Molecular Validation of the Schizophrenia Spectrum

Background: Early descriptive work and controlled family and adoption studies support the hypothesis that a range of personality and nonschizophrenic psychotic disorders aggregate in families of schizophrenic probands. Can we validate, using molecular polygene scores from genome-wide association studies (GWAS), this schizophrenia spectrum? Methods: The predictive value of polygenic findings reported by the Psychiatric GWAS Consortium (PGC) was applied to 4 groups of relatives from the Irish Study of High-Density Schizophrenia Families (ISHDSF; N = s) differing on their assignment within the schizophrenia spectrum. Genome-wide single nucleotide polymorphism data for affected and unaffected relatives were used to construct per-individual polygene risk scores based on the PGC stage-I results. We compared mean polygene scores in the ISHDSF with mean scores in ethnically matched population controls (N = 929). Results: The schizophrenia polygene score differed significantly across diagnostic categories and was highest in those with narrow schizophrenia spectrum, lowest in those with no psychiatric illness, and in-between in those classified in the intermediate, broad, and very broad schizophrenia spectrum. Relatives of all of these groups of affected subjects, including those with no diagnosis, had schizophrenia polygene scores significantly higher than the control sample. Conclusions: In the relatives of high-density families, the observed pattern of enrichment of molecular indices of schizophrenia risk suggests an underlying, continuous liability distribution and validates, using aggregate common risk alleles, a genetic basis for the schizophrenia spectrum disorders. In addition, as predicted by genetic theory, nonpsychotic members of multiply-affected schizophrenia families are significantly enriched for replicated, polygenic risk variants compared with the general population.

Irish study on high-density schizophrenia families:field methods and power to detect linkage

Large samples of multiplex pedigrees will probably be needed to detect susceptibility loci for schizophrenia by linkage analysis. Standardized ascertainment of such pedigrees from culturally and ethnically homogeneous populations may improve the probability of detection and replication of linkage. The Irish Study of High-Density Schizophrenia Families (ISHDSF) was formed from standardized ascertainment of multiplex schizophrenia families in 39 psychiatric facilities covering over 90% of the population in Ireland and Northern Ireland. We here describe a phenotypic sample and a subset thereof, the linkage sample. Individuals were included in the phenotypic sample if adequate diagnostic information, based on personal interview and/or hospital record, was available. Only individuals with available DNA were included in the linkage sample. Inclusion of a pedigree into the phenotypic sample required at least two first, second, or third degree relatives with non-affective psychosis (NAP), one whom had schizophrenia (S) or poor-outcome schizo-affective disorder (PO-SAD). Entry into the linkage sample required DNA samples on at least two individuals with NAP, of whom at least one had S or PO-SAD. Affection was defined by narrow, intermediate, and broad criteria. The phenotypic sample contained 277 pedigrees and 1,770 individuals and the linkage sample 265 pedigrees and 1,408 individuals. Using the intermediate definition of affection, the phenotypic sample contained 837 affected individuals and 526 affected sibling pairs. Parallel figures for the linkage sample were 700 and 420. Individuals with schizophrenia from these multiplex pedigrees resembled epidemiologically sampled cases with respect to age at onset, gender distribution, and most clinical symptoms, although they were more thought-disordered and had a poorer outcome. Power analyses based on the model of linkage heterogeneity indicated that the ISHDSF should be able to detect a major locus that influences susceptibility to schizophrenia in as few as 20% of families. Compared to first-degree relatives of epidemiologically sampled schizophrenic probands, first-degree relatives of schizophrenic members from the ISHDSF had a similar risk for schizotypal personality disorder, affective illness, alcoholism, and anxiety disorder. With sufficient resources, large-scale ascertainment of multiplex schizophrenia pedigrees is feasible, especially in countries with catchmented psychiatric care and stable populations. Although somewhat more severely ill, schizophrenic members of such pedigrees appear to clinically resemble typical schizophrenic patients. Our ascertainment process for multiplex schizophrenia families did not select for excess familial risk for affective illness or alcoholism. With its large sample ascertained in a standardized manner from a relatively homogeneous population, the ISHDSF provides considerable power to detect susceptibility loci for schizophrenia.

Evaluation of a Psychoeducational intervention for patients with Advanced Cancer who have Cachexia and their lay Carers (EPACaCC): study protocol

Aim: To evaluate a psychoeducational intervention for patients with advanced cancer who have cachexia and their lay carers.

Background: Cachexia is a frequent and devastating syndrome of advanced cancer. It has an impact on patients biologically, psychologically and socially and has profound impact on their lay carers. Prior research has predominately focused on the biological components of cachexia and associated potential treatment modalities. At present, there is no standardized supportive healthcare intervention in current practice that targets the psychosocial impact of this syndrome.

Design: A pragmatic multicentre randomized controlled trial.

Methods: Patient/carer dyads (n = 200) will be recruited into a randomized controlled trial of a DVD intervention for cachexia management. The sample will be recruited from two urban hospices in the UK. The primary outcome measure will be the General Health Questionnaire-12. Additional questionnaires focusing on distress, readiness to give care and coping skills will be used as secondary outcome measures. In addition, lay carers in the intervention group will be asked to participate in semi-structured interviews following the death of their loved one. Both Office for Research Ethics Committee approval and local governance approval at both hospices have been obtained as of February 2013.

Discussion: This is the first time that a psychoeducational DVD has been tested in a randomized controlled trial in this population. Dissemination of findings will make a significant contribution to international knowledge and understanding in this area. Findings will inform education, practice and policy.

De-linkage Processes and Grassroots Movements in Transitional Justice

Transitional justice literature has highlighted a negative relationship between enforced disappearances and reconciliation in post-conflict settings. Little attention has been paid to how human rights issues can become stepping-stones to reconciliation. The article explains the transformation of the Cypriot Committee on Missing Persons (CMP) from an inoperative body into a successful humanitarian forum, paving the way for the pro-rapprochement bi-communal grassroots mobilization of the relatives of the missing. By juxtaposing the experience of Cyprus with other societies confronting similar problems, the article shows how the issue of the missing can become a driving force for reconciliation. The findings indicate that a policy delinking humanitarian exhumations from the prospect of a wider political settlement facilitates positive transformation in protracted human rights problems and opens up a window of opportunity to grassroots actors.

Delaying Truth Recovery for Missing Persons

The fate of missing persons is a central issue in post-conflict societies facing truth recovery and human rights dilemmas. Despite widespread public sympathy towards relatives, societies emerging from conflict often defer the recovery of missing for decades. More paradoxically, in post-1974 Cyprus, the official authorities delayed unilateral exhumations of victims buried within cemeteries in their own jurisdiction. Analysis of official post-1974 discourse reveals a Greek-Cypriot consensus to emphasise the issue as one of Turkish aggression, thus downplaying in-group responsibilities and the legacy of intra-communal violence. We compare the experience of Cyprus with other post-conflict societies such as Spain, Northern Ireland, and Mozambique and explore the linkages between institutions and beliefs about transitional justice. We argue that elite consensus initiates and facilitates the transition to democracy but often leads to the institutionalization of groups opposing truth recovery even for in-group members.

Cable Crossings: The Aran Jumper as Myth and Merchandise

This article considers the Aran jumper as a cultural artefact from an anthropological perspective. As an internationally recognized symbol of Irishness that comes with its own myth of origin, the Aran jumper carries emotionally charged ideas about kinship and nativeness. Whether read as an ID document, family tree, representation of the landscape or reference to Christian or pre-Christian spirituality, the Aran jumper’s stitch patterns seem to invite interpretation. Emerging at a particular period in the relationship between Ireland and America, this garment and the story that accompanies it have been shaped by migration and tourism, but may be understood very differently on either side of the Atlantic. The resilience of the myth of a fisherman lost at sea, whose corpse is identifiable only by designs his relatives have stitched into his clothing, is explained in light of its resonance with diasporic narratives and transnational longings.

Exploring lay views on physical activity and their implications for public health policy. A case study from East Belfast

It is now recognised that inactive lifestyles underpin much of the disease burden evident in the richer nations of the world. Indeed, the WHO has identified physical inactivity as a 'global public health problem' and has established minimum physical activity (PA) targets for people at different stages of the life-course. Yet, according to WHO, just under 1/3 of working age adults across the globe meet those targets and it is not at all clear how the disjunction between the recommendations of policy makers and the behaviour of ordinary people might be surmounted. Using an opportunity to examine the impact of an urban regeneration project on community residents in East Belfast (Northern Ireland) this paper examines the views of some 113 people on how to increase rates of PA in an area of multiple deprivation. The results of the analysis suggest that lay people rarely consider PA as a discrete issue, or one that centres on individuals and their motivation, but rather as one component in a complex web of concerns, processes and events that include such things as the actions of neighbours and relatives, material and political environments, vandalism, violence, and the weather. We explore and unravel the nature of those concerns using novel methods of content analysis that generate 'issue webs'. Particular attention is paid to the ways in which lay people conceptualize 'activity' and to the manner in which they point to ways of encouraging activity that are rooted in everyday life rather than in the corpocentric, agent-centred and often sport dominated strategies favoured by local policy makers. Our results support those who argue that interventions to increase rates of PA need to move beyond behavioural approaches that focus on individuals and consider the social, political and material contexts in which 'activity' occurs.

How Prepared are UK Medical Graduates for Practice? Final report from a programme of research commissioned by the General Medical Council

This programme of research aimed to understand the extent to which current UK medical graduates are prepared for practice. Commissioned by the General Medical Council, we conducted: (1) A Rapid Review of the literature between 2009 and 2013; (2) narrative interviews with a range of stakeholders; and (3) longitudinal audio-diaries with Foundation Year 1 doctors. The Rapid Review (RR) resulted in data from 81 manuscripts being extracted and mapped against a coding framework (including outcomes from Tomorrow's Doctors (2009) (TD09)). A narrative synthesis of the data was undertaken. Narrative interviews were conducted with 185 participants from 8 stakeholder groups: F1 trainees, newly registered trainee doctors, clinical educators, undergraduate and postgraduate deans and foundation programme directors, other healthcare professionals, employers, policy and government and patient and public representatives. Longitudinal audio-diaries were recorded by 26 F1 trainees over 4 months. The data were analysed thematically and mapped against TD09. Together these data shed light onto how preparedness for practice is conceptualised, measured, how prepared UK medical graduates are for practice, the effectiveness of transition interventions and the currently debated issue of bringing full registration forward to align with medical students’ graduation. Preparedness for practice was conceptualised as both a long- and short-term venture that included personal readiness as well as knowledge, skills and attitudes. It has mainly been researched using self-report measures of generalised incidents that have been shown to be problematic. In terms of transition interventions: assistantships were found to be valuable and efficacious for proactive students as team members, shadowing is effective when undertaken close to employment/setting of F1 post and induction is generally effective but of inconsistent quality. The August transition was highlighted in our interview and audio-diary data where F1s felt unprepared, particularly for the step-change in responsibility, workload, degree of multitasking and understanding where to go for help. Evidence of preparedness for specific tasks, skills and knowledge was contradictory: trainees are well prepared for some practical procedures but not others, reasonably well prepared for history taking and full physical examinations, but mostly unprepared for adopting an holistic understanding of the patient, involving patients in their care, safe and legal prescribing, diagnosing and managing complex clinical conditions and providing immediate care in medical emergencies. Evidence for preparedness for interactional and interpersonal aspects of practice was inconsistent with some studies in the RR suggesting graduates were prepared for team working and communicating with colleagues and patients, but other studies contradicting this. Interview and audio-diary data highlights concerns around F1s preparedness for communicating with angry or upset patients and relatives, breaking bad news, communicating with the wider team (including interprofessionally) and handover communication. There was some evidence in the RR to suggest that graduates were unprepared for dealing with error and safety incidents and lack an understanding of how the clinical environment works. Interview and audio-diary data backs this up, adding that F1s are also unprepared for understanding financial aspects of healthcare. In terms of being personally prepared, RR, interview and audio diary evidence is mixed around graduates’ preparedness for identifying their own limitations, but all data points to graduates’ difficulties in the domain of time management. In terms of personal and situational demographic factors, the RR found that gender did not typically predict perceptions of preparedness, but graduates from more recent cohorts, graduate entry students, graduates from problem based learning courses, UK educated graduates and graduates with an integrated degree reported feeling better prepared. The longitudinal audio-diaries provided insights into the preparedness journey for F1s. There seems to be a general development in the direction of trainees feeling more confident and competent as they gain more experience. However, these developments were not necessarily linear as challenging circumstances (e.g. new specialty, new colleagues, lack of staffing) sometimes made them feel unprepared for situations where they had previously indicated preparedness.

Factors affecting the successful implementation and sustainability of the Liverpool Care Pathway for dying patients – a realist evaluation

Objectives: The Liverpool Care Pathway for the dying patient (LCP) was designed to improve end-of-life care in generalist health care settings. Controversy has led to its withdrawal in some jurisdictions. The main objective of this research was to identify the influences that facilitated or hindered successful LCP implementation.

Method: An organisational case study using realist evaluation in one health and social care trust in Northern Ireland. Two rounds of semi-structured interviews were conducted with two policy makers and twenty two participants with experience and/or involvement in management of the LCP during 2011 and 2012.

Results: Key resource inputs included facilitation with a view to maintaining LCP ‘visibility’, reducing anxiety among nurses and increasing their confidence regarding the delivery of end-of-life care; and nurse and medical education designed to increase professional self-efficacy and reduce misuse and misunderstanding of the LCP. Key enabling contexts were consistent senior management support; ongoing education and training tailored to the needs of each professional group; and an organisational cultural change in the hospital setting that encompassed end-of-life care.

Conclusion: There is a need to appreciate the organizationally complex nature of intervening to improve end-of-life care. Successful implementation of evidence-based interventions for end-of-life care requires commitment to planning, training and ongoing review that takes account of different perspectives, institutional hierarchies and relationships and the educational needs of professional disciplines. There is a need also to recognise that medical consultants require particular support in their role as gatekeepers and as a lead communication channel with patients and their relatives.

Urban and rural differences in risk of admission to a care home: a census-based follow-up study

Research on admissions to care homes for older people has paid more attention to individual and social characteristics than to geographical factors. This paper considers rural-urban differences in household composition and admission rates. Cohort: 51,619 people aged 65 years or older at the time of the 2001 Census and not living in a care home, drawn from a data linkage study based on c.28% of the Northern Ireland population.Living alone was less common in rural areas; 25% of older people in rural areas lived with children compared to 18% in urban areas. Care home admission was more common in urban (4.7%) and intermediate (4.3%) areas than in rural areas (3.2%). Even after adjusting for age, sex, health and living arrangements, the rate of care home admission in rural areas was still only 75% of that in urban areas.People in rural areas experience better family support by living as part of two or three generation households. Even after accounting for this difference, older rural dwellers are less likely to enter care homes; suggesting that neighbours and relatives in rural areas provide more informal care; or that there may be differential deployment of formal home care services.

Understanding the practice nurse’s role in the cancer care tapestry

Background: The are currently 2 million people in the UK living with or
after cancer, and this number is expected to double by 2030 (Maddams et
al, 2012). However, many report unmet physical and psychological needs.

Aim: To determine the learning needs of practice nurses to take on an
enhanced role with people affected by cancer, particularly after primary
treatment, and to develop a course to meet these needs.

Method: The Macmillan Steering Group designed and developed a course for practice
nurses to identify their learning needs, enabling participating practice
nurses to work collaboratively with each other and the course facilitator.
There was strong patient involvement throughout. The course was
evaluated by self-assessment of knowledge, skills and confidence, patient
satisfaction questionnaires and in-depth, qualitative telephone interviews
with the participants and their supporting GPs.

Results: The practice nurses reported changed practice, with increased confidence in discussing
issues relating to cancer and its treatment with patients and relatives.
They understood the importance of supported self-management and were
able to signpost patients to appropriate sources of information and
support. Many of the practice nurses started initiating and undertaking
Cancer Care Reviews, both as planned appointments and opportunistically.
Over the past year, a further nine pilots have been completed throughout
the UK, demonstrating that these results are reproducible in other settings.

Conclusions: With appropriate support and training and protected time
to include cancer care into their everyday work, practice nurses can take
on an important role in the support and care of people affected by cancer

A small predatory core genome in the divergent marine Bacteriovorax marinus SJ and the terrestrial Bdellovibrio bacteriovorus

Bacteriovorax marinus SJ is a predatory delta-proteobacterium isolated from a marine environment. The genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium Bdellovibrio bacteriovorus HD100. Based on their predatory lifestyle, Bacteriovorax were originally designated as members of the genus Bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. B. marinus attaches to gram-negative bacteria, penetrates through the cell wall to form a bdelloplast, in which it replicates, as shown using microscopy. Bacteriovorax is distinct, as it shares only 30% of its gene products with its closest sequenced relatives. Remarkably, 34% of predicted genes over 500 nt in length were completely unique with no significant matches in the databases. As expected, Bacteriovorax shares several characteristic loci with the other delta-proteobacteria. A geneset shared between Bacteriovorax and Bdellovibrio that is not conserved among other delta-proteobacteria such as Myxobacteria (which destroy prey bacteria externally via lysis), or the non-predatory Desulfo-bacteria and Geobacter species was identified. These 291 gene orthologues common to both Bacteriovorax and Bdellovibrio may be the key indicators of host-interaction predatory-specific processes required for prey entry. The locus from Bdellovibrio bacteriovorus is implicated in the switch from predatory to prey/host-independent growth. Although the locus is conserved in B. marinus, the sequence has only limited similarity. The results of this study advance understanding of both the similarities and differences between Bdellovibrio and Bacteriovorax and confirm the distant relationship between the two and their separation into different families.

‘A picture of who we are as a family’: conceptualizing post-adoption contact as practices of family display

Social work has a central role in negotiating and supporting birth family contact following adoption from care. This paper argues that family display (Finch) offers a useful conceptual resource for understanding relationships in the adoptive kinship network as they are enacted through contact. It reports on an interpretative phenomenological analysis of adoptive parents' accounts of open adoption from care that revealed direct and indirect contact to be contexts in which they and birth relatives performed family display practices: communicating the meaning of their respective relationships with the adopted child and seeking recognition that this was a legitimate family relationship. The analysis explores how family display was performed, and the impact of validating or invalidating responses. It aims to illuminate these social and interpretive processes involved in adoptive kinship in order to inform social work support for contact. The findings suggest that successful contact may be promoted by helping adoptive and birth relatives validate the legitimacy of the other's kin connection with the child, and through arrangements that facilitate family-like interactions.

Heterozygous ATM mutations do not contribute to early onset of breast cancer

Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition, attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene. AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise approximately 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer, raising the possibility that germline ATM mutations may account for approximately 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years. To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT. We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer.

Understanding informal kinship care: a critical narrative review of theory and research

Many children are cared for on a full-time basis by relatives or adult friends, rather than their biological parents, and often in response to family crises. These kinship care arrangements have received increasing attention from the social science academy and social care professions. However, more information is needed on informal kinship care that is undertaken without official ratification by welfare agencies and often unsupported by the state. This article presents a comprehensive, narrative review of international, research literature on informal, kinship care to address this gap. Using systematic search and review protocols, it synthesises findings regarding: (i) the way that informal kinship care is defined and conceptualised; (ii) the needs of the carers and children; and (iii) ways of supporting this type of care. A number of prominent themes are highlighted including the lack of definitional clarity; the various adversities experienced by the families; and the requirement to understand the interface between formal and informal supports. Key messages are finally identified to inform the development of family friendly policies, interventions, and future research.