The Loving of the Game: A Study of Basketry in the Mammoth Cave Area

The production and marketing of baskets in the Mammoth Cave area of Kentucky from 1880 to the present is observed in light of the cultural, technical, aesthetic, ad traditional aspects involved. The process of making a white oak ribbed basket is documented, as well as the technical and aesthetic variables from which the basket maker renders his product. The changing role of social organization and communication in the production and marketing of a traditional craft objects is also considered

The dynamics of a spatial data infrastructure– a national case study

It widely cited that 80% of government data is spatial in nature and the accessibility of this data is a critical aspect of E-government. Many countries are developing standardised infrastructures, which will allow sharing and reuse of spatial data. This paper presents the findings of a national level case study of the Spatial Data Infrastructure implementation in Ireland. The study draws on concepts from Corporate Information Infrastructure (CII), most notably the power of the installed base, role of standardisation, multiple actors and top-down versus bottom-up tensions. A significant outcome of this paper is the application of the CII concepts to a national level case study

Current and future treatments of pulmonary arterial hypertension

Therapeutic options for pulmonary arterial hypertension (PAH) have increased over the last decades. The advent of pharmacological therapies targeting the prostacyclin, endothelin, and NO pathways has significantly improved outcomes. However, for the vast majority of patients, PAH remains a life‐limiting illness with no prospect of cure. PAH is characterised by pulmonary vascular remodelling. Current research focusses on targeting the underlying pathways of aberrant proliferation, migration, and apoptosis. Despite success in preclinical models, using a plethora of novel approaches targeting cellular GPCRs, ion channels, metabolism, epigenetics, growth factor receptors, transcription factors, and inflammation, successful transfer to human disease with positive outcomes in clinical trials is limited. This review provides an overview of novel targets addressed by clinical trials and gives an outlook on novel preclinical perspectives in PAH

Metastatic breast cancer incidence, site and survival in Australia, 2001-2016: A population-based health record linkage study protocol

Introduction: Advances in systemic therapy for early and metastatic breast cancer (BC) over the last two decades have improved patients’ survival, but their impact on metastatic disease outcomes at a population level is not well described. The aim of this study is to investigate changes in the incidence, site and survival of metastatic disease for women with a first diagnosis of BC in 2001– 2002 vs 2006–2007. Methods and analysis: Population-based retrospective cohort study of women with first primary invasive BC registered in the New South Wales (NSW) Cancer Registry in 2001–2002 and 2006–2007. We will use linked records from NSW hospitals, dispensed medicines, outpatient services and death registrations to determine: women’s demographic and tumour characteristics; treatments received; time to first distant metastasis; site of first metastasis and survival. We will use the Kaplan-Meier method to estimate cumulative incidence of distant metastasis, distant recurrence-free interval and postmetastasis survival by extent of disease at initial diagnosis, site of metastasis and treatment-defined tumour receptor type (hormone receptor-positive, human epidermal growth factor receptor-2-positive, triple negative). We will use Cox proportional hazards regression to estimate the relative effects of prognostic factors, and we will compare systemic therapy patterns by area-of- residence and area-level socioeconomic status to examine equity of access to healthcare. Ethics and dissemination: Research ethics committee approval was granted by the Australian Institute of Health and Welfare (#EO2017/2/255), NSW Population and Health Services (#HREC/17/CIPHS/19) and University of Notre Dame Australia (#0 17 144S). We will disseminate research findings to oncology, BC consumer and epidemiology audiences through national and international conference presentations, lay summaries to BC consumer groups and publications in international peer-reviewed oncology and cancer epidemiology journals

RACK(1) to the future - a historical perspective

Abstract This perspective summarises the first and long overdue RACK1 meeting held at the University of Limerick, Ireland, May 2013, in which RACK1's role in the immune system, the heart and the brain were discussed and its contribution to disease states such as cancer, cardiac hypertrophy and addiction were described. RACK1 is a scaffolding protein and a member of the WD repeat family of proteins. These proteins have a unique architectural assembly that facilitates protein anchoring and the stabilisation of protein activity. A large body of evidence is accumulating which is helping to define the versatile role of RACK1 in assembling and dismantling complex signaling pathways from the cell membrane to the nucleus in health and disease. In this commentary, we first provide a historical perspective on RACK1. We also address many of the pertinent and topical questions about this protein such as its role in transcription, epigenetics and translation, its cytoskeletal contribution and the merits of targeting RACK1 in disease. Historical perspective It has been 20 years since RACK1 was cloned as the first identified binding protein for Protein Kinase C (PKC), and the road the Mochly-Rosen group took toward its discovery was not trivial. The role of scaffolding proteins in the temporal and spatial regulation of signal transduction seems obvious today, however, this was not the case in the late 1980s when Prof. Daria Mochly-Rosen developed the hypothesis that anchoring/scaffolding proteins control the specificity of substrate phosphorylation and function of Protein Kinase C (PKC) isozymes. An alpha phage display library/overlay assay strategy was used to identify binding proteins that interact with active PKC isoforms. To this day Dr. Ron remembers when one gene product was identified and was termed RACK1 for Receptor for Activated C Kinase RACK1 as a scaffolding protein The conserved seven blade propeller structure of RACK1 facilitates the folding order into constituent propeller blades. These propeller blades are intrinsic to RACK1's protein binding capacity and allow RACK1 to function as a signaling hub RACK1: a scaffolding protein with a central role in transcription, epigenetics & translation RACK1 has a strong effect on transcription and translation by acting at critical points; principally the ribosomal small subunit and via nuclear translocation and regulation of chromatin and transcriptional complexes RACK1 and cytoskeletal proteins: a new frontier The cellular cytoskeleton, whose major components comprise of actin, microtubules and intermediate filaments, maintains cellular integrity and regulates multiple cellular functions including migration RACK1 as a potential therapeutic target As the number of binding partners and validated cellular functions for RACK1 has increased, so has its link with an array of disease states [38] are amongst the first describing beta-propeller/small molecule complexes. Interestingly, the report by Senisterra et al. Concluding comments There are, of course, numerous remaining questions that are of great interest. For example, how can one protein play such an important role in many and diverse biological functions? Is it possible that a number of RACK1 binding partners share common binding sites on RACK1? Is RACK1 function and/or expression levels regulated by posttranslational modifications such as phosphorylation, sumoylation and ubiquitination? Does RACK1 contribute to a large number of disease states and can RACK1 be used as a target for drug development? These are exciting times for RACK1 biologists. As more and more research areas converge on RACK1, we can expect answers to these questions to unfold. RACK1 biology would benefit greatly from detailed mechanistic mathematical modelling and quantitative experimentation to help us comprehend how RACK1 functions in systems biology, beyond its role as a scaffolding protein. We look forward to the next RACK1 conference, which we have no doubt will bring more exciting new data on the role of our favorite protein in cellular functions

17 ways to say yes:Toward nuanced tone of voice in AAC and speech technology

People with complex communication needs who use speech-generating devices have very little expressive control over their tone of voice. Despite its importance in human interaction, the issue of tone of voice remains all but absent from AAC research and development however. In this paper, we describe three interdisciplinary projects, past, present and future: The critical design collection Six Speaking Chairs has provoked deeper discussion and inspired a social model of tone of voice; the speculative concept Speech Hedge illustrates challenges and opportunities in designing more expressive user interfaces; the pilot project Tonetable could enable participatory research and seed a research network around tone of voice. We speculate that more radical interactions might expand frontiers of AAC and disrupt speech technology as a whole

The illusion of competency versus the desirability of expertise: Seeking a common standard for support professions in sport

In this paper we examine and challenge the competency-based models which currently dominate accreditation and development systems in sport support disciplines, largely the sciences and coaching. Through consideration of exemplar shortcomings, the limitations of competency-based systems are presented as failing to cater for the complexity of decision making and the need for proactive experimentation essential to effective practice. To provide a better fit with the challenges of the various disciplines in their work with performers, an alternative approach is presented which focuses on the promotion, evaluation and elaboration of expertise. Such an approach resonates with important characteristics of professions, whilst also providing for the essential ‘shades of grey’ inherent in work with human participants. Key differences between the approaches are considered through exemplars of evaluation processes. The expertise-focused method, although inherently more complex, is seen as offering a less ambiguous and more positive route, both through more accurate representation of essential professional competence and through facilitation of future growth in proficiency and evolution of expertise in practice. Examples from the literature are also presented, offering further support for the practicalities of this approach

Reduced level of arousal and increased mortality in adult acute medical admissions: a systematic review and meta-analysis

Abstract Background Reduced level of arousal is commonly observed in medical admissions and may predict in-hospital mortality. Delirium and reduced level of arousal are closely related. We systematically reviewed and conducted a meta-analysis of studies in adult acute medical patients of the relationship between reduced level of arousal on admission and in-hospital mortality. Methods We conducted a systematic review (PROSPERO: CRD42016022048), searching MEDLINE and EMBASE. We included studies of adult patients admitted with acute medical illness with level of arousal assessed on admission and mortality rates reported. We performed meta-analysis using a random effects model. Results From 23,941 studies we included 21 with 14 included in the meta-analysis. Mean age range was 33.4 - 83.8 years. Studies considered unselected general medical admissions (8 studies, n=13,039) or specific medical conditions (13 studies, n=38,882). Methods of evaluating level of arousal varied. The prevalence of reduced level of arousal was 3.1%-76.9% (median 13.5%). Mortality rates were 1.7%-58% (median 15.9%). Reduced level of arousal was associated with higher in-hospital mortality (pooled OR 5.71; 95% CI 4.21-7.74; low quality evidence: high risk of bias, clinical heterogeneity and possible publication bias). Conclusions Reduced level of arousal on hospital admission may be a strong predictor of in-hospital mortality. Most evidence was of low quality. Reduced level of arousal is highly specific to delirium, better formal detection of hypoactive delirium and implementation of care pathways may improve outcomes. Future studies to assess the impact of interventions on in-hospital mortality should use validated assessments of both level of arousal and delirium

DEAR project: Lunar dust surface interactions, risk and removal investigations

The DEAR project (Dusty Environment Application Research) investigates the interaction between lunar regolith and surfaces and components relevant for lunar exploration. Based on the TUBS regolith simulant which is representative in chemistry, size and shape properties to Moon soils to study the regolith transport, adhesion and strategies for cleaning. The regolith simulant will be applied to thermal, structural, optical sensor, sealing and other astronautic systems, providing input for requirements, justification and verification. The key applications are split in human space flight regolith investigations, wrinkled surface with random movement and hardware surfaces, flat material defined movement. The paper provides an overview of the DEAR project including a discussion of the first results, in particular vibration, shock and micro-vibration on regolith bearing surfaces. The investigation shall enable better understand the regolith layers interaction and the release mechanism, as well as potential cross contamination and cleaning strategies. The research is complemented by simulation of the regolith motion as parameter surface plasma interactions. The project is funded and supported by the European Space Agency (ESA). DEAR specifically addresses the development and testing of lunar dust removal strategies on optics, mechanisms and human space flight hardware (e.g., space suits). As the Moons regolith is known to be highly abrasive, electrically chargeable, and potentially chemically reactive, lunar dust might reduce the performance of hardware, such as cameras, thermal control surfaces and solar cells. The dust can cause malfunction on seals for on/off mechanisms or space suits. Of particular interest are risk assessment, avoidance, and cleaning techniques such as the use of electric fields to remove lunar dust from surfaces. Representative dust (e.g., regolith analogues of interesting landing sites) will be used in a dedicated test setup to evaluate risks and effects of lunar dust. We describe designs and methods developed by the DEAR consortium to deal with the regolith-related issues, in particular an electrode design to deflect regolith particles, cleaning of astronautical systems with CO2, design of a robotic arm for the testing within the DEAR chamber, regolith removal via shock, and regolith interaction with cleanroom textile