11,869 research outputs found
The Professional Identity of Doctors who Provide Abortions: A Sociological Investigation
Abortion is a medicalised problem in England and Wales, where the law places doctors at the centre of legal provision and puts doctors in control of who has an abortion. However, the sex-selection abortion scandal of 2012 presented a very real threat to 'abortion doctors', when the medical profession's values and practices were questioned in the media, society and by Members of Parliament. Doctors found themselves at the centre of a series of claims that stated doctors were acting both illegally and unethically, driven by profit rather than patient needs. Yet, the perspectives of those doctors who provide abortions has been under-researched; this thesis aims to fill that gap by examining the beliefs and values of this group of doctors. Early chapters highlight the ambiguous position of the abortion provider in Britain, where doctors are seen as a collective group of professionals motivated by medical dominance and medical autonomy. They outline how this position is then questioned and contested, with doctors being presented as unethical. By studying abortion at the macro-, meso- and micro-levels, this thesis seeks to better understand the values of the 'abortion doctor', and how these levels shape the work and experiences of abortion providers in England and Wales. This thesis thus addresses the question: 'What do abortion doctors' accounts of their professional work suggest about the contemporary dynamics of the medicalisation of abortion in Britain?'. It investigates the research question using a qualitative methodological approach: face-to-face and telephone interviews were conducted with 47 doctors who provide abortions in England and Wales. The findings from this empirical study show how doctors' values are linked to how they view the 'normalisation of abortion'. At the macro-level doctors, openly resisted the medicalisation of abortion through the position ascribed to them by the legal framework, yet at the meso-level doctors construct an identity where normalising abortion is based on further medicalising services. Finally, at the micro-level, the ambiguous position of the abortion provider is further identified in terms of being both a proud provider and a stigmatised individual. This thesis shows that while the existing medicalisation literature has some utility, it has limited explanatory power when investigating the problem of abortion. The thesis thus provides some innovative insights into the relevance and value of medicalisation through a comprehensive study on doctors' values, beliefs and practices
Supernatural crossing in Republican Chinese fiction, 1920sâ1940s
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 intellectualsâ 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 charactersâ crossing to voice their discontent with contemporary society or to reflect on the notion of reality. âCrossingâ relates to charactersâ 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 âhauntedâ houses. This includes (intangible) human agency crossing into domestic spaces and revealing secrets and truths concealed by the scary, feigned âhauntingâ, thus exposing the hidden evil and the other house occupiersâ silenced, suffocated state.
Type 2 is men crossing into female ghostsâ 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 charactersâ delusional/hallucinatory realities. While they physically remain in the empirical world, the charactersâ 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 authorsâ 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 humanityâs vices and destructive potential.
The primary sources demonstrate their writersâ 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 peopleâs 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
TOWARDS AN UNDERSTANDING OF EFFORTFUL FUNDRAISING EXPERIENCES: USING INTERPRETATIVE PHENOMENOLOGICAL ANALYSIS IN FUNDRAISING RESEARCH
Physical-activity oriented community fundraising has experienced an exponential growth in popularity over the past 15 years. The aim of this study was to explore the value of effortful fundraising experiences, from the point of view of participants, and explore the impact that these experiences have on peopleâs lives. This study used an IPA approach to interview 23 individuals, recognising the role of participants as proxy (nonprofessional) fundraisers for charitable organisations, and the unique organisation donor dynamic that this creates. It also bought together relevant psychological theory related to physical activity fundraising experiences (through a narrative literature review) and used primary interview data to substantiate these. Effortful fundraising experiences are examined in detail to understand their significance to participants, and how such experiences influence their connection with a charity or cause. This was done with an idiographic focus at first, before examining convergences and divergences across the sample. This study found that effortful fundraising experiences can have a profound positive impact upon community fundraisers in both the short and the long term. Additionally, it found that these experiences can be opportunities for charitable organisations to create lasting meaningful relationships with participants, and foster mutually beneficial lifetime relationships with them. Further research is needed to test specific psychological theory in this context, including self-esteem theory, self determination theory, and the martyrdom effect (among others)
Investigating the mechanism of human beta defensin-2-mediated protection of skin barrier in vitro
The human skin barrier is a biological imperative. Chronic inflammatory skin diseases, such as Atopic Dermatitis (AD), are characterised by a reduction in skin barrier function and an increased number of secondary infections. Staphyloccocus aureus (S. aureus) has an increased presence on AD lesional skin and contributes significantly to AD pathology. It was previously demonstrated that the damage induced by a virulence factor of S. aureus, V8 protease, which causes further breakdown in skin barrier function, can be reduced by induction of human ÎČ- defensin (HBD)2 (by IL-1ÎČ) or exogenous HBD2 application. Induction of this defensin is impaired in AD skin. This thesis examines the mechanism of HBD2-mediated barrier protection in vitro; demonstrating that in this system, HBD2 was not providing protection through direct protease inhibition, nor was it altering keratinocyte proliferation or migration, or exhibiting specific localisation within the monolayer. Proteomics data demonstrated that HBD2 did not induce expression of known antiproteases but suggested that HBD2 stimulation may function by modulating expression of extracellular matrix proteins, specifically collagen- IVα2 and Laminin-ÎČ-1. Alternative pathways of protection initiated by IL-1ÎČ and TNFα stimulation were also investigated, as well as their influence over generalised wound healing. Finally, novel 3D human skin epidermal models were used to better recapitulate the structure of human epidermis and examine alterations to skin barrier function in a more physiological system. These data validate the barrier-protective properties of HBD2 and extended our knowledge of the consequences of exposure to this peptide in this context
Optimizing transcriptomics to study the evolutionary effect of FOXP2
The field of genomics was established with the sequencing of the human genome, a pivotal achievement that has allowed us to address various questions in biology from a unique perspective. One question in particular, that of the evolution of human speech, has gripped philosophers, evolutionary biologists, and now genomicists. However, little is known of the genetic basis that allowed humans to evolve the ability to speak. Of the few genes implicated in human speech, one of the most studied is FOXP2, which encodes for the transcription factor Forkhead box protein P2 (FOXP2). FOXP2 is essential for proper speech development and two mutations in the human lineage are believed to have contributed to the evolution of human speech. To address the effect of FOXP2 and investigate its evolutionary contribution to human speech, one can utilize the power of genomics, more specifically gene expression analysis via ribonucleic acid sequencing (RNA-seq).
To this end, I first contributed in developing mcSCRB-seq, a highly sensitive, powerful, and efficient single cell RNA-seq (scRNA-seq) protocol. Previously having emerged as a central method for studying cellular heterogeneity and identifying cellular processes, scRNA-seq was a powerful genomic tool but lacked the sensitivity and cost-efficiency of more established protocols. By systematically evaluating each step of the process, I helped find that the addition of polyethylene glycol increased sensitivity by enhancing the cDNA synthesis reaction. This, along with other optimizations resulted in developing a sensitive and flexible protocol that is cost-efficient and ideal in many research settings.
A primary motivation driving the extensive optimizations surrounding single cell transcriptomics has been the generation of cellular atlases, which aim to identify and characterize all of the cells in an organism. As such efforts are carried out in a variety of research groups using a number of different RNA-seq protocols, I contributed in an effort to benchmark and standardize scRNA-seq methods. This not only identified methods which may be ideal for the purpose of cell atlas creation, but also highlighted optimizations that could be integrated into existing protocols.
Using mcSCRB-seq as a foundation as well as the findings from the scRNA-seq benchmarking, I helped develop prime-seq, a sensitive, robust, and most importantly, affordable bulk RNA-seq protocol. Bulk RNA-seq was frequently overlooked during the efforts to optimize and establish single-cell techniques, even though the method is still extensively used in analyzing gene expression. Introducing early barcoding and reducing library generation costs kept prime-seq cost-efficient, but basing it off of single-cell methods ensured that it would be a sensitive and powerful technique. I helped verify this by benchmarking it against TruSeq generated data and then helped test the robustness by generating prime-seq libraries from over seventeen species. These optimizations resulted in a final protocol that is well suited for investigating gene expression in comprehensive and high-throughput studies.
Finally, I utilized prime-seq in order to develop a comprehensive gene expression atlas to study the function of FOXP2 and its role in speech evolution. I used previously generated mouse models: a knockout model containing one non-functional Foxp2 allele and a humanized model, which has a variant Foxp2 allele with two human-specific mutations. To study the effect globally across the mouse, I helped harvest eighteen tissues which were previously identified to express FOXP2. By then comparing the mouse models to wild-type mice, I helped highlight the importance of FOXP2 within lung development and the importance of the human variant allele in the brain.
Both mcSCRB-seq and prime-seq have already been used and published in numerous studies to address a variety of biological and biomedical questions. Additionally, my work on FOXP2 not only provides a thorough expression atlas, but also provides a detailed and cost-efficient plan for undertaking a similar study on other genes of interest. Lastly, the studies on FOXP2 done within this work, lay the foundation for future studies investigating the role of FOXP2 in modulating learning behavior, and thereby affecting human speech
SYSTEMS METHODS FOR ANALYSIS OF HETEROGENEOUS GLIOBLASTOMA DATASETS TOWARDS ELUCIDATION OF INTER-TUMOURAL RESISTANCE PATHWAYS AND NEW THERAPEUTIC TARGETS
In this PhD thesis is described an endeavour to compile litterature about Glioblastoma key molecular mechanisms into a directed network followin Disease Maps standards, analyse its topology and compare results with quantitative analysis of multi-omics datasets in order to investigate Glioblastoma resistance mechanisms. The work also integrated implementation of Data Management good practices and procedures
A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia
© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/ by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study. Two-hundred and seventy-five presymptomatic and 127 symptomatic carriers of mutations in GRN, C9orf72 or MAPT, as well as 247 non-carriers, were selected from the GENFI cohort based on availability of one or more of the aforementioned biomarkers. Nine presymptomatic carriers developed symptoms within 18 months of sample collection ('converters'). Sequences of biomarker abnormalities were modelled for the entire group using discriminative event-based modelling (DEBM) and for each genetic subgroup using co-initialized DEBM. These models estimate probabilistic biomarker abnormalities in a data-driven way and do not rely on previous diagnostic information or biomarker cut-off points. Using cross-validation, subjects were subsequently assigned a disease stage based on their position along the disease progression timeline. CSF NPTX2 was the first biomarker to become abnormal, followed by blood and CSF neurofilament light chain, blood phosphorylated neurofilament heavy chain, blood glial fibrillary acidic protein and finally CSF C3b and C1q. Biomarker orderings did not differ significantly between genetic subgroups, but more uncertainty was noted in the C9orf72 and MAPT groups than for GRN. Estimated disease stages could distinguish symptomatic from presymptomatic carriers and non-carriers with areas under the curve of 0.84 (95% confidence interval 0.80-0.89) and 0.90 (0.86-0.94) respectively. The areas under the curve to distinguish converters from non-converting presymptomatic carriers was 0.85 (0.75-0.95). Our data-driven model of genetic frontotemporal dementia revealed that NPTX2 and neurofilament light chain are the earliest to change among the selected biomarkers. Further research should investigate their utility as candidate selection tools for pharmaceutical trials. The model's ability to accurately estimate individual disease stages could improve patient stratification and track the efficacy of therapeutic interventions.This study was supported in the Netherlands by two Memorabel grants from Deltaplan Dementie (The Netherlands Organisation for Health Research and Development and Alzheimer Nederland; grant numbers 733050813,733050103 and 733050513), the Bluefield Project to Cure Frontotemporal Dementia, the Dioraphte foundation (grant number 1402 1300), the European Joint ProgrammeâNeurodegenerative Disease Research and the Netherlands Organisation for Health Research and Development (PreFrontALS: 733051042, RiMod-FTD: 733051024); V.V. and S.K. have received funding from the European Unionâs Horizon 2020 research and innovation programme under grant agreement no. 666992 (EuroPOND). E.B. was supported by the Hartstichting (PPP Allowance, 2018B011); in Belgium by the Mady Browaeys Fonds voor Onderzoek naar Frontotemporale Degeneratie; in the UK by the MRC UK GENFI grant (MR/M023664/1); J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH); I.J.S. is supported by the Alzheimerâs Association; J.B.R. is supported by the Wellcome Trust (103838); in Spain by the FundaciĂł MaratĂł de TV3 (20143810 to R.S.V.); in Germany by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germanyâs Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergyâID 390857198) and by grant 779357 âSolve-RDâ from the Horizon 2020 Research and Innovation Programme (to MS); in Sweden by grants from the Swedish FTD Initiative funded by the Schörling Foundation, grants from JPND PreFrontALS Swedish Research Council (VR) 529â2014-7504, Swedish Research Council (VR) 2015â02926, Swedish Research Council (VR) 2018â02754, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Swedish Demensfonden, Stohnes foundation, Gamla TjĂ€narinnor, Karolinska Institutet Doctoral Funding and StratNeuro. H.Z. is a Wallenberg Scholar.info:eu-repo/semantics/publishedVersio
Chinese Benteng Womenâs Participation in Local Development Affairs in Indonesia: Appropriate means for struggle and a pathway to claim citizenâ right?
It had been more than two decades passing by aftermath the devastating Asiaâs Financial Crisis in 1997, subsequently followed by Suhartoâs step down from his presidential throne which he occupied for more than three decades. The financial turmoil turned to a political disaster furthermore has led to massive looting that severely impacted Indonesians of Chinese descendant, including unresolved mystery of the most atrocious sexual violation against women and covert killings of students and democracy activists in this country. Since then, precisely aftermath May 1998, which publicly known as âReformasiâ1, Indonesia underwent political reform that eventually corresponded positively to its macroeconomic growth. Twenty years later, in 2018, Indonesia captured worldwide attention because it has successfully hosted two internationally renowned events, namely the Asian Games 2018 â the most prestigious sport events in Asia â conducted in Jakarta and Palembang; and the IMF/World Bank Annual Meeting 2018 in Bali. Particularly in the IMF/World Bank Annual Meeting, this event has significantly elevated Indonesiaâs credibility and international prestige in the global economic powerplay as one of the nations with promising growth and openness. However, the narrative about poverty and inequality, including increasing racial tension, religious conservatism, and sexual violation against women are superseded by friendly climate for foreign investment and eventually excessive glorification of the nationâs economic growth. By portraying the image of promising new economic power, as rhetorically promised by President Joko Widodo during his presidential terms, Indonesia has swept the growing inequality in this highly stratified society that historically compounded with religious and racial tension under the carpet of digital economy.Arte y Humanidade
Genetics and genomics of myxomatous mitral valve disease in dogs
As a result of its unique evolutionary history, the modern dog (Canis lupus familiaris) has a simplified genetic landscape that makes it a strong model for investigating the genetic basis of breed specific traits and diseases. This thesis applies genomic methodologies to a complex disease, myxomatous mitral valve disease (MMVD), with the primary aim of improving our understanding of its genetic basis. MMVD is an acquired disease of the dog that causes valvular dysfunction and may result in the development of congestive heart failure (CHF). In dogs, MMVD is the most frequent cause of cardiovascular morbidity and mortality, and despite a thorough understanding of the clinical aspects, the genetic mechanisms that drive disease onset and progression are uncertain. Current MMVD research supports a polygenic mode of inheritance and exemplifies the difficulty in identifying disease risk variants in complex traits. In this thesis, genomic workflows are used to investigate MMVD in an Australian population of Cavalier King Charles Spaniels (CKCS), a breed disproportionately affected by the trait. I first assessed the strength of MMVD phenotypes for use in comparative genomic studies. Then, through bioinformatic approaches, I investigated the genetic landscape of the disease in this breed. Using genomic tools developed for the dog and a combined approach of objective phenotyping, I was able to thoroughly explore the genetics and genomics of MMVD in the CKCS using different types of genomic analyses. In doing so, I was able to demonstrate the utility of pedigreed breeds in the investigation of complex traits and the versatility of genomic datasets. Throughout this thesis MMVD associated loci, candidate genes and putative functional variants are reported
- âŠ