An fMRI Compatible Touchscreen to Measure Hand Kinematics During a Complex Drawing Task

ACKNOWLEDGMENTS This study was funded by the Northwood Trust and the Aberdeen Biomedical Imaging Centre, University of Aberdeen. GDW is part of the SINASPE collaboration (Scottish Imaging Network - A Platform for Scientific Excellence www.SINAPSE.ac.uk). The authors thank Baljit Jagpal, Nichola Crouch, Beverly Maclennan and Katrina Klaasen for their help with running the experiment and Dawn Younie and Teresa Morris for their help with recruitment and scheduling. We also thank the participants for their generous participation.Peer reviewedPublisher PD

Ophthalmology training in sub-Saharan Africa: a scoping review.

Sub-Saharan Africa is home to 12% of the global population, and 4.3 million are blind and over 15 million are visually impaired. There are only 2.5 ophthalmologists per million people in SSA. Training of ophthalmologists is critical. We designed a systematic literature review protocol, searched MEDLINE Ovid and Embase OVID on 1 August 2019 and limited these searches to the year 2000 onwards. We also searched Google Scholar and websites of ophthalmic institutions for additional information. We include a total of 49 references in this review and used a narrative approach to synthesise the results. There are 56 training institutions for ophthalmologists in eleven Anglophone, eleven Francophone, and two Lusophone SSA countries. The median duration of ophthalmology training programmes was 4 years. Most curricula have been regionally standardised. National, regional and international collaborations are a key feature to ophthalmology training in more than half of ophthalmology training programmes. There is a drive, although perhaps not always evidence-based, for sub-specialisation in the region. Available published scientific data on ophthalmic medical and surgical training in SSA is sparse, especially for Francophone and Lusophone countries. However, through a broad scoping review strategy it has been possible to obtain a valuable and detailed view of ophthalmology training in SSA. Training of ophthalmologists is a complex and multi-faceted task. There are challenges in appropriate selection, capacity, and funding of available training institutions. Numerous learning outcomes demand curriculum, time, faculty, support, and appropriate assessment. There are opportunities provided by modern training approaches. Partnership is key

Excitatory Amino Acids Contribute to the Pathogenesis of Perinatal Hypoxic-Ischemic Brain Injury

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75512/1/j.1750-3639.1992.tb00697.x.pd

The Motivations and Aspirations of Indian Physiotherapists Who Migrate Overseas to Study and Work: A Grounded Theory Study

Objective: To explore why Indian physiotherapists seek to migrate overseas for study and work. Design: Qualitative research using Constructivist Grounded Theory (CGT) methodology. Setting: Individual interviews and focus groups were conducted in the UK and India, at university, clinic or hotel locations convenient to the participants. Participants: Nineteen physiotherapists from across India. Thirteen had studied or worked in the UK, Australia or Kuwait, and six had no overseas experience. Findings: The participants desired a ‘better life’ due to factors perceived as less favourable in India: pay levels, professional respect and professional development. These elements were inter-dependent and their importance varied between participants and according to gender. Indian societal values amplified the importance of pay for male physiotherapists, whereas females prioritised professional development. Migrant physiotherapists aspired to professional autonomy through the development of knowledge, skills and experience. Respect was important, but there were different perspectives on its achievement and the relevance of titles. For those studying overseas, work was sought to recoup the cost of that study, and, importantly to consolidate learning and experience of autonomous physiotherapy practice. They all planned to return to India and wished to transfer their knowledge and skills back into practice in India. Conclusion: Pay, respect and professional development are all motivators for Indian physiotherapists to study and work overseas. An ability to practise physiotherapy autonomously is a key factor underpinning the achievement of each of these elements and thus the ultimate aspiration to have a ‘better life’

R-h-erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis

Anaemia of chronic disease (ACD) is a common extra-articular manifestation of rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNFα) plays an important role in the development of ACD. The objective of the present study was to assess inhibition of in vitro colony-forming unit erythrocyte (CFUe) and blast-forming unit erythrocyte (BFUe) growth by TNFα and to examine whether this suppression could be counteracted by adding increasing concentrations of recombinant human erythropoietin (EPO) (r-h-EPO) to bone marrow cultures of RA patients with ACD and without anaemia (controls). Bone marrow cells of RA patients with ACD and control patients were cultured. The cultures were incubated with increasing concentrations of r-h-EPO (0.25; 0.5; 1; 2 U/ml), each in combination with increasing quantities of TFNα (0; 50; 100; 200; 400 U/ml). CFUe and BFUe were assessed after 7 and 14 days, respectively. Dose-dependent inhibition of BFUe and CFUc by increasing concentrations of TNFα was observed in ACD and controls. Regarding CFUe (ACD patients) incubated with 0.25 U/ml EPO, 50 U/ml TNFα caused 28% suppression compared to cultures without TNFα. Increasing the concentration of r-h-EPO from 0.25 U/ml to 2 U/ml completely restored the number of CFUe. A similar pattern was observed in BFUe growth in both groups. These data demonstrated the suppressive effects of TNFα on erythropoiesis in vitro and that the suppresed erythropoiesis could be partly corrected by the addition of excess r-h-EPO to the cultures. No significant differences were observed between ACD and control RA patients. This in vitro model may help explain the clinical response to r-h-EPO therapy as documented in RA patients with ACD

Comparative efficacy and safety of alternative glucocorticoids regimens in patients with ANCA-associated vasculitis: a systematic review.

OBJECTIVE: To compare the efficacy and safety of alternative glucocorticoids (GCs) regimens as induction therapy for patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis. DESIGN: Systematic review of randomised controlled trials (RCTs). DATA SOURCES: Medline, Embase, Clinicaltrials.gov and Cochrane Central Register of Controlled Trials up to 10 April 2020. STUDY SELECTION AND REVIEW METHODS: RCTs comparing two (or more) different dose regimens of GC in ANCA-associated vasculitis during induction of remission, regardless of other therapies. Pairs of reviewers independently screened records, extracted data and assessed risk of bias. Two reviewers rated certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of 3912 records identified, the full texts of two records met the eligibility criteria. Due to the heterogeneity of population and dose regimen of GCs between the two trials, we descriptively presented the two trials and did not combine the results using meta-analysis. Compared with the standard-dose regimen, the reduced-dose regimen of GC may reduce death risk difference (RD): from -1.7% to -2.1%, low certainty), while not increasing end-stage kidney disease (ESKD) (RD: from -1.5% to 0.4%, moderate certainty). The reduced-dose regimen probably has an important reduction in serious infections at 1 year (RD: from -12.8% to -5.9%, moderate certainty). Reduced-dose regimen of GCs probably has trivial or no effect in disease remission, relapse or health-related quality of life (moderate to high certainty). CONCLUSIONS: The reduced-dose regimen of GC may reduce death at the follow-up of 6 months to longer than 1 year and serious infections while not increasing ESKD. PROSPERO REGISTRATION NUMBER: CRD42020179087

Cohort profile for the STratifying Resilience and Depression Longitudinally (STRADL) study:A depression-focused investigation of Generation Scotland, using detailed clinical, cognitive, and neuroimaging assessments

Grant information: STRADL is supported by the Wellcome Trust through a Strategic Award (104036/Z/14/Z). GS:SFHS received core support from the CSO of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). ADM is supported by Innovate UK, the European Commission, the Scottish Funding Council via the Scottish Imaging Network SINAPSE, and the CSO. HCW is supported by a JMAS SIM Fellowship from the Royal College of Physicians of Edinburgh, by an ESAT College Fellowship from the University of Edinburgh, and has received previous funding from the Sackler Trust. LR has previously received financial support from Pfizer (formerly Wyeth) in relation to imaging studies of people with schizophrenia and bipolar disorder. JDH is supported by the MRC. DJM is an NRS Clinician, funded by the CSO. RMR is supported by the British Heart Foundation. ISP-V and MRM are supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health; and MRM is also supported by the MRC MC_UU_12013/6). JMW is supported by MRC UK Dementia Research Institute and MRC Centre and project grants, EPSRC, Fondation Leducq, Stroke Association, British Heart Foundation, Alzheimer Society, and the European Union H2020 PHC-03-15 SVDs@Target grant agreement (666881). DJP is supported by Wellcome Trust Longitudinal Population Study funding (216767/Z/19/Z) the Eva Lester bequest to the University of Edinburgh. AMM is additionally supported by the MRC (MC_PC_17209, MC_PC_MR/R01910X/1, MR/S035818/1), The Wellcome Trust (216767/Z/19/Z ), The Sackler Trust, and has previously received research funding from Pfizer, Eli Lilly, and Janssen. Both AMM and IJD are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the BBSRC and MRC is gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Tracking the Late Jurassic apparent (or true) polar shift in U-Pb-dated kimberlites from cratonic North America (Superior Province of Canada)

Different versions of a composite apparent polar wander (APW) path of variably selected global poles assembled and averaged in North American coordinates using plate reconstructions show either a smooth progression or a large (∼30°) gap in mean paleopoles in the Late Jurassic, between about 160 and 145 Ma. In an effort to further examine this issue, we sampled accessible outcrops/subcrops of kimberlites associated with high-precision U-Pb perovskite ages in the Timiskaming area of Ontario, Canada. The 154.9 ± 1.1 Ma Peddie kimberlite yields a stable normal polarity magnetization that is coaxial within less than 5° of the reverse polarity magnetization of the 157.5 ± 1.2 Ma Triple B kimberlite. The combined ∼156 Ma Triple B and Peddie pole (75.5°N, 189.5°E, A95 = 2.8°) lies about midway between igneous poles from North America nearest in age (169 Ma Moat volcanics and the 146 Ma Ithaca kimberlites), showing that the polar motion was at a relatively steady yet rapid (∼1.5°/Myr) pace. A similar large rapid polar swing has been recognized in the Middle to Late Jurassic APW path for Adria-Africa and Iran-Eurasia, suggesting a major mass redistribution. One possibility is that slab breakoff and subduction reversal along the western margin of the Americas triggered an episode of true polar wander

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis:a randomised, double-blind, placebo-controlled, phase 2b trial

Background: Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis. Methods: We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50–90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene–liposome complex or 0·9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01621867. Findings: Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3·7%, 95% CI 0·1–7·3; p=0·046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups. Interpretation: Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials