Evolutionary dynamics of residual disease in human glioblastoma.

BACKGROUND: Glioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery and chemoradiation provide limited benefit. Even when a good treatment response is obtained, recurrence inevitably occurs either locally (∼80%) or distally (∼20%), driven by cancer clones that are often genomically distinct from those in the primary tumour. Glioblastoma cells display a characteristic infiltrative phenotype, invading the surrounding tissue and often spreading across the whole brain. Cancer cells responsible for relapse can reside in two compartments of residual disease that are left behind after treatment: the infiltrated normal brain parenchyma and the sub-ventricular zone. However, these two sources of residual disease in glioblastoma are understudied because of the difficulty in sampling these regions during surgery. PATIENT AND METHODS: Here, we present the results of whole-exome sequencing of 69 multi-region samples collected using fluorescence-guided resection from 11 patients, including the infiltrating tumour margin and the sub-ventricular zone for each patient, as well as matched blood. We used a phylogenomic approach to dissect the spatio-temporal evolution of each tumour and unveil the relation between residual disease and the main tumour mass. We also analysed two patients with paired primary-recurrence samples with matched residual disease. RESULTS: Our results suggest that infiltrative subclones can arise early during tumour growth in a subset of patients. After treatment, the infiltrative subclones may seed the growth of a recurrent tumour, thus representing the 'missing link' between the primary tumour and recurrent disease. CONCLUSIONS: These results are consistent with recognised clinical phenotypic behaviour and suggest that more specific therapeutic targeting of cells in the infiltrated brain parenchyma may improve patient's outcome.

Diel vertical migration of adult Pacific cod Gadus macrocephalus in Alaska.

The diel vertical migration (DVM) of Pacific cod Gadus macrocephalus was examined using depth and temperature data from 250 recaptured archival tags deployed on G. macrocephalus in the eastern Bering Sea and in the Gulf of Alaska near Kodiak Island. DVM of two types, deeper during daytime (type I) and deeper during night-time (type II), occurred frequently (15-40% of all days) in G. macrocephalus released at all sites. Most individuals displayed both diel types, with each type of behaviour lasting up to 58 contiguous days, and day and night depth differences averaging c. 8 m. Despite high among-individual variability, the occurrence of DVM varied significantly with the release site, season (i.e. day-of-year) and bottom depth, with the trend in seasonal occurrence nearly opposite for type I compared to type II DVM. No significance could be attributed to G. macrocephalus fork length, sex or ambient (tag) temperature. Trends in the magnitude of G. macrocephalus depth change were observed, with increased movement often occurring during night-time, dawn and dusk, and at release sites where the bathymetry was more complex. Both type I and type II DVMs were attributed to foraging on prey species that also undergo DVM, and increased vertical movements of G. macrocephalus during crepuscular and night-time periods were attributed to more active foraging during dim-light conditions when G. macrocephalus can potentially exploit a sensory advantage over some of their prey.

Limbic system function and dream content in university students.

This study explored the relationship between limbic system function and threatening dream content. Recently it has been proposed that dreams are an evolutionary mechanism designed to facilitate the rehearsal of coping strategies in dangerous situations. It is known that the limbic system is active both during times of threat and during REM sleep. Therefore, it was hypothesized that individuals with relative limbic hyperfunction, as indexed by increased scores on the Limbic System Checklist (LSCL-33), would report more threatening dream content. The data of the present research confirmed the hypothesis.

Understanding the principles of traction.

As the use of traction has declined in recent years, nurses' skills in this area have consequently decreased. Standards of care for patients in traction might now be called into question. This article attempts to redress this imbalance by describing the principles behind safe and effective traction.

The managerial revolution: medicine as a business.

Medicine and management should be more closely integrated not just at the level of health policy and health services management but also in matters of professional education and training. Learning is a continuous process from entering medical school to retirement and should reflect the transition from learning shaped by the curriculum to learning driven by the needs of the qualified professional in a career service post. The senior clinician does much more than practise clinically. He or she is a leader, a manager, a resource allocator, a teacher and team player. In these roles the values and priorities of the professional and the organization will not always coincide. In postgraduate training and in continuing medical education more joint activity should be developed around 'medicine for non-medical managers' and 'management for doctors'. Much of this shared learning and development will be local and problem-based around local issues of quality, resources and priorities. However, the 'regional' postgraduate dean will play an increasingly pivotal role in maintaining the balance between the needs of the individual and the organization. To achieve this objective of closer integration postgraduate medical education funding should be brought together under a national finance levy against purchasers and allocated through devolved budgets managed by 'regional' postgraduate deans against explicit performance criteria agreed between the professional organizations, universities and health services management.