Talent management in triadic organizational architectures

We study a model of team problem-solving over a large solution space. Compared to the existing literature, we allow for heterogeneity both in the organizational architectures and in the agents' cognitive abilities; moreover, we introduce a more expressive performance measure. We find a robust ranking of the triadic architectures with respect to their effectiveness and provide a key recommendation for talent management in partial hierarchies

The accuracy of pulse oximetry in emergency department patients with severe sepsis and septic shock: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Pulse oximetry is routinely used to continuously and noninvasively monitor arterial oxygen saturation (SaO₂) in critically ill patients. Although pulse oximeter oxygen saturation (SpO₂) has been studied in several patient populations, including the critically ill, its accuracy has never been studied in emergency department (ED) patients with severe sepsis and septic shock. Sepsis results in characteristic microcirculatory derangements that could theoretically affect pulse oximeter accuracy. The purposes of the present study were twofold: 1) to determine the accuracy of pulse oximetry relative to SaO2 obtained from ABG in ED patients with severe sepsis and septic shock, and 2) to assess the impact of specific physiologic factors on this accuracy.</p> <p>Methods</p> <p>This analysis consisted of a retrospective cohort of 88 consecutive ED patients with severe sepsis who had a simultaneous arterial blood gas and an SpO₂value recorded. Adult ICU patients that were admitted from any Calgary Health Region adult ED with a pre-specified, sepsis-related admission diagnosis between October 1, 2005 and September 30, 2006, were identified. Accuracy (SpO₂- SaO₂) was analyzed by the method of Bland and Altman. The effects of hypoxemia, acidosis, hyperlactatemia, anemia, and the use of vasoactive drugs on bias were determined.</p> <p>Results</p> <p>The cohort consisted of 88 subjects, with a mean age of 57 years (19 - 89). The mean difference (SpO₂- SaO₂) was 2.75% and the standard deviation of the differences was 3.1%. Subgroup analysis demonstrated that hypoxemia (SaO₂< 90) significantly affected pulse oximeter accuracy. The mean difference was 4.9% in hypoxemic patients and 1.89% in non-hypoxemic patients (p < 0.004). In 50% (11/22) of cases in which SpO₂was in the 90-93% range the SaO2 was <90%. Though pulse oximeter accuracy was not affected by acidoisis, hyperlactatementa, anemia or vasoactive drugs, these factors worsened precision.</p> <p>Conclusions</p> <p>Pulse oximetry overestimates ABG-determined SaO₂by a mean of 2.75% in emergency department patients with severe sepsis and septic shock. This overestimation is exacerbated by the presence of hypoxemia. When SaO₂needs to be determined with a high degree of accuracy arterial blood gases are recommended.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Multiple mechanisms underlie defective recognition of melanoma cells cultured in three-dimensional architectures by antigen-specific cytotoxic T lymphocytes

Cancer cells` growth in three-dimensional (3D) architectures promotes resistance to drugs, cytokines, or irradiation. We investigated effects of 3D culture as compared to monolayers (2D) on melanoma cells` recognition by tumour-associated antigen (TAA)-specific HLA-A*0201-restricted cytotoxic T-lymphocytes (CTL). Culture of HBL, D10 (both HLA-A*0201+, TAA+) and NA8 (HLA-A* 0201+, TAA-) melanoma cells on polyHEMA-coated plates, resulted in generation of 3D multicellular tumour spheroids (MCTS). Interferon-gamma (IFN-gamma) production by HLA-A*0201-restricted Melan-A/MART-1(27-35) or gp100(280-288)-specific CTL clones served as immunorecognition marker. Co-culture with melanoma MCTS, resulted in defective TAA recognition by CTL as compared to 2D as witnessed by decreased IFN-gamma production and decreased Fas Ligand, perforin and granzyme B gene expression. A multiplicity of mechanisms were potentially involved. First, MCTS per se limit CTL capacity of recognising HLA class I restricted antigens by reducing exposed cell surfaces. Second, expression of melanoma differentiation antigens is downregulated in MCTS. Third, expression of HLA class I molecules can be downregulated in melanoma MCTS, possibly due to decreased interferonregulating factor-1 gene expression. Fourth, lactic acid production is increased in MCTS, as compared to 2D. These data suggest that melanoma cells growing in 3D, even in the absence of immune selection, feature characteristics capable of dramatically inhibiting TAA recognition by specific CTL