Path analysis of biomarkers for cognitive decline in early Parkinson's disease.

Clinical and biochemical diversity of Parkinson's disease (PD) and numerous demographic, clinical, and pathological measures influencing cognitive function and its decline in PD create problems with the determination of effects of individual measures on cognition in PD. This is particularly the case where these measures significantly interrelate with each other producing intricate networks of direct and indirect effects on cognition. Here, we use generalized structural equation modelling (GSEM) to identify and characterize significant paths for direct and indirect effects of 14 baseline measures on global cognition in PD at baseline and at 4 years later. We consider 269 drug-naïve participants from the Parkinson's Progression Marker Initiative database, diagnosed with idiopathic PD and observed for at least 4 years after baseline. Two GSEM networks are derived, highlighting the possibility of at least two different molecular pathways or two different PD sub-types, with either CSF p-tau181 or amyloid beta (1-42) being the primary protein variables potentially driving progression of cognitive decline. The models provide insights into the interrelations between the 14 baseline variables, and determined their total effects on cognition in early PD. High CSF amyloid concentrations (> 500 pg/ml) are associated with nearly full protection against cognitive decline in early PD in the whole range of baseline age between 40 and 80 years, and irrespectively of whether p-tau181 or amyloid beta (1-42) are considered as the primary protein variables. The total effect of depression on cognition is shown to be strongly amplified by PD, but not at the time of diagnosis or at prodromal stages. CSF p-tau181 protein could not be a reliable indicator of cognitive decline because of its significantly heterogeneous effects on cognition. The outcomes will enable better understanding of the roles of the clinical and pathological measures and their mutual effects on cognition in early PD.

Parkinson's disease prognostic scores for progression of cognitive decline.

Clinical and biochemical diversity of Parkinson's disease (PD) presents a major challenge for accurate diagnosis and prediction of its progression. We propose, develop and optimize PD clinical scores as efficient integrated progression biomarkers for prediction of the likely rate of cognitive decline in PD patients. We considered 269 drug-naïve participants from the Parkinson's Progression Marker Initiative database, diagnosed with idiopathic PD and observed between 4 and 6 years. Nineteen baseline clinical and pathological measures were systematically considered. Relative variable importance and logistic regressions were used to optimize combinations of significant baseline measures as integrated biomarkers. Parkinson's disease cognitive decline scores were designed as new clinical biomarkers using optimally categorized baseline measures. Specificities and sensitivities of the biomarkers reached ~93% for prediction of severe rate of cognitive decline (with more than 5 points decline in 4 years on the Montreal Cognitive Assessment scale), and up to ~73% for mild-to-moderate decline (between 1 and 5 points decline). The developed biomarkers and clinical scores could resolve the long-standing clinical problem about reliable prediction of PD progression into cognitive deterioration. The outcomes also provide insights into the contributions of individual clinical and pathological measures to PD progression, and will assist with better-targeted treatment regiments, stratification of clinical trial and their evaluation.

Boosting Local Field Enhancement by on-Chip Nanofocusing and Impedance-Matched Plasmonic Antennas.

Strongly confined surface plasmon-polariton modes can be used for efficiently delivering the electromagnetic energy to nanosized volumes by reducing the cross sections of propagating modes far beyond the diffraction limit, that is, by nanofocusing. This process results in significant local-field enhancement that can advantageously be exploited in modern optical nanotechnologies, including signal processing, biochemical sensing, imaging, and spectroscopy. Here, we propose, analyze, and experimentally demonstrate on-chip nanofocusing followed by impedance-matched nanowire antenna excitation in the end-fire geometry at telecom wavelengths. Numerical and experimental evidence of the efficient excitation of dipole and quadrupole (dark) antenna modes are provided, revealing underlying physical mechanisms and analogies with the operation of plane-wave Fabry-Pérot interferometers. The unique combination of efficient nanofocusing and nanoantenna resonant excitation realized in our experiments offers a major boost to the field intensity enhancement up to ∼12000, with the enhanced field being evenly distributed over the gap volume of 30 × 30 × 10 nm(3), and promises thereby a variety of useful on-chip functionalities within sensing, nonlinear spectroscopy and signal processing.

Plasmon nanofocusing in a dielectric hemisphere covered in tapered metal film.

We propose and analyze a new type of mechanically robust optical nanofocusing probe with minimized external environmental interference. The probe consists of a dielectric optical fiber terminated by a dielectric hemisphere - both covered in thin gold film whose thickness is reduced (tapered) along the surface of the hemisphere toward its tip. Thus the proposed probe combines the advantages of the diffraction-limited focusing due to annular propagation of the plasmon with its nanofocusing by a tapered metal wedge (i.e. a metal film with reducing local thickness). The numerical finite-element analysis demonstrates strongly subwavelength resolution of the described structure with the achievable size of the focal spot of ~20 nm with up to ~150 times enhancement of the local electric field intensity. Detailed physical interpretations of the obtained results are presented and possible application as a new type of SNOM probe for subwavelength imaging, spectroscopy and sensing are also discussed.

Gap surface plasmon waveguides with enhanced integration and functionality.

We propose and investigate theoretically and experimentally L-shaped gap surface plasmon waveguides (L-GSPWs) formed by a dielectric film (strip) partially enclosed between two metal films. The proposed L-GSPWs combine the benefits of strong plasmon localization in a nanogap, significant propagation distance, low cross-talk between two neighboring waveguides, high transmission through a sharp 90° bend, and simplicity of fabrication by means of the standard lithography combined with the thin film deposition.

Continuous layer gap plasmon resonators.

We demonstrate both theoretically and experimentally that a gold nanostrip supported by a thin dielectric (silicon dioxide) film and a gold underlay forms an efficient (Fabry-Perot) resonator for gap surface plasmons. Periodic nanostrip arrays are shown to exhibit strong and narrow resonances with nearly complete absorption and quality factors of ~15-20 in the near-infrared. Two-photon luminescence microscopy measurements reveal intensity enhancement factors of ~120 in the 400-nm-period array of 85-nm-wide gold strips atop a 23-nm-thick silica film at the resonance wavelength of ~770 nm. Excellent resonant characteristics, the simplicity of tuning the resonance wavelength by adjusting the nanostrip width and/or the dielectric film thickness and the ease of fabrication with (only) one lithography step required make the considered plasmonic configuration very attractive for a wide variety of applications, ranging from surface sensing to photovoltaics.

Psychological stress and psychosomatic treatment: major impact on serious blood disorders?

OBJECTIVE: To demonstrate evidence of possible major impacts of psychological stress and psychosomatic interventions on myeloproliferative blood disorders and develop new approaches for the unification and quantified analysis of stress and psychosomatic treatments. METHODS: This 3.5- year longitudinal study was based upon the regular blood tests of a person with myelofibrosis who experienced severe and repeated work-related psychological stress and was subjected to psychosomatic treatment in the form of regular (approximately 4 h per day) self-hypnosis sessions. Statistical data analysis was conducted on the basis of an introduced concept of generalized stress that mathematically unifies psychological stress and psychosomatic treatment. RESULTS: Severe stress and psychosomatic treatment were statistically shown to have a major (dominant) impact on blood platelet counts well described by an exponential dependence on cumulative levels of generalized stress. The typical relaxation time for the impacts of both stress and treatment was shown to be approximately 2 months. Only approximately 12% of the total variation in platelet counts could be attributed to factors other than psychological stress and psychosomatic treatment. The psychosomatic intervention resulted in a consistent reduction of high platelet counts from approximately 1,400 x 109 l⁻¹ to approximately the middle of the normal range, with other blood parameters being either approximately stable or showing indications of a strengthening immune system. CONCLUSIONS: Our findings give hope for a possible development of psychosomatic treatments of at least some blood disorders. They also indicate a highly instrumental role of platelets in the quantified analysis of stress, psychosomatic interventions, and their neuroimmunological pathways.

Monitoring and analysis of combustion aerosol emissions from fast moving diesel trains.

In this paper we report the results of the detailed monitoring and analysis of combustion emissions from fast moving diesel trains. A new highly efficient monitoring methodology is proposed based on the measurements of the total number concentration (TNC) of combustion aerosols at a fixed point (on a bridge overpassing the railway) inside the violently mixing zone created by a fast moving train. Applicability conditions for the proposed methodology are presented, discussed and linked to the formation of the stable and uniform mixing zone. In particular, it is demonstrated that if such a mixing zone is formed, the monitoring results are highly consistent, repeatable (with typically negligible statistical errors and dispersion), stable with respect to the external atmospheric turbulence and result in an unusual pattern of the aerosol evolution with two or three distinct TNC maximums. It is also shown that the stability and uniformity of the created mixing zone (as well as the repeatability of the monitoring results) increase with increasing length of the train (with an estimated critical train length of ~10 carriages, at the speed of ~150km/h). The analysis of the obtained evolutionary dependencies of aerosol TNC suggests that the major possible mechanisms responsible for the formation of the distinct concentration maximums are condensation (the second maximum) and thermal fragmentation of solid nanoparticle aggregates (third maximum). The obtained results and the new methodology will be important for monitoring and analysis of combustion emissions from fast moving trains, and for the determination of the impact of rail networks on the atmospheric environment and human exposure to combustion emissions.

Nonlinear nanofocusing in tapered plasmonic waveguides.

We suggest using tapered waveguides for compensating losses of surface plasmon-polaritons in order to enhance nonlinear effects at the nanoscale. We study nonlinear plasmon self-focusing in tapered metal-dielectric-metal slot waveguides and demonstrate that, by an appropriate choice of the taper angle, we can effectively suppress the mode attenuation achieving stable propagation of a spatial plasmon soliton. For larger tapering angles we observe plasmon-beam nanofocusing in both spatial dimensions.

Wavelength-dependent transmission through sharp 90 degrees bends in sub-wavelength metallic slot waveguides.

In this paper, we present a comprehensive numerical study of the wavelength-dependence of transmission through sharp 90 degrees bends in metallic slot waveguides with sub-wavelength localization and varying geometrical parameters. In particular, it is demonstrated that increasing the plasmon wavelength results in a significant increase (up to nearly 100%) of transmission through the bend, combined with a reduction in the mode asymmetry in the second arm of the bend. The mode asymmetry and its relaxation are explained by interference of the transmitted mode with non-propagating and leaky modes generated at the bend. Comparison with the two-dimensional case of a metal-dielectric-metal waveguide is also conducted, showing significant differences for the slot waveguides based on the presence of different non-propagating and leaky modes.

Exact solution for stochastic degradation and fragmentation processes in arbitrary chain and ring aggregates with multiple bonds.

This paper presents a statistical theory of stochastic evaporation and degradation processes in complex polymerlike ring and chain aggregates with multiple degrading bonds between the primary particles (monomers). The exact kinetic solution fully describing fragmentation processes is obtained for such aggregates with arbitrary number of primary particles (monomers) and bonds between them. The effects of additional interaction of multiple bonds with each other is shown to have a drastic impact on the predicted kinetic processes and time-dependent particle size distributions during aggregate degradation. Structural effects associated with different distributions of multiple bonds and bonding configurations in the aggregates are also investigated and shown to have a significant impact on typical fragmentation time and accumulation of fragmenting aggregates in intermediate modes. The developed theory and its results will be important for degradation of multistranded polymers, polymer networks, self-assembling structures, surface nanoclusters and nanotechnology, and formation and evolution of aerosol aggregates resulting from transport and industry emissions.

On long-range plasmonic modes in metallic gaps.

Satuby and Orenstein [Opt. Express 15, 4247-4252 (2007)] reported the discovery and numerical and experimental investigation of long-range surface plasmon-polariton eigenmodes guided by wide (6 to 12 mum) rectangular gaps in 400 nm thick gold films using excitation of vacuum wavelength lambda(vac) = 1.55 mum. In this paper, we carry out a detailed numerical analysis of the two different types of plasmonic modes in these structures. We show that no long-range eigenmodes exists for these gap plasmon waveguides, and that the reported "modes" are likely to be beams of bulk waves and surface plasmons, rather than guided modes of the considered structures.

Anomalous absorption of bulk shear sagittal acoustic waves in a layered structure with viscous fluid.

It is demonstrated theoretically that the absorptivity of bulk shear sagittal waves by an ultra-thin layer of viscous fluid between two different elastic media has a strong maximum (in some cases as good as 100%) at an optimal layer thickness. This thickness is usually much smaller than the penetration depths and lengths of transverse and longitudinal waves in the fluid. The angular dependencies of the absorptivity are demonstrated to have significant and unusual structure near critical angles of incidence. The effect of non-Newtonian properties and non-uniformities of the fluid layer on the absorptivity is also investigated. In particular, it is shown that the absorption in a thin layer of viscous fluid is much more sensitive to non-zero relaxation time(s) in the fluid layer than the absorption at an isolated solid-fluid interface.