Using behavioural theories to optimise shared haemodialysis care: a qualitative intervention development study of patient and professional experience

Background Patients in control of their own haemodialysis report better outcomes than those receiving professional controlled care in a hospital setting, even though home and hospital haemodialysis are largely equivalent from mechanical and physiological perspectives. Shared Haemodialysis Care (SHC) describes an initiative in which hospital haemodialysis patients are supported by dialysis staff to become as involved as they wish in their own care; and can improve patient safety, satisfaction and may reduce costs. We do not understand why interventions to support self-management in other conditions have variable effects or how to optimise the delivery of SHC. The purpose of this study was to identify perceived patient and professional (nurses and healthcare assistants) barriers to the uptake of SHC, and to use these data to identify intervention components to optimise care. Methods Individual semi-structured interviews with patients and professionals were conducted to identify barriers and facilitators. Data were coded to behavioural theory to identify solutions. A national UK learning event with multiple stakeholders (patients, carers, commissioners and professionals) explored the salience of these barriers and the acceptability of solutions. Results A complex intervention strategy was designed to optimise SHC for patients and professionals. Interviews were conducted with patients (n = 15) and professionals (n = 7) in two hospitals and three satellite units piloting SHC. Data from patient and professional interviews could be coded to behavioural theory. Analyses identified key barriers (knowledge, beliefs about capabilities, skills and environmental context and resources). An intervention strategy that focuses on providing, first, patients with information about the shared nature of care, how to read prescriptions and use machines, and second, providing professionals with skills and protected time to teach both professionals/patients, as well as providing continual review, may improve the implementation of SHC and be acceptable to stakeholders. Conclusions We have developed an intervention strategy to improve the implementation of SHC for patients and professionals. While this intervention strategy has been systematically developed using behavioural theory, it should be rigorously tested in a subsequent effectiveness evaluation study prior to implementation to ensure that shared haemodialysis care can be delivered equitably, efficiently and safely for all patients

A Robust Approach to Identifying Tissue-Specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells

Normal variation in gene expression due to regulatory polymorphisms is often masked by biological and experimental noise. In addition, some regulatory polymorphisms may become apparent only in specific tissues. We derived human induced pluripotent stem (iPS) cells from adult skin primary fibroblasts and attempted to detect tissue-specific cis-regulatory variants using in vitro cell differentiation. We used padlock probes and high-throughput sequencing for digital RNA allelotyping and measured allele-specific gene expression in primary fibroblasts, lymphoblastoid cells, iPS cells, and their differentiated derivatives. We show that allele-specific expression is both cell type and genotype-dependent, but the majority of detectable allele-specific expression loci remains consistent despite large changes in the cell type or the experimental condition following iPS reprogramming, except on the X-chromosome. We show that our approach to mapping cis-regulatory variants reduces in vitro experimental noise and reveals additional tissue-specific variants using skin-derived human iPS cells

PDGF in gliomas: more than just a growth factor?

Platelet-derived growth factor B (PDGF-B) is a growth factor promoting and regulating cell migration, proliferation, and differentiation, involved in both developmental processes and in maintaining tissue homeostasis under strict regulation. What are the implications of prolonged or uncontrolled growth factor signaling in vivo, and when does a growth factor such as PDGF-B become an oncogene? Under experimental conditions, PDGF-B induces proliferation and causes tumor induction. It is not known whether these tumors are strictly a PDGF-B-driven proliferation of cells or associated with secondary genetic events such as acquired mutations or methylation-mediated gene silencing promoting neoplasia. If PDGF-B-driven tumorigenesis was only cellular proliferation, associated changes in gene expression would thus be correlated with proliferation and not associated with secondary events involved in tumorigenesis and neoplastic transformation such as cycle delay, DNA damage response, and cell death. Changes in gene expression might be expected to be reversible, as is PDGF-B-driven proliferation under normal circumstances. Since PDGF signaling is involved in oligodendrocyte progenitor cell differentiation and maintenance, it is likely that PDGF-B stimulates proliferation of a pool of cells with that phenotype, and inhibition of PDGF-B signaling would result in reduced expression of oligodendrocyte-associated genes. More importantly, inhibition of PDGF signaling would be expected to result in reversion of genes induced by PDGF-B accompanied by a decrease in proliferation. However, if PDGF-B-driven tumorigenesis is more than simply a proliferation of cells, inhibition of PDGF signaling may not reverse gene expression or halt proliferation. These fundamental questions concerning PDGF-B as a potential oncogene have not been resolved

The effect of thermal annealing on dopant site choice in conjugated polymers

Solution-processed organic electronic devices often consist of layers of polar and non-polar polymers. In addition, either of these layers could be doped with small molecular dopants. It is extremely important for device stability to understand the diffusion behavior of these molecular dopants under the thermal stress and whether the dopants have preference for the polar or the non-polar polymer layers. In this work, a widely used molecular dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) was chosen to investigate dopant site preference upon thermal annealing between the polar thiophene poly(thiophene-3-[2-(2-methoxy-ethoxy)ethoxy]-2,5-diyl) (S-P3MEET) and non-polar thiophene poly(3-hexylthiophene) (P3HT). F4TCNQ is able to p-type dope both P3HT and S-P3MEET. Further doping studies of S-P3MEET using near edge X-ray absorption fine structure spectroscopy, conductivity measurements and atomic force microscopy show that the F4TCNQ additive competes for doping sites with the covalently attached dopants on the S-P3MEET. Calorimetry measurements reveal that the F4TCNQ interacts strongly with the side-chains of the S-P3MEET, increasing the melting temperature of the side-chains by 30 °C with 5 wt% dopant loading. Next, the thermal stability of doping in the polar/non-polar (S-P3MEET/P3HT) bilayer architectures was investigated. Steady-state absorbance and fluorescence results show that F4TCNQ binds much more strongly in S-P3MEET than P3HT and very little F4TCNQ is found in the P3HT layer after annealing. In combination with reflectometry measurements, we show that F4TCNQ remains in the SP3MEET layer with annealing to 210 °C even though the sublimation temperature for neat F4TCNQ is about 80 °C. In contrast, F4TCNQ slowly diffuses out of P3HT at room temperature. We attribute this difference in binding the F4TCNQ anion to the ability of the ethyl-oxy side-chains of the S-P3MEET to orient around the charged dopant molecule and thereby to stabilize its position. This study suggests that polar side-chains could be engineered to increase the thermal stability of molecular dopant position