Effect of varying skin surface electrode position on electroretinogram responses recorded using a handheld stimulating and recording system

Purpose A handheld device (the RETeval system, LKC Technologies) aims to increase the ease of electroretinogram (ERG) recording by using specially designed skin electrodes, rather than corneal electrodes. We explored effects of electrode position on response parameters recorded using this device. Methods Healthy adult twins were recruited from the TwinsUK cohort and underwent recording of light-adapted flicker ERGs (corresponding to international standard stimuli). In Group 1, skin electrodes were placed in a “comfortable” position, which was up to 20 mm below the lid margin. For subsequent participants (Group 2), the electrode was positioned 2 mm from the lid margin as recommended by the manufacturer. Amplitudes and peak times (averaged from both eyes) were compared between groups after age-matching and inclusion of only one twin per pair. Light-adapted flicker and flash ERGs were recorded for an additional 10 healthy subjects in two consecutive recording sessions: in the test eye, electrode position was varied from 2 to 10–20 mm below the lid margin between sessions; in the fellow (control) eye, the electrode was 2 mm below the lid margin throughout. Amplitudes and peak times (test eye normalised to control eye) were compared for the two sessions. Results Including one twin per pair, and age-matching yielded 28 individuals per group. Flicker ERG amplitudes were significantly lower for Group 1 than Group 2 participants (p = 0.0024). However, mean peak times did not differ between groups (p = 0.54). For the subjects in whom electrode position was changed between recording sessions, flash and flicker amplitudes were significantly lower when positioned further from the lid margin (p  0.5). Conclusions Moving the skin electrodes further from the lid margin significantly reduces response amplitudes, highlighting the importance of consistent electrode positioning. However, this does not significantly affect peak times. Thus, it may be feasible to adopt a more comfortable position in participants who cannot tolerate the recommended position if analysis is restricted to peak time parameters

The relationship between stimulus intensity and response amplitude for the photopic negative response of the flash electroretinogram

The aim of this study was to investigate the relationship between stimulus intensity and response amplitude for the photopic negative response (PhNR) of the flash ERG. Specific aims were (i) to determine whether a generalized Naka-Rushton function provided a good fit to the intensity-response data and (ii) to determine the variability of the parameters of the best-fitting Naka-Rushton models. Electroretinograms were recorded in 18 participants, on two occasions, using both DTL fibre and skin active electrodes, in response to Ganzfeld red stimuli (Lee filter "terry red") ranging in stimulus strength from -1.30 to 0.53 log cd.s.m(-2) (0.28-2.11 log phot td.s) presented over a steady blue background (Schott glass filter BG28; 3.9 log scot td). PhNR amplitude was measured from b-wave peak and from pre-stimulus baseline. The Naka-Rushton function was fitted to all intensity-response data, and parameters, 'n', 'Vmax' and 'K' were obtained. Coefficients of variation (CoV), and inter-ocular and inter-session limits of agreement (LoA) were calculated for both Naka-Rushton parameters. A generalized Naka-Rushton function was found to provide a good fit to the intensity-response data, except at the highest stimulus intensity, where a reduction in amplitude occurred in many individuals. The 'Vmax' parameter was less variable than 'K' for all intensity-response data. Variability was lower for DTL than skin electrodes, and for peak-to-trough PhNR measurements, compared to baseline-to-trough. This study has demonstrated for the first time that the Naka-Rushton model provides a useful means of quantifying the intensity-response relationship of the PhNR

Detection of early age-related macular degeneration using novel functional parameters of the focal cone electroretinogram

The focal cone electroretinogram is a sensitive marker for macular disease, but have we unlocked its full potential? Typically assessment of waveform parameters is subjective and focuses on a small number of locations (e.g. the a-wave). This study evaluated the discriminatory and diagnostic potential of 4 conventional and 15 novel, objectively determined, parameters in patients with early Age-related Macular Degeneration. Focal cone electroretinograms were recorded in 54 participants with early Age-related Macular Degeneration (72.9±8.2 years) and 54 healthy controls (69±7.7 years). Conventional a and b wave amplitudes and implicit times were measured and compared to novel parameters derived from both the 1st and 2nd derivatives and the frequency-domain power spectrum of the electroretinogram.Statistically significant differences between groups were shown for all conventional parameters, the majority of 1st and 2nd derivative parameters and the power spectrum at 25 and 30 Hz. Receiver operating characteristics showed that both conventional and 1st and 2nd derivative implicit times had provided the best diagnostic potential. A regression model showed a small improvement over any individual parameter investigated. The non-conventional parameters enhanced the objective evaluation of the focal electroretinogram, especially when the amplitude was low. Furthermore, the novel parameters described here allow the implicit time of the electroretinogram to be probed at points other than the peaks of the a and b waves. Consequently these novel analysis techniques could prove valuable in future electrophysiological investigation, detection and monitoring of Age-related Macular Degeneration

No iron fertilization in the equatorial Pacific Ocean during the last ice age

The equatorial Pacific Ocean is one of the major high-nutrient, low-chlorophyll regions in the global ocean. In such regions, the consumption of the available macro-nutrients such as nitrate and phosphate is thought to be limited in part by the low abundance of the critical micro-nutrient iron1. Greater atmospheric dust deposition2 could have fertilized the equatorial Pacific with iron during the last ice age—the Last Glacial Period (LGP) but the effect of increased ice-age dust fluxes on primary productivity in the equatorial Pacific remains uncertain. Here we present meridional transects of dust (derived from the 232Th proxy), phytoplankton productivity (using opal, 231Pa/230Th and excess Ba), and the degree of nitrate consumption (using foraminifera-bound δ15N) from six cores in the central equatorial Pacific for the Holocene (0–10,000 years ago) and the LGP (17,000–27,000 years ago). We find that, although dust deposition in the central equatorial Pacific was two to three times greater in the LGP than in the Holocene, productivity was the same or lower, and the degree of nitrate consumption was the same. These biogeochemical findings suggest that the relatively greater ice-age dust fluxes were not large enough to provide substantial iron fertilization to the central equatorial Pacific. This may have been because the absolute rate of dust deposition in the LGP (although greater than the Holocene rate) was very low. The lower productivity coupled with unchanged nitrate consumption suggests that the subsurface major nutrient concentrations were lower in the central equatorial Pacific during the LGP. As these nutrients are today dominantly sourced from the Subantarctic Zone of the Southern Ocean, we propose that the central equatorial Pacific data are consistent with more nutrient consumption in the Subantarctic Zone, possibly owing to iron fertilization as a result of higher absolute dust fluxes in this region7,8. Thus, ice-age iron fertilization in the Subantarctic Zone would have ultimately worked to lower, not raise, equatorial Pacific productivity

Observations of Lyα\alpha Emitters at High Redshift

In this series of lectures, I review our observational understanding of high-$z$ Ly$\alpha$ emitters (LAEs) and relevant scientific topics. Since the discovery of LAEs in the late 1990s, more than ten (one) thousand(s) of LAEs have been identified photometrically (spectroscopically) at $z\sim 0$ to $z\sim 10$. These large samples of LAEs are useful to address two major astrophysical issues, galaxy formation and cosmic reionization. Statistical studies have revealed the general picture of LAEs' physical properties: young stellar populations, remarkable luminosity function evolutions, compact morphologies, highly ionized inter-stellar media (ISM) with low metal/dust contents, low masses of dark-matter halos. Typical LAEs represent low-mass high-$z$ galaxies, high-$z$ analogs of dwarf galaxies, some of which are thought to be candidates of population III galaxies. These observational studies have also pinpointed rare bright Ly$\alpha$ sources extended over $\sim 10-100$ kpc, dubbed Ly$\alpha$ blobs, whose physical origins are under debate. LAEs are used as probes of cosmic reionization history through the Ly$\alpha$ damping wing absorption given by the neutral hydrogen of the inter-galactic medium (IGM), which complement the cosmic microwave background radiation and 21cm observations. The low-mass and highly-ionized population of LAEs can be major sources of cosmic reionization. The budget of ionizing photons for cosmic reionization has been constrained, although there remain large observational uncertainties in the parameters. Beyond galaxy formation and cosmic reionization, several new usages of LAEs for science frontiers have been suggested such as the distribution of {\sc Hi} gas in the circum-galactic medium and filaments of large-scale structures. On-going programs and future telescope projects, such as JWST, ELTs, and SKA, will push the horizons of the science frontiers.Comment: Lecture notes for `Lyman-alpha as an Astrophysical and Cosmological Tool', Saas-Fee Advanced Course 46. Verhamme, A., North, P., Cantalupo, S., & Atek, H. (eds.) --- 147 pages, 103 figures. Abstract abridged. Link to the lecture program including the video recording and ppt files : https://obswww.unige.ch/Courses/saas-fee-2016/program.cg

Calcific aortic valve disease: A consensus summary from the alliance of investigators on calcific aortic valve disease

Calcific aortic valve disease (CAVD) is increasingly prevalent worldwide with significant morbidity and mortality. Therapeutic options beyond surgical valve replacement are currently limited. In 2011, the National Heart Lung and Blood Institute assembled a working group on aortic stenosis. This group identified CAVD as an actively regulated disease process in need of further study. As a result, the Alliance of Investigators on CAVD was formed to coordinate and promote CAVD research, with the goals of identifying individuals at risk, developing new therapeutic approaches, and improving diagnostic methods. The group is composed of cardiologists, geneticists, imaging specialists, and basic science researchers. This report reviews the current status of CAVD research and treatment strategies with identification of areas in need of additional investigation for optimal management of this patient population