Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families

In our genome scan for schizophrenia genes in 265 Irish pedigrees, marker D5S818 in 5q22 produced the second best result of the first 223 markers tested (P = 0.002). We then tested an additional 13 markers and the evidence suggests the presence of a vulnerability locus for schizophrenia in region 5q22-31. This region appears to be distinct from those chromosome 5 regions studied in two prior reports, but the same as that producing positive results in the report by Wildenauer and colleagues found elsewhere in this issue. The largest pairwise heterogeneity LOD (H-LOD) score was found with marker D5S393 (max 3.04, P = 0.0005), assuming a narrow phenotypic category, and a genetic model with intermediate heterozygotic liability. In marked contrast to the H-LOD scores from our sample with markers from the regions of interest on chromosomes 6p and 8p, expanding the disease definition to include schizophrenia spectrum or nonspectrum disorders produced substantially smaller scores, with a number of markers failing to yield positive values at any recombination fraction. Using multipoint H-LODS, the strongest evidence for linkage occurs under the narrow phenotypic definition and recessive genetic model, with a peak at marker D5S804 (max 3.35, P = 0.0002). Multipoint nonparametric linkage analysis produced a peak in the same location (max z = 2.84, P = 0.002) with the narrow phenotypic definition. This putative vulnerability locus appears to be segregating in 10-25% of the families studied, but this estimate is tentative. Comparison of individual family multipoint H-LOD scores at the regions of interest on chromosomes 6p, 8p and 5q showed that only a minority of families yield high lod scores in two or three regions.

A schizophrenia locus may be located in region 10p15-p11

In our genomic scan of 265 Irish families with schizophrenia, we have thus far generated modest evidence for the presence of vulnerability genes in three chromosomal regions, i.e., 5q21-q31, 6p24-p22, and 8p22-p21. Outside of those regions, of all markers tested to date, D10S674 produced one of the highest pairwise heterogeneity lod (H-LOD) scores, 3.2 (P = 0.0004), when initially tested on a subset of 88 families. We then tested a total of 12 markers across a region of 32 centimorgans in region 10p15-p11 of all 265 families. The strongest evidence for linkage occurred assuming an intermediate phenotypic definition, and a recessive genetic model. The largest pairwise H-LOD score was found with marker D10S2443 (maximum 1.95, P = 0.005). Using multipoint H-LODs, we found a broad peak (maximum 1.91, P = 0.006) extending over the 11 centimorgans from marker D10S674 to marker D10S1426. Multipoint nonparametric linkage analysis produced a much broader peak, but with the maximum in the same location near D10S2443 (maximum z = 1.88, P = 0.03). Based on estimates from the multipoint analysis, this putative vulnerability locus appears to be segregating in 5-15% of the families studied, but this estimate should be viewed with caution. When evaluated in the context of our genome scan results, the evidence suggests the possibility of a fourth vulnerability locus for schizophrenia in these Irish families, in region 10p15-p11.

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial: study protocol for a randomized controlled trial

Background: Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI.

Methods/Design: Patients fulfilling the American-European Consensus Conference Definition of ALI will be randomized in a 1: 1 ratio to receive enteral simvastatin 80 mg or placebo once daily for a maximum of 28 days. Allocation to randomized groups will be stratified with respect to hospital of recruitment and vasopressor requirement. Data will be recorded by participating ICUs until hospital discharge, and surviving patients will be followed up by post at 3, 6 and 12 months post randomization. The primary outcome is number of ventilator-free days to day 28. Secondary outcomes are: change in oxygenation index and sequential organ failure assessment score up to day 28, number of non pulmonary organ failure free days to day 28, critical care unit mortality; hospital mortality; 28 day post randomization mortality and 12 month post randomization mortality; health related quality of life at discharge, 3, 6 and 12 months post randomization; length of critical care unit and hospital stay; health service use up to 12 months post-randomization; and safety. A total of 540 patients will be recruited from approximately 35 ICUs in the UK and Ireland. An economic evaluation will be conducted alongside the trial. Plasma and urine samples will be taken up to day 28 to investigate potential mechanisms by which simvastatin might act to improve clinical outcomes.

How Outcomes Are Defined in Clinical Trials of Mechanically Ventilated Adults and Children

Systematic reviews have considerable potential to provide evidence-based data to aid clinical decision-making. However, there is growing recognition that trials involving mechanical ventilation lack consistency in the definition and measurement of ventilation outcomes, creating difficulties in combining data for meta-analyses. To address the inconsistency in outcome definitions, international standards for trial registration and clinical trial protocols published recommendations, effectively setting the “gold standard” for reporting trial outcomes. In this Critical Care Perspective, we review the problems resulting from inconsistent outcome definitions and inconsistent reporting of outcomes (outcome sets). We present data highlighting the variability of the most commonly reported ventilation outcome definitions. Ventilation outcomes reported in trials over the last 6 years typically fall into four domains: measures of ventilator dependence; adverse outcomes; mortality; and resource use. We highlight the need, first, for agreement on outcome definitions and, second, for a minimum core outcome set for trials involving mechanical ventilation. A minimum core outcome set would not restrict trialists from measuring additional outcomes, but would overcome problems of variability in outcome selection, measurement, and reporting, thereby enhancing comparisons across trials.

A Case Study in Policy Delivery:Examining Social Inclusion through Interpretation and Practice

The current body of literature regarding social inclusion and the arts tends to focus
on two areas: the lack of clear or common understanding of the terminology involved
(GLLAM, 2000) and the difficulty in measuring impact (Newman 2001). Further, much
of the literature traces the historical evolution of social inclusion policy within the arts
from a political and social perspective (Belfiore & Bennett, 2007), whilst others
examine the situation in the context of the museum as an institution more generally
(Sandell, 2002b). Such studies are essential; however they only touch on the
importance of understanding the context of social inclusion programmes. As each
individual’s experience of exclusion (or inclusion) is argued to be different (Newman
et al., 2005) and any experience is also process-based (SEU 2001), there is a need
for more thorough examination of the processes underpinning project delivery
(Butterfoss, 2006), particularly within a field that has its own issues of exclusion, such
as the arts (Bourdieu & Darbel, 1991). This paper presents case study findings of a
programme of contemporary arts participation for adults with learning difficulties
based at an arts centre in Liverpool. By focusing on practice, the paper applies
Wenger’s (1998) social theory of learning in order to assert that rather than search
for measurable impacts, examining the delivery of programmes within their individual
contexts will provide the basis for a more reflective practice and thus more effective
policy making.

Shame, intimacy and self-definition: An assessment of the emotional foundation and intimate relationship consequences of an introjective personality orientation.

The current study sought to elaborate and test a theoretical proposition that introjective personality functioning, which has been implicated in various psychological difficulties (e.g., self-critical depression, obsessive-compulsive disorder), has an emotional foundation in the self-conscious emotion of shame and is supported by dissociation. Moreover, introjective functioning was predicted to be associated with reduced interpersonal intimacy. To test the model, a Web-based survey design using path analysis was used. Three hundred and fifteen university students were assessed with measures of self-conscious emotions (i.e., shame, guilt, and embarrassment), introjective (self-definition) and anaclitic (relational) personality style, pathological dissociation, and interpersonal intimacy. Introjective personality was found to be associated with increased shame and reduced interpersonal intimacy. However, the path between pathological dissociation and introjective functioning was not significant. The results are discussed with reference to the moderating influence of introjective functioning between shame and reduced interpersonal intimacy.

Practice and Policy in the UK with Children and Young People who Display Harmful Sexual Behaviour: An analysis and critical review

This article considers the trajectory and effectiveness of policy, procedures and practice in the UK since the early 1990s in responding to young people who display problematic and harmful sexual behaviours. It draws on data from three publications in which research, policy and practice in the last 20 years have been reviewed. Key themes raised by Masson and Hackett are revisited including: denial and minimisation; terminology and categorisation; similarities with other young offenders; the child protection and youth justice systems; and assessment and interventions. The authors find that there is improvement in recognition of, and practice in response to, this group of young people, but good practice standards are inconsistently applied. With devolution of political powers, Scotland and Northern Ireland are now embarking on a more strategic response than England. The absence of a public debate and prioritising of primary prevention of child sexual abuse is noted.

An Enchanted Tool? Humanitarian Assistance and the ILC Draft Articles on the Protection of Persons in the Event of Disasters

Despite previous attempts at codification of international law regarding international responses to natural and human-made disasters, there is currently no binding international legal framework to regulate the provision of humanitarian assistance outside armed conflicts. Nevertheless, since the International Law Commission (ILC) included the protection of persons in the event of disasters on its programme of work in 2006, it has provisionally adopted eleven draft articles that have the potential to create binding obligations on states and humanitarian actors in disaster settings. Draft articles adopted include the definition of ‘a disaster’, the relationship of the draft articles to the international humanitarian law of armed conflict, recognition of the inherent dignity of the human person, and the duty of international cooperation. However, the final form of the draft articles has not been agreed. The Codification Division of the UN Office of Legal Affairs has proposed a framework convention format, which has seen support in the ILC and the UN General Assembly Sixth Committee. The overall aim of this article is to provide an analysis of the potential forms of international regulation open to the ILC and states in the context of humanitarian responses to disasters. However to avoid enchanting the ILC draft articles with unwarranted power, any examination of form requires an understanding of the substantive subject matter of the planned international regulation. The article therefore provides an overview of the international legal regulation of humanitarian assistance following natural and human-made disasters, and the ILC’s work to date on the topic. It then examines two key issues that remain to be addressed by the ILC and representatives of states in the UN General Assembly Sixth Committee. Drawing on the UN Guiding Principles on Internal Displacement, the development and implications of binding and non-binding international texts are examined, followed by an analysis of the suggested framework convention approach identified by the Special Rapporteur as a potential outcome of the ILC work.

From Francis Hutcheson to James McCosh: Irish Presbyterians and Defining the Scottish Philosophy in the Nineteenth Century

This article examines the disputes amongst Irish Presbyterians about the teaching of moral philosophy by Professor John Ferrie in the college department of the Royal Belfast Academical Institution in the early nineteenth century and the substantive philosophical and theological issues that were raised. These issues have largely been ignored by Irish historians, but a discussion of them is of general relevance to historians of ideas as they illuminate a series of broader questions about the definition and development of Scottish philosophy. These are represented in the move from two philosophers who had strong connections with Irish Presbyterianism—Francis Hutcheson, the early eighteenth-century moral sense philosopher and theological moderate from County Down, and James McCosh, nineteenth-century exponent of modified Common Sense philosophy at Queen's College Belfast and a committed evangelical. In particular, this article addresses three important themes—the definition and character of ‘the Scottish philosophy’, the relationship between evangelicalism and Common Sense philosophy, and the process of development and adaptation that occurred in eighteenth-century Scottish thought during the first half of the nineteenth century.

Disturbance, neutral theory and patterns of beta diversity in soil communities

Beta diversity describes how local communities within an area or region differ in species composition/abundance. There have been attempts to use changes in beta diversity as a biotic indicator of disturbance, but lack of theory and methodological caveats have hampered progress. We here propose that the neutral theory of biodiversity plus the definition of beta diversity as the total variance of a community matrix provide a suitable, novel, starting point for ecological applications. Observed levels of beta diversity (BD) can be compared to neutral predictions with three possible outcomes: Observed BD equals neutral prediction or is larger (divergence) or smaller (convergence) than the neutral prediction. Disturbance might lead to either divergence or convergence, depending on type and strength. We here apply these ideas to datasets collected on oribatid mites (a key, very diverse soil taxon) under several regimes of disturbances. When disturbance is expected to increase the heterogeneity of soil spatial properties or the sampling strategy encompassed a range of diverging environmental conditions, we observed diverging assemblages. On the contrary, we observed patterns consistent with neutrality when disturbance could determine homogenization of soil properties in space or the sampling strategy encompassed fairly homogeneous areas. With our method, spatial and temporal changes in beta diversity can be directly and easily monitored to detect significant changes in community dynamics, although the method itself cannot inform on underlying mechanisms. However, human-driven disturbances and the spatial scales at which they operate are usually known. In this case, our approach allows the formulation of testable predictions in terms of expected changes in beta diversity, thereby offering a promising monitoring tool.

Evaluation of infilled frames: an updated in-plane-stiffness macro-model considering the effects of vertical loads

The influence of masonry infills on the in-plane behaviour of RC framed structures is a central topic in the seismic evaluation and retrofitting of existing buildings. Many models in the literature use an equivalent strut member in order to represent the infill but, among the parameters influencing the equivalent strut behaviour, the effect of vertical loads acting on the frames is recognized but not quantified. Nevertheless a vertical load causes a non-negligible variation in the in-plane behaviour of infilled frames by influencing the effective volume of the infill. This results in a change in the stiffness and strength of the system. This paper presents an equivalent diagonal pin-jointed strut model taking into account the stiffening effect of vertical loads on the infill in the initial state. The in-plane stiffness of a range of infilled frames was evaluated using a finite element model of the frame-infill system and the cross-section of the strut equivalent to the infill was obtained for different levels of vertical loading by imposing the equivalence between the frame containing the infill and the frame containing the diagonal strut. In this way a law for identifying the equivalent strut width depending on the geometrical and mechanical characteristics of the infilled frame was generalized to consider the influence of vertical loads for use in the practical applications. The strategy presented, limited to the initial stiffness of infilled frames, is preparatory to the definition of complete non-linear cyclic laws for the equivalent strut.

Region-based Mixture of Gaussians Modelling for Foreground Detection in Dynamic Scenes

One of the most widely used techniques in computer vision for foreground detection is to model each background pixel as a Mixture of Gaussians (MoG). While this is effective for a static camera with a fixed or a slowly varying background, it fails to handle any fast, dynamic movement in the background. In this paper, we propose a generalised framework, called region-based MoG (RMoG), that takes into consideration neighbouring pixels while generating the model of the observed scene. The model equations are derived from Expectation Maximisation theory for batch mode, and stochastic approximation is used for online mode updates. We evaluate our region-based approach against ten sequences containing dynamic backgrounds, and show that the region-based approach provides a performance improvement over the traditional single pixel MoG. For feature and region sizes that are equal, the effect of increasing the learning rate is to reduce both true and false positives. Comparison with four state-of-the art approaches shows that RMoG outperforms the others in reducing false positives whilst still maintaining reasonable foreground definition. Lastly, using the ChangeDetection (CDNet 2014) benchmark, we evaluated RMoG against numerous surveillance scenes and found it to amongst the leading performers for dynamic background scenes, whilst providing comparable performance for other commonly occurring surveillance scenes.

Women, letter-writing and the life of the mind in England, c.1650-1750

Drawing on national and regional letter collections dating from the late seventeenth and early eighteenth centuries, this article explores women's experiences of the life of the mind through an analysis of their letter-writing. This study also highlights the shortcomings of the compartmentalised nature of scholarship on women's writing and intellectual lives and proposes the letter both as a beneficial historical source and methodological tool for research on women's mental worlds. By employing an inclusive definition of intellectual and creative life, and eschewing traditional benchmarks of achievement, this article contends that women took a full part in the cultures of knowledge of their time. 

How should teaching on whole person medicine, including spiritual issues, be delivered in the undergraduate medical curriculum in the United Kingdom?

Background

Although the General Medical Council recommends that United Kingdom medical students are taught ‘whole person medicine’, spiritual care is variably recognised within the curriculum. Data on teaching delivery and attainment of learning outcomes is lacking. This study ascertained views of Faculty and students about spiritual care and how to teach and assess competence in delivering such care.

A questionnaire comprising 28 questions exploring attitudes to whole person medicine, spirituality and illness, and training of healthcare staff in providing spiritual care was designed using a five-point Likert scale. Free text comments were studied by thematic analysis. The questionnaire was distributed to 1300 students and 106 Faculty at Queen’s University Belfast Medical School.

351 responses (54 staff, 287 students; 25 %) were obtained. >90 % agreed that whole person medicine included physical, psychological and social components; 60 % supported inclusion of a spiritual component within the definition. Most supported availability of spiritual interventions for patients, including access to chaplains (71 %), counsellors (62 %), or members of the patient’s faith community (59 %). 90 % felt that personal faith/spirituality was important to some patients and 60 % agreed that this influenced health. However 80 % felt that doctors should never/rarely share their own spiritual beliefs with patients and 67 % felt they should only do so when specifically invited. Most supported including training on provision of spiritual care within the curriculum; 40-50 % felt this should be optional and 40 % mandatory. Small group teaching was the favoured delivery method. 64 % felt that teaching should not be assessed, but among assessment methods, reflective portfolios were most favoured (30 %). Students tended to hold more polarised viewpoints but generally were more favourably disposed towards spiritual care than Faculty. Respecting patients’ values and beliefs and the need for guidance in provision of spiritual care were identified in the free-text comments.

Students and Faculty generally recognise a spiritual dimension to health and support provision of spiritual care to appropriate patients. There is lack of consensus whether this should be delivered by doctors or left to others. Spiritual issues impacting patient management should be included in the curriculum; agreement is lacking about how to deliver and assess.

A strategy towards professionalism in the dissecting room

The teaching and cultivation of professionalism is an integral part of medical education as professionalism is central to maintaining the public’s trust in the medical profession. Traditionally professional values would have been acquired through an informal process of socialisation and observation of role models. Recently, however, medical educators have accepted the responsibility to explicitly teach and effectively evaluate professionalism. A comprehensive working definition of the term professionalism and a universally agreed list of the constituent elements of professionalism are currently debated. The School of Medicine and Dentistry of The Queen’s University of Belfast uses an approach of self-directed learning for teaching anatomy, and students are given the opportunity to learn anatomy from human dissection. Self-directed learning teams have been found to be underutilised as educational strategies and presented an opportunity to utilise the first year dissection room teaching environment to nurture the development of the attributes of professionalism. An educational strategy based on role-playing was developed to engage all students around the dissection table. Students received comprehensive background reviews on professionalism, its attributes and the identification of such attributes in the context of the dissection room. Roles, with specific duties attached, were allocated to each team member. Circulating academic staff members directly observed student participation and gave formative feedback. Students were given the opportunity to reflect on their ability to identify the attributes and reflect on their own and their peer’s ability to develop and practise these attributes. This strategy indicated that small group learning teams in the dissection room utilise widely accepted principles of adult learning and offer an opportunity to create learning activities that will instil in students the knowledge, values, attitudes and behaviours that characterise medical professionalism. Anatomy faculty have a responsibility to nurture and exemplify professionalism and play a significant role in the early promotion and inculcation of professionalism. It remains imperative not only to assess this strategy but also to create opportunities for critical reflection and evaluation within the strategy. Key words: Medical Education – Professionalism – Anatomy - Reflective Practise – Role-play