Neurology and psychiatry: waking up to opportunities of sleep. State of the art and clinical/research priorities for the next decade.

In recent years, evidence has emerged for a bidirectional relationship between sleep and neurological and psychiatric disorders. First, sleep-wake disorders (SWDs) are very common and may be the first/main manifestation of underlying neurological and psychiatric disorders. Secondly, SWDs may represent an independent risk factor for neuropsychiatric morbidities. Thirdly, sleep-wake function (SWF) may influence the course and outcome of neurological and psychiatric disorders. This review summarizes the most important research and clinical findings in the fields of neuropsychiatric sleep and circadian research and medicine, and discusses the promise they bear for the next decade. The findings herein summarize discussions conducted in a workshop with 26 European experts in these fields, and formulate specific future priorities for clinical practice and translational research. More generally, the conclusion emerging from this workshop is the recognition of a tremendous opportunity offered by our knowledge of SWF and SWDs that has unfortunately not yet entered as an important key factor in clinical practice, particularly in Europe. Strengthening pre-graduate and postgraduate teaching, creating academic multidisciplinary sleep-wake centres and simplifying diagnostic approaches of SWDs coupled with targeted treatment strategies yield enormous clinical benefits for these diseases.

Queensland Aborigines, multiple realities and the social sources of suffering: Psychiatry and moral regions of being (Part 1)

This two part paper considers the experience of a range of magico-religious experiences (such as visions and voices) and spirit beliefs in a rural Aboriginal town. The papers challenge the tendency of institutionalised psychiatry to medicalise the experiences and critiques the way in which its individualistic practice is intensified in the face of an incomprehensible Aboriginal „other‟ to become part of the power imbalance that characterises the relationship between Indigenous and white domains. The work reveals the internal differentiation and politics of the Aboriginal domain, as the meanings of these experiences and actions are contested and negotiated by the residents and in so doing they decentre the concerns of the white domain and attempt to control their relationship with it. Thus the plausibility structure that sustains these multiple realities reflects both accommodation and resistance to the material and historical conditions imposed and enacted by mainstream society on the residents, and to current socio- political realities. I conclude that the residents‟ narratives chart the grounds of moral adjudication as the experiences were rarely conceptualised by local people as signs of individual pathology but as reflections of social reality. Psychiatric drug therapy and the behaviourist assumptions underlying its practice posit atomised individuals as the appropriate site of intervention as against the multiple realities revealed by the phenomenology of the experiences. The papers thus call into question Australian mainstream „commonsense‟ that circulates about Aboriginal and Torres Strait Islander people which justifies representations of them as sickly outcasts in Australian society.

Exercise for health : a randomized, controlled trial evaluating impact of a pragmatic, translational exercise intervention on quality of life, function and treatment-related side effects following breast cancer

Purpose Exercise for Health was a randomized, controlled trial designed to evaluate two modes of delivering (face-to-face [FtF] and over-the-telephone [Tel]) an 8-month translational exercise intervention, commencing 6-weeks post-breast cancer surgery (PS). Methods Outcomes included quality of life (QoL), function (fitness and upper-body) and treatment-related side effects (fatigue, lymphoedema, body mass index, menopausal symptoms, anxiety, depression and pain). Generalised estimating equation modelling determined time (baseline [5-weeks PS], mid-intervention [6-months PS], post-intervention [12-months PS]), group (FtF, Tel, Usual Care [UC]) and time-by-group effects. 194 women representative of the breast cancer population were randomised to the FtF (n=67), Tel (n=67) and UC (n=60) groups. Results: There were significant (p<0.05) interaction effects on QoL, fitness and fatigue, with differences being observed between the treatment groups and the UC group. Trends observed for the treatment groups were similar. The treatment groups reported improved QoL, fitness and fatigue over time and changes observed between baseline and post-intervention were clinically relevant. In contrast, the UC group experienced no change, or worsening QoL, fitness and fatigue, mid-intervention. Although improvements in the UC group occurred by 12-months post-surgery, the change did not meet the clinically relevant threshold. There were no differences in other treatment-related side-effects between groups. Conclusion This translational intervention trial, delivered either face-to-face or over-the-telephone, supports exercise as a form of adjuvant breast cancer therapy that can prevent declines in fitness and function during treatment and optimise recovery post-treatment.

Towards a translational medical research ecosystem

In this paper we introduce a novel design for a translational medical research ecosystem. Translational medical research is an emerging field of work, which aims to bridge the gap between basic medical science research and clinical research/patient care. We analyze the key challenges of digital ecosystems for translational research, based on real world scenarios posed by the Lab for Translational Research at the Harvard Medical School and the Genomics Research Centre of the Griffith University, and show how traditional IT approaches fail to fulfill these challenges. We then introduce our design for a translational research ecosystem. Several key contributions are made: A novel approach to managing ad-hoc research ecosystems is introduced; a new security approach for translational research is proposed which allows each participating site to retain control over its data and define its own policies to ensure legal and ethical compliance; and a design for a novel interactive access control framework which allows users to easily share data, while adhering to their organization's policies is presented.

Changing parental high risk behaviour in the reduction of SIDS : the imperative of translational research

Objectives To investigate the factors associated with sudden infant death syndrome (SIDS) from birth to age 2 years, whether recent advice has been followed, whether any new risk factors have emerged, and the specific circumstances in which SIDS occurs while cosleeping (infant sharing the same bed or sofa with an adult or child). Design Four year population based case-control study. Parents were interviewed shortly after the death or after the reference sleep (within 24 hours) of the two control groups. Setting South west region of England (population 4.9 million, 184 800 births). Participants 80 SIDS infants and two control groups weighted for age and time of reference sleep: 87 randomly selected controls and 82 controls at high risk of SIDS (young, socially deprived, multiparous mothers who smoked). Results The median age at death (66 days) was more than three weeks less than in a study in the same region a decade earlier. Of the SIDS infants, 54% died while cosleeping compared with 20% among both control groups. Much of this excess may be explained by a significant multivariable interaction between cosleeping and recent parental use of alcohol or drugs (31% v 3% random controls) and the increased proportion of SIDS infants who had coslept on a sofa (17% v 1%). One fifth of SIDS infants used a pillow for the last sleep (21% v 3%) and one quarter were swaddled (24% v 6%). More mothers of SIDS infants than random control infants smoked during pregnancy (60% v 14%), whereas one quarter of the SIDS infants were preterm (26% v 5%) or were in fair or poor health for the last sleep (28% v 6%). All of these differences were significant in the multivariable analysis regardless of which control group was used for comparison. The significance of covering the infant’s head, postnatal exposure to tobacco smoke, dummy use, and sleeping in the side position has diminished although a significant proportion of SIDS infants were still found prone (29% v 10%). Conclusions Many of the SIDS infants had coslept in a hazardous environment. The major influences on risk, regardless of markers for socioeconomic deprivation, are amenable to change and specific advice needs to be given, particularly on use of alcohol or drugs before cosleeping and cosleeping on a sofa.

Contemporary research on parenting: conceptual, methodological, and translational issues.

Researchers over the last decade have documented the association between general parenting style and numerous factors related to childhood obesity (e.g., children's eating behaviors, physical activity, and weight status). Many recent childhood obesity prevention programs are family focused and designed to modify parenting behaviors thought to contribute to childhood obesity risk. This article presents a brief consideration of conceptual, methodological, and translational issues that can inform future research on the role of parenting in childhood obesity. They include: (1) General versus domain specific parenting styles and practices; (2) the role of ethnicity and culture; (3) assessing bidirectional influences; (4) broadening assessments beyond the immediate family; (5) novel approaches to parenting measurement, and; (6) designing effective interventions. Numerous directions for future research are offered.

Translational approaches to medication development

Alcohol accounts for major disability worldwide and available treatments are insufficient. A massive growth in the area of addiction neuroscience over the last several decades has not resulted in a corresponding expansion of treatment options available to patients. In this chapter, we describe our experience with building translational research programs aimed at developing novel pharmacotherapies for alcoholism. The narrative is based on experience and considerations made in the course of building these programs, and work on four mechanisms targeted by our libraries: cholinergic nicotine receptors, receptors for corticotropin-releasing hormone (CRH), neurokinin 1 (NK1) receptors for substance P (SP) and hypocretin/orexin receptors. Around this experience, we discuss issues we believe to be critical for successful translation of basic addiction neuroscience into treatments, and complementarities between academic and other actors that in our assessment need to be harnessed in order to bring treatments to the clinic.

Specialist versus generic models of psychiatry training and service provision for people with intellectual disabilities

Background  Models of service provision and professional training differ between countries. This study aims to investigate a specialist intellectual disabilities model and a generic mental health model, specifically comparing psychiatrists’ knowledge and competencies, and service quality and accessibility in meeting the mental health needs of people with intellectual disabilities. Method  Data were collected from consultant and trainee psychiatrists within a specialist intellectual disabilities model (UK) and a generic mental health model (Australia). Results  The sample sizes were 294 (UK) and 205 (Australia). Statistically significant differences were found, with UK participants having positive views about the specialist intellectual disabilities service model they worked within, demonstrating flexible and accessible working practices and service provision, responsive to the range of mental health needs of the population with intellectual disabilities, and providing a wide range of treatments and supports. The UK participants were knowledgeable, well trained and confident in their work. They wanted to work with people with intellectual disabilities. In all of these areas, the converse was found from the Australian generic mental health service model. Conclusions  The specialist intellectual disabilities model of service provision and training has advantages over the generic mental health model.

Gene regulation by translational inhibition is determined by Dicer partnering proteins

MicroRNAs (miRNAs) are small regulatory RNAs produced by Dicer proteins that regulate gene expression in development and adaptive responses to the environment1,​2,​3,​4. In animals, the degree of base pairing between a miRNA and its target messenger RNA seems to determine whether the regulation occurs through cleavage or translation inhibition1. In contrast, the selection of regulatory mechanisms is independent of the degree of mismatch between a plant miRNA and its target transcript5. However, the components and mechanism(s) that determine whether a plant miRNA ultimately regulates its targets by guiding cleavage or translational inhibition are unknown6. Here we show that the form of regulatory action directed by a plant miRNA is determined by DRB2, a DICER-LIKE1 (DCL1) partnering protein. The dependence of DCL1 on DRB1 for miRNA biogenesis is well characterized7,​8,​9, but we show that it is only required for miRNA-guided transcript cleavage. We found that DRB2 determines miRNA-guided translational inhibition and represses DRB1 expression, thereby allowing the active selection of miRNA regulatory action. Furthermore, our results reveal that the core silencing proteins ARGONAUTE1 (AGO1) and SERRATE (SE) are highly regulated by miRNA-guided translational inhibition. DRB2 has been remarkably conserved throughout plant evolution, raising the possibility that translational repression is the ancient form of miRNA-directed gene regulation in plants, and that Dicer partnering proteins, such as human TRBP, might play a similar role in other eukaryotic systems.

The development of a guideline of care for patients with a Sengstaken-Blakemore Tube insitu in a general Intensive Care Unit using translational change theory

Aims & Objectives - identify and diagnose the current problems associated with patient care with regard to the nursing management of patients with Sengstaken-Blakemore tubes insitu; - Identify current nursing practice currently in place within the ICU and the hospital; identify the method by which the assessment and provision of nursing care is delivered in the ICU

Lost in space: The place of the architectural milieu in the aetiology and treatment of schizophrenia

Purpose – Psychological and epidemiological literature suggests that the built environment plays both causal and therapeutic roles in schizophrenia, but what are the implications for designers? The purpose of this paper is to focus on the role the built environment plays in psycho‐environmental dynamics, in order that negative effects can be avoided and beneficial effects emphasised in architectural design. Design/methodology/approach – The approach taken is a translational exploration of the dynamics between the built environment and psychotic illness, using primary research from disciplines as diverse as epidemiology, neurology and psychology. Findings – The built environment is conceived as being both an agonist and as an antagonist for the underlying processes that present as psychosis. The built environment is implicated through several means, through the opportunities it provides. These may be physical, narrative, emotional, hedonic or personal. Some opportunities may be negative, and others positive. The built environment is also an important source of unexpected aesthetic stimulation, yet in psychotic illnesses, aesthetic sensibilities characteristically suffer from deterioration. Research limitations/implications – The findings presented are based on research that is largely translated from very different fields of enquiry. Whilst findings are cogent and logical, much of the support is correlational rather than empirical. Social implications – The WHO claims that schizophrenia destroys 24 million lives worldwide, with an exponential effect on human and financial capital. Because evidence implicates the built environment, architectural and urban designers may have a role to play in reducing the human costs wrought by the illness. Originality/value – Never before has architecture been so explicitly implicated as a cause of mental illness. This paper was presented to the Symposium of Mental Health Facility Design, and is essential reading for anyone involved in designing for improved mental health.

Editorial: Biomarker and translational prostate cancer research

The existing clinical biomarkers for prostate cancer (PCa) are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid overtreatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two-thirds of the biopsies performed are still unnecessary. Thus, the discovery of noninvasive PCa biomarkers remains an urgent unmet medical need. Once metastasized, there is still no curative therapy. A better understanding of sustained androgen receptor signalling in castration resistant prostate cancer (CRPC) has now led to the development of more effective therapies. We need a better understanding of the molecular and cellular aspects of prostate carcinogenesis and progression. Identification of cancer initiating cells and therapies against these populations is a promising way forward to fight this disease.