Genetic characterisation and structural analysis of the O-specific polysaccharide of Yersinia pseudotuberculosis serotype O:1c

Many, but not all, of the current 21 serotypes of Yersinia pseudotuberculosis have been investigated with regard to the chemical structures of their O-specific polysaccharide (OPS) and the genetic basis of their biosynthesis. Completion of the genetics and structures of the remaining serotypes will enhance our understanding of the emerging relationship between genetics and structures within this species. Here, we present a structural and genetic analysis of the Y. pseudotuberculosis serotype O:1c OPS. Our results showed that this OPS has the same backbone as Y. pseudotuberculosis O:2b, but with a 3,6-dideoxy-D-ribo-hexofuranose (paratofuranose, Parf) side-branch instead of a 3,6-dideoxy-D-xylo-hexopyranose (abequopyranose, Abep). The 3'-end of the gene cluster is the same as for O:2b and has the genes for synthesis of the backbone and for processing the completed repeat unit. The 5'-end of the cluster consists of the same genes as O:1b for synthesis of Parf and a related gene for its transfer to the repeating unit backbone.

Development of a cost-effective and flexible vibration DAQ system for long-term continuous structural health monitoring

In the structural health monitoring (SHM) field, long-term continuous vibration-based monitoring is becoming increasingly popular as this could keep track of the health status of structures during their service lives. However, implementing such a system is not always feasible due to on-going conflicts between budget constraints and the need of sophisticated systems to monitor real-world structures under their demanding in-service conditions. To address this problem, this paper presents a comprehensive development of a cost-effective and flexible vibration DAQ system for long-term continuous SHM of a newly constructed institutional complex with a special focus on the main building. First, selections of sensor type and sensor positions are scrutinized to overcome adversities such as low-frequency and low-level vibration measurements. In order to economically tackle the sparse measurement problem, a cost-optimized Ethernet-based peripheral DAQ model is first adopted to form the system skeleton. A combination of a high-resolution timing coordination method based on the TCP/IP command communication medium and a periodic system resynchronization strategy is then proposed to synchronize data from multiple distributed DAQ units. The results of both experimental evaluations and experimental–numerical verifications show that the proposed DAQ system in general and the data synchronization solution in particular work well and they can provide a promising cost-effective and flexible alternative for use in real-world SHM projects. Finally, the paper demonstrates simple but effective ways to make use of the developed monitoring system for long-term continuous structural health evaluation as well as to use the instrumented building herein as a multi-purpose benchmark structure for studying not only practical SHM problems but also synchronization related issues.

Structural complexity in structural health monitoring: Design of laboratory model and test plan

Many researchers in the field of civil structural health monitoring (SHM) have developed and tested their methods on simple to moderately complex laboratory structures such as beams, plates, frames, and trusses. Fieldwork has also been conducted by many researchers and practitioners on more complex operating bridges. Most laboratory structures do not adequately replicate the complexity of truss bridges. Informed by a brief review of the literature, this paper documents the design and proposed test plan of a structurally complex laboratory bridge model that has been specifically designed for the purpose of SHM research. Preliminary results have been presented in the companion paper.

Structural complexity in structural health monitoring: Preliminary experimental modal testing and analysis

Many researchers in the field of civil structural health monitoring have developed and tested their methods on simple to moderately complex laboratory structures such as beams, plates, frames, and trusses. Field work has also been conducted by many researchers and practitioners on more complex operating bridges. Most laboratory structures do not adequately replicate the complexity of truss bridges. This paper presents some preliminary results of experimental modal testing and analysis of the bridge model presented in the companion paper, using the peak picking method, and compares these results with those of a simple numerical model of the structure. Three dominant modes of vibration were experimentally identified under 15 Hz. The mode shapes and order of the modes matched those of the numerical model; however, the frequencies did not match.

Depth of anaesthesia monitoring during procedural sedation and analgesia: A systematic review protocol

Background Procedural sedation and analgesia (PSA) is used to attenuate the pain and distress that may otherwise be experienced during diagnostic and interventional medical or dental procedures. As the risk of adverse events increases with the depth of sedation induced, frequent monitoring of level of consciousness is recommended. Level of consciousness is usually monitored during PSA with clinical observation. Processed electroencephalogram-based depth of anaesthesia (DoA) monitoring devices provide an alternative method to monitor level of consciousness that can be used in addition to clinical observation. However, there is uncertainty as to whether their routine use in PSA would be justified. Rigorous evaluation of the clinical benefits of DoA monitors during PSA, including comprehensive syntheses of the available evidence, is therefore required. One potential clinical benefit of using DoA monitoring during PSA is that the technology could improve patient safety by reducing sedation-related adverse events, such as death or permanent neurological disability. We hypothesise that earlier identification of lapses into deeper than intended levels of sedation using DoA monitoring leads to more effective titration of sedative and analgesic medications, and results in a reduction in the risk of adverse events caused by the consequences of over-sedation, such as hypoxaemia. The primary objective of this review is to determine whether using DoA monitoring during PSA in the hospital setting improves patient safety by reducing the risk of hypoxaemia (defined as an arterial partial pressure of oxygen below 60 mmHg or percentage of haemoglobin that is saturated with oxygen [SpO2] less than 90 %). Other potential clinical benefits of using DoA monitoring devices during sedation will be assessed as secondary outcomes. Methods/design Electronic databases will be systematically searched for randomized controlled trials comparing the use of depth of anaesthesia monitoring devices with clinical observation of level of consciousness during PSA. Language restrictions will not be imposed. Screening, study selection and data extraction will be performed by two independent reviewers. Disagreements will be resolved by discussion. Meta-analyses will be performed if suitable. Discussion This review will synthesise the evidence on an important potential clinical benefit of DoA monitoring during PSA within hospital settings.

Genetic risk score analysis indicates migraine with and without comorbid depression are genetically different disorders

Migraine and major depressive disorder (MDD) are comorbid, moderately heritable and to some extent influenced by the same genes. In a previous paper, we suggested the possibility of causality (one trait causing the other) underlying this comorbidity. We present a new application of polygenic (genetic risk) score analysis to investigate the mechanisms underlying the genetic overlap of migraine and MDD. Genetic risk scores were constructed based on data from two discovery samples in which genome-wide association analyses (GWA) were performed for migraine and MDD, respectively. The Australian Twin Migraine GWA study (N = 6,350) included 2,825 migraine cases and 3,525 controls, 805 of whom met the diagnostic criteria for MDD. The RADIANT GWA study (N = 3,230) included 1,636 MDD cases and 1,594 controls. Genetic risk scores for migraine and for MDD were used to predict pure and comorbid forms of migraine and MDD in an independent Dutch target sample (NTR-NESDA, N = 2,966), which included 1,476 MDD cases and 1,058 migraine cases (723 of these individuals had both disorders concurrently). The observed patterns of prediction suggest that the 'pure' forms of migraine and MDD are genetically distinct disorders. The subgroup of individuals with comorbid MDD and migraine were genetically most similar to MDD patients. These results indicate that in at least a subset of migraine patients with MDD, migraine may be a symptom or consequence of MDD. © 2013 Springer-Verlag Berlin Heidelberg.

The future for genetic studies in reproduction

Genetic factors contribute to risk of many common diseases affecting reproduction and fertility. In recent years, methods for genome-wide association studies(GWAS) have revolutionized gene discovery forcommontraits and diseases. Results of GWAS are documented in the Catalog of Published Genome-Wide Association Studies at the National Human Genome Research Institute and report over 70 publications for 32 traits and diseases associated with reproduction. These include endometriosis, uterine fibroids, age at menarche and age at menopause. Results that pass appropriate stringent levels of significance are generally well replicated in independent studies. Examples of genetic variation affecting twinning rate, infertility, endometriosis and age at menarche demonstrate that the spectrum of disease-related variants for reproductive traits is similar to most other common diseases.GWAS 'hits' provide novel insights into biological pathways and the translational value of these studies lies in discovery of novel gene targets for biomarkers, drug development and greater understanding of environmental factors contributing to disease risk. Results also show that genetic data can help define sub-types of disease and co-morbidity with other traits and diseases. To date, many studies on reproductive traits have used relatively small samples. Future genetic marker studies in large samples with detailed phenotypic and clinical information will yield new insights into disease risk, disease classification and co-morbidity for many diseases associated with reproduction and infertility.

Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 × 10(-9)), rs7521902 near WNT4 (P = 1.8 × 10(-15)), rs10859871 near VEZT (P = 4.7 × 10(-15)), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10(-8)), rs7739264 near ID4 (P = 6.2 × 10(-10)) and rs13394619 in GREB1 (P = 4.5 × 10(-8)). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10(-8)) and rs4141819 on 2p14 (P = 9.2 × 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways.

Redefining dermatologists’ role in skin cancer early detection and follow-up care

Early diagnosis of melanoma leads to the best prognosis for patients and may be more likely achieved when those who are at high risk for melanoma undergo regular and systematic monitoring. However, many people rarely or never see a dermatologist. Risk prediction models (recently reviewed by Usher-Smith et al ) could assist to triage people into preventive care appropriate for their risk profile. Most risk prediction models contain measures of phenotype including skin, eye and hair colour as well as genetic mutations. Almost all also contain the number and size of naevi, as well as the presence of naevi with atypical features which are independently associated with melanoma risk. In the absence of formal population-based screening programs for melanoma in most countries worldwide, people with high risk phenotypes may need to consider regular monitoring or self-monitoring of their naevi , especially since the vast majority of melanomas are found by people themselves or their friend and relatives. Another group of patients that will require regular monitoring are patients who have been successfully treated for their first melanoma, whose risk to develop a second melanoma is greatly increased . In a US study of 89,515 melanoma survivors those with a previous diagnosis of melanoma had a 9-fold increased risk of developing subsequent melanoma compared with the general population, equating to a rate of 3.76 per 1000 person-years, while in an Australian study, risk of subsequent melanoma was 6 per 1000 person-years. Regular follow-up is therefore essential for melanoma survivors, especially during the first few years after initial melanoma diagnosis.

Inhaled particle surface area dose: Stationary vs personal monitoring

The aim of this paper is to determine the suitability of solely stationary measurements for exposure assessment and management applications. For this purpose, quantified inhaled particle surface area (IPSA) doses using both stationary and personal particle exposure monitors were evaluated and compared.

Different approaches of applying single-objective binary genetic algorithm on the wind farm design

This paper discusses three different ways of applying the single-objective binary genetic algorithm into designing the wind farm. The introduction of different applications is through altering the binary encoding methods in GA codes. The first encoding method is the traditional one with fixed wind turbine positions. The second involves varying the initial positions from results of the first method, and it is achieved by using binary digits to represent the coordination of wind turbine on X or Y axis. The third is the mixing of the first encoding method with another one, which is by adding four more binary digits to represent one of the unavailable plots. The goal of this paper is to demonstrate how the single-objective binary algorithm can be applied and how the wind turbines are distributed under various conditions with best fitness. The main emphasis of discussion is focused on the scenario of wind direction varying from 0° to 45°. Results show that choosing the appropriate position of wind turbines is more significant than choosing the wind turbine numbers, considering that the former has a bigger influence on the whole farm fitness than the latter. And the farm has best performance of fitness values, farm efficiency, and total power with the direction between 20°to 30°.

Acoustic sensing: Roles and applications in monitoring avian biodiversity

This thesis examined the use of acoustic sensors for monitoring avian biodiversity. Acoustic sensors have the potential to significantly increase the spatial and temporal scale of ecological observations, however acoustic recordings of the environment can be opaque and complex. This thesis developed methods for analysing large volumes of acoustic data to maximise the detection of bird species, and compared the results of acoustic sensor biodiversity surveys with traditional bird survey techniques.

Molecular genetic investigation of mitochondrial dysfunction in relation to migraine susceptibility

The aim of this research was to assess the role of genetic variation in mitochondrial function and how this relates to migraine pathophysiology. Using our unique Norfolk Island population, a custom in-house next generation sequencing methodology was developed. This data for the first time showed that there is a molecular genetic link between mitochondrial dysfunction and migraine susceptibility. This work has provided the foundation for further studies aimed at utilising the identified markers in improved migraine diagnostic and therapeutic strategies.

A practical guide to terminology for kimberlite facies: A systematic progression from descriptive to genetic, including a pocket guide

Kimberlite terminology remains problematic because both descriptive and genetic terms are mixed together in most existing terminology schemes. In addition, many terms used in existing kimberlite terminology schemes are not used in mainstream volcanology, even though kimberlite bodies are commonly the remains of kimberlite volcanic vents and edifices. We build on our own recently published approach to kimberlite facies terminology, involving a systematic progression from descriptive to genetic. The scheme can be used for both coherent kimberlite (i.e. kimberlite that was emplaced without undergoing any fragmentation processes and therefore preserving coherent igneous textures) and fragmental kimberlites. The approach involves documentation of components, textures and assessing the degree and effects of alteration on both components and original emplacement textures. This allows a purely descriptive composite component, textural and compositional petrological rock or deposit name to be constructed first, free of any biases about emplacement setting and processes. Then important facies features such as depositional structures, contact relationships and setting are assessed, leading to a composite descriptive and genetic name for the facies or rock unit that summarises key descriptive characteristics, emplacement processes and setting. Flow charts summarising the key steps in developing a progressive descriptive to genetic terminology are provided for both coherent and fragmental facies/deposits/rock units. These can be copied and used in the field, or in conjunction with field (e.g. drill core observations) and petrographic data. Because the approach depends heavily on field scale observations, characteristics and process interpretations, only the first descriptive part is appropriate where only petrographic observations are being made. Where field scale observations are available the progression from developing descriptive to interpretative terminology can be used, especially where some petrographic data also becomes available.