Impaired decidual natural killer cell regulation of vascular remodelling in early human pregnancies with high uterine artery resistance

During human pregnancy, natural killer (NK) cells accumulate in the maternal decidua, but their specific roles remain to be determined. Decidual NK (dNK) cells are present during trophoblast invasion and uterine spiral artery remodelling. These events are crucial for successful placentation and the provision of an adequate blood supply to the developing fetus. Remodelling of spiral arteries is impaired in the dangerous pregnancy complication pre-eclampsia. We studied dNK cells isolated from pregnancies at 9-14 weeks' gestation, screened by uterine artery Doppler ultrasound to determine resistance indices which relate to the extent of spiral artery remodelling. dNK cells were able to promote the invasive behaviour of fetal trophoblast cells, partly through HGF. Cells isolated from pregnancies with higher resistance indices were less able to do this and secreted fewer pro-invasive factors. dNK cells from pregnancies with normal resistance indices could induce apoptotic changes in vascular smooth muscle and endothelial cells in vitro, events of importance in vessel remodelling, partly through Fas signalling. dNK cells isolated from high resistance index pregnancies failed to induce vascular apoptosis and secreted fewer pro-apoptotic factors. We have modelled the cellular interactions at the maternal-fetal interface and provide the first demonstration of a functional role for dNK cells in influencing vascular cells. A potential mechanism contributing to impaired vessel remodelling in pregnancies with a higher uterine artery resistance is presented. These findings may be informative in determining the cellular interactions contributing to the pathology of pregnancy disorders where remodelling is impaired, such as pre-eclampsia. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

Methods for estimating the case fatality ratio for a novel, emerging infectious disease.

During the course of an epidemic of a potentially fatal disease, it is important that the case fatality ratio be well estimated. The authors propose a novel method for doing so based on the Kaplan-Meier survival procedure, jointly considering two outcomes (death and recovery), and evaluate its performance by using data from the 2003 epidemic of severe acute respiratory syndrome in Hong Kong, People's Republic of China. They compare this estimate obtained at various points in the epidemic with the case fatality ratio eventually observed; with two commonly quoted, naïve estimates derived from cumulative incidence and mortality statistics at single time points; and with estimates in which a parametric mixture model is used. They demonstrate the importance of patient characteristics regarding outcome by analyzing subgroups defined by age at admission to the hospital

The association between muscular power from childhood to adulthood and adult measures of glucose homeostasis

This study aimed to assess whether the longitudinal association between childhood muscular fitness and adult measures of glucose homeostasis persist despite changes in muscular fitness across the life course. This prospective longitudinal study included 586 participants who had their muscular power (standing long jump distance), cardiorespiratory fitness (CRF), and waist circumference measured as children (aged 9, 12, 15 years) and again 20 years later as adults. In adulthood, these participants also provided a fasting blood sample which was tested for glucose and insulin. Glucose homeostasis measures including insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β) were estimated. Child and adult muscular power levels were separated into thirds, and tracking groups (persistently low, decreasing, persistently moderate, increasing, and persistently high) were created. Sex-stratified multivariable linear regression models were used to examine the association between muscular power tracking groups and adult measures of glucose homeostasis. Compared with males with persistently high muscular power, males with increasing and persistently low muscular power had higher fasting insulin (increasing: β = 1.12 mU/L, P = .04; persistently low: β = 2.12 mU/L, P = .001) and HOMA2-β (increasing: β = 8.50%, P = .03; persistently low: β = 11.27%, P = .01) independent of CRF and males with persistently low muscular power had greater fasting insulin (β = 1.22 mU/L, P = .02) and HOMA2-IR (β = 0.14, P = .02) independent of waist circumference. Non-significant associations were present for females. For males, maintaining persistently high muscular power between childhood and adulthood could lead to a healthier adult glucose homeostasis profile

Continental margin subsidence from shallow mantle convection: Example from West Africa

Spatial and temporal evolution of the uppermost convecting mantle plays an important role in determining histories of magmatism, uplift, subsidence, erosion and deposition of sedimentary rock. Tomographic studies and mantle flow models suggest that changes in lithospheric thickness can focus convection and destabilize plates. Geologic observations that constrain the processes responsible for onset and evolution of shallow mantle convection are sparse. We integrate seismic, well, gravity, magmatic and tomographic information to determine the history of Neogene-Recent (+100 °C providing ∼103 m of support. Beneath the Mauritania basin average excess temperatures are <−100 °C drawing down the lithosphere by ∼102 to 103 m. Up- and downwelling mantle has generated a bathymetric gradient of ∼1/300 at a wavelength of ∼103 km during the last ∼23 Ma. Our results suggest that asthenospheric flow away from upwelling mantle can generate downwelling beneath continental margins

Observation and Simulation of Solid Sedimentary Flux: Examples From Northwest Africa

The sedimentary archive preserved at passive margins provides important clues about the evolution of continental topography. For example, histories of African uplift, erosion, and deposition of clastic sedimentary rock provide information about mantle convection. Furthermore, relating histories of uplift and erosion from regions where sediment is generated to measurements of efflux is important for understanding basin evolution and the distribution of natural resources. We focus on constraining Mesozoic to Recent solid sedimentary flux to northwest Africa's passive margin, which today is fed by rivers draining dynamically supported topography. Histories of sedimentary flux are calculated by mapping stratigraphy using seismic reflection and well data courtesy of Tullow Oil Plc and TGS. Stratigraphic ages, conversion from two-way time to depth and compaction, are parameterized using biostratigraphic and check-shot records from exploration, International Ocean Discovery Program and Deep Sea Drilling Project wells. Results indicate that Late Cretaceous to Oligocene (∼100–23 Ma) sedimentary flux decreased gradually. A slight increase in Neogene sedimentary flux is observed, which is concomitant with a change from carbonate to clastic sedimentation. Pliocene to Recent (∼5–0 Ma) flux increased by an order of magnitude. This history of sedimentary flux and facies change is similar to histories observed at other African deltas. To constrain sources of sedimentary flux, 14,700 longitudinal river profiles were inverted to calculate a history of continental uplift. These results were used to parameterize a simple “source-to-sink” model of fluvial erosion and sedimentary efflux. Results suggest that increased clastic flux to Africa's deltas from ∼30 Ma was driven by denudation induced by dynamic support

Revisiting the Thermodynamic Stability of Indomethacin Polymorphs with Low-Frequency Vibrational Spectroscopy and Quantum Mechanical Simulations

The two major polymorphs of the active pharmaceutical ingredient indomethacin were studied using a combination of experimental low-frequency vibrational spectroscopies, theoretical solid-state density functional theory and ab initio molecular dynamics calculations. The results enable a complete spectral assignment of the low-frequency IR and Raman spectra, and yield new insight into the energetic and dynamical factors present within the solids to be understood. Ultimately, these results are used to rationalize the thermodynamic properties of the two crystals, which result in a contradiction to the long-held belief that the γ-form is the more stable polymorph at ambient conditions due to its predominant abundance. Overall, the study highlights the combined role that molecular conformation, bulk packing arrangement, and intermolecular forces have on the ultimate properties of pharmaceutical crystals, and the need for detailed analyses into all of these effects in order to predict the properties of materials

Revealing lithium-silicide phase transformations in nano-structured silicon-based lithium ion batteries via in situ NMR spectroscopy.

Nano-structured silicon anodes are attractive alternatives to graphitic carbons in rechargeable Li-ion batteries, owing to their extremely high capacities. Despite their advantages, numerous issues remain to be addressed, the most basic being to understand the complex kinetics and thermodynamics that control the reactions and structural rearrangements. Elucidating this necessitates real-time in situ metrologies, which are highly challenging, if the whole electrode structure is studied at an atomistic level for multiple cycles under realistic cycling conditions. Here we report that Si nanowires grown on a conducting carbon-fibre support provide a robust model battery system that can be studied by (7)Li in situ NMR spectroscopy. The method allows the (de)alloying reactions of the amorphous silicides to be followed in the 2nd cycle and beyond. In combination with density-functional theory calculations, the results provide insight into the amorphous and amorphous-to-crystalline lithium-silicide transformations, particularly those at low voltages, which are highly relevant to practical cycling strategies.K.O acknowledges a research fellowship from Japanese Society for the Promotion of Science (JSPS). E.S acknowledges support by a Marie Curie Intra European Fellowship within the 7th European Community Framework Programme and thanks Churchill College (Cambridge, UK) for a non-stipendiary Raymond and Beverly Sackler Research fellowship. C.J.K and A.E.F acknowledge a research studentship from the Cambridge Nano Science and Technology Doctoral Training Centre (NanoDTC). A.J.M acknowledges the support from the Winton Programme for the Physics of Sustainability. S.H acknowledges funding from ERC grant InsituNANO (project number 279342). C.P.G and C.D thank the Royal Society, and C.P.G thanks European Research Council (ERC). C.P.G. acknowledges support from the Assistant Secretary for Energy Efficiency and Renewable Energy, Office of Vehicle Technologies of the U.S. Department of Energy, under Contract DE-AC02-05CH11231, subcontract 6952000.This is the accepted manuscript. The final version is available from Nature Communications at http://www.nature.com/ncomms/2014/140203/ncomms4217/full/ncomms4217.html

The association between grip strength measured in childhood, young- and mid-adulthood and prediabetes or type 2 diabetes in mid-adulthood

Background: Although low child and adult grip strength is associated with adverse cardiometabolic health, how grip strength across the life course associates with type 2 diabetes is unknown. This study identified the relative contribution of grip strength measured at specific life stages (childhood, young adulthood, mid-adulthood) with prediabetes or type 2 diabetes in mid-adulthood. Methods: Between 1985 and 2019, 263 participants had their grip strength measured using an isometric dynamometer in childhood (9-15 years), young adulthood (28-36 years) and mid-adulthood (38-49 years). In mid-adulthood, a fasting blood sample was collected and tested for glucose and glycated haemoglobin (HbA1c). Participants were categorized as having prediabetes or type 2 diabetes if fasting glucose levels were ≥ 5.6 mmol or if HbA1c levels were ≥ 5.7% (≥ 39 mmol/mol). A Bayesian relevant life course exposure model examined the association between lifelong grip strength and prediabetes or type 2 diabetes. Results: Grip strength at each time point was equally associated with prediabetes or type 2 diabetes in mid-adulthood (childhood: 37%, young adulthood: 36%, mid-adulthood: 28%). A one standard deviation increase in cumulative grip strength was associated with 34% reduced odds of prediabetes or type 2 diabetes in mid-adulthood (OR 0.66, 95% credible interval 0.40, 0.98). Conclusions: Greater grip strength across the life course could protect against the development of prediabetes and type 2 diabetes. Strategies aimed at increasing muscular strength in childhood and maintaining behaviours to improve strength into adulthood could improve future cardiometabolic health. The Association Between Grip Strength Measured in Childhood, Young- and Mid-adulthood and Prediabetes or Type 2 Diabetes in Mid-adulthood

The OPAL bugs count survey: exploring the effects of urbanisation and habitat characteristics using citizen science

Citizen science projects can gather datasets with observation counts and spatiotemporal coverage far in excess of what can easily be achieved using only professional scientists. However, there exists a potential trade-off between the number of participants and the quality of data gathered. The Bugs Count citizen science project had thousands of participants because of its few barriers to taking part, allowing participation by anyone in England with access to any area of outdoor space. It was designed to scope for both the effects of variation in local habitat and urbanisation on broad taxonomic groups of invertebrates, and the responses of six target ‘Species Quest’ species (Adalia bipunctata, Ocypus olens, Aglais urticae, Palomena prasina, Limax maximus, and Bombus hypnorum) to urbanisation. Participants were asked to search for invertebrates in three areas: ‘soft ground surfaces’, ‘human-made hard surfaces’, and ‘plants’ for 15 min per search. Participants recorded counts of taxa found and a range of environmental information about the survey area. Data samples were weighted according to identification experience and participant age and analysed using canonical correspondence analysis, and tests of observation homogeneity. Species Quest species showed species-specific relationships with urbanisation, but broad taxonomic groups did not show significant relationships with urbanisation. The latter were instead influenced by habitat type and microhabitat availability. The approach used demonstrates that citizen science projects with few barriers to entry can gather viable datasets for scoping broad trends, providing that the projects are carefully designed and analysed to ensure data quality