Current usage of explainer animations in trials: a survey of the UKCRC registered clinical trial units in the UK

Background: Explainer animations are a means to communicate aspects of clinical trials to participants in a more engaging and accessible way. Delivered well these have the potential to enhance recruitment and retention. The range of media technology used to deliver this material is expanding rapidly but is highly fragmented. Usage of explainer animations across the UK is unknown, the aim of this research was to determine current usage across the 52 registered UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) to understand the current landscape and any barriers that could be preventing wider uptake of this functionality. Methods: A survey link was emailed to all UKCRC CTU Directors and Trial Management Leads to ascertain current usage of explainer animations within their CTU. The survey ran between 01 February 2023 and 07 March 2023. Results: Responses were received from 35 CTUs—representing a response rate of 67%. 24 CTUs (69%) reported that they had created/used at least one explainer animation within their unit, although the usage, cost, length and production activities varied among the units. Conclusions: The survey showed that a high proportion of the UKCRC CTUs have used explainer animations to provide information to participants about clinical studies. For those not using the technology yet, the most common reasons cited were a lack of expertise, lack of resources and costs to produce them. One of the desired outcomes of this project is the creation of a free-to-use library of animations to encourage wider uptake and avoid duplication

Using the Responsible Suicide Reporting Model to increase adherence to global media reporting guidelines

Numerous guidelines on responsible reporting of suicide are available to journalists globally, offering advice on best practice regarding approaches and suitability of content. Whilst their advice is compelling and legitimate, their use is uneven at best. With a suicide death every 40 seconds worldwide, it is imperative journalists understand and recognise the best ethical practices in order to report suicide responsibly. To address these shortcomings, the authors present a model for responsible suicide reporting (RSR) that is grounded in news-work and embeds media reporting guidelines within journalistic storytelling practices. The RSR model consists of a typology of suicide narratives and ‘othering’, ethical rules and a standard of moderation. Methodologically, these typologies emerged from analysis of 159 suicide news stories published in 2018–19, with particular focus on adherence and non-adherence to global media reporting guidelines. We posit through the process of producing stories using the RSR model, journalists should interact more effectively with critical risk factors for example, stigmatisation, copycat effects, harmful speculation, highlighted by media reporting guidelines

Use of oxygen-loaded nanobubbles to improve tissue oxygenation: bone-relevant mechanisms of action and effects on osteoclast differentiation

Gas-loaded nanobubbles have potential as a method of oxygen delivery to increase tumour oxygenation and therapeutically alleviate tumour hypoxia. However, the mechanism(s) whereby oxygen-loaded nanobubbles increase tumour oxygenation are unknown; with their calculated oxygen-carrying capacity being insufficient to explain this effect. Intra-tumoural hypoxia is a prime therapeutic target, at least partly due to hypoxia-dependent stimulation of the formation and function of bone-resorbing osteoclasts which establish metastatic cells in bone. This study aims to investigate potential mechanism(s) of oxygen delivery and in particular the possible use of oxygen-loaded nanobubbles in preventing bone metastasis via effects on osteoclasts. Lecithin-based nanobubbles preferentially interacted with phagocytic cells (monocytes, osteoclasts) via a combination of lipid transfer, clathrin-dependent endocytosis and phagocytosis. This interaction caused general suppression of osteoclast differentiation via inhibition of cell fusion. Additionally, repeat exposure to oxygen-loaded nanobubbles inhibited osteoclast formation to a greater extent than nitrogen-loaded nanobubbles. This gas-dependent effect was driven by differential effects on the fusion of mononuclear precursor cells to form pre-osteoclasts, partly due to elevated potentiation of RANKL-induced ROS by nitrogen-loaded nanobubbles. Our findings suggest that oxygen-loaded nanobubbles could represent a promising therapeutic strategy for cancer therapy; reducing osteoclast formation and therefore bone metastasis via preferential interaction with monocytes/macrophages within the tumour and bone microenvironment, in addition to known effects of directly improving tumour oxygenation

Ductile damage evolution and experimental simulation under high rates of strain in 10100 copper.

The high strain-rate damage evolution and Eracture behavior of half-hard 10 LOO Cu was investigated by experiments and computer simulations. Testing of uniaxial stress and axisymmetric notched bars of the Hancock-Mackenzie geometries were performetl using a momentum trapped tensile split Hopkinson pressure bar. Specimens were. tested to fracture and to several stages of incipient failure prior to fracture. Recovered specimens were sectioned and metallographically examined using image analysis and optical profilornelry to quantify the resulting damage. The quantified damage is described by spatially resolved porosity distributions, spatially resolved volumetric number densiries, and spatia Ily resolved void size distributions. Concurrent to mechanical testing, explicit finite element simulations of the tensile split Hopkinson pressure bar experiments were perfornicd to quantify the local stress-state and strain-state within the material and to determine the evolution of damage within the notch region. The coinpressive plasticity behavior of the material was fit to the mechanical threshold stress constitutive model, and was used in the simulations. The quantified damage was coniprued with damage model (TEPLA) predictions and used to refine model parameters and damage nucleation criteria. The simulation results also show that the maximum stress triaxiality in the specimens quickly enlarges after the onset of plastic flow or tensile instability to almost twice that of the Bridgman predicted levels

Augmented visual feedback of movement performance to enhance walking recovery after stroke : study protocol for a pilot randomised controlled trial

Increasing evidence suggests that use of augmented visual feedback could be a useful approach to stroke rehabilitation. In current clinical practice, visual feedback of movement performance is often limited to the use of mirrors or video. However, neither approach is optimal since cognitive and self-image issues can distract or distress patients and their movement can be obscured by clothing or limited viewpoints. Three-dimensional motion capture has the potential to provide accurate kinematic data required for objective assessment and feedback in the clinical environment. However, such data are currently presented in numerical or graphical format, which is often impractical in a clinical setting. Our hypothesis is that presenting this kinematic data using bespoke visualisation software, which is tailored for gait rehabilitation after stroke, will provide a means whereby feedback of movement performance can be communicated in a more meaningful way to patients. This will result in increased patient understanding of their rehabilitation and will enable progress to be tracked in a more accessible way. The hypothesis will be assessed using an exploratory (phase II) randomised controlled trial. Stroke survivors eligible for this trial will be in the subacute stage of stroke and have impaired walking ability (Functional Ambulation Classification of 1 or more). Participants (n = 45) will be randomised into three groups to compare the use of the visualisation software during overground physical therapy gait training against an intensity-matched and attention-matched placebo group and a usual care control group. The primary outcome measure will be walking speed. Secondary measures will be Functional Ambulation Category, Timed Up and Go, Rivermead Visual Gait Assessment, Stroke Impact Scale-16 and spatiotemporal parameters associated with walking. Additional qualitative measures will be used to assess the participant's experience of the visual feedback provided in the study. Results from the trial will explore whether the early provision of visual feedback of biomechanical movement performance during gait rehabilitation demonstrates improved mobility outcomes after stroke and increased patient understanding of their rehabilitation

Heavy Quark Spectroscopy and Matrix Elements: A Lattice Study using the Static Approximation

We present results of a lattice analysis of the $B$ parameter, $B_B$, the decay constant $f_B$, and several mass splittings using the static approximation. Results were obtained for 60 quenched gauge configurations computed at $\beta=6.2$ on a lattice size of $24^3\times48$. Light quark propagators were calculated using the $O(a)$-improved Sheikholeslami-Wohlert action. We find \Bbstat(m_b) = 0.69\er{3}{4} {\rm(stat)}\er{2}{1} {\rm(syst)}, corresponding to \Bbstat = 1.02\er{5}{6}\er{3}{2}, and \fbstat = 266\err{18}{20}\err{28}{27} \mev, f_{B_s}^2 B_{B_s}/f_B^2 B_B = 1.34\er{9}{8}\er{5}{3}, where a variational fitting technique was used to extract \fbstat. For the mass splittings we obtain M_{B_s}-M_{B_d} = 87\err{15}{12}\err{6}{12} \mev, M_{\Lambda_b}-M_{B_d} = 420\errr{100}{90}\err{30}{30} \mev and M_{B^*}^2-M_B^2 = 0.281\err{15}{16}\err{40}{37} \gev^2. We compare different smearing techniques intended to improve the signal/noise ratio. From a detailed assessment of systematic effects we conclude that the main systematic uncertainties are associated with the renormalisation constants relating a lattice matrix element to its continuum counterpart. The dependence of our findings on lattice artefacts is to be investigated in the future.Comment: 40 pages, uuencoded compressed tar file, containing one LaTeX file and 14 postscript files (to be included with epsf). Minor change in the value of the B parameter. Contains corrected value for the B*-B mass splitting. Version accepted for publication in Phys. Rev.

Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

Complete loss of ATM function augments replication catastrophe induced by ATR inhibition and gemcitabine in pancreatic cancer models

Abstract: Background: Personalised medicine strategies may improve outcomes in pancreatic ductal adenocarcinoma (PDAC), but validation of predictive biomarkers is required. Having developed a clinical trial to assess the ATR inhibitor, AZD6738, in combination with gemcitabine (ATRi/gem), we investigated ATM loss as a predictive biomarker of response to ATRi/gem in PDAC. Methods: Through kinase inhibition, siRNA depletion and CRISPR knockout of ATM, we assessed how ATM targeting affected the sensitivity of PDAC cells to ATRi/gem. Using flow cytometry, immunofluorescence and immunoblotting, we investigated how ATRi/gem synergise in ATM-proficient and ATM-deficient cells, before assessing the impact of ATM loss on ATRi/gem sensitivity in vivo. Results: Complete loss of ATM function (through pharmacological inhibition or CRISPR knockout), but not siRNA depletion, sensitised to ATRi/gem. In ATM-deficient cells, ATRi/gem-induced replication catastrophe was augmented, while phospho-Chk2-T68 and phospho-KAP1-S824 persisted via DNA-PK activity. ATRi/gem caused growth delay in ATM-WT xenografts in NSG mice and induced regression in ATM-KO xenografts. Conclusions: ATM loss augments replication catastrophe-mediated cell death induced by ATRi/gem and may predict clinical responsiveness to this combination. ATM status should be carefully assessed in tumours from patients with PDAC, since distinction between ATM-low and ATM-null could be critical in maximising the success of clinical trials using ATM expression as a predictive biomarker

Complete loss of ATM function augments replication catastrophe induced by ATR inhibition and gemcitabine in pancreatic cancer models

Abstract: Background: Personalised medicine strategies may improve outcomes in pancreatic ductal adenocarcinoma (PDAC), but validation of predictive biomarkers is required. Having developed a clinical trial to assess the ATR inhibitor, AZD6738, in combination with gemcitabine (ATRi/gem), we investigated ATM loss as a predictive biomarker of response to ATRi/gem in PDAC. Methods: Through kinase inhibition, siRNA depletion and CRISPR knockout of ATM, we assessed how ATM targeting affected the sensitivity of PDAC cells to ATRi/gem. Using flow cytometry, immunofluorescence and immunoblotting, we investigated how ATRi/gem synergise in ATM-proficient and ATM-deficient cells, before assessing the impact of ATM loss on ATRi/gem sensitivity in vivo. Results: Complete loss of ATM function (through pharmacological inhibition or CRISPR knockout), but not siRNA depletion, sensitised to ATRi/gem. In ATM-deficient cells, ATRi/gem-induced replication catastrophe was augmented, while phospho-Chk2-T68 and phospho-KAP1-S824 persisted via DNA-PK activity. ATRi/gem caused growth delay in ATM-WT xenografts in NSG mice and induced regression in ATM-KO xenografts. Conclusions: ATM loss augments replication catastrophe-mediated cell death induced by ATRi/gem and may predict clinical responsiveness to this combination. ATM status should be carefully assessed in tumours from patients with PDAC, since distinction between ATM-low and ATM-null could be critical in maximising the success of clinical trials using ATM expression as a predictive biomarker

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation