Deriving chemosensitivity from cell lines: Forensic bioinformatics and reproducible research in high-throughput biology

High-throughput biological assays such as microarrays let us ask very detailed questions about how diseases operate, and promise to let us personalize therapy. Data processing, however, is often not described well enough to allow for exact reproduction of the results, leading to exercises in "forensic bioinformatics" where aspects of raw data and reported results are used to infer what methods must have been employed. Unfortunately, poor documentation can shift from an inconvenience to an active danger when it obscures not just methods but errors. In this report we examine several related papers purporting to use microarray-based signatures of drug sensitivity derived from cell lines to predict patient response. Patients in clinical trials are currently being allocated to treatment arms on the basis of these results. However, we show in five case studies that the results incorporate several simple errors that may be putting patients at risk. One theme that emerges is that the most common errors are simple (e.g., row or column offsets); conversely, it is our experience that the most simple errors are common. We then discuss steps we are taking to avoid such errors in our own investigations.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS291 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Limitation of Trypanosoma brucei parasitaemia results from a combination of density-dependent parasite differentiation and parasite killing by the host immune response

In the bloodstream of its mammalian host, the "slender" form of Trypanosoma brucei replicates extracellularly, producing a parasitaemia. At high density, the level of parasitaemia is limited at a sublethal level by differentiation to the non-replicative "stumpy" form and by the host immune response. Here, we derive continuous time equations to model the time-course, cell types and level of trypanosome parasitaemia, and compare the best fits with experimental data. The best fits that were obtained favour a model in which both density-dependent trypanosome differentiation and host immune response have a role in limiting the increase of parasites, much poorer fits being obtained when differentiation and immune response are considered independently of one another. Best fits also favour a model in which the slender-to-stumpy differentiation progresses in a manner that is essentially independent of the cell cycle. Finally, these models also make the prediction that the density-dependent trypanosome differentiation mechanism can give rise to oscillations in parasitaemia level. These oscillations are independent of the immune system and are not due to antigenic variation

Fractal Location and Anomalous Diffusion Dynamics for Oil Wells from the KY Geological Survey

Utilizing data available from the Kentucky Geonet (KYGeonet.ky.gov) the fossil fuel mining locations created by the Kentucky Geological Survey geo-locating oil and gas wells are mapped using ESRI ArcGIS in Kentucky single plain 1602 ft projection. This data was then exported into a spreadsheet showing latitude and longitude for each point to be used for modeling at different scales to determine the fractal dimension of the set. Following the porosity and diffusivity studies of Tarafdar and Roy1 we extract fractal dimensions of the fossil fuel mining locations and search for evidence of scaling laws for the set of deposits. The Levy index is used to determine a match to a statistical mechanically motivated generalized probability function for the wells. This probability distribution corresponds to a solution of a dynamical anomalous diffusion equation of fractional order that describes the Levy paths which can be solved in the diffusion limit by the Fox H function ansatz.Comment: : 8 pages, 3 figures, AIPG Conference Meeting, Grand Junction CO, Oct. 200

Status Quo Analysis of the Flathead River Conflict

Status quo analysis algorithms developed within the paradigm of the graph model for conflict resolution are applied to an international river basin conflict involving the United States and Canada to assess the likeliness of various compromise resolutions. The conflict arose because the state of Montana feared that further expansion of the Sage Creek Coal Company facilities in Canada would pollute the Flathead River, which flows from British Columbia into Montana. Significant insights not generally available from a static stability analysis are obtained about potential resolutions of the conflict under study and about how decision makers’ interactions may direct the conflict to distinct resolutions. Analyses also show how political considerations may affect a particular decision maker’s choice, thereby influencing the evolution of the conflict

The ‘Goal-Corrected Partnership’ in Attachment Theory: A Critical Assessment of the Research Programme

The ‘Goal-Corrected Partnership’ in Attachment Theory: A Critical Assessment of the Research Programme ABSTRACT Despite counting as one of the largest research programmes in human development, the contours of Attachment Theory remain quite difficult to define. A pressing requirement to clarify what the ‘theory’ actually contends remains. This thesis is an interdisciplinary project that brings the dual lens of history and philosophy to shed new light on the theory. John Bowlby’s (1907-1990) hopes for Attachment Theory were both radical and innovative. First, he set out to ‘radically’ overhaul the entire of edifice of psychoanalysis—what he would call Freud’s original metapsychology. Second, Bowlby combined three fields in a manner that anticipated today’s more integrative non-dualist, non-reductive approaches to the human mind: (1) Tinbergen’s four questions in behavioural biology, (2) questions in emotion research, and (3) a range of concepts from the cognitive sciences, especially Craik’s notion of mental models. The thesis distinguishes 13 attachment constructs—the initial 12 allocated across the Tinbergen framework. This supports a clarification of the expanding complexity of the theory. Equally, a 13th construct—the organisational perspective—provides a plank for tying attachment to lifespan insights within Developmental Systems Theory. Bowlby’s Goal-Corrected Partnership (GCP) proposed that attachment relationships beyond infancy required engagement with newly emerging cognitive skills. The thesis argues that the GCP offers an important corrective to conceptualisations that somehow limit attachment phenomena to a purely implicit, infancy derived, affectively triggered protection function only. Attachment Theory makes possible a reintroduction of a developmental perspective into psychiatry. Its causal credentials could also provide a breath of fresh air for a mental health arena. Finally, an acknowledgement of GCP relationships matches the growing empirical awareness that behaviour, emotion and cognition are more integrated phenomena than current studies may allow

Economic Analysis of the Changing Structure of the South Dakota Pork Industry

In 1979, 3,232,000 hogs were slaughtered in South Dakota. Only seven states in the nation exceeded this total. This places South Dakota in a position of prominence in the national pork industry. There is considerable physical potential for further growth of the South Dakota pork industry. With ample supplies of land, labor, and feed grain available, the number of hogs and pigs in the state could expand. For this expansion in production to occur, state swine growers would have to alter production plans. The decision to increase numbers of hogs and pigs is influenced by many factors at both the individual and industry level. If those limiting factors can be overcome, South Dakota can advance to an even higher ranking in the pork industry. The South Dakota pork industry has changed over time with fewer firms, larger inventories per farm, and more enterprise specialization. In 1969, 42 percent of South Dakota farms and ranches (19,366 of 45,729) sold hogs and pigs. By 1978, only 33 percent of South Dakota’s farms and ranches (12,999 of 39,600) sold hogs and pigs. Despite the 33 percent reduction in number of hog farms, total inventories of hogs and pigs remained nearly constant. Average inventory increased from 90.3 hogs and pigs per farm in 1969 to 142.3 hogs and pigs per farm in 1978. The only Census inventory category showing an increase in number of hog farms and number of hogs and pigs was the inventory category of farms with 500 or more hogs and pigs. The average number of feeder pigs sold per farm has increased from 115 feeder pigs in 1969 to 209 feeder pigs in 1978. Feeder pig cooperatives are gaining in importance in the state. The number of these specialized operations has increased to approximately 12 in recent years. These changes in pork production have led to the need for more diverse methods of marketing and a higher level of managerial ability for the individual producer. South Dakota\u27s role in the pork industry could change. This study was conducted, in part, to provide a means of gauging the direction in which the state pork industry is moving. Swine numbers could expand, but this decision lies with the producers and the production plans they advocate. This study begins the accumulation of information on this currently unaddressed issue

Status Review and Conservation Initiatives for American Bison: A Continental Perspective

Five hundred years ago, there were tens of millions of American bison (Bison bison) roaming free on the plains of North America from Alaska to northern Mexico. The decimation of the American bison in the late 1800s inspired the first recovery of bison and an entire conservation movement that protected wildlife and wild places across North America. As of 2008, there were ~ 400,000 bison in commercial herds in North America, some 93 percent of the continental population. There were 61 plains bison conservation herds containing ~ 20,500 animals, and 11 conservation herds of wood bison, containing nearly 11,000 animals. Little progress has been made in recent decades to increase the number of animals in conservation herds. Many factors affect survival of bison populations, including limited habitat and severe winters. Yet, the greatest challenge is to overcome the common perception that the bison, which has had a profound influence on the human history of North America, socially, culturally and ecologically, no longer belongs on the landscape. The key to recovery of this species is recognition that the American bison is a wildlife species and needs to be conserved as wildlife. Recently a new conservation strategy was developed by the IUCN bison specialist group and a new vision for the ecological restoration of bison was described by the Wildlife Conservation Society under our American Bison Society initiative. A new Continental vision for the American bison is inspiring a second recovery and helping to restore functional grassland ecosystems

Corporate social responsibility:reviewed, rated, revised

Purpose: Critical literature review of CSR research in both general management and hospitality management literature. Discusses trends,commonalities, and inconsistencies to better understand the state of contemporary scholarship, and calls for a context-specific conceptual engagement with the phenomenon.Design/Methodology/Approach: Systematic literature review, noting and critiquing a general tendency towards measurement of financial and other internal benefit impacts.Findings: Hospitality management is well-positioned to evaluate the opportunities and challenges of CSR, yet research has uncritically adopted the instrumental emphasis on assessing processes, perceptions, and private profitability from the general management literature, without engaging on a contextually-specific and/or theoretical level.Research limitations: CSR research is abundant and therefore difficult to summarise in one article.The primarily Anglo-American and Asian contextual bias is reflected in this review.Practical implications: Consistently inconsistent results challenge the portability of financial impact studies.Studies are needed to re-evaluate the concept of CSR as it pertains to hospitality, and measure the effectiveness of CSR activities relative to context and resource availability.Social implications: Further research into the scope of CSR in hospitality management, with an emphasis on recuperating social value, would lead to widespread positive social implications.Originality/value: This critical review offers a new perspective on CSR in the hospitality literature and industry, calling for a reconsideration of the concept in context, and formulates a working definition