19 research outputs found
Advances in lung cancer basic and translational research in 2025 - Overview and perspectives focusing on non-small cell lung cancer
No full textBasic and translational research in lung cancer is a rapidly evolving field with transformational impact in early detection, diagnosis, therapeutic development and personalization of care. Recent advances have greatly increased our understanding in the molecular genomics, proteomics, pathogenesis and cellular biology of this deadly malignancy. The International Association for the Study of Lung Cancer (IASLC) recently formed a Basic and Translational Science (BaTS) Committee to further enhance the scientific leadership of IASLC in thoracic cancer research. This review by members of the committee highlights the breadth of current research in NSCLC, with a focus on molecular risk factors and processes in tumorigenesis, heterogeneity, phenotypic plasticity, metabolic reprograming, immunobiology, the immune microenvironment and microbiome. This review also identifies future research areas that may lead to further improvement in survival outcomes and curative therapies especially for patients with advanced NSCLC.Versión Aceptad
Advances in Lung Cancer Basic and Translational Research in 2025 – Overview and Perspectives Focusing on NSCLC
No full textInternational audienceBasic and translational research in lung cancer is a rapidly evolving field with a transformational impact on early detection, diagnosis, therapeutic development, and personalization of care. Recent advances have greatly increased our understanding of the molecular genomics, proteomics, pathogenesis, and cellular biology of this deadly malignancy. The International Association for the Study of Lung Cancer (IASLC) recently formed a Basic and Translational Science (BaTS) Committee to further enhance the scientific leadership of IASLC in thoracic cancer research. This review by members of the committee highlights the breadth of current research in NSCLC, with a focus on molecular risk factors and processes in tumorigenesis, heterogeneity, phenotypic plasticity, metabolic reprogramming, immunobiology, the immune microenvironment, and microbiome. This review also identifies future research areas that may lead to further improvement in survival outcomes and curative therapies especially for patients with advanced NSCLC
Ethical relationships between science and society: Understanding the social responsibility of scientists
No full textThe wider social responsibility of scientists has received theoretical discussion but little previous empirical research. To elucidate the construct, this thesis investigated scientists’ attitudes, values and beliefs about social responsibility, with a focus on Promethean gene technologies. The thesis articulates a framework for the construct domain and develops and validates a set of new measures related to scientific social responsibility. Five technology fuelled, social and ecological, existential threats to Earth are identified, establishing the need for an increased ethic of social responsibility for the scientific endeavour and scientists in an age of Promethean technologies. The power of developing gene technologies and their social and moral implications are examined, followed by a discussion of relevant normative, meta-ethical and applied ethics theories. Next, Kohlberg’s (1969) cognitive moral development theory, Rest’s (1979) theory of moral behaviour, and Schwartz’s (1992) theory of personal value orientation are discussed as a psychological context for scientific social responsibility. The few empirical studies addressing the issue are reviewed. Original empirical contributions are presented in two studies. Study 1 is an explorative, qualitative research project using face-to-face, in-depth, unstructured interviews to investigate a purposive sample of scientists’ (N = 22) beliefs about the social role of science, and scientists, in research and technology development. The participants all worked in the field of genetic engineering, or studied its social or ecological impacts. From a data-driven, manifest, thematic analysis, three themes emerged, each with several sub-themes: doing public good (sub-themes: benefit/harm, knowledge, technologies, and foresight); engagement (sub-themes: informing society, becoming informed, and integrity) and; compliance (sub-themes: scientific norms, business norms, laws and regulations, societal mores, and personal values). A theoretically-driven, latent, thematic analysis, examined the normative and meta-ethical reasoning underlying participants’ manifest positions. Evidence was found for normative ethical reasoning (i.e., deontological, teleological and virtue ethics) and a range of meta-ethical approaches (i.e., ethical relativism, conventionalism, objectivism, moral absolutism, subjectivism, emotivism, and cultural relativism). From Study 1 items were proposed for two measures of social responsibility based on the first two stages of Rest’s model of moral behaviour. Study 2, a quantitative survey of scientists from six New Zealand Crown Research Institutes (N = 733, 40.9% female), used a nomological network of 39 hypothesised directional relationships (correlations) to help infer construct validity to five new instruments related to social responsibility: moral awareness, moral judgement regarding personal behaviour, technological optimism, attitude to the commercialisation of science, and attitude to the democratisation of science. Five existing instruments also comprised the nomological network: the four Schwartz higher-order value dimensions and a concurrent criterion, general attitude to genetic engineering. Exploratory factor analysis was used to select items for single factor instruments and confirmatory factor analysis to purify the instruments’ dimensionality, followed by reliability analyses. Four new instruments demonstrated good psychometric properties. Twenty-seven of 39 hypothesised correlations were significant in the right direction (at the Bonferroni adjusted p < .001 level), providing initial support for the new instruments’ construct validities and study results regarding participants’ attitudes, beliefs and values towards conducting socially responsible Promethean science
Guide to the nature and methods of analysis of the clay fraction of tephras from the South Auckland region, New Zealand.
No full textThe manual outlines some of the more common laboratory procedures available for qualitatively and quantitatively analysing the composition of the tephric clays, many of which are difficult to determine because of their short range order or 'amorphous' nature. Techniques described and assessed in terms of their rapidity and quantitativeness include XRD, IR, DTA, TEM and SEM, sodium fluoride reactivity, chemical dissolution analyses, and surface area measurements. No one technique alone produces a definitive clay fraction analysis of tephric deposits. -from Author
The early pathogenesis of foot-and-mouth disease in cattle after aerosol inoculation
No full textDepartment Head: Edward Arthur Hoover.2010 Summer.Includes bibliographical references.The goal of the efforts described in this dissertation was to characterize the early pathogenesis of foot-and-mouth disease (FMD) in cattle after simulated natural infection. More specifically, emphasis was placed upon two critical knowledge gaps: identification of the primary site(s) of infection of FMD virus (FMDV) and the mechanism of establishment of viremia. In order to investigate these processes, novel systems were developed for (1) consistent experimental aerosol infection of steers, (2) molecular and virological detection of FMDV in bovine tissues, and (3) microscopic localization of FMDV antigens in bovine tissues. These novel tools were then applied to a thorough, prospective, time-course analysis of bovine FMD. Screening of antemortem samples indicated that establishment of primary infection in the respiratory tract was detectable between 4 - 6 hours post aerosol inoculation (hpa); establishment of viremia was detectable between 24 - 48 hpa. Examination of tissue samples collected postmortem demonstrated that in previremic steers, FMDV was most consistently localized to nasopharyngeal tissues by all detection methods indicating this region as the most important site of primary viral replication. The earliest site of microscopic localization of FMDV antigens was the lymphoid follicle-associated epithelium of the pharyngeal mucosa - associated lymphoid tissue (PALT) of the nasopharynx. At early time points after aerosol inoculation, viral antigens colocalized with cytokeratin-positive pharyngeal epithelial cells; intraepithelial, FMDV-negative, MHCII/CD11c-double positive dendritic cells were present in close proximity to FMDV-positive cells. Onset of viremia coincided with marked increase of viral loads in pulmonary tissues and substantial decrease of viral detection in nasopharyngeal tissues. These data indicate that subsequent to aerogenous exposure to FMDV, the temporally defined critical pathogenesis events are (1) primary replication in epithelial cells of the PALT crypts, (2) subsequent widespread replication in pneumocytes in the lungs which coincides with (3) the establishment of sustained viremia. This body of work is unique for its breadth and depth of investigation of FMD in cattle; the importance of the conclusions described herein may be separated into three tiers. The detailed characterization of the early virus-host interactions provides a greater level of understanding of the pathogenesis of this important disease and thus directly contributes to basic science knowledge. Additionally, the novel techniques described herein may be applied to a wide range of subsequent pathogenesis studies which will further elucidate FMDV-host interactions in various species and stages of infection. However, the translational implications of the findings are likely to, ultimately, have greatest significance by contributing to the development of rationally designed FMDV vaccines and biotherapeutics. Specifically, the data described in the chapters which follow strongly suggest that improved mucosal immunity (particularly in the nasopharynx) should be a high-priority goal of "next generation" FMDV prophylaxis
Common susceptibility variants are shared between schizophrenia and psoriasis in the Han Chinese population
No full textBackground Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants (h(SNP)(2) = 29% 5.0%, p = 2.00 x 10(-8)), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen (HLA) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 x 10(-16)). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.National Natural Science Foundation of China [81370044, 81000692, 81273301, 81072461, 81130031, 81222022, 81222017]; China Council of Scholarship [201208340003]; Youth Project of the Outstanding Talents of Organization Department of the CPC Central Committee Program [31200939]; Pre-National Basic Research Program of China (973 Plan) [2012CB722404]; Anhui Province Natural Science Foundation [1208085QH145]; Anhui High Education Young Talent; Anhui Medical University [XJ201429]; NIH [1UL1TR001114, U19 AG023122-09, R01 DA030976-05, R01 MH094483-03, R01 AG035020-05, R01 MH100351-02, R21 AG045789-01A1]; Human Longevity, Inc.; Johnson and Johnson; Tanner Foundation; Stand-Up-to-Cancer organization; National Research Foundation Singapore under the National Medical Research Council Translational and Clinical Research Flagship Program [NMRC/TCR/003/2008]SCI(E)[email protected]; [email protected]
Global Research and Exchange between Institutions: Pre-Clinical, Translational, Clinical and Applied Research: Panel #2
No full textMichael J. Vergare, MD (Moderator)
Michael J. Vergare is the Daniel Lieberman Professor and Chair of the Department of Psychiatry and Human Behavior, Sidney Kimmel Medical College and the Executive Vice President for Partnerships and Affiliations, Thomas Jefferson University. He joined Jefferson as Chair in 1998 and in addition to his work in psychiatry, he served as Interim Dean of Jefferson Medical College (2007-2008) and the Senior Vice President for Academic Affairs (Provost) (2008-2014) of TJU.
Dr. Vergare received a Bachelor of Arts degree from LaSalle University and a Doctor of Medicine degree from Hahnemann Medical College/Drexel. He completed his residency in Adult Psychiatry at Hahnemann, during which he received a six month grant to study under the direction of Anna Freud, PhD at the Hampstead Clinic in London. He is a Distinguished Life Fellow of the American Psychiatric Association, a Distinguished Fellow of the American College of Psychiatrists and a Fellow of the College of Physicians of Philadelphia. Throughout his distinguished career, Dr. Vergare has received many honors including the Presidential Medal of the American Psychiatric Association, the Judicare Medical Services Award, the Einstein Society Physician Leader Award, the Bell of Hope Award of the Mental Health Association of Southeastern and the Philadelphia Psychiatric Society’s Edward Lawlor Award, Daniel Blain Award and Paul J. Fink Leadership Award at the 2016 Benjamin Rush Gala through the Philadelphia Psychiatry Society (PPS).
Dr. Vergare has served on the several councils as well as the Alliance of Independent Academic Medical Centers board and Health Partners of Philadelphia board. He has also been a member and chair of the Pennsylvania Governor’s Advisory Committee for Mental Health and Mental Retardation and has served on the National Advisory Council of the Center for Mental Health Services of the Substance Abuse and Mental Health Services Administration of Health and Human Services. Currently, he is chair of the Practice Guidelines Steering and Executive Committees of the American Psychiatric Association.
Cataldo Doria, MD, PhD, MBA
Cataldo Doria received his degrees at the University of Perugia in Italy and completed a research fellowship in small bowel transplantation at the University of Pittsburgh Transplantation Institute and a clinical fellowship in multi-organ transplantation at the Thomas E. Starzl Transplantation Institute of the University of Pittsburgh. Dr. Doria is Professor of Surgery at Sidney Kimmel Medical College at Thomas Jefferson University. Dr. Doria is the inaugural Nicoletti Family Professor of Transplant Surgery at Sidney Kimmel Medical College at Thomas Jefferson University, as well as the Director of the Jefferson Transplant Institute, the Director of the Division of Transplantation, and the Surgical-Director of the Sidney Kimmel Cancer Center and Liver Tumor Center. Dr. Doria came to Jefferson from the Mediterranean Institute for Transplantation and Advanced Specialized Therapies, a partnership between the University of Pittsburgh Medical Center and the Italian National Government.
His research interests include the development of inhibitory pathways for liver cancer growth, immunology of solid organ transplantation, innovative application of artificial liver treatment. Among many awards, Dr. Doria was named “surgeon of the year” by the Delaware Chapter of the American Liver Foundation, and named by the President of the Italian Republic, Giorgio Napolitano, Cavaliere dell’Ordine “Al merito della Repubblica Italiana” (Knight of the Italian Republic). Dr. Doria is author of 256 publications: 88 refereed articles; 74 proceedings of conference and symposia, 3 monographs; 8 book chapters; 78 published abstracts; 5 other publication.
Dr. Doria is Principal Investigator and co-Investigator of numerous clinical as well as basic science research trials. He is a member of numerous professional and scientific societies. He served as Associate Editor the American Society of Transplantation Newsletter, and is part of the Editorial Board of many journals.
Mohammadreza Hojat, PhD
Mohammadreza Hojat is a Research Professor, Department of Psychiatry and Human Behavior and Director of the Jefferson Longitudinal Study, Sidney Kimmel Medical College at Thomas Jefferson University. He received his doctoral degree in psychological services from the University of Pennsylvania. Dr. Hojat is a licensed psychologist, and has published more than 200 articles in peer reviewed journals and 13 book chapters on educational, psychological, and social issues.
Dr. Hojat has led the development of 10 psychometrically sound instruments (including the Jefferson Scale of Empathy) for the assessment of health professions education and patient outcomes. He has served as a co-editor of “Loneliness: Theory, Research, and Applications” (Sage, 1987), and “Assessment Measures in Medical School, Residency, and Practice: The Connections” (Springer, 1993). The original edition of his book “Empathy in Patient Care: Antecedents, Development, Measurement, and Outcomes” was published in 2007 (Springer Science). An expanded and updated version of the book under a new title: “Empathy in Health Professions Education and Patient Care” was released in 2016.
Vittorio Maio, PharmD, MS, MSPH
Vittorio Maio is a Research Professor in the Jefferson College of Population Health, Thomas Jefferson University. His research interests are in the areas of outcomes analysis and medication usage and policy. Dr. Maio is principal investigator on multi-year collaborative projects funded by various Healthcare Authorities in the Regione Emilia-Romagna, Italy, mainly looking at the appropriateness of medication prescribing and the assessment of the quality of care in inpatient and outpatient settings.
Dr. Maio teaches Pharmacoepidemiology in the Master of Science Program in Pharmacology, Sidney Kimmel Medical College for the trainees in the NIH K30 Training Program. He lectures on health policy issues in the Master in Management of Healthcare Organizations, Faculty of Economics, and University of Pisa, Italy. He also lectures on health services and outcomes research in the Residency Program of Hygiene and Preventive Medicine, School of Medicine, University of Parma, Italy. Dr. Maio is a reviewer for Pharmacoepidemiology and Drug Safety, Drugs & Aging, and The Lancet. He is Associate Editor of the American Journal of Medical Quality.
Daniel Z. Louis
Daniel Z. Louis is Managing Director of the Center for Research in Medical Education and Health Care and Research Associate Professor of Family and Community Medicine, Sidney Kimmel Medical College at Thomas Jefferson University. He is principal investigator of a series of multi-year collaborative projects with the Regione Emilia-Romagna, Italy, which use a large population-based database to address a variety of issues relating to organization, financing, and quality of care. He teaches health policy as a part of the Introduction to Clinical Medicine course for first year medical students. He is a guest lecturer at the Università Cattolica del Sacro Cuore, Rome, in their master’s program in health administration and at the University of Pisa, Faculty of Economics, Master’s Program in management of health care organizations.
He has been appointed by the Italian Minister of Health to the Scientific Committee of Progetto IT.DRG, a multi-year project to develop the next generation hospital coding and financing systems. He is a reviewer for the Annals of Internal Medicine and Medical Care and a member of the editorial board of the Jefferson Health Policy Newsletter.
Mrityunjay Metgud, MBBS, MD
Mrityunjay Metgud serves as the country coordinator for the newest NIH-funded Global Network trial employing low-dose aspirin to prevent pre-term birth.
He is professor of Obstetrics and Gynecology at K.L.E. University’s J N Medical College and has served on the research team for the Global Network Corticosteroid trial and for the Estimation of Gestational Age by the use of a simplified Tape. He is also consultant obstetrician/gynecologist and gynec- oncologist at KLES Dr. Prabhakar Kore Hospital and MRC Belgaum.
Dr. Metgud is a nationally recognized leader in laparoscopic gynecologic surgery and a trainer in obstetrical ultrasound. He is a member of several associations, including IMA, Belgaum North Branch, FOGSI, Belgaum Branch, Karnataka State Obstetrics and Gynecological Society and is a Life Member of the Association of Gynecologic Oncologists of India (AGOI). He became president of the Belgaum OBGYN Society in 2015. Dr. Metgud has contributed to many books, written articles and presented at national conferences
Rigorous review and editorial oversight of clinical preprints
No full textThe urgent need to understand and control COVID-19, and to effectively treat people with the disease, has mobilized global scientific and medical communities like nothing in human history. It has also ushered in a new era in medical publishing. Notably, the desire to share results rapidly, widely and openly has led to an explosion of submissions to the preprint server medRxiv. But even as the pandemic has demonstrated the potential for rapid, author-driven publication to democratize access and accelerate research, it has exposed the challenges of this model of scholarly communication. With intense public appetite for information about the virus and pandemic, there has been a real danger that individuals and institutions will act hastily on information about risks, mitigation strategies and treatments before it is adequately scrutinized. Such opportunities and challenges, best illustrated during the pandemic, lie ahead as medicine moves towards the goal of providing evidence-based care to patients no matter where they live. This trajectory also opens up real opportunities for speed, transparency and rich evaluation across peer review in medicine. We are therefore excited to announce that eLife’s reinvigorated Medicine section will offer a whole new approach to publishing in medicine, including public health and health policy. We will apply our system of editorial oversight by practicing clinicians and clinician-investigators, and rigorous, consultative peer review to produce public reviews of preprints with significant potential to impact clinical practice. Our goal is to transform unrefereed manuscripts posted on medRxiv into refereed preprints that provide readers and potential users with a detailed assessment of the science, comments on its potential impact, and perspectives on its use. In essence, by providing rich and rapid evaluation of preprints, we hope that refereed preprints become a currency of trust in medicine. We will continue to operate like a traditional journal, providing authors who submit their preprints to us with feedback from the reviewers and editors, and we will select a subset of papers for formal publication in eLife. Our scope is broad, covering all areas of the health sciences ranging from cellular and murine models of disease, to human genetics and genomic sciences, to therapeutic discovery, to all phases of clinical investigation, to population health outcomes, to health policy and clinical decision making. eLife was launched in 2012 by three funders – Howard Hughes Medical Institute, Wellcome Trust and Max Planck Society, later joined by the Knut and Alice Wallenberg Foundation – who were eager to take a more active role in promoting best practices in scientific and medical publishing. Founding Editor-in-Chief Randy Schekman focused on improving the culture of peer review, pioneering a consultative approach in which reviewers and editors come together to discuss their assessments, reach a collective decision on whether the strengths of the work merit publication in eLife and which, if any, weaknesses need to be addressed before publication. The authors are then provided with a clear and concise decision letter that is free of the conflicting opinions and recommendations often found in reviews. Since 2019, with one of us (MBE) as Editor-in-Chief, eLife has moved to embrace and encourage the growth of preprints even more strongly in all areas of science and medicine, and has developed a new concept of 'publish, then review' to serve readers and users, as well as authors (Eisen et al., 2020). This new system of creating public reviews of preprints, described briefly above, is the first major product of these efforts. The re-launch of eLife’s Medicine section is the second. While eLife has traditionally focused on basic science, many of our editors are practicing clinicians who run research groups that cross the proverbial line between basic and clinical research. We have published papers in early translational research, but over the past few years have received many requests to bring our innovations in peer review and preprint review into the full spectrum of research in medicine. To answer these calls, and to ensure we do so successfully, we have recruited two Deputy Editors in Medicine (DMH and MZ) and a group of Senior Editors that includes accomplished women and men from around the globe. These Senior Editors in turn have the responsibility of overseeing the review process through our Board of Reviewing Editors, which has also been greatly expanded (and will continue to expand) to include clinicians, public health specialists, and basic, translational and clinical researchers spanning a wide range of disciplines. In building the team, we have emphasized not only clinical expertise, scientific excellence and intellectual breadth, but also equity, diversity and inclusion, in order to ensure that we address patient-centered research for everyone. The result is an editorial board that can truly aim to cover all areas of modern biology and medicine, with the ability to handle any paper in any discipline, especially those that span and knit together work from fields whose practitioners do not traditionally publish in or read the same journals. For example, we are now well equipped to evaluate all aspects of papers whose topics range from behavioral sciences and social determinants of health to clinical genetics, structural biology, drug discovery and early–stage efficacy studies. We are equally equipped to handle papers describing new COVID-19 virus mutations, their coverage by vaccines, and modeling future infections in different population settings. In keeping with our desire to tackle the most difficult issues in publishing, we have also created a new Ethics Committee – a think tank of ethicists and individuals with long-standing experience in different aspects of science, medicine and publishing – to provide guidance on issues including, but not limited to, publishing, medical and animal ethics, biosecurity and biosafety, environmental justice, competing interests, data availability, and issues surrounding studies with minority populations in the developing world. These issues are of growing importance across both biology and medicine
Expression and function of osteopontin variants in HCV-related liver disease and hepatocellular carcinoma.
No full textOsteopontin (OPN) is a highly secreted multi-functional sialoprotein that is widely expressed in tissues, blood and urine. It is involved in a number of normal physiological functions, but is also significantly elevated in a number of cancers. While OPN is significantly expressed in hepatocellular carcinoma (HCC) little is known as to its role and if it is expressed in the pre-cancerous hepatitis C virus (HCV) infected liver. In this thesis we show that OPN is expressed in the liver and in HCC as three variants, the full-length protein OPN-A and two splice variants OPN-B and OPN-C. Through production of stable Huh-7 cells expressing the OPN variants, we show for the first time that all variants increase proliferation of a range of cultured hepatoma cell lines in a paracrine manner through
interactions with the cell surface OPN receptor CD44. Similarly, OPN-A (and to a lesser extent OPN-B and –C) accelerated Huh-7 derived tumor growth in a nude mouse model. We also show for the first time expression of all three OPN variants in the non-diseased liver as it was previously thought that splicing was a feature specific for tumor cells. Clinically, OPN is known to be highly expressed in HCC, however, its expression in chronic hepatitis C is not well documented. In this thesis we show that OPN mRNA expression is elevated in the HCV-infected liver with a trend towards increased expression as liver disease progresses. Consistent with an increase in mRNA, serum OPN levels were also increased in the HCV-infected liver although we could find no correlation with degree of liver disease. However, our sample size was small and this section of the thesis needs repeating with a larger HCV-infected patient cohort. Furthermore, we show that elevated OPN expression is not specific to the HCV-infected liver as OPN is also elevated in the HBV-infected and alcoholic liver suggesting that HCV does not drive OPN expression but is more likely as a result of the inflammatory process in the viral infected liver. Interestingly we also show that there is a shift of OPN expression from bile duct epithelial cells in the non-diseased liver to the hepatocyte in the HCV-infected liver which raises the question as to the role of OPN in hepatocyte transformation to facilitate the development of HCC. Our evaluation of serum OPN expression also suggests that OPN has potential as both a diagnostic and potentially prognostic biomarker for not only HCC (arising from HBV and HCV infections and alcohol abuse) but also the earlier stages of HCV-related liver disease. This work for the first time characterises the expression of all OPN variants in the liver including HCC and may be useful for identifying targeted OPN-based therapeutic approaches for HCC and other cancers. Furthermore it also suggests that monitoring OPN in chronic hepatitis C may be
useful in monitoring liver disease progression and early detection of HCC.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 201
Women's experience of coping with termination of pregnancy for fetal abnormality: coping strategies, perinatal grief and posttraumatic growth
No full textPregnancy termination for fetal abnormality (TFA) represents 2% of all terminations in England and Wales. In recent years, the number of TFAs has risen (3,099 in 2014 compared to 2,085 in 2009) due to technological developments in prenatal diagnosis and increased maternal age, which have led to a growing number of fetal abnormalities being identified, and this earlier in pregnancy. Research suggests that TFA can have negative, long-lasting psychological consequences for women. These include depression, posttraumatic stress disorder and complicated grief. However, at the inception of the research programme, no research had been conducted on women’s coping processes when dealing with TFA despite clear evidence of a relationship between coping processes and psychological adjustment in other areas of health research. Similarly, although research indicates that some individuals experience positive growth as a result of trauma, no empirical work had been undertaken on potential positive psychological outcomes following TFA. Finally, a dearth of research on health professionals’ understanding of women’s coping with TFA was also identified, despite the likely impact this understanding would have upon women’s experience of care and the
way they cope with TFA.
This thesis aims to address these knowledge gaps in order to further our understanding of women’s experience of TFA. Specifically, the research had three main
objectives: 1) to gain an understanding of women’s coping strategies when dealing with TFA; 2) to examine the relationship between coping and psychological outcomes, as defined by perinatal grief and posttraumatic growth; and 3) to investigate health professionals’ perceptions of women’s coping to identify potential disparities between health professionals’ and women’s accounts. To answer these objectives, a mixed methodology was utilised and five studies were
conducted: a systematic review of the qualitative evidence pertaining to women’s experiences of TFA; two qualitative studies: the first one exploring women’s coping strategies when dealing with TFA, and the second one investigating health professionals’ perceptions of women’s coping; and, finally, two quantitative studies: the first one examining the relationship between coping strategies and perinatal grief, and the second one assessing the relationship between coping, perinatal grief and posttraumatic growth. The empirical work relating to the women was carried out online, with participants recruited from a specialist support organisation. The empirical work concerning the health professionals was conducted face-to-face, with participants recruited from three hospitals in England. Ethical approval was obtained for all studies prior to fieldwork commencing.
The research generated several important findings, which both build upon existing evidence and further our insights into women’s experience of TFA. Firstly, the research clearly indicates that women regard TFA as a traumatic event, which is akin to an existential crisis and which can have negative psychological consequences. Women view TFA as a unique form of bereavement, which can be misunderstood and stigma-bearing. The research also indicates that TFA is an individual as well as a social phenomenon with women’s experiences both shaping and reflecting the political and sociocultural environment within which TFA occurs.
Secondly, the research shows that coping with TFA involves four main strategies: ‘support,’ ‘acceptance,’ ‘avoidance,’ and ‘meaning attribution’ which are relevant to both the termination procedure and its aftermath. The findings also reveal that, despite mainly using coping strategies considered to be adaptive, women’s levels of grief are high, and that, for some individuals, distress persists long after the termination. The research also provides evidence of a relationship between coping and psychological adjustment to TFA, with strong associations observed between several coping strategies and psychological adjustment. In particular, the research shows that coping strategies such as ‘acceptance’ and ‘positive reframing’ are closely associated with lower levels of grief, whilst ‘self-blame’ and ‘behavioural disengagement’ relate to higher grief levels.
Thirdly, the research offers new insights into the potential for personal growth following TFA. This is particularly manifest in the qualitative investigations and, although it is less evident in the quantitative study, moderate levels of growth were observed for several growth dimensions: ‘relating to others,’ ‘personal strengths’ and ‘appreciation of others.’ The findings also indicate that a relationship exists between coping and posttraumatic growth, with ‘positive reframing’ being a significant predictor of growth.
Lastly, the findings reveal that health professionals have a valid understanding of women’s short-term coping strategies when dealing with TFA, but have limited insights into their long-term coping processes. This points to a deficit in aftercare, an issue which was raised by the women in this research.
Collectively, these findings have important implications in terms of theory, practice and future research in the area of TFA, which are considered in this thesis. Among the most significant ones are the need to identify women at risk of poor psychological adjustment, the need for a truly women-centred care that continues well beyond the termination, as well as the importance of ‘acceptance’ and ‘positive reframing’ as potential protective factors against distress and of ‘positive reframing’ as a potential foundation for growth. A corollary of the research is the development and implementation of a psychological intervention to support women following TFA. This proposed intervention is underpinned by the reported high levels of grief, the deficit in aftercare, and the potential for growth following TFA, and represents the next step of the research programme
