Notes

Determination to cover a COVID-19 Vaccine.
Pembrolizumab monotherapy is standard first-line therapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) ≥ 50% without actionable driver mutations. It is not known whether adding ipilimumab to pembrolizumab improves efficacy over pembrolizumab alone in this population.

In the randomized, double-blind, phase III KEYNOTE-598 trial (ClinicalTrials.gov identifier NCT03302234), eligible patients with previously untreated metastatic NSCLC with PD-L1 TPS ≥ 50% and no sensitizing
or
aberrations were randomly allocated 11 to ipilimumab 1 mg/kg or placebo every 6 weeks for up to 18 doses; all participants received pembrolizumab 200 mg every 3 weeks for up to 35 doses. Primary end points were overall survival and progression-free survival.

Of the 568 participants, 284 were randomly allocated to each group. Median overall survival was 21.4 months for pembrolizumab-ipilimumab versus 21.9 months for pembrolizumab-placebo (hazard ratio, 1.08; as first-line treatment for metastatic NSCLC with PD-L1 TPS ≥ 50% and no targetable EGFR or ALK aberrations. These data do not support use of pembrolizumab-ipilimumab in place of pembrolizumab monotherapy in this population.In the face of unreplicable results, statistical anomalies, and outright fraud, introspection and changes in the psychological sciences have taken root. Vibrant reform and metascience movements have emerged. These are exciting developments and may point toward practical improvements in the future. Yet there is nothing so practical as good theory. This article outlines aspects of reform and metascience in psychology that are ripe for an injection of theory, including a lot of excellent and overlooked theoretical work from different disciplines. I review established frameworks that model the process of scientific discovery, the types of scientific networks that we ought to aspire to, and the processes by which problematic norms and institutions might evolve, focusing especially on modeling from the philosophy of science and cultural evolution. We have unwittingly evolved a toxic scientific ecosystem; existing interdisciplinary theory may help us intelligently design a better one.Classroom settings bring to light many differences between children-differences that children notice and attempt to explain. learn more Here, we advance theory on the psychological processes underlying how children explain the differences they observe in the classroom. Integrating evidence from cognitive, social, cultural, developmental, and educational psychology, we propose that young children tend to explain differences among their peers by appealing to the inherent characteristics of those individuals and, conversely, tend to overlook extrinsic reasons for such differences-that is, reasons having to do with external circumstances and structural factors. We then outline how this inherence bias in children's explanations affects their motivation and performance in school, exacerbating inequalities in achievement and making these inequalities seem legitimate. We conclude by suggesting several means of counteracting the inherence bias in children's explanations and its effects on their educational outcomes. Throughout, we highlight new directions for research on the relation between children's explanations, their motivation and achievement, and the inequalities observed in elementary school and beyond.Pleural organization may occur after empyema or complicated parapneumonic effusion and can result in restrictive lung disease with pleural fibrosis (PF). Pleural mesothelial cells (PMCs) may contribute to PF through acquisition of a profibrotic phenotype, mesothelial-mesenchymal transition (MesoMT), which is characterized by increased expression of α-SMA (α-smooth muscle actin) and other myofibroblast markers. Although MesoMT has been implicated in the pathogenesis of PF, the role of the reactive oxygen species and the NOX (nicotinamide adenine dinucleotide phosphate oxidase) family in pleural remodeling remains unclear. Here, we show that NOX1 expression is enhanced in nonspecific human pleuritis and is induced in PMCs by THB (thrombin). 4-Hydroxy-2-nonenal, an indicator of reactive oxygen species damage, was likewise increased in our mouse model of pleural injury. NOX1 downregulation blocked THB- and Xa (factor Xa)-mediated MesoMT, as did pharmacologic inhibition of NOX1 with ML-171. NOX1 inhibition also reduced phosphorylation of Akt, p65, and tyrosine 216-GSK-3β, signaling molecules previously shown to be implicated in MesoMT. Conversely, ML-171 did not reverse established MesoMT. NOX4 downregulation attenuated TGF-β- and THB-mediated MesoMT. However, NOX1 downregulation did not affect NOX4 expression. NOX1- and NOX4-deficient mice were also protected in our mouse model of Streptococcus pneumoniae-mediated PF. These data show that NOX1 and NOX4 are critical determinants of MesoMT.Multidimensional motivational theories postulate that the type of motivation is as important as the quantity of motivation, with implications for human functioning and well-being. An extensive amount of research has explored how constructs contained within these theories relate to the activation of the endocrine system. However, research is fragmented across several theories, and determining the current state of the science is complicated. In line with contemporary trends for theoretical integration, this systematic review aims to evaluate the association between multidimensional motivational constructs and endocrine-related responses to determine which theories are commonly used and what inferences can be made. Forty-one studies were identified incorporating five distinct motivation theories and multiple endocrine-related responses. There was evidence across several theories that high-quality motivation attenuated the cortisol response in evaluative environments. There was also evidence that motivational needs for power and affiliation were associated with lower and higher levels of salivary immunoglobulin A, respectively. The need for power may play a role in increasing testosterone when winning a contest; however, this evidence was not conclusive. Overall, this review can shape the future integration of motivational theories by characterizing the nature of physiological responses to motivational processes and examining the implications for well-being.
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