement. This is because the contribution to the scattered signal is necessarily considerably stronger than for atomic labels. Here we demonstrate through simulations, the feasibility of the technique to determine the end-to-end distances of labelled nucleic acid molecules as well as other internal distances mimicking a labelled DNA binding protein if the labels are dissimilar metal nanocrystals. Of crucial importance is the ratio of mass of the nanocrystals to that of the labelled macromolecule, as well as the level of statistical errors in the scattering intensity measurements. The mathematics behind the distance determination process is presented, along with a fitting routine than incorporates maximum entropy regularisation

Predictors of ophthalmology career success (POCS) study

OBJECTIVE: Ophthalmology is the busiest outpatient specialty with demand predicted to rise over 40% in the next 20 years. A significant increase in the number of trainee ophthalmologists is required to fill currently vacant consultant posts and meet the UK’s workforce demands by 2038. Our aim was to understand what determines success in ophthalmology training, in order to inform future ophthalmologists, refine recruitment and facilitate workforce planning. METHODS AND ANALYSIS: This was a retrospective longitudinal cohort study using routinely collected data available from UK Medical Education Database (UKMED) (https://www.ukmed.ac.uk/). Data were analysed on 1350 candidates who had applied for ophthalmology specialty training (OST) between 2012 and 2018, as well as 495 candidates who had attempted Fellow of the Royal College of Ophthalmologists (FRCOphth) Part 1 between 2013 and 2018. Participants who had not obtained their primary medical qualification from the UK medical schools were excluded. Primary outcome measures included gaining a place on the OST programme and passing the FRCOphth Part 1 examination on first attempt. RESULTS: Higher education performance measure decile scores at medical school are strongly predictive in securing an OST post and passing the part 1 examination first time (p<0.001). Candidates who attempt FRCOphth Part 1 prior to their ST1 application are more likely to get a place on OST on first attempt. Socioeconomic factors, gender and ethnicity do not influence success in OST entry. Male trainees are more likely to pass FRCOphth Part 1 on their first attempt. CONCLUSION: This study is the first quantitative assessment of the factors that determine success in OST recruitment and ophthalmology postgraduate examinations in the UK. Similar studies should be undertaken in all other medical and surgical specialties to understand what factors predict success

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

Corneal endothelial cell density loss following glaucoma surgery alone or in combination with cataract surgery: a systematic review protocol

Objective: We aim to systematically assess and compare corneal endothelial cell density (ECD) loss in patients with glaucoma following glaucoma surgery and cataract surgery. / Introduction: Corneal ECD loss may occur due to intraoperative surgical trauma in glaucoma surgery or postoperatively with chronic endothelial cell trauma or irritation. Corneal oedema and decompensation after aqueous shunt glaucoma surgery has been reported but the long-term ECD loss is still unknown. / Inclusion criteria: Trabeculectomy, glaucoma filtration surgery or microinvasive glaucoma surgery in adults with ocular hypertension, primary and secondary open angle glaucoma, normal tension glaucoma and angle-closure glaucoma. Participants with pre-existing corneal disease will be excluded. Glaucoma laser treatments and peripheral iridotomy will be excluded. The outcomes include preoperative and postoperative corneal ECD, percentage change of corneal ECD and adverse events. / Methods: We will conduct an electronic database search for randomised controlled trials, prospective non-randomised studies, observational studies in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov and The International Prospective Register of Systematic Reviews (PROSPERO). Eligibility criteria will include quantitative articles published after and including the year 2000, written in English and containing data on ECD loss. Two independent reviewers will screen titles and abstracts and extract data from full texts, reporting outcomes according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data extraction of key characteristics will be completed using customised forms. Methodological quality will be assessed using the Joanna Briggs Institute critical appraisal forms. / Ethics and dissemination: Ethics approval is not required for this review, as it will only include published data. Findings will be published in a peer-reviewed journal and disseminated across ophthalmic networks. / PROSPERO registration number: PROSPERO CRD42020192303

Development of virtual ophthalmic surgical skills training

Background: This study aims to assess whether ophthalmic surgical skills can be taught successfully online to a diverse international and interprofessional student group. Methods: Mixed methods study involving 20 students and 5 instructors. Each student completed a pre-session and post-session questionnaire to assess their perceptions regarding online instruction. Changes in questionnaire responses were analysed using Wilcoxon signed rank (SPSS 25). Semi-structured interviews were conducted to assess instructor perceptions towards virtual surgical skills teaching. Thematic analysis was undertaken using NVivo 12.0 software. Results: There was a 100% completion rate of pre- and post-session questionnaires. Prior to the session, lack of instructor supervision and inability to provide constructive feedback were emergent themes from students. Pre-session concerns regarding online delivery: 40% of students thought their view of skills demonstration would be negatively impacted, 60% their level of supervision and 55% their interaction with instructors. Following the session 10%, 15% and 5% held this view respectively. All students were ‘satisfied’ or ‘very satisfied’ regarding the ‘Surgeon’s View’ camera angle as well as the use of breakout rooms. 75% perceived an improvement in their confidence in instrument handling, 80% in cable knot tying and 70% in suture tying. Overall student rating for the virtual surgical skills session was 8.85 (±1.19) out of 10 (10 being most satisfied). Conclusions: We demonstrate that successful delivery of a virtual ophthalmic surgical skills course is feasible. We were able to widen accessibility and participation through virtual delivery, which has future implications for ophthalmic surgical teaching and its reach

Cardiorespiratory and perceptual responses to self-regulated and imposed submaximal arm-leg ergometry

Purpose: This study compared cardiorespiratory and perceptual responses to exercise using self-regulated and imposed power outputs distributed between the arms and legs. Methods Ten males (age 21.7 ± 3.4 years) initially undertook incremental arm-crank ergometry (ACE) and cycle ergometry (CYC) tests to volitional exhaustion to determine peak power output (Wpeak). Two subsequent tests involved 20-min combined arm–leg ergometry (ALE) trials, using imposed and self-regulated protocols, both of which aimed to elicit an exercising heart rate of 160 beats min−1. During the imposed trial, arm and leg intensity were set at 40% of each ergometer-specific Wpeak. During the self-regulated trial, participants were asked to self-regulate cadence and resistance to achieve the target heart rate. Heart rate (HR), oxygen uptake (V˙O2 ), pulmonary ventilation (V˙E ), and ratings of perceived exertion (RPE) were recorded continuously. Results As expected, there were no differences between imposed and self-regulated trials for HR, V˙O2 , and V˙E (all P ≥ 0.05). However, central RPE and local RPE for the arms were lower during self-regulated compared imposed trials (P ≤ 0.05). Lower RPE during the self-regulated trial was related to preferential adjustments in how the arms (33 ± 5% Wpeak) and legs (46 ± 5% Wpeak) contributed to the exercise intensity. Conclusions: This study demonstrates that despite similar metabolic and cardiovascular strain elicited by imposed and self-regulated ALE, the latter was perceived to be less strenuous, which is related to participants doing more work with the legs and less work with the arms to achieve the target intensity

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

An online glaucoma educational course for patients to facilitate remote learning and patient empowerment

In both face-to-face and teleophthalmology glaucoma clinics, there are significant time constraints and limited resources available to educate the patient and their carers regarding the glaucoma condition. Glaucoma patients are often not satisfied with the content and amount of information they receive and have demonstrated a substantial lack of knowledge regarding their condition. Innovative educational tools that facilitate accessible digital remote patient education can be a powerful adjunct to empower patients in becoming healthcare partners. We describe the development of a free, comprehensive, multimodal online glaucoma patient education course for adults with glaucoma, their family and friends and carers, with the aim of providing a readable resource to aid remote learning and understanding of the condition. The working group for the development of the course comprised of consultants, medical practitioners and education specialists and expert patients. Given the specialised nature of ophthalmology and glaucoma, certain aspects can be difficult to conceptualise, and, therefore, clear and adequate explanations of concepts are provided in the course using diagrams, flow charts, medical illustrations, images, videos, written text, analogies and quizzes. The course is available in a short and long version to suit different learning needs which take approximately 2 hours and 10 hours to complete respectively. The contents list allows course takers to find sections relevant to them and it can be taken anywhere, as long as there is Internet access. We invite you to share this resource with your patients and their families, friends and carers

The Evolution of Religion: How Cognitive By-Products, Adaptive Learning Heuristics, Ritual Displays, and Group Competition Generate Deep Commitments to Prosocial Religio

Understanding religion requires explaining why supernatural beliefs, devotions, and rituals are both universal and variable across cultures, and why religion is so often associated with both large-scale cooperation and enduring group conflict. Emerging lines of research suggest that these oppositions result from the convergence of three processes. First, the interaction of certain reliably developing cognitive processes, such as our ability to infer the presence of intentional agents, favors—as an evolutionary by-product—the spread of certain kinds of counterintuitive concepts. Second, participation in rituals and devotions involving costly displays exploits various aspects of our evolved psychology to deepen people's commitment to both supernatural agents and religious communities. Third, competition among societies and organizations with different faith-based beliefs and practices has increasingly connected religion with both within-group prosociality and between-group enmity. This connection has strengthened dramatically in recent millennia, as part of the evolution of complex societies, and is important to understanding cooperation and conflict in today's world