Longer Duration of Diabetes Strongly Impacts Fracture Risk Assessment: The Manitoba BMD Cohort

Context: Type 2 diabetes is associated with a higher risk for major osteoporotic fracture (MOF) and hip fracture than predicted by the World Health Organization fracture risk assessment (FRAX) tool. Objective: The objective of the study was to examine the impact of diabetes duration on fracture risk. Methods: Using a clinical dual-energy x-ray absorptiometry registry linked with the Manitoba administrative databases, we identified all women age 40 years or older with 10 or more years of prior health care coverage undergoing hip dual-energy x-ray absorptiometry measurements (1996 –2013). Incident MOF and incident hip fractures were each studied over 7 years. Cox proportional hazards models were adjusted for FRAX (FRAX adjusted) and then FRAX plus comorbidity, falls, osteoporosis therapy, or insulin (fully adjusted). FRAX calibration was assessed comparing observed vs predicted probabilities. Results: There were 49 098 women without and 8840 women with diabetes (31.4%10 y duration; 20.1% 5–10 y; 23.7%5 y; 24.8% new onset). In FRAX-adjusted analyses, only duration longer than 10 years was associated with a higher risk for MOF (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.30 –1.66), and this was similar in the fully adjusted models (HR 1.34, 95% CI 1.17–1.54). In contrast, a higher risk for hip fracture was seen for all durations in a dose-dependent fashion (eg, FRAX adjusted HR 2.10, 95% CI 1.71–2.59 for duration 10 y vs HR 1.32, 95% CI 1.03–1.69 for new onset). FRAX significantly underestimated the MOF risk (calibration ratio 1.24, 95% CI 1.08 –1.39) and hip fracture risk (1.93, 95% CI 1.50 –2.35) in those with a diabetes duration longer than 10 years. Conclusion: Diabetes is a FRAX-independent risk factor for MOF only in women with a long duration of diabetes, but diabetes increases hip fracture risk, regardless of duration. Those with diabetes longer than 10 years are at particularly high risk of fracture, and this elevated risk is currently underestimated by FRAX

Magnetic Field Effects on Neutron Diffraction in the Antiferromagnetic Phase of UPt3UPt_3

We discuss possible magnetic structures in UPt$_3$ based on our analysis of elastic neutron-scattering experiments in high magnetic fields at temperatures $T<T_N$. The existing experimental data can be explained by a single-{\bf q} antiferromagnetic structure with three independent domains. For modest in-plane spin-orbit interactions, the Zeeman coupling between the antiferromagnetic order parameter and the magnetic field induces a rotation of the magnetic moments, but not an adjustment of the propagation vector of the magnetic order. A triple-{\bf q} magnetic structure is also consistent with neutron experiments, but in general leads to a non-uniform magnetization in the crystal. New experiments could decide between these structures.Comment: 5 figures included in the tex

Reassessment intervals for transition from low to high fracture risk among adults older than 50 years

Importance Fracture risk scores are used to identify individuals at high risk of major osteoporotic fracture or hip fracture for antiosteoporosis treatment. For those not meeting treatment thresholds at baseline, the optimal interval for reassessing fracture risk is uncertain. Objective To examine reassessment intervals for transition from low to high fracture risk under guidelines-defined treatment thresholds. Design, Setting, and Participants This retrospective cohort study included persons aged 50 years or older with fracture risk below treatment thresholds at baseline who had fracture risk reassessed at least 1 year later. Data were obtained from a population-based bone mineral density registry (baseline assessment during 1996-2015; reassessment to 2016) in the Province of Manitoba, Canada. Primary analysis was performed from May to June 2019. Analysis for the revision was performed in October 2019. Main Outcomes and Measures The primary outcome was time to transition from low (below the treatment threshold) to high fracture risk (treatment-qualifying risk score using osteoporosis clinical practice guidelines strategies for Canada, the United States, and the United Kingdom). Results The study population consisted of 10 564 individuals (94.1% women; mean [SD] age at baseline, 63.2 [8.2] years). At the time of reassessment (a mean [SD] interval of 5.2 [2.9] years between initial and subsequent fracture risk assessment), 690 (6.6%) had reached the fixed major osteoporotic fracture treatment threshold of 20%, 1546 (16.2%) had reached the fixed hip treatment threshold of 3%, and 932 (9.4%) had reached the age-dependent major osteoporotic fracture treatment threshold. Among those below 25% of the treatment threshold at baseline for each guideline, few (0%-3.0%) reached guidelines-defined high fracture risk at follow-up. In contrast, among those at the upper end of the scale for each guideline (75%-99% of the treatment threshold at baseline), 30.6% to 74.4% reached guidelines-defined high fracture risk. An increased number of clinical risk factors was associated with increased likelihood of reaching guidelines-defined high fracture risk (range for 3 guidelines, 17.1%-28.2%) compared with unchanged or decreased clinical risk factors (range for 3 guidelines, 3.3%-12.8%) (P < .001). Estimated time for 10% of the population to reach treatment-qualifying high fracture risk ranged from fewer than 3 years to more than 15 years. Conclusions and Relevance The findings suggest that baseline fracture risk (as a fraction of the treatment threshold) and change in clinical risk factors can identify individuals with low and high probability of guidelines-defined high fracture risk during follow-up, thereby potentially helping to inform the reassessment interval

DNA synthesis determines the binding mode of the human mitochondrial single-stranded DNA-binding protein

[EN] Single-stranded DNA-binding proteins (SSBs) play a key role in genome maintenance, binding and organizing single-stranded DNA (ssDNA) intermediates. Multimeric SSBs, such as the human mitochondrial SSB (HmtSSB), present multiple sites to interact with ssDNA, which has been shown in vitro to enable them to bind a variable number of single-stranded nucleotides depending on the salt and protein concentration. It has long been suggested that different binding modes might be used selectively for different functions. To study this possibility, we used optical tweezers to determine and compare the structure and energetics of long, individual HmtSSB¿DNA complexes assembled on preformed ssDNA and on ssDNA generated gradually during `in situ¿ DNA synthesis. We show that HmtSSB binds to preformed ss-DNA in two major modes, depending on salt and protein concentration. However, when protein binding was coupled to strand-displacement DNA synthesis, only one of the two binding modes was observed under all experimental conditions. Our results reveal a key role for the gradual generation of ssDNA in modulating the binding mode of a multimeric SSB protein and consequently, in generating the appropriate nucleoprotein structure for DNA synthetic reactions required for genome maintenance.We are grateful to Prof. M. Salas laboratory (CBMSO-CSIC) for generously providing the Phi29 DNA polymerase and to Juan P. García Villaluenga (UCM) for useful discussions. Spanish Ministry of Economy and Competitiveness [MAT2015-71806-R to J.R.A-G, FIS2010-17440, FIS2015-67765-R to F.J.C., BFU2012-31825, BFU2015-63714-R to B.I.]; Spanish Ministry of Education, Culture and Sport [FPU13/02934 to J.J., FPU13/02826 to E.B-H.]; National Institutes of Health [GM45925 to L.S.K.]; University of Tampere (to G.L.C.); Programa de Financiacion Universidad Complutense de Madrid-Santander Universidades [CT45/15-CT46/15 to F.C.]. Funding for open access charge: Spanish Ministry of Economy and Competitiveness [BFU2015-63714-R].Morin, J.; Cerrón, F.; Jarillo, J.; Beltran-Heredia, E.; Ciesielski, G.; Arias-Gonzalez, JR.; Kaguni, L.... (2017). DNA synthesis determines the binding mode of the human mitochondrial single-stranded DNA-binding protein. Nucleic Acids Research. 45(12):7237-7248. https://doi.org/10.1093/nar/gkx395S723772484512Shereda, R. D., Kozlov, A. G., Lohman, T. M., Cox, M. M., & Keck, J. L. (2008). SSB as an Organizer/Mobilizer of Genome Maintenance Complexes. Critical Reviews in Biochemistry and Molecular Biology, 43(5), 289-318. doi:10.1080/10409230802341296Flynn, R. L., & Zou, L. (2010). Oligonucleotide/oligosaccharide-binding fold proteins: a growing family of genome guardians. Critical Reviews in Biochemistry and Molecular Biology, 45(4), 266-275. doi:10.3109/10409238.2010.488216Murzin, A. G. (1993). OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. The EMBO Journal, 12(3), 861-867. doi:10.1002/j.1460-2075.1993.tb05726.xKozlov, A. G., Weiland, E., Mittal, A., Waldman, V., Antony, E., Fazio, N., … Lohman, T. M. (2015). Intrinsically Disordered C-Terminal Tails of E. coli Single-Stranded DNA Binding Protein Regulate Cooperative Binding to Single-Stranded DNA. Journal of Molecular Biology, 427(4), 763-774. doi:10.1016/j.jmb.2014.12.020Kuznetsov, S. V., Kozlov, A. G., Lohman, T. M., & Ansari, A. (2006). Microsecond Dynamics of Protein–DNA Interactions: Direct Observation of the Wrapping/Unwrapping Kinetics of Single-stranded DNA around the E.coli SSB Tetramer. Journal of Molecular Biology, 359(1), 55-65. doi:10.1016/j.jmb.2006.02.070Lohman, T. M., & Ferrari, M. E. (1994). Escherichia Coli Single-Stranded DNA-Binding Protein: Multiple DNA-Binding Modes and Cooperativities. Annual Review of Biochemistry, 63(1), 527-570. doi:10.1146/annurev.bi.63.070194.002523Maier, D., Farr, C. L., Poeck, B., Alahari, A., Vogel, M., Fischer, S., … Schneuwly, S. (2001). Mitochondrial Single-stranded DNA-binding Protein Is Required for Mitochondrial DNA Replication and Development in Drosophila melanogaster. Molecular Biology of the Cell, 12(4), 821-830. doi:10.1091/mbc.12.4.821Ruhanen, H., Borrie, S., Szabadkai, G., Tyynismaa, H., Jones, A. W. E., Kang, D., … Yasukawa, T. (2010). Mitochondrial single-stranded DNA binding protein is required for maintenance of mitochondrial DNA and 7S DNA but is not required for mitochondrial nucleoid organisation. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1803(8), 931-939. doi:10.1016/j.bbamcr.2010.04.008Farr, C. L., Matsushima, Y., Lagina, A. T., Luo, N., & Kaguni, L. S. (2004). Physiological and Biochemical Defects in Functional Interactions of Mitochondrial DNA Polymerase and DNA-binding Mutants of Single-stranded DNA-binding Protein. Journal of Biological Chemistry, 279(17), 17047-17053. doi:10.1074/jbc.m400283200Van Tuyle, G. C., & Pavco, P. A. (1985). The rat liver mitochondrial DNA-protein complex: displaced single strands of replicative intermediates are protein coated. The Journal of Cell Biology, 100(1), 251-257. doi:10.1083/jcb.100.1.251Clayton, D. A. (1982). Replication of animal mitochondrial DNA. Cell, 28(4), 693-705. doi:10.1016/0092-8674(82)90049-6Farr, C. L., Wang, Y., & Kaguni, L. S. (1999). Functional Interactions of Mitochondrial DNA Polymerase and Single-stranded DNA-binding Protein. Journal of Biological Chemistry, 274(21), 14779-14785. doi:10.1074/jbc.274.21.14779Korhonen, J. A., Gaspari, M., & Falkenberg, M. (2003). TWINKLE Has 5′ → 3′ DNA Helicase Activity and Is Specifically Stimulated by Mitochondrial Single-stranded DNA-binding Protein. Journal of Biological Chemistry, 278(49), 48627-48632. doi:10.1074/jbc.m306981200Miralles Fusté, J., Shi, Y., Wanrooij, S., Zhu, X., Jemt, E., Persson, Ö., … Falkenberg, M. (2014). In Vivo Occupancy of Mitochondrial Single-Stranded DNA Binding Protein Supports the Strand Displacement Mode of DNA Replication. PLoS Genetics, 10(12), e1004832. doi:10.1371/journal.pgen.1004832Oliveira, M. T., & Kaguni, L. S. (2011). Reduced Stimulation of Recombinant DNA Polymerase γ and Mitochondrial DNA (mtDNA) Helicase by Variants of Mitochondrial Single-stranded DNA-binding Protein (mtSSB) Correlates with Defects in mtDNA Replication in Animal Cells. Journal of Biological Chemistry, 286(47), 40649-40658. doi:10.1074/jbc.m111.289983Williams, A. J., & Kaguni, L. S. (1995). Stimulation ofDrosophilaMitochondrial DNA Polymerase by Single-stranded DNA-binding Protein. Journal of Biological Chemistry, 270(2), 860-865. doi:10.1074/jbc.270.2.860Bogenhagen, D. F., Wang, Y., Shen, E. L., & Kobayashi, R. (2003). Protein Components of Mitochondrial DNA Nucleoids in Higher Eukaryotes. Molecular & Cellular Proteomics, 2(11), 1205-1216. doi:10.1074/mcp.m300035-mcp200BARAT-GUERIDE, M., DUFRESNE, C., & RICKWOOD, D. (1989). Effect of DNA conformation on the transcription of mitochondrial DNA. European Journal of Biochemistry, 183(2), 297-302. doi:10.1111/j.1432-1033.1989.tb14928.xYang, C., Curth, U., Urbanke, C., & Kang, C. (1997). Crystal structure of human mitochondrial single-stranded DNA binding protein at 2.4 Å resolution. Nature Structural Biology, 4(2), 153-157. doi:10.1038/nsb0297-153Raghunathan, S., Ricard, C. S., Lohman, T. M., & Waksman, G. (1997). Crystal structure of the homo-tetrameric DNA binding domain of Escherichia coli single-stranded DNA-binding protein determined by multiwavelength x-ray diffraction on the selenomethionyl protein at 2.9-A resolution. Proceedings of the National Academy of Sciences, 94(13), 6652-6657. doi:10.1073/pnas.94.13.6652CURTH, U., URBANKE, C., GREIPEL, J., GERBERDING, H., TIRANTI, V., & ZEVIANI, M. (1994). Single-stranded-DNA-binding proteins from human mitochondria and Escherichia coli have analogous physicochemical properties. European Journal of Biochemistry, 221(1), 435-443. doi:10.1111/j.1432-1033.1994.tb18756.xOverman, L. B., & Lohman, T. M. (1994). Linkage of pH, Anion and Cation Effects in Protein-Nucleic Acid Equilibria. Journal of Molecular Biology, 236(1), 165-178. doi:10.1006/jmbi.1994.1126Bhattacharyya, B., George, N. P., Thurmes, T. M., Zhou, R., Jani, N., Wessel, S. R., … Keck, J. L. (2013). Structural mechanisms of PriA-mediated DNA replication restart. Proceedings of the National Academy of Sciences, 111(4), 1373-1378. doi:10.1073/pnas.1318001111Carlini, L. E., Porter, R. D., Curth, U., & Urbanke, C. (1993). Viability and preliminary in vivo characterization of site directed mutants of Escherichia coli single-stranded DNA-binding protein. Molecular Microbiology, 10(5), 1067-1075. doi:10.1111/j.1365-2958.1993.tb00977.xGriffith, J. D., Harris, L. D., & Register, J. (1984). Visualization of SSB-ssDNA Complexes Active in the Assembly of Stable RecA-DNA Filaments. Cold Spring Harbor Symposia on Quantitative Biology, 49(0), 553-559. doi:10.1101/sqb.1984.049.01.062Morrical, S. W., & Cox, M. M. (1990). Stabilization of recA protein-ssDNA complexes by the single-stranded DNA binding protein of Escherichia coli. Biochemistry, 29(3), 837-843. doi:10.1021/bi00455a034Muniyappa, K., Williams, K., Chase, J. W., & Radding, C. M. (1990). Active nucleoprotein filaments of single-stranded binding protein and recA protein on single-stranded DNA have a regular repeating structure. Nucleic Acids Research, 18(13), 3967-3973. doi:10.1093/nar/18.13.3967Wessel, S. R., Marceau, A. H., Massoni, S. C., Zhou, R., Ha, T., Sandler, S. J., & Keck, J. L. (2013). PriC-mediated DNA Replication Restart Requires PriC Complex Formation with the Single-stranded DNA-binding Protein. Journal of Biological Chemistry, 288(24), 17569-17578. doi:10.1074/jbc.m113.478156Bell, J. C., Liu, B., & Kowalczykowski, S. C. (2015). Imaging and energetics of single SSB-ssDNA molecules reveal intramolecular condensation and insight into RecOR function. eLife, 4. doi:10.7554/elife.08646Suksombat, S., Khafizov, R., Kozlov, A. G., Lohman, T. M., & Chemla, Y. R. (2015). Structural dynamics of E. coli single-stranded DNA binding protein reveal DNA wrapping and unwrapping pathways. eLife, 4. doi:10.7554/elife.08193Zhou, R., Kozlov, A. G., Roy, R., Zhang, J., Korolev, S., Lohman, T. M., & Ha, T. (2011). SSB Functions as a Sliding Platform that Migrates on DNA via Reptation. Cell, 146(2), 222-232. doi:10.1016/j.cell.2011.06.036Pant, K., Karpel, R. L., Rouzina, I., & Williams, M. C. (2004). Mechanical Measurement of Single-molecule Binding Rates: Kinetics of DNA Helix-destabilization by T4 Gene 32 Protein. Journal of Molecular Biology, 336(4), 851-870. doi:10.1016/j.jmb.2003.12.025Pant, K., Karpel, R. L., Rouzina, I., & Williams, M. C. (2005). Salt Dependent Binding of T4 Gene 32 Protein to Single and Double-stranded DNA: Single Molecule Force Spectroscopy Measurements. Journal of Molecular Biology, 349(2), 317-330. doi:10.1016/j.jmb.2005.03.065Robberson, D. L., & Clayton, D. A. (1972). Replication of Mitochondrial DNA in Mouse L Cells and Their Thymidine Kinase- Derivatives: Displacement Replication on a Covalently-Closed Circular Template. Proceedings of the National Academy of Sciences, 69(12), 3810-3814. doi:10.1073/pnas.69.12.3810Ciesielski, G. L., Bermek, O., Rosado-Ruiz, F. A., Hovde, S. L., Neitzke, O. J., Griffith, J. D., & Kaguni, L. S. (2015). Mitochondrial Single-stranded DNA-binding Proteins Stimulate the Activity of DNA Polymerase γ by Organization of the Template DNA. Journal of Biological Chemistry, 290(48), 28697-28707. doi:10.1074/jbc.m115.673707Lázaro, J. M., Blanco, L., & Salas, M. (1995). [5] Purification of bacteriophage φ29 DNA polymerase. DNA Replication, 42-49. doi:10.1016/0076-6879(95)62007-9Ibarra, B., Chemla, Y. R., Plyasunov, S., Smith, S. B., Lázaro, J. M., Salas, M., & Bustamante, C. (2009). Proofreading dynamics of a processive DNA polymerase. The EMBO Journal, 28(18), 2794-2802. doi:10.1038/emboj.2009.219Morin, J. A., Cao, F. J., Lazaro, J. M., Arias-Gonzalez, J. R., Valpuesta, J. M., Carrascosa, J. L., … Ibarra, B. (2012). Active DNA unwinding dynamics during processive DNA replication. Proceedings of the National Academy of Sciences, 109(21), 8115-8120. doi:10.1073/pnas.1204759109Smith, S. B., Cui, Y., & Bustamante, C. (2003). [7] Optical-trap force transducer that operates by direct measurement of light momentum. Biophotonics, Part B, 134-162. doi:10.1016/s0076-6879(03)61009-8Bosco, A., Camunas-Soler, J., & Ritort, F. (2013). Elastic properties and secondary structure formation of single-stranded DNA at monovalent and divalent salt conditions. Nucleic Acids Research, 42(3), 2064-2074. doi:10.1093/nar/gkt1089Smith, S., Finzi, L., & Bustamante, C. (1992). Direct mechanical measurements of the elasticity of single DNA molecules by using magnetic beads. Science, 258(5085), 1122-1126. doi:10.1126/science.1439819Longley, M. J., Smith, L. A., & Copeland, W. C. (2009). Preparation of Human Mitochondrial Single-Stranded DNA-Binding Protein. Mitochondrial DNA, 73-85. doi:10.1007/978-1-59745-521-3_5Li, K., & Williams, R. S. (1997). Tetramerization and Single-stranded DNA Binding Properties of Native and Mutated Forms of Murine Mitochondrial Single-stranded DNA-binding Proteins. Journal of Biological Chemistry, 272(13), 8686-8694. doi:10.1074/jbc.272.13.8686Jarillo, J., Morín, J. A., Beltrán-Heredia, E., Villaluenga, J. P. G., Ibarra, B., & Cao, F. J. (2017). Mechanics, thermodynamics, and kinetics of ligand binding to biopolymers. PLOS ONE, 12(4), e0174830. doi:10.1371/journal.pone.0174830Bujalowski, W., & Lohman, T. M. (1986). Escherichia coli single-strand binding protein forms multiple, distinct complexes with single-stranded DNA. Biochemistry, 25(24), 7799-7802. doi:10.1021/bi00372a003Thömmes, P., Farr, C. L., Marton, R. F., Kaguni, L. S., & Cotterill, S. (1995). Mitochondrial Single-stranded DNA-binding Protein fromDrosophilaEmbryos. Journal of Biological Chemistry, 270(36), 21137-21143. doi:10.1074/jbc.270.36.21137Rodriguez, I., Lazaro, J. M., Blanco, L., Kamtekar, S., Berman, A. J., Wang, J., … de Vega, M. (2005). A specific subdomain in  29 DNA polymerase confers both processivity and strand-displacement capacity. Proceedings of the National Academy of Sciences, 102(18), 6407-6412. doi:10.1073/pnas.0500597102Kamtekar, S., Berman, A. J., Wang, J., Lázaro, J. M., de Vega, M., Blanco, L., … Steitz, T. A. (2004). Insights into Strand Displacement and Processivity from the Crystal Structure of the Protein-Primed DNA Polymerase of Bacteriophage φ29. Molecular Cell, 16(4), 609-618. doi:10.1016/j.molcel.2004.10.019Chrysogelos, S., & Griffith, J. (1982). Escherichia coli single-strand binding protein organizes single-stranded DNA in nucleosome-like units. Proceedings of the National Academy of Sciences, 79(19), 5803-5807. doi:10.1073/pnas.79.19.5803Hamon, L., Pastre, D., Dupaigne, P., Breton, C. L., Cam, E. L., & Pietrement, O. (2007). High-resolution AFM imaging of single-stranded DNA-binding (SSB) protein--DNA complexes. Nucleic Acids Research, 35(8), e58-e58. doi:10.1093/nar/gkm147Takamatsu, C., Umeda, S., Ohsato, T., Ohno, T., Abe, Y., Fukuoh, A., … Kang, D. (2002). Regulation of mitochondrial D‐loops by transcription factor A and single‐stranded DNA‐binding protein. EMBO reports, 3(5), 451-456. doi:10.1093/embo-reports/kvf099Wang, Y., & Bogenhagen, D. F. (2006). Human Mitochondrial DNA Nucleoids Are Linked to Protein Folding Machinery and Metabolic Enzymes at the Mitochondrial Inner Membrane. Journal of Biological Chemistry, 281(35), 25791-25802. doi:10.1074/jbc.m604501200Brown, T. A. (2005). Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism. Genes & Development, 19(20), 2466-2476. doi:10.1101/gad.135210

Fracture prediction from FRAX for Canadian ethnic groups: a registry-based cohort study

Summary We identified large between-ethnicity calibration differences in the Canadian FRAX® tool which substantially overestimated the major osteoporotic fracture (MOF) risk in Asian women and Black women, and overestimated hip fracture risk in Asian women. Purpose FRAX® is calibrated using population-specific fracture and mortality data. The need for FRAX to accommodate ethnic diversity within a country is uncertain. We addressed this question using the population-based Manitoba Bone Mineral Density (BMD) Program registry and self-reported ethnicity. Methods The study population was women aged 40 years or older with baseline FRAX assessments (Canadian and other ethnic calculators), fracture outcomes, and self-reported ethnicity (White N = 68,907 [referent], Asian N = 1910, Black N = 356). Adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to MOF and hip fracture were estimated. We examined candidate variables from DXA that might contribute to ethnic differences including skeletal size, hip axis length (HAL), trabecular bone score (TBS), and estimated body composition. Results Adjusted for baseline risk using the Canadian FRAX tool with BMD, Asian women compared with White women were at much lower risk for MOF (HR 0.46, 95% CI 0.35–0.59) and hip fracture (0.16, 95% CI 0.08–0.34). Black women were also at lower MOF risk (HR 0.58, 95% CI 0.32–1.00); there were no hip fractures. The US ethnic-specific FRAX calculators accounted for most of the between-ethnicity differences in MOF risk (86% for Asian, 92% for Black) but only partially accounted for lower hip fracture risk in Asian women (40%). The candidate variables explained only a minority of the effect of ethnicity. Gradient of risk in analyses was similar (p-interactions ethnicity*FRAX non-significant). Conclusions We identified significant ethnic differences in performance of the Canadian FRAX tool with fracture probability overestimated among Asian and Black women. The US ethnic calculators helped to address this discrepancy for MOF risk assessment, but not for hip fracture risk among Asian women

Octupolar ordering of Gamma8 ions in magnetic field

We study f-electron lattice models which are capable of supporting octupolar, as well dipolar and quadrupolar, order. Analyzing the properties of the Gamma8 ground state quartet, we find that (111)-type combinations of the Gamma5 octupoles Tbeta(111)=Tbeta(x)+Tbeta(y)+Tbeta(z) are the best candidates for octupolar order parameters. Octupolar ordering induces Gamma5-type quadrupoles as secondary order parameter. Octupolar order is to some extent assisted, but in its basic nature unchanged, by allowing for the presence of quadrupolar interactions. In the absence of an external magnetic field, equivalent results hold antiferro-octupolar ordering on the fcc lattice. In this sense, the choice of our model is motivated by the recent suggestion of octupolar ordering in NpO2. The bulk of our paper is devoted to a study of the effect of an external magnetic field on ferro-octupolar ordering. We found that octupolar order survives up to a critical magnetic field if the field is lying in specific directions, while for general field directions, the underlying symmetry of the model is destroyed and therefore the phase transition suppressed even in weak fields. Field-induced multipoles and field-induced couplings between various order parameters are discussed on the basis of a group theoretical analysis of the Helmholtz potential. We also studied the effect of octupolar ordering on the non-linear magnetic susceptibility which satisfies Ehrenfest-type relations at continuous octupolar transitions.Comment: 29 pages, 10 figures LaTeX In its contents, the present version agrees with the published one (see Journal Reference below). Essential additions to the text in Sec. III, otherwise some change of wording, and minor correction

Forest dynamics following spruce budworm outbreaks in the northern and southern mixedwoods of central Quebec

The effects of 20th century spruce budworm (Choristoneura fumiferana (Clem.)) outbreaks on forest dynamics was examined in the southern and northern parts of the mixedwood forest zone in central Quebec, Canada. In each region, three study areas were placed in unmanaged stands that had not burned for more than 200 years. Disturbance impacts and forest succession were evaluated using aerial photographs and dendrochronology. Spruce budworm outbreaks occurred around 1910, 1950, and 1980 in both regions. The 1910 outbreak seemed to have limited impact in both regions, and the 1950 outbreak caused heavy mortality in conifer stands (mostly of balsam fir, Abies balsamea (L.) Mill.) in the southern region. The 1980 outbreak caused major mortality in the northern region, but had little impact in the southern region. Successive spruce budworm outbreaks led to a massive invasion by hardwood species in the last century in the southern region but not in the northern region. The reason for such contrasting dynamics between regions is unknown, but we hypothesize that differences in disturbance intensities, influenced by climate, played a major role. Results from this study emphasize that generalizations about the effect of spruce budworm outbreaks on forest dynamics cannot be derived from observations made during a single outbreak or at a single location