Evaluation and pharmacovigilance of projects promoting cultivation and local use of Artemisia annua for malaria

<p>Abstract</p> <p>Background</p> <p>Several non-governmental organisations (NGOs) are promoting the use of <it>Artemisia annua </it>teas as a home-based treatment for malaria in situations where conventional treatments are not available. There has been controversy about the effectiveness and safety of this approach, but no pharmacovigilance studies or evaluations have been published to date.</p> <p>Method</p> <p>A questionnaire about the cultivation of <it>A. annua</it>, treatment of patients, and side-effects observed, was sent to partners of the NGO Anamed in Kenya and Uganda. Some of the respondents were then selected purposively for more in-depth semi-structured interviews.</p> <p>Results</p> <p>Eighteen partners in Kenya and 21 in Uganda responded. 49% reported difficulties in growing the plant, mainly due to drought. Overall about 3,000 cases of presumed malaria had been treated with <it>A. annua </it>teas in the previous year, of which about 250 were in children and 54 were in women in the first trimester of pregnancy. The commonest problem observed in children was poor compliance due to the bitter taste, which was improved by the addition of sugar or honey. Two miscarriages were reported in pregnant patients. Only four respondents reported side-effects in other patients, the commonest of which was vomiting. 51% of respondents had started using <it>A. annua </it>tea to treat illnesses other than malaria.</p> <p>Conclusions</p> <p>Local cultivation and preparation of <it>A. annua </it>are feasible where growing conditions are appropriate. Few adverse events were reported even in children and pregnant women. Where ACT is in short supply, it would make sense to save it for young children, while using <it>A. annua </it>infusions to treat older patients who are at lower risk. An ongoing pharmacovigilance system is needed to facilitate reporting of any adverse events.</p

Domestication as innovation : the entanglement of techniques, technology and chance in the domestication of cereal crops

The origins of agriculture involved pathways of domestication in which human behaviours and plant genetic adaptations were entangled. These changes resulted in consequences that were unintended at the start of the process. This paper highlights some of the key innovations in human behaviours, such as soil preparation, harvesting and threshing, and how these were coupled with genetic ‘innovations’ within plant populations. We identify a number of ‘traps’ for early cultivators, including the needs for extra labour expenditure on crop-processing and soil fertility maintenance, but also linked gains in terms of potential crop yields. Compilations of quantitative data across a few different crops for the traits of nonshattering and seed size are discussed in terms of the apparently slow process of domestication, and parallels and differences between different regional pathways are identified. We highlight the need to bridge the gap between a Neolithic archaeobotanical focus on domestication and a focus of later periods on crop-processing activities and labour organization. In addition, archaeobotanical data provide a basis for rethinking previous assumptions about how plant genetic data should be related to the origins of agriculture and we contrast two alternative hypotheses: gradual evolution with low selection pressure versus metastable equilibrium that prolonged the persistence of ‘semi-domesticated’ populations. Our revised understanding of the innovations involved in plant domestication highlight the need for new approaches to collecting, modelling and integrating genetic data and archaeobotanical evidence

Doublet structures in quantum well absorption spectra due to Fano-related interference

In this theoretical investigation we predict an unusual interaction between a discrete state and a continuum of states, which is closely related to the case of Fano-interference. It occurs in a GaAs/AlxGa1-xAs quantum well between the lowest light-hole exciton and the continuum of the second heavy-hole exciton. Unlike the typical case for Fano-resonance, the discrete state here is outside the continuum; we use uniaxial stress to tune its position with respect to the onset of the continuum. State-of-the art calculations of absorption spectra show that as the discrete state approaches the continuum, a doublet structure forms which reveals anticrossing behaviour. The minimum separation energy of the anticrossing depends characteristically on the well width and is unusually large for narrow wells. This offers striking evidence for the strong underlying valence-band mixing. Moreover, it proves that previous explanations of similar doublets in experimental data, employing simple two-state models, are incomplete.Comment: 21 pages, 5 figures and 5 equations. Accepted for publication in Physical Review

Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohort

We studied prospectively the midlife handgrip strength, living habits, and parents’ longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu–Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965–1968, when they were 56–68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment. Longevity was categorized as centenarian (≥100 years, n = 47), nonagenarian (90–99 years, n = 545), octogenarian (80–89 years, n = 847), and ≤79 years (n = 801, reference). The average survival after baseline was 20.8 years (SD = 9.62). Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23–5.10) more often to the highest third of grip strength in midlife, were never smokers (OR = 5.75 95% CI = 3.06–10.80), had participated in physical activity outside work (OR = 1.13 per daily hour, 95% CI = 1.02–1.25), and had a long-lived mother (≥80 vs. ≤60 years, OR = 2.3, 95% CI = 1.06–5.01). Associations for nonagenarians and octogenarians were parallel, but weaker. Multivariate modeling showed that mother’s longevity and offspring’s grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity

Genetic Studies of Sulfadiazine-resistant and Methionine-requiring \u3cem\u3eNeisseria\u3c/em\u3e Isolated From Clinical Material

Deoxyribonucleate (DNA) preparations were extracted from Neisseria meningitidis (four isolates from spinal fluid and blood) and N. gonorrhoeae strains, all of which were resistant to sulfadiazine upon primary isolation. These DNA preparations, together with others from in vitro mutants of N. meningitidis and N. perflava, were examined in transformation tests by using as recipient a drug-susceptible strain of N. meningitidis (Ne 15 Sul-s Met+) which was able to grow in a methionine-free defined medium. The sulfadiazine resistance typical of each donor was introduced into the uniform constitution of this recipient. Production of p-aminobenzoic acid was not significantly altered thereby. Transformants elicited by DNA from the N. meningitidis clinical isolates were resistant to at least 200 μg of sulfadiazine/ml, and did not show a requirement for methionine (Sul-r Met+). DNA from six strains of N. gonorrhoeae, which were isolated during the period of therapeutic use of sulfonamides, conveyed lower degrees of resistance and, invariably, a concurrent methionine requirement (Sul-r/Met−). The requirement of these transformants, and that of in vitro mutants selected on sulfadiazine-agar, was satisfied by methionine, but not by vitamin B12, homocysteine, cystathionine, homoserine, or cysteine. Sul-r Met+ and Sul-r/Met− loci could coexist in the same genome, but were segregated during transformation. On the other hand, the dual Sul-r/Met− properties were not separated by recombination, but were eliminated together. DNA from various Sul-r/Met− clones tested against recipients having nonidentical Sul-r/Met− mutant sites yielded Sul-s Met+ transformants. The met locus involved is genetically complex, and will be a valuable tool for studies of genetic fine structure of members of Neisseria, and of genetic homology between species

Evidence for population inversion in excited electron states of a double barrier resonant tunneling structure

We report evidence for a population inversion between excited electron states of the quantum well of a GaAs‐AlGaAs double barrier resonant tunneling structure (DBRTS). The relative populations of the states are determined by photoluminescence spectroscopy of the tunneling electrons in the structure. When the DBRTS is biased at the fourth electron resonance, the population of the n=4 confined level is found to be greater than that of the n=3 state. We show that such a population inversion is consistent with a rate equation analysis of the relative populations of the two levels when electrons tunnel into n=4

Dental microwear texture analysis of Homo sapiens sapiens: foragers, farmers, and pastoralists

Objectives. The current study seeks to determine if a sample of foragers, farmers, and pastoralists can be distinguished by their dental microwear texture signatures. Materials and Methods. The study included a sample of 719 individuals from 51 archaeological sites (450 farmers, 192 foragers, 77 pastoralists). All were over age 12 and sexes were pooled. Using a Sensofar® white-light confocal profiler we collected dental microwear texture analysis (DMTA) data from a single first or second molar from each individual. We leveled and cleaned data clouds following standard procedures and analyzed the data with Sfrax® and Toothfrax® software. The DMTA variables were complexity and anisotropy. Statistics included ANOVA with partial eta squared and Hedges's g. We also performed a follow-up K-means cluster analysis. Results. We found significant differences between foragers and farmers and pastoralists for complexity and anisotropy, with foragers having greater complexity than either the farmers or the pastoralists. The farmers and pastoralists had greater anisotropy than the foragers. The Old World foragers had significantly higher anisotropy values than New World foragers. Old and New World farmers did not differ. Among the Old World farmers, those dating from the Neolithic through the Late Bronze Age had higher complexity values than those from the Iron Age through the medieval period. The cluster analysis discerned foragers and farmers but also indicated similarity between hard food foragers and hard food farmers. Discussion. Our findings reaffirm that DMTA is capable of distinguishing human diets. We found that foragers and farmers, in particular, differ in their microwear signatures across the globe. There are some exceptions, but nothing that would be unexpected given the range of human diets and food preparation techniques. This study indicates that in general DMTA is an efficacious means of paleodietary reconstruction in humans

Comparison of some Reduced Representation Approximations

In the field of numerical approximation, specialists considering highly complex problems have recently proposed various ways to simplify their underlying problems. In this field, depending on the problem they were tackling and the community that are at work, different approaches have been developed with some success and have even gained some maturity, the applications can now be applied to information analysis or for numerical simulation of PDE's. At this point, a crossed analysis and effort for understanding the similarities and the differences between these approaches that found their starting points in different backgrounds is of interest. It is the purpose of this paper to contribute to this effort by comparing some constructive reduced representations of complex functions. We present here in full details the Adaptive Cross Approximation (ACA) and the Empirical Interpolation Method (EIM) together with other approaches that enter in the same category

Anti-plasmodial polyvalent interactions in Artemisia annua L. aqueous extract – possible synergistic and resistance mechanisms

Artemisia annua hot water infusion (tea) has been used in in vitro experiments against P. falciparum malaria parasites to test potency relative to equivalent pure artemisinin. High performance liquid chromatography (HPLC) and mass spectrometric analyses were employed to determine the metabolite profile of tea including the concentrations of artemisinin (47.5±0.8 mg L-1), dihydroartemisinic acid (70.0±0.3 mg L-1), arteannuin B (1.3±0.0 mg L-1), isovitexin (105.0±7.2 mg L-1) and a range of polyphenolic acids. The tea extract, purified compounds from the extract, and the combination of artemisinin with the purified compounds were tested against chloroquine sensitive and chloroquine resistant strains of P. falciparum using the DNA-intercalative SYBR Green I assay. The results of these in vitro tests and of isobologram analyses of combination effects showed mild to strong antagonistic interactions between artemisinin and the compounds (9-epi-artemisinin and artemisitene) extracted from A. annua with significant (IC50 <1 μM) anti-plasmodial activities for the combination range evaluated. Mono-caffeoylquinic acids, tri-caffeoylquinic acid, artemisinic acid and arteannuin B showed additive interaction while rosmarinic acid showed synergistic interaction with artemisinin in the chloroquine sensitive strain at a combination ratio of 1:3 (artemisinin to purified compound). In the chloroquine resistant parasite, using the same ratio, these compounds strongly antagonised artemisinin anti-plasmodial activity with the exception of arteannuin B, which was synergistic. This result would suggest a mechanism targeting parasite resistance defenses for arteannuin B’s potentiation of artemisinin