The experience of mindfulness in Western therapeutic encounters; practitioner's perspective

Background: Mindfulness has become increasingly popular in recent psychotherapeutic literature that strongly indicates its use for the treatment of a variety of psychiatric disorders. It has been incorporated into cognitive behaviour based models such as Mindfulness-Based Cognitive Behavioural Therapy (MBCBT), and Dialectical Behavioural Therapy (DBT), as well as specific model of treatment for chronic pain, Mindfulness Based Stress Reduction (MBSR). These models in particular have attracted a significant amount of outcome research that consistently suggests that they are of benefit to specific clinical populations. MBCBT and DBT are recognised as evidence based treatments of choice by organisations such as the National Institute for Clinical Excellence (NICE) in the United Kingdom. Clinically, it is something that I have some limited awareness (during DBT training, and through awareness clinical literature), and have been interested in finding out more about it. Despite these findings however, there is no established definition of mindfulness, no consensus of what it does, and no shared understanding in literature of what it means to be Mindful. Furthermore, Mindfulness originated in Buddhism around 2,500 years ago and is therefore closely related to this discipline and Eastern culture in general. These are issues that have also received little attention in the research. Mindfulness therefore finds itself in a relatively unusual position in terms of therapeutic research, generally being accepted as a beneficial and helpful practice, but with no clear understanding of what it really is, or how it works. This research attempts to explore these questions further by presenting the perspectives of psychological practitioners who routinely use Mindfulness in their therapeutic practice. Working back perhaps from the outcome literature, this research attempts to capture the participant's experience of Mindfulness therapeutically, what they feel it is, how they experience it in their clinical work with clients, and what it means to them personally, professionally and culturally. Method/ Analysis: Given that the research is based on capturing individual, phenomenological processes, qualitative methods were seen as the most appropriate methodology. As the research involves exploring the each participant's perspective with the aim of providing general themes between accounts, Interpretative Phenomenological Analysis (IPA) was chosen. IPA also recognises the role of the researcher and their potential biases, e.g. a therapist with some basic awareness of Mindfulness, as a feature within the research methodology. Recruitment letters were sent to Community Mental Teams (CMHTs), Psychology, Psychotherapy and Psychiatry Departments, and local University throughout a specific region in the United Kingdom (Devon). Participants were required to be currently working as therapists who described themselves as using Mindfulness within their clinical practice. Five from an initial response of nine participants were interviewed. Reasons for attrition included, moving job, moving area, and pregnancy resulting in change of life circumstances. The participants were three women and two men aged between their late thirties to late fifties. Professional backgrounds included Social Work Occupational Therapy, and Core Process psychotherapy, and all worked within NHS settings, and some private work. Interviews were transcribed and subject to a thematic analysis using IPA that produced three master themes. Cohen's Kappa was used to test for inter-rater reliability. Results/ Conclusion: Three master themes were identified; the Culture and Context of Mindfulness, The Subjective Experience of Mindfulness and Being a Mindfulness Practitioner. These were explored in terms a concept called 'Being-With'. 'Being-With' explored the results in terms of literature concerning core therapeutic conditions, therapeutic process, and the presence of the therapist. It was concluded that this term described the interpersonal and process based nature of Mindfulness, as well as capturing the participant's perspective that Mindfulness was not a technique but a therapeutic attitude or way of being based on ongoing personal and experiential practice. The findings are critiqued and suggestions for further research discussed

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a genetically complex autoimmune disease characterized by loss of immune tolerance to nuclear and cell surface antigens. Previous genome-wide association studies (GWAS) had modest sample sizes, reducing their scope and reliability. Our study comprised 7,219 cases and 15,991 controls of European ancestry, constituting a new GWAS, a meta-analysis with a published GWAS and a replication study. We have mapped 43 susceptibility loci, including ten new associations. Assisted by dense genome coverage, imputation provided evidence for missense variants underpinning associations in eight genes. Other likely causal genes were established by examining associated alleles for cis-acting eQTL effects in a range of ex vivo immune cells. We found an over-representation (n = 16) of transcription factors among SLE susceptibility genes. This finding supports the view that aberrantly regulated gene expression networks in multiple cell types in both the innate and adaptive immune response contribute to the risk of developing SLE

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Distinct Kinetics of Memory B-Cell and Plasma-Cell Responses in Peripheral Blood Following a Blood-Stage Plasmodium chabaudi Infection in Mice

B cell and plasma cell responses take place in lymphoid organs, but because of the inaccessibility of these organs, analyses of human responses are largely performed using peripheral blood mononuclear cells (PBMC). To determine whether PBMC are a useful source of memory B cells and plasma cells in malaria, and whether they reflect Plasmodium-specific B cell responses in spleen or bone marrow, we have investigated these components of the humoral response in PBMC using a model of Plasmodium chabaudi blood-stage infections in C57BL/6 mice. We detected memory B cells, defined as isotype-switched IgD− IgM− CD19+ B cells, and low numbers of Plasmodium chabaudi Merozoite Surface Protein-1 (MSP1)-specific memory B cells, in PBMC at all time points sampled for up to 90 days following primary or secondary infection. By contrast, we only detected CD138+ plasma cells and MSP1-specific antibody-secreting cells within a narrow time frame following primary (days 10 to 25) or secondary (day 10) infection. CD138+ plasma cells in PBMC at these times expressed CD19, B220 and MHC class II, suggesting that they were not dislodged bone-marrow long-lived plasma cells, but newly differentiated migratory plasmablasts migrating to the bone marrow; thus reflective of an ongoing or developing immune response. Our data indicates that PBMC can be a useful source for malaria-specific memory B cells and plasma cells, but extrapolation of the results to human malaria infections suggests that timing of sampling, particularly for plasma cells, may be critical. Studies should therefore include multiple sampling points, and at times of infection/immunisation when the B-cell phenotypes of interest are likely to be found in peripheral blood

Microarray-Based Analysis of Differential Gene Expression between Infective and Noninfective Larvae of Strongyloides stercoralis

Strongyloides stercoralis is a soil-transmitted helminth that affects an estimated 30–100 million people worldwide. Chronically infected persons who are exposed to corticosteroids can develop disseminated disease, which carries a high mortality (87–100%) if untreated. Despite this, little is known about the fundamental biology of this parasite, including the features that enable infection. We developed the first DNA microarray for this parasite and used it to compare infective third-stage larvae (L3i) with non-infective first stage larvae (L1). Using this method, we identified 935 differentially expressed genes. Functional characterization of these genes revealed L3i biased expression of heat shock proteins and genes with products that have previously been shown to be immunoreactive in infected humans. Genes putatively involved in transcription were found to have L1 biased expression. Potential chemotherapeutic and vaccine targets such as far-1, ucr 2.1 and hsp-90 were identified for further study

Genome-wide analysis identifies a role for common copy number variants in specific language impairment

An exploratory genome-wide copy number variant (CNV) study was performed in 127 independent cases with specific language impairment (SLI), their first-degree relatives (385 individuals) and 269 population controls. Language-impaired cases showed an increased CNV burden in terms of the average number of events (11.28 vs 10.01, empirical P=0.003), the total length of CNVs (717 vs 513 Kb, empirical P=0.0001), the average CNV size (63.75 vs 51.6 Kb, empirical P=0.0005) and the number of genes spanned (14.29 vs 10.34, empirical P=0.0007) when compared with population controls, suggesting that CNVs may contribute to SLI risk. A similar trend was observed in first-degree relatives regardless of affection status. The increased burden found in our study was not driven by large or de novo events, which have been described as causative in other neurodevelopmental disorders. Nevertheless, de novo CNVs might be important on a case-by-case basis, as indicated by identification of events affecting relevant genes, such as ACTR2 and CSNK1A1, and small events within known micro-deletion/-duplication syndrome regions, such as chr8p23.1. Pathway analysis of the genes present within the CNVs of the independent cases identified significant overrepresentation of acetylcholine binding, cyclic-nucleotide phosphodiesterase activity and MHC proteins as compared with controls. Taken together, our data suggest that the majority of the risk conferred by CNVs in SLI is via common, inherited events within a ‘common disorder–common variant’ model. Therefore the risk conferred by CNVs will depend upon the combination of events inherited (both CNVs and SNPs), the genetic background of the individual and the environmental factors