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We develop a Stackelberg differential game to analyze the economic effects of the reduction plan through two policy instruments, tradable permits and taxes on emissions. Emissions are a by‐product of firm output. The authority acts as a Stackelberg leader, able to set the optimal instrument's level in the light of a finite‐horizon environmental target. We show that the optimal solution of the game is dynamically consistent. Moreover, optimal environmental policies substantially impact the level and composition of economic activity. The differentiation between "clean" and "dirty" firms allows us to assess distributional effects and how environmental technology may influence the game's outcome. Results are shown to be robust under different parameterizations. [ABSTRACT FROM AUTHOR]

Aim: It is still unclear if the magnitude of early postnatal weight loss (PWL) could be associated with neurodevelopmental outcomes in preterm infants. We studied the association between PWL and neurodevelopment at 2‐year corrected age in preterm infants. Methods: We retrospectively reviewed data of preterm infants with a gestational age between 24 + 0 and 31 + 6 weeks/days, admitted at the G.Salesi Children's Hospital, Ancona, Italy, between 1 January 2006 and 31 December 2019. Infants with PWL greater than or equal to 10% (PWL ≥ 10%) were compared with those with PWL of less than 10% (PWL < 10%). A matched cohort analysis was also performed using gestational age and birth weight as matching variables. Results: We analysed 812 infants: 471 (58%) PWL ≥ 10% and 341 (42%) PWL < 10%. A subgroup of 247 PWL ≥ 10% was closely match‐paired with 247 PWL < 10% infants. There were no differences in amino acid and energy intakes from birth to day 14 of life and from birth to 36 weeks. Although at 36 weeks, body weight and total length were lower in PWL ≥ 10% than PWL < 10%, anthropometry and neurodevelopment at 2 years were similar between groups. Conclusion: Given similar amino acid and energy intakes on PWL ≥ 10% and PWL < 10% preterm infants of less than 32 + 0 weeks/days, PWL does not affect 2‐year neurodevelopment. [ABSTRACT FROM AUTHOR]

Stable isotope tracing can be safely used for metabolic studies in animals and humans. The endogenous biosynthesis of lipids (lipogenesis) is a key process throughout the entire life but especially during brain and lung growth. Adequate synthesis of pulmonary surfactant lipids is indispensable for life. With this study, we report the use of deuterium‐depleted water (DDW), suitable for human consumption, as metabolic precursor for lipogenesis. We studied 13 adult rabbits for 5 days. Four rabbits drank tap water (TW) and served as controls; in four animals, DDW was substituted to drinking water, whereas five drank deuterium‐enriched water (DEW). After 5 days, a blood sample and a bronchoalveolar lavage (BAL) sample were collected. The 2H/1H (δ2H) of BAL palmitic acid (PA) desaturated phosphatidylcholine (DSPC), the major phospholipid of pulmonary surfactant, and of plasma water was determined by high‐resolution mass spectrometry. We found that the δ2H values of DDW, DEW and TW were −984 ± 2‰, +757 ± 2‰ and −58 ± 1‰, respectively. After 5 days, plasma water values were −467 ± 87‰, +377 ± 56‰ and −53 ± 6‰, and BAL DSPC‐PA was −401 ± 27‰, −96 ± 38‰ and −249 ± 9‰ in the DDW, DEW and TW, respectively. With this preliminary study, we demonstrated the feasibility of using DDW to label pulmonary surfactant lipids. This novel approach can be used in animals and in humans, and we speculate that it could be associated with more favourable study compliance than DEW in human studies. [ABSTRACT FROM AUTHOR]

Variation of the isotopic abundance of selected nutrients and molecules has been used for pharmacological and kinetics studies under the premise that the administered molecule has a different isotopic enrichment from the isotopic background of the recipient subject. The aim of this study is to test the feasibility of assessing the contribution of exogenous surfactant phospholipids to the endogenous alveolar pool in vivo after exogenous surfactant replacement therapy in rabbits. The study consisted in measuring the consistency of 13C/12C ratio of disaturatedphosphatidylcholine palmitate (DSPC-PA) in 7 lots of poractant alfa, produced over a year, and among bronchoalveolar lavages of 20 rabbits fed with a standard chow. A pilot study was performed in a rabbit model of lavage-induced surfactant deficiency: 7 control rabbits and 4 treated with exogenous surfactant. The contribution of exogenous surfactant to the alveolar pool was assessed after intra-tracheal administration of 200 mg/kg of poractant alfa. The 13C content of DSPC-PA was measured by isotope ratio mass spectrometry. The mean DSPC-PA 13C/12C ratio of the 7 lots of poractant alfa was -18.8‰ with a SD of 0.1‰ (range: -18.9‰; -18.6‰). The mean 13C/12C ratio of surfactant DSPC recovered from the lung lavage of 20 rabbits was -28.8 ± 1.2‰ (range: -31.7‰; -25.7‰). The contribution of exogenous surfactant to the total alveolar surfactant could be calculated in the treated rabbits, and it ranged from 83.9% to 89.6%. This pilot study describes a novel method to measure the contribution of the exogenous surfactant to the alveolar pool. This method is based on the natural variation of 13C, and therefore it does not require the use of chemically synthetized tracers. This method could be useful in human research and especially in surfactant replacement studies in preterm infants. [ABSTRACT FROM AUTHOR]

Abstract: Parenteral nutrition‐associated cholestasis (PNAC) has been linked to plasma accumulation of phytosterols in infants receiving vegetable‐oil‐based lipid emulsions (LE). To date, information on the ability of infants with PNAC to metabolize intravenous (IV) phytosterols has been very limited. We characterized plasma phytosterol half‐life in very low birth weight (VLBW) preterm infants with PNAC. As part of a prospective cohort study, VLBW infants with PNAC underwent serial blood sample measurements of sitosterol (Sito), campesterol (Camp), and stigmasterol (Stigma). Infants without PNAC served as controls (CTRL, control infants). Thirty‐seven PNAC infants and 14 CTRL were studied. On PN day 7 and PN day 14, PNAC infants had higher plasma phytosterol concentrations compared to those of CTRL (p < 0.05). A significant and positive correlation was found between plasma Camp, Stigma, Sito concentrations, and IV phytosterol intake from birth to PN day 7 (p = 0.001, p = 0.001, and p = 0.005, respectively). Stigma concentration was positively correlated with conjugated bilirubin on PN day 7 (p = 0.012). After stopping IV LE, half‐lives of Camp, Stigma, and Sito became significantly longer in PNAC infants than in CTRL (Camp: 18.8 ±6.2 vs 11.8 ±3.0 days, p = 0.001; Stigma: 13.8 ±5.8 vs 9.4 ±3.4 days, p = 0.023; Sito: 15.3 ±5.0 vs 9.8 ±3.0 days, p = 0.002). In conclusion, phytosterols increased earlier during PN and were eliminated slowly after stopping IV LE in PNAC infants than in CTRL. The Stigma concentration on PN day 7 could represent an early marker of cholestasis. Our results provide additional evidence on the relationship between IV phytosterols and PNAC. [ABSTRACT FROM AUTHOR]

Several studies reported the association between total plasma phytosterol concentrations and the parenteral nutrition-associated cholestasis (PNAC). To date, no data are available on phytosterol esterification in animals and in humans during parenteral nutrition (PN). We measured free and esterified sterols (cholesterol, campesterol, stigmasterol, and sitosterol) plasma concentrations during PN in 16 preterm infants (500-1249 g of birth weight; Preterm-PN), in 11 term infants (Term-PN) and in 12 adults (Adult-PN). Gas chromatography-mass spectrometry was used for measurements. Plasma concentrations of free cholesterol (Free-CHO), free phytosterols (Free-PHY) and esterified phytosterols (Ester-PHY) were not different among the three PN groups. Esterified cholesterol (Ester-CHO) was statistically lower in Preterm-PN than Adult-PN. Preterm-PN had significantly higher Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios than Adult-PN (Free-CHO/Ester-CHO: 1.1 ± 0.7 vs. 0.6 ± 0.2; Free-PHY/Ester-PHY: 4.1 ± 2.6 vs. 1.3 ± 0.8; *P < 0.05). Free-CHO/Ester-CHO and Free-PHY/Ester-PHY ratios of Term-PN (Free-CHO/Ester-CHO: 1.1 ± 0.4; Free-PHY/Ester-PHY: 2.9 ± 1.7) were not different from either Preterm-PN or from Adult-PN. Plasma Free-CHO/Ester-CHO and Free-PHY/Ester-PHY were unchanged after 24 h on fat-free PN both in Preterm-PN and in Adult-PN. Free-PHY/Ester-PHY did not correlate with phytosterol intake in Preterm-PN. Free-PHY/Ester-PHY of Preterm-PN was positively correlated with the Free-CHO/Ester-CHO and negatively correlated with gestational age and birth weight. In conclusion, PHY were esterified to a lesser extent than CHO in all study groups; the esterification was markedly decreased in Preterm-PN compared to Adult-PN. The clinical consequences of these findings warrant further investigations. [ABSTRACT FROM AUTHOR]