Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

Background The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry. Objectives To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009. Selection criteria All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow). Data collection and analysis Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one. Main results Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day). Authors' conclusions Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the six studies and found only modest benefit at best and potentially higher doses of inhaled corticosteroids in children. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids cannot be routinely recommended for clinical practice at this stage and remains uncertain.

Review : "Genetic Privacy: A challenge to Medico-Legal Norms" by Laurie, G

The discovery by Watson and Crick of the structure of DNA is one of the great scientific discoveries. In the period since that discovery new areas of genetic research have opened up which hold out the hope of developing treatments or cures for many illnesses and diseases. Yet with these discoveries have also come an array of ethical and legal dilemmas about the use of genetic information and concerns about the potential for those with genetic diseases or conditions to be stigmatised and discriminated against. The discussion about the developments in genetic science has become increasingly, a debate about the use of genetic information within our society. Graeme Laurie’s book, Genetic Privacy: A Challenge to Medico-Legal Norms, guides the reader through the complexities of these debates by considering what we mean by privacy and asking whether our existing concepts are adequate to meet the challenges posed by the new genetics.

Synthesis of MgB2 at low temperature and autogenous pressure

High quality, micron-sized interpenetrating grains of MgB2 with high density are produced at low temperatures (~420oC < T < ~500oC) under autogenous pressure by pre-mixing Mg powder and NaBH4 and heating in an Inconel 601 alloy reactor for 5−15 hours. Optimum production of MgB2 with yields greater than 75% occurs for autogenous pressure in the range 1.0 MPa to 2.0 MPa with the reactor at ~500oC. Autogenous pressure is induced by the decomposition of NaBH4 in the presence of Mg and/or other Mg-based compounds. The morphology, transition temperature and magnetic properties of MgB2 are dependent on the heating regime. Significant improvement in physical properties accrues when the reactor temperature is held at 250oC for >20minutes prior to a hold at 500oC.

An outcome evaluation of the ‘Skipper’ designated driver program

The general aim of designated driver programs is to reduce the level of drink driving by encouraging potential drink drivers to travel with a driver who has abstained from (or at least limited) consuming alcohol. Designated driver programs appear to be quite widespread around the world, however a limited number have been subject to rigorous evaluation. This paper reports results from an outcome evaluation of a designated driver program called ‘Skipper’, which was trialled in a provincial city in Queensland, Australia. The outcome evaluation included surveys three weeks prior to (baseline), four months following (1st follow-up), and 16 months following (2nd follow-up) the commencement of the trial in both the ‘intervention area’ (baseline, n = 202; 1st follow-up, n = 211; 2nd follow-up, n = 200) and a ‘comparison area’(baseline, n = 203; 1st follow-up, n = 199; 2nd follow-up, n = 201); and a comparison of random breath testing and crash data before and after the trial. The survey results indicate that awareness of the program in the intervention area was quite high four months following its introduction and that this was maintained at 16 months. The results also suggest that the ‘Skipper’ program and the related publicity had positive impacts on behaviour with an increase in the proportion of people participating in designated driver as a passenger. It is less clear, however, whether the ‘Skipper’ program impacted on other behaviours of interest, such as drink driving or involvement in alcohol-related crashes. Suggestions for further research and program improvement are discussed as well as limitations of the research.

Cravings and Expectancies

Drug-dependent individuals commonly report craving, which is an urge to consume a substance to experience pleasure or provide relief. However, the motivation to use drugs is also influenced by the expectancies we hold about drug ingestion. Drug expectancies are among a range of internal and external cues that can elicit craving. Scientific advances in the neurobiology of reward have illuminated individual differences in the neurotransmitter systems involved in associative learning that underpin drug use motivation and expectancies. We have begun to elaborate the interrelationships of these constructs and mechanisms to inform new treatments that incorporate recent models of reward learning.

Epithelial mesenchymal transition traits in human breast cancer cell lines

Epithelial mesenchymal transition (EMT) has long been associated with breast cancer cell invasiveness and evidence of EMT processes in clinical samples is growing rapidly. Genome-wide transcriptional profiling of increasingly larger numbers of human breast cancer (HBC) cell lines have confirmed the existence of a subgroup of cell lines (termed Basal B/Mesenchymal) with enhanced invasive properties and a predominantly mesenchymal gene expression signature, distinct from subgroups with predominantly luminal (termed Luminal) or mixed basal/luminal (termed Basal A) features (Neve et al Cancer Cell 2006). Studies providing molecular and cellular analyses of EMT features in these cell lines are summarised, and the expression levels of EMT-associated factors in these cell lines are analysed. Recent clinical studies supporting the presence of EMT-like changes in vivo are summarised. Human breast cancer cell lines with mesenchymal properties continue to hold out the promise of directing us towards key mechanisms at play in the metastatic dissemination of breast cancer.

Comparison of accelerometer cut points for predicting activity intensity in youth

The absence of comparative validity studies has prevented researchers from reaching consensus regarding the application of intensity-related accelerometer cut points for children and adolescents. PURPOSE This study aimed to evaluate the classification accuracy of five sets of independently developed ActiGraph cut points using energy expenditure, measured by indirect calorimetry, as a criterion reference standard. METHODS A total of 206 participants between the ages of 5 and 15 yr completed 12 standardized activity trials. Trials consisted of sedentary activities (lying down, writing, computer game), lifestyle activities (sweeping, laundry, throw and catch, aerobics, basketball), and ambulatory activities (comfortable walk, brisk walk, brisk treadmill walk, running). During each trial, participants wore an ActiGraph GT1M, and VO 2 was measured breath-by-breath using the Oxycon Mobile portable metabolic system. Physical activity intensity was estimated using five independently developed cut points: Freedson/Trost (FT), Puyau (PU), Treuth (TR), Mattocks (MT), and Evenson (EV). Classification accuracy was evaluated via weighted κ statistics and area under the receiver operating characteristic curve (ROC-AUC). RESULTS Across all four intensity levels, the EV (κ = 0.68) and FT (κ = 0.66) cut points exhibited significantly better agreement than TR (κ = 0.62), MT (κ = 0.54), and PU (κ = 0.36). The EV and FT cut points exhibited significantly better classification accuracy for moderate-to vigorous-intensity physical activity (ROC-AUC = 0.90) than TR, PU, or MT cut points (ROC-AUC = 0.77-0.85). Only the EV cut points provided acceptable classification accuracy for all four levels of physical activity intensity and performed well among children of all ages. The widely applied sedentary cut point of 100 counts per minute exhibited excellent classification accuracy (ROC-AUC = 0.90). CONCLUSIONS On the basis of these findings, we recommend that researchers use the EV ActiGraph cut points to estimate time spent in sedentary, light-, moderate-, and vigorous-intensity activity in children and adolescents. Copyright © 2011 by the American College of Sports Medicine.

Predictive validity of three ActiGraph energy expenditure equations for children

Purpose This Study evaluated the predictive validity of three previously published ActiGraph energy expenditure (EE) prediction equations developed for children and adolescents. Methods A total of 45 healthy children and adolescents (mean age: 13.7 +/- 2.6 yr) completed four 5-min activity trials (normal walking. brisk walking, easy running, and fast running) in ail indoor exercise facility. During each trial, participants were all ActiGraph accelerometer oil the right hip. EE was monitored breath by breath using the Cosmed K4b(2) portable indirect calorimetry system. Differences and associations between measured and predicted EE were assessed using dependent t-tests and Pearson correlations, respectively. Classification accuracy was assessed using percent agreement, sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. Results None of the equations accurately predicted mean energy expenditure during each of the four activity trials. Each equation, however, accurately predicted mean EE in at least one activity trial. The Puyau equation accurately predicted EE during slow walking. The Trost equation accurately predicted EE during slow running. The Freedson equation accurately predicted EE during fast running. None of the three equations accurately predicted EE during brisk walking. The equations exhibited fair to excellent classification accuracy with respect to activity intensity. with the Trost equation exhibiting the highest classification accuracy and the Puyau equation exhibiting the lowest. Conclusions These data suggest that the three accelerometer prediction equations do not accurately predict EE on a minute-by-minute basis in children and adolescents during overground walking and running. The equations maybe, however, for estimating participation in moderate and vigorous activity.

Disparate companions : tissue engineering meets cancer research

Recreating an environment that supports and promotes fundamental homeostatic mechanisms is a significant challenge in tissue engineering. Optimizing cell survival, proliferation, differentiation, apoptosis and angiogenesis, and providing suitable stromal support and signalling cues are keys to successfully generating clinically useful tissues. Interestingly, those components are often subverted in the cancer setting, where aberrant angiogenesis, cellular proliferation, cell signalling and resistance to apoptosis drive malignant growth. In contrast to tissue engineering, identifying and inhibiting those pathways is a major challenge in cancer research. The recent discovery of adult tissue-specific stem cells has had a major impact on both tissue engineering and cancer research. The unique properties of these cells and their role in tissue and organ repair and regeneration hold great potential for engineering tissue-specific constructs. The emerging body of evidence implicating stem cells and progenitor cells as the source of oncogenic transformation prompts caution when using these cells for tissue-engineering purposes. While tissue engineering and cancer research may be considered as opposed fields of research with regard to their proclaimed goals, the compelling overlap in fundamental pathways underlying these processes suggests that cross-disciplinary research will benefit both fields. In this review article, tissue engineering and cancer research are brought together and explored with regard to discoveries that may be of mutual benefit.

Sleep-related eye symptoms and their potential for identifying driver sleepiness

The majority of individuals appear to have insight into their own sleepiness, but there is some evidence that this does not hold true for all, for example treated patients with obstructive sleep apnoea. Identification of sleep-related symptoms may help drivers determine their sleepiness, eye symptoms in particular show promise. Sixteen participants completed four motorway drives on two separate occasions. Drives were completed during daytime and night-time in both a driving simulator and on the real road. Ten eye symptoms were rated at the end of each drive, and compared with driving performance and subjective and objective sleep metrics recorded during driving. ‘Eye strain’, ‘difficulty focusing’, ‘heavy eyelids’ and ‘difficulty keeping the eyes open’ were identified as the four key sleep-related eye symptoms. Drives resulting in these eye symptoms were more likely to have high subjective sleepiness and more line crossings than drives where similar eye discomfort was not reported. Furthermore, drivers having unintentional line crossings were likely to have ‘heavy eyelids’ and ‘difficulty keeping the eyes open’. Results suggest that drivers struggling to identify sleepiness could be assisted with the advice ‘stop driving if you feel sleepy and/or have heavy eyelids or difficulty keeping your eyes open’.

The Quantum Probability Ranking Principle for Information Retrieval

While the Probability Ranking Principle for Information Retrieval provides the basis for formal models, it makes a very strong assumption regarding the dependence between documents. However, it has been observed that in real situations this assumption does not always hold. In this paper we propose a reformulation of the Probability Ranking Principle based on quantum theory. Quantum probability theory naturally includes interference effects between events. We posit that this interference captures the dependency between the judgement of document relevance. The outcome is a more sophisticated principle, the Quantum Probability Ranking Principle, that provides a more sensitive ranking which caters for interference/dependence between documents’ relevance.

Predictive validity of accelerometer prediction equations for energy expenditure (EE) during overland walking and running in children and adolescents

Purpose The aim of this study was to assess the predictive validity of three accelerometer prediction equations (Freedson et aL, 1997; Trost et aL, 1998; Puyau et al., 2002) for energy expenditure (EE) during overland walking and running in children and adolescents. Methods 45 healthy children and adolescents aged 10-18 completed the following protocol, each task 5-mins in duration, with a 5-min rest period in between; walking normally; walking briskly; running easily and running fast. During each task participants wore MTI (WAM 7164) Actigraphs on the left and right hips. VO2 was monitored breath by breath using the Cosmed K4b2 portable indirect calorimetry system. For each prediction equation, difference scores were calculated as EE measured minus EE predicted. The percentage of 1-min epochs correctly categorized as light (<3 METs), moderate (3-5.9 METs), and vigorous (≥6 METS) was also calculated. Results The Freedson and Trost equations consistently overestimated MET level. The level of overestimation was statistically significant across all tasks for the Freedson equation, and was significant for only the walking tasks for the Trost equation. The Puyau equation consistently underestimated AEE with the exception of the walking normally task. In terms of categorisation, the Freedson equation (72.8% agreement) demonstrated better agreement than the Puyau (60.6%). Conclusions These data suggest that the three accelerometer prediction equations do not accurately predict EE on a minute-by-minute basis in children and adolescents during overland walking and running. However, the cut points generated by these equations maybe useful for classifying activity as either, light, moderate, or vigorous.

International hermelin brain tumor symposium on matricellular proteins in normal and cancer cell-matrix interactions

The second of the Hermelin Brain Tumor Center Symposia was held once again at Henry Ford Hospital in Detroit, Michigan on October 24th and 25th, 2003. A public conference was held on the 24th while a closed-door session took place on the 25th. The purpose of these symposia is to bring together experts in a particular field of study with the aim to share information with each other and the public, but then to meet privately to present novel data, hold discussions, and share concepts. While the interaction is intended to benefit all involved, the incentive is the expectation that the shared information will aid researchers at the Hermelin Brain Tumor Center in their quest to identify potential therapeutic targets and explore translational therapeutic strategies for the treatment of patients suffering nervous system tumors...

OCIS and Beyond: International Relations in Australia: Introduction

The Oceanic Conference for International Studies (OCIS) has grown from a small, mostly Australian and New Zealand, affair to an international biennial gathering of scholars from North America, Europe, Asia and the Pacific. Established by a small organising committee drawn from universities across Australia and New Zealand, the principal aim of OCIS was to bring together the Oceanic International Relations (IR) community in an organic and inclusive fashion. There would be no secretariat, minimal bureaucracy, costs would be kept as low as possible, and assistance provided to graduate students. The first OCIS, held at the Australian National University in 2004, proved more successful than the organisers had envisaged. The conference continued to grow at its subsequent meetings at the University of Melbourne (2006) and the University of Queensland (2008). With each conference, a new organising committee was established to take carriage of OCIS. At the 2008 meeting, the question of creating a permanent organising meeting and beginning the transition towards a professional association was discussed in detail. If the transition happens at all, it will be gradual, organic, inclusive, and will prioritise the maintenance of the sense of community OCIS has helped establish. Whilst OCIS itself has flourished, associated initiatives such as OCIS working groups and the OCIS newsletter and listserv have withered on the vine, confirming the original organising committee’s view that endeavours such as this will only prosper to the extent that they are derived and driven from the community as a whole. In 2010, OCIS will hold its first conference in New Zealand, hosted by the University of Auckland...

In conversation with the Honourable Ian Callinan AC

When, in 1977, the Australian electorate provided a double majority to effect a change of section 72 of the Commonwealth Constitution requiring judges of the High Court of Australia to retire at the age of 70 years old, I doubt we understood the continuing capacity of these esteemed members of the judiciary. For the opportunity to sit and talk with Ian Callinan AC who, in compliance with that amendment, retired from the High Court in September 2007, I needed to wait until he returned from The Hague where he was sitting as a Judge ad hoc on the International Court of Justice. Although a native of Casino, New South Wales, Mr Callinan is regarded as a Queenslander. Indeed, he grew up in Brisbane, finished high school at Brisbane Grammar and graduated in law at The University of Queensland. Appointed in 1978 as a Queen’s Counsel, Mr Callinan enjoyed this period of his legal career and we discussed an aspect of the Christopher Skase case, which reinforced my belief that Mr Callinan is an incredibly skilful advocate. On 14 September 1998, ABC Four Corners broadcasted the views of some prominent Australians on the appointment of Mr Callinan to the High Court. In assessing the type of person Mr Callinan is, Tony Morris QC said: “Ian Callinan isn't a coward”, while former Commonwealth Attorney-General, Michael Lavarch, said: “He was regarded as an absolutely outstanding criminal lawyer within the Queensland legal profession, I mean really a top-notch advocate”. I was not interested in raising any of the controversial issues that Mr Callinan has encountered as an advocate in high profile matters. I wanted to know how he felt about his time on the High Court, what his thoughts are on the operation of the High Court, the IP cases he decided, the real life issues that he feels impact on counsel who are appearing before the High Court and the people he regarded as role models. During our conversation, Mr Callinan laughed often and when he did his eyes lit up, revealing his passion for life. He is an incredibly genuine Australian who loved his time as a barrister, enjoyed his role on the High Court, enjoys his current job as mediator, loves writing novels, has a great desire for continual improvement in the quality of legal education and legal advocacy and sees a need for change in IP law. When I asked: “So, what might the future hold for you?”, he laughed and said: “Well, at my age I don’t have a long horizon time”. I said: “Just enjoy the journey?”, to which Mr Callinan responded: “Exactly”.