Can we improve the prediction of hip fracture by assessing bone structure using shape and appearance modelling?

Copyright 2013 Elsevier B.V., All rights reserved.Peer reviewedPreprin

Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium

The muscular layer of the uterus (myometrium) undergoes profound changes in global excitability prior to parturition. Here, a mathematical model of the myocyte network is developed to investigate the hypothesis that spatial heterogeneity is essential to the transition from local to global excitation which the myometrium undergoes just prior to birth. Each myometrial smooth muscle cell is represented by an element with FitzHugh–Nagumo dynamics. The cells are coupled through resistors that represent gap junctions. Spatial heterogeneity is introduced by means of stochastic variation in coupling strengths, with parameters derived from physiological data. Numerical simulations indicate that even modest increases in the heterogeneity of the system can amplify the ability of locally applied stimuli to elicit global excitation. Moreover, in networks driven by a pacemaker cell, global oscillations of excitation are impeded in fully connected and strongly coupled networks. The ability of a locally stimulated cell or pacemaker cell to excite the network is shown to be strongly dependent on the local spatial correlation structure of the couplings. In summary, spatial heterogeneity is a key factor in enhancing and modulating global excitability

Reinventing College Physics for Biologists: Explicating an epistemological curriculum

The University of Maryland Physics Education Research Group (UMd-PERG) carried out a five-year research project to rethink, observe, and reform introductory algebra-based (college) physics. This class is one of the Maryland Physics Department's large service courses, serving primarily life-science majors. After consultation with biologists, we re-focused the class on helping the students learn to think scientifically -- to build coherence, think in terms of mechanism, and to follow the implications of assumptions. We designed the course to tap into students' productive conceptual and epistemological resources, based on a theoretical framework from research on learning. The reformed class retains its traditional structure in terms of time and instructional personnel, but we modified existing best-practices curricular materials, including Peer Instruction, Interactive Lecture Demonstrations, and Tutorials. We provided class-controlled spaces for student collaboration, which allowed us to observe and record students learning directly. We also scanned all written homework and examinations, and we administered pre-post conceptual and epistemological surveys. The reformed class enhanced the strong gains on pre-post conceptual tests produced by the best-practices materials while obtaining unprecedented pre-post gains on epistemological surveys instead of the traditional losses.Comment: 35 pages including a 15 page appendix of supplementary material

The contribution of teacher education to universities: a case study for international teacher educators

This paper reports on the initial stage of a research project which aims to develop deeper understanding of the contribution teacher education, as a sub-discipline within Education, makes to Higher Education in England. The study is located in the intersection between the domains of teacher education and higher education scholarship, which in England represents a contested and ambiguous professional space. Tensions between competing accountability measures, pulling away from university-based to exclusively school-based teacher education, are exacerbated by proposed policy changes arising from the government's recent market review. Findings drawn from analysis of qualitative data from a national survey are discussed in the context of Elizabeth Povinelli's critique of late liberalism and previous scholarship on the nature of teacher educators’ work. Evidence from the study demonstrates numerous benefits to higher education of hosting teacher education departments, including contributions to standard metrics, regional development and knowledge exchange within a strategic social justice agenda. However, teacher educators themselves may find articulating these benefits difficult, because of marginalisation from the dominant ways of achieving and accounting for excellence in the modern university. These findings offer a cautionary tale to international colleagues whose governments may be embarking on equivalent paths of teacher education reform

Global impact of COVID-19 on non-communicable disease management: descriptive analysis of access to FRAX fracture risk online tool for prevention of osteoporotic fractures

Summary The COVID-19 pandemic, and its management, is markedly impacting the management of osteoporosis as judged by access to online FRAX fracture risk assessments. Globally, access was 58% lower in April than in February 2020. Strategies to improve osteoporosis care, with greater use of fracture risk assessments, offer a partial solution. Introduction The COVID-19 pandemic is having a significant detrimental impact on the management of chronic diseases including osteoporosis. We have quantified the global impact by examining changes in the usage of online FRAX fracture risk assessments before and after the declaration of the pandemic (11 March 2020). Methods The study comprised a retrospective analysis using GoogleAnalytics data on daily sessions on the FRAX® website (www.sheffield.ac.uk/FRAX) from November 2019 to April 2020 (main analysis period February–April 2020), and the geographical source of that activity. Results Over February–April 2020, the FRAX website recorded 460,495 sessions from 184 countries, with 210,656 sessions in February alone. In March and April, the number of sessions fell by 23.1% and 58.3% respectively, a pattern not observed over the same period in 2019. There were smaller reductions in Asia than elsewhere, partly related to earlier and less-marked nadirs in some countries (China, Taiwan, Hong Kong, South Korea and Vietnam). In Europe, the majority of countries (24/31, 77.4%) reduced usage by at least 50% in April. Seven countries showed smaller reductions (range − 2.85 to − 44.1%) including Poland, Slovakia, Czech Republic, Germany, Norway, Sweden and Finland. There was no significant relationship between the reduction in FRAX usage and measures of disease burden such as COVID-attributed deaths per million of the population. Conclusion This study documents a marked global impact of the COVID-19 pandemic on the management of osteoporosis as reflected by FRAX online fracture risk assessments. The analysis suggests that impact may relate to the societal and healthcare measures taken to ameliorate the pandemic

A surrogate FRAX model for the Kyrgyz Republic

Summary The hip fracture rates from Kazakhstan were used to create a surrogate FRAX® model for the Kyrgyz Republic. Introduction The International Society for Clinical Densitometry and International Osteoporosis Foundation recommend utilizing a surrogate FRAX model, based on the country-specific risk of death, and fracture data based on a country where fracture rates are considered to be representative of the index country. Objective This paper describes a surrogate FRAX model for the Kyrgyz Republic. Methods The FRAX model used the incidence of hip fracture from the neighbouring country of Kazakhstan and the death risk for the Kyrgyz Republic. Results Compared with the model for Kazakhstan, the surrogate model gave somewhat higher 10-year fracture probabilities for men between 60 and 80 years of age and lower probabilities for men above the age of 80. For women the probabilities were similar up to the age of 75–80 years and then lower. There were very close correlations in fracture probabilities between the surrogate and authentic models (1.00) so that the use of the Kyrgyz model had little impact on the rank order of risk. It was estimated that 2752 hip fractures arose in 2015 in individuals over the age of 50 years in the Kyrgyz Republic, with a predicted increase by 207% to 8435 in 2050. Conclusion The surrogate FRAX model for the Kyrgyz Republic provides the opportunity to determine fracture probability among the Kyrgyz population and help guide decisions about treatment

Ultrahigh power and energy density in partially ordered lithium-ion cathode materials

The rapid market growth of rechargeable batteries requires electrode materials that combine high power and energy and are made from earth-abundant elements. Here we show that combining a partial spinel-like cation order and substantial lithium excess enables both dense and fast energy storage. Cation overstoichiometry and the resulting partial order is used to eliminate the phase transitions typical of ordered spinels and enable a larger practical capacity, while lithium excess is synergistically used with fluorine substitution to create a high lithium mobility. With this strategy, we achieved specific energies greater than 1,100 Wh kg–1 and discharge rates up to 20 A g–1. Remarkably, the cathode materials thus obtained from inexpensive manganese present a rare case wherein an excellent rate capability coexists with a reversible oxygen redox activity. Our work shows the potential for designing cathode materials in the vast space between fully ordered and disordered compounds

Estimating the future clinical and economic benefits of improving osteoporosis diagnosis and treatment among postmenopausal women across eight European countries

Summary A population-level, cross-sectional model was developed to estimate the clinical and economic burden of osteoporosis among women (≥ 70 years) across eight European countries. Results demonstrated that interventions aimed at improving fracture risk assessment and adherence would save 15.2% of annual costs in 2040. Purpose Osteoporosis is associated with significant clinical and economic burden, expected to further increase with an ageing population. This modelling analysis assessed clinical and economic outcomes under different hypothetical disease management interventions to reduce this burden. Methods A population-level, cross-sectional cohort model was developed to estimate numbers of incident fractures and direct costs of care among women (≥ 70 years) in eight European countries under different hypothetical interventions: (1) an improvement in the risk assessment rate, (2) an improvement in the treatment adherence rate and (3) a combination of interventions 1 and 2. A 50% improvement from the status quo, based on existing disease management patterns, was evaluated in the main analysis; scenario analyses evaluated improvement of either 10 or 100%. Results Based on existing disease management patterns, a 44% increase in the annual number of fractures and costs was predicted from 2020 to 2040: from 1.2 million fractures and €12.8 billion in 2020 to 1.8 million fractures and €18.4 billion in 2040. Intervention 3 provided the greatest fracture reduction and cost savings (a decrease of 17.9% and 15.2% in fractures and cost, respectively) in 2040 compared with intervention 1 (decreases of 8.7% and 7.0% in fractures and cost, respectively) and intervention 2 (10.0% and 8.8% reductions in fracture and cost, respectively). Scenario analyses showed similar patterns. Conclusion These analyses suggest that interventions which improve fracture risk assessment and adherence to treatments would relieve the burden of osteoporosis, and that a combination strategy would achieve greatest benefits

A pooled analysis of fall incidence from placebo‐controlled trials of denosumab

Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo‐controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo‐controlled period of each trial. A time‐to‐event analysis of first fall and exposure‐adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome