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Ageing and the economy: a literature review of political and policy mechanisms
No full textPopulation ageing, and the decline in the working-age population, represent a profound global demographic shift. What political consequences do ageing populations have for the economies of advanced democracies? To address this question, we carry out a wide-ranging, systematic literature review using network-based community detection algorithms and manual coding to select almost 150 articles. We find that research in this area typically focuses on a few mechanisms and is therefore – by design – unable to identify gaps in existing knowledge or assess interactions between different strands of literature. Our review suggests that ageing has important implications for a variety of domains including electoral behaviour, social policy preferences, and public spending. Taken together, the political consequences of population ageing are likely to have previously overlooked and indirect impacts on economic outcomes. Future research should, therefore, examine how population ageing shapes political dynamics and policy choices in ways that also affect the economy
Superconducting joint structures for Bi-2212 wires using a powder-in-tube technique
No full textBi-2212/Ag superconducting wires are being considered as key conductor candidates for the development of high-field magnets. This work focuses on the design and testing of the various joint structures for multifilamentary Bi-2212 wires using powder-in-tube techniques. The joints are made between the unreacted wires and subsequently heat treated with the wires. The microstructure and transport properties of different joint architectures including step joints, scarf joints and etched joints have been explored. The performance of etched-joints are found to be very sensitive to the etching parameters including etching time, making it difficult to develop a reliable jointing process. Scarf joints and step joints can carry higher currents (320 A and 475 A in self-field at 4 K) than the etched joints (225 A in self-field at 4 K) as a result of connecting a larger area of the exposed filaments without damaging the filaments
The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis
No full textDown syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10-8) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N = 30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome
An idealized model study of eddy energetics in the western boundary "graveyard"
No full textRecent studies show that the western boundary acts as a “graveyard” for westward-propagating ocean eddies. However, how the eddy energy incident on the western boundary is dissipated remains unclear. Here we investigate the energetics of eddy–western boundary interaction using an idealized MIT ocean circulation model with a spatially variable grid resolution. Four types of model experiments are conducted: 1) single eddy cases, 2) a sea of random eddies, 3) with a smooth topography, and 4) with a rough topography. We find significant dissipation of incident eddy energy at the western boundary, regardless of whether the model topography at the western boundary is smooth or rough. However, in the presence of rough topography, not only the eddy energy dissipation rate is enhanced, but more importantly, the leading process for removing eddy energy in the model switches from bottom frictional drag as in the case of smooth topography to viscous dissipation in the ocean interior above the rough topography. Further analysis shows that the enhanced eddy energy dissipation in the experiment with rough topography is associated with greater anticyclonic, ageostrophic instability (AAI), possibly as a result of lee wave generation and nonpropagating form drag effect
Introducing SPHINX-MHD: the impact of primordial magnetic fields on the first galaxies, reionization, and the global 21-cm signal
No full textWe present the first results from SPHINX-MHD, a suite of cosmological
radiation-magnetohydrodynamics simulations designed to study the impact of
primordial magnetic fields (PMFs) on galaxy formation and the evolution of the
intergalactic medium during the epoch of reionization. The simulations are
among the first to employ on-the-fly radiation transfer and constrained
transport ideal MHD in a cosmological context to simultaneously model the
inhomogeneous process of reionization and the growth of PMFs. We run a series
of cosmological volumes, varying both the strength of the seed
magnetic field and its spectral index. We find that PMFs with a spectral index
() and a comoving amplitude () that have
produce electron optical depths
() that are inconsistent with CMB constraints due to the
unrealistically early collapse of low-mass dwarf galaxies. For ,
our constraints are considerably tighter than the constraints
from Planck. PMFs that do not satisfy our constraints have little impact on the
reionization history or the shape of the UV luminosity function. Likewise,
detecting changes in the Ly forest due to PMFs will be challenging
because photoionisation and photoheating efficiently smooth the density field.
However, we find that the first absorption feature in the global 21cm signal is
a particularly sensitive indicator of the properties of the PMFs, even for
those that satisfy our constraint. Furthermore, strong PMFs can
increase the escape of LyC photons by up to 25% and shrink the effective radii
of galaxies by 44% which could increase the completeness fraction of galaxy
surveys. Finally, our simulations show that surveys with a magnitude limit of
can probe the sources that provide the 50% of
photons for reionization out to
Molecular epidemiology and evolutionary trajectory of emerging echovirus 30, Europe
No full textIn 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016–2018. Most E30 cases affected persons 0–4 years of age (29%) and 25–34 years of age (27%). Sequences were divided into 6 genetic clades (G1–G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections
Natural variants modify Klebsiella pneumoniae carbapenemase (KPC) acyl-enzyme conformational dynamics to extend antibiotic resistance.
No full textClass A serine β-lactamases (SBLs) are key antibiotic resistance determinants in Gram-negative bacteria. SBLs neutralize β-lactams via a hydrolytically labile covalent acyl-enzyme intermediate. Klebsiella pneumoniae carbapenemase (KPC) is a widespread SBL that hydrolyzes carbapenems, the most potent β-lactams; known KPC variants differ in turnover of expanded-spectrum oxyimino-cephalosporins (ESOCs), for example, cefotaxime and ceftazidime. Here, we compare ESOC hydrolysis by the parent enzyme KPC-2 and its clinically observed double variant (P104R/V240G) KPC-4. Kinetic analyses show that KPC-2 hydrolyzes cefotaxime more efficiently than the bulkier ceftazidime, with improved ESOC turnover by KPC-4 resulting from enhanced turnover (kcat), rather than altered KM values. High-resolution crystal structures of ESOC acyl-enzyme complexes with deacylation-deficient (E166Q) KPC-2 and KPC-4 mutants show that ceftazidime acylation causes rearrangement of three loops; the Ω, 240, and 270 loops, which border the active site. However, these rearrangements are less pronounced in the KPC-4 than the KPC-2 ceftazidime acyl-enzyme and are not observed in the KPC-2:cefotaxime acyl-enzyme. Molecular dynamics simulations of KPC:ceftazidime acyl-enyzmes reveal that the deacylation general base E166, located on the Ω loop, adopts two distinct conformations in KPC-2, either pointing "in" or "out" of the active site; with only the "in" form compatible with deacylation. The "out" conformation was not sampled in the KPC-4 acyl-enzyme, indicating that efficient ESOC breakdown is dependent upon the ordering and conformation of the KPC Ω loop. The results explain how point mutations expand the activity spectrum of the clinically important KPC SBLs to include ESOCs through their effects on the conformational dynamics of the acyl-enzyme intermediate
Association between blood pressure categories and cardiovascular disease mortality in China
No full textBackground
Blood pressure (BP) categories are useful to simplify preventions in public health, and diagnostic and treatment approaches in clinical practice. Updated evidence about the associations of BP categories with cardiovascular diseases (CVDs) and its subtypes is warranted.
Methods and findings
About 0.5 million adults aged 30 to 79 years were recruited from 10 areas in China during 2004–2008. The present study included 430 977 participants without antihypertension treatment, cancer, or CVD at baseline. BP was measured at least twice in a single visit at baseline and CVD deaths during follow-up were collected via registries and the national health insurance databases. Multivariable Cox regression was used to estimate the associations between BP categories and CVD mortality.
Overall, 16.3% had prehypertension-low, 25.1% had prehypertension-high, 14.1% had isolated systolic hypertension (ISH), 1.9% had isolated diastolic hypertension (IDH), and 9.1% had systolic-diastolic hypertension (SDH). During a median 10-year follow-up, 9660 CVD deaths were documented. Compared with normal, the hazard ratios (95% CI) of prehypertension-low, prehypertension-high, ISH, IDH, SDH for CVD were 1.10 (1.01–1.19), 1.32 (1.23–1.42), 2.04 (1.91–2.19), 2.20 (1.85–2.61), and 3.81 (3.54–4.09), respectively. All hypertension subtypes were related to the increased risk of CVD subtypes, with a stronger association for hemorrhagic stroke than for ischemic heart disease. The associations were stronger in younger than older adults.
Conclusions
Prehypertension-high should be considered in CVD primary prevention given its high prevalence and increased CVD risk. All hypertension subtypes were independently associated with CVD and its subtypes mortality, though the strength of associations varied substantially
From using heat to using work: reconceptualising the zero carbon energy transition
No full textRecent evidence indicates that the key sources of energy for the zero carbon transition will be renewable electricity sources. The most rapidly expanding sources, photovoltaics and wind produce work, as electricity, directly rather than via heat engines. Making the assumption that these will be the dominant sources of energy in a future zero carbon system, the paper makes two new related and innovative contributions to the literature on the energy transition. First, it shows that the energy transition will be more than just a shift away from carbonaceous fuels, and that it is more usefully thought of as including a systemic shift from heat-producing to work-producing energy sources. Secondly, it shows that this enables very large improvements in the conversion efficiency of final energy, through the use of electricity and hydrogen, in particular in heating and transportation. The paper presents a thought experiment showing a reduction in final energy demand of up to 40% is likely from this effect alone. Technical standards and product regulation for end use conversion efficiency and/or service delivery efficiency seem likely to be key policy instruments
Effects of multiple stressors on northern leopard frogs in agricultural wetlands
No full textNatural and anthropogenic stressors, including parasites and pesticides, may induce oxidative stress in animals. Measuring oxidative stress responses in sentinel species that are particularly responsive to environmental perturbations not only provides insight into host physiology but is also a useful readout of ecosystem health. Newly metamorphosed northern leopard frogs (Lithobates pipiens), a sentinel species, were collected from agricultural and non-agricultural wetlands exposed to varying concentrations of the herbicide atrazine. Significant effects of certain parasites' abundance and their interaction with atrazine exposure on frog oxidative stress were identified. Specifically, increased protein levels were detected in frogs infected with echinostome metacercariae. In addition, the nematode Oswaldocruzia sp. was significantly associated with increased thiol concentration and catalase activity. Significant parasite × atrazine interactions were observed for atrazine exposure and the abundance of Oswaldocruzia sp. on thiol, as thiol concentrations increased with parasite abundance at low atrazine localities and decreased in high atrazine wetlands. In addition, a significant interaction between the abundances of Oswaldocruzia sp. and gorgoderid trematodes on thiol concentrations was observed. These findings demonstrate that studies of oxidative stress on animals in natural ecosystems should account for the confounding effects of parasitism, particularly for amphibians in agricultural landscapes