Spring Composers Forum

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Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Limited Access to Aortic Valve Procedures in Socioeconomically Disadvantaged Areas

Background To explore how differences in local socioeconomic deprivation impact access to aortic valve procedures and the treatment of aortic valve disease, in comparison to other open and minimally invasive surgical procedures. Methods and Results Procedure volume data were obtained from the Healthcare Cost and Utilization Project from 18 states from 2016 to 2019 and merged with area deprivation index data, an index of zip code‐level socioeconomic distress. We estimate the relationship between local deprivation ranking and differences in volumes of aortic valve replacement, which include transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR), versus coronary artery bypass graft surgery and laparoscopic colectomy (LC). All regressions control for state and year fixed effects and an array of zip code‐level characteristics. TAVR procedures have increased over time across all zip codes. The rate of increase is negatively correlated with deprivation ranking, regardless of the higher share of hospitalizations per population in high deprivation areas. Distributional analysis further supports these findings, showing that lower area deprivation index areas account for a disproportionately large share of SAVR, TAVR, and LC procedures in our sample relative to their share of all hospitalizations in our sample. By comparison, the cumulative distribution of coronary artery bypass graft procedures was nearly identical to that of total hospitalizations, suggesting that this procedure is equitably distributed. Regressions show high area deprivation index areas have lower prevalence of SAVR (β=−15.1%, [95% CI, −26.8 to −3.5]), TAVR (β=−9.1%, [95% CI, −18.0 to −0.2]), and LC (β=−19.9%, [95% CI, −35.4 to −4.4]), with no statistical difference in the prevalence of coronary artery bypass graft (β=−2.5%, [95% CI, −12.7 to 7.6]), a widespread and commonly performed procedure. In the population aged ≥80 years, results show high area deprivation index areas have a lower prevalence of TAVR (β=−11.9%, [95% CI, −18.7 to −5.2]) but not SAVR (β=−0.8%, [95% CI, 8.1 to 6.3]), LC (β=−3.5%, [95% CI, −13.4 to −6.4]), or coronary artery bypass graft (β=5.2%, [95% CI, −1.1 to 1.1]). Conclusions People living in high deprivation areas have less access to life‐saving technologies, such as SAVR, and even moreso to device‐intensive minimally invasive procedures such as TAVR and LC

Genomic Instability in the Type II TGF-␤ 1 Receptor Gene in Atherosclerotic and Restenotic Vascular Cells

Abstract Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-␤ 1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-␤ 1 (T ␤ R-II), causing acquired resistance to TGF-␤ 1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A 10 microsatellite within T ␤ R-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in T ␤ R-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A 10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-␤ 1. We propose that microsatellite instability in T ␤ R-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions. ( J. Clin. Invest. 1997

The Integration of Personal Identity, Religious Identity, and Moral Identity in Emerging Adulthood

The present study investigated the relative roles of identity structure (i.e., personal identity) and identity contents (i.e., religious identity and moral identity) in predicting emerging adults' prosocial and antisocial behaviors. The sample included 9,495 college students. A variable-centered analysis (path analysis) used personal identity, religious identity, and moral identity as predictors of prosocial and antisocial behavior and tested interactions of personal identity with religious identity and moral identity. Moral identity was the strongest predictor of both behaviors, and religious identity and moral identity both interacted with personal identity in predicting antisocial behavior. A person-centered analysis (latent profile analysis) found three classes: integrated, moral identity-focused, and religious identity-focused, with integrated being most adaptive on both outcomes

Consenso mundial de Río de Janeiro sobre hitos, definiciones y clasificaciones del esófago de Barrett: estudio Delphi de la Organización Mundial de Endoscopia

12 páginasBackground & Aims Despite the significant advances made in the diagnosis and treatment of Barrett’s esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. Methods The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. Results After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett’s endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett’s International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. Conclusions We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BEAntecedentes y objetivos A pesar de los importantes avances realizados en el diagnóstico y tratamiento del esófago de Barrett (EB), todavía existe la necesidad de definiciones estandarizadas, reconocimiento apropiado de puntos de referencia endoscópicos y uso consistente de sistemas de clasificación. Las controversias actuales en las definiciones básicas de BE y la relativa falta de conocimiento anatómico son barreras importantes para una documentación uniforme. Nuestro objetivo era proporcionar recomendaciones impulsadas por consenso para informes uniformes y aplicación global. Métodos El Comité de Esófago de Barrett de la Organización Mundial de Endoscopia nombró líderes para desarrollar un estudio Delphi basado en evidencia. Un grupo de trabajo de 6 miembros identificó y formuló 23 declaraciones, y 30 expertos reconocidos internacionalmente de 18 países participaron en 3 rondas de votación. Definimos el consenso como el acuerdo de ≥80% de los expertos para cada afirmación y utilizamos la herramienta Grading of Recommendations, Assessment, Development and Evaluaciones (GRADE) para evaluar la calidad de la evidencia y la solidez de las recomendaciones. Resultados Después de 3 rondas de votación, los expertos lograron consenso sobre 6 puntos de referencia endoscópicos (vasos en empalizada, unión gastroesofágica, unión escamoso-cilíndrica, ubicación de la lesión, compresiones extraluminales y orientación de los cuadrantes), 13 definiciones (BE, hernia de hiato, islas escamosas, islas columnares, endoscopia de Barrett). terapéutica, resección endoscópica, ablación endoscópica, inspección sistemática, erradicación completa de la metaplasia intestinal, erradicación completa de la displasia, enfermedad residual, enfermedad recurrente y fracaso de la terapia endoscópica) y 4 sistemas de clasificación (Praga, Los Ángeles, París y Barrett's International Grupo NBI). En la ronda 1, 18 declaraciones (78%) alcanzaron consenso y 12 (67%) recibieron un fuerte acuerdo de más de la mitad de los expertos. En la ronda 2, 4 de las declaraciones restantes (80%) alcanzaron consenso, y 1 declaración recibió un fuerte acuerdo del 50% de los expertos. En la tercera ronda se llegó a un consenso sobre la declaración restante. Conclusiones Desarrollamos declaraciones basadas en evidencia y consensuadas sobre puntos de referencia, definiciones y clasificaciones endoscópicas de BE. Estas recomendaciones pueden facilitar la presentación de informes uniformes a nivel mundial en BE