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Purpose: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Method(s): Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. Result(s): HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients = 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. Conclusion(s): In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.Copyright © 2021, Crown.

Purpose: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. Method(s): Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. Result(s): HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients = 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. Conclusion(s): In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.Copyright © 2021, Crown.

In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they a

In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they a

In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they a

In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they a

In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they a

© 2018 The behavioural responses of migrating humpback whales to an air gun, a small clustered seismic array and a commercial array were used to develop a dose-response model, accounting for the presence of the vessel, array towpath relative to the migration and social and environmental parameters. Whale groups were more likely to show an avoidance response (increasing their distance from the source) when the received sound exposure level was over 130 dB re 1 µPa2·s and they were within 4 km of the source. The 50% probability of response occurred where received levels were 150–155 dB re 1 µPa2·s and they were within 2.5 km of the source. A small number of whales moving rapidly close to the source vessel did not exhibit an avoidance response at the highest received levels (160–170 dB re 1 µPa2·s) meaning it was not possible to estimate the maximum response threshold.

© 2017 The Author(s) Published by the Royal Society. All rights reserved. Despite concerns on the effects of noise from seismic survey airguns on marine organisms, there remains uncertainty as to the biological significance of any response. This study quantifies and interprets the response of migrating humpback whales (Megaptera novaeangliae) to a 3130 in 3 (51.3l) commercial airgun array. We compare the behavioural responses to active trials (array operational; n = 34 whale groups), with responses to control trials (source vessel towing the array while silent; n = 33) and baseline studies of normal behaviour in the absence of the vessel (n = 85). No abnormal behaviours were recorded during the trials. However, in response to the active seismic array and the controls, the whales displayed changes in behaviour. Changes in respiration rate were of a similar magnitude to changes in baseline groups being joined by other animals suggesting any change group energetics was within their behavioural repertoire. However, the reduced progression southwards in response to the active treatments, for some cohorts, was below typical migratory speeds. This response was more likely to occur within 4 km from the array at recei ved levels over 135 dB re 1 µPa 2 .s.

The effect of various anthropogenic sources of noise (e.g. sonar, seismic surveys) on the behaviour of marine mammals is sometimes quantified as a dose-response relationship, where the probability of an animal behaviourally 'responding' (e.g. avoiding the source) increases with 'dose' (or received level of noise). To do this, however, requires a definition of a 'significant' response (avoidance), which can be difficult to quantify. There is also the potential that the animal 'avoids' not only the source of noise but also the vessel operating the source, complicating the relationship. The proximity of the source is an important variable to consider in the response, yet difficult to account for given that received level and proximity are highly correlated. This study used the behavioural response of humpback whales to n oise from two different air gun arrays (20 and 140 cubic inch air gun array) to determine whether a dose-response relationship existed. To do this, a measure of avoidance of the source was developed, and the magnitude (rather than probability) of this response was tested against dose. The proximity to the source, and the vessel itself, was included within the one-analysis model. Humpback whales were more likely to avoid the air gun arrays (but not the controls) within 3 km of the source at levels over 140 re. 1 µPa 2 s -1 , meaning that both the proximity and the received level were important factors and the relationship between dose (received level) and response is not a simple one.

Studying the behavioral response of whales to noise presents numerous challenges. In addition to the characteristics of the noise exposure, many factors may affect the response and these must be measured and accounted for in the analysis. An adequate sample size that includes matching controls is crucial if meaningful results are to be obtained. Field work is thus complicated, logistically difficult, and expensive. This paper discusses some of the challenges and how they are being met in a large-scale multiplatform project in which humpback whales are exposed to the noise of seismic air guns.

Seismic surveys are widely used for exploration for oil and gas deposits below the sea floor. Despite concern they may have an impact on whale behav­iour, our knowledge of marine mammal responses is limited. In the first of a series of experiments (the last one involving a full seismic array), this study tested the response of migrating humpback whale (Megaptera novaeangliae) groups to a 20 cubic inch air gun. Experiments were carried out during the southward migration of humpback whales along the east coast of Australia. Groups of whales were focally followed from land sta­tions and/or small boats with observations before, during, and after exposure to a vessel towing the air gun. The source vessel moved either eastwards across the migratory flow or northwards into the migratory flow. In total, there were 18 control trials (where the source vessel ran the compressor and towed the air gun without it firing; n = 35 whale groups) and 16 active trials (where the air gun was firing every 11 s; n = 32 whale groups). The air gun source level was 199 dB re 1 μPa2.s (Sound Exposure Level [SEL]) at 1 m, and SELs received by the whales varied from 105 to 156 dB re 1 μPa2.s (modal value 128 dB re μPa2.s) for SELs at least 10 dB above the background noise (mea­sured as dB re 1 μPa). Other baseline groups were focal followed when there was no source vessel in the area (n = 25). Results suggested that hump­back whale groups responded by decreasing both dive time and speed of southwards movement though the response magnitude was not found to be related to the proximity of the source vessel, the received level of the air gun, the tow path direction, or the exposure time within the during phase. There was no evidence of orientation of the groups towards, or away from, the source vessel in the during phase. Interestingly, this behavioural response was found in the control trials as well as the active trials suggesting a response to the source vessel.

© 2016 Elsevier Ltd. 'Ramp-up', or 'soft start', is a mitigation measure used in seismic surveys and involves increasing the radiated sound level over 20-40. min. This study compared the behavioural response in migrating humpback whales to the first stages of ramp-up with the response to a 'constant' source, 'controls' (in which the array was towed but not operated) with groups in the absence of the source vessel used as the 'baseline'. Although the behavioural response, in most groups, resulted in an increase in distance from the source (potential avoidance), there was no evidence that either 'ramp-up' or the constant source at a higher level was superior for triggering whales to move away from the source vessel. 'Control' groups also responded suggesting the presence of the source vessel had some effect. However, the majority of groups appeared to avoid the source vessel at distances greater than the radius of most mitigation zones.

Background:The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.Methods and Findings:We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0-48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96-1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63-2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration. Conclusion(s):Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.Trial registration:http://www.ClinicalTrials.gov NCT00221013 Please see later

Background:The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.Methods and Findings:We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0-48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96-1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63-2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.Conclusions:Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.Trial registration:http://www.ClinicalTrials.gov NCT00221013 Please see later in

Background:The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.Methods and Findings:We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0-48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96-1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63-2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration. Conclusion(s):Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.Trial registration:http://www.ClinicalTrials.gov NCT00221013 Please see later

A study of the response of humpback whales to seismic air guns is being conducted in Australian waters and two of four major experiments have been completed. It aims to assess the impact of seismic surveys on the whales and the effectiveness of ramp-up in mitigation. In separate trials, whales were exposed to a 20 cu in air gun, ramp-up in level from 20 cu in to 440 cu in with an air gun array, and a 'hard start' of 140 cu in. Whales were tracked using theodolites on high points ashore and behavioral observations were made from these points and from three small vessels and the source vessel. Vocalising whales were tracked with an array of hydrophones. DATGs were attached to some whales. Observations were made before, during and after exposure. Trials exposing whales to air gun treatments were balanced by controls without air guns firing. Characterization of the sound field throughout the area and the exposure at each whale were determined from propagation measurements and recordings on the hydrophone array and several moored acoustic recording systems. © 2013 Acoustical Society of America.

The concern about the effects of the noise of human activities on marine mammals, particularly whales, has led to a substantial amount of research but there is still much that is not understood, particularly in terms of the behavioural responses to noise and the longer term biological consequences of these responses. There are many challenges in conducting experiments that adequately assess behavioural reactions of whales to noise. These include the need to obtain an adequate sample size with the necessary controls and to measure the range of variables likely to affect the observed response. Analysis is also complex. Well designed experiments are complex and logistically difficult, and thus expensive. This paper discusses the challenges involved and how these are being met in a major series of experiments in Australian waters on the response of humpback whales to the noise of seismic airgun arrays. The project is known as BRAHSS (Behavioural Response of Australian Humpback whales to Seismic Surveys) and aims to provide the information that will allow seismic surveys to be conducted efficiently with minimal impact on whales. It also includes a study of the response to ramp-up in sound level which is widely used at the start of operations, but for which there is little information to show that it is effective. BRAHSS also aims to infer the longer term biological significance of the responses from the results and the knowledge of normal behaviour. The results are expected to have relevance to other sources and species.

The first of four major experiments in project behavioural response of australian humpback whales to seismic surveys (BRAHSS) was conducted on the east coast of Australia in September and October 2010. The project aims to understand how humpback whales respond to seismic surveys and to provide the information that will allow these surveys to be conducted efficiently with minimal impact on whales. It also aims to determine how the whales react to ramp up or soft start, and to assess how effective this is in mitigation. The 2010 experiment used a single air gun. Four air guns will be used in the next two experiments and a full seismic array in the final experiment in 2013. During the 2010 experiment, behavior and tracks of whales were recroded by four theodolite stations on elevated coastal positions and DTAGs used on some whales. Vocalizing whales were tracked with a wide base line hydrophone array. A further four acoustic recorders were used to measure propagation loss and to characterize the sound field throughout the area. A wide range of variables likely to affect whale response was measured. [Work sponsored by the JIP E&P Sound & Marine Life and Bureau of Ocean Energy Management, Regulation and Enforcement.]

Beaked whales have been over-represented in whale strandings that have occurred at similar times and places of some naval exercises in the northern hemisphere. Although whale strandings are common, it is unusual to find beaked whales stranded in such large numbers. Consequently, the environmental management of naval exercises requires mitigation measures to avoid potential impact on beaked whales. This requires some knowledge of beaked whale distributions and behavior, but little is known about beaked whales, less than for all other whales. Beaked whales are small whales that inhabit deep water. They are particularly elusive and rarely seen at sea. Much of what little is known about them results from the few that have been washed ashore. Visual surveying has proved to be generally ineffective. Beaked whale vocalizations are, however, sufficiently distinctive to allow passive acoustic detection and classification [1]. The sounds are sufficiently distinctive to distinguish them from those of other toothed whales, though these distinctions are subtle. All toothed whales produce echolocation clicks or pulses with a small number of cycles and most energy at ultrasonic frequencies. Beaked whale clicks can be distinguished by the frequency range, duration and number of cycles but other species have clicks that are close in one or other of the characteristics. In 2008 and 2009 we conducted two passive acoustic surveys of a naval exercise area in deep water in the Coral Sea (north east of Fraser Is.) in an attempt to determine the distributions of beaked whales in the area of about 18, 900 square km. Each survey was three weeks duration and involved acoustic and visual observations. A towed array of two hydrophones with frequency response to 150 kHz, and two drifting systems with hydrophones at 400 m depth and response to 96 kHz were used (beaked whale sounds have an upper limit of about 80 kHz). The drifting systems were tracked using a radio link suspended from a buoy that

This study investigated time and distance halo effects of mobile overt speed cameras. It was hypothesised that there would be a substantial reduction in vehicle speeds at an operational camera site and that this effect would gradually dissipate over distance from the camera vehicle. It was tentatively predicted that vehicles’ speeds may remain below baseline levels for some time after removal of the speed camera. Electronic data loggers were used to accurately record each vehicle’s speed as it crossed a set of induction loops buried in the road. Loops were spaced every 500 metres for 3.5 kilometres of a 100 kph high quality and high volume road section. Speeds were compared with baseline measures for each data collection point and across points. The first hypothesis was supported. There was a significant 6 kph reduction in mean and a 7 kph reduction in 85th percentile vehicle speeds, and the number of vehicles exceeding the speed limit fell from 53 % to 16 % immediately adjacent to the operational camera. However, these effects had completely disappeared by 1,500 metres downstream. Upstream halos were negligible. There was no time halo effect. In conclusion, this research found that mobile overt speed cameras are effective in reducing vehicle speeds. However, the reduction in speed is only for a relatively short distance and in a one-off trial only occurs while the camera is in operation.

Injury is the leading cause of death for adolescents in Australia. This is of particularly great concern as the leading cause of these injuries (those that are transport related) could be largely preventable by reducing risk-taking behaviour. In order to reduce such behaviour, effective road safety interventions should seek the input of the target participants. A series of focus groups were conducted with 30 high-risk adolescents, to seek information on their understanding of transport related risk-taking and injury. Primarily risk-taking involved car use, motorbike use, bicycle use, pedestrian behaviour and skateboarding. Further alcohol and drug use in the context of such behaviours were frequently reported. Most injuries were minor (for example, cuts and bruises) however participants identified more serious injury consequences (for example, head injuries and miscarriage). It was also found that the risk-taking was done in the context of peers, who exert a direct and indirect pressure to conform. Multiple risk and protective factors were also identified related to the individual and their environment. The results will be further discussed in terms of the value of seeking target participants’ perspective of road safety issues and how this information will be used to design a prevention program.

A case-control study of serious crashes in an extensive rural area of North Queensland, Australia, is currently underway. Planning for the study took several years to bring to completion. Its original design involved interviews with persons admitted to major hospitals in the region as a consequence of a traffic crash and with drivers recruited at the roadside optimally at or near the same site one week later. To date this is the plan that has been followed, although problems with roadside recruitment have been encountered. We propose to examine several issues which arose, and continue to arise, in the process of designing, piloting and execution of the study. Operational definitions of concepts such as "rural", "remote" and "serious", and unanticipated methodological and practical challenges involved in recruiting a comparison series will be explored. We will also present some of the many ethical, legal, organisational and logistic complications which we faced and still face in mounting such a study and the solutions proposed and subsequently employed to overcome them.

Research into work-related driver safety in corporate vehicle fleets has provided some descriptive information about driving for work and some of the common approaches to fleet safety. However, a lack of theoretical underpinnings has constrained the scope of this research. This paper outlines some theories and conceptual approaches from organisational and industrial psychology which are applicable for researching work-related driving and designing fleet safety countermeasures. Approaches described relate to contextual performance, occupational stress, organisational culture and climate. In using these approaches, work-related driving is conceptualised as an organisational behaviour – a behaviour of employees which occurs in the organisational setting. These are consolidated into an integrated approach to fleet safety. In addition to enhancing the understanding of work-related driving, utilising this integrated approach will result in intervention strategies designed to target the key psychosocial and organisational factors involved.

Rates of fatalities and serious injuries are higher in rural and remote crashes and have been less responsive to road safety strategies. In 2004 the research team began a study funded by Queensland Government to develop a close understanding of such crashes and to obtain data to inform targeted interventions. The study aims to recruit all persons hospitalized in North Queensland after a road crash that occurred in a non-urban site in the region. Data is collected from patient interviews on trip experience, behavioural and social variables and attitudes to road safety. Location of crash, vehicle characteristics and medical and ambulance retrieval information are collected separately and linked to the data base. The response rate has been high (80%+) and this paper reports on the first 150 cases. It presents the crash trip experiences, driver characteristics including their self reported use of alcohol and other licit and illicit drugs. Drivers’ residential characteristics relative to crash site and type and other sociogeographical characteristics and the types and severity of injuries are also considered.

Epidemiological evidence regarding the occurrence of drug driving amongst young drivers is concerning. This study examined the prevalence of drug driving in a sample of 331 young Australian drivers (average age 24 years), as well as a number of social and psychological influences associated with the behaviour. Results revealed that 26% reported having driven under the influence of psychoactive drugs at least once in their lifetime, and 15% indicated driving within 6 hours of taking drugs and alcohol. While no participants reported being convicted of a drug driving offence, 3% had been involved in one or more crashes whilst drug driving (10% of those who had ever drug driven). Investigations revealed that drug driving behaviour was significantly correlated with vicarious punishment avoidance (r = .41) and direct punishment avoidance (r = .35), suggesting an important link between young peoples’ perceptions about detection and punishment and their own propensity to drug drive. Sensation seeking (r = .24) and attitudes (r = .34) were also significantly correlated with drug driving. Further evidence indicated that those who perceived more social and non-social rewards than punishments associated with drug driving, were more likely to engage in the behaviour. Results suggest that perceptions about detection and punishment are an important influence upon drug driving behaviour for young drivers. The social and non-social rewards associated with drug driving also play an important role.

Over the last few years, it has been clearly established that normal plasma contains low levels of oxidized polypeptides, and that these accumulate in tissues during several age-related pathologies. In contrast, normal mammalian aging, contrary to conventional dogma, is not clearly associated with enhanced levels of oxidized proteins, except in extracellular connective tissues, whose proteins can, for example, be oxidized by the neutrophil oxidative burst. Since mildly oxidized proteins are susceptible to accelerated degradation in most experimental systems, the question arises as to how the accumulation of oxidized proteins can take place. Such accumulation requires an excess of production (or deposition) over removal, which might reflect alterations in capacity or rate of production or removal. This chapter discusses our presently limited knowledge of rates and control of proteolysis of oxidized proteins in two pathologies, cataractogenesis and atherogenesis. It commences with a brief summary of current understanding of the mechanisms of protein oxidation, and of the observed accumulation of oxidized proteins in several pathologies.

Over the last few years, it has been clearly established that normal plasma contains low levels of oxidized polypeptides, and that these accumulate in tissues during several age-related pathologies. In contrast, normal mammalian aging, contrary to conventional dogma, is not clearly associated with enhanced levels of oxidized proteins, except in extracellular connective tissues, whose proteins can, for example, be oxidized by the neutrophil oxidative burst. Since mildly oxidized proteins are susceptible to accelerated degradation in most experimental systems, the question arises as to how the accumulation of oxidized proteins can take place. Such accumulation requires an excess of production (or deposition) over removal, which might reflect alterations in capacity or rate of production or removal. This chapter discusses our presently limited knowledge of rates and control of proteolysis of oxidized proteins in two pathologies, cataractogenesis and atherogenesis. It commences with a brief summary of current understanding of the mechanisms of protein oxidation, and of the observed accumulation of oxidized proteins in several pathologies.

The primary ore at El Teniente is a high-cohesion impermeable rock mass. Its mining at the Sub6 sector utilised mechanised panel caving with an increased column height to control dilution. Six months after the beginning of production, the sector was affected by induced seismicity with associated rock bursts, with the consequence that all mining became controlled tactically by the rock mass response. Mining ceased and resumed subsequently with the application of a revised mining plan. A global digital seismic monitoring network was introduced for both tectonic and mining-induced seismicity. Since seismic activity is a result of rockmass rupture, the mining parameters, such as undercutting advance rate and extraction rate, were controlled by modifying these in relation to the rock mass characteristics. Control of local interactions and mine operations was also required. A production plan modified using these concepts was implemented and the sector has had no significant rockbursts since. The results of the programme showed that the most critical stage in developing a caving operation in a new sector is the period before connection to an upper crater or abandoned upper sector., The primary ore at El Teniente is a high-cohesion impermeable rock mass. Its mining at the Sub6 sector utilised mechanised panel caving with an increased column height to control dilution. Six months after the beginning of production, the sector was affected by induced seismicity with associated rock bursts, with the consequence that all mining became controlled tactically by the rock mass response. Mining ceased and resumed subsequently with the application of a revised mining plan. A global digital seismic monitoring network was introduced for both tectonic and mining-induced seismicity. Since seismic activity is a result of rockmass rupture, the mining parameters, such as undercutting advance rate and extraction rate, were controlled by modifying these in relation to the rock mass characteristics. Control of local interactions and mine operations was also required. A production plan modified using these concepts was implemented and the sector has had no significant rockbursts since. The results of the programme showed that the most critical stage in developing a caving operation in a new sector is the period before connection to an upper crater or abandoned upper sector.

Cancer pain can be relieved with pharmacological agents as indicated by the World Health Organization (WHO). All too frequently pain management is reported to be poor.

Since the beginning of a massive extraction of primary copper ore in 1980, El Teniente has been affected by induced seismicity. The first approach to monitoring was local, using analog networks installed in some productive sectors, and this evolved to global monitoring with a digital system. Caving, particularly panel retreat caving, is the main method used and is an autonomous rock breaking process driven by gravity; seismicity is an essential part of the process. Seismicity, as a dynamic process, depends mainly on the way that mining is performed, with geometry and rock mass geology as parameters. The induced seismicity is directly related to the programmed extraction rate and exploitation sequences. If induced seismicity is interpreted as a cost associated with the necessary repair following a rockburst, then this cost could be a relevant mine planning variable in planned productive sectors that could be affected by rock bursts., Since the beginning of a massive extraction of primary copper ore in 1980, El Teniente has been affected by induced seismicity. The first approach to monitoring was local, using analog networks installed in some productive sectors, and this evolved to global monitoring with a digital system. Caving, particularly panel retreat caving, is the main method used and is an autonomous rock breaking process driven by gravity; seismicity is an essential part of the process. Seismicity, as a dynamic process, depends mainly on the way that mining is performed, with geometry and rock mass geology as parameters. The induced seismicity is directly related to the programmed extraction rate and exploitation sequences. If induced seismicity is interpreted as a cost associated with the necessary repair following a rockburst, then this cost could be a relevant mine planning variable in planned productive sectors that could be affected by rock bursts.

Mine taxation regimes have been compared for Canada, the USA, Australia, Brazil, Chile, Indonesia, Papua New Guinea, Peru, South Africa and Zambia. The central focus was an analysis of the effective tax rates experienced by a mine project in different countries. The impact of various economic conditions on the rate of effective taxation was investigated by applying models of mineral income tax legislation in the various countries to the same mine model. Special attention was paid to the tax treatment of capital items and the impacts of incentives for capital investment. The study also investigated how changing levels of profitability, inflation and product price cycles alter effective taxation rates. Tax systems which provide significant investment incentives were found, in most cases, to be progressive with respect to profitability, i.e. the effective tax rate varies directly with the rate of profit., Mine taxation regimes have been compared for Canada, the USA, Australia, Brazil, Chile, Indonesia, Papua New Guinea, Peru, South Africa and Zambia. The central focus was an analysis of the effective tax rates experienced by a mine project in different countries. The impact of various economic conditions on the rate of effective taxation was investigated by applying models of mineral income tax legislation in the various countries to the same mine model. Special attention was paid to the tax treatment of capital items and the impacts of incentives for capital investment. The study also investigated how changing levels of profitability, inflation and product price cycles alter effective taxation rates. Tax systems which provide significant investment incentives were found, in most cases, to be progressive with respect to profitability, i.e. the effective tax rate varies directly with the rate of profit.