Cryptococcus neoformans is a significant fungal pathogen of immunocompromised patients. Many questions remain regarding the function of macrophages in normal clearance of cryptococcal infection and the defects present in uncontrolled cryptococcosis. Two current limitations are: 1) The difficulties in interpreting studies using isolated macrophages in the context of the progression of infection, and 2) The use of high resolution imaging in understanding immune cell behavior during animal infection. Here we describe a high-content imaging method in a zebrafish model of cryptococcosis that permits the detailed analysis of macrophage interactions with C. neoformans during infection. Using this approach we demonstrate that, while macrophages are critical for control of C. neoformans, a failure of macrophage response is not the limiting defect in fatal infections. We find phagocytosis is restrained very early in infection and that increases in cryptococcal number are driven by intracellular proliferation. We show that macrophages preferentially phagocytose cryptococci with smaller polysaccharide capsules and that capsule size is greatly increased over twenty-four hours of infection, a change that is sufficient to severely limit further phagocytosis. Thus, high-content imaging of cryptococcal infection in vivo demonstrates how very early interactions between macrophages and cryptococci are critical in the outcome of cryptococcosis.

No abstract

Bere is a landrace of barley, adapted to the marginal conditions of northern Scotland, especially those of the Northern and Western Isles. The history of bere on these islands is long and, in an era of diminishing landrace cultivation, bere now represents one of the oldest cereal landraces in Europe still grown commercially. The longevity of bere raises the possibility of using grain characteristics of present-day specimens to identify bere in the archaeological record. Geometric modern morphometric (GMM) analysis of grains from bere and other barley landraces is conducted to determine whether landraces can be differentiated on grain morphology. Results indicate that there are morphological differences between bere and other British and Scandinavian landraces, and between bere from Orkney and the Western Isles, both of which are apparent in genetic analysis. This finding paves the way for the identification of bere archaeologically, helping to establish its status as living heritage and securing its commercial future. More broadly, this work indicates the potential of grain GMM for the recognition of cereal landraces, permitting the ancestry and exchange of landraces to be traced in the archaeological record.

The detection of fraud and other systematic data irregularities in clinical trials is an important issue. While awareness of the problem is growing and willingness to combat it is clear, there still appears to be a lack of detection procedures suitable for routine implementation by trial coordinators. The shortage is particularly acute for discrete data, since the majority of methods which are available have been developed for continuous responses. In this paper, we examine the suitability of existing methods for discrete outcomes and propose a new technique for questionnaire data in both an informal graphical mode and as a randomization test. This method exploits the underlying correlation structure of a questionnaire and the difficulty in fabricating such details. A data set concerning a trial of a novel drug for treatment of schizophrenia, in which the Brief Psychiatric Rating Scale was used to assess patient mental health, is used for illustration.

No abstract