198 research outputs found

    The Impact of coordination and targets on monetary and fiscal policy

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    Treballs Finals del MĂ ster d'Economia, Facultat d'Economia i Empresa, Universitat de Barcelona, Curs: 2017-2018, Tutor: JesĂșs MarĂ­n SolanoThis paper analyzes the implications of coordination of fiscal and monetary policy. We construct a differential game between a government and a central bank, which are set with the task of stabilizing the economy after an external shock. The mechanics of the game are created by assuming that the authorities must balance the cost of using their policy instruments against the cost of a slower convergence to equilibrium. We compare the competitive and cooperative equilibria under two types of shocks and when the policy makers operate under inflation targeting and output targeting respectively. The main conclusion is that policy coordination can be important for allowing the authorities to reach their targets, especially when they operate under inflation targeting

    Poboljơanje fizičko-mehaničkih svojstava karbamazepina prekristalizacijom pri različitim pH

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    The morphology of crystals has an appreciable impact on the physicochemical properties of drugs. Drug properties such as flowability, dissolution, hardness and bioavailability may be affected by crystallinity behaviors of drugs. The objective of this study was to achieve improved physicomechanical properties of carbamazepine powder through recrystallization from aqueous solutions at different pH values. For this purpose, carbamazapine was recrystallized from aqueous solutions at different pH values (1, 7, 11). The morphology of crystals was investigated using scanning electron microscopy; X-ray powder diffraction (XRPD) was used to identify polymorphism; thermodynamic properties were analyzed using differential scanning calorimetery (DSC). Dissolution was determined using USP dissolution apparatus. Mechanical behavior of recrystallized carbamazepine powders was investigated by making tablets under different compaction pressures and measuring their hardness. SEM studies showed that carbamazepine crystallization in different media affected the morphology and size of carbamazepine crystals. The shape of carbamazepine crystals changed from flaky or thin plate-like to needle-shaped. XRPD and DSC results ruled out any crystallinity changes occurring due to the temperature or pH of crystallization media. The crushing strength of tablets indicated that all the recrystallized carbamazepine samples had better compactibility than the original carbamazepine powder. In vitro dissolution studies of carbamazepine samples showed a higher dissolution rate of carbamazepine crystals obtained from media with pH 11 and 1. Carbamazepine particles recrystallized from aqueous solutions of different pH values (all media) appeared to have superior mechanical properties to those of the original carbamazepine sample.Morfologija kristala ima značajan utjecaj na fizičko-mehanička svojstva lijekova. Kristaliničnost moĆŸe utjecati na tečnost, oslobađanje, tvrdoću i bioraspoloĆŸivost lijekova. Cilj ovog rada bio je poboljĆĄati fizičko-mehanička svojstva praha karbamazepina prekristalizacijom iz vodenih otopina pri različitim pH vrijednostima (1, 7 i 11). Fizičko-mehanička svojstva prekristaliziranog karbamazepina određivana su na sljedeći način: morfologija kristala ispitivana je pretraĆŸnom elektronskom mikroskopijom, polimorfi su identificirani rendgenskom difrakcijom praha (XRPD), a termodinamička svojstva analizirana su diferencijalnom pretraĆŸnom kalorimetrijom (DSC). Topljivost je određena pomoću aparata prema USP. Mehanička svojstva prekristaliziranog karbamazepina ispitivana su tijekom tabletiranja pri različitim tlakovima i mjerenjem tvrdoće nastalih tableta. SEM ispitivanja pokazala su da kristalizacija karbamazepina iz različitih medija utječe na morfologiju i veličinu kristala. Oblik kristala mijenjao se od pahuljastog ili pločastog do igličastog. Rezultati dobiveni XRPD i DSC metodama isključili su promjene kristaliničnosti zbog temperature ili pH medija. Mjerenjem lomljivosti tableta utvrđeno je da su svi prekristalizirani uzorci karbamazepina bili kompaktniji od polaznog praĆĄkastog uzorka. Ispitivanja topljivosti in vitro pokazala su da su kristali dobiveni iz otopine s pH 11 i 1 topljiviji. Uzorci karbamazepina dobiveni prekristalizacijom iz vodenih otopina različite pH vrijednosti imali su bolja mehanička svojstva od originalnog uzorka karbamazepina

    Effects of the granule composition on the compaction behavior of deformable dry granules

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    Calibration of the Drucker Prager Cap (DPC) model parameters provides a means for a deeper understanding of the impact of granule composition on the compaction properties of dry granules independent of their solid fraction (SF). In this study, monodisperse granules of mixtures of microcrystalline cellulose and mannitol (0%, 25%, 50%, 75% and 100% mannitol) prepared as small cylindrical compacts with well-defined size, shape and SF (0.58) were used as model dry granules. DPC parameters--namely, cohesion, internal friction angle, cap eccentricity, and hydrostatic yield strength of materials--were determined from the diametrical and uniaxial compression, and in-die compaction tests. Elastic properties such as Young’s modulus and Poisson’s ratios were also determined from the in-die compaction test. Higher level of MNT in granules required a lower compression pressure to obtain a low SF tablet but higher compression pressure to obtain a high SF tablets. Properties such as cohesion and diametrical tensile strength go through a maximum as the mannitol level increases in the binary granules, and clearly do not follow the linear mixing rule. At an industrially-relevant tablet solid fraction of 0.88, granules with 75% mannitol exhibited the highest cohesion, and produced the strongest tablet. Other properties either approximately follow the linear mixing rule (e.g., hydrostatic yield strength, young's modulus and Poisson’s ratio) where some interactions between the constituents are present, or not sensitive to the composition (e.g., internal angle of friction). In general, the compaction behavior of granules of a multicomponent system may not be precisely estimated from the properties of individual components, simply by using the linear mixing rule

    Compaction mechanics of plastically deformable dry granules

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    To improve the understanding of how dry granulation and in particular, granule solid fraction (SF) impact the compaction behavior of plastically deformable microcrystalline cellulose (MCC), in this study, the Drucker Prager Cap (DPC) model parameters were calibrated using monodisperse MCC dry granules as model granules. Dry granules were produced as directly compressed small cylindrical compacts of MCC with SF in the range of 0.40 to 0.70 which were monodisperse in both size and SF. Virgin MCC powder and granules were compressed into tablets with SF in the range of 0.70 to 0.90. The DPC parameters (cohesion, internal friction angle, cap eccentricity, and hydrostatic yield stress), Young's modulus and Poisson's ratio were experimentally determined from diametrical and uniaxial compression, and in-die compaction tests. Results showed that calibration of the shear failure surface only may be adequate for MCC granules when the DPC model is completely calibrated for virgin MCC. Increasing granule SF significantly decreased the cohesion only. All other parameters were impacted by the tablet SF only. In the 2D yield surface, only the shear failure surface expanded as the granule SF increased. MCC of any granulation status requires the same in-die compaction stress state for densification to a given tablet solid fraction

    Epigenetic Gene Promoter Methylation at Birth Is Associated With Child’s Later Adiposity

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    Objective: fixed genomic variation explains only a small proportion of the risk of adiposity. In animal models, maternal diet alters offspring body composition, accompanied by epigenetic changes in metabolic control genes. Little is known about whether such processes operate in humans.Research design and methods: using Sequenom MassARRAY we measured the methylation status of 68 CpGs 5? from five candidate genes in umbilical cord tissue DNA from healthy neonates. Methylation varied greatly at particular CpGs: for 31 CpGs with median methylation ?5% and a 5–95% range ?10%, we related methylation status to maternal pregnancy diet and to child’s adiposity at age 9 years. Replication was sought in a second independent cohort.Results: in cohort 1, retinoid X receptor-? (RXRA) chr9:136355885+ and endothelial nitric oxide synthase (eNOS) chr7:150315553+ methylation had independent associations with sex-adjusted childhood fat mass (exponentiated regression coefficient [?] 17% per SD change in methylation [95% CI 4–31], P = 0.009, n = 64, and ? = 20% [9–32], P < 0.001, n = 66, respectively) and %fat mass (? = 10% [1–19], P = 0.023, n = 64 and ? =12% [4–20], P = 0.002, n = 66, respectively). Regression analyses including sex and neonatal epigenetic marks explained >25% of the variance in childhood adiposity. Higher methylation of RXRA chr9:136355885+, but not of eNOS chr7:150315553+, was associated with lower maternal carbohydrate intake in early pregnancy, previously linked with higher neonatal adiposity in this population. In cohort 2, cord eNOS chr7:150315553+ methylation showed no association with adiposity, but RXRA chr9:136355885+ methylation showed similar associations with fat mass and %fat mass (? = 6% [2–10] and ? = 4% [1–7], respectively, both P = 0.002, n = 239).Conclusions: our findings suggest a substantial component of metabolic disease risk has a prenatal developmental basis. Perinatal epigenetic analysis may have utility in identifying individual vulnerability to later obesity and metabolic diseas

    Evolution of Plant-Made Pharmaceuticals

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    The science and policy of pharmaceuticals produced and/or delivered by plants has evolved over the past twenty-one years from a backyard remedy to regulated, purified products. After seemingly frozen at Phase I human clinical trials with six orally delivered plant-made vaccines not progressing past this stage over seven years, plant-made pharmaceuticals have made a breakthrough with several purified plant-based products advancing to Phase II trials and beyond. Though fraught with the usual difficulties of pharmaceutical development, pharmaceuticals made by plants have achieved pertinent milestones albeit slowly compared to other pharmaceutical production systems and are now at the cusp of reaching the consumer. Though the current economic climate begs for cautious investment as opposed to trail blazing, it is perhaps a good time to look to the future of plant-made pharmaceutical technology to assist in planning for future developments in order not to slow this technology’s momentum. To encourage continued progress, we highlight the advances made so far by this technology, particularly the change in paradigms, comparing developmental timelines, and summarizing the current status and future possibilities of plant-made pharmaceuticals
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