Antimicrobial resistance (AMR) in clinically relevant bacteria is a growing threat to public health globally. In these bacteria, antimicrobial resistance genes are often associated with mobile ...genetic elements (MGEs), which promote their mobility, enabling them to rapidly spread throughout a bacterial community.
The tool MobileElementFinder was developed to enable rapid detection of MGEs and their genetic context in assembled sequence data. MGEs are detected based on sequence similarity to a database of 4452 known elements augmented with annotation of resistance genes, virulence factors and detection of plasmids.
MobileElementFinder was applied to analyse the mobilome of 1725 sequenced Salmonella enterica isolates of animal origin from Denmark, Germany and the USA. We found that the MGEs were seemingly conserved according to multilocus ST and not restricted to either the host or the country of origin. Moreover, we identified putative translocatable units for specific aminoglycoside, sulphonamide and tetracycline genes. Several putative composite transposons were predicted that could mobilize, among others, AMR, metal resistance and phosphodiesterase genes associated with macrophage survivability. This is, to our knowledge, the first time the phosphodiesterase-like pdeL has been found to be potentially mobilized into S. enterica.
MobileElementFinder is a powerful tool to study the epidemiology of MGEs in a large number of genome sequences and to determine the potential for genomic plasticity of bacteria. This web service provides a convenient method of detecting MGEs in assembled sequence data. MobileElementFinder can be accessed at https://cge.cbs.dtu.dk/services/MobileElementFinder/.
It is hypothesized that environmental contamination by per- and polyfluoroalkyl substances (PFAS) defines a separate planetary boundary and that this boundary has been exceeded. This hypothesis is ...tested by comparing the levels of four selected perfluoroalkyl acids (PFAAs) (i.e., perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) in various global environmental media (i.e., rainwater, soils, and surface waters) with recently proposed guideline levels. On the basis of the four PFAAs considered, it is concluded that (1) levels of PFOA and PFOS in rainwater often greatly exceed US Environmental Protection Agency (EPA) Lifetime Drinking Water Health Advisory levels and the sum of the aforementioned four PFAAs (Σ4 PFAS) in rainwater is often above Danish drinking water limit values also based on Σ4 PFAS; (2) levels of PFOS in rainwater are often above Environmental Quality Standard for Inland European Union Surface Water; and (3) atmospheric deposition also leads to global soils being ubiquitously contaminated and to be often above proposed Dutch guideline values. It is, therefore, concluded that the global spread of these four PFAAs in the atmosphere has led to the planetary boundary for chemical pollution being exceeded. Levels of PFAAs in atmospheric deposition are especially poorly reversible because of the high persistence of PFAAs and their ability to continuously cycle in the hydrosphere, including on sea spray aerosols emitted from the oceans. Because of the poor reversibility of environmental exposure to PFAS and their associated effects, it is vitally important that PFAS uses and emissions are rapidly restricted.
Summary
Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk of fractures due to osteoporosis.
Introduction
The International Osteoporosis ...Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2008. This manuscript updates these in a European setting.
Methods
Systematic literature reviews.
Results
The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk, general and pharmacological management of osteoporosis, monitoring of treatment, assessment of fracture risk, case finding strategies, investigation of patients and health economics of treatment.
Conclusions
A platform is provided on which specific guidelines can be developed for national use.
Summary
A fracture risk assessment tool (FRAX™) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK.
Introduction
The aim of this study ...was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily.
Methods
Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions.
Results
Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m
2
) ranged from 0.2% at the age of 50 years for women without CRF’s to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter.
Conclusion
The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.
A novel control strategy for multi-agent coordination with event-based broadcasting is presented. In particular, each agent decides itself when to transmit its current state to its neighbors and the ...local control laws are based on these sampled state measurements. Three scenarios are analyzed: Networks of single-integrator agents with and without communication delays, and networks of double-integrator agents. The novel event-based scheduling strategy bounds each agent’s measurement error by a time-dependent threshold. For each scenario it is shown that the proposed control strategy guarantees either asymptotic convergence to average consensus or convergence to a ball centered at the average consensus. Moreover, it is shown that the inter-event intervals are lower-bounded by a positive constant. Numerical simulations show the effectiveness of the novel event-based control strategy and how it compares to time-scheduled control.
Event-driven strategies for multi-agent systems are motivated by the future use of embedded microprocessors with limited resources that will gather information and actuate the individual agent ...controller updates. The controller updates considered here are event-driven, depending on the ratio of a certain measurement error with respect to the norm of a function of the state, and are applied to a first order agreement problem. A centralized formulation is considered first and then its distributed counterpart, in which agents require knowledge only of their neighbors' states for the controller implementation. The results are then extended to a self-triggered setup, where each agent computes its next update time at the previous one, without having to keep track of the state error that triggers the actuation between two consecutive update instants. The results are illustrated through simulation examples.
Summary
The country-specific risk of hip fracture and the 10-year probability of a major osteoporotic fracture were determined on a worldwide basis from a systematic review of literature. There was a ...greater than 10-fold variation in hip fracture risk and fracture probability between countries.
Introduction
The present study aimed to update the available information base available on the heterogeneity in the risk of hip fracture on a worldwide basis. An additional aim was to document variations in major fracture probability as determined from the available FRAX models.
Methods
Studies on hip fracture risk were identified from 1950 to November 2011 by a Medline OVID search. Evaluable studies in each country were reviewed for quality and representativeness and a study (studies) chosen to represent that country. Age-specific incidence rates were age-standardised to the world population in 2010 in men, women and both sexes combined. The 10-year probability of a major osteoporotic fracture for a specific clinical scenario was computed in those countries for which a FRAX model was available.
Results
Following quality evaluation, age-standardised rates of hip fracture were available for 63 countries and 45 FRAX models available in 40 countries to determine fracture probability. There was a greater than 10-fold variation in hip fracture risk and fracture probability between countries.
Conclusions
Worldwide, there are marked variations in hip fracture rates and in the 10-year probability of major osteoporotic fractures. The variation is sufficiently large that these cannot be explained by the often multiple sources of error in the ascertainment of cases or the catchment population. Understanding the reasons for this heterogeneity may lead to global strategies for the prevention of fractures.
We analyze 40 cosmological re-simulations of individual massive galaxies with present-day stellar masses of M * > 6.3 X 1010 M in order to investigate the physical origin of the observed strong ...increase in galaxy sizes and the decrease of the stellar velocity dispersions since redshift z 2. At present 25 out of 40 galaxies are quiescent with structural parameters (sizes and velocity dispersions) in agreement with local early-type galaxies. At z = 2 all simulated galaxies with M * 1011 M (11 out of 40) at z = 2 are compact with projected half-mass radii of 0.77 (?0.24) kpc and line-of-sight velocity dispersions within the projected half-mass radius of 262 (?28) km s--1 (3 out of 11 are already quiescent). Similar to observed compact early-type galaxies at high redshift, the simulated galaxies are clearly offset from the local mass-size and mass-velocity dispersion relations. Toward redshift zero the sizes increase by a factor of ~5-6, following R 1/2(1 + z) Delta *a with Delta *a = --1.44 for quiescent galaxies ( Delta *a = --1.12 for all galaxies). The velocity dispersions drop by about one-third since z 2, following Delta *s1/2(1 + z) Delta *b with Delta *b = 0.44 for the quiescent galaxies ( Delta *b = 0.37 for all galaxies). The simulated size and dispersion evolution is in good agreement with observations and results from the subsequent accretion and merging of stellar systems at z 2, which is a natural consequence of the hierarchical structure formation. A significant number of the simulated massive galaxies (7 out of 40) experience no merger more massive than 1:4 (usually considered as major mergers). On average, the dominant accretion mode is stellar minor mergers with a mass-weighted mass ratio of 1:5. We therefore conclude that the evolution of massive early-type galaxies since z 2 and their present-day properties are predominantly determined by frequent 'minor' mergers of moderate mass ratios and not by major mergers alone.
Given its velocity dispersion, the early-type galaxy NGC 1600 has an unusually massive (M = 1.7 × 1010 M ) central supermassive black hole (SMBH) surrounded by a large core (rb = 0.7 kpc) with a ...tangentially biased stellar distribution. We present high-resolution equal-mass merger simulations including SMBHs to study the formation of such systems. The structural parameters of the progenitor ellipticals were chosen to produce merger remnants resembling NGC 1600. We test initial stellar density slopes of ∝ r−1 and ∝ r−3/2 and vary the initial SMBH masses from 8.5 × 108 to 8.5 × 109 M . With increasing SMBH mass, the merger remnants show a systematic decrease in central surface brightness, an increasing core size, and an increasingly tangentially biased central velocity anisotropy. Two-dimensional kinematic maps reveal decoupled, rotating core regions for the most massive SMBHs. The stellar cores form rapidly as the SMBHs become bound, while the velocity anisotropy develops more slowly after the SMBH binaries become hard. The simulated merger remnants follow distinct relations between the core radius and the sphere of influence, and the SMBH mass, similar to observed systems. We find a systematic change in the relations as a function of the progenitor density slope and present a simple scouring model reproducing this behavior. Finally, we find the best agreement with NGC 1600 using SMBH masses totaling the observed value of M = 1.7 × 1010 M . In general, density slopes of ∝ r−3/2 for the progenitor galaxies are strongly favored for the equal-mass merger scenario.
Summary
The number of individuals aged 50 years or more at high risk of osteoporotic fracture worldwide in 2010 was estimated at 158 million and is set to double by 2040.
Introduction
The aim of this ...study was to quantify the number of individuals worldwide aged 50 years or more at high risk of osteoporotic fracture in 2010 and 2040.
Methods
A threshold of high fracture probability was set at the age-specific 10-year probability of a major fracture (clinical vertebral, forearm, humeral or hip fracture) which was equivalent to that of a woman with a BMI of 24 kg/m
2
and a prior fragility fracture but no other clinical risk factors. The prevalence of high risk was determined worldwide and by continent using all available country-specific FRAX models and applied the population demography for each country.
Results
Twenty-one million men and 137 million women had a fracture probability at or above the threshold in the world for the year 2010. The greatest number of men and women at high risk were from Asia (55 %). Worldwide, the number of high-risk individuals is expected to double over the next 40 years.
Conclusion
We conclude that individuals with high probability of osteoporotic fractures comprise a very significant disease burden to society, particularly in Asia, and that this burden is set to increase markedly in the future. These analyses provide a platform for the evaluation of risk assessment and intervention strategies.
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