Resolving length-scale-dependent transient disorder through an ultrafast phase transition.

Material functionality can be strongly determined by structure extending only over nanoscale distances. The pair distribution function presents an opportunity for structural studies beyond idealized crystal models and to investigate structure over varying length scales. Applying this method with ultrafast time resolution has the potential to similarly disrupt the study of structural dynamics and phase transitions. Here we demonstrate such a measurement of CuIr2S4 optically pumped from its low-temperature Ir-dimerized phase. Dimers are optically suppressed without spatial correlation, generating a structure whose level of disorder strongly depends on the length scale. The redevelopment of structural ordering over tens of picoseconds is directly tracked over both space and time as a transient state is approached. This measurement demonstrates the crucial role of local structure and disorder in non-equilibrium processes as well as the feasibility of accessing this information with state-of-the-art XFEL facilities.

Extraordinary Magnetic Response of an Anisotropic 2D Antiferromagnet via Site Dilution.

A prominent characteristic of 2D magnetic systems is the enhanced spin fluctuations, which reduce the ordering temperature. We report that a magnetic field of only 1000th of the Heisenberg superexchange interaction can induce a crossover, which for practical purposes is the effective ordering transition, at temperatures about 6 times the Néel transition in a site-diluted two-dimensional anisotropic quantum antiferromagnet. Such a strong magnetic response is enabled because the system directly enters the antiferromagnetically ordered state from the isotropic disordered state, skipping the intermediate anisotropic stage. The underlying mechanism is achieved on a pseudospin-half square lattice realized in the [(SrIrO3)1/(SrTiO3)2] superlattice thin film that is designed to linearly couple the staggered magnetization to external magnetic fields by virtue of the rotational symmetry-preserving Dzyaloshinskii-Moriya interaction. Our model analysis shows that the skipping of the anisotropic regime despite finite anisotropy is due to the enhanced isotropic fluctuations under moderate dilution.

Verwey transition as evolution from electronic nematicity to trimerons via electron-phonon coupling.

Understanding the driving mechanisms behind metal-insulator transitions (MITs) is a critical step toward controlling material's properties. Since the proposal of charge order-induced MIT in magnetite Fe3O4 in 1939 by Verwey, the nature of the charge order and its role in the transition have remained elusive. Recently, a trimeron order was found in the low-temperature structure of Fe3O4; however, the expected transition entropy change in forming trimeron is greater than the observed value, which arises a reexamination of the ground state in the high-temperature phase. Here, we use electron diffraction to unveil that a nematic charge order on particular Fe sites emerges in the high-temperature structure of bulk Fe3O4 and that, upon cooling, a competitive intertwining of charge and lattice orders arouses the Verwey transition. Our findings discover an unconventional type of electronic nematicity in correlated materials and offer innovative insights into the transition mechanism in Fe3O4 via the electron-phonon coupling.

Real-space observation of fluctuating antiferromagnetic domains.

Magnetic domains play a fundamental role in physics of magnetism and its technological applications. Dynamics of antiferromagnetic domains is poorly understood, although antiferromagnets are expected to be extensively used in future electronic devices wherein it determines the stability and operational speed. Dynamics of antiferromagnets also features prominently in the studies of topological quantum matter. Real-space imaging of fluctuating antiferromagnetic domains is therefore highly desired but has never been demonstrated. We use coherent x-ray diffraction to obtain videos of fluctuating micrometer-scale antiferromagnetic domains in Ni2MnTeO6 on time scales from 10-1 to 103 s. In the collinear phase, thermally activated domain wall motion is observed in the vicinity of the Néel temperature. Unexpectedly, the fluctuations persist through the full range of the higher-temperature helical phase. These observations illustrate the high potential significance of the dynamic domain imaging in phase transition studies and in magnetic device research.

Investigating the association between blood transfusion and clinical outcomes in patients with acute coronary syndromes: a data linkage approach to Patient Blood Management.

BACKGROUND: The appropriateness of the use of blood transfusion in patients with acute coronary syndromes (ACS) remains contested. In general, studies addressing this issue were based on data from clinical trials, registries, or electronic medical records, and were conducted across different settings. Our study aimed to use a linked patient blood management data system from existing hospital databases to examine the association between blood transfusion and in-hospital mortality, length of stay (LOS) and readmission rates among patients with ACS, and to investigate this relationship at different haemoglobin (Hb) concentrations. MATERIALS AND METHODS: This was a retrospective observational study of patients admitted to participating hospitals between 1st January 2014 to 31st December 2017 with ACS recorded as primary diagnosis. Admission and nadir Hb concentrations were categorised as ≤100 g/L and >100 g/L. Generalised estimating equations were used to investigate the association between transfusion and clinical outcomes, while accounting for the correlation of multiple admissions from the same patients across hospitals over the study period. RESULTS: Of the 9,952 admissions included, blood transfusions occurred in 705 (7.1%). In unadjusted analyses, transfusion was associated with an increased risk of in-hospital mortality (OR: 2.97; 95% CI: 2.14-4.13) and an average LOS 3.55 (95% CI: 3.38-3.72) times longer. After adjusting for demographic and clinical factors, transfusion was associated with an increased risk of in-hospital mortality when Hb >100 g/L. Transfusion was not associated with the risk of readmission. DISCUSSION: The effect of transfusion on in-hospital mortality was largely dependent on the pre-transfusion Hb concentration. When Hb was >100 g/L transfusion was associated with increased mortality, whereas when Hb ≤100 g/L no association was observed.

Laser-induced transient magnons in Sr3Ir2O7 throughout the Brillouin zone.

Although ultrafast manipulation of magnetism holds great promise for new physical phenomena and applications, targeting specific states is held back by our limited understanding of how magnetic correlations evolve on ultrafast timescales. Using ultrafast resonant inelastic X-ray scattering we demonstrate that femtosecond laser pulses can excite transient magnons at large wavevectors in gapped antiferromagnets and that they persist for several picoseconds, which is opposite to what is observed in nearly gapless magnets. Our work suggests that materials with isotropic magnetic interactions are preferred to achieve rapid manipulation of magnetism.

Real Space Imaging of Spin Stripe Domain Fluctuations in a Complex Oxide.

Understanding the formation and dynamics of charge and spin-ordered states in low-dimensional transition metal oxide materials is crucial to understanding unconventional high-temperature superconductivity. La_{2-x}Sr_{x}NiO_{4+δ} (LSNO) has attracted much attention due to its interesting spin dynamics. Recent x-ray photon correlation spectroscopy studies have revealed slow dynamics of the spin order (SO) stripes in LSNO. Here, we applied resonant soft x-ray ptychography to map the spatial distribution of the SO stripe domain inhomogeneity in real space. The reconstructed images show the SO domains are spatially anisotropic, in agreement with previous diffraction studies. For the SO stripe domains, it is found that the correlation lengths along different directions are strongly coupled in space. Surprisingly, fluctuations were observed in the real space amplitude signal, rather than the phase or position. We attribute the observed slow dynamics of the stripe domains in LSNO to thermal fluctuations of the SO domain boundaries.

Strain-Modulated Slater-Mott Crossover of Pseudospin-Half Square-Lattice in (SrIrO_{3})_{1}/(SrTiO_{3})_{1} Superlattices.

We report on the epitaxial strain-driven electronic and antiferromagnetic modulations of a pseudospin-half square-lattice realized in superlattices of (SrIrO_{3})_{1}/(SrTiO_{3})_{1}. With increasing compressive strain, we find the low-temperature insulating behavior to be strongly suppressed with a corresponding systematic reduction of both the Néel temperature and the staggered moment. However, despite such a suppression, the system remains weakly insulating above the Néel transition. The emergence of metallicity is observed under large compressive strain but only at temperatures far above the Néel transition. These behaviors are characteristics of the Slater-Mott crossover regime, providing a unique experimental model system of the spin-half Hubbard Hamiltonian with a tunable intermediate coupling strength.

Strong Orbital Polarization in a Cobaltate-Titanate Oxide Heterostructure.

Through a combination of experimental measurements and theoretical modeling, we describe a strongly orbital-polarized insulating ground state in an (LaTiO_{3})_{2}/(LaCoO_{3})_{2} oxide heterostructure. X-ray absorption spectra and ab initio calculations show that an electron is transferred from the titanate to the cobaltate layers. The charge transfer, accompanied by a large octahedral distortion, induces a substantial orbital polarization in the cobaltate layer of a size unattainable via epitaxial strain alone. The asymmetry between in-plane and out-of-plane orbital occupancies in the high-spin cobaltate layer is predicted by theory and observed through x-ray linear dichroism experiments. Manipulating orbital configurations using interfacial coupling within heterostructures promises exciting ground-state engineering for realizing new emergent electronic phases in metal oxide superlattices.

Depth-Resolved Modulation of Metal-Oxygen Hybridization and Orbital Polarization across Correlated Oxide Interfaces.

Interface-induced modifications of the electronic, magnetic, and lattice degrees of freedom drive an array of novel physical properties in oxide heterostructures. Here, large changes in metal-oxygen band hybridization, as measured in the oxygen ligand hole density, are induced as a result of interfacing two isovalent correlated oxides. Using resonant X-ray reflectivity, a superlattice of SrFeO3 and CaFeO3 is shown to exhibit an electronic character that spatially evolves from strongly O-like in SrFeO3 to strongly Fe-like in CaFeO3 . This alternating degree of Fe electronic character is correlated with a modulation of an Fe 3d orbital polarization, giving rise to an orbital superstructure. At the SrFeO3 /CaFeO3 interfaces, the ligand hole density and orbital polarization reconstruct in a single unit cell of CaFeO3 , demonstrating how the mismatch in these electronic parameters is accommodated at the interface. These results provide new insight into how the orbital character of electrons is altered by correlated oxide interfaces and lays out a broadly applicable approach for depth-resolving band hybridization.

The empirical relationship between nonstandard economic behaviors.

We study the joint distribution of 11 behavioral phenomena in a group of 190 laboratory subjects and compare it to the predictions of existing models as a step in the development of a parsimonious, general model of economic choice. We find strong correlations between most measures of risk and time preference, between compound lottery and ambiguity aversion, and between loss aversion and the endowment effect. Our results support some, but not all attempts to unify behavioral economic phenomena. Overconfidence and gender are also predictive of some behavioral characteristics.

Outcomes based on prior therapy in the phase 3 METEOR trial of cabozantinib versus everolimus in advanced renal cell carcinoma.

BACKGROUND: In the phase 3 METEOR trial, cabozantinib improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS) versus everolimus in patients with advanced renal cell carcinoma (RCC), after prior antiangiogenic therapy. METHODS: Outcomes were evaluated for subgroups defined by prior therapy with sunitinib or pazopanib as the only prior VEGFR inhibitor, or prior anti-PD-1/PD-L1 therapy. RESULTS: For the prior sunitinib subgroup (N = 267), median PFS for cabozantinib versus everolimus was 9.1 versus 3.7 months (HR 0.43, 95% CI 0.32-0.59), ORR was 16% versus 3%, and median OS was 21.4 versus 16.5 months (HR 0.66, 95% CI 0.47-0.93). For the prior pazopanib subgroup (N = 171), median PFS for cabozantinib versus everolimus was 7.4 versus 5.1 months (HR 0.67, 95% CI 0.45-0.99), ORR was 19% versus 4%, and median OS was 22.0 versus 17.5 months (HR 0.66, 95% CI 0.42-1.04). For prior anti-PD-1/PD-L1 therapy (N = 32), median PFS was not reached for cabozantinib versus 4.1 months for everolimus (HR 0.22, 95% CI 0.07-0.65), ORR was 22% versus 0%, and median OS was not reached versus 16.3 months (HR 0.56, 95% CI 0.21-1.52). CONCLUSIONS: Cabozantinib was associated with improved clinical outcomes versus everolimus in patients with advanced RCC, irrespective of prior therapy, including checkpoint inhibitor therapy.

Bioimage Informatics for Big Data.

Bioimage informatics is a field wherein high-throughput image informatics methods are used to solve challenging scientific problems related to biology and medicine. When the image datasets become larger and more complicated, many conventional image analysis approaches are no longer applicable. Here, we discuss two critical challenges of large-scale bioimage informatics applications, namely, data accessibility and adaptive data analysis. We highlight case studies to show that these challenges can be tackled based on distributed image computing as well as machine learning of image examples in a multidimensional environment.

Testing the reward prediction error hypothesis with an axiomatic model.

Neuroimaging studies typically identify neural activity correlated with the predictions of highly parameterized models, like the many reward prediction error (RPE) models used to study reinforcement learning. Identified brain areas might encode RPEs or, alternatively, only have activity correlated with RPE model predictions. Here, we use an alternate axiomatic approach rooted in economic theory to formally test the entire class of RPE models on neural data. We show that measurements of human neural activity from the striatum, medial prefrontal cortex, amygdala, and posterior cingulate cortex satisfy necessary and sufficient conditions for the entire class of RPE models. However, activity measured from the anterior insula falsifies the axiomatic model, and therefore no RPE model can account for measured activity. Further analysis suggests the anterior insula might instead encode something related to the salience of an outcome. As cognitive neuroscience matures and models proliferate, formal approaches of this kind that assess entire model classes rather than specific model exemplars may take on increased significance.

MEASURING BELIEFS AND REWARDS: A NEUROECONOMIC APPROACH.

The neurotransmitter dopamine is central to the emerging discipline of neuroeconomics; it is hypothesized to encode the difference between expected and realized rewards and thereby to mediate belief formation and choice. We develop the first formal test of this theory of dopaminergic function, based on a recent axiomatization by Caplin and Dean [2008A]. These tests are satisfied by neural activity in the nucleus accumbens, an area rich in dopamine receptors. We find evidence for separate positive and negative reward prediction error signals, suggesting that behavioral asymmetries in response to losses and gains may parallel asymmetries in nucleus accumbens activity.

Extensive bruising secondary to vitamin C deficiency.

An otherwise fit and well 56-year-old man presented with extensive ecchymosis and soft-tissue haematomas affecting his legs. Coagulation studies were normal. Further questioning revealed a severely restricted diet. The bruising improved rapidly after commencing oral vitamin C supplementation. Serum vitamin C level was low, supporting the clinical diagnosis of scurvy.

Axiomatic methods, dopamine and reward prediction error.

The phasic firing rate of midbrain dopamine neurons has been shown to respond both to the receipt of rewarding stimuli, and the degree to which such stimuli are anticipated by the recipient. This has led to the hypothesis that these neurons encode reward prediction error (RPE)-the difference between how rewarding an event is, and how rewarding it was expected to be. However, the RPE model is one of a number of competing explanations for dopamine activity that have proved hard to disentangle, mainly because they are couched in terms of latent, or unobservable, variables. This article describes techniques for dealing with latent variables common in economics and decision theory, and reviews work that uses these techniques to provide simple, non-parametric tests of the RPE hypothesis, allowing clear differentiation between competing explanations.

Trading off speed and accuracy in rapid, goal-directed movements.

Many studies have shown that humans face a trade-off between the speed and accuracy with which they can make movements. In this article, we asked whether humans choose movement time to maximize expected gain by taking into account their own speed-accuracy trade-off (SAT). We studied this question within the context of a rapid pointing task in which subjects received a reward for hitting a target on a monitor. The experimental design we used had two parts. First, we estimated individual trade-offs by motivating subjects to perform the pointing task under four different time constraints. Second, we tested whether subjects selected movement time optimally in an environment where they were rewarded for both speed and accuracy; the value of the target decreased linearly over time to zero. We ran two conditions in which the subjects faced different decay rates. Overall, the performance of 13 out of 16 subjects was indistinguishable from optimal. We concluded that in planning movements, humans take into account their own SAT to maximize expected gain.

Entropy and oligomerization in GPCRs.

Evolutionary trace (ET) and entropy are two related methods for analyzing a multiple sequence alignment to determine functionally important residues in proteins. In this article, these methods have been enhanced with a view to reinvestigate the issue ofGPCR dimerization and oligomerization. In particular, cluster analysis has replaced the subjective visual analysis element of the original ET method. Previous applications of the ET method predicted two dimerization interfaces on the external transmembrane lipid-facing region of GPCRs; these were discussed in terms of dimerization and linear oligomers. Removing the subjective element of the ET method gives rise to the prediction of functionally important residues on the external face of each transmembrane helix for a large number of class A GPCRs. These results are consistent with a growing body of experimental information that, taken over many receptor subtypes, has implicated each transmembrane helix in dimeric interactions. In this application, entropy gave superior results to those obtained from the ET method in that its use gives rise to higher z-scores and fewer instances of z-scores below 3.