Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Double-strand breaks and the concept of short- and long-term epigenetic memory

Double-strand breaks represent an extremely cytolethal form of DNA damage and thus pose a serious threat to the preservation of genetic and epigenetic information. Though it is well-known that double-strand breaks such as those generated by ionising radiation are among the principal causative factors behind mutations, chromosomal aberrations, genetic instability and carcino-genesis, significantly less is known about the epigenetic consequences of double-strand break formation and repair for carcinogenesis. Double-strand break repair is a highly coordinated process that requires the unravelling of the compacted chromatin structure to facilitate repair machinery access and then restoration of the original undamaged chromatin state. Recent experimental findings have pointed to a potential mechanism for double-strand break-induced epigenetic silencing. This review will discuss some of the key epigenetic regulatory processes involved in double-strand break (DSB) repair and how incomplete or incorrect restoration of chromatin structure can leave a DSB-induced epigenetic memory of damage with potentially pathological repercussions

Audit committee effectiveness : informal processes and behavioural effects

Purpose This paper seeks to investigate the conditions and processes affecting the operation and potential effectiveness of audit committees (ACs), with particular focus on the interaction between the AC, individuals from financial reporting and internal audit functions and the external auditors. Design/methodology/approach A case study approach is employed, based on direct engagement with participants in AC activities, including the AC chair, external auditors, internal auditors, and senior management. Findings The authors find that informal networks between AC participants condition the impact of the AC and that the most significant effects of the AC on governance outcomes occur outside the formal structures and processes. An AC has pervasive behavioural effects within the organization and may be used as a threat, an ally and an arbiter in bringing solutions to issues and conflicts. ACs are used in organizational politics, communication processes and power plays and also affect interpretations of events and cultural values. Research limitations/implications Further research on AC and governance processes is needed to develop better understanding of effectiveness. Longitudinal studies, focusing on the organizational and institutional context of AC operations, can examine how historical events in an organization and significant changes in the regulatory environment affect current structures and processes. Originality/value The case analysis highlights a number of significant factors which are not fully recognised either in theorizing the governance role of ACs or in the development of policy and regulations concerning ACs but which impinge on their governance contribution. They include the importance of informal processes around the AC; its influence on power relations between organizational participants; the relevance of the historical development of governance in an organization; and the possibility that the AC’s impact on governance may be greatest in non-routine situations.

Regulating audit quality : restoring trust and legitimacy

The global financial crsis, corporate failures and scandals in amny countries raise significant questions audit quality. In the UK, the FRC took the unprecedented step of codifying audit quality in its ‘Audit Quality Framework’. We analyze the extent to which audit firms, professional bodies, and investors considered the FRC proposals sufficient for addressing concerns about audit quality. Using impression management and legitimacy as a framework to analyze stakeholder responses we go beyond audit quality drivers identified by the FRC. In contrast to the drivers identified by the FRC, our focus on transparency, expertise, professionalism and commercialization of the audit shows that FRC, audit firms and professional bodies have mainly focused on issues which possibly do not pose a threat to the commercial interest of audit firms. Overall, our analysis shows that regulatory and professional bodies engaged in image management and the promotion of audit quality in an attempt to remedy tarnished image and augment their legitimacy and standing. In attempting to restore trust and legitimacy regulatory bodies, such as the FRC, have to reconcile complex often contradictory stakeholder demands.

The role of university research centres in building road safety capacity : implications for China

In recent decades, highly motorised countries, such as Australia, have witnessed significant improvements in population health through reductions in fatalities and injuries from road traffic crashes. In Australia, concerted efforts have been made to reduce the road trauma burden since road fatalities reached their highest level in in the early 1970s. Since that time, many improvements have been made drawing on various disciplines to reduce the trauma burden (e.g., road and vehicle design, road user education, traffic law enforcement practices and enforcement technologies). While road fatalities have declined significantly since the mid-1970s, road trauma remains a serious public health concern in Australia. China has recently become the largest car market in the world (Ma, Li, Zhou, Duan, & Bishai, 2012). This rapid motorisation has been accompanied by substantial expansion of the road network as well as a large road trauma burden. Road traffic injuries are a major cause of death in China, reported as accounting for one third of all injury-deaths between 2002 and 2006 (Ma et al., 2012). In common with Australia, China has experienced a reported decline in fatalities since 2002 (see Hu, Wen & Baker, 2008). However, there remains a strong need for action in this area as rates of motorisation continue to climb in China. In Australia, a wide range of organisations have contributed to the improvements in road safety including government agencies, professional organisations, advocacy groups and research centres. In particular, Australia has several highly regarded and multi-disciplinary, university-based research centres that work across a range of road safety fields, including engineering, intelligent transportation systems, the psychology of road user behaviour, and traffic law enforcement. Besides conducting high-quality research, these centres fulfil an important advocacy role in promoting safer road use and facilitating collaborations with government and other agencies, at both the national and international level. To illustrate the role of these centres, an overview will be provided of the Centre for Accident Research and Road Safety-Queensland (CARRS-Q), which was established in 1996 and has gone on to become a recognised world-leader in road safety and injury prevention research. The Centre’s research findings are used to provide evidence-based recommendations to government and have directly contributed to promoting safer road use in Australia. Since 2006, CARRS-Q has also developed strong collaborative links with various universities and organisations in China to assist in building understanding, connections and capacity to assist in reducing the road trauma burden. References Hu, G., Wen, M., Baker, T. D., & Baker, S. P. (2008). Road-traffic deaths in China, 1985–2005: threat and opportunity. Injury Prevention, 14, 149-153. Ma, S., Li, Q., Zhou, M., Duan, L., & Bishai, D. (2012). Road Traffic Injury in China: A Review of National Data Sources. Traffic Injury Prevention, 13(S1), 57-63.

The conservation status of New Zealand bats, 2009

The New Zealand Threat Classification System (NZTCS) is a national system used to assess the risk of extinction faced by New Zealand plants, animals and fungi. The system is specifically designed to be relevant to New Zealand's unusual ecological and geographic conditions. We undertook a re-evaluation of the status of seven bat taxa based on our knowledge of New Zealand bats using revised NZTCS criteria. Five taxa were listed as Threatened or At Risk: one as Nationally Critical (long-tailed bat Chalinolobus tuberculatus ‘South Island’), one as Nationally Endangered (southern lesser short-tailed bat Mystacina tuberculata tuberculata), two as Nationally Vulnerable (long-tailed bat ‘North Island’ and northern lesser short-tailed bat M. t. aupourica) and one as Declining (central lesser short-tailed bat M. t. rhyacobia). One taxon was assessed as Data Deficient (greater short-tailed bat M. robusta) and one (little red flying fox Pteropus scapulatus) as Vagrant. We suspect declines result primarily from predation and competition from introduced mammals, habitat degradation, and disturbance.

Retinal tissue thickness is reduced in diabetic peripheral neuropathy

Aim Retinal tissue integrity in relation to diabetic neuropathy is not known. The aim of this study was to investigate retinal tissue thickness in relation to diabetic peripheral neuropathy (DPN) with and without diabetic retinopathy (DR). Methods Full retinal thickness at the parafoveal and perifoveal macula and neuro-retinal thickness around the optic nerve head (ONH) and at the macula was examined using spectral domain optical coherence tomography. The eye on the hand-dominant side of 85 individuals with type 1 diabetes and 66 individuals with type 2 diabetes, with or without DR and DPN, were compared to the eyes (n=45) of age-matched non-diabetic controls. Diabetic neuropathy was defined as Neuropathy Disability Score (NDS) ≥3 on a scale of 0-10. A general linear model was used to examine the relationship between diabetic neuropathy and foveal, parafoveal and perifoveal retinal thickness and neuro-retinal thickness, in relation to DR status, age, gender, HbA1c levels and duration of diabetes. A p-value of <0.05 was considered statistically significant. Results Perifoveal retinal thickness is reduced with increasing severity of neuropathy, especially in the inferior hemisphere (p=0.004); this effect was not related to age (p=0.088). For every unit increase in NDS score, the inferior perifoveal retinal thickness reduced by 1.64 μm. Neuro-retinal thickness around the ONH decreased with increasing severity of neuropathy (p<0.014 for average and hemisphere thicknesses); for every unit increase in NDS, neuro-retinal thickness around the ONH reduced by 1.23 μm. Retinal thickness in the parafovea was increased in the absence of DR (p<0.017 for average and hemisphere thicknesses). Neuro-retinal thickness at the macula was inversely related to age alone (p<0.001). All retinal parameters, except the inferior perifovea, reduced with advancing age (p<0.007 for all). Conclusions Diabetic neuropathy is associated with changes in full retinal thickness and neuro-retinal layers. This may represent a second threat to vision integrity, in addition to the better-characterised retinopathy. This study provides new knowledge about the anatomical aspects of the retinal tissue in relation to neuropathy and retinopathy.

Mississippi Delta subsidence primarily caused by compaction of Holocene strata

Coastal subsidence causes sea-level rise, shoreline erosion and wetland loss, which poses a threat to coastal populations. This is especially evident in the Mississippi Delta in the southern United States, which was devastated by Hurricane Katrina in 2005. The loss of protective wetlands is considered a critical factor in the extensive flood damage. The causes of subsidence in coastal Louisiana, attributed to factors as diverse as shallow compaction and deep crustal processes, remain controversial. Current estimates of subsidence rates vary by several orders of magnitude. Here, we use a series of radiocarbon-dated sediment cores from the Mississippi Delta to analyse late Holocene deposits and assess compaction rates. We find that millennial-scale compaction rates primarily associated with peat can reach 5mm per year, values that exceed recent model predictions. Locally and on timescales of decades to centuries, rates are likely to be 10 mm or more per year. We conclude that compaction of Holocene strata contributes significantly to the exceptionally high rates of relative sea-level rise and coastal wetland loss in the Mississippi Delta, and is likely to cause subsidence in other organic-rich and often densely populated coastal plains.

Urban citizenship in a sensor rich society

Urban public spaces are sutured with a range of surveillance and sensor technologies that claim to enable new forms of ‘data based citizen participation’, but also increase the tendency for ‘function-creep’, whereby vast amounts of data are gathered, stored and analysed in a broad application of urban surveillance. This kind of monitoring and capacity for surveillance connects with attempts by civic authorities to regulate, restrict, rebrand and reframe urban public spaces. A direct consequence of the increasingly security driven, policed, privatised and surveilled nature of public space is the exclusion or ‘unfavourable inclusion’ of those considered flawed and unwelcome in the ‘spectacular’ consumption spaces of many major urban centres. In the name of urban regeneration, programs of securitisation, ‘gentrification’ and ‘creative’ and ‘smart’ city initiatives refashion public space as sites of selective inclusion and exclusion. In this context of monitoring and control procedures, in particular, children and young people’s use of space in parks, neighbourhoods, shopping malls and streets is often viewed as a threat to the social order, requiring various forms of remedial action. This paper suggests that cities, places and spaces and those who seek to use them, can be resilient in working to maintain and extend democratic freedoms and processes enshrined in Marshall’s concept of citizenship, calling sensor and surveillance systems to account. Such accountability could better inform the implementation of public policy around the design, build and governance of public space and also understandings of urban citizenship in the sensor saturated urban environment.

A neuronal topography of visual and acoustic fear conditioning within the amygdala

The lateral amygdala (LA) receives information from auditory and visual sensory modalities, and uses this information to encode lasting memories that predict threat. One unresolved question about the amygdala is how multiple memories, derived from different sensory modalities, are organized at the level of neuronal ensembles. We previously showed that fear conditioning using an auditory conditioned stimulus (CS) was spatially allocated to a stable topography of neurons within the dorsolateral amygdala (LAd) (Bergstrom et al, 2011). Here, we asked how fear conditioning using a visual CS is topographically organized within the amygdala. To induce a lasting fear memory trace we paired either an auditory (2 khz, 55 dB, 20 s) or visual (1 Hz, 0.5 s on/0.5 s off, 35 lux, 20 s) CS with a mild foot shock unconditioned stimulus (0.6 mA, 0.5 s). To detect learning-induced plasticity in amygdala neurons, we used immunohistochemistry with an antibody for phosphorylated mitogen-activated protein kinase (pMAPK). Using a principal components analysis-based approach to extract and visualize spatial patterns, we uncovered two unique spatial patterns of activated neurons in the LA that were associated with auditory and visual fear conditioning. The first spatial pattern was specific to auditory cued fear conditioning and consisted of activated neurons topographically organized throughout the LAd and ventrolateral nuclei (LAvl) of the LA. The second spatial pattern overlapped for auditory and visual fear conditioning and was comprised of activated neurons located mainly within the LAvl. Overall, the density of pMAPK labeled cells throughout the LA was greatest in the auditory CS group, even though freezing in response to the visual and auditory CS was equivalent. There were no differences detected in the number of pMAPK activated neurons within the basal amygdala nuclei. Together, these results provide the first basic knowledge about the organizational structure of two different fear engrams within the amygdala and suggest they are dissociable at the level of neuronal ensembles within the LA

From the bush to the burbs : a comparison of driver situation awareness at rural and urban railway level crossings

The problem of collisions between road users and trains at rail level crossings (RLXs) remains resistant to current countermeasures. One factor underpinning these collisions is poor Situation Awareness (SA) on behalf of the road user involved (i.e. not being aware of an approaching train). Although this is a potential threat at any RLX, the factors influencing SA may differ depending on whether the RLX is located in a rural or urban road environment. Despite this, there has been no empirical investigation regarding how road user SA might differ across distinct RLX environments. This knowledge is needed to establish the extent to which a uniform approach to RLX design and safety is acceptable. The aim of this paper is to investigate the differences in driver SA at rural versus urban RLXs. We present analyses of driver SA in both rural and urban RLX environments based on two recent on-road studies undertaken in Victoria, Melbourne. The findings demonstrate that driver SA is markedly different at rural and urban RLXs, and also that poor SA regarding approaching trains may be caused by different factors. The implications for RLX design and safety are discussed.

Investigating the link between carbon dioxide emissions and transport-related social exclusion in rural Northern Ireland

Carbon dioxide (CO2) is considered the most harmful of the greenhouse gases. Despite policy efforts, transport is the only sector experiencing an increase in the level of CO2 emissions and thereby possesses a major threat to sustainable development. In contrast, a reduced level of mobility has been associated with an increasing risk of being socially excluded. However, despite being the two key elements in transport policy, little effort has so far been made to investigate the links between CO2 emissions and social exclusion. This research contributes to this gap by analysing data from 157 weekly activity-travel diaries collected in rural Northern Ireland. CO2 emission levels were calculated using average speed models for different modes of transport. Regression analyses were then conducted to identify the socio-spatial patterns associated with these CO2 emissions, mode choice behaviour, and patterns of participation in activities. This research found that despite emitting a higher level of carbon dioxide, groups in rural areas possess the risk of being socially excluded due to their higher levels of mobility.

Never at Home? Migrants Between Societies

This chapter explores the dialectic meaning of ‘home’, and movement away from home. Movement away from home – migration – is characterized as a dynamic, dialectic, and developmental experience. We emphasize the sense of being at home and the intertwined sense of identity as interlinked and mutually defining anchors of our existence that become inevitably shaken and ruptured in the experience of migration. But when looking at how this rupture is experienced and managed, we highlight the inherently complex and dialectic nature of migration, instead of seeing it as a unidirectional sequence of rupture → shock → coping → new stable being. We discuss the complexities of migration experiences as entailing dialectics of home and non-home, rupture and continuity, novelty and everydayness, changing and remaining. The sense of being at home is simultaneously enabling and constraining, helping us to build self-continuity in a new environment, yet also holding us back and distancing us from novelty. Similarly, migration is a threat, yet also a promise; it is a painful, yet possibly exhilarating experience that makes us lose our centre of security and familiarity, yet also opens up opportunities for transformation and re-invention.

Male and female cyclist and driver perceptions of crash risk

Many drivers and non-cyclists perceive cycling as an extremely risky activity with women in particular being concerned about the risk of injury. The low rates of cycling participation by women pose a threat to the achievement of government targets for cycling participation and restrict the potential transport, health and environmental benefits that increased levels of cycling could provide. This study seeks to extend earlier research in gender and cycling by comparing the risks perceived by female and male cyclists and drivers in specific on-road situations while accounting for other potentially gender-related factors such as travel patterns and experience, perceived skill, and risk taking behaviors. In an online survey, 444 regular cyclists and 151 (non-cyclist) car drivers rated the level of risk in six situations: Failing to yield; Going through a red light; Not signaling when turning; Swerving; Tailgating; and Not checking traffic. The study found that the higher levels of risk perceived by women are not completely accounted for by differences in cycling patterns or perceptions of skill. Compared to their male counterparts, female cyclists and car drivers had similarly elevated perceptions of risk suggesting that these gender differences are not specific to cycling, but reflect wider differences in risk perception. Not all of the gender differences were consistent across cyclists and drivers. Higher levels of perceived skill were evident for male cyclists but not for male car drivers. Further research is needed to explore the robustness and interpretation of this finding.