The provision requires from state parties to “respect, preserve a

The provision requires from state parties to “respect, preserve and maintain knowledge, innovations and practices” of such communities and to “promote their wider application with the approval and involvement of the holders of such knowledge, innovations and practices and encourage the equitable sharing of benefits arising from the utilization of such knowledge, innovations and practices”. The obligations for a national government to protect such traditional knowledge arise, however, “subject to its national legislation”. In line with the utilitarian view of biodiversity conservation, Article 11 CBD foresees further that governments shall

“as far as possible and as appropriate, adopt economically and socially sound measures that act as incentives for the conservation and sustainable use of components of biological diversity”. “Incentives” Compound C datasheet has been interpreted as including not only economic but also social and legal measures (Biber-Klemm and Szymura Berglas 2006, pp. 31–34). This in turn may include property right mechanisms such as the granting of intellectual property screening assay rights to holders of traditional knowledge (Newell 2008, p. 85). The International

Treaty on Plant Genetic Resources for Food and Agriculture (ITPGR), negotiated under the auspices of FAO in 2001 and in force since 2004, aims at playing a similar role as the CBD for agricultural biodiversity. Its objectives are “the conservation and sustainable use of plant genetic resources for food and agriculture and the fair

and equitable sharing of the benefits arising out of their use, in harmony with the Convention on Biological Diversity, for sustainable agriculture and food security” (Article 1.1). According to the preamble it sees questions regarding the management of plant genetic resources for food and agriculture as being “at the meeting point between agriculture, the environment and commerce” and it aims to promote “synergy among these sectors”. Similarly as the CBD, the ITPGR establishes a special role Montelukast Sodium for farmers, indigenous and local communities. It requires from parties to “promote or support, as appropriate, farmers and local communities’ efforts to manage and conserve on-farm their plant genetic resources for food and agriculture” (Article 5.1 (c)); and “to promote in situ conservation of wild crop relatives and wild plants for food production, including in protected areas, by supporting, inter alia, the efforts of indigenous and local communities” (Article 5.1 (d)). Intellectual property rights in the CBD and in TRIPS The CBD recognises and respects intellectual property rights (Article 16.2. CBD), but foresees in Article 16.5.

TatB (specifies a WT copy of tatB), and pRB TAT Panel C: Growth

TatB (specifies a WT copy of tatB), and pRB.TAT. Panel C: Growth of O35E is compared to that of its tatC isogenic mutant strain, O35E.TC, carrying the plasmid pWW115 and pRB.TatC (contains a WT copy of tatC). Growth of the bro-2 isogenic mutant strain O35E.Bro is also shown. The results are shown as a composite image representative

of individual experiments that were performed in duplicate on at least 3 separate occasions. The effect of tat mutations on the β-lactamase activity of M. catarrhalis was quantitatively measured using the chromogenic β-lactamase substrate nitrocefin. These assays were performed using suspensions of freshly plate-grown bacteria placed into the wells of a 48-well tissue culture plate. A solution containing nitrocefin was added ATM Kinase Inhibitor mw to these suspensions and the change of color from yellow to red (indicative of cleavage of the β-lactam ring) was monitored by measuring the absorbance of well contents at a wavelength of 486 nm. Substantially less β-lactamase activity was observed for the tatA, tatB and tatC mutants compared to the WT strain O35E (Figure 6). Complementation of the tatA and tatB mutants with plasmids containing only the WT copies of the inactivated genes did not restore β-lactamase activity, as expected based on the results of the experiments

depicted in Figures 3 and 5. The plasmid pRB.TAT, which specifies the entire tatABC locus, restored the ability of the mutants O35E.TA (Figure 6A) EPZ-6438 cost and O35E.TB (Figure 6B) to hydrolyze nitrocefin. The plasmid pRB.TatC was sufficient to rescue β-lactamase activity in the tatC mutant strain O35E.TC to near WT levels (Figure 6C). The tatC mutant of strain O12E was tested in this manner and the results were consistent with those obtained with O35E.TC (data not shown). Cobimetinib The control strain, O35E.Bro, was impaired in its ability to hydrolyze nitrocefin at levels comparable to those of the tatA, tatB and tatC mutants (Figure 6A, B and C). Taken together, these results suggest that the M. catarrhalis tatABC locus is necessary for secretion of the β-lactamase BRO-2 into the periplasm where the enzyme can protect the peptidoglycan

cell wall from the antimicrobial activity of β-lactam antibiotics. Figure 6 Quantitative measurement of the β-lactamase activity produced by the M. catarrhalis WT isolate O35E and tat mutant strains. The β-lactamase activity of strains was measured using the chromogenic compound nitrocefin. Bacterial suspensions were mixed with a 250 μg/mL nitrocefin solution and the absorbance at 486 nm (A486) was immediately measured and recorded as time “0” (open bars). The A486 of the AR-13324 samples was measured again after a 30-min incubation at room temperature (black bars). Panel A: The β-lactamase activity of O35E is compared to that of the tatA mutant strain, O35E.TA, carrying the plasmid pWW115 (control), pRB.TatA (specifies a WT copy of tatA), and pRB.TAT (harbors the entire tatABC locus).

2006) Interestingly, BP86-optimized geometries

2006). Interestingly, BP86-optimized geometries Blasticidin S were better than those obtained from B3LYP; however, B3LYP yielded exchange coupling constants in excellent

agreement with experiment. The coupled perturbed Kohn–Sham equations were employed for the g-tensor calculations, and a strategy for the computation of g-tensor site values was presented that provided single-site g-tensors in good agreement with the expectations for the respective Mn formal oxidation states. Spin projection gave the g-tensor of the coupled manganese complex in good agreement with the experimental results. Small values were found for the nuclear quadrupole splitting of 55Mn. Hyperfine tensors were furthermore calculated and spin-projected. 14N and 1H ligand hyperfine data were found to compare well with experiment. 55Mn HFCs were qualitatively in line with experimental Epoxomicin order results, tracing the source of anisotropy to the MnIII center. However, isotropic 55Mn HFCs were distinctly underestimated. The authors indicated that this deficiency is systematic in character and does not originate from the broken symmetry approach. Similar deviations were found between theory and experiment for DFT calculations on mononuclear Mn complexes, suggesting that the use of a universal scaling factor of approximately 1.5 might be appropriate.

Summary and Selleckchem MK 2206 perspectives Density functional theory methods have already been established as a valuable research tool both in independent applications and as a complement of experimental investigations. In favorable cases, the calculated properties are sufficiently accurate to discriminate between structural alternatives for reaction intermediates or other species that are not amenable to experimental structure elucidation. DFT appears generally reliable for geometries, vibrational frequencies, and total energies, having over wavefunction-based methods the

advantage of quick convergence to the basis set limit. DFT appears to be quite successful for the prediction of molecular properties as well, since a number of spectroscopic properties of interest to the bioinorganic community can be predicted with good accuracy. Hybrid functionals are in most cases better performers, with the TPSSh functional emerging as a potential new standard. There are still cases, however, where quantitative accuracy may be difficult to achieve, especially Carnitine dehydrogenase for the prediction of EPR parameters or optical spectra, necessitating a cautious and critical approach from the part of the researcher. It is important for both practitioners of DFT and the nontechnical audience of DFT studies to keep in mind that errors do arise and they can be significant. Despite the enormous advances in density functional implementations and the sufficiently documented accuracy of results for many applications, there is no systematic way of improving DFT or converging its results to the “correct” answer, in contrast to some of the traditional wavefunction-based methods.

In Y enterocolitica, several other virulence factors such as inv

In Y. enterocolitica, several other virulence factors such as invasin, Myf fibrillae and enterotoxin have also been reported to be regulated by growth phase and the growth temperature [50]. A 10-fold increase in urease activity following supplementation of growth medium with nickel was not accompanied by increase in the expression of urease structural proteins suggesting that increased activity was probably

due to the activation of pre-existing apoenzyme. Nickel has been reported to regulate both expression and activity of urease in H. pylori [51]. In silico analysis of whole genome of Y. enterocolitica 8081 (biovar 1B) revealed two systems (ureH and Vorinostat supplier ynt) for transport of nickel. It would be interesting to determine the role Small molecule library high throughput of multiple nickel transport genes in urease activity and its regulation in Y. enterocolitica. The Mw of Y. enterocolitica biovar 1A urease as assessed from native PAGE was > 545 kDa. The molecular mass of urease is known to vary from as low as 130 kDa in B. suis [52] to as high as 620 kDa in Providencia rettgeri or > 700

kDa in M. morganii [53]. The difference in the molecular mass of urease of Y. enterocolitica biovar 1A vis-à-vis Y. enterocolitica biovar 1B and biovar 4 seems to be due to difference in the size of UreB (β-subunit), which is smaller in the former and thus may account for its lower molecular mass. The isoelectric point (pI) of 5.2 of biovar 1A urease was close to that reported for Proteus penneri (pI = 5.1) and H. pylori (pI = 5.9) urease [33, 54]. No data on molecular mass and isoelectric point of ureases produced by Y. Janus kinase (JAK) enterocolitica strains belonging to other biovars has been reported. The ability of Y. enterocolitica biovar 1A strains to survive at pH 2.5

in vitro in the presence of 3.4 mM urea implicated urease in their survival. This suggested the Ruboxistaurin order possible role urease might play in the survival of Y. enterocolitica biovar 1A under acidic conditions in the gut. However, this needs to be confirmed by comparison of wild type strain with an isogenic urease mutant. The role of urease in survival during transit through gut has been reported for B. suis, B. abortus, H. pylori and E. ictaluri [18, 19, 36, 55, 56]. Interestingly, the biovar 1A strains have also been reported to resist killing, and survive within macrophages [13]. It would therefore be worthwhile to determine the role urease may play in the survival of Y. enterocolitica biovar 1A strains in the acidic environment of phagolysosomes. Conclusions The ure gene cluster of Y. enterocolitica biovar 1A though broadly similar to that of biovar 1B and biovar 4 strains showed differences in structural (ureB) genes and the intergenic regions thereof. The kinetic data indicated that urease produced by Y. enterocolitica biovar 1A strain would be active at low concentration of urea typically present in the gut. The ability of biovar 1A strain to survive at acidic pH in the presence of urea suggested that urease might play role in their survival in the gut.

Indeed, this effect was not observed with other classes of antibi

Indeed, this effect was not observed with other classes of antibiotics [19–25]. In the present work and for the first time, an effect similar to that of beta-lactams is reported with tetracycline. Curiously, this antibiotic

induced larger plaques than beta-lactams. In the light of the foregoing discussion, this may be expected since it is well established that tetracycline can cause cell elongation and filamentation, so it is potentially able to increase phage production [34–36]. However, in the check details light of the results obtained, filamentation (or cell size elongation) seems not to be the only determinant of plaque size increase. In fact we observed that tetracycline induced the greatest increase in plaque size, but cells subjected to it were smaller than those incubated with the other antibiotics tested. Indeed, we found no correlation between plaque size and cell size. An unexpected

observation in this work was the conspicuous effect of glycerol in increasing phage plaque size and contrast. Glycerol produced a huge improvement in plaque observations when tetracycline was used. It allowed plaques to be observed that had very little contrast and were difficult to observe when tetracycline alone was used. This difficulty in observing the plaques obtained with tetracycline and no glycerol may explain why the effect of tetracycline, and even of other classes of antibiotics, has not been observed previously. STI571 ic50 We conclude that glycerol plays a critical role in improving plaque observation. Glycerol may increase phage

diffusion in the medium Docetaxel cost resulting in enhanced plaque size. Since it is a nonfermentative carbon source for these bacteria its presence will result in increased biomass or delay the onset of stationary phase. A plaque is unlikely to increase in size as the lawn cells enter late log growth stage [10, 37–39]. All in all, the influence of antibiotics on burst size, latent period and adsorption rate and the influence of glycerol on the BKM120 diffusivity of phages in the medium and on bacterial growth seem to act together leading to a great increase in plaque size. Moreover, it was demonstrated here that antibiotics not only have the ability to increase phage plaques, they also do not suppress bacteriophage development at subminimal inhibitory concentrations (sub-MICs). In addition, the present results allow us to conclude that the new method (PAMA) can be applied to both Gram-negative and Gram-positive bacteria with lytic phages. The phages used represent the three families in the order Caudovirales, which include 96% of all observed phages [16]. Obviously, the antibiotic to be used in the PAMA, as well its concentration, have to be optimized for each bacterial host. Conclusion It is well known that some phages in the classical DLA technique produce plaques that are difficult or impossible to observe with the naked eye, leading to erroneous phage enumeration.

PubMedCrossRef 43 Bikard D, Hatoum-Aslan A, Mucida D, Marraffini

PubMedCrossRef 43. Bikard D, Hatoum-Aslan A, Mucida D, Marraffini LA: CRISPR interference can prevent natural transformation buy Repotrectinib and virulence acquisition during in vivo bacterial infection. Cell Host Microbe 2012, 12:177–186.PubMedCrossRef 44. Díez-Villaseñor C, Almendros C, García-Martínez J, Mojica FJ: Diversity of CRISPR loci in Escherichia coli. Microbiology 2010, 156:1351–1361.PubMedCrossRef 45. Touchon M, Rocha EP: The small, slow and specialized CRISPR and anti-CRISPR of Escherichia and Salmonella. PLoS One 2010, 5:e11126.PubMedCrossRef 46. Stern A, Keren L, Wurtzel O, Amitai G, Sorek R: Self-targeting by CRISPR: gene regulation or autoimmunity.

Trends Genet 2010, 26:335–340.PubMedCrossRef 47. Goren MG, Yosef I, Auster O, Qimron U: Experimental definition of a clustered regularly interspaced short palindromic duplicon in Escherichia coli. J Mol Biol 2012, 423:14–16.PubMedCrossRef 48. Brodt A, Lurie-Weinberger MN, Gophna U: CRISPR loci reveal networks of gene exchange in archaea. Biol Direct 2011, 6:65.PubMedCrossRef 49. Bateman A, Rawlings ND: The CHAP domain: a large family of amidases including GSP amidase and peptidoglycan hydrolases. Trends Biochem Sci 2003, 28:234–237.PubMedCrossRef 50. Kjos M, Snipen L, Salehian Z, Nes IF, Diep DB: The Abi proteins and their involvement in bacteriocin self-immunity.

J Bacteriol 2010, 192:2068–2076.PubMedCrossRef 51. Teixeira GS, Soares-Brandão KL, Branco KM, Sampaio JL, Nardi RM, Mendonça M, Almeida RB, selleck kinase inhibitor Farias LM, Carvalho MA, Nicoli JR: Antagonism and synergism in Gardnerella vaginalis strains isolated from women with bacterial vaginosis. J Med Microbiol 2010, 59:891–897.PubMedCrossRef Carnitine dehydrogenase 52. Piot P, van Dyke E, Peeters M, Hale J, Totten PA, Holmes KK: Biotypes of Gardnerella vaginalis. J Clin Microbiol 1984, 20:667–679. 53. Vestergaard AL, Knudsen UB, Munk T, Rosbach H, Bialasiewicz S, Sloots TP, Martensen PM, Antonsson A: Low

prevalence of DNA viruses in the human endometrium and endometriosis. Arch Virol 2010, 155:693–703.CrossRef 54. Marazzo JM, Fiedler TL, Srinivasan S, Thomas KK, Liu C, Ko D, Xie H, Saracino M, Fredricks DN: Extravaginal reservoirs of vaginal bacteria as risk factors for incident bacterial vaginosis. J Infect Dis 2012, 205:1580–1588.CrossRef 55. Palmer KL, Gilmore MS: Multidrug-resistant enterococci lack CRISPR-cas. mBio 2010, 1:e00227–10.PubMedCrossRef 56. Delaney NF, Balenger S, Bonneaud C, Marx CJ, Hill GE, Ferguson-Noel N, Tsai P, Rodrigo A, Edwards S: Ultrafast evolution and loss of CRISPRs find more following a host shift in a novel wildlife pathogen, Mycoplasma gallisepticum. PLoS Genet 2012, 8:e1002511.PubMedCrossRef 57. Gasiunas G, Barrangou R, Horvath P, Siksnys V: Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria. Proc Natl Sci USA 2012, 109:E2579-E2586.CrossRef Competing interests The authors declare no competing interests.

This can be explained by the significant differences in physical

This can be explained by the significant differences in physical therapy and occupational therapy options available for patients in rehabilitation programs compared with patients at ALF. Selection bias of patients in a poorer overall condition to ALF could also explain these findings. There are a number of significant strengths and limitations of this study. Inclusion criteria were ISS >15 thus making this cohort of patients appropriate for the study of long term survival. We excluded patients who died in the hospital from the analysis of delayed

long term mortality because the acute mortality from major trauma is determined largely by the severity of the initial injury. This study design allowed click here us to potentially separate the effects of the initial injury, but rather to use the initial data of patient admission JPH203 to predict long term outcome. The major limitation of this study is related to retrospective data analysis. In our trauma registry co-morbidities are listed by

reviewing previous discharge letters with the incumbent limitations of such data. Finally, data on pre-injury living status for the 148 patients who returned home is not available, and therefore, we cannot draw any definitive conclusions regarding the home status of this group. In conclusion, we have shown that clinical and demographic factors are associated with long term, post-discharge outcome following severe trauma in geriatric patients, and we noted that almost 2/3 of elderly patients injured following a trauma were discharged from the hospital with a favorable long term outcome. We noted that common demographic and clinical parameters, including age ≥ 80, lower GCS upon arrival and fall as the mechanism of injury are clear predictors of a poor long term outcome for severely injured geriatric trauma patients. Although most studies commonly evaluate in hospital, < 30 day mortality, our findings expands our understanding of factors contributing

towards long term post-discharge survival. Given the substantial and increasing burden of the elderly sustaining traumatic injury, our findings underscore the importance of additional research to further identify risks and prognostic factors to improve our trauma care and performance Cytidine deaminase improvement, in order to ultimately impact survival in the injured elderly patient. The role of a geriatric consultation service could be crucial in their care and play an important role in the framework of a multi-disciplinary team. References 1. Habot B, Tsin S: Geriatrics in the new millennium, Israel. IMAJ 2003, 5:319–321.PubMed 2. World Health Organization (WHO): WHO Statistical Information System (WHOSIS). http://​www.​who.​int/​whosis 3. McMahon DJ, Shapiro MB, Kauder DR: The injured elderly in the trauma intensive care unit. Surg Clin North Am 2000, 80:1005–1019.PubMedCrossRef 4.

doi:10 ​1371/​journal ​pone ​0008320 Gunderson LH, Holling CS (ed

doi:10.​1371/​journal.​pone.​0008320 Gunderson LH, Holling CS (eds) (2002) Panarchy: understanding transformations in human and natural systems. Island Press, Washington Hannah L, Midgley GF, Lovejoy T, Bond WJ, Bush M, Lovett JC, Scott D, Woodward FI (2002a) Conservation of biodiversity in a changing climate. Conserv Biol 16:264–268CrossRef Hannah L, Midgley GF, Millar D (2002b) Climate change-integrated conservation strategies. Glob Ecol Biogeogr 11:485–495CrossRef Harris JA, Hobbs RJ, Higgs E, Aronson J (2006) Ecological restoration and global

climate change. Restor Ecol 14:170–176CrossRef Heller NE, Zavaleta ES (2009) Biodiversity management in the face of climate change: a review of 22 years of recommendations. Biol Conserv 142:14–32CrossRef Holling CS (1973) Resilience BAY 11-7082 and stability of ecological systems. Annu Rev Ecol Syst 4:1–23CrossRef Hulme PE (2005) Adapting to climate change: is there scope for ecological management in the face of a global threat? J Appl Ecol 42:784–794CrossRef Hunter M, Dinerstein E, Hoekstra J, Lindenmayer D (2010) Conserving

biodiversity in the face of climate change: a call to action. Conserv Biol 24:1169–1171PubMedCrossRef Kareiva P, Marvier M (2007) Conservation for the people. Sci Am 297:50–57PubMedCrossRef Kareiva P, Enquist C, Johnson A, Julius SH, Lawler J, Petersen B, Pitelka L, Shaw R, West J (2008) Synthesis and conclusions, Chap 9. In: Julius

SH, West JM (eds) Preliminary review of adaptation options for climate-sensitive ecosystems and resources. see more selleckchem A report by the U.S. climate change science program and the subcommittee on global change research. U.S. EPA, Washington, DC Krosby M, Tewksbury J, Haddad NM, Hoekstra J (2010) Ecological connectivity for a changing climate. Conserv Biol. doi:10.​1111/​j.​1523-1739.​2010.​01585.​x Lawler JJ (2009) Climate change adaptation strategies for resource management and conservation planning. Year Ecol Conserv Biol, NY Acad Sci 1162:79–98 Lawler JJ, Tear T, Pyke CR, Shaw R, Gonzalez P, Kareiva P, Hansen L, Hannah L, Klausmeyer K, Aldous A, Bienz C, Pearsall S (2009) Resource management in a changing and uncertain climate. Front Ecol Environ 7. doi:10.​1890/​070146 Mawdsley JR, O’Malley R, Ojima DS (2009) A review of climate-change adaptation strategies for wildlife management of biodiversity conservation. Conserv Biol 23:1080–1089PubMedCrossRef McClanahan TR, Cinner J, Maina J, Graham NAJ, Daw TM, Stead SM, Wamukota A, Brown K, Ateweberhan M, Venus V, Polunin NVC (2008) Conservation action in a changing climate. Conserv Lett 1:53–59CrossRef Orr DW (2008) Land use and climate change. Conserv Biol 22:1372–1374PubMedCrossRef Parmesan C (2006) Ecological and evolutionary responses to recent climate change.

Carvedilol produces dose-related improvements in left ventricular

Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with Autophagy inhibitor chronic heart failure. MOCHA Investigators. Circulation. 1996;94:2807–16.PubMedCrossRef 8. Lowes BD, Gill EA, Abraham WT, Larrain JR, Robertson AD, Bristow MR, et al. Effects of carvedilol on left ventricular mass, chamber geometry, and mitral

regurgitation in chronic heart failure. Am J Cardiol. 1999;83:1201–5.PubMedCrossRef 9. Francis GS, Benedict C, Johnstone DE, Kirlin PC, Nicklas J, Liang CS, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive check details heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation. 1990;82:1724–9.PubMedCrossRef 10. Gilbert EM, Abraham WT, Olsen S, Hattler B, White M, Mealy P, et al. Comparative hemodynamic, left ventricular functional, and antiadrenergic effects of chronic treatment with metoprolol versus carvedilol in the failing heart. Circulation. 1996;94:2817–25.PubMedCrossRef Temsirolimus ic50 11. Morimoto S, Shimizu K, Yamada K, Hiramitsu S, Hishida H. Can beta-blocker therapy be withdrawn from patients with dilated cardiomyopathy? Am Heart J. 1999;138:456–9.PubMedCrossRef 12. Carson P, Ziesche S, Johnson G, Cohn

JN. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail. 1999;5:178–87.PubMedCrossRef Cytidine deaminase 13. Yancy CW. Heart failure in African Americans: a cardiovascular engima. J Card Fail. 2000;6:183–6.PubMedCrossRef 14. Thomas KL, East MA, Velazquez EJ, Tuttle RH, Shaw LK, O’Connor CM, et al. Outcomes by race and etiology of patients with left ventricular systolic dysfunction. Am J Cardiol. 2005;96:956–63.PubMedCrossRef 15. Liggett SB, Mialet-Perez J, Thaneemit-Chen S, Weber SA, Greene SM, Hodne D, et al. A polymorphism within a conserved beta(1)-adrenergic receptor motif alters cardiac function and beta-blocker response in human heart failure. Proc Natl Acad Sci USA. 2006;103:11288–93.PubMedCrossRef

16. Yancy CW, Fowler MB, Colucci WS, Gilbert EM, Bristow MR, Cohn JN, et al. Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure. N Engl J Med. 2001;344:1358–65.PubMedCrossRef 17. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349–55.PubMedCrossRef 18. Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.PubMedCrossRef 19. Effect of metoprolol CR/XL in chronic heart failure. Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001–7.CrossRef 20.

Conflicts of interest None Appendix Table 3 Studies used to comp

Conflicts of interest None. Appendix Table 3 Studies used to compute age-standardised hip fracture incidence Country Citation Notes Argentina Morosano M, Masoni A, Sánchez A (2005) Incidence of hip fractures in the city of Rosario, Argentina. Osteoporos Int 16: 1339–1344 Supplementary information from authors Australia Crisp A, Dixon T, Jones, Selleck RG7112 Ebeling P, Cumming R (2012) Declining

incidence of osteoporotic hip fracture in Australia. Manuscript in preparation Supplementary information from Australian Institute of Health and Welfare Austria Dimai H P (2008) Personal communication Supplementary information Statistic Austria Dimai HP, Svedbom A, Fahrleitner-Pammer A, et al. (2011) Epidemiology of hip fractures in Austria: evidence for a change in the secular trend. Osteoporos Int22: 685–692 Belgium Hiligsmann M, personal communication, June 2011 Update of FRAX model with more extensive data Brazil Silveira C, Medeiros M, Coelho-Filho JM et al. (2005) Incidência de fratura do quadril em area urbana do Nordeste brasileiro. Cad. Saúde Pública. 21: 907–912 Average taken of all data from Brazil Komatsu RS, Ramos LR, Szejnfeld A (2004) Incidence of proximal femur fractures in Marilia, Brazil. J Nut Health Aging. 8: 362 Shwartz AV, Kelsey JL, Maggi S et al. find more (1999)

Cytoskeletal Signaling International variation in the incidence of hip fractures: cross-national project on osteoporosis for the World Health Organization Program for Research on Aging. Osteoporos Dapagliflozin Int 9: 242–253 Castro da Rocha FA, Ribeiro AR (2003) Low incidence of hip fractures in an equatorial area. Osteoporos Int 14:496–499 Canada Leslie WD, O’Donnell S, Lagacé C et al. (2010) Osteoporosis surveillance expert working group. Population-based Canadian hip

fracture rates with international comparisons. Osteoporos Int. 21: 1317–1322 Supplementary information from WB Leslie Leslie WD, Lix LM, Langsetmo L et al. (2011) Construction of a FRAX® model for the assessment of fracture probability in Canada and implications for treatment. Osteoporos Int 22: 817–827 Chile Pablo Riedemann and Oscar Neira, personal communication 4th Oct 2011 Source: Health Ministry, June 2010 China Schwartz AV, Kelsey JL, Maggi S et al. (1999) International variation in the incidence of hip fractures: cross-national project on osteoporosis for the World Health Organization Program for Research on Aging. Osteoporos Int 9: 242–253 Mean of Schwartz 1999, Ling 1996, Yan 1999 and Zhang 2000 used in FRAX model Ling X, Aimin, L, Xihe Z, Xaioshu C, Cummings SR (1996) Very low rates of hip fracture in Beijing, Peoples Republic of China. The Beijing Osteoporosis Project. Am J Epidemiol 144; 901–907 Yan L, Zhou B, Prentice A, Wang X, Golden MH (1999) Epidemiological study of hip fracture in Shenyang, People’s Republic of China.