Contraindications to intravenous thrombolysis in prehospital triage of thrombectomy candidates.

BACKGROUND AND PURPOSE: The existence of contraindications to intravenous thrombolysis (IVT) is considered a criterion for direct transfer of patients with suspected acute stroke to thrombectomy-capable centers in the prehospital setting. Our aim was to assess the utility of this criterion in a setting where routing protocols are defined by the Madrid - Direct Referral to Endovascular Center (M-DIRECT) prehospital scale. METHODS: This was a post hoc analysis of the M-DIRECT study. Reported contraindications to IVT were retrospectively collected from emergency medical services reports and categorized into late window, anticoagulant treatment and other contraindications. Final diagnosis and treatment rates were compared between patients with and without reported IVT contraindications and according to anticoagulant treatment or late window categories. RESULTS: The M-DIRECT study included 541 patients. Reported IVT contraindications were present in 227 (42.0%) patients. Regarding final diagnosis no significant differences were found between patients with or without reported IVT contraindications: ischaemic stroke (any) 65.6% vs. 62.1%, ischaemic stroke with large vessel occlusion (LVO) 32.2% vs. 28.3%, hemorrhagic stroke 15.4% vs. 15.6%, stroke mimic 18.9% vs. 22.3% respectively. Amongst patients with LVO, endovascular thrombectomy (EVT) was performed less often in the presence of IVT contraindications (56.2% vs. 74.2%). M-DIRECT-positive patients had higher rates of LVO and EVT compared with M-DIRECT-negative patients independent of reported IVT contraindications. CONCLUSIONS: Reported IVT contraindications alone do not increase EVT likelihood and should not be considered to determine routing in urban stroke networks.

Dynamics of Turing and Faraday instabilities in a longitudinally modulated fiber-ring cavity.

We experimentally investigate the round-trip-to-round-trip dynamics of the modulation instability spectrum in a passive fiber-ring cavity presenting an inhomogeneous dispersion profile. By implementing a real-time spectroscopy technique, we are able to record successive single-shot spectra, which display the evolution of the system toward a stationary state. We find that the two instability regimes (Turing and Faraday) that compete in this kind of inhomogeneous cavity not only differ by their characteristic frequency but also by their dynamical behavior. The dynamic transition between those two regimes of instability is also presented.

Spectral broadening of picosecond pulses forming dispersive shock waves in optical fibers.

We investigate analytically, numerically, and experimentally the spectral broadening of pulses that undergo the formation of dispersive shocks, addressing in particular pulses in the range of tens of ps generated via electro-optic modulation of a continuous-wave laser. We give an analytical estimate of the maximal spectral extension and show that super-Gaussian waveforms favor the generation of flat-topped spectra. We also show that the weak residual background of the modulator produces undesired spectral ripples. Spectral measurements confirm our estimates and agree well with numerical integration of the nonlinear Schrödinger equation.

Shock wave generation triggered by a weak background in optical fibers.

We experimentally report the observation of dispersive shock waves from a short pulse superimposed onto a small continuous wave background in optical fibers. We show that the background allows us to strongly enhance the extension and contrast of the oscillatory wave train inherent to the dispersive shock. More than seven periods of oscillations with high contrast are observed experimentally and confirmed with numerical simulations. The dynamics of the process are simply explained from spectro-temporal representations.

Heteroclinic Structure of Parametric Resonance in the Nonlinear Schrödinger Equation.

We show that the nonlinear stage of modulational instability induced by parametric driving in the defocusing nonlinear Schrödinger equation can be accurately described by combining mode truncation and averaging methods, valid in the strong driving regime. The resulting integrable oscillator reveals a complex hidden heteroclinic structure of the instability. A remarkable consequence, validated by the numerical integration of the original model, is the existence of breather solutions separating different Fermi-Pasta-Ulam recurrent regimes. Our theory also shows that optimal parametric amplification unexpectedly occurs outside the bandwidth of the resonance (or Arnold tongues) arising from the linearized Floquet analysis.

Experimental Observation and Theoretical Description of Multisoliton Fission in Shallow Water.

We observe the dispersive breaking of cosine-type long waves [Phys. Rev. Lett. 15, 240 (1965)] in shallow water, characterizing the highly nonlinear "multisoliton" fission over variable conditions. We provide new insight into the interpretation of the results by analyzing the data in terms of the periodic inverse scattering transform for the Korteweg-de Vries equation. In a wide range of dispersion and nonlinearity, the data compare favorably with our analytical estimate, based on a rigorous WKB approach, of the number of emerging solitons. We are also able to observe experimentally the universal Fermi-Pasta-Ulam recurrence in the regime of moderately weak dispersion.

Optimal frequency conversion in the nonlinear stage of modulation instability.

We investigate multi-wave mixing associated with the strongly pump depleted regime of induced modulation instability (MI) in optical fibers. For a complete transfer of pump power into the sideband modes, we theoretically and experimentally demonstrate that it is necessary to use a much lower seeding modulation frequency than the peak MI gain value. Our experiment shows that, at such optimal modulation frequency, a record 95 % of the output pump power is frequency converted into the comb of sidebands, in good quantitative agreement with analytical predictions based on the simplest exact breather solution of the nonlinear Schrodinger ¨ equation.

Zero focusing via competing nonlinearities in beta-barium-borate crystals.

We investigate nonlinear focusing behavior of light beams propagating in beta-barium-borate crystals under mismatched second-harmonic generation. We clearly identify experimentally multiple self-focusing and defocusing regions against the orientation angle and the condition where competing quadratic and cubic nonlinearities perfectly compensate each other (zero-focusing point).

Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 10 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3 to 6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P =  .03), focal deficits (P = .001), and encephalopathy (P < .001) showing a statistically significant association with poor prognosis (mRS > 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

Optimizing pump-probe switching ruled by free-carrier dispersion.

We address theoretically and numerically pump-probe switching in a nonlinear semiconductor nanocavity where tuning is achieved via a dominant mechanism of free-carrier plasma dispersion. By using coupled-mode approach we give a set of guidelines to optimize the switching performances both in terms of avoiding self-pulsation and keeping switching power to the minimum, ending up by showing that such devices can achieve high-performances with relatively low-power consumption.

Competing wave-breaking mechanisms in quadratic media.

We show that second-harmonic generation in the regime of weak dispersion/diffraction can exhibit a coexistence of wave breaking mechanisms, such that a gradient catastrophe yielding a dispersive shock wave competes with modulational instability, leading to the generation of wavetrains with incommensurate frequencies and eventually to the destruction of the shock wave-train.

Low-power spontaneous oscillations driven by band-filling effect.

We predict that self-sustained oscillations can be generated in a semiconductor nanocavity in which the dominant effect is band-filling dispersion. Linear stability analysis, validated through numerical integration of a mean-field model, leads us to envisage oscillations typically at tens of gigahertz, with onset at much lower input power (~100 µW) compared with those driven by two-photon absorption.

Observation of modulationally unstable multi-wave mixing.

We demonstrate experimentally that multiple four-wave mixing (FWM) pumped by a dual-frequency input in a single-mode fiber is modulationally unstable. This collective type of instability leads, in the anomalous dispersion regime, to sideband growth around all orders of FWM. This is in contrast with the normal dispersion regime where our measurements show that FWM exhibits no instability. Our conclusions are based on the first systematic mapping of the phenomenon as a function of the dual-pump input frequency separation.

[Bilateral vocal cord paralysis with acute airway obstruction and urgent tracheotomy in a patient with an acute vertebrobasilar stroke]. / Parálisis bilateral de las cuerdas vocales con obstrucción aguda de la vía aérea y traqueotomía urgente en una paciente con ictus vertebrobasilar agudo.

INTRODUCTION: Vertebrobasilar stroke can be a diagnostic challenge. Bilateral vocal cord paralysis is very rare as a manifestation of acute stroke, yet it is potentially life-threatening because of the possibility of acute airway obstruction. No cases of bilateral vocal cord paralysis have been reported as a presenting symptom of acute stroke of mixed central and peripheral neurological aetiology. CASE REPORT: An 88-year-old woman with dysphonia resulting from paralysis of the right vocal cord following a thyroidectomy presented with sudden onset of vertigo, dysmetria and mild dysarthria (National Institutes of Health Stroke Scale: 2) associated with arterial hypertension. An urgent brain computed tomography (CT) scan evidenced distal occlusive thrombosis of the left vertebral artery without established ischaemia. Due to the improvement of symptoms achieved with control of her blood pressure, revascularisation therapy was not performed. Four hours later, the patient suddenly developed inspiratory stridor and severe respiratory failure due to bilateral vocal cord paralysis with complete airway obstruction. An urgent tracheotomy was performed, which resulted in an improvement in her breathing. A control brain CT scan performed at 24 hours showed established infarction in the left hemicerebellum and lateral medullary region, consistent with the territory of the left posterior inferior cerebellar artery. CONCLUSION: Our case illustrates the possibility of the rare occurrence of acute bilateral vocal cord paralysis in the context of acute stroke in conjunction with chronic peripheral involvement of the recurrent laryngeal nerve. Although exceptional, it exemplifies the potential risk associated with vertebrobasilar strokes. A more aggressive reperfusion therapy may be appropriate in these cases, despite an initially mild deficit, because of the possibility of progression to life-threatening complications.

TITLE: Parálisis bilateral de las cuerdas vocales con obstrucción aguda de la vía aérea y traqueotomía urgente en una paciente con ictus vertebrobasilar agudo.Introducción. El ictus vertebrobasilar puede suponer un reto diagnóstico. La parálisis bilateral de las cuerdas vocales como manifestación de ictus agudo es muy rara, pero potencialmente mortal, por la posibilidad de obstrucción aguda de la vía aérea. No hay casos descritos de parálisis bilateral de las cuerdas vocales como presentación de ictus agudo de etiología neurológica mixta central y periférica. Caso clínico. Mujer de 88 años con disfonía secuelar a parálisis de la cuerda vocal derecha postiroidectomía que presentó un cuadro brusco de vértigo, dismetría y disartria leve (National Institutes of Health Stroke Scale: 2) asociado a hipertensión arterial. La tomografía computarizada cerebral urgente demostró trombosis distal oclusiva de la arteria vertebral izquierda sin isquemia establecida. Por mejoría sintomática con control tensional, no se realizó terapia de revascularización. Cuatro horas después, la paciente desarrolló de forma brusca estridor inspiratorio e insuficiencia respiratoria grave por parálisis bilateral de las cuerdas vocales con obstrucción completa de la vía aérea. Se realizó una traqueotomía urgente con mejoría respiratoria. Una tomografía computarizada cerebral de control a las 24 horas mostró un infarto establecido en el hemicerebelo izquierdo y la región bulbar lateral, congruente con territorio de la arteria cerebelosa posterior inferior izquierda. Conclusión. Nuestro caso ilustra la posibilidad de la rara aparición de una parálisis bilateral aguda de las cuerdas vocales en el contexto de un ictus agudo junto con una afectación periférica crónica del nervio recurrente laríngeo. Aunque es excepcional, ejemplifica el potencial riesgo asociado a los ictus vertebrobasilares. Un tratamiento más agresivo de reperfusión podría ser adecuado en estos casos, pese a un déficit inicialmente leve, por la posibilidad de progresar a complicaciones vitales.

Dispersive shock waves in phase-mismatched second-harmonic generation.

We investigate wave-breaking and dispersive shock wave formation driven by a pulse undergoing second-harmonic generation in a quadratic medium. We show that the process is accessible in the regime of high phase-mismatch (cascading limit) and weak dispersion. Insight into the phenomenon is obtained by means of a suitable hydrodynamic reduction of the equations that govern the mixing.

Measurement of scaling laws for shock waves in thermal nonlocal media.

We are able to detect the details of spatial optical collisionless wave breaking through the high aperture imaging of a beam suffering shock in a fluorescent nonlinear nonlocal thermal medium. This allows us to directly measure how nonlocality and nonlinearity affect the point of shock formation and compare results with numerical simulations.

Temporal gap solitons and all-optical control of group delay in line-defect waveguides.

We show that a model based on anticrossing between highly group velocity-mismatched gap-guided and index-guided modes describes gap soliton propagation in photonic crystal waveguides. Such nonlinear solutions can be exploited for exploring new regimes such as all-optical control of group velocity (dispersionless slow light) over a submillimeter length scale, and propagation beyond the linear modal cutoff. The results are validated by means of finite-difference time domain simulations.

Blue self-frequency shift of slow solitons and radiation locking in a line-defect waveguide.

We investigate experimentally resonant radiation processes driven by slow solitons in a dispersion-engineered photonic crystal waveguide in a regime virtually free of dissipative nonlinear processes (two-photon absorption and Raman scattering). Strong (30% energy conversion) Cherenkov-like radiation accompanied by the blue self-frequency shift of the soliton is observed close to the zero dispersion point, and is explained in terms of the soliton-radiation locking of the velocity.

Extreme wave excitation from localized phase-shift perturbations.

The modulation instability is a focusing mechanism responsible for the formation of strong wave localizations not only on the water surface, but also in a variety of nonlinear dispersive media. Such dynamics is initiated from the injection of sidebands, which translate into an amplitude modulation of the wave field. The nonlinear stage of unstable wave evolution can be described by exact solutions of the nonlinear Schrödinger equation (NLSE). In that case, the amplitude modulation of such coherent extreme wave structures is connected to a particular phase-shift seed in the carrier wave. In this Letter, we show that phase-shift localization applied to the background, excluding any amplitude modulation excitation, can indeed trigger extreme events. Such rogue waves can be for instance generated by considering the parametrization of fundamental breathers, and thus by seeding only the local phase-shift information to the regular carrier wave. Our wave tank experiments show an excellent agreement with the expected NLSE hydrodynamics and confirm that even though delayed in their evolution, breather-type extreme waves can be generated from a purely regular wave train. Such a focusing mechanism awaits experimental confirmation in other nonlinear media, such optics, plasma, and Bose-Einstein condensates.

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1.

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death. This increase was consistently blunted by the Ca(2+) chelator ethylene glycol tetraacetic acid; neocortical Ca(2+) levels were significantly higher in all six patients; no difference in AGC transport rates was found in isolated mitochondria from patients and controls following removal of the Ca(2+)-containing postmitochondrial supernatant. Expression of AGC1, the predominant AGC isoform in brain, and cytochrome c oxidase activity were both increased in autistic patients, indicating an activation of mitochondrial metabolism. Furthermore, oxidized mitochondrial proteins were markedly increased in four of the six patients. Variants of the AGC1-encoding SLC25A12 gene were neither correlated with AGC activation nor associated with autism-spectrum disorders in 309 simplex and 17 multiplex families, whereas some unaffected siblings may carry a protective gene variant. Therefore, excessive Ca(2+) levels are responsible for boosting AGC activity, mitochondrial metabolism and, to a more variable degree, oxidative stress in autistic brains. AGC and altered Ca(2+) homeostasis play a key interactive role in the cascade of signaling events leading to autism: their modulation could provide new preventive and therapeutic strategies.