Andrea Rocco

The diffusion coefficient of propagating fronts with multiplicative noise

Recent studies have shown that in the presence of noise, both fronts propagating into a metastable state and so-called pushed fronts propagating into an unstable state, exhibit diffusive wandering about the average position. In this paper, we derive an expression for the effective diffusion coefficient of such fronts, which was motivated before on the basis of a multiple scale ansatz. Our systematic derivation is based on the decomposition of the fluctuating front into a suitably positioned average profile plus fluctuating eigenmodes of the stability operator. While the fluctuations of the front position in this particular decomposition are a Wiener process on all time scales, the fluctuations about the time-averaged front profile relax exponentially.

The multiscale nature of streamers

Streamers are a generic mode of electric breakdown of large gas volumes. They play a role in the initial stages of sparks and lightning, in technical corona reactors and in high altitude sprite discharges above thunderclouds. Streamers are characterized by a self-generated field enhancement at the head of the growing discharge channel. We briefly review recent streamer experiments and sprite observations. Then we sketch our recent work on computations of growing and branching streamers, we discuss concepts and solutions of analytical model reductions and we review different branching concepts and outline a hierarchy of model reductions.

Fractional Calculus and the Evolution of Fractal Phenomena

It is argued that the evolution of complex phenomena ought to be described by fractional, differential, stochastic equations whose solutions have scaling properties and are therefore random, fractal functions. To support this argument we demonstrate that the fractional derivative (integral) of a generalized Weierstrass function (GWF) is another fractal function with a greater (lesser) fractal dimension. We also determine that the GWF is a solution to such a fractional differential stochastic equation of motion.

IV thrombolysis and statins

Objective: To examine whether prior statin use affects outcome and intracranial hemorrhage (ICH) rates in stroke patients receiving IV thrombolysis (IVT). Methods: In a pooled observational study of 11 IVT databases, we compared outcomes between statin users and nonusers. Outcome measures were excellent 3-month outcome (modified Rankin scale 0–1) and ICH in 3 categories. We distinguished all ICHs (ICHall), symptomatic ICH based on the criteria of the ECASS-II trial (SICHECASS-II), and symptomatic ICH based on the criteria of the National Institute of Neurological Disorders and Stroke (NINDS) trial (SICHNINDS). Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals were calculated. Results: Among 4,012 IVT-treated patients, 918 (22.9%) were statin users. They were older, more often male, and more frequently had hypertension, hypercholesterolemia, diabetes, coronary heart disease, and concomitant antithrombotic use compared with nonusers. Fewer statin users (35.5%) than nonusers (39.7%) reached an excellent 3-month outcome (ORunadjusted 0.84 [0.72–0.98], p = 0.02). After adjustment for age, gender, blood pressure, time to thrombolysis, and stroke severity, the association was no longer significant (0.89 [0.74–1.06], p = 0.20). ICH occurred by trend more often in statin users (ICHall 20.1% vs 17.4%; SICHNINDS 9.2% vs 7.5%; SICHECASS-II 6.9% vs 5.1%). This difference was statistically significant only for SICHECASS-II (OR = 1.38 [1.02–1.87]). After adjustment for age, gender, blood pressure, use of antithrombotics, and stroke severity, the ORadjusted for each category of ICH (ICHall 1.15 [0.93–1.41]; SICHECASS-II 1.32 [0.94–1.85]; SICHNINDS 1.16 [0.87–1.56]) showed no difference between statin users and nonusers. Conclusion: In stroke patients receiving IVT, prior statin use was neither an independent predictor of functional outcome nor ICH. It may be considered as an indicator of baseline characteristics that are associated with a less favorable course.

Fractional calculus as a macroscopic manifestation of randomness

Istituto di Biofisica del Consiglio Nazionale delle Ricerche, Via S. Lorenzo 26, 56127 Pisa, Italy(February 1, 2008)We generalize the method of Van Hove so as to deal with the case ofnon-ordinary statistical mechanics, that being phenomena with no time-scaleseparation. We show that in the case of ordinary statistical mechanics, even ifthe adoption of the Van Hove method imposes randomness upon Hamiltoniandynamics, the resulting statistical process is described using normal calculustechniques. On the other hand, in the case where there is no time-scaleseparation, this generalized version of Van Hove’s method not only imposesrandomness upon the microscopic dynamics, but it also transmits randomnessto the macroscopic level. As a result, the correct description of macroscopicdynamics has to be expressed in terms of the fractional calculus.PACS number(s): 05.40.+j, 05.45.+b, 05.60.+wI. INTRODUCTION

Monitoring After the Acute Stage of Stroke A Prospective Study

Background and Purposes— In the early stage of stroke, the occurrence of neurologic and medical complications is associated with clinical deterioration. Previous studies were focused on the first week after stroke onset. The aim of this study was to evaluate the impact of complications on clinical outcome in patients with stroke in the early subacute stage. Methods— We prospectively evaluated the influence on the outcome of complications feasible (MC) and not feasible for monitoring (NMC) in all patients with stroke admitted consecutively in our subacute stroke unit. Patients were divided into three classes according to stroke severity evaluated by the National Institutes of Health Stroke Scale score. A change in the National Institutes of Health Stroke Scale score group from admission to discharge was considered clinically significant. Results— We included 261 patients. Sixty percent of patients had complications (105 MC, 118 NMC). Hyperthermia (OR=14.12; 95% CI: 6.01 to 33.20), urinary infections (OR=4.92; 95% CI: 2.19 to 11.04), hypertension (OR=2.86; 95% CI: 1.21 to 6.76), hypoxia (OR=15.75; 95% CI: 6.73 to 36.84), and neuroradiologic damage progression (OR=58.31; 95% CI, 19.48 to 174.55) were associated with a change to a more severe class at discharge and with a higher risk of mortality. Conclusions— A high percentage of patients can develop both MC and NMC during this subacute stage of stroke. The occurrence of complications influences outcome and raises the question about the need for a prolonged stay in a dedicated ward for patients with stroke.

Branching of negative streamers in free flight

We have recently shown that a negative streamer in a sufficiently high homogeneous field can branch spontaneously due to a Laplacian instability, rather than approach a stationary mode of propagation with fixed radius. In our previous simulations, the streamer started from a wide initial ionization seed on the cathode. We here demonstrate, in improved simulations, that a streamer emerging from a single electron branches in the same way. In fact, though the evolving streamer is much more narrow, it branches after an even shorter propagation distance.

An Iterative Genetic and Dynamical Modelling Approach Identifies Novel Features of the Gene Regulatory Network Underlying Melanocyte Development

The mechanisms generating stably differentiated cell-types from multipotent precursors are key to understanding normal development and have implications for treatment of cancer and the therapeutic use of stem cells. Pigment cells are a major derivative of neural crest stem cells and a key model cell-type for our understanding of the genetics of cell differentiation. Several factors driving melanocyte fate specification have been identified, including the transcription factor and master regulator of melanocyte development, Mitf, and Wnt signalling and the multipotency and fate specification factor, Sox10, which drive mitf expression. While these factors together drive multipotent neural crest cells to become specified melanoblasts, the mechanisms stabilising melanocyte differentiation remain unclear. Furthermore, there is controversy over whether Sox10 has an ongoing role in melanocyte differentiation. Here we use zebrafish to explore in vivo the gene regulatory network (GRN) underlying melanocyte specification and differentiation. We use an iterative process of mathematical modelling and experimental observation to explore methodically the core melanocyte GRN we have defined. We show that Sox10 is not required for ongoing differentiation and expression is downregulated in differentiating cells, in response to Mitfa and Hdac1. Unexpectedly, we find that Sox10 represses Mitf-dependent expression of melanocyte differentiation genes. Our systems biology approach allowed us to predict two novel features of the melanocyte GRN, which we then validate experimentally. Specifically, we show that maintenance of mitfa expression is Mitfa-dependent, and identify Sox9b as providing an Mitfa-independent input to melanocyte differentiation. Our data supports our previous suggestion that Sox10 only functions transiently in regulation of mitfa and cannot be responsible for long-term maintenance of mitfa expression; indeed, Sox10 is likely to slow melanocyte differentiation in the zebrafish embryo. More generally, this novel approach to understanding melanocyte differentiation provides a basis for systematic modelling of differentiation in this and other cell-types.

C-Reactive-Protein Levels Associated with Infection Predict Short- and Long-Term Outcome after Supratentorial Intracerebral Hemorrhage

Background: The aim of the current study was to assess the occurrence of infection and its impact on the short- and long-term outcome of patients with supratentorial intracerebral hemorrhage (ICH). Methods: 247 patients suffering from supratentorial ICH were extracted from our local stroke database. Complete data sets including long-term functional outcome measured by the modified Rankin Scale (mRS), and baseline computed tomography data could be obtained in 113. The charts of these patients were screened for the presence and cause of infection, and baseline and maximal C-reactive protein (CRP) levels were recorded. Results: We identified 52 patients (50.5%) with infection during their hospital stay. Patients with infection, had significantly larger hemorrhages (28.7 vs. 11.9 ml; p = 0.002), a poorer admission status (National Institutes of Health Stroke Scale, NIHSS, score 14 vs. 6; p = 0.002) and more frequently intraventricular hemorrhage extension (46.2 vs. 23.5%; p = 0.016) than those without infection. In a multivariate logistic regression model, baseline NIHSS score (odds ratio, OR, 1.2, 95% confidence interval, CI, 1.1–1.31, p < 0.001), age (OR 1.1, 95% CI 1.03–1.16, p = 0.002) and maximal CRP levels (OR 1.72, 95% CI 1.12–2.64, p = 0.013) were independent predictors of poor long-term functional outcome (mRS >2). Conclusion: Infections were frequent complications in our cohort of ICH patients and occurred significantly more often in patients with poor functional outcome. Maximal CRP levels were an independent predictor of poor outcome in a multivariate model.

Glycosylated Hemoglobin A1 Predicts Risk for Symptomatic Hemorrhage After Thrombolysis for Acute Stroke

Background and Purpose— Symptomatic intracerebral hemorrhage (sICH) is the most feared acute complication after intravenous thrombolysis. The aim of this study was to determine the predictive value of parameters of glycosylated hemoglobin A1 (HbA1c) on sICH. Methods— In a retrospective single center series, 1112 consecutive patients treated with thrombolysis were studied. Baseline blood glucose was obtained at admission. HbA1c was determined within hospital stay. A second head computed tomography was obtained after 24 hours or when neurological worsening occurred. Modified Rankin Scale was used to assess outcome at 90 days. Results— A total of 222 patients (19.9%) had any hemorrhage; 43 of those had sICH (3.9%) per Safe Implementation of Treatments in Stroke definition and 95 (8.5%) per National Institute of Neurological Disorders and Stroke definition; 33.2% of patients had a dependent outcome (modified Rankin Scale score 3–5). In univariate analysis history of diabetes mellitus, HbA1c, blood glucose, and National Institute of Health Stroke Scale score on admission were associated with any hemorrhage and sICH. In multivariate analysis National Institute of Health Stroke Scale score, a history of diabetes mellitus, and HbA1c were predictors of sICH per National Institute of Neurological Disorders and Stroke, and only HbA1c when Safe Implementation of Treatments in Stroke criteria were used. Conclusions— In our study, HbA1c turns out to be an important predictor of sICH after thrombolysis for acute stroke. These results suggest that hemorrhage after thrombolysis may be a consequence of long-term vascular injury rather than of acute hyperglycemia, and that HbA1c may be a better predictor than acute blood glucose or a history of diabetes mellitus.