Incorporating adverse event relatedness into dose-finding clinical trial designs

Dose-finding designs estimate the dose level of a drug based on observed adverse events. Relatedness of the adverse event to the drug has been generally ignored in all proposed design methodologies. These designs assume that the adverse events observed during a trial are definitely related to the drug, which can lead to flawed dose-level estimation. We incorporate adverse event relatedness into the so-called continual reassessment method. Adverse events that have ‘doubtful’ or ‘possible’ relationships to the drug are modelled using a two-parameter logistic model with an additive probability mass. Adverse events ‘probably’ or ‘definitely’ related to the drug are modelled using a cumulative logistic model. To search for the maximum tolerated dose, we use the maximum estimated toxicity probability of these two adverse event relatedness categories. We conduct a simulation study that illustrates the characteristics of the design under various scenarios. This article demonstrates that adverse event relatedness is important for improved dose estimation. It opens up further research pathways into continual reassessment design methodologies.

An objective study of acid reflux and cough in children using an ambulatory pHmetry-cough logger

Objective There are no objective ambulatory studies on the temporal relationship between reflux and cough in children. Commercial pHmetry loggers have slow capture rates (0.25 Hz) that limit objective quantification of reflux and cough. The authors aimed to evaluate if there is a temporal association between cough and acid pH in ambulatory children with chronic cough. setting and patients The authors studied children (aged <14 years) with chronic cough, suspected of acid reflux and considered for pHmetry using a specifically built ambulatory pHmetry–cough logger that enabled the simultaneous ambulatory recording of cough and pH with a fast (10 Hz) capture rate. Main outcome measures Coughs within (before and after) 10, 30, 60 and 120 s of a reflux episode (pH<4 for >0.5 s). Results Analysis of 5628 coughs in 20 children. Most coughs (83.9%) were independent of a reflux event. Cough–reflux (median 19, IQR 3–45) and reflux–cough (24.5, 13–51) sequences were equally likely to occur within 120 s. Within the 10 and 30 s time frame, reflux–cough (10 s=median 2.5, IQR 0–7.25; 30 s=6.5, 1.25–22.25) sequences were significantly less frequent than reflux–no cough (10 s=27, IQR 15–65; 30 s=24.5, 14.5–55.5) sequences, (p=0.0001 and p=0.001, respectively). No differences were found for 60 and 120 s time frame. Cough–reflux sequence (median 1.0, IQR 0–8) within 10 s was significantly less (p=0.0001) than no cough–reflux sequences (median 29.5, 15–67), within 30 s (p=0.006) and 60 s (p=0.048) but not within 120 s (p=0.47). Conclusions In children with chronic cough and suspected of having gastro-oesophageal reflux disease, the temporal relationship between acid reflux and cough is unlikely causal.

Is there an international duty to protect persons in the event of an epidemic?

In 2006, the International Law Commission began a study into the role of states and international organizations in protecting persons in the event of a disaster. Special Rapporteur Mr. Eduardo Valencia-Ospina was appointed to head the study, and in 2011 the findings of the study will be presented to the United Nations General Assembly. Of interest to this paper has been the inclusion of “epidemics” under the natural disaster category in all of the reports detailing the Commission’s program of work on the protection of persons. This paper seeks to examine the legal and political ramifications involved in including “epidemic” into the concept of protection by exploring where sovereign responsibility for epidemic control begins and ends, particularly in light of the revisions to the International Health Regulations by the World Health Assembly in 2005. The paper will first analyze the findings already presented by the Special Rapporteur, examining the existing “responsibilities” of both states and international organizations. Then, the paper will consider to what extent the concept of protection entails the duty to assist individuals when an affected state proves unwilling or unable to assist their own population in the event of a disease outbreak. In an attempt to answer this question, the third part of the paper will examine the recent cholera outbreak in Zimbabwe.

Semantic interference in object naming : an fMRI study of the postcue naming paradigm

It is well established that the time to name target objects can be influenced by the presence of categorically related versus unrelated distractor items. A variety of paradigms have been developed to determine the level at which this semantic interference effect occurs in the speech production system. In this study, we investigated one of these tasks, the postcue naming paradigm, for the first time with fMRI. Previous behavioural studies using this paradigm have produced conflicting interpretations of the processing level at which the semantic interference effect takes place, ranging from pre- to post-lexical. Here we used fMRI with a sparse, event-related design to adjudicate between these competing explanations. We replicated the behavioural postcue naming effect for categorically related target/distractor pairs, and observed a corresponding increase in neuronal activation in the right lingual and fusiform gyri-regions previously associated with visual object processing and colour-form integration. We interpret these findings as being consistent with an account that places the semantic interference effect in the postcue paradigm at a processing level involving integration of object attributes in short-term memory.

Perturbing event logs to identify cost reduction opportunities: a genetic algorithm-based approach

Organisations are constantly seeking new ways to improve operational efficiencies. This research study investigates a novel way to identify potential efficiency gains in business operations by observing how they are carried out in the past and then exploring better ways of executing them by taking into account trade-offs between time, cost and resource utilisation. This paper demonstrates how they can be incorporated in the assessment of alternative process execution scenarios by making use of a cost environment. A genetic algorithm-based approach is proposed to explore and assess alternative process execution scenarios, where the objective function is represented by a comprehensive cost structure that captures different process dimensions. Experiments conducted with different variants of the genetic algorithm evaluate the approach's feasibility. The findings demonstrate that a genetic algorithm-based approach is able to make use of cost reduction as a way to identify improved execution scenarios in terms of reduced case durations and increased resource utilisation. The ultimate aim is to utilise cost-related insights gained from such improved scenarios to put forward recommendations for reducing process-related cost within organisations.

Using the Event Analysis of Systemic Teamwork (EAST) to explore conflict between different road user groups when making right hand turns at urban intersections

Collisions between different types of road users at intersections form a substantial component of the road toll. This paper presents an analysis of driver, cyclist, motorcyclist and pedestrian behaviour at intersections that involved the application of an integrated suite of ergonomics methods, the Event Analysis of Systemic Teamwork (EAST) framework, to on-road study data. EAST was used to analyse behaviour at three intersections using data derived from an on-road study of driver, cyclist, motorcyclist and pedestrian behaviour. The analysis shows the differences in behaviour and cognition across the different road user groups and pinpoints instances where this may be creating conflicts between different road users. The role of intersection design in creating these differences in behaviour and resulting conflicts is discussed. It is concluded that currently intersections are not designed in a way that supports behaviour across the four forms of road user studied. Interventions designed to improve intersection safety are discussed.

Designing for grassroots food production : an event-based urban agriculture community

As urbanisation of the global population has increased above 50%, growing food in urban spaces increases in importance, as it can contribute to food security, reduce food miles, and improve people’s physical and mental health. Approaching the task of growing food in urban environments is a mixture of residential growers and groups. Permablitz Brisbane is an event-centric grassroots community that organises daylong ‘working bee’ events, drawing on permaculture design principles in the planning and design process. Permablitz Brisbane provides a useful contrast from other location-centric forms of urban agriculture communities (such as city farms or community gardens), as their aim is to help encourage urban residents to grow their own food. We present findings and design implications from a qualitative study with members of this group, using ethnographic methods to engage with and understand how this group operates. Our findings describe four themes that include opportunities, difficulties, and considerations for the creation of interventions by Human-Computer Interaction (HCI) designers.

Performing Rural Masculinities : A Case Study of Diggers and Dealers

This chapter examines what Parpart and Zalewski (2008) label 'the man question' in terms of the rural. That is, 'how masculinity comes to be "made" as a continuing process within the social context' of rural places and spaces (Kerfoot and Knights 1993: 662). Our understanding of masculinities as discursively produced, relational, multiple and changing is given empirical force through a case study of the annual resource conference, Diggers and Dealers. The conference, held in the remote mining town of Kalgoorlie in Western Australia since 1992, is today the largest international meeting for the resource sector, attracting over 2000 attendees. Through an analysis of 120 texts related to the conference from 2006 to the present, including media repotis, blogs and conference programs and speeches, we demonstrate how, what is essentially a corporate event, is imported into the rural and constructed through the intersecting discourses of rurality, masculinity and heterosexuality. That is, though the first such meeting may have taken place spontaneously in Kalgoorlie, the delegates, and the 'skimpy' barmaids who serve patrons in their underwear or sometimes topless and are seen as central to the event, are flown into town for the conference. Kalgoorlie, as a working mining community on the edge of the deseti, provides both spectacle and conditions for the enactment of frontier masculinity not possible in the metropole.

Urban Aboriginal and Torres Strait Islander children's exposure to stressful events : a cross sectional study

Objectives To determine the frequency and types of stressful events experienced by urban Aboriginal and Torres Strait Islander children, and to explore the relationship between these experiences and the children’s physical health and parental concerns about their behaviour and learning ability. Design, setting and participants Cross-sectional study of Aboriginal and Torres Strait Islander children aged ≤ 14 years presenting to an urban Indigenous primary health care service in Brisbane for annual child health checks between March 2007 and March 2010. Main outcome measures Parental or carer report of stressful events ever occurring in the family that may have affected the child. Results Of 344 participating children, 175 (51%) had experienced at least one stressful event. Reported events included the death of a family member or close friend (40; 23%), parental divorce or separation (28; 16%), witness to violence or abuse (20; 11%), or incarceration of a family member (7; 4%). These children were more likely to have parents or carers concerned about their behaviour (P < 0.001) and to have a history of ear (P < 0.001) or skin (P = 0.003) infections. Conclusions Children who had experienced stressful events had poorer physical health and more parental concern about behavioural issues than those who had not. Parental disclosure in the primary health care setting of stressful events that have affected the child necessitates appropriate medical, psychological or social interventions to ameliorate both the immediate and potential lifelong negative impact. However, treating the impact of stressful events is insufficient without dealing with the broader political and societal issues that result in a clustering of stressful events in the Aboriginal and Torres Strait Islander population.

The second chance project: A multi-level examination of secondary prevention practices for Saudi people following a recent cardiac event

The study examined the health-related behaviours of Saudi people following a recent cardiac event and identified the factors that influence these behaviours using McLeroy et al.'s (1988) Ecological Model of Health Behaviours as a guiding framework. The study was one of the first in Saudi Arabia to examine the health-related behaviours of Saudi people following a recent cardiac event. The study findings emphasise the importance of a program that integrates secondary prevention practices, educational approaches and targeted supportive services in cardiac care in Saudi Arabia.

Stress during the rebuilding phase influenced mental health following two Queensland flood disasters more than the event itself

It has long been known that disasters can have mental health consequences such as increased rates of PTSD, depression and anxiety. While some research has shown that secondary stressors during the aftermath of a disaster can influence psychological outcomes, this aspect of the disaster experience has not been widely studied. This paper reports on two studies that investigated which aspects of the experience of being flooded were most predictive of mental health outcomes. The first study was a qualitative study of adults whose homes had been inundated in the Mackay flood of 2008 (n=16). Thematic analysis of interviews conducted 18-20 months post-flood found that stressors during the flood aftermath such as difficulties and delays during the rebuilding process and a difficult experience with an insurance company were nominated as the most stressful aspect of the flood by the majority of participants. The second study surveyed Mackay flood survivors three and a half years post-flood, and Brisbane 2011 flood survivors 7-9 months post-flood (n=158). Findings indicated aftermath stress contributed to mental health outcomes over and above the contribution of perceived trauma, objective flood severity, prior mental health, self-efficacy and demographic factors. The implications of these results for the provision of community recovery services following natural disasters are discussed, including the need to provide effective targeting of support services throughout the lengthy rebuilding phase; a possible role for co-ordinating tradespeople; and training for insurance company staff aimed at minimising the incidence of insurance company staff inadvertently adding to disaster victims’ stress.

Well-trained, healthy triathletes experience no adverse health risks regarding oxidative stress and DNA damage by participating in an ultra-endurance event

Also physical exercise in general is accepted to be protective, acute and strenuous exercise has been shown to induce oxidative stress. Enhanced formation of free radicals leads to oxidation of macromolecules and to DNA damage. On the other hand ultra-endurance events which require strenuous exercise are very popular and the number of participants is continuously increasing worldwide. Since only few data exists on Ironman triathletes, who are prototypes of ultra-endurance athletes, this study was aimed at assessing the risk of oxidative stress and DNA damage after finishing a triathlon and to predict a possible health risk. Blood samples of 42 male athletes were taken 2 days before, within 20 min after the race, 1, 5 and 19 days post-race. Oxidative stress marker increased only moderately after the race and returned to baseline after 5 days. Marker of DNA damage measured by the SCGE assay with and without restriction enzymes as well as by the sister chromatid exchange assay did either show no change or deceased within the first day after the race. Due to intake during the race and the release by the cells plasma concentrations of vitamin C and α-tocopherol increased after the event and returned to baseline 1 day after. This study indicates that despite a temporary increase in some oxidative stress markers, there is no persistent oxidative stress and no DNA damage in response to an Ironman triathlon in trained athletes, mainly due to an appropriate antioxidant intake and general protective alterations in the antioxidant defence system.

Diabetes mellitus and the risk of depressive and anxiety disorders in Australian women: A longitudinal study

Background Longitudinal studies examining the risk of depressive and anxiety disorders associated with diabetes are limited. This study examined the association between diabetes and the risk of depressive and anxiety disorders in Australian women using longitudinal data. Methods Datawere froma sample of women who were part of anAustralian pregnancy and birth cohort study. Data comprised self-reported diabetes mellitus and the subsequent reporting of depressive and anxiety disorders. Mood disorders were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, obtained from participants using Composite International Diagnostic Interview (CIDI)-Auto (WHO WMH-CIDI CAPI, version 21.1.3). Multiple regression models with adjustment for important covariates were used. Results Women with diabetes had a higher lifetime prevalence of any depressive and/or anxiety disorder than women without diabetes. About 3 in 10 women with diabetes experienced a lifetime event of any depressive disorder, while 1 in 2 women with diabetes experienced a lifetime event of any anxiety disorder. In prospective analyses, diabetes was only significantly associated with a 30-day episode of any anxiety disorder (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.09–2.15). In the case of lifetime disorders, diabetes was significantly associated with any depressive disorder (OR 1.37, 95% CI 1.03–1.84), major depressive disorder (OR 1.36, 95% CI 1.01–1.85), and posttraumatic stress disorder (OR 1.42, 95% CI 1.01–2.02). Conclusions The findings suggest that the presence of diabetes is a significant risk factor for women experiencing current anxiety disorders. However, in the case of depression, the association with diabetes only held for women who had experienced past episodes, there was no association with current depression. This suggests that the evidence is not strong enough to support a direct effect of diabetes as a cause of mood disorders.

A Deweyan experience economy for higher education : The case of the Australian Indie 100 Music Event

In this essay we argue that a Deweyan experience economy will best support the higher education (HE) sector in the future, and we draw a contrast between that economy and the sector’s current focus on informational concerns, as expressed by the recent rush to Massive Open Online Courses (MOOCs) and other mass online informational offerings. We base our argument on current developments in music education and music technology that we see as being preemptive of wider trends. We use examples from a three-year study of online and offline music pedagogies and outline a four-year experiment in developing a pedagogical experience economy to illustrate a theoretical position informed by John Dewey’s theory of experience,Pierre Bourdieu’s theory of habitus and capital, and recent work in economic geography on epistemic communities. We argue further that the future of the HE sector is local rather than global, experiential rather than informational, and that therefore a continued informational approach to the future of HE risks undermining the sector.