Mixing and dispersion of pollutants emitted from an outboard motor

This paper quantifies the mixing and dispersion from an outboard motor by field experiments in a small subtropical waterway. Organic dye was used as a surrogate for exhaust emissions and was mixed with uncontaminated creek water before being dispersed into the creek. Dye concentrations were measured with an array of concentration probes stationed in the creek. The data were then processed and fitted with a power law function. The corresponding dispersion constants agreed well with the literature. However, the amplitude was lower than the IMO equation but higher than the correlation from laboratory tests. Results for dye concentration intermittency (presence of dye) are presented for the first time from such field measurements and show significant mixing in-homogeneity.

Double standards in special medical research : questioning the discrepancy between requirements for medical research involving incompetent adults and medical research involving children

Medical research represents a substantial departure from conventional medical care. Medical care is patient-orientated, with decisions based on the best interests and/or wishes of the person receiving the care. In contrast, medical research is future-directed. Primarily it aims to contribute new knowledge about illness or disease, or new knowledge about interventions, such as drugs, that impact upon some human condition. Current State and Territory laws and research ethics guidelines in Australia relating to the review of medical research appropriately acknowledge that the functions of medical care and medical research differ. Prior to a medical research project commencing, the study must be reviewed and approved by a Human Research Ethics Committee (HREC). For medical research involving incompetent adults, some jurisdictions require an additional, independent safeguard by way of tribunal or court approval of medical research protocols. This extra review process reflects the uncertainty of medical research involvement, and the difficulties surrogate decision-makers of incompetent adults face in making decisions about others, and deliberating about the risks and benefits of research involvement. Parents of children also face the same difficulties when making decisions about their child’s research involvement. However, unlike the position concerning incompetent adults, there are no similar safeguards under Australian law in relation to the approval of medical research involving children. This column questions why this discrepancy exists with a view to generating further dialogue on the topic.

Building an augmented map for road risk assessment

Recent road safety statistics show that the decades-long fatalities decreasing trend is stopping and stagnating. Statistics further show that crashes are mostly driven by human error, compared to other factors such as environmental conditions and mechanical defects. Within human error, the dominant error source is perceptive errors, which represent about 50% of the total. The next two sources are interpretation and evaluation, which accounts together with perception for more than 75% of human error related crashes. Those statistics show that allowing drivers to perceive and understand their environment better, or supplement them when they are clearly at fault, is a solution to a good assessment of road risk, and, as a consequence, further decreasing fatalities. To answer this problem, currently deployed driving assistance systems combine more and more information from diverse sources (sensors) to enhance the driver's perception of their environment. However, because of inherent limitations in range and field of view, these systems' perception of their environment remains largely limited to a small interest zone around a single vehicle. Such limitations can be overcomed by increasing the interest zone through a cooperative process. Cooperative Systems (CS), a specific subset of Intelligent Transportation Systems (ITS), aim at compensating for local systems' limitations by associating embedded information technology and intervehicular communication technology (IVC). With CS, information sources are not limited to a single vehicle anymore. From this distribution arises the concept of extended or augmented perception. Augmented perception allows extending an actor's perceptive horizon beyond its "natural" limits not only by fusing information from multiple in-vehicle sensors but also information obtained from remote sensors. The end result of an augmented perception and data fusion chain is known as an augmented map. It is a repository where any relevant information about objects in the environment, and the environment itself, can be stored in a layered architecture. This thesis aims at demonstrating that augmented perception has better performance than noncooperative approaches, and that it can be used to successfully identify road risk. We found it was necessary to evaluate the performance of augmented perception, in order to obtain a better knowledge on their limitations. Indeed, while many promising results have already been obtained, the feasibility of building an augmented map from exchanged local perception information and, then, using this information beneficially for road users, has not been thoroughly assessed yet. The limitations of augmented perception, and underlying technologies, have not be thoroughly assessed yet. Most notably, many questions remain unanswered as to the IVC performance and their ability to deliver appropriate quality of service to support life-saving critical systems. This is especially true as the road environment is a complex, highly variable setting where many sources of imperfections and errors exist, not only limited to IVC. We provide at first a discussion on these limitations and a performance model built to incorporate them, created from empirical data collected on test tracks. Our results are more pessimistic than existing literature, suggesting IVC limitations have been underestimated. Then, we develop a new CS-applications simulation architecture. This architecture is used to obtain new results on the safety benefits of a cooperative safety application (EEBL), and then to support further study on augmented perception. At first, we confirm earlier results in terms of crashes numbers decrease, but raise doubts on benefits in terms of crashes' severity. In the next step, we implement an augmented perception architecture tasked with creating an augmented map. Our approach is aimed at providing a generalist architecture that can use many different types of sensors to create the map, and which is not limited to any specific application. The data association problem is tackled with an MHT approach based on the Belief Theory. Then, augmented and single-vehicle perceptions are compared in a reference driving scenario for risk assessment,taking into account the IVC limitations obtained earlier; we show their impact on the augmented map's performance. Our results show that augmented perception performs better than non-cooperative approaches, allowing to almost tripling the advance warning time before a crash. IVC limitations appear to have no significant effect on the previous performance, although this might be valid only for our specific scenario. Eventually, we propose a new approach using augmented perception to identify road risk through a surrogate: near-miss events. A CS-based approach is designed and validated to detect near-miss events, and then compared to a non-cooperative approach based on vehicles equiped with local sensors only. The cooperative approach shows a significant improvement in the number of events that can be detected, especially at the higher rates of system's deployment.

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.

Predicting invasion in grassland ecosystems: is exotic dominance the real embarrassment of richness?

Invasions have increased the size of regional species pools, but are typically assumed to reduce native diversity. However, global-scale tests of this assumption have been elusive because of the focus on exotic species richness, rather than relative abundance. This is problematic because low invader richness can indicate invasion resistance by the native community or, alternatively, dominance by a single exotic species. Here, we used a globally replicated study to quantify relationships between exotic richness and abundance in grass-dominated ecosystems in 13 countries on six continents, ranging from salt marshes to alpine tundra. We tested effects of human land use, native community diversity, herbivore pressure, and nutrient limitation on exotic plant dominance. Despite its widespread use, exotic richness was a poor proxy for exotic dominance at low exotic richness, because sites that contained few exotic species ranged from relatively pristine (low exotic richness and cover) to almost completely exotic-dominated ones (low exotic richness but high exotic cover). Both exotic cover and richness were predicted by native plant diversity (native grass richness) and land use (distance to cultivation). Although climate was important for predicting both exotic cover and richness, climatic factors predicting cover (precipitation variability) differed from those predicting richness (maximum temperature and mean temperature in the wettest quarter). Herbivory and nutrient limitation did not predict exotic richness or cover. Exotic dominance was greatest in areas with low native grass richness at the site- or regional-scale. Although this could reflect native grass displacement, a lack of biotic resistance is a more likely explanation, given that grasses comprise the most aggressive invaders. These findings underscore the need to move beyond richness as a surrogate for the extent of invasion, because this metric confounds monodominance with invasion resistance. Monitoring species' relative abundance will more rapidly advance our understanding of invasions.

A computer image analysis system for microvessel density measurement in solid tumours

Microvessel density (MVD) is a widely used surrogate measure of angiogenesis in pathological specimens and tumour models. Measurement of MVD can be achieved by several methods. Automation of counting methods aims to increase the speed, reliability and reproducibility of these techniques. The image analysis system described here enables MVD measurement to be carried out with minimal expense in any reasonably equipped pathology department or laboratory. It is demonstrated that the system translates easily between tumour types which are suitably stained with minimal calibration. The aim of this paper is to offer this technique to a wider field of researchers in angiogenesis.

Molecular approaches to diagnosis and management of ovarian cancer

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.

Angiogenesis as a biomarker and target in cancer chemoprevention

Angiogenesis, the formation of new blood vessels from existing vasculature, is essential to the late stages of carcinogenesis, allowing tumours to grow beyond 1-2 mm in diameter, invade surrounding tissue, and metastasise. However, more than two decades ago, angiogenesis that preceded neoplastic transformation was seen. Indeed, it can be detected in inflammatory and infectious diseases that increase the risk of developing cancer. Recent advances in fluorescence endoscopy and histological assessment suggest that, for certain cancers, the degree of new blood-vessel formation may differ between the early and late stages of carcinogenic progression. The association between angiogenesis and cancer occurrence, and ease of detection of this process in accessible tissues early in carcinogenesis, mean that angiogenesis fulfils the criteria for a biomarker of the effectiveness of chemopreventive intervention. There is also some evidence that biochemical assays of angiogenic growth factors may after similar potential as surrogate biomarkers. Many natural and synthetic chemopreventive agents in development or in clinical use inhibit new vessel formation in vivo. Validation of angiogenesis as a biomarker for the effectiveness of chemoprevention should further the advancement of some chemopreventive agents.

Longitudinal assessment of neuropathy in type 1 diabetes using novel ophthalmic markers (LANDMark) : study design and baseline characteristics

Aims Corneal nerve morphology and corneal sensation threshold have recently been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of the ‘Longitudinal Assessment of Neuropathy in type 1 Diabetes using novel ophthalmic Markers’(LANDMark) study. Methods The LANDMark study is a 4-year, two-site, natural history study of three participant groups: type 1 diabetes with neuropathy (T1W), type 1 diabetes without neuropathy (T1WO) and control participants without diabetes or neuropathy. All participants undergo a detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal aesthesiometry. Results 76 T1W, 166 T1WO and 154 control participants were enrolled into the study. Corneal sensation threshold (mbars) was significantly higher (i.e. sensitivity was lower) in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (p < 0.001), with no difference between T1WO and controls. Corneal nerve fibre length was lower in T1W (14.0 ± 6.4 mm/mm2) compared to T1WO (19.1 ± 5.8 mm/mm2) and controls (23.2 ± 6.3 mm/mm2) (p < 0.001). Corneal nerve fibre length was lower in T1WO compared to controls. Conclusions The LANDMark baseline findings confirm a reduction in corneal sensitivity only in Type 1 patients with neuropathy. However, corneal nerve fibre length is reduced even in Type 1 patients without neuropathy with an even greater deficit in Type 1 patients with neuropathy.

Longitudinal assessment of neuropathy in diabetes using novel ophthalmic markers (LANDMark) : baseline findings

Purpose Over the past decade, corneal nerve morphology and corneal sensation threshold have been explored as potential surrogate markers for the evaluation of diabetic neuropathy. We present the baseline findings of a Longitudinal Assessment of Neuropathy in Diabetes using novel ophthalmic Markers (LANDMark). Methods The LANDMark Study is a 5-year, two-site, natural history (observational) study of individuals with Type 1 diabetes stratified into those with (T1W) and without (T1WO) neuropathy according to the Toronto criteria, and control subjects. All study participants undergo detailed annual assessment of neuropathy including corneal nerve parameters measured using corneal confocal microscopy and corneal sensitivity measured using non-contact corneal esthesiometry. Results 396 eligible individuals (208 in Brisbane and 188 in Manchester) were assessed: 76 T1W, 166 T1WO and 154 controls. Corneal sensation threshold (mbars) was significantly higher in T1W (1.0 ± 1.1) than T1WO (0.7 ± 0.7) and controls (0.6 ± 0.4) (P=0.002); post-hoc analysis (PHA) revealed no difference between T1WO and controls (Tukey HSD, P=0.502). Corneal nerve fiber length (mm/mm2) (CNFL) was lower in T1W (13.8 ± 6.4) than T1WO (19.1 ± 5.8) and controls (23.2 ± 6.3) (P<0.001); PHA revealed CNFL to be lower in T1W than T1WO, and lower in both of these groups than controls (P<0.001). Corneal nerve branch density (branches/mm2) (CNBD) was significantly lower in T1W (40 ± 32) than T1WO (62 ± 37) and controls (83 ± 46) (P<0.001); PHA showed CNBD was lower in T1W than T1WO, and lower in both groups than controls (P<0.001). Alcohol and cigarette consumption did not differ between groups, although age, BMI, BP, waist circumference, HbA1c, albumin-creatinine ratio, and cholesterol were slightly greater in T1W than T1WO (p<0.05). Some site differences were observed. Conclusions The LANDMark baseline findings confirm that corneal sensitivity and corneal nerve morphometry can detect differences in neuropathy status in individuals with Type 1 diabetes and healthy controls. Corneal nerve morphology is significantly abnormal even in diabetic patients ‘without neuropathy’ compared to control participants. Results of the longitudinal trial will assess the capability of these tests for monitoring change in these parameters over time as potential surrogate markers for neuropathy.

Use of cadavers and anthropometric test devices (ATDs) for assessing lower limb injury outcome from under‐vehicle explosions

Lower extremities are particularly susceptible to injury in an under‐vehicle explosion. Operational fitness of military vehicles is assessed through anthropometric test devices (ATDs) in full‐scale blast tests. The aim of this study was to compare the response between the Hybrid‐III ATD, the MiL‐Lx ATD and cadavers in our traumatic injury simulator, which is able to replicate the response of the vehicle floor in an under‐vehicle explosion. All specimens were fitted with a combat boot and tested on our traumatic injury simulator in a seated position. The load recorded in the ATDs was above the tolerance levels recommended by NATO in all tests; no injuries were observed in any of the 3 cadaveric specimens. The Hybrid‐III produced higher peak forces than the MiL‐Lx. The time to peak strain in the calcaneus of the cadavers was similar to the time to peak force in the ATDs. Maximum compression of the sole of the combat boot was similar for cadavers and MiL‐Lx, but significantly greater for the Hybrid‐III. These results suggest that the MiL‐Lx has a more biofidelic response to under‐vehicle explosive events compared to the Hybrid‐III. Therefore, it is recommended that mitigation strategies are assessed using the MiL‐Lx surrogate and not the Hybrid‐III.

Cough and exhaled nitric oxide levels : what happens with exercise?

Cough associated with exertion is often used as a surrogate marker of asthma. However, to date there are no studies that have objectively measured cough in association with exercise in children. Our primary aim was to examine whether children with a pre-existing cough have an increase in cough frequency during and post-exercise. We hypothesized that children with any coughing illness will have an increase in cough frequency post-exercise regardless of the presence of exercise-induced broncho-constriction (EIB) or atopy. In addition, we hypothesized that Fractional exhaled nitric oxide (FeNO) levels decreases post-exercise regardless of the presence of EIB or atopy. Children with chronic cough and a control group without cough undertook an exercise challenge, FeNO measurements and a skin prick test, and wore a 24-h voice recorder to objectively measure cough frequency. The association between recorded cough frequency, exercise, atopy, and presence of EIB was tested. We also determined if the change in FeNO post exercise related to atopy or EIB. Of the 50 children recruited (35 with cough, 15 control), 7 had EIB. Children with cough had a significant increase in cough counts (median 7.0, inter-quartile ranges, 0.5, 24.5) compared to controls (2.0, IQR 0, 5.0, p = 0.028) post-exercise. Presence of atopy or EIB did not influence cough frequency. FeNO level was significantly lower post-exercise in both groups but the change was not influenced by atopy or EIB. Cough post-exertion is likely a generic response in children with a current cough. FeNO level decreases post-exercise irrespective of the presence of atopy or EIB. A larger study is necessary confirm or refute our findings.

Benthic metabolism as an indicator of stream ecosystem health

We tested direct and indirect measures of benthic metabolism as indicators of stream ecosystem health across a known agricultural land-use disturbance gradient in southeast Queensland, Australia. Gross primary production (GPP) and respiration (R24) in benthic chambers in cobble and sediment habitats, algal biomass (as chlorophyll a) from cobbles and sediment cores, algal biomass accrual on artificial substrates and stable carbon isotope ratios of aquatic plants and benthic sediments were measured at 53 stream sites, ranging from undisturbed subtropical rainforest to catchments where improved pasture and intensive cropping are major land-uses. Rates of benthic GPP and R24 varied by more than two orders of magnitude across the study gradient. Generalised linear regression modelling explained 80% or more of the variation in these two indicators when sediment and cobble substrate dominated sites were considered separately, and both catchment and reach scale descriptors of the disturbance gradient were important in explaining this variation. Model fits were poor for net daily benthic metabolism (NDM) and production to respiration ratio (P/R). Algal biomass accrual on artificial substrate and stable carbon isotope ratios of aquatic plants and benthic sediment were the best of the indirect indicators, with regression model R2 values of 50% or greater. Model fits were poor for algal biomass on natural substrates for cobble sites and all sites. None of these indirect measures of benthic metabolism was a good surrogate for measured GPP. Direct measures of benthic metabolism, GPP and R24, and several indirect measures were good indicators of stream ecosystem health and are recommended in assessing process-related responses to riparian and catchment land use change and the success of ecosystem rehabilitation actions.

Accurately defining the reference condition for summary biotic metrics: A comparison of four approaches

Protocols for bioassessment often relate changes in summary metrics that describe aspects of biotic assemblage structure and function to environmental stress. Biotic assessment using multimetric indices now forms the basis for setting regulatory standards for stream quality and a range of other goals related to water resource management in the USA and elsewhere. Biotic metrics are typically interpreted with reference to the expected natural state to evaluate whether a site is degraded. It is critical that natural variation in biotic metrics along environmental gradients is adequately accounted for, in order to quantify human disturbance-induced change. A common approach used in the IBI is to examine scatter plots of variation in a given metric along a single stream size surrogate and a fit a line (drawn by eye) to form the upper bound, and hence define the maximum likely value of a given metric in a site of a given environmental characteristic (termed the 'maximum species richness line' - MSRL). In this paper we examine whether the use of a single environmental descriptor and the MSRL is appropriate for defining the reference condition for a biotic metric (fish species richness) and for detecting human disturbance gradients in rivers of south-eastern Queensland, Australia. We compare the accuracy and precision of the MSRL approach based on single environmental predictors, with three regression-based prediction methods (Simple Linear Regression, Generalised Linear Modelling and Regression Tree modelling) that use (either singly or in combination) a set of landscape and local scale environmental variables as predictors of species richness. We compared the frequency of classification errors from each method against set biocriteria and contrast the ability of each method to accurately reflect human disturbance gradients at a large set of test sites. The results of this study suggest that the MSRL based upon variation in a single environmental descriptor could not accurately predict species richness at minimally disturbed sites when compared with SLR's based on equivalent environmental variables. Regression-based modelling incorporating multiple environmental variables as predictors more accurately explained natural variation in species richness than did simple models using single environmental predictors. Prediction error arising from the MSRL was substantially higher than for the regression methods and led to an increased frequency of Type I errors (incorrectly classing a site as disturbed). We suggest that problems with the MSRL arise from the inherent scoring procedure used and that it is limited to predicting variation in the dependent variable along a single environmental gradient.

Automatic inference of driving task demand from visual cues of emotion and attention

Sensing the mental, physical and emotional demand of a driving task is of primary importance in road safety research and for effectively designing in-vehicle information systems (IVIS). Particularly, the need of cars capable of sensing and reacting to the emotional state of the driver has been repeatedly advocated in the literature. Algorithms and sensors to identify patterns of human behavior, such as gestures, speech, eye gaze and facial expression, are becoming available by using low cost hardware: This paper presents a new system which uses surrogate measures such as facial expression (emotion) and head pose and movements (intention) to infer task difficulty in a driving situation. 11 drivers were recruited and observed in a simulated driving task that involved several pre-programmed events aimed at eliciting emotive reactions, such as being stuck behind slower vehicles, intersections and roundabouts, and potentially dangerous situations. The resulting system, combining face expressions and head pose classification, is capable of recognizing dangerous events (such as crashes and near misses) and stressful situations (e.g. intersections and way giving) that occur during the simulated drive.