Spatial assessment of intertidal seagrass meadows using optical imaging systems and a lightweight drone

Seagrass ecosystems are highly sensitive to environmental change. They are also in global decline and under threat from a variety of anthropogenic factors. There is now an urgency to establish robust monitoring methodologies so that changes in seagrass abundance and distribution in these sensitive coastal environments can be understood. Typical monitoring approaches have included remote sensing from satellites and airborne platforms, ground based ecological surveys and snorkel/scuba surveys. These techniques can suffer from temporal and spatial inconsistency, or are very localised making it hard to assess seagrass meadows in a structured manner. Here we present a novel technique using a lightweight (sub 7 kg) drone and consumer grade cameras to produce very high spatial resolution (∼4 mm pixel−1) mosaics of two intertidal sites in Wales, UK. We present a full data collection methodology followed by a selection of classification techniques to produce coverage estimates at each site. We trialled three classification approaches of varying complexity to investigate and illustrate the differing performance and capabilities of each. Our results show that unsupervised classifications perform better than object-based methods in classifying seagrass cover. We also found that the more sparsely vegetated of the two meadows studied was more accurately classified - it had lower root mean squared deviation (RMSD) between observed and classified coverage (9–9.5%) compared to a more densely vegetated meadow (RMSD 16–22%). Furthermore, we examine the potential to detect other biotic features, finding that lugworm mounds can be detected visually at coarser resolutions such as 43 mm pixel−1, whereas smaller features such as cockle shells within seagrass require finer grained data (<17 mm pixel−1)

Adenosine metabolic signature in circulating CD4+ T cells predicts remission in rheumatoid arthritis

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Objectives Long-term outcomes in rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate (MTX) remains the first-line disease modifying therapy, however there are no biomarkers with which to identify those most likely to achieve remission. To address this unmet need we explored metabolic pathways involved in MTX mechanism of action within circulating CD4+T cells in a cohort of treatment naive patients with early RA. Methods Purified CD4+T cells were isolated from peripheral blood of 68 patients with early RA commencing MTX. The expression of a range of putative MTX metabolism and mechanism of action targets were explored by flow-cytometry and transcriptional analysis. From these data significant predictors of Disease Activity Score 28-C reactive protein (DAS28-CRP) remission (&lt;2.4 at 6 months) were determined by logistic regression (clinical; flow-cytometry data) and linear modelling (gene expression data). Results Low baseline DAS28-CRP was associated with remission at 6 months (p=0.02). Expression of the ectonucleotidase CD39, involved in ATP-ADP conversion during adenosine synthesis, was higher on CD4+CD25 High regulatory T cells at baseline in those achieving remission (molecules of equivalent fluorescence 1264 vs 847; p=0.007). Expression of other adenosine signalling elements in CD4+T cells were also upregulated at baseline in patients achieving remission: AMPD1 (p&lt;0.001), ADORA2b (p=0.039) and ADORA3 (p=0.047). When combined into a single predictive metric, a combination of these variables outperformed baseline DAS28-CRP in prediction of early remission (area under the curve 0.92 vs 0.67, p=0.001) Conclusions Adenosine signalling is important in the achievement of early remission with MTX in RA and biomarkers of adenosine activity may hold utility for the stratification of therapy in early disease

Developing collaboration skills in first year undergraduate business students

Collaboration skills are defined as the set of skills and capabilities required to work effectively within and across groups to achieve group goals. The development of these skills are assumed but not taught directly or evaluated in undergraduate group assessments in many university subjects. This paper discusses a research project investigating the development of student collaboration skills in the compulsory first year undergraduate subject 21129 Managing People and Organisations. One of the key aims of the subject is to help students understand and acquire a range of collaboration skills that will enhance their work readiness. During August 2008, 290 student surveys were completed by students after their initial formation into groups during tutorials. These surveys asked students about their past experiences of group work, and their expectations and motivations with respect to group work in this subject over the coming semester. A follow-up survey was conducted in November, and attempts to capture the extent of changes, if any, in student perceptions of their experience developing collaboration skills over the semester. This paper reports on the findings of stage one of this project. An overview of student attitudes and perceptions is presented, as well as findings on the systematic variation of these with respondent characteristics. The finding of a number of statistically significant associations of student satisfaction with the method of group formation employed in tutorials is then discussed as a surprise finding from this research

Surface modification of hydrophobic polymers for improvement of endothelial cell-surface interactions

The aim of this study is to improve the interaction of endothelial cells with polymers used in vascular prostheses. Polytetrafluoroethylene (PTFE; Teflon) films were treated by means of nitrogen and oxygen plasmas. Depending on the plasma exposure time, modified PTFE surfaces showed water-contact angles of 15¿58° versus 96° for unmodified PTFE. Electron spectroscopy in chemical analysis (ESCA) measurements revealed incorporation of both nitrogenand oxygen-containing groups into the PTFE surfaces, dependent on the plasma composition and exposure time. In-vitro biological evaluation of unmodified and modified PTFE surfaces showed that human endothelial cells, seeded from 20% human serum-containing culture medium, adhered well on to modified PTFE surfaces, but not on to unmodified films. Adhesion of endothelial cells on to expanded PTFE graft material (Gore-Tex) was also stimulated by plasma treatment of this substrate. On plasma-treated expanded PTFE, the adhering endothelial cells formed a monolayer, which covered the textured surface. The latter observation is important in view of the hemocompatibility of vascular grafts seeded with endothelial cells before implantation

Operational complexities in international clinical trials: a systematic review of challenges and proposed solutions

\ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. OBJECTIVE: International trials can be challenging to operationalise due to incompatibilities between country-specific policies and infrastructures. The aim of this systematic review was to identify the operational complexities of conducting international trials and identify potential solutions for overcoming them. DESIGN: Systematic review. DATA SOURCES: Medline, Embase and Health Management Information Consortium were searched from 2006 to 30 January 2023. ELIGIBILITY CRITERIA: All studies reporting operational challenges (eg, site selection, trial management, intervention management, data management) of conducting international trials were included. DATA EXTRACTION AND SYNTHESIS: Search results were independently screened by at least two reviewers and data were extracted into a proforma. RESULTS: 38 studies (35 RCTs, 2 reports and 1 qualitative study) fulfilled the inclusion criteria. The median sample size was 1202 (IQR 332-4056) and median number of sites was 40 (IQR 13-78). 88.6% of studies had an academic sponsor and 80% were funded through government sources. Operational complexities were particularly reported during trial set-up due to lack of harmonisation in regulatory approvals and in relation to sponsorship structure, with associated budgetary impacts. Additional challenges included site selection, staff training, lengthy contract negotiations, site monitoring, communication, trial oversight, recruitment, data management, drug procurement and distribution, pharmacy involvement and biospecimen processing and transport. CONCLUSIONS: International collaborative trials are valuable in cases where recruitment may be difficult, diversifying participation and applicability. However, multiple operational and regulatory challenges are encountered when implementing a trial in multiple countries. Careful planning and communication between trials units and investigators, with an emphasis on establishing adequately resourced cross-border sponsorship structures and regulatory approvals, may help to overcome these barriers and realise the benefits of the approach. OPEN SCIENCE FRAMEWORK REGISTRATION NUMBER: osf-registrations-yvtjb-v1

Targeting the rheumatoid arthritis synovial fibroblast via cyclin dependent kinase inhibition: An early phase trial

Introduction: Targeted biologic therapies demonstrate similar efficacies in rheumatoid arthritis despite distinct mechanisms of action. They also exhibit a ceiling effect, with 10% to 20% of patients achieving remission in clinical trials. None of these therapies target synovial fibroblasts, which drive and maintain synovitis. Seliciclib (R-roscovitine) is an orally available cyclin-dependent kinase inhibitor that suppresses fibroblast proliferation, and is efficacious in preclinical arthritis models. We aim to determine the toxicity and preliminary efficacy of seliciclib in combination with biologic therapies, to inform its potential as an adjunctive therapy in rheumatoid arthritis. Methods and analysis: TRAFIC is a non-commercial, multi-center, rolling phase Ib/IIa trial investigating the safety, tolerability, and efficacy of seliciclib in patients with moderate to severe rheumatoid arthritis receiving biologic therapies. All participants receive seliciclib with no control arm. The primary objective of part 1 (phase Ib) is to determine the maximum tolerated dose and safety of seliciclib over 4 weeks of dosing. Part 1 uses a restricted 1-stage Bayesian continual reassessment method based on a target dose-limiting toxicity probability of 35%. Part 2 (phase IIa) assesses the potential efficacy of seliciclib, and is designed as a single arm, single stage early phase trial based on a Fleming-A’Hern design using the maximum tolerated dose recommended from part 1. The primary response outcome after 12 weeks of therapy is a composite of clinical, histological and magnetic resonance imaging scores. Secondary outcomes include adverse events, pharmacodynamic and pharmacokinetic parameters, autoantibodies, and fatigue. Ethics and dissemination: The study has been reviewed and approved by the North East - Tyne & Wear South Research Ethics Committee (reference 14/NE/1075) and the Medicines and Healthcare Products Regulatory Agency (MHRA), United Kingdom. Results will be disseminated through publication in relevant peer-reviewed journals and presentation at national and international conferences. Trials Registration: ISRCTN, ISRCTN36667085. Registered on September 26, 2014; http://www.isrctn.com/ISRCTN36667085 Current protocol version: Protocol version 11.0 (March 21, 2019

Intracranial delivery of AAV9 gene therapy partially prevents retinal degeneration and visual deficits in CLN6-Batten disease mice

Batten disease is a family of rare, fatal, neuropediatric diseases presenting with memory/learning decline, blindness, and loss of motor function. Recently, we reported the use of an AAV9-mediated gene therapy that prevents disease progression in a mouse model of CLN6-Batten disease (Cln6nclf), restoring lifespans in treated animals. Despite the success of our viral-mediated gene therapy, the dosing strategy was optimized for delivery to the brain parenchyma and may limit the therapeutic potential to other disease-relevant tissues, such as the eye. Here, we examine whether cerebrospinal fluid (CSF) delivery of scAAV9.CB.CLN6 is sufficient to ameliorate visual deficits in Cln6nclf mice. We show that intracerebroventricular (i.c.v.) delivery of scAAV9.CB.CLN6 completely prevents hallmark Batten disease pathology in the visual processing centers of the brain, preserving neurons of the superior colliculus, thalamus, and cerebral cortex. Importantly, i.c.v.-delivered scAAV9.CB.CLN6 also expresses in many cells throughout the central retina, preserving many photoreceptors typically lost in Cln6nclf mice. Lastly, scAAV9.CB.CLN6 treatment partially preserved visual acuity in Cln6nclf mice as measured by optokinetic response. Taken together, we report the first instance of CSF-delivered viral gene reaching and rescuing pathology in both the brain parenchyma and retinal neurons, thereby partially slowing visual deterioration

Joining the conspiracy? Negotiating ethics and emotions in researching (around) AIDS in southern Africa

AIDS is an emotive subject, particularly in southern Africa. Among those who have been directly affected by the disease, or who perceive themselves to be personally at risk, talking about AIDS inevitably arouses strong emotions - amongst them fear, distress, loss and anger. Conventionally, human geography research has avoided engagement with such emotions. Although the ideal of the detached observer has been roundly critiqued, the emphasis in methodological literature on 'doing no harm' has led even qualitative researchers to avoid difficult emotional encounters. Nonetheless, research is inevitably shaped by emotions, not least those of the researchers themselves. In this paper, we examine the role of emotions in the research process through our experiences of researching the lives of 'Young AIDS migrants' in Malawi and Lesotho. We explore how the context of the research gave rise to the production of particular emotions, and how, in response, we shaped the research, presenting a research agenda focused more on migration than AIDS. This example reveals a tension between universalised ethics expressed through ethical research guidelines that demand informed consent, and ethics of care, sensitive to emotional context. It also demonstrates how dualistic distinctions between reason and emotion, justice and care, global and local are unhelpful in interpreting the ethics of research practice