Supporting home care for the dying: an evaluation of healthcare professionals' perspectives of an individually tailored hospice at home service

AIMS AND OBJECTIVES: To explore health care professionals' perspective of hospice at home service that has different components, individually tailored to meet the needs of patients. BACKGROUND: Over 50% of adults diagnosed with a terminal illness and the majority of people who have cancer, prefer to be cared for and to die in their own home. Despite this, most deaths occur in hospital. Increasing the options available for patients, including their place of care and death is central to current UK policy initiatives. Hospice at home services aim to support patients to remain at home, yet there are wide variations in the design of services and delivery. A hospice at home service was developed to provide various components (accompanied transfer home, crisis intervention and hospice aides) that could be tailored to meet the individual needs of patients. DESIGN: An evaluation study. METHODS: Data were collected from 75 health care professionals. District nurses participated in one focus group (13) and 31 completed an electronic survey. Palliative care specialist nurses participated in a focus group (9). One hospital discharge co-ordinator and two general practitioners participated in semi-structured interviews and a further 19 general practitioners completed the electronic survey. RESULTS: Health care professionals reported the impact and value of each of the components of the service, as helping to support patients to remain at home, by individually tailoring care. They also positively reported that support for family carers appeared to enable them to continue coping, rapid access to the service was suggested to contribute to faster hospital discharges and the crisis intervention service was identified as helping patients remain in their own home, where they wanted to be. CONCLUSIONS: Health care professionals perceived that the additional individualised support provided by this service contributed to enabling patients to continue be cared for and to die at home in their place of choice. RELEVANCE TO CLINICAL PRACTICE: This service offers various components of a hospice at home service, enabling a tailor made package to meet individual and local area needs. Developing an individually tailored package of care appears to be able to meet specific needs

The interaction of wood nanocellulose dressings and the wound pathogen P. aeruginosa

Chronic wounds pose an increasingly significant worldwide economic burden (over £1 billion per annum in the UK alone). With the escalation in global obesity and diabetes, chronic wounds will increasingly be a significant cause of morbidity and mortality. Cellulose nanofibrils (CNF) are highly versatile and can be tailored with specific physical properties to produce an assortment of three-dimensional structures (hydrogels, aerogels or films), for subsequent utilization as wound dressing materials. Growth curves using CNF (diameter 0.05) over 24 h. These data demonstrate the potential of nanocellulose materials in the development of novel dressings that may afford significant clinical potential

Quantification of Extracellular DNA Network Abundance and Architecture within Streptococcus gordonii Biofilms Reveals Modulatory Factors

Extracellular DNA (eDNA) is an important component of biofilm matrix that serves to maintain biofilm structural integrity, promotes genetic exchange within the biofilm, and provides protection against antimicrobial compounds. Advances in microscopy techniques have provided evidence of the cobweb- or lattice-like structures of eDNA within biofilms from a range of environmental niches. However, methods to reliably assess the abundance and architecture of eDNA remain lacking. This study aimed to address this gap by development of a novel, high-throughput image acquisition and analysis platform for assessment of eDNA networks in situ within biofilms. Utilizing Streptococcus gordonii as the model, the capacity for this imaging system to reliably detect eDNA networks and monitor changes in abundance and architecture (e.g., strand length and branch number) was verified. Evidence was provided of a synergy between glucans and eDNA matrices, while it was revealed that surface-bound nuclease SsnA could modify these eDNA structures under conditions permissive for enzymatic activity. Moreover, cross talk between the competence and hexaheptapeptide permease systems was shown to regulate eDNA release by S. gordonii. This novel imaging system can be applied across the wider field of biofilm research, with potential to significantly advance interrogation of the mechanisms by which the eDNA network architecture develops, how it can influence biofilm properties, and how it may be targeted for therapeutic benefit. IMPORTANCE Extracellular DNA (eDNA) is critical for maintaining the structural integrity of many microbial biofilms, making it an attractive target for the management of biofilms. However, our knowledge and targeting of eDNA are currently hindered by a lack of tools for the quantitative assessment of eDNA networks within biofilms. Here, we demonstrate use of a novel image acquisition and analysis platform with the capacity to reliably monitor the abundance and architecture of eDNA networks. Application of this tool to Streptococcus gordonii biofilms has provided new insights into how eDNA networks are stabilized within the biofilm and the pathways that can regulate eDNA release. This highlights how exploitation of this novel imaging system across the wider field of biofilm research has potential to significantly advance interrogation of the mechanisms by which the eDNA network architecture develops, how it can influence biofilm properties, and how it may be targeted for therapeutic benefit

Evaluating the role of admixture in cancer therapy via in vitro drug response and multivariate genome-wide associations

We investigate the role of ethnicity and admixture in drug response across a broad group of chemotherapeutic drugs. Also, we generate hypotheses on the genetic variants driving differential drug response through multivariate genome-wide association studies

Supporting physiotherapy learners in practice settings: a mixed methods evaluation of experiences of physiotherapy educators

Background Practice-based education is an essential component of pre-registration physiotherapy programs, and there is a need for a contemporary review of practice-based educational experiences. Purpose The aim of this study was to explore physiotherapy practice educators’ experiences of supporting learners to inform considerations for future workforce development. Methods This was a mixed methods sequential explanatory study based in the United Kingdom (UK). Phase one of the study utilized an online survey disseminated via the Chartered Society of Physiotherapy (CSP) professional networks. Phase two consisted of three semi-structured focus group interviews with participants who expressed an interest via completion of the online survey. All were registered or associate CSP members who actively support practice-based education. Results A total of 208 participants completed the online survey and a sub-set of 15 participated in online focus groups. Quantitative survey data were analyzed using descriptive statistics. Initial thematic analysis of qualitative data from both phases was undertaken by one researcher. Subsequent analyses were carried out independently by the remaining research team, and comparisons were made to agree on codes, categories, and themes. The practice educator is vital in developing the future workforce (30%, n = 61, strongly agree). Identified challenges included supervising more than one learner (34%, n = 67 not at all experienced) and using technology to provide alternative placement models (45%, n = 87 not at all experienced). Conclusion Practice educators need accessible opportunities for professional development. Practice-based education should be embedded as an integral component of all staff roles. A team approach is essential to developing the future physiotherapy workforce

Intercultural ethics: questions of methods in language and intercultural communication

This paper explores how questions of ethics and questions of method are intertwined and unavoidable in any serious study of language and intercultural communication. It argues that the focus on difference and solution orientations to intercultural conflict has been a fundamental driver for theory, data collection and methods in the field. These approaches, the paper argues, have created a considerable consciousness raising industry, with methods, trainings and ‘critical incidents’, which ultimately focus intellectual energy in areas which may be productive in terms of courses and publications but which have a problematic basis in their ethical terrain. Dieser Artikel untersucht wie ethische und methodische Fragen nicht nur ineinander greifen, sondern in keiner ernstzunehmenden Studie ueber Sprache und interkulturelle Kommunikation ausgelassen werden duerfen. Es wird hier argumentiert, dass der Schwerpunkt auf Verschiedenheit und Problemorientierung im interkulturellen Konflikt einen wesentlichen Einfluss auf theoretische Entwicklungen, Datenerhebung und Methoden in diesem Bereich hatte. Dieser Artikel legt auch dar, wie diese Ansaetze eine betraechtliche ‘Bewusstseinsbildungs – Branche' erzeugt haben, mit Methoden, Trainings, und ‘kritischen Interaktionssituationen’, welche letztendlich allen intellektuellen Arbeitseifer auf Bereiche konzentriert hat, die zwar ertragreich sind in Bezug auf Kurse und Publikationen, jedoch eine problematische Grundlage im ethischen Bereich aufweisen

Upregulation of Trem2 expression occurs exclusively on microglial contact with plaques

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia touching plaques, neighboring plaques, and far from plaques in 18-month-old APPNLF/NLF knock-in mice with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H. We report that, in AppNLF/NLF mice, expression of 35/55 PIGs, is exclusively upregulated in microglia that are touching plaques. In 7 PIGs including Trem2 this upregulation is prevented by the Trem2R47H/R47H mutation. Unlike in young mice, knockin of the Trem2R47H/R47H mutation does not significantly decrease the Trem2 expression but decreases protein levels by 20% in the absence of plaques. On plaques, despite the mutation preventing increased gene expression, TREM2 protein levels increased by 1.6-fold (compared to 3-fold with Trem2WT/WT) and microglial density increased 20-fold compared to 30-fold. Hence microglia must touch plaques before Trem2 gene expression is increased but small changes in protein expression can increase microglia density without a change in gene expression

Modulation of the tumour promoting functions of cancer associated fibroblasts by phosphodiesterase type 5 inhibition increases the efficacy of chemotherapy in human preclinical models of esophageal adenocarcinoma

Background and aims: Esophageal adenocarcinoma (EAC) is chemoresistant in the majority of cases. The tumor-promoting biology of cancer associated fibroblasts (CAF) make them a target for novel therapies. Phosphodiesterase type 5 inhibitors (PDE5i) have been shown to regulate the activated fibroblast phenotype in benign disease. We investigated the potential for CAF modulation in EAC using PDE5i to enhance the efficacy of chemotherapy. Methods: EAC fibroblasts were treated with PDE5i and phenotypic effects examined using immunoblotting, immunohistochemistry, gel contraction, transwell invasion, organotypics, single cell RNAseq and shotgun proteomics. The combination of PDE5i with standard-of-care chemotherapy (Epirubicin, 5-Fluorouracil and Cisplatin) was tested for safety and efficacy in validated near-patient model systems (3D tumor growth assays (3D-TGAs) and patient derived xenograft (PDX) mouse models). Results: PDE5i treatment reduced alpha-SMA expression in CAFs by 50% (p<0.05), associated with a significant reduction in the ability of CAFs to contract collagen-1 gels and induce cancer cell invasion, (p<0.05). RNAseq and proteomic analysis of CAF and EAC cell lines revealed PDE5i specific regulation of pathways related to fibroblast activation and tumor promotion. 3D-TGA assays confirmed the importance of stromal cells to chemoresistance in EAC, which could be attenuated by PDE5i. Chemotherapy+PDE5i in PDX-bearing mice was safe and significantly reduced PDX tumor volume (p<0.05). Conclusion: PDE5 is a candidate for clinical trials to alter the fibroblast phenotype in esophageal cancer. We demonstrate the specificity of PDE5i for fibroblasts to prevent transdifferentiation and revert the CAF phenotype. Finally, we confirm the efficacy of PDE5i in combination with chemotherapy in close-to-patient in vitro and in vivo PDX-based model systems

Plaque contact and unimpaired Trem2 is required for the microglial response to amyloid pathology

Using spatial cell-type-enriched transcriptomics, we compare plaque-induced gene (PIG) expression in microglia-touching plaques, neighboring plaques, and far from plaques in an aged Alzheimer’s mouse model with late plaque development. In 18-month-old APPNL-F/NL-F knockin mice, with and without the Alzheimer’s disease risk mutation Trem2R47H/R47H, we report that expression of 38/55 PIGs have plaque-induced microglial upregulation, with a subset only upregulating in microglia directly contacting plaques. For seven PIGs, including Trem2, this upregulation is prevented in APPNL-F/NL-FTrem2R47H/R47H mice. These TREM2-dependent genes are all involved in phagocytic and degradative processes that we show correspond to a decrease in phagocytic markers and an increase in the density of small plaques in Trem2-mutated mice. Furthermore, despite the R47H mutation preventing increased Trem2 gene expression, TREM2 protein levels and microglial density are still marginally increased on plaques. Hence, both microglial contact with plaques and functioning TREM2 are necessary for microglia to respond appropriately to amyloid patholog