Modernising Orodispersible Film Characterisation to Improve Palatability and Acceptability Using a Toolbox of Techniques

Orodispersible films (ODFs) have been widely used in paediatric, geriatric and dysphagic patients due to ease of administration and precise and flexible dose adjustments. ODF fabrication has seen significant advancements with the move towards more technologically advanced production methods. The acceptability of ODFs is dependent upon film composition and process of formation, which affects disintegration, taste, texture and mouthfeel. There is currently a lack of testing to accurately assess ODFs for these important acceptability sensory perceptions. This study produced four ODFs formed of polyvinyl alcohol and sodium carboxymethylcellulose using 3D printing. These were assessed using three in vitro methods: Petri dish and oral cavity model (OCM) methods for disintegration and bio-tribology for disintegration and oral perception. Increasing polymer molecular weight (MW) exponentially increased disintegration time in the Petri dish and OCM methods. Higher MW films adhered to the OCM upper palate. Bio-tribology analysis showed that films of higher MW disintegrated quickest and had lower coefficient of friction, perhaps demonstrating good oral perception but also stickiness, with higher viscosity. These techniques, part of a toolbox, may enable formulators to design, test and reformulate ODFs that both disintegrate rapidly and may be better perceived when consumed, improving overall treatment acceptability

Socio-cultural influences on the behaviour of South Asian women with diabetes in pregnancy: qualitative study using a multi-level theoretical approach

BACKGROUND: Diabetes in pregnancy is common in South Asians, especially those from low-income backgrounds, and leads to short-term morbidity and longer-term metabolic programming in mother and offspring. We sought to understand the multiple influences on behaviour (hence risks to metabolic health) of South Asian mothers and their unborn child, theorise how these influences interact and build over time, and inform the design of culturally congruent, multi-level interventions. METHODS: Our sample for this qualitative study was 45 women of Bangladeshi, Indian, Sri Lankan, or Pakistani origin aged 21-45 years with a history of diabetes in pregnancy, recruited from diabetes and antenatal services in two deprived London boroughs. Overall, 17 women shared their experiences of diabetes, pregnancy, and health services in group discussions and 28 women gave individual narrative interviews, facilitated by multilingual researchers, audiotaped, translated, and transcribed. Data were analysed using the constant comparative method, drawing on sociological and narrative theories. RESULTS: Key storylines (over-arching narratives) recurred across all ethnic groups studied. Short-term storylines depicted the experience of diabetic pregnancy as stressful, difficult to control, and associated with negative symptoms, especially tiredness. Taking exercise and restricting diet often worsened these symptoms and conflicted with advice from relatives and peers. Many women believed that exercise in pregnancy would damage the fetus and drain the mother's strength, and that eating would be strength-giving for mother and fetus. These short-term storylines were nested within medium-term storylines about family life, especially the cultural, practical, and material constraints of the traditional South Asian wife and mother role and past experiences of illness and healthcare, and within longer-term storylines about genetic, cultural, and material heritage - including migration, acculturation, and family memories of food insecurity. While peer advice was familiar, meaningful, and morally resonant, health education advice from clinicians was usually unfamiliar and devoid of cultural meaning. CONCLUSIONS: 'Behaviour change' interventions aimed at preventing and managing diabetes in South Asian women before and during pregnancy are likely to be ineffective if delivered in a socio-cultural vacuum. Individual education should be supplemented with community-level interventions to address the socio-material constraints and cultural frames within which behavioural 'choices' are made

Identification of five fundamental implicit theories underlying cognitive distortions in child abusers : a preliminary study

Qualitative analysis of interviews with 22 child abusers found strong evidence for Ward and Keenan\u27s (1999) proposal that there are five implicit theories in child abusers that account for the majority of their cognitive distortions/thinking errors. These implicit theories are: Child as a sexual being where children are perceived as being able to and wanting to engage in sexual activity with adults and also are not be harmed by such sexual contact; Nature of harm where the offender perceives that sexual activity does not cause harm (and may in fact be beneficial) to the child; Entitlement where the child abuser perceives that he is superior and more important than others: and hence is able to have sex with whoever, and whenever, he wants; Dangerous world where the offender perceives that that others are abusive and rejecting and he must fight to regain control; and Uncontrollable where the offender perceives the world as uncontrollable and hence he believes that circumstances are outside of his control. There was no evidence for any other type of implicit theory. Results of the study also indicated that there was a significant difference in terms of the endorsement of the Dangerous world implicit theory between participants reporting a history of child sexual abuse and those who did not. Offenders against male victims were significantly more likely to endorse the Child as a sexual being and Dangerous world implicit theories compared to men who had offended against female children

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Characterisation of a bone morphogenetic protein 2 system in pituitary gonadotroph cells

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Advantages and limitations of virtual online consultations in a NHS acute trust: the VOCAL mixed-methods study

Background: There is much enthusiasm from clinicians, industry and the government to utilise digital technologies and introduce alternatives to face-to-face consultations. Objective(s): To define good practice and inform digital technology implementation in relation to remote consultations via Skype™ (Microsoft Corporation, Redmond, WA, USA) and similar technologies. Design: Multilevel mixed-methods study of remote video consultations (micro level) embedded in an organisational case study (meso level), taking account of the national context and wider influences (macro level). Setting: Three contrasting clinical settings (Diabetes, Antenatal Diabetes and Cancer Surgery) in a NHS acute trust. Data collection and analysis: Macro level – interviews with 12 national-level stakeholders combined with document analysis. Meso level – longitudinal organisational ethnography comprising over 300 hours of observations, 24 staff interviews and analysis of 16 documents. Micro level – 30 video-recorded remote consultations; 17 matched audio-recorded face-to-face consultations. Interview and ethnographic data were analysed thematically and theorised using strong structuration theory. Consultations were transcribed verbatim and analysed using the Roter interaction analysis system (RIAS), producing descriptive statistics on different kinds of talk and interaction. Results: Policy-makers viewed remote video consultations as a way of delivering health care efficiently in the context of rising rates of chronic illness and growing demand for services. However, the reality of establishing such services in a busy and financially stretched NHS acute trust proved to be far more complex and expensive than anticipated. Embedding new models of care took much time and many resources, and required multiple workarounds. Considerable ongoing effort was needed to adapt and align structures, processes and people within clinics and across the organisation. For practical and safety reasons, virtual consultations were not appropriate for every patient or every consultation. By the end of this study, between 2% and 20% of all consultations were being undertaken remotely in participating clinics. Technical challenges in setting up such consultations were typically minor, but potentially prohibitive. When clinical, technical and practical preconditions were met, virtual consultations appeared to be safe and were popular with both patients and staff. Compared with face-to-face consultations, virtual consultations were very slightly shorter, patients did slightly more talking and both parties sometimes needed to make explicit things that typically remained implicit in a traditional encounter. Virtual consultations appeared to work better when the clinician and the patient knew and trusted each other. Some clinicians used Skype adaptively to support ad hoc clinician-initiated and spontaneous patient-initiated encounters. Other clinicians chose not to use the new service model at all. Conclusions: Virtual consultations appear to be safe, effective and convenient for patients who are preselected by their clinicians as ‘suitable’, but such patients represent a small fraction of clinic workloads. There are complex challenges to embedding virtual consultation services within routine practice in the NHS. Roll-out (across the organisation) and scale-up (to other organisations) are likely to require considerable support. Limitations: The focus on a single NHS organisation raises questions about the transferability of findings, especially quantitative data on likely uptake rates. Future research: Further studies on the micro-analysis of virtual consultations and on the spread and scale-up of virtual consulting services are planned. Funding: The National Institute for Health Research Health Services and Delivery Research programme

X-ray absorption spectroscopy of dimethylsulfoxide reductase from Rhodobacter capsulatus

Mo K-edge X-ray absorption spectroscopy (XAS) has been used to probe the environment of Mo in dimethylsulfoxide (DMSO) reductase from Rhodobacter capsulatus in concert with protein crystallographic studies. The oxidised (Mo(VI)) protein has been investigated in solution at 77 K; the Mo K-edge position (20006.4 eV) is consistent with the presence of MO(VI) and, in agreement with the protein crystallographic results, the extended X-ray absorption fine structure (EXAFS) is also consistent with a seven-coordinate site. The site is composed of one oxo-group (Mo = O 1.71 Å), four S atoms (considered to arise from the dithiolene groups of the two molybdopterins, two at 2.32 Å and two at 2.47 Å, and two O atoms, one at 1.92 Å (considered to be H-bonded to Trp 116) and one at 2.27 Å (considered to arise from Ser 147). The Mo K-edge XAS recorded for single crystals of oxidised (Mo(VI)) DMSO reductase at 77 K showed a close correspondence to the data for the frozen solution but had an inferior signal:noise ratio. The dithionite-reduced form of the enzyme and a unique form of the enzyme produced by the addition of dimethylsulfide (DMS) to the oxidised (Mo(VI)) enzyme have essentially identical energies for the Mo K-edge, at 20004.4 eV and 20004.5 eV, respectively; these values, together with the lack of a significant presence of Mo(V) in the samples as monitored by EPR spectroscopy, are taken to indicate the presence of Mo(IV). For the dithionite-reduced sample, the Mo K-edge EXAFS indicates a coordination environment for Mo of two O atoms, one at 2.05 Å and one at 2.51 Å, and four S atoms at 2.36 Å. The coordination environment of the Mo in the DMS- reduced form of the enzyme involves three O atoms, one at 1.69 Å, one at 1.91 Å and one at 2.11 Å, plus four S atoms, two at 2.28 Å and two at 2.37 Å. The EXAFS and the protein crystallographic results for the DMS-reduced form of the enzyme are consistent with the formation of the substrate, DMSO, bound to Mo(IV) with an Mo-O bond of length 1.92 Å