People with aphasia creating an aphasia friendly website: The DMU4 experience

People with aphasia creating an aphasia friendly website: The DMU4 experience Bixley,M., DMU4, Hall, R., Weale, R., Collingwood, J., Marshall, F. & Hamilton, C. Background Information The DMU4 Conversation group is part of Aphasia Leicester; a community based, voluntary sector, long term support organisation for People with Aphasia (PWA). Members of DMU4 have experienced being unable to access information about their condition because of the way in which the information is presented. These personal experiences are supported by research such as the Care Quality Commission’s (2011) report that suggested that only 40% of social services in Britain provided information in an accessible way for PWA post stroke. In 2011, DMU4 created a leaflet about aphasia that was designed to be used in acute hospitals to educate stroke survivors, relatives and hospital staff about aphasia (Bixley et al, 2011). This leaflet has been distributed to hospitals, surgeries and Speech and Language Therapy Departments in Leicestershire and Rutland. Last year DMU4 decided that they would like to embark on a new project; creating a website about aphasia that was also accessible to PWA. Method The group decided that there were three main factors that needed to guide the construction and structure of the website. Firstly, people with aphasia would appear on the website as aphasia experts. Secondly, navigation around the website should be aphasia friendly, based on visual images and accessible written language. Lastly, members of DMU4 would retain copyright over their own images. For this reason, the site was hosted on “Our DMU Commons” a self organising space that allows users to co construct their own website using open source software. The content of the website was agreed through group discussions. Following these discussions, nine DMU4 members attended a whole day filming session in which their perceptions of aphasia were recorded. Films were then transcribed and edited into eleven themes using a grounded approach. Skeat & Perry (2007) suggest this approach is useful when investigating information that is not available anywhere else, such as the information presented in this website. Informed consent was elicited through discussions, meetings, film and website screenings and signed agreement. Results and discussion The DMU4 website project has two tangible outcomes. The first is that the site will be available to people who want to learn about aphasia. The second is that the resource will be available for Speech and Language Therapy students. Learning activities will enable students to practise recognising and understand aphasia from the perspective of those who live with the loss of language post stroke. The practices of DMU4 are rooted firmly in the social approach to aphasia therapy (Pound, Parr, Lindsay and Woolf, 2000). It is hoped that the website’s third, less measurable, outcome will be a contribution to overcoming the attitudinal and informational barriers that are experienced by PWA post stoke. References BIXLEY, M., DMU4 & HAMILTON, C. (2011) Aphasia – an information leaflet designed by people with aphasia. British Aphasiology Society Biennial International Conference Book of Abstracts, 12. CARE QUALITY COMMISSION (2011) Supporting life after stroke: A review of services for people who have had a stroke and their carers. London: Care Quality Commission. SKEAT, J. & PERRY, A. (2008). Grounded theory as a method for research in speech and language therapy. International Journal of Language and Communication Disorders, 43, 2, 95-109. POUND, C., PARR, S., LINDSAY, J. & WOOLF, C. (2000) Beyond Aphasia: Therapies for Living with Communication Disability. Bicester: Winslow

On all possible static spherically symmetric EYM solitons and black holes

We prove local existence and uniqueness of static spherically symmetric solutions of the Einstein-Yang-Mills equations for any action of the rotation group (or SU(2)) by automorphisms of a principal bundle over space-time whose structure group is a compact semisimple Lie group G. These actions are characterized by a vector in the Cartan subalgebra of g and are called regular if the vector lies in the interior of a Weyl chamber. In the irregular cases (the majority for larger gauge groups) the boundary value problem that results for possible asymptotically flat soliton or black hole solutions is more complicated than in the previously discussed regular cases. In particular, there is no longer a gauge choice possible in general so that the Yang-Mills potential can be given by just real-valued functions. We prove the local existence of regular solutions near the singularities of the system at the center, the black hole horizon, and at infinity, establish the parameters that characterize these local solutions, and discuss the set of possible actions and the numerical methods necessary to search for global solutions. That some special global solutions exist is easily derived from the fact that su(2) is a subalgebra of any compact semisimple Lie algebra. But the set of less trivial global solutions remains to be explored.Comment: 26 pages, 2 figures, LaTeX, misprints corrected, 1 reference adde

Feasibility and Informative Value of Environmental Sample Collection in the National Children\u27s Vanguard Study

Background: Birth cohort studies provide the opportunity to advance understanding of the impact of environmental factors on childhood health and development through prospective collection of environmental samples. Methods: We evaluated the feasibility and informative value of the environmental sample collection methodology in the initial pilot phase of the National Children\u27s Study, a planned U.S. environmental birth cohort study. Environmental samples were collected from January 2009–September 2010 at up to three home visits: pre-pregnancy (n¼306), pregnancy (n¼807), and 6-months postnatal (n¼117). Collections included air for particulate matter r2.5 mm (PM2.5), nitrogen dioxide, ozone, volatile organic compounds (VOCs), and carbonyls; vacuum dust for allergens/endotoxin; water for VOCs, trihalomethanes (THMs), and haloacetic acids (HAAs); and wipe samples for pesticides, semi-volatile organics, and metals. We characterized feasibility using sample collection rates and times and informative value using analyte detection frequencies (DF). Results: Among the 1230 home visits, environmental sample collection rates were high across all sample types (mean¼89%); all samples except the air PM2.5 samples had collection times o30 min. Informative value was low for water VOCs (median DF¼0%) and pesticide floor wipes (median DF¼5%). Informative value was moderate for air samples (median DF¼35%) and high for water THMs and HAAs (median DF¼91% and 75%, respectively). Conclusions: Though collection of environmental samples was feasible, some samples (e.g., wipe pesticides and water VOCs) yielded limited information. These results can be used in conjunction with other study design considerations, such as target population size and hypotheses of interest, to inform the method selection of future environmental health birth cohort studies

Solid-phase synthesis of duocarmycin analogues and the effect of C-terminal substitution on biological activity

YesThe duocarmycins are potent antitumour agents with potential in the development of antibody drug conjugates (ADCs) as well as being clinical candidates in their own right. In this paper, we describe the synthesis of a duocarmycin monomer (DSA) that is suitably protected for utilisation in solid phase synthesis. The synthesis was performed on a large scale and the resulting racemic protected Fmoc-DSA subunit was separated by supercritical fluid chromatography (SFC) into the single enantiomers. Application to solid phase synthesis methodology gave a series of monomeric and extended duocarmycin analogues with amino acid substituents. The DNA sequence selectivity was similar to previous reports for both the monomeric and extended compounds. The substitution at the C-terminus of the duocarmycin caused a decrease in antiproliferative activity for all of the compounds studied. An extended compound containing an alanine at the C-terminus was converted to the primary amide or to an extended structure containing a terminal tertiary amine but this had no beneficial effects on biological activity.MJS was funded by Novartis and UEA. We thank the EPSRC Mass Spectrometry Service, Swansea. We thank Richard Robinson and Julia Hatto at Novartis for help in the large scale synthesis

An exploration of the effectiveness of artificial mini-magnetospheres as a potential solar storm shelter for long term human space missions

If mankind is to explore the solar system beyond the confines of our Earth and Moon the problem of radiation protection must be addressed. Galactic cosmic rays and highly variable energetic solar particles are an ever-present hazard in interplanetary space. Electric and/or magnetic fields have been suggested as deflection shields in the past, but these treated space as an empty vacuum. In fact it is not empty. Space contains a plasma known as the solar wind; a constant flow of protons and electrons coming from the Sun. In this paper we explore the effectiveness of a “mini-magnetosphere” acting as a radiation protection shield. We explicitly include the plasma physics necessary to account for the solar wind and its induced effects. We show that, by capturing/containing this plasma, we enhance the effectiveness of the shield. Further evidence to support our conclusions can be obtained from studying naturally occurring “mini-magnetospheres” on the Moon. These magnetic anomalies (related to “lunar swirls”) exhibit many of the effects seen in laboratory experiments and computer simulations. If shown to be feasible, this technology could become the gateway to manned exploration of interplanetary space

Nilpotent orbits and codimension-two defects of 6d N=(2,0) theories

We study the local properties of a class of codimension-2 defects of the 6d N=(2,0) theories of type J=A,D,E labeled by nilpotent orbits of a Lie algebra \mathfrak{g}, where \mathfrak{g} is determined by J and the outer-automorphism twist around the defect. This class is a natural generalisation of the defects of the 6d theory of type SU(N) labeled by a Young diagram with N boxes. For any of these defects, we determine its contribution to the dimension of the Higgs branch, to the Coulomb branch operators and their scaling dimensions, to the 4d central charges a and c, and to the flavour central charge k.Comment: 57 pages, LaTeX2

Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features

The ‘neurodegeneration with brain iron accumulation’ (NBIA) disease family entails movement or cognitive impairment, often with psychiatric features. To understand how iron loading affects the brain, we studied mice with disruption of two iron regulatory genes, hemochromatosis (Hfe) and transferrin receptor 2 (Tfr2). Inductively coupled plasma atomic emission spectroscopy demonstrated increased iron in the Hfe-/- × Tfr2mut brain (P=0.002, n =5/group), primarily localized by Perls’ staining to myelinated structures. Western immunoblotting showed increases of the iron storage protein ferritin light polypeptide and microarray and real-time reverse transcription-PCR revealed decreased transcript levels (P<0.04, n =5/group) for five other NBIA genes, phospholipase A2 group VI, fatty acid 2-hydroxylase, ceruloplasmin, chromosome 19 open reading frame 12 and ATPase type 13A2. Apart from the ferroxidase ceruloplasmin, all are involved in myelin homeostasis; 16 other myelin-related genes also showed reduced expression (P<0.05), although gross myelin structure and integrity appear unaffected (P>0.05). Overlap (P<0.0001) of differentially expressed genes in Hfe-/- × Tfr2mut brain with human gene co-expression networks suggests iron loading influences expression of NBIA-related and myelin-related genes co-expressed in normal human basal ganglia. There was overlap (P<0.0001) of genes differentially expressed in Hfe-/- × Tfr2mut brain and post-mortem NBIA basal ganglia. Hfe-/- × Tfr2mut mice were hyperactive (P<0.0112) without apparent cognitive impairment by IntelliCage testing (P>0.05). These results implicate myelin-related systems involved in NBIA neuropathogenesis in early responses to iron loading. This may contribute to behavioral symptoms in NBIA and hemochromatosis and is relevant to patients with abnormal iron status and psychiatric disorders involving myelin abnormalities or resistant to conventional treatments

Gene co-expression networks shed light into diseases of brain iron accumulation

Aberrant brain iron deposition is observed in both common and rare neurodegenerative disorders, including those categorized as Neurodegeneration with Brain Iron Accumulation (NBIA), which are characterized by focal iron accumulation in the basal ganglia. Two NBIA genes are directly involved in iron metabolism, but whether other NBIA-related genes also regulate iron homeostasis in the human brain, and whether aberrant iron deposition contributes to neurodegenerative processes remains largely unknown. This study aims to expand our understanding of these iron overload diseases and identify relationships between known NBIA genes and their main interacting partners by using a systems biology approach. We used whole-transcriptome gene expression data from human brain samples originating from 101 neuropathologically normal individuals (10 brain regions) to generate weighted gene co-expression networks and cluster the 10 known NBIA genes in an unsupervised manner. We investigated NBIA-enriched networks for relevant cell types and pathways, and whether they are disrupted by iron loading in NBIA diseased tissue and in an in vivo mouse model. We identified two basal ganglia gene co-expression modules significantly enriched for NBIA genes, which resemble neuronal and oligodendrocytic signatures. These NBIA gene networks are enriched for iron-related genes, and implicate synapse and lipid metabolism related pathways. Our data also indicates that these networks are disrupted by excessive brain iron loading. We identified multiple cell types in the origin of NBIA disorders. We also found unforeseen links between NBIA networks and iron-related processes, and demonstrate convergent pathways connecting NBIAs and phenotypically overlapping diseases. Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention

Classifying supersymmetric solutions in 3D maximal supergravity

The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS) 10.13039/501100001691. This work is part of the research programme of the Foundation for Fundamental Research on Matter (FOM) 10.13039/ 501100003404, which is part of the Netherlands Organization for Scientific Research (NWO).The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS) 10.13039/501100001691. This work is part of the research programme of the Foundation for Fundamental Research on Matter (FOM) 10.13039/ 501100003404, which is part of the Netherlands Organization for Scientific Research (NWO).The work of MS was supported in part by Grant-in-Aid for Young Scientists (B) 24740159 from the Japan Society for the Promotion of Science (JSPS) 10.13039/501100001691. This work is part of the research programme of the Foundation for Fundamental Research on Matter (FOM) 10.13039/ 501100003404, which is part of the Netherlands Organization for Scientific Research (NWO

Cohort profile: Scottish Health and Ethnicity Linkage Study of 4.65 million people exploring ethnic variations in disease in Scotland

Many countries require health services to show that they are meeting the needs of ethnic minority populations. This requires data on health status, healthcare uptake and outcomes and population denominators. Weaknesses in routine data collection often make such requirements difficult to meet. Routine data sources in Scotland, as in most countries, may not include a patient’s ethnicity. In Scotland, the need for such data is driven by both policy and legislation responding to rapidly increasing ethnic diversity. Fair For All (2003), Scotland’s policy, provides a strategic approach to improve the health of minority ethnic groups. The UK Race Relations (Amendment) Act (2000) placed a duty on public bodies to promote racial equality. These mandates are reflected in guidance on ethnic monitoring. Appropriate service and research is undermined by the lack of data. Ethnic variations occur in all of Scotland’s national health priority areas, including coronary heart disease/stroke, cancer, maternal and child health and mental health. In view of the mismatch between need for and availability of data by ethnic group, Bhopal proposed a demonstration project to explore retrospective approaches. The project tested proposals including name search methods, analyses by country of birth, modelling/extrapolation from other nations’ datasets, and linkage methods. The demonstration project concluded that census health records linkage methods— in the context of this project first mooted by Povey— held most promise. To our knowledge, attempting matching of a national health dataset to a complete national census using demographic identifiers rather than national identity numbers had not been reported though health data linkage is well-established in the UK and internationally, including exploring ethnicity and health