We studied whether elderly women at risk for fractures receive primary care treatment to prevent fracture. We found that across Europe, women at risk are often not identified, and less than half of such women receive appropriate treatment. Finally, women diagnosed with osteoporosis are much more likely to receive treatment. Purpose: To examine the relationship between risk factors for fragility fracture (FF) and osteoporosis (OP) treatment gap in elderly women across Europe, and compare the prevalence of risk factors between countries. Methods: Demographic and clinical information was collected from women ≥ 70 years visiting primary care physicians in Belgium, France, Germany, Ireland, Poland, Slovakia, Switzerland, and the UK. Increased risk of FF was defined by the presence of 1 or more criteria (history of fracture, 10-year fracture probability, or T-score ≤ - 2.5). Results: There were 3798 women in total. Treatment gap (proportion at increased risk of FF not receiving treatment for OP) varied from 53.1 to 90.8% across countries, and the proportion of patients at increased risk of FF varied from 41.2 to 76.1%. Across countries, less than 50% of patients with increased risk of FF had a diagnosis of OP. Previous fracture was the most common risk factor, with similar prevalence across most countries; other risk factors varied widely. The treatment gap was reduced in patients with an OP diagnosis in all countries, but this reduction varied from 36.5 to 79.4%. The countries with the lowest rates of bone densitometry scans (Poland, France, and Germany; 8.3-12.3%) also had the highest treatment gap (82.2 to 90.8%). Conclusions: This study highlights differences across Europe in clinical risk factors for fracture, rates of densitometry scanning, and the rates of OP diagnosis. More emphasis is needed on risk assessment to improve the identification and treatment of elderly women at risk for fracture.
The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of sampling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are presampled, independent of the hard scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such presampled event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.
The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with Geant4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.
Background Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment. Results 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. Conclusions The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.
Background Physical exercise has favorable effects on the structure of gut microbiota and metabolite production in sedentary subjects. However, little is known whether adjustments in an athletic program impact overall changes of gut microbiome in high-level athletes. We therefore characterized fecal microbiota and serum metabolites in response to a 7-week, high-intensity training program and consumption of probiotic Bryndza cheese. Methods Fecal and blood samples and training logs were collected from young competitive male ( n = 17) and female ( n = 7) swimmers. Fecal microbiota were categorized using specific primers targeting the V1–V3 region of 16S rDNA, and serum metabolites were characterized by NMR-spectroscopic analysis and by multivariate statistical analysis, Spearman rank correlations, and Random Forest models. Results We found higher α-diversity, represented by the Shannon index value (HITB-pre 5.9 [± 0.4]; HITB-post 6.4 [± 0.4], p = 0.007), (HIT-pre 5.5 [± 0.6]; HIT-post 5.9 [± 0.6], p = 0.015), after the end of the training program in both groups independently of Bryndza cheese consumption. However, Lactococcus spp . increased in both groups, with a higher effect in the Bryndza cheese consumers (HITB-pre 0.0021 [± 0.0055]; HITB-post 0.0268 [± 0.0542], p = 0.008), (HIT-pre 0.0014 [± 0.0036]; HIT-post 0.0068 [± 0.0095], p = 0.046). Concomitant with the increase of high-intensity exercise and the resulting increase of anaerobic metabolism proportion, pyruvate ( p [HITB] = 0.003; p [HIT] = 0.000) and lactate ( p [HITB] = 0.000; p [HIT] = 0.030) increased, whereas acetate ( p [HITB] = 0.000; p [HIT] = 0.002) and butyrate ( p [HITB] = 0.091; p [HIT] = 0.019) significantly decreased. Conclusions Together, these data demonstrate a significant effect of high-intensity training (HIT) on both gut microbiota composition and serum energy metabolites. Thus, the combination of intensive athletic training with the use of natural probiotics is beneficial because of the increase in the relative abundance of lactic acid bacteria.
The colouring defect of a cubic graph, introduced by Steffen in 2015, is the minimum number of edges that are left uncovered by any set of three perfect matchings. Since a cubic graph has defect 0 if and only if it is 3-edge-colourable, this invariant can measure how much a cubic graph differs from a 3-edge-colourable graph. Our aim is to examine the relationship of colouring defect to oddness, an extensively studied measure of uncolourability of cubic graphs, defined as the smallest number of odd circuits in a 2-factor. We show that there exist cyclically 5-edge-connected snarks (cubic graphs with no 3-edge-colouring) of oddness 2 and arbitrarily large colouring defect. This result is achieved by means of a construction of cyclically 5-edge-connected snarks with oddness 2 and arbitrarily large girth. The fact that our graphs are cyclically 5-edge-connected significantly strengthens a similar result of Jin and Steffen (2017), which only guarantees graphs with cyclic connectivity at most 3. At the same time, our result improves Kochol's original construction of snarks with large girth (1996) in that it provides infinitely many nontrivial snarks of any prescribed girth g≥5, not just girth at least g.
In this paper, we adopt a new approach to study the controllability and observability of linear quaternion-valued systems (QVS) from the point of complex-valued systems, which is much different from the method used in the previous paper. We show the equivalence relation of complete controllability for linear QVS and its complex-valued system. Then we establish two effective criteria for controllability and observability of the linear QVS in the sense of complex representation. In addition, we give a direct method to solve the control function. Finally, we use numerical examples to illustrate our theoretical results.
Theoretical calculations based on the Dirac--Coulomb--Breit relativistic coupled cluster method have been carried out for the electron affinities and ionization potentials of the superheavy element nihonium (Nh) and its lighter homologues In and Tl. The In and Tl calculations are in agreement with measurement within uncertainties. For Nh, where experiment is yet unknown, we predict the ionization potential of 7.569(48) eV and electron affinity of 0.776(30) eV.
Distribution trends and temporal variations of ²⁴¹Am and Pu isotopes in the south-eastern Baltic Sea during the study period of 1999–2001 and 2011–2015 were investigated with the aim to study temporal changes of radionuclide levels in seawater, suspended particles and sediment, to estimate ²⁴¹Am and 239,240Pu levels in marine biota and to assess the radiation doses received by the biota. The activities of ²⁴¹Am and 239,240Pu were measured by alpha spectrometry after radiochemical purification. ²⁴¹Pu was determined radiometrically via the ingrown daughter ²⁴¹Am after 10–12 years of storage, while the ²⁴⁰Pu/²³⁹Pu atom ratio of was measured by accelerator mass spectrometry. The 239,240Pu activities in suspended particles collected in the coastal waters of the Baltic Sea decreased by a factor of ∼3 during the study period, while they decreased about fourfold in the Curonian Lagoon. This could indicate a decrease in the influx of particles containing Pu isotopes into the Baltic Sea. While in the Curonian Lagoon, the 239,240Pu activities in the sediment samples varied insignificantly during the study periods, in the Baltic Sea, the maximum activity decreased by a factor of 6, and the mean/median values decreased by ∼4 times. The assessment tool ERICA was used to calculate the dose rates for biota. The total dose rate from all analysed radionuclides was <0.1 μGy/h, therefore no risk to organisms was identified.
We studied the southern part of the NW-SE trending Sudetic Marginal fault (SMF), situated at the northeastern limit of the Bohemian Massif in central Europe, to assess its Quaternary activity. Eighteen trenches and thirty-four electric resistivity profiles were performed at Bílá Voda to study the fault zone and 3-dimensional distribution of a beheaded alluvial fan on the NE side of the fault. We interpret a small drainage, located about 29-45 m to the SE of the fan apex, as the only plausible source channel implying a similar amount of left-lateral offset. The alluvial fan deposits' radiometric ages range between about 24 and 63 ka, but postglacial deposits younger than 11 ka are not displaced, indicating that all motion occurred in the late Pleistocene. The site lies ∼150 km south of the late Pleistocene Weichselian maximum (∼20 ka) ice sheet front. We model the effects of the ice load on lithospheric flexure and resolved fault stresses, and show that slip on the SMF was promoted by the presence of the ice sheet, resulting in a late Pleistocene slip rate of ∼1.1 +2.3 / −0.6 mm/yr. As the most favorable time for glacial loading-induced slip would be during the glacial maximum between about 24 and 12 ka, it is doubtful that the slip rate remained constant during the entire period of activity, and if most slip occurred during this period, the short-term rate may have been even higher. Considering that the modern maximum principal stress (σ 1) is oriented nearly parallel to the Sudetic Marginal fault (NNW-SSE) and is thus unfavorable for fault motion, our observations suggest that the likelihood of continued motion and earthquake production is much lower in the absence of an ice sheet.
Kynurenines have immunomodulatory and neuroactive properties and can influence the central nervous system. Previous studies showed the involvement of the kynurenines in the pathogenesis and progression of neurodegenerative disease. In neurodegenerative disorders, including tauopathies, the tryptophan metabolism is shifted toward neurotoxic agents and the reduction of neuroprotectant products. Astrocyte-derived kynurenic acid serves as a neuroprotectant. However, systemic administration of kynurenic acid is not effective because of low permeability across the blood-brain barrier (BBB). We used a kynurenic acid analog with similar biological activity but higher brain permeability to overcome BBB limitations. In the present study, we used amide derivate of kynurenic acid N-(2-N, N-dimethylaminoethyl)− 4-oxo-1 H-quinoline-2-carboxamid (KYNA-1). We administered KYNA-1 for three months to tau transgenic rats SHR-24 and analyzed the effect on tau pathology and activation of glial cells. Primary glial cell cultures were applied to identify the mechanism of the KYNA-1 effect. KYNA-1 was not toxic to rats after chronic three-month administration. When chronically administered, KYNA-1 reduced hyperphosphorylation of insoluble tau in the brain of transgenic rats. Noteworthily, the plasma total tau was also reduced. We determined that the effect of KYNA-1 on tau pathology was induced through the modulation of glial activation. KYNA-1 inhibited LPS induced activation of astrocytes and induced transformation of microglia to M2 phenotype. We identified that the administration of KYNA-1 reduced tau hyperphosphorylation and neuroinflammation. KYNA-1 may serve as a promising treatment for tauopathies.
Coworking spaces are flexible and shared work environments that make a significant effort to connect users with supportive networks that commonly result in efficient work outputs, a high level of collaboration and knowledge transfer. Recent years have seen swift growth and popularisation of the coworking model, making these spaces an integral part of local entrepreneurial ecosystems and transforming them into the localised pools of specialised talent. However, little research has been conducted to understand the role of human talent in coworking spaces, indicating a knowledge gap in human resource management and the role of contemporary coworking environments. Therefore, the purpose of the following paper is to contextualize coworking spaces as (local) talent hubs by investigating how they tend to build their identity on their userbase. The manuscript explores the managerial practices and mediation techniques by presenting empirical evidence and subsequent analysis of talent attraction and retention mechanisms commonly used in coworking environments. The study shows that by facilitating interaction and collaboration between users, coworking spaces offer support throughout the business life cycle and identify themselves as local accelerators of entrepreneurship and talent development within their local environments.
Edge-elimination is an operation of removing an edge of a cubic graph together with its endvertices and suppressing the resulting 2-valent vertices. We study the effect of this operation on the cyclic connectivity of a cubic graph. Disregarding a small number of cubic graphs with no more than six vertices, this operation cannot decrease cyclic connectivity by more than two. We show that apart from three exceptional graphs (the cube, the twisted cube, and the Petersen graph) every 2-connected cubic graph on at least eight vertices contains an edge whose elimination decreases cyclic connectivity by at most one. The proof reveals an unexpected behaviour of connectivity 6, which requires a detailed structural analysis featuring the Isaacs flower snarks and their natural generalisation, the twisted Isaacs graphs, as forced structures. A complete characterisation of this family, which includes the Heawood graph as a sporadic case, serves as the main tool for excluding the existence of exceptional graphs in connectivity 6. As an application we show that every cyclically 5-edge-connected cubic graph has a decycling set of vertices whose removal leaves a tree and the set itself has at most one edge between its vertices. This strengthens a classical result of Payan and Sakarovitch (1975) about the structure of minimum decycling sets in cyclically 4-edge-connected graphs.
This article enriches the existing literature on the importance and role of the social sciences and humanities (SSH) in renewable energy sources research by providing a novel approach to instigating the future research agenda in this field. Employing a series of in-depth interviews, deliberative focus group workshops and a sys- tematic horizon scanning process, which utilised the expert knowledge of 85 researchers from the field with diverse disciplinary backgrounds and expertise, the paper develops a set of 100 priority questions for future research within SSH scholarship on renewable energy sources. These questions were aggregated into four main directions: (i) deep transformations and connections to the broader economic system (i.e. radical ways of (re) arranging socio-technical, political and economic relations), (ii) cultural and geographical diversity (i.e. contextual cultural, historical, political and socio-economic factors influencing citizen support for energy tran- sitions), (iii) complexifying energy governance (i.e. understanding energy systems from a systems dynamics perspective) and (iv) shifting from instrumental acceptance to value-based objectives (i.e. public support for energy transitions as a normative notion linked to trust-building and citizen engagement). While this agenda is not intended to be—and cannot be—exhaustive or exclusive, we argue that it advances the understanding of SSH research on renewable energy sources and may have important value in the prioritisation of SSH themes needed to enrich dialogues between policymakers, funding institutions and researchers. SSH scholarship should not be treated as instrumental to other research on renewable energy but as intrinsic and of the same hierarchical importance.
Long-term temporal variations of plutonium in Sea of Japan (SOJ) surface waters have been examined with the aim to better understand its behavior during several decades. The first observation is that 239,240Pu activity concentrations in surface waters of the SOJ during 1977–2019 were 6.5 ± 4.7 mBq m⁻³ in average, and 5.1 mBq m⁻³ as the median, whereas ¹³⁷Cs and ⁹⁰Sr activity concentrations decreased with time, except of the perturbation due to the 2011 Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident. Another observation is that sporadic high 239,240Pu activity concentrations occurred in the east Japan Basin, ranging from 1 to 39 mBq m⁻³. The spatial distribution of 239,240Pu activity concentrations in surface waters revealed that high 239,240Pu levels (>20 mBq m⁻³) occurred in 1994 in the northern SOJ, which was considered to be due to winter convection. To elucidate factors controlling the temporal variability of surface 239,240Pu levels in the SOJ, a relationship between surface 239,240Pu activity concentrations and vertical diffusion coefficients was examined. The results revealed that this relationship could be classified into two groups: one group did not show a change with increasing diffusion coefficient, while the other group showed a positive correlation. The vertical 239,240Pu distribution in SOJ waters suggests that the high surface 239,240Pu levels occurred due to the upwelling of cyclonic eddy. The rapid recycling of deeper plutonium occurred in the SOJ due to deep winter convection and upwelling associated with cyclonic eddy. The plutonium levels in the SOJ have been found to be sensitive to climate changes. Warming of the SOJ may cause a reduction of winter convection and eddy activity as a result of increasing sea surface temperature. This leads to a decline of recirculation of plutonium and other bioavailable elements from Japan Sea Proper Water (JSPW) to surface water layers. Plutonium would be, therefore, an important indicator of biogeochemical processes in the marine environment, helping to assess climate change impacts on marine ecological systems.
Metabolomics has emerged as a powerful new tool in precision medicine. No studies have yet been published on the metabolomic changes in cerebrospinal fluid (CSF) produced by acute endurance exercise. CSF and plasma were collected from 19 young active adults (13 males and 6 females) before and 60 min after a 90‐min monitored outdoor run. The median age, BMI, and VO2 max of subjects was 25 years (IQR 22–31), 23.2 kg/m2 (IQR 21.7–24.5), and 47 ml/kg/min (IQR 38–51), respectively. Targeted, broad‐spectrum metabolomics was performed by liquid chromatography, tandem mass spectrometry (LC–MS/MS). In the CSF, purines and pyrimidines accounted for 32% of the metabolic impact after acute endurance exercise. Branch chain amino acids, amino acid neurotransmitters, fatty acid oxidation, phospholipids, and Krebs cycle metabolites traceable to mitochondrial function accounted for another 52% of the changes. A narrow but important channel of metabolic communication was identified between the brain and body by correlation network analysis. By comparing these results to previous work in experimental animal models, we found that over 80% of the changes in the CSF correlated with a cascade of mitochondrial and metabolic changes produced by ATP signaling. ATP is released as a co‐neurotransmitter and neuromodulator at every synapse studied to date. By regulating brain mitochondrial function, ATP release was identified as an early step in the kinetic cascade of layered benefits produced by endurance exercise.
Hypertensive disorders in pregnancy represent severe complications of pregnancy, which, if not treated, can result in serious health consequences for the mother and the child. Flavonoids are bioactive secondary metabolites commonly found in fruits, vegetables, green tea, whole grains, and medicinal plants. Flavonoids exert potent protective efficacy in experimental models of hypertensive disorders in pregnancy, especially preeclampsia, demonstrated through their capacity to modulate inflammatory responses, oxidative stress, and vascular dysfunction. In addition to their potential as therapeutics, flavonoids or flavonoid-rich food could be helpful to decrease the risk of hypertensive disorders in pregnancy when included in the diet pattern before and during pregnancy. However, the clinical evaluation of the potential capacity of flavonoids in hypertensive disorders in pregnancy is insufficient. Due to promising results from experimental studies, we highlight the need for the evaluation of flavonoids also in an appropriate clinical setting, which can be, together with proper preventive strategies, helpful in the overall management of hypertensive disorders in pregnancy.
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