Compact medical fluorosensor for minimally invasive tissue characterization

A compact fiber-optic point-measuring fluorosensor fully adapted to clinical studies is described. The system can use two excitation wavelengths, 337 and 405 nm, obtained from a nitrogen laser directly, or after dye laser conversion, respectively. The image intensifier used in the spectrometer can be gated with a variable time delay, allowing also time-resolved spectra to be extracted, with a time resolution of about 4 ns. Moreover, diffusely scattered white light can be spectrally recorded. The system is fully computer controlled enabling short recording times in clinical application, which are illustrated

Vortex Waves and Channel Capacity: Hopes and Reality

Several recent contributions have envisioned the possibility of increasing currently exploitable maximum channel capacity of a free space link, both at optical and radio frequencies, by using vortex waves, i.e. carrying Orbital Angular Momentum (OAM). Our objective is to disprove these claims by showing that they are in contradiction with very fundamental properties of Maxwellian fields. We demonstrate that the Degrees of Freedom (DoF) of the field cannot be increased by the helical phase structure of electromagnetic vortex waves beyond what can be done without invoking this property. We also show that the often-advocated over-quadratic power decay of OAM beams with distance does not play any fundamental role in the determination of the channel DoF.Comment: 8 pages, 7 figure

Suppression of Alzheimer-Associated Inflammation by Microglial Prostaglandin-E-2 EP4 Receptor Signaling

A persistent and nonresolving inflammatory response to accumulating Aβ peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating Aβ peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many proinflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing Aβ-induced inflammation represent a relatively unexplored area. Here we report that signaling through the prostaglandin-E2 (PGE2) EP4 receptor potently suppresses microglial inflammatory responses to Aβ42 peptides. In cultured microglial cells, EP4 stimulation attenuated levels of Aβ42-induced inflammatory factors and potentiated phagocytosis of Aβ42. Microarray analysis demonstrated that EP4 stimulation broadly opposed Aβ42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-κB transcription factors. In vivo, conditional deletion of microglial EP4 in APPSwe-PS1ΔE9 (APP-PS1) mice conversely increased inflammatory gene expression, oxidative protein modification, and Aβ deposition in brain at early stages of pathology, but not at later stages, suggesting an early anti-inflammatory function of microglial EP4 signaling in the APP-PS1 model. Finally, EP4 receptor levels decreased significantly in human cortex with progression from normal to AD states, suggesting that early loss of this beneficial signaling system in preclinical AD development may contribute to subsequent progression of pathology

Circulating levels of vascular endothelial growth factor and post-stroke long-term functional outcome

OBJECTIVES: Vascular endothelial growth factor (VEGF) acts in angiogenesis and neuroprotection, although the beneficial effects on experimental ischemic stroke (IS) have not been replicated in clinical studies. We investigated serum VEGF (s-VEGF) in the acute stage (baseline) and 3 months post-stroke in relation to stroke severity and functional outcome. METHODS: The s-VEGF and serum high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in patients enrolled in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS) at the acute time-point (median 4 days, N=492, 36% female; mean age, 57 years) and at 3 months post-stroke (N=469). Baseline stroke severity was classified according to the National Institutes of Health Stroke Scale (NIHSS) and functional outcomes (3 months and 2 years) were evaluated using the modified Rankin Scale (mRS), dichotomized into good (mRS 0-2) and poor (mRS 3-6) outcomes. Multivariable logistic regression analyses were adjusted for covariates. RESULTS: The baseline s-VEGF did not correlate with stroke severity but correlated moderately with hs-CRP (r=0.17, p<0.001). The baseline s-VEGF was 39.8% higher in total anterior cerebral infarctions than in lacunar cerebral infarctions. In binary logistic regression analysis, associations with 3-month functional outcome were non-significant. However, an association between the 3-month s-VEGF and poor 2-year outcome withstood adjustments for age, sex, cardiovascular covariates, and stroke severity (per ten-fold increase in s-VEGF, odds ratio [OR], 2.56, 95% confidence interval [CI] 1.12-5.82) or hs-CRP (OR 2.53, CI 1.15-5.55). CONCLUSIONS: High 3-month s-VEGF is independently associated with poor 2-year functional outcome but not with 3-month outcome

Circulating granulocyte colony-stimulating factor and functional outcome after ischemic stroke: an observational study

Objectives: While granulocyte colony-stimulating factor (G-CSF) has shown beneficial effects in experimental ischemic stroke (IS), these effects have not been reproduced clinically. Small-to-medium-sized observational studies have reported varying associations for G-CSF with stroke severity and post-stroke functional outcome, prompting their investigation in a larger study. Methods: Endogenous serum G-CSF (S-GCSF) was measured in the acute phase and after 3 months in patients with IS (N = 435; 36% females; mean age, 57 years) from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was scored according to the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) assessed functional outcomes at 3-month and 2-year post-stroke. Correlation and logistic regression analyses with confounder adjustments assessed the relationships. Results: The acute S-GCSF level was 23% higher than at 3-month post-stroke (p < 0.001). Acute G-CSF correlated weakly with stroke severity quintiles (r = 0.12, p = 0.013) and with high-sensitivity C-reactive protein (r = 0.29, p < 0.001). The association between S-GCSF (as quintiles, q) and poor functional outcome at 3 months (mRS 3–6; S-GCSF-q5 vs. S-GCSF-q1, age- and sex-adjusted odds ratio: 4.27, 95% confidence interval: 1.82–9.99; p = 0.001) withstood adjustment for cardiovascular risk factors and stroke subtype, but not additional correction for stroke severity. Post-stroke changes in S-GSCF and absolute 3-month S-GCSF were not associated with 3-month or 2-year functional outcomes. Discussion: Early post-stroke S-GCSF is increased in severe IS and associated with 3-month poor functional outcomes. The change in S-GCSF and the 3-month S-GCSF appear to be less-important, and S-GCSF likely reflects inflammation in large infarctions

The MAP-HAND : psychometric properties and differences in activity performance between patients with carpometacarpal osteoarthritis and rheumatoid arthritis

Objective: To assess construct validity (Rasch analyses) of the Measure of Activity Performance of the Hand (MAP-Hand) in people with carpometacarpal osteoarthritis (CMC1 OA), and to explore differences in activity performance between people with CMC1 OA and those with rheumatoid arthritis. Design: Cross-sectional study. Subjects: A total of 180 people with CMC1 OA referred for surgical consultation were recruited from rheumatology clinics in Norway, and 340 people with rheumatoid arthritis were recruited from outpatient rheumatology clinics in the UK. Methods: The MAP-Hand consists of 18 predefined items scored on a 4-point scale from 1 (no difficulty) to 4 (unable to do), from which a mean score is calculated. Construct validity was assessed using Rasch analyses. Differences between the 2 groups were assessed using an independent sample t-test at the group level and differential item functioning (condition as grouping variable) at the item level. Results: Some mis-targeting of data and clusters of dependency were found, but the MAP-Hand scores showed an overall fit to the model. No between group difference in total mean MAP-Hand score was found, but there were significant differences between the 2 groups on item levels. Conclusion: The MAP-Hand showed satisfactory construct validity and could differentiate between people with CMC1 OA and those with rheumatoid arthritis on item levels

Autocatalytic amplification of Alzheimer-associated Aβ42 peptide aggregation in human cerebrospinal fluid

Alzheimer’s disease is linked to amyloid β (Aβ) peptide aggregation in the brain, and a detailed understanding of the molecular mechanism of Aβ aggregation may lead to improved diagnostics and therapeutics. While previous studies have been performed in pure buffer, we approach the mechanism in vivo using cerebrospinal fluid (CSF). We investigated the aggregation mechanism of Aβ42 in human CSF through kinetic experiments at several Aβ42 monomer concentrations (0.8–10 µM). The data were subjected to global kinetic analysis and found consistent with an aggregation mechanism involving secondary nucleation of monomers on the fibril surface. A mechanism only including primary nucleation was ruled out. We find that the aggregation process is composed of the same microscopic steps in CSF as in pure buffer, but the rate constant of secondary nucleation is decreased. Most importantly, the autocatalytic amplification of aggregate number through catalysis on the fibril surface is prevalent also in CSF

Long-lasting XUV activation of helium nanodroplets for avalanche ionization

We study the dynamics of avalanche ionization of pure helium nanodroplets activated by a weak extreme-ultraviolet (XUV) pulse and driven by an intense near-infrared (NIR) pulse. In addition to a transient enhancement of ignition of a nanoplasma at short delay times $\sim200$~fs, long-term activation of the nanodroplets lasting up to a few nanoseconds is observed. Molecular dynamics simulations suggest that the short-term activation is caused by the injection of seed electrons into the droplets by XUV photoemission. Long-term activation appears due to electrons remaining loosely bound to photoions which form stable `snowball' structures in the droplets. Thus, we show that XUV irradiation can induce long-lasting changes of the strong-field optical properties of nanoparticles, potentially opening new routes to controlling avalanche-ionization phenomena in nanostructures and condensed-phase systems

Gravastar energy conditions revisited

We consider the gravastar model where the vacuum phase transition between the de Sitter interior and the Schwarzschild or Schwarzschild-de Sitter exterior geometries takes place at a single spherical delta-shell. We derive sharp analytic bounds on the surface compactness (2m/r) that follow from the requirement that the dominant energy condition (DEC) holds at the shell. In the case of Schwarzschild exterior, the highest surface compactness is achieved with the stiff shell in the limit of vanishing (dark) energy density in the interior. In the case of Schwarzschild-de Sitter exterior, in addition to the gravastar configurations with the shell under surface pressure, gravastar configurations with vanishing shell pressure (dust shells), as well as configurations with the shell under surface tension, are allowed by the DEC. Respective bounds on the surface compactness are derived for all cases. We also consider the speed of sound on the shell as derived from the requirement that the shell is stable against the radial perturbations. The causality requirement (sound speed not exceeding that of light) further restricts the space of allowed gravastar configurations.Comment: LaTeX/IOP-style, 16 pages, 2 figures, changes wrt v1: motivation for eq. (6) clarified, several referecnes added (to appear in Class. Quantum Grav.