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Precision medicine aims to treat an individual based on their clinical characteristics. A differential drug response, critical to using these features for therapy selection, has never been examined directly in type 2 diabetes. In this study, we tested two hypotheses: (1) individuals with body mass index (BMI) > 30 kg/m2, compared to BMI ≤ 30 kg/m2, have greater glucose lowering with thiazolidinediones than with DPP4 inhibitors, and (2) individuals with estimated glomerular filtration rate (eGFR) 60–90 ml/min/1.73 m2, compared to eGFR >90 ml/min/1.73 m2, have greater glucose lowering with DPP4 inhibitors than with SGLT2 inhibitors. The primary endpoint for both hypotheses was the achieved HbA1c difference between strata for the two drugs. In total, 525 people with type 2 diabetes participated in this UK-based randomized, double-blind, three-way crossover trial of 16 weeks of treatment with each of sitagliptin 100 mg once daily, canagliflozin 100 mg once daily and pioglitazone 30 mg once daily added to metformin alone or metformin plus sulfonylurea. Overall, the achieved HbA1c was similar for the three drugs: pioglitazone 59.6 mmol/mol, sitagliptin 60.0 mmol/mol and canagliflozin 60.6 mmol/mol (P = 0.2). Participants with BMI > 30 kg/m2, compared to BMI ≤ 30 kg/m2, had a 2.88 mmol/mol (95% confidence interval (CI): 0.98, 4.79) lower HbA1c on pioglitazone than on sitagliptin (n = 356, P = 0.003). Participants with eGFR 60–90 ml/min/1.73 m2, compared to eGFR >90 ml/min/1.73 m2, had a 2.90 mmol/mol (95% CI: 1.19, 4.61) lower HbA1c on sitagliptin than on canagliflozin (n = 342, P = 0.001). There were 2,201 adverse events reported, and 447/525 (85%) randomized participants experienced an adverse event on at least one of the study drugs. In this precision medicine trial in type 2 diabetes, our findings support the use of simple, routinely available clinical measures to identify the drug class most likely to deliver the greatest glycemic reduction for a given patient. (ClinicalTrials.gov registration: NCT02653209; ISRCTN registration: 12039221.)

Cr2O3 is the only known uniaxial antiferromagnetic material that is also magnetoelectric at room temperature. This renders Cr2O3 a technologically relevant playground for the realisation of different device ideas for prospective antiferromagnetic spintronics. We discovered the presence of flexomagnetic effects in Cr2O3, which come about due to the impact of a strain gradient on the thermodynamic properties, namely on the Neel temperature. By combining magnetotransport and Nitrogen Vacancy magnetometry characterizations, we experimentally determine the presence of the gradient of the Neel temperature in a 50-nm-thick Cr2O3 thin film and quantify that the magnetic moment, generated by this new effect, can be as high as 15 μB/nm2. Furthermore, due to good oxide-oxide heteroepitaxy and respective compressive strain, the Neel temperature in Cr2O3 thin films can be enhanced persistently up to 100degC, which is 60degC higher than the bulk transition temperature. The emergent flexomagnetism-driven ferromagnetic order parameter in antiferromagnetic thin films offers more flexibility in the design of spintronic and magnonic devices and can be of relevance for other antiferromagnetic materials. P. Makushko, T. Kosub, O. V. Pylypovskyi et al., Nature Communications (2022), in press.

A search for high-speed and low-energy memory devices puts antiferromagnetic thin films at the forefront of spintronic research. Here, we develop a material model of a granular antiferromagnetic thin film with uniaxial anisotropy and provide fundamental insight into the interaction of antiferromagnetic domain walls with grain boundaries. This model is validated on thin films of the antiferromagnetic insulator \ch{Cr2O3}, revealing complex maze-like domain patterns hosting localized nanoscale domains down to 50 nm. We show that the inter-grain magnetic parameters can be estimated based on an analysis of high-resolution images of antiferromagnetic domain patterns examining the domain patterns' self-similarity and the statistical distribution of domain sizes. Having a predictive material model and understanding of the pinning of domain walls on grain boundaries, we put forth design rules to realize granular antiferromagnetic recording media.

Understanding behavior of magnetic texture in antiferromagnetic nanostructures and thin films is crucial for the design of novel magnetic data storage and logic devices. Here, we derive the boundary conditions for the Néel vector in a two-sublattice antiferromagnet (AFM) and apply them to describe the shape of the domain walls [1,2] and skyrmions [2] in confined samples. In general, the surface of a 3D domain wall behaves as an elastic ribbon which bends in response on the topographic features of the single crystal Cr2 O3 [1]. In presence of the Dzyaloshinskii-Moriya interaction, topologically non-trivial AFM textures possess broadening near the surface. In thin films, the sample’s granularity becomes crucial. We present a model of a granular AFM and, by comparison with Nitrogen Vacancy magnetometry of 200-nm-thick Cr2O3 films, estimate the inter-grain exchange strength. The grain boundaries act as strong pinning sites for the AFM texture. [1] N. Hedrich et al., Nat. Phys. 17, 574 (2021); [2] O. Pylypovskyi et al., Phys. Rev. B 103, 134413 (2021).

Antiferromagnetic insulators are a prospective material science platform for magnonics, spin superfluidity, THz spintronics, and non-volatile data storage. A magnetomechanical coupling in antiferromagnets offers vast advantages in the control and manipulation of the primary order parameter yet remains largely unexplored both fundamentally and technologically. Here, we discover a new member in the family of flexoeffects in thin films of technologically relevant antiferromagnetic Cr2O3. We demonstrate that a gradient of mechanical strain can impact the magnetic phase transition resulting in the distribution of the N ́eel temperature along the thickness of a 50-nm-thick film and induces a sizable flexomagnetic coefficient of about 15 μb/nm2 originating from the inhomogeneous reduction of the antiferromagnetic order parameter. The antiferromagnetic ordering in inhomogeneously strained thin films of Cr2O3 can persist up to 100◦ C, rendering Cr2O3 relevant for industrial electronics applications. The presence of a strain gradient in thin films of Cr2O3 may therefore allow for the realization of reconfigurable antiferromagnetic racetracks, magnonic waveguides and magnon crystals. The presence of a strain gradient in ultrathin films of Cr2O3 enables new fundamental research directions on magnetomechanics and thermodynamics of antiferromagnetic solitons, spin waves and artificial spin ice systems in magnetic materials with continuously graded parameters.

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Thin films of the magnetoelectric insulator α-Cr2O3 are technologically relevant for energy-efficient magnetic memory devices controlled by electric fields. In contrast to single crystals, the quality of thin Cr2O3 films is usually compromised by the presence of point defects and their agglomerations at grain boundaries, putting into question their application potential. Here, we study the impact of the defect nanostructure including sparse small-volume defects and their complexes on the magnetic properties of Cr2O3 thin films. By tuning the deposition temperature, we tailor the type, size, and relative concentration of defects, which we then analyze based on positron annihilation spectroscopy complemented with local electron microscopy studies. The structural characterization is correlated with magnetotransport measurements and nitrogen vacancy microscopy of antiferromagnetic domain patterns. Defects pin antiferromagnetic domain walls and stabilize complex multidomain states with a typical domain size in the sub-micrometer range. Despite their influence on the domain configuration, we demonstrate that neither small open-volume defects nor grain boundaries in Cr2O3 thin films affect the Néel temperature in a broad range of deposition parameters. Our results pave the way towards the realization of spin-orbitronic devices where magnetic domain patterns can be tailored based on defect nanostructures without affecting their operation temperature.

Aims Most people with Type 1 diabetes have low levels of persistent endogenous insulin production. The Diabetes Control and Complications Trial showed that close to diagnosis preserved endogenous insulin was associated with lower HbA1c, hypoglycaemia and complication rates, when intensively treated. We aimed to assess the clinical impact of persistent C‐peptide on rate of hypoglycaemia and HbA1c in those with long duration (> 5 years) Type 1 diabetes. Methods We conducted a cross‐sectional case–control study of 221 people (median age 24 years) with Type 1 diabetes. We confirmed ongoing endogenous insulin secretion by measuring C‐peptide after a mixed‐meal tolerance test. We compared self‐reported hypoglycaemia (n = 160), HbA1c, insulin dose and microvascular complications (n = 140) in those with preserved and low C‐peptide. Results Stimulated median (IQR) C‐peptide was 114 (43, 273) pmol/l and, What's new? Little is known about the clinical impact of persistent C‐peptide in long‐duration Type 1 diabetes.We found that in adults with long‐duration Type 1 diabetes, persistent C‐peptide was associated with reduced self‐reported hypoglycaemia and insulin dose but was not associated with reduced HbA1c.This suggests that individuals with persistent C‐peptide receiving routine care are potentially undertreated.Routinely testing C‐peptide and subsequently setting personalized targets for treatment intensification in adults with persistent C‐peptide may improve glycaemic control and complication rates in this group.

Antiferromagnets (AFMs) have regained strong attention from the magnetism community especially with the advent of antiferromagnetic spintronics [1]. The key operational element of spintronic devices is represented by information carriers, such as domain walls (DWs) and skyrmions. The simplest AFM DW separates two regions with the opposite orientation of the Neel order parameter. Although highly relevant, the experimental studies of AFM DWs (visualization, dynamics, mechanics) are challenging because of strict requirements on measurement techniques to access their properties. Here, we overcome these limitations and conduct detailed, quantitative studies of the mechanics and the nanoscale properties of individual, antiferromagnetic DWs in a single crystal Cr2O3 – a room-temperature, magnetoelectric, insulating AFM [2]. Our results reveal a remarkably pristine DW behaviour, which is governed by DW energy minimization and boundary conditions, but largely unaffected by pinning or disorder – a “textbook example” of antiferromagnetic DW physics. In our experiment, the crystal’s (0001) surface is patterned by a grid of mesas with mean thickness and width t=166 nm and w=2400 nm, respectively. The DW is nucleated by means of magnetoelectric field cooling by inverting the electric bias field over opposite halves of the sample. The DW may also be dragged through the mesa pattern by a focused laser spot. The magnetic texture is imaged using Nitrogen Vacancy (NV) magnetometry [3]. We find that the DW mimics an elastic surface with specific mechanical properties, determined by the interaction with the topographic features of the sample where the DW is (i) deflected from the straight plane crossing the mesa; (ii) bent around mesa corners. To address the DW behaviour theoretically, we perform large-scale spin-lattice simulations with GPU speed-up [4]. The analytical Ansatz is developed based on the numerically-obtained, three-dimensional DW profile. All main features of the DW behaviour can be determined taking into account the nearest-neighbour exchange and uniaxial anisotropy for a general model of a bipartite AFM. Crossing the mesa, the DW experiences an S-shaped distortion observed at the mesa surface, which is the result of exchange-driven boundary conditions at the side faces of the mesa, see Fig. 1. Below the top surface, the DW possesses a twist to match this distortion with the straight plane far below the sample’s surface. We find that the DW surface is deflected from the plane over a characteristic depth of 0.34w. Comparison of the equilibrium DW direction in bulk and at the mesa’s top surface allows us to derive an effective Snell’s law for the DW behaviour at the sample’s surface with the given incidence and refraction angles θ1 and θ2. The effective refraction coefficient is determined by the analytical energy minimization and reads neff = 1 + 3.1t/w + O(θ1). Controlled manipulation via laser not only enables DW dragging through the mesa, but also pinning at mesa corners. The shape of the DW surface is governed by its intrinsic elasticity. In terms of mechanics of an elastic ribbon, the corresponding tension coefficient is determined by the temperature-dependent exchange stiffness and anisotropy coefficient. This allows for curved DW states in which it is pinned at the opposite mesa sides. Using mesas as bistable pinning sites, we propose a potential DW-based AFM memory concept. Here, the memory state “0” or “1” is associated with the direction of the Neel order parameter at the mesa surface. We have realized such pinning sites experimentally and have shown manipulation of the state via laser dragging. In summary, we realize engineered DW potentials and control over DW trajectories by topographic structuring and manipulation of the DW position by means. The physics of AFM DWs in a single crystal with non-trivial surface topography is described theoretically by means of spin-lattice simulations and analytical model. A novel nanoscale AFM memory architecture is suggested. [1] T. Jungwirth, J. Sinova, A. Manchon et al, Nat. Phys. Vol. 14, p. 200 (2018); T. Jungwirth, X. Marti, P. Wadley et al, Nat. Nano. Vol. 11, p. 231 (2016); V. Baltz, A. Manchon, M. Tsoi et al, Rev. Mod. Phys. Vol. 90, p. 015005 (2018); O. V. Pylypovskyi, D. Y. Kononenko, K. V. Yershov et al, Nano Lett. Vol. 20, p. 8157 (2020) [2] N. Hedrich, K. Wagner, O. V. Pylypovskyi et al, arXiv:2009.08086 [3] L. Rondin, J.-P. Tetienne, T. Hingant et al, Rep. Prog. Phys. Vol. 77, p. 056503 (2014); N. Hedrich, D. Rohner, M. Batzer et al, Phys. Rev. Applied, Vol. 14, p. 064007 (2020) [4] SLaSi simulation package, http://slasi.knu.ua; O. V. Pylypovskyi, D. D. Sheka, Book of Abstracts, EUROPT Workshop, p. 11 (2013)

Magneto-electric antiferromagnets hold promise for future spintronic devices, as they offer magnetic field hardness, high switching speeds combined with electric and magnetic control of their order parameters, owing to the magneto-electric coupling [1]. As information and functionality is encoded in the antiferromagnetic order parameter, its manipulation, read-out and nanoscale texture are paramount for device operation, as well as interesting from a fundamental point of view. E.g. spin-textures in such materials are theorized to carry an intrinsic magnetization [2]. Here we study a single crystal ‘textbook’ magneto-electric antiferromagnet, Cr2O3, by nanoscale imaging of its surface magnetization via magnetic stray field imaging by scanning nitrogen vacancy magnetometry [3]. This surface magnetization is directly linked to the bulk Neel vector of Cr2O3 and thereby allows for nanoscale imaging of antiferromagnet spin textures. After confirming magneto-electric poling [4], local electrodes are utilized to nucleate single domain walls, which we then study on the nanometer scale. Manipulation of the domain wall is demonstrated both by local laser heating [5], as well as the creation of an energy landscape for the domain wall via topographic structuring [3]. We analyze the interaction of the domain wall with topographic islands both experimentally and in simulations. This analysis yields information about the domain wall boundary conditions at topographic edges and an estimate of the full 3D-profile of the texture based on minimizing the domain walls surface energy. A Snell like refraction of the domain wall path is found, that can be represented in an analytical approximation as a ‘refractive index’ for a given island dimension as demonstrated for a range of incidence angles. We then observe bistable domain wall paths configurations and switching between them is demonstrated and imaged experimentally. This pinning and control of the domain wall position constitutes the main ingredients for logic devices based on domain walls in magneto-electric antiferromagnets and their fundamental study.

Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers. Tis work was supported by Fondation pour la Recherche Médical (ref DEI20151234405) and Investissements d’Avenir programme ANR-11-IDEX-0005-02, Sorbonne Paris Cite, Laboratoire d’excellence INFLAMEX. Te authors thank the students that participated to the wisdom of the crowd exercise.