Multiple Myeloma : an update on disease biology and therapy

Multiple myeloma is a malignancy of immunoglobulin producing plasma cells. Clinical features include bone pain due to lytic bone lesions or pathological fractures, anemia, symptomatic hypercalcemia, renal insufficiency, recurrent infections and amyloidosis. In the last few years, there have been considerable advances in the understanding of the biology of this disease. While multiple myeloma is biologically diverse, several oncogenes are activated in this illness. In addition, the role of the bone marrow microenvironment to support the growth and survival of the malignant cells has been well described. In this review, we discuss recent developments in the molecular pathogenesis of myeloma. These recent observations are being translated into novel therapeutic approaches that target both the tumor cell as well as the stroma. Current therapeutic strategies are discussed.peer-reviewe

Regulation of T cell migration by the guanidine exchange factor Vav1

T cell migration to sites of inflammation is an essential step of an effective immune response. T cell recruitment is enhanced by the recognition of their cognate antigen presented by the endothelium and their retention in the tissue is controlled by resident antigen presenting cells. Vav1 is a guanidine exchange factor for RhoGTPases that is activated through TCR signalling and is important for the cytoskeletal re-arrangements occurring during T cell activation and migration. In this study we have investigated the role of Vav1 in the recruitment and retention of antigen-specific T cells to sites of inflammation. HY-specific Ab-restricted WT and Vav1-/- T cells were generated and fully characterised for specificity and expression of migration-related markers. Vav1-/- T cells showed defects in adhesion, migration in response to ICAM-1, CXCL12 and CXCL10 and increased migratory speed in in vitro assays. Despite displaying defective motility in vitro, both constitutive migration and recruitment of Vav1-/- T cells to antigenic sites occurred normally. However, retention of Vav-1-/- T cells into antigenic tissue was profoundly impaired. This may be due to the inability by Vav-1-/- T cells to respond to ‘stop’ signals delivered by co-engagement of TCR and CD28. In contrast to recent reports on wild type T cells, Vav1-/- T cell migration and retention to sites of inflammation was not affected by engagement of the co-stimulatory molecule CD28, suggesting that Vav-1 recruitment during CD28-mediated signalling is instrumental for Vav-1-mediated regulation of T cell traffi

Food security, risk management and climate change

This report identifies major constraints to the adaptive capacity of food organisations operating in Australia. This report is about food security, climate change and risk management. Australia has enjoyed an unprecedented level of food security for more than half a century, but there are new uncertainties emerging and it would be unrealistic – if not complacent – to assume the same level of food security will persist simply because of recent history. The project collected data from more than 36 case study organisations (both foreign and local) operating in the Australian food-supply chain, and found that for many businesses,  risk management practices require substantial improvement to cope with and exploit the uncertainties that lie ahead. Three risks were identified as major constraints to adaptive capacity of food organisations operating in Australia:  risk management practices; an uncertain regulatory environment – itself a result of gaps in risk management; climate change uncertainty and projections about climate change impacts, also related to risk management

The Economic Diversity of Immigration Across the United States

While it is well known that some areas of the United States receive more immigrants than others, less is understood about the extent to which the character of immigration varies as well. There is much broader geographic variation in the skill and demographic composition of immigrants than natives, with important implications for their economic effects. This paper provides a new perspective by focusing on heterogeneity in outcomes such as the share of population growth due to immigration, the presence of immigrant children in schools, and the effect of immigration on the age, sex, language, and educational composition of the local population and workforce.

Evaluating a virtual learning environment in the context of its community of practice

The evaluation of virtual learning environments (VLEs) and similar applications has, to date, largely consisted of checklists of system features, phenomenological studies or measures of specific forms of educational efficacy. Although these approaches offer some value, they are unable to capture the complex and holistic nature of a group of individuals using a common system to support the wide range of activities that make up a course or programme of study over time. This paper employs Wenger's theories of 'communities of practice' to provide a formal structure for looking at how a VLE supports a pre-existing course community. Wenger proposes a Learning Architecture Framework for a learning community of practice, which the authors have taken to provide an evaluation framework. This approach is complementary to both the holistic and complex natures of course environments, in that particular VLE affordances are less important than the activities of the course community in respect of the system. Thus, the VLE's efficacy in its context of use is the prime area of investigation rather than a reductionist analysis of its tools and components. An example of this approach in use is presented, evaluating the VLE that supports the undergraduate medical course at the University of Edinburgh. The paper provides a theoretical grounding, derives an evaluation instrument, analyses the efficacy and validity of the instrument in practice and draws conclusions as to how and where it may best be used

Climate 2030: A National Blueprint for a Clean Energy Economy (Executive Summary)

Courage of conviction, unyielding stamina to underscore the dangerous realities of unchanging lifestyle habits and doing business as usual in today’s world, and unfettered tenacity necessary to build an ever-growing network of dedicated individuals and scientists struggling to express the need for public awareness and governmental action, describes this nationwide group. The Union of Concerned Scientists, primarily headquartered in Cambridge, Massachusetts, presents its forecast for 2030 – complete with the recipe needed to be undertaken for individuals and businesses to both survive and thrive

Automatic Detection of Egg Shell Cracks

The challenge was to find a reliable, non-intrusive means of detecting cracks in eggs. Intensity data from eggs were collected by VisionSmart for the group to analyse. Given the short time period three main questions were addressed. 1) Is there a feature of the intensity data which detects, and discriminates between pinholes, cage marks and cracks? 2) Are there ways to improve the current data collection process? 3) Are there other data collection methods which should be tried? A partial positive response to 1) is presented and describes the many problems that arose. Some answers to 2) and 3) are also presented

Detecting Unresolved Binaries in TESS Data with Speckle Imaging

The Transiting Exoplanet Survey Satellite (TESS) is conducting a two-year wide-field survey searching for transiting exoplanets around nearby bright stars that will be ideal for follow-up characterization. To facilitate studies of planet compositions and atmospheric properties, accurate and precise planetary radii need to be derived from the transit light curves. Since 40 - 50% of exoplanet host stars are in multiple star systems, however, the observed transit depth may be diluted by the flux of a companion star, causing the radius of the planet to be underestimated. High angular resolution imaging can detect companion stars that are not resolved in the TESS Input Catalog, or by seeing-limited photometry, to validate exoplanet candidates and derive accurate planetary radii. We examine the population of stellar companions that will be detectable around TESS planet candidate host stars, and those that will remain undetected, by applying the detection limits of speckle imaging to the simulated host star populations of Sullivan et al. (2015) and Barclay et al. (2018). By detecting companions with contrasts of delta m < 7 - 9 and separations of ~0.02 - 1.2'', speckle imaging can detect companion stars as faint as early M stars around A - F stars and stars as faint as mid-M around G - M stars, as well as up to 99% of the expected binary star distribution for systems located within a few hundred parsecs.Comment: Accepted for publication in The Astronomical Journal; 16 pages, 8 figures, 2 table