Recanalization and Collaterals Predict Outcome in Proximal MCA Occlusion, but neither Penumbra nor Core of Stroke

Data on new predictors of outcome include penumbra core or collaterals.Objective: To test the predictive value of recanalization, collaterals, penumbra and core of ischemia for functional outcome in a large group of patients with MCA occlusion. Method: Consecutive events included prospectively in the Acute Stroke Registry and Analysis of Lausanne from April 2002 to April 2009 with an acute stroke due to proximal MCA occlusion (M1) were considered for analysis. Acute CTA were reviewed to grade the collaterals (dichotomized in poor __50% or good _50% compared to the normal side) and localization of M1 occlusion (proximal or mid-distal). Acute CTP were reviewed and reconstructed to determine penumbra, core and stroke index (penumbra/penumbra_core) of brain ischemia. Good outcome was defined by mRS 0-2 at 3 months.Results: Among 242 events (115 male, mean NIHSS 18.1, SD 5.8, mean age 66, SD 15), 42% were treated with intravenous thrombolysis, and 3% with intraarterial thrombolysis. Collateral status was rated as poor in 53% of events and proximal M1 occlusion was present in 64%. Recanalization determined at 24 hours with CTA was complete in 26% events and partial/absent in 54%.CTP was available for 212 events. Mean penumbra was 88.6 cm3 (median 84.4, SD 53.8), mean core was 54.1 cm3 (median 46.2, SD 45.7) and stroke index was 64% (median 68%, SD 25%). Good outcome was observed in 87 events (36%) and was associated in multivariate logistic regression with thrombolysis (p_0.02, OR_2.5, 95% CI 1.2-5.4), recanalization (p_0.001, OR_4.1, 95% CI 1.9-8.9), lower NIHSS (p_0.001, OR_0.84, 95% CI 0.78-0.91), male gender (p_0.01, OR_2.8, 95% CI 1.3-5.9), mRS prior to stroke (p_0.02, OR_0.5, 95% CI 0.28-0.9) and good collateral status (p_0.005, OR_3, 95% CI 1.4-6.4). Nor penumbra, nor core, nor stroke index were significant in the multivariate model, even if an association was present in the univariate model between good functional outcome and penumbra (p_0.004, OR_1.008, 95% CI 1.003-1.01), core (p_0.001, OR_0.98, 95% CI 0.976-0.99) and strokeindex (p_0.001, OR_16.7, 95% CI 4.6 59.9).Conclusion: MCA recanalization is the best predictor for good functional outcome, followed by collateral status. CTP data did not predict the functional outcome in our large group of M1 occlusion. Author Disclosures: C. Odier: None. P. Michel: Research Grant; Significant; Paion, Lundbeck. Speakers; Modest; Boehringer-Ingelheim. Consultant/Advisory Board; Modest; Boehringer- Ingelheim. Consultant/Advisory Board; Significant; Servier, Lundbeck.

Garnet-chloritoid-kyanite metapelites from the Raspas Complex (SW Ecuador): a key eclogite-facies assemblage

The Raspas Complex (Ecuador) contains one of the few eclogitic bodies in the northern Andes. It consists of metaperidotites, eclogites, and metapelites. The latter display three assemblages: (i) garnet + chloritoid + kyanite, (ii) garnet + chloritoid and (iii) garnet + chlorite, in all cases with quartz and muscovite in addition. The growth of these assemblages was coeval with the main ductile deformation, and was followed by minor reequilibration (chlorite growth in garnet + chloritoid samples and chloritoid + quartz aggregates replacing garnet and kyanite in garnet + chloritoid + kyanite samples). Detailed microprobe analyses show increasing magnesian compositions for garnet (from core to rim) and chloritoid (inclusions within garnet compared to matrix grains) in kyanite-bearing samples. The above data are interpreted in the framework of the KFMASH system. Reaction progress along the divariant reaction Cld = Grt + Ky explains the change in chemistry of coexisting phases. The divariant Grt-Cld-Ky assemblage has a narrow stability field, and the P-T conditions are estimated at about 20 kbar, 550-600degreesC. Decompression, recorded by chloritoid-quartz pseudomorphs of garnet, probably occurred as temperature decreased.

Stochastic stability and the evolution of coordination in spatially structured populations.

Animals can often coordinate their actions to achieve mutually beneficial outcomes. However, this can result in a social dilemma when uncertainty about the behavior of partners creates multiple fitness peaks. Strategies that minimize risk ("risk dominant") instead of maximizing reward ("payoff dominant") are favored in economic models when individuals learn behaviors that increase their payoffs. Specifically, such strategies are shown to be "stochastically stable" (a refinement of evolutionary stability). Here, we extend the notion of stochastic stability to biological models of continuous phenotypes at a mutation-selection-drift balance. This allows us to make a unique prediction for long-term evolution in games with multiple equilibria. We show how genetic relatedness due to limited dispersal and scaled to account for local competition can crucially affect the stochastically-stable outcome of coordination games. We find that positive relatedness (weak local competition) increases the chance the payoff dominant strategy is stochastically stable, even when it is not risk dominant. Conversely, negative relatedness (strong local competition) increases the chance that strategies evolve that are neither payoff nor risk dominant. Extending our results to large multiplayer coordination games we find that negative relatedness can create competition so extreme that the game effectively changes to a hawk-dove game and a stochastically stable polymorphism between the alternative strategies evolves. These results demonstrate the usefulness of stochastic stability in characterizing long-term evolution of continuous phenotypes: the outcomes of multiplayer games can be reduced to the generic equilibria of two-player games and the effect of spatial structure can be analyzed readily.

Biosciences Path for Development: Economic and Core Competency Analyses, March 2004

Report produced by Iowa Department of Economic Development

The equity core and the Lorenz-maximal allocations in the equal division core

In this paper, we characterize the non-emptiness of the equity core (Selten, 1978) and provide a method, easy to implement, for computing the Lorenz-maximal allocations in the equal division core (Dutta-Ray, 1991). Both results are based on a geometrical decomposition of the equity core as a finite union of polyhedrons. Keywords: Cooperative game, equity core, equal division core, Lorenz domination. JEL classification: C71

Molecular mechanism of myosin Va recruitment to dense core secretory granules.

The brain-spliced isoform of Myosin Va (BR-MyoVa) plays an important role in the transport of dense core secretory granules (SGs) to the plasma membrane in hormone and neuropeptide-producing cells. The molecular composition of the protein complex that recruits BR-MyoVa to SGs and regulates its function has not been identified to date. We have identified interaction between SG-associated proteins granuphilin-a/b (Gran-a/b), BR-MyoVa and Rab27a, a member of the Rab family of GTPases. Gran-a/b-BR-MyoVa interaction is direct, involves regions downstream of the Rab27-binding domain, and the C-terminal part of Gran-a determines exon specificity. MyoVa and Gran-a/b are partially colocalised on SGs and disruption of Gran-a/b-BR-MyoVa binding results in a perinuclear accumulation of SGs which augments nutrient-stimulated hormone secretion in pancreatic beta-cells. These results indicate the existence of at least another binding partner of BR-MyoVa that was identified as rabphilin-3A (Rph-3A). BR-MyoVa-Rph-3A interaction is also direct and enhanced when secretion is activated. The BR-MyoVa-Rph-3A and BR-MyoVa-Gran-a/b complexes are linked to a different subset of SGs, and simultaneous inhibition of these complexes nearly completely blocks stimulated hormone release. This study demonstrates that multiple binding partners of BR-MyoVa regulate SG transport, and this molecular mechanism is universally used by neuronal, endocrine and neuroendocrine cells.

A repeated GGA motif is critical for the activity and stability of the riboregulator RsmY of Pseudomonas fluorescens.

The riboregulator RsmY of Pseudomonas fluorescens strain CHA0 is an example of small regulatory RNAs belonging to the global Rsm/Csr regulatory systems controlling diverse cellular processes such as glycogen accumulation, motility, or formation of extracellular products in various bacteria. By binding multiple molecules of the small regulatory protein RsmA, RsmY relieves the negative effect of RsmA on the translation of several target genes involved in the biocontrol properties of strain CHA0. RsmY and functionally related riboregulators have repeated GGA motifs predicted to be exposed in single-stranded regions, notably in the loops of hairpins. The secondary structure of RsmY was corroborated by in vivo cleavage with lead acetate. RsmY mutants lacking three or five (out of six) of the GGA motifs showed reduced ability to derepress the expression of target genes in vivo and failed to bind the RsmA protein efficiently in vitro. The absence of GGA motifs in RsmY mutants resulted in reduced abundance of these transcripts and in a shorter half-life (< or = 6 min as compared with 27 min for wild type RsmY). These results suggest that both the interaction of RsmY with RsmA and the stability of RsmY strongly depend on the GGA repeats and that the ability of RsmY to interact with small regulatory proteins such as RsmA may protect this RNA from degradation.

Simulation methods with extended stability for stiff biochemical kinetics

Background: With increasing computer power, simulating the dynamics of complex systems in chemistry and biology is becoming increasingly routine. The modelling of individual reactions in (bio)chemical systems involves a large number of random events that can be simulated by the stochastic simulation algorithm (SSA). The key quantity is the step size, or waiting time, τ, whose value inversely depends on the size of the propensities of the different channel reactions and which needs to be re-evaluated after every firing event. Such a discrete event simulation may be extremely expensive, in particular for stiff systems where τ can be very short due to the fast kinetics of some of the channel reactions. Several alternative methods have been put forward to increase the integration step size. The so-called τ-leap approach takes a larger step size by allowing all the reactions to fire, from a Poisson or Binomial distribution, within that step. Although the expected value for the different species in the reactive system is maintained with respect to more precise methods, the variance at steady state can suffer from large errors as τ grows. Results: In this paper we extend Poisson τ-leap methods to a general class of Runge-Kutta (RK) τ-leap methods. We show that with the proper selection of the coefficients, the variance of the extended τ-leap can be well-behaved, leading to significantly larger step sizes.Conclusions: The benefit of adapting the extended method to the use of RK frameworks is clear in terms of speed of calculation, as the number of evaluations of the Poisson distribution is still one set per time step, as in the original τ-leap method. The approach paves the way to explore new multiscale methods to simulate (bio)chemical systems.

The control of microtubule stability in vitro and in transfected cells by MAP1B and SCG10.

In neurons, the regulation of microtubules plays an important role for neurite outgrowth, axonal elongation, and growth cone steering. SCG10 family proteins are the only known neuronal proteins that have a strong destabilizing effect, are highly enriched in growth cones and are thought to play an important role during axonal elongation. MAP1B, a microtubule-stabilizing protein, is found in growth cones as well, therefore it was important to test their effect on microtubules in the presence of both proteins. We used recombinant proteins in microtubule assembly assays and in transfected COS-7 cells to analyze their combined effects in vitro and in living cells, respectively. Individually, both proteins showed their expected activities in microtubule stabilization and destruction respectively. In MAP1B/SCG10 double-transfected cells, MAP1B could not protect microtubules from SCG10-induced disassembly in most cells, in particular not in cells that contained high levels of SCG10. This suggests that SCG10 is more potent to destabilize microtubules than MAP1B to rescue them. In microtubule assembly assays, MAP1B promoted microtubule formation at a ratio of 1 MAP1B per 70 tubulin dimers while a ratio of 1 SCG10 per two tubulin dimers was needed to destroy microtubules. In addition to its known binding to tubulin dimers, SCG10 binds also to purified microtubules in growth cones of dorsal root ganglion neurons in culture. In conclusion, neuronal microtubules are regulated by antagonistic effects of MAP1B and SCG10 and a fine tuning of the balance of these proteins may be critical for the regulation of microtubule dynamics in growth cones.

Review of Stability Berm Alternatives for Environmentally Senstitive Areas, 2005

Stability berms are commonly constructed where roadway embankments cross soft or unstable ground conditions. Under certain circumstances, the construction of stability berms cause unfavorable environmental impacts, either directly or indirectly, through their effect on wetlands, endangered species habitat, stream channelization, longer culvert lengths, larger right-of-way purchases, and construction access limits. Due to an ever more restrictive regulatory environment, these impacts are problematic. The result is the loss of valuable natural resources to the public, lengthy permitting review processes for the department of transportation and permitting agencies, and the additional expenditures of time and money for all parties. The purpose of this project was to review existing stability berm alternatives for potential use in environmentally sensitive areas. The project also evaluates how stabilization technologies are made feasible, desirable, and cost-effective for transportation projects and determines which alternatives afford practical solutions for avoiding and minimizing impacts to environmentally sensitive areas. An online survey of engineers at state departments of transportation was also conducted to assess the frequency and cost effectiveness of the various stabilization technologies. Geotechnical engineers that responded to the survey overwhelmingly use geosynthetic reinforcement as a suitable and cost-effective solution for stabilizing embankments and cut slopes. Alternatively, chemical stabilization and installation of lime/cement columns is rarely a remediation measure employed by state departments of transportation.

Core Analysis of Portland Cement Concrete Slip Formed Barriers, January 2000

Premature deterioration of slip formed portland cement concrete (PCC) barriers is an ongoing problem in the Iowa Primary and Interstate highway system. The requirement to have a concrete mix which can be sufficiently pliable to be readily molded into the barrier shape and yet be sufficiently stiff to maintain a true shape and height immediately after molding is difficult to meet. A concrete mix which is stiff enough to maintain its shape immediately after molding is usually difficult to work with. It often contains open or hidden tears and large voids. One way to minimize the molding resistance is by additional vibration. If intensive vibration is applied, the entrapped air voids and tears in the concrete can usually be eliminated, however, in that process, the essential entrained air content can also be lost. In the evaluation of slip formed PCC barriers, it is common to find large voids, tears and a low entrained air content, all contributing to premature deterioration. A study was initiated to evaluate core samples taken from good and from bad appearing areas of various median barriers. Evaluations were done covering visual appearance, construction information, air content and chloride content.

Canzonetta : mélodie : [Quanto è folle quell'amante] / Bernado Pasquini, comp.. Aria : mélodie : [Alma del core, spirto dell'alma] / Antonio Caldara, comp. ; Leila Ben-Sedira, S ; Mme Simone Gouat, p

Comprend : Canzonetta / Bernado Pasquini, comp. ; Aria / Antonio Caldara, comp.

Reliability and validity of the cross-culturally adapted French version of the Core Outcome Measures Index (COMI) in patients with low back pain.

PURPOSE: To conduct a cross-cultural adaptation of the Core Outcome Measures Index (COMI) into French according to established guidelines. METHODS: Seventy outpatients with chronic low back pain were recruited from six spine centres in Switzerland and France. They completed the newly translated COMI, and the Roland Morris disability (RMQ), Dallas Pain (DPQ), adjectival pain rating scale, WHO Quality of Life, and EuroQoL-5D questionnaires. After ~14 days RMQ and COMI were completed again to assess reproducibility; a transition question (7-point Likert scale; "very much worse" through "no change" to "very much better") indicated any change in status since the first questionnaire. RESULTS: COMI whole scores displayed no floor effects and just 1.5% ceiling effects. The scores for the individual COMI items correlated with their corresponding full-length reference questionnaire with varying strengths of correlation (0.33-0.84, P < 0.05). COMI whole scores showed a very good correlation with the "multidimensional" DPQ global score (Rho = 0.71). 55 patients (79%) returned a second questionnaire with no/minimal change in their back status. The reproducibility of individual COMI 5-point items was good, with test-retest differences within one grade ranging from 89% for 'social/work disability' to 98% for 'symptom-specific well-being'. The intraclass correlation coefficient for the COMI whole score was 0.85 (95% CI 0.76-0.91). CONCLUSIONS: In conclusion, the French version of this short, multidimensional questionnaire showed good psychometric properties, comparable to those reported for German and Spanish versions. The French COMI represents a valuable tool for future multicentre clinical studies and surgical registries (e.g. SSE Spine Tango) in French-speaking countries.