DISCOMAP: A System to Support Distributed Cognition in Inquiring Organizations

Inquiring systems theory (Churchman, 1971), cognitive mapping (Lee, et al., 1992) and hermeneutics (Boland, et al., 1994) have provided the basis for systems to support organizational learning, distributed cognition, and knowledge management. Boland, et al. (1994) describe three entities in such systems and six principles for their design. Richardson (2005) argues that communication is neglected element in these systems and integrates Habermas’s (1984, 1985) theory of communicative action, specifically discursive action, to develop revised design principles. This paper describes DISCOMAP, a system that instantiates and tests the revised design principles using discussion forums and The Planners Laboratory©, a new software package that provides advanced modeling, graphical and network capabilities to provide shareable models with engaging visual interfaces for decision makers

Management of the aggressive emergency department patient: Non-pharmacological perspectives and evidence base

Introduction: Aggression in the Emergency Department (ED) remains an ongoing issue, described as reaching epidemic proportions, with an impact on staff recruitment, retention, and ability to provide quality care. Most literature has focused on the definition (or lack of) core concepts, efforts to quantify the phenomenon or provide an epidemiological profile. Relatively little offers evidence-based interventions or evaluations of the same. Aim: To identify the range of suggested practices and the evidence base for currently recommended actions relating to the management of the aggressive Emergency Department patient. Methods: A meta-synthesis of existing reviews of violence and aggression in the acute health-care setting, including management of the aggressive patient, was undertaken. This provided the context for critical consideration of the management of this patient group in the ED and implications for clinical practice. Results: An initial outline of issues was followed by a systematic search and 15 reviews were further assessed. Commonly identified interventions are grouped around educational, interpersonal, environmental, and physical responses. These actions can be focused in terms of overall responses to the wider issues of violence and aggression, targeted at the pre-event, event, or post-event phase in terms of strategies; however, there is a very limited evidence base to show the effectiveness of strategies suggested. Clinical Implications: The lack of evidence-based intervention strategies leaves clinicians in a difficult situation, often enacting practices based on anecdote rather than evidence. Local solutions to local problems are occurring in a pragmatic manner, but there needs to be clarification and integration of workable processes for evaluating and disseminating best practice. Conclusion: There is limited evidence reporting on interventional studies, in addition to identification of the need for high quality longitudinal and evaluation studies to determine the efficacy of those responses that have been identified

Churchman\u27s Inquiring Systems: Kernel Theories for Knowledge Management

Churchman [1971] defines inquiry as an activity that produces knowledge. He examines the epistemologies of five schools of philosophy from the perspective of general systems theory, asking the question as to whether each is suitable as the basis for the design of computer-based inquiring systems. He considers systems design and design theory in some detail. We believe that Churchman\u27s inquiring systems can form the basis for the design of knowledge management systems and that the IS research community has hardly tapped the potential of inquiring systems in that regard. Mason and Mitroff [1973] brought inquiring systems into the IS literature early on, essentially making the work endogenous to the field. We argue that building on inquiring systems can contribute to developing IS as a discipline by maintaining continuity in research and developing a theory that IS can call its own. We believe that the lack of use of Churchman\u27s work may be due to its lack of visibility in recent years and attempt to remedy that by summarizing the basics of the inquirers in some detail, trying not to interpret, but to remain faithful to the original. The paper encourages readers to study the original and develop their own notion of how the inquirers might be used in knowledgemanagement work. There are probably as many different perspectives on how inquiring systems could support KMS as there are IS researchers willing to study them. We would like to encourage a proliferation of such perspectives

Nanopore Sequencing Enables Comprehensive Transposable Element Epigenomic Profiling

Transposable elements (TEs) drive genome evolution and are a notable source of pathogenesis, including cancer. While CpG methylation regulates TE activity, the locus-specific methylation landscape of mobile human TEs has to date proven largely inaccessible. Here, we apply new computational tools and long-read nanopore sequencing to directly infer CpG methylation of novel and extant TE insertions in hippocampus, heart, and liver, as well as paired tumor and non-tumor liver. As opposed to an indiscriminate stochastic process, we find pronounced demethylation of young long interspersed element 1 (LINE-1) retrotransposons in cancer, often distinct to the adjacent genome and other TEs. SINE-VNTR-Alu\ua0(SVA) retrotransposons, including their internal tandem repeat-associated CpG island, are near-universally methylated. We encounter allele-specific TE methylation and demethylation of aberrantly expressed young LINE-1s in normal tissues. Finally, we recover the complete sequences of tumor-specific LINE-1 insertions and their retrotransposition hallmarks, demonstrating how long-read sequencing can simultaneously survey the epigenome and detect somatic TE mobilization

Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya

Background: Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at time of ART initiation. Methods: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1,000 copies/mL) at 6 month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. Results: Among 386 participants, TDR was detected by OLA in 3.89% [95% Confidence Interval (CI), 2.19-6.33], and was associated with a 10-fold higher rate of virologic failure [Hazard Ratio (HR), 10.39; 95% CI, 3.23-32.41; p Conclusions: Detection of TDR by a point mutation assay may prevent use of sub-optimal ART

Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme

Background: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers. Results: Here, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu-Alu recombination event adjacent to an L1. These mutations included PCR validated intronic events in MeCP2 and EGFR. Despite sequencing L1 integration sites at up to 250× depth by RC-seq, we found no tumour-specific, endonuclease-dependent L1 insertions. Whole genome sequencing analysis of the tumours carrying the MeCP2 and EGFR L1 mutations also revealed no endonuclease-dependent L1 insertions. In a complementary in vitro assay, wild-type and endonuclease mutant L1 reporter constructs each mobilised very inefficiently in four cultured GBM cell lines. Conclusions: These experiments altogether highlight the consistent absence of canonical L1 retrotransposition in GBM tumours and cultured cell lines, as well as atypical L1-associated sequence rearrangements following DNA damage in vivo