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With an introduction by John Lasseter-- and very little else in the way of words-- this second book in The Artist Series lavishly showcases the most brilliant animation created by such luminaries as Ub Iwerks, Norm Ferguson, Ben Sharpsteen, Hamilton Luske, Dick Huemer, Grim Natwick, Art Babbitt, Fred Moore, Bill Tytla, Frank Thomas, Ollie Johnston, Milt Kahl, Marc Davis, John Lounsbery, Ward Kimball, Eric Larson, Les Clark, Wolfgang Reitherman, John Sibley, Bill Justice, Clyde Geronimi, Ted Berman, Glen Keane, Andreas Deja, Eric Goldberg, Mark Henn and Tony Bancroft. The artwork-- much of which has never before been published-- offers the opportunity to marvel at the those magical lines of pencil that brought life to so many unforgettable Disney characters. Animation represents a rare opportunity to enjoy a glimpse into the truly spectacular trove of treasures from the Walt Disney Animation Research Library.

In a double-blind, randomized trial involving nearly 1000 patients followed for a median of 2 years, pembrolizumab injections for 1 year after surgery led to improved disease-free survival at 24 months as compared with placebo (77% vs. 68%). Almost one third of patients in the pembrolizumab group had a grade 3 adverse event, but no deaths were due to pembrolizumab.

Readmission following hospital discharge is common and is a major financial burden on healthcare systems. Our objectives were to 1) identify studies describing post-discharge interventions and their efficacy with respect to reducing risk of mortality and rate of hospital readmission; and 2) identify intervention characteristics associated with efficacy. A systematic review of the literature was performed. We searched MEDLINE, PubMed, Cochrane, EMBASE and CINAHL. Our selection criteria included randomized controlled trials comparing post-discharge interventions with usual care on rates of hospital readmission and mortality in high-risk chronic disease patient populations. We used random effects meta-analyses to estimate pooled risk ratios for all-cause and cause-specific mortality as well as all-cause and cause-specific hospitalization. We included 31 randomized controlled trials encompassing 9654 patients (24 studies in CHF, 4 in COPD, 1 in both CHF and COPD, 1 in CKD and 1 in an undifferentiated population). Meta-analysis showed post-discharge interventions reduced cause-specific (RR = 0.71, 95% CI = 0.63-0.80) and all cause (RR = 0.90, 95% CI = 0.81-0.99) hospitalization, all-cause (RR = 0.73, 95% CI = 0.65-0.83) and cause-specific mortality (RR = 0.68, 95% CI = 0.54-0.84) in CHF studies, and all-cause hospitalization (RR = 0.52, 95% CI = 0.32-0.83) in COPD studies. The inclusion of a cardiac nurse in the multidisciplinary team was associated with greater efficacy in reducing all-cause mortality among patients discharged after heart failure admission (HR = 0.64, 95% CI = 0.54-0.75 vs. HR = 0.87, 95% CI = 0.73-1.03). Post-discharge interventions reduced all-cause mortality, cause-specific mortality, and cause-specific hospitalization in CHF patients and all-cause hospitalization in COPD patients. The presence of a cardiac nurse was associated with greater efficacy in included studies. Additional research is needed on the impact of post-discharge intervention strategies in COPD and CKD patients.

This paper examines the value of connections between German industry and the Nazi movement in early 1933. Drawing on previously unused contemporary sources about management and supervisory board composition and stock returns, we find that one out of seven firms, and a large proportion of the biggest companies, had substantive links with the National Socialist German Workers' Party. Firms supporting the Nazi movement experienced unusually high returns, outperforming unconnected ones by 5% to 8% between January and March 1933. These results are not driven by sectoral composition and are robust to alternative estimators and definitions of affiliation.

The immune response goes haywire during sepsis, a deadly condition triggered by infection. Richard S. Hotchkiss and his colleagues take the focus off of the prevailing view that the key aspect of this response is an exuberant inflammatory reaction. They assess recent human studies bolstering the notion that immunosuppression is also a major contributor to the disease. Many people with sepsis succumb to cardiac dysfunction, a process examined by Peter Ward. He showcases the factors that cause cardiomyocyte contractility to wane during the disease.

Immunotherapy-based combinations including pembrolizumab plus lenvatinib are the standard of care for patients with first-line clear-cell renal cell carcinoma, but these combinations are not well characterised in non-clear-cell renal cell carcinoma. We aimed to assess the activity and safety of pembrolizumab plus lenvatinib as a first-line treatment for patients with advanced non-clear-cell renal cell carcinoma. KEYNOTE-B61 is a single-arm, phase 2 trial being conducted at 48 sites (hospitals and cancer centres) in 14 countries (Australia, Canada, France, Hungary, Ireland, Italy, Poland, South Korea, Russia, Spain, Türkiye, Ukraine, the UK, and the USA). Adult patients (aged ≥18 years) with previously untreated stage IV non-clear-cell renal cell carcinoma and a Karnofsky performance status of 70% or higher were eligible for enrolment. All enrolled patients received pembrolizumab 400 mg intravenously every 6 weeks for up to 18 cycles (2 years) plus lenvatinib 20 mg orally once daily or until disease progression, unacceptable toxicity, or withdrawal; lenvatinib could be continued beyond 2 years. The primary endpoint was the proportion of patients with a confirmed objective response as per adjusted Response Evaluation Criteria in Solid Tumours (version 1.1) assessed by independent central review. Activity and safety were analysed in all patients who received at least one dose of study treatment (the as-treated population). This trial is registered with ClinicalTrials.gov (NCT04704219) and is no longer recruiting participants but is ongoing. Between Feb 23, 2021, and Jan 21, 2022, 215 patients were screened; 158 were enrolled and received treatment. Median age at baseline was 60 years (IQR 52–69), 112 (71%) of 158 patients were male, 46 (29%) were female, 128 (81%) were White, 12 (8%) were Asian, three (2%) were Black or African American, and 15 (9%) were missing data on race. As of data cutoff (Nov 7, 2022), median study follow-up was 14·9 months (IQR 11·1–17·4). 78 of 158 patients had a confirmed objective response (49%; 95% CI 41–57), including nine (6%) patients with a confirmed complete response and 69 (44%) with a confirmed partial response. Grade 3–4 treatment-related adverse events occurred in 81 (51%) of 158 patients, the most common of which were hypertension (37 [23%] of 158), proteinuria (seven [4%]), and stomatitis (six [4%]). Serious treatment-related adverse events occurred in 31 (20%) of 158 patients. Eight (5%) patients died due to adverse events, none of which was considered related to the treatment by the investigators (one each of cardiac failure, peritonitis, pneumonia, sepsis, cerebrovascular accident, suicide, pneumothorax, and pulmonary embolism). Pembrolizumab plus lenvatinib has durable antitumour activity in patients with previously untreated advanced non-clear-cell renal cell carcinoma, with a safety profile consistent with that of previous studies. Results from KEYNOTE-B61 support the use of pembrolizumab plus lenvatinib as a first-line treatment option for these patients. Merck Sharp & Dohme (a subsidiary of Merck & Co, NJ, USA), and Eisai.

The immune response goes haywire during sepsis, a deadly condition triggered by infection. Richard S. Hotchkiss and his colleagues take the focus off of the prevailing view that the key aspect of this response is an exuberant inflammatory reaction. They assess recent human studies bolstering the notion that immunosuppression is also a major contributor to the disease. Many people with sepsis succumb to cardiac dysfunction, a process examined by Peter Ward. He showcases the factors that cause cardiomyocyte contractility to wane during the disease.

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 y of age in at least three continents. Choroidal neovascularization (CNV) is the process by which abnormal blood vessels develop underneath the retina. CNV develops in 10% of patients with AMD but accounts for up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD remains unknown, the macrophage component of the inflammatory response, which has been shown to promote tumor growth and support atherosclerotic plaque formation, is thought to stimulate aberrant angiogenesis in blinding eye diseases. The current theory is that macrophage infiltration promotes the development of neovascularization in CNV. We examined the role of macrophages in a mouse model of CNV. IL-10(-/-) mice, which have increased inflammation in response to diverse stimuli, have significantly reduced CNV with increased macrophage infiltrates compared to wild type. Prevention of macrophage entry into the eye promoted neovascularization while direct injection of macrophages significantly inhibited CNV. Inhibition by macrophages was mediated by the TNF family death molecule Fas ligand (CD95-ligand). Immune vascular interactions can be highly complex. Normal macrophage function is critical in controlling pathologic neovascularization in the eye. IL-10 regulates macrophage activity in the eye and is an attractive therapeutic target in order to suppress or inhibit CNV in AMD that can otherwise lead to blindness.

Logical frameworks that are sensitive to features of sentences’ subject-matter—like Berto’s topic-sensitive intentional modals (TSIMs)—demand a maximally faithful model of the topics of sentences. This is an especially difficult task in the case in which topics are assigned to intensional formulae. In two previous papers, a framework was developed whose model of intensional subject-matter could accommodate a wider range of intuitions about particular intensional conditionals. Although resolving a number of counterintuitive features, the work made an implicit assumption that the subject-matter of an intensional conditional is a function of the subject-matters of its subformulae. This assumption—which I will call a principle of topic sufficiency—runs counter to some natural intuitions concerning topic. In this paper, we will investigate topic sufficiency and offer a semantic account that is state-sensitive, providing an implementation through the introduction of topic-sensitive logics related to William Parry’s prototypical $\\mathsf {PAI}$ .