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As the basis for managing the risks of chemical exposure, the Chemical Risk Assessment (CRA) process can impact a substantial part of the economy, the health of hundreds of millions of people, and the condition of the environment. However, the number of properly assessed chemicals falls short of societal needs due to a lack of experts for evaluation, interference of third party interests, and the sheer volume of potentially relevant information on the chemicals from disparate sources. In order to explore ways in which computational methods may help overcome this discrepancy between the number of chemical risk assessments required on the one hand and the number and adequateness of assessments actually being conducted on the other, the European Commission's Joint Research Centre organised a workshop on Artificial Intelligence for Chemical Risk Assessment (AI4CRA). The workshop identified a number of areas where Artificial Intelligence could potentially increase the number and quality of regulatory risk management decisions based on CRA, involving process simulation, supporting evaluation, identifying problems, facilitating collaboration, finding experts, evidence gathering, systematic review, knowledge discovery, and building cognitive models. Although these are interconnected, they are organised and discussed under two main themes: scientific-technical process and social aspects and the decision making process.

Tox21 and ToxCast are high-throughput in vitro screening programs coordinated by the U.S. National Toxicology Program and the U.S. Environmental Protection Agency, respectively, with the goal of forecasting biological effects in vivo based on bioactivity profiling. The present study investigated whether mechanistic insights in the biological targets of food-relevant chemicals can be obtained from ToxCast results when the chemicals are grouped according to structural similarity. Starting from the 556 direct additives that have been identified in the ToxCast database by Karmaus et al. [Karmaus, A. L., Trautman, T. D., Krishan, M., Filer, D. L., and Fix, L. A. (2017). Curation of food-relevant chemicals in ToxCast. Food Chem. Toxicol. 103, 174-182.], the results showed that, despite the limited number of assays in which the chemical groups have been tested, sufficient results are available within so-called "DNA binding" and "nuclear receptor" target families to profile the biological activities of the defined chemical groups for these targets. The most obvious activity identified was the estrogen receptor-mediated actions of the chemical group containing parabens and structurally related gallates, as well the chemical group containing genistein and daidzein (the latter 2 being particularly active toward estrogen receptor β as a potential health benefit). These group effects, as well as the biological activities of other chemical groups, were evaluated in a series of case studies. Overall, the results of the present study suggest that high-throughput screening data could add to the evidence considered for regulatory risk assessment of food chemicals and to the evaluation of desirable effects of nutrients and phytonutrients. The data will be particularly useful for providing mechanistic information and to fill data gaps with read-across.

Sentence severity has increased in England and Wales in recent years. The causes of the increase remain unclear. One possible explanation relates to the introduction of sentencing guidelines, which seem to coincide in time with the increase in sentence severity. To date, investigations of this hypothesis have been limited to simple exploratory analyses or to specific offences. We use a new scale of sentence severity—developed using Thurstone scaling and the participation of 21 magistrates— and time-series modelling to explore whether a causal effect can be attributed to seven different guidelines. We corroborate the existence of an increase in sentence severity; however, we do not find conclusive evidence pointing at the guidelines having caused it.

Objective: Insomnia and anxiety commonly co-occur, yet the mechanisms underlying this remain unclear. The current paper describes the impact of an Internet-based intervention for insomnia on anxiety, and explores the influence of two cognitive-behavioural constructs – dysfunctional beliefs about sleep and sleep-threat monitoring. Methods: A large-scale, 9-week, two-arm randomised controlled trial (N = 1149) of community-dwelling Australian adults with insomnia and elevated yet subclinical depression symptoms was conducted, comparing a cognitive behavioural therapy–based online intervention for insomnia (Sleep Healthy Using The Internet) with an attention-matched online control intervention (HealthWatch). Symptoms of anxiety were assessed at pretest, posttest, and 6-month follow-up. Dysfunctional beliefs about sleep and sleep threat monitoring were assessed only at pretest. Results: Sleep Healthy Using The Internet led to a greater reduction in anxiety symptoms at both posttest (t724.27 = –6.77, p < 0.001) and at 6-month follow-up (t700.67 = –4.27, p < 0.001) than HealthWatch. At posttest and follow-up, this effect was found to moderated by sleep-threat monitoring (t713.69 = –2.39, p < 0.05 and t694.77 = –2.98, p < 0.01 respectively) but not by dysfunctional beliefs about sleep at either posttest or follow-up (t717.53 = –0.61, p = 0.55 and t683.79 = 0.22, p = 0.83 respectively). Participants in the Sleep Healthy Using The Internet condition with higher levels of sleep-threat monitoring showed a greater reduction in anxiety than those with lower levels from pretest to posttest, (t724.27 = –6.77, p < 0.001) and through to 6-month follow-up (t700.67 = –4.27, p < 0.001). This result remained after controlling for baseline anxiety levels. Conclusion: The findings suggest that online cognitive behavioral therapy interventions for insomnia are beneficial for reducing anxiety regardless of people’s beliefs about their sleep and insomnia, and this is particularly the case for

Upon analysis of Luke's Gospel and the Acts of the Apostles conjoined theoretically in the reading event, the basis of Israel's mandate became pellucid in Lukan terms. This kind of analysis required the viable assumption of conceptual unity behind the gospel and Acts, and the application of the appropriate methodological approach of structural criticism. Morpho-syntactical analysis yielded positive results that suggested text-based evidence concerning Israel's calling. It was observed that the covenant concept presented in its operative aspect of service to God was the basis of Israel's mandate. Luke and Acts appeared to agree that Israel was called to live in obedient righteousness following the call to Abraham to walk blamelessly. The covenant-based calling was affirmed by Isaianic allusions to Israel's mandate to be a light to the nations in her righteousness. The mandate's disruption had disabled Israel, requiring the resolution of God's deliverance

BACKGROUND: Suicidal thoughts are common in the general population, causing significant disability. However, a substantial number of people struggling with suicidality do not access appropriate services. Online self-help may help overcome barriers to help-seeking. This study aims to examine the effectiveness of an online self-help program targeted at reducing suicidal thoughts compared with an attention-matched control condition in the Australian adult population. This trial is based on a Dutch self-help program, which was found to be effective in reducing suicidal thoughts. METHODS/DESIGN: A total of 570 community-dwelling adults (18 to 65 years old) with suicidal thoughts will be recruited via various media and randomly assigned to the 6-week online program aimed at reducing suicidal thoughts or a 6-week attention-matched control program. Primary outcome measure is the severity of suicidal thoughts. Secondary outcome measures include suicide plans, capacity to cope with suicidal thoughts, reasons for living, symptoms of depression, hopelessness, anxiety/worry, rumination, panic, perceived burdensomeness and thwarted belongingness, acquired capability, alcohol consumption, insomnia, and various cost-effectiveness measures. DISCUSSION: Although the original Dutch trial found web-based self-help to be effective in reducing suicidal thoughts, randomized controlled trials (RCT) of online programs for suicidal thoughts are rare. The present study extends previous research by running the first English language RCT of this sort. As a result of the original study, the current RCT includes refinements to the design, including greater levels of participant anonymity and longer follow-up periods. Limitations of this trial include the potential for high drop-out and the inability to ascertain whether any suicides occur during the study.

Computer simulators of real-world processes are often computationally expensive and require many inputs. The problem of the computational expense can be handled using emulation technology; however, highly multidimensional input spaces may require more simulator runs to train and validate the emulator. We aim to reduce the dimensionality of the problem by screening the simulators inputs for nonlinear effects on the output rather than distinguishing between negligible and active effects. Our proposed method is built upon the elementary effects (EE) method for screening and uses a threshold value to separate the inputs with linear and nonlinear effects. The technique is simple to implement and acts in a sequential way to keep the number of simulator runs down to a minimum, while identifying the inputs that have nonlinear effects. The algorithm is applied on a set of simulated examples and a rabies disease simulator where we observe run savings ranging between 28% and 63% compared with the batch EE method. Supplementary materials for this article are available online.

BACKGROUND Cognitive Behaviour Therapy for Insomnia (CBT-I) delivered through the Internet is effective as a treatment in reducing insomnia in individuals seeking help for insomnia. CBT-I also lowers levels of depression in this group. However, it is not known if targeting insomnia using CBT-I will lower depressive symptoms, and thus reduce the risk of major depressive episode onset, in those specifically at risk for depression. Therefore, this study aims to examine whether Internet delivery of fully automated self-help CBT-I designed to reduce insomnia will prevent depression. METHOD/DESIGN A sample of 1,600 community-dwelling adults (aged 18-64), who screen positive for both subclinical levels of depressive symptoms and insomnia, will be recruited via various media and randomised to either a 9-week online insomnia treatment programme, Sleep Healthy Using The internet (SHUTi), or an online attention-matched control group (HealthWatch). The primary outcome variable will be depression symptom levels at the 6-month post-intervention on the Patient Heath Questionnaire-9 (PHQ-9). A secondary outcome will be onset of major depressive episodes assessed at the 6-month post-intervention using 'current' and 'time from intervention' criteria from the Mini International Neuropsychiatric Interview. DISCUSSION This trial is the first randomised controlled trial of an Internet-based insomnia intervention as an indicated preventative programme for depression. If effective, online provision of a depression prevention programme will facilitate dissemination. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry (ANZCTR), Registration number: ACTRN12611000121965.

BACKGROUND Research in suicide prevention using psychosocial interventions is rapidly advancing. However, randomised controlled trials are published across a range of medical, psychological and sociology journals, and it can be difficult to locate a full set of research studies. In this paper, we present a database of randomised controlled outcome studies on psychosocial interventions targeting suicidal behaviour. The database is updated annually and can be accessed by contacting the corresponding author. DESCRIPTION A comprehensive literature search of the major bibliographical databases (PsycINFO; PubMed; Cochrane Central Register of Controlled Trials) was conducted for articles published between 1800 to July 30 2013, and examined reference lists of previous relevant reviews and included papers to locate additional references. Studies were included if they featured a randomised controlled design in which the effects of a psychosocial intervention were compared to a control condition (no intervention, attention placebo, wait-list, treatment-as-usual [TAU]), another psychosocial intervention or a pharmacological intervention. In total, 12,250 abstracts were identified. Of these, 131 studies met eligibility criteria and were included. Each paper was then coded into categories of participant characteristics (age, gender, formal diagnosis, primary reason for recruitment); details of the intervention (recruitment setting, content, intervention setting, administering individual, delivery type, delivery format, delivery frequency, delivery length); and study characteristics (control and experimental conditions, primary outcome/s, secondary outcome/s, follow-up period). One paper has been published from the database using studies collected and coded prior to 2012. CONCLUSION The database and listing of 131 studies is available for use by suicide prevention researchers. It provides a strong starting point for systematic reviews and meta-analyses of treatments and interventi

Objective: To determine the role of health status and social support in the relationship between job stress and sleep disturbance, for both intermittent and chronic sleep disturbance. Methods: A total of 1946 mid-life adults completed three questionnaires spanning an 8-year time frame. Sleep disturbance was assessed at each time point, and participants were classified as experiencing intermittent, chronic or no sleep disturbance across this 8-year period. Independent variables included a range of job stress measures, social support, physical and mental health, and demographic characteristics. Results: After controlling for physical and mental health, perceived lack of job marketability increased risk of intermittent sleep disturbance (odds ratio (OR)=1.33, p=0.012). No other job stress measures were associated with either intermittent or chronic sleep disturbance after adjusting for years of education, social support, and employment status. Poorer mental and physical health status, although significantly increasing odds for intermittent sleep disturbance, represented a significantly greater increase in the odds for chronic sleep disturbance over and above intermittent disturbance (OR=0.96, p<. 0.001 for both SF-12 mental and physical health). Conclusion: This population-based cohort study found little evidence that job stress had an independent effect on chronic or intermittent sleep disturbance independent of health, social support, and education. Risk profiles for intermittent and chronic sleep disturbance did not differ with regard to job stress; however, various demographic and social support factors were distinguishing factors. Health status, both physical and mental, also showed a significantly greater impact on chronic sleep disturbance than intermittent sleep disturbance. Karasek's model of job strain had little value in predicting sleep disturbance outcomes.

Objective: Over the last decade, Australia has seen an increase in investment in mental health services, primarily through the funding of headspace and Better Access to Mental Health Outcomes programs. Concurrently there has been a policy focus on prevention and early intervention, suicide reduction and ‘hard-to-target’ groups such as Indigenous groups. It is not clear, however, whether research funding targeting health services or prevention or promotion has been prioritized, or whether funding priorities in general have shifted over the last decade. Methods: A total of 1008 Australian-authored research publications and 126 competitive research grants in 2008 were coded in terms of their target of research, research goal setting and target group. These characteristics were compared with the research priorities of 570 stakeholders, burden of disease estimates and similar data collected 10 years earlier. Results: The proportion of research funding for affective disorders, dementia and psychosis has increased, but not for anxiety disorders or suicide. Funding for childhood disorders has decreased. Funding for prevention and promotion is low and decreasing. With respect to research publications, substance abuse was associated with the most publications, followed by affective disorders, anxiety disorders and psychosis. When publications and funding are compared to stakeholder priorities and the burden of disease, the areas of suicide and self-harm, personality disorders, anxiety disorders, childhood conditions and dementia are all insufficiently funded. Conclusion: Despite mental health policy reforms through the last decade, there has been little change in the focus of research funding or publication output. There is modest evidence for a shift in support towards affective disorders as a major focus for research. However, the remaining gaps were very similar to those identified 10 years earlier showing that suicide, personality disorders and anxiety disorders are under

Objective: Cognitive models have identified a number of factors that maintain sleep disturbance. It is unknown whether similar factors lead to initial onset. This study tested whether three cognitive-behavioural factors: ruminative style, somatic sensitivity, and behavioural avoidance predicted sleep disturbance onset at four-year follow-up. Methods: Participants (n= 4,042) were assessed using a) a composite measure of Somatic Sensitivity, b) the Ruminative Style Scale, c) the Behavioural Inhibition Scale of the BISBAS and d) sleep-related items from the Goldberg Depression and Anxiety Scale. Results: Sleep disturbance at 4. years was significantly predicted by all three cognitive-behavioural factors - somatic sensitivity, ruminative style and behavioural avoidance - and, in the final analysis, was independently predicted by somatic sensitivity (OR = 1.427, p<. 0.001) and ruminative style (OR = 1.035, p=. 0.002). Conclusion: This study tested whether three cognitive-behavioural factors: ruminative style, somatic sensitivity, and behavioural avoidance were predictive of the onset of sleep disturbance after 4. years. Although all three factors were significantly associated with the onset of sleep disturbance, only ruminative style and somatic sensitivity were found to independently predict sleep disturbance, supporting these constructs as predisposing cognitive-behavioural risk factors.

When constructing and using environmental models, it is typical that many of the inputs to the models will not be known perfectly. In some cases, it will be possible to make observations, or occasionally physics-based uncertainty propagation, to ascertain the uncertainty on these inputs. However, such observations are often either not available or even possible, and another approach to characterising the uncertainty on the inputs must be sought. Even when observations are available, if the analysis is being carried out within a Bayesian framework then prior distributions will have to be specified. One option for gathering or at least estimating this information is to employ expert elicitation. Expert elicitation is well studied within statistics and psychology and involves the assessment of the beliefs of a group of experts about an uncertain quantity, (for example an input / parameter within a model), typically in terms of obtaining a probability distribution. One of the challenges in expert elicitation is to minimise the biases that might enter into the judgements made by the individual experts, and then to come to a consensus decision within the group of experts. Effort is made in the elicitation exercise to prevent biases clouding the judgements through well-devised questioning schemes. It is also important that, when reaching a consensus, the experts are exposed to the knowledge of the others in the group. Within the FP7 UncertWeb project (http://www.uncertweb.org/), there is a requirement to build a Webbased tool for expert elicitation. In this paper, we discuss some of the issues of building a Web-based elicitation system - both the technological aspects and the statistical and scientific issues. In particular, we demonstrate two tools: a Web-based system for the elicitation of continuous random variables and a system designed to elicit uncertainty about categorical random variables in the setting of landcover classification uncertainty. The first of these ex