High resolution melt analysis : a novel method for studying the genetic relatedness of Pseudomonas aeruginosa isolates from clinical and environmental sources

A novel method was developed for studying the genetic relatedness of Pseudomonas aeruginosa isolates from clinical and environmental sources. This bacterium is ubiquitous in the natural environment and is an important pathogen known to infect Cystic Fibrosis (CF) patients. The transmission route of strains has not yet been defined; current theories include acquisition from an environmental source or through patient-to-patient spread. A highly discriminatory, bioinformatics based, DNA typing method was developed to investigate the relatedness of clinical and environmental isolates. This study found a similarity between the environmental and several CF clonal strains and also highlighted occurrence of environmental P. aeruginosa strains in CF infections.

Familial typical migraine: Linkage to chromosome 19p13 and evidence for genetic heterogeneity

Migraine is a frequent familial disorder that, in common with most multifactorial disorders, has an unknown etiology. The authors identified several families with multiple individuals affected by typical migraine using a single set of diagnostic criteria and studied these families for cosegregation between the disorder and markers on chromosome 19, the location of a mutation that causes a rare form of familial hemiplegic migraine (FHM). One large tested family showed both cosegregation and significant allele sharing for markers situated within or adjacent to the FHM locus. Multipoint GENEHUNTER results indicated significant excess allele sharing across a 12.6- cM region containing the FHM Ca2+ channel gene, CACNL1A4 (maximum nonparametric linkage Z score = 6.64, p = 0.0026), with a maximum parametric lod score of 1.92 obtained for a (CAG)(n) triplet repeat polymorphism situated in exon 47 of this gene. The CAG expansion did not, however, appear to be the cause of migraine in this pedigree. Other tested families showed neither cosegregation nor excess allele sharing to chromosome 19 markers. HOMOG analysis indicated heterogeneity, generating a maximum HLOD score of 3.6. It was concluded that Chr19 mutations either in the CACNL1A4 gene or a closely linked gene are implicated in some pedigrees with familial typical migraine, and that the disorder is genetically heterogeneous.

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.

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.

Integrated Lean Six Sigma approach for patient flow improvement in hospital emergency department

Because of increased competition between healthcare providers, higher customer expectations, stringent checks on insurance payments and new government regulations, it has become vital for healthcare organisations to enhance the quality of the care they provide, to increase efficiency, and to improve the cost effectiveness of their services. Consequently, a number of quality management concepts and tools are employed in the healthcare domain to achieve the most efficient ways of using time, manpower, space and other resources. Emergency departments are designed to provide a high-quality medical service with immediate availability of resources to those in need of emergency care. The challenge of maintaining a smooth flow of patients in emergency departments is a global problem. This study attempts to improve the patient flow in emergency departments by considering Lean techniques and Six Sigma methodology in a comprehensive conceptual framework. The proposed research will develop a systematic approach through integration of Lean techniques with Six Sigma methodology to improve patient flow in emergency departments. The results reported in this paper are based on a standard questionnaire survey of 350 patients in the Emergency Department of Aseer Central Hospital in Saudi Arabia. The results of the study led us to determine the most significant variables affecting patient satisfaction with patient flow, including waiting time during patient treatment in the emergency department; effectiveness of the system when dealing with the patient’s complaints; and the layout of the emergency department. The proposed model will be developed within a performance evaluation metric based on these critical variables, to be evaluated in future work within fuzzy logic for continuous quality improvement.

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.

Investigation of genetic diversity and development of vaccine for Chlamydia pecorum infections in koala (Phascolarctos cinereus)

Many wild koala populations in Australia continue to experience serious declines due to factors such as disease caused by Chlamydia. This thesis is the first of its kind to investigate diversity of the chlamydial infections in wild koala populations across Australia and has made significant progress towards the development of a vaccine for koalas. The findings in this study have demonstrated that it is feasible to develop a safe and effective recombinant vaccine against Chlamydia in both disease free as well as severely diseased koalas. Most importantly, this study is also first of its kind to evaluate a multi-component vaccine that should be effective against the range of Chlamydia pecorum strains circulating in both captive as well as wild koala populations.

Food availability, cost disparity and improvement in relation to accessibility and remoteness in Queensland

This study is the first to describe disparity and change in the food supply between metropolitan, rural and remote stores by Accessibility/Remoteness Index of Australia (ARIA)1 category. A total of 92 stores (97% response rate) within five aggregate ARIA categories participated throughout Queensland in 2000. There was a strong association between ARIA category and the cost of the basket of basic foods, with prices being significantly higher (20% and 31% respectively) in the ‘remote’ and ‘very remote’ categories than in the ‘highly accessible’ category. The association with ARIA was less marked for fruit and vegetables than for other food groups, but not for tobacco and take-away food items. Basic food items were less available in the more remote stores. Over the past two years, relative improvements in food prices have been seen in stores in the ‘very remote’ category, with observed increases less than the consumer price index (CPI) for food. Some factors which may have contributed to this improvement are discussed.

Providing 'best practice' placements begins with mentoring skills : overview of the Program of Experience in the Palliative Approach (PEPA) quality improvement initiatives for mentors

Objectives PEPA is funded by the Department of Health and Ageing and aims to further improve the skill and confidence of the generalist workforce to work with people with palliative care needs. Recent quality improvement initiatives to promote transfer of learning into practice include appointment of a clinical educator, implementation of an online module for mentors and delivery of a mentoring workshop (collaborating with NSAP and PCC4U). This paper presents an overview of outcomes from these quality improvement initiatives. Methods PEPA host sites are selected based on their specialist palliative care level. Host site managers are surveyed six-monthly and participants are surveyed pre and three months post-placement to collect open and fixed response data on their experience of the program. Participants in the mentoring workshop (n=39) were asked to respond to a survey regarding the workshop outcomes. Results The percentage of placement participants who strongly agreed they ‘have the ability to implement the interventions required for people who have a life-limiting illness’ increased from 35% in 2011 (n=34) to 51% in 2012 (n=91) post-placement. Responses from mentor workshop participants indicated that 76% of respondents (n=25) agreed that they were able to identify principles for mentoring in the context of palliative care. In 2012, 61% of host site managers (n=54) strongly agreed that PEPA supports clinician working with people with a life-limiting illness. Conclusion Strategies to build the capabilities of palliative care professionals to mentor and support the learning experience of PEPA participants are critical to ongoing improvements of the program.

Voltage unbalance improvement in low voltage residential feeders with rooftop PVs using custom power devices

Voltage unbalance is a major power quality problem in low voltage residential feeders due to the random location and rating of single-phase rooftop photovoltaic cells (PV). In this paper, two different improvement methods based on the application of series (DVR) and parallel (DSTATCOM) custom power devices are investigated to improve the voltage unbalance problem in these feeders. First, based on the load flow analysis carried out in MATLAB, the effectiveness of these two custom power devices is studied vis-à-vis the voltage unbalance reduction in urban and semi-urban/rural feeders containing rooftop PVs. Their effectiveness is studied from the installation location and rating points of view. Later, a Monte Carlo based stochastic analysis is carried out to investigate their efficacy for different uncertainties of load and PV rating and location in the network. After the numerical analyses, a converter topology and control algorithm is proposed for the DSTATCOM and DVR for balancing the network voltage at their point of common coupling. A state feedback control, based on pole-shift technique, is developed to regulate the voltage in the output of the DSTATCOM and DVR converters such that the voltage balancing is achieved in the network. The dynamic feasibility of voltage unbalance and profile improvement in LV feeders, by the proposed structure and control algorithm for the DSTATCOM and DVR, is verified through detailed PSCAD/EMTDC simulations.

Prioritizing process improvement : an example from the Australian financial services sector

Process improvement has become a number one business priority, and more and more project requests are raised in organizations, seeking approval and resources for process-related projects. Realistically, the total of the requested funds exceeds the allocated budget, the number of projects is higher than the available bandwidth, and only some of these (very often only few) can be supported and most never see any light. Relevant resources are scarce, and correct decisions must be made to make sure that those projects that are of best value are implemented. How can decision makers make the right decision on the following: Which project(s) are to be approved and when to commence work on them? Which projects are most aligned with corporate strategy? How can the project’s value to the business be calculated and explained? How can these decisions be made in a fair, justifiable manner that brings the best results to the company and its stakeholders? This chapter describes a business value scoring (BVS) model that was built, tested, and implemented by a leading financial institution in Australia to address these very questions. The chapter discusses the background and motivations for such an initiative and describes the tool in detail. All components and underlying concepts are explained, together with details on its application. This tool has been successfully implemented in the case organization. The chapter provides practical guidelines for organizations that wish to adopt this approach.

A hybrid genetic algorithm for the energy-efficient virtual machine placement problem in data centers

Server consolidation using virtualization technology has become an important technology to improve the energy efficiency of data centers. Virtual machine placement is the key in the server consolidation technology. In the past few years, many approaches to the virtual machine placement have been proposed. However, existing virtual machine placement approaches consider the energy consumption by physical machines only, but do not consider the energy consumption in communication network, in a data center. However, the energy consumption in the communication network in a data center is not trivial, and therefore should be considered in the virtual machine placement. In our preliminary research, we have proposed a genetic algorithm for a new virtual machine placement problem that considers the energy consumption in both physical machines and the communication network in a data center. Aiming at improving the performance and efficiency of the genetic algorithm, this paper presents a hybrid genetic algorithm for the energy-efficient virtual machine placement problem. Experimental results show that the hybrid genetic algorithm significantly outperforms the original genetic algorithm, and that the hybrid genetic algorithm is scalable.