22 research outputs found
Appreciative Methods Applied to the Assessment of Complex Systems
Complex systems have characteristics that challenge traditional systems engineering processes and methods. These characteristics have been defined in various ways. INCOSE has previously identified characteristics of complex systems and potential methods to deal with complexity in system development. The purpose of this paper is to provide definitions and describe distinguishing characteristics of complexity using example systems to illustrate approaches to assessing the extent of complexity. The paper applies Appreciative Inquiry to identify and assess complex system characteristics. The characteristics are used to examine several different examples of systems to illuminate areas of complexity. These examples range from seemingly simple systems to complicated systems to complex systems. Different tiers of complexity are identified as a result of the assessment. The paper also identified and introduces topics on managing complexity and the integrating system perspective that represent new directions for the engineering of complex systems. The Appreciative Inquiry approach provides a method for systems engineering practitioners to more readily identify complexity when they encounter it, and to deal more effectively with this complexity once it has been identified
Beaver Ponds: Resurgent Nitrogen Sinks for Rural Watersheds in the Northeastern United States
Beaver-created ponds and dams, on the rise in the northeastern United States, reshape headwater stream networks from extensive, free-flowing reaches to complexes of ponds, wetlands, and connecting streams. We examined seasonal and annual rates of nitrate transformations in three beaver ponds in Rhode Island under enriched nitrate-nitrogen (N) conditions through the use of 15N mass balance techniques on soil core mesocosm incubations. We recovered approximately 93% of the nitrate N from our mesocosm incubations. Of the added nitrate N, 22 to 39% was transformed during the course of the incubation. Denitrification had the highest rates of transformation (97–236 mg N m−2 d−1), followed by assimilation into the organic soil N pool (41–93 mg N m−2 d−1) and ammonium generation (11–14 mg N m−2 d−1). Our denitrification rates exceeded those in several studies of freshwater ponds and wetlands; however, rates in those ecosystems may have been limited by low concentrations of nitrate. Assuming a density of 0.7 beaver ponds km−2 of catchment area, we estimated that in nitrate-enriched watersheds, beaver pond denitrification can remove approximately 50 to 450 kg nitrate N km−2 catchment area. In rural watersheds of southern New England with high N loading (i.e., 1000 kg km−2), denitrification from beaver ponds may remove 5 to 45% of watershed nitrate N loading. Beaver ponds represent a relatively new and substantial sink for watershed N if current beaver populations persist
Phosphodiesterase 4 Inhibition Reduces Innate Immunity and Improves Isoniazid Clearance of Mycobacterium tuberculosis in the Lungs of Infected Mice
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the leading infectious disease causes of morbidity and mortality worldwide. Though current antibiotic regimens can cure the disease, treatment requires at least six months of drug therapy. One reason for the long duration of therapy is that the currently available TB drugs were selected for their ability to kill replicating organisms and are less effective against subpopulations of non-replicating persistent bacilli. Evidence from in vitro models of Mtb growth and mouse infection studies suggests that host immunity may provide some of the environmental cues that drive Mtb towards non-replicating persistence. We hypothesized that selective modulation of the host immune response to modify the environmental pressure on the bacilli may result in better bacterial clearance during TB treatment. For this proof of principal study, we compared bacillary clearance from the lungs of Mtb-infected mice treated with the anti-TB drug isoniazid (INH) in the presence and absence of an immunomodulatory phosphodiesterase 4 inhibitor (PDE4i), CC-3052. The effects of CC-3052 on host global gene expression, induction of cytokines, and T cell activation in the lungs of infected mice were evaluated. We show that CC-3052 modulates the innate immune response without causing generalized immune suppression. Immune modulation combined with INH treatment improved bacillary clearance and resulted in smaller granulomas and less lung pathology, compared to treatment with INH alone. This novel strategy of combining anti-TB drugs with an immune modulating molecule, if applied appropriately to patients, may shorten the duration of TB treatment and improve clinical outcome
Genomewide Linkage Analyses of Bipolar Disorder: A New Sample of 250 Pedigrees from the National Institute of Mental Health Genetics Initiative
We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P<.05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P<.10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder