Proteogenomics of selective susceptibility to endotoxin using circulating acute phase biomarkers and bioassay development in sheep: a review

Scientists have injected endotoxin into animals to investigate and understand various pathologies and novel therapies for several decades. Recent observations have shown that there is selective susceptibility to Escherichia coli lipopolysaccharide (LPS) endotoxin in sheep, despite having similar breed characteristics. The reason behind this difference is unknown, and has prompted studies aiming to explain the variation by proteogenomic characterisation of circulating acute phase biomarkers. It is hypothesised that genetic trait, biochemical, immunological and inflammation marker patterns contribute in defining and predicting mammalian response to LPS. This review discusses the effects of endotoxin and host responses, genetic basis of innate defences, activation of the acute phase response (APR) following experimental LPS challenge, and the current approaches employed in detecting novel biomarkers including acute phase proteins (APP) and micro-ribonucleic acids (miRNAs) in serum or plasma. miRNAs are novel targets for elucidating molecular mechanisms of disease because of their differential expression during pathological, and in healthy states. Changes in miRNA profiles during a disease challenge may be reflected in plasma. Studies show that gel-based two-dimensional electrophoresis (2-DE) coupled with either matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) or liquid chromatography-mass spectrometry (LC-MS/MS) are currently the most used methods for proteome characterisation. Further evidence suggests that proteomic investigations are preferentially shifting from 2-DE to non-gel based LC-MS/MS coupled with data extraction by sequential window acquisition of all theoretical fragment-ion spectra (SWATH) approaches that are able to identify a wider range of proteins. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and most recently proteomic methods have been used to quantify low abundance proteins such as cytokines. qRT-PCR and next generation sequencing (NGS) are used for the characterisation of miRNA. Proteogenomic approaches for detecting APP and novel miRNA profiling are essential in understanding the selective resistance to endotoxin in sheep. The results of these methods could help in understanding similar pathology in humans. It might also be helpful in the development of physiological and diagnostic screening assays for determining experimental inclusion and endpoints, and in clinical trials in future

Micro inverter with a front-end current-fed converter

The reliability of micro inverters is an important factor as it would be necessary to reduce cost and maintenance of the small and medium scale distributed PV power conversion systems. Electrolytic capacitors and active power decouple circuits can be avoided in micro inverters with the use of medium voltage DC-link. Such a DC-link based micro inverter is proposed with a front-end dual inductor current-fed push-pull converter. The primary side power switches of the front-end converter have reduced switching losses due to multi-resonant operation. In addition, the voltage and current stresses on the diodes of the secondary diode voltage doubler rectifier are reduced due to the presence of a series resonant circuit in the front-end converter. The operation of the proposed micro inverter is explained using an in-depth analysis of the switching characteristics of the power semiconductor devices. The theoretical analysis of the proposed micro inverter is validated using simulation result.

Bayesian predictive modeling and comparison of oil samples

Statistical comparison of oil samples is an integral part of oil spill identification, which deals with the process of linking an oil spill with its source of origin. In current practice, a frequentist hypothesis test is often used to evaluate evidence in support of a match between a spill and a source sample. As frequentist tests are only able to evaluate evidence against a hypothesis but not in support of it, we argue that this leads to unsound statistical reasoning. Moreover, currently only verbal conclusions on a very coarse scale can be made about the match between two samples, whereas a finer quantitative assessment would often be preferred. To address these issues, we propose a Bayesian predictive approach for evaluating the similarity between the chemical compositions of two oil samples. We derive the underlying statistical model from some basic assumptions on modeling assays in analytical chemistry, and to further facilitate and improve numerical evaluations, we develop analytical expressions for the key elements of Bayesian inference for this model. The approach is illustrated with both simulated and real data and is shown to have appealing properties in comparison with both standard frequentist and Bayesian approaches

Current research: Neurocognitive risk assessment

The current research began from the starting point that what we are grappling with when we are dealing with violent extremists by and large is essentially ‘normal people’. What follows in this third major section of this research paper is the theoretical and conceptual search for making researchable the following question: ‘How do you assess someone who is normal?’

The production mechanisms of OH radicals in a pulsed direct current plasma jet

The production mechanism of OH radicals in a pulsed DC plasma jet is studied by a two-dimensional (2-D) plasma jet model and a one-dimensional (1-D) discharge model. For the plasma jet in the open air, electron-impact dissociation of H2O, electron neutralization of H2O+, as well as dissociation of H2O by O(1D) are found to be the main reactions to generate the OH species. The contribution of the dissociation of H2O by electron is more than the others. The additions of N2, O2, air, and H2O into the working gas increase the OH density outside the tube slightly, which is attributed to more electrons produced by Penning ionization. On the other hand, the additions of O2 and H2O into the working gas increase the OH density inside the tube substantially, which is attributed to the increased O (1D) and H2O concentration, respectively. The gas flow will transport high density OH out of the tube during pulse off period. It is also shown that the plasma chemistry and reactivity can be effectively controlled by the pulse numbers. These results are supported by the laser induced fluorescence measurements and are relevant to several applications of atmospheric-pressure plasmas in health care, medicine, and materials processing.

Performance assessment in a heat exchanger tube fitted with double counter twisted tape inserts

The present study explored the effects of the double counter twisted tapes on heat transfer and fluid friction characteristics in a heat exchanger tube. The double counter twisted tapes were used as counter-swirl flow generators in the test section. The experiments were performed with double counter twisted tapes of four different twist ratios (y = 1.95, 3.85, 5.92 and 7.75) using air as the testing fluid in a circular tube turbulent flow regime where the Reynolds number was varied from 6950 to 50,050. The experimental results demonstrated that the Nusselt number, friction factor and thermal enhancement efficiency were increased with decreasing twist ratio. The results also revealed that the heat transfer rate in the tube fitted with double counter twisted tape was significantly increased with corresponding increase in pressure drop. In the range of the present work, heat transfer rate and friction factor were obtained to be around 60 to 240% and 91 to 286% higher than those of the plain tube values, respectively. The maximum thermal enhancement efficiency of 1.34 was achieved by the use of double counter twisted tapes at constant blower power. In addition, the empirical correlations for the Nusselt number, friction factor and thermal enhancement efficiency were also developed, based on the experimental data.

Determination of imidacloprid in paddy water and soil by liquid chromatography electrospray ionization-tandem mass spectrometry

A method for the determination of imidacloprid in paddy water and soil was developed using liquid chromatography electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS). Separation of imidacloprid was carried out on a Shimadzu C18 column (150 mm × 4.6 mm, 4.6 μm) with an acetonitrile?water (50 : 50, v/v) mobile phase containing 0.1% of acetic acid. The flow rate was 0.3 mL/min in isocratic mode. The product ion at 209 m/z was selected for quantification in multiple-reaction monitoring scan mode. Imidacloprid residues in soil were extracted by a solid-liquid extraction method with acetonitrile. Water samples were filtered and directly injected for analysis without extraction. Detection limits of 0.5 μg/kg and 0.3 μg/L were achieved for soil and water samples, respectively. The method had recoveries of 90 ± 2% (n = 4) for soil samples and 100 ± 2% (n = 4) for water samples. A linear relationship was observed throughout the investigated range of concentrations (1-200 μg/L), with the correlation coefficients ranging from 0.999 to 1.000. © Pleiades Publishing, Ltd., 2010.

Determination of tricyclazole in water using solid phase extraction and liquid chromatography

A method for determination of tricyclazole in water using solid phase extraction and high performance liquid chromatography (HPLC) with UV detection at 230nm and a mobile phase of acetonitrile:water (20:80, v/v) was developed. A performance comparison between two types of solid phase sorbents, the C18 sorbent of Supelclean ENVI-18 cartridge and the styrene-divinyl benzene copolymer sorbent of Sep-Pak PS2-Plus cartridge was conducted. The Sep-Pak PS2-Plus cartridges were found more suitable for extracting tricyclazole from water samples than the Supelclean ENVI-18 cartridges. For this cartridge, both methanol and ethyl acetate produced good results. The method was validated with good linearity and with a limit of detection of 0.008gL-1 for a 500-fold concentration through the SPE procedure. The recoveries of the method were stable at 80% and the precision was from 1.1-6.0% within the range of fortified concentrations. The validated method was also applied to measure the concentrations of tricyclazole in real paddy water.

Bone-anchored prosthesis: Current developments worldwide and challenges

Background Individuals with limb amputation fitted with conventional socket-suspended prostheses often experience socket related discomfort leading to a significant decrease in quality of life. Most of these concerns can be overcome by surgical techniques enabling bone-anchored prostheses. In this case, the prosthesis is attached directly to the residual skeleton through a percutaneous implant (e.g., screw type fixation, press-fit implant).[46, 48, 51, 52, 77, 78] The aim of this study is to present the current advances in these surgical techniques worldwide with a strong focus on the current challenges. Methods The current advances will be extracted from a systematic literature review including approximately 40 articles. The outcomes measured will include the estimation of the population worldwide as well as the complications (e.g., infection, loosening, fractures, and breakage) and the benefits (e.g., functional outcomes, health-related quality of life).[5-19, 51-53, 55, 57, 58, 62, 73, 79] Results The population of individuals fitted with a bone-anchored prosthesis is approximately 550 worldwide. Publications focusing on infection are sparse. However, the rate of superficial infection is estimated at 20%. Deep infection occurs rarely. Loosening and peri-prosthetic fractures are fairly uncommon. Breakage of implant parts occurs regularly mainly due to fall. All studies reported a significant improvement in functional level and overall quality of life. Conclusions Several commercial implants are in developments in Europe and US. The number of procedures is consistently growing worldwide. This technique might be primary way to fit a prosthesis to young and active amputees by 2025.

Bone-anchored prosthesis: Current developments worldwide and challenges

Background Individuals with limb amputation fitted with conventional socket-suspended prostheses often experience socket related discomfort leading to a significant decrease in quality of life. Most of these concerns can be overcome by surgical techniques enabling bone-anchored prostheses. In this case, the prosthesis is attached directly to the residual skeleton through a percutaneous implant (e.g., screw type fixation, press-fit implant).[46, 48, 51, 52, 77, 78] The aim of this study is to present the current advances in these surgical techniques worldwide with a strong focus on the current challenges. Methods The current advances will be extracted from a systematic literature review including approximately 40 articles. The outcomes measured will include the estimation of the population worldwide as well as the complications (e.g., infection, loosening, fractures, and breakage) and the benefits (e.g., functional outcomes, health-related quality of life).[5-19, 51-53, 55, 57, 58, 62, 73, 79] Results The population of individuals fitted with a bone-anchored prosthesis is approximately 550 worldwide. Publications focusing on infection are sparse. However, the rate of superficial infection is estimated at 20%. Deep infection occurs rarely. Loosening and peri-prosthetic fractures are fairly uncommon. Breakage of implant parts occurs regularly mainly due to fall. All studies reported a significant improvement in functional level and overall quality of life. Conclusions Several commercial implants are in developments in Europe and US. The number of procedures is consistently growing worldwide. This technique might be primary way to fit a prosthesis to young and active amputees by 2025.

Current management of transitional feeding issues in preterm neonates born in Queensland, Australia

Background: Many preterm neonates display difficulty establishing suck-feeding competence in the weeks following birth. Ineffective management of transitional feeding issues may cause patient complications, and can contribute to increased length of stay. Aims: Given that many neonatal nurseries appear to vary in their neonatal feeding management practices, the aim of this study was to investigate and document the routine level of support and intervention currently provided for preterm neonates with transitional feeding issues across the various level II (special care) nurseries (SCNs) in Queensland, Australia. Methods: A questionnaire was mailed to all Queensland SCNs in 2005 (n = 36). The questionnaire contained a series of closed-choice and short-answer questions designed to obtain information from each SCN regarding their current practices for managing transitional feeding issues in preterm neonates. Results were confirmed during a follow-up phone call. Results: Responses were obtained from 29 SCNs (80.6%). None of these nurseries reported having any formal, written policies regarding the management of transitional feeding issues in preterm neonates. Wide variations were reported in relation to the suck-feeding assessments and interventions used by staff within the various SCNs. Of the 29 nurseries, 4 (13.8%) reported using checklists or assessments to judge readiness for suck-feeds, and 5 (17.2%) reported using pulse oximetry to judge tolerance of suck-feeding attempts. Eighteen SCNs (62.1%) reported offering some form of active intervention to assist neonates with transitional feeding issues, with the most common intervention techniques reported being non-nutritive sucking during tube feeds, pre-feeding oral stimulation, and actively pacing suck-feeds. Twenty-two SCNs (75.4%) reported having access to a lactation consultant to assist mothers with breastfeeding issues. Conclusions: Differences were reported in the routine management of transitional feeding issues in preterm neonates across the various SCNs in Queensland. It is suggested that evidence based guidelines need to be developed, and that, in order to do this, further research studies are required to determine current best practice, as well as to answer remaining questions. © 2008 Elsevier Ireland Ltd. All rights reserved.

Consent for third molar tooth extractions in Australia and New Zealand: A review of current practice

Background Informed consent is the legal requirement to educate a patient about a proposed medical treatment or procedure so that he or she can make informed decisions. The purpose of the study was to examine the current practice for obtaining informed consent for third molar tooth extractions (wisdom teeth) by Oral and Maxillofacial Surgeons in Australia and New Zealand. Methods An online survey was sent to 180 consultant Oral and Maxillofacial Surgeons in Australia and New Zealand. Surgeons were asked to answer (yes/no) whether they routinely warned of a specific risk of third molar tooth extraction in their written consent. Results 71 replies were received (39%). The only risks that surgeons agreed should be routinely included in written consent were a general warning of infection (not alveolar osteitis), inferior alveolar nerve damage (temporary and permanent) and lingual nerve damage (temporary and permanent). Conclusions There is significant variability among Australian and New Zealand Oral and Maxillofacial Surgeons regarding risk disclosure for third molar tooth extractions. We aim to improve consistency in consent for third molar extractions by developing an evidence-based consent form.

Discovery of candidate serum proteomic and metabolomic biomarkers in ankylosing spondylitis

Ankylosing Spondylitis (AS) is a common inflammatory rheumatic disease with a predilection for the axial skeleton, affecting 0.2% of the population. Current diagnostic criteria rely on a composite of clinical and radiological changes, with a mean time to diagnosis of 5 to 10 years. In this study we employed nano liquid-chromatography mass spectrometry analysis to detect and quantify proteins and small compounds including endogenous peptides and metabolites in serum from 18 AS patients and nine healthy individuals. We identified a total of 316 proteins in serum, of which 22 showed significant up- or down-regulation (p < 0.05) in AS patients. Receiver operating characteristic analysis of combined levels of serum amyloid P component and inter-α-trypsin inhibitor heavy chain 1 revealed high diagnostic value for Ankylosing Spondylitis (area under the curve = 0.98). We also depleted individual sera of proteins to analyze endogenous peptides and metabolic compounds. We detected more than 7000 molecular features in patients and healthy individuals. Quantitative MS analysis revealed compound profiles that correlate with the clinical assessment of disease activity. One molecular feature identified as a Vitamin D3 metabolite-(23S,25R)-25-hydroxyvitamin D3 26,23-peroxylactone-was down-regulated in AS. The ratio of this vitamin D metabolite versus vitamin D binding protein serum levels was also altered in AS as compared with controls. These changes may contribute to pathological skeletal changes in AS. Our study is the first example of an integration of proteomic and metabolomic techniques to find new biomarker candidates for the diagnosis of Ankylosing Spondylitis

Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....