The AgeWell study of behavior change to promote health and wellbeing in later life: study protocol for a randomized controlled trial.

This is the final version of the article. Available from Biomed Central via the DOI in this record.BACKGROUND: Lifestyle factors playing a role in the development of late-life disability may be modifiable. There is a need for robust evidence about the potential for prevention of disability through behavior change interventions. METHODS/DESIGN: This feasibility study involves the development, implementation and initial testing of a behavior change intervention in a naturalistic setting. A small-scale randomized controlled trial (RCT) will investigate the implementation of a goal-setting intervention aimed at promoting behavior change in the domains of physical and cognitive activity in the context of a community resource center for over-50s. Healthy older participants attending the center (n = 75) will be randomized to one of three conditions: control (an interview involving a general discussion about the center); goal-setting (an interview involving identification of up to five personal goals in the domains of physical activity, cognitive activity, diet and health, and social engagement); or goal-setting with mentoring (the goal-setting interview followed by bi-monthly telephone mentoring). All participants will be reassessed after 12 months. Primary outcomes are levels of physical and cognitive activity. Secondary outcomes address psychosocial (self-efficacy, mood, quality of life), cognitive (memory and executive function), and physical fitness (functional and metabolic) domains. Cost-effectiveness will also be examined. DISCUSSION: This study will provide information about the feasibility of a community-based lifestyle intervention model for over-50s and of the implementation of a goal-setting intervention for behavior change, together with initial evidence about the short-term effects of goal-setting on behavior. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30080637 (http://www.controlled-trials.com).This study is funded by the Medical Research Council (UK) through the Lifelong Health and Well-being programme. The funder plays no role in the design of the study, in the collection, analysis and interpretation of data, or in the decision to submit the manuscript for publication. Professors Carol Brayne, Martin Knapp, Mike Martin, and Robin Morris advised on and critically reviewed the study proposal. John Clifford Jones, Maldwyn Roberts, and Stephen Williams of Age Cymru Gwynedd a Môn are responsible for setting up and managing the Nefyn AgeWell Centre. Julie Nixon is conducting the interviews and Jennifer Cooney is contributing to data collection. Anne Krayer will collect and analyze qualitative data for the biographical narrative analysis. Blood samples are analyzed by NHS laboratory staff at Ysbyty Gwynedd, Bangor. Sources of funding for each author are as follows: LC: Higher Education Funding Council for Wales; JVH: National Health Service/ Welsh Assembly Government; IRJ: Higher Education Funding Council for Wales; SMN: Medical Research Council grant; JT: Higher Education Funding Council for Wales; CJW: Welsh Assembly Government

Awareness and perceptions of Long COVID among people in the REACT programme: early insights from a pilot interview study

BACKGROUND: Long COVID is a patient-made term describing new or persistent symptoms experienced following SARS-CoV-2 infection. The Real-time Assessment of Community Transmission-Long COVID (REACT-LC) study aims to understand variation in experiences following infection, and to identify biological, social, and environmental factors associated with Long COVID. We undertook a pilot interview study to inform the design, recruitment approach, and topic guide for the REACT-LC qualitative study. We sought to gain initial insights into the experience and attribution of new or persistent symptoms and the awareness or perceived applicability of the term Long COVID. METHODS: People were invited to REACT-LC assessment centres if they had taken part in REACT, a random community-based prevalence study, and had a documented history of SARS-CoV-2 infection. We invited people from REACT-LC assessment centres who had reported experiencing persistent symptoms for more than 12 weeks to take part in an interview. We conducted face to face and online semi-structured interviews which were transcribed and analysed using Thematic Analysis. RESULTS: We interviewed 13 participants (6 female, 7 male, median age 31). Participants reported a wide variation in both new and persistent symptoms which were often fluctuating or unpredictable in nature. Some participants were confident about the link between their persistent symptoms and COVID-19; however, others were unclear about the underlying cause of symptoms or felt that the impact of public health measures (such as lockdowns) played a role. We found differences in awareness and perceived applicability of the term Long COVID. CONCLUSION: This pilot has informed the design, recruitment approach and topic guide for our qualitative study. It offers preliminary insights into the varied experiences of people living with persistent symptoms including differences in symptom attribution and perceived applicability of the term Long COVID. This variation shows the value of recruiting from a nationally representative sample of participants who are experiencing persistent symptoms

The Agewell trial: a pilot randomised controlled trial of a behaviour change intervention to promote healthy ageing and reduce risk of dementia in later life.

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: Lifestyle factors represent prime targets for behaviour change interventions to promote healthy ageing and reduce dementia risk. We evaluated a goal-setting intervention aimed at promoting increased cognitive and physical activity and improving mental and physical fitness, diet and health. METHODS: This was a pilot randomised controlled trial designed to guide planning for a larger-scale investigation, provide preliminary evidence regarding efficacy, and explore feasibility and acceptability. Primary outcomes were engagement in physical and cognitive activity. Participants aged over 50 living independently in the community were recruited through a community Agewell Centre. Following baseline assessment participants were randomly allocated to one of three conditions: control (IC) had an interview in which information about activities and health was discussed; goal-setting (GS n = 24) had an interview in which they set behaviour change goals relating to physical, cognitive and social activity, health and nutrition; and goal-setting with mentoring (GM, n = 24) had the goal-setting interview followed by bi-monthly telephone mentoring. Participants and researchers were blinded to group assignment. Participants were reassessed after 12 months. RESULTS: Seventy-five participants were randomised (IC n = 27, GS n = 24, GM n = 24). At 12-month follow-up, the two goal-setting groups, taken together (GS n = 21, GM n = 22), increased their level of physical (effect size 0.37) and cognitive (effect size 0.15) activity relative to controls (IC n = 27). In secondary outcomes, the two goal-setting groups taken together achieved additional benefits compared to control (effect sizes ≥ 0.2) in memory, executive function, cholesterol level, aerobic capacity, flexibility, balance, grip strength, and agility. Adding follow-up mentoring produced further benefits compared to goal-setting alone (effect sizes ≥ 0.2) in physical activity, body composition, global cognition and memory, but not in other domains. Implementation of the recruitment procedure, assessment and intervention was found to be feasible and the approach taken was acceptable to participants, with no adverse effects. CONCLUSIONS: A brief, low-cost goal-setting intervention is feasible and acceptable, and has the potential to achieve increased activity engagement. TRIAL REGISTRATION: Current Controlled Trials ISRCTN30080637.This trial was funded by Medical Research Council grant G1001888/1 to LC, JVH, IRJ, JT and CJW. The funding body played no role in the design of the study, in collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the manuscript for publication. We acknowledge the support of Age Cymru Gwynedd a Môn including John Clifford Jones, Maldwyn Roberts, Stephen Williams and Mici Plwm. We would like to thank Sharman Harris and Catrin Searell, Department of Clinical Chemistry, Ysbyty Gwynedd, Bangor, the volunteers at the Nefyn Agewell Centre, and all the members of the Nefyn Agewell Centre, and especially all those who took part in the research project. We are grateful to Professor Carol Brayne, Cambridge University, Professor Martin Knapp, London School of Economics, Professor Mike Martin, Zürich University, and Professor Robin Morris, King’s College London Institute of Psychiatry, who acted as external advisors to the project. Special thanks go to Andrew Brand for statistical advice

Metabolic flexibility as a major predictor of spatial distribution in microbial communities

A better understand the ecology of microbes and their role in the global ecosystem could be achieved if traditional ecological theories can be applied to microbes. In ecology organisms are defined as specialists or generalists according to the breadth of their niche. Spatial distribution is often used as a proxy measure of niche breadth; generalists have broad niches and a wide spatial distribution and specialists a narrow niche and spatial distribution. Previous studies suggest that microbial distribution patterns are contrary to this idea; a microbial generalist genus (Desulfobulbus) has a limited spatial distribution while a specialist genus (Methanosaeta) has a cosmopolitan distribution. Therefore, we hypothesise that this counter-intuitive distribution within generalist and specialist microbial genera is a common microbial characteristic. Using molecular fingerprinting the distribution of four microbial genera, two generalists, Desulfobulbus and the methanogenic archaea Methanosarcina, and two specialists, Methanosaeta and the sulfate-reducing bacteria Desulfobacter were analysed in sediment samples from along a UK estuary. Detected genotypes of both generalist genera showed a distinct spatial distribution, significantly correlated with geographic distance between sites. Genotypes of both specialist genera showed no significant differential spatial distribution. These data support the hypothesis that the spatial distribution of specialist and generalist microbes does not match that seen with specialist and generalist large organisms. It may be that generalist microbes, while having a wider potential niche, are constrained, possibly by intrageneric competition, to exploit only a small part of that potential niche while specialists, with far fewer constraints to their niche, are more capable of filling their potential niche more effectively, perhaps by avoiding intrageneric competition. We suggest that these counter-intuitive distribution patterns may be a common feature of microbes in general and represent a distinct microbial principle in ecology, which is a real challenge if we are to develop a truly inclusive ecology

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations

Validation of a digital photographic method for assessment of dietary quality of school lunch sandwiches brought from home.

Background: It is a challenge to assess children's dietary intake. The digital photographic method (DPM) may be an objective method that can overcome some of these challenges. Objective: The aim of this study was to evaluate the validity and reliability of a DPM to assess the quality of dietary intake from school lunch sandwiches brought from home among children aged 7–13 years. Design: School lunch sandwiches (n=191) were prepared to represent randomly selected school lunch sandwiches from a large database. All components were weighed to provide an objective measure of the composition. The lunches were photographed using a standardised DPM. From the digital images, the dietary components were estimated by a trained image analyst using weights or household measures and the dietary quality was assessed using a validated Meal Index of Dietary Quality (Meal IQ). The dietary components and the Meal IQ obtained from the digital images were validated against the objective weighed foods of the school lunch sandwiches. To determine interrater reliability, the digital images were evaluated by a second image analyst. Results: Correlation coefficients between the DPM and the weighed foods ranged from 0.89 to 0.97. The proportion of meals classified in the same or an adjacent quartile ranged from 98% (starch) to 100% (fruits, vegetables, fish, whole grain, and Meal IQ). There was no statistical difference between fish, fat, starch, whole grains, and Meal IQ using the two methods. Differences were found for fruits and vegetables; Bland–Altman analyses showed a tendency to underestimate high amounts of these variables using the DPM. For interrater reliability, kappa statistics ranged from 0.59 to 0.82 across the dietary components and Meal IQ. Conclusions: The standardised DPM is a valid and reliable method for assessing the dietary quality of school lunch sandwiches brought from home

Improved eradication of Clostridium difficile spores from toilets of hospitalized patients using an accelerated hydrogen peroxide as the cleaning agent

<p>Abstract</p> <p>Background</p> <p><it>C. difficle </it>spores in the environment of patients with <it>C. difficile </it>associated disease (CDAD) are difficult to eliminate. Bleach (5000 ppm) has been advocated as an effective disinfectant for the environmental surfaces of patients with CDAD. Few alternatives to bleach for non-outbreak conditions have been evaluated in controlled healthcare studies.</p> <p>Methods</p> <p>This study was a prospective clinical comparison during non-outbreak conditions of the efficacy of an accelerated hydrogen peroxide cleaner (0.5% AHP) to the currently used stabilized hydrogen peroxide cleaner (0.05% SHP at manufacturer recommended use-dilution) with respect to spore removal from toilets in a tertiary care facility. The toilets used by patients who had diarrhea with and without <it>C. difficile </it>associated disease (CDAD) were cultured for <it>C. difficile </it>and were monitored using an ultraviolet mark (UVM) to assess cleaning compliance on a daily basis 5 days per week. A total of 243 patients and 714 samples were analysed. The culture results were included in the analysis only if the UVM audit from the same day confirmed that the toilet had been cleaned.</p> <p>Results</p> <p>Our data demonstrated that the efficacy of spore killing is formulation specific and cannot be generalized. The Oxivir_TB^®AHP formulation resulted in statistically significantly (p = 0.0023) lower levels of toxigenic <it>C. difficile </it>spores in toilets of patients with CDAD compared to the SHP formulation that was routinely being used (28% vs 45% culture positive). The background level of toxigenic <it>C. difficile </it>spores was 10% in toilets of patients with diarrhea not due to CDAD. The UVM audit indicated that despite the enhanced twice-daily cleaning protocol for CDAD patients cleaning was not achieved on approximately 30 - 40% of the days tested.</p> <p>Conclusion</p> <p>Our data indicate that the AHP formulation evaluated that has some sporicidal activity was significantly better than the currently used SHP formulation. This AHP formulation provides a one-step process that significantly lowers the <it>C. difficile </it>spore level in toilets during non-outbreak conditions without the workplace safety concerns associated with 5000 ppm bleach.</p

Clinical characteristics associated with the prescribing of SSRI medication in adolescents with major unipolar depression.

Unipolar major depressions (MD) emerge markedly during adolescence. National Institute for Health and Care Excellence (NICE) UK recommends psychological therapies, with accompanying selective serotonin reuptake inhibitors (SSRIs) prescribed in severe cases only. Here, we seek to determine the extent and rationale of SSRI prescribing in adolescent MD before entering a randomised clinical trial. SSRI prescribing, together with their clinical characteristics was determined in 465 adolescent patients with MD prior to receiving a standardised psychological therapy as part of the Improving mood with psychoanalytic and cognitive therapies (IMPACT) clinical trial. Overall, 88 (19 %) had been prescribed antidepressants prior to psychological treatment. The clinical correlates varied by gender: respectively, depression severity in boys and self-harming behaviours in girls. Prescribing also differed between clinical research centres. Medical practitioners consider severity of depression in boys as an indicator for antidepressant prescribing. Self-injury in girls appears to be utilised as a prescribing aid which is inconsistent with past and current revised UK NICE guidelines.RCT Study supported by a grant to IMG (Chief Investigator) from the NIHR-HTA (trial number ISRCTN83033550, grant number 06/05/01).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Springer

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Hereditary sensory neuropathy type I

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease