The effect of nutritional supplementation on the multifocal electroretinogram in healthy eyes

BACKGROUND: Previous studies have demonstrated an increase in macular pigment optical density (MPOD) with lutein (L)-based supplementation in healthy eyes. However, not all studies have assessed whether this increase in MPOD is associated with changes to other measures of retinal function such as the multifocal ERG (mfERG). Some studies also fail to report dietary levels of L and zeaxanthin (Z). Because of the associations between increased levels of L and Z, and reduced risk of AMD, this study was designed to assess the effects of L-based supplementation on mfERG amplitudes and latencies in healthy eyes. METHODS: Multifocal ERG amplitudes, visual acuity, contrast sensitivity, MPOD and dietary levels of L and Z were assessed in this longitudinal, randomized clinical trial. Fifty-two healthy eyes from 52 participants were randomly allocated to receive a L-based supplement (treated group), or no supplement (non-treated group). RESULTS: There were 25 subjects aged 18-77 (mean age ± SD; 48 ± 17) in the treated group and 27 subjects aged 21-69 (mean age ± SD; 43 ± 16) in the non-treated group. All participants attended for three visits: visit one at baseline, visit two at 20 weeks and visit three at 40 weeks. A statistically significant increase in MPOD (F = 17.0, p ≤ 0.001) and shortening of mfERG ring 2 P1 latency (F = 3.69, p = 0.04) was seen in the treated group. CONCLUSIONS: Although the results were not clinically significant, the reported trend for improvement in MPOD and mfERG outcomes warrants further investigation.

The AGN, star-forming, and morphological properties of luminous ir-bright/optically-faint galaxies

We present the active galactic nucleus (AGN), star-forming, and morphological properties of a sample of 13 MIR-luminous (∫_24 700 μJy) IR-bright/optically-faint galaxies (IRBGs, ∫_24/f_R≲ 1000). While these z ∼ 2 sources were drawn from deep Chandra fields with >200 ks X-ray coverage, only seven are formally detected in the X-ray and four lack X-ray emission at even the 2σ level. Spitzer InfraRed Spectrograph (IRS) spectra, however, confirm that all of the sources are AGN-dominated in the mid-IR, although half have detectable polycyclic aromatic hydrocarbon (PAH) emission responsible for ∼25% of their mid-infrared flux density. When combined with other samples, this indicates that at least 30%–40% of luminous IRBGs have star formation rates in the ultraluminous infrared galaxy (ULIRG) range (∼100–2000 M_⨀ yr^−1). X-ray hardness ratios and MIR to X-ray luminosity ratios indicate that all members of the sample contain heavily X-ray obscured AGNs, 80% of which are candidates to be Compton thick. Furthermore, the mean X-ray luminosity of the sample, log L_2–10 keV(erg s^−1) ∼44.6, indicates that these IRBGs are Type 2 QSOs, at least from the X-ray perspective. While those sources most heavily obscured in the X-ray are also those most likely to display strong silicate absorption in the mid-IR, silicate absorption does not always accompany X-ray obscuration. Finally, ∼70% of the IRBGs are merger candidates, a rate consistent with that of sub-mm galaxies (SMGs), although SMGs appear to be physically larger than IRBGs. These characteristics are consistent with the proposal that these objects represent a later, AGN-dominated, and more relaxed evolutionary stage following soon after the star-formation-dominated one represented by the SMGs.

Infrared Excess sources: Compton thick QSOs, low-luminosity Seyferts or starbursts?

We explore the nature of Infrared Excess sources (IRX), which are proposed as candidates for luminous [L_X(2–10 keV) > 10^43 erg s^−1] Compton thick (NH > 2 × 1024 cm−2) QSOs at z≈ 2. Lower redshift, z≈ 1, analogues of the distant IRX population are identified by first redshifting to z= 2 the spectral energy distributions (SEDs) of all sources with secure spectroscopic redshifts in the AEGIS (6488) and the GOODS-North (1784) surveys and then selecting those that qualify as IRX sources at that redshift. A total of 19 galaxies are selected. The mean redshift of the sample is z≈ 1. We do not find strong evidence for Compton thick QSOs in the sample. For nine sources with X-ray counterparts, the X-ray spectra are consistent with Compton thin active galactic nucleus (AGN). Only three of them show tentative evidence for Compton thick obscuration. The SEDs of the X-ray undetected population are consistent with starburst activity. There is no evidence for a hot dust component at the mid-infrared associated with AGN heated dust. If the X-ray undetected sources host AGN, an upper limit of L_X(2–10 keV) = 10^43 erg s^−1 is estimated for their intrinsic luminosity. We propose that a large fraction of the z≈ 2 IRX population is not Compton thick quasi-stellar objects (QSOs) but low-luminosity [L_X(2–10 keV) < 10^43 erg s^−1], possibly Compton thin, AGN or dusty starbursts. It is shown that the decomposition of the AGN and starburst contribution to the mid-IR is essential for interpreting the nature of this population, as star formation may dominate this wavelength regime.

The host galaxies and black holes of typical z~0.5-1.4 AGNs

We study the stellar and star formation properties of the host galaxies of 58 X-ray-selected AGNs in the GOODS portion of the Chandra Deep Field South (CDF-S) region at z ~ 0.5-1.4. The AGNs are selected such that their rest-frame UV to near-infrared spectral energy distributions (SEDs) are dominated by stellar emission; i.e., they show a prominent 1.6 μm bump, thus minimizing the AGN emission "contamination." This AGN population comprises approximately 50% of the X-ray-selected AGNs at these redshifts. We find that AGNs reside in the most massive galaxies at the redshifts probed here. Their characteristic stellar masses (M_* ~ 7.8 × 10^10 and M_* ~ 1.2 × 10^11 M_☉ at median redshifts of 0.67 and 1.07, respectively) appear to be representative of the X-ray-selected AGN population at these redshifts and are intermediate between those of local type 2 AGNs and high-redshift (z ~ 2) AGNs. The inferred black hole masses (M_BH ~ 2 × 10^8 M_☉) of typical AGNs are similar to those of optically identified quasars at similar redshifts. Since the AGNs in our sample are much less luminous (L_2–10 keV < 10^44 erg s^−1) than quasars, typical AGNs have low Eddington ratios (η ~ 0.01-0.001). This suggests that, at least at intermediate redshifts, the cosmic AGN "downsizing" is due to both a decrease in the characteristic stellar mass of typical host galaxies and less efficient accretion. Finally, there is no strong evidence in AGN host galaxies for either highly suppressed star formation (expected if AGNs played a role in quenching star formation) or elevated star formation when compared to mass-selected (i.e., IRAC-selected) galaxies of similar stellar masses and redshifts.

Rôle des neuromodulateurs dans les fonctions visuelles : l'angiotensine II et la dopamine

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Blue flicker modifies the subfoveal choroidal blood flow in the human eye

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Spectral sensitivity, spatial resolution and temporal resolution and their implications for conspecific signalling in cleaner shrimp.

Cleaner shrimp (Decapoda) regularly interact with conspecifics and client reef fish, both of which appear colourful and finely patterned to human observers. However, whether cleaner shrimp can perceive the colour patterns of conspecifics and clients is unknown, because cleaner shrimp visual capabilities are unstudied. We quantified spectral sensitivity and temporal resolution using electroretinography (ERG), and spatial resolution using both morphological (inter-ommatidial angle) and behavioural (optomotor) methods in three cleaner shrimp species: Lysmata amboinensis, Ancylomenes pedersoni and Urocaridella antonbruunii. In all three species, we found strong evidence for only a single spectral sensitivity peak of (mean ± s.e.m.) 518 ± 5, 518 ± 2 and 533 ± 3 nm, respectively. Temporal resolution in dark-adapted eyes was 39 ± 1.3, 36 ± 0.6 and 34 ± 1.3 Hz. Spatial resolution was 9.9 ± 0.3, 8.3 ± 0.1 and 11 ± 0.5 deg, respectively, which is low compared with other compound eyes of similar size. Assuming monochromacy, we present approximations of cleaner shrimp perception of both conspecifics and clients, and show that cleaner shrimp visual capabilities are sufficient to detect the outlines of large stimuli, but not to detect the colour patterns of conspecifics or clients, even over short distances. Thus, conspecific viewers have probably not played a role in the evolution of cleaner shrimp appearance; rather, further studies should investigate whether cleaner shrimp colour patterns have evolved to be viewed by client reef fish, many of which possess tri- and tetra-chromatic colour vision and relatively high spatial acuity.

Rôle des neuromodulateurs dans les fonctions visuelles : l'angiotensine II et la dopamine

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal.

Blue flicker modifies the subfoveal choroidal blood flow in the human eye

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Revisiting the Late Jurassic-Early Cretaceous of the NW South Iberian Basin: new ages and sedimentary environments

The study of the Upper Jurassic-Lower Cretaceous deposits (Higueruelas, Villar del Arzobispo and Aldea de Cortés Formations) of the South Iberian Basin (NW Valencia, Spain) reveals new stratigraphic and sedimentological data, which have significant implications on the stratigraphic framework, depositional environments and age of these units. The Higueruelas Fm was deposited in a mid-inner carbonate platform where oncolitic bars migrated by the action of storms and where oncoid production progressively decreased towards the uppermost part of the unit. The overlying Villar del Arzobispo Fm has been traditionally interpreted as an inner platform-lagoon evolving into a tidal-flat. Here it is interpreted as an inner-carbonate platform affected by storms, where oolitic shoals protected a lagoon, which had siliciclastic inputs from the continent. The Aldea de Cortés Fm has been previously interpreted as a lagoon surrounded by tidal-flats and fluvial-deltaic plains. Here it is reinterpreted as a coastal wetland where siliciclastic muddy deposits interacted with shallow fresh to marine water bodies, aeolian dunes and continental siliciclastic inputs. The contact between the Higueruelas and Villar del Arzobispo Fms, classically defined as gradual, is also interpreted here as rapid. More importantly, the contact between the Villar del Arzobispo and Aldea de Cortés Fms, previously considered as unconformable, is here interpreted as gradual. The presence of Alveosepta in the Villar del Arzobispo Fm suggests that at least part of this unit is Kimmeridgian, unlike the previously assigned Late Tithonian-Middle Berriasian age. Consequently, the underlying Higueruelas Fm, previously considered Tithonian, should not be younger than Kimmeridgian. Accordingly, sedimentation of the Aldea de Cortés Fm, previously considered Valangian-Hauterivian, probably started during the Tithonian and it may be considered part of the regressive trend of the Late Jurassic-Early Cretaceous cycle. This is consistent with the dinosaur faunas, typically Jurassic, described in the Villar del Arzobispo and Aldea de Cortés Fms.

Testing quasar unification: radiative transfer in clumpy winds

Various unification schemes interpret the complex phenomenology of quasars and luminous active galactic nuclei (AGN) in terms of a simple picture involving a central black hole, an accretion disc and an associated outflow. Here, we continue our tests of this paradigm by comparing quasar spectra to synthetic spectra of biconical disc wind models, produced with our state-of-the-art Monte Carlo radiative transfer code. Previously, we have shown that we could produce synthetic spectra resembling those of observed broad absorption line (BAL) quasars, but only if the X-ray luminosity was limited to 1043 erg s-1. Here, we introduce a simple treatment of clumping, and find that a filling factor of ˜0.01 moderates the ionization state sufficiently for BAL features to form in the rest-frame UV at more realistic X-ray luminosities. Our fiducial model shows good agreement with AGN X-ray properties and the wind produces strong line emission in, e.g., Lyα and C IV 1550 Å at low inclinations. At high inclinations, the spectra possess prominent LoBAL features. Despite these successes, we cannot reproduce all emission lines seen in quasar spectra with the correct equivalent-width ratios, and we find an angular dependence of emission line equivalent width despite the similarities in the observed emission line properties of BAL and non-BAL quasars. Overall, our work suggests that biconical winds can reproduce much of the qualitative behaviour expected from a unified model, but we cannot yet provide quantitative matches with quasar properties at all viewing angles. Whether disc winds can successfully unify quasars is therefore still an open question.

Magnetic Flux Cancellation in Ellerman Bombs

Ellerman Bombs (EBs) are often found to be co-spatial with bipolar photospheric magnetic fields. We use Hα imaging spectroscopy along with Fe i 6302.5 Å spectropolarimetry from the Swedish 1 m Solar Telescope (SST), combined with data from the Solar Dynamic Observatory, to study EBs and the evolution of the local magnetic fields at EB locations. EBs are found via an EB detection and tracking algorithm. Using NICOLE inversions of the spectropolarimetric data, we find that, on average, (3.43 ± 0.49) × 1024 erg of stored magnetic energy disappears from the bipolar region during EB burning. The inversions also show flux cancellation rates of 1014–1015 Mx s‑1 and temperature enhancements of 200 K at the detection footpoints. We investigate the near-simultaneous flaring of EBs due to co-temporal flux emergence from a sunspot, which shows a decrease in transverse velocity when interacting with an existing, stationary area of opposite polarity magnetic flux, resulting in the formation of the EBs. We also show that these EBs can be fueled further by additional, faster moving, negative magnetic flux regions.

Cabazitaxel for Hormone-Relapsed Metastatic Prostate Cancer Previously Treated With a Docetaxel-Containing Regimen: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the company's submission to NICE. Clinical evidence for cabazitaxel was derived from a multinational randomised open-label phase III trial (TROPIC) of cabazitaxel plus prednisone or prednisolone compared with mitoxantrone plus prednisone or prednisolone, which was assumed to represent best supportive care. The NICE final scope identified a further three comparators: abiraterone in combination with prednisone or prednisolone; enzalutamide; and radium-223 dichloride for the subgroup of people with bone metastasis only (no visceral metastasis). The company did not consider radium-223 dichloride to be a relevant comparator. Neither abiraterone nor enzalutamide has been directly compared in a trial with cabazitaxel. Instead, clinical evidence was synthesised within a network meta-analysis (NMA). Results from TROPIC showed that cabazitaxel was associated with a statistically significant improvement in both overall survival and progression-free survival compared with mitoxantrone. Results from a random-effects NMA, as conducted by the company and updated by the ERG, indicated that there was no statistically significant difference between the three active treatments for both overall survival and progression-free survival. Utility data were not collected as part of the TROPIC trial, and were instead taken from the company's UK early access programme. Evidence on resource use came from the TROPIC trial, supplemented by both expert clinical opinion and a UK clinical audit. List prices were used for mitoxantrone, abiraterone and enzalutamide as directed by NICE, although commercial in-confidence patient-access schemes (PASs) are in place for abiraterone and enzalutamide. The confidential PAS was used for cabazitaxel. Sequential use of the advanced hormonal therapies (abiraterone and enzalutamide) does not usually occur in clinical practice in the UK. Hence, cabazitaxel could be used within two pathways of care: either when an advanced hormonal therapy was used pre-docetaxel, or when one was used post-docetaxel. The company believed that the former pathway was more likely to represent standard National Health Service (NHS) practice, and so their main comparison was between cabazitaxel and mitoxantrone, with effectiveness data from the TROPIC trial. Results of the company's updated cost-effectiveness analysis estimated a probabilistic incremental cost-effectiveness ratio (ICER) of £45,982 per quality-adjusted life-year (QALY) gained, which the committee considered to be the most plausible value for this comparison. Cabazitaxel was estimated to be both cheaper and more effective than abiraterone. Cabazitaxel was estimated to be cheaper but less effective than enzalutamide, resulting in an ICER of £212,038 per QALY gained for enzalutamide compared with cabazitaxel. The ERG noted that radium-223 is a valid comparator (for the indicated sub-group), and that it may be used in either of the two care pathways. Hence, its exclusion leads to uncertainty in the cost-effectiveness results. In addition, the company assumed that there would be no drug wastage when cabazitaxel was used, with cost-effectiveness results being sensitive to this assumption: modelling drug wastage increased the ICER comparing cabazitaxel with mitoxantrone to over £55,000 per QALY gained. The ERG updated the company's NMA and used a random effects model to perform a fully incremental analysis between cabazitaxel, abiraterone, enzalutamide and best supportive care using PASs for abiraterone and enzalutamide. Results showed that both cabazitaxel and abiraterone were extendedly dominated by the combination of best supportive care and enzalutamide. Preliminary guidance from the committee, which included wastage of cabazitaxel, did not recommend its use. In response, the company provided both a further discount to the confidential PAS for cabazitaxel and confirmation from NHS England that it is appropriate to supply and purchase cabazitaxel in pre-prepared intravenous-infusion bags, which would remove the cost of drug wastage. As a result, the committee recommended use of cabazitaxel as a treatment option in people with an Eastern Cooperative Oncology Group performance status of 0 or 1 whose disease had progressed during or after treatment with at least 225 mg/m(2) of docetaxel, as long as it was provided at the discount agreed in the PAS and purchased in either pre-prepared intravenous-infusion bags or in vials at a reduced price to reflect the average per-patient drug wastage.

Ocular manifestations of microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) syndrome associated with mutations in KIF11

Purpose Microcephaly with or without chorioretinopathy, lymphedema or intellectual disability (MCLID) is an autosomal dominant condition. Mutations in KIF11 have been found to be causative in approximately 75% of cases. This study describes the ocular phenotype in patients with confirmed KIF11 mutations. Methods Standard ophthalmic examination and investigation including visual acuity, refraction and fundus examination was carried out in all patients. Fundus autofluorescence imaging (FAF) was performed in three patients, and four patients underwent spectral domain optical coherence tomography (OCT). Flash electroretinography (ERG) was performed in seven patients, and five underwent additional pattern electroretinography (PERG). Results The patients ranged in age from 2 to 10 years. Most presented with visual acuity loss. Fundus examination revealed lacunae of chorioretinal atrophy. Pigmentary macular changes and optic disc pallor were present in three of seven patients. Fundus autofluorescence demonstrated hypoautofluorescence at the macula in two of three patients. The lacunae of chorioretinal atrophy were hypoautofluorescent. The OCT showed atrophic maculae in three of four patients. Follow-up in one patient showed no deterioration of the vision over a 9-year period. The lesions appear not to be progressive on the follow-up imaging. Electrophysiology showed generalized rod and cone dysfunction and severe macular dysfunction. Inner retinal dysfunction was evident in three of seven patients. Conclusions Patients with KIF11 mutations show a specific ocular phenotype with variable expressivity and intrafamilial variability. Macular atrophy and dysfunction have not been consistently documented before. The fundus lesions appear non-progressive. The findings assist in providing an accurate diagnosis and thus improving the management and follow-up of patients with this syndrome.

Simulating the formation of a sigmoidal flux rope in AR10977 from SOHO/MDI magnetograms

The modeling technique of Mackay et al. is applied to simulate the coronal magnetic field of NOAA active region AR10977 over a seven day period (2007 December 2-10). The simulation is driven with a sequence of line-of-sight component magnetograms from SOHO/MDI and evolves the coronal magnetic field though a continuous series of non-linear force-free states. Upon comparison with Hinode/XRT observations, results show that the simulation reproduces many features of the active region's evolution. In particular, it describes the formation of a flux rope across the polarity inversion line during flux cancellation. The flux rope forms at the same location as an observed X-ray sigmoid. After five days of evolution, the free magnetic energy contained within the flux rope was found to be 3.9 × 1030 erg. This value is more than sufficient to account for the B1.4 GOES flare observed from the active region on 2007 December 7. At the time of the observed eruption, the flux rope was found to contain 20% of the active region flux. We conclude that the modeling technique proposed in Mackay et al.—which directly uses observed magnetograms to energize the coronal field—is a viable method to simulate the evolution of the coronal magnetic field.