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Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
Get PDFPURPOSE: The International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.
METHODS: Evidence for the relationship between BTMs and subsequent fractures was gathered from prospective studies through literature review of the Medline database from years 2011 to May 2024. The impact of treatment on BTMs was also studied by examining publications in that period. Studies of the accuracy of BTMs in the assessment of bone turnover in the setting of advanced chronic kidney disease were also examined.
RESULTS: Increased BTM concentrations are associated with higher fracture risk in postmenopausal women. PINP and β-CTX-I measured in blood are associated with fracture risk but their interaction with other risk factors has not been sufficiently studied limiting their incorporation into fracture risk algorithms. Treatment-induced changes in PINP and β-CTX-I account for a substantial proportion of fracture risk reduction and are useful for improving adherence; they are recommended for inclusion in studies to examine adherence in individual patients. However, total PINP (tPINP) and β-CTX-I may be elevated in CKD due to renal retention. Bone alkaline phosphatase (BALP), intact PINP (iPINP), and tartrate resistant acid phosphatase 5b (TRACP5b) show the most promise in discriminating high and low turnover bone diseases in patients with advanced CKD and for predicting fracture risk, monitoring treatment response, and assessing the risk of treatment-related complications.
CONCLUSION: We re-affirm the use of serum/plasma tPINP and plasma β-CTX-I as reference BTMs with appropriate patient preparation and sample handling and measurement by standardized/harmonized assays in clinical studies to accumulate further data, and for monitoring treatment of osteoporosis in the setting of normal renal function in clinical practice. BALP and TRACP5b, measured by standardized assays, are recommended as reference BTMs for CKD-associated osteoporosis and should be included in observational and intervention studies to ascertain their utility for risk-evaluation, treatment initiation, and assessment of treatment response in CKD-associated osteoporosis
Wear control and friction reduction in newly developed multilayer Mg-DLC coatings using organic base oil and sustainable lubrication additives
Get PDFTwo sets of DLC coatings, doped with identical Mg concentrations (6-15 at.%) but exhibiting different monolayer and multilayer microstructures, were deposited via DC magnetron sputtering (DCMS) with varying substrate rotational speeds. The investigation focused mainly on the physical, mechanical, and tribological properties of the coatings. The multilayer coatings demonstrated superior mechanical performance compared to their monolayer counterparts. Specifically, the multilayer coating with 6.1 at.% Mg exhibited a 46% improvement in reduced modulus and a 26% increase in hardness compared to monolayer coatings. Furthermore, the multilayer coating with 15 at.% Mg significantly reduced wear on both the disc and ball during testing with a synthetic oil containing an ashless, sulphur-free anti-wear phosphate ester additive with an amine group in its chemical structure
A rapid-application emissions-to-impacts tool for scenario assessment: Probabilistic Regional Impacts from Model patterns and Emissions (PRIME)
Get PDFClimate policies evolve quickly, and new scenarios designed around these policies are used to illustrate how they impact global mean temperatures using simple climate models (or climate emulators). Simple climate models are extremely efficient, although some can only provide global estimates of climate metrics such as mean surface temperature, CO2 concentration and effective radiative forcing. Within the Intergovernmental Panel on Climate Change (IPCC) framework, understanding of the regional impacts of scenarios that include the most recent science is needed to allow targeted policy decisions to be made quickly. To address this, we present PRIME (Probabilistic Regional Impacts from Model patterns and Emissions), a new flexible probabilistic framework which aims to provide an efficient mechanism to run new scenarios without the significant overheads of larger, more complex Earth system models (ESMs). PRIME provides the capability to include features of the most recent ESM projections, science and scenarios to run ensemble simulations on multi-centennial timescales and include analyses of many key variables that are relevant and important for impact assessments. We use a simple climate model to provide the global temperature response to emissions scenarios. These estimated temperatures are used to scale monthly mean patterns from a large number of CMIP6 ESMs. These patterns provide the inputs to a "weather generator"algorithm and a land surface model. The PRIME system thus generates an end-to-end estimate of the land surface impacts from the emissions scenarios. We test PRIME using known scenarios in the form of the shared socioeconomic pathways (SSPs), to demonstrate that our model reproduces the ESM climate responses to these scenarios. We show results for a range of scenarios: the SSP5-8.5 high-emissions scenario was used to define the patterns, and SSP1-2.6, a mitigation scenario with low emissions, and SSP5-3.4-OS, an overshoot scenario, were used as verification data. PRIME correctly represents the climate response (and spread) for these known scenarios, which gives us confidence our simulation framework will be useful for rapidly providing probabilistic spatially resolved information for novel climate scenarios, thereby substantially reducing the time between new scenarios being released and the availability of regional impact information
Non-linear saturation of gravito-inertial modes excited by tidal resonances in binary neutron stars
No full textDuring the last seconds of a binary neutron-star merger, the tidal force can excite stellar oscillation modes to large amplitudes. From the perspective of premerger electromagnetic emissions and next-generation gravitational-wave detectors, gravity (g−) modes constitute a propitious class. However, existing estimates for their impact employ linear schemes which may be inaccurate for large amplitudes, as achieved by tidal resonances. With rotation, inertial modes can be excited as well and while their non-linear saturation has been studied, an extension to fully-consistent gravito-inertial modes, especially in the neutron-star context, is an open problem. We study the linear and non-linear saturation of gravito-inertial modes and investigate the astrophysical consequences for binary neutron-star mergers, including the possibility of resonance-induced dynamo activity. A new (non-)linear formulation based on the separation of equilibrium and dynamical tides is developed. Implementing this into the 3D pseudo-spectral code MagIC, a suite of non-linear simulations of tidally-excited flows with an entropy/composition gradient in a stably-stratified Boussinesq spherical-shell are carried out. The new formulation accurately reproduces results of linear calculations for gravito-inertial modes with a free surface for low frequencies. For a constant-density cavity, we show that the axisymmetric differential rotation induced by nonlinear 2g and 1g modes may theoretically be large enough to amplify an ambient magnetic field to ≳1014 G. In addition, rich non-linear dynamics are observed in the form of a parametric instability for the 1g mode. The stars are also spun-up, which extends the resonance window for any given mode
Reinforcement learning based estimation of shortest paths in dynamically changing transportation networks
Get PDFFinding the shortest path in a network is a classical problem, and a variety of search strategies have been proposed to solve it. In this paper, we review traditional approaches for finding shortest paths, namely, uninformed search, informed search and incremental search. The above traditional algorithms have been put to successful use for fixed networks with static link costs. However, in many practical contexts, such as transportation networks, the link costs can vary over time. We investigate the applicability of the aforementioned benchmark search strategies in a simulated transportation network where link costs (travel times) are dynamically estimated with vehicle mean speeds. As a comparison, we present performance metrics for a reinforcement learning based routing algorithm, which can interact with the network and learn the changing link costs through experience. Our results suggest that reinforcement learning algorithm computes optimal paths dynamically
Immigration Detention Inc. The Big Business of Locking up Migrants
No full textThe United States has the most extensive immigration detention system in the world, expanding from a capacity of less than 5,000 detainees per day in the 1980s to 52,000 by 2019. While the most vociferous anti-immigrant rhetoric may be attributed to Republicans, US detention infrastructure has grown exponentially regardless of the political party in power, as reports of abysmal detention conditions pile up.
Nancy Hiemstra and Deirdre Conlon provide a damning exposé of the ways immigration detention generates income while those detained are starved, sickened, and exploited as a matter of routine detention operation. Drawing on over a decade of research and focusing on detention centers in New Jersey and New York, the authors map public-private financial relationships and trace how detention contracts for food, medical care, and in-facility stores are fought over to the penny. By dissecting the inner workings of immigration detention, they show a system governed by a capitalist logic that produces sickening and corrupting dependencies in communities across the US.
Coming at a pivotal social and political moment, Immigration Detention Inc. makes the case for dismantling immigration detention regimes everywhere
Evaluation of the psychometric properties of patient-reported outcome measures of health-related quality of life across the European cancer continuum: a systematic review protocol using COSMIN methodology
Get PDFIntroduction
Over the past decades, there has been increasing recognition that assessing patients with cancer’s health-related quality of life (HRQoL) is pivotal to delivering optimal patient-centred healthcare. However, with the increasing number of patient-reported outcome measures (PROMs) available, it becomes more and more challenging to identify the most appropriate PROM to capture HRQoL. Therefore, the aim of this systematic review is to (1) identify all available PROMs assessing HRQoL across the European cancer continuum and (2) critically appraise, compare and summarise the psychometric properties of the identified PROMs.
Methods and analysis
Bibliographic databases MEDLINE and PubMed Central (through PubMed) and EMBASE (through Scopus) will be comprehensively searched from database inception until March 2024. Studies reporting on the measurement properties of PROMs assessing HRQoL throughout the European cancer continuum will be included. The evaluation of the psychometric properties, data extraction and data synthesis will be conducted according to the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology. Two reviewers will independently assess the methodological quality using the COSMIN risk of bias checklist and the COSMIN criteria for good measurement properties. Subsequently, findings will be qualitatively summarised. The Grading of Recommendations Assessment, Development and Evaluations (GRADE) guidelines will be used to grade and summarise the quality of the evidence.
Ethics and dissemination
Ethical clearance for this research is not required, as the systematic review will only use information from previously published research. The results of this review will be submitted for publication in a peer-reviewed journal and will be used to provide a set of evidence-based recommendations for a European project (EUonQOL), which aims at developing a new PROM (EUonQOL toolkit) to assess HRQoL across the European cancer continuum. Moreover, findings will be disseminated to a clinical audience and policymakers through conferences, supporting researchers and clinicians in choosing the best measure to evaluate HRQoL in patients with cancer and survivors in Europe
Use of truncated Fisher sensitivity analysis for design verification of mechanical systems under uncertainty
Get PDFSensitivity analysis is becoming an essential part of simulation based engineering design, but few sensitivity methods can directly consider measurement data for design verification. Here we present a new data-driven method, based on the truncated Fisher Information Matrix (tFIM), to identify the key drivers of the discrepancy between simulated and measured frequency response function and to guide the design verification process. We found tFIM is as effective as the more commonly used Monte Carlo Filtering (MCF) for design verification, but offers additional insights to sensitivity information from parameter interactions and from within the truncated region. To overcome the non-desirable issue of a fixed truncation, we discuss the augmentation of the input parameters by random truncation thresholds. Application of tFIM to the dynamics verification of a model floating wind turbine successfully identifies the most important parameter out of 15 input random variables, and the sensitivity guided design update is parsimonious and interpretable. Thanks to its efficiency as a one-sample approach, we expect the new tFIM method to complement global uncertainty and sensitivity analysis and become an integral part of design verification for the dynamic performance of mechanical systems under uncertainties
Evaluation of the Performance and Utility of Global Gridded Precipitation Products for Health Applications and Impact Assessments in South America
Get PDFGlobally gridded precipitation products (GGPPs) are commonly used in impact assessments as substitutes for weather station data, each with unique strengths and limitations. Reanalysis products are among the most widely used for driving impact models, evaluating climate models, or bias-correcting and downscaling model outputs to generate climate change projections. However, they are often outperformed in accuracy by other GGPPs, particularly in tropical regions, including areas of the Global South. Therefore, we assessed the utility and suitability of GGPPs for climate and health research by examining how differences and uncertainties in these products affect area-level precipitation estimates, often used in health studies when epidemiological data are linked to administrative units. We compared reanalysis (ERA5/-Land) with satellite-based (CHIRPS, PERSIANN-CDR) and interpolated gauge-based products (CRUTS, GPCC), each a viable candidate to serve as reference climatology in climate change impact assessments. We focused on seasonal patterns, disease-related bioclimatic variables, and climate change-relevant indices, such as the number of wet or dry periods. Our findings revealed substantial variation in the accuracy of local precipitation estimates across GGPPs, with differences in maximum pixel precipitation values exceeding 75% between ERA5-Land and CHIRPS. These differences in GGPPs translated into area-level precipitation and, consequently, in vector carrying capacity estimates, demonstrating their impact on health assessments. Our analysis focused on Brazil and Colombia, two diverse countries differing for example, in orography, climate, and size. Each product was evaluated against national station data. Our results indicate that estimating tropical precipitation is particularly challenging for reanalysis, while CHIRPS demonstrated the best overall performance
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