Composition - structure - property relationships in bioactive glasses

Hench developed the first bioactive material, Bioglass®, based on a soda-lime phospho-silicate glass. Most materials, elicit a neutral response when implanted into the human body. Bioglass®, however, was seen to create a positive response by depositing the body’s natural bone substance, Hydroxyapatite on its surface. Although it is recognised that compositional modifications effect bioactivity, there is very little comprehension of the composition-structureproperty relationships that result in such bioactivity. The objective of this investigation, therefore, was to study such fundamental relationships with respect to two components often found in bioactive glass compositions – P2O5 and MgO. The first component studied was P2O5. The design of two series was undertaken – the first, a straight substitution of silicon for phosphorus, varying the network connectivity, NC, and the second, a charge compensating series, keeping the NC constant. 31P and 29Si MAS NMR of the two series provided evidence that the glasses were phase separated, with a predominantly Q2 silicate structure co-existing with phosphorus in a predominantly Q0 orthophosphate environment. Raman, FTIR, density measurements, differential thermal analysis and dilatometric analysis all further supported the existence of this structure. Dissolution studies in SBF highlighted the importance of phosphorus on bioactivity, with the glass dissolution rates of both series increasing with the addition of phosphorus. Instead of the dissolution of a glass depending solely on ion exchange reactions, as previously thought, it is proposed that dissolution depends upon the balance existing between the NC of the silicate phase and the existence of isolated orthophosphate rich domains. It is hypothesised that phosphorus in a phase separated structure is far more important than previously suspected, with its ability to preferentially dissolve into solution, dominating over the effect of NC on the resultant bioactivity of the glass and apatite formation. The second component investigated was magnesium oxide and its influence on the glass structure when substituted for calcium oxide. Two series of glasses were designed, the first series with a high sodium content and the second series with a low sodium content. In order to eliminate any influence due to silicate network disruption, all glasses were designed to have a constant NC of 2.04. All physical parameters were seen to be related strongly to the substitution of magnesium oxide, in both series. 31P, 29Si and 25Mg MAS-NMR of the high sodium magnesium glasses highlighted that magnesium, rather than acting to depolymerise the silicate network by acting as a network modifier, was acting partially as an intermediate oxide with a proportion entering the network as MgO4 tetrahedra. The decreasing Tg and Ts values and increasing thermal expansion coefficients, with increasing MgO substitution, supported this theory; with the significantly weaker bond strength of Mg-O, compared to Si-O, explaining the experimentally observed weakening of the network. The corresponding results for the low sodium magnesium glasses also pointed to magnesium acting as an intermediate oxide, however, with a smaller proportion entering the silicate network as MgO4 tetrahedra. It is suggested that magnesium acts as an intermediate oxide in highly disrupted glasses, with a more disrupted glass giving a higher proportion of MgO4. Dissolution studies in SBF settled the previously controversial subject of magnesium and bioactivity, with the addition of magnesium resulting in decreased glass dissolution rates and apatite formation in both series. This work has highlighted the importance of having a detailed understanding of the composition-structure-property relationships which exist in a bioactive glass. It is suggested that, from the contribution this work makes to this understanding, coupled with the knowledge gained from parallel studies, we are now at the point where a specific bioactive glass composition could be engineered, and tailored for a particular biomedical application

'We've just had to hit the ground running': Health professionals' experiences of cancer immunotherapy: A qualitative study

Background This paper reports early findings from a qualitative investigation of people’s experiences of cancer immunotherapy with immune checkpoint inhibitors. Cancer immunotherapy is transforming outcomes for some people affected by cancer. Clinical trials have found that immune checkpoint inhibitors (ICIs) demonstrate clinical benefit across various cancers. Several ICIs are now approved for a range of cancers and used across UK cancer centres. However, there is little research focused on UK healthcare professionals’ experiences of delivering and supporting people receiving ICI’s together with their associated education and training needs. Method This study sought to obtain in-depth insight into healthcare professionals’ experiences of caring for people receiving cancer immunotherapy and their associated education, training and support needs. NHS ethical approval was granted for the participating NHS sites. UK healthcare professionals (11 nurses, 3 doctors and 2 pharmacists) from oncology services, primary and secondary care (acute oncology) were recruited using purposive and snowball sampling. In view of COVID-19 physical distancing requirements, digitally-recorded, semi-structured telephone interviews were conducted between May and September 2020. Transcribed, anonymised data were analysed using Braun and Clarke’s reflexive, thematic analysis. Results Data suggest healthcare professionals have variable educational and training needs relative to supportive care in cancer immunotherapy. The provision of immunotherapy care, particularly within oncology, is currently approached predominantly through the biomedical lens of toxicity management. Perspectives on holistic patient care, including psychological support, were limited. This disparity might be owing to ICI treatment as relatively novel compared with other anti-cancer treatments. Professionals considered ICIs as complex to manage, with significant efforts to establish a range of toxicities from both single-agent and combination ICI treatment ongoing, with many still considered unknown. Conclusion Further research should consider how healthcare professionals’ ongoing education and training needs for holistic supportive care can be best addressed. Impact statement This study seeks to make recommendations for ICI supportive care guidance development, cancer immunotherapy education materials for healthcare professionals, cancer policy and further research

Guidelines for the use and reuse of animals for teaching within veterinary medical education programs

Use and reuse of animals for educational purposes could adversely affect animal welfare. Guidelines for quantifying, monitoring and planning the use and reuse of animals have been developed. Within this framework animals are assigned points for usage, with more points being allocated to procedures that may have a greater adverse effect on animal welfare. Usage of individual animals is limited to a maximum of 8 points in a calendar week, 24 points in a month or 60 points within a 16-week study period and any associated examination period. Advantages and disadvantages of the system are discussed while modification is expected as knowledge emerges on the impact of procedures on animal welfare

Trial Protocol: Communicating DNA-based risk assessments for Crohn's disease: a randomised controlled trial assessing impact upon stopping smoking.

BACKGROUND: Estimates of the risk of developing Crohn's disease (CD) can be made using DNA testing for mutations in the NOD2 (CARD15) gene, family history, and smoking status. Smoking doubles the risk of CD, a risk that is reduced by stopping. CD therefore serves as a timely and novel paradigm within which to assess the utility of predictive genetic testing to motivate behaviour change to reduce the risk of disease. The aim of the study is to describe the impact upon stopping smoking of communicating a risk of developing CD that incorporates DNA analysis. We will test the following main hypothesis:Smokers who are first degree relatives (FDRs) of CD probands are more likely to make smoking cessation attempts following communication of risk estimates of developing CD that incorporate DNA analysis, compared with an equivalent communication that does not incorporate DNA analysis. METHODS/DESIGN: A parallel groups randomised controlled trial in which smokers who are FDRs of probands with CD are randomly allocated in families to undergo one of two types of assessment of risk for developing CD based on either: i. DNA analysis, family history of CD and smoking status, or ii. Family history of CD and smoking status. The primary outcome is stopping smoking for 24 hours or longer in the six months following provision of risk information. The secondary outcomes are seven-day smoking abstinence at one week and six month follow-ups. Randomisation of 470 smoking FDRs of CD probands, with 400 followed up (85%), provides 80% power to detect a difference in the primary outcome of 14% between randomised arms, at the 5% significance level. DISCUSSION: This trial provides one of the strongest tests to date of the impact of communicating DNA-based risk assessment on risk-reducing behaviour change. Specific issues regarding the choice of trial design are discussed.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

A novel grass hybrid to reduce flood generation in temperate regions

We report on the evaluation of a novel grass hybrid that provides efficient forage production and could help mitigate flooding. Perennial ryegrass (Lolium perenne) is the grass species of choice for most farmers, but lacks resilience against extremes of climate. We hybridised L. perenne onto a closely related and more stress-resistant grass species, meadow fescue Festuca pratensis. We demonstrate that the L. perenne × F. pratensis cultivar can reduce runoff during the events by 51% compared to a leading UK nationally recommended L. perenne cultivar and by 43% compared to F. pratensis over a two year field experiment. We present evidence that the reduced runoff from this Festulolium cultivar was due to intense initial root growth followed by rapid senescence, especially at depth. Hybrid grasses of this type show potential for reducing the likelihood of flooding, whilst providing food production under conditions of changing climate

Access, acceptance and adherence to cancer prehabilitation: a mixed-methods systematic review

Purpose The purpose of this systematic review is to better understand access to, acceptance of and adherence to cancer prehabilitation. Methods MEDLINE, CINAHL, PsychINFO, Embase, Physiotherapy Evidence Database, ProQuest Medical Library, Cochrane Library, Web of Science and grey literature were systematically searched for quantitative, qualitative and mixed-methods studies published in English between January 2017 and June 2023. Screening, data extraction and critical appraisal were conducted by two reviewers independently using Covidence™ systematic review software. Data were analysed and synthesised thematically to address the question ‘What do we know about access, acceptance and adherence to cancer prehabilitation, particularly among socially deprived and minority ethnic groups?’ The protocol is published on PROSPERO CRD42023403776 Results Searches identified 11,715 records, and 56 studies of variable methodological quality were included: 32 quantitative, 15 qualitative and nine mixed-methods. Analysis identified facilitators and barriers at individual and structural levels, and with interpersonal connections important for prehabilitation access, acceptance and adherence. No study reported analysis of facilitators and barriers to prehabilitation specific to people from ethnic minority communities. One study described health literacy as a barrier to access for people from socioeconomically deprived communities. Conclusions There is limited empirical research of barriers and facilitators to inform improvement in equity of access to cancer prehabilitation

State–Space Forecasting of Schistosoma haematobium Time-Series in Niono, Mali

Adequate forecasting and early warning systems are based upon observations of human behavior, population, disease time-series, climate, environment, and/or a combination thereof, whichever option best compromises among realism, feasibility, robustness, and parsimony. Fully automatic and user-friendly state–space forecasting frameworks, incorporating myriad options (e.g., expert opinion, univariate, multivariate, and spatial-temporal), could considerably enhance disease control and hazard mitigation efforts in regions where vulnerability to neglected tropical diseases is pervasive and statistical expertise is scarce. The operational simplicity, generality, and flexibility of state–space frameworks, encapsulating multiple methods, could conveniently allow for 1) unsupervised model selection without disease-specific methodological tailoring, 2) on-line adaptation to disease time-series fluctuations, and 3) automatic switches between distinct forecasting methods as new time-series perturbations dictate. In this investigation, a univariate state–space framework with the aforementioned properties was successfully applied to the Schistosoma haematobium time-series for the district of Niono, Mali, to automatically generate contemporaneous on-line forecasts and hence, providing a basis for local re-organization and strengthening public health programs in this and potentially other Sahelian districts