A Real Options Perspective On R&D Portfolio Diversification

This paper shows that the conditionality of investment decisions in R&D has a critical impact on portfolio risk, and implies that traditional diversification strategies should be reevaluated when a portfolio is constructed. Real option theory argues that research projects have conditional or option-like risk and return properties, and are different from unconditional projects. Although the risk of a portfolio always depends on the correlation between projects, a portfolio of conditional R&D projects with real option characteristics has a fundamentally different risk than a portfolio of unconditional projects. When conditional R&D projects are negatively correlated, diversification only slightly reduces portfolio risk. When projects are positively correlated, however, diversification proves more effective than conventional tools predict.real options;portfolio analysis;research & development

Loss and Recovery of Genetic Diversity in Adapting Populations of HIV

The evolution of drug resistance in HIV occurs by the fixation of specific, well-known, drug-resistance mutations, but the underlying population genetic processes are not well understood. By analyzing within-patient longitudinal sequence data, we make four observations that shed a light on the underlying processes and allow us to infer the short-term effective population size of the viral population in a patient. Our first observation is that the evolution of drug resistance usually occurs by the fixation of one drug-resistance mutation at a time, as opposed to several changes simultaneously. Second, we find that these fixation events are accompanied by a reduction in genetic diversity in the region surrounding the fixed drug-resistance mutation, due to the hitchhiking effect. Third, we observe that the fixation of drug-resistance mutations involves both hard and soft selective sweeps. In a hard sweep, a resistance mutation arises in a single viral particle and drives all linked mutations with it when it spreads in the viral population, which dramatically reduces genetic diversity. On the other hand, in a soft sweep, a resistance mutation occurs multiple times on different genetic backgrounds, and the reduction of diversity is weak. Using the frequency of occurrence of hard and soft sweeps we estimate the effective population size of HIV to be ( confidence interval ). This number is much lower than the actual number of infected cells, but much larger than previous population size estimates based on synonymous diversity. We propose several explanations for the observed discrepancies. Finally, our fourth observation is that genetic diversity at non-synonymous sites recovers to its pre-fixation value within 18 months, whereas diversity at synonymous sites remains depressed after this time period. These results improve our understanding of HIV evolution and have potential implications for treatment strategies

A method to increase the pulsatility in hemodynamic variables in an LVAD supported human circulation system

Left Ventricular Assist Devices (LVADs) generally operate at a constant speed in the human body. This causes a decrease in the pulsatility of hemodynamic variables. To increase the pulsatility a stepwise change was applied to the LVAD operating speed over a cardiac cycle. To do this, a numerical cardiovascular system model and a pump model were used. The model was developed by considering the static characteristics of the MicroMed DeBakey LVAD. First, the simulations were performed at constant operating speeds, 8500 rpm, 9500 rpm and 10500 rpm. Pulsatility indexes were calculated for left ventricular (LV) pressure, aortic pressure, LV volume and LVAD flow. Cardiac output (CO) was calculated at constant operating speed and these values used for comparing the pulsatility indexes with stepwise and constant operating speeds. The LVAD was operated at two different constant speeds in the stepwise operating speed simulations. Low and high operating speeds were adjusted so as to obtain the same cardiac output values with the constant operating speed simulations. The operating speeds in the simulations were 7800-11250 rpm, 9300-11250 rpm and 10300-11250 rpm. The same cardiac output values were obtained with an increase in the pulsatility of the hemodynamic variables without significant changes in their shapes except the LVAD flow. The obtained results show that it is possible to obtain more physiological results by applying a stepwise change to LVAD operating speed over a cardiac cycle

‘What are you going to do, confiscate their passports?’ Professional perspectives on cross-border reproductive travel

Objective: This article reports findings from a UK-based study which explored the phenomenon of overseas travel for fertility treatment. The first phase of this project aimed to explore how infertility clinicians and others professionally involved in fertility treatment understand the nature and consequences of cross-border reproductive travel. Background: There are indications that, for a variety of reasons, people from the UK are increasingly travelling across national borders to access assisted reproductive technologies. While research with patients is growing, little is known about how ‘fertility tourism’ is perceived by health professionals and others with a close association with infertility patients. Methods: Using an interpretivist approach, this exploratory research included focussed discussions with 20 people professionally knowledgeable about patients who had either been abroad or were considering having treatment outside the UK. Semi-structured interviews were recorded, transcribed verbatim and subjected to a thematic analysis. Results: Three conceptual categories are developed from the data: ‘the autonomous patient’; ‘cross-border travel as risk’, and ‘professional responsibilities in harm minimisation’. Professionals construct nuanced, complex and sometimes contradictory narratives of the ‘fertility traveller’, as vulnerable and knowledgeable; as engaged in risky behaviour and in its active minimisation. Conclusions: There is little support for the suggestion that states should seek to prevent cross-border treatment. Rather, an argument is made for less direct strategies to safeguard patient interests. Further research is required to assess the impact of professional views and actions on patient choices and patient experiences of treatment, before, during and after travelling abroad

Directional dark field retrieval with single-grid x-ray imaging

Directional dark-field imaging is an emerging x-ray modality that is sensitive to unresolved anisotropic scattering from sub-pixel sample microstructures. A single-grid imaging set-up can be used to capture dark-field images by looking at changes in a grid pattern projected upon the sample. By creating analytical models for the experiment, we have developed a single-grid directional dark field retrieval algorithm that can extract dark-field parameters such as the dominant scattering direction, and the semi-major and -minor scattering angles. We show that this method is effective even in the presence of high image noise, allowing for low dose and time sequence imaging