Distinct neuroinflammatory signatures exist across genetic and sporadic ALS cohorts

Acknowledgments This research was funded in part by the Wellcome Trust (108890/Z/15/Z) to OMR, a Pathological Society and Jean Shanks Foundation grant (JSPS CLSG 202002) to JMG and JOS, an NIH grant (5-R01-NS127186-02) to JMG, FMW, and JOS, a Motor Neuron Disease (MND) Scotland grant to JMG and CRS (2021/MNDS/RP/8440GREG), and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (215454/Z/19/Z) to CRS. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work would not be possible without the resources of the Edinburgh Brain Bank. The authors declare no conflicts of interest.Preprin

Distinct neuroinflammatory signatures exist across genetic and sporadic amyotrophic lateral sclerosis cohorts

Acknowledgements This work would not be possible without the resources of the Edinburgh Brain Bank, and the tissue donors and their families. Funding This research was funded in part by the Wellcome Trust (108890/Z/15/Z) to O.M.R., a Pathological Society of Great Britain & Ireland and Jean Shanks Foundation grant (JSPS CLSG 202002) to J.M.G. and J.O., a National Institutes of Health (NIH) grant (5-R01-NS127186-02) to J.M.G., F.M.W., and J.O., a Motor Neuron Disease (MND) Scotland grant to J.M.G. and C.R.S. (2021/MNDS/RP/8440GREG), and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (215454/Z/19/Z) to C.R.S.Peer reviewedPublisher PD

Random forest modelling demonstrates microglial and protein misfolding features to be key phenotypic markers in C9orf72 ‐ALS

Acknowledgments We gratefully acknowledge Professor Tom Gillingwater for his helpful comments and support. This work would not have been possible without the resources of the Edinburgh Brain Bank, and the people with ALS and their families who have generously donated tissue. This research was funded in part by a studentship from the Wellcome Trust (108890/Z/15/Z) to OMR and MDES, a Pathological Society and Jean Shanks foundation grant (217CHA R46564) to JMG and JO, and a Sir Henry Dale fellowship jointly funded by the Wellcome Trust and the Royal Society (215454/Z/19/Z) to CRS.Peer reviewedPublisher PD

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

A National Network of Safe Havens:A Scottish Perspective

For over a decade, Scotland has implemented and operationalized a system of Safe Havens, which provides secure analytics platforms for researchers to access linked, deidentified electronic health records (EHRs) while managing the risk of unauthorized reidentification. In this paper, a perspective is provided on the state-of-the-art Scottish Safe Haven network, including its evolution, to define the key activities required to scale the Scottish Safe Haven network’s capability to facilitate research and health care improvement initiatives. A set of processes related to EHR data and their delivery in Scotland have been discussed. An interview with each Safe Haven was conducted to understand their services in detail, as well as their commonalities. The results show how Safe Havens in Scotland have protected privacy while facilitating the reuse of the EHR data. This study provides a common definition of a Safe Haven and promotes a consistent understanding among the Scottish Safe Haven network and the clinical and academic research community. We conclude by identifying areas where efficiencies across the network can be made to meet the needs of population-level studies at scale

Chronic disease and falls in community-dwelling Canadians over 65 years old: a population-based study exploring associations with number and pattern of chronic conditions

Abstract Background Falls and chronic disease are both important health issues in older adults. The objectives of this study were to quantify the prevalence of falls and multi-morbidity (≥2 chronic conditions) in Canadian older adults; examine associations between falls and number of chronic conditions; and explore whether certain patterns of chronic disease were associated with a greater risk of falling. Methods Data were derived from the Canadian Community Health Survey- Healthy Aging. Primary outcomes from 16,357 community-dwelling adults aged 65 years and over were self-reported falls in the previous 12 months and presence of 13 chronic conditions. Prevalence estimates were calculated with normalized sampling weights, and hierarchical cluster analysis was used to identify clusters based on chronic condition patterns, and tested for association to falls with logistic regression. Results Overall prevalence of falling and multi-morbidity were 19.8% and 62.0% respectively. Fall risk was significantly greater in individuals with one, two, four, five and six or more chronic conditions relative to those with none (all p < 0.05). A seven-cluster model was selected, including groups with low prevalence of chronic disease, or high prevalence of hypertension and arthritis, visual impairment, hypertension, chronic obstructive pulmonary disease (COPD), diabetes, or heart disease and hypertension. Only the hypertension cluster (Odds Ratio [OR] = 1.2) and COPD cluster (OR = 1.6) were significantly associated with increased falls relative to the low prevalence group. Conclusions Both the number and pattern of chronic conditions were related to falls. COPD emerged as a significant predictor of falls despite affecting a smaller proportion of respondents. Continued study is warranted to verify this association and determine how to incorporate consideration of chronic disease and multi-morbidity into fall risk assessments

Clinical balance assessment: perceptions of commonly-used standardized measures and current practices among physiotherapists in Ontario, Canada

Abstract Background Balance impairment is common in multiple clinical populations, and comprehensive assessment is important for identifying impairments, planning individualized treatment programs, and evaluating change over time. However, little information is available regarding whether clinicians who treat balance are satisfied with existing assessment tools. In 2010 we conducted a cross-sectional survey of balance assessment practices among physiotherapists in Ontario, Canada, and reported on the use of standardized balance measures (Sibley et al. 2011 Physical Therapy; 91: 1583-91). The purpose of this study was to analyse additional survey data and i) evaluate satisfaction with current balance assessment practices and standardized measures among physiotherapists who treat adult or geriatric populations with balance impairment, and ii) identify factors associated with satisfaction. Methods The questionnaire was distributed to 1000 practicing physiotherapists. This analysis focuses on questions in which respondents were asked to rate their general perceptions about balance assessment, the perceived utility of individual standardized balance measures, whether they wanted to improve balance assessment practices, and why. Data were summarized with descriptive statistics and utility of individual measures was compared across clinical practice areas (orthopaedic, neurological, geriatric or general rehabilitation). Results The questionnaire was completed by 369 respondents, of which 43.4% of respondents agreed that existing standardized measures of balance meet their needs. In ratings of individual measures, the Single Leg Stance test and Berg Balance Scale were perceived as useful for clinical decision-making and evaluating change over time by over 70% of respondents, and the Timed Up-and-Go test was perceived as useful for decision-making by 56.9% of respondents and useful for evaluating change over time by 62.9% of respondents, but there were significant differences across practice groups. Seventy-nine percent of respondents wanted to improve their assessments, identifying individual, environmental and measure-specific barriers. The most common barriers were lack of time and knowledge. Conclusions This study offers new information on issues affecting the evaluation of balance in clinical settings from a broad sample of physiotherapists. Continued work to address barriers by specific practice area will be critical for the success of any intervention attempting to implement optimal balance assessment practices in the clinical setting

‘Doing’ or ‘using’ intersectionality? Opportunities and challenges in incorporating intersectionality into knowledge translation theory and practice

Abstract Intersectionality is a widely adopted theoretical orientation in the field of women and gender studies. Intersectionality comes from the work of black feminist scholars and activists. Intersectionality argues identities such as gender, race, sexuality, and other markers of difference intersect and reflect large social structures of oppression and privilege, such as sexism, racism, and heteronormativity. The reach of intersectionality now extends to the fields of public health and knowledge translation. Knowledge translation (KT) is a field of study and practice that aims to synthesize and evaluate research into an evidence base and move that evidence into health care practice. There have been increasing calls to bring gender and other social issues into the field of KT. Yet, as scholars outline, there are few guidelines for incorporating the principles of intersectionality into empirical research. An interdisciplinary, team-based, national health research project in Canada aimed to bring an intersectional lens to the field of knowledge translation. This paper reports on key moments and resulting tensions we experienced through the project, which reflect debates in intersectionality: discomfort with social justice, disciplinary divides, and tokenism. We consider how our project advances intersectionality practice and suggests recommendations for using intersectionality in health research contexts. We argue that while we encountered many challenges, our process and the resulting co-created tools can serve as a valuable starting point and example of how intersectionality can transform fields and practices