Variation in the psychosocial determinants of the intention to prescribe hormone therapy prior to the release of the Women's Health Initiative trial: a survey of general practitioners and gynaecologists in France and Quebec

BACKGROUND: Theory-based approaches are advocated to improve our understanding of prescription behaviour. This study is an application of the theory of planned behaviour (TPB) with additional variables. It was designed to assess which variables were associated with the intention to prescribe hormone therapy (HT). In addition, variations in the measures across medical specialities (GPs and gynaecologists) and across countries (France and Quebec) were investigated. METHODS: A survey among 2,000 doctors from France and 1,044 doctors from Quebec was conducted. Data were collected by means of a self-administered questionnaire. A clinical vignette was used to elicit doctors' opinions. The following TPB variables were assessed: attitude, subjective norm, perceived behavioural control, attitudinal beliefs, normative beliefs and power of control beliefs. Additional variables (role belief, moral norm and practice pattern-related factors) were also assessed. A stepwise logistic regression was used to assess which variables were associated with the intention to prescribe HT. GPs and gynaecologists were compared to each other within countries and the two countries were compared within the specialties. RESULTS: Overall, 1,085 doctors from France returned their questionnaire and 516 doctors from Quebec (response rate = 54% and 49%, respectively). In the overall regression model, power of control beliefs, moral norm and role belief were significantly associated with intention (all at p < 0.0001). The models by specialty and country were: for GPs in Quebec, power of control beliefs (p < 0.0001), moral norm (p < 0.01) and cytology and hormonal dosage (both at p < 0.05); for GPs in France, power of control beliefs and role belief (both at p < 0.0001) and perception of behavioural control (p < 0.05) and cessation of menses (p < 0.01); for gynaecologists in Quebec, moral norm and power of control beliefs (both at p = 0.01); and for gynaecologists in France, power of control beliefs (p < 0.0001), and moral norm, role belief and lipid profile (all at p < 0.05). CONCLUSION: In both countries, compared with GPs, intention to prescribe HT was higher for gynaecologists. Psychosocial determinants of doctors' intention to prescribe HT varied according to the specialty and the country thus, suggesting an influence of contextual factors on these determinants

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Accumulation of lipophilic dications by mitochondria and cells

Lipophilic monocations can pass through phospholipid bilayers and accumulate in negatively-charged compartments such as the mitochondrial matrix, driven by the membrane potential. This property is used to visualize mitochondria, to deliver therapeutic molecules to mitochondria and to measure the membrane potential. In theory, lipophilic dications have a number of advantages over monocations for these tasks, as the double charge should lead to a far greater and more selective uptake by mitochondria, increasing their therapeutic potential. However, the double charge might also limit the movement of lipophilic dications through phospholipid bilayers and little is known about their interaction with mitochondria. To see whether lipophilic dications could be taken up by mitochondria and cells, we made a series of bistriphenylphosphonium cations comprising two triphenylphosphonium moieties linked by a 2-, 4-, 5-, 6- or 10-carbon methylene bridge. The 5-, 6- and 10-carbon dications were taken up by energized mitochondria, whereas the 2- and 4-carbon dications were not. The accumulation of the dication was greater than that of the monocation methyltriphenylphosphonium. However, the uptake of dications was only described by the Nernst equation at low levels of accumulation, and beyond a threshold membrane potential of 90–100 mV there was negligible increase in dication uptake. Interestingly, the 5- and 6-carbon dications were not accumulated by cells, due to lack of permeation through the plasma membrane. These findings indicate that conjugating compounds to dications offers only a minor increase over monocations in delivery to mitochondria. Instead, this suggests that it may be possible to form dications within mitochondria that then remain within the cell