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Weight loss interventions on health‐related quality of life in those with moderate to severe obesity: findings from an individual patient data meta‐analysis of randomized trials
No full textThe relationship between BMI and health-related quality of life (HRQoL) critically affects regulatory approval of interventions for weight loss, but evidence of the association is inconsistent. A higher standard of evidence than that available was sought with an IPD meta-analysis of 10,884 people enrolled in five randomized controlled trials of intentional weight loss interventions. Cross-sectional and longitudinal associations of BMI and HRQoL were estimated in mixed effects models specifying a latent variable for HRQoL. Spline regressions captured nonlinear associations across the range of BMI. In cross-sectional spline regressions, BMI was not associated with HRQoL for people with a BMI
Pentaradial eukaryote suggests expansion of suspension feeding in White Sea-aged Ediacaran communities
No full textSuspension feeding is a key ecological strategy in modern oceans that provides a link between pelagic and benthic systems. Establishing when suspension feeding first became widespread is thus a crucial research area in ecology and evolution, with implications for understanding the origins of the modern marine biosphere. Here, we use three-dimensional modelling and computational fluid dynamics to establish the feeding mode of the enigmatic Ediacaran pentaradial eukaryote Arkarua. Through comparisons with two Cambrian echinoderms, Cambraster and Stromatocystites, we show that flow patterns around Arkarua strongly support its interpretation as a passive suspension feeder. Arkarua is added to the growing number of Ediacaran benthic suspension feeders, suggesting that the energy link between pelagic and benthic ecosystems was likely expanding in the White Sea assemblage (~ 558–550 Ma). The advent of widespread suspension feeding could therefore have played an important role in the subsequent waves of ecological innovation and escalation that culminated with the Cambrian explosion
Characterising lithium-ion electrolytes via operando Raman microspectroscopy
No full textKnowledge of electrolyte transport and thermodynamic properties in Li-ion and beyond Li-ion technologies is vital for their continued development and success. Here, we present a method for fully characterising electrolyte systems. By measuring the electrolyte concentration gradient over time via operando Raman microspectroscopy, in tandem with potentiostatic electrochemical impedance spectroscopy, the Fickian “apparent” diffusion coefficient, transference number, thermodynamic factor, ionic conductivity and resistance of charge-transfer were quantified within a single experimental setup. Using lithium bis(fluorosulfonyl)imide (LiFSI) in tetraglyme (G4) as a model system, our study provides a visualisation of the electrolyte concentration gradient; a method for determining key electrolyte properties, and a necessary technique for correlating bulk intermolecular electrolyte structure with the described transport and thermodynamic properties
Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets
No full textTissue-resident memory T (T_RM) cells provide key adaptive immune responses in infection, cancer, and autoimmunity. However, transcriptional heterogeneity of human intestinal T_RM cells remains undefined. Here, we investigate transcriptional and functional heterogeneity of human T_RM cells through study of donor-derived T_RM cells from intestinal transplant recipients. Single-cell transcriptional profiling identifies two transcriptional states of CD8+ T_RM cells, delineated by ITGAE and ITGB2 expression. We define a transcriptional signature discriminating these populations, including differential expression of cytotoxicity- and residency-associated genes. Flow cytometry of recipient-derived cells infiltrating the graft, and lymphocytes from healthy gut, confirm these CD8+ T_RM phenotypes. CD8+ CD69+CD103+ T_RM cells produce interleukin-2 (IL-2) and demonstrate greater polyfunctional cytokine production, whereas β2-integrin+CD69+CD103− T_RM cells have higher granzyme expression. Analysis of intestinal CD4+ T cells identifies several parallels, including a β2-integrin+ population. Together, these results describe the transcriptional, phenotypic, and functional heterogeneity of human intestinal CD4+ and CD8+ T_RM cells
Generating adversarial examples with graph neural networks
No full textRecent years have witnessed the deployment of adversarial attacks to evaluate the robustness of Neural Networks. Past work in this field has relied on traditional optimization algorithms that ignore the inherent structure of the problem and data, or generative methods that rely purely on learning and often fail to generate adversarial examples where they are hard to find. To alleviate these deficiencies, we propose a novel attack based on a graph neural network (GNN) that takes advantage of the strengths of both approaches; we call it AdvGNN. Our GNN architecture closely resembles the network we wish to attack. During inference, we perform forward-backward passes through the GNN layers to guide an iterative procedure towards adversarial examples. During training, its parameters are estimated via a loss function that encourages the efficient computation of adversarial examples over a time horizon. We show that our method beats state-of-the-art adversarial attacks, including PGD-attack, MI-FGSM, and Carlini and Wagner attack, reducing the time required to generate adversarial examples with small perturbation norms by over 65%. Moreover, AdvGNN achieves good generalization performance on unseen networks. Finally, we provide a new challenging dataset specifically designed to allow for a more illustrative comparison of adversarial attacks
The virtue of religion: rethinking America’s approach to international religious freedom
No full textNGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma
No full textPain is a central feature of soft tissue trauma, which under certain contexts, results in aberrant osteochondral differentiation of tissue-specific stem cells. Here, the role of sensory nerve fibers in this abnormal cell fate decision is investigated using a severe extremity injury model in mice. Soft tissue trauma results in NGF (Nerve growth factor) expression, particularly within perivascular cell types. Consequently, NGF-responsive axonal invasion occurs which precedes osteocartilaginous differentiation. Surgical denervation impedes axonal ingrowth, with significant delays in cartilage and bone formation. Likewise, either deletion of Ngf or two complementary methods to inhibit its receptor TrkA (Tropomyosin receptor kinase A) lead to similar delays in axonal invasion and osteochondral differentiation. Mechanistically, single-cell sequencing suggests a shift from TGFβ to FGF signaling activation among pre-chondrogenic cells after denervation. Finally, analysis of human pathologic specimens and databases confirms the relevance of NGF-TrkA signaling in human disease. In sum, NGF-mediated TrkA-expressing axonal ingrowth drives abnormal osteochondral differentiation after soft tissue trauma. NGF-TrkA signaling inhibition may have dual therapeutic use in soft tissue trauma, both as an analgesic and negative regulator of aberrant stem cell differentiation
Existence and uniqueness results on biphasic mixture model for an in-vivo tumor
No full textIn this article, we propose a mathematical model that describes hydrodynamics and deformation mechanics within a solid tumor which is embedded in or adjacent to a healthy (normal) tissue. The tumor and normal tissue regions are assumed to be deformable and the theory of mixtures is adapted to mass and momentum balance equations for fluid flow and tissue deformation mechanics in each region. The momentum balance equations are coupled via forces that interact between the phases (fluid and solid). Continuity of normal velocities, displacements, and normal stresses along with the Beaver–Joseph–Saffman condition are imposed at the interface between the tumor and tissue regions. The physiological transport parameters (such as hydraulic resistivity or permeability) are assumed to be heterogeneous and deformation dependent which makes the model nonlinear. We establish the existence of a weak solution using Galerkin and weak convergence methods. We show further that the solution is unique and depends continuously on the given data
Anatomy of high-uniform unidirectional volatile switching behavior in SiO2/TiO2-based selection device
No full textUnidirectional volatile switching behavior is a typical resistive switching phenomenon in oxides, which has been proposed as attractive candidates for selection devices for high density memory and neuromorphic systems applications with cross-point arrays. However, the microscopic origin of the underlying mechanism is still unclear due to the lack of direct experimental evidence. Here, a high performance selection device with a low forming voltage, low OFF-state current, high nonlinearity, and excellent uniformity is proposed in SiO2/TiO2 stacked structure. The underlying nature of the unidirectional volatile switching behavior in the Pt/Ag/SiO2/TiO2/Ti selection device is revealed by using scanning electron microscope and energy-dispersive X-ray spectroscopy analysis in planar structure devices, which can be attributed to the unstable conductive filament (CF) consisting of Ag nanoparticles formed in the SiO2 layer, and the Schottky contact formed between the Ag CF and TiO2 interface. This work provides clearly experimental evidence to deepen understanding of themechanism for unidirectional volatile switching behavior, which can provide a guide to further improve the device performances for high density memory and neuromorphic systems applications