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Confrontation at Lepanto : Christendom vs. Islam
In 1571, the Pope formed a Holy League to oppose the growing Turkish domination of the Eastern Mediterranean. A year later a vast fleet of Christian ships confronted the Turkish fleet at Lepanto and in the course of a single day they turned the tide of history.
Book
A Non–D2-Receptor-Binding Drug for the Treatment of Schizophrenia
In a randomized trial involving schizophrenic patients with acute psychosis, a new oral drug that does not have a dopamine D2-receptor–binding mechanism of action led to a greater reduction in the severity of overall symptoms than placebo over 4 weeks. The incidence of extrapyramidal symptoms was 3% with the new drug, a finding similar to that with placebo.
Journal Article
Stagnation points control chaotic fluctuations in viscoelastic porous media flow
Viscoelastic flows through porous media become unstable and chaotic beyond critical flow conditions, impacting widespread industrial and biological processes such as enhanced oil recovery and drug delivery. Understanding the influence of the pore structure or geometry on the onset of flow instability can lead to fundamental insights into these processes and, potentially, to their optimization. Recently, for viscoelastic flows through porous media modeled by arrays of microscopic posts, Walkama et al. [D. M. Walkama, N. Waisbord, J. S. Guasto, Phys. Rev. Lett. 124, 164501 (2020)] demonstrated that geometric disorder greatly suppressed the strength of the chaotic fluctuations that arose as the flow rate was increased. However, in that work, disorder was only applied to one originally ordered configuration of posts. Here, we demonstrate experimentally that, given a slightly modified ordered array of posts, introducing disorder can also promote chaotic fluctuations. We provide a unifying explanation for these contrasting results by considering the effect of disorder on the occurrence of stagnation points exposed to the flow field, which depends on the nature of the originally ordered post array. This work provides a general understanding of how pore geometry affects the stability of viscoelastic porous media flows.
Journal Article
Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia
Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 clinical development for the treatment of schizophrenia. Ulotaront was discovered through a unique, target-agnostic approach optimized to identify drug candidates lacking D2 and 5-HT2A receptor antagonism, while demonstrating an antipsychotic-like phenotypic profile in vivo. The mechanism of action (MOA) of ulotaront is thought to be mediated by agonism at TAAR1 and serotonin 5-HT1A receptors. Ulotaront has completed two Phase 2 trials (4-week acute study and 26-week open-label extension) which led to Breakthrough Therapy Designation from the US Food and Drug Administration for the treatment of schizophrenia. In the double-blind, placebo-controlled, acute study, ulotaront was associated with significant (p < 0.001) improvement in Positive and Negative Syndrome Scale (PANSS) total score (effect size [ES]: 0.45), with improvements vs. placebo also observed across secondary endpoints. Post-hoc analyses of the acute trial revealed additional evidence to support the effect of ulotaront on negative symptoms. In the 4-week study, ulotaront was well-tolerated, with an incidence of adverse events (AEs) numerically lower compared to placebo (45.8% vs. 50.4%; with a number needed to harm [NNH] for individual ulotaront AEs all > 40). The open-label extension demonstrated further improvement across schizophrenia symptoms and confirmed the tolerability of ulotaront, with a 6-month completion rate of 67%. Based on current data, ulotaront shows potential to be a first-in-class TAAR1 agonist for the treatment of schizophrenia with a safety and efficacy profile distinct from current antipsychotics.
Journal Article
The Curie Society : Eris eternal
\"Our heroic teen science prodigies are back for a new mission with the Curie Society, an elite secret organization where brilliant women can pursue the furthest reaches of their intellect, and this time they face a threat more serious and more sinister than anything they've encountered before! Maya, Taj, and Simone are supposed to be spending their summer broadening their horizons, but their plans take a strange and puzzling turn when the Curie Society's original chapter, at the Sorbonne in Paris, calls on them for help. Daksha, a Society alumna, is promoting cutting-edge science and technology startups at a showcase event, but someone has threatened to stop her and the proceedings. When Daksha is poisoned, the team swings into action to investigate. Along with new friends from the Paris chapter of the Curie Society, the team is thrown into a globe-spanning quest and a dangerous game of cat and mouse with a shadowy villain intent on controlling the world's wealth through advanced biotech. The Curie Society will need all their specialized science skills to stop this scheme before it's too late!\"-- Provided by publisher.
Book
Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study
The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined.
A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days.
Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204-733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278-1043.5, p = 0.005).
Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.
Journal Article
Transition between solid and liquid state of yield-stress fluids under purely extensional deformations
We report experimental microfluidic measurements and theoretical modeling of elastoviscoplastic materials under steady, planar elongation. Employing a theory that allows the solid state to deform, we predict the yielding and flow dynamics of such complex materials in pure extensional flows. We find a significant deviation of the ratio of the elongational to the shear yield stress from the standard value predicted by ideal viscoplastic theory, which is attributed to the normal stresses that develop in the solid state prior to yielding. Our results show that the yield strain of the material governs the transition dynamics from the solid state to the liquid state. Finally, given the difficulties of quantifying the stress field in such materials under elongational flow conditions, we identify a simple scaling law that enables the determination of the elongational yield stress from experimentally measured velocity fields.
Journal Article
Inhibition of BMP signaling suppresses metastasis in mammary cancer
Bone morphogenetic proteins (BMPs) are secreted cytokines/growth factors that have differing roles in cancer. BMPs are overexpressed in human breast cancers, but loss of BMP signaling in mammary carcinomas can accelerate metastasis. We show that human breast cancers display active BMP signaling, which is rarely downregulated or homozygously deleted. We hypothesized that systemic inhibition of BMP signaling in both the tumor and the surrounding microenvironment could prevent tumor progression and metastasis. To test this hypothesis, we used DMH1, a BMP antagonist, in MMTV.PyVmT expressing mice. Treatment with DMH1 reduced lung metastasis and the tumors were less proliferative and more apoptotic. In the surrounding tumor microenvironment, treatment with DMH1 altered fibroblasts, lymphatic vessels and macrophages to be less tumor promoting. These results indicate that inhibition of BMP signaling may successfully target both the tumor and the surrounding microenvironment to reduce tumor burden and metastasis.
Journal Article