Mass spectrometry-based metabolomics towards understanding of gene functions with a diversity of biological contexts

Currently, mass spectrometry-based metabolomics studies extend beyond conventional chemical categorization and metabolic phenotype analysis to understanding gene function in various biological contexts (e.g., mammalian, plant, and microbial). These novel utilities have led to many innovative discoveries in the following areas: disease pathogenesis, therapeutic pathway or target identification, the biochemistry of animal and plant physiological and pathological activities in response to diverse stimuli, and molecular signatures of host-pathogen interactions during microbial infection. In this review, we critically evaluate the representative applications of mass spectrometry-based metabolomics to better understand gene function in diverse biological contexts, with special emphasis on working principles, study protocols, and possible future development of this technique. Collectively, this review raises awareness within the biomedical community of the scientific value and applicability of mass spectrometry-based metabolomics strategies to better understand gene function, thus advancing this application's utility in a broad range of biological fields

Pharmacokinetics-based elucidation on disparity in clinical effectiveness between varieties of Zhi Zhu Wan, a traditional Chinese medical formula

AIM: Zhi Zhu Wan (ZZW) is a classical Chinese medical formulation used for the treatment of functional dyspepsia that attributed to Spleen-deficiency Syndrome. ZZW contains Atractylodes Rhizome and Fructus Citrus Immaturus, the later originates from both Citrus aurantium L. (BZZW) and Citrus sinensis Osbeck (RZZW). The present study is designed to elucidate disparities in the clinical efficacy of two ZZW varieties based on the pharmacokinetics of naringenin and hesperetin. MEHTOD: After oral administration of ZZWs, blood sample was collected from healthy volunteers at designed time points. Naringenin and hesperetin were detected in plasma by RP-HPLC, pharmacokinetic parameters were processed using mode-independent methods with WINNONLIN. RESULTS: After oral administration of BZZW, both naringenin and hesperetin were detected in plasma, and demonstrated similar pharmacokinetic parameters. Ka was 0.384+/-0.165 and 0.401+/-0.159, T(1/2(ke))(h) was 5.491+/-3.926 and 5.824+/-3.067, the AUC (mg/Lh) was 34.886+/-22.199 and 39.407+/-19.535 for naringenin and hesperetin, respectively. However, in the case of RZZW, only hesperetin was found in plasma, but the pharmacokinetic properties for hesperetin in RZZW was different from that in BZZW. T(max) for hesperetin in RZZW is about 8.515h, and its C(max) is much larger than that of BZZW. Moreover, it was eliminated slowly as it possessed a much larger AUC value. CONCLUSION: The distinct therapeutic orientations of the Chinese medical formula ZZWs with different Fructus Citrus Immaturus could be elucidated based on the pharmacokinetic parameters of constituents after oral administration.

European and Polynesian admixture in the Norfolk Island population

The Norfolk Island population in the South Pacific is primarily the product of recent admixture between a small number of British male and Polynesian female founders. We identified and genotyped 128 Ancestry Informative Markers (AIMs) spread across the autosomes, X/Y chromosomes and mitochondrial DNA genome, to explore and quantify the current levels of genetic admixture in the Norfolk Islanders. On the basis of autosomal AIMs, the population shows mean European and Polynesian ancestry proportions of 88 and 12%, respectively. However, there is a substantial variation between individuals ranging from total European ancestry to near total Polynesian origin. There is a strong correlation between individual genetic estimates of Polynesian ancestry and those derived from the extensive pedigree and genealogical records of Islanders. Also in line with historical accounts, there is a substantial asymmetry in the maternal and paternal origins of the Islanders with almost all Y-chromosomes of European origin whereas at least 25% of mtDNAs appear to have a Polynesian origin. Accurate knowledge of ancestry will be important in future attempts to use the Island population in admixture mapping approaches to find the genes that underlie differences in the risk to some diseases between Europeans and Polynesians.

High efficiency auxiliary power converters

The auxiliary load DC-DC converters of the Sunshark solar car have never been examined. An analysis of the current design reveals it is complicated, and inefficient. Some simple measures to greatly improve the efficiency are present which will achieve an overall worthwhile power saving. Two switch-mode power supply DC-DC converter designs are presented. One is a constant current supply for the LED brake and turn indicators, which allows them to be powered directly from the main DC bus, and switched only as necessary. The second is a low power flyback converter, which employs synchronous rectification among other techniques to achieve good efficiency and regulation over a large range of output powers. Practical results from both converters, and an indication of the overall improvement in system efficiency will be offered.

Inpatients had mostly negative experiences of seclusion during short term treatment in a mental health facility

Design Semi-structured interviews. Setting 2 open, acute care units of a large tertiary mental health facility in Queensland, Australia. Patients 12 patients (58% men) who were 18–52 years of age and were secluded in the previous 7 days (mean duration 3.4 h). Methods Semi-structured, thematically organised interviews were audiotaped and transcribed. Transcripts were checked for errors against the audiotaped versions and were analysed using the process of meaning categorisation. Themes were identified and coded to produce categories. All members of the research team agreed on the final categorisations. These broad categories were further analysed, and themes were used to reflect patients' experiences of seclusion. Main findings 5 recurrent themes emerged. (1) Patients described the use of seclusion. Some patients thought that seclusion was used inappropriately and that the seclusion period was of more benefit to …

Anodic formation of a thick three-dimensional nanoporous WO3 film and its photocatalytic property

We report an efficient solar-light-driven photocatalyst based on three-dimensional nanoporous tungsten trioxide (WO3) films. These films are obtained by anodizing W foils in fluoride-containing electrolytes at room temperature and under low applied voltages with an efficient growth rate of 2 μm h− 1. The maximum thickness of the films is ~ 3 μm that exceeds those of previously reported anodized WO3 films in fluoride-containing electrolytes. By investigating the photocatalytic properties of the films with thicknesses ranging from ~ 0.5 to ~ 3 μm, the optimum thickness of the nanoporous film is found to be ~ 1 μm, which demonstrates an impressive 120% improvement in the photocatalytic performance compared to that of a RF-sputtered nanotextured film with similar weights. We mainly ascribe this to large surface area and smaller bandgap.

Retaining rural and remote area nurses : The Queensland, Australia experience

Because higher-than-average turnover rates for nurses who work in remote and rural areas are the norm, the authors conducted a study to identify professional and personal factors that influenced rural nurses’ decisions to resign. Using a mail survey, the authors gathered qualitative and quantitative data from nurses who had resigned from rural and remote areas in Queensland, Australia. Their findings, categorized into professional and rural influences, highlight the importance of work force planning strategies that capitalize on the positive aspects of rural and remote area practice, to retain nurses in nonmetropolitan areas.

V: Rewriting and reclaiming history : an analysis of the emergence of restorative justice in western criminal justice systems

During the last three decades, restorative justice has emerged in numerous localities around the world as an accepted approach to responding to crime. This article, which stems from a doctoral study on the history of restorative justice, provides a critical analysis of accepted histories of restorative practices. It revisits the celebrated historical texts of the restorative justice movement, and re-evaluates their contribution to the emergence of restorative justice measures. It traces the emergence of the term 'restorative justice', and reveals that it emerged in much earlier writings than is commonly thought to be the case by scholars in the restorative justice field. It also briefly considers some 'power struggles' in relation to producing an accepted version of the history of restorative justice, and scholars' attempts to 'rewrite history' to align with current views on restorative justice. Finally, this article argues that some histories of restorative justice selectively and inaccurately portray key figures from the history of criminology as restorative justice supporters. This, it is argued, gives restorative justice a false lineage and operates to legitimise the widespread adoption of restorative justice around the globe.

The “Engineers without Borders” Challenge : does it engage Australian and New Zealand students with sustainability?

This paper explores the rationale, experience and impact of thirteen Australia and New Zealand universities that have integrated the Engineers Without Borders (EWB) challenge into their first year engineering curriculum. EWB is a national competition for university students, who work in teams to develop conceptual designs for real sustainable development projects across the globe. This project investigated “what works and what doesn’t” in engineering curriculum renewal, utilising content analysis, multiple in-depth interviews with students and staff (coordinators, lecturers, tutors) and observation. EWB comprises between 25 to 100% of the total assessment items. This paper specifically focuses on student’s experience of EWB, documenting how the project teaches sustainability and systems-thinking approaches, engages students with different cultures, and fosters teamwork, new ways of thinking and communication skills. We identify key benefits and challenges of EWB, as well as mechanisms and contexts that foster student engagement and learning outcomes.

Response to chemotherapy is predictive in relation to longer overall survival in an individual patient combined-analysis with pleural mesothelioma

Background: There is currently no early predictive marker of survival for patients receiving chemotherapy for malignant pleural mesothelioma (MPM). Tumour response may be predictive for overall survival (OS), though this has not been explored. We have thus undertaken a combined-analysis of OS, from a 42 day landmark, of 526 patients receiving systemic therapy for MPM. We also validate published progression-free survival rates (PFSRs) and a progression-free survival (PFS) prognostic-index model. Methods: Analyses included nine MPM clinical trials incorporating six European Organisation for Research and Treatment of Cancer (EORTC) studies. Analysis of OS from landmark (from day 42 post-treatment) was considered regarding tumour response. PFSR analysis data included six non-EORTC MPM clinical trials. Prognostic index validation was performed on one non-EORTC data-set, with available survival data. Results: Median OS, from landmark, of patients with partial response (PR) was 12·8 months, stable disease (SD), 9·4 months and progressive disease (PD), 3·4 months. Both PR and SD were associated with longer OS from landmark compared with disease progression (both p < 0·0001). PFSRs for platinum-based combination therapies were consistent with published significant clinical activity ranges. Effective separation between PFS and OS curves provided a validation of the EORTC prognostic model, based on histology, stage and performance status. Conclusion: Response to chemotherapy is associated with significantly longer OS from landmark in patients with MPM. © 2012 Elsevier Ltd. All rights reserved.

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy : a subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit. Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033). Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Measuring Nutrition Work Across Queensland

The public health and community nutrition workforce in Queensland has experienced significant change. These changes happened following a new government in 2012, and its response to the National Health and Hospitals Reform and budget constraints. This research documented and analysed current roles and activities of the preventative health nutrition workforce. An online survey was conducted with all positions known to be working in nutrition prevention (n=320). The sample population was generated using existing databases which were validated by comparisons with workforce data from the Queensland Health Department and sector consultation. Snowballing was also used. 128 practitioners responded to the survey (response rate =40%). This was made up of those whose job title included the words “nutritionist” or “dietitian” (n=64) and those whose job title did not (n=61). Three respondents did not supply a title. Ninety-four practitioners had a nutrition or dietetic qualification indicating that a number of the workforce have shifted to more generalist positions. Between 2009 and 2013 there has been a 90% reduction in the state-funded nutrition prevention workforce. The existing reduced workforce is now dispersed across a range of organisations. Areas of workforce growth such as Medicare Locals tend to attract less experienced practitioners (50% had ≤ 5years’ experience). These changes present challenges for the co-ordination and communication of nutrition work and equity and access of service delivery. This research highlights the need for adaptability of the public health and community nutrition workforce. These issues require consideration by the profession.

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.

The landlord's duty and unsafe premises

Case note on Sheehy v Hobbs [2012]. It is well established that a landlord owes a tenant a duty of care to “take reasonable care to avoid foreseeable risk of injury to their prospective tenants and members of their household”.1 What often arises is the question of how far the scope of that duty extends. In Sheehy v Hobbs [2012] QSC 333 the plaintiff was injured when she fell down a flight of internal stairs of the townhouse she leased from the defendants. The plaintiff claimed damages for a breach of duty owed to her in negligence, and also alleged breaches of the duties owed to her pursuant to s 103 of the Residential Tenancies Act 1994 (Qld) and her tenancy agreement.

Fetuin-A : a major fetal serum protein that promotes "wound closure" and scarless healing [Letter to the Editor]

Burn-wound healing is a dynamic, interactive process involving a number of cellular and molecular events and is characterized by inflammation, granulation tissue formation, re-epithelialization, and tissue remodeling (Greenhalgh, 2002; Linares, 2002). Unlike incisional-wound healing, it also requires extensive re-epithelialization due to a predominant horizontal loss of tissue and often heals with abnormal scarring when burns involve deep dermis. The early mammalian fetus has the remarkable ability to regenerate normal epidermis and dermis and to heal dermal incisional wounds with no signs of scarring. Extensive research has indicated that scarless healing appears to be intrinsic to fetal skin (McCallion and Ferguson, 1996; Ferguson and O’Kane, 2004). Previously, we reported a fetal burn model, in which 80-day-old ovine fetuses (gestation¼ 145–153 days) healed deep dermal partial thickness burns without scars, whereas postnatal lambs healed equal depth burns with significant scarring (Cuttle et al., 2005; Fraser et al., 2005). This burn model provided early evidence that fetal skin has the capacity to repair and restore dermal horizontal loss, not just vertical injuries.