The Influence of High-Impact Exercise on Cortical and Trabecular Bone Mineral Content and 3D Distribution Across the Proximal Femur in Older Men: A Randomized Controlled Unilateral Intervention.

Regular exercisers have lower fracture risk, despite modest effects of exercise on bone mineral content (BMC). Exercise may produce localized cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical CT. Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localized cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualized and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty-four men aged mean (SD) 70 (4) years exercised for 12-months, attending 92% of prescribed sessions. In traditional regions of interest, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whereas femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; p 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; p 12% at the anterior femoral neck, trochanter, and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise-induced changes were localized rather than being evenly distributed across the proximal femur.This research was financially supported by a National Osteoporosis Innovative Award, Medical Research Council UK Interdisciplinary Bridging Award, and a Loughborough University Scholarship. KESP acknowledges support of the Cambridge NIHR Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/jbmr.249

The influence of high impact exercise on cortical and trabecular bone mineral content and 3D distribution across the proximal femur in older men: a randomised controlled unilateral intervention

Regular exercisers have lower fracture risk, despite modest effects of exercise on BMC. Exercise may produce localised cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical computed tomography (CT). Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localised cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualised and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty-four men aged 70 (4) years exercised for 12-months, attending 92% of prescribed sessions. In traditional ROIs, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whilst femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; P 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; P 12% at the anterior femoral neck, trochanter and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise-induced changes were localised rather than being evenly distributed across the proximal femur. This article is protected by copyright. All rights reserved

A Smartphone App to Reduce Sugar-Sweetened Beverage Consumption Among Young Adults in Australian Remote Indigenous Communities: Design, Formative Evaluation and User-Testing

©Emma Tonkin, Lauren Jeffs, Thomas Philip Wycherley, Carol Maher, Ross Smith, Jonathon Hart, Beau Cubillo, Julie Brimblecombe. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 12.12.2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR mhealth and uhealth, is properly cited. The complete bibliographic information, a link to the original publication on http://mhealth.jmir.org/, as well as this copyright and license information must be included.Background: The disproportionate burden of noncommunicable disease among Indigenous Australians living in remote Indigenous communities (RICs) is a complex and persistent problem. Smartphones are increasingly being used by young Indigenous adults and therefore represent a promising method to engage them in programs seeking to improve nutritional intake. Objective: This study aimed to consult RIC members to inform the content of a smartphone app that can be used to monitor and reduce sugar-sweetened beverage intake in RICs. Methods: The study was conducted in two phases. The formative phase involved a simulated grocery selection activity with think aloud (“think aloud shop”), a semistructured interview, a questionnaire outlining current smartphone and app use, and a paper prototyping activity. A preliminary end-user testing phase involved a think aloud prototype test and a semistructured interview regarding user satisfaction. Convenience sampling was used to recruit 20 18- to 35-year-old smartphone users for each phase from two RICs in the Northern Territory, Australia. Thematic analysis of transcribed audio recordings was used to identify determinants of food choice from the think aloud shop; themes related to the Theory of Planned Behavior (TPB) from the eating behaviors interview; and usability, comprehension, and satisfaction with the app from the preliminary end-user testing. Results: Smartphone use in RICs is currently different to that found in urban environments; in particular, extremely low use of Facebook, restricted variety of phone types, and limited Internet access. Findings regarding promoting app engagement indicate that utilizing an opt-in approach to social features such as leader boards and team challenges is essential. The inclusion of games was also shown to be important for satisfaction, as were the use of audio features, contextually embedded dissemination, and streamlined app design for comprehension in this target group. Conclusions: This research provides critical insights and concrete recommendations for the development of lifestyle improvement apps targeted toward disadvantaged young adults in nonurban settings, specifically RICs. It serves as a framework for future app development projects using a consultative user-centered design approach, supporting calls for the increased use of this strategy in app development

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine