Implementation and perceived impact of the SWAN model of end-of-life and bereavement care: a realist evaluation

Objectives To evaluate the End-of-Life and Bereavement Care model (SWAN) from conception to current use. Design A realist evaluation was conducted to understand what works for whom and in what circumstances. The programme theory, derived from a scoping review, comprised: person and family centred care, institutional approaches and infrastructure. Data were collected across three stages (May 2021 to December 2021): semi-structured, online interviews and analysis of routinely collected local and national data. Setting Stage 1: Greater Manchester area of England where the SWAN model was developed and implemented. Stage 2: Midlands. Stage 3: National data. Participants Twenty-three participants were interviewed: Trust SWAN leads, end-of-life care nurses, board members, bereavement services, faith leadership, quality improvement, medicine, nursing, patient transport, mortuary, police and coroners. Results Results from all three stages were integrated within themes, linked to the mechanisms, context and outcomes for the SWAN model. The mechanisms are: SWAN is a values-based model, promoting person/family-centred care and emphasising personhood after death. Key features are: memory-making, normalisation of death and ‘one chance’ to get things right. SWAN is an enablement and empowerment model for all involved. The branding is recognisable and raises the profile of end-of-life and bereavement care. The contextual factors for successful implementation and sustainability include leadership, organisational support, teamwork and integrated working, education and engagement and investment in resources and facilities. The outcomes are perceived to be: a consistent approach to end-of-life and bereavement care; a person/family-centred approach to care; empowered and creative staff; an organisational culture that prioritises end-of-life and bereavement care. Conclusion The SWAN model is agile and has transferred to different settings and circumstances. This realist evaluation revealed the mechanisms of the SWAN model, the contextual factors supporting implementation and perceived outcomes for patients, families, staff and the organisation

Off-axis reflective optical apparatus

Embodiments of the present invention are directed to a simple apparatus and a convenient and accurate method of mounting the components to form an off-axis reflective optical apparatus such as a collimator. In one embodiment, an off-axis reflective optical apparatus comprises a mounting block having a ferrule holder support surface and an off-axis reflector support surface which is generally perpendicular to the ferrule holder support surface. An optical reflector is mounted on the off-axis reflector support surface and has a reflected beam centerline. The optical reflector has a conic reflective surface and a conic center. A ferrule holder is mounted on the ferrule holder support surface. The ferrule holder provides a ferrule for coupling to an optical fiber and orienting a fiber tip of the optical fiber along a fiber axis toward the optical reflector. The fiber axis is nonparallel to the reflected beam centerline. Prior to mounting the optical reflector to the off-axis reflector support surface and prior to mounting the ferrule holder to the ferrule holder support surface, the optical reflector is movable on the off-axis reflector surface and the ferrule holder is movable on the ferrule holder support surface to align the conic center of the optical reflector with respect to the fiber tip of the optical fiber, and the apparatus has at least one of the following features: (1) the optical reflector is movable on the off-axis reflector support surface to adjust a focus of the fiber tip with respect to the optical reflector, and (2) the ferrule holder is movable on the ferrule holder support surface to adjust the focus of the fiber tip with respect to the optical reflector

The importance of high-throughput cell separation technologies for genomics/proteomics-based clinical diagnostics

Gene expression microarray analyses of mixtures of cells approximate a weighted average of the gene expression profiles (GEPs) of each cell type according to its relative abundance in the overall cell sample being analyzed. If the targeted subpopulation of cells is in the minority, or the expected perturbations are marginal, then such changes will be masked by the GEP of the normal/unaffected cells. We show that the GEP of a minor cell subpopulation is often lost when that cell subpopulation is of a frequency less than 30 percent. The GEP is almost always masked by the other cell subpopulations when that frequency drops to 10 percent or less. On the basis of these results one should always assume that the GEP of a given cell subpopulation is probably seriously affected by, the presence of significant numbers of other "contaminating" cell types. Several methodologies can be employed to enrich the target cells submitted for microarray analyses. These include magnetic sorting and laser capture microdissection. If a cell subpopulation of interest is small, very high-throughput cell separation technologies are needed to separate enough cells for conventional microarrays. However, high-throughput flow cytometry/cell sorting overcomes many restrictions of experimental enrichment conditions. This technology can also be used to sort smaller numbers of cells of specific cell subpopulations and subsequently amplify their mRNAs before microarray analyses. When purification techniques are applied to unfixed samples, the potential for changes in gene levels during the process of collection is an additional concern. Since RNA rapidly degrades, and specific mRNAs turn over in minutes or hours, the cell separation process must be very rapid. Hence, high-throughput cell separation (HTS) technologies are needed that can process the necessary number of cells expeditiously in order to avoid such uncontrolled changes in the target cells GEP. In cases where even the use of HTS yields only a small number of cells, the mRNAs (after reverse transcription to cDNA's) must be amplified to yield enough material for conventional microarray analyses. However, the problem of using "microamplification" PCR methods to expand the amount of cDNAs (from mRNAs) is that it is very difficult to amplify equally all of the mRNAs. Unequal amplification leads to a distorted gene expression profile on the microarray. Linear amplifications is difficult to achieve. Unfortunately, present-day gene-chips need to be about 100 times more sensitive than they are now to be able to do many biologically and biomedically meaningful experiments and clinical tests

Biosensor-controlled gene therapy/drug delivery with nanoparticles for nanomedicine

Nanomedicine involves cell-by-cell regenerative medicine, either repairing cells one at a time or triggering apoptotic pathways in cells that are not repairable. Multilayered nanoparticle systems are being constructed for the targeted delivery of gene therapy to single cells. Cleavable shells containing targeting, biosensing, and gene therapeutic molecules are being constructed to direct nanoparticles to desired intracellular targets. Therapeutic gene sequences are controlled by biosensor-activated control switches to provide the proper amount of gene therapy on a single cell basis. The central idea is to set up gene therapy "nanofactories" inside single living cells. Molecular biosensors linked to these genes control their expression. Gene delivery is started in response to a biosensor detected problem; gene delivery is halted when the cell response indicates that more gene therapy is not needed

Multifunctional nanoparticles for drug/gene delivery in nanomedicine

Multifunctional nanoparticles hold great promise for drug/gene delivery. Multilayered nanoparticles can act as nanomedical systems with on-board "molecular programming" to accomplish complex multi-step tasks. For example, the targeting process has only begun when the nanosystem has found the correct diseased cell of interest. Then it must pass the cell membrane and avoid enzymatic destruction within the endosomes of the cell. Since the nanosystem is only about one millionth the volume of a human cell, for it to have therapeutic efficacy with its contained package, it must deliver that drug or gene to the appropriate site within the living cell. The successive delayering of these nanosystems in a controlled fashion allows the system to accomplish operations that would be difficult or impossible to do with even complex single molecules. In addition, portions of the nanosystem may be protected from premature degradation or mistargeting to non-diseased cells. All of these problems remain major obstacles to successful drug delivery with a minimum of deleterious side effects to the patient. This paper describes some of the many components involved in the design of a general platform technology for nanomedical systems. The feasibility of most of these components has been demonstrated by our group and others. But the integration of these interacting sub-components remains a challenge. We highlight four components of this process as examples. Each subcomponent has its own sublevels of complexity. But good nanomedical systems have to be designed/engineered as a full nanomedical system, recognizing the need for the other components

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies.

Three mitochondria-encoded subunits form the catalytic core of cytochrome c oxidase, the terminal enzyme of the respiratory chain. COX1 and COX2 contain heme and copper redox centers, which are integrated during assembly of the enzyme. Defects in this process lead to an enzyme deficiency and manifest as mitochondrial disorders in humans. Here we demonstrate that COA6 is specifically required for COX2 biogenesis. Absence of COA6 leads to fast turnover of newly synthesized COX2 and a concomitant reduction in cytochrome c oxidase levels. COA6 interacts transiently with the copper-containing catalytic domain of newly synthesized COX2. Interestingly, similar to the copper metallochaperone SCO2, loss of COA6 causes cardiomyopathy in humans. We show that COA6 and SCO2 interact and that corresponding pathogenic mutations in each protein affect complex formation. Our analyses define COA6 as a constituent of the mitochondrial copper relay system, linking defects in COX2 metallation to cardiac cytochrome c oxidase deficiency

The Experiences of Specialist Nurses Working Within the Uro-oncology Multidisciplinary Team in the United Kingdom.

PURPOSE: United Kingdom prostate cancer nursing care is provided by a variety of urology and uro-oncology nurses. The experience of working in multidisciplinary teams (MDT) was investigated in a national study. DESIGN: The study consisted of a national survey with descriptive statistics and thematic analysis. METHODS: A secondary analysis of a data subset from a UK whole population survey was undertaken (n = 285) of the specialist nursing workforce and the services they provide. Data were collected on the experience of working in the MDT. RESULTS: Forty-five percent of the respondents felt that they worked in a functional MDT, 12% felt that they worked in a dysfunctional MDT, and 3.5% found the MDT meeting intimidating. Furthermore, 34% of the nurses felt that they could constructively challenge all members of the MDT in meetings. Themes emerging from open-ended questions were lack of interest in nonmedical concerns by other team members, ability to constructively challenge decisions or views within the meeting, and little opportunity for patients' wishes to be expressed. CONCLUSIONS: Despite expertise and experience, nurses had a variable, often negative, experience of the MDT. It is necessary to ensure that all participants can contribute and are heard and valued. More emphasis should be given to patients' nonmedical needs