Metabolite profiling and pathway analysis of acute hepatitis rats by UPLC-ESI MS combined with pattern recognition methods

BACKGROUND & AIMS Metabolomics is comprehensive analysis of low-molecular-weight endogenous metabolites in a biological sample. It could enable mapping of perturbations of early biochemical changes in diseases and hence provide an opportunity to develop predictive biomarkers that could provide valuable insights into the mechanisms of diseases. The aim of this study was to elucidate the changes in endogenous metabolites and to phenotype the metabolic profiling of d-galactosamine (GalN)-inducing acute hepatitis in rats by UPLC-ESI MS. METHODS The systemic biochemical actions of GalN administration (ip, 400 mg/kg) have been investigated in male wistar rats using conventional clinical chemistry, liver histopathology and metabolomic analysis of UPLC- ESI MS of urine. The urine was collected predose (-24 to 0 h) and 0-24, 24-48, 48-72, 72-96 h post-dose. Mass spectrometry of the urine was analysed visually and via conjunction with multivariate data analysis. RESULTS Results demonstrated that there was a time-dependent biochemical effect of GalN dosed on the levels of a range of low-molecular-weight metabolites in urine, which was correlated with developing phase of the GalN-inducing acute hepatitis. Urinary excretion of beta-hydroxybutanoic acid and citric acid was decreased following GalN dosing, whereas that of glycocholic acid, indole-3-acetic acid, sphinganine, n-acetyl-l-phenylalanine, cholic acid and creatinine excretion was increased, which suggests that several key metabolic pathways such as energy metabolism, lipid metabolism and amino acid metabolism were perturbed by GalN. CONCLUSION This metabolomic investigation demonstrates that this robust non-invasive tool offers insight into the metabolic states of diseases.

Principal component and linkage analysis of cardiovascular risk traits in the Norfolk isolate

OBJECTIVE(S): An individual's risk of developing cardiovascular disease (CVD) is influenced by genetic factors. This study focussed on mapping genetic loci for CVD-risk traits in a unique population isolate derived from Norfolk Island. METHODS: This investigation focussed on 377 individuals descended from the population founders. Principal component analysis was used to extract orthogonal components from 11 cardiovascular risk traits. Multipoint variance component methods were used to assess genome-wide linkage using SOLAR to the derived factors. A total of 285 of the 377 related individuals were informative for linkage analysis. RESULTS: A total of 4 principal components accounting for 83% of the total variance were derived. Principal component 1 was loaded with body size indicators; principal component 2 with body size, cholesterol and triglyceride levels; principal component 3 with the blood pressures; and principal component 4 with LDL-cholesterol and total cholesterol levels. Suggestive evidence of linkage for principal component 2 (h(2) = 0.35) was observed on chromosome 5q35 (LOD = 1.85; p = 0.0008). While peak regions on chromosome 10p11.2 (LOD = 1.27; p = 0.005) and 12q13 (LOD = 1.63; p = 0.003) were observed to segregate with principal components 1 (h(2) = 0.33) and 4 (h(2) = 0.42), respectively. CONCLUSION(S): This study investigated a number of CVD risk traits in a unique isolated population. Findings support the clustering of CVD risk traits and provide interesting evidence of a region on chromosome 5q35 segregating with weight, waist circumference, HDL-c and total triglyceride levels.

Identification and simultaneous analysis of harmane, harmol, isovitexin and vitexin in Passiflora incarnata extracts with a novel HLPC method

A high performance liquid chromatographic method for the simultaneous analysis of two flavonoids (iso-vitexin and vitexin), and three indole alkaloids (harmane, harmine, and harmol) was developed. This method was then utilised to quantitate levels of these five constituents in methanolic extracts of Australian Passiflora incarnata. HPLC analysis was performed using a Waters™ Novapak C18 (150 × 4 mm, 4 μm) column, with a gradient solvent system of methanol-water-acetic acid. Detection was achieved by PDA UV (254 nm) and fluorescence (excitation 254 nm, emission 414 nm), utilising the external standard method to obtain quantification.

Measurement, modelling and capacity analysis for novel, fixed multi-user single-antenna MIMO-OFDM system, in rural environments

High-speed broadband internet access is widely recognised as a catalyst to social and economic development. However, the provision of broadband Internet services with the existing solutions to rural population, scattered over an extensive geographical area, remains both an economic and technical challenge. As a feasible solution, the Commonwealth Scientific and Industrial Research Organization (CSIRO) proposed a highly spectrally efficient, innovative and cost-effective fixed wireless broadband access technology, which uses analogue TV frequency spectrum and Multi-User MIMO (MUMIMO) technology with Orthogonal-Frequency-Division-Multiplexing (OFDM). MIMO systems have emerged as a promising solution for the increasing demand of higher data rates, better quality of service, and higher network capacity. However, the performance of MIMO systems can be significantly affected by different types of propagation environments e.g., indoor, outdoor urban, or outdoor rural and operating frequencies. For instance, large spectral efficiencies associated with MIMO systems, which assume a rich scattering environment in urban environments, may not be valid for all propagation environments, such as outdoor rural environments, due to the presence of less scatterer densities. Since this is the first time a MU-MIMO-OFDM fixed broadband wireless access solution is deployed in a rural environment, questions from both theoretical and practical standpoints arise; For example, what capacity gains are available for the proposed solution under realistic rural propagation conditions?. Currently, no comprehensive channel measurement and capacity analysis results are available for MU-MIMO-OFDM fixed broadband wireless access systems which employ large scale multiple antennas at the Access Point (AP) and analogue TV frequency spectrum in rural environments. Moreover, according to the literature, no deterministic MU-MIMO channel models exist that define rural wireless channels by accounting for terrain effects. This thesis fills the aforementioned knowledge gaps with channel measurements, channel modeling and comprehensive capacity analysis for MU-MIMO-OFDM fixed wireless broadband access systems in rural environments. For the first time, channel measurements were conducted in a rural farmland near Smithton, Tasmania using CSIRO's broadband wireless access solution. A novel deterministic MU-MIMO-OFDM channel model, which can be used for accurate performance prediction of rural MUMIMO channels with dominant Line-of-Sight (LoS) paths, was developed under this research. Results show that the proposed solution can achieve 43.7 bits/s/Hz at a Signal-to- Noise Ratio (SNR) of 20 dB in rural environments. Based on channel measurement results, this thesis verifies that the deterministic channel model accurately predicts channel capacity in rural environments with a Root Mean Square (RMS) error of 0.18 bits/s/Hz. Moreover, this study presents a comprehensive capacity analysis of rural MU-MIMOOFDM channels using experimental, simulated and theoretical models. Based on the validated deterministic model, further investigations on channel capacity and the eects of capacity variation, with different user distribution angles (θ) around the AP, were analysed. For instance, when SNR = 20dB, the capacity increases from 15.5 bits/s/Hz to 43.7 bits/s/Hz as θ increases from 10° to 360°. Strategies to mitigate these capacity degradation effects are also presented by employing a suitable user grouping method. Outcomes of this thesis have already been used by CSIRO scientists to determine optimum user distribution angles around the AP, and are of great significance for researchers and MU-MUMO-OFDM system developers to understand the advantages and potential capacity gains of MU-MIMO systems in rural environments. Also, results of this study are useful to further improve the performance of MU-MIMO-OFDM systems in rural environments. Ultimately, this knowledge contribution will be useful in delivering efficient, cost-effective high-speed wireless broadband systems that are tailor-made for rural environments, thus, improving the quality of life and economic prosperity of rural populations.

Conceptual and thematic analysis of policies and guidelines on engineering asset management of different states in Australia

The role of government in developing policies and guidelines for asset management is becoming increasingly important especially in view of ageing infrastructure and increasing financial risks for building infrastructure. This paper reviews policies and guidelines developed by Australian state authorities against industry developed principles. It utilizes the software program Leximancer to; a) produce conceptual visualisations of the key themes and concepts embedded within state-wide policies and guidelines, and b) systematically compare the differing asset management foci between states. The analyses reveal mixed results in terms of policy priorities and guidelines for managing assets at a strategic level across states. This paper outlines a rigorous analytical methodology to inform specific policy changes.

Enabling open access to and re-use of publicly funded research data in Malaysian public universities : a legal and policy analysis

Numerous statements and declarations have been made over recent decades in support of open access to research data. The growing recognition of the importance of open access to research data has been accompanied by calls on public research funding agencies and universities to facilitate better access to publicly funded research data so that it can be re-used and redistributed as public goods. International and inter-governmental bodies such as the ICSU/CODATA, the OECD and the European Union are strong supporters of open access to and re-use of publicly funded research data. This thesis focuses on the research data created by university researchers in Malaysian public universities whose research activities are funded by the Federal Government of Malaysia. Malaysia, like many countries, has not yet formulated a policy on open access to and re-use of publicly funded research data. Therefore, the aim of this thesis is to develop a policy to support the objective of enabling open access to and re-use of publicly funded research data in Malaysian public universities. Policy development is very important if the objective of enabling open access to and re-use of publicly funded research data is to be successfully achieved. In developing the policy, this thesis identifies a myriad of legal impediments arising from intellectual property rights, confidentiality, privacy and national security laws, novelty requirements in patent law and lack of a legal duty to ensure data quality. Legal impediments such as these have the effect of restricting, obstructing, hindering or slowing down the objective of enabling open access to and re-use of publicly funded research data. A key focus in the formulation of the policy was the need to resolve the various legal impediments that have been identified. This thesis analyses the existing policies and guidelines of Malaysian public universities to ascertain to what extent the legal impediments have been resolved. An international perspective is adopted by making a comparative analysis of the policies of public research funding agencies and universities in the United Kingdom, the United States and Australia to understand how they have dealt with the identified legal impediments. These countries have led the way in introducing policies which support open access to and re-use of publicly funded research data. As well as proposing a policy supporting open access to and re-use of publicly funded research data in Malaysian public universities, this thesis provides procedures for the implementation of the policy and guidelines for addressing the legal impediments to open access and re-use.

Traffic safety risks trends and patterns analysis on motorways

Crashes that occur on motorways contribute to a significant proportion (40-50%) of non-recurrent motorway congestion. Hence, reducing the frequency of crashes assist in addressing congestion issues (Meyer, 2008). Analysing traffic conditions and discovering risky traffic trends and patterns are essential basics in crash likelihood estimations studies and still require more attention and investigation. In this paper we will show, through data mining techniques, that there is a relationship between pre-crash traffic flow patterns and crash occurrence on motorways, compare them with normal traffic trends, and that this knowledge has the potentiality to improve the accuracy of existing crash likelihood estimation models, and opens the path for new development approaches. The data for the analysis was extracted from records collected between 2007 and 2009 on the Shibuya and Shinjuku lines of the Tokyo Metropolitan Expressway in Japan. The dataset includes a total of 824 rear-end and sideswipe crashes that have been matched with crashes corresponding traffic flow data using an incident detection algorithm. Traffic trends (traffic speed time series) revealed that crashes can be clustered with regards to the dominant traffic patterns prior to the crash occurrence. K-Means clustering algorithm applied to determine dominant pre-crash traffic patterns. In the first phase of this research, traffic regimes identified by analysing crashes and normal traffic situations using half an hour speed in upstream locations of crashes. Then, the second phase investigated the different combination of speed risk indicators to distinguish crashes from normal traffic situations more precisely. Five major trends have been found in the first phase of this paper for both high risk and normal conditions. The study discovered traffic regimes had differences in the speed trends. Moreover, the second phase explains that spatiotemporal difference of speed is a better risk indicator among different combinations of speed related risk indicators. Based on these findings, crash likelihood estimation models can be fine-tuned to increase accuracy of estimations and minimize false alarms.

Changes of mortality and causes of death from 1970 to 2005 and decomposition analysis in Shandong province [山东省1970-2005年人群死亡率极死因变化与差别分解分析]

Objective To describe the trend of overall mortality and major causes of death in Shandong population from 1970 to 2005,and to quantitatively estimate the influential factors. Methods Trends of overall mortality and major causes of death were described using indicators such as mortality rates and age-adjusted death rates by comparing three large-scale mortality surveys in Shandong province. Difference decomposing method was applied to estimate the contribution of demographic and non-demographic factors for the change of mortality. Results The total mortality had had a slight change since 1970s,but had increased since 1990s.However,both the mortality rates of age-adjusted and age-specific decreased significantly. The mortality of Group Ⅰ diseases including infectious diseases as well maternal and perinatal diseases decreased drastically. By contrast, the mortality of non-communicable chronic diseases (NCDs)including cardiovascular diseases(CVDs),cancer and injuries increased. The sustentation of recent overall mortality was caused by the interaction of demographic and non-demographic factors which worked oppositely. Non-demographic factors were responsible for the decrease of Group Ⅰ disease and the increase of injuries. With respect to the increase of NCDs as a whole. Demographic factors might take the full responsibility and the non-demographic factors were the opposite force to reduce the mortality. Nevertheless, for the increase of some leading NCD diseases as CVDs and cancer, the increase was mainly due to non-demographic rather than demographic factors. Conclusion Through the interaction of the aggravation of ageing population and the enhancement of non-demographic effect, the overall mortality in Shandong would maintain a balance or slightly rise in the coming years. Group Ⅰ diseases in Shandong had been effectively under control. Strategies focusing on disease control and prevention should be transferred to chronic diseases, especially leading NCDs, such as CVDs and cancer.

Interventions for increasing ankle joint dorsiflexion : a systematic review and meta-analysis

BACKGROUND: Ankle joint equinus, or restricted dorsiflexion range of motion (ROM), has been linked to a range of pathologies of relevance to clinical practitioners. This systematic review and meta-analysis investigated the effects of conservative interventions on ankle joint ROM in healthy individuals and athletic populations. METHODS: Keyword searches of Embase Medline Cochrane and CINAHL databases were performed with the final search being run in August 2013. Studies were eligible for inclusion if they assessed the effect of a non-surgical intervention on ankle joint dorsiflexion in healthy populations. Studies were quality rated using a standard quality assessment scale. Standardised mean differences (SMDs) and 95% confidence intervals (CIs) were calculated and results were pooled where study methods were homogenous. RESULTS: Twenty-three studies met eligibility criteria, with a total of 734 study participants. Results suggest that there is some evidence to support the efficacy of static stretching alone (SMDs: range 0.70 to 1.69) and static stretching in combination with ultrasound (SMDs: range 0.91 to 0.95), diathermy (SMD 1.12), diathermy and ice (SMD 1.16), heel raise exercises (SMDs: range 0.70 to 0.77), superficial moist heat (SMDs: range 0.65 to 0.84) and warm up (SMD 0.87) in improving ankle joint dorsiflexion ROM. CONCLUSIONS: Some evidence exists to support the efficacy of stretching alone and stretching in combination with other therapies in increasing ankle joint ROM in healthy individuals. There is a paucity of quality evidence to support the efficacy of other non-surgical interventions, thus further research in this area is warranted.

Postoperative chemotherapy for non-small cell lung cancer : a systematic review and meta-analysis

Background Postoperative chemotherapy is currently not recommended for resected non-small cell lung cancer in many countries and centers. Recently, results of several large randomized clinical trials were reported with conflicting evidence. Accordingly, we sought to determine whether postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Methods Randomized clinical trials with cisplatin- or uracil plus ftorafur-containing regimens were included and evaluated separately. A systematic review that included randomized clinical trials performed before 1995 was identified and found to be of adequate quality. Further randomized controlled trials were identified by searching MEDLINE, EMBASE, and the Cochrane Controlled Trials Register from 1995 through 2004. In addition, the reference lists of articles and conference abstracts were searched. The logarithm of the hazard ratio and its standard error were calculated, and a fixed-effect model was used to combine the estimates. Results There were 7200 patients enrolled in 19 trials included in the analyses. An overall estimate of 13% relative reduction in mortality (95% confidence interval, 7%-19%) was found. There was 11% relative reduction in mortality associated with postoperative cisplatin (95% confidence interval, 4%-18%; P = .004) and 17% associated with uracil plus ftorafur (95% confidence interval, 5%-27%; P = .006) compared with that after surgical intervention alone. This means that there would be an additional survivor at 5 years for 25 patients treated with cisplatin or for 30 patients treated with uracil plus ftorafur. Conclusions Postoperative chemotherapy is associated with improved survival compared with that after surgical intervention alone. Selected patients with completely resected non-small cell lung cancer should be offered chemotherapy. Copyright © 2004 by The American Association for Thoracic Surgery.

Biomechanical characteristics of peripheral diabetic neuropathy : a systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

Background: Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Methods: Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Findings: Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes.; Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.

Incidence of unilateral arm lymphoedema after breast cancer : a systematic review and meta-analysis

Background The body of evidence related to breast-cancer-related lymphoedema incidence and risk factors has substantially grown and improved in quality over the past decade. We assessed the incidence of unilateral arm lymphoedema after breast cancer and explored the evidence available for lymphoedema risk factors. Methods We searched Academic Search Elite, Cumulative Index to Nursing and Allied Health, Cochrane Central Register of Controlled Trials (clinical trials), and Medline for research articles that assessed the incidence or prevalence of, or risk factors for, arm lymphoedema after breast cancer, published between January 1, 2000, and June 30, 2012. We extracted incidence data and calculated corresponding exact binomial 95% CIs. We used random effects models to calculate a pooled overall estimate of lymphoedema incidence, with subgroup analyses to assess the effect of different study designs, countries of study origin, diagnostic methods, time since diagnosis, and extent of axillary surgery. We assessed risk factors and collated them into four levels of evidence, depending on consistency of findings and quality and quantity of studies contributing to findings. Findings 72 studies met the inclusion criteria for the assessment of lymphoedema incidence, giving a pooled estimate of 16·6% (95% CI 13·6–20·2). Our estimate was 21·4% (14·9–29·8) when restricted to data from prospective cohort studies (30 studies). The incidence of arm lymphoedema seemed to increase up to 2 years after diagnosis or surgery of breast cancer (24 studies with time since diagnosis or surgery of 12 to <24 months; 18·9%, 14·2–24·7), was highest when assessed by more than one diagnostic method (nine studies; 28·2%, 11·8–53·5), and was about four times higher in women who had an axillary-lymph-node dissection (18 studies; 19·9%, 13·5–28·2) than it was in those who had sentinel-node biopsy (18 studies; 5·6%, 6·1–7·9). 29 studies met the inclusion criteria for the assessment of risk factors. Risk factors that had a strong level of evidence were extensive surgery (ie, axillary-lymph-node dissection, greater number of lymph nodes dissected, mastectomy) and being overweight or obese. Interpretation Our findings suggest that more than one in five women who survive breast cancer will develop arm lymphoedema. A clear need exists for improved understanding of contributing risk factors, as well as of prevention and management strategies to reduce the individual and public health burden of this disabling and distressing disorder.

Internet-enabled tourism entrepreneurs. International entrepreneurial values elicited through repertory test and laddering analysis

Although the tourism industry has been dramatically altered due to the Internet, there has been limited research published about international entrepreneurial values and Internet use in tourism firms. The findings of this study point to a relationship between the values of Internet-enabled international entrepreneurs in small-sized to medium-sized enterprises and the inclination of the firm to develop and initiate international activity. The findings of this study suggest that Internet-enabled tourism entrepreneurs share similar construct values. Two effective but underutilized qualitative methods were used in this study. The first method, repertory test, is an efficient technique for exploring constructs in decision making; the second method, laddering analysis, facilitates understanding of the perceived consequences and personal values guiding behaviour.

Prevention and treatment of acute radiation-induced skin reactions : a systematic review and meta-analysis of randomized controlled trials

Background Radiation-induced skin reaction (RISR) is a common side effect that affects the majority of cancer patients receiving radiation treatment. RISR is often characterised by swelling,redness, pigmentation, fibrosis, and ulceration, pain, warmth, burning, and itching of the skin. The aim of this systematic review was to assess the effects of interventions which aim to prevent or manage RISR in people with cancer. Methods We searched the following databases up to November 2012: Cochrane Skin Group Specialised Register, CENTRAL (2012, Issue 11), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), CINAHL (from 1981) and LILACS (from 1982). Randomized controlled trials evaluating interventions for preventing or managing RISR in cancer patients were included. The primary outcomes were development of RISR, and levels of RISR and symptom severity. Secondary outcomes were time taken to develop erythema or dry desquamation; quality of life; time taken to heal, a number of skin reaction and symptom severity measures; cost, participant satisfaction; ease of use and adverse effects. Where appropriate, we pooled results of randomized controlled trials using mean differences (MD) or odd ratios (OR) with 95% confidence intervals (CI). Results Forty-seven studies were included in this review. These evaluated six types of interventions (oral systemic medications; skin care practices; steroidal topical therapies; non-steroidal topical therapies; dressings and other). Findings from two meta-analyses demonstrated significant benefits of oral Wobe-Mugos E for preventing RISR (OR 0.13 (95% CI 0.05 to 0.38)) and limiting the maximal level of RISR (MD −0.92 (95% CI −1.36 to −0.48)). Another meta-analysis reported that wearing deodorant does not influence the development of RISR (OR 0.80 (95% CI 0.47 to 1.37)). Conclusions Despite the high number of trials in this area, there is limited good, comparative research that provides definitive results suggesting the effectiveness of any single intervention for reducing RISR. More research is required to demonstrate the usefulness of a wide range of products that are being used for reducing RISR. Future efforts for reducing RISR severity should focus on promising interventions, such as Wobe-Mugos E and oral zinc.

A simulation-based large deflection and inelastic analysis of steel frames under fire

This paper presents an accurate and robust geometric and material nonlinear formulation to predict structural behaviour of unprotected steel members at elevated temperatures. A fire analysis including large displacement effects for frame structures is presented. This finite element formulation of beam-column elements is based on the plastic hinge approach to model the elasto-plastic strain-hardening material behaviour. The Newton-Raphson method allowing for the thermal-time dependent effect was employed for the solution of the non-linear governing equations for large deflection in thermal history. A combined incremental and total formulation for determining member resistance is employed in this nonlinear solution procedure for the efficient modeling of nonlinear effects. Degradation of material strength with increasing temperature is simulated by a set of temperature-stress-strain curves according to both ECCS and BS5950 Part 8, which implicitly allows for creep deformation. The effects of uniform or non-uniform temperature distribution over the section of the structural steel member are also considered. Several numerical and experimental verifications are presented.