Inferring tumor progression from genomic heterogeneity

Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form of the phylogenetic relationships. We have developed a method we call Sector-Ploidy-Profiling (SPP) to study the clonal composition of breast tumors. SPP involves macro-dissecting tumors, flow-sorting genomic subpopulations by DNA content, and profiling genomes using comparative genomic hybridization (CGH). Breast carcinomas display two classes of genomic structural variation: (1) monogenomic and (2) polygenomic. Monogenomic tumors appear to contain a single major clonal subpopulation with a highly stable chromosome structure. Polygenomic tumors contain multiple clonal tumor subpopulations, which may occupy the same sectors, or separate anatomic locations. In polygenomic tumors, we show that heterogeneity can be ascribed to a few clonal subpopulations, rather than a series of gradual intermediates. By comparing multiple subpopulations from different anatomic locations, we have inferred pathways of cancer progression and the organization of tumor growth. © 2010 by Cold Spring Harbor Laboratory Press

Poverty and Well-being in Post-Apartheid South Africa: An Overview of Data, Outcomes and Policy

WP 2006-03 January 2006This is an overview of poverty and well-being in the first decade of post-apartheid South Africa. It is an introduction to a volume that brings together some of the most prominent academic research done on this topic for the 10-year review process in South Africa. This overview highlights three key aspects of the picture that the detailed research paints. First, data quality and comparability has been a constant issue in arriving at a consensus among analysts on the outcomes for households and individuals in postapartheid South Africa. Second, while the outcomes on unemployment, poverty and inequality are indeed bad, the outcomes on social indicators and access to public services are much more encouraging. Third, the prospects for rapid and sustained economic growth, without which poverty and well-being cannot be addressed in the long run, are themselves negatively affected by increasing inequality, poverty and unemployment

Scenario-Based Design Theorizing:The Case of a Digital Idea Screening Cockpit

As ever more companies encourage employees to innovate, a surplus of ideas has become reality in many organizations – often exceeding the available resources to execute them. Building on insights from a literature review and a 3-year collaboration with a banking software provider, the paper suggests a Digital Idea Screening Cockpit (DISC) to address this challenge. Following a design science research approach, it suggests a prescriptive design theory that provides practitioner-oriented guidance for implementing a DISC. The study shows that, in order to facilitate the assessment, selection, and tracking of ideas for different stakeholders, such a system needs to play a dual role: It needs to structure decision criteria and at the same be flexible to allow for creative expression. Moreover, the paper makes a case for scenario-based design theorizing by developing design knowledge via scenarios

Complications and pitfalls of lumbar interlaminar and transforaminal epidural injections

Lumbar interlaminar and transforaminal epidural injections are used in the treatment of lumbar radicular pain and other lumbar spinal pain syndromes. Complications from these procedures arise from needle placement and the administration of medication. Potential risks include infection, hematoma, intravascular injection of medication, direct nerve trauma, subdural injection of medication, air embolism, disc entry, urinary retention, radiation exposure, and hypersensitivity reactions. The objective of this article is to review the complications of lumbar interlaminar and transforaminal epidural injections and discuss the potential pitfalls related to these procedures. We performed a comprehensive literature review through a Medline search for relevant case reports, clinical trials, and review articles. Complications from lumbar epidural injections are extremely rare. Most if not all complications can be avoided by careful technique with accurate needle placement, sterile precautions, and a thorough understanding of the relevant anatomy and contrast patterns on fluoroscopic imaging

The Impact of Growth and Redistribution on Poverty and Inequality in South Africa

This country study evaluates the experience of the South African economy with respect to growth, poverty and inequality trends since the advent of democracy in 1994

Advancing social equity in and through marine conservation

Substantial efforts and investments are being made to increase the scale and improve the effectiveness of marine conservation globally. Though it is mandated by international law and central to conservation policy, less attention has been given to how to operationalize social equity in and through the pursuit of marine conservation. In this article, we aim to bring greater attention to this topic through reviewing how social equity can be better integrated in marine conservation policy and practice. Advancing social equity in marine conservation requires directing attention to: recognition through acknowledgment and respect for diverse peoples and perspectives; fair distribution of impacts through maximizing benefits and minimizing burdens; procedures through fostering participation in decision-making and good governance; management through championing and supporting local involvement and leadership; the environment through ensuring the efficacy of conservation actions and adequacy of management to ensure benefits to nature and people; and the structural barriers to and institutional roots of inequity in conservation. We then discuss the role of various conservation organizations in advancing social equity in marine conservation and identify the capacities these organizations need to build. We urge the marine conservation community, including governments, non-governmental organizations and donors, to commit to the pursuit of socially equitable conservation

Chronic and structural poverty in South Africa: Challenges for action and research

Ten years after liberation, the persistence of poverty is one of the most important and urgent problems facing South Africa. This paper reflects on some of the findings based on research undertaken as part of the participation of the Programme for Land and Agrarian Studies (PLAAS) at the University of the Western Cape in the work of the Chronic Poverty Research Centre (CPRC), situates it within the broader literature on poverty in South Africa, and considers some emergent challenges. Although PLAAS’s survey, being only the first wave of a panel study, does not yet cast light on short term poverty dynamics, it illuminates key aspects of the structural conditions that underpin long-term poverty: the close interactions between asset poverty, employment-vulnerability and subjection to unequal social power relations. Coming to grips with these dynamics requires going beyond the limitations of conventional ‘sustainable livelihoods’ analyses; and functionalist analyses of South African labour markets. The paper argues for a re-engagement with the traditions of critical sociology, anthropology and the theoretical conventions that allow a closer exploration of the political economy of chronic poverty at micro and macro level

DBC2 significantly influences cell-cycle, apoptosis, cytoskeleton and membrane-trafficking pathways

The tumor suppressor DBC2 belongs to a previously uncharacterized gene family, RHOBTB (Bric-a-brac, Tramtrack, Broad-complex). The biological roles of RHOBTB proteins, including DBC2, remain unclear. To understand the physiological functions of DBC2, a global approach was applied. Expression of DBC2 was manipulated in HeLa cells and RNA profiling of the cells was performed by microarray analyses. DBC2 was introduced into HeLa cells by a mammalian expression vector with a constitutive promoter. DBC2 knockdown was achieved by RNA interference with small interfering RNA. RNA profiles of these samples were performed by microarray analysis using Affymetrix GeneChip HG-U133A 2.0. The microarray data were analyzed by Microarray Suite 5.0 (MAS 5.0) and Robust Multichip Average (RMA). A list of genes whose expression was significantly altered (p<0.001) was generated and overlaid onto a cellular pathway map in the Ingenuity Systems' Pathway Knowledge Base (Winter'04 Release). Two networks were found to react substantially to DBC2 expression; namely, more than half of participating genes are affected. One of the networks regulates cell growth through cell-cycle control and apoptosis. The other network is related to cytoskeleton and membrane trafficking. Our findings suggest that the biological roles of DBC2 are related directly and/or indirectly to these cellular machineries