Melanopsin mediated post-illumination pupil response in early age-related macular degeneration

Purpose To determine whether melanopsin expressing intrinsically photosensitive Retinal Ganglion Cell (ipRGC) inputs to the pupil light reflex (PLR) are affected in early age-related macular degeneration (AMD). Methods The PLR was measured in 40 participants (20 early AMD and 20 age-matched controls) using a custom-built Maxwellian-view pupillometer. Sinusoidal stimuli (0.5 Hz, 11.9 s duration, 35.6° diameter) were presented to the study eye and the consensual pupil response was measured for stimuli with high melanopsin excitation (464nm; blue) and with low melanopsin excitation (638 nm; red) that biased activation to the outer retina. Two melanopsin PLR metrics were quantified: the Phase Amplitude Percentage (PAP) during the sinusoidal stimulus presentation and the Post-Illumination Pupil Response (PIPR). The PLR during stimulus presentation was analyzed using latency to constriction, transient pupil response and maximum pupil constriction metrics. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. Results The blue PIPR was significantly less sustained in the early AMD group (p<0.001). The red PIPR was not significantly different between groups (p>0.05). The PAP and blue stimulus constriction amplitude were significantly lower in the early AMD group (p < 0.05). There was no significant difference between groups in the latency or transient amplitude for both stimuli (p>0.05). ROC analysis showed excellent diagnostic accuracy for the blue PIPR metrics (AUC>0.9). Conclusions This is the initial report that the melanopsin controlled PIPR is dysfunctional in early AMD. The non-invasive, objective measurement of the ipRGC controlled PIPR has excellent diagnostic accuracy for early AMD.

The post-illumination pupil response of melanopsin expressing retinal ganglion cells

Purpose The post-illumination pupil response (PIPR) has been quantified in the literature by four metrics. The spectral sensitivity of only one metric is known and this study quantifies the other three. To optimize the measurement of the PIPR in humans, we also determine the stimulus protocol producing the largest PIPR, the duration of the PIPR, and the metric(s) with the lowest coefficient of variation. Methods The consensual pupil light reflex (PLR) was measured with a Maxwellian view pupillometer (35.6° diameter stimulus). - Experiment 1: Spectral sensitivity of four PIPR metrics [plateau, 6 s, area under curve (AUC) early and late recovery] was determined from a criterion PIPR (n = 2 participants) to a 1 s pulse at five wavelengths (409-592nm) and fitted with Vitamin A nomogram (ƛmax = 482 nm). - Experiment 2: The PLR was measured in five healthy participants [29 to 42 years (mean = 32.6 years)] as a function of three stimulus durations (1 s, 10 s, 30 s), five irradiances spanning low to high melanopsin excitation levels (retinal irradiance: 9.8 to 14.8 log quanta.cm-2.s-1), and two wavelengths, one with high (465 nm) and one with low (637 nm) melanopsin excitation. Intra and inter-individual coefficients of variation (CV) were calculated. Results The melanopsin (opn4) photopigment nomogram adequately described the spectral sensitivity derived from all four PIPR metrics. The largest PIPR amplitude was observed with 1 s short wavelength pulses (retinal irradiance ≥ 12.8 log quanta.cm-2.s-1). Of the 4 PIPR metrics, the plateau and 6 s PIPR showed the least intra and inter-individual CV (≤ 0.2). The maximum duration of the sustained PIPR was 83.4 ± 48.0 s (mean ± SD) for 1 s pulses and 180.1 ± 106.2 s for 30 s pulses (465 nm; 14.8 log quanta.cm-2.s-1). Conclusions All current PIPR metrics provide a direct measure of intrinsic melanopsin retinal ganglion cell function. To measure progressive changes in melanopsin function in disease, we recommend that the intrinsic melanopsin response should be measured using a 1 s pulse with high melanopsin excitation and the PIPR should be analyzed with the plateau and/or 6 s metrics. That the PIPR can have a sustained constriction for as long as 3 minutes, our PIPR duration data provide a baseline for the selection of inter-stimulus intervals between consecutive pupil testing sequences.

Melanopsin ganglion cell function in early age-related macular degeneration

Purpose Melanopsin-expressing retinal ganglion cells (mRGCs) have non-image forming functions including mediation of the pupil light reflex (PLR). There is limited knowledge about mRGC function in retinal disease. Initial retinal changes in age-related macular degeneration (AMD) occur in the paracentral region where mRGCs have their highest density, making them vulnerable during disease onset. In this cross-sectional clinical study, we measured the PLR to determine if mRGC function is altered in early stages of macular degeneration. Methods Pupil responses were measured in 8 early AMD patients (AREDS 2001 classification; mean age 72.6 ± 7.2 years, 5M, and 3F) and 12 healthy control participants (mean age 66.6 ± 6.1 years, 8M and 4F) using a custom-built Maxwellian-view pupillometer. Stimuli were 0.5 Hz sinewaves (10 s duration, 35.6° diameter) of short wavelength light (464nm, blue; retinal irradiance = 14.5 log quanta.cm-2.s-1) to produce high melanopsin excitation and of long wavelength light (638nm, red; retinal irradiance = 14.9 log quanta.cm-2.s-1), to bias activation to outer retina and provide a control. Baseline pupil diameter was determined during a 10 s pre-stimulus period. The post illumination pupil response (PIPR) was recorded for 40 s. The 6 s PIPR and maximum pupil constriction were expressed as percentage baseline (M ± SD). Results The blue PIPR was significantly less sustained (p<0.01) in the early AMD group (75.49 ± 7.88%) than the control group (58.28 ± 9.05%). The red PIPR was not significantly different (p>0.05) between the early AMD (84.79 ± 4.03%) and control groups (82.01 ± 5.86%). Maximum constriction amplitude in the early AMD group for blue (43.67 ± 6.35%) and red (48.64 ± 6.49%) stimuli were not significantly different to the control group for blue (39.94 ± 3.66%) and red (44.98 ± 3.15%) stimuli (p>0.05). Conclusions These results are suggestive of inner retinal mRGC deficits in early AMD. This non-invasive, objective measure of pupil responses may provide a new method for quantifying mRGC function and monitoring AMD progression.

Lopsided spiral galaxies

The light distribution in the disks of many galaxies is ‘lopsided’ with a spatial extent much larger along one half of a galaxy than the other, as seen in M101. Recent observations show that the stellar disk in a typical spiral galaxy is significantly lopsided, indicating asymmetry in the disk mass distribution. The mean amplitude of lopsidedness is 0.1, measured as the Fourier amplitude of the m=1 component normalized to the average value. Thus, lopsidedness is common, and hence it is important to understand its origin and dynamics. This is a new and exciting area in galactic structure and dynamics, in contrast to the topic of bars and two-armed spirals (m=2) which has been extensively studied in the literature. Lopsidedness is ubiquitous and occurs in a variety of settings and tracers. It is seen in both stars and gas, in the outer disk and the central region, in the field and the group galaxies. The lopsided amplitude is higher by a factor of two for galaxies in a group. The lopsidedness has a strong impact on the dynamics of the galaxy, its evolution, the star formation in it, and on the growth of the central black hole and on the nuclear fuelling. We present here an overview of the observations that measure the lopsided distribution, as well as the theoretical progress made so far to understand its origin and properties. The physical mechanisms studied for its origin include tidal encounters, gas accretion and a global gravitational instability. The related open, challenging problems in this emerging area are discussed.

Pulse-echo ultrasound transit time spectroscopy: A comparison of experimental measurements and simulation prediction

Considering ultrasound propagation through complex composite media as an array of parallel sonic rays, a comparison of computer simulated prediction with experimental data has previously been reported for transmission mode (where one transducer serves as transmitter, the other as receiver) in a series of ten acrylic step-wedge samples, immersed in water, exhibiting varying degrees of transit time inhomogeneity. In this study, the same samples were used but in pulse-echo mode, where the same ultrasound transducer served as both transmitter and receiver, detecting both ‘primary’ (internal sample interface) and ‘secondary’ (external sample interface) echoes. A transit time spectrum (TTS) was derived, describing the proportion of sonic rays with a particular transit time. A computer simulation was performed to predict the transit time and amplitude of various echoes created, and compared with experimental data. Applying an amplitude-tolerance analysis, 91.7±3.7% of the simulated data was within ±1 standard deviation (STD) of the experimentally measured amplitude-time data. Correlation of predicted and experimental transit time spectra provided coefficients of determination (R2) ranging from 100.0% to 96.8% for the various samples tested. The results acquired from this study provide good evidence for the concept of parallel sonic rays. Further, deconvolution of experimental input and output signals has been shown to provide an effective method to identify echoes otherwise lost due to phase cancellation. Potential applications of pulse-echo ultrasound transit time spectroscopy (PE-UTTS) include improvement of ultrasound image fidelity by improving spatial resolution and reducing phase interference artefacts.

Solid volume fraction estimation of bone:marrow replica models using ultrasound transit time spectroscopy

The acceptance of broadband ultrasound attenuation (BUA) for the assessment of osteoporosis suffers from a limited understanding of both ultrasound wave propagation through cancellous bone and its exact dependence upon the material and structural properties. It has recently been proposed that ultrasound wave propagation in cancellous bone may be described by a concept of parallel sonic rays; the transit time of each ray defined by the proportion of bone and marrow propagated. A Transit Time Spectrum (TTS) describes the proportion of sonic rays having a particular transit time, effectively describing the lateral inhomogeneity of transit times over the surface aperture of the receive ultrasound transducer. The aim of this study was to test the hypothesis that the solid volume fraction (SVF) of simplified bone:marrow replica models may be reliably estimated from the corresponding ultrasound transit time spectrum. Transit time spectra were derived via digital deconvolution of the experimentally measured input and output ultrasonic signals, and compared to predicted TTS based on the parallel sonic ray concept, demonstrating agreement in both position and amplitude of spectral peaks. Solid volume fraction was calculated from the TTS; agreement between true (geometric calculation) with predicted (computer simulation) and experimentally-derived values were R2=99.9% and R2=97.3% respectively. It is therefore envisaged that ultrasound transit time spectroscopy (UTTS) offers the potential to reliably estimate bone mineral density and hence the established T-score parameter for clinical osteoporosis assessment.

EPR observation of phase transitions in calcium cadmium acetate hexahydrate: Using Mn2+ and Cu2+ ions as probe

Results of temperature dependence of EPR spectra of Mn2+ and Cu2+ ions doped calcium cadmium acetate hexahydrate (CaCd(CH3COO)4•6H2O) have been reported. The investigation has been carried out in the temperature range between room temperature ( 300 K) and liquid nitrogen temperature. A I-order phase transition at 146 ± 0.5 K has been confirmed. In addition a new II-order phase transition at 128 ± 1 K has been detected for the first time. There is evidence of large amplitude hindered rotations of CH3 groups which become frozen at 128 K. The incorporation of Cu2+ and Mn2+ probes at Ca2+ and Cd2+ sites respectively provide evidence that the phase transitions are caused by the molecular rearrangements of the common coordinating acetate groups between Ca2+ and Cd2+ sites. In contradiction to the previous reports of a change of symmetry from tetragonal to orthorhombic below 140 K, the symmetry of the host is concluded to remain tetragonal in all the three observed phases between room temperature and liquid nitrogen temperature.

Non-linear flapping vibrations of rotating blades

The non-linear equations of motion of a rotating blade undergoing extensional and flapwise bending vibration are derived, including non-linearities up to O (ε3). The strain-displacement relationship derived is compared with expressions derived by earlier investigators and the errors and the approximations made in some of those are brought out. The equations of motion are solved under the inextensionality condition to obtain the influence of the amplitude on the fundamental flapwise natural frequency of the rotating blade. It is found that large finite amplitudes have a softening effect on the flapwise frequency and that this influence becomes stronger at higher speeds of rotation.

Time dependent rotational flow of a viscous fluid over an infinite porous disk with a magnetic field

Both the semi-similar and self-similar flows due to a viscous fluid rotating with time dependent angular velocity over a porous disk of large radius at rest with or without a magnetic field are investigated. For the self-similar case the resulting equations for the suction and no mass transfer cases are solved numerically by quasilinearization method whereas for the semi-similar case and injection in the self-similar case an implicit finite difference method with Newton's linearization is employed. For rapid deceleration of fluid and for moderate suction in the case of self-similar flow there exists a layer of fluid, close to the disk surface where the sense of rotation is opposite to that of the fluid rotating far away. The velocity profiles in the absence of magnetic field are found to be oscillatory except for suction. For the accelerating freestream, (semi-similar flow) the effect of time is to reduce the amplitude of the oscillations of the velocity components. On the other hand the effect of time for the oscillating case is just the opposite.

Comparison of Rectangular and Polar Quantizers in Digital Holography

Complex amplitude encoded in any digital hologram must undergo quantization, usually in either polar or rectangular format . In this paper these two schemes are compared under the constraints and conditions inherent in digital holography . For Fourier transform holograms when the spectrum is levelled through phase coding, the rectangular format is shown to be optimal . In the absence of phase coding, and also if the amplitude spectrum has a large dynamic range, the polar format may be preferable .

Pattern visual evoked potentials in dyslexic versus normal children

Purpose: Presence of neurophysiological abnormalities in dyslexia has been a conflicting issue. This study was performed to evaluate the role of sensory visual deficits in the pathogenesis of dyslexia. Methods: Pattern visual evoked potentials (PVEP) were recorded in 72 children including 36 children with dyslexia and 36 children without dyslexia (controls) who were matched for age, sex and intelligence. Two check sizes of 15 and 60 min of arc were used with temporal frequencies of 1.5 Hz for transient and 6 Hz for steady‑state methods. Results: Mean latency and amplitude values for 15 min arc and 60 min arc check sizes using steady state and transient methods showed no significant difference between the two study groups (P values: 0.139/0.481/0.356/0.062).Furthermore, no significant difference was observed between two methods of PVEPs in dyslexic and normal children using 60min arc with high contrast(Pvalues: 0.116, 0.402, 0.343 and 0.106). Conclusion: The sensitivity of PVEP has high validity to detect visual deficits in children with dyslexic problem. However, no significant difference was found between dyslexia and normal children using high contrast stimuli.

Chlorophyll fluorescence measures of seagrasses Halophila ovalis and Zostera capricorni reveal differences in response to experimental shading

In coastal waters and estuaries, seagrass meadows are often subject to light deprivation over short time scales (days to weeks) in response to increased turbidity from anthropogenic disturbances. Seagrasses may exhibit negative physiological responses to light deprivation and suffer stress, or tolerate such stresses through photo-adaptation of physiological processes allowing more efficient use of low light. Pulse Amplitude Modulated (PAM) fluorometery has been used to rapidly assess changes in photosynthetic responses along in situ gradients in light. In this study, however, light is experimentally manipulated in the field to examine the photosynthesis of Halophila ovalis and Zostera capricorni. We aimed to evaluate the tolerance of these seagrasses to short-term light reductions. The seagrasses were subject to four light treatments, 0, 5, 60, and 90% shading, for a period of 14 days. In both species, as shading increased the photosynthetic variables significantly (P < 0.05) decreased by up to 40% for maximum electron transport rates (ETRmax) and 70% for saturating irradiances (Ek). Photosynthetic efficiencies (a) and effective quantum yields (ΔF/Fm′ ) increased significantly (P < 0.05), in both species, for 90% shaded plants compared with 0% shaded plants. H. ovalis was more sensitive to 90% shading than Z. capricorni, showing greater reductions in ETR max, indicative of a reduced photosynthetic capacity. An increase in Ek, Fm′ and ΔF/Fm′ for H. ovalis and Z. capricorni under 90% shading suggested an increase in photochemical efficiency and a more efficient use of low-photon flux, consistent with photo-acclimation to shading. Similar responses were found along a depth gradient from 0 to10 m, where depth related changes in ETRmax and Ek in H. ovalis implied a strong difference of irradiance history between depths of 0 and 5-10 m. The results suggest that H. ovalis is more vulnerable to light deprivation than Z. capricorni and that H. ovalis, at depths of 5-10 m, would be more vulnerable to light deprivation than intertidal populations. Both species showed a strong degree of photo-adaptation to light manipulation that may enable them to tolerate and adapt to short-term reductions in light. These consistent responses to changes in light suggest that photosynthetic variables can be used to rapidly assess the status of seagrasses when subjected to sudden and prolonged periods of reduced light

Photosynthetic responses of subtidal seagrasses to a daily light cycle in Torres Strait: A comparative study

In this study, we examined the photosynthetic responses of five common seagrass species from a typical mixed meadow in Torres Strait at a depth of 5–7 m using pulse amplitude modulated (PAM) fluorometry. The photosynthetic response of each species was measured every 2 h throughout a single daily light cycle from dawn (6 am) to dusk (6 pm). PAM fluorometry was used to generate rapid light curves from which measures of electron transport rate (ETRmax), photosynthetic efficiency (α), saturating irradiance (Ek) and light-adapted quantum yield (ΔF/F′m) were derived for each species. The amount of light absorbed by leaves (absorption factor) was also determined for each species. Similar diurnal patterns were recorded among species with 3–4 fold increases in maximal electron rate from dawn to midday and a maintenance of ETRmax in the afternoon that would allow an optimal use of low light by all species. Differences in photosynthetic responses to changes in the daily light regime were also evident with Syringodium isoetifolium showing the highest photosynthetic rates and saturating irradiances suggesting a competitive advantage over other species under conditions of high light. In contrast Halophila ovalis, Halophila decipiens and Halophila spinulosa were characterised by comparatively low photosynthetic rates and minimum light requirements (i.e. low Ek) typical of shade adaptation. The structural makeup of each species may explain the observed differences with large, structurally complex species such as Syringodium isoetifolium and Cymodocea serrulata showing high photosynthetic effciciencies (α) and therefore high-light-adapted traits (e.g. high ETRmax and Ek) compared with the smaller Halophila species positioned lower in the canopy. For the smaller Halophila species these shade-adapted traits are features that optimise their survival during low-light conditions. Knowledge of these characteristics and responses improves our understanding of the underlying causes of changes in seagrass biomass, growth and survival that occur when modifications in light quantity and quality arise from anthropogenic and climatic disturbances that commonly occur in Torres Strait.

Patterns in tropical seagrass photosynthesis in relation to light, depth and habitat

Seagrass meadows across north-eastern Australia, survive a range of environmental conditions in coastal bays, reefs, estuarine and deepwater habitats through adaptation of a range of structural, morphological and physiological features. The aim of this study was to investigate the influence of spatial features (habitat type, site and depth) and photon flux on the photosynthetic performance of 11 tropical seagrass species. Pulse amplitude modulated (PAM) fluorometry was used to generate rapid light curves from which measures of maximal electron transport rate (ETRmax), photosynthetic efficiency (?), saturating irradiance (Ek) and effective quantum yield (?F/Fm?) were derived. The amount of light absorbed by leaves (absorption factor) was also determined for each population. In intertidal habitats many seagrass species exhibited typical sun-type responses with a close coupling of both ETRmax and Ek with photon flux. Photosynthetic performance ranged from minima in Thalassodendron ciliatum to maxima in Syringodium isoetifolium. The absence of a coupling between photosynthetic performance and photon flux in subtidal populations was most likely due to highly variable light climates and possible light attenuation, and hence the photo-biology of estuarine and deepwater seagrasses exhibited photosynthetic responses indicative of light limitation. In contrast seagrass species from shallow reef and coastal habitats for the most part exhibited light saturation characteristics. Of all the variables examined ETRmax, Ek and ?F/Fm? were most responsive to changing light climates and provide reliable physiological indicators of real-time photosynthetic performance of tropical seagrasses under different light conditions.

Quantum-Ohmic Resistance Fluctuation In Disordered Conductors - An Invariant Imbedding Approach

It is now well known that in extreme quantum limit, dominated by the elastic impurity scattering and the concomitant quantum interference, the zero-temperature d.c. resistance of a strictly one-dimensional disordered system is non-additive and non-self-averaging. While these statistical fluctuations may persist in the case of a physically thin wire, they are implicitly and questionably ignored in higher dimensions. In this work, we have re-examined this question. Following an invariant imbedding formulation, we first derive a stochastic differential equation for the complex amplitude reflection coefficient and hence obtain a Fokker-Planck equation for the full probability distribution of resistance for a one-dimensional continuum with a Gaussian white-noise random potential. We then employ the Migdal-Kadanoff type bond moving procedure and derive the d-dimensional generalization of the above probability distribution, or rather the associated cumulant function –‘the free energy’. For d=3, our analysis shows that the dispersion dominates the mobilitly edge phenomena in that (i) a one-parameter B-function depending on the mean conductance only does not exist, (ii) an approximate treatment gives a diffusion-correction involving the second cumulant. It is, however, not clear whether the fluctuations can render the transition at the mobility edge ‘first-order’. We also report some analytical results for the case of the one dimensional system in the presence of a finite electric fiekl. We find a cross-over from the exponential to the power-low length dependence of resistance as the field increases from zero. Also, the distribution of resistance saturates asymptotically to a poissonian form. Most of our analytical results are supported by the recent numerical simulation work reported by some authors.