Production of 3D printed scale models from microscope volume datasets for use in STEM education

Understanding the three-dimensional morphology of a biological sample at the microscopic level is a prerequisite to a functional understanding of cell biology, tissue development and growth. Images of microscopic samples obtained by compound light microscopy are customarily recorded and represented in two dimensions from a single orientation making it difficult to extrapolate 3D context from the 2D information. The commercialisation of fast, laser-based microscope systems (e.g. confocal, multi-photon or lightsheet microscopy) capable of generating volume datasets of microscopic samples through optical sectioning, coupled with advances in computer technology allowing accurate volume rendering of these datasets, have facilitated significant improvement in our 3D understanding of the microscopic world in virtual space. The advent of affordable 3D printing technology now offers the prospect of generating morphologically accurate, physical models from these microscope volume datasets for use in science education, outreach and engagement. 3D printed scale replicas will provide improved sensory perception, offering tactile as well as visual interaction, leading to improved understanding of structure function relationships. Here we present a technique to reliably generate detailed, physical 3D models from Z-stacks of optical sections from confocal and lightsheet microscopes using affordable, entry-level 3D printing technology. We use the technique to generate 3D printed models of a variety of different biological samples at a range of scales including pollen grains from two species of plant; blood cells from both human and earthworm species, a section of plant root; the compound eye of an ant; and a developing Zebrafish larva; all of which have been used in our teaching, engagement and outreach activities. Our methods can, in principle, be used to generate 3D printed models from microscope volume datasets of any small fluorescent or reflective samples

Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice

The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, D9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/ kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABAA receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes

Effect of Sarcobesity Index and Body Adipose Tissue Variables on Cardiopulmonary Exercise Testing Performance in Colorectal Surgery Setting: A Retrospective Cohort Study

Aims/Background: The prognostic significance of body composition variables has become a popular area of research over the recent years. This study aimed to determine whether adipose tissue variables and sarcobesity index measured by computed tomography (CT) could predict cardiopulmonary exercise testing (CPET) performance and long-term mortality in patients undergoing major colorectal surgery. Methods: The Strengthening the Reporting of Cohort Studies in Surgery (STROCSS) statement standards were followed to conduct a retrospective cohort study of consecutive patients who had CPET prior to major colorectal surgery between January 2011 and January 2017. Receiver Operating Characteristic curve analysis was conducted to assess the discriminative performances of adipose tissue variables. The association between CT-derived adipose tissue variables (sarcobesity index, visceral adipose tissue, subcutaneous adipose tissue, and total adipose tissue) and CPET performance and mortality were assessed using regression analyses. Results: 457 patients were included. Total adipose tissue evaluated via 2-dimensional (2D) and 3-dimensional (3D) approaches predicted oxygen uptake (V̇O2) Rest, V̇O2 anaerobic threshold (AT), ventilatory equivalents for carbon dioxide (V̇E/V̇CO2) AT, ventilatory equivalents for oxygen (V̇E/V̇O2) AT, V̇O2 peak, exercise time, maximum work, peak metabolic equivalents (METS), peak respiratory rate (RER), and peak oxygen pulse. Sarcobesity index (2D and 3D) predicted V̇O2 Rest, V̇O2 AT, V̇E/V̇CO2 AT, V̇O2 peak, maximum work, peak METS, maximum heart rate, and peak RER. Neither total adipose tissue nor sarcobesity index (2D and 3D) predicted 1-year, 3-year, or 5-year mortality. There was no difference in the discriminative performance of adipose tissue variables in predicting mortality. Conclusion: The CPET performance may be predicted by radiologically measured adipose tissue variables and sarcobesity index. However, the prognostic value of the variables may not be significant in this setting

High operational and environmental stability of high-mobility conjugated polymer field-effect transistors through the use of molecular additives.

Due to their low-temperature processing properties and inherent mechanical flexibility, conjugated polymer field-effect transistors (FETs) are promising candidates for enabling flexible electronic circuits and displays. Much progress has been made on materials performance; however, there remain significant concerns about operational and environmental stability, particularly in the context of applications that require a very high level of threshold voltage stability, such as active-matrix addressing of organic light-emitting diode displays. Here, we investigate the physical mechanisms behind operational and environmental degradation of high-mobility, p-type polymer FETs and demonstrate an effective route to improve device stability. We show that water incorporated in nanometre-sized voids within the polymer microstructure is the key factor in charge trapping and device degradation. By inserting molecular additives that displace water from these voids, it is possible to increase the stability as well as uniformity to a high level sufficient for demanding industrial applications.We gratefully acknowledge financial support from Innovate UK (PORSCHED project) and the Engineering and Physical Sciences Research Council though a Programme Grant (EP/M005141/1). I.N. acknowledges studentship support from FlexEnable Ltd. K.B. gratefully acknowledges financial support from the Deutsche Forschungsgemeinschaft (BR 4869/1-1). B.R., M.K.R., and J.L.B. thank the financial support from King Abdullah University of Science and Technology (KAUST), the KAUST Competitive Research Grant program, and the Office of Naval Research Global (Award N62909-15-1-2003 );This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/nmat478

Production of 3D printed scale models from microscope volume datasets for use in STEM education

Understanding the three-dimensional morphology of a biological sample at the microscopic level is a prerequisite to a functional understanding of cell biology, tissue development and growth. Images of microscopic samples obtained by compound light microscopy are customarily recorded and represented in two dimensions from a single orientation making it difficult to extrapolate 3D context from the 2D information. The commercialisation of fast, laser-based microscope systems (e.g. confocal, multi-photon or lightsheet microscopy) capable of generating volume datasets of microscopic samples through optical sectioning, coupled with advances in computer technology allowing accurate volume rendering of these datasets, have facilitated significant improvement in our 3D understanding of the microscopic world in virtual space. The advent of affordable 3D printing technology now offers the prospect of generating morphologically accurate, physical models from these microscope volume datasets for use in science education, outreach and engagement. 3D printed scale replicas will provide improved sensory perception, offering tactile as well as visual interaction, leading to improved understanding of structure function relationships. Here we present a technique to reliably generate detailed, physical 3D models from Z-stacks of optical sections from confocal and lightsheet microscopes using affordable, entry-level 3D printing technology. We use the technique to generate 3D printed models of a variety of different biological samples at a range of scales including pollen grains from two species of plant; blood cells from both human and earthworm species, a section of plant root; the compound eye of an ant; and a developing Zebrafish larva; all of which have been used in our teaching, engagement and outreach activities. Our methods can, in principle, be used to generate 3D printed models from microscope volume datasets of any small fluorescent or reflective samples

Improving Mobility Performance in Low Vision With a Distance-Based Representation of the Visual Scene

Citation: van Rheede JJ, Wilson IR, Qian RI, Downes SM, Kennard C, Hicks SL. Improving mobility performance in low vision with a distancebased representation of the visual scene. Invest Ophthalmol Vis Sci. 2015;56:4802-4809. DOI:10.1167/ iovs.14-16311 PURPOSE. Severe visual impairment can have a profound impact on personal independence through its effect on mobility. We investigated whether the mobility of people with vision low enough to be registered as blind could be improved by presenting the visual environment in a distance-based manner for easier detection of obstacles. METHODS. We accomplished this by developing a pair of ''residual vision glasses'' (RVGs) that use a head-mounted depth camera and displays to present information about the distance of obstacles to the wearer as brightness, such that obstacles closer to the wearer are represented more brightly. We assessed the impact of the RVGs on the mobility performance of visually impaired participants during the completion of a set of obstacle courses. Participant position was monitored continuously, which enabled us to capture the temporal dynamics of mobility performance. This allowed us to find correlates of obstacle detection and hesitations in walking behavior, in addition to the more commonly used measures of trial completion time and number of collisions. RESULTS. All participants were able to use the smart glasses to navigate the course, and mobility performance improved for those visually impaired participants with the worst prior mobility performance. However, walking speed was slower and hesitations increased with the altered visual representation. CONCLUSIONS. A depth-based representation of the visual environment may offer low vision patients improvements in independent mobility. It is important for further work to explore whether practice can overcome the reductions in speed and increased hesitation that were observed in our trial

Low microplastic loads in riverine European eel (Anguilla anguilla) from SW England during their marine-freshwater transition.

The microplastic loads in elvers of the critically endangered European eel Anguilla anguilla, sampled in the lower reaches of three English rivers, were very low (incidence: 3.3 %, mean ± SD: 0.03 ± 0.18 particles) and did not vary with body length or between rivers. Particles were mostly black, polyolefins, fibres and fragments of size 101-200 μm. Current levels indicate a low contamination pressure locally and, consequently, management efforts might prioritise mitigating the effects of other stressors affecting the species. This article is protected by copyright. All rights reserved

OpenSAFELY: A platform for analysing electronic health records designed for reproducible research

Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID‐19 pandemic, we developed the secure, transparent, analytic open‐source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code‐sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY's reproducibility‐by‐design approach in detail