Selecting rainfall events for effective Water Sensitive Urban Design (WSUD) implementation

The current approach for protecting the receiving water environment from urban stormwater pollution is the adoption of structural measures commonly referred to as Water Sensitive Urban Design (WSUD). The treatment efficiency of WSUD measures closely depends on the design of the specific treatment units. As stormwater quality can be influenced by rainfall characteristics, the selection of appropriate rainfall events for treatment design is essential to ensure the effectiveness of WSUD systems. Based on extensive field investigation of four urban residential catchments and computer modelling, this paper details a technically robust approach for the selection of rainfall events for stormwater treatment design using a three-component model. The modelling outcomes indicate that selecting smaller average recurrence interval (ARI) events with high intensity-short duration as the threshold for the treatment system design is the most feasible since these events cumulatively generate a major portion of the annual pollutant load compared to the other types of rainfall events, despite producing a relatively smaller runoff volume. This implies that designs based on small and more frequent rainfall events rather than larger rainfall events would be appropriate in the context of efficiency in treatment performance, cost-effectiveness and possible savings in land area needed.

Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8+ T-cell epitopes

Post-transplantation lymphoproliferative disorders (PTLD) arise in the immunosuppressed and are frequently Epstein-Barr virus (EBV) associated. The most common PTLD histological sub-type is diffuse large B-cell lymphoma (EBV+DLBCL-PTLD). Restoration of EBV-specific T-cell immunity can induce EBV+DLBCL-PTLD regression. The most frequent B-cell lymphoma in the immunocompetent is also DLBCL. ‘EBV-positive DLBCL of the elderly’ (EBV+DLBCL) is a rare but well-recognized DLBCL entity that occurs in the overtly immunocompetent, that has an adverse outcome relative to EBV-negative DLBCL. Unlike PTLD (which is classified as viral latency III), literature suggests EBV+DLBCL is typically latency II, i.e. expression is limited to the immuno-subdominant EBNA1, LMP1 and LMP2 EBV-proteins. If correct, this would be a major impediment for T-cell immunotherapeutic strategies. Unexpectedly we observed EBV+DLBCL-PTLD and EBV+DLBCL both shared features consistent with type III EBV-latency, including expression of the immuno-dominant EBNA3A protein. Extensive analysis showed frequent polymorphisms in EBNA1 and LMP1 functionally defined CD8+ T-cell epitope encoding regions, whereas EBNA3A polymorphisms were very rare making this an attractive immunotherapy target. As with EBV+DLBCL-PTLD, the antigen presenting machinery within lymphomatous nodes was intact. EBV+DLBCL express EBNA3A suggesting it is amenable to immunotherapeutic strategies.

A large scale quantitative study of pedestrian railway level crossing behaviour : deliberate violations, errors and deterrence

Every year a number of pedestrians are struck by trains resulting in death and serious injury. While much research has been conducted on train-vehicle collisions, very little is currently known about the aetiology of train-pedestrian collisions. To date, scant research has been undertaken to investigate the demographics of rule breakers, the frequency of deliberate violation versus error making and the influence of the classic deterrence approach on subsequent behaviours. Aim This study aimed to to identify pedestrians’ self-reported reasons for engaging in violations at crossing, the frequency and nature of rule breaking and whether the threat of sanctions influence such events. Method A questionnaire was administered to 511 participants of all ages. Results Analysis revealed that pedestrians (particularly younger groups) were more likely to commit deliberate violations rather than make crossing errors e.g., mistakes. The most frequent reasons given for deliberate violations were participants were running late and did not want to miss their train or participants believed that the gate was taking too long to open so may be malfunctioning. In regards to classical deterrence, an examination of the perceived threat of being apprehended and fined for a crossing violation revealed participants reported the highest mean scores for swiftness of punishment, which suggests they were generally aware that they would receive an “on the spot” fine. However, the overall mean scores for certainty and severity of sanctions (for violating the rules) indicate that the participants did not perceive the certainty and severity of sanctions as very high. This paper will further discuss the research findings in regards to the development of interventions designed to improve pedestrian crossing safety.

Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma

We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas. Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas. Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS. Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 9.2% of sun-exposed melanomas. This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain. Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration. These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit.

A single dose of azithromycin does not improve clinical outcomes of children hospitalised with bronchiolitis : a randomised, placebo-controlled trial

Objective Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. Methods Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. Results 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. Conclusion Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children.

Public policy, disaster risk management and climate change adaptation

Public policymakers are caught in a dilemma : there is a growing list of urgent issues to address, at the same time that public expenditure is being cut. Adding to this dilemma is a system of government designed in the 19th century and competing theories of policymaking dating back to the 1950s. The interlinked problems of disaster risk management and climate change adaptation are cases in point. As the climate changes, there will be more frequent, intense and/or prolonged disasters such as floods and bushfires. Clearly a well integrated whole of government response is needed, but how might this be achieved? Further, how could academic research contribute to resolving this dilemma in a way that would produce something of theoretical interest as well as practical outcomes for policymakers? These are the questions addressed by our research via a comparative analysis of the 2009 Victorian bushfires, the 2011 Perth Hills bushfires, and the 2011 Brisbane floods. Our findings suggest that there is a need to: improve community engagement and communication; refocus attention on resilience; improve interagency communication and collaboration; and, develop institutional arrangements that support continual improvement and policy learning. These findings have implications for all areas of public policy theory and practice.

Identifying the determinants of concealed and obvious texting while driving : are they distinct behaviours?

Concealed texting (CT) while driving involves a conscious effort to hide one’s texting while obvious texting (OT) does not involve such efforts to conceal the behaviour. Young drivers are the most frequent users of mobile phones while driving which is associated with heightened crash risk. This study investigated the extent to which CT and OT may be discrete behaviours to ascertain whether countermeasures would need to utilise distinct approaches. An extended Theory of Planned Behaviour (TPB) including moral norm, mobile phone involvement, and anticipated regret guided the research. Participants (n = 171) were aged 17 to 25 years, owned a mobile phone, had a current driver’s licence, and resided in Queensland. A repeated measures MANOVA found significant differences between CT and OT on all standard and extended TPB constructs. Hierarchical multiple regression analyses showed the standard TPB constructs accounted for 68.7% and 54.6% of the variance in intentions to engage in CT and OT, respectively. The extended predictors contributed additional variance in intentions over and above the standard TPB constructs. Further, in the final regression model, differences emerged in the significant predictors of each type of texting. These findings provide initial evidence that CT and OT are distinct behaviours. This distinction is important to the extent that it may influence the nature of advertising countermeasures aimed at reducing/preventing young drivers’ engagement in these risky behaviours.

Acute poststreptococcal glomerulonephritis : public health implications of recent clusters in New South Wales and epidemiology of hospital admissions

Acute poststreptococcal glomerulonephritis (APSGN) is an inflammatory kidney condition that can complicate Group A streptococcal infections. Two clusters of APSGN occurred recently in New South Wales (NSW), Australia; one in a rural town in December 1999 and the other in a Sydney suburb in January 2000. We interviewed carers of the affected children but found no common exposures except three of the Sydney cases were cousins in frequent contact. To assess the probability of these clusters occurring, we analysed hospital admissions for acute glomerulonephritis, as a proxy for APSGN in younger patients. The incidence of acute glomerulonephritis in NSW during 1989/90-1997/8 in residents aged under 20 years was 2(.)2/100000/year (95% CI 2(.)0-2(.)5). Incidence was highest in children aged 5-9 years, boys and Aboriginal children. We found no evidence for other clusters during that period. The recent clusters highlight the continued potential for unexpected future outbreaks of APSGN.

Hospitalisation of Indigenous children in the Northern Territory for lower respiratory illness in the first year of life

Objective To describe the epidemiology of acute lower respiratory infection (ALRI) and bronchiectasis in Northern Territory Indigenous infants hospitalised in the first year of life. Design A historical cohort study constructed from the NT Hospital Discharge Dataset and the NT Imm(u)nisation Register. Participants and setting All NT resident Indigenous infants, born 1 January 1999 to 31 December 2004, admitted to NT public hospitals and followed up to 12 months of age. Main outcome measures Incidence of ALRI and bronchiectasis (ICD-10-AM codes) and radiologically confirmed pneumonia (World Health Organization protocol). Results Data on 9295 infants, 8498 child-years of observation and 15 948 hospitalised episodes of care were analysed. ALRI incidence was 426.7 episodes per 1000 child-years (95% Cl, 416.2-437.2). Incidence rates were two times higher (relative risk, 2.12; 95% Cl, 1.98-2.27) for infants in Central Australia compared with those in the Top End. The median age at first admission for an ALRI was 4.6 months (interquartile range, 2.6-7.3). Bronchiolitis accounted for most of the disease burden, with a rate of 227 per 1000 child-years. The incidence of first diagnosis of bronchiectasis was 1.18 per 1000 child-years (95% Cl, 0.60-2.16). One or more key comorbidities were present in 1445 of the 3227 (44.8%) episodes of care for ALRI. Conclusions Rates of ALRI and bronchiectasis in NT Indigenous infants are excessive, with early onset, frequent repeat episodes, and a high prevalence of comorbidities. These high rates of disease demand urgent attention.

Concealing their communication : exploring psychosocial predictors of young drivers’ intentions and engagement in concealed texting

Making a conscious effort to hide the fact that you are texting while driving (i.e., concealed texting) is a deliberate and risky behaviour involving attention diverted away from the road. As the most frequent users of text messaging services and mobile phones while driving, young people appear at heightened risk of crashing from engaging in this behaviour. This study investigated the phenomenon of concealed texting while driving, and utilised an extended Theory of Planned Behaviour (TPB) including the additional predictors of moral norm, mobile phone involvement, and anticipated regret to predict young drivers’ intentions and subsequent behaviour. Participants (n = 171) were aged 17 to 25 years, owned a mobile phone, and had a current driver’s licence. Participants completed a questionnaire measuring their intention to conceal texting while driving, and a follow-up questionnaire a week later to report their behavioural engagement. The results of hierarchical multiple regression analyses showed overall support for the predictive utility of the TPB with the standard constructs accounting for 69% of variance in drivers’ intentions, and the extended predictors contributing an additional 6% of variance in intentions over and above the standard constructs. Attitude, subjective norm, PBC, moral norm, and mobile phone involvement emerged as significant predictors of intentions; and intention was the only significant predictor of drivers’ self-reported behaviour. These constructs can provide insight into key focal points for countermeasures including advertising and other public education strategies aimed at influencing young drivers to reconsider their engagement in this risky behaviour.

Effective punishment experiences : the need for a more comprehensive approach to conceptualising behavioural punishers and reinforcers in a road safety context

Determining what consequences are likely to serve as effective punishment for any given behaviour is a complex task. This chapter focuses specifically on illegal road user behaviours and the mechanisms used to punish and deter them. Traffic law enforcement has traditionally used the threat and/or receipt of legal sanctions and penalties to deter illegal and risky behaviours. This process represents the use of positive punishment, one of the key behaviour modification mechanisms. Behaviour modification principles describe four types of reinforcers: positive and negative punishments and positive and negative reinforcements. The terms ‘positive’ and ‘negative’ are not used in an evaluative sense here. Rather, they represent the presence (positive) or absence (negative) of stimuli to promote behaviour change. Punishments aim to inhibit behaviour and reinforcements aim to encourage it. This chapter describes a variety of punishments and reinforcements that have been and could be used to modify illegal road user behaviours. In doing so, it draws on several theoretical perspectives that have defined behavioural reinforcement and punishment in different ways. Historically, the main theoretical approach used to deter risky road use has been classical deterrence theory which has focussed on the perceived certainty, severity and swiftness of penalties. Stafford and Warr (1993) extended the traditional deterrence principles to include the positive reinforcement concept of punishment avoidance. Evidence of the association between punishment avoidance experiences and behaviour has been established for a number of risky road user behaviours including drink driving, unlicensed driving, and speeding. We chose a novel way of assessing punishment avoidance by specifying two sub-constructs (detection evasion and punishment evasion). Another theorist, Akers, described the idea of competing reinforcers, termed differential reinforcement, within social learning theory (1977). Differential reinforcement describes a balance of reinforcements and punishments as influential on behaviour. This chapter describes comprehensive way of conceptualising a broad range of reinforcement and punishment concepts, consistent with Akers’ differential reinforcement concept, within a behaviour modification framework that incorporates deterrence principles. The efficacy of three theoretical perspectives to explain self-reported speeding among a sample of 833 Australian car drivers was examined. Results demonstrated that a broad range of variables predicted speeding including personal experiences of evading detection and punishment for speeding, intrinsic sensations, practical benefits expected from speeding, and an absence of punishing effects from being caught. Not surprisingly, being younger was also significantly related to more frequent speeding, although in a regression analysis, gender did not retain a significant influence once all punishment and reinforcement variables were entered. The implications for speed management, as well as road user behaviour modification more generally, are discussed in light of these findings. Overall, the findings reported in this chapter suggest that a more comprehensive approach is required to manage the behaviour of road users which does not rely solely on traditional legal penalties and sanctions.

A brief staff dementia education program : implementation and evaluation

Brief dementia education training programs appear to be effective in improving knowledge about dementia and self-confidence in interacting with patients with dementia. It is recommended that brief dementia training sessions be provided on a regular, on-going basis, particularly in view of frequent staff changes in the acute hospital environment.

Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer

INTRODUCTION: Performance status (PS) 2 patients with non-small cell lung cancer (NSCLC) experience more toxicity, lower response rates, and shorter survival times than healthier patients treated with standard chemotherapy. Paclitaxel poliglumex (PPX), a macromolecule drug conjugate of paclitaxel and polyglutamic acid, reduces systemic exposure to peak concentrations of free paclitaxel and may lead to increased concentrations in tumors due to enhanced vascular permeability. METHODS: Chemotherapy-naive PS 2 patients with advanced NSCLC were randomized to receive carboplatin (area under the curve = 6) and either PPX (210 mg/m/10 min without routine steroid premedication) or paclitaxel (225 mg/m/3 h with standard premedication) every 3 weeks. The primary end point was overall survival. RESULTS: A total of 400 patients were enrolled. Alopecia, arthralgias/myalgias, and cardiac events were significantly less frequent with PPX/carboplatin, whereas grade ≥3 neutropenia and grade 3 neuropathy showed a trend of worsening. There was no significant difference in the incidence of hypersensitivity reactions despite the absence of routine premedication in the PPX arm. Overall survival was similar between treatment arms (hazard ratio, 0.97; log rank p = 0.769). Median and 1-year survival rates were 7.9 months and 31%, for PPX versus 8 months and 31% for paclitaxel. Disease control rates were 64% and 69% for PPX and paclitaxel, respectively. Time to progression was similar: 3.9 months for PPX/carboplatin versus 4.6 months for paclitaxel/carboplatin (p = 0.210). CONCLUSION: PPX/carboplatin failed to provide superior survival compared with paclitaxel/carboplatin in the first-line treatment of PS 2 patients with NSCLC, but the results with respect to progression-free survival and overall survival were comparable and the PPX regimen was more convenient. © 2008International Association for the Study of Lung Cancer.

The role of epigenetics in resistance to cisplatin chemotherapy in lung cancer

Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20-30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Prognostic value of TP53, KRAS and EGFR mutations in nonsmall cell lung cancer : the EUELC cohort

Nonsmall cell lung cancer samples from the European Early Lung Cancer biobank were analysed to assess the prognostic significance of mutations in the TP53, KRAS and EGFR genes. The series included 11 never-smokers, 86 former smokers, 152 current smokers and one patient without informed smoking status. There were 110 squamous cell carcinomas (SCCs), 133 adenocarcinomas (ADCs) and seven large cell carcinomas or mixed histologies. Expression of p53 was analysed by immunohistochemistry. DNA was extracted from frozen tumour tissues. TP53 mutations were detected in 48.8% of cases and were more frequent among SCCs than ADCs (p<0.0001). TP53 mutation status was not associated with prognosis. G to T transversions, known to be associated with smoking, were marginally more common among patients who developed a second primary lung cancer or recurrence/metastasis (progressive disease). EGFR mutations were almost exclusively found in never-smoking females (p=0.0067). KRAS mutations were detected in 18.5% of cases, mainly ADC (p<0.0001), and showed a tendency toward association with progressive disease status. These results suggest that mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception of KRAS mutation, which may have a prognostic value in ADC. Copyright©ERS 2012.