Capture the fracture: a best practice framework and global campaign to break the fragility fracture cycle

Summary The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. Introduction FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. Methods Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. Results The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. Conclusion Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.</p

Measurement of the hadronic photon structure function F_{2}^{γ} at LEP2

The hadronic structure function of the photon F_{2}^{γ} (x, Q²) is measured as a function of Bjorken x and of the photon virtuality Q² using deep-inelastic scattering data taken by the OPAL detector at LEP at e⁺e⁻ centre-of-mass energies from 183 to 209 GeV. Previous OPAL measurements of the x dependence of F_{2}^{γ} are extended to an average Q² of 〈Q²〉=780 GeV² using data in the kinematic range 0.15<x<0.98. The Q² evolution of F_{2}^{γ} is studied for 12.1<〈Q²〉<780 GeV² using three ranges of x. As predicted by QCD, the data show positive scaling violations in F_{2}^{γ} with F_{2}^{γ} (Q²)/α = (0.08±0.02⁺⁰·⁰⁵_₀.₀₃) + (0.13±0.01⁺⁰·⁰¹_₀.₀₁) lnQ², where Q² is in GeV², for the central x region 0.10–0.60. Several parameterisations of F_{2}^{γ} are in qualitative agreement with the measurements whereas the quark-parton model prediction fails to describe the data

Measurement of the charm structure function F_{2,c)^{γ} of the photon at LEP

The production of charm quarks is studied in deep-inelastic electron–photon scattering using data recorded by the OPAL detector at LEP at nominal e⁺e⁻ centre-of-mass energies from 183 to 209 GeV. The charm quarks have been identified by full reconstruction of charged D* mesons using their decays into D⁰π with the D⁰ observed in two decay modes with charged particle final states, Kπ and Kπππ. The cross-section σ^{D*} for production of charged D* in the reaction e⁺e⁻→e⁺e⁻D*Χ is measured in a restricted kinematical region using two bins in Bjorken x, 0.00140.1 the perturbative QCD calculation at next-to-leading order agrees perfectly with the measured cross-section. For x<0.1 the measured cross-section is 43.8±14.3±6.3±2.8 pb with a next-to-leading order prediction of 17.0⁺²·⁹_₂.₃ pb

Estimating Heritabilities and Genetic Correlations: Comparing the ‘Animal Model’ with Parent-Offspring Regression Using Data from a Natural Population

Quantitative genetic parameters are nowadays more frequently estimated with restricted maximum likelihood using the ‘animal model’ than with traditional methods such as parent-offspring regressions. These methods have however rarely been evaluated using equivalent data sets. We compare heritabilities and genetic correlations from animal model and parent-offspring analyses, respectively, using data on eight morphological traits in the great reed warbler (Acrocephalus arundinaceus). Animal models were run using either mean trait values or individual repeated measurements to be able to separate between effects of including more extended pedigree information and effects of replicated sampling from the same individuals. We show that the inclusion of more pedigree information by the use of mean traits animal models had limited effect on the standard error and magnitude of heritabilities. In contrast, the use of repeated measures animal model generally had a positive effect on the sampling accuracy and resulted in lower heritabilities; the latter due to lower additive variance and higher phenotypic variance. For most trait combinations, both animal model methods gave genetic correlations that were lower than the parent-offspring estimates, whereas the standard errors were lower only for the mean traits animal model. We conclude that differences in heritabilities between the animal model and parent-offspring regressions were mostly due to the inclusion of individual replicates to the animal model rather than the inclusion of more extended pedigree information. Genetic correlations were, on the other hand, primarily affected by the inclusion of more pedigree information. This study is to our knowledge the most comprehensive empirical evaluation of the performance of the animal model in relation to parent-offspring regressions in a wild population. Our conclusions should be valuable for reconciliation of data obtained in earlier studies as well as for future meta-analyses utilizing estimates from both traditional methods and the animal model

Altered Metabolic Signature in Pre-Diabetic NOD Mice

Altered metabolism proceeding seroconversion in children progressing to Type 1 diabetes has previously been demonstrated. We tested the hypothesis that non-obese diabetic (NOD) mice show a similarly altered metabolic profile compared to C57BL/6 mice. Blood samples from NOD and C57BL/6 female mice was collected at 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13 and 15 weeks and the metabolite content was analyzed using GC-MS. Based on the data of 89 identified metabolites OPLS-DA analysis was employed to determine the most discriminative metabolites. In silico analysis of potential involved metabolic enzymes was performed using the dbSNP data base. Already at 0 weeks NOD mice displayed a unique metabolic signature compared to C57BL/6. A shift in the metabolism was observed for both strains the first weeks of life, a pattern that stabilized after 5 weeks of age. Multivariate analysis revealed the most discriminative metabolites, which included inosine and glutamic acid. In silico analysis of the genes in the involved metabolic pathways revealed several SNPs in either regulatory or coding regions, some in previously defined insulin dependent diabetes (Idd) regions. Our result shows that NOD mice display an altered metabolic profile that is partly resembling the previously observation made in children progressing to Type 1 diabetes. The level of glutamic acid was one of the most discriminative metabolites in addition to several metabolites in the TCA cycle and nucleic acid components. The in silico analysis indicated that the genes responsible for this reside within previously defined Idd regions

Platelet and Neutrophil Responses to Gram Positive Pathogens in Patients with Bacteremic Infection

BACKGROUND: Many Gram-positive pathogens aggregate and activate platelets in vitro and this has been proposed to contribute to virulence. Platelets can also form complexes with neutrophils but little is however known about platelet and platelet-neutrophil responses in bacterial infection. METHODOLOGY/PRINCIPAL FINDINGS: We added isolates of Gram-positive bacteria from 38 patients with a bacteremic infection to blood drawn from the same patient. Aggregometry and flow cytometry were used to assess platelet aggregation and to quantify activation of platelets, neutrophils, and platelet-neutrophils complexes (PNCs) induced by the bacteria. Fifteen healthy persons served as controls. Most isolates of Staphylococcus aureus, beta hemolytic streptococci, and Enterococcus faecalis induced aggregation of platelets from their respective hosts, whereas pneumococci failed to do so. S. aureus isolates induced platelet aggregation more rapidly in patients than in controls, whereas platelet activation by S. aureus was lower in patients than in controls. PNCs were more abundant in baseline samples from patients than in healthy controls and most bacterial isolates induced additional PNC formation and neutrophil activation. CONCLUSION/SIGNIFICANCE: We have demonstrated for the first time that bacteria isolated from patients with Gram-positive bacteremia can induce platelet activation and aggregation, PNC formation, and neutrophil activation in the same infected host. This underlines the significance of these interactions during infection, which could be a target for future therapies in sepsis

Relation between dietary cadmium intake and biomarkers of cadmium exposure in premenopausal women accounting for body iron stores

<p>Abstract</p> <p>Background</p> <p>Cadmium is a widespread environmental pollutant with adverse effects on kidneys and bone, but with insufficiently elucidated public health consequences such as risk of end-stage renal diseases, fractures and cancer. Urinary cadmium is considered a valid biomarker of lifetime kidney accumulation from overall cadmium exposure and thus used in the assessment of cadmium-induced health effects. We aimed to assess the relationship between dietary cadmium intake assessed by analyses of duplicate food portions and cadmium concentrations in urine and blood, taking the toxicokinetics of cadmium into consideration.</p> <p>Methods</p> <p>In a sample of 57 non-smoking Swedish women aged 20-50 years, we assessed Pearson's correlation coefficients between: 1) Dietary intake of cadmium assessed by analyses of cadmium in duplicate food portions collected during four consecutive days and cadmium concentrations in urine, 2) Partial correlations between the duplicate food portions and urinary and blood cadmium concentrations, respectively, and 3) Model-predicted urinary cadmium concentration predicted from the dietary intake using a one-compartment toxicokinetic model (with individual data on age, weight and gastrointestinal cadmium absorption) and urinary cadmium concentration.</p> <p>Results</p> <p>The mean concentration of cadmium in urine was 0.18 (+/- s.d.0.12) μg/g creatinine and the model-predicted urinary cadmium concentration was 0.19 (+/- s.d.0.15) μg/g creatinine. The partial Pearson correlations between analyzed dietary cadmium intake and urinary cadmium or blood concentrations were r = 0.43 and 0.42, respectively. The correlation between diet and urinary cadmium increased to r = 0.54 when using a one-compartment model with individual gastrointestinal cadmium absorption coefficients based on the women's iron status.</p> <p>Conclusions</p> <p>Our results indicate that measured dietary cadmium intake can reasonably well predict biomarkers of both long-term kidney accumulation (urine) and short-term exposure (blood). The predictions are improved when taking data on the iron status into account.</p

Associations of Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene With Subsequent Coronary Heart Disease: An Individual-Level Meta-Analysis

Background: The knowledge of factors influencing disease progression in patients with established coronary heart disease (CHD) is still relatively limited. One potential pathway is related to peroxisome proliferator–activated receptor gamma coactivator-1 alpha (PPARGC1A), a transcription factor linked to energy metabolism which may play a role in the heart function. Thus, its associations with subsequent CHD events remain unclear. We aimed to investigate the effect of three different SNPs in the PPARGC1A gene on the risk of subsequent CHD in a population with established CHD. Methods: We employed an individual-level meta-analysis using 23 studies from the GENetIcs of sUbSequent Coronary Heart Disease (GENIUS-CHD) consortium, which included participants (n = 80,900) with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. Three variants in the PPARGC1A gene (rs8192678, G482S; rs7672915, intron 2; and rs3755863, T528T) were tested for their associations with subsequent events during the follow-up using a Cox proportional hazards model adjusted for age and sex. The primary outcome was subsequent CHD death or myocardial infarction (CHD death/myocardial infarction). Stratified analyses of the participant or study characteristics as well as additional analyses for secondary outcomes of specific cardiovascular disease diagnoses and all-cause death were also performed. Results: Meta-analysis revealed no significant association between any of the three variants in the PPARGC1A gene and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline: rs8192678, hazard ratio (HR): 1.01, 95% confidence interval (CI) 0.98–1.05 and rs7672915, HR: 0.97, 95% CI 0.94–1.00; rs3755863, HR: 1.02, 95% CI 0.99–1.06. Similarly, no significant associations were observed for any of the secondary outcomes. The results from stratified analyses showed null results, except for significant inverse associations between rs7672915 (intron 2) and the primary outcome among 1) individuals aged ≥65, 2) individuals with renal impairment, and 3) antiplatelet users. Conclusion: We found no clear associations between polymorphisms in the PPARGC1A gene and subsequent CHD events in patients with established CHD at baseline

Sex Differences in Sand Lizard Telomere Inheritance: Paternal Epigenetic Effects Increases Telomere Heritability and Offspring Survival

To date, the only estimate of the heritability of telomere length in wild populations comes from humans. Thus, there is a need for analysis of natural populations with respect to how telomeres evolve.Here, we show that telomere length is heritable in free-ranging sand lizards, Lacerta agilis. More importantly, heritability estimates analysed within, and contrasted between, the sexes are markedly different; son-sire heritability is much higher relative to daughter-dam heritability. We assess the effect of paternal age on Telomere Length (TL) and show that in this species, paternal age at conception is the best predictor of TL in sons. Neither paternal age per se at blood sampling for telomere screening, nor corresponding age in sons impact TL in sons. Processes maintaining telomere length are also associated with negative fitness effects, most notably by increasing the risk of cancer and show variation across different categories of individuals (e.g. males vs. females). We therefore tested whether TL influences offspring survival in their first year of life. Indeed such effects were present and independent of sex-biased offspring mortality and offspring malformations.TL show differences in sex-specific heritability with implications for differences between the sexes with respect to ongoing telomere selection. Paternal age influences the length of telomeres in sons and longer telomeres enhance offspring survival

Network analysis of sea turtle movements and connectivity: A tool for conservation prioritization

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available in the Supplementary Material of this article and Zenodo (https://doi.org/10.5281/zenodo.5898578). Details for all animals included in this study are provided in Appendices S1 and S2. Data used to create the spatial networks are listed in the Appendices S3 and S4. The geospatial files for all networks are available on the Migratory Connectivity in the Ocean Project website (https://mico.eco) and Dryad (https://doi.org/10.5061/dryad.j3tx95xg9). Additional data that support the findings of this study are available from the corresponding author upon reasonable request.Aim Understanding the spatial ecology of animal movements is a critical element in conserving long-lived, highly mobile marine species. Analyzing networks developed from movements of six sea turtle species reveals marine connectivity and can help prioritize conservation efforts. Location Global. Methods We collated telemetry data from 1235 individuals and reviewed the literature to determine our dataset's representativeness. We used the telemetry data to develop spatial networks at different scales to examine areas, connections, and their geographic arrangement. We used graph theory metrics to compare networks across regions and species and to identify the role of important areas and connections. Results Relevant literature and citations for data used in this study had very little overlap. Network analysis showed that sampling effort influenced network structure, and the arrangement of areas and connections for most networks was complex. However, important areas and connections identified by graph theory metrics can be different than areas of high data density. For the global network, marine regions in the Mediterranean had high closeness, while links with high betweenness among marine regions in the South Atlantic were critical for maintaining connectivity. Comparisons among species-specific networks showed that functional connectivity was related to movement ecology, resulting in networks composed of different areas and links. Main conclusions Network analysis identified the structure and functional connectivity of the sea turtles in our sample at multiple scales. These network characteristics could help guide the coordination of management strategies for wide-ranging animals throughout their geographic extent. Most networks had complex structures that can contribute to greater robustness but may be more difficult to manage changes when compared to simpler forms. Area-based conservation measures would benefit sea turtle populations when directed toward areas with high closeness dominating network function. Promoting seascape connectivity of links with high betweenness would decrease network vulnerability.International Climate Initiative (IKI)German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU