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In other words, crucial questions remain unanswered—such as: are patients who benefit from the treatment more, or less, likely to experience harmful events? [...]many clinical trials are underpowered to detect meaningful differences in infrequent efficacy or safety outcomes,5 further complicating the decision-making process.4 Quantitative BRAs (qBRAs), in contrast, offer a structured framework to formally balance benefits and risks within a single metric. The preferred summary measure is the net treatment benefit (termed win difference in their paper), an absolute effect measure representing the difference in the proportion of favourable outcomes between treatment arms.3 11 Its interpretation is straightforward and intuitive: zero indicates no difference, positive values reflect a benefit and negative values reflect harm.3 11 Because it is expressed on an absolute scale, the inverse of the net treatment benefit can be interpreted as the number needed to treat (or harm).3 11 The win ratio, by contrast, is less suitable, as it cannot be decomposed by endpoint component and tends to overestimate treatment effects when many ties occur,3 11 as seen in d’Entremont et al.7 If a relative measure is desired, the win odds are preferable.3 11 Decomposition of GPC results increases transparency by clarifying how individual outcomes contribute to the overall treatment effect. Another strength of GPC is the ability to perform sensitivity analyses. Since outcome priorities, relative weights and thresholds may differ among patients, clinicians and regulators, exploring multiple scenarios can clarify the robustness of conclusions.3 9 10 Patient heterogeneity must also be addressed. A systematic assessment of the characteristics of randomized controlled trials cited by acute coronary syndrome clinical practice guidelines.

Electron energy loss spectroscopy (EELS) is a well established technique in electron microscopy that yields information on the elemental content of a sample in a very direct manner. One of the persisting limitations of EELS is the requirement for manual identification of core-loss edges and their corresponding elements. This can be especially bothersome in spectrum imaging, where a large amount of spectra are recorded when spatially scanning over a sample area. This paper introduces a synthetic dataset with 736,000 labeled EELS spectra, computed from available generalized oscillator strength tables, that represents 107 K, L, M or N core-loss edges and 80 chemical elements. Generic lifetime broadened peaks are used to mimic the fine structure due to band structure effects present in experimental core-loss edges. The proposed dataset is used to train and evaluate a series of neural network architectures, being a multilayer perceptron, a convolutional neural network, a U-Net, a residual neural network, a vision transformer and a compact convolutional transformer. An ensemble of neural networks is used to further increase performance. The ensemble network is used to demonstrate fully automated elemental mapping in a spectrum image, both by directly mapping the predicted elemental content and by using the predicted content as input for a physical model-based mapping.

By focusing electrons on probes with a diameter of 50 pm, aberration-corrected scanning transmission electron microscopy (STEM) is currently crossing the border to probing subatomic details. A major challenge is the measurement of atomic electric fields using differential phase contrast (DPC) microscopy, traditionally exploiting the concept of a field-induced shift of diffraction patterns. Here we present a simplified quantum theoretical interpretation of DPC. This enables us to calculate the momentum transferred to the STEM probe from diffracted intensities recorded on a pixel array instead of conventional segmented bright-field detectors. The methodical development yielding atomic electric field, charge and electron density is performed using simulations for binary GaN as an ideal model system. We then present a detailed experimental study of SrTiO 3 yielding atomic electric fields, validated by comprehensive simulations. With this interpretation and upgraded instrumentation, STEM is capable of quantifying atomic electric fields and high-contrast imaging of light atoms. Advances in electron microscopy are enabling ever smaller features to be probed, with the measurement of atomic electric fields standing as a major challenge. Towards that aim, Müller et al. present a simplified theoretical approach for enhancing the resolution in differential phase contrast microscopy.

In order to bring the diverse functionalities of transition metal oxides into modern electronics, it is imperative to integrate oxide films with controllable properties onto the silicon platform. Here, we present asymmetric LaMnO 3 /BaTiO 3 /SrTiO 3 superlattices fabricated on silicon with layer thickness control at the unit-cell level. By harnessing the coherent strain between the constituent layers, we overcome the biaxial thermal tension from silicon and stabilize c -axis oriented BaTiO 3 layers with substantially enhanced tetragonality, as revealed by atomically resolved scanning transmission electron microscopy. Optical second harmonic generation measurements signify a predominant out-of-plane polarized state with strongly enhanced net polarization in the tricolor superlattices, as compared to the BaTiO 3 single film and conventional BaTiO 3 /SrTiO 3 superlattice grown on silicon. Meanwhile, this coherent strain in turn suppresses the magnetism of LaMnO 3 as the thickness of BaTiO 3 increases. Our study raises the prospect of designing artificial oxide superlattices on silicon with tailored functionalities. Integrating multifunctional oxides on silicon is highly desirable. Here, the authors present asymmetric BaTiO3 superlattices on silicon exhibiting enhanced out-of-plane polarization by harnessing the interfacial strain and broken inversion symmetry.

Decades ago, Aharonov and Bohm showed that electrons are affected by electromagnetic potentials in the absence of forces due to fields. Zeilinger’s theorem describes this absence of classical force in quantum terms as the “dispersionless” nature of the Aharonov-Bohm effect. Shelankov predicted the presence of a quantum “force” for the same Aharonov-Bohm physical system as elucidated by Berry. Here, we report an experiment designed to test Shelankov’s prediction and we provide a theoretical analysis that is intended to elucidate the relation between Shelankov’s prediction and Zeilinger’s theorem. The experiment consists of the Aharonov-Bohm physical system; free electrons pass a magnetized nanorod and far-field electron diffraction is observed. The diffraction pattern is asymmetric confirming one of Shelankov’s predictions and giving indirect experimental evidence for the presence of a quantum “force”. Our theoretical analysis shows that Zeilinger’s theorem and Shelankov’s result are both special cases of one theorem. The dispersionless nature of Aharonov-Bohm effect is still debated. Here, the authors show an asymmetry in the diffraction pattern of an electron beam induced and controlled by an inaccessible magnetic flux, which means electrons behave “as if” an Aharonov-Bohm “force” was present.

Background Over the past four years, the COVID-19 pandemic has exerted a profound impact on public health, including on mortality trends. This study investigates mortality patterns in Belgium by examining all-cause mortality, excess mortality, and cause-specific mortality. Methods We retrieved all-cause mortality data from January 1, 2009, to December 31, 2022, stratified by age group and sex. A linear mixed model, informed by all-cause mortality from 2009 to 2019, was used to predict non-pandemic all-cause mortality rates in 2020–2022 and estimate excess mortality. Further, we also analyzed trends in cause-specific and premature mortality. Results Different all-cause mortality patterns could be observed between the younger (<45 years) and older age groups. The impact of the COVID-19 pandemic was particularly evident among older age groups. The highest excess mortality occurred in 2020, while a reversal in this trend was evident in 2022. We observed a notable effect of COVID-19 on cause-specific and premature mortality patterns over the three-year period. Conclusions Despite a consistent decline in COVID-19 reported mortality over this three-year period, it remains imperative to meticulously monitor mortality trends in the years ahead.

Electrostriction is a property of dielectric materials whereby an applied electric field induces a mechanical deformation proportional to the square of that field. The magnitude of the effect is usually minuscule (<10 –19  m 2  V –2 for simple oxides). However, symmetry-breaking phenomena at the interfaces can offer an efficient strategy for the design of new properties 1 , 2 . Here we report an engineered electrostrictive effect via the epitaxial deposition of alternating layers of Gd 2 O 3 -doped CeO 2 and Er 2 O 3 -stabilized δ-Bi 2 O 3 with atomically controlled interfaces on NdGaO 3 substrates. The value of the electrostriction coefficient achieved is 2.38 × 10 –14  m 2  V –2 , exceeding the best known relaxor ferroelectrics by three orders of magnitude. Our theoretical calculations indicate that this greatly enhanced electrostriction arises from coherent strain imparted by interfacial lattice discontinuity. These artificial heterostructures open a new avenue for the design and manipulation of electrostrictive materials and devices for nano/micro actuation and cutting-edge sensors. A system consisting of alternating thin films of two dielectrics is used to produce greatly enhanced electrostriction derived from coherent strain imparted by interfacial lattice discontinuity.

In transition metal perovskites ABO₃, the physical properties are largely driven by the rotations of the BO₆ octahedra, which can be tuned in thin films through strain and dimensionality control. However, both approaches have fundamental and practical limitations due to discrete and indirect variations in bond angles, bond lengths, and film symmetry by using commercially available substrates. Here, we introduce modulation tilt control as an approach to tune the ground state of perovskite oxide thin films by acting explicitly on the oxygen octahedra rotation modes—that is, directly on the bond angles. By intercalating the prototype SmNiO₃ target material with a tilt-control layer, we cause the system to change the natural amplitude of a given rotation mode without affecting the interactions. In contrast to strain and dimensionality engineering, our method enables a continuous fine-tuning of the materials’ properties. This is achieved through two independent adjustable parameters: the nature of the tilt-control material (through its symmetry, elastic constants, and oxygen rotation angles), and the relative thicknesses of the target and tilt-control materials. As a result, a magnetic and electronic phase diagram can be obtained, normally only accessible by A-site element substitution, within the single SmNiO₃ compound. With this unique approach, we successfully adjusted the metal–insulator transition (MIT) to room temperature to fulfill the desired conditions for optical switching applications.

Background Considering multiple endpoints in clinical trials provide a more comprehensive understanding of treatment effects and may lead to increased power or reduced sample size, which may be beneficial in rare diseases. Besides the small sample sizes, allocation bias is an issue that affects the validity of these trials. We investigate the impact of allocation bias on testing decisions in clinical trials with multiple endpoints and offer a tool for selecting an appropriate randomization procedure (RP). Methods We derive a model for quantifying the effect of allocation bias depending on the RP in the case of two-arm parallel group trials with continuous multiple endpoints. We focus on two approaches to analyze multiple endpoints, either the Šidák procedure to show efficacy in at least one endpoint and the all-or-none procedure to show efficacy in all endpoints. Results To evaluate the impact of allocation bias on the test decision we propose a biasing policy for multiple endpoints. The impact of allocation on the test decision is measured by the family-wise error rate of the Šidák procedure and the type I error rate of the all-or-none procedure. Using the biasing policy we derive formulas to calculate these error rates. In simulations we show that, for the Šidák procedure as well as for the all-or-none procedure, allocation bias leads to inflation of the mean family-wise error and mean type I error, respectively. The strength of this inflation is affected by the choice of the RP. Conclusion Allocation bias should be considered during the design phase of a trial to increase validity. The developed methodology is useful for selecting an appropriate RP for a clinical trial with multiple endpoints to minimize allocation bias effects.

Amorphous alumina is hard but brittle like all ceramic type materials which affects durability under impact or scratch. Here we show that alumina layers below 100 nm thickness when stacked with aluminum interlayers exhibit exceptional performances including toughness equal to 300 J.m −2 determined by on chip nanomechanics. This is almost two orders of magnitude higher than bulk alumina and higher than any other thin hard coatings. In addition, a hardness above 8 GPa combines with a fracture strain above 5%. The origin of this superior set of properties is unravelled via in-situ TEM and mechanical models. The combination of constrained alumina layers with ductile behavior, strong “accommodating” interfaces, giant shear deformability of Al layers, and plasticity-controlled crack shielding cooperate to stabilize deformation, dissipate energy and arrest cracks. These performances unlock several options of applications of Al 2 O 3 in which brittleness under contacts prevents benefiting from remarkable functional properties and chemical stability. Alumina layers below 100 nm thickness stacked with aluminum interlayers combine exceptional properties including high toughness, strength and ductility. The origin of this optimal tryptic is unraveled by advanced nanomechanics and in-situ TEM.