PURPOSE Effective treatments are needed for melanoma that progresses on inhibitors of programmed cell death protein-1 (PD-1) or its ligand (PD-L1). We conducted the phase II LEAP-004 study to evaluate the combination of the multikinase inhibitor lenvatinib and the PD-1 inhibitor pembrolizumab in this population (ClinicalTrials.gov identifier: NCT03776136).METHODSEligible patients with unresectable

Research Question/Issue: Motivated by the agency theory and the findings of linguistic studies, we analyze the association between the internationalization of a firm's audit committee and its corporate governance. Research Findings/Insights: Based on data from 2159 publicly traded European firms from 15 countries for the period 2000–2018, we find that firms with foreign directors on their audit co

Microbes inhabiting deep soil layers are known to be different from their counterpart in topsoil yet remain under investigation in terms of their structure, function, and how their diversity is shaped. The microbiome of deep soils (>1 m) is expected to be relatively stable and highly independent from climatic conditions. Much less is known, however, on how these microbial communities vary along cl

Introduction: The ancient city of Tel Megiddo in the Jezreel Valley (Israel), which lasted from the Neolithic to the Iron Age, has been continuously excavated since 1903 and is now recognized as a World Heritage Site. The site features multiple ruins in various areas, including temples and stables, alongside modern constructions, and public access is allowed in designated areas. The site has been

Melanin pigments play a critical role in physiological processes and shaping animal behaviour. Fossil melanin is a unique resource for understanding the functional evolution of melanin but the impact of fossilisation on molecular signatures for eumelanin and, especially, phaeomelanin is not fully understood. Here we present a model for the chemical taphonomy of fossil eumelanin and phaeomelanin ba

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the success rate of the lateral decubitus, sitting and prone positions for lumbar puncture in newborn infants.

Background: Optimal fluid status is an important issue in hemodialysis. Clinical evaluation of volume status and different diagnostic tools are used to determine hydration status in these patients. However, there is still no accurate method for this assessment. Purpose: To propose and evaluate relative lean water signal (LWSrel) as a water–fat MRI-based tissue hydration measurement. Study Type: Pr

Tbx4 protein, expressed in mesenchyme of the developing lung, contributes to airway branching and distal lung growth. An association between pediatric onset of pulmonary arterial hypertension (PAH) and genetic variations coding for the T-box transcription factor 4 gene (TBX4) has been increasingly recognized. Tbx4-related PAH onset has a bimodal age distribution, including severe to lethal PAH in

We carried out deep mapping observations of the atomic hydrogen (H i) 21 cm line emission in a field centered on the famous galaxy group Stephan's Quintet (SQ), using the Five-hundred-meter Aperture Spherical Telescope (FAST) equipped with a 19-beam receiver. The final data cube reaches an H i column density sensitivity of 5σ = 2.1 × 1017 cm-2 per 20 km s-1 channel with an angular resolution of 4.

Background: There are two primary phenotypic models of comorbidity between post-traumatic stress disorder (PTSD) and drug use disorder (DUD), i.e. self-medication (PTSD precedes and causes DUD) and susceptibility (DUD precedes and causes PTSD). We sought to clarify the longitudinal relationship between PTSD and DUD, while examining sex differences. Method: We used approximately 23 years of longitu

This article sheds light upon the cultural politics of fear in post-war Nepal by narrowing in on the Nepal banda–a recurring political spectacle in which the organizers seek to shut down Nepalese society through violent means–tracing both how it shapes and is appropriated in (offline and online) everyday life. In doing so I demonstrate how the online tactics that people employ to navigate the Nepa

In recent years, detailed studies of three-pion systems have become possible in lattice QCD. This has in turn led to interest in 3-to-3 scattering of pions in the chiral perturbation theory framework. In addition to being an interesting study of multi-meson dynamics in its own right, it provides a valuable handle on finite-volume effects and the pion mass dependence, thus complementing the lattice

We report confocal microscopy experiments of electric-field-driven crystal-crystal transformations in microgel colloids with varying particle softness. The transformation kinetics are well described by phenomenological nucleation and growth theory. Using a spatial projection formalism, we determine local susceptibilities to affine shear deformation and nonaffine defect formation in the parent crys

Starting from the recently proposed dynamical exchange-correlation field framework, the equation of motion of the diagonal part of the many-electron Green function is derived, from which the spectral function can be obtained. The resulting equation of motion takes the form of the continuity equation of charge and current densities in electrodynamics with a source. An unknown quantity in this equat

Background: There is limited information on the distribution of retroperitoneal lymph node metastases (LNMs) in upper tract urothelial carcinoma (UTUC). Objective: To investigate the location of LNMs in UTUC of the renal pelvis or proximal ureter and short-term complications after radical nephroureterectomy (RNU) with lymph node dissection (LND). Design, setting, and participants: This was a prosp

We argue that people may resist temptations not only with the aim of acquiring more self-control, but also because they want to convince others that they are patient and already possess self-control.

Objective: The aim of this study was to evaluate the associations among the intake of total polyphenols, polyphenol classes, and polyphenol subclasses and body weight change over 5 years. Methods: A total of 349,165 men and women aged 25 to 70 years were recruited in the Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home and Obesity (PANACEA) project of the European Pr

Advancing ultrafast high-repetition-rate lasers to shortest pulse durations comprising only a few optical cycles while pushing their energy into the multi-millijoule regime opens a route toward terawatt-class peak powers at unprecedented average power. We explore this route via efficient post-compression of high-energy 1.2 ps pulses from an ytterbium InnoSlab laser to 9.6 fs duration using gas-fil

In this study, a three-dimensional computational fluid dynamics (CFD) model is employed to investigate the hydrodynamic and combustion characteristics of biomass particles in an industrial-scale circulating fluidized bed (CFB) furnace. The CFD model considered here is based on the Eulerian-Lagrangian framework, the multi-phase particle-in-cell (MP-PIC) collision model, the coarse grain method (CGM

Characteristic modes of arbitrary 2-D periodic systems are analyzed using scattering parameter data. This approach bypasses the need for periodic integral equations and allows for characteristic modes to be computed from generic simulation or measurement data. Example calculations demonstrate the efficacy of the method through comparison against a periodic method of moments (MoM) formulation for a