Devising an Online Resource to Help Undergraduate Science Students Critically Evaluate Research Articles

Critically evaluating research papers is an important vehicle for promoting acculturation into a scientific discipline. As science students progress through their undergraduate studies, their critical abilities are expected to become heightened, and research papers are read and cited in order to support a variety of assignments, such as essays, critical reviews and presentations, progressing to shaping laboratory research projects and dissertation-writing. This article describes the process of designing a modular online resource. The resource is aimed at familiarising students with the structural conventions and argumentative devices used in research papers and supporting them in deep-reading a research paper in life sciences or chemistry. The modules employ audio- and video-recorded extracts from interviews with a key author to provide a context for the origins, motivations and processes behind the writing of a specific paper, plus scaffolded questions to encourage critical evaluation of the paper. Notable features of the project were the employment of a multi-disciplinary team of staff and research postgraduates coupled with the developmental testing of the resource by undergraduates. Lessons learnt from the project are considered, including the resource’s integration within the curriculum and the challenges of writing such interactive resources for different disciplines

Feedback from winds and supernovae in massive stellar clusters

This thesis contains a study of the mechanical feedback from winds and supernovae on inhomogeneous molecular material left over from the formation of a massive stellar cluster. Firstly, the mechanical input from a cluster with three massive O-stars into a giant molecular cloud (GMC) clump containing 3240M⊙ of molecular material within a 4 pc radius is investigated using a 3D hydrodynamcial model. The cluster wind blows out of the molecular clump along low-density channels, into which denser clump material is entrained. The densest regions are surprisingly resistant to ablation by the cluster wind, in part due to shielding by other dense regions close to the cluster. Nonetheless, molecular material is gradually removed by the cluster wind during which mass-loading factors in excess of several hundred are obtained. Because the clump is very porous, 60-75% of the injected wind energy escapes the simulation domain. After 4.4Myrs the massive stars in the simulation start to explode as supernovae. The highly structured environment into which the SN energy is released allows even weaker coupling to the remaining dense material and practically all of the SN energy reaches the wider environment. Secondly, the X-ray emission from the simulated stellar cluster is presented. The GMC clump causes short–lived attenuation effects on the X-ray emission of the cluster. However, once most of the material has been ablated away by the winds the remaining dense clumps do not have a noticable effect on the attenuation compared with the assumed interstellar medium (ISM) column. The evolution of the X-ray luminosity and spectra are presented, and synthetic images of the emission are generated. The X-ray luminosity is initially high whilst the winds are “bottled up”, but reduce to a near constant value once the GMC clump has been mostly destroyed. The luminosity decreases slighly during the red supergiant phase of the stars due to the depressurization of the hot gas. However, the luminosity dramatically increases during the Wolf-Rayet stage of each star. The X-ray luminosity is enhanced by 2-3 orders of magnitude for at least 466 yrs after each supernova explosion, at which time the blast wave leaves the grid. Comparisons between the simulated cluster and both theoretical models and observations of young stellar clusters are presented. Thirdly, the radio emission from the simulated cluster is presented. Similar to the X-ray emission, the thermal radio emission is intially high when the winds are confined in the GMC clump and reduce as the material is ablated away. The evolution of the radio flux density and spectra are presented, and synthetic images of the emission are generated. The radio emission is compared with the X-ray results throughout the evolution of the cluster. The flux density increases during the RSG phase, and remains high during the WR phgase of the stars. The radio flux density is enhanced by three orders of magnitude during the first supernova explosion. Comparisons between the simulated cluster and observations of young stellar clusters are made. Finally, a preliminary investigation of the interaction of stellar winds within a massive cluster are presented. The hydrodynamcial simulations examine the energy and mass input of a stellar cluster into the ISM

Achieving change in primary care—causes of the evidence to practice gap : systematic reviews of reviews

Acknowledgements The Evidence to Practice Project (SPCR FR4 project number: 122) is funded by the National Institute of Health Research (NIHR) School for Primary Care Research (SPCR). KD is part-funded by the National Institute for Health Research (NIHR) Collaborations for Leadership in Applied Research and Care West Midlands and by a Knowledge Mobilisation Research Fellowship (KMRF-2014-03-002) from the NIHR. This paper presents independent research funded by the National Institute of Health Research (NIHR). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Funding This study is funded by the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR).Peer reviewedPublisher PD

Fetal liver blood flow distribution: role in human developmental strategy to prioritize fat deposition versus brain development

Among primates, human neonates have the largest brains but also the highest proportion of body fat. If placental nutrient supply is limited, the fetus faces a dilemma: should resources be allocated to brain growth, or to fat deposition for use as a potential postnatal energy reserve? We hypothesised that resolving this dilemma operates at the level of umbilical blood distribution entering the fetal liver. In 381 uncomplicated pregnancies in third trimester, we measured blood flow perfusing the fetal liver, or bypassing it via the ductus venosus to supply the brain and heart using ultrasound techniques. Across the range of fetal growth and independent of the mother's adiposity and parity, greater liver blood flow was associated with greater offspring fat mass measured by dual-energy X-ray absorptiometry, both in the infant at birth (r = 0.43, P<0.001) and at age 4 years (r = 0.16, P = 0.02). In contrast, smaller placentas less able to meet fetal demand for essential nutrients were associated with a brain-sparing flow pattern (r = 0.17, p = 0.02). This flow pattern was also associated with a higher degree of shunting through ductus venosus (P = 0.04). We propose that humans evolved a developmental strategy to prioritize nutrient allocation for prenatal fat deposition when the supply of conditionally essential nutrients requiring hepatic inter-conversion is limited, switching resource allocation to favour the brain if the supply of essential nutrients is limited. Facilitated placental transfer mechanisms for glucose and other nutrients evolved in environments less affluent than those now prevalent in developed populations, and we propose that in circumstances of maternal adiposity and nutrient excess these mechanisms now also lead to prenatal fat deposition. Prenatal developmental influences play important roles in the human propensity to deposit fa

Supratentorial and spinal pediatric ependymomas display a hypermethylated phenotype which includes the loss of tumor suppressor genes involved in the control of cell growth and death

Epigenetic alterations, including methylation, have been shown to be an important mechanism of gene silencing in cancer. Ependymoma has been well characterized at the DNA copy number and mRNA expression levels. However little is known about DNA methylation changes. To gain a more global view of the methylation profile of ependymoma we conducted an array-based analysis. Our data demonstrated tumors to segregate according to their location in the CNS, which was associated with a difference in the global level of methylation. Supratentorial and spinal tumors displayed significantly more hypermethylated genes than posterior fossa tumors, similar to the ‘CpG island methylator phenotype’ (CIMP) identified in glioma and colon carcinoma. This hypermethylated profile was associated with an increase in expression of genes encoding for proteins involved in methylating DNA, suggesting an underlying mechanism. An integrated analysis of methylation and mRNA expression array data allowed us to identify methylation-induced expression changes. Most notably genes involved in the control of cell growth and death and the immune system were identified, including members of the JNK pathway and PPARG. In conclusion, we have generated a global view of the methylation profile of ependymoma. The data suggests epigenetic silencing of tumor suppressor genes is an important mechanism in the pathogenesis of supratentorial and spinal, but not posterior fossa ependymomas. Hypermethylation correlated with a decrease in expression of a number of tumor suppressor genes and pathways that could be playing an important role in tumor pathogenesis

On internal wave breaking and tidal dissipation near the centre of a solar-type star

We study the fate of internal gravity waves, which are excited by tidal forcing by a short-period planet at the interface of convection and radiation zones, approaching the centre of a solar-type star. We study at what amplitude these wave are subject to instabilities. These instabilities lead to wave breaking whenever the amplitude exceeds a critical value. Below this value, the wave reflects perfectly from the centre of the star. Wave breaking results in spinning up the central regions of the star, and the formation of a critical layer, which acts as an absorbing barrier for ingoing waves. As these waves are absorbed, the star is spun up from the inside out. This results in an important amplitude dependence of the tidal quality factor Q'. If the tidal forcing amplitude exceeds the value required for wave breaking, efficient dissipation results over a continuous range of tidal frequencies, leading to Q' \approx 10^5 (P/1day)^(8/3), for the current Sun. This varies by less than a factor of 5 throughout the range of G and K type main sequence stars, for a given orbit. We predict fewer giant planets with orbital periods of less than about 2 days around such stars, if they cause breaking at the centre, due to the efficiency of this process. This mechanism would, however, be ineffective in stars with a convective core, such as WASP-18, WASP-12 and OGLE-TR-56, perhaps partly explaining the survival of their close planetary companions.Comment: 22 pages, 10 figures, accepted in MNRAS, abstract shortened (!

Epen-23. A computational analysis of the tumour immune microenvironment in paediatric ependymoma

Ependymoma is the third commonest childhood brain tumour. Relapse is frequent, often fatal and current therapeutic strategies are inadequate. Previous ependymoma research describes an immunosuppressive environment with T-cell exhaustion, indicating a lack of response to T-cell directed immunotherapy. Understanding the immune microenvironment is therefore critical. We present a computational analysis of ependymoma, gene expression derived, immune profiles. Using 465 ependymoma samples from gene expression datasets (GSE64415, GSE50385, GSE100240) and two RNA-seq databases from UK ependymomas, we applied bulk tumour deconvolution methods (CIBERSORT and xCell) to infer immune cell populations. Additionally, we measured checkpoint blockade related mRNAs and used immunohistochemistry to investigate cell populations in ependymoma sections. CIBERSORT indicated high proportions of M2-like macrophages and smaller proportions of activated natural killer (NK) cells, T follicular helper cells, CD4+ memory T-cells and B-cells. xCell overlapped with the M2-like macrophage and CD4+ memory T-cell signatures seen in CIBERSORT. On immunohistochemistry, T and B cells were scarce, with small numbers of CD8+, CD4+ and CD20+ cells in the parenchyma but greater numbers in surrounding regions. CD68 was more highly expressed in the parenchyma. Analysis of nine checkpoint ligands and receptors demonstrated only the TIM3/GAL9 combination was reliably detectable. GAL9 is implicated in tumour interactions with T-cells and macrophages elsewhere, possibly contributing to poorer outcomes. Our study supports the presence of myeloid cells being leading contributors to the ependymoma immune microenvironment. Further work will delineate the extent of myeloid contribution to immunosuppression across molecular subtypes. Modulation of tumour immunity may contribute to better clinical outcomes

Interactions between social learning and technological learning in electric vehicle futures

The transition to electric vehicles is an important strategy for reducing greenhouse gas emissions from passenger cars. Modelling transition pathways helps identify critical drivers and uncertainties. Global integrated assessment models (IAMs) have been used extensively to analyse climate mitigation policy. IAMs emphasise technological change processes but are largely silent on important social and behavioural dimensions to technological transitions. Here, we develop a novel conceptual framing and empirical evidence base on social learning processes relevant for vehicle adoption. We then implement this formulation of social learning in IMAGE, a widely-used global IAM. We apply this new modelling approach to analyse how technological learning and social learning interact to influence electric vehicle transition dynamics. We find that technological learning and social learning processes can be mutually reinforcing. Increased electric vehicle market shares can induce technological learning which reduces technology costs while social learning stimulates diffusion from early adopters to more risk-averse adopter groups. In this way, both types of learning process interact to stimulate each other. In the absence of social learning, however, the perceived risks of electric vehicle adoption among later adopting groups remains prohibitively high. In the absence of technological learning, electric vehicles remain relatively expensive and therefore only for early adopters an attractive choice. This first-of-its-kind model formulation of both social and technological learning is a significant contribution to improving the behavioural realism of global IAMs. Applying this new modelling approach emphasises the importance of market heterogeneity, real-world consumer decision-making, and social dynamics as well as technology parameters, to understand climate mitigation potentials