Most of the Ross Sea has been designated a marine protected area (MPA), proposed ‘to protect ecosystem structure and function’. To assess effectiveness, the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) selected Adélie (Pygoscelis adeliae) and emperor (Aptenodytes forsteri) penguins, Weddell seals (Leptonychotes weddellii) and Antarctic toothfish (Dissostichus mawsoni) as ecosystem change ‘indicator species’. Stable for decades, penguin and seal populations increased during 1998–2018 to surpass historical levels, indicating that change in ecosystem structure and function is underway. We review historical impacts to population trends, decadal datasets of ocean climate and fishing pressure on toothfish. Statistical modelling for Adélie penguins and Weddell seals indicates that variability in climate factors and cumulative extraction of adult toothfish may explain these trends. These mesopredators, and adult toothfish, all prey heavily on Antarctic silverfish (Pleuragramma antarcticum). Toothfish removal may be altering intraguild predation dynamics, leading to competitive release of silverfish and contributing to penguin and seal population changes. Despite decades of ocean/weather change, increases in indicator species numbers around Ross Island only began once the toothfish fishery commenced. The rational-use, ecosystem-based viewpoint promoted by CCAMLR regarding toothfish management needs re-evaluation, including in the context of the Ross Sea Region MPA.

Many believe that weaker legal constraints make unilateral action easier to reverse than legislation. Yet in some cases, unilateralism survives a successor's determined opposition. I argue that legislative persistence and unilateral transience may arise not only from differences in legal status but also from a selection effect: unilateralism and subsequent rescission can both stem from weak underlying policy-demanding groups. But if unilateralism itself alters the landscape of group power through policy feedback effects, it can survive a purportedly opposed new president. An example is the Trump Administration's failure to depart from the Obama Justice Department's lax stance on cannabis. Weak constituents’ policy demands may thus need to rely on a sympathetic president's unilateral action to begin a feedback loop, subsequently softening opposition. This paper therefore identifies unilateral action as a key tool for shifting policy in an enduring way, explaining its success or failure in terms of interest group power.

Measurement is the weak link between theory and empirical test. Complex concepts such as ideology, identity, and legitimacy are difficult to measure; yet, without measurement that matches theoretical constructs, careful empirical studies may not be testing that which they had intended. Item response theory (IRT) models offer promise by producing transparent and improvable measures of latent factors thought to underlie behavior. Unfortunately, those factors have no intrinsic substantive interpretations. Prior solutions to the substantive interpretation problem require exogenous information about the units, such as legislators or survey respondents, which make up the data; limit analysis to one latent factor; and/or are difficult to generalize. We propose and validate a solution, IRT-M, that produces multiple, potentially correlated, generalizable, latent dimensions, each with substantive meaning that the analyst specifies before analysis to match theoretical concepts. We offer an R package and step-by-step instructions in its use, via an application to survey data.

OBJECTIVES/GOALS: Silicosis is a highly fatal progressive fibrotic disease of the lungs characterized by accumulation and persistence of fibroblasts that excessively deposit Collagen1a1. We sought to eliminate Collagen1a1-expressing fibroblasts through a targeted genetic ablation strategy and hypothesized that this would arrest the progression of Silicosis. METHODS/STUDY POPULATION: Silicosis was induced with a single intratracheal (i.t.) instillation of silica particles ( RESULTS/ANTICIPATED RESULTS: Targeted ablation of Col1a1+ fibroblast in established Silicosis resulted in a decrease in: 1) Col1a1+ fibroblasts by flow cytometry and within fibrotic nodules by immunofluorescent staining, 2) total lung collagen content by histology and hydroxyproline assay, 3) tissue-associated disease by microCT and an increase in arterial oxygen saturation by pulse oximetry. Cessation of targeted Col1a1+ fibroblast ablation resulted in a rebound effect in Silicosis disease progression. Following ablation, Col1a1+ fibroblasts expanded by proliferation (Ki67+) and total lung collagen levels returned to pre-ablation levels. DISCUSSION/SIGNIFICANCE: Silicosis is a often fatal disease with no FDA approved therapies. These results suggest that targeted loss of Col1a1+ fibroblasts in Silicosis is sufficient to arrest disease progression. Thus, it is essential to understand how targeted loss of pro-fibrotic fibroblasts can alter disease progression as a tool to develop novel therapeutic strategies.

Twenty years ago the first publications began to appear in Argentina of a loosely confederated group of writers, leftist in political persuasion, who took strident exception in culture to both the old oligarchic tradition and to the parvenu peronista establishment. During the years of the peronista government, the writers and intellectuals who supported Perón had been successful in imposing their own persuasions on the universities and publishing media at the expense of the old guard, represented by the literary supplements, Sur, the Academia Argentina de Letras, and the Jockey Club. The young leftists born around 1920 had been snubbed by the old-time writers and persecuted by the peronista regime. Their emergence as a loosely unified assertion of leftist political and cultural values, supported by a similar affirmation in postwar Europe, is a major literary phenomenon in mid-century Argentia.

It was inevitable that after the demise of the series of military dictatorships that ruled Argentina so violently between 1976 and 1983, the return to democratic institutions would occasion an outpouring of the kinds of writing and cultural activities banned or censored by the generals. Movie distributors in Argentina today cannot keep up with the demand for films that could not be seen during these years (or were seen only with extensive and capricious cuts). Theaters are competing with each other to present works dealing with human rights violations and related themes. Television programming, which the military assiduously controlled, has now begun to evince some social consciousness. Meanwhile, the print media have filled bookstores and kiosks with myriad publications bearing witness to the attempt to recover a cultural tradition altered and fragmented by the so-called Proceso de Reorganización Nacional.

Numerical estimators of differential entropy and mutual information can be slow to converge as sample size increases. The offset Kozachenko–Leonenko (KLo) method described here implements an offset version of the Kozachenko–Leonenko estimator that can markedly improve convergence. Its use is illustrated in applications to the comparison of trivariate data from successive scene color images and the comparison of univariate data from stereophonic music tracks. Publicly available code for KLo estimation of both differential entropy and mutual information is provided for R, Python, and MATLAB computing environments at https://github.com/imarinfr/klo.

Protected areas have numerous roles (such as biodiversity preservation, the development of scientific research and the sustainable use of natural resources), but they are under threat from political and economic forces. The 837 000-ha Serra do Divisor National Park (SDNP) in the south-western Brazilian Amazon combines the conservation of natural resources and the maintenance of the productive activities of c. 400 resident families. The Brazilian and Peruvian governments have proposed a road linking Acre (Brazil) to Ucayali (Peru) that would bisect the SDNP. Another threat to the SDNP is a bill proposing its downgrading to an ‘environmental protection area’. This study aims to map the land cover of the SDNP and its surroundings from 1988 to 2018 and to analyse the dynamics of land-use change. Analysis of Landsat satellite images with supervised classification using the MaxVer algorithm show that, during the 30-year period, pasture showed the highest absolute land-cover gain, with 1986 ha in the interior and 7661 ha along the periphery of the SDNP. Only 1% of the park’s primary forest was lost by 2018, but the proposed road and potential downgrading may result in accelerated deforestation and forest degradation in the near future.

Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.

Trial registry: ClinicalTrials.gov Identifier: NCT01526785 https://clinicaltrials.gov/ct2/show/NCT01526785.

Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.

Reconstructions of prehistoric vegetation composition help establish natural baselines, variability, and trajectories of forest dynamics before and during the emergence of intensive anthropogenic land use. Pollen–vegetation models (PVMs) enable such reconstructions from fossil pollen assemblages using process-based representations of taxon-specific pollen production and dispersal. However, several PVMs and variants now exist, and the sensitivity of vegetation inferences to PVM selection, variant, and calibration domain is poorly understood. Here, we compare the reconstructions, parameter estimates, and structure of a Bayesian hierarchical PVM, STEPPS, both to observations and to REVEALS, a widely used PVM, for the pre–Euro-American settlement-era vegetation in the northeastern United States (NEUS). We also compare NEUS-based STEPPS parameter estimates to those for the upper midwestern United States (UMW). Both PVMs predict the observed macroscale patterns of vegetation composition in the NEUS; however, reconstructions of minor taxa are less accurate and predictions for some taxa differ between PVMs. These differences can be attributed to intermodel differences in structure and parameter estimates. Estimates of pollen productivity from STEPPS broadly agree with estimates produced for use in REVEALS, while comparison between pollen dispersal parameter estimates shows no significant relationship. STEPPS parameter estimates are similar between the UMW and NEUS, suggesting that STEPPS parameter estimates are transferable between floristically similar regions and scales.