We examine the equilibrium fractionation of Mg isotopes between forsterite, diopside, and a coexisting melt at liquidus temperatures using a combination of analyses of petrological-experiment products and atomic-scale simulations. Our experiment yields ∆²⁶Mgol/melt = -0.058 ± 0.032 ‰ (2s.e.) and ∆²⁶Mgcpx/melt = 0.060 ± 0.034 ‰ (2s.e.) for crystals grown from a near-cotectic basaltic melt in the CMAS system, which combine to give ∆26Mgcpx/ol = 0.131 ± 0.045 ‰ at 1300 °C. The value of ∆²⁶Mgol/melt is within the uncertainty of the mean olivine-melt fractionation determined for unzoned phenocrysts and naturally quenched glass from ocean island and mid-ocean ridge basalts. We compare the experimentally determined Mg isotope fractionation between olivine and clinopyroxene with ab initio calculations using different DFT functionals. We demonstrate that when using the revised Perdew–Burke–Ernzerhof (PBESOL) exchange-correlation functional, accounting for thermal expansion, and site-averaging for forsterite, our ab initio results are in good agreement with our experiments, yielding ∆26Mgcpx/ol = 0.134‰ at 1300°C. Using the Local Density Approximation (LDA) or other Generalised Gradient Approximation (GGA) functionals, or neglecting thermal expansion, lowers ∆26Mgcpx/ol values to approximately 0.03–0.06 ‰ below the experimentally measured values. Neglecting site-averaging in forsterite results in positive (using only M1) or negative (using only M2) deviations in fractionation of 0.08‰ from averaged isotope ratios. Comparison of our experimentally and theoretically derived ∆26Mgcpx/ol values with empirical estimates from natural samples reveals a systematic offset, underscoring the need to distinguish equilibrium mineral–mineral fractionation from empirically derived relationships that may incorporate kinetic or compositional effects.

We use density functional theory to investigate the fractionation of Mg isotopes between phases in the lower mantle. Our results support previous work and show that coordination number plays an important role in controlling isotopic fractionation, with bridgmanite (perovskite-structured MgSiO3) preferentially incorporating lighter Mg isotopes into its highly coordinated site compared to periclase (MgO). Increasing pressure enhances this fractionation while increasing temperature decreases it. These two effects trade-off such that the preference is evident across all lower mantle conditions explored, even to the high temperatures of the chondritic liquidus (e.g. Delta 26/24MgPer-Bdm is 0.04 parts per thousand at 4200 K and 87 GPa). In additional numerical experiments we separate the effect of coordination number from differences in bond length between different phases and these allow us to build an ionic model which parameterises magnesium isotope fractionation as a function of bond length, coordination number, and temperature. This model provides us with a preliminary means to describe isotope partitioning between solid and liquid phases when making predictions of Mg isotopic differences generated during terrestrial magma ocean crystallisation. We find that Mg isotopic fractionation between bridgmanite and melt, at lower mantle conditions, is sufficient to generate detectable differences in the Mg isotopic compositions of a residual melt or solid cumulate phase, relative to bulk Earth. More specifically, we show that isolation of a reservoir of cumulate bridgmanite that is some 3%-15% by mass of the mantle could account for the superchondritic 26Mg/24Mg of accessible terrestrial peridotite samples. Whether such a reservoir can be dynamically preserved over Earth history remains an open question, but our results help quantify possible tests of such a scenario.

Surface-waves carry important information about upper mantle structure, especially in poorly sampled areas such as oceanic regions. Surface-wave tomography models can be used to assess geodynamic simulations by comparing observed and predicted structures. However, surface-wave data are noisy and sparse resulting in tomography models being noisy and blurred pictures of the Earth's structure. As a result, tomography models can hardly be compared directly to geodynamic predictions which aim to predict the true structure of the Earth. Although challenging, assessing geodynamic simulations with surface-wave tomography requires accounting for full 3D resolution and robust uncertainties. In this study, we present a workflow to quantitatively assess geodynamic model predictions using surface-wave tomography. Specifically, we measure dispersion data for paths crossing the Pacific ocean and estimate data uncertainties including measurement and theoretical errors. We use a finite-frequency forward theory to linearly relate data to the three-dimensional Vsv structure in the upper mantle. Subsequently, we apply the SOLA (Backus-Gilbert-style) method in 3D to control and produce the full three-dimensional resolution and robust model uncertainties together with the Vsv tomography model. Equipped with this, we assess predictions for the Pacific upper mantle from a set of geodynamic simulations based on different input parameters. Preliminary results highlight physical parameters of mantle convection influencing significantly the misfit between observed and predicted structure in the Pacific upper mantle; and, for quantitative parameters, inform us on values that provide the best fits.

Slurry regions may exist in the cores of several terrestrial bodies and are expected to influence the dynamics of deep planetary interiors and the viability of maintaining global magnetic fields. Here, we develop a two-component slurry model of the lowermost outer core of the Earth (the F-layer). In contrast to most previous models of slurries in planetary cores, we explicitly model the physics controlling the nucleation, growth and sinking of individual iron crystals and do not assume that the layer is in phase equilibrium. We assume that falling crystals do not interact and that the temperature and the overall composition are imposed, which allows us to solve for the volume fraction of solid in the layer and the size distribution of crystals. Models that produce a plausible heat budget and density excess compared with the bulk core yield a solid fraction that is far below that predicted by phase equilibrium and have a crystal size distribution dominated by the smallest particles with a maximum particle radii of 3 cm. The model can be used to understand the role of non-equilibrium effects in other planetary cores.

The growth of Earth's solid inner core powers the geodynamo in the liquid outer core, creating a global magnetic field that helps to shield the planet from harmful solar radiation. However, the origins of the inner core are still not fully understood. Traditional models of core evolution overlook the necessity for liquids to be supercooled below their melting point before freezing. Recent estimates of the required supercooling for the inner core's homogeneous nucleation are unrealistically high and conflict with the expected current thermal structure of the core. Through molecular dynamics simulations, we show that nucleation from an Fe1-xCx liquid, with x=0.1-0.15, reduces the supercooling requirement to 250-400 K, broadly compatible with expected current thermal profiles of the core. Though these compositions are not a complete description of core chemistry, which requires at least ternary systems, they are consistent with a number of constraints derived from seismology, mineral physics, and geochemistry. Crucially, our results demonstrate that whilst some potential compositions of the core cannot explain the presence of the inner core, others can. The nucleation process of the inner core can therefore provide a new and strong constraint on core composition.

AIMS:Heart failure (HF) is frequently associated with multiple comorbidities. We aimed to define their trajectory of accrual to identify opportunities for disease prevention. METHODS AND RESULTS:We identified all participants in the UK Biobank cohort study diagnosed with HF prior to enrolment or during follow-up, who had disease occurrence data available from both primary and secondary care records (n = 9824). We established the time between diagnosis of HF and 16 common comorbidities to determine the rate and sequence of comorbidity accrual in relation to HF. Stratified analyses considered associations with sex and age at diagnosis of HF. In chronological sequence, HF was the median fourth diagnosis for men and women. As the age at HF diagnosis increased, HF came later in the sequence of diseases (median second in under 50 years to fifth in those aged 80-90 years). In all age strata, comorbidities accumulated for over a decade before HF and this accelerated in the years immediately before HF. The median time between comorbidity and HF diagnoses ranged from depression preceding HF by 10.7 years to dementia proceeding HF by 0.7 years; all comorbidities presented earlier in women. Atrial fibrillation/flutter was the commonest disease to immediately precede HF, followed by hypertension, cancer, myocardial infarction and osteoarthritis. CONCLUSION:Heart failure is most often diagnosed in people with established multiple long-term conditions. There is a protracted window of opportunity during which interventions to prevent HF could be applied, often in disease contexts where this is not routine care, such as cancer and osteoarthritis.

The composition of Earth's core is a fundamental property of the Earth's deep interior, defining its present structure and long term thermal and magnetic evolution. However, the composition of the core is not well understood, with several combinations of light elements being able to satisfy the traditional constraints from cosmochemistry, core formation and seismology. The classic view of inner core formation does not include the necessity for liquids to be supercooled to below their melting point before freezing. Attempts to calculate the magnitude of this supercooling have found that several binary core compositions are incompatible with inner core nucleation. Here we show, through molecular dynamics simulations, that nucleation from an Fe1-xCx=0.1-0.15 composition is compatible with a range of geophysical constraints. Whilst not a complete description of core chemistry, our results demonstrate that inner core nucleation places a strong constraint on the composition of Earth's core that may allow discrimination between previously identified potential compositions.

During recent decades, changes in lifestyle have led to widespread nutritional obesity and its related complications. Remodelling adipose tissue as a therapeutic goal for obesity and its complications has attracted much attention and continues to be actively explored. The endothelium lines all blood vessels and is close to all cells, including adipocytes. The endothelium has been suggested to act as a paracrine organ. We explore the role of endothelial insulin-like growth factor-1 receptor (IGF-1R), as a paracrine modulator of white adipose phenotype. We show that a reduction in endothelial IGF-1R expression in the presence of high-fat feeding in male mice leads to depot-specific beneficial white adipose tissue remodelling, increases whole-body energy expenditure and enhances insulin sensitivity via a non-cell-autonomous paracrine mechanism. We demonstrate that increased endothelial malonate may be contributory and that malonate prodrugs have potentially therapeutically relevant properties in the treatment of obesity-related metabolic disease.

Mantle circulation in the Earth acts to remove heat from its interior and is thus a critical driver of our planet’s internal and surface evolution. Numerical mantle circulation models (MCMs) driven by plate motion history allow us to model relevant physical and chemical processes and help answer questions related to mantle properties and circulation. Predictions from MCMs can be tested using a variety of observations. Here, we illustrate how the combination of many disparate observations leads to constraints on mantle circulation across space and time. We present this approach by first describing the set-up of the example test MCM, including the parameterization of melting, and the methodology used to obtain elastic Earth models. We subsequently describe different constraints, that either provide information about present-day mantle (e.g. seismic velocity structure and surface deflection) or its temporal evolution (e.g. geomagnetic reversal frequency, geochemical isotope ratios and temperature of upper mantle sampled by lavas). We illustrate the information that each observation provides by applying it to a single MCM. In future work, we shall apply these observational constraints to a large number of MCMs, which will allow us to address questions related to Earth-like mantle circulation.

Large low velocity provinces (LLVPs) dominate Earth's lowermost mantle, but their detailed thermochemical nature remains a topic of discussion. In particular, it is unclear to what extent the bridgmanite to post-perovskite phase transition is able to explain their seismic velocity characteristics. Robust constraints on the origin of these seismic structures would shed light on large-scale mantle dynamics and Earth's thermal and chemical evolution. Here, we examine the combined effects of temperature, chemical heterogeneity and phase transitions on lowermost mantle tomographic signatures. To investigate this, we calculate synthetic seismic velocities expected from a range of scenarios for the stability of post-perovskite combined with models of different lowermost mantle temperatures and compositions using recent thermodynamic data. These are filtered to account for limited tomographic resolution, allowing for quantitative comparisons between our synthetic seismic velocities and a recent Backus-Gilbert based tomography model. Crucially, this model provides robust ratios and correlations of velocity anomalies derived from nearly identical Vp and Vs resolution, and includes uncertainty quantification that accounts for both data and theoretical errors. Given the tomographic uncertainties and limited resolution, our comparisons focus on globally and depth averaged seismic characteristics, which capture the effects of lateral compositional and mineralogical variability. By rejecting synthetic models that do not fit within tomographic uncertainties, we quantitatively eliminate the following: (i) models containing LLVPs with an iron-rich primordial composition, as these generate anomalously high root mean square seismic velocity anomalies; and (ii) models without post-perovskite in the lowermost mantle, as these cannot explain observations of elevated ratios of shear-wave to compressional-wave velocity (R_{s/p}) and a negative correlation between variations in shear-wave and bulk sound velocity (r_{s-c}). Additionally, we demonstrate that observations of R_{s/p} and r_{s-c} in the lowermost mantle cannot be explained by thermochemical LLVPs alone, but require bridgmanite and post-perovskite to co-occur at depth in the mantle. As such, we demonstrate that globally averaged seismic velocity characteristics can distinguish between composition and mineralogy in the lowermost mantle.

The growth of the solid inner core from the liquid outer core provides crucial power for generating the geomagnetic field. However, the traditional view of inner core growth does not include the physical requirement that liquids must be supercooled below the melting point before freezing can begin. In this Review, we explore the impact of supercooling the Earth’s core on inner core formation, growth and dynamics, and the interpretation of seismic and palaeomagnetic observations. Mineral physics calculations suggest that at least 450 K of supercooling is needed to spontaneously nucleate the inner core. However, when satisfying inferences from geophysical constraints, the maximum available supercooling is estimated at 420 K and more probably <100 K. Supercooling the Earth’s core requires that the inner core had at least two growth regimes. The first regime is a rapid phase that freezes supercooled liquids at rates comparable to outer core dynamics (cm yr−1), followed by the second regime that is a traditional in-equilibrium growth phase proportional to the cooling rate of the core (mm yr−1). Future research should seek evidence for rapid growth in the palaeomagnetic and seismic records and the mechanisms that produce deformation texture, particularly those owing to heterogeneous inner core growth, inner core convection, and coupling between freezing and the magnetic field. Nucleation and growth of Earth’s solid inner core has a crucial role powering the geomagnetic field. This Review explores the timing and mechanisms of inner core growth consistent with physical constraints and first-order observations of the thermal evolution of Earth.

Alfred Wilson, Andrew Walker, Dario Alfe and Chris Davies report on a meeting bringing together experimental, theoretical, and observational studies of the deep mantles and cores of terrestrial bodies Abstract Alfred Wilson, Andrew Walker, Dario Alfe and Chris Davies report on a meeting bringing together experimental, theoretical, and observational studies of the deep mantles and cores of terrestrial bodies

Seismic observations show the Earth's inner core has significant and unexplained variation in seismic attenuation with position, depth and direction. Interpreting these observations is difficult without knowledge of the visco- or anelastic dissipation processes active in iron under inner core conditions. Here, a previously unconsidered attenuation mechanism is observed in zinc, a low pressure analog of hcp-iron, during small strain sinusoidal deformation experiments. The experiments were performed in a deformation-DIA combined with X-radiography, at seismic frequencies (similar to 0.003-0.1 Hz), high pressure and temperatures up to similar to 80% of melting temperature. Significant dissipation (0.077 <= Q(-1)(omega) <= 0.488) is observed along with frequency dependent softening of zinc's Young's modulus and an extremely small activation energy for creep (<= 7 kJ mol(-1)). In addition, during sinusoidal deformation the original microstructure is replaced by one with a reduced dislocation density and small, uniform, grain size. This combination of behavior collectively reflects a mode of deformation called "internal stress superplasticity"; this deformation mechanism is unique to anisotropic materials and activated by cyclic loading generating large internal stresses. Here we observe a new form of internal stress superplasticity, which we name as "elastic strain mismatch superplasticity." In it the large stresses are caused by the compressional anisotropy. If this mechanism is also active in hcp-iron and the Earth's inner-core it will be a contributor to inner-core observed seismic attenuation and constrain the maximum inner-core grain-size to less than or similar to 10 km.

It is widely believed that seismic anisotropy in the lowermost mantle is caused by the flow-induced alignment of anisotropic crystals such as post-perovskite. What is unclear, however, is whether the anisotropy observations in the lowermost mantle hold information about past mantle flow, or if they only inform us about the present-day flow field. To investigate this, we compare the general and seismic anisotropy calculated using Earth-like mantle convection models where one has a time-varying flow, and another where the present-day flow is constant throughout time. To do this, we track a post-perovskite polycrystal through the flow fields and calculate texture development using the sampled strain rate and the visco-plastic self-consistent approach. We assume dominant slip on (001) and test the effect of the relative importance of this glide plane over others by using three different plasticity models with different efficiencies at developing texture. We compare the radial anisotropy parameters and the anisotropic components of the elastic tensors produced by the flow field test cases at the same location. We find, under all ease-of-texturing cases, the radial anisotropy is very similar (difference <2%) in the majority of locations and in some regions, the difference can be very large (>10%). The same is true when comparing the elastic tensors directly. Varying the ease-of-texture development in the crystal aggregate suggests that easier-to-texture material may hold a stronger signal from past flow than harder-to-texture material. Our results imply that broad-scale observations of seismic anisotropy such as those from seismic tomography, 1-D estimates and normal mode observations, will be mainly sensitive to present-day flow. Shear-wave splitting measurements, however, could hold information about past mantle flow. In general, mantle memory expressed in anisotropy may be dependent on path length in the post-perovskite stability field. Our work implies that, as knowledge of the exact causative mechanism of lowermost mantle anisotropy develops, we may be able to constrain both present-day and past mantle convection.

Objective Reduced IGF-1 signalling is an evolutionarily conserved mediator of longevity, yet the magnitude of this effect is substantially larger in organisms retaining a common insulin and IGF-1 receptor. Whether this reflects the failure to simultaneously reduce IGF-1 and insulin signalling in mammalian model systems remains unexplored, as is the associated impact on markers of healthy ageing. We set out to address these uncertainties. Methods We compared the duration of healthy life (healthspan) in male mice with haploinsufficiency of the insulin receptor (IRKO), IGF-1 receptor (IGF-1RKO), or both (DKO), versus wildtype (WT) littermates. Cognitive performance was defined using nesting studies at 3- and 24-months of age. Brain transcriptome was characterised at 3- and 18-months of age using RNA-seq. Results Healthspan was longer in DKO versus WT, with IRKO and IGF-1RKO being intermediate. At 2 years of age, DKO also exhibited preserved nesting behaviour in contrast with all other genotypes. Differential insulin sensitivity or weight gain during ageing did not explain the preserved healthspan of DKO, since these were comparable to IRKO littermates. Brain transcriptomics at 18 months of age revealed lower expression of canonical ageing-associated genes in DKO versus WT, although many of these findings were replicated in IRKO versus WT or IGF-1RKO vs WT. Conclusions Reduced insulin and IGF-1 receptor expression have both common and synergistic effects upon elements of healthy mammalian ageing, suggesting future ageing studies should consider targeting both insulin and IGF-1 signalling.

The formation mechanism of pallasite meteorites, which are mixtures of Fe-Ni metal and olivine (Figure 1), is not agreed upon within the literature. Formation hypotheses as diverse as relict core-mantle region material [1], catastrophic impact-related mixing [2], metallic volcanism [3], fractional melting of a chondritic body [4] or a combination of the above [1] have been suggested. In this abstract, we build on the recently published results of Murphy Quinlan et al., 2021 [5], with a focus on the formation of pallasite meteorites and constraint of their formation environment using coupled numerical models. Numerical models of the thermal evolution of planetesimals provide us with insights into the geological context of meteorite samples. Temperature-dependent properties such as thermal conductivity and volumetric heat capacity control the thermal evolution of these early-Solar System bodies. We explore the effect of incorporating T-dependent material properties on the thermal evolution of a meteorite parent body, and investigate whether this results in different interpretations of meteorite samples, for example the depth of formation of pallasite samples based on cooling rates recorded in their metal portion [6]. We have developed an open source Python package, Pytesimal [7], to perform numerical models of conductively cooling planetesimals with T-dependent conductivity, heat capacity and density. We observe that including temperature dependent properties produces differences in thermal history, and in turn the timing and depth of formation of meteorite samples [Figure 2]. When implemented in a model of a 250 km radius pallasite parent body, T-dependent properties delay the onset of core crystallisation and the inferred period of dynamo activity by ∼40 Myr, approximately equivalent to increasing the planetary radius by 10% [5]. This result cannot be reproduced by using the best-fitting constant values for thermal properties, and reduces the acceptable range of planetesimal radii and core sizes that are compatible with paleomagnetic evidence from pallasite meteorites [5–8]. The output of this model can be used to investigate the thermal evolution of the pallasite formation region for different parent body geometries in order to test different formation mechanisms. Figure 3 shows the cooling rates in this region of the mantle for a 250 km radius planetesimal with a core size of 50% the total planetary radius, in comparison to a "stripped mantle" model with a core size 70% of the total 300 km planetesimal radius. The differing temperatures and cooling rates between parent body models can be combined with petrological and geochemical evidence to interrogate the likelihood of different formation scenarios. 1. S. J. McKibbin, L. Pittarello, C. Makarona, C. Hamann, L. Hecht, S. M. Chernonozhkin, S. Goderis, & P. Claeys, Petrogenesis of main group pallasite meteorites based on relationships among texture, mineralogy, and geochemistry. Meteoritics & Planetary Science, 54 (2019) 2814–2844. https://doi.org/10.1111/maps.13392. 2. J. A. Tarduno, R. D. Cottrell, F. Nimmo, J. Hopkins, J. Voronov, A. Erickson, E. Blackman, E. R. D. Scott, & R. McKinley, Evidence for a dynamo in the main group pallasite parent body. Science, 338 (2012) 939–942. https://doi.org/10.1126/science.1223932. 3. B. C. Johnson, M. M. Sori, & A. J. Evans, Ferrovolcanism on metal worlds and the origin of pallasites. Nature Astronomy, 4 (2019) 41–44. https://doi.org/10.1038/s41550-019-0885-x. 4. J. S. Boesenberg, J. S. Delaney, & R. H. Hewins, A petrological and chemical reexamination of main group pallasite formation. Geochimica et Cosmochimica Acta, 89 (2012) 134–158. https://doi.org/10.1016/j.gca.2012.04.037. 5. M. Murphy Quinlan, A. M. Walker, C. J. Davies, J. E. Mound, T. Müller, & J. Harvey, The conductive cooling of planetesimals with temperature-dependent properties. Journal of Geophysical Research: Planets, 126 (2021). https://doi.org/10.1029/2020JE006726. 6. J. Yang, J. I. Goldstein, & E. R. D. Scott, Main-group pallasites: Thermal history, relationship to IIIAB irons, and origin. Geochimica et Cosmochimica Acta, 74 (2010) 4471–4492. https://doi.org/10.1016/j.gca.2010.04.016. 7. M. Murphy Quinlan, A. M. Walker, P. Selves, & L. S. E. Teggin, Pytesimal software package: v2.0.0. (2021). https://doi.org/10.5281/zenodo.4762445. 8. J. F. J. Bryson, C. I. O. Nichols, J. Herrero-Albillos, F. Kronast, T. Kasama, H. Alimadadi, G. van der Laan, F. Nimmo, & R. J. Harrison, Long-lived magnetism from solidification-driven convection on the pallasite parent body. Nature, 517 (2015) 472–475. https://doi.org/10.1038/nature14114.

Abstract Introduction People with heart failure (HF) usually have multiple comorbidities and these confer adverse prognosis. The chronology of comorbidity development in relation to HF has not been investigated, which hinders development of preventative strategies. Purpose We aimed to define the chronology of comorbidity diagnoses in relation to HF diagnosis and hypothesised that HF is preceded by most of its comorbidities. Methods We used UK Biobank data to identify 21,127 people with HF diagnosis at any stage before or after recruitment. Comorbidities were defined using primary care records, and were not included if self-reported or their date of diagnosis unknown. Comorbidities were selected based on methods of Conrad et al. (Lancet 2018; 391(10120): 572-580), and defined using CALIBER or UK Biobank criteria. We investigated the time between first diagnosis of HF and first diagnosis of 15 common comorbidities, including after stratification by sex and age at HF diagnosis. Analysis was conducted using RStudio. Results For all studied comorbidities, except dementia, at least half of diagnoses predated or developed synchronously with HF. For myocardial infarction, obesity, cancer, atrial fibrillation, hypertension, diabetes and depression, at least three quarters of diagnoses predated or developed synchronously with HF. The median time between comorbidity and HF diagnoses varied substantially between comorbidities, ranging from depression preceding HF by 10.7 years to dementia proceeding HF by 0.7 years. The interquartile range of time between comorbidity and HF diagnoses varied substantially, ranging from 2.4 years for myocardial infarction to 15.2 years for depression, indicating most cases of the former develop in a narrow window (usually prior to HF diagnosis). All comorbidities presented earlier in women, with this being most marked for cancer (median time between cancer and HF -2.6 years for men and -7.1 years for women). As the age of HF diagnosis increased, the time spent with all studied comorbidities also increased. Indeed, in HF diagnosed before the age of 60, a majority of comorbidity diagnoses (except for depression) occurred after HF. Conclusion HF most often develops late in the process of comorbidity accrual, although this pattern is reversed in people developing HF at younger ages. Sex differences are also notable, with women developing comorbidities earlier in relation to their HF diagnosis. Understanding the chronology of comorbidity development may help to guide strategies to prevent multimorbidity, which are likely to require a personalised approach. For people with established HF, our data also emphasise the importance of holistic care that accounts for complex multimorbidity.Figure 1