Real analysis Stein, Elias M; Shakarchi, Rami
2005., 20091128, 2009, 2005, 2009-11-28, Letnik:
3
eBook
Real Analysis is the third volume in the Princeton Lectures in Analysis, a series of four textbooks that aim to present, in an integrated manner, the core areas of analysis. Here the focus is on the ...development of measure and integration theory, differentiation and integration, Hilbert spaces, and Hausdorff measure and fractals. This book reflects the objective of the series as a whole: to make plain the organic unity that exists between the various parts of the subject, and to illustrate the wide applicability of ideas of analysis to other fields of mathematics and science. After setting forth the basic facts of measure theory, Lebesgue integration, and differentiation on Euclidian spaces, the authors move to the elements of Hilbert space, via the L2 theory. They next present basic illustrations of these concepts from Fourier analysis, partial differential equations, and complex analysis. The final part of the book introduces the reader to the fascinating subject of fractional-dimensional sets, including Hausdorff measure, self-replicating sets, space-filling curves, and Besicovitch sets. Each chapter has a series of exercises, from the relatively easy to the more complex, that are tied directly to the text. A substantial number of hints encourage the reader to take on even the more challenging exercises.
This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature ...is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype‐guided warfarin dosing to achieve a target international normalized ratio of 2–3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
Despite heightened awareness of the clinical significance of social phobia, information is still lacking about putative subtypes, functional impairment, and treatment-seeking. New epidemiologic data ...on these topics are presented from the National Comorbidity Survey Replication (NCS-R).
The NCS-R is a nationally representative household survey fielded in 2001-2003. The World Health Organization (WHO) Composite International Diagnostic Interview Version 3.0 (CIDI 3.0) was used to assess 14 performance and interactional fears and DSM-IV social phobia.
The estimated lifetime and 12-month prevalence of social phobia are 12.1% and 7.1% respectively. Performance and interactional fears load onto a single latent factor, and there is little evidence for distinct subtypes based either on the content or the number of fears. Social phobia is associated with significant psychiatric co-morbidity, role impairment, and treatment-seeking, all of which have a dose-response relationship with number of social fears. However, social phobia is the focus of clinical attention in only about half of cases where treatment is obtained. Among non-co-morbid cases, those with the most fears were least likely to receive social phobia treatment.
Social phobia is a common, under-treated disorder that leads to significant functional impairment. Increasing numbers of social fears are associated with increasingly severe manifestations of the disorder.
On July 18, 1924, a mob in Tehran killed U.S. foreign service officer Robert Whitney Imbrie. His violent death, the first political murder in the history of the service, outraged the American people. ...Though Imbrie's loss briefly made him a cause célèbre, subsequent events quickly obscured his extraordinary life and career. Susan M. Stein tells the story of a figure steeped in adventure and history. Imbrie rejected a legal career to volunteer as an ambulance driver during World War I and joined the State Department when the United States entered the war. Assigned to Russia, he witnessed the October Revolution, fled ahead of a Bolshevik arrest order, and continued to track communist activity in Turkey even as the country's war of independence unfolded around him. His fateful assignment to Persia led to his death at age forty-one and set off political repercussions that cloud relations between the United States and Iran to this day. Drawing on a wealth of untapped materials, On Distant Service returns readers to an era when dash and diplomacy went hand-in-hand.
While we know much about what differentiates the conflict behavior of democracies from autocracies, we know relatively little about why some democracies are more belligerent than others. In contrast ...to existing studies, I argue that it is public opinion and not institutions that drives these differences. All democratic leaders have an incentive to take public opinion into account, but public opinion is not the same everywhere. Individuals’ attitudes towards war are shaped by core beliefs about revenge, which vary across countries. Leaders with more vengeful populations will be more likely to initiate conflicts because they generate popular support for war more effectively. Using retention of capital punishment as a proxy for broad endorsement of revenge, I find that democracies that have retained the death penalty for longer periods of time are significantly more likely to initiate conflicts. This research has important implications for existing theories of democracy and war.
Recurrent mutations in isocitrate dehydrogenase 2 (IDH2) occur in ∼12% of patients with acute myeloid leukemia (AML). Mutated IDH2 proteins neomorphically synthesize 2-hydroxyglutarate resulting in ...DNA and histone hypermethylation, which leads to blocked cellular differentiation. Enasidenib (AG-221/CC-90007) is a first-in-class, oral, selective inhibitor of mutant-IDH2 enzymes. This first-in-human phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in patients with mutant-IDH2 advanced myeloid malignancies. We assessed safety outcomes for all patients and clinical efficacy in the largest patient subgroup, those with relapsed or refractory AML, from the phase 1 dose-escalation and expansion phases of the study. In the dose-escalation phase, an MTD was not reached at doses ranging from 50 to 650 mg per day. Enasidenib 100 mg once daily was selected for the expansion phase on the basis of pharmacokinetic and pharmacodynamic profiles and demonstrated efficacy. Grade 3 to 4 enasidenib-related adverse events included indirect hyperbilirubinemia (12%) and IDH-inhibitor–associated differentiation syndrome (7%). Among patients with relapsed or refractory AML, overall response rate was 40.3%, with a median response duration of 5.8 months. Responses were associated with cellular differentiation and maturation, typically without evidence of aplasia. Median overall survival among relapsed/refractory patients was 9.3 months, and for the 34 patients (19.3%) who attained complete remission, overall survival was 19.7 months. Continuous daily enasidenib treatment was generally well tolerated and induced hematologic responses in patients for whom prior AML therapy had failed. Inducing differentiation of myeloblasts, not cytotoxicity, seems to drive the clinical efficacy of enasidenib. This trial was registered at www.clinicaltrials.gov as #NCT01915498.
•Enasidenib, a selective inhibitor of mutant IDH2 enzymes, was safe and well tolerated in patients with IDH2-mutated myeloid malignancies.•Enasidenib induced hematologic responses in patients with relapsed/refractory AML in this dose-escalation and expansion study.
How can an open access database annotating pictures, films, music and texts support adults as existential exemplars? This article explores the opportunities of a Norwegian database called the ...OE-database. Its target group is all adults who want to become better exemplars for children through encounters with art and conversations in small groups. Educational sources contain many annotations of art and literature for the education of children and youth, but material for adults' self-education, published in databases and thus easily accessible for all, are lacking. The article invites readers to a critical conversation on the purpose and potential of the OE-database and to create similar databases in other languages. The narratives that provide the foundation of the OE-database are influenced by Aristotle, Thomas Aquinas and Søren Kierkegaard. The article highlights Kierkegaard's concept 'upbuilding' (edification) and three stages in a process that encourage adults to let themselves be 'built up' as exemplars.
The 2010 and 2017 editions of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults are widely recognized among physicians and ...investigators. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update that includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations.
The mechanisms that contribute to emotion dysregulation in anxiety disorders are not well understood. Two common disorders, generalized anxiety disorder (GAD) and panic disorder (PD), were examined ...to test the hypothesis that both disorders are characterized by hypo-activation in prefrontal cortex (PFC) during emotion regulation. A competing hypothesis that GAD in particular is characterized by PFC hyper-activation during emotion regulation (reflecting overactive top-down control) was also evaluated. Method Twenty-two medication-free healthy control (HC), 23 GAD, and 18 PD participants underwent functional magnetic resonance imaging (fMRI) during a task that required them to reappraise (i.e. reduce) or maintain emotional responses to negative images.
GAD participants reported the least reappraisal use in daily life, and reappraisal use was inversely associated with anxiety severity and functional impairment in these participants. During fMRI, HCs demonstrated greater activation during both reappraisal and maintenance than either GAD or PD participants (who did not differ) in brain areas important for emotion regulation (e.g. dorsolateral and dorsomedial PFC). Furthermore, across all anxious participants, activation during reappraisal in dorsolateral and dorsomedial PFC was inversely associated with anxiety severity and functional impairment.
Emotion dysregulation in GAD and PD may be the consequence of PFC hypo-activation during emotion regulation, consistent with insufficient top-down control. The relationship between PFC hypo-activation and functional impairment suggests that the failure to engage PFC during emotion regulation may be part of the critical transition from dispositionally high anxiety to an anxiety disorder.
CYP2C19 is one of the principal enzymes involved in the bioactivation of the antiplatelet prodrug clopidogrel. A common loss‐of‐function allele, CYP2C19*2 (c.681G>A; rs4244285), is associated with ...increased risk for serious adverse cardiovascular events in both heterozygous and homozygous patients (~25–50% of the population) with acute coronary syndromes (ACSs) who are receiving clopidogrel, particularly among those undergoing percutaneous coronary intervention (PCI). We provide evidence from published literature and guidelines for CYPC19 genotype–directed antiplatelet therapy (periodically updated at http://www.pharmgkb.org).
Clinical Pharmacology & Therapeutics (2011) 90 2, 328–332. doi:10.1038/clpt.2011.132
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