What is a mental disorder? An exemplar-focused approach

The question of ‘what is a mental disorder?’ is central to the philosophy of psychiatry, and has crucial practical implications for psychiatric nosology. Rather than approaching the problem in terms of abstractions, we review a series of exemplars – real-world examples of problematic cases that emerged during work on and immediately after DSM-5, with the aim of developing practical guidelines for addressing future proposals. We consider cases where (1) there is harm but no clear dysfunction, (2) there is dysfunction but no clear harm, and (3) there is possible dysfunction and/or harm, but this is controversial for various reasons. We found no specific criteria to determine whether future proposals for new entities should be accepted or rejected; any such proposal will need to be assessed on its particular merits, using practical judgment. Nevertheless, several suggestions for the field emerged. First, while harm is useful for defining mental disorder, some proposed entities may require careful consideration of individual v. societal harm, as well as of societal accommodation. Second, while dysfunction is useful for defining mental disorder, the field would benefit from more sharply defined indicators of dysfunction. Third, it would be useful to incorporate evidence of diagnostic validity and clinical utility into the definition of mental disorder, and to further clarify the type and extent of data needed to support such judgments

Modelling the effects of calcium waves and oscillations on saliva secretion

An understanding of Ca2+Ca2+ signalling in saliva-secreting acinar cells is important, as Ca2+Ca2+ is the second messenger linking stimulation of cells to production of saliva. Ca2+Ca2+ signals affect secretion via the ion channels located both apically and basolaterally in the cell. By approximating Ca2+Ca2+ waves with periodic functions on the apical and basolateral membranes, we isolate individual wave properties and investigate them for their effect on fluid secretion in a mathematical model of the acinar cell. Mean Ca2+Ca2+ concentration is found to be the most significant property in signalling secretion. Wave speed was found to encode a range of secretion rates. Ca2+Ca2+ oscillation frequency and amplitude had little effect on fluid secretion

After the Left–Right (Dis)continuum: Globalization and the Remaking of Europe’s Ideological Geography

This article examines the status of globalization as a causal factor in political mobilization and proposes a research agenda for diagnosing the impact of global socio-economic dynamics on ideological orientation in national polities. Focusing on Europe’s established democracies, the article outlines recent shifts in Europe’s ideological landscape and explores the mechanisms generating a new pattern of political conflict and electoral competition. It advances the hypothesis that the knowledge economy of open borders has brought about a political cleavage inti- mately linked to citizens’ perceptions of the social impact of global eco- nomic integration. In this context, the polarization of life chances is determined by institutionally mediated exposure to both the economic opportunities and the hazards of globalization. Fostered by the increas- ing relevance of the international for state-bound publics, new fault-lines of social conflict are emerging, giving shape to a new, ‘‘opportunity- risk,’’ axis of political competition. As the novel political cleavage challenges the conventional left–right divide, it is likely to radically alter Europe’s ideological geography

Potential use of clinical polygenic risk scores in psychiatry – ethical implications and communicating high polygenic risk

Abstract Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations

What do aquaporin knockout studies tell us about fluid transport in epithelia?

The investigation of near-isosmotic water transport in epithelia goes back over 100 years; however, debates over mechanism and pathway remain. Aquaporin (AQP) knockouts have been used by various research groups to test the hypothesis of an osmotic mechanism as well as to explore the paracellular versus transcellular pathway debate. Nonproportional reductions in the water permeability of a water-transporting epithelial cell (e.g., a reduction of around 80–90 %) compared to the reduction in overall water transport rate in the knockout animal (e.g., a reduction of 50–60 %) are commonly found. This nonproportionality has led to controversy over whether AQP knockout studies support or contradict the osmotic mechanism. Arguments raised for and against an interpretation supporting the osmotic mechanism typically have partially specified, implicit, or incorrect assumptions. We present a simple mathematical model of the osmotic mechanism with clear assumptions and, for models based on this mechanism, establish a baseline prediction of AQP knockout studies. We allow for deviations from isotonic/isosmotic conditions and utilize dimensional analysis to reduce the number of parameters that must be considered independently. This enables a single prediction curve to be used for multiple epithelial systems. We find that a simple, transcellular-only osmotic mechanism sufficiently predicts the results of knockout studies and find criticisms of this mechanism to be overstated. We note, however, that AQP knockout studies do not give sufficient information to definitively rule out an additional paracellular pathway

A pilot feasibility trial of alcohol screening and brief intervention in the police custody setting (ACCEPT): study protocol for a cluster randomised controlled trial

BACKGROUND: There is evidence of an association between alcohol use and offending behaviour and around a quarter of police time is spent on alcohol-related incidents. Police custody, therefore, provides an important opportunity to intervene. This pilot trial aims to investigate whether a definitive evaluation of screening and brief interventions aimed at reducing risky drinking in arrestees is acceptable and feasible in the custody suite setting. METHODS: Screening will be carried out by trained detention officers or drug and alcohol workers in four police forces across two geographical areas (North East and South West England). Detention officers (or drug and alcohol workers) will be cluster randomised to one of three conditions: screening only (control group), screening followed immediately by 10 min of manualised brief structured advice delivered by the individual responsible for screening (intervention 1) or screening followed by 10 min of manualised brief structured advice delivered by the individual responsible for screening plus the offer of a subsequent 20-min session of behaviour change counselling delivered by a trained alcohol health worker (intervention 2). Participants will be arrestees aged 18+ who screen positive on the Alcohol Use Disorders Identification Test. Participants will be followed up at 6 and 12 months post-intervention. An embedded qualitative process evaluation will explore acceptability of alcohol screening and brief intervention to staff and arrestees as well as facilitators and barriers to the delivery of such approaches in this setting. RESULTS: Recruitment is currently underway and due to end May 2015. CONCLUSION: Results from this pilot trial will determine if a definitive evaluation is possible in the future and will provide stakeholder input to its design. TRIAL REGISTRATION: Reference number: ISRCTN89291046

Efficiency of primary saliva secretion: an analysis of parameter dependence in dynamic single-cell and acinus models, with application to aquaporin knockout studies

Secretion from the salivary glands is driven by osmosis following the establishment of osmotic gradients between the lumen, the cell and the interstitium by active ion transport. We consider a dynamic model of osmotically driven primary saliva secretion and use singular perturbation approaches and scaling assumptions to reduce the model. Our analysis shows that isosmotic secretion is the most efficient secretion regime and that this holds for single isolated cells and for multiple cells assembled into an acinus. For typical parameter variations, we rule out any significant synergistic effect on total water secretion of an acinar arrangement of cells about a single shared lumen. Conditions for the attainment of isosmotic secretion are considered, and we derive an expression for how the concentration gradient between the interstitium and the lumen scales with water- and chloride-transport parameters. Aquaporin knockout studies are interpreted in the context of our analysis and further investigated using simulations of transport efficiency with different membrane water permeabilities. We conclude that recent claims that aquaporin knockout studies can be interpreted as evidence against a simple osmotic mechanism are not supported by our work. Many of the results that we obtain are independent of specific transporter details, and our analysis can be easily extended to apply to models that use other proposed ionic mechanisms of saliva secretion

Road Trauma in Teenage Male Youth with Childhood Disruptive Behavior Disorders: A Population Based Analysis

Donald Redelmeier and colleagues conducted a population-based case-control study of 16-19-year-old males hospitalized for road trauma or appendicitis and showed that disruptive behavior disorders explained a significant amount of road trauma in this group

Cross-sectional measures and modelled estimates of blood alcohol levels in UK nightlife and their relationships with drinking behaviours and observed signs of inebriation

<p>Abstract</p> <p>Background</p> <p>Management of nightlife in UK cities focuses on creating safe places for individuals to drink. Little is known about intoxication levels as measuring total alcohol consumption on nights out is complicated by early evening interviews missing subsequent consumption and later interviews risking individuals being too drunk to recall consumption or participate at all. Here we assess mixed survey and modelling techniques as a methodological approach to examining these issues.</p> <p>Methods</p> <p>Interviews with a cross sectional sample of nightlife patrons (n = 214) recruited at different locations in three cities established alcohol consumption patterns up to the point of interview, self-assessed drunkenness and intended drinking patterns throughout the remaining night out. Researchers observed individuals' behaviours to independently assess drunkenness. Breath alcohol tests and general linear modelling were used to model blood alcohol levels at participants' expected time of leaving nightlife settings.</p> <p>Results</p> <p>At interview 49.53% of individuals regarded themselves as drunk and 79.43% intended to consume more alcohol before returning home, with around one in ten individuals (15.38% males; 4.35% females) intending to consume >40 units (equal to 400 mls of pure alcohol). Self-assessed drunkenness, researcher observed measures of sobriety and blood alcohol levels all correlated well. Modelled estimates for blood alcohol at time of going home suggested that 71.68% of males would be over 0.15%BAC (gms alcohol/100 mls blood). Higher blood alcohol levels were related to drinking later into the night.</p> <p>Conclusions</p> <p>UK nightlife has used substantive health and judicial resources with the aim of creating safer and later drinking environments. Survey and modelling techniques together can help characterise the condition of drinkers when using and leaving these settings. Here such methods identified patrons as routinely getting drunk, with risks of drunkenness increasing over later nights. Without preventing drunkenness and sales to intoxicated individuals, extended drinking hours can simply act as havens for drunks. A public health approach to nightlife is needed to better understand and take into account the chronic effects of drunkenness, the damages arising after drunk individuals leave city centres and the costs of people avoiding drunken city centres at night.</p