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.

Team change climate : a group-level analysis of the relationships among change information and change participation, role stressors, and well-being

We explored whether teams develop shared perceptions regarding the quantity and quality of information and the extent of participation in decision making provided in an environment of continuous change. In addition, we examined whether change climate strength moderated relationships between change climate level and team outcomes. We examined relationships among aggregated change information and change participation and aggregated team outcomes, including two role stressors (i.e., role ambiguity and role overload) and two indicators of well-being (i.e., quality of worklife and distress). Questionnaires were distributed in an Australian law enforcement agency and data were used from 178 teams. Structural equation modelling analyses, controlling for a marker variable, were conducted to examine the main effects of aggregated change information and aggregated change participation on aggregated team outcomes. Results provided support for a model that included method effects due to a marker variable. In this model, change information climate was significantly negatively associated with role ambiguity, role overload, and distress, and significantly positively associated with quality of worklife. Change participation climate was significantly positively associated with quality of worklife. Change climate strength did not moderate relationships among change climate level and team outcomes.

The relevance of shared experiences : a multi-level study of collective efficacy as a moderator of job control in the stressor-strain relationship

Karasek's Job Demand-Control model proposes that control mitigates the positive effects of work stressors on employee strain. Evidence to date remains mixed and, although a number of individual-level moderators have been examined, the role of broader, contextual, group factors has been largely overlooked. In this study, the extent to which control buffered or exacerbated the effects of demands on strain at the individual level was hypothesized to be influenced by perceptions of collective efficacy at the group level. Data from 544 employees in Australian organizations, nested within 23 workgroups, revealed significant three-way cross-level interactions among demands, control and collective efficacy on anxiety and job satisfaction. When the group perceived high levels of collective efficacy, high control buffered the negative consequences of high demands on anxiety and satisfaction. Conversely, when the group perceived low levels of collective efficacy, high control exacerbated the negative consequences of high demands on anxiety, but not satisfaction. In addition, a stress-exacerbating effect for high demands on anxiety and satisfaction was found when there was a mismatch between collective efficacy and control (i.e. combined high collective efficacy and low control). These results provide support for the notion that the stressor-strain relationship is moderated by both individual- and group-level factors.

Self-labelling versus behavioural experience of workplace bullying : differences in sector- and industry-level prevalence and sources

This study reports on differences in self-labelling versus the behavioural experience of workplace bullying across sectors and industries for a sample of 6,406 Australian employees, as well as differences in source of workplace bullying. It was found that overall prevalence rates of workplace bullying were 2.9% (self-labelling method) and 4.0% (behavioural experience method). Exposure to workplace bullying was found to decrease with age. There was no significant difference between the public and private sectors, or among industries, in the prevalence of workplace bullying; however, two industries (Construction; Health and Community Services) showed a significantly higher rate of workplace bullying with the behavioural experience method compared to the self-labelling method. For the overall sample, the most prevalent source of workplace bullying was reported to be coworkers (49.1%), followed by clients (35.7%), and then supervisors (27.4%). Subordinates were rated as the source in 7.9% of cases. Closer examination of source as a function of sector and industry revealed a number of significant differences specific to sectors and industries, highlighting the need for tailored approaches for managing workplace bullying.

Polysubstance use in cannabis users referred for treatment: drug use profiles, psychiatric comorbidity and cannabis-related beliefs

Background: Population-based surveys demonstrate cannabis users are more likely to use both illicit and licit substances, compared with non-cannabis users. Few studies have examined the substance use profiles of cannabis users referred for treatment. Co-existing mental health symptoms and underlying cannabis-related beliefs associated with these profiles remains unexplored. Methods: Comprehensive drug use and dependence severity (Severity of Dependence Scale-Cannabis) data were collected on a sample of 826 cannabis users referred for treatment. Patients completed the General Health Questionnaire, Cannabis Expectancy Questionnaire, Cannabis Refusal Self-Efficacy Questionnaire, and Positive Symptoms and Manic-Excitement subscales of the Brief Psychiatric Rating Scale. Latent class analysis was performed on last month use of drugs to identify patterns of multiple drug use. Mental health comorbidity and cannabis beliefs were examined by identified drug use pattern. Results: A three-class solution provided the best fit to the data: (1) cannabis and tobacco users (n = 176), (2) cannabis, tobacco, and alcohol users (n = 498), and (3) wide-ranging sub- stance users (n = 132). Wide-ranging substance users (3) reported higher levels of cannabis dependence severity, negative cannabis expectancies, lower opportunistic, and emotional relief self-efficacy, higher levels of depression and anxiety and higher manic-excitement and positive psychotic symptoms. Conclusion: In a sample of cannabis users referred for treatment, wide-ranging substance use was associated with elevated risk on measures of cannabis dependence, co-morbid psychopathology, and dysfunctional cannabis cognitions. These findings have implications for cognitive-behavioral assessment and treatment.

National and state-level politics on social media : Twitter, Australian political discussions, and the online commentariat

This paper examines the use of Twitter for long-term discussions around Australian politics, at national and state levels, tracking two hashtags during 2012: #auspol, denoting national political topics, and #wapol, which provides a case study of state politics (representing Western Australia). The long-term data collection provides the opportunity to analyse how the Twitter audience responds to Australian politics: which themes attract the most attention and which accounts act as focal points for these discussions. The paper highlights differences in the coverage of state and national politics. For #auspol, a small number of accounts are responsible for the majority of tweets, with politicians invoked but not directly contributing to the discussion. In contrast, #wapol stimulates a much lower level of tweeting. This example also demonstrates that, in addition to citizen accounts, traditional participants within political debate, such as politicians and journalists, are among the active contributors to state-oriented discussions on Twitter.

Preclinical drug development must consider the impact on metastasis

Recently, two landmark reports on antiangiogenic therapy were published: Paez-Ribes and colleagues and Ebos and colleagues . The Board of the Metastasis Research Society (MRS) congratulates the authors for their informative articles that help to explain the puzzle of why antiangiogenic agents have had a relatively minor or no significant impact on patient survival. Using four model systems and several different strategies, these researchers showed that inhibition of angiogenesis reduced primary tumor growth and microvessel density in keeping with many earlier reports, but strikingly, accelerated invasion and metastasis.

Smart resource control in distribution network to improve the integration level of PV

This project was an innovative approach in developing smart coordination of available energy resources to improve the integration level of PV in distribution network. Voltage and loading issues are considered as the main concerns for future electricity grid which need to be avoided using such resources. A distributed control structure was proposed for the resources in distribution network to avoid noted power quality issues.

Diode-clamped three-level inverter-based battery/supercapacitor direct integration scheme for renewable energy systems

This paper describes a diode-clamped three-level inverter-based battery/supercapacitor direct integration scheme for renewable energy systems. The study is carried out for three different cases. In the first case, one of the two dc-link capacitors of the inverter is replaced by a battery bank and the other by a supercapacitor bank. In the second case, dc-link capacitors are replaced by two battery banks. In the third case, ordinary dc-link capacitors are replaced by two supercapacitor banks. The first system is supposed to mitigate both long-term and short-term power fluctuations while the last two systems are intended for smoothening long-term and short-term power fluctuations, respectively. These topologies eliminate the need for interfacing dc-dc converters and thus considerably improve the overall system efficiency. The major issue in aforementioned systems is the unavoidable imbalance in dc-link voltages. An analysis on the effects of unbalance and a space vector modulation method, which can produce undistorted current even in the presence of such unbalances, are presented in this paper. Furthermore, small vector selection-based power sharing and state of charge balancing techniques are proposed. Experimental results, obtained from a laboratory prototype, are presented to verify the efficacy of the proposed modulation and control techniques.

Role of intratumoural heterogeneity in cancer drug resistance : molecular and clinical perspectives

Drug resistance continues to be a major barrier to the delivery of curative therapies in cancer. Historically, drug resistance has been associated with over-expression of drug transporters, changes in drug kinetics or amplification of drug targets. However, the emergence of resistance in patients treated with new-targeted therapies has provided new insight into the complexities underlying cancer drug resistance. Recent data now implicate intratumoural heterogeneity as a major driver of drug resistance. Single cell sequencing studies that identified multiple genetically distinct variants within human tumours clearly demonstrate the heterogeneous nature of human tumours. The major contributors to intratumoural heterogeneity are (i) genetic variation, (ii) stochastic processes, (iii) the microenvironment and (iv) cell and tissue plasticity. Each of these factors impacts on drug sensitivity. To deliver curative therapies to patients, modification of current therapeutic strategies to include methods that estimate intratumoural heterogeneity and plasticity will be essential.

Five-level Z-source diode-clamped inverter

This study proposes a five-level Z-source diode-clamped inverter designed with two intermediate Z-source networks connected between the dc input sources and rear-end inverter circuitry. By partially shorting the Z-source networks, new operating states not previously reported for two-level Z-source inverter are introduced here for operating the proposed inverter with voltage buck-boost energy conversion ability and five-level phase voltage switching. These characteristic features are in fact always ensured at the inverter terminal output by simply adopting a properly designed carrier modulation scheme, which always inserts two partial shoot-through states per half carrier cycle for smooth balanced operation. Theoretical findings and practical issues identified are eventually verified by constructing a scaled down laboratory prototype for testing.

Five-level current-source inverters with buck-boost and inductive-current balancing capabilities

This paper presents new five-level current-source inverters (CSIs) with voltage/current buck-boost capability, unlike existing five-level CSIs where only voltage-boost operation is supported. The proposed inverters attain self-inductive-current-balancing per switching cycle at their dc front ends without having to include additional balancing hardware or complex control manipulation. The inverters can conveniently be controlled by using the well-established phase-shifted carrier modulation scheme with only two additional linear references and a mapping logic table needed. Existing modulators can therefore be conveniently retrofitted for controlling the presented inverters. By appropriately coordinating the inverter gating signals, their implementations can be realized by using the least number of components without degrading performance. These enhanced features of the inverters have already been verified in simulation and experimentally using a scaled-down laboratory platform.

High level of MT-MMP expression is associated with invasiveness of cervical cancer cells

MMP-2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo. It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane-associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF-β, but its physiological regulation is still largely unresolved. MT-MMP was recently discovered and described as a potential gelatinase-A activator. In the present study, we investigated the expression of MT-MMP (membrane-type metalloproteinase) in cervical cancer cells both in vitro and in vivo. Comparing several in vitro-transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT-MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP expression in invasive cervical carcinoma and lymphnode metastases compared to its expression in non-invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT-MMP. Taken together, our results clearly correlated high level MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a crucial role in cervical tumor invasion.

Low-cost railway level crossings - breaking down the barriers

Level crossing risk continues to be a significant safety concern for the security of rail operations around the world. Over the last decade or so, a third of railway related fatalities occurred as a direct result of collisions between road and rail vehicles in Australia. Importantly, nearly half of these collisions occurred at railway level crossings with no active protection, such as flashing lights or boom barriers. Current practice is to upgrade level crossings that have no active protection. However, the total number of level crossings found across Australia exceed 23,500, and targeting the proportion of these that are considered high risk (e.g. public crossings with passive controls) would cost in excess of AU$3.25 billion based on equipment, installation and commissioning costs of warning devices that are currently type approved. Level crossing warning devices that are low-cost provide a potentially effective control for reducing risk; however, over the last decade, there have been significant barriers and legal issues in both Australia and the US that have foreshadowed their adoption. These devices are designed to have significantly lower lifecycle costs compared with traditional warning devices. They often make use of use of alternative technologies for train detection, wireless connectivity and solar energy supply. This paper describes the barriers that have been encountered for the adoption of these devices in Australia, including the challenges associated with: (1) determining requisite safety levels for such devices; (2) legal issues relating to duty of care obligations of railway operators; and (3) issues of Tort liability around the use of less than fail-safe equipment. This paper provides an overview of a comprehensive safety justification that was developed as part of a project funded by a collaborative rail research initiative established by the Australian government, and describes the conceptual framework and processes being used to justify its adoption. The paper provides a summary of key points from peer review and discusses prospective barriers that may need to be overcome for future adoption. A successful outcome from this process would result in the development of a guideline for decision-making, providing a precedence for adopting low-cost level crossing warning devices in other parts of the world. The framework described in this paper also provides relevance to the review and adoption of analogous technologies in rail and other safety critical industries.