Open Access and the REF: Issues and Potential Solutions Workshop

This report provides a summary of the discussion and findings of the Open Access and the REF: Issues and Potential Solutions workshop held as part of the End-to-End Project. The workshop was highly interactive and feedback received indicated it was considered an excellent event, and that it was vital and useful to bring together various key stakeholders to discuss problems and procedures and develop ideas

Open Access and the REF: Issues and Potential Solutions Workshop: Executive Summary

This report provides a summary of the discussion and findings of the Open Access and the REF: Issues and Potential Solutions workshop held as part of the End-to-End Project. The workshop was highly interactive and feedback received indicated it was considered an excellent event, and that it was vital and useful to bring together various key stakeholders to discuss problems and procedures and develop ideas

Synthesis of Oxetane- and Azetidine-Containing Spirocycles Related to the 2,5-Diketopiperazine Framework

A simple two-step sequence is used to efficiently make novel spirocyclic analogues of the diketopiperazine nucleus. Conjugate addition of chiral α-amino esters to nitroalkenes, generated from oxetan-3-one or N-Boc-azetidin-3-one, followed by nitro group reduction provides, after spontaneous cyclization, the spirocycles in good overall yields. These rigid scaffolds can be functionalized by selective N-alkylations as well as by carbonyl reduction to the corresponding piperazines

Synthesis of oxetane- and azetidine-containing spirocycles related to the 2,5-diketopiperazine framework

A simple two-step sequence is used to efficiently make novel spirocyclic analogues of the diketopiperazine nucleus. Conjugate addition of chiral α-amino esters to nitroalkenes, generated from oxetan-3-one or N-Boc-azetidin-3-one, followed by nitro group reduction provides, after spontaneous cyclization, the spirocycles in good overall yields. These rigid scaffolds can be functionalized by selective N-alkylations as well as by carbonyl reduction to the corresponding piperazines

Understanding the training and education needs of homecare workers supporting people with dementia and cancer: a systematic review of reviews

Many people with dementia, supported by family carers, prefer to live at home and may rely on homecare support services. People with dementia are also often living with multimorbidities, including cancer. The main risk factor for both cancer and dementia is age and the number of people living with dementia and cancer likely to rise. Upskilling the social care workforce to facilitate more complex care is central to national workforce strategies and challenges. Training and education development must also respond to the key requirements of a homecare workforce experiencing financial, recruitment and retention difficulties. This systematic review of reviews provides an overview of dementia and cancer training and education accessible to the homecare workforce. Findings reveal there is a diverse range of training and education available, with mixed evidence of effectiveness. Key barriers and facilitators to effective training and education are identified in order to inform future training, education and learning development for the homecare workforce supporting people with dementia and cancer

Platinum(IV)-azido monocarboxylato complexes are photocytotoxic under irradiation with visible light

Complexes trans,trans,trans-[Pt(N-3)(2)(OH)(OCOR)(py)(2)] where py = pyridine and where OCOR = succinate (1); 4-oxo-4-propoxybutanoate (2) and N-methylisatoate (3) have been synthesized by derivation of trans, trans,trans-[Pt(OH)(2)(N-3)(2)(py)(2)] (4) and characterised by NMR and EPR spectroscopy, ESI-MS and X-ray crystallography. Irradiation of 1-3 with green (517 nm) light initiated photoreduction to Pt(II) and release of the axial ligands at a 3-fold faster rate than for 4. TD-DFT calculations showed dissociative transitions at longer wavelengths for 1 compared to 4. Complexes 1 and 2 showed greater photocytotoxicity than 4 when irradiated with 420 nm light (A2780 cell line IC50 values: 2.7 and 3.7 mu M) and complex 2 was particularly active towards the cisplatin-resistant cell line A2780cis (IC50 3.7 mu M). Unlike 4, complexes 1-3 were phototoxic under green light irradiation (517 nm), with minimal toxicity in the dark. A pK(a)(H2O) of 5.13 for the free carboxylate group was determined for 1, corresponding to an overall negative charge during biological experiments, which crucially, did not appear to impede cellular accumulation and photocytotoxicity.NF thanks the Wellcome Trust (201406/Z/16/Z); Cancer Research UK (CR-UK) grant number C5255/A18085 through the Cancer Research UK Oxford Centre and the John Fell Fund for funding. NF thanks Profs. Stephen Faulkner for support. PJS and NF thank the EPSRC (for grant EP/P030572/1 and studentship for ES), PJS also thanks the ERC (grant 247450). L. S. performed this work under the Severo Ochoa Centres of Excellence Programme run by the Spanish State Research Agency, grant no. CEX2018-000867-S (DIPC). L. S. also thanks the Spanish Multi-MetDrugs network (RED2018-102471-T) for fruitful discussio

Reporting stAndards for research in PedIatric Dentistry (RAPID):a development protocol

Reporting guidelines can improve the quality of reports of research findings. Some specialities in health care however require guidance on areas that are not captured within the existing guidelines, and this is the case for Paediatric Dentistry where no such standards are available to guide the reporting of different types of study designs. The ‘Reporting stAndards for research in PedIatric Dentistry’ (RAPID) group aims to address this need by developing guidelines on reporting elements of research of particular relevance to Paediatric Dentistry. The development of RAPID guidelines will involve a five‐phase process including a Delphi study, which is an explicit consensus development method designed and implemented in accordance with the Guidance on Conducting and REporting DElphi Studies. The guideline development process will be overseen by an Executive Group. Themes specific to areas in Paediatric Dentistry will be selected, and items to be included under each theme will be identified by members of the Executive Group reviewing at least five reports of experimental and analytical study types using existing reporting guidelines. For the Delphi study, the Executive Group will identify an international multidisciplinary RAPID Delphi Group (RDG) of approximately 60 participants including academics, Paediatric Dentists, parents, and other stakeholders. Each item will be evaluated by RDG on clarity using a dichotomous scale (‘well phrased’ or ‘needs revision’) and on suitability for inclusion in the Delphi study using a 9‐point Likert scale (1 = ‘definitely not include’ to 9 = ‘definitely include’). The items will then be included in an online Delphi study of up to four rounds, with participants invited from stakeholder groups across Paediatric Dentistry. Items scored 7 or above by at least 80% of respondents will be included in the checklist and further discussed in a face‐to‐face Delphi consensus meeting. Following this, the Executive Group will finalize the RAPID guidelines. The guidelines will be published in peer‐reviewed scientific journals and disseminated at scientific meetings and conferences. All the outputs from this project will be made freely available on the RAPID website: www.rapid-statement.org

Reporting stAndards for research in PedIatric Dentistry (RAPID):an expert consensus-based statement

Abstract Background Reporting guidelines for different study designs are currently available to report studies with accuracy and transparency. There is a need to develop supplementary guideline items that are specific to areas within Pediatric Dentistry. This study aims to develop Reporting stAndards for research in PedIatric Dentistry (RAPID) guidelines using a pre-defined expert consensus-based Delphi process. Methods The development of the RAPID guidelines was based on the Guidance for Developers of Health Research Reporting Guidelines. Following a comprehensive search of the literature, the Executive Group identified ten themes in Pediatric Dentistry and compiled a draft checklist of items under each theme. The themes were categorized as: General, Oral Medicine, Pathology and Radiology, Children with Special Health Care Needs, Sedation and Hospital Dentistry, Behavior Guidance, Dental Caries, Preventive and Restorative Dentistry, Pulp Therapy, Traumatology, and Interceptive Orthodontics. A RAPID Delphi Group (RDG) was formed comprising of 69 members from 15 countries across six continents. Items were scored using a 9-point rating Likert scale. Items achieving a score of seven and above, marked by at least 70% of RDG members were accepted into the RAPID checklist items. Weighted mean scores were calculated for each item. Statistical significance was set at p < 0.05 and one-way ANOVA was used to calculate the difference in the weighted mean scores between the themes. Results The final RAPID checklist comprised of 128 items that were finalized and approved by the RDG members in the online consensus meeting. The percentage for high scores (scores 7 to 9) ranged from 69.57 to 100% for individual items. The overall weighted mean score of the final items ranged from 7.51 to 8.28 (out of 9) and the difference was statistically significant between the themes (p < 0.05). Conclusions The RAPID statement provides guidance to researchers, authors, reviewers and editors, to ensure that all elements relevant to particular studies are adequately reported

Right at home: living with dementia and multi-morbidities

Dementia is recognised as the biggest health crisis of our time in terms of high personal and social costs and wider impact on health and social care systems. Increases in people living with dementia and multimorbidities presents critical challenges for homecare worldwide. Healthcare systems struggle to provide adequate home-care services, delivering limited care restricted to a single-condition focus. This study explored the experiences and expectations of homecare from the multiple perspectives of people living with dementia and multimorbidities and homecare workers providing support. Findings draw from qualitative semi-structured interviews with people with dementia (n=2), their partners (n=2), other partners or family carers (n=6) and homecare workers (n=26). Three themes are identified: (a) the preference for and value of home; (b) inadequate homecare provision and enhanced care-burden; (c) limited training and education. Despite continued calls for homecare investment, the focus on reduction in costs hides key questions and further dialogue required exploring how people with dementia can be supported to live independently and flourish at-home. This study considers these complex experiences and care requirements through the prism of disability and human rights frameworks. This paper concludes with consideration of more recent human social rights debate. We critically discuss what this may mean for people living with dementia and consider the implications for corequisite policy development to optimise available homecare support. Keywords: dementia, multimorbidities, homecare, independent-living, social right

Metallohelices that kill Gram-negative pathogens using intracellular antimicrobial peptide pathways

A range of new water-compatible optically pure metallohelices – made by self-assembly of simple non-peptidic organic components around Fe ions – exhibit similar architecture to some natural cationic antimicrobial peptides (CAMPs) and are found to have high, structure-dependent activity against bacteria, including clinically problematic Gram-negative pathogens. A key compound is shown to freely enter rapidly dividing E. coli cells without significant membrane disruption, and localise in distinct foci near the poles. Several related observations of CAMP-like mechanisms are made via biophysical measurements, whole genome sequencing of tolerance mutants and transcriptomic analysis. These include: high selectivity for binding of G-quadruplex DNA over double stranded DNA; inhibition of both DNA gyrase and topoisomerase I in vitro; curing of a plasmid that contributes to the very high virulence of the E. coli strain used; activation of various two-component sensor/regulator and acid response pathways; and subsequent attempts by the cell to lower the net negative charge of the surface. This impact of the compound on multiple structures and pathways corresponds with our inability to isolate fully resistant mutant strains, and supports the idea that CAMP-inspired chemical scaffolds are a realistic approach for antimicrobial drug discovery, without the practical barriers to development that are associated with natural CAMPS