Heartfelt - The possibilities for physical objects to act as mediators in emotional exchange and implications for the design process

This paper draws on practice centred research conducted within the field of contemporary jewellery. Its aim is to understand the process and dynamics by which objects create meaning, in particular that of an emotional nature. The key objective is to propose methods for researching this critical field of enquiry. The research itself focuses on the commissioning process which as evidence shows is increasingly relevant as a means of consumption. The research considers the micro dynamics of a situation through which a client's needs are communicated. The research draws on cultural theory and design to develop an appropriate hybrid conceptual model. Significant elements in the interpretation and identification of emotional dimensions are identified and observed. The analysis of the data questioned the relationship between the communication process and the interpretation of an object. The hybrid conceptual model used is summarised in the paper. There then follows an explanation of a method for analysing the communicative role of objects, which focuses specifically on the commissioning process. This research is directly relevant to the fields of the applied arts and design. However it is also relevant to other industries and could contribute to the meaningful development of mass customisation. Key words: Jewellery, Design, Commission, Emotion, Mediatio

Economic appraisal of health technology in the United Kingdom

In this paper we assess the current state of the art of economic appraisal of health technologies in the United Kingdom. The paper is organised along the lines suggested in the Workshop proposal. Although the main interest of the Workshop is in 'high' technology, such as imaging techniques and advanced therapeutic interventions, we have included (in Appendix I) details of economic appraisals of other health care innovations, such as community care options for the elderly and mentally handicapped. We believe that these appraisals both give interest in high technology a sense of perspective and raise methodological issues that are relevant in the evaluation of advanced medical procedures. We have not included a discussion of a major case study in economic evaluation of health technology in the UK. The most appropriate example would be the recently completed appraisal of heart transplants, comissioned by the Department of Health and Social Seciruty (DHSS). This is to be discussed in another paper presented at the workshop (Buxton, 1985).

Tau protein is cross-linked by transglutaminase in P301L tau transgenic mice

This is the publisher's version, also available electronically from "http://www.jneurosci.org".The microtubule-associated protein tau is highly soluble under physiological conditions. However, in tauopathies, tau protein aggregates into insoluble filaments and neurofibrillary tangles (NFTs). The mechanisms underlying the formation of tau filaments and NFTs in tauopathies remain unclear. Several lines of evidence suggest that transglutaminase may cross-link tau into stable, insoluble aggregates, leading to the formation of NFTs in Alzheimer's disease and progressive supranuclear palsy. To further determine the contribution of transglutaminase in the formation of NFTs, we compared the levels of cross-linked tau protein from P301L tau transgenic mice that develop NFTs to four-repeat wild-type (4RWT) tau transgenic and nontransgenic mice that do not develop NFT pathology. Immunoprecipitation and immunoblotting experiments show that transglutaminase cross-links phosphorylated tau in the hindbrain of P301L tau transgenic mice but not in mice overexpressing 4RWT tau and nontransgenic mice. Cross-linked, phosphorylated tau from P301L tau transgenic mice runs as high-molecular mass aggregates on Western blots, similar to cross-linked tau from paired helical filaments of Alzheimer's disease. We also used double-label immunofluorescence to demonstrate colocalization of PHF-1-immunoreactive tau and the transglutaminase-catalyzed cross-link in the hindbrain, spinal cord, and cortex of P301L tau transgenic mice. In the spinal cord, 87% of PHF-1-labeled cells colocalize with the transglutaminase-catalyzed cross-link. Additionally, transglutaminase enzymatic activity is significantly elevated in the spinal cord of P301L tau transgenic mice. These studies further implicate transglutaminase in the formation and/or stabilization of NFT and paired helical filaments and provide a model system to investigate the therapeutic potential of transglutaminase inhibitors in tauopathies

Conference: ESTRO 2023, Vienna. Oral Presentation: Design and evaluation of a virtual tour of a Radiotherapy department to improve patient experience

Oral presentation at ESTRO 2023, Vienna. Presented by Nicola Hutton. The abstract for this work was nominated for the "Elsevier Young Researcher Award"

Patient reported outcome measures (PROMs) in Radiotherapy: Qualitative results of a survey of healthcare professionals

Background: Radiotherapy provides an effective treatment modality in the management of various malignancies. However, many patients develop acute and long-term toxicities that present a significant burden to their quality of life1,2. Such toxicities are often underreported by clinicians, and therefore patient-reported outcome measures(PROMs) present a more robust assessment3. Despite the clear advantages of PROMs including stratified follow-up and evaluation of clinical effectiveness, safety and cost, barriers exist at patient, healthcare professional(HCP) and service levels3,4. Most commonly, perceived lack of time/PROMs training for HCPS, poor IT infrastructure and lack of PROMs integration into existing systems create barriers3. The NHS England Radiotherapy Service Specification calls for routine use of PROMS, which requires effective implementation within radiotherapy5. Several ‘enablers’ to PROMs implementation have been identified, including use of electronic PROMs, automatic data interpretation and HCP training3,4,6. This study aimed to identify current PROMs use within radiotherapy nationally, to evaluate current attitudes, barriers and enablers to PROMs use, and to develop practical recommendations to implement PROMs within UK radiotherapy services. The qualitative findings are presented here. Methods: An e-questionnaire consisting of 12 open and multiple-choice questions was developed. The questionnaire was piloted by radiotherapy professionals, and disseminated via email across all radiotherapy operational delivery network(ODN) managers, covering the entirety of England. 182 participants were recruited across a range of professions including therapeutic radiographers, nurses and researchers. A mixed-methods approach was utilised; thematic analysis of free-text responses provided qualitative data, whilst statistical analysis was performed on quantitative results. Results: Inductive thematic analysis of questionnaire responses resulted in identification of key themes related to the barriers and enablers of PROMs use within radiotherapy. Interestingly, identical themes emerged associated with participants’ perceptions of both barriers/enablers, with an additional theme identified pertaining to potential enablers of PROMs: Barriers - Themes: 1. I.T. Infrastructure 2. Time 3. Resources(Human/Financial) 4. Training/Education Enablers - Themes: 1. I.T. Infrastructure 2. Time 3. Resources(Human/Financial) 4. Training/Education 5. Standardisation Conclusion: Our findings further demonstrate the paucity of routine PROMs use within radiotherapy. Here, we provide recommendations to mitigate barriers and implement PROMs; such steps include HCP training on PROMs and development/integration of electronic systems. Standardisation of PROMs tools and centralised data storage is essential to assessing radiotherapy toxicity data nationally and informing practice. Referral pathways to existing specialist services are fundamental to ensuring PROMs data are used meaningfully. This study provides an important first step in driving PROMs implementation within UK radiotherapy services. References 1. Miller, K., Nogueira, L., Mariotto, A., Rowland, J., Yabroff, R., Alfano, C., et al. (2019). Cancer treatment and survivorship statistics 2019. CA: A Cancer Journal For Clincians. https://doi.org/10.3322/caac.21565 2. Macmillan Cancer Support. Cured – but at what cost? Long-term consequences of cancer and its treatment. [ Internet] (2013). Available at: https://www.macmillan.org.uk/documents/aboutus/newsroom/consequences_of_treatment_june2013.pdf [Accessed online 28th March 2021]. 3. Nguyen, H., Butow, P., Dhillon, H. & Sundaresan, P. (2020a). A review of the barriers to using Patient-Reported Outcomes (PROs) and Patient-Reported Outcome Measures (PROMs) in routine cancer care. Journal of Medical Radiation Sciences. 00, 1-10. Doi: 10.1002/jmrs.421 4. Kingsley, C. & Patel, S. (2017). Patient-reported outcome measures and patient-reported experience measures. British Journal of Anaesthesia. 17, 137-144. doi: 10.1093/bjaed/mkw060 5. National Health Service (NHS) England (2019). Service Specification 170091S: Adult External Beam Radiotherapy Services Delivered as Part of a Radiotherapy Network. Available at: https://www.england.nhs.uk/wp-content/uploads/2019/01/External-Beam-Radiotherapy-Services-Delivered-as-Part-of-a-Radiotherapy-Network-Adults.pdf [Accessed online 10th April 2021]. 6. Howell, D., Molloy, S., Wilkinson, K., Green, E., Orchard, K., Wang, K. & Liberty, J. (2015). Patient-reported outcomes in routine cancer clinical practice: a scoping review of use, impact on health outcomes, and implementation factors. Annals of Oncology. 26, 1846-1858. doi: 10.1093/annonc/mdv18

Contact Sports as a Risk Factor for Amyotrophic Lateral Sclerosis: A Systematic Review.

Study Design: Systematic review. Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, ultimately resulting in paralysis and death. The condition is considered to be caused by a complex interaction between environmental and genetic factors. Although vast genetic research has deciphered many of the molecular factors in ALS pathogenesis, the environmental factors have remained largely unknown. Recent evidence suggests that participation in certain types of sporting activities are associated with increased risk for ALS. Objective: To test the hypothesis that competitive sports at the highest level that involve repetitive concussive head and cervical spinal trauma result in an increased risk of ALS compared with the general population or nonsport controls. Methods: Electronic databases from inception to November 22, 2017 and reference lists of key articles were searched to identify studies meeting inclusion criteria. Results: Sixteen studies met the inclusion criteria. Sports assessed (professional or nonprofessional) included soccer (n = 5), American football (n = 2), basketball (n = 1), cycling (n = 1), marathon or triathlon (n = 1), skating (n = 1), and general sports not specified (n = 11). Soccer and American football were considered sports involving repetitive concussive head and cervical spinal trauma. Professional sports prone to repetitive concussive head and cervical spinal trauma were associated with substantially greater effects (pooled rate ratio [RR] 8.52, 95% CI 5.18-14.0) compared with ( Conclusions: Our review suggests that increased susceptibility to ALS is significantly and independently associated with 2 factors: professional sports and sports prone to repetitive concussive head and cervical spinal trauma. Their combination resulted in an additive effect, further increasing this association to ALS

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Assessing the cost of global biodiversity and conservation knowledge

Knowledge products comprise assessments of authoritative information supported by stan-dards, governance, quality control, data, tools, and capacity building mechanisms. Considerable resources are dedicated to developing and maintaining knowledge productsfor biodiversity conservation, and they are widely used to inform policy and advise decisionmakers and practitioners. However, the financial cost of delivering this information is largelyundocumented. We evaluated the costs and funding sources for developing and maintain-ing four global biodiversity and conservation knowledge products: The IUCN Red List ofThreatened Species, the IUCN Red List of Ecosystems, Protected Planet, and the WorldDatabase of Key Biodiversity Areas. These are secondary data sets, built on primary datacollected by extensive networks of expert contributors worldwide. We estimate that US$160million (range: US$116–204 million), plus 293 person-years of volunteer time (range: 278–308 person-years) valued at US$14 million (range US$12–16 million), were invested inthese four knowledge products between 1979 and 2013. More than half of this financingwas provided through philanthropy, and nearly three-quarters was spent on personnelcosts. The estimated annual cost of maintaining data and platforms for three of these knowl-edge products (excluding the IUCN Red List of Ecosystems for which annual costs were notpossible to estimate for 2013) is US$6.5 million in total (range: US$6.2–6.7 million). We esti-mated that an additional US$114 million will be needed to reach pre-defined baselines ofdata coverage for all the four knowledge products, and that once achieved, annual mainte-nance costs will be approximately US$12 million. These costs are much lower than those tomaintain many other, similarly important, global knowledge products. Ensuring that biodi-versity and conservation knowledge products are sufficiently up to date, comprehensiveand accurate is fundamental to inform decision-making for biodiversity conservation andsustainable development. Thus, the development and implementation of plans for sustain-able long-term financing for them is critical

Catastrophic Cervical Spine Injuries in Contact Sports.

Study Design Systematic review. Objectives To determine the incidence of catastrophic cervical spine injuries (CCSIs) among elite athletes participating in contact team sports and whether the incidence varies depending on the use of protective gear or by player position. Methods Electronic databases and reference lists of key articles published from January 1, 2000, to January 29, 2016, were searched. Results Fourteen studies were included that reported CCSI in rugby (n = 10), American football (n = 3), and Irish hurling (n = 1). Among Rugby Union players, incidence of CCSI was 4.1 per 100,000 player-hours. Among National Football League players, the CCSI rate was 0.6 per 100,000 player-exposures. At the collegiate level, the CCSI rate ranged from 1.1 to 4.7 per 100,000 player-years. Mixed populations of elite and recreational rugby players in four studies report a CCSI rate of 1.4 to 7.2 per 100,000 player-years. In this same population, the scrum accounted for 30 to 51% of total reported CCSIs in Rugby Union versus 0 to 4% in Rugby League. The tackle accounted for 29 to 39% of injuries in Rugby Union and 78 to 100% of injuries in Rugby League. Making a tackle was responsible for 29 to 80% of injuries in American football. Conclusion CCSIs are infrequent among elite athletes. There is insufficient evidence to determine the effect of protective gear (e.g., helmets, padding) on CCSI incidence. Scrum and tackle in rugby and tackling in American football account for the majority of CCSIs in each respective sport.This article is freely available via Open Access. Click on the Additional link above to access the full-text via the publisher's site.Published (Open Access