A reporter for amyloid precursor protein γ-secretase activity in Drosophila

A key event in the pathogenesis of Alzheimer's disease (AD) is the deposition of senile plaques consisting largely of a peptide known as β-amyloid (Aβ) that is derived from the amyloid precursor protein (APP). A proteolytic activity called γ-secretase cleaves APP in the transmembrane domain and is required for Aβ generation. Aberrant γ-secretase cleavage of APP underlies the majority of early onset, familial AD. γ-Secretase resides in a large multi-protein complex, of which Presenilin, Nicastrin, APH-1 and PEN-2 are four essential components. Thus, identifying components and pathways by which the γ-secretase activity is regulated is crucial to understanding the mechanisms underlying AD pathogenesis, and may provide new diagnostic tools and therapeutic targets. Here we describe the generation of Drosophila that act as living reporters of γ-secretase activity in the fly eye. In these reporter flies the size of the eye correlates with the level of endogenous γ-secretase activity, and is very sensitive to the levels of three genes required for APP γ-secretase activity, presenilin, nicastrin and aph-1. Thus, these flies provide a sensitized system with which to identify other components of the γ-secretase complex and regulators of its activity. We have used these flies to carry out a screen for mutations that suppress γ-secretase activity and have identified a small chromosomal region that contains a gene or genes whose products may promote γ-secretase activity

Acuity and colour vision changes post intravitreal dexamethasone implant injection in patients with diabetic macular oedema

Purpose To evaluate changes in colour vision following intravitreal injection of Dexamethasone implant (Ozurdex) in patients with diabetic macular oedema (DMO). Both red-green (RG) and yellow-blue (YB) chromatic sensitivity were assessed using the Colour Assessment & Diagnosis (CAD) test which isolates the use of colour signals and provides age-corrected, statistical limits for normal trichromats. To determine whether colour changes and visual acuity (VA) post-treatment relate to central sub-field retinal thickness (CST). Methods Fourteen patients with DMO who were undergoing treatment with Ozurdex were recruited for this study. RG and YB colour thresholds were measured using the CAD test, best corrected visual acuity was assessed using the ETDRS chart and CST was measured using spectral domain optical coherence tomography (SD-OCT). All tests were performed monocularly at baseline and 24 weeks post injection. Results All patients (n = 14 eyes), had significant loss of RG and YB chromatic sensitivity at baseline (p<0.05). The mean age was 56 ± 9.5 years. The age specific, monocular, upper normal limits for a 56 year old subject are 2.66 for RG and 2.85 for YB. In this study, the measured, pre injection thresholds (mean±SD) were 22.6 ± 11.3 for RG and 16.2 ± 3.76 for YB. There was significant improvement in RG threshold post injection (i.e., 19.2 ± 10.8 (p<0.05)). No significant changes were found in the YB thresholds with corresponding mean and range values of: 15.8 ± 4.6 (p = 0.23). CST pre-treatment was 542 ±135 μm. After treatment and by week 24 the CST values decreased to 435 ±127 μm. Conclusions RG colour thresholds provide a sensitive measure of functional change in diabetic subjects with macular oedema. The YB system is damaged severely in the DMO patients studied and shows little or no recovery post treatment. The improvement in VA and particularly in RG colour vision correlate well with the measured decrease in CST. The results suggest that the improvement in the RG chromatic sensitivity can provide a useful biomarker for monitoring the efficacy of treatment in DMO

Incontinence-specific quality of life measures used in trials of treatments for female urinary incontinence: a systematic review.

This systematic review examined the use of incontinence-specific QOL measures in clinical trials of female incontinence treatments, and systematically evaluated their quality using a standard checklist. Of 61 trials included in the review, 58 (95.1%) used an incontinence-specific QOL measure. The most commonly used were IIQ (19 papers), I-QoL (12 papers) and UDI (9 papers). Eleven papers (18.0%) used measures which were not referenced or were developed specifically for the study. The eight QOL measures identified had good clinical face validity and measurement properties. We advise researchers to evaluate carefully the needs of their specific study, and select the QOL measure that is most appropriate in terms of validity, utility and relevance, and discourage the development of new measures. Until better evidence is available on the validity and comparability of measures, we recommend that researchers consider using IIQ or I-QOL with or without UDI in trials of incontinence treatments

Measured Sensitivity of the First Mark II Phased Array Feed on an ASKAP Antenna

This paper presents the measured sensitivity of CSIRO's first Mk. II phased array feed (PAF) on an ASKAP antenna. The Mk. II achieves a minimum system-temperature-over-efficiency $T_\mathrm{sys}/\eta$ of 78 K at 1.23 GHz and is 95 K or better from 835 MHz to 1.8 GHz. This PAF was designed for the Australian SKA Pathfinder telescope to demonstrate fast astronomical surveys with a wide field of view for the Square Kilometre Array (SKA).Comment: 5 pages, 2 figures, accepted for publication in Electromagnetics in Advanced applications (ICEAA), 2015 International Conference o

Chromatic sensitivity changes in Type I and Type II diabetics

Purpose: Previous studies have shown that patients with type I diabetes can exhibit significant loss of colour vision that often precedes any clinical signs of retinopathy. In this study we investigated loss of red-green (RG) and yellow-blue (YB) chromatic sensitivity in both type I and type II diabetic patients. The aim was to establish how the type, onset, retinal thickness and the glycated haemoglobin (HbA1c) level affect the severity of RG and YB loss. Methods: 110 patients diagnosed with diabetes (90 type II and 20 type I) took part in this study. BCVA, duration of diabetes, HbA1c and central subfield thickness (CST) were recorded in each patient. RG and YB colour thresholds were measured monocularly using the CAD (Colour Assessment & Diagnosis) test (Expert Rev. Ophthalmol. 6:409-420, 2011). Results: Both type I and II diabetic patients showed significant loss of both RG and YB chromatic sensitivity with thresholds that ranged from just above the upper, age-corrected threshold limits for normal colour vision to complete absence of chromatic sensitivity. There was little or no correlation with type, duration of diabetes, loss of visual acuity, retinal thickness changes or the HbA1C index. The diabetics examined separated into two groups, the majority have RG (72%) and YB (65%) thresholds below ~ 6 standard normal CAD units with little or no difference between type I and II. A subgroup of patients (mostly type II) exhibit much larger thresholds, but no correlation with age or duration of diabetes. Conclusions: RG and YB colour thresholds provide a sensitive measure of functional change in diabetics. Both type I and II diabetic patients exhibit loss of both RG and YB chromatic sensitivity, with little or no difference between the two types. Neural changes in diabetes that cause loss of colour vision do not appear to be linked directly to type, duration or the HbA1c level

Regional agriculture surveys using ERTS-1 data

The Center for Remote Sensing Research has conducted studies designed to evaluate the potential application of ERTS data in performing agricultural inventories, and to develop efficient methods of data handling and analysis useful in the operational context for performing large area surveys. This work has resulted in the development of an integrated system utilizing both human and computer analysis of ground, aerial, and space imagery, which has been shown to be very efficient for regional crop acreage inventories. The technique involves: (1) the delineation of ERTS images into relatively homogeneous strata by human interpreters, (2) the point-by-point classification of the area within each strata on the basis of crop type using a human/machine interactive digital image processing system; and (3) a multistage sampling procedure for the collection of supporting aerial and ground data used in the adjustment and verification of the classification results

Testing the recovery of stellar rotation signals from Kepler light curves using a blind hare-and-hounds exercise

We present the results of a blind exercise to test the recoverability of stellar rotation and differential rotation in Kepler light curves. The simulated light curves lasted 1000 days and included activity cycles, Sun-like butterfly patterns, differential rotation and spot evolution. The range of rotation periods, activity levels and spot lifetime were chosen to be representative of the Kepler data of solar like stars. Of the 1000 simulated light curves, 770 were injected into actual quiescent Kepler light curves to simulate Kepler noise. The test also included five 1000-day segments of the Sun's total irradiance variations at different points in the Sun's activity cycle. Five teams took part in the blind exercise, plus two teams who participated after the content of the light curves had been released. The methods used included Lomb-Scargle periodograms and variants thereof, auto-correlation function, and wavelet-based analyses, plus spot modelling to search for differential rotation. The results show that the `overall' period is well recovered for stars exhibiting low and moderate activity levels. Most teams reported values within 10% of the true value in 70% of the cases. There was, however, little correlation between the reported and simulated values of the differential rotation shear, suggesting that differential rotation studies based on full-disk light curves alone need to be treated with caution, at least for solar-type stars. The simulated light curves and associated parameters are available online for the community to test their own methods.Comment: Accepted for publication in MNRAS. Accepted, 13 April 2015. Received, 26 March 2015; in original form, 9 November 201

Risk factors for bovine respiratory disease in Australian feedlot cattle: use of a causal diagram-informed approach to estimate effects of animal mixing and movements before feedlot entry

A nationwide longitudinal study was conducted to investigate risk factors for bovine respiratory disease (BRD) in cattle in Australian feedlots. After induction (processing), cattle were placed in feedlot pens (cohorts) and monitored for occurrence of BRD over the first 50 days on feed. Data from a national cattle movement database were used to derive variables describing mixing of animals with cattle from other farms, numbers of animals in groups before arrival at the feedlot, exposure of animals to saleyards before arrival at the feedlot, and the timing and duration of the animal's move to the vicinity of the feedlot. Total and direct effects for each risk factor were estimated using a causal diagram-informed process to determine covariates to include in four-level Bayesian logistic regression models. Mixing, group size and timing of the animal's move to the feedlot were important predictors of BRD. Animals not mixed with cattle from other farms prior to 12 days before induction and then exposed to a high level of mixing (≥4 groups of animals mixed) had the highest risk of developing BRD (OR 3.7) compared to animals mixed at least 4 weeks before induction with less than 4 groups forming the cohort. Animals in groups formed at least 13 days before induction comprising 100 or more (OR 0.5) or 50-99 (OR 0.8) were at reduced risk compared to those in groups of less than 50 cattle. Animals moved to the vicinity of the feedlot at least 27 days before induction were at reduced risk (OR 0.4) compared to cattle undergoing short-haul transportation

Education in the working-class home: modes of learning as revealed by nineteenth-century criminal records

The transmission of knowledge and skills within the working-class household greatly troubled social commentators and social policy experts during the first half of the nineteenth century. To prove theories which related criminality to failures in working-class up-bringing, experts and officials embarked upon an ambitious collection of data on incarcerated criminals at various penal institutions. One such institution was the County Gaol at Ipswich. The exceptionally detailed information that survives on families, literacy, education and apprenticeships of the men, women and children imprisoned there has the potential to transform our understanding of the nature of home schooling (broadly interpreted) amongst the working classes in nineteenth-century England. This article uses data sets from prison registers to chart both the incidence and ‘success’ of instruction in reading and writing within the domestic environment. In the process, it highlights the importance of schooling in working-class families, but also the potentially growing significance of the family in occupational training