THE COPYRIGHT WORK OF AUTHORSHIP

The “work of authorship” lies at the heart of the Copyright Act of 1976. It is what copyright protects. Central though the concept is, the Act never defines what a work of authorship might be. According to the Act, it can be perceived in tangible fixations, but is distinct from the fixations. The Act also provides examples: writings, drawings, computer programs, but never describes how these might be distinguished from their fixations. Unlike the Patent Act, where “metes and bounds” of a patentable invention are defined by a patent’s claims, the Copyright Act provides no guidance as to what the “metes and bounds” of a copyright work of authorship might be. Most copyright practitioners and commentators are so inured to the concept that they never pause to consider what the “work of authorship” is, and what it means to say that it exists independently of its fixations. This paper addresses these questions. It will consider when and how the copyright concept of an incorporeal “work of authorship” (which for brevity I will call the copyright Work) arose in federal US law. The paper will compare the concept to Platonic forms, outline the forces that supported its creation, and conclude that the concept is a manifestation of cultural and technological developments in the Nineteenth and Twentieth Centuries that required the range of copyright infringement to expand. The paper will then address the question of how the copyright Work might be defined, concluding that it is not distinct from its fixations, but is instead a set of fixations, defined by the rules of copyright infringement.Building on this definition, the paper then considers whether cultural and technological developments in the current Century, including social media, streaming, open-source licensing, and, most recently, generative artificial intelligence, will shrink the range of copyright infringement, and as a result, diminish the size of the set comprising the copyright Work. Finally, the paper will extrapolate from these copyright developments to suggest some more general conclusions about the nature of law as something that cannot be separated from a particularculture, technology, and time

Czynność i hemodynamika prawej połowy serca w nadciśnieniu płucnym

Głównym wyzwaniem w leczeniu pacjentów z zaawansowanym tętniczym nadciśnieniem płucnym (PAH) jest dysfunkcja prawej komory (RV), która wiąże się z występowaniem prawokomorowej niewydolności serca. Przeżywalność w tej chorobie ściśle wiąże się z czynnością prawej połowy serca, której ocena budzi rosnące zainteresowanie. Choć echokardiografia i rezonans magnetyczny serca (CMR) zwiększyły możliwości obrazowania RV, głównym sposobem oceny czynności prawej połowy serca pozostaje jego inwazyjne cewnikowanie. Wykazano, że kilka obecnie dostępnych sposobów leczenia PAH wpływa na RV, a nie tylko na naczynia płucne, natomiast w przyszłości metody terapeutyczne mające na celu optymalizację czynności RV mogą pozwolić na poprawę rokowania w tej trudnej do leczenia chorobie. Nowe kierunki oceny RV i krążenia małego, w tym pomiar impedancji naczyń płucnych, oraz powszechniejsza dostępność CMR mogą się przyczynić do rozwoju wiedzy na temat prawej połowy serca - dotychczas słabo zbadanej, ale niezwykle ważnej

Role of biomarkers in evaluation, treatment and clinical studies of pulmonary arterial hypertension

Pulmonary arterial hypertension is a complex disease resulting from the interplay of myriad biological and environmental processes that lead to remodeling of the pulmonary vasculature with consequent pulmonary hypertension. Despite currently available therapies, there remains significant morbidity and mortality in this disease. There is great interest in identifying and applying biomarkers to help diagnose patients with pulmonary arterial hypertension, inform prognosis, guide therapy, and serve as surrogate endpoints. An extensive literature on potential biomarker candidates is available, but barriers to the implementation of biomarkers for clinical use in pulmonary arterial hypertension are substantial. Various omic strategies have been undertaken to identify key pathways regulated in pulmonary arterial hypertension that could serve as biomarkers including genomic, transcriptomic, proteomic, and metabolomic approaches. Other biologically relevant components such as circulating cells, microRNAs, exosomes, and cell-free DNA have recently been gaining attention. Because of the size of the datasets generated by these omic approaches and their complexity, artificial intelligence methods are being increasingly applied to decipher their meaning. There is growing interest in imaging the lung with various modalities to understand and visualize processes in the lung that lead to pulmonary vascular remodeling including high resolution computed tomography, Xenon magnetic resonance imaging, and positron emission tomography. Such imaging modalities have the potential to demonstrate disease modification resulting from therapeutic interventions. Because right ventricular function is a major determinant of prognosis, imaging of the right ventricle with echocardiography or cardiac magnetic resonance imaging plays an important role in the evaluation of patients and may also be useful in clinical studies of pulmonary arterial hypertension

Impact of the COVID-19 pandemic on chronic disease management and patient reported outcomes in patients with pulmonary hypertension: The Pulmonary Hypertension Association Registry

To better understand the impact of the COVID-19 pandemic on the care of patients with pulmonary hypertension, we conducted a retrospective cohort study evaluating health insurance status, healthcare access, disease severity, and patient reported outcomes in this population. Using the Pulmonary Hypertension Association Registry (PHAR), we defined and extracted a longitudinal cohort of pulmonary arterial hypertension (PAH) patients from the PHAR\u27s inception in 2015 until March 2022. We used generalized estimating equations to model the impact of the COVID-19 pandemic on patient outcomes, adjusting for demographic confounders. We assessed whether insurance status modified these effects via covariate interactions. PAH patients were more likely to be on publicly-sponsored insurance during the COVID-19 pandemic compared with prior, and did not experience statistically significant delays in access to medications, increased emergency room visits or nights in the hospital, or worsening of mental health metrics. Patients on publicly-sponsored insurance had higher healthcare utilization and worse objective measures of disease severity compared with privately insured individuals irrespective of the COVID-19 pandemic. The relatively small impact of the COVID-19 pandemic on pulmonary hypertension-related outcomes was unexpected but may be due to pre-established access to high quality care at pulmonary hypertension comprehensive care centers. Irrespective of the COVID-19 pandemic, patients who were on publicly-sponsored insurance seemed to do worse, consistent with prior studies highlighting outcomes in this population. We speculate that previously established care relationships may lessen the impact of an acute event, such as a pandemic, on patients with chronic illness

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

<p>Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH. Dfen mediates PAH via a serotonergic mechanism and we have shown serotonin to up-regulate expression of CYP1B1 in human pulmonary artery smooth muscle cells (PASMCs). Thus here we assess the role of CYP1B1 in the development of Dfen-induced PAH.</p> <p>Methods and results: Dfen (5 mg kg−1 day−1 PO for 28 days) increased right ventricular pressure and pulmonary vascular remodelling in female mice only. Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1−/− mice. In line with this, Dfen up-regulated expression of CYP1B1 in PASMCs from PAH patients (PAH-PASMCs) and Dfen-mediated proliferation of PAH-PASMCs was ablated by pharmacological inhibition of CYP1B1. Dfen increased expression of tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin) in PAH-PASMCs and both Dfen-induced proliferation and Dfen-induced up-regulation of CYP1B1 were ablated by inhibition of Tph1. 17β-Oestradiol increased expression of both Tph1 and CYP1B1 in PAH-PASMCs, and Dfen and 17β-oestradiol had synergistic effects on proliferation of PAH-PASMCs. Finally, ovariectomy protected against Dfen-induced PAH in female mice.</p> <p>Conclusion: CYP1B1 is critical in the development of Dfen-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro. CYP1B1 may provide a novel therapeutic target for PAH.</p&gt

BMPR2 expression is suppressed by signaling through the estrogen receptor

<p>Abstract</p> <p>Background</p> <p>Studies in multiple organ systems have shown cross-talk between signaling through the bone morphogenetic protein receptor type 2 (BMPR2) and estrogen pathways. In humans, pulmonary arterial hypertension (PAH) has a female predominance, and is associated with decreased BMPR2 expression. The goal of this study was to determine if estrogens suppress BMPR2 expression.</p> <p>Methods</p> <p>A variety of techniques were utilized across several model platforms to evaluate the relationship between estrogens and BMPR2 gene expression. We used quantitative RT-PCR, gel mobility shift, and luciferase activity assays in human samples, live mice, and cell culture.</p> <p>Results</p> <p>BMPR2 expression is reduced in lymphocytes from female patients compared with male patients, and in whole lungs from female mice compared with male mice. There is an evolutionarily conserved estrogen receptor binding site in the BMPR2 promoter, which binds estrogen receptor by gel-shift assay. Increased exogenous estrogen decreases BMPR2 expression in cell culture, particularly when induced to proliferate. Transfection of increasing quantities of estrogen receptor alpha correlates strongly with decreasing expression of BMPR2.</p> <p>Conclusions</p> <p>BMPR2 gene expression is reduced in females compared to males in live humans and in mice, likely through direct estrogen receptor alpha binding to the BMPR2 promoter. This reduced BMPR2 expression may contribute to the increased prevalence of PAH in females.</p