Ensuring the statistical soundness of competitive gene set approaches: gene filtering and genome-scale coverage are essential

In this article, we focus on the analysis of competitive gene set methods for detecting the statistical significance of pathways from gene expression data. Our main result is to demonstrate that some of the most frequently used gene set methods, GSEA, GSEArot and GAGE, are severely influenced by the filtering of the data in a way that such an analysis is no longer reconcilable with the principles of statistical inference, rendering the obtained results in the worst case inexpressive. A possible consequence of this is that these methods can increase their power by the addition of unrelated data and noise. Our results are obtained within a bootstrapping framework that allows a rigorous assessment of the robustness of results and enables power estimates. Our results indicate that when using competitive gene set methods, it is imperative to apply a stringent gene filtering criterion. However, even when genes are filtered appropriately, for gene expression data from chips that do not provide a genome-scale coverage of the expression values of all mRNAs, this is not enough for GSEA, GSEArot and GAGE to ensure the statistical soundness of the applied procedure. For this reason, for biomedical and clinical studies, we strongly advice not to use GSEA, GSEArot and GAGE for such data sets.

A school based study of psychological disturbance in children following the Omagh bomb

Objective
To assess the extent and nature of psychiatric morbidity among children (aged 8 to 13 years) 15 months after a car bomb explosion in the town of Omagh, Northern Ireland.

Method
A survey was conducted of 1945 school children attending 13 schools in the Omagh district. Questionnaires included demographic details, measures of exposure, the Horowitz Impact of Events Scale, the Birleson Self-Rating Depression Scale, and the Spence Children’s Anxiety Scale.

Results
Children directly exposed to the bomb reported higher levels of probable PTSD (70%), and psychological distress than those not exposed. Direct exposure was more closely associated with an increase in PTSD symptoms than in general psychiatric distress. Significant predictors of increased IES scores included being male, witnessing people injured and reporting a perceived life threat but when co-morbid anxiety and depression are included as potential predictors anxiety remains the only significant predictor of PTSD scores.

Conclusions
School-based studies are a potentially valuable means of screening and assessing for PTSD in children after large-scale tragedies. Assessment should consider type of exposure, perceived life threat and other co-morbid anxiety as risk factors for PTSD.

The Role of Personality Factors in the Reduction of Intergroup Anxiety and Amelioration of Outgroup Attitudes via Intergroup Contact

Two studies investigated the role of personality factors in the amelioration of outgroup attitudes via intergroup contact. In study 1, the effect of extraversion on outgroup attitude operated via an increase in cross-group friendship, whereas openness to experience and agreeableness had a direct effect on outgroup attitude. In study 2, we included intergroup anxiety as a mediator explaining these relationships, and we ruled out ingroup friendship as a potential confound. We found that the relationships between openness to experience and agreeableness on the one hand and outgroup attitude on the other were mediated by reduced intergroup anxiety. In addition, the effect of extraversion on outgroup attitude operated via an increase in cross-group friendship that was in turn associated with lower levels of intergroup anxiety. Across both studies, the friendship–attitude relationship was stronger among those low in agreeableness and extraversion. We discuss the importance of integrating personality and situational approaches to prejudice reduction in optimizing the impact of contact-based interventions. Copyright © 2013 John Wiley & Sons, Ltd.

Out-group trust, intergroup anxiety, and out-group attitude as mediators of the effect of imagined intergroup contact on intergroup behavioural tendencies.

We investigated whether imagining contact with an out-group member would change behavioral tendencies toward the out-group. In Experiment 1, British high school students who imagined talking to an asylum seeker reported a stronger tendency to approach asylum seekers than did participants in a control condition. Path analysis revealed this relationship was mediated by out-group trust and, marginally, by out-group attitude. In Experiment 2, straight undergraduates who imagined an interaction with a gay individual reported a stronger tendency to approach, and a weaker tendency to avoid, gay people. Path analyses showed that these relationships were mediated by out-group trust, out-group attitude, and less intergroup anxiety. These findings highlight the potential practical importance of imagined contact and important mediators of its effects.

Effectiveness of a programme of exercise on physical function in survivors of critical illness following discharge from the ICU: study protocol for a randomised controlled trial (REVIVE)

Background: Following discharge home from the ICU, patients often suffer from reduced physical function, exercise capacity, health-related quality of life and social functioning. There is usually no support to address these longer term problems, and there has been limited research carried out into interventions which could improve patient outcomes. The aim of this study is to investigate the effectiveness and cost-effectiveness of a 6-week programme of exercise on physical function in patients discharged from hospital following critical illness compared to standard care.

Methods/Design: The study design is a multicentre prospective phase II, allocation-concealed, assessor-blinded, randomised controlled clinical trial. Participants randomised to the intervention group will complete three exercise sessions per week (two sessions of supervised exercise and one unsupervised session) for 6 weeks. Supervised sessions will take place in a hospital gymnasium or, if this is not possible, in the participants home and the unsupervised session will take place at home. Blinded outcome assessment will be conducted at baseline after hospital discharge, following the exercise intervention, and at 6 months following baseline assessment (or equivalent time points for the standard care group). The primary outcome measure is physical function as measured by the physical functioning subscale of the Short-Form-36 health survey following the exercise programme. Secondary outcomes are health-related quality of life, exercise capacity, anxiety and depression, self efficacy to exercise and healthcare resource use. In addition, semi-structured interviews will be conducted to explore participants’ perceptions of the exercise programme, and the feasibility (safety, practicality and acceptability) of providing the exercise programme will be assessed. A within-trial cost-utility analysis to assess the cost-effectiveness of the intervention compared to standard care will also be conducted.

Discussion: If the exercise programme is found to be effective, this study will improve outcomes that are meaningful to patients and their families. It will inform the design of a future multicentre phase III clinical trial of exercise following recovery from critical illness. It will provide useful information which will help the development of services for patients after critical illness.

Adolescent ecstasy use and depression: cause and effect, or two outcomes of home environment?

Background: This study assessed the association between adolescent ecstasy use and depressive symptoms in adolescence. Methods: The Belfast Youth Development Study surveyed a cohort annually from age 11 to 16 years. Gender, Strengths and Difficulties Questionnaire emotional subscale, living arrangements, parental affluence, parent and peer attachment, tobacco, alcohol, cannabis and ecstasy use were investigated as predictors of Short Mood and Feelings Questionnaire (SMFQ) outcome. Results: Of 5371 respondents, 301 (5.6%) had an SMFQ > 15, and 1620 (30.2) had missing data for SMFQ. Around 8% of the cohort had used ecstasy by the end of follow-up. Of the non-drug users, ∼2% showed symptoms of depression, compared with 6% of those who had used alcohol, 6% of cannabis users, 6% of ecstasy users and 7% of frequent ecstasy users. Without adjustment, ecstasy users showed around a 4-fold increased odds of depressive symptoms compared with non-drug users [odds ratio (OR) = 0.26; 95% confidence interval (CI) = 0.10, 0.68]. Further adjustment for living arrangements, peer and parental attachment attenuated the association to under a 3-fold increase (OR = 0.37; 95% CI = 0.15, 0.94). There were no differences by frequency of use. Conclusions: Ecstasy use during adolescence may be associated with poorer mental health; however, this association can be explained by the confounding social influence of family dynamics. These findings could be used to aid effective evidence-based drug policies, which concentrate criminal justice and public health resources on reducing harm.

Older women living and coping with domestic violence

Although domestic violence is seen as a serious public health issue for women worldwide, international evidence suggests that women aged over 50 who are victims are suffering in silence because the problem is often ignored by health professionals. More UK research is needed to identify the extent of the problem, and services to meet the needs of older women. This study aims to bridge this gap by gaining a deeper understanding of how ‘older women’ cope with domestic violence and how it affects their wellbeing. Eighteen older women who were currently, or had been in an abusive relationship were recruited. Semi-structured interview schedules were used to discuss the personal nature of DV and its effects on wellbeing, ways of coping and sources of support. Findings suggest that living in a domestically violent context has extremely negative effects on older women’s wellbeing leading to severe anxiety and depression. Three-quarters of the women defined themselves as in ‘very poor’ mental and physical health and were using pathogenic coping mechanisms, such as excessive and long-term use of alcohol, prescription and non-prescription drugs and cigarettes. This negative coping increased the likelihood of these women experiencing addiction to drugs and alcohol dependence and endangered their health in the longer term. Our findings suggest that health professionals must receive appropriate education to gain knowledge and skills in order to deal effectively and support older women experiencing domestic violence.

Older Women Living with Domestic Violence: Coping Resources and Mental Health and Wellbeing

Background: Domestic violence represents a serious public health issue for women and their children worldwide. International evidence suggests that women aged over 50 who are victims of domestic violence are suffering in silence because the problem is ignored by professionals and policy makers. More UK research is needed to identify the extent of the problem, and services to meet the needs of older women.

Study aims: To bridge this gap by seeking to gain a deeper, systematic understanding of how ‘older women’ cope with domestic violence and how it effects their wellbeing, using a theoretical framework of ‘salutogenesis’ to consider coping resources used in lifelong abuse.

Methods: The study recruited a convenience sample of eighteen older women who are currently, or had been in an abusive relationship. A semi-structured interview schedule was used to discuss the personal nature, of domestic violence in their lives, and the pattern of abuse over time and its effects on their wellbeing, ways of coping and sources of support, barriers to reporting and accessing support, and experiences in seeking help.

Results: Living in a domestically violent context has extremely negative effects on older women’s wellbeing. Living with a perpetrator of long-term violence is predisposing these women to extremely negative health outcomes such as Post Traumatic Stress Disorder, anxiety and depression. Three-quarters of the women defined themselves as in poor mental health and were using pathogenic coping mechanisms, such as excessive and long-term use of alcohol, prescription and non-prescription drugs and cigarettes. This negative coping increased the likelihood of these women experiencing addiction to drugs and alcohol dependence and endangering their health and wellbeing in the longer term. Conclusions Public health interventions can work well from a ‘salutogenic’ perspective by finding ways to promote healthy behaviours that increase older women’s sense of wellbeing and coping. The application of this theoretical framework offers the potential for new knowledge to contribute to the discourse about wellbeing in older women dealing with domestic violence.

Dyslexia in higher education: Implications for maths anxiety, statistics anxiety and psychological well-being

This study examined levels of mathematics and statistics anxiety, as well as general mental health amongst undergraduate students with dyslexia (n = 28) and those without dyslexia (n = 71). Students with dyslexia had higher levels of mathematics anxiety relative to those without dyslexia, while statistics anxiety and general mental health were comparable for both reading ability groups. In terms of coping strategies, undergraduates with dyslexia tended to use planning-based strategies and seek instrumental support more frequently than those without dyslexia. Higher mathematics anxiety was associated with having a dyslexia diagnosis, as well as greater levels of worrying, denial, seeking instrumental support and less use of the positive reinterpretation coping strategy. By contrast, statistics anxiety was not predicted by dyslexia diagnosis, but was instead predicted by overall worrying and the use of denial and emotion focused coping strategies. The results suggest that disability practitioners should be aware that university students with dyslexia are at risk of high mathematics anxiety. Additionally, effective anxiety reduction strategies such as positive reframing and thought challenging would form a useful addition to the support package delivered to many students with dyslexia.

Micro- and Nano-scale Tribo-Corrosion of Cast CoCrMo

Previous studies have established that some of the wear damage seen on cast CoCrMo joint surface is caused by entrained third-body hard particles. In this study, wet-cell micro-indentation and nano-scratch tests have been carried out with the direct aim of simulating wear damage induced by single abrasive particles entrained between the surfaces of cast CoCrMo hip implants. In situ electrochemical current noise measurements were uniquely performed to detect and study the wear-induced corrosion as well as the repassivation kinetics under the micro-/nano-scale tribological process. A mathematical model has been explored for the CoCrMo repassivation kinetics after surface oxide film rupture. Greater insights into the nature of the CoCrMo micro-/nano-scale wear-corrosion mechanisms and deformation processes are determined, including the identification of slip band formation, matrix/carbide deformation, nanocrystalline structure formation and strain-induced phase transformation. The electrochemical current noise provides evidence of instantaneous transient corrosion activity at the wearing surface resulting from partial oxide rupturing and stripping, concurrent with the indent/scratch.

Psychosocial aspects in cardiac rehabilitation: From theory to practice. A position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology

A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality of life (HRQoL) and prognosis in patients with established CHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system. Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention, integrating counselling for PSRFs and coping with illness should be included within comprehensive CR. Patients with clinically significant symptoms of distress should be referred for psychological counselling or psychologically focused interventions and/or psychopharmacological treatment. To conclude, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.

A review of the global pesticide legislation and the scale of challenge in reaching the global harmonization of food safety standards

Pesticide use is important in agriculture to protect crops and improve productivity. However, they have the potential to cause adverse human health or environmental effects, dependent on exposure levels. This review examines existing pesticide legislation worldwide, focusing on the level of harmonisation, and impacts of differing legislation on food safety and trade. Pesticide legislation varies greatly worldwide as countries have different requirements guidelines and legal limits for plant protection. Developed nations have more stringent regulations than developing countries, which lack the resources and expertise to adequately implement and enforce legislation. Global differences in pesticide legislation act as a technical barrier to trade. International parties such as the European Union (EU), Codex Alimentarius Commission (Codex), and North American Free Trade Agreement (NAFTA) have attempted to harmonise pesticide legislation by providing maximum residue limits (MRLs), but globally these limits remain variable. Globally harmonised pesticide standards would serve to increase productivity, profits and trade, and enhance the ability to protect public health and the environment. 

Impact of political violence, social trust, and depression on civic participation in Colombia

Civic participation is important for peacebuilding and democratic development; however, the role of mental health has been largely overlooked by policymakers aiming to stimulate engagement in civil society. This study investigated antecedents of civic participation in Colombia, a setting of protracted political conflict, using bootstrapped mediation in path analysis. Past exposure to violence, experience with community antisocial behavior, and perceived social trust were all significantly related to civic participation. In addition, depression mediated the impact of past exposure to political violence and perceived social trust, but not community antisocial behavior, on civic participation. In this context, findings challenged depictions of helpless victims and instead suggested that when facing greater risk (past violence exposure and community antisocial behavior), individuals responded in constructive ways, taking on agency in their communities. Social trust in one’s neighbors and community also facilitated deeper engagement in civic life. Relevant to the mediation test, interventions aiming to increase civic participation should take mental health into account. Limitations and possible future research are discussed.