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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., Competing Interests: The authors have declared that no competing interests exist.

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.

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.

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., (© 2011 Optical Society of America)

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.

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.

What we believe to be a new type of resonant coupling of an incident bulk wave into guided modes of a slab with a thick holographic grating is shown to occur in the presence of strong frequency detunings of the Bragg condition. This happens through the reflection of the strongly noneigen +1 diffracted order with the slab-grating boundaries, the resultant reflected waves forming a guided slab mode. Rigorous coupled-wave analysis is used for the numerical analysis of the predicted resonant effects. Possible applications include enhanced options for the design of multiplexing and demultiplexing systems, optical signal-processing devices, optical sensors, and measurement techniques.

The extremely asymmetrical scattering (EAS) of bulk and guided electromagnetic waves in nonuniform periodic Bragg arrays with steplike variations of the grating amplitude is analyzed theoretically by means of a recently developed approach based on allowance for the diffractional divergence of the scattered wave. Arrays of finite and infinite widths are investigated. It is shown that, for thin nonuniform arrays, EAS has the same pattern as for uniform arrays with mean grating amplitude. On the contrary, for wide nonuniform arrays, the scattered wave amplitudes are well determined by local values of the grating amplitude. In this case, the energy of the scattered wave is shown to concentrate mainly in regions with smaller grating amplitude. The sensitivity of EAS to small imperfections of periodic arrays is investigated theoretically. The physical explanation of the observed effects is based on the diffractional divergence of the scattered wave.

A new analytic approach to the analysis of grating-assisted couplers is proposed and used for description of the noncollinear coupling of two slab waveguides with arbitrary mode polarizations (TE and TM), propagation directions, and phase velocities. This approach is based on the boundary-perturbation theory, the method of successive approximations, and the energy-conservation law, and does not use any overlap integrals. The specific case in which the converted mode propagates parallel to a periodic array boundary (extremely asymmetric coupling) is considered by means of an original simple analytic approach that allows for the diffractional divergence of the converted wave. Applicability conditions of the results obtained are derived in both the cases of conventional and extremely asymmetrical coupling. Comparison with the previous methods is carried out for the collinear coupling.