LiDAR, UAV or compass-clinometer? Accuracy, coverage and the effects on structural models

This study was carried out as part of a University of Aberdeen provided PhD supported by The NERC Centre for Doctoral Training in Oil & Gas, (grant reference: NE/M00578X/1). Thanks to Magda Chmielewska for her training and help with LiDAR processing, without which this study could not have been undertaken. Midland Valley Exploration is thanked for academic use of Move 2016 software. We gratefully acknowledge the detailed and constructive reviews by Mike James and an anonymous reviewer, and thanks to Bill Dunne for careful and thorough editorial comments, all of which greatly improved the manuscript.Peer reviewedPublisher PD

Functional alleles of the flowering time regulator FRIGIDA in the Brassica oleracea genome

Background Plants adopt different reproductive strategies as an adaptation to growth in a range of climates. In Arabidopsis thaliana FRIGIDA (FRI) confers a vernalization requirement and thus winter annual habit by increasing the expression of the MADS box transcriptional repressor FLOWERING LOCUS C (FLC). Variation at FRI plays a major role in A. thaliana life history strategy, as independent loss-of-function alleles that result in a rapid-cycling habit in different accessions, appear to have evolved many times. The aim of this study was to identify and characterize orthologues of FRI in Brassica oleracea. Results We describe the characterization of FRI from Brassica oleracea and identify the two B. oleracea FRI orthologues (BolC.FRI.a and BolC.FRI.b). These show extensive amino acid conservation in the central and C-terminal regions to FRI from other Brassicaceae, including A. thaliana, but have a diverged N-terminus. The genes map to two of the three regions of B. oleracea chromosomes syntenic to part of A. thaliana chromosome 5 suggesting that one of the FRI copies has been lost since the ancient triplication event that formed the B. oleracea genome. This genomic position is not syntenic with FRI in A. thaliana and comparative analysis revealed a recombination event within the A. thaliana FRI promoter. This relocated A. thaliana FRI to chromosome 4, very close to the nucleolar organizer region, leaving a fragment of FRI in the syntenic location on A. thaliana chromosome 5. Our data show this rearrangement occurred after the divergence from A. lyrata. We explored the allelic variation at BolC.FRI.a within cultivated B. oleracea germplasm and identified two major alleles, which appear equally functional both to each other and A. thaliana FRI, when expressed as fusions in A. thaliana. Conclusions We identify the two Brassica oleracea FRI genes, one of which we show through A. thaliana complementation experiments is functional, and show their genomic location is not syntenic with A. thaliana FRI due to an ancient recombination event. This has complicated previous association analyses of FRI with variation in life history strategy in the Brassica genus

Executable network of SARS-CoV-2-host interaction predicts drug combination treatments

The COVID-19 pandemic has pushed healthcare systems globally to a breaking point. The urgent need for effective and affordable COVID-19 treatments calls for repurposing combinations of approved drugs. The challenge is to identify which combinations are likely to be most effective and at what stages of the disease. Here, we present the first disease-stage executable signalling network model of SARS-CoV-2-host interactions used to predict effective repurposed drug combinations for treating early- and late stage severe disease. Using our executable model, we performed in silico screening of 9870 pairs of 140 potential targets and have identified nine new drug combinations. Camostat and Apilimod were predicted to be the most promising combination in effectively supressing viral replication in the early stages of severe disease and were validated experimentally in human Caco-2 cells. Our study further demonstrates the power of executable mechanistic modelling to enable rapid pre-clinical evaluation of combination therapies tailored to disease progression. It also presents a novel resource and expandable model system that can respond to further needs in the pandemic

Defining Terms Used for Animals Working in Support Roles for People with Support Needs

The nomenclature used to describe animals working in roles supporting people can be confusing. The same term may be used to describe different roles, or two terms may mean the same thing. This confusion is evident among researchers, practitioners, and end users. Because certain animal roles are provided with legal protections and/or government-funding support in some jurisdictions, it is necessary to clearly define the existing terms to avoid confusion. The aim of this paper is to provide operationalized definitions for nine terms, which would be useful in many world regions: “assistance animal”, “companion animal”, “educational/school support animal”, “emotional support animal”, “facility animal”, “service animal”, “skilled companion animal”, “therapy animal”, and “visiting/visitation animal”. At the International Society for Anthrozoology (ISAZ) conferences in 2018 and 2020, over 100 delegates participated in workshops to define these terms, many of whom co-authored this paper. Through an iterative process, we have defined the nine terms and explained how they differ from each other. We recommend phasing out two terms (i.e., “skilled companion animal” and “service animal”) due to overlap with other terms that could potentially exacerbate confusion. The implications for several regions of the world are discussed

Exploring the spectral diversity of low-redshift Type Ia supernovae using the Palomar Transient Factory

We present an investigation of the optical spectra of 264 low-redshift (z < 0.2) Type Ia supernovae (SNe Ia) discovered by the Palomar Transient Factory, an untargeted transient survey. We focus on velocity and pseudo-equivalent width measurements of the Si II 4130, 5972, and 6355 A lines, as well those of the Ca II near-infrared (NIR) triplet, up to +5 days relative to the SN B-band maximum light. We find that a high-velocity component of the Ca II NIR triplet is needed to explain the spectrum in ~95 per cent of SNe Ia observed before -5 days, decreasing to ~80 per cent at maximum. The average velocity of the Ca II high-velocity component is ~8500 km/s higher than the photospheric component. We confirm previous results that SNe Ia around maximum light with a larger contribution from the high-velocity component relative to the photospheric component in their Ca II NIR feature have, on average, broader light curves and lower Ca II NIR photospheric velocities. We find that these relations are driven by both a stronger high-velocity component and a weaker contribution from the photospheric Ca II NIR component in broader light curve SNe Ia. We identify the presence of C II in very-early-time SN Ia spectra (before -10 days), finding that >40 per cent of SNe Ia observed at these phases show signs of unburnt material in their spectra, and that C II features are more likely to be found in SNe Ia having narrower light curves.Comment: 18 page, 10 figures, accepted for publication in MNRA

Primary care Identification and Referral to Improve Safety of women experiencing domestic violence (IRIS): protocol for a pragmatic cluster randomised controlled trial

BACKGROUND: Domestic violence, which may be psychological, physical, sexual, financial or emotional, is a major public health problem due to the long-term health consequences for women who have experienced it and for their children who witness it. In populations of women attending general practice, the prevalence of physical or sexual abuse in the past year from a partner or ex-partner ranges from 6 to 23%, and lifetime prevalence from 21 to 55%. Domestic violence is particularly important in general practice because women have many contacts with primary care clinicians and because women experiencing abuse identify doctors and nurses as professionals from whom they would like to get support. Yet health professionals rarely ask about domestic violence and have little or no training in how to respond to disclosure of abuse. METHODS/DESIGN: This protocol describes IRIS, a pragmatic cluster randomised controlled trial with the general practice as unit of randomisation. Our trial tests the effectiveness and cost-effectiveness of a training and support programme targeted at general practice teams. The primary outcome is referral of women to specialist domestic violence agencies. Forty-eight practices in two UK cities (Bristol and London) are randomly allocated, using minimisation, into intervention and control groups. The intervention, based on an adult learning model in an educational outreach framework, has been designed to address barriers to asking women about domestic violence and to encourage appropriate responses to disclosure and referral to specialist domestic violence agencies. Multidisciplinary training sessions are held with clinicians and administrative staff in each of the intervention practices, with periodic feedback of identification and referral data to practice teams. Intervention practices have a prompt to ask about abuse integrated in the electronic medical record system. Other components of the intervention include an IRIS champion in each practice and a direct referral pathway to a named domestic violence advocate. DISCUSSION: This is the first European randomised controlled trial of an intervention to improve the health care response to domestic violence. The findings will have the potential to inform training and service provision. TRIAL REGISTRATION: ISRCTN74012786

Localized immune surveillance of primary melanoma in the skin deciphered through executable modeling

While skin is a site of active immune surveillance, primary melanomas often escape detection. Here, we have developed an in silico model to determine the local cross-talk between melanomas and Langerhans cells (LCs), the primary antigen-presenting cells at the site of melanoma development. The model predicts that melanomas fail to activate LC migration to lymph nodes until tumors reach a critical size, which is determined by a positive TNF-α feedback loop within melanomas, in line with our observations of murine tumors. In silico drug screening, supported by subsequent experimental testing, shows that treatment of primary tumors with MAPK pathway inhibitors may further prevent LC migration. In addition, our in silico model predicts treatment combinations that bypass LC dysfunction. In conclusion, our combined approach of in silico and in vivo studies suggests a molecular mechanism that explains how early melanomas develop under the radar of immune surveillance by LC

Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype

ims/hypothesis The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes. Methods Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8+ T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs. Results Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors (p < 0.05). The phenotypic characteristics of CD4+ and CD8+ T cells were similar in slow progressors and healthy donors. Lower frequencies of CD4+ T cells with a central memory phenotype (CD27int, CD127+, CD95int) were observed in slow progressors compared with healthy donors (mean percentage of total CD4+ T cells was 3.00% in slow progressors vs 4.67% in healthy donors, p < 0.05). Autoreactive B cell responses to proinsulin were detected at higher frequencies in slow progressors compared with healthy donors (median no. of spots was 0 in healthy donors vs 24.34 in slow progressors, p < 0.05) in an ELISpot assay. Islet autoantigen-specific CD8+ T cell responses were largely absent in slow progressors and healthy donors. Serum levels of DcR3, the decoy receptor for CD95L, were elevated in slow progressors compared with healthy donors (median was 1087 pg/ml in slow progressors vs 651 pg/ml in healthy donors, p = 0.06). Conclusions/interpretation In this study, we found that slow progression to type 1 diabetes was associated with a loss of islet autoantibodies and a distinct B cell phenotype, consistent with enhanced apoptotic regulation of peripheral autoreactivity via CD95. These phenotypic changes warrant further studies in larger cohorts to determine their functional implications

Patterns of debate in tertiary level asynchronous text-based conferencing

Argumentation can be defined at different levels and serve different purposes, but its role in knowledge understanding and construction has given it a central place in education, particularly at tertiary level. The advent of computer-supported text-based conferences has created new sites where such educational dialogues can take place, but the quality of the interaction and whether it is serving its educational purpose is still uncertain. This paper reports on a framework of analysis that has been developed to illuminate the arguing process within an asynchronous electronic conferencing environment, showing how it is both similar to, and different from, argumentation in the more traditional forums of multi-party, face-to-face discussion and traditional written essays. The framework develops earlier work by the authors and is applied to two electronic conferences within the same postgraduate course, comparing overall patterns of argumentation. Findings are presented on the extent to which the technology of electronic conferencing shapes and supports students’ participation in academic literacy practices relating to argumentation, proposing, at the same time, that the teaching strategy adopted by the lecturer is also an important variable

Designing informative warning signals: Effects of indicator type, modality, and task demand on recognition speed and accuracy

An experiment investigated the assumption that natural indicators which exploit existing learned associations between a signal and an event make more effective warnings than previously unlearned symbolic indicators. Signal modality (visual, auditory) and task demand (low, high) were also manipulated. Warning effectiveness was indexed by accuracy and reaction time (RT) recorded during training and dual task test phases. Thirty-six participants were trained to recognize 4 natural and 4 symbolic indicators, either visual or auditory, paired with critical incidents from an aviation context. As hypothesized, accuracy was greater and RT was faster in response to natural indicators during the training phase. This pattern of responding was upheld in test phase conditions with respect to accuracy but observed in RT only in test phase conditions involving high demand and the auditory modality. Using the experiment as a specific example, we argue for the importance of considering the cognitive contribution of the user (viz., prior learned associations) in the warning design process. Drawing on semiotics and cognitive psychology, we highlight the indexical nature of so-called auditory icons or natural indicators and argue that the cogniser is an indispensable element in the tripartite nature of signification