Early modern Oxford bindings in twenty-first century markup

Purpose – The Bodleian Binders Book contains nearly 150 pages of seventeenth century library records, revealing information about the binders used by the library and the thousands of bindings they produced. The purpose of this paper is to explore a pilot project to survey and record bindings information contained in the Binders Book. Design/methodology/approach – A sample size of seven pages (91 works, 65 identifiable bindings) to develop a methodology for surveying and recording bindings listed in the manuscript. To create a successful product that would be useful to bindings researchers, it addressed questions of bindings terminology and the role of the library in the knowledge creation process within the context that text encoding is changing the landscape of library functions. Text encoding formats were examined, and a basic TEI (Text Encoding Initiative) transcription was produced. This facilitates tagging of names and titles and the display of transcriptions with text images. Findings – Encoding was found not only to make the manuscript content more accessible, but to allow for the construction of new knowledge: characteristic Oxford binding traits were revealed and bindings were matched to binders. Plans for added functionality were formed. Originality/value – This research presents a “big picture” analysis of Oxford bindings as a result of text encoding and the foundation for qualitative and statistical analysis. It exemplifies the benefits of interdisciplinary methods – in this case from Digital Humanities – to enhance access to and interpretation of specialist materials and the library's provenance record

The Neuromodulator Adenosine Regulates Oligodendrocyte Migration at Motor Exit Point Transition Zones

During development, oligodendrocyte progenitor cells (OPCs) migrate extensively throughout the spinal cord. However, their migration is restricted at transition zones (TZs). At these specialized locations, unique glial cells in both zebrafish and mice play a role in preventing peripheral OPC migration, but the mechanisms of this regulation are not understood. To elucidate the mechanisms that mediate OPC segregation at motor exit point (MEP) TZs, we performed an unbiased small-molecule screen. Using chemical screening and in vivo imaging, we discovered that inhibition of A2a adenosine receptors (ARs) causes ectopic OPC migration out of the spinal cord. We provide in vivo evidence that neuromodulation, partially mediated by adenosine, influences OPC migration specifically at the MEP TZ. This work opens exciting possibilities for understanding how OPCs reach their final destinations during development and identifies mechanisms that could promote their migration in disease

Evaluating Tradeoffs Between Hazard-Resistance and Environmental Impacts: a Multi-Criteria Approach to Building Design and Life Cycle Performance

Principles of green building design and hazard-resistant design are often employed individually to enhance building performance, but for different objectives and evaluated with different units of measurement. At a fundamental level, however, hazard resistant design and green building design are motivated by shared principles and evaluated with shared assessment tools, although often with outcomes presented in different units of measurement. The goal of this research is to quantify the influence of hazard resistant design principles on green building performance—namely, life cycle environmental impact—and, conversely, to quantify the influence of green building design principles on hazard resilience, focused here on seismic performance. This dissertation represents a compilation of three studies that combine to evaluate and quantify how a) structural design principles for hazard resistance influence life cycle environmental impacts of a building and b) principles of green building design influence building hazard-resistance. Each chapter examines the life cycle environmental impacts and seismic performance of a series of code-conforming, reinforced concrete office buildings in southern Los Angeles, varied with respect to non-structural green building features, structural frame and member configurations, and structural concrete properties. When taken together, the results of each study provide insight into the tradeoffs and synergies between life cycle hazard performance and environmental impact. The results also support broader goals for the intersection of hazard-resistant and green design, not limited in application to buildings (nor only reinforced concrete as a structural material). A key methodological contribution of this dissertation is development of an innovative approach that transforms building component damage fragilities into specific material volumes for post-hazard component restoration and then translates these material quantities into distributions of post-hazard environmental impacts. Finally, this dissertation applies the concepts of multi-objective analysis and life cycle assessment to evaluate the multi-metric, systems-based nature of building design, construction, operation, and performance in the 21st century

Evaluating Tradeoffs Between Hazard-Resistance and Environmental Impacts: a Multi-Criteria Approach to Building Design and Life Cycle Performance

Principles of green building design and hazard-resistant design are often employed individually to enhance building performance, but for different objectives and evaluated with different units of measurement. At a fundamental level, however, hazard resistant design and green building design are motivated by shared principles and evaluated with shared assessment tools, although often with outcomes presented in different units of measurement. The goal of this research is to quantify the influence of hazard resistant design principles on green building performance&mdash;namely, life cycle environmental impact&mdash;and, conversely, to quantify the influence of green building design principles on hazard resilience, focused here on seismic performance. This dissertation represents a compilation of three studies that combine to evaluate and quantify how a) structural design principles for hazard resistance influence life cycle environmental impacts of a building and b) principles of green building design influence building hazard-resistance. Each chapter examines the life cycle environmental impacts and seismic performance of a series of code-conforming, reinforced concrete office buildings in southern Los Angeles, varied with respect to non-structural green building features, structural frame and member configurations, and structural concrete properties. When taken together, the results of each study provide insight into the tradeoffs and synergies between life cycle hazard performance and environmental impact. The results also support broader goals for the intersection of hazard-resistant and green design, not limited in application to buildings (nor only reinforced concrete as a structural material). A key methodological contribution of this dissertation is development of an innovative approach that transforms building component damage fragilities into specific material volumes for post-hazard component restoration and then translates these material quantities into distributions of post-hazard environmental impacts. Finally, this dissertation applies the concepts of multi-objective analysis and life cycle assessment to evaluate the multi-metric, systems-based nature of building design, construction, operation, and performance in the 21st century.</p

Measuring the impact and costs of a universal group based parenting programme : protocol and implementation of a trial

Background Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. Methods/Design A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. Discussion Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these

Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention

Correlating Remote Sensing Data with the Abundance of Pupae of the Dengue Virus Mosquito Vector, Aedes aegypti, in Central Mexico

Using a geographic transect in Central Mexico, with an elevation/climate gradient, but uniformity in socio-economic conditions among study sites, this study evaluates the applicability of three widely-used remote sensing (RS) products to link weather conditions with the local abundance of the dengue virus mosquito vector, Aedes aegypti (Ae. aegypti). Field-derived entomological measures included estimates for the percentage of premises with the presence of Ae. aegypti pupae and the abundance of Ae. aegypti pupae per premises. Data on mosquito abundance from field surveys were matched with RS data and analyzed for correlation. Daily daytime and nighttime land surface temperature (LST) values were obtained from Moderate Resolution Imaging Spectroradiometer (MODIS)/Aqua cloud-free images within the four weeks preceding the field survey. Tropical Rainfall Measuring Mission (TRMM)-estimated rainfall accumulation was calculated for the four weeks preceding the field survey. Elevation was estimated through a digital elevation model (DEM). Strong correlations were found between mosquito abundance and RS-derived night LST, elevation and rainfall along the elevation/climate gradient. These findings show that RS data can be used to predict Ae. aegypti abundance, but further studies are needed to define the climatic and socio-economic conditions under which the correlations observed herein can be assumed to apply

Seismic Vulnerability of Hillside Buildings in Northeast India

In northeast India, rapid urbanization and limited available land leads to the construction of multi-story, reinforced concrete frames with masonry infill walls on steep hillsides with weak soils. This thesis analyzes the seismic performance of archetypical hillside reinforced concrete buildings with stepped foundations in Aizawl, Mizoram using the results of incremental dynamic analysis to quantify collapse risk and identify potential failure mechanisms. The findings show that shear critical columns exacerbate structural vulnerabilities created by stepped hillside configurations. In an earthquake, structural failure likely will begin with axial failure of the half-length base columns at the top of the slope, followed by sequential failures in downslope columns. Collapse is predicted to occur from exceedance of column shear capacity in stories supported by half-length columns on stepped, not flat, foundations. The findings demonstrate that improved column shear capacity and above-code detailing may mitigate the seismic vulnerability of Aizawl’s hillside reinforced concrete buildings

Virus-like particles: A flexible platform for universal influenza vaccine development

Human influenza remains a global public health threat, namely due to its evolutionary adaptability, which hinders effective prevention. Vaccination is currently the predominant tool in the prevention of infectious disease. However, current production methods for influenza vaccines are not only logistically inadequate in the face of a pandemic, but also rely on targeting two surface proteins on the influenza virus, which are prone to antigenic drift. As a consequence, a new vaccine needs to be developed for each new seasonal epidemic. Additionally, the vaccine strain needs to be selected around eight months prior to administration and can often be mismatched leaving the population unprotected. A ‘universal’ vaccine, effective irrespective of the surface proteins, would be desirable to offer cross-protectivity across strains. Tandem core virus-like particles (VLPs), expressed in methylotrophic yeast Pichia pastoris, are an exciting alternative to current manufacturing methods. VLPs, due to their inherent safety profile and advances in genetic engineering, have excellent potential both as standalone vaccines for the virus from which they are derived, or as platforms for the display of foreign antigens. The hepatitis B core antigen (HBcAg) is able to spontaneously self-assemble, forming icosahedral particles that are inherently immunogenic. Moreover, the HBcAg is capable of carrying antigen inserts in the major insertion region (MIR) which are displayed on the particle surface. In order for VLPs to be considered a viable alternative, their bioprocessing must be optimized. Currently, various issues are at play including problems with formation, solubility and immunogenicity, often clone dependent. In this work, two genetically linked HBcAg monomers, carrying different inserts in the MIR, were used to study the effects on fermentation efficiencies using two different induction strategies. Rationalizing an induction strategy would enable the development of an efficient process to produce and purify VLPs. Results indicate that increased biomass is not always synonymous with increased protein expression. Moreover, protein expression and solubility appear to be linked with the complexity of the inserts displayed on the VLP surface. The aim of this work is to improve the bioprocessing of VLPs in a microbial expression system, using tandem core technology. This proposed method is cheap and rapidly scalable, reduces the cost per dose and eliminates the long production timelines associated with current manufacturing. The very nature of VLPs and the comparable ease of production would enable this to be promoted as a platform process, for a myriad of disease targets