When non-significance may be significant : lessons learned from a study of the development, implementation and evaluation of a fleet risk assessment tool

This paper reports on the development and implementation of a self-report risk assessment tool that was developed in an attempt to increase the efficacy of crash prediction within Australian fleet settings. This study forms a part of a broader program of research into work related road safety and identification of driving risk. The first phase of the study involved a series of focus groups being conducted with 217 professional drivers which revealed that the following factors were proposed to influence driving performance: Fatigue, Knowledge of risk, Mood, Impatience and frustration, Speed limits, Experience, Other road users, Passengers, Health, and Culture. The second phase of the study involved piloting the newly developed 38 item Driving Risk Assessment Scale - Work Version (DRAS-WV) with 546 professional drivers. Factor analytic techniques identified a 9 factor solution that was comprised of speeding, aggression, time pressure, distraction, casualness, awareness, maintenance, fatigue and minor damage. Speeding and aggressive driving manoeuvres were identified to be the most frequent aberrant driving behaviours engaged in by the sample. However, a series of logistic regression analyses undertaken to determine the DRAS-WV scale’s ability to predict self-reported crashes revealed limited predictive efficacy e.g., 10% of crashes. This paper outlines proposed reasons for this limited predictive ability of the DRAS-WV as well as provides suggestions regarding the future of research that aims to develop methods to identify “at risk” drivers.

The impacts of power outages on the residents of contemporary multistorey apartment buildings in subtropical environments

With significant population growth experienced in South East Queensland over the past two decades and a high rate of growth expected to continue in coming decades, the Queensland Government is promoting urban consolidation planning policies to manage growth sustainably. Multi-residential buildings will play an important role in facilitating the increased densities which urban consolidation policies imply. However, a major flood event in January 2011 has brought to light the vulnerability of certain types of multi-residential typologies to power outages. The crisis conditions exposed how contemporary building design and construction practices, coupled with regulatory and planning issues, appear to have compromised the resilience and habitability of multi-storey residential buildings. In the greater urban area of Brisbane, Queensland, the debilitating dependence that certain types of apartment buildings have on mains electricity was highlighted by residents’ experiences of the Brisbane River flood disaster, before, during and after the event. This research examined high density residential buildings in West End, Brisbane, an inner city suburb which was severely affected by the flood and is earmarked for significant urban densification under the Brisbane City Plan. Medium-to-high-density residential buildings in the suburb were mapped in flooded and non-flooded locations and a database containing information about the buildings was created. Parameters included date of construction, number of storeys, systems of access and circulation, and potential for access to natural light and ventilation for habitable areas. A series of semi-structured interviews were conducted with residents involved in the owners’ management committees of several buildings to verify information the mapping could not provide. The interviews identified a number of critical systems failures due to power outage which had a significant impact on residents’ wellbeing, comfort and safety. Building services such as lifts, running water, fire alarms, security systems and air-conditioning ceased to operate when power was disconnected to neighbourhoods and buildings in anticipation of rising flood waters. Lack of access to buildings and dwellings, lack of safety, lack of building security, and lack of thermal comfort affected many residents whether or not their buildings were actually subjected to inundation, with some buildings rendered uninhabitable for a prolonged period. The extent of the impact on residents was dramatically influenced by the scale and type of building inhabited, with those dwelling in buildings under a 25m height limit, with a single lift, found to be most affected. The energy-dependency and strong trend of increasing power demands of high-rise buildings is well-documented. Extended electricity outages such as the one brought about by the 2011 flood in Queensland are likely to happen more frequently than the 50-year average of the flood event itself. Electricity blackouts can result from a number of man-made or natural causes, including shortages caused by demand exceeding supply. This paper highlights the vulnerability of energy-dependent buildings to power outages and investigates options for energy security for occupants of multi-storey buildings and makes recommendations to increase resilience and general liveability in multi-residential buildings in the subtropics through design modifications.

Assessment of daily light and ultraviolet exposure in young adults

Purpose: There are some limited reports, based on questionnaire data, which suggest that outdoor activity decreases the risk of myopia in children and may offset the myopia risk associated with prolonged near work. The aim of this study was to explore the relationship between near work, indoor illumination, daily sunlight and ultraviolet (UV) exposure in emmetropic and myopic University students, given that University students perform significant amounts of near work and as a group have a high prevalence of myopia. Methods: Participants were 35 students, aged 17 to 25 years who were classified as being emmetropic (n=13), or having stable (n=12) or progressing myopia (n=10). During waking hours on three separate days participants wore a light sensor data logger (HOBO) and a polysulphone UV dosimeter; these devices measured daily illuminance and accumulative UV exposure respectively; participants also completed a daily activity log. Results: No significant between group differences were observed for average daily illuminance (p=0.732), number of hours per day spent in sunlight (p=0.266), outdoor shade (p=0.726), bright indoor/dim outdoor light (p=0.574) or dim room illumination (p=0.484). Daily UV exposure was significantly different across the groups (p=0.003); with stable myopes experiencing the greatest UV exposure (versus emmetropes p=0.002; versus progressing myopes p=0.004). Conclusions: The current literature suggests there is a link between myopia protection and spending time outdoors in children. Our data provides some evidence of this relationship in young adults and highlights the need for larger studies to further investigate this relationship longitudinally.

ASAP ECMO : antibiotic, sedative and analgesic pharmacokinetics during extracorporeal membrane oxygenation : a multi-centre study to optimise drug therapy during ECMO

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure

Sentencing indigenous and non-indigenous women in Western Australia's higher courts : A summary of the main findings of a narrative study

This paper presents the main findings of a narrative examination of higher court sentencing remarks to explore the relationship between Indigeneity and sentencing for female defendants in Western Australia. Using the theoretical framework of focal concerns, we found that key differences in the construction of blameworthiness and risk between the sentencing stories of Indigenous and non-Indigenous female offenders, through the identification of issues such as mental health, substance abuse, familial trauma and community ties. Further, in the sentencing narratives, Indigenous women were viewed differently in terms of social costs of imprisonment.

Structure of the immature retroviral capsid at 8 Å resolution by cryo-electron microscopy

The assembly of retroviruses such as HIV-1 is driven by oligomerization of their major structural protein, Gag. Gag is a multidomain polyprotein including three conserved folded domains: MA (matrix), CA (capsid) and NC (nucleocapsid)(1). Assembly of an infectious virion proceeds in two stages(2). In the first stage, Gag oligomerization into a hexameric protein lattice leads to the formation of an incomplete, roughly spherical protein shell that buds through the plasma membrane of the infected cell to release an enveloped immature virus particle. In the second stage, cleavage of Gag by the viral protease leads to rearrangement of the particle interior, converting the non-infectious immature virus particle into a mature infectious virion. The immature Gag shell acts as the pivotal intermediate in assembly and is a potential target for anti-retroviral drugs both in inhibiting virus assembly and in disrupting virus maturation(3). However, detailed structural information on the immature Gag shell has not previously been available. For this reason it is unclear what protein conformations and interfaces mediate the interactions between domains and therefore the assembly of retrovirus particles, and what structural transitions are associated with retrovirus maturation. Here we solve the structure of the immature retroviral Gag shell from Mason-Pfizer monkey virus by combining cryo-electron microscopy and tomography. The 8-angstrom resolution structure permits the derivation of a pseudo-atomic model of CA in the immature retrovirus, which defines the protein interfaces mediating retrovirus assembly. We show that transition of an immature retrovirus into its mature infectious form involves marked rotations and translations of CA domains, that the roles of the amino-terminal and carboxy-terminal domains of CA in assembling the immature and mature hexameric lattices are exchanged, and that the CA interactions that stabilize the immature and mature viruses are almost completely distinct.

Cryo-electron tomography of Marburg Virus particles and their morphogenesis within infected cells

Several major human pathogens, including the filoviruses, paramyxoviruses, and rhabdoviruses, package their single-stranded RNA genomes within helical nucleocapsids, which bud through the plasma membrane of the infected cell to release enveloped virions. The virions are often heterogeneous in shape, which makes it difficult to study their structure and assembly mechanisms. We have applied cryo-electron tomography and sub-tomogram averaging methods to derive structures of Marburg virus, a highly pathogenic filovirus, both after release and during assembly within infected cells. The data demonstrate the potential of cryo-electron tomography methods to derive detailed structural information for intermediate steps in biological pathways within intact cells. We describe the location and arrangement of the viral proteins within the virion. We show that the N-terminal domain of the nucleoprotein contains the minimal assembly determinants for a helical nucleocapsid with variable number of proteins per turn. Lobes protruding from alternate interfaces between each nucleoprotein are formed by the C-terminal domain of the nucleoprotein, together with viral proteins VP24 and VP35. Each nucleoprotein packages six RNA bases. The nucleocapsid interacts in an unusual, flexible "Velcro-like" manner with the viral matrix protein VP40. Determination of the structures of assembly intermediates showed that the nucleocapsid has a defined orientation during transport and budding. Together the data show striking architectural homology between the nucleocapsid helix of rhabdoviruses and filoviruses, but unexpected, fundamental differences in the mechanisms by which the nucleocapsids are then assembled together with matrix proteins and initiate membrane envelopment to release infectious virions, suggesting that the viruses have evolved different solutions to these conserved assembly steps.

A boy and his toys : technology and gadgetry in the James Bond films

This chapter provides an indepth examination of the history of product placement in the James Bond film series, specifically focusing on the emergence of technology and gadgetry in the series and the impact this had on the number and types of products that were placed in the films.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Extracorporeal lessons from sheep

Background: Extracorporeal circulation (ECC), the diversion of blood flow through a circuit located outside of the body, has been one of the major advances in modern medicine. Cardio-pulmonary bypass (CPB), renal dialysis, apheresis and extracorporeal membrane oxygenation (ECMO) are all different forms of ECC. Despite its major benefits, when blood comes into contact with foreign material, both the coagulation and inflammation cascades are activated simultaneously. Short periods of exposure to ECC e.g. CPB (�2 h duration), are known to be associated with haemolysis, coagulopathies, bleeding and inflammation which demand blood product support. Therefore, it is not unexpected that these complications would be exaggerated with prolonged periods of ECC such as in ECMO (days to weeks duration). The variability and complexities of the underlying pathologies of patients requiring ECC makes it difficult to study the cause and effect of these complications. To overcome this problem we developed an ovine (sheep) model of ECC. Method: Healthy female sheep (1–3 y.o.) weighing 40–50 kg were fasted overnight, anaesthetised, intubated and ventilated [1]. Half the group received smoke induced acute lung injury (S-ALI group) (n = 8) and the other half did not (healthy group) (n = 8). Sheep were subsequently cannulated (Medtronic Inc, Minneapolis, MN, USA) and veno-venous ECMO commenced using PLS ECMO circuit and Quadrox D oxygenator (Maquet Cardiopulmonary AG, Hechinger Straße, Germany). There was continuous physiological monitoring and blood was collected at specified time intervals for full blood counts, platelet function analysis (by Multiplate®), routine coagulation and assessment of clot formation and lysis (by ROTEM®). Preliminary results Full blood counts and routine coagulation results from normal healthy sheep were comparable to those of normal human adults. Within 15 min of initiating of ECMO, PT, PTT and EXTEM clot formation time increased, whilst EXTEM maximum clot firmness decreased in both cohorts. Discussion & Conclusions: Preliminary results of sheep from both 2 h ECMO cohorts showed that the anatomy, haematology and coagulation parameters of an adult sheep are comparable to that a human adult. Experiments are currently underway with healthy (n = 8) and S-ALI (n = 8) sheep on ECMO for 24 h. In addition to characterising how ECMO alters haematology and coagulation parameters, we hope that it will also define which blood components will be most effective to correct bleeding or clotting complications during ECMO support.

ECMO : the clinician’s view

Background: Extra corporeal membrane oxygenation (ECMO) is a complex rescue therapy used to provide cardiac and/or respiratory support for critically ill patients who have failed maximal conventional medical management. ECMO is based on a modified cardiopulmonary bypass (CPB) circuit, and can provide cardiopulmonary support for up-to several months. It can be used in a veno venous configuration for isolated respiratory failure, (VV-ECMO), or in a veno arterial configuration (VA-ECMO) where support is necessary for cardiac +/- respiratory failure. The ECMO circuit consists of five main components: large bore cannulae (access cannulae) for drainage of the venous system, and return cannulae to either the venous (in VV-ECMO) or arterial (in VA ECMO) system. An oxygenator, with a vast surface area of hollow filaments, allows addition of oxygen and removal of carbon dioxide; a centrifugal blood pump allows propulsion of blood through the circuit at upto 10 L/minute; a control module and a thermoregulatory unit, which allows for exact temperature control of the extra corporeal blood. Methods: The first successful use of ECMO for ARDS in adults occurred in 1972, and its use has become more commonplace over the last 30 years, supported by the improvement in design and biocompatibility of the equipment, which has reduced the morbidity associated with this modality. Whilst the use of ECMO in neonatal population has been supported by numerous studies, the evidence upon which ECMO was integrated into adult practice was substantially less robust. Results: Recent data, including the CESAR study (Conventional Ventilatory Support versus Extra corporeal membrane oxygenation for Severe Respiratory failure) has added a degree of evidence to the role of ECMO in such a patient population. The CESAR study analysed 180 patients, and confirmed that ECMO was associated with an improved rate of survival. More recently, ECMO has been utilized in numerous situations within the critical care area, including support in high-risk percutaneous interventions in cardiac catheter lab; the operating room, emergency department, as well in specialized inter-hospital retrieval services. The increased understanding of the risk:benefit profile of ECMO, along with a reduction in morbidity associated with its use will doubtless lead to a substantial rise in the utilisation of this modality. As with all extra-corporeal circuits, ECMO opposes the basic premises of the mammalian inflammation and coagulation cascade where blood comes into foreign circulation, both these cascades are activated. Anti-coagulation is readily dealt with through use of agents such as heparin, but the inflammatory excess, whilst less macroscopically obvious, continues un-abated. Platelet consumption and neutrophil activation occur rapidly, and the clinician is faced with balancing the need of anticoagulation for the circuit, against haemostasis in an acutely bleeding patient. Alterations in pharmacokinetics may result in inadequate levels of disease modifying therapeutics, such as antibiotics, hence paradoxically delaying recovery from conditions such as pneumonia. Key elements of nutrition and the innate immune system maysimilarly be affected. Summary: This presentation will discuss the basic features of ECMO to the nonspecialist, and review the clinical conundrum faced by the team treating these most complex cases.