Unmasking Chaotic Attributes in Time Series of Living Cell Populations

. Such complicated dynamics are generally the result of a combination of stochastic events and deterministic regulation. Assessing the role, if any, of chaotic regulation is difficult. However, unmasking chaotic dynamics is essential for analysis of cellular processes related to proliferation rate, including metabolic activity, telomere homeostasis, gene expression, and tumor growth.Using a simple, original, nonlinear method based on return maps, we previously found a geometrical deterministic structure coordinating such fluctuations in populations of various cell types. However, nonlinearity and determinism are only necessary conditions for chaos; they do not by themselves constitute a proof of chaotic dynamics. Therefore, we used the same analytical method to analyze the oscillations of four well-known, low-dimensional, chaotic oscillators, originally designed in diverse settings and all possibly well-adapted to model the fluctuations of cell populations: the Lorenz, Rössler, Verhulst and Duffing oscillators. All four systems also display this geometrical structure, coordinating the oscillations of one or two variables of the oscillator. No such structure could be observed in periodic or stochastic fluctuations.Theoretical models predict various cell population dynamics, from stable through periodically oscillating to a chaotic regime. Periodic and stochastic fluctuations were first described long ago in various mammalian cells, but by contrast, chaotic regulation had not previously been evidenced. The findings with our nonlinear geometrical approach are entirely consistent with the notion that fluctuations of cell populations can be chaotically controlled

External validation of the Ottawa subarachnoid hemorrhage clinical decision rule in patients with acute headache ☆

We aim to externally validate the Ottawa subarachnoid hemorrhage (OSAH) clinical decision rule. This rule identifies patients with acute nontraumatic headache who require further investigation. We conducted a medical record review of all patients presenting to the emergency department (ED) with headache from January 2011 to November 2013. Per the OSAH rule, patients with any of the following predictors require further investigation: age 40 years or older, neck pain, stiffness or limited flexion, loss of consciousness, onset during exertion, or thunderclap. The rule was applied following the OSAH rule criteria. Patients were followed up for repeat visits within 7 days of initial presentation. Data were electronically harvested from the electronic medical record and manually abstracted from individual patient charts using a standardized data abstraction form. Calibration between trained reviewers was performed periodically. A total of 5034 ED visits with acute headache were reviewed for eligibility. There were 1521 visits that met exclusion criteria, and 3059 had headache of gradual onset or time to maximal intensity greater than or equal to 1 hour. The rule was applied to 454 patients (9.0%). There were 9 cases of subarachnoid hemorrhage (SAH), yielding an incidence of 2.0% (95% confidence interval [CI], 1.0%-3.9%) in the eligible cohort. The sensitivity for SAH was 100% (95% CI, 62.9%-100%); specificity, 7.6% (95% CI, 5.4%-10.6%); positive predictive value, 2.1% (95% CI 1.0%-4.2%); and negative predictive value, 100% (95% CI, 87.4%-100%). The OSAH rule was 100% sensitive for SAH in the eligible cohort. However, its low specificity and applicability to only a minority of ED patients with headache (9%) reduce its potential impact on practice

Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of “emergency” granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis

Synthesis of 5-substituted pyrrolo[1,2-b]pyridazines with antioxidant properties

Synthesis of 5-substituted pyrrolo[1,2-b]pyridazines with antioxidant properties. Ostby OB, Gundersen LL, Rise F, Antonsen O, Fosnes K, Larsen V, Bast A, Custers I, Haenen GR. Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway. 5-Substituted pyrrolo[1,2-b]pyridazines have been prepared by cyclisation of pyridazine with diphenylcyclopropenone followed by further functionalisations in the pyrrolo[1,2-b]pyridazine 5-position. Several compound exhibit profound inhibition of lipid peroxidation in vitro. Lipid peroxidation of boiled rat liver microsomes was induced by ascorbic acid/FeSO4 and the peroxidation was determined by measuring the thiobarbituric acid reactive materia