Political history in the digital age: the challenges of archiving and analysing born digital sources

The vast bulk of source material for historical research is still paper-based. But this is bound to change. Dr Helen McCarthy considers the lessons from the Mile End Institute’s conference on Contemporary Political History in the Digital Age. The specific challenges of using a ‘born digital source’ is an area that requires considerable attention. For political historians, the advent of ‘e-government’ and personal digital archives, and the many formats and artefacts involved, is thrilling but also intimidating

The Diplomatic History of Global Women’s Rights: The British Foreign Office and International Women’s Year, 1975

This article explores the British Foreign Office's engagement with International Women's Year (IWY) in 1975, an event which has been viewed as a milestone in histories of transnational feminist activism, and a moment when the status of women became part of mainstream thinking about development, human rights and global security. Much of the existing literature on IWY dwells on the role of non-state actors, especially women's NGOs active at the United Nations (UN). In contrast, this article shifts the lens on to state actors, in order to ask what role diplomats, politicians and ministries of foreign affairs played in the construction of ‘women’ as a global political subject in the late twentieth century. It finds that the Foreign Office's reading of IWY was refracted through the prism of Cold War power politics and postcolonial struggles. Gender politics was conceptualised as essentially a proxy for these larger ideological battles, an approach dating back to Britain's semi-clandestine anti-communist propaganda campaigns after the Second World War. British women's NGOs, by contrast, insisted that women's activism should be accorded an independent dynamic of its own, imagining the possibilities of gender-based solidarities operating across political, social and economic divides. IWY and the subsequent UN Decade for Women tempered this idealism and set the international women's movement on a political learning curve. But, as the article will suggest, the 1970s was also a moment when state elites were forced to confront a new kind of global politics, the repercussions of which for the conduct of foreign policy and diplomatic relations only further fine-grained archival research can fully reveal

Whose outcomes are they anyway? Report of the pilot evaluation of a joint service\ud

Health and social care partnership working is often predicated on the notion that it improves outcomes for service users. Yet there is a lack of evidence linking partnerships to changes in outcomes. Against this background, the Health Services Management Centre at the University of Birmingham designed the Partnership Outcomes Evaluation Toolkit (POET) specifically to evaluate health and social care partnerships in terms of service user outcomes. This paper reports on the field testing of POET with Sandwell Integrated Support Service. This research provided a number of interesting insights into this service, and indicated some dissonance between staff and service user and carer expectations

The regulation of osteoprotegerin and dickkopf-1 production in osteoblastic cells

Bone is a highly specialised living tissue and has both mechanical and metabolical functions. Remodelling of the bone ensures a healthy bone mass and is regulated by a trio of secreted proteins, namely receptor-activator of NFKB (RANK), receptor-activator of NFKB ligand (RANKL) and osteoprotegerin (OPG). OPG, a major regulator of osteoclastogenesis, bone resorption and vascular calcification, is produced by various cell types including mesenchymally derived cells, particularly osteoblastic cells. Wnt signalling also plays a role in maintaining healthy bone mass. Dickkopf- 1 (DKK-1) is a soluble inhibitor of Wnt signalling and its excessive expression contributes to bone loss in rheumatoid arthritis and multiple myeloma. Recently, NDKK-1 has been demonstrated to be over-produced in osteoblasts of patients with Paget's disease of bone (PDB). The osteoblastic cell lines MG63 and Saos-2 were subjected to a series of different growth factors, hormones and cytokines to investigate the production of OPG, DKK-1 and the expression of various Wnt proteins. These results demonstrate that during standard culture conditions, both OPG and DKK-1 production in osteoblastic cells depend on a factor present in serum. Serum deprivation resulted in the up-regulation of Wnt4 and Wnt11, while down-regulating the expression of Wnt7b. Serum-induced OPG and DKK-1 production and Wnt expression was found to be regulated via a number of different signalling pathways. OPG production and expression was stimulated by platelet-derived growth factor-AB (PDGF-AB) not only in MG63 and Saos-2 osteosarcoma cells, but also a mouse pre-osteoblastic cell line (MC3T3-E1) and human bone marrow stromal cells (BMSC). PDGF-AB was shown to act through the PDGF receptor, PKC, PI3K, ERK and P38 and not via NFKB or JNK. PDGF isoforms AA, BB and AB demonstrated a similar stimulation of OPG production. The importance of PDGF in fracture healing suggests a role for OPG production in countering bone resorption during the early phase of this process. BIO, an inhibitor of canonical Wnt signalling resulted in the down-regulation of DKK-1 and the up-regulation of WntSa. Phorbol ester (PE), a known stimulator of PKC resulted in the up-regualtion of DKK-1, Wnt4, WntTa and Wnt16. The effects of PE were inhibited by bisindolymaleamide but not staurosporine. DKK-1 production, but not expression, was observed to be stimulated by calcium along with an up-regulation of WntTb and a down-regulation of WntWa and Wnt11. Incubation of pre-stimulated cells with Triton-X demonstrated the ability of calcium to increase DKK-1 secretion. DKK-1 was shown to be significantly elevated in the serum of PDB patients compared to healthy controls and did not correlate with ALP levels. Immunohistochemistry demonstrated that DKK-1 production is increased in both osteoblasts and fibrotic cells within the marrow cavity in PDB patients compared to fracture callus. B-catenin was found to be localised to intercellular membranes of plump osteoblasts, demonstrating its alternate role as a cell adhesion protein. DKK-1 therefore may be a useful biomarker of PDB and that Dkk-1 may play a central role in the aetiology of PDB. In summary, the results presented in this thesis have investigated the ways in which OPG and DKK-1 production in osteoblastic cells can be modulated with various effectors and the effect of Wnt signalling. These results may therefore be beneficial to increase the understanding of bone biology, improve fracture repair and generate further research into the role DKK-1 and the osteoblast in the aetiology of PDB to enable improved treatments to be developed.Charles Salt Centre, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Trust in Oswestr

The Distribution and Economic Significance of he Genus Polygonum in Sacramento County of California

The genus Polygonum belongs to the family of plants, the Polygonaceae, which includes about forty genera and seven hundred and fifty species. About two hundred end seventy-five of these belong within Polygonum. Scientists have also found distinctly recognizable fossil Polygonums which date from prehistoric ages. Dr. F. H. Knowlton¹ of the U. S. National Museum has listed twelve species which have been found in fossil form. While studying collection of Colorado fossil plants in the Geological Tunes et Columbia College, Small discovered a remarkably distinct Polygonum belonging to the subgenus Persicaria

Backboards to blackboards : rebounding from the margins ; a critical auto/ethnographic study of the struggle for culturally-sensitive educational pathways for Aboriginal girls

This PhD research journey describes my personal and professional involvement with the Yolngu, Nyoongar and Wongi peoples, where I consistently observed Aboriginal parents and Aboriginal teachers express dissatisfaction with the way mainstream Anglo-Celtic education was delivered in their schools and communities. This disparity never sat well with me and I had always wanted to write about the unacceptable inequity.As a consequence this doctoral research deploys a critical auto/ethnographic research design within an interpretive paradigm where “the writing process and the writing product are deeply intertwined”. The research became the site of exploration about the struggle for culturally-sensitive educational pathways for Aboriginal adolescent girls.The investigation took place at a metropolitan Aboriginal secondary school, where staff developed an emergent curriculum framework known as the Yorgas Program to re-engage Aboriginal learners in their schooling, through a sporting program known as the “Girls‟ Academy”. As a consequence of the Yorgas Program there were observable improvements in the girls behaviour leading to regular attendance, improved personal hygiene, greater commitment to study, self-regulation and willingness to defer risk-taking social behaviours resulting in a significantly larger number of Year 12 graduates completing their studies with the majority of students going on to traineeships or further studies

Current status of gene therapy for breast cancer: progress and challenges

Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development

Women, Marriage and Paid Work in Post-war Britain

This article explores the effects of the growth in married women's employment upon the dynamics of British marriages in the post-war period. Drawing on popular sociology, newspapers and women's magazines from the 1950s and 1960s, it shows how shifting patterns of women's labour, linked to longer term demographic and socio-economic trends, prompted considerable debate about the stability and future of marriage. Whilst some argued optimistically that the employment of wives strengthened marriage through the material security guaranteed by a second wage and by building greater commonality of interests between spouses, other sources point to a more complex picture. Working wives were seen to imperil marital harmony because of the challenge they posed to men's ‘traditional’ identity as providers and to the legitimacy and modernity of the full-time housewife-worker in the home. The article concludes that paid work made a significance difference to marital power relations in this period; women's wages did not free them wholly from economic dependency, but they nonetheless offered a small slice of financial autonomy and elevated wives' status within the marriage relationship. Paid work thus offers historians an analytical thread of continuity linking the 1950s to later decades of change in women's lives

Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers

The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting. Development of multifunctional delivery systems holds much promise for the progression of gene delivery, and a growing body of evidence supports this approach involving rational design of vectors, with a unique molecular architecture. In addition, the potential application of composite gene delivery platforms is highlighted which may provide an alternative delivery strategy to traditional systemic administration. </jats:p