Evaluating Retinal Function in Age-Related Maculopathy with the ERG Photostress Test

PURPOSE. To evaluate the diagnostic potential of the electroretinogram (ERG) photostress test and the focal cone ERG in age-related maculopathy (ARM). METHODS. The cohort comprised 31 patients with ARM and 27 age-matched control subjects. The ERG photostress test was used to monitor cone adaptation after intense light adaptation. Focal 41- and 5-Hz cone ERGs were recorded monocularly (central 20°) to assess steady state retinal function. Univariate analysis identified electrophysiological parameters that differed between groups, and receiver operating characteristic (ROC) curves were constructed to assess their diagnostic potential. Logistic regression analysis determined the diagnostic potential of a model incorporating several independent predictors of ARM. RESULTS. The rate of recovery of the ERG photostress test was reduced (recovery was slower) in subjects with ARM. The parameter exhibited good diagnostic potential (P = 0.002, area under ROC curve = 0.74). The implicit times of the 5-Hz (a-wave, P = 0.002; b-wave, P < 0.001) and the 41-Hz (P < 0.001) focal cone ERGs were increased, and the 41-Hz focal cone ERG amplitude (P = 0.003) and focal to full-field amplitude ratio (P = 0.001) were reduced in the ARM group. Logistic regression analysis identified three independent predictors of ARM, including the rate of recovery of the ERG photostress test. CONCLUSIONS. Early ARM has a marked effect on the kinetics of cone adaptation. The clinical application of the ERG photostress test increases the sensitivity and specificity of a model for the diagnosis of ARM. Improved assessment of the functional integrity of the central retina will facilitate early diagnosis and evaluation of therapeutic interventions

Blood pressure variability and closed-loop baroreflex assessment in adolescent chronic fatigue syndrome during supine rest and orthostatic stress

Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to explore blood pressure variability and closed-loop baroreflex function at rest and during mild orthostatic stress in adolescents with CFS. We included a consecutive sample of 14 adolescents 12–18 years old with CFS diagnosed according to a thorough and standardized set of investigations and 56 healthy control subjects of equal sex and age distribution. Heart rate and blood pressure were recorded continuously and non-invasively during supine rest and during lower body negative pressure (LBNP) of –20 mmHg to simulate mild orthostatic stress. Indices of blood pressure variability and baroreflex function (α-gain) were computed from monovariate and bivariate spectra in the low-frequency (LF) band (0.04–0.15 Hz) and the high–frequency (HF) band (0.15–0.50 Hz), using an autoregressive algorithm. Variability of systolic blood pressure in the HF range was lower among CFS patients as compared to controls both at rest and during LBNP. During LBNP, compared to controls, α-gain HF decreased more, and α-gain LF and the ratio of α-gain LF/α-gain HF increased more in CFS patients, all suggesting greater shift from parasympathetic to sympathetic baroreflex control. CFS in adolescents is characterized by reduced systolic blood pressure variability and a sympathetic predominance of baroreflex heart rate control during orthostatic stress. These findings may have implications for the pathophysiology of CFS in adolescents

A phase 1b open label study of sodium selenate as a disease‐modifying treatment for behavioural variant fronto‐temporal dementia

Abstract Background Hyperphosphorylated tau is a pathological hallmark of ∼45% of behavioural variant frontotemporal dementia (bvFTD). For this reason, hyperphosphorylated tau represents a promising treatment target for this population. Sodium selenate stimulates the PP2A enzyme, which directly dephosphorylates hyperphosphorylated tau. This Phase 1b, open‐labelled, study investigated sodium selenate as a disease‐modifying treatment for patients with bvFTD. Method Twelve patients with bvFTD were treated with sodium selenate (15mg tds) for twelve months. Participants underwent a cognitive and behavioural battery, MRI, lumbar puncture and safety assessments at screening, baseline, and at regular intervals following treatment commencement. Adverse events were monitored via diary cards between clinic visits. Result All 12 patients completed the study. Safety analysis found that sodium selenate was safe and well tolerated, with no study withdrawals. Commonly reported mild‐moderate adverse events were nail changes (n=6), muscles aches (n=4), headache, fatigue, hair loss and fall (n=3). Five patients reduced their dose to 10mg tds due to adverse events. No treatment‐related serious adverse events occurred. Analyses of efficacy data are ongoing. A mixed‐effects analysis showed an overall small but significant decline on cognition and behaviour, including total NUCOG score (b=‐0.18, 95% CI=‐0.28–0.08) Cambridge Behavioural Index (b=0.32, 95% CI=0.18‐0.46) and Carer Burden Scale score (b=0.1, 95% CI = 0.02‐0.18). Percentage change in whole‐brain volume from baseline to week 52 ranged from ‐0.26% to ‐6.51% (n=7 &gt;‐1.8%, n=4 &lt;‐1.8%). Plasma tau levels (n=6) did not change from baseline (3.73±0.26pg/mL) to week 52 (4.66±0.24pg/mL). CSF tau also showed no change from baseline (167.8±11.2pg/mL) to week 52 (156.1±2.49pg/mL). Although not significant, the directional changes are in line with the proposed mechanism of sodium selenate. Exploratory analyses of “responders” (brain volume change &gt;‐1.8%, n=7) found no change in NUCOG total score (b=‐0.03, 95% CI ‐0.14‐0.07) or CBS score (b=‐0.05, 95% CI ‐0.04‐0.13) over time. Conclusion Sodium selenate is safe and well tolerated in patients with bvFTD. Exploratory analyses indicate it may reduce atrophy and halt cognitive decline in a subset of bvFTD patients. Sodium selenate should be further investigated as a potential treatment for bvFTD, and biomarkers to identify the subset of “responder” patients explored

Factors affecting the groundwater chemistry in a highly urbanized coastal area in Hong Kong: An example from the Mid-Levels area

Coastal areas of Hong Kong Island are one of the most extensively urbanized areas in the world. Groundwater samples in natural slopes and developed spaces in the regions centered by the Mid-Levels area, Hong Kong Island, were collected and analyzed to investigate the natural and anthropogenic processes affecting the groundwater chemistry. The results presented may be of value to other coastal areas in the world for the identification of possible groundwater contamination sources. Groundwater samples in the natural slopes were in low total dissolved solid (TDS) (<100 mg/l), indicating that the waters were in the early evolutionary stage. Using chloride as a normalizing factor, the "non-marine" components of different major ions in the samples were calculated. The correlation analysis indicated the occurrence of weathering of plagioclase feldspars in the natural slopes. However, the breakdown of biotite and K-feldspar seems to be limited by short groundwater residence time and high resistance to weathering. The high variety in hydrochemical facies may suggest the presence of extremely heterogeneous subsurface geological conditions. In the developed spaces, groundwater samples exhibited a high range of TDS (∼100-5300 mg/l) and were mainly dominated by Na-Cl and Na-Ca-Cl water types. Besides water-rock interactions, the groundwater chemistry was significantly affected by leakage from service pipes and the dissolution of concrete materials. Some chemicals were used as signatures to identify the leakage from various service pipes. The area generally suffered from widespread, but small amount of leakages, and no obvious leakage was discovered. The strong correlations among major cations and chloride suggested that even a small amount of leakage from salty flushing water pipes can significantly affect the groundwater chemistry. Groundwater is found to be highly aggressive toward concrete as supported by three commonly used aggressiveness indices. Additional Ca 2+ may be released to groundwater by corrosion of subsurface concrete materials such as building foundations and basements. The strength of those subsurface engineering structures may be weakened. Besides, excess Ca 2+ may deposit in the dewatering systems in the area, which may affect their performance in lowering high water tables. The findings regarding leakage from service pipes will be useful for various government organizations such as the Water Supplies Department and Drainage Services Department. Discussion of the behavior of Ca 2+ is instructional to foundation and slope dewatering designs in the area. © Springer-Verlag 2005.link_to_subscribed_fulltex

Geochemistry, petrogenesis and metallogenesis of the panzhihua gabbroic layered intrusion and associated Fe-Ti-V Oxide deposits, sichuan province, SW China

The Panzhihua gabbroic layered intrusion is associated with the 260 Ma Emeishan Large Igneous Province in SW China. This sill-like body hosts a giant Fe-Ti-V oxide deposit with 1333 million ton ore reserves, which makes China a major producer of these metals. The intrusion has a Marginal zone of fine-grained hornblende-bearing gabbro and olivine gabbro, followed upward by Lower, Middle, and Upper zones. The Lower and Middle zones consist of layered melanogabbro and gabbro composed of cumulate clinopyroxene, plagioclase, and olivine. These zones also contain magnetite layers. The Upper zone consists chiefly of leucogabbro composed of plagioclase and clinopyroxene with minor olivine. Most rocks in the body show variable-scale rhythmic modal layering in which dark minerals, primarily clinopyroxene, dominate in the lower parts of each layer, and lighter minerals, primarily plagioclase, dominate in the upper parts. The oxide ores occur as layers and lenses within the gabbros and are concentrated in the lower parts of the intrusion. Ore textures and associated mineral assemblages indicate that the ore bodies formed by very late-stage crystallization of V-rich titanomagnetite from an immiscible oxide liquid in a fluid-rich environment. The rocks of the Panzhihua intrusion become more evolved in chemistry upward and follow a tholeiitic differentiation trend with enrichment in Fe, Ti, and V. They are enriched in light rare earth elements relative to heavy rare earth elements, and exhibit positive Nb, Ta, and Ti anomalies and negative Zr and Hf anomalies. The silicate rocks and oxide ores of the Panzhihua intrusion formed from highly evolved Fe-Ti-V-rich ferrobasaltic or ferropicritic magmas. The textures of the ores and the abundance of minor hydrous phases indicate that addition of fluids from upper crustal wall-rocks induced the separation of the immiscible oxide melts from which the Fe-Ti-V oxide ore bodies in the lower part of the intrusion crystallized. © The Author 2005. Published by Oxford University Press. All rights reserved.link_to_subscribed_fulltex

A study protocol for a phase II randomised, double-blind, placebo-controlled trial of sodium selenate as a disease-modifying treatment for behavioural variant frontotemporal dementia

INTRODUCTION: Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder often neuropathologically associated with the accumulation of abnormally hyperphosphorylated tau, for which there is currently no disease-modifying treatment. Previous work by our group has shown sodium selenate upregulates the activity of protein phosphatase 2 in the brain, increasing the rate of tau dephosphorylation. The objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying treatment for bvFTD. METHODS AND ANALYSIS: This will be a multisite, phase IIb, double-blind placebo-controlled trial of sodium selenate. One hundred and twenty participants will be enrolled across 4 Australian academic hospitals. Following screening eligible participants will be randomised (1:1) to sodium selenate (15 mg three times a day) or placebo for 52 weeks. Participants will have regular safety and efficacy visits throughout the study period. The primary study outcome will be percentage brain volume change (PBVC) as measured on MRI over 52 weeks of treatment. This will be analysed with a general linear model (analysis of covariance (ANCOVA)) with the PBVC as an output, the treatment as an input and the baseline brain volume as covariate for adjustment purposes. Secondary outcomes include safety and tolerability measures, and efficacy measures; change in cerebrospinal fluid total-tau, Addenbrooke's Cognitive Examination-III and Cambridge Behavioural Inventory-Revised scores over the 52 weeks of treatment. These will also be analysed with ANCOVA where the corresponding baseline measure will be incorporated in the model. Additional exploratory outcomes will include other imaging, cognitive and biospecimen analyses. ETHICS AND DISSEMINATION: The study was approved by the Human Research and Ethics Committee of the lead site as part of the Australian Multisite Ethics approval system. The results of the study will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12620000236998