Publications by authors named "Iain Williamson"

35 Publications

MUC4 is not expressed in cell lines used for live cell imaging.

Wellcome Open Res 2021 19;6:265. Epub 2021 Nov 19.

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland, EH42XU, UK.

The ability to visualise specific mammalian gene loci in living cells is important for understanding the dynamic processes linked to transcription. However, some of the tools used to target mammalian genes for live cell imaging, such as dCas9, have been reported to themselves impede processes linked to transcription. The gene is a popular target for live cell imaging studies due to the repetitive nature of sequences within some exons of this gene. We set out to compare the impact of dCas9 and TALE-based imaging tools on expression, including in human cell lines previously reported as expressing . : We were unable to detect mRNA in these cell lines. Moreover, analysis of publicly available data for histone modifications associated with transcription, and data for transcription itself, indicate that neither , nor any of the mucin gene family are significantly expressed in the cell lines where dCas9 targeting has been reported to repress and expression, or in the cell lines where dCas13 has been used to report RNA detection in live cells. Methods for visualising specific gene loci and gene transcripts in live human cells are very challenging. Our data suggest that care should be given to the choice of the most appropriate cell lines for these analyses and that orthogonal methods of assaying gene expression be carefully compared.
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http://dx.doi.org/10.12688/wellcomeopenres.17229.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567686.2PMC
November 2021

Linking the obesity rs1421085 variant circuitry to cellular, metabolic, and organismal phenotypes in vivo.

Sci Adv 2021 Jul 21;7(30). Epub 2021 Jul 21.

Mammalian Genetics Unit, MRC Harwell Institute, Oxfordshire OX11 0RD, UK.

Variants in FTO have the strongest association with obesity; however, it is still unclear how those noncoding variants mechanistically affect whole-body physiology. We engineered a deletion of the rs1421085 conserved cis-regulatory module (CRM) in mice and confirmed in vivo that the CRM modulates and gene expression and mitochondrial function in adipocytes. The CRM affects molecular and cellular phenotypes in an adipose depot-dependent manner and affects organismal phenotypes that are relevant for obesity, including decreased high-fat diet-induced weight gain, decreased whole-body fat mass, and decreased skin fat thickness. Last, we connected the CRM to a genetically determined effect on steroid patterns in males that was dependent on nutritional challenge and conserved across mice and humans. Together, our data establish cross-species conservation of the rs1421085 regulatory circuitry at the molecular, cellular, metabolic, and organismal level, revealing previously unknown contextual dependence of the variant's action.
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http://dx.doi.org/10.1126/sciadv.abg0108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294759PMC
July 2021

Extensive pleiotropism and allelic heterogeneity mediate metabolic effects of and .

Science 2021 06;372(6546):1085-1091

Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.

Whereas coding variants often have pleiotropic effects across multiple tissues, noncoding variants are thought to mediate their phenotypic effects by specific tissue and temporal regulation of gene expression. Here, we investigated the genetic and functional architecture of a genomic region within the gene that is strongly associated with obesity risk. We show that multiple variants on a common haplotype modify the regulatory properties of several enhancers targeting and from megabase distances. We demonstrate that these enhancers affect gene expression in multiple tissues, including adipose and brain, and impart regulatory effects during a restricted temporal window. Our data indicate that the genetic architecture of disease-associated loci may involve extensive pleiotropy, allelic heterogeneity, shared allelic effects across tissues, and temporally restricted effects.
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http://dx.doi.org/10.1126/science.abf1008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386003PMC
June 2021

Acceptance, grief and adaptation amongst caregivers of partners with acquired brain injury: an interpretative phenomenological enquiry.

Disabil Rehabil 2020 Oct 12:1-10. Epub 2020 Oct 12.

Division of Psychology, De Montfort University, Leicester, UK.

Purpose: Families provide vital support to relatives with brain injury yet shoulder significant stress and anxiety with little help threatening family cohesion and rehabilitative outcomes. This paper analyses the accounts of people caring for a long-term partner with brain injury to identify coping mechanisms and support systems that enhanced well-being. This study used semi-structured interviews with eight participants and interpretative phenomenological analysis. Three themes are reported-"moving through denial toward acceptance"; "confronting and managing ambiguous loss"; and "becoming an expert carer". Theme one describes participants' struggles to accept the longevity of brain injury and use of strenuous care practices to deny or fight disability; this proved counterproductive and was later remedied by individuals embracing change and making adaptations. Theme two reports how participants split their partners' identities -before and after brain injury- to help grieve for the marital relationships they lost. Theme three looks at participants' development of self-reliant attitudes to caregiving due to perceived limited state help, while embracing peer support that enhanced information and emotion-based coping. Findings support therapeutic practices that help family members confront the permanence of brain injury, and target feelings of complex and unresolved grief. Future research proposals are discussed.IMPLICATIONS FOR REHABILITATION:Caregivers typically provide considerable rehabilitative support to spouses living with Acquired Brain Injury to manage the physical and psychosocial burdens of long-term disability.Therapeutic interventions should reconcile notions of hope and acceptance in order to help carers confront the permanence of brain injury and develop sustainable care practices.We recommend that interventions address feelings of unresolved grief and ambiguous loss and develop tailored support for caregivers which targets pertinent psychological concerns.
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http://dx.doi.org/10.1080/09638288.2020.1829104DOI Listing
October 2020

Evaluating approaches to designing effective Co-Created hand-hygiene interventions for children in India, Sierra Leone and the UK.

PLoS One 2020 15;15(9):e0239234. Epub 2020 Sep 15.

Infectious Disease Research Group, Leicester Institute for Pharmaceutical Innovation, De Montfort University, Leicester, United Kingdom.

Effective and culturally appropriate hand-hygiene education is essential to promote health-related practices to control and prevent diseases such as Diarrhoea, Ebola and COVID-19. In this paper we outline and evaluate the Co-Creation processes underpinning a handwashing intervention for young children (A Germ's Journey) developed and delivered in India, Sierra Leone and the UK, and consider the implications surrounding Imperialist/Colonial discourse and the White Saviour Complex. The paper focuses both on the ways Co-Creation was conceptualised by our collaborators in all three countries and the catalysts and challenges encountered. Qualitative data have been drawn from in-depth interviews with five key stakeholders, focus group data from 37 teachers in Sierra Leone and responses to open-ended questionnaires completed by teachers in India (N = 66) and UK (N = 63). Data were analysed using thematic analysis and three themes, each with three constituent subthemes are presented. In the theme 'Representations of and Unique Approaches to Co-Creation' we explore the ways in which Co-Creation was constructed in relation to teamwork, innovative practice and more continuous models of evaluation. In 'Advantages of Co-Creation' we consider issues around shared ownership, improved outcomes and more meaningful insights alongside the mitigation of risks and short-circuiting of problems. In 'Challenges of Co-Creation' we discuss issues around timing and organisation, attracting and working with appropriate partners and understanding the importance of local context with inherent social, economic and structural barriers, especially in low-and-middle-income countries. We consider how theoretical elements of Co-Creation can inform effective international public health interventions; crucial during a global pandemic in which handwashing is the most effective method to control the transmission of COVID-19. Finally we reflect on some of the methodological challenges of our own work and in managing the potentially conflicting goals of the ethical and participatory values of Co-Creation with pragmatic considerations about ensuring an effective final 'product'.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239234PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491735PMC
September 2020

A central role for canonical PRC1 in shaping the 3D nuclear landscape.

Genes Dev 2020 07 21;34(13-14):931-949. Epub 2020 May 21.

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom.

Polycomb group (PcG) proteins silence gene expression by chemically and physically modifying chromatin. A subset of PcG target loci are compacted and cluster in the nucleus; a conformation that is thought to contribute to gene silencing. However, how these interactions influence gross nuclear organization and their relationship with transcription remains poorly understood. Here we examine the role of Polycomb-repressive complex 1 (PRC1) in shaping 3D genome organization in mouse embryonic stem cells (mESCs). Using a combination of imaging and Hi-C analyses, we show that PRC1-mediated long-range interactions are independent of CTCF and can bridge sites at a megabase scale. Impairment of PRC1 enzymatic activity does not directly disrupt these interactions. We demonstrate that PcG targets coalesce in vivo, and that developmentally induced expression of one of the target loci disrupts this spatial arrangement. Finally, we show that transcriptional activation and the loss of PRC1-mediated interactions are separable events. These findings provide important insights into the function of PRC1, while highlighting the complexity of this regulatory system.
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http://dx.doi.org/10.1101/gad.336487.120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328521PMC
July 2020

Disturbance at the dinner table: Exploring mothers' experiences of mealtimes when caring for their son or daughter with anorexia nervosa.

J Health Psychol 2020 Feb 7:1359105320904756. Epub 2020 Feb 7.

University of Warwick, UK.

This study examined mothers' ( = 9) mealtime experiences when caring for their son or daughter with anorexia nervosa through semi-structured interviews. Interpretative Phenomenological Analysis identified three themes: (1) managing mealtime combat through accommodation and acceptance; (2) feeling isolated, inauthentic and ill-equipped and (3) a need for understanding and to be understood. The overarching concepts of 'combat' and 'distortion' also underpin the analysis, uniquely outlining how mothers come to understand this daily situation. Mealtime-related interventions need to be developed which prioritise promoting skills and confidence in managing mealtimes and helping carers to address the emotional challenges of these occasions.
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http://dx.doi.org/10.1177/1359105320904756DOI Listing
February 2020

DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency.

Cell Rep 2019 11;29(7):1974-1985.e6

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XU, UK. Electronic address:

The DNA hypomethylation that occurs when embryonic stem cells (ESCs) are directed to the ground state of naive pluripotency by culturing in two small molecule inhibitors (2i) results in redistribution of polycomb (H3K27me3) away from its target loci. Here, we demonstrate that 3D genome organization is also altered in 2i, with chromatin decompaction at polycomb target loci and a loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground state, we are able to restore to ESC in 2i the H3K27me3 distribution, as well as polycomb-mediated 3D genome organization that is characteristic of primed ESCs grown in serum. However, these cells retain the functional characteristics of 2i ground-state ESCs. Our findings demonstrate the central role of DNA methylation in shaping major aspects of 3D genome organization but caution against assuming causal roles for the epigenome and 3D genome in gene regulation and function in ESCs.
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http://dx.doi.org/10.1016/j.celrep.2019.10.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856714PMC
November 2019

Developmentally regulated expression is robust to TAD perturbations.

Development 2019 09 30;146(19). Epub 2019 Sep 30.

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK

Topologically associating domains (TADs) have been proposed to both guide and constrain enhancer activity. is located within a TAD known to contain all its enhancers. To investigate the importance of chromatin conformation and TAD integrity on developmental gene regulation, we have manipulated the TAD - creating internal deletions, deleting CTCF sites, and deleting and inverting sequences at TAD boundaries. Chromosome conformation capture and fluorescence hybridisation assays were used to investigate the changes in chromatin conformation that result from these manipulations. Our data suggest that these substantial alterations in TAD structure have no readily detectable effect on expression patterns or levels of expression during development - except where enhancers are deleted - and result in no detectable phenotypes. Only in the case of a larger deletion at one TAD boundary could ectopic influence of the limb enhancer be detected on a gene () in the neighbouring TAD. Our data suggests that, contrary to expectations, the developmental regulation of expression is remarkably robust to TAD perturbations.
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http://dx.doi.org/10.1242/dev.179523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212092PMC
September 2019

Decreased Enhancer-Promoter Proximity Accompanying Enhancer Activation.

Mol Cell 2019 11 4;76(3):473-484.e7. Epub 2019 Sep 4.

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK. Electronic address:

Enhancers can regulate the promoters of their target genes over very large genomic distances. It is widely assumed that mechanisms of enhancer action involve the reorganization of three-dimensional chromatin architecture, but this is poorly understood. The predominant model involves physical enhancer-promoter interaction by looping out the intervening chromatin. However, studying the enhancer-driven activation of the Sonic hedgehog gene (Shh), we have identified a change in chromosome conformation that is incompatible with this simple looping model. Using super-resolution 3D-FISH and chromosome conformation capture, we observe a decreased spatial proximity between Shh and its enhancers during the differentiation of embryonic stem cells to neural progenitors. We show that this can be recapitulated by synthetic enhancer activation, is impeded by chromatin-bound proteins located between the enhancer and the promoter, and appears to involve the catalytic activity of poly (ADP-ribose) polymerase. Our data suggest that models of enhancer-promoter communication need to encompass chromatin conformations other than looping.
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http://dx.doi.org/10.1016/j.molcel.2019.07.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838673PMC
November 2019

Disclosure in lesbian, gay and bisexual cancer care: towards a salutogenic healthcare environment.

BMC Cancer 2019 Jul 10;19(1):678. Epub 2019 Jul 10.

Leicester Academy for the Study of Ageing (LASA) The Leicester School of Nursing and Midwifery, De Montfort University, The Gateway, Leicester, LE1 9BH, UK.

Background: The literature on sexual orientation disclosure is arguably one of the most developed in the field of lesbian, gay and bisexual (LGB) people in healthcare in English speaking countries however, relatively little research has been conducted into disclosure in cancer care. Studies have been mainly undertaken in primary care where distinct circumstances pertain and where the benefits of disclosure include obtaining appropriate health information, treatment advice and avoiding misdiagnosis.

Methods: We conducted an in-depth qualitative study primarily recruiting patients through oncology care in hospital settings and through LGB community cancer support groups. Data were gathered through semi-structured interviews with 30 LGB patients with different cancer types.

Results: Data were analysed using thematic analysis and interpreted and interrogated through salutogenesis theory which offers a useful lens through which to consider the health promoting effects of sexual orientation disclosure in cancer care. We present three themes as part of the analysis: Authenticity as a driver for disclosure in cancer care, Partners as a (potential) salutogenic resource and Creating safe, healing environments conducive to disclosure. The findings are reported and discussed in relation to three inter-related concepts from current salutogenesis theorising including a sense of coherence, generalised resistance resources and healing environments which can facilitate sexual orientation disclosure.

Conclusion: Our findings enable a more nuanced approach to understanding disclosure in this context. This study contributes to the literature through its articulation of the salutogenic potential of disclosure (if responded to appropriately) for LGB patients as individuals, in relationship to their partners or carers and the role of creating a visible healing-oriented optimal environment to promote quality of life and recovery.
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http://dx.doi.org/10.1186/s12885-019-5895-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617610PMC
July 2019

"It's always on the safe list": Investigating experiential accounts of picky eating adults.

Appetite 2018 11 24;130:1-10. Epub 2018 Jul 24.

Division of Psychology, Faculty of Health & Life Sciences, Hawthorn Building, De Montfort University, Leicester, LE1 9BH, UK.

Previous research into severely restricted eating for reasons which are not cultural, medical, due to a lack of food or due to concerns about body image has focused predominantly on "picky/fussy eating" in children. Despite evidence that picky eating does continue into adulthood and recognition in the new diagnostic category Avoidant Restrictive Food Intake Disorder (ARFID) that problematically avoidant and restrictive patterns of eating affect people across the lifespan, relatively little is known about the challenges and consequences faced by older adolescents and adults. This research employs qualitative methods to explore the experience of living as an adult with picky eating behaviours. Semi-structured interviews were undertaken with thirteen adults who identify as picky eaters and eat a highly limited diet, as determined by a checklist food questionnaire. Data were analysed using interpretative phenomenological analysis (IPA). Two themes are presented in this paper: "Constructions of food" and "Motivators for and barriers to change". These themes show the importance of how individuals perceive food, their diet and themselves, and implications for clinical practice and future research in light of these findings are considered.
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http://dx.doi.org/10.1016/j.appet.2018.07.023DOI Listing
November 2018

Why aren't you stopping now?!' Exploring accounts of white women breastfeeding beyond six months in the East of England.

Appetite 2018 10 22;129:228-235. Epub 2018 Jun 22.

School of Applied Social Sciences, Leicester, UK. Electronic address:

Breastfeeding infants for a period of two years is endorsed by international health agencies such as the World Health Organisation. However, discourses of breastfeeding in a British context are complex and contradictory, juxtaposing representations of breastfeeding as healthy and a moral obligation for mothers with views of the act as unseemly and an expectation that nursing women practice 'socially sensitive lactation' especially in public spaces. Sustained breastfeeding rates in the UK are poor and most British women discontinue breastfeeding well before six months. Mothers who elect to feed their infants at the breast for longer than these normative periods appear to experience suspicion and disapproval, especially in a public context and breastfeeding women are only legally protected in feeding their infants in public for up to six months. Although breastfeeding research is flourishing, research on this particular population of mothers remains relatively limited. Therefore, in this study, we explore in-depth experiential accounts of eight women, resident in a town in the East of England, who breastfed their infants beyond six months. Using interpretative phenomenological analysis four themes are presented. Really horrible looks': stigma from families and the community', 'Feeling quite exposed': managing extended breastfeeding etiquette', 'Weird freaky paedophiles': representations of extended breastfeeding women in the media' and 'You really need that': the importance of support for longer-term breastfeeding women'. Applications to extended breastfeeding promotion and advocacy are discussed.
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http://dx.doi.org/10.1016/j.appet.2018.06.018DOI Listing
October 2018

Exploring accounts of collaborative working between speech and language therapists and stroke association communication support coordinators following stroke.

J Interprof Care 2018 Jul 9;32(4):490-500. Epub 2018 Mar 9.

c Psychology Division , De Montfort University , Leicester , UK.

In the United Kingdom, speech and language therapists (SLTs) and Stroke Association communication support coordinators (CSCs) are both employed to provide services for people with communication difficulties following stroke. There is very little literature of this type of collaborative working. This research is unique because it explores collaborative working between SLTs who are employed by the National Health Service and CSCs who are employed by the Stroke Association. Five CSCs and seven SLTs from the East of England participated in a series of in-depth interviews. Data were analysed using thematic analysis informed by an interpretative phenomenological approach. The analysis suggested complex negotiation processes occur at a number of different levels. These levels include negotiation of individual relationships between SLTs and CSCs, negotiating the particular challenges involved in working across organisations and professions, and the need for both roles to negotiate and promote the value of their services at a societal level. The findings of this research are discussed in relation to existing theories and research within the field of collaborative working. Clinical applications are suggested for collaborative working within communication services. We propose that our findings may have relevance to other individuals and organisations delivering services collaboratively.
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http://dx.doi.org/10.1080/13561820.2018.1446921DOI Listing
July 2018

'It's a silver lining': A template analysis of satisfaction and quality of life following post-mastectomy breast reconstruction.

Br J Health Psychol 2018 05 2;23(2):455-475. Epub 2018 Mar 2.

Faculty of Health & Life Sciences, Centre for Technology Enabled Health Research, Coventry University, UK.

Objective: In the United Kingdom, the number of women undergoing post-mastectomy breast reconstruction is increasing. Consequently, exploring patient-reported outcomes in breast surgery has become increasingly important. This study investigated satisfaction and quality of life following post-mastectomy breast reconstruction.

Design: Qualitative research design.

Methods: In-depth, semi-structured telephone interviews were conducted with 25 women (age, M = 53.08, SD = 8.41) following breast reconstruction in the United Kingdom. Data were analysed using template analysis which produced three-first-level, 13 second-level, and 19 third-level themes.

Results: Following reconstruction, women reported improved emotional functioning, although this was often accompanied by deterioration in physical, sexual, and/or social functioning. Women positively appraised their breast appearance, although some reported a decline in satisfaction over time, attributing this decline to their chosen reconstructive technique. Many women accepted the inevitability of scarring and most perceived their scars as a representation of their journey, signifying survival. Generally, women were satisfied with the outcome of their reconstruction, although on reflection some would not have opted for reconstruction. Following breast reconstruction, women were increasingly likely to experience the fear of recurrence, attributed to no longer being able to have a mammogram on the affected breast(s).

Conclusions: This study provides new insights into post-mastectomy breast reconstruction and is a novel application of template analysis. The analysis demonstrates only slight variation in some categories of experience among women, despite a heterogeneous sample. The findings allow researchers and clinicians to focus on specific dimensions of satisfaction and quality of life to support the needs of women following reconstruction. Statement of contribution What is already known on this subject? Patient satisfaction and quality of life are key patient-reported outcomes of breast reconstruction, although relatively few studies distinguish between types of satisfaction. The number of women electing to undergo reconstructive surgery is steadily increasing. As a consequence, exploring patient-reported outcomes in reconstructive breast surgery has become increasingly important for research and clinical practice. It is often suggested that breast reconstruction offers psychosocial benefits, although within the literature some mixed findings have been reported. Therefore, a qualitative exploration has the potential to add some clarity to the experiences of women following post-mastectomy breast reconstruction. What does this study add? To our knowledge, this is the first study to employ template analysis to explore the experiences of women following post-mastectomy breast reconstruction. Template analysis demonstrated that there was only slight variation in some categories of experience among women, despite a heterogeneous sample. This study distinguishes between the patient-reported outcomes breast satisfaction and outcome satisfaction to identify the key factors that are involved in determining satisfaction. The findings allow researchers and clinicians to focus on specific dimensions of satisfaction and quality of life which require improvement to support the unmet needs of women following breast reconstruction. The study presents two novel findings. Women attributed the fear of cancer recurrence to no longer being able to have a mammogram on the affected breast(s). Women also reported a decline in appearance-related satisfaction over time due to either the ptotic nature of autologous-based reconstruction or the fuller projected breast implant-based reconstruction affords.
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http://dx.doi.org/10.1111/bjhp.12299DOI Listing
May 2018

"Stuck in a loop of fear": a phenomenological exploration of carers' experiences supporting a spouse with acquired brain injury.

Disabil Rehabil 2018 12 9;40(24):2907-2915. Epub 2017 Aug 9.

a Division of Psychology , De Montfort University , Leicester , UK.

Purpose: Family caregivers are important to facilitating the rehabilitation of individuals with brain injury. However, research shows spousal carers often reporting poorer health and well-being with psychosocial challenges including increased marital dissatisfaction. This study explores the accounts of participants caring for a spouse with brain injury.

Materials And Methods: This study used semi-structured interviewing and interpretative phenomenological analysis.

Results: One theme, "Living in and beyond the loop of fear", with two subheadings is reported. Participants' attempts to manage their fears prominently defined their early caregiving. Fears were aggravated by the vulnerability of their spouse's health which partially owed to brain injury sometimes having no symptoms prior to its onset. Consequently, participants anxiously strove to prevent further harm to their spouse's health due to what they perceived as the continued "hidden" threat of brain injury. Therefore, participants became hypervigilant, leaving themselves vulnerable to burnout. Over time, some participants modified care practices and managed fears using beliefs accepting their limits to protect their spouses' health.

Conclusions: Findings suggest that beliefs conducive to acceptance helped carers to develop more sustainable, less over-protective, care. Interventions to help carers develop similar beliefs could be provided in therapeutic settings. Recommendations for future research are made. Implications for Rehabilitation Caring for a long-term partner with acquired brain injury has considerable challenges which can threaten an individual's health and well-being. Our research reports on carers' experiences of anxiety which they managed through hypervigilant and overprotective practices which put them at risk of burnout. Consequently, we recommend the promotion of care beliefs that reframe caregiving: recognising the carer's limitations to safeguard a spouse, whilst accepting the vulnerability of the spouse's health. We propose that promoting such principles in therapeutic settings may better equip carers emotionally to provide sustainable care, something which could benefit the carer and spouse's rehabilitation alike.
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http://dx.doi.org/10.1080/09638288.2017.1363299DOI Listing
December 2018

Identity management strategies among HIV-positive Colombian gay men in London.

Cult Health Sex 2017 Dec 2;19(12):1374-1388. Epub 2017 May 2.

a Faculty of Health and Life Sciences , De Montfort University , Leicester , UK.

This study set out to explore the social-psychological aspects of living with HIV among a group of HIV-positive Colombian gay men in London, and the strategies that they deployed to manage ensuing threats to their identities. Focus group and individual interview data were collected from 14 Colombian gay men living with HIV, and were analysed using qualitative thematic analysis and identity process theory. The following themes are discussed: (1) identity struggles and conflicts in Colombia, (2), managing multiple layers of social stigma in England, and (3) changing interpersonal and intergroup dynamics, which highlight the inter-connections between sexual prejudice, sexual risk-taking and HIV stigma. Identity may be chronically threatened due to the multiple layers of stigma, which can limit the coping strategies available to individuals. Findings strongly support the need for action and programmes to highlight and tackle both racism and HIV stigma on the gay scene and to fund more specific resources for sub-communities of gay, bisexual and other men who have sex with men, which employ appropriately trained and culturally competent staff.
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http://dx.doi.org/10.1080/13691058.2017.1314012DOI Listing
December 2017

Equality in sexual health promotion: a systematic review of effective interventions for black and minority ethnic men who have sex with men.

BMC Public Health 2016 08 17;16(1):810. Epub 2016 Aug 17.

School of Applied Social Sciences, Faculty of Health & Life Sciences, De Montfort University, Leicester, LE1 9BH, UK.

Background: Over the past decade, new diagnoses of HIV have increased eightfold among men who have sex with men (MSM) of other or of mixed ethnicity in the UK. Yet there is little intervention research on HIV among black and minority ethnic (BME) MSM. This article aimed to identify effective HIV and sexual health prevention strategies for BME MSM.

Methods: We searched three databases PubMed, Scopus and PsychInfo using a combination of search terms: MSM or men who have sex with men and women (MSMW); Black and Minority Ethnic; HIV or sexual health; and evaluation, intervention, program* or implementation. We identified a total of 19 studies to include in the review including those which used randomised control, pre/post-test and cross-sectional design; in addition, we included intervention development studies.

Results: A total of 12 studies reported statistically significant results in at least one of the behavioural outcomes assessed; one study reported significant increases in HIV knowledge and changes in safer sex practices. In 10 studies, reductions were reported in unprotected anal intercourse (UAI), number of sexual partners, or in both of these measures. Six out of the 13 studies reported reductions in UAI; while seven reported reductions in number of sexual partners. Seven were intervention development studies.

Conclusions: Research into the mechanisms and underpinnings of future sexual health interventions is urgently needed in order to reduce HIV and other sexually transmitted infection (STI) among UK BME MSM. The design of interventions should be informed by the members of these groups for whom they are targeted to ensure the cultural and linguistic sensitivity of the tools and approaches generated.
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http://dx.doi.org/10.1186/s12889-016-3418-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4989329PMC
August 2016

Shh and ZRS enhancer colocalisation is specific to the zone of polarising activity.

Development 2016 08 11;143(16):2994-3001. Epub 2016 Jul 11.

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, Crewe Road, Edinburgh EH4 2XU, UK

Limb-specific Shh expression is regulated by the (∼1 Mb distant) ZRS enhancer. In the mouse, limb bud-restricted spatiotemporal Shh expression occurs from ∼E10 to E11.5 at the distal posterior margin and is essential for correct autopod formation. Here, we have analysed the higher-order chromatin conformation of Shh in expressing and non-expressing tissues, both by fluorescence in situ hybridisation (FISH) and by chromosome conformation capture (5C). Conventional and super-resolution light microscopy identified significantly elevated frequencies of Shh/ZRS colocalisation only in the Shh-expressing regions of the limb bud, in a conformation consistent with enhancer-promoter loop formation. However, in all tissues and at all developmental stages analysed, Shh-ZRS spatial distances were still consistently shorter than those to a neural enhancer located between Shh and ZRS in the genome. 5C identified a topologically associating domain (TAD) over the Shh/ZRS genomic region and enriched interactions between Shh and ZRS throughout E11.5 embryos. Shh/ZRS colocalisation, therefore, correlates with the spatiotemporal domain of limb bud-specific Shh expression, but close Shh and ZRS proximity in the nucleus occurs regardless of whether the gene or enhancer is active. We suggest that this constrained chromatin configuration optimises the opportunity for the active enhancer to locate and instigate the expression of Shh.
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http://dx.doi.org/10.1242/dev.139188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004883PMC
August 2016

Polycomb-mediated chromatin compaction weathers the STORM.

Genome Biol 2016 Feb 25;17:35. Epub 2016 Feb 25.

MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK.

A recent super-resolution imaging study by Boettiger et al. elegantly demonstrates that three epigenetically defined, and functionally disparate, chromatin states have distinct folding characteristics in Drosophila nuclei.
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http://dx.doi.org/10.1186/s13059-016-0899-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768414PMC
February 2016

Caught between compassion and control: exploring the challenges associated with inpatient adolescent mental healthcare in an independent hospital.

J Adv Nurs 2016 May 8;72(5):1042-53. Epub 2016 Jan 8.

School of Applied Social Sciences, De Montfort University, Leicester, UK.

Aim: To extend our understanding of how healthcare assistants construct and manage demanding situations in a secure mental health setting and to explore the effects on their health and well-being, to provide recommendations for enhanced support.

Background: Contemporary literature acknowledges high rates of occupational stress and burnout among healthcare assistants, suggesting the context in which they work places them at elevated risk of physical harm and psychological distress. Yet, there is a deficit of qualitative research exploring the experiences of healthcare assistants in adolescent inpatient facilities.

Design: An exploratory multi-method qualitative approach was used to collect data about the challenges faced by healthcare assistants working on secure adolescent mental health wards in an independent hospital during 2014.

Method: Fifteen sets of data were collected. Ten participants completed diary entries and five participants were also interviewed allowing for triangulation. Data were analysed using Interpretive Phenomenological Analysis.

Findings: The findings illustrated how inpatient mental healthcare is a unique and distinctive area of nursing, where disturbing behaviour is often normalized and detached from the outside world. Healthcare assistants often experienced tension between their personal moral code which orientate them towards empathy and support and the emotional detachment and control expected by the organization, contributing to burnout and moral distress.

Conclusions: This study yielded insights into mental health nursing and specifically the phenomenon of moral distress. Given the ever-increasing demand for healthcare professionals, the effects of moral distress on both the lives of healthcare assistants and patient care, merits further study.
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http://dx.doi.org/10.1111/jan.12889DOI Listing
May 2016

'Marginalised malignancies': A qualitative synthesis of men's accounts of living with breast cancer.

Soc Sci Med 2016 Jan 26;149:17-25. Epub 2015 Nov 26.

Division of Psychology, Faculty of Health and Life Sciences, De Montfort University, Leicester, UK. Electronic address:

Rationale: Breast cancer in men is a rare, under-researched illness frequently overlooked within both clinical and third-sector healthcare systems. Increased prevalence and high profile awareness-raising, advocacy and activism around breast cancer in women has led to pervasive feminisation of the disease, prompting a misperception of breast cancer as a women-only illness. This deters men from seeking medical attention, professional and social support, and increases sensitivity to body image concerns.

Methods: Drawing on the principles of critical health psychology, we offer an interpretive and evaluative qualitative synthesis of existing academic literature in the field, and reveal how the marginalisation of men with breast cancer poses a host of psychosocial and psychosexual difficulties for patient-survivors beyond the primary cancer challenge at all stages of the illness trajectory.

Results: We discuss how identities, masculinities, coping responses and resources, and relationships are often affected, and demonstrate how current approaches to breast cancer serve to isolate men who develop the illness, potentially alienating and emasculating them.

Conclusion: Our analysis integrates and enhances the findings of the original papers through more theorised considerations of stigma, masculinity and marginalisation. Further, we briefly consider some of the ways men's experiences diverge and converge with women's accounts, and discuss the importance of re-appraising 'pink ribbon culture' for both men and women. We conclude with some recommendations for advocacy and intervention in professional and lay contexts.
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http://dx.doi.org/10.1016/j.socscimed.2015.11.032DOI Listing
January 2016

An Overview of Genome Organization and How We Got There: from FISH to Hi-C.

Microbiol Mol Biol Rev 2015 Sep;79(3):347-72

Department of Biochemistry, and Goodman Cancer Research Center, McGill University, Montréal, Québec, Canada

In humans, nearly two meters of genomic material must be folded to fit inside each micrometer-scale cell nucleus while remaining accessible for gene transcription, DNA replication, and DNA repair. This fact highlights the need for mechanisms governing genome organization during any activity and to maintain the physical organization of chromosomes at all times. Insight into the functions and three-dimensional structures of genomes comes mostly from the application of visual techniques such as fluorescence in situ hybridization (FISH) and molecular approaches including chromosome conformation capture (3C) technologies. Recent developments in both types of approaches now offer the possibility of exploring the folded state of an entire genome and maybe even the identification of how complex molecular machines govern its shape. In this review, we present key methodologies used to study genome organization and discuss what they reveal about chromosome conformation as it relates to transcription regulation across genomic scales in mammals.
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http://dx.doi.org/10.1128/MMBR.00006-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517094PMC
September 2015

Spatial genome organization: contrasting views from chromosome conformation capture and fluorescence in situ hybridization.

Genes Dev 2014 Dec;28(24):2778-91

MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom;

Although important for gene regulation, most studies of genome organization use either fluorescence in situ hybridization (FISH) or chromosome conformation capture (3C) methods. FISH directly visualizes the spatial relationship of sequences but is usually applied to a few loci at a time. The frequency at which sequences are ligated together by formaldehyde cross-linking can be measured genome-wide by 3C methods, with higher frequencies thought to reflect shorter distances. FISH and 3C should therefore give the same views of genome organization, but this has not been tested extensively. We investigated the murine HoxD locus with 3C carbon copy (5C) and FISH in different developmental and activity states and in the presence or absence of epigenetic regulators. We identified situations in which the two data sets are concordant but found other conditions under which chromatin topographies extrapolated from 5C or FISH data are not compatible. We suggest that products captured by 3C do not always reflect spatial proximity, with ligation occurring between sequences located hundreds of nanometers apart, influenced by nuclear environment and chromatin composition. We conclude that results obtained at high resolution with either 3C methods or FISH alone must be interpreted with caution and that views about genome organization should be validated by independent methods.
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http://dx.doi.org/10.1101/gad.251694.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4265680PMC
December 2014

Development of five digits is controlled by a bipartite long-range cis-regulator.

Development 2014 Apr;141(8):1715-25

MRC-Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, UK.

Conservation within intergenic DNA often highlights regulatory elements that control gene expression from a long range. How conservation within a single element relates to regulatory information and how internal composition relates to function is unknown. Here, we examine the structural features of the highly conserved ZRS (also called MFCS1) cis-regulator responsible for the spatiotemporal control of Shh in the limb bud. By systematically dissecting the ZRS, both in transgenic assays and within in the endogenous locus, we show that the ZRS is, in effect, composed of two distinct domains of activity: one domain directs spatiotemporal activity but functions predominantly from a short range, whereas a second domain is required to promote long-range activity. We show further that these two domains encode activities that are highly integrated and that the second domain is crucial in promoting the chromosomal conformational changes correlated with gene activity. During limb bud development, these activities encoded by the ZRS are interpreted differently by the fore limbs and the hind limbs; in the absence of the second domain there is no Shh activity in the fore limb, and in the hind limb low levels of Shh lead to a variant digit pattern ranging from two to four digits. Hence, in the embryo, the second domain stabilises the developmental programme providing a buffer for SHH morphogen activity and this ensures that five digits form in both sets of limbs.
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http://dx.doi.org/10.1242/dev.095430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978833PMC
April 2014

Making use of expertise: a qualitative analysis of the experience of breastfeeding support for first-time mothers.

Matern Child Nutr 2015 Oct 5;11(4):687-702. Epub 2013 Apr 5.

Psychology Department, De Montfort University, Leicester, UK.

There is now a body of research evaluating breastfeeding interventions and exploring mothers' and health professionals' views on effective and ineffective breastfeeding support. However, this literature leaves relatively unexplored a number of questions about how breastfeeding women experience and make sense of their relationships with those trained to provide breastfeeding support. The present study collected qualitative data from 22 breastfeeding first-time mothers in the United Kingdom on their experiences of, and orientation towards, relationships with maternity care professionals and other breastfeeding advisors. The data were obtained from interviews and audio-diaries at two time points during the first 5 weeks post-partum. We discuss a key theme within the data of 'Making use of expertise' and three subthemes that capture the way in which the women's orientation towards those assumed to have breastfeeding expertise varied according to whether the women (1) adopted a position of consulting experts vs. one of deferring to feeding authorities; (2) experienced difficulty interpreting their own and their baby's bodies; and (3) experienced the expertise of health workers as empowering or disempowering. Although sometimes mothers felt empowered by aligning themselves with the scientific approach and 'normalising gaze' of health care professionals, at other times this gaze could be experienced as objectifying and diminishing. The merits and limitations of a person-centred approach to breastfeeding support are discussed in relation to using breastfeeding expertise in an empowering rather than disempowering way.
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http://dx.doi.org/10.1111/mcn.12033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860267PMC
October 2015

Socially sensitive lactation: exploring the social context of breastfeeding.

Psychol Health 2013 6;28(4):450-68. Epub 2012 Nov 6.

Division of Psychology and Counselling, University of Huddersfield, Huddersfield, UK.

Many women report difficulties with breastfeeding and do not maintain the practice for as long as intended. Although psychologists and other researchers have explored some of the difficulties they experience, fuller exploration of the relational contexts in which breastfeeding takes place is warranted to enable more in-depth analysis of the challenges these pose for breastfeeding women. This article is based on qualitative data collected from 22 first-time breastfeeding mothers through two phases of interviews and audio-diaries which explored how the participants experienced their relationships with significant others and the wider social context of breastfeeding in the first five weeks postpartum. Using a thematic analysis informed by symbolic interactionism, we develop the overarching theme of 'Practising socially sensitive lactation' which captures how participants felt the need to manage tensions between breastfeeding and their perceptions of the needs, expectations and comfort of others. We argue that breastfeeding remains a problematic social act, despite its agreed importance for child health. While acknowledging the limitations of our sample and analytic approach, we suggest ways in which perinatal and public health interventions can take more effective account of the social challenges of breastfeeding in order to facilitate the health and psychological well-being of mothers and their infants.
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http://dx.doi.org/10.1080/08870446.2012.737465DOI Listing
June 2013

Anterior-posterior differences in HoxD chromatin topology in limb development.

Development 2012 Sep;139(17):3157-67

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh EH4 2XU, UK.

A late phase of HoxD activation is crucial for the patterning and growth of distal structures across the anterior-posterior (A-P) limb axis of mammals. Polycomb complexes and chromatin compaction have been shown to regulate Hox loci along the main body axis in embryonic development, but the extent to which they have a role in limb-specific HoxD expression, an evolutionary adaptation defined by the activity of distal enhancer elements that drive expression of 5' Hoxd genes, has yet to be fully elucidated. We reveal two levels of chromatin topology that differentiate distal limb A-P HoxD activity. Using both immortalised cell lines derived from posterior and anterior regions of distal E10.5 mouse limb buds, and analysis in E10.5 dissected limb buds themselves, we show that there is a loss of polycomb-catalysed H3K27me3 histone modification and a chromatin decompaction over HoxD in the distal posterior limb compared with anterior. Moreover, we show that the global control region (GCR) long-range enhancer spatially colocalises with the 5' HoxD genomic region specifically in the distal posterior limb. This is consistent with the formation of a chromatin loop between 5' HoxD and the GCR regulatory module at the time and place of distal limb bud development when the GCR participates in initiating Hoxd gene quantitative collinearity and Hoxd13 expression. This is the first example of A-P differences in chromatin compaction and chromatin looping in the development of the mammalian secondary body axis (limb).
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http://dx.doi.org/10.1242/dev.081174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3413162PMC
September 2012

Maintaining the 'good maternal body': expressing milk as a way of negotiating the demands and dilemmas of early infant feeding.

J Adv Nurs 2013 Mar 20;69(3):590-9. Epub 2012 May 20.

Division of Psychology, University of Bradford, UK.

Aim: To report a descriptive study of early infant feeding experiences focusing on ACCOUNTS OF WOMEN WHO EXPRESSED MILK EXTENSIVELY IN THE FIRST FEW WEEKS POSTPARTUM.

Background: Relatively little is known about the reasons for expressing milk following healthy term births. Evidence indicates it is an increasingly common practice during early infant feeding in Westernized countries. A more comprehensive understanding of this practice will help midwives and nurses assist mothers negotiate early feeding challenges.

Design: Qualitative data were collected in two phases in the first few weeks postpartum.

Method: Audio-diary and semi-structured interview data from seven British women who extensively expressed milk in the first month postpartum were analysed. These data were drawn from a larger qualitative longitudinal study which took place in 2006-2007. Themes, discursive constructions and discourses are identified through the use of a feminist informed analysis.

Findings: The practice of expressing was employed as a solution to managing the competing demands and dilemmas of early breastfeeding and ensuring the continued provision of breast milk, thereby deflecting potential accusations of poor mothering. In addition, the practice may afford a degree of freedom to new mothers.

Conclusions: The need to maintain the 'good maternal body' can account for the motivation to express milk, although there may be reasons to be cautious about promoting expression as a solution to breastfeeding difficulties. Education for health professionals, which emphasizes the complexities and contradictions of mothering and which challenges prescriptive notions of 'good mothering' could better support new mothers in their feeding 'choices'.
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http://dx.doi.org/10.1111/j.1365-2648.2012.06035.xDOI Listing
March 2013

Opposing functions of the ETS factor family define Shh spatial expression in limb buds and underlie polydactyly.

Dev Cell 2012 Feb;22(2):459-67

MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.

Sonic hedgehog (Shh) expression during limb development is crucial for specifying the identity and number of digits. The spatial pattern of Shh expression is restricted to a region called the zone of polarizing activity (ZPA), and this expression is controlled from a long distance by the cis-regulator ZRS. Here, members of two groups of ETS transcription factors are shown to act directly at the ZRS mediating a differential effect on Shh, defining its spatial expression pattern. Occupancy at multiple GABPα/ETS1 sites regulates the position of the ZPA boundary, whereas ETV4/ETV5 binding restricts expression outside the ZPA. The ETS gene family is therefore attributed with specifying the boundaries of the classical ZPA. Two point mutations within the ZRS change the profile of ETS binding and activate Shh expression at an ectopic site in the limb bud. These molecular changes define a pathogenetic mechanism that leads to preaxial polydactyly (PPD).
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http://dx.doi.org/10.1016/j.devcel.2011.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3314984PMC
February 2012
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