Comparative Effectiveness of Step-up Therapies in Children with Asthma Prescribed Inhaled Corticosteroids : A Historical Cohort Study

This work was supported by the Respiratory Effectiveness Group. Acknowledgments We thank the Respiratory Effectiveness Group for funding this work, Annie Burden for assistance with statistics, and Simon Van Rysewyk and Lisa Law for assistance with medical writing.Peer reviewedPostprin

A transthalamic pathway crucial for perception

Perception is largely supported by cortical processing that involves communication among multiple areas, typically starting with primary sensory cortex and then involving higher order cortices. This communication is served in part by transthalamic (cortico-thalamo-cortical) pathways, which ubiquitously parallel direct corticocortical pathways, but their role in sensory processing has largely remained unexplored. Here, we suggest that transthalamic processing propagates task-relevant information required for correct sensory decisions. Using optogenetics, we specifically inhibited the pathway at its synapse in higher order somatosensory thalamus of mice performing a texture-based discrimination task. We concurrently monitored the cellular effects of inhibition in primary or secondary cortex using two-photon calcium imaging. Inhibition severely impaired performance despite intact direct corticocortical projections, thus challenging the purely corticocentric map of perception. Interestingly, the inhibition did not reduce overall cell responsiveness to texture stimulation in somatosensory cortex, but rather disrupted the texture selectivity of cells, a discriminability that develops over task learning. This discriminability was more disrupted in the secondary than primary somatosensory cortex, emphasizing the feedforward influence of the transthalamic route. Transthalamic pathways may therefore act to deliver performance-relevant information to higher order cortex and are underappreciated hierarchical pathways in perceptual decision-making

'They're battle scars, I wear them well': A phenomenological exploration of young women's experiences of building resilience following adversity in adolescence

This is an Author's Accepted Manuscript of an article published in Journal of Youth Studies, 13(3), 273 - 290, 2010 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/13676260903520886.This phenomenological study explored young women's accounts of building resilience following chains of adverse life experiences in adolescence. Six participants were interviewed, aged 20–25 years. Most had, or were receiving, a university education. They described their recovery from adversity as starting with certain pivotal moments, followed by both short-term and longer-term strategies. Short-term strategies tended to offer respite from distress and emotional comfort, increased clarity about their experiences and social affirmation. Recovery involved gaining new perspectives on their adverse situation and recovering a positive self-image through three longer-term strategies. These involved making visible progress in their education, rebuilding relationships with family and friends, and participating in the ‘normalizing’ activities and developmental projects of adolescence. Participants believed that they were stronger and more compassionate although positive achievements co-existed with some regrets. Most perceived the adversity as catalyzing personal growth. These accounts of resilience revealed the complex psychosocial processes and resources available to some adolescents

Intelligent and adaptive tutoring for active learning and training environments

Active learning facilitated through interactive and adaptive learning environments differs substantially from traditional instructor-oriented, classroom-based teaching. We present a Web-based e-learning environment that integrates knowledge learning and skills training. How these tools are used most effectively is still an open question. We propose knowledge-level interaction and adaptive feedback and guidance as central features. We discuss these features and evaluate the effectiveness of this Web-based environment, focusing on different aspects of learning behaviour and tool usage. Motivation, acceptance of the approach, learning organisation and actual tool usage are aspects of behaviour that require different evaluation techniques to be used

First Detection of HCO+^+ Absorption in the Magellanic System

We present the first detection of HCO$^+$ absorption in the Magellanic System. Using the Australia Telescope Compact Array (ATCA), we observed 9 extragalactic radio continuum sources behind the Magellanic System and detected HCO$^+$ absorption towards one source located behind the leading edge of the Magellanic Bridge. The detection is located at LSR velocity of $v=214.0 \pm 0.4\rm\,km\,s^{-1}$, with a full width at half maximum of $\Delta v=4.5\pm 1.0\rm\,km\,s^{-1}$ and optical depth of $\tau(\rm HCO^+)=0.10\pm 0.02$. Although there is abundant neutral hydrogen (HI) surrounding the sightline in position-velocity space, at the exact location of the absorber the HI column density is low, $<10^{20}\rm\,cm^{-2}$, and there is little evidence for dust or CO emission from Planck observations. While the origin and survival of molecules in such a diffuse environment remains unclear, dynamical events such as HI flows and cloud collisions in this interacting system likely play an important role.Comment: Accepted for publication in ApJ. 6 pages, 2 figures, 2 table

First detection of HCO+ absorption in the magellanic system

We present the first detection of HCO+ absorption in the Magellanic System. Using the ATCA, we observed nine extragalactic radio continuum sources behind the Magellanic System and detected HCO+ absorption toward one source located behind the leading edge of the Magellanic Bridge. The detection is located at an LSR velocity of v 214.0 0.4 km s = -1 , with an FWHM of v 4.5 1.0 km s D = -1 , and an optical depth of t (HCO ) 0.10 0.0 = 2 + . Although there is abundant neutral hydrogen (H I) surrounding the sight line in position–velocity space, at the exact location of the absorber the H I column density is low, <10 cm 20 2 - , and there is little evidence for dust or CO emission from Planck observations. While the origin and survival of molecules in such a diffuse environment remain unclear, dynamical events such as H I flows and cloud collisions in this interacting system likely play an important role

Molecular profiling of signet ring cell colorectal cancer provides a strong rationale for genomic targeted and immune checkpoint inhibitor therapies

We would like to thank all patients whose samples were used in this study. We are also thankful to the Northern Ireland Biobank and Grampian Biorepository for providing us with tissue blocks and patient data; and Dr HG Coleman (Queen’s University Belfast) for her advice on statistical analyses. This work has been carried out with financial support from Cancer Research UK (grant: C11512/A18067), Experimental Cancer Medicine Centre Network (grant: C36697/A15590 from Cancer Research UK and the NI Health and Social Care Research and Development Division), the Sean Crummey Memorial Fund and the Tom Simms Memorial Fund. The Northern Ireland Biobank is funded by HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre; additional support was received from Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory which is responsible for creating resources for the Northern Ireland Biobank has received funding from Cancer Research UK, Friends of the Cancer Centre and Sean Crummey Foundation.Peer reviewedPublisher PD

Accessible Data Curation and Analytics for International-Scale Citizen Science Datasets

The Covid Symptom Study, a smartphone-based surveillance study on COVID-19 symptoms in the population, is an exemplar of big data citizen science. Over 4.7 million participants and 189 million unique assessments have been logged since its introduction in March 2020. The success of the Covid Symptom Study creates technical challenges around effective data curation for two reasons. Firstly, the scale of the dataset means that it can no longer be easily processed using standard software on commodity hardware. Secondly, the size of the research group means that replicability and consistency of key analytics used across multiple publications becomes an issue. We present ExeTera, an open source data curation software designed to address scalability challenges and to enable reproducible research across an international research group for datasets such as the Covid Symptom Study dataset

Observation of Binding and Rotation of Methane and Hydrogen within a Functional Metal-Organic Framework

The key requirement for a portable store of natural gas is to maximize the amount of gas within the smallest possible space. The packing of methane (CH₄) in a given storage medium at the highest possible density is, therefore, a highly desirable but challenging target. We report a microporous hydroxyl-decorated material, MFM-300­(In) (MFM = Manchester Framework Material, replacing the NOTT designation), which displays a high volumetric uptake of 202 v/v at 298 K and 35 bar for CH₄ and 488 v/v at 77 K and 20 bar for H₂. Direct observation and quantification of the location, binding, and rotational modes of adsorbed CH₄ and H₂ molecules within this host have been achieved, using neutron diffraction and inelastic neutron scattering experiments, coupled with density functional theory (DFT) modeling. These complementary techniques reveal a very efficient packing of H₂ and CH₄ molecules within MFM-300­(In), reminiscent of the condensed gas in pure component crystalline solids. We also report here, for the first time, the experimental observation of a direct binding interaction between adsorbed CH₄ molecules and the hydroxyl groups within the pore of a material. This is different from the arrangement found in CH₄/water clathrates, the CH₄ store of nature