Bayesian and Frequentist Inference for Synthetic Controls

The synthetic control method has become a widely popular tool to estimate causal effects with observational data. Despite this, inference for synthetic control methods remains challenging. Often, inferential results rely on linear factor model data generating processes. In this paper, we characterize the conditions on the factor model primitives (the factor loadings) for which the statistical risk minimizers are synthetic controls (in the simplex). Then, we propose a Bayesian alternative to the synthetic control method that preserves the main features of the standard method and provides a new way of doing valid inference. We explore a Bernstein-von Mises style result to link our Bayesian inference to the frequentist inference. For linear factor model frameworks we show that a maximum likelihood estimator (MLE) of the synthetic control weights can consistently estimate the predictive function of the potential outcomes for the treated unit and that our Bayes estimator is asymptotically close to the MLE in the total variation sense. Through simulations, we show that there is convergence between the Bayes and frequentist approach even in sparse settings. Finally, we apply the method to re-visit the study of the economic costs of the German re-unification and the Catalan secession movement. The Bayesian synthetic control method is available in the bsynth R-package

The Genus Galanthus: A Source of Bioactive Compounds

The Amaryllidaceae family is one of the 20 most important alkaloid-containing plant families (Zhong, 2005). It comprises about 1100 perennial bulbous species classified in 85 genera, distributed throughout the tropics and warm temperate regions of the world (Willis, 1988). The specific alkaloids produced by the amaryllidaceous plants have attracted considerable attention due to their interesting pharmacological activities. One of them, galanthamine, is a long acting, selective, reversible and competitive inhibitor of the acetylcholinesterase enzyme (Thomsen et al., 1998), which is marketed as a hydrobromide salt under the name of Razadyne® (formerly Reminyl®) and Nivalin® for the treatment of Alzheimer’s disease, poliomyelitis and other neurological diseases (Heinrich and Teoh, 2004). After its discovery in Galanthus woronowii by Proskurina and co-authors in 1955 (Proskurina et al., 1955), the pharmacological properties of galanthamine soon attracted the attention of the pharmaceutical industry. It was first produced by Sopharma (Bulgaria) under the name of Nivalin® from G. nivalis in the early 1960s, but due to the small plant size and variability of galanthamine content, this species was soon replaced by other plant sources (Berkov et al., 2009b). The genus Galanthus (Snowdrop; Greek gála "milk", ánthos "flower") comprises about 19 species (World Checklist of Selected Plant Families), and to our knowledge 11 have been investigated for their alkaloid content. Although the genus has only been partially studied, phytochemical work has revealed an exceptional diversity of alkaloid structures, many of them reported for the first time and with still unknown bioactivity. The present article provides a brief overview of the phytochemical studies within the genus Galanthus

Alkaloid profile in Pyrolirion albicans Herb. (Amaryllidaceae), a Peruvian endemic species

The Amaryllidaceae family is widely distributed in different regions of the neotropics and temperate areas of the world. Species of the subfamily Amaryllidoideae are unique in producing the alkaloid galanthamine, which inhibits the action of acetylcholinesterase and is used for the treatment of Alzheimer's disease. In Perú, 15 genera and 68 species belonging to the Amaryllidoideae have been reported in different types of forest, ranging from wet montane to dry, as well as the sandy biomes of the Pacific coastal region, with the greatest diversity in the south. In the tribe Eustephieae, the Andean genus Pyrolirion Herb has eight species, six of which are endemic to Peru. In this work, the leaves and bulbs of Pyrolirion albicans were analyzed for their alkaloid content for the first time, using gas chromatography (GC) coupled to mass spectrometry (MS). The alkaloids determined in the leaves were galanthamine, chlidanthine, tazettine and lycorine and those in the bulbs were galanthamine, N-demethylgalanthamine, vittatine/crinine, montanine, pancracine, sternbergine, lycorine and hippeastrine. Owing to their important bioactive properties, the high quantity of montanine and galanthamine determined in the bulbs is of particular interest. Keywords Amaryllidaceae alkaloids, GC-MS, Galanthamine, Montanine, Pyrolirion albicans, Endemis

QToF exact mass and ESI fragmentation of bioactive Amaryllidaceae alkaloids

Amaryllidaceae alkaloids are a particular group of alkaloids exclusive to the Amarylloideae subfamily. Important from a biological and pharmacological point of view, they have antiparasitic, antiviral and antitumoral activities. Notably, galanthamine has been approved by the FDA as an acetylcholinesterase inhibitory drug for the treatment of Alzheimer's disease. Overall, Amaryllidaceae alkaloids are easy to analyse by GC–MS, but some are difficult to differentiate or detect. In the current study, some of these problems were resolved by applying an alternative analytical technique, high resolution ESI-MS/MS, a soft ionisation method producing different fragmentation patterns. Amongst the Amaryllidaceae alkaloids, only galanthamine has been previously analysed by high resolution ESI-MS/MS. In this work, a large number of Amaryllidaceae alkaloids were studied by high resolution ESI-MS/MS, providing important new structural information

Research in natural products: Amaryllidaceae ornamental plants as sources of bioactive compounds

Podeu consultar el llibre complet a: http://hdl.handle.net/2445/12071

Revised NMR data for Incartine: an alkaloid from Galanthus elwesii

Phytochemical studies on Galanthus elwesii resulted in the isolation of five alkaloids: incartine, hordenine, hippeastrine, 8-O-demethylhomolycorine and lycorine. The NMR data given previously for incartine were revised and completed by two-dimensional 1H-1H and 1H-13C chemical shift correlation experiments. In vitro studies on the bioactivity of incartine were carried out

Alkaloid Composition and Biological Activities of the Amaryllidaceae Species <i>Ismene amancaes</i> (Ker Gawl.) Herb.

Natural products have always played a significant role in the search for new drugs. One of the most relevant alkaloid-containing plant groups is the Amaryllidaceae family, a source of exclusive structures with a wide variety of pharmacological activities. The aim of this work was to determine the alkaloid composition and biological potential of an extract from the bulbs of an endemic Peruvian Amaryllidaceae species Ismene amancaes (Ker Gawl.) Herb. The alkaloid profiling was carried out by GC-MS, which revealed the presence of 13 compounds, 2 of them unidentified. The plant extract was found to contain high amounts of lycoramine, a galanthamine-type alkaloid. The extract also presented low inhibitory potential against the enzymes AChE and BuChE, with IC50 values of 14.6 ± 0.6 and 37.6 ± 1.4 μg·mL-1, respectively, and good to moderate inhibitory activity against the protozoan Plasmodium falciparum strain FCR-3 (chloroquine-resistant), with IC50 values of 3.78 ± 0.3 μg·mL-1. This is the first report of the alkaloid profile of a plant of the Ismene genus, which could be an interesting source of bioactive compounds. Keywords: Alzheimer’s disease; Amaryllidaceae; Ismene amancaes; Plasmodium falciparum; alkaloids; malaria