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We examine how agricultural subsidies may induce deforestation and interact with conservation programs by analyzing two large-scale national programs in Mexico that have existed simultaneously for more than a decade: an agricultural subsidy for livestock (PROGAN) and a program of payments for ecosystem services (PES). Looking across the entire Mexican landscape, we exploit the surprises in the timing of enrollment in PROGAN's waves, fluctuations in program payments, and the change in the value of the subsidy induced by inflation and currency fluctuations to identify the impacts of the livestock subsidy on environmental outcomes. We find that PROGAN increased municipal deforestation by 7 per cent. The deforestation effects of PROGAN were smaller in municipalities with higher concentrations of PES recipients. We suggest that livestock subsidies could be better targeted to places with low deforestation risk and high livestock productivity to maximize food production and minimize negative externalities caused by deforestation. [ABSTRACT FROM AUTHOR]

A role of IL‐10 is down‐regulating T‐cell responses to schistosome antigens. Since SmATPDases can be correlated to modulation of the immune response, we evaluated the expression of enzymes in S. mansoni eggs. Faecal samples were collected from 40 infected individuals to detect coding regions of the SmATPDases. The cytokines were measured in supernatants of PBMC. The analysis was performed by the global median determination and set up high producers (HP) of cytokines. Six individuals expressed SmATPDase1, six expressed SmATPDase2 and six expressed both enzymes. The group who expressed only SmATPDase1 showed a high frequency of IFN‐γ, TNF IL‐4 HP; individuals who expressed only SmATPDase2 showed a high frequency of IFN‐γ, IL‐6 and IL‐4 HP; and individuals who expressed both enzymes showed a high frequency of IL‐10 HP. The comparison of the IFN‐γ/IL‐10 ratio presented higher indices in the group who had SmATPDase 2 expression than those who had the expression of both enzymes. The positive correlation between infection intensity and IL‐10 levels remained only in the positive SmATPDase group. The IL‐10 is the only cytokine induced by the expression of both enzymes. Our data suggest that the expression of both enzymes seems to be a factor that modulates the host immune response by inducing high IL‐10 production. [ABSTRACT FROM AUTHOR]

Background and Aims: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study., Approach and Results: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings., Conclusions: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)