The Economic Impacts and Risks Associated with Electric Power Generation in Appalachia

This report provides a detailed examination of the economic impacts of changes in electric power generation in Appalachia between 2005 and 2015. It finds that while coal represented around 74 percent of total electric generation in Appalachia in 2005, that percentage dropped to 53 percent in 2015. However, despite this decline, Appalachia remains more dependent on coal for electricity generation when compared with the rest of the country. This report also offers a risk factor analysis for coal-fired generation retirements and repowerings, and notes that coal prices have little influence on coal-fired power plant retirement decisions

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy

<b>Background:</b> Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2–3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.<p></p> <b>Objective:</b> To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or genes that may be reactivated in CRPC.<p></p> <b>Design, setting, and participants:</b> RNA sequencing (RNA-seq) was performed on tumour-rich, targeted prostatic biopsies from seven patients with locally advanced or metastatic PCa before and approximately 22 wk after ADT initiation. Differentially regulated genes were identified in treatment pairs and further investigated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) on cell lines and immunohistochemistry on a separate CRPC patient cohort. Functional assays were used to determine the effect of pathway modulation on cell phenotypes.<p></p> <b>Outcome measurements and statistical analysis:</b> We searched for gene expression changes affecting key cell signalling pathways that may be targeted as proof of principle in a CRPC in vitro cell line model.<p></p> <b>Results and limitations:</b> We identified ADT-regulated signalling pathways, including the Wnt/β-catenin signalling pathway, and observed overexpression of β-catenin in a subset of CRPC by immunohistochemistry. We validated 6 of 12 (50%) pathway members by qRT-PCR on LNCaP/LNCaP-AI cell RNAs, of which 4 (67%) demonstrated expression changes consistent with RNA-seq data. We show that the tankyrase inhibitor XAV939 (which promotes β-catenin degradation) reduced androgen-independent LNCaP-AI cell line growth compared with androgen-responsive LNCaP cells via an accumulation of cell proportions in the G0/G1 phase and reduction in the S and G2/M phases. Our biopsy protocol did not account for tumour heterogeneity, and pathway inhibition was limited to pharmacologic approaches.<p></p> <b>Conclusions:</b> RNA-seq of paired PCa samples revealed ADT-regulated signalling pathways. Proof-of-principle inhibition of the Wnt/β-catenin signalling pathway specifically delays androgen-independent PCa cell cycle progression and proliferation and warrants further investigation as a potential target for therapy for CRPC.<p></p&gt

Validation of the HADRIAN system with a train station design case study

The HADRIAN (Human Anthropometric Data Requirements Investigation & Analysis) human modelling system is under development at Loughborough University as part of the EPSRC funded AUNT-SUE (Accessibility and User Needs in Transport for Sustainable Urban Environments) project. The HADRIAN system aims to foster a ‘design for all’ ethos by allowing ergonomists and designers to see the effects of different kinds of disability on the physical capabilities of elderly and disabled people. This system is based upon the long established SAMMIE system (System for Aiding Man Machine Interaction Evaluation), and uses data collected from 102 elderly and disabled individuals (Joint range of motion and anthropometry, ability to use steps and stairs, lifts escalators etc.). The HADRIAN system allows three dimensional CAD data of new products to be imported, with subsequent analysis using all of 102 sample members. The 102 sample includes a stature range of 1st% UK female to 99th%ile UK male, and also includes a range of disabilities that have been assessed using scales from Martin et al (1994). In this way the needs of people with specific conditions, such as arthritis, can be demonstrated and where possible, design accommodation can be improved. This paper describes the validation activity that is underway with the HADRIAN system. The validation reflects the transport focus of the AUNT SUE project by using HADRIAN to analyse the user interaction points that people encounter when using the Docklands Light Railway in London. This includes the use of ticket machines, the use of the train station infrastructure such as lifts and steps and stairs, and the use of ATMs to obtain cash. The validation is being performed by comparing the predicted results from HADRIAN and the abilities of users when performing real life tasks such as retrieving a ticket from a machine, or pressing a floor button when in a lift

A design ergonomics approach to accessibility and user needs in transport

This paper describes research carried out into the area of accessibility and 'design for all'. The Accessibility and User Needs in Transport (AUNT-SUE) project was initiated to develop and test sustainable policies and practice that would deliver effective socially inclusive design and operation in transport and the public realm. Loughborough University's role in the project focuses on the provision of data on users that is accessible, valid, and applicable and a means of utilising the data to assess the accessibility of designs during the early stages of development. These needs have led to the development of the authors' inclusive design tool called HADRIAN. Data were collected on 100 people the majority of whom are older or have some form of impairment. These data include size, shape, capability, preferences and experiences with a range of daily activities and transport related tasks. These are partnered with a simple task analysis system. The system supports the construction of a task linked to a CAD model of a design to be evaluated. The task is then carried out by the virtual individuals in the database. Accessibility issues are reported by the system allowing excluded people to be investigated. Thus HADRIAN supports designers and ergonomists in attempting to 'design for all' by fostering empathy with the intended users, meeting their data needs through an accessible and applicable database and providing a means of gaining some of the feedback possible with a real user trial at a much earlier stage in the design process

The psychological stress perspective: a unifying view of accessibility in public transport and beyond

Making public transport accessible to all is important because of its role in social inclusion and environmental sustainability. The UK public transport network is a complex system with a multitude of operators providing services on different scales with different vehicles. A single journey can put a variety of demands on a person wishing to travel and these demands that can exclude people from using public transport take many different forms. A range of physical, sensory, cognitive, and emotional factors effect how people with different of abilities, ages, genders, ethnicities and socioeconomic status use public transport. This complexity makes the task of assessing access to the system problematic. This paper proposes that all the factors that contribute to people’s non-participation in public transport and other human systems can be regarded as stressors. Psychological stress theory provides a language to explain exclusion and a unifying perspective with which all accessibility barriers can be viewed in the same way. A method called Human System Stressor Analysis (HSSA) has been devised to identify, assess and compare stressors that are found in a system. An example of HSSA being applied to public transport use is provided. This was used to identify an opportunity for a product design solution and led to the design of a journey planning kiosk. An understanding of psychological stress was applied throughout the design process with two new tools used to inform design decisions: the Panic Matrix to generate empathy and STUD Tables (Stressors as a function of Time, Uncertainty and Difficulty) to compare alternative solutions. The AUNT-SUE (Accessibility and User Needs in Transport for Sustainable Urban Environments) project is currently developing a tool that applies the stress perspective to journey accessibility assessment. This tool is intended to model journey stress for a range of individual people in the HADRIAN (Human Anthropometric Data Requirements Investigation and Analysis) database. Finally it is suggested that the psychological stress perspective could be used as a unifying measure throughout ergonomics, the potential benefits and problems with this approach are discussed and opportunities for further research to establish its validity and practicality are identified

Digital human modelling for virtual fitting trials

A recognised difficulty with the conventional use of Digital Human Modelling (DHM) systems is that they typically use percentile data to describe anthropometry and joint constraints. Hence any model is a synthesis of the set of data rather than a representation of any particular human. Implicit in this is that an acceptable degree of correlation exists between body dimensions whereas it has long been known that only weak correlations exist. The consequences are obvious in that products are designed/evaluated against models of humans that do not exist. An alternative approach is to use pre-defined families of manikins that together ‘enclose’ and represent the necessary diversity of human form. In the real world, rather than the digital world, ergonomists use real people in ‘fitting trials’. These people might be selected on the basis of the need for diversity covering the range of anthropometry that is thought necessary for the product evaluation but the practical considerations rarely allow an exhaustive evaluation. This paper describes an amalgam of the two approaches where the anthropometry and other aspects of more than 150 people has been collected experimentally. This data is used within the HADRIAN system as discrete sets of data rather than as the basis for a percentile representation. i.e. the data is maintained as sets relating to each individual and used to construct digital models of individuals. This is combined with a task description language that is used to drive the product or workplace evaluation in a way that is analogous to a physical fitting trial. The approach is being used within AUNT-SUE (Accessibility and User Needs in Transport – Sustainable Urban Environments) a wide–ranging research project looking at exclusion in public transport systems. The use of the HADRIAN approach is illustrated through a focus on the creation of a journey planner that meets the needs of a diverse range of people including the elderly and disabled

Proinsulin Secretion Is a Persistent Feature of Type 1 Diabetes

OBJECTIVE: Abnormally elevated proinsulin secretion has been reported in type 2 and early type 1 diabetes when significant C-peptide is present. We questioned whether individuals with long-standing type 1 diabetes and low or absent C-peptide secretory capacity retained the ability to make proinsulin. RESEARCH DESIGN AND METHODS: C-peptide and proinsulin were measured in fasting and stimulated sera from 319 subjects with long-standing type 1 diabetes (≥3 years) and 12 control subjects without diabetes. We considered three categories of stimulated C-peptide: 1) C-peptide positive, with high stimulated values ≥0.2 nmol/L; 2) C-peptide positive, with low stimulated values ≥0.017 but <0.2 nmol/L; and 3) C-peptide <0.017 nmol/L. Longitudinal samples were analyzed from C-peptide-positive subjects with diabetes after 1, 2, and 4 years. RESULTS: Of individuals with long-standing type 1 diabetes, 95.9% had detectable serum proinsulin (>3.1 pmol/L), while 89.9% of participants with stimulated C-peptide values below the limit of detection (<0.017 nmol/L; n = 99) had measurable proinsulin. Proinsulin levels remained stable over 4 years of follow-up, while C-peptide decreased slowly during longitudinal analysis. Correlations between proinsulin with C-peptide and mixed-meal stimulation of proinsulin were found only in subjects with high stimulated C-peptide values (≥0.2 nmol/L). Specifically, increases in proinsulin with mixed-meal stimulation were present only in the group with high stimulated C-peptide values, with no increases observed among subjects with low or undetectable (<0.017 nmol/L) residual C-peptide. CONCLUSIONS: In individuals with long-duration type 1 diabetes, the ability to secrete proinsulin persists, even in those with undetectable serum C-peptide

Benchtop magnetic shielding for benchmarking atomic magnetometers

Here, a benchtop hybrid magnetic shield containing four mumetal cylinders and nine internal flexible printed circuit boards is designed, constructed, tested, and operated. The shield is designed specifically as a test-bed for building and operating ultra-sensitive quantum magnetometers. The geometry and spacing of the mumetal cylinders are optimized to maximize shielding efficiency while maintaining Johnson noise $<15$ fT/$\sqrt{}$Hz. Experimental measurements at the shield's center show passive shielding efficiency of $\left(1.0\pm0.1\right){\times}10^6$ for a $0.2$ Hz oscillating field applied along the shield's axis. The nine flexible printed circuit boards generate three uniform fields, which all deviate from perfect uniformity by ${\leq}0.5$% along $50$% of the inner shield axis, and five linear field gradients and one second-order gradient, which all deviate by ${\leq}4$% from perfect linearity and curvature, respectively, over measured target regions. Together, the target field amplitudes are adjusted to minimize the remnant static field along $40$% of the inner shield axis, as mapped using an atomic magnetometer. In this region, the active null reduces the norm of the magnitudes of the three uniform fields and six gradients by factors of $19.5$ and $19.8$, respectively, thereby reducing the total static field from $1.68$ nT to $0.23$ nT.Comment: 8 pages, 9 figures; This work has been submitted to the IEEE for possible publication. Copyright may be transferred without notice, after which this version may no longer be accessibl

Family day care educators : an exploration of their understanding and experiences promoting children\u27s social and emotional wellbeing

This study aimed to explore family day care (FDC) educators&rsquo; knowledge of child social and emotional wellbeing and mental health problems, the strategies used to promote children&rsquo;s wellbeing, and barriers and opportunities for promoting children&rsquo;s social and emotional wellbeing. Thirteen FDC educators participated in individual semi-structured interviews. FDC educators were more comfortable defining children&rsquo;s social and emotional wellbeing than they were in identifying causes and early signs of mental health problems. Strategies used to promote children&rsquo;s mental health were largely informal and dependent on educator skills and capacities rather than a systematic scheme-wide approach. Common barriers to mental health promotion were limited financial resources, a need for more training and hesitance raising child mental health issues with parents. There is a need to build FDC educators&rsquo; knowledge of child social and emotional wellbeing and for tailored mental health promotion strategies in FDC.<br /

Cenozoic Antarctic DiatomWare/BugCam: An aid for research and teaching

Cenozoic Antarctic DiatomWare/BugCam© is an interactive, icon-driven digital-imagedatabase/software package that displays over 500 illustrated Cenozoic Antarctic diatom taxa along with original descriptions (including over 100 generic and 20 family-group descriptions). This digital catalog is designed primarily for use by micropaleontologists working in the field (at sea or on the Antarctic continent) where hard-copy literature resources are limited. This new package will also be useful for classroom/lab teaching as well as for any paleontologists making or refining taxonomic identifications at the microscope. The database (Cenozoic Antarctic DiatomWare) is displayed via a custom software program (BugCam) written in Visual Basic for use on PCs running Windows 95 or later operating systems. BugCam is a flexible image display program that utilizes an intuitive thumbnail “tree” structure for navigation through the database. The data are stored on Micrsosoft EXCEL spread sheets, hence no separate relational database program is necessary to run the package