Impact of KRAS mutation status on the efficacy of immunotherapy in lung cancer brain metastases

Immune checkpoint inhibitors (ICIs) have resulted in improved outcomes in non-small cell lung cancer (NSCLC) patients. However, data demonstrating the efficacy of ICIs in NSCLC brain metastases (NSCLCBM) is limited. We analyzed overall survival (OS) in patients with NSCLCBM treated with ICIs within 90 days of NSCLCBM diagnosis (ICI-90) and compared them to patients who never received ICIs (no-ICI). We reviewed 800 patients with LCBM who were diagnosed between 2010 and 2019 at a major tertiary care institution, 97% of whom received stereotactic radiosurgery (SRS) for local treatment of BM. OS from BM was compared between the ICI-90 and no-ICI groups using the Log-Rank test and Cox proportional-hazards model. Additionally, the impact of KRAS mutational status on the efficacy of ICI was investigated. After accounting for known prognostic factors, ICI-90 in addition to SRS led to significantly improved OS compared to no-ICI (12.5 months vs 9.1, p \u3c 0.001). In the 109 patients who had both a known PD-L1 expression and KRAS status, 80.4% of patients with KRAS mutation had PD-L1 expression vs 61.9% in wild-type KRAS patients (p = 0.04). In patients without a KRAS mutation, there was no difference in OS between the ICI-90 vs no-ICI cohort with a one-year survival of 60.2% vs 54.8% (p = 0.84). However, in patients with a KRAS mutation, ICI-90 led to a one-year survival of 60.4% vs 34.1% (p = 0.004). Patients with NSCLCBM who received ICI-90 had improved OS compared to no-ICI patients. Additionally, this benefit appears to be observed primarily in patients with KRAS mutations that may drive the overall benefit, which should be taken into account in the development of future trials

A Survey of Geometric Analysis in Cultural Heritage

We present a review of recent techniques for performing geometric analysis in cultural heritage (CH) applications. The survey is aimed at researchers in the areas of computer graphics, computer vision and CH computing, as well as to scholars and practitioners in the CH field. The problems considered include shape perception enhancement, restoration and preservation support, monitoring over time, object interpretation and collection analysis. All of these problems typically rely on an understanding of the structure of the shapes in question at both a local and global level. In this survey, we discuss the different problem forms and review the main solution methods, aided by classification criteria based on the geometric scale at which the analysis is performed and the cardinality of the relationships among object parts exploited during the analysis. We finalize the report by discussing open problems and future perspectives

A review of literature on the use of clickers in the business and management discipline

YesClassroom response systems (clickers), in their various forms, are widely used across disciplines, demonstrating effectiveness across a range of different educational settings. However, only a few literature reviews on this technology have been undertaken in general, and no review has yet been performed on this topic in the business and management context. Realising the existing research gap, this article reviews 33 clicker-related studies from the business and management discipline that are largely focused on student perceptions and outcomes. The purpose of this paper is to provide a critical and balanced review of articles from the business and management discipline on various themes such as learner's engagement, performance, learning, participation, satisfaction, feedback, attendance, enjoyability, motivation, and interactivity, to name a few. The review also provides a brief account of lessons learned from the literature published in other disciplines and recommendations provided by studies from the business and management discipline

THE LIFE AND WORKS OF PEDRO ANTONIO DE ALARCON

Pedro Antonio de Alarcón was born in Guadix in Andalucia, March 10, 1833. Since his early childhood was so precocious that he began to attend school at the age of three and a half, began the study of Latin grammar at the age of nine, studied philosophy at the age of eleven and received the title of bachiller in 1847 at the age of fourteen, we might well expect great things from Pedro Antonio de Alarcón. This is especially true when we realize that a serious illness had left him blind for a time at the age of two. This information concerning the very early years of Alarcón comes from a notebook with autobiographical notes which members of his descendants made available to Martinez Kleiser

Outcomes of Sphincter Pharyngoplasty in the Cleft Population.

INTRODUCTION: Sphincter pharyngoplasty (SP) is becoming increasingly popular for correction of velopharyngeal insufficiency (VPI) after cleft palate repair because of high success rate, low incidence of postoperative obstructive sleep apnea (OSA), and ease of revision in case of failure. This study is a meta-analysis of SP outcomes, reasons for failure, and revision strategies. METHODS: A comprehensive review of the literature on SP outcomes was conducted. Sphincter pharyngoplasty failure was defined as persistent hypernasality, incomplete velopharyngeal port (VP) closure on instrumental evaluation with concomitant VPI, or nonresolving hyponasality and/or OSA persisting \u3e3 months after surgery. Two-tailed paired Student t test was used to compare outcomes between syndromic versus nonsyndromic patients and preoperative versus postoperative OSA rates. RESULTS: Forty-four publications evaluating 2402 patients were included. Overall SP success rate was 78.4% (77.3% in nonsyndromic vs 84.8% in syndromic patients, P = 0.11). Overall primary revision rate was 17.8% (20% in nonsyndromic vs 15.4% in syndromic patients P = 0.97). Most failures (89.5%) manifested as persistent VPI with continued hypernasality requiring revision, whereas 10.5% of failures manifested as obstructive symptoms and/or severe hyponasality requiring revision. Causal factors of SP failure were the following: large central port (62.8%), dehiscence (15.5%), tight port (12.1%), and low-inset (9.7%). Primary revision success rate was 75.6%. Obstructive sleep apnea rates increased from 5.1% to 18.4% (P = 0.02). CONCLUSIONS: This study suggests that SP can resolve VPI in 78.4% of patients, which can be increased to 94.7% after one revision. Most failures are technique-dependent; therefore, there could be significant ground for improvement of outcomes

Cold War Nostalgia in The Game

This article explores how nostalgia for both the Cold War and the 1970s became a key feature of the BBC drama The Game (2014). It argues that the serial situated the Cold War as a more stable era in international relations in which the enemy played by a specific set of rules, thus leading to a manageable and predictable danger compared to the terror threat of the twentyfirst century. Furthermore, the article argues that the serial presents the 1970s as a golden age which was defined by the continuity of consensus politics and communities of class and family. Finally, the article examines how this nostalgia is reinforced by narrative devices which engage with generic features such as the storyline playing out like a game. However, in the re-imagined Cold War of the twenty-first century, the traditional chess trope has been replaced by the more complex game of Alice Chess