Developing and implementing a social prescribing initiative in primary care: insights into the possibility of normalization and sustainability from a UK case study

Aim: To conduct a process based evaluation of the inception and early implementation of a social prescribing initiative ('Healthy Connections Stewartry') in two UK General Practices. Background: Prescribing a range of social, cultural, arts and educational activities to clients in primary care (known as 'social prescribing' or 'community linking schemes') as a means of addressing long-term physical health conditions and promoting mental health and wellbeing is becoming increasingly prominent and popular. However, concerns exist over a lack of evidence of effectiveness and formalised insights into how such initiatives may be optimally implemented. Methods: Within a case study design and using 1-1 semi-structured interviews, 3 related datasets were developed over a 12 month period from 30 purposively sampled informants: the project steering group; the wider primary care team; and various community groups. Data analysis drew on various theoretical resources, particularly those pertaining to nurturing sufficient capacity for the organisational 'normalisation' of this practice and understanding the dynamic flows and linkages between potential clients, 'prescribing' primary care staff and the available community resources. Findings: The inception and implementation of the initiative had been broadly successful and that more generally, there were grounds to suggest that these practices were becoming 'normalised' into the day-to-day cultures and routines of the primary care organisations. A series of procedural features are considered significant in achieving such ends. Some specific barriers to change are identified and ultimately in the context of potential 'transferability', a wider reflection is undertaken of the potential for such innovative practice to become established in less advantageous organisational circumstances. Fundamental difficulties are recognised and thus the need for formally implemented 'change' processes. Furthermore, for social prescribing to become a pervasive feature of health care provision, the need for necessary capacity and resources is stressed

Bullying and school disruption assessment: studies with Portuguese adolescent students

Problem Statement: The question of bullying and school disruptive behavior has emerged as a powerful issue in Portuguese educational context. The lack of evaluation instruments, with studied psychometric characteristics, has constituted a problem. Purpose of Study: School disruption and bullying assessment, in Portuguese adolescents, was the focus of this research. Research Methods: The psychometric qualities — internal consistency and the external validity — were analyzed in different scales. Findings: The analyses carried out confirm the scales as reliable and valid instruments. Conclusions: These instruments may be a useful avenue for teachers, psychologists and other education professionals

Discrimination between prion-infected and normal blood samples by protein misfolding cyclic amplification

BACKGROUND:Diagnosis of prion disease from blood samples requires the detection of minute quantities of misfolded protein (PrPSc) against a high background of correctly folded material (PrPC). Protein misfolding cyclic amplification (PMCA) is a technique that can amplify small amounts of seed PrPSc to a level detectable by conventional methods. Application of PMCA to the testing of whole blood samples enhances the ability to detect PrPSc and allows antemortem detection of prion infection and could facilitate blood screening.STUDY DESIGN AND METHODS:The PMCA method was used to detect prion infection in blood samples obtained from mice experimentally infected with prion disease. Mice were culled at various time points throughout the incubation period for disease and subjected to serial PMCA (sPMCA). Amplified samples were then analyzed by Western blotting to confirm the presence or absence of infection.RESULTS:After sPMCA, blood samples from Rocky Mountain Laboratory-infected mice showed amplification of PrPSc to levels readily detectable by Western blotting. Control samples obtained from mice mock inoculated with sterile phosphate-buffered saline did not yield any amplification products.CONCLUSION:sPMCA performed on small volumes of whole blood gave amplification of PK-resistant material to a level detectable by standard methods. Discrimination between infected and control samples was achieved without the need for processing or fractionation of whole blood. The use of whole blood as an analyte circumvents the need to identify the optimal blood compartment for analysis and guarantees the totality of misfolded PrP will be available for detection

Ex vivomammalian prions are formed of paired double helical prion protein fibrils

Mammalian prions are hypothesized to be fibrillar or amyloid forms of prion protein (PrP), but structures observed to date have not been definitively correlated with infectivity and the three-dimensional structure of infectious prions has remained obscure. Recently, we developed novel methods to obtain exceptionally pure preparations of prions from mouse brain and showed that pathogenic PrP in these high-titre preparations is assembled into rod-like assemblies. Here, we have used precise cell culture-based prion infectivity assays to define the physical relationship between the PrP rods and prion infectivity and have used electron tomography to define their architecture. We show that infectious PrP rods isolated from multiple prion strains have a common hierarchical assembly comprising twisted pairs of short fibres with repeating substructure. The architecture of the PrP rods provides a new structural basis for understanding prion infectivity and can explain the inability to systematically generate high-titre synthetic prions from recombinant PrP

A highly sensitive immunoassay for the detection of prion-infected material in whole human blood without the use of proteinase K

BACKGROUND:The causal association of variant Creutzfeldt-Jakob disease (vCJD) with bovine spongiform encephalopathy has raised significant concerns for public health. Assays for vCJD infection are vital for the application of therapeutics, for the screening of organ donations, and to maintain a safe blood supply. Currently the best diagnostic tools for vCJD depend upon the detection of disease-associated prion protein (PrPSc), which is distinguished from normal background PrP (PrPC) by proteinase K (PK) digestion, which can also degrade up to 90% of the target antigen.STUDY DESIGN AND METHODS:A sandwich enzyme-linked immunosorbent assay method was developed using unique antibodies for the detection of disease-associated PrP in the absence of PK treatment. In combination with immunoprecipitation the assay was optimized for the detection of pathogenic PrP in large volumes of whole blood.RESULTS:Optimization of the assay allowed detection of 2 x 104 LD50 units/mL spiked in whole blood. Application of the assay to clinically relevant volumes enabled the detection of 750 LD50 units/mL in 8 mL of whole blood.CONCLUSION:By combining the use of a unique antibody that selectively immunoprecipitates PrPSc with glycoform-restrictive antibodies we have developed a rapid assay for vCJD infection that does not require any PK treatment to achieve high levels of specificity in whole human blood, the most challenging potential analyte. The sensitivity of detection of vCJD infection is greater than the equivalent of a more than 2.5 million-fold dilution of infected brain, providing a highly sensitive immunoassay compatible with blood screening

Prion 2016 poster abstracts

Until now, the 3-dimensional structure of infectious mammalian prions and how this differs from non-infectious amyloid fibrils remained unknown. Mammalian prions are hypothesized to be fibrillar or amyloid forms of prion protein (PrP), but structures observed to date have not been definitively correlated with infectivity. One of the major challenges has been the production of highly homogeneous material of demonstrable high specific infectivity to allow direct correlation of particle structure with infectivity. We have recently developed novel methods to obtain exceptionally pure preparations of prions from prion-infected murine brain and have shown that pathogenic PrP in these high-titer preparations is assembled into rod-like assemblies (Wenborn et al. 2015. Sci. Rep. 10062). Our preparations contain very high titres of infectious prions which faithfully transmit prion strain-specific phenotypes when inoculated into mice making them eminently suitable for detailed structural analysis. We are now undertaking structural characterization of prion assemblies and comparing these to the structure of non-infectious PrP fibrils generated from recombinant Pr

Teachers' and pupils' definitions of bullying.

BACKGROUND: Comparison of teachers' and pupils' definitions of bullying is important for considering the implications for reports of its incidence in schools, for the study of developmental trends in children's and adolescents' perceptions of the phenomenon and for evaluating the effectiveness of interventions designed to combat bullying. AIMS: To investigate the effects of gender, teacher/pupil status and, for pupils, bullied/non-bullied (target/non-target) status and age on the definition of bullying. SAMPLES: Teachers (N=225: 158 women, 67 men) and pupils (N=1,820: 466 boys, 460 girls were 11-12 years old, year 7, and 415 boys, 479 girls were 13-14 years, year 9) in 51 UK secondary schools participated in a questionnaire survey. A total of 557 of the pupils (117 girls and 117 boys aged 11-12 years, and 197 girls and 126 boys aged 13-14 years) reported that they had been bullied at some time in their present school. METHODS: Written questionnaire responses to the question, 'Say what you think bullying is' have been content analysed to derive two sets of categories, one of bullying behaviour and the other of effects of bullying on the target. RESULTS: Regarding both bullying behaviour and the effects of bullying on the target, teachers - by comparison with pupils - have been found to express more comprehensive ideas in their definitions. Specifically, pupils compared with teachers are more likely to restrict their definitions to direct bullying (verbal and/or physical abuse) and are less likely to refer to social exclusion, a power imbalance in the bully's favour and the bully's intention to cause the target hurt or harm and to feel threatened. Analysis of definitions on the bases of sex, pupil age and target/non-target status show that: targets are more likely than non-targets are to refer to the bully's physically and verbally abusive behaviour, and for Year 7 compared with Year 9 pupils, to suggest that bullies socially exclude targets; girls are more likely than boys are to mention verbal abuse and the effects on the target of 'Feels hurt/harm', but boys are more likely than girls are to construe bullying as involving repetition; older pupils are more likely than younger ones are to refer to a power imbalance in the bully's favour but, for bully targets, younger ones compared with older ones are more likely to invoke the idea of social exclusion in their definitions. CONCLUSIONS: The most important implication of the findings of this study that there are important differences between teachers' and pupils' definitions of bullying is that teachers need to listen carefully to what pupils have to say about bullying and work with and help them to develop their conceptions of the phenomenon. Some teachers, too, need to develop their conceptions of bullying

The first national subject benchmark statement for UK higher education in policing: the importance of effective partnership and collaboration

Purpose (limit 100 words) The Quality Assurance Agency (QAA) for Higher Education in the UK focuses on maintaining, enhancing and standardising the quality of higher education. Of significant impact are the development of subject benchmark statements (SBS) by the QAA, which describe the type and content of study along with the academic standards expected of graduates in specific disciplines. Prior to 2022, the QAA did not have a SBS to which higher education policing programmes could be directly aligned. Design/methodology/approach (limit 100 words) Over 12-months, a SBS advisory group with representatives from higher education across England, Scotland, Wales and Northern Ireland, The College of Policing, QAA, Police Federation of England and Wales, and policing, worked in partnership to harness their collective professional experience and knowledge to create the first UK SBS for policing. Post publication of the SBS, permission was sought and granted from both the College of Policing and QAA for members of the advisory group to reflect in an article on their experiences of collaborating and working in partnership to achieve the SBS. Findings (limit 100 words) There is great importance of creating a shared vision and mutual trust, developed through open facilitated discussions, with representatives championing their cause and developing a collaborative and partnership approach to completing the SBS. Practical implications (limit 100 words) A collaborative and partnership approach is essential in developing and recognising the academic discipline of policing. This necessarily requires the joint development of initiatives, one of which is the coming together of higher education institutions, PSRBs and practitioner groups to collaborate and design QAA benchmark statements. Originality/value (limit 100 words) The SBS for policing is the first across the UK. The authors experiences can be used to assist others in their developments of similar subject specific benchmarking or academic quality standards. Social implications (limit 100 words) The SBS advisory group has further driven forward the emergence of policing as a recognised academic discipline to benefit multiple stakeholders

A systematic investigation of production of synthetic prions from recombinant prion protein

According to the protein-only hypothesis, infectious mammalian prions, which exist as distinct strains with discrete biological properties, consist of multichain assemblies of misfolded cellular prion protein (PrP). A critical test would be to produce prion strains synthetically from defined components. Crucially, high-titre 'synthetic' prions could then be used to determine the structural basis of infectivity and strain diversity at the atomic level. While there have been multiple reports of production of prions from bacterially expressed recombinant PrP using various methods, systematic production of high-titre material in a form suitable for structural analysis remains a key goal. Here, we report a novel high-throughput strategy for exploring a matrix of conditions, additives and potential cofactors that might generate high-titre prions from recombinant mouse PrP, with screening for infectivity using a sensitive automated cell-based bioassay. Overall, approximately 20 000 unique conditions were examined. While some resulted in apparently infected cell cultures, this was transient and not reproducible. We also adapted published methods that reported production of synthetic prions from recombinant hamster PrP, but again did not find evidence of significant infectious titre when using recombinant mouse PrP as substrate. Collectively, our findings are consistent with the formation of prion infectivity from recombinant mouse PrP being a rare stochastic event and we conclude that systematic generation of prions from recombinant PrP may only become possible once the detailed structure of authentic ex vivo prions is solved