Prevalence of chronic ocular diseases in a genetic isolate : the Norfolk Island Eye Study (NIES)

Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18 th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. Methods: All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy. Results: We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.

A genetic variant located in miR-423 is associated with reduced breast cancer risk

Background/Aim: Since microRNAs (miRNAs) act as translational regulators of multiple genes, single nucleotide polymorphisms (SNP) in them can have potentially wide-ranging effects. Using an association approach, this research examined the effects of the rs6505162 SNP, an A>C polymorphism located in the premiRNA region of miR-423, on breast cancer development. Materials and Methods: Caucasian Australian women with breast cancer and controls matched for age and ethnicity were genotyped for rs6505162 and their genotypic and allelic frequencies analysed for significant differences. Results: Analysis indicated that there were significant differences between the case and control populations (χ 2=6.70, p=0.035), with the CC genotype conferring reduced risk of breast cancer development (odds ratio=0.50 95% confidence interval=0.27-0.92, p=0.03). Conclusion: Further functional research is required to determine the mechanism of action of this SNP on miRNA function.

Genetic variation in cytokine-related genes and migraine susceptibility

Migraine is classified by the World Health Organization (WHO) as being one of the top 20 most debilitating diseases. According to the neurovascular hypothesis, neuroinflammation may promote the activation and sensitisation of meningeal nociceptors, inducing the persistent throbbing headache characterized in migraine. The tumor necrosis factor (TNF) gene cluster, made up of TNFα, lymphotoxin α (LTA), and lymphotoxin β (LTB), has been implicated to influence the intensity and duration of local inflammation. It is thought that sterile inflammation mediated by LTA, LTB, and TNFα contributes to threshold brain excitability, propagation of neuronal hyperexcitability and thus initiation and maintenance of a migraine attack. Previous studies have investigated variants within the TNF gene cluster region in relation to migraine susceptibility, with largely conflicting results. The aim of this study was to expand on previous research and utilize a large case-control cohort and range of variants within the TNF gene cluster to investigate the role of the TNF gene cluster in migraine. Nine single nucleotide polymorphisms (SNPs) were selected for investigation as follows: rs1800683, rs2229094, rs2009658, rs2071590, rs2239704, rs909253, rs1800630, rs1800629, and rs3093664. No significant association with migraine susceptibility was found for any of the SNPs tested, with further testing according to migraine subtype and gender also showing no association for disease risk. Haplotype analysis showed that none of the tested haplotypes were significantly associated with migraine.

Molecular genetic analyses of RFLPs for PCR-amplified growth hormone gene, renal kallikrein gene and atrial natriuretic factor gene in essential hypertension

The present study examined polymorphisms of genes that might be involved in the onset of essential hypertension (HT). These included the (i) growth hormone gene (GH1), whose locus has recently been linked to elevated blood pressure (BP) in the stroke-prone SHR, although recent sib-pair analysis of a polymorphism near the human chorionic somatomammotropin gene (a member of the GH cluster) was unable to show linkage with HT; (ii) renal kallikrein gene (KLK1); and (iii) atrial natriuretic factor gene (ANF), where a primary defect in production or activity of kallikrein or ANF could cause NaCl retention and vasoconstriction. Association analyses were conducted to compare restriction fragment length polymorphisms (RFLPs) of each gene in 85 HT and 95 normotensive (NT) Caucasian subjects whose parents had a similar BP status at age ≥50 years. The frequency of the minor allele of (i) a RsaI RFLP in the promoter of GH1, amplified from leukocyte DNA by the polymerase chain reaction, was 0.15 in the HT group and 0.14 in the NT group (χ1=0.34, P=0.55); (ii) a TaqI RFLP for KLK1 was 0.035 in the HT group and 0.015 in the NT group (χ2=1.5, P=0.21); and (iii) a XhoI RFLP for ANF was 0.50 in HTs and 0.46 in NTs (χ2=0.20, P=0.65). Studies of HT pedigrees found one family in which the ANF locus and HT were not linked, owing to an obligate recombinant. The present data thus provide no evidence for involvement of the growth hormone, renal kallikrein, nor ANF gene in the causation of essential hypertension.

Continuous monitoring of reservoir water quality: The Wivenhoe Project

The Lake Wivenhoe Integrated Wireless Sensor Network is conceptually similar to traditional SCADA monitoring and control approaches. However, it is applied in an open system using wireless devices to monitor processes that affect water quality at both a high spatial and temporal frequency. This monitoring assists scientists to better understand drivers of key processes that influence water quality and provide the operators with an early warning system if below standard water enters the reservoir. Both of these aspects improve the safety and efficient delivery of drinking water to the end users.

Genetic susceptibility to complex traits : moving towards informed analysis of whole-genome screens

Susceptibility to complex traits, by definition, involves aetiological polymorphisms at multiple genetic loci combined with variable contributions by environmental factors. However, the approaches taken to identifying genetic loci implicated in susceptibility to complex traits frequently overlooks the compounding contribution of multiple loci in favour of highlighting a single gene solely responsible for predisposition. It is only in a small minority of cases that this has resulted in clear disease heritability associated with polymorphisms in a single gene. More often, this approach has led to an accumulation of single-gene associations with minor contributions to disease susceptibility. As the genomic era advances and genome-wide screens become higher in resolution and throughput, the need for simultaneous consideration of multiple loci is becoming more important. With special reference to non-Hodgkin’s lymphoma (NHL), this chapter will overview the current progress made in elucidating genetic polymorphisms associated with disease susceptibility. We also present novel data from a high-resolution single nucleotide polymorphism (SNP) microarray screen for susceptibility loci that are involved in NHL. Using an ‘informed approach’, the findings are highlighted within the context of cellular pathways, and provide insight and new ideas for methods of analysis for genome-wide screens for susceptibility.

Voltammetric monitoring of gold nanoparticle formation facilitated by glycyl-L-tyrosine : relation to electronic spectra and transmission electron microscopy images

Voltammetric techniques have been introduced to monitor the formation of gold nanoparticles produced via the reaction of the amino acid glycyl-L-tyrosine with Au(III) (bromoaurate) in 0.05 M KOH conditions. The alkaline conditions facilitate amino acid binding to Au(III), inhibit the rate of reduction to Au(0), and provide an excellent supporting electrolyte for voltammetric studies. Data obtained revealed that a range of time-dependent gold solution species are involved in gold nanoparticle formation and that the order in which reagents are mixed is critical to the outcome. Concomitantly with voltammetric measurements, the properties of gold nanoparticles formed are probed by examination of electronic spectra in order to understand how the solution environment present during nanoparticle growth affects the final distribution of the nanoparticles. Images obtained by the ex situ transmission electron microscopy (TEM) technique enable the physical properties of the nanoparticles isolated in the solid state to be assessed. Use of this combination of in situ and ex situ techniques provides a versatile framework for elucidating the details of nanoparticle formation.

Monitoring cuprous ion transport by scanning electrochemical microscopy during the course of copper electrodeposition

Scanning electrochemical microscopy (SECM), in the substrate generation–tip collection (SG-TC) mode, has been used to detect the cuprous ion intermediate formed during the course of electrodeposition of Cu metal from aqueous solution. Addition of chloride is confirmed to strongly stabilize the ion in aqueous solution and enhance the rate of Cu electrodeposition. This SECM method in the SG-TC mode offers an alternative to the rotating ring disk electrode (RRDE) technique for in situ studies on the effect of plating bath additives in metal electrodeposition. An attractive feature of the SECM relative to the RRDE method is that it allows qualitative aspects of the electrodeposition process to be studied in close proximity to the substrate in a simple and direct fashion using an inexpensive probe, and without the need for forced convection.

Condition monitoring and operational decision making in semiconductor manufacturing

Today, the majority of semiconductor fabrication plants (fabs) conduct equipment preventive maintenance based on statistically-derived time- or wafer-count-based intervals. While these practices have had relative success in managing equipment availability and product yield, the cost, both in time and materials, remains high. Condition-based maintenance has been successfully adopted in several industries, where costs associated with equipment downtime range from potential loss of life to unacceptable affects to companies’ bottom lines. In this paper, we present a method for the monitoring of complex systems in the presence of multiple operating regimes. In addition, the new representation of degradation processes will be used to define an optimization procedure that facilitates concurrent maintenance and operational decision-making in a manufacturing system. This decision-making procedure metaheuristically maximizes a customizable cost function that reflects the benefits of production uptime, and the losses incurred due to deficient quality and downtime. The new degradation monitoring method is illustrated through the monitoring of a deposition tool operating over a prolonged period of time in a major fab, while the operational decision-making is demonstrated using simulated operation of a generic cluster tool.

Monitoring style drift : evidence from U.S. Equity funds

This thesis examines the stewardship and investment style monitoring by managers and boards of U.S. equity funds. Results indicate that complying with a fund’s declared style, especially in value-growth dimension, remains a challenge for fund managers and boards, and that style-based investors should be aware of the risk of style drift since fund managers and boards do not always monitor the fund’s investment style as stated in the prospectus. Results also show that the quality of fund stewardship, as reflected by fund board quality, corporate culture, manager compensation, regulatory history, and fees are effective in ensuring that fund managers and boards perform their fiduciary obligation by increasing monitoring of the fund investment style.

Evaluation of the alkaline comet assay and urinary 3-methyladenine excretion for monitoring DNA damage in melanoma patients treated with dacarbazine and tamoxifen

Purpose: To develop, using dacarbazine as a model, reliable techniques for measuring DNA damage and repair as pharmacodynamic endpoints for patients receiving chemotherapy. Methods: A group of 39 patients with malignant melanoma were treated with dacarbazine 1 g/m2 i.v. every 21 days. Tamoxifen 20 mg daily was commenced 24 h after the first infusion and continued until 3 weeks after the last cycle of chemotherapy. DNA strand breaks formed during dacarbazine-induced DNA damage and repair were measured in individual cells by the alkaline comet assay. DNA methyl adducts were quantified by measuring urinary 3-methyladenine (3-MeA) excretion using immunoaffinity ELISA. Venous blood was taken on cycles 1 and 2 for separation of peripheral blood lymphocytes (PBLs) for measurement of DNA strand breaks. Results: Wide interpatient variation in PBL DNA strand breaks occurred following chemotherapy, with a peak at 4 h (median 26.6 h, interquartile range 14.75- 40.5 h) and incomplete repair by 24 h. Similarly, there was a range of 3-MeA excretion with peak levels 4-10 h after chemotherapy (median 33 nmol/h, interquartile range 20.448.65 nmol/h). Peak 3-MeA excretion was positively correlated with DNA strand breaks at 4 h (Spearman's correlation coefficient, r = 0.39, P = 0.036) and 24 h (r = 0.46, P = 0.01). Drug-induced emesis correlated with PBL DNA strand breaks (Mann Whitney U-test, P = 0.03) but not with peak 3-MeA excretion. Conclusions: DNA damage and repair following cytotoxic chemotherapy can be measured in vivo by the alkaline comet assay and by urinary 3-MeA excretion in patients receiving chemotherapy.

The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC

The majority of patients with non-small-cell lung cancer (NSCLC) present with advanced disease, with targeted therapies providing some improvement in clinical outcomes. The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. Tyrosine kinase inhibitors (TKIs), which target the EGFR TK domain, have proven to be an effective treatment strategy; however, patient responses to treatment vary considerably. Therefore, the identification of patients most likely to respond to treatment is essential to optimise the benefit of TKIs. Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. Nonetheless, the majority of patients relapse within a year of starting treatment. Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/panerb inhibitors. A number of techniques have been employed for genotypic assessment of tumourassociated DNA to identify EGFR mutations, each of which has advantages and disadvantages. This review presents an overview of the current methodologies used to identify such molecular markers. Recent developments in technology may make the monitoring of changes in patients' tumour genotypes easier in clinical practice, which may enable patients' treatment regimens to be tailored during the course of their disease, potentially leading to improved patient outcomes.

Continuous remote emissions monitoring – the lynchpin for air quality management

Diesel particulate matter (DPM), in particular, has been likened in a somewhat inflammatory manner to be the ‘next asbestos’. From the business change perspective, there are three areas holding the industry back from fully engaging with the issue: 1. There is no real feedback loop in any operational sense to assess the impact of investment or application of controls to manage diesel emissions. 2. DPM are getting ever smaller and more numerous, but there is no practical way of measuring them to regulate them in the field. Mass, the current basis of regulation, is becoming less and less relevant. 3. Diesel emissions management is generally wholly viewed as a cost, yet there are significant areas of benefit available from good management. This paper discusses a feedback approach to address these three areas to move the industry forward. The six main areas of benefit from providing a feedback loop by continuously monitoring diesel emissions have been identified: 1. Condition-based maintenance. Emissions change instantaneously if engine condition changes. 2. Operator performance. An operator can use a lot more fuel for little incremental work output through poor technique or discipline. 3. Vehicle utilisation. Operating hours achieved and ratios of idling to under power affect the proportion of emissions produced with no economic value. 4. Fuel efficiency. This allows visibility into other contributing configuration and environmental factors for the vehicle. 5. Emission rates. This allows scope to directly address the required ratio of ventilation to diesel emissions. 6. Total carbon emissions - for NGER-type reporting requirements, calculating the emissions individually from each vehicle rather than just reporting on fuel delivered to a site.

Effective technologies for noninvasive remote monitoring in heart failure

Background Trials of new technologies to remotely monitor for signs and symptoms of worsening heart failure are continually emerging. The extent to which technological differences impact the effectiveness of non-invasive remote monitoring for heart failure management is unknown. Objective To examine the effect of specific technology used for non-invasive remote monitoring of people with heart failure on all-cause mortality and heart failure-related hospitalisations. Methods A sub-analysis of a large systematic review and meta-analysis was conducted. Studies were stratified according to the specific type of technology used and separate meta-analyses were performed. Four different types of non-invasive remote monitoring technologies were identified including structured telephone calls, videophone, interactive voice response devices and telemonitoring. Results Only structured telephone calls and telemonitoring were effective in reducing the risk of all-cause mortality (RR 0.87; 95% CI=0.75-1.01; p=0.06 and 0.62; 95% CI=0.50-0.77; p<0.0001) and heart failure-related hospitalisations (RR 0.77; 95% CI=0.68-0.87; p<0.001) and 0.75; 95% CI=0.63-0.91; p=0.003). More research data is required for videophone and interactive voice response technologies. Conclusions This sub-analysis identified that only two of the four specific technologies used for non-invasive remote monitoring in heart failure improved outcomes. When results of studies that involved these disparate technologies were combined in previous meta-analyses, significant improvements in outcomes were identified. As such, this study has highlighted implications for future meta-analyses of randomised controlled trials focused on evaluating the effectiveness of remote monitoring in heart failure.

Monitoring the price and affordability of foods and diets globally

Food prices and food affordability are important determinants of food choices, obesity and non-communicable diseases. As governments around the world consider policies to promote the consumption of healthier foods, data on the relative price and affordability of foods, with a particular focus on the difference between ‘less healthy’ and ‘healthy’ foods and diets, are urgently needed. This paper briefly reviews past and current approaches to monitoring food prices, and identifies key issues affecting the development of practical tools and methods for food price data collection, analysis and reporting. A step-wise monitoring framework, including measurement indicators, is proposed. ‘Minimal’ data collection will assess the differential price of ‘healthy’ and ‘less healthy’ foods; ‘expanded’ monitoring will assess the differential price of ‘healthy’ and ‘less healthy’ diets; and the ‘optimal’ approach will also monitor food affordability, by taking into account household income. The monitoring of the price and affordability of ‘healthy’ and ‘less healthy’ foods and diets globally will provide robust data and benchmarks to inform economic and fiscal policy responses. Given the range of methodological, cultural and logistical challenges in this area, it is imperative that all aspects of the proposed monitoring framework are tested rigorously before implementation.