Microbial diversity of a disused copper mine site (Parys Mountain, UK), dominated by intensive eukaryotic filamentous growth

The Parys Mountain copper mine (Wales, UK) contains a wide range of discrete environmental microniches with various physicochemical conditions that shape microbial community composition. Our aim was to assess the microbial community in the sediments and overlying water column in an acidic mine drainage (AMD) site containing abundant filamentous biogenic growth via application of a combination of chemical analysis and taxonomic profiling using 16S rRNA gene amplicon sequencing. Our results were then compared to previously studied sites at Parys Mt. Overall, the sediment microbiome showed a dominance of bacteria over archaea, particularly those belonging to Proteobacteria (genera Acidiphilium and Acidisphaera), Acidobacteriota (subgroup 1), Chloroflexota (AD3 cluster), Nitrospirota (Leptospirillum) and the uncultured Planctomycetota/CPIa-3 termite group. Archaea were only present in the sediment in small quantities, being represented by the Terrestrial Miscellaneous Euryarchaeota Group (TMEG), Thermoplasmatales and Ca. Micrarchaeota (Ca. Micracaldota). Bacteria, mostly of the genera Acidiphilium and Leptospirillum, also dominated within the filamentous streamers while archaea were largely absent. This study found pH and dissolved solutes to be the most important parameters correlating with relative proportions of bacteria to archaea in an AMD environment and revealed the abundance patterns of native acidophilic prokaryotes inhabiting Parys Mt sites and their niche specificities

Deterministically Driven Avalanche Models of Solar Flares

We develop and discuss the properties of a new class of lattice-based avalanche models of solar flares. These models are readily amenable to a relatively unambiguous physical interpretation in terms of slow twisting of a coronal loop. They share similarities with other avalanche models, such as the classical stick--slip self-organized critical model of earthquakes, in that they are driven globally by a fully deterministic energy loading process. The model design leads to a systematic deficit of small scale avalanches. In some portions of model space, mid-size and large avalanching behavior is scale-free, being characterized by event size distributions that have the form of power-laws with index values, which, in some parameter regimes, compare favorably to those inferred from solar EUV and X-ray flare data. For models using conservative or near-conservative redistribution rules, a population of large, quasiperiodic avalanches can also appear. Although without direct counterparts in the observational global statistics of flare energy release, this latter behavior may be relevant to recurrent flaring in individual coronal loops. This class of models could provide a basis for the prediction of large solar flares.Comment: 24 pages, 11 figures, 2 tables, accepted for publication in Solar Physic

Cost-effectiveness of exercise referral schemes enhanced by self-management strategies to battle sedentary behaviour in older adults: Protocol for an economic evaluation alongside the SITLESS three-armed pragmatic randomised controlled trial

Introduction: Promoting physical activity (PA) and reducing sedentary behaviour (SB) may exert beneficial effects on the older adult population, improving behavioural, functional, health and psychosocial outcomes in addition to reducing health, social care and personal costs. This paper describes the planned economic evaluation of SITLESS, a multicountry three-armed pragmatic randomised controlled trial (RCT) which aims to assess the short-term and long-term effectiveness and cost-effectiveness of a complex intervention on SB and PA in community-dwelling older adults, based on exercise referral schemes enhanced by a group intervention providing self-management strategies to encourage lifestyle change. Methods and analysis: A within-trial economic evaluation and long-term model from both a National Health Service/personal social services perspective and a broader societal perspective will be undertaken alongside the SITLESS multinational RCT. Healthcare costs (hospitalisations, accident and emergency visits, appointment with health professionals) and social care costs (eg, community care) will be included in the economic evaluation. For the cost-utility analysis, quality-adjusted life-years will be measured using the EQ-5D-5L and capability well-being measured using the ICEpop CAPability measure for Older people (ICECAP-O) questionnaire. Other effectiveness outcomes (health related, behavioural, functional) will be incorporated into a cost-effectiveness analysis and cost-consequence analysis. The multinational nature of this RCT implies a hierarchical structure of the data and unobserved heterogeneity between clusters that needs to be adequately modelled with appropriate statistical and econometric techniques. In addition, a long-term population health economic model will be developed and will synthesise and extrapolate within-trial data with additional data extracted from the literature linking PA and SB outcomes with longer term health states. Methods guidance for population health economic evaluation will be adopted including the use of a long-time horizon, 1.5% discount rate for costs and benefits, cost consequence analysis framework and a multisector perspective. Ethics and dissemination: The study design was approved by the ethics and research committee of each intervention site: the Ethics and Research Committee of Ramon Llull University (reference number: 1314001P) (Fundació Blanquerna, Spain), the Regional Committees on Health Research Ethics for Southern Denmark (reference number: S-20150186) (University of Southern Denmark, Denmark), Office for Research Ethics Committees in Northern Ireland (ORECNI reference number: 16/NI/0185) (Queen’s University of Belfast) and the Ethical Review Board of Ulm University (reference number: 354/15) (Ulm, Germany). Participation is voluntary and all participants will be asked to sign informed consent before the start of the study. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 634 270. This article reflects only the authors' view and the Commission is not responsible for any use that may be made of the information it contains. The findings of the study will be disseminated to different target groups (academia, policymakers, end users) through different means following the national ethical guidelines and the dissemination regulation of the Horizon 2020 funding agency. Use of the EuroQol was registered with the EuroQol Group in 2016. Use of the ICECAP-O was registered with the University of Birmingham in March 2017. Trial registration number: NCT02629666; Pre-results

Genetically modified NT2N human neuronal cells mediate long-term gene expression as CNS grafts in vivo and improve functional cognitive outcome following experimental traumatic brain injury

Human Ntera-2 (NT2) cells can be differentiated in vitro into well-characterized Populations of NT2N neurons that engraft and mature when transplanted into the adult CNS of rodents and humans. Them ha e shown promise as treatments for neurologic disease, trauma, and ischemic stroke. Although these features suggest that NT2N neurons would be an excellent platform for ex vivo gene therapy in the CNS, stable gene expression has been surprisingly difficult to achieve in these cells. In this report we demonstrate stable, efficient. and nontoxic gene transfer into undifferentiated NT2 cells using a pseudotyped lentiviral vector encoding the human elongation factor 1-alpha promoter and the reporter gene eGFP, Expression of eGFP was maintained when the NT2 cells were differentiated into NT2N neurons after treatment with retinoic acid, When transplanted into the striatum of adult nude mice, transduced NT2N neurons survived, engrafted, and continued to express the reporter gene for long-term time points in vivo. Furthermore. transplantation of NT2N neurons genetically modified to express nerve growth factor significantly attenuated cognitive dysfunction following traumatic brain injure in mice. These results demonstrate that defined populations of genetically modified human NT2N neurons are a practical and effective platform for stable ex vivo gene delivery into the CNS

Functional diversity of chemokines and chemokine receptors in response to viral infection of the central nervous system.

Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS

Recent Advances in Understanding Particle Acceleration Processes in Solar Flares

We review basic theoretical concepts in particle acceleration, with particular emphasis on processes likely to occur in regions of magnetic reconnection. Several new developments are discussed, including detailed studies of reconnection in three-dimensional magnetic field configurations (e.g., current sheets, collapsing traps, separatrix regions) and stochastic acceleration in a turbulent environment. Fluid, test-particle, and particle-in-cell approaches are used and results compared. While these studies show considerable promise in accounting for the various observational manifestations of solar flares, they are limited by a number of factors, mostly relating to available computational power. Not the least of these issues is the need to explicitly incorporate the electrodynamic feedback of the accelerated particles themselves on the environment in which they are accelerated. A brief prognosis for future advancement is offered.Comment: This is a chapter in a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

A framework for analysis of linear ultrasound videos to detect fetal presentation and heartbeat.

Confirmation of pregnancy viability (presence of fetal cardiac activity) and diagnosis of fetal presentation (head or buttock in the maternal pelvis) are the first essential components of ultrasound assessment in obstetrics. The former is useful in assessing the presence of an on-going pregnancy and the latter is essential for labour management. We propose an automated framework for detection of fetal presentation and heartbeat from a predefined free-hand ultrasound sweep of the maternal abdomen. Our method exploits the presence of key anatomical sonographic image patterns in carefully designed scanning protocols to develop, for the first time, an automated framework allowing novice sonographers to detect fetal breech presentation and heartbeat from an ultrasound sweep. The framework consists of a classification regime for a frame by frame categorization of each 2D slice of the video. The classification scores are then regularized through a conditional random field model, taking into account the temporal relationship between the video frames. Subsequently, if consecutive frames of the fetal heart are detected, a kernelized linear dynamical model is used to identify whether a heartbeat can be detected in the sequence. In a dataset of 323 predefined free-hand videos, covering the mother's abdomen in a straight sweep, the fetal skull, abdomen, and heart were detected with a mean classification accuracy of 83.4%. Furthermore, for the detection of the heartbeat an overall classification accuracy of 93.1% was achieved