Percolation limited emission intensity from upconverting NaYF4:Yb3+,Er3+ nanocrystals - a single nanocrystal optical study.

Upconverting nanocrystals (UCNC) have recently been subjected to intensive investigation due to their interesting optical properties and high potential for practical applications. Despite the level of attention paid to these materials, very low quantum yield is still an important issue. In order to break through this limitation, understanding of the emission intensity limitation is crucial. In this paper, we investigate the influence of percolation phenomena on the limitation of the emission intensity from NaYF4:Yb3+,Er3+ nanocrystals. We propose a numerical model and support this experimentally at the single nanocrystal level, explaining the influence of Yb3+ concentration on the optical properties of UCNC. Moreover, based on the experimental and numerical results, we explain the existence of the optimal Yb3+ concentration in the core architecture often reported in the literature. All the measurements have been performed using a custom-built wide-field fluorescence microscope to analyze the emission from hundreds of single nanocrystals and thus make analysis independent of UCNC concentration.

Complex Dynamics of Photo-Switchable Guest Molecules in All-Optical Poling Close to the Glass Transition: Kinetic Monte Carlo Modeling.

We study theoretically the kinetics of noninteracting photoswitchable guest molecules (model azo-dye) dispersed at low concentration in host (model polymer matrix) in the all-optical poling process close to the glass transition temperature Tg. We modify kinetic Monte Carlo model used in our previous studies of nonlinear optical processes in host-guest systems. The polymer matrix is simulated using the bond-fluctuation model. The kinetics of multiple trans-cis-trans cycles is formulated in terms of transition probabilities which depend on local free volume in the matrix and its dynamics. Close to Tg, the buildup of polar order, monitored in terms of angular probability density functions, follows a power-law in time while the evolution of the nonlinear susceptibilities related to second harmonic generation effect follows the stretched-exponential law. This complex dynamics of guest molecules implies the presence of dynamic heterogeneities of the matrix in space and time which spread the complexity from the matrix to the otherwise simple dynamics of noninteracting guest molecules. A qualitative physical picture of mosaic-like states-intertwined areas of free- and hindered angular motion of guest molecules-is proposed and the role of related short and longer scales in space for the promotion of complex dynamics of guest molecules is discussed. A brief comparison of the theory to available experimental data is given.

Multiband Monte Carlo modeling of upconversion emission in sub 10 nm ß-NaGdF4:Yb3+, Er3+ nanocrystals-Effect of Yb3+ content.

In this work, we report the results of theoretical modeling supported and confirmed by experimentally measured emission, emission decay curves, and power dependent emission spectra for sub 10 nm ß-NaGdF4:Er3+,Yb3+ nanocrystals with different Yb3+ content (0.5%-15%). For the theoretical analysis, we develop a stochastic Monte Carlo model which is based on two components: (i) formation of clusters composed of Er3+ ion and Yb3+ neighbors, which gives insight into the role of local parameters and (ii) a simplified kinetic model of excitation and relaxation phenomena in pairs of Er3+and Yb3+ ions. The quantitative agreement between experimental data and modeling was obtained for the relative emission ratio of upconversion luminescence in green, red, and blue spectral ranges. Theoretical predictions of impact of excitation pulse duration and pumping light power on upconversion luminescence are presented.

Ion-ion interactions in ß-NaGdF4:Yb(3+),Er(3+) nanocrystals--the effect of ion concentration and their clustering.

In this work we report co-thermolysis as a suitable method for nanomaterial synthesis which allows the creation of hexagonal upconverting nanocrystals, NaGdF4:Yb(3+),Er(3+), in a wide range of sizes (20-120 nm). Only a very high Yb(3+) concentration (above 70%) results in pure cubic-phase nanocrystals with irregular shape. Additionally, we showed that the impact of Yb(3+), Er(3+) and Gd(3+) ions on the size and optical properties of nanocrystals is significant. We found that the main changes in optical properties do not depend on the nanocrystal size mostly, but are determined by the ion-ion interactions which include both Er(3+)-Er(3+) and Er(3+)-Yb(3+) cross relaxation.

Liquid crystal hyperbolic metamaterial for wide-angle negative-positive refraction and reflection.

We show that nanosphere dispersed liquid crystal (NDLC) metamaterial can be characterized in near IR spectral region as an indefinite medium whose real parts of effective ordinary and extraordinary permittivities are opposite in signs. Based on this fact we designed an electro-optic effect: an external electric-field-driven switch between normal refraction, negative refraction, and reflection of TM incident electromagnetic wave from the boundary vacuum/NDLC. A detailed analysis of its functionality is given based on effective medium theory combined with a study of negative refraction in anisotropic metamaterials and finite elements simulations.

Infrared cylindrical cloak in nanosphere dispersed liquid crystal metamaterial.

We present a design of an infrared cylindrical cloak using nanosphere dispersed nematic liquid crystal (NLC) metamaterial following the approach of Smith's group [Science 314, 977 (2006)]. Cloaking conditions require spatial distribution of liquid crystal birefringence with constant extraordinary index of refraction and radially dependent ordinary index of refraction. An approximate analytical formula for the latter is derived. Finite element (FE) simulations confirm the cloaking effect. Owing to the tunable birefringence of the liquid crystal component, such cloaking material offers the interesting possibilities of real-time control of invisibility. The possibility of experimental realization is briefly discussed.

[Ischemic stroke patients following intravenous thrombolysis. Outcome in a regional stroke center]. / Intravenöse Thrombolyse des ischämischen Schlaganfalls. Ergebnisse in einem regionalen Schlaganfallzentrum.

BACKGROUND: We wanted to compare the outcome following IV thrombolysis in our patients with ischemic stroke with the outcome reported from the phase 3 registration trials and other large trials. PATIENTS AND METHODS: From January 2008 through December 2009 we treated 225 patients with ischemic stroke with IV thrombolysis. Retrospectively, we analyzed their clinical data upon admission, during their stay, and upon discharge with special reference to eligibility criteria for IV thrombolysis, symptomatic hemorrhage, and clinical outcome. RESULTS: The average age of the patients was 74 years, with 34% being older than 80 years. The median time between stroke onset and initiation of treatment was 112 min. The initial median NIHSS was 11 points (Rankin score ≥ 4 in 79% of patients). The rate of symptomatic hemorrhage was 3%. The median follow-up was 14 days. At the end of the observation period, clinical symptoms had improved in 73% of patients (Rankin score ≤ 2 in 45% of patients). The mortality rate was 12%. In 55% of patients, IV thrombolysis was off label (age > 80 years in 34% of patients). CONCLUSION: The clinical results of IV thrombolysis in our stroke center are similar to the outcome reported from the registration trials and larger clinical series although we treated off label in more than half of the patients. Even larger studies have since shown that the age limit under 80 years for patients is not reasonable. The eligibility criteria should be adapted to reality at this point.

On effective electric field nano-octupoling in two dimensions.

Conditions towards effective electric field poling in two dimensions (2D) of octupolar molecules which can be achieved are being addressed, based on a lattice model which mimics the basic features of poling. The model is studied using the complementary approaches of analytical methods in statistical mechanics and Monte Carlo simulations. The poling field is imparted by a system of adequately shaped cylindrical electrodes. A topologically rich structure of local and global inhomogeneous octupolar order, including octupolar vortices, is present in the system. The poling criteria are shown to vary strongly throughout the cell: in close proximity to the contact points of neighboring electrodes, a high quality local octupolar order appears at temperature T ≃ 0.1 K while octupoling in the center of the cell requires temperatures as low as 10(-4) K. The highly demanding octupoling criteria are ascribed to symmetry-driven effects which decrease the quality of the octupolar phase even in the ground state, as well as to thermal fluctuations and numerical factors at above zero temperatures. Based on our results and using plausible conjectures related to the generalization of the model, it is argued that a weak global octupolar order can be reached at liquid Helium temperatures (a few Kelvins), based on current advances in optical techniques and nanotechnologies.

Second-harmonic generation in poled polymers: pre-poling history paradigm.

Experimental studies of second harmonic generation (SHG) from electric-field poled PMMA - DR1 system show occurrence of a maximum in diagonal and off diagonal tensor components χ(2)(-2ω;ω,ω) at 15 mol % concentration and a rapid decrease above, with a stabilization. The origin of the observed concentration dependence is studied using the Monte Carlo (MC) modeling. We find that presence of maximum is conditioned by the pre-poling history of the sample, when entanglement of linear dipolar structures takes place. Length of the pre-poling interval is an important kinetic parameter which differentiates between various nonexponential kinetics of build-up of polar phase responsible for strong/weak SHG susceptibility.

Thermodynamics of entropy-driven phase transformations.

Thermodynamic properties of one-dimensional lattice models exhibiting entropy-driven phase transformations are discussed in quantum and classical regimes. Motivated by the multistability of compounds exhibiting photoinduced phase transitions, we consider systems with asymmetric, double, and triple well on-site potential. One finds that among a variety of regimes, quantum versus classical, discrete versus continuum, a key feature is asymmetry distinguished as a "shift" type and "shape" type in limiting cases. The behavior of the specific heat indicates one phase transformation in a "shift" type and a sequence of two phase transformations in "shape"-type systems. Future analysis in higher dimensions should allow us to identify which of these entropy-driven phase transformations would evolve into phase transitions of the first order.

Impaired benzodiazepine receptor binding in peri-lesional cortex of patients with symptomatic epilepsies studied by [(11)C]-flumazenil PET.

Individual benzodiazepine receptor (BZR) binding of peri-lesional cortex was investigated in symptomatic epilepsies. Eleven patients aged 19-44 years were studied whose diagnosis was established by medical history, clinical, electroencephalographic, and magnetic resonance imaging (MRI) findings. Three-dimensional [11C]-flumazenil (FMZ) positron emission tomography and MRI scans were obtained and coregistered. Lesions (five low-grade brain tumours, one AV malformation, one cavernoma, one cystic lesion of unknown aetiology, one traumatic brain injury, one post-operative and one post-haemorrhagic defect) were outlined on individual MRI scans. Adjacent to those lesions, and in homologous contralateral structures, FMZ binding was analysed in four pairs of cortical 9 x 9-mm regions of interest (ROIs) placed on transaxial and coronal slices, respectively, as well as in the lesion volume and its mirror region. Percentage asymmetry ratios were calculated and those at or outside the 90-110% range were operationally defined significant. Peri-lesional FMZ binding asymmetries ranged from 70 to 125%, lesional asymmetries from 38 to 82%. Only one patient showed no significant change, whilst nine exhibited significant reductions of FMZ binding in at least one ROI (3 x 1, 4 x 2, 1 x 3, 1 x 4), and significant increases were observed in two ROIs of another patient. Therefore, peri-lesional disturbances of BZR binding are common but variable in location. Because a close correlation between regional decreases in FMZ binding and spiking activity was recently demonstrated in neocortical epilepsies, abnormal peri-lesional FMZ binding may bear some relation to the mechanisms of epileptogenesis in symptomatic epilepsies.

Penumbral probability thresholds of cortical flumazenil binding and blood flow predicting tissue outcome in patients with cerebral ischaemia.

Active treatment of acute ischaemic stroke can only be successful as long as tissue in the area of ischaemic compromise is still viable. Therefore, the identification of the area of irreversible damage, and its distinction from the penumbral zone, may improve the estimation of the potential efficacy of various therapeutic strategies. Ten patients (seven male, three female, aged 52-75 years) with acute ischaemic stroke, in whom MRI delineated an infarct involving the cortex 3 weeks after the attack, were studied by [(11)C]flumazenil (FMZ) PET to assess their neuronal integrity, and regional cerebral blood flow (CBF) was measured by H(2)(15)O PET 2-12 h (median interval 6 h) after onset of symptoms. Cortical volumes of interest (3 mm radius) were placed on co-registered CBF, FMZ and on late MRI scans. Using initial CBF and FMZ binding data from volumes of interest finally located within or outside the cortical infarct, cumulative probability curves were computed to predict eventual infarction or non-infarction. Positive (at least 95% chance of infarct) and negative (at least 95% chance of non-infarct) prediction limits for CBF (4.8 and 14.1 ml/100 g/min, respectively) and for FMZ binding (3.4 and 5.5 times the mean of normal white matter, respectively) were determined to define the penumbral range. Using the lower FMZ binding threshold of 3.4 for irreversible tissue damage and the upper CBF value of 14.1 ml/ 100 g/min for the threshold of critical perfusion at or above which tissue will likely be preserved, various cortical subcompartments were identified: of the final cortical infarct (median size 25.7 cm(3)) a major portion comprising, on average, 55.1% showed FMZ binding critically decreased, thus predicting necrosis. In 20.5% of the final infarct, on average, CBF was in the penumbral range (<14.1 ml/100 g/min) and FMZ binding was above the critical threshold of irreversible damage. Only 12.9% of the final infarct exhibited neuronal integrity and CBF values above the penumbral range. Therefore, most of the final infarct is irreversibly damaged already at the time of the initial evaluation, when studied several hours after stroke onset. A much smaller portion is still viable but suffers from insufficient blood supply: this tissue may be salvaged by effective reperfusion. Only an even smaller compartment is viable and sufficiently perfused, but eventually becomes necrotic, mainly owing to delayed mechanisms, and may benefit from neuroprotective or other measures targeted at secondary damage. Therefore, early reperfusion is crucial in acute ischaemic stroke.

Interictal hippocampal benzodiazepine receptors in temporal lobe epilepsy: comparison with coregistered hippocampal metabolism and volumetry.

The significance of benzodiazepine receptor (BZR) concentration in comparison with hippocampal metabolism and volumetry was assessed in 14 patients diagnosed with temporal lobe epilepsy (TLE) without hippocampal signal change on T2-weighted magnetic resonance imaging (MRI) scans. Focus lateralization was achieved by clinical, electroencephalographic and neuropsychological examinations. Three-dimensional positron emission tomography (PET) and MRI scans were coregistered for determination of hippocampal 11C-flumazenil (FMZ) binding, normalized to average cortical values for glucose metabolism (rCMRglc) and volume. The hippocampi were individually outlined on T1-weighted MRI. Volumes of interest (VOI) were used for calculation of asymmetries between clinically affected and unaffected sides. Eleven out of 14 TLE patients presented a significant reduction in hippocampal volume. In nine of these 11 patients hippocampal FMZ binding and in seven cases hippocampal CMRglc was also reduced. In two patients without hippocampal volume asymmetry FMZ binding was markedly reduced in the mesial temporal lobe appropriately to the clinically diagnosed side. In our study volumetry is therefore the most sensitive tool for the detection of hippocampal abnormality in TLE. However, in cases without hippocampal atrophy the reduction of FMZ may indicate functional impairment of BZR before neuronal loss becomes evident. Our results emphasize the complementary nature of these tests in TLE patients.

Apheresis and selective adsorption plus immunoglobulin treatment in Guillain-Barré syndrome.

Plasma exchange (PE) and administration of intravenous immunoglobulin (i.v. IgG) are established treatments for Guillain-Barré syndrome (GBS). Combination treatment with elimination of postulated pathogenetic factors by PE or selective adsorption (SA) treatment and subsequent immunomodulation by intravenous IgG may provide a more effective treatment. In a single-center randomized study, 45 patients with acute GBS were prospectively examined using a clinical score. We treated 11 patients by PE, 13 with SA using a tryptophan-linked polyvinyl alcohol gel adsorbent, and 21 with SA followed by intravenous IgG. The patients treated sequentially by selective adsorption and intravenous IgG improved significantly better than the patients who received plasma treatment only. The results suggest that combination treatment of GBS may be superior to plasma treatment alone.

Early [(11)C]Flumazenil/H(2)O positron emission tomography predicts irreversible ischemic cortical damage in stroke patients receiving acute thrombolytic therapy.

BACKGROUND AND PURPOSE: Central benzodiazepine receptor ligands, such as [(11)C]flumazenil (FMZ), are markers of neuronal integrity and therefore might be useful in the differentiation of functionally and morphologically damaged tissue early in ischemic stroke. We sought to assess the value of a benzodiazepine receptor ligand for the early identification of irreversible ischemic damage to cortical areas that cannot benefit from reperfusion. METHODS: Eleven patients (7 male, 4 female, aged 52 to 75 years) with acute, hemispheric ischemic stroke were treated with alteplase (recombinant tissue plasminogen activator; 0.9 mg/kg according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms. At the beginning of thrombolysis, cortical cerebral blood flow ([(15)O]H(2)O) and FMZ binding were assessed by positron emission tomography (PET). Those early PET findings were related to the change in neurological deficit (National Institutes of Health Stroke Scale) and to the extent of cortical damage on MRI or CT 3 weeks after the stroke. RESULTS: Hypoperfusion was observed in all cases, and in 8 patients the values were below critical thresholds estimated at 12 mL/100 g per minute, comprising 1 to 174 cm(3) of cortical tissue. Substantial reperfusion was seen in most of these regions 24 hours after thrombolysis. In 4 cases, distinct areas of decreased FMZ binding were detected. Those patients suffered permanent lesions in cortical areas corresponding to their FMZ defects (112 versus 146, 3 versus 3, 2 versus 1, and 128 versus 136 cm(3)). In the other patients no morphological defects were detected on MRI or CT, although blood flow was critically decreased in areas ranging in size up to 78 cm(3) before thrombolysis. CONCLUSIONS: These findings suggest that imaging of benzodiazepine receptors by FMZ PET distinguishes between irreversibly damaged and viable penumbra tissue early after acute stroke.

Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke.

Thrombolytic therapy of acute ischemic stroke can be successful only as long as there is penumbral tissue perfused at rates between the thresholds of normal function and irreversible structural damage, respectively. To determine the proportion of tissue at risk of infarction, cerebral perfusion was studied in 12 patients with acute ischemic stroke who underwent treatment with systemic recombinant tissue plasminogen activator (0.9 mg/kg body weight according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms, using [15O]-H2O positron emission tomography (PET) before or during, and repeatedly after thrombolysis. The size of the regions of critically hypoperfused gray matter were identified on the initial PET scans, and changes of perfusion in those areas were related to the clinical course (followed by the National Institutes of Health stroke scale) and to the volume of infarcted gray matter demarcated on magnetic resonance imaging 3 weeks after the stroke. Whereas the initial clinical score was unrelated to the size of the ischemic area, after 3 weeks there was a strong correlation between clinical deficit and volume size of infarcted gray matter (Spearman's rho, 0.96; P < 0.001). All patients with a severely hypoperfused (< 12 mL/100 g/min) gray matter region measuring less than 15 mL on first PET showed full morphologic and clinical recovery (n = 5), whereas those with ischemic areas larger than 20 mL developed infarction and experienced persistent neurologic deficits of varying degree. Infarct sizes, however, were smaller than expected from previous correlative PET and morphologic studies of patients with acute stroke: only 22.7% of the gray matter initially perfused at rates below the conventional threshold of critical ischemia became necrotic. Actually, the percentage of initially ischemic voxels that became reperfused at almost normal levels clearly predicted the degree of clinical improvement achieved within 3 weeks. These sequential blood flow PET studies demonstrate that critically hypoperfused tissue can be preserved by early reperfusion, perhaps related to thrombolytic therapy. The results correspond with experimental findings demonstrating the prevention of large infarcts by early reperfusion to misery perfused but viable tissue.

Contribution of initial median-nerve somatosensory evoked potentials and brainstem auditory evoked potentials to prediction of clinical outcome in cerebrovascular critical care patients: a statistical evaluation.

In a prospective study of 200 patients with cerebrovascular disease (48 intracerebral hemorrhages, [ICH]; 64 subarachnoid hemorrhages, [SAH]; 48 supratentorial and 40 infratentorial ischemic strokes), we assessed the individual and combined prognostic value of median-nerve somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) within 72 hours of admission. Clinical outcome was graded in three ranked categories according to a modified Glasgow Outcome Scale. Likewise, the initial SEP and BAEP findings were graded in a three-class score. In all groups, the SEP were significantly correlated with outcome (P < 0.01). Likewise, after partialling out the prognostic effect of SEP, the contingency between BAEP and outcome was statistically significant, except in ICH (P = 0.07). The contingencies of SEP and outcome in ICH and supratentorial infarcts were higher than the corresponding partial contingencies for BAEP, while the latter were higher in infratentorial infarction and SAH. Therefore, in all disease groups except for SAH, the multiple contingency coefficients ranging from 0.67 to 0.75 were statistically significant and greater than either simple or partial contingencies alone. The results of the two evoked potential modalities combined permit statistically significant superior prognostication in most cerebrovascular diseases when compared to those of either of the modalities alone.

Performance of a randomization test for single-subject (15)O-water PET activation studies.

We adapted and implemented a permutation test (Holmes 1994) to single-subject positron emission tomography (PET) activation studies with multiple replications of conditions. That test determines the experimentwise alpha error as well as location and extent of focal activations in each individual. Its performance was assessed in five normal volunteers, using (15)O-H2O-PET data acquired on a high-resolution scanner, with septa retracted (3D mode), during functional activation by repeating words versus resting (four replications each). Calculated alpha errors decreased and the size of activated tissue volumes (voxels with P < or = 0.05) increased with increasing filter kernel size applied to the difference images. At a filter kernel of 12 mm Gaussian full width at half maximum, significant focal activations were seen bilaterally in superior temporal cortex, including Brodmann's areas 41 and 42, in all five subjects. Additional foci were detected in the precentral gyrus, left inferior frontal gyrus, supplementary motor area, and cerebellum of several subjects. The average CBF increase in activated voxels ranged from 17.6% to 28.7%. Activated volumes were smaller than those detected with a standard parametric test procedure. We conclude that the permutation test is a less sensitive procedure, having the advantage of not depending on unproven distributional assumptions, that detects strong activation foci in individual subjects with high reproducibility.

Speech-induced cerebral metabolic activation reflects recovery from aphasia.

Six stroke patients with clinically significant aphasia were studied 4 weeks and again 12-18 months after their first left hemispheric ictus. The regional cerebral metabolic rate of glucose (rCMRglc) was measured repeatedly by PET at rest and during word repetition, and severity of speech impairment was assessed by a neuropsychologic test battery. The patterns of speech-associated activation of glucose metabolism were related to improvement in language performance as measured by the Token test. Three patients experienced significant recovery from aphasia (Token test: 47 to 3, 45 to 12, and 37 to 5 points, respectively), whereas 3 patients had poor outcome (Token test from 48 to 45, and from 47 to 39 and 24, respectively). Good recovery was related to activation of left hemispheric speech areas surrounding the infarct, especially left superior temporal gyrus. In contrast, the 3 patients with persistent aphasia showed rCMRglc recruitment in right hemispheric regions and were unable to activate left hemispheric speech areas on follow-up. These results indicate that favorable outcome is related to partial sparing of speech areas of the dominant hemisphere that can be (re-) activated. Predominant recruitment of contralateral areas is not efficacious for a considerable recovery from aphasia. It rather indicates unspecific involvement of widespread networks in the effort to perform a complex task.