Managing chronic widespread pain in primary care : a qualitative study of patient perspectives and implications for treatment delivery

Funding The MUSICIAN trial was supported by an award from Arthritis Research UK, Chesterfield, UK. Grant number: 17292. The funding body approved the design of the study. They played no role in the collection, analysis, and interpretation of data or the writing of the manuscript.

Identifying the Structure and Fate of Wastewater Derived Organic Micropollutants by High-resolution Mass Spectrometry

Human activities represent a significant burden on the global water cycle, with large and increasing demands placed on limited water resources by manufacturing, energy production and domestic water use. In addition to changing the quantity of available water resources, human activities lead to changes in water quality by introducing a large and often poorly-characterized array of chemical pollutants, which may negatively impact biodiversity in aquatic ecosystems, leading to impairment of valuable ecosystem functions and services. Domestic and industrial wastewaters represent a significant source of pollution to the aquatic environment due to inadequate or incomplete removal of chemicals introduced into waters by human activities. Currently, incomplete chemical characterization of treated wastewaters limits comprehensive risk assessment of this ubiquitous impact to water. In particular, a significant fraction of the organic chemical composition of treated industrial and domestic wastewaters remains uncharacterized at the molecular level. Efforts aimed at reducing the impacts of water pollution on aquatic ecosystems critically require knowledge of the composition of wastewaters to develop interventions capable of protecting our precious natural water resources.

The goal of this dissertation was to develop a robust, extensible and high-throughput framework for the comprehensive characterization of organic micropollutants in wastewaters by high-resolution accurate-mass mass spectrometry. High-resolution mass spectrometry provides the most powerful analytical technique available for assessing the occurrence and fate of organic pollutants in the water cycle. However, significant limitations in data processing, analysis and interpretation have limited this technique in achieving comprehensive characterization of organic pollutants occurring in natural and built environments. My work aimed to address these challenges by development of automated workflows for the structural characterization of organic pollutants in wastewater and wastewater impacted environments by high-resolution mass spectrometry, and to apply these methods in combination with novel data handling routines to conduct detailed fate studies of wastewater-derived organic micropollutants in the aquatic environment.

In Chapter 2, chemoinformatic tools were implemented along with novel non-targeted mass spectrometric analytical methods to characterize, map, and explore an environmentally-relevant “chemical space” in municipal wastewater. This was accomplished by characterizing the molecular composition of known wastewater-derived organic pollutants and substances that are prioritized as potential wastewater contaminants, using these databases to evaluate the pollutant-likeness of structures postulated for unknown organic compounds that I detected in wastewater extracts using high-resolution mass spectrometry approaches. Results showed that application of multiple computational mass spectrometric tools to structural elucidation of unknown organic pollutants arising in wastewaters improved the efficiency and veracity of screening approaches based on high-resolution mass spectrometry. Furthermore, structural similarity searching was essential for prioritizing substances sharing structural features with known organic pollutants or industrial and consumer chemicals that could enter the environment through use or disposal.

I then applied this comprehensive methodological and computational non-targeted analysis workflow to micropollutant fate analysis in domestic wastewaters (Chapter 3), surface waters impacted by water reuse activities (Chapter 4) and effluents of wastewater treatment facilities receiving wastewater from oil and gas extraction activities (Chapter 5). In Chapter 3, I showed that application of chemometric tools aided in the prioritization of non-targeted compounds arising at various stages of conventional wastewater treatment by partitioning high dimensional data into rational chemical categories based on knowledge of organic chemical fate processes, resulting in the classification of organic micropollutants based on their occurrence and/or removal during treatment. Similarly, in Chapter 4, high-resolution sampling and broad-spectrum targeted and non-targeted chemical analysis were applied to assess the occurrence and fate of organic micropollutants in a water reuse application, wherein reclaimed wastewater was applied for irrigation of turf grass. Results showed that organic micropollutant composition of surface waters receiving runoff from wastewater irrigated areas appeared to be minimally impacted by wastewater-derived organic micropollutants. Finally, Chapter 5 presents results of the comprehensive organic chemical composition of oil and gas wastewaters treated for surface water discharge. Concurrent analysis of effluent samples by complementary, broad-spectrum analytical techniques, revealed that low-levels of hydrophobic organic contaminants, but elevated concentrations of polymeric surfactants, which may effect the fate and analysis of contaminants of concern in oil and gas wastewaters.

Taken together, my work represents significant progress in the characterization of polar organic chemical pollutants associated with wastewater-impacted environments by high-resolution mass spectrometry. Application of these comprehensive methods to examine micropollutant fate processes in wastewater treatment systems, water reuse environments, and water applications in oil/gas exploration yielded new insights into the factors that influence transport, transformation, and persistence of organic micropollutants in these systems across an unprecedented breadth of chemical space.

Occurrence and Function of Hoogsteen Base Pairs in Nucleic Acids

Nucleic acids (DNA and RNA) play essential roles in the central dogma of biology for the storage and transfer of genetic information. The unique chemical and conformational structures of nucleic acids – the double helix composed of complementary Watson-Crick base pairs, provide the structural basis to carry out their biological functions. DNA double helix can dynamically accommodate Watson-Crick and Hoogsteen base-pairing, in which the purine base is flipped by ~180° degrees to adopt syn rather than anti conformation as in Watson-Crick base pairs. There is growing evidence that Hoogsteen base pairs play important roles in DNA replication, recognition, damage or mispair accommodation and repair. Here, we constructed a database for existing Hoogsteen base pairs in DNA duplexes by a structure-based survey from the Protein Data Bank, and structural analyses based on the resulted Hoogsteen structures revealed that Hoogsteen base pairs occur in a wide variety of biological contexts and can induce DNA kinking towards the major groove. As there were documented difficulties in modeling Hoogsteen or Watson-Crick by crystallography, we collaborated with the Richardsons’ lab and identified potential Hoogsteen base pairs that were mis-modeled as Watson-Crick base pairs which suggested that Hoogsteen can be more prevalent than it was thought to be. We developed solution NMR method combined with the site-specific isotope labeling to characterize the formation of, or conformational exchange with Hoogsteen base pairs in large DNA-protein complexes under solution conditions, in the absence of the crystal packing force. We showed that there are enhanced chemical exchange, potentially between Watson-Crick and Hoogsteen, at a sharp kink site in the complex formed by DNA and the Integration Host Factor protein. In stark contrast to B-form DNA, we found that Hoogsteen base pairs are strongly disfavored in A-form RNA duplex. Chemical modifications N1-methyl adenosine and N1-methyl guanosine that block Watson-Crick base-pairing, can be absorbed as Hoogsteen base pairs in DNA, but rather potently destabilized A-form RNA and caused helix melting. The intrinsic instability of Hoogsteen base pairs in A-form RNA endows the N1-methylation as a functioning post-transcriptional modification that was known to facilitate RNA folding, translation and potentially play roles in the epitranscriptome. On the other hand, the dynamic property of DNA that can accommodate Hoogsteen base pairs could be critical to maintaining the genome stability.

Modern major element concentrations and ratios measured in Atlantic surface sediments (36°N-49°S)

Numerous studies use major element concentrations measured on continental margin sediments to reconstruct terrestrial climate variations. The choice and interpretation of climate proxies however differ from site to site. Here we map the concentrations of major elements (Ca, Fe, Al, Si, Ti, K) in Atlantic surface sediments (36°N-49°S) to assess the factors influencing the geochemistry of Atlantic hemipelagic sediments and the potential of elemental ratios to reconstruct different terrestrial climate regimes. High concentrations of terrigenous elements and low Ca concentrations along the African and South American margins reflect the dominance of terrigenous input in these regions. Single element concentrations and elemental ratios including Ca (e.g., Fe/Ca) are too sensitive to dilution effects (enhanced biological productivity, carbonate dissolution) to allow reliable reconstructions of terrestrial climate. Other elemental ratios reflect the composition of terrigenous material and mirror the climatic conditions within the continental catchment areas. The Atlantic distribution of Ti/Al supports its use as a proxy for eolian versus fluvial input in regions of dust deposition that are not affected by the input of mafic rock material. The spatial distributions of Al/Si and Fe/K reflect the relative input of intensively weathered material from humid regions versus slightly weathered particles from drier areas. High biogenic opal input however influences the Al/Si ratio. Fe/K is sensitive to the input of mafic material and the topography of Andean river drainage basins. Both ratios are suitable to reconstruct African and South American climatic zones characterized by different intensities of chemical weathering in well-understood environmental settings.

(Table T1) Lithologic and ichnologic description of ODP Hole 174-1073A

When examined in their sedimentologic and stratigraphic context, ichnofabrics and component ichnofossils can help decipher paleoceanography and sea-level histories from marine deposits (Savrda, 1995, http://www.jstor.org/stable/3515095). Thus far, applications of ichnology in paleoceanographic investigations have been restricted to slowly deposited, predominantly biogenic sediments and/or strata deposited in oxygen-deficient, tectonically active basins. Moreover, ichnologic applications in sequence stratigraphic studies largely have been restricted to strata deposited in relatively shallow-water shelf or foreland basin settings. The limits of previous studies provided impetus for detailed postcruise examination of Quaternary deposits recovered at Ocean Drilling Program (ODP) Site 1073 on the New Jersey margin. These deposits provide the opportunity to assess the sedimentary and ichnofabric record of glacio-eustatic cycles in a passive continental slope setting characterized by relatively rapid accumulation of siliciclastic sediments in an area not far removed from the Laurentide ice margin. The primary purpose of this data report is to present basic sedimentologic and ichnologic observations made at the decimeter scale throughout the Quaternary sequence from Site 1073. Data analysis and interpretation in the context of climate and sea-level histories, as inferred from oxygen isotopic, palynologic, and seismic studies, are ongoing and will be presented in subsequent papers prepared for open literature (e.g., Savrda et al., in press).

Organizing and Interpreting Unstructured Qualitative Data

In the last several years there has been an increase in the amount of qualitative research using in-depth interviews and comprehensive content analyses in sport psychology. However, no explicit method has been provided to deal with the large amount of unstructured data. This article provides common guidelines for organizing and interpreting unstructured data. Two main operations are suggested and discussed: first, coding meaningful text segments, or creating tags, and second, regrouping similar text segments,or creating categories. Furthermore, software programs for the microcomputer are presented as away to facilitate the organization and interpretation of qualitative data

Defining ‘Community’ for Community Translation

Unlike community interpreting, community translation engages with the members of the community both at individual and group levels. This duality of the process makes the identification of the community as a socio-cultural entity and of its individual members all the more important. There have been several attempts to define the concept of ‘community’ in different professional and academic contexts. Mindful of the difficulty of defining community, the paper proposes three methods that can help community translators in visualizing the characteristics of the intended audience and in making informed translation decisions. The three methods, derived from user-centred translation, are scrutinized using a case study based on a real-life National Health Service (NHS) text.

Welcoming International Visitors - Communication and Culture

It is extremely rare for an international visitor to museums and galleries in the UK to find information in foreign languages which is anything more than a relatively literal translation of an English source text. At the same time, a huge body of research and theory in the humanities and social sciences implies that major cultural differences are likely to accompany the differences in first language of international visitors. As such, in spite of the fact that museums and galleries often declare their intention to meet the needs of their visitors, it is fairly clear that, in this instance, they are at best meeting their international visitors’ linguistic needs whilst ignoring their broader cultural needs. With this in mind, staff from the University of Westminster together with a number of London’s major museums and galleries obtained UK Research Council funding to work on the production of leaflets in foreign languages fully acknowledging cultural differences amongst international visitors. The collaboration was intended to generate reflection on how such materials might be most effectively produced, what impact they might have and what forms of policy review museums and galleries might as a result wish to undertake. The collaboration confirmed that cultural difference, and therefore difference in need, between visitors with different first languages is a simple reality. Translations, including ones which are culturally ‘adapted’ or ‘sensitive’, will always fall short of acknowledging the intercultural complexity of the experience of international visitors. Materials acknowledging that complexity are more effective. Museums and galleries need, therefore, to ask themselves how far and in what ways they wish to acknowledge this reality in the nature of the welcome they offer. The core of this article will draw on the outcomes of this collaboration, and also on aspects of translation and intercultural theory, to offer a critical exploration of some of the options museums and galleries therefore have in producing materials to welcome international visitors in ways which acknowledge the intercultural complexity of their experience.

Sobre Κρῆτες de Sófocles

En este artículo se estudia una obra atribuida a Sófocles titulada Κρῆτες (Los cretenses), una tragedia sólo conocida por dos dudosos testimonios de Hesiquio y Ateneo de Náucratis. A finales del siglo xviii una nueva lectura de ambos los adscribía a otra tragedia, con lo que se negaba la existencia de Κρῆτες. A pesar de esto, este título se sigue manteniendo en las ediciones de la obra sofoclea, ahora relacionado con nuevos hallazgos de fragmentos papiráceos del autor. Nuestro objetivo es el de analizar los testimonios en profundidad para concluir si la obra pudo o no haberse escrito.

La traducción de la literatura china en España

En general, España es un país que no tiene una tradición sólida en la sinología. La traducción de la literatura china en España todavía no llega a un nivel satisfactorio y muchas obras originales todavía siguen sumidas en el desconocimiento. En comparación con los flujos de traducción de las obras occidentales, sobre todo las obras literarias de Gran Bretaña, Francia y Estados Unidos, la traducción de aquellas todavía ocupa una cuota reducida. En la recepción de la narrativa china en España, la traducción indirecta ha desempeñado un papel de suma importancia, lo que se debe en gran medida a la dependencia del círculo editorial español de las culturas europeas de poder. Esta situación desequilibrada pone de manifiesto las relaciones asimétricas entre lenguas y culturas.

Motivating film title translation: a cognitive análisis

This proposal is a non-quantitative study based on a corpus of real data which offers a principled account of the translation strategies employed in the translation of English film titles into Spanish in terms of cognitive modeling. More specifically, we draw on Ruiz de Mendoza and Galera’s (2014) work on what they term content (or low-level) cognitive operations, based on either ‘stands for’ or ‘identity’ relations, in order to investigate possible motivating factors for translations which abide by oblique procedures, i.e. for non-literal renderings of source titles. The present proposal is made in consonance with recent findings within the framework of Cognitive Linguistics (Samaniego 2007), which evidence that this linguistic approach can fruitfully address some relevant issues in Translation Studies, the most outstanding for our purposes being the exploration of the cognitive operations which account for the use of translation strategies (Rojo and Ibarretxe-Antuñano 2013: 10), mainly expansion and reduction operations, parameterization, echoing, mitigation and comparison by contrast. This fits in nicely with a descriptive approach to translation and particularly with skopos theory, whose main aim consists in achieving functionally adequate renderings of source texts.

Sherman Alexie’s "The Toughest Indian in the World": Amalgamating the Oral and the Written Traditions

This article argues that The Toughest Indian in the World (2000) by Native-American author Sherman Alexie combines elements of his tribal (oral) tradition with others coming from the Western (literary) short-story form. Like other Native writers — such as Momaday, Silko or Vizenor — , Alexie is seen to bring into his short fiction characteristics of his people’s oral storytelling that make it much more dialogical and participatory. Among the author’s narrative techniques reminiscent of the oral tradition, aggregative repetitions of patterned thoughts and strategically-placed indeterminacies play a major role in encouraging his readers to engage in intellectual and emotional exchanges with the stories. Assisted by the ideas of theorists such as Ong (1988), Evers and Toelken (2001), and Teuton (2008), this article shows how Alexie’s short fiction is enriched and revitalized by the incorporation of oral elements. The essay also claims that new methods of analysis and assessment may be needed for this type of bicultural artistic forms. Despite the differences between the two modes of communication, Alexie succeeds in blending features and techniques from both traditions, thus creating a new hybrid short-story form that suitably conveys the trying experiences faced by his characters.

Digitizing dissent: cyborg politics and fluid networks in contemporary Cuban activism

Communication technologies shape how political activist networks are produced and maintain themselves. In Cuba, despite ideologically and physically oppressive practices by the state, a severe lack of Internet access, and extensive government surveillance, a small network of bloggers and cyberactivists has achieved international visibility and recognition for its critiques of the Cuban government. This qualitative study examines the blogger collective known as Voces Cubanas in Havana, Cuba in 2012, advancing a new approach to the study of transnational activism and the role of technology in the construction of political narrative. Voces Cubanas is analyzed as a network of connections between human and non-human actors that produces and sustains powerful political alliances. Voces Cubanas and its allies work collectively to co-produce contentious political discourses, confronting the dominant ideologies and knowledges produced by the Cuban state. Transnational alliances, the act of translation, and a host of unexpected and improvised technologies play central roles in the production of these narratives, indicating new breed of cyborg sociopolitical action reliant upon fluid and flexible networks and the act of writing. 

An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation

Objectives This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses.
Design and setting Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions.
Participants Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients’ PCPs and cancer treatment specialists (CTSs) are surveyed, and ‘data rules’ are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases.
Main outcomes Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types.
Conclusion An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

Role and modulation of maternal transcripts during the first cleavage divisions in bovine embryos

Ce travail porte sur l’identification, la fonction et la régulation des molécules maternelles d’ARNm qui dirigent la compétence développementale juste après la fécondation chez les bovins. Tout d’abord, en utilisant le modèle du temps écoulé jusqu’au premier clivage zygotique et à travers l’évaluation du transcriptome des embryons à 2-cellules, il fut possible de déterminer la signature moléculaire des niveaux extrêmes de compétence au développement et sélectionner des molécules candidates pour des études postérieures. Les résultats ont montré que les embryons de capacité développementale variable diffèrent dans certaines fonctions comme la réparation de l’ADN, le traitement de l’ARN, la synthèse de protéines et l’expression génique définies par des ARNm synthétisés par l’ovocyte. Pour obtenir une confirmation fonctionnelle, une paire de transcrits maternels (l’un détecté dans notre sondage précédent et l’autre étant une molécule reliée) ont été inhibés par « knock-down » dans des ovocytes. Les effets du knock-down de ces facteurs de transcription sont apparus avant la formation des blastocystes dû à une diminution de la capacité au clivage et celle à progresser après le stage de 8-cellules. L’analyse moléculaire des embryons knock-down survivants suggère qu’un de ces facteurs de transcription est un contrôleur crucial de l’activation du génome embryonnaire, qui représente une fenêtre développementale dans l’embryogenèse précoce. Dans la dernièr étude, nous avons testé si les facteurs de transcription d’intérêt sont modulés au niveau traductionnel. Des ARNm rapporteurs couplés à la GFP (Protéine fluorescente) contenant soit la version courte ou la version longue de la séquence 3’-UTR des deux molécules furent injectées dans des zygotes pour évaluer leur dynamique traductionnelle. Les résultats ont montré que les éléments cis-régulateurs localisés dans les 3’-UTRs contrôlent leur synchronisation traductionnelle et suggèrent une association entre la compétence développementale et la capacité de synthèse de ces protéines. Ceci conduit à l’idée que ces facteurs de transcription cruciaux sont aussi contrôlés au niveau traductionnel chez les embryons précoces. Les connaissances acquises ont joué un rôle essentiel pour définir le contrôle potentiel des molécules maternelles sur les embryons au début de leur développement. Cette étude nous montre aussi une utilisation potentielle de cette information ainsi que les nouveaux défis présents dans le secteur des technologies reproductives.