9,952 research outputs found

    Incentivising research data sharing : a scoping review

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    Background: Numerous mechanisms exist to incentivise researchers to share their data. This scoping review aims to identify and summarise evidence of the efficacy of different interventions to promote open data practices and provide an overview of current research. Methods: This scoping review is based on data identified from Web of Science and LISTA, limited from 2016 to 2021. A total of 1128 papers were screened, with 38 items being included. Items were selected if they focused on designing or evaluating an intervention or presenting an initiative to incentivise sharing. Items comprised a mixture of research papers, opinion pieces and descriptive articles. Results: Seven major themes in the literature were identified: publisher/journal data sharing policies, metrics, software solutions, research data sharing agreements in general, open science ‘badges’, funder mandates, and initiatives. Conclusions: A number of key messages for data sharing include: the need to build on existing cultures and practices, meeting people where they are and tailoring interventions to support them; the importance of publicising and explaining the policy/service widely; the need to have disciplinary data champions to model good practice and drive cultural change; the requirement to resource interventions properly; and the imperative to provide robust technical infrastructure and protocols, such as labelling of data sets, use of DOIs, data standards and use of data repositories

    Supernatural crossing in Republican Chinese fiction, 1920s–1940s

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    This dissertation studies supernatural narratives in Chinese fiction from the mid-1920s to the 1940s. The literary works present phenomena or elements that are or appear to be supernatural, many of which remain marginal or overlooked in Sinophone and Anglophone academia. These sources are situated in the May Fourth/New Culture ideological context, where supernatural narratives had to make way for the progressive intellectuals’ literary realism and their allegorical application of supernatural motifs. In the face of realism, supernatural narratives paled, dismissed as impractical fantasies that distract one from facing and tackling real life. Nevertheless, I argue that the supernatural narratives do not probe into another mystical dimension that might co-exist alongside the empirical world. Rather, they imagine various cases of the characters’ crossing to voice their discontent with contemporary society or to reflect on the notion of reality. “Crossing” relates to characters’ acts or processes of trespassing the boundary that separates the supernatural from the conventional natural world, thus entailing encounters and interaction between the natural and the supernatural. The dissertation examines how crossing, as a narrative device, disturbs accustomed and mundane situations, releases hidden tensions, and discloses repressed truths in Republican fiction. There are five types of crossing in the supernatural narratives. Type 1 is the crossing into “haunted” houses. This includes (intangible) human agency crossing into domestic spaces and revealing secrets and truths concealed by the scary, feigned ‘haunting’, thus exposing the hidden evil and the other house occupiers’ silenced, suffocated state. Type 2 is men crossing into female ghosts’ apparitional residences. The female ghosts allude to heart-breaking, traumatic experiences in socio-historical reality, evoking sympathetic concern for suffering individuals who are caught in social upheavals. Type 3 is the crossing from reality into the characters’ delusional/hallucinatory realities. While they physically remain in the empirical world, the characters’ abnormal perceptions lead them to exclusive, delirious, and quasi-supernatural experiences of reality. Their crossings blur the concrete boundaries between the real and the unreal on the mental level: their abnormal perceptions construct a significant, meaningful reality for them, which may be as real as the commonly regarded objective reality. Type 4 is the crossing into the netherworld modelled on the real world in the authors’ observation and bears a spectrum of satirised objects of the Republican society. The last type is immortal visitors crossing into the human world. This type satirises humanity’s vices and destructive potential. The primary sources demonstrate their writers’ witty passion to play with super--natural notions and imagery (such as ghosts, demons, and immortals) and stitch them into vivid, engaging scenes using techniques such as the gothic, the grotesque, and the satirical, in order to evoke sentiments such as terror, horror, disgust, dis--orientation, or awe, all in service of their insights into realist issues. The works also creatively tailor traditional Chinese modes and motifs, which exemplifies the revival of Republican interest in traditional cultural heritage. The supernatural narratives may amaze or disturb the reader at first, but what is more shocking, unpleasantly nudging, or thought-provoking is the problematic society and people’s lives that the supernatural (misunderstandings) eventually reveals. They present a more compre--hensive treatment of reality than Republican literature with its revolutionary consciousness surrounding class struggle. The critical perspectives of the supernatural narratives include domestic space, unacknowledged history and marginal individuals, abnormal mentality, and pervasive weaknesses in humanity. The crossing and supernatural narratives function as a means of better understanding the lived reality. This study gathers diverse primary sources written by Republican writers from various educational and political backgrounds and interprets them from a rare perspective, thus filling a research gap. It promotes a fuller view of supernatural narratives in twentieth-century Chinese literature. In terms of reflecting the social and personal reality of the Republican era, the supernatural narratives supplement the realist fiction of the time

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    The company she keeps : The social and interpersonal construction of girls same sex friendships

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    This thesis begins a critical analysis of girls' 'private' interpersonal and social relations as they are enacted within two school settings. It is the study of these marginal subordinated worlds productivity of forms of femininity which provides the main narrative of this project. I seek to understand these processes of (best) friendship construction through a feminist multi-disciplinary frame, drawing upon cultural studies, psychoanalysis and accounts of gender politics. I argue that the investments girls bring to their homosocial alliances and boundary drawing narry a psychological compulsion which is complexly connected to their own experiences within the mother/daughter bond as well as reflecting positively an immense social debt to the permissions girls have to be nurturant and ; negatively their own reproduction of oppressive exclusionary practices. Best friendship in particular gives girls therefore, the experience of 'monogamy' continuous of maternal/daughter identification, reminiscent of their positioning inside monopolistic forms of heterosexuality. But these subcultures also represent a subversive discontinuity to the public dominance of boys/teachers/adults in schools and to the ideologies and practices of heterosociality and heterosexuality. By taking seriously their transmission of the values of friendship in their chosen form of notes and diaries for example, I was able to access the means whereby they were able to resist their surveillance and control by those in power over them. I conclude by arguing that it is through a recognition of the valency of these indivisiblly positive and negative aspects to girls cultures that Equal Opportunities practitioners must begin if they are serious about their ambitions. Methods have to be made which enable girls to transfer their 'private' solidarities into the 'public' realm, which unquestionably demands contesting with them the causes and consequences of their implication in the divisions which also contaminate their lives and weaken them

    Epistemologies of possibility: social movements, knowledge production and political transformation

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    Urgent global problems - whether military conflicts, economic insecurities, immigration controls or mass incarceration-not only call for new modes of political action but also demand new forms of knowledge. For if knowledge frameworks both shape the horizons of social intelligibility and chart t he realms of political possibility, then epistemological interventions constitute a crucial part of social change. Social movements play a key role in this work by engaging in dissident knowledge practices that open up space for political transformation. But what are the processes and conditions through which social movements generate new ways of knowing?'What is politically at stake in the various knowledge strategies that activists use to generate social change? Despite a growing literature on the role of epistemological dimensions of protest, social movement studies tend to neglect specific questions of epistemological change. Often treating knowledge as a resource or object rather than a power relation and a social practice, social movement scholars tend to focus on content rather than production, frames rather than practices, taxonomies rather than processes. Missing is a more dynamic account of the conditions, means and power relations through which transformative knowledge practices come to be constituted and deployed. Seeking to better understand processes of epistemological transformation, this thesis explores the relationship between social movements, knowledge production and political change. Starting from an assumption that knowledge not only represents the world, but also works to constitute it, this thesis examines the role of social movement knowledge practices in shaping the conditions of political possibility. Drawing from the context of grassroots queer, transgender and feminist organizing around issues of prisons and border controls in North America, the project explores how activists generate new forms of knowledge and forge new spaces of political possibility. Working through a series of concepts-transformation, resistance, experience, co-optation, solidarity and analogy - this thesis explores different ways of understanding processes of epistemological change with in social movement contexts. It considers processes that facilitate or enable epistemological change and those that limit or prohibit such change. Bringing together a range of theoretical perspectives, including feminist, queer, critical race and post-structuralist analyses, and drawing on interviews with grassroots activists, the thesis explores what is politically at stake in the different ways we conceptualise, imagine and engage in processes of epistemological change

    Identification of new regenerative therapies in reproductive medicine and their application as a future therapeutic approach for endometrial regeneration

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    El Ăștero es uno de los principales Ăłrganos internos del sistema reproductor femenino. EstĂĄ compuesto de tres capas tisulares: perimetrio, miometrio y endometrio. Esta Ășltima capa recubre la cavidad intrauterina y es responsable directa de la implantaciĂłn embrionaria (para la cual necesita un grosor endometrial mĂ­nimo). Entre las patologĂ­as que afectan al endometrio pueden distinguirse, entre otras, la atrofia endometrial (insuficiente grosor endometrial) y el sĂ­ndrome de Asherman (presencia de adhesiones intrauterinas y tejido fibrĂłtico), las cuales conforman el hilo conductor de esta tesis, compuesta de 4 artĂ­culos cientĂ­ficos. En ambos casos, el tejido endometrial se encuentra degenerado, lo que dificulta la implantaciĂłn embrionaria, ocasionando problemas de fertilidad. A dĂ­a de hoy, ninguna de estas patologĂ­as cuenta con una cura totalmente efectiva. Hasta el momento, una de las opciones terapĂ©uticas mĂĄs prometedora es la inyecciĂłn de cĂ©lulas madre. Por ello, el primer objetivo de esta tesis fue evaluar como la inyecciĂłn de cĂ©lulas madre derivadas de la mĂ©dula Ăłsea (aisladas con la detecciĂłn del antĂ­geno CD133), que habĂ­a resultado ser efectiva tanto en un modelo humano como en uno animal, estaba modificando el endometrio molecularmente. Para asĂ­, intentar entender cuĂĄles son los mecanismos paracrinos a travĂ©s de los cuales llevan a cabo su acciĂłn terapĂ©utica. Este primer estudio revelĂł que estas cĂ©lulas madre parecĂ­an estar promoviendo la regeneraciĂłn endometrial mediante la creaciĂłn de un escenario inmunomodulador (sub-expresiĂłn del gen CXCL8), que darĂ­a paso a la sobreexpresiĂłn de genes involucrados en la regeneraciĂłn tisular, como SERPINE1, IL4, y JUN. Otro tratamiento que ha ido ganando acepciĂłn con los años es el plasma rico en plaquetas, eje central del manuscrito 2. Este manuscrito evidencia como este plasma, especialmente si proviene de sangre de cordĂłn umbilical, es capaz de promover procesos celulares, como la migraciĂłn y la proliferaciĂłn de las cĂ©lulas endometriales, asĂ­ como eventos regenerativos en un modelo animal con daño endometrial inducido. Sea cual sea la aproximaciĂłn terapĂ©utica de elecciĂłn, se ha hipotetizado que esta regeneraciĂłn tisular podrĂ­a surgir de la estimulaciĂłn del nicho de cĂ©lulas madre presente en el endometrio. Es por ello que el objetivo 3 supuso el estudio de los trabajos publicados, tanto de modelos murinos como humanos, relativos a esta poblaciĂłn de cĂ©lulas madre endometriales. Esta bĂșsqueda permitiĂł concluir que aĂșn quedan lagunas de conocimiento, bien sea en la definiciĂłn de marcadores celulares especĂ­ficos o en de la contribuciĂłn de la mĂ©dula Ăłsea a este nicho de cĂ©lulas madre endometriales. Finalmente, dada la mencionada falta actual de una terapia definitiva para las pacientes con atrofia endometrial o sĂ­ndrome de Asherman, el cuarto y Ășltimo objetivo de esta tesis supuso el estudio de todas aquellas aproximaciones que se han llevado a cabo en modelos animales que simulan este tipo de patologĂ­as humanas. Este trabajo concluyĂł que si bien estĂĄn emergiendo nuevas terapias muy prometedoras, como son aquellas derivadas de la bioingenierĂ­a (por ejemplo, uso de hidrogeles o biomoldes), todavĂ­a falta perfeccionar y estandarizar los modelos tanto animales como in vitro que permitan una mejor traslaciĂłn clĂ­nica de las mismas.The uterus is one of the main internal organs of the female reproductive system. It is composed of three different tissue layers: perimetrium, myometrium, and endometrium. This last layer covers the intrauterine cavity and is directly responsible for embryo implantation (for which it needs a certain minimum endometrial thickness). Among the pathologies affecting the endometrium, we can distinguish, among others, endometrial atrophy (characterized by an insufficient endometrial thickness) and Asherman's syndrome (a rare disease characterized by the presence of intrauterine adhesions and fibrotic tissue), which form the common thread of this thesis, composed of four original manuscripts. In both cases, the endometrial tissue is degenerated, which hinders the correct embryo implantation, causing then fertility problems. To date, none of these pathologies has a totally effective cure. So far, one of the most promising therapeutic options is the injection of stem cells. Therefore, the first objective was to evaluate how the infusion of bone marrow-derived stem cells (isolated with the antigen CD133), which had proven effective in both a human and an animal model, was modifying the endometrium at the molecular level. Then, this work aimed to understand the paracrine mechanisms through which these cells were carrying out their therapeutic and regenerative action over the endometrial tissue. This first study revealed that these stem cells appeared to be promoting endometrial regeneration by creating an immunomodulatory scenario (down-regulation of the CXCL8 gene), which would give way to the over-expression of genes (SERPINE1, IL4, and JUN) involved in tissue regeneration. Another treatment gaining acceptance over the years is a blood derivate, platelet-rich plasma, which was the focus of the second manuscript. This work shows how this plasma, mainly derived from umbilical cord blood rather than adult peripheral blood, can promote cellular processes, such as cell migration and proliferation of different types of endometrial cells (from primary culture and from stem cell lines). These plasmas also revealed how they triggered the over-expression of certain proteins involved in regenerative events in a mouse model with induced endometrial damage. Whatever the therapeutic approach of choice, it has been hypothesized that regeneration could arise from stimulation of the stem cell niche present in the endometrium. That is why objective three involved studying those works, both murine and human models, concerning this population of endometrial stem cells. This search concluded that there are still gaps in knowledge, either in the definition of specific endometrial stem cell markers or in the contribution of the bone marrow to this endogenous endometrial stem cell niche. Finally, given the aforementioned current lack of definitive therapy for patients with endometrial atrophy or Asherman's syndrome, the last objective involved studying all those approaches that have been carried out in animal models that simulate this type of human pathology. This work concluded that although new therapies are emerging, such as those derived from bioengineering (e.g. use of decellularized scaffolds or hydrogels), there is still a need to perfect and standardize both animal and in vitro models to allow a better clinical translation of these therapies

    Towards thinking classrooms: foundation stage possibilities in Northern Ireland

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    The integration of thinking skills programmes into primary and secondary school curricula has gained increasing prominence in global educational policy over the past two decades. This research investigated the factors that influence how a particular approach to the development of thinking skills adopted in the Northern Ireland (NI) context is interpreted and implemented by teachers in early years classrooms. The Thinking Skills and Personal Capabilities Framework (TSPC) was introduced as a statutory component of the revised NI curriculum in 2007 and this study explores its enactment through the perceptions of key groups that interface with the policy from a range of different contexts: teachers and Head Teachers, Curriculum Advisory and Support staff, university academics and Initial Teacher Education staff. The study adopted an interpretive approach, utilising interviews with members of these key groups to explore their perceptions of the factors that influence the effective and consistent implementation of the TSPC and to explain possible reasons why it has embedded effectively in some NI primary schools and not in others. In addition to interviews, policy analysis of key texts that shape teachers’ approaches to the TSPC was undertaken using a framework based on Fairclough’s three-dimensional approach to critical discourse analysis. The purpose of this analysis was to explore the connection between the discourses used in these texts, and the extent to which the ideological cues that underpin them exert an influence on how teachers interpret and implement thinking skills in their practice. The study also explored how human capital theory, and an ecological approach to the enactment of the TSPC based on Bronfenbrenner’s Ecological Systems Model (1979), provide different frameworks for understanding how the TSPC is interpreted and implemented in practice, with particular reference to Northern Ireland. The findings suggest that there are a number of significant factors that both enable and constrain the effective implementation of the TSPC across schools. The region’s political, social and historical context was viewed by participants as playing a key role in how policy reforms are interpreted and implemented. School leaders can play a central role in mediating the impact of these reforms to ensure that they are implemented in ways that take account of diverse and specific school contexts. From the perspective of participants, Head Teachers and school leaders also play a pivotal role in nurturing teachers’ professional learning, skill, and motivation in the teaching of thinking skills. Consistent opportunities for professional development, including collaborative working, and sharing of practice, both in and beyond the school, was viewed as the primary means of ensuring the development of a shared vision and language about thinking skills, and participants agreed that this is central to its consistent implementation across all schools. Analysis of the participants’ understandings of the purpose of teaching thinking skills, and the aims of education more broadly, highlighted a tension between approaches to education that focus on children’s holistic development, and policy discourses, especially those related to Human Capital Theory that view education as a mechanism for achieving economic goals. The influence of these discourses across a range of public policy areas, as well as the disconnect between what participants and policy-makers viewed as the purpose of thinking, was highlighted in the analysis. For participants, the integration of thinking skills into the curriculum was about developing autonomy, criticality, and independence in children’s thinking, whereas policy-makers viewed it from a human capital perspective and strongly linked it to discourses of ‘lifelong learning’, ‘employability’ and ‘skill’. From the perspective of participants, the findings indicate that for policy makers in Northern Ireland to better understand how to embed the TSPC as a core component of the curriculum in all schools a number of cross-system actions need to be undertaken. These include a baseline review of the impact of the TSPC in the ten years since its inception as part of the comprehensive review of education announced by the Minister for Education in January 2021. The data suggests that this review should ensure that teachers and school leaders are central to its design and approach and that it is fully inclusive of all schools in Northern Ireland that sit within its scope. A return to more localised support and advice services with a coordinated approach to the development of the TSPC in all schools was also viewed by participants as essential to its development and embedding in all schools. A more coordinated, multi-disciplinary approach to implementation would, it was argued, ensure that ongoing professional learning in thinking skills was accessible, including the establishment of more strategic, collaborative partnerships with higher education, ITE and Inspection Services. This changed focus, I conclude, requires a move away from human capital and sector specific approaches to the consistent development of thinking skills programmes in all Northern Ireland schools. Recommendations also centre on future policy reforms that are inclusive and that give teachers their professional place as the primary implementers for the development of thinking skills programmes in schools

    Machine learning and large scale cancer omic data: decoding the biological mechanisms underpinning cancer

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    Many of the mechanisms underpinning cancer risk and tumorigenesis are still not fully understood. However, the next-generation sequencing revolution and the rapid advances in big data analytics allow us to study cells and complex phenotypes at unprecedented depth and breadth. While experimental and clinical data are still fundamental to validate findings and confirm hypotheses, computational biology is key for the analysis of system- and population-level data for detection of hidden patterns and the generation of testable hypotheses. In this work, I tackle two main questions regarding cancer risk and tumorigenesis that require novel computational methods for the analysis of system-level omic data. First, I focused on how frequent, low-penetrance inherited variants modulate cancer risk in the broader population. Genome-Wide Association Studies (GWAS) have shown that Single Nucleotide Polymorphisms (SNP) contribute to cancer risk with multiple subtle effects, but they are still failing to give further insight into their synergistic effects. I developed a novel hierarchical Bayesian regression model, BAGHERA, to estimate heritability at the gene-level from GWAS summary statistics. I then used BAGHERA to analyse data from 38 malignancies in the UK Biobank. I showed that genes with high heritable risk are involved in key processes associated with cancer and are often localised in genes that are somatically mutated drivers. Heritability, like many other omics analysis methods, study the effects of DNA variants on single genes in isolation. However, we know that most biological processes require the interplay of multiple genes and we often lack a broad perspective on them. For the second part of this thesis, I then worked on the integration of Protein-Protein Interaction (PPI) graphs and omics data, which bridges this gap and recapitulates these interactions at a system level. First, I developed a modular and scalable Python package, PyGNA, that enables robust statistical testing of genesets' topological properties. PyGNA complements the literature with a tool that can be routinely introduced in bioinformatics automated pipelines. With PyGNA I processed multiple genesets obtained from genomics and transcriptomics data. However, topological properties alone have proven to be insufficient to fully characterise complex phenotypes. Therefore, I focused on a model that allows to combine topological and functional data to detect multiple communities associated with a phenotype. Detecting cancer-specific submodules is still an open problem, but it has the potential to elucidate mechanisms detectable only by integrating multi-omics data. Building on the recent advances in Graph Neural Networks (GNN), I present a supervised geometric deep learning model that combines GNNs and Stochastic Block Models (SBM). The model is able to learn multiple graph-aware representations, as multiple joint SBMs, of the attributed network, accounting for nodes participating in multiple processes. The simultaneous estimation of structure and function provides an interpretable picture of how genes interact in specific conditions and it allows to detect novel putative pathways associated with cancer
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