Validation of a fornix depth measurer: a putative tool for the assessment of progressive cicatrising conjunctivitis

Background/aims Documentation of conjunctival forniceal foreshortening in cases of progressive cicatrising conjunctivitis (PCC) is important in ascertaining disease stage and progression. Lower fornix shortening is often documented subjectively or semi-objectively, whereas upper forniceal obliteration is seldom quantified. Although tools such as fornix depth measurers (FDMs) have been described, their designs limit upper fornix measurement. The purpose of this study was to custom-design a FDM to evaluate the upper fornix and to assess variability in gauging fornix depth. \ud \ud Methods A polymethylmethacrylate FDM was constructed using industry-standard jewellery computer software and machinery. Two observers undertook a prospective independent evaluation of central lower fornix depth in a heterogeneous cohort of patients with clinically normal and abnormal conjunctival fornices both subjectively and by using the FDM (in mm). Upper central fornix depth was also measured. Agreement was assessed using Bland–Altman plots. \ud \ud Results Fifty-one eyes were evaluated. There was 100% intraobserver agreement to within 1 mm for each observer for lower fornix measurement. The mean difference in fornix depth loss using the FDM between observer 1 and 2 was 1.19%, with 95% confidence of agreement (±2SD) of −15% to +20%. In total, 86% (44/51) of measurements taken by the two observers agreed to within 10% of total lower fornix depth (ie, ±1 mm) versus only 63% (32/51) of the subjective measurements. Mean upper fornix difference was 0.57 mm, with 95% confidence of agreement of between −2 and + 3 mm. \ud \ud Conclusions This custom-designed FDM is well tolerated by patients and shows low intraobserver and interobserver variability. This enables repeatable and reproducible measurement of upper and lower fornix depths, facilitating improved rates of detection and better monitoring of progression of conjunctival scarring

Antiretroviral therapy initiated soon after HIV diagnosis as standard care: potential to save lives?

In 2008, an estimated 33.4 million people were infected with human immunodeficiency virus (HIV) and ~4 million people were receiving antiretroviral therapy (ART). However, in 2007, an estimated 6.7 million people were in need of ART under the current World Health Organization guidelines, and 2.7 million more people became infected with HIV. Most of those not currently eligible for ART will become eligible within the next decade, making the current treatment strategy unsustainable. The development of cheaper, less toxic, and more potent antiretrovirals over the past decade has made it possible to consider novel strategies of arresting the HIV/AIDS epidemic. Evidence is growing that ART can be used to prevent HIV transmission and that earlier initiation of treatment is beneficial for those infected with HIV. A mathematical model predicts that by testing whole communities annually and treating all who are infected immediately, up to 7.2 million AIDS-related deaths could be prevented in the next 40 years, long-term funding required to fight the HIV epidemic could be reduced, and, most importantly, control of the HIV/ AIDS epidemic could be regained within 1–2 years of full-scale implementation of the strategy. We discuss the development of the concept of ART for the prevention of HIV transmission and the modeled impact that a test-and-treat strategy could have on the HIV epidemic, and consequently argue that a field trial should be carried out to confirm model parameters, highlight any practical problems, and test the model’s predictions

A New Method of Blind Deconvolution for Colour Fundus Retinal Images

Fundus retinal imaging is widely used in the diagnosis and management of eye disease. Blur commonly occurs in the acquisition and when it is severe the resulting loss of resolution hampers accurate clinical assessment. In this paper, we present a new technique to address this challenging problem. We make use of implicitly constrained image deblurring, which is known to provide improved results over unconstrained and explicitly constrained methods, and build this into a multi-channel variational framework for parametric deblurring. We propose a new method for automatically selecting the regularisation parameter in the absence of the true (sharp) image using vessel segmentation. We then modify the model to include a regularisation coefficient function which is dependent on an available image mask in order to avoid potential inaccuracies caused by the addition of artificial masks. We present experimental results to demonstrate the effectiveness of our new method

A Controlled Study on the Characterisation of Bioaerosols Emissions from Compost

Bioaerosol emissions arising from biowaste treatment are an issue of public concern. To better characterise the bioaerosols, and to assess a range of measurement methods, we aerosolised green waste compost under controlled conditions. Viable and non-viable Andersen samplers, cyclone samplers and a real time bioaerosol detection system (Spectral Intensity Bioaerosol Sensor (SIBS)) were deployed simultaneously. The number-weighted fraction of fluorescent particles was in the range 22–26% of all particles for low and high emission scenarios. Overall fluorescence spectral profiles seen by the SIBS exhibited several peaks across the 16 wavelength bands from 298 to 735 nm. The size-fractionated endotoxin profile showed most endotoxin resided in the 2.1–9 μm aerodynamic diameter fraction, though up to 27% was found in a finer size fraction. A range of microorganisms were detected through culture, Matrix Assisted Laser Desorption and Ionisation Time of Flight Mass Spectrometry (MALDI-TOF) and quantitative polymerase chain reaction (qPCR), including Legionella pneumophila serogroup 1. These findings contribute to our knowledge of the physico-chemical and biological characteristics of bioaerosols from composting sites, as well as informing future monitoring approaches and data interpretation for bioaerosol measurement

Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.

The neuronal ceroid lipofuscinoses (NCLs or Batten disease) are a group of inherited, fatal neurodegenerative disorders of childhood. In these disorders, glial (microglial and astrocyte) activation typically occurs early in disease progression and predicts where neuron loss subsequently occurs. We have found that in the most common juvenile form of NCL (CLN3 disease or JNCL) this glial response is less pronounced in both mouse models and human autopsy material, with the morphological transformation of both astrocytes and microglia severely attenuated or delayed. To investigate their properties, we isolated glia and neurons from Cln3-deficient mice and studied their basic biology in culture. Upon stimulation, both Cln3-deficient astrocytes and microglia also showed an attenuated ability to transform morphologically, and an altered protein secretion profile. These defects were more pronounced in astrocytes, including the reduced secretion of a range of neuroprotective factors, mitogens, chemokines and cytokines, in addition to impaired calcium signalling and glutamate clearance. Cln3-deficient neurons also displayed an abnormal organization of their neurites. Most importantly, using a co-culture system, Cln3-deficient astrocytes and microglia had a negative impact on the survival and morphology of both Cln3-deficient and wildtype neurons, but these effects were largely reversed by growing mutant neurons with healthy glia. These data provide evidence that CLN3 disease astrocytes are functionally compromised. Together with microglia, they may play an active role in neuron loss in this disorder and can be considered as potential targets for therapeutic interventions

A simplification of rigorous atmospheric raytracing based on judicious rectilinear paths for near-surface GNSS reflectometry

Atmospheric delays are known to cause biases in Global Navigation Satellite System Reflectometry (GNSS-R) altimetry applications, such as for sea-level monitoring. The main quantity of interest is the reflection-minus-direct or interferometric atmospheric delay. Recently, we have presented a rigorous raytracing procedure to account for linear and angular refraction in conjunction with reflection as observed from near-surface platforms. Here, we demonstrate the feasibility of simplifying the ray trajectory by imposing a rectilinear wave propagation model. Two variants were assessed, based on the apparent or refracted satellite direction on the one hand and the geometric or vacuum conditions on the other hand. The former was shown to agree with rigorous results in terms of interferometric radio length while the latter agreed in terms of the interferometric vacuum distance. Upon a judicious combination of the best aspects of the two rectilinear cases, we have defined a mixed variant with excellent agreement with rigorous raytracing in terms of interferometric atmospheric delay. We further showed that mapping functions developed for GNSS positioning cannot be reused for GNSS-R purposes without adaptations. Otherwise, the total atmospheric delay may be underestimated by up to 50% at low elevation angles. The present work facilitates the adaptation of existing atmospheric raytracing software for GNSS-R purposes

Which environmental variables should I use in my biodiversity model?

Appropriate selection of environmental variables is critical to the performance of biodiversity models, but has received less attention than the choice of modelling method. Online aggregators of biological and environmental data, such as the Global Biodiversity Information Facility and the Atlas of Living Australia, necessitate a rational approach to variable selection. We outline a set of general principles for systematically identifying, compiling, evaluating and selecting environmental variables for a biodiversity model. Our approach aims to maximise the information obtained from the analysis of biological records linked to a potentially large suite of spatial environmental variables. We demonstrate the utility of this structured framework through case studies with Australian vascular plants: regional modelling of a species distribution, continent-wide modelling of species compositional turnover and environmental classification. The approach is informed by three components of a biodiversity model: (1) an ecological framework or conceptual model, (2) a data model concerning availability, resolution and variable selection and (3) a method for analysing data. We expand the data model in structuring the problem of choosing environmental variables. The case studies demonstrate a structured approach for the: (1) cost-effective compilation of variables in the context of an explicit ecological framework for the study, attribute accuracy and resolution; (2) evaluation of non-linear relationships between variables using knowledge of their derivation, scatter plots and dissimilarity matrices; (3) selection and grouping of variables based on hypotheses of relative ecological importance and perceived predictor effectiveness; (4) systematic testing of variables as predictors through the process of model building and refinement and (5) model critique, inference and synthesis using direct gradient analysis to evaluate the shape of response curves in the context of ecological theory by presenting predictions in both geographic and environmental space

An N-terminal alpha-Synuclein fragment binds lipid vesicles to modulate lipid induced aggregation

Misfolding and aggregation of alpha-synuclein (αS) into toxic conformations is involved in numerous neurodegenerative diseases. In Parkinson's disease (PD), this occurs within dopaminergic neurons, causing cell death and disease symptoms. During αS aggregation, many protein-protein interactions (PPIs) form over broad and flat protein surfaces, limiting potential for small-molecule intervention. Peptides, however, harbor great therapeutic promise since they can selectively engage with and modulate the large surface areas involved yet are small enough to function as druggable agents if suitably structured. Here, we explore the first 25 residues of αS (αS 1–25) as a template for peptide-based αS aggregation antagonists. We report that αS 1–25 inhibits lipid-induced αS aggregation in a dose-dependent manner. αS 1–25 functions by binding to lipids to prevent αS binding, with both αS and peptide requiring lipid for inhibition to occur. These findings present a potential mechanistic route for the treatment or prevention of PD.</p