Cytostatic lung perfusion results in heterogeneous spatial regional blood flow and drug distribution: evaluation of different cytostatic lung perfusion techniques in a porcine model.

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.

Characterisation of the prodrome to a first episode of psychotic mania: results of a retrospective study.

BACKGROUND: Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative "high-risk" studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a sub-group of at-risk subjects. METHODS: Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses. RESULTS: Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are however likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania. LIMITATIONS: This is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies. CONCLUSIONS: Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD could be a sign of impending first episode mania.

Three essays in Swiss corporate governance

This dissertation is a combination of three relatively independent chapters on the subject of corporate governance. Corporate governance is presently at the epicenter of the global financial crisis. The lack of regulation and the misalignment of objectives have greatly contributed to the major crisis we are now in. Most governance research has been conducted in the United States in a context of widely held corporations and great executive power. It does not reflect the variety of situations around the world and we question the validity of this model in other contexts. The aim of this dissertation is to look at other governance models, in particular the Swiss corporate governance not only from a practical point of view, but also from a multi-theoretical approach. Traditional corporate governance literature has focused on the Anglo-American model that mainly follows the agency theory (Jensen and Meckling, 1976) in a shareholder-manager context, and overlooked other approaches. We focus on three different aspects of corporate governance using three different theories. First, we look at the ownership type of various corporations, using the agency theory in a context where issues between shareholders predominate over the typical shareholder-manager relationship. Second, we explore the adoption process of several governance mechanisms that, due to changes in legislation, has taken place in Switzerland since 2002. We use the institutional theory (DiMaggio and Powell, 1983), in a context where the environmental pressures are particularly high. Finally, we spotlight the board of directors as a key element of the governance of publicly listed corporations. Particularly, we focus on the independence of the board of directors, using a combination of the agency and resource dependence theories (Pfeffer, 1972; Pfeffer and Salancik, 1978).

Can Families Resist Managerial and Financial Revolutions? Swiss Family Firms in the Twentieth Century

The aim of this contribution is to highlight the long-term evolution of family capitalism in Switzerland during the twentieth century. We focus on 22 large companies of the machine, electrotechnical and metallurgy (MEM) sector whose boards of directors and general managers have been identified in five benchmark years across the twentieth century, which allows us to distinguish between family-owned and family-controlled firms. Our results show that family firms prevailed until the 1980s and thus contradict the dominance of 'managerial capitalism'. Although we observe a decline of family capitalism during the last decade of the century, the significant remaining presence of family firms in 2000 allows us to relativise the advent of investor capitalism.

A new pathway for the regulation and governance of health research

The Academy's review, 'A new pathway for the regulation and governance of health research' was published in January 2011. The report was prepared by a working group, chaired by Professor Sir Michael Rawlins FMedSci, convened in response to an invitation from Government to review the regulation and governance of UK health research involving human participants, their tissue or their data.The report proposes four key principles that should underpin the regulation and governance framework around health research in the UK, and makes recommendations to:Create a new Health Research Agency (HRA) to rationalise the regulation and governance of all health research. Include within the HRA a new National Research Governance Service to facilitate timely approval of research studies by NHS Trusts. Improve the UK environment for clinical trials.Provide access to patient data that protects individual interests and allows approved research to proceed effectively. Embed a culture that values research within the NHS.

Research Governance Guidance Note 1

HSC Trust Research Governance Permission - Pre-application guidance for applicants

Research Governance Guidance Note 2

HSC Trust Research Governance Permission - Submission of Application

Hepatitis C - what now? Patient results factsheet (English and 6 translations)

Factsheet for patients who have tested positive for the hepatitis C virus.

Hepatitis C positive, PCR positive: Clinician results factsheet

Factsheet for clinicians with patients who are antibody positive, and polymerase chain reaction (PCR) positive, and therefore have chronic hepatitis C infection.

Preliminary results on interleukin-4 and interleukin-10 cytokine production in malnourished, inducible nitric oxide synthase-deficient mice with schistosomiasis mansoni infection

Schistosoma mansoni infected C57Bl/6 inducible nitric oxide synthase (iNOS)-deficient and non-deficient malnourished mice, both fed a balanced controlled diet were studied. Interleukins, IL-4 and IL-10 responses to soluble egg antigens (SEA) 90 days after infection, were determined. Our results suggest that in iNOS deficient, malnourished mice, 90 days after of infection, nitric oxide has a downregulating effect on IL-4 and IL-10 production. We are currently investigating the biological significance of these findings.

Health at the time of Native-European contact in Southern Patagonia: First steps, results, and prospects

The objective of this paper is to present the first steps into the study of health in southern Patagonia during pre and post Native-European contact. Thus, our work has a double purpose. First, to discuss characteristics and relevance of human bone records of southern Patagonia, in order to study health in a population context. Second, to show some new lines of information, which include paleoparasitology, nutritional paleopathologies, and the study of lifestyles from human remains. In this context, we have started working on the first Spanish settlement "Nombre de Jesus", founded in 1584, and with historical documentation of "La Candelaria" Mission in Rio Grande (1896-1931).

Cervical screening: your results explained (English and 11 translations)

Testing for high-risk human papillomavirus (HR-HPV) as triage and test of cure was introduced into the Northern Ireland Cervical Screening Programme on Monday 28 January 2013. This policy change will significantly alter the screening pathway for women with a mild dyskaryosis or borderline smear result.