A scoping review comparing two common surgical approaches to the hip for hemiarthroplasty

This is the final version. Available from the publisher via the DOI in this record.Background: Hemiarthroplasty for hip fracture is a common surgical procedure. A number of distinct approaches are used to access the hip joint. The most commonly used are the direct lateral approach (DLA), and the posterior approach (PA). Internationally there is little consensus on which of these approaches to use. Current guidance is based on a limited selection of evidence and choice of approach is frequently based on surgeon preference. Historically, recommendations have been made based on dislocation rates. In light of technical advancements and greater recognition of patient priorities, outcomes such as post-operative function and pain may be considered more important in the modern context. The aim of this scoping review was to summarise the literature pertaining to the comparison of common surgical approaches to the hip for hemiarthroplasty. Methods: A scoping review methodology was used to examine the range and nature of primary research. Using systematic methods we searched for studies that directly compared the DLA and PA. Studies reporting the following outcomes were considered; dislocation, mortality, pain, activities of daily living, functionality, health-related quality of life, length of stay, surgeon assessment of difficulty, and adverse events. MEDLINE, EMBASE and The Cochrane Library were searched. Relevant information was extracted and synthesis of the retrieved data followed a basic content analytical approach. Results: A total of 13 studies were retrieved: 12 observational studies and 1 randomised trial. The majority of studies were based at single sites. Larger observational studies using multi-site and national registry data have emerged in recent years. Reporting of technique and outcomes is inconsistent. A trend for higher rates of dislocation using the PA was observed and eight studies recommended the use of the DLA over the PA. Conclusions: This scoping review demonstrates that the existing evidence is highly heterogeneous in nature and not of a sufficient quality to inform practice recommendations. This issue would be best addressed by additional RCTs, and high quality national-level observational data. Standardisation of the recording of patient risk factors, surgical and post-operative intervention protocols, and outcomes in all study designs would strengthen the potential for valid comparison of future findings.National Institute for Health Research (NIHR

Intervention development and treatment success in UK Health Technology Assessment funded trials of physical rehabilitation: a mixed methods analysis

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: No data are available.Objectives Physical rehabilitation is a complex process, and trials of rehabilitation interventions are increasing in number but often report null results. This study aimed to establish treatment success rates in physical rehabilitation trials funded by the National Institute of Health Research Health Technology Assessment (NIHR HTA) programme and examine any relationship between treatment success and the quality of intervention development work undertaken. Design This is a mixed methods study. Setting This study was conducted in the UK. Methods The NIHR HTA portfolio was searched for all completed definitive randomised controlled trials of physical rehabilitation interventions from inception to July 2016. Treatment success was categorised according to criteria developed by Djulbegovic and colleagues. Detailed textual data regarding any intervention development work were extracted from trial reports and supporting publications and informed the development of quality ratings. Mixed methods integrative analysis was undertaken to explore the relationship between quantitative and qualitative data using joint displays. Results Fifteen trials were included in the review. Five reported a definitive finding, four of which were in favour of the ‘new’ intervention. Eight trials reported a true negative (no difference) outcome. Integrative analysis indicated those with lower quality intervention development work were less likely to report treatment success. Conclusions Despite much effort and funding, most physical rehabilitation trials report equivocal findings. Greater focus on high quality intervention development may reduce the likelihood of a null result in the definitive trial, alongside high quality trial methods and conduct.National Institute for Health Research (NIHR

The impact of a teaching practicum on the selves of cooperating teachers.

This study is based on the impact of a five-week teaching practicum on the selves of nine cooperating teachers who voluntarily handed over their classrooms to student teachers. Cooperating teachers in Ireland do not have an official role in either mentoring or assessing their student teachers. Because the study focused on aspects of the self that included identity, role, perspectives, relationships and emotions, I used symbolic intercationism as a theoretical framework. I decided that semi-structured interviewing was the most effective method of accessing the selves of the teachers in allowing them to articulate their experience of the practicum. The teachers were interviewed prior to, during and after the practicum. The process of literature review and data analysis was iterative in that each of these two components informed the other. Four main themes emerged: defining the situation, negotiation, perspectives and emotions.A meta-analysis of the data in relation to the theoretical framework revealed how cooperating and student teacher held competing definitions of the same situation and how cooperating teachers used a range of strategies to negotiate the meaning of the practicum. It also showed that the practicum impacted strongly on the self-identities of the teachers. A strong sense of self was evident prior to the practicum. This was followed by a period of mortification arising from an erosion of their self-identities as their role became peripheral in the classroom. In response they had to re-define the situation by assuming other roles, leading to a re-affirmation of self, gaining a better knowledge of their pupils and realising their own competence as teachers. While the focus of this study is at the micro-interactionist level, there are broader implications. Because of the emotional impact of the practicum, there is an urgent need for the teacher education institution to engage with cooperating teachers and to recognise and support them for the emotional journeys that engagement in the teaching practice involves. There are also structural implications insofar as the design and conducting of any mentoring programme should take cognisance of the self of the cooperating teacher

Sustainability Indicators When Utilising Nature for Mental Health

The MARCH Network[1], a UKRI funded national mental health research network, set out in 2018 to transform our understanding of how social, cultural and community assets enhance mental health and wellbeing, help prevent mental illness, and support those living with mental health conditions. A key objective was to support collaborative research that addressed the challenges facing mental health provision and practices in the UK. The ‘Sustainability Indicators When Utilising Nature for Mental Health’ resource is an outcome of one of the MARCH network funded research projects. This project represented a unique attempt to collate and explore sustainability-related concerns with service users and stakeholders in this rapidly growing sector. The work was particularly concerned with how these types of approaches can best achieve ethical and effective delivery for long term benefit. A key outcome of the project, The Six P Sustainability Framework, is intended for organisations utilising Nature for Mental Health. It provides a structure from which a practical set of sustainability indicators have been derived and collated into a self-assessment tool. The range of associated indicators offered in the tool can be used to review and self-assess sustainability across key domains related to the delivery of outdoor mental health interventions

‘Digital Dancing’ – “Can you see, what I feel” – An exploration of the physical ‘experience’ of dance for Parkinson’s through 3-dimensional motion analysis

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.  Background : Parkinson’s is a common, progressive, neurodegenerative movement disorder of the central nervous system. Research has consistently shown that dancing can have a positive impact on the lives of people living with Parkinson’s (PwP). PwP who dance report that current measurement of the effects fails to appreciate the multifactorial presentation of the condition as well as the biopsychosocial potential of dance holistically. Aim : To explore the feasibility of combining measurements of whole-body movement using 3-dimensional motion analysis with the lived experience of dance for PwP, to see if it is possible to ‘see (measure)’ what PwP say they ‘feel (experience)’ when dancing, in a ‘mind/body approach’ Method : Thirteen PwP and ten Carers took part in three community delivered ‘Parkinson’s Dance Science’ classes followed by focus group reflection. Three PwP wore a 3-dimensional, motion capture suit that recorded whole-body movement throughout the class and were interviewed about their experiences. Data were analysed using a ‘Convergent Parallel’ mixed methods design, mapping participant’s experiences and reflections over six biomechanical movement variables. Results : Quantitative results indicate that it is possible to use 3-dimensional motion capture to measure biomechanical change during and following dance in PwP but the amount and direction of change was different for each participant. Qualitative results showed PwP felt the methods were feasible and reported a positive immediate and long-term effect of dance in a complete ‘mind/body experience’. The sample size did not permit further analysis, but areas of development suggest it may not be the change in physical ability that is important, but more the perception of change following dance that is unique to each individual. Thus single measures of the effects of dance for PwP are likely to be insufficient when trying to understand the effect holistically. Conclusion : A ‘Convergent Parallel’ mixed methods research design, mapping the experience of dance for PwP (‘what I feel’) and their peers against biomechanical change (‘what you see’) following dance is feasible. Further research is required to develop the method with a larger sample to truly begin to understand the potential and effects of dance for PwP.NIHRSteve Brown Bursary Scheme – Dance for Parkinson’s Partnership U

Evaluation of the Antimicrobial Activity of Cationic Polymers against Mycobacteria: Toward Antitubercular Macromolecules.

Antimicrobial resistance is a global healthcare problem with a dwindling arsenal of usable drugs. Tuberculosis, caused by Mycobacterium tuberculosis, requires long-term combination therapy and multi- and totally drug resistant strains have emerged. This study reports the antibacterial activity of cationic polymers against mycobacteria, which are distinguished from other Gram-positive bacteria by their unique cell wall comprising a covalently linked mycolic acid-arabinogalactan-peptidoglycan complex (mAGP), interspersed with additional complex lipids which helps them persist in their host. The present study finds that poly(dimethylaminoethyl methacrylate) has particularly potent antimycobacterial activity and high selectivity over two Gram-negative strains. Removal of the backbone methyl group (poly(dimethylaminoethyl acrylate)) decreased antimycobacterial activity, and poly(aminoethyl methacrylate) also had no activity against mycobacteria. Hemolysis assays revealed poly(dimethylaminoethyl methacrylate) did not disrupt red blood cell membranes. Interestingly, poly(dimethylaminoethyl methacrylate) was not found to permeabilize mycobacterial membranes, as judged by dye exclusion assays, suggesting the mode of action is not simple membrane disruption, supported by electron microscopy analysis. These results demonstrate that synthetic polycations, with the correctly tuned structure are useful tools against mycobacterial infections, for which new drugs are urgently required

Using causal loop diagrams to develop evaluative research propositions: opportunities and challenges in applications to nature‐based solutions

This is the final version. Available from Wiley via the DOI in this record. Causal loop diagrams (CLDs) are often used to provide an overview of important systemic elements related to an issue, rather than to inform empirical evaluations (studies which assess changes following an intervention using observed data). We suggest that empirical evaluations may benefit from the development of systems‐informed research propositions (specific testable causal assumptions with an emphasis on feedback loops) used to guide subsequent data collection, hypothesis testing and interpretation. We describe a qualitative systems‐thinking informed approach building on preexisting CLDs, published evidence, and expert/stakeholder consultation and reflect on our experience applying this to the early stages of two nature‐based solution (NBS) evaluations. We reflect on our experience and suggest that CLDs can be usefully employed to develop systems‐informed research propositions to inform subsequent empirical evaluation. This may lead to novel policy‐relevant research propositions which differ substantially from effectiveness‐oriented (“did it work?”) research questions.European Union’s Horizon 2020European Union’s Horizon 202

Street trees and mental health: developing systems thinking-informed hypotheses using causal loop diagraming

This is the final version. Available on open access from the Resilience Alliance via the DOI in this recordData availability: The data that support the findings of this study are openly available in the Appendix.We considered the relationship between street trees and mental health with the aim of developing systems thinking-informed hypotheses to improve the implementation and evaluation of this popular nature-based solution (NBS). We integrated qualitative and quantitative evidence using causal loop diagraming (CLD), and then further analyzed and extended these diagrams with the aid of systems archetypes to identify key system structures. From these CLDs, we identified three systems thinking-informed hypotheses: 1) although there are many ways in which street trees may improve mental health, tree health is critical in realizing many of these benefits and minimizing dis-benefits; 2) communities which have benefited from street trees in the past are more likely to be able to advocate for additional trees, further entrenching historical inequities in street tree distribution; and 3) efforts to address these inequities through new tree planting initiatives may ultimately fail or even exacerbate existing challenges if they do not include sustained resources for tree maintenance, with direct and indirect impacts on inequities in mental health. Using a systems thinking lens was a useful way to deeply consider a purported but under-theorized co-benefit of a popular nature-based solution and identify policy-relevant hypotheses to guide future research.European Union Horizon 202

Osmium–arene complexes with high potency towards Mycobacterium tuberculosis

The treatment of tuberculosis (TB) poses a major challenge as frontline therapeutic agents become increasingly ineffective with the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). To combat this global health problem, new antitubercular agents with novel modes of action are needed. We have screened a close family of 17 organometallic half-sandwich Os(II) complexes [(arene)Os(phenyl-azo/imino-pyridine)(Cl/I)]+Y– containing various arenes (p-cymene, biphenyl, or terphenyl), and NMe2, F, Cl, or Br phenyl or pyridyl substituents, for activity towards Mtb in comparison with normal human lung cells (MRC5). In general, complexes with a monodentate iodido ligand were more potent than chlorido complexes, and the five most potent iodido complexes (MIC 1.25–2.5 µM) have an electron-donating Me2N or OH substituent on the phenyl ring. As expected, the counter anion Y (PF6–, Cl–, I–) had little effect on the activity. The pattern of potency of the complexes towards Mtb is similar to that towards human cells, perhaps because in both cases intracellular thiols are likely to be involved in their activation and their redox mechanism of action. The most active complex against Mtb is the p-cymene Os(II) NMe2-phenyl-azopyridine iodido complex (2), a relatively inert complex that also exhibits potent activity towards cancer cells. The uptake of Os from complex 2 by Mtb is rapid and peaks after 6 h, with temperature-dependence studies suggesting a major role for active transport. Significance to Metallomics Antimicrobial resistance is a global health problem. New advances are urgently needed in the discovery of new antibiotics with novel mechanisms of action. Half-sandwich organometallic complexes offer a versatile platform for drug design. We show that with an appropriate choice of the arene, an N,N-chelated ligand, and monodentate ligand, half-sandwich organo–osmium(II) complexes can exhibit potent activity towards Mycobacterium tuberculosis (Mtb), the leading cause of death from a single infectious agent. The patterns of activity of the 17 azo- and imino-pyridine complexes studied here towards Mtb and normal lung cells suggest a common redox mechanism of action involving intracellular thiols

Piperidinols that show anti-tubercular activity as inhibitors of arylamine N-acetyltransferase: an essential enzyme for mycobacterial survival inside macrophages

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3-16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs