Focal brachytherapy treatment planning using multi-parametric MRI and biological dose optimisation

We describe a novel approach to treatment planning for focal brachytherapy utilizing a biologically based inverse optimization algorithm and biological imaging to target an ablative dose at known regions of significant tumour burden and a lower, therapeutic dose to low risk regions.

Disease Diplomacy

In the age of air travel and globalized trade, pathogens that once took months or even years to spread beyond their regions of origin can now circumnavigate the globe in a matter of hours. Amid growing concerns about such epidemics as Ebola, SARS, MERS, and H1N1, disease diplomacy has emerged as a key foreign and security policy concern as countries work to collectively strengthen the global systems of disease surveillance and control. The revision of the International Health Regulations (IHR), eventually adopted by the World Health Organization’s member states in 2005, was the foremost manifestation of this novel diplomacy. The new regulations heralded a profound shift in international norms surrounding global health security, significantly expanding what is expected of states in the face of public health emergencies and requiring them to improve their capacity to detect and contain outbreaks. Drawing on Martha Finnemore and Kathryn Sikkink’s "norm life cycle" framework and based on extensive documentary analysis and key informant interviews, Disease Diplomacy traces the emergence of these new norms of global health security, the extent to which they have been internalized by states, and the political and technical constraints governments confront in attempting to comply with their new international obligations. The authors also examine in detail the background, drafting, adoption, and implementation of the IHR while arguing that the very existence of these regulations reveals an important new understanding: that infectious disease outbreaks and their management are critical to national and international security. The book will be of great interest to academic researchers, postgraduate students, and advanced undergraduates in the fields of global public health, international relations, and public policy, as well as health professionals, diplomats, and practitioners with a professional interest in global health security.

The business of myth-making: Mary Poppins, P.L. Travers and the Disney effect

In just one of the many extraordinary moments during the spectacular Opening Ceremony of the 2012 London Olympic Games, thirty Mary Poppinses floated into the stadium on their umbrellas to battle a 40 foot-long inflatable Lord Voldemort. This multi-million pound extravaganza was telecast to a global audience of over one billion people, highlighting in an extremely effective manner the grandeur and eccentricities of the host nation, and featuring uniquely British icons such as Mr Bean, James Bond, The Beatles and Harry Potter, as well as those quintessential icons of Englishness, the Royal Family, double-decker red buses and the National Health Service.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.