Oral activated charcoal prevents experimental cerebral malaria in mice and in a randomized controlled clinical trial in man did not interfere with the pharmacokinetics of parenteral artesunate.

BACKGROUND: Safe, cheap and effective adjunct therapies preventing the development of, or reducing the mortality from, severe malaria could have considerable and rapid public health impact. Oral activated charcoal (oAC) is a safe and well tolerated treatment for acute poisoning, more recently shown to have significant immunomodulatory effects in man. In preparation for possible efficacy trials in human malaria, we sought to determine whether oAC would i) reduce mortality due to experimental cerebral malaria (ECM) in mice, ii) modulate immune and inflammatory responses associated with ECM, and iii) affect the pharmacokinetics of parenteral artesunate in human volunteers. METHODS/PRINCIPAL FINDINGS: We found that oAC provided significant protection against P. berghei ANKA-induced ECM, increasing overall survival time compared to untreated mice (p<0.0001; hazard ratio 16.4; 95% CI 6.73 to 40.1). Protection from ECM by oAC was associated with reduced numbers of splenic TNF(+) CD4(+) T cells and multifunctional IFNgamma(+)TNF(+) CD4(+) and CD8(+) T cells. Furthermore, we identified a whole blood gene expression signature (68 genes) associated with protection from ECM. To evaluate whether oAC might affect current best available anti-malarial treatment, we conducted a randomized controlled open label trial in 52 human volunteers (ISRCTN NR. 64793756), administering artesunate (AS) in the presence or absence of oAC. We demonstrated that co-administration of oAC was safe and well-tolerated. In the 26 subjects further analyzed, we found no interference with the pharmacokinetics of parenteral AS or its pharmacologically active metabolite dihydroartemisinin. CONCLUSIONS/SIGNIFICANCE: oAC protects against ECM in mice, and does not interfere with the pharmacokinetics of parenteral artesunate. If future studies succeed in establishing the efficacy of oAC in human malaria, then the characteristics of being inexpensive, well-tolerated at high doses and requiring no sophisticated storage would make oAC a relevant candidate for adjunct therapy to reduce mortality from severe malaria, or for immediate treatment of suspected severe malaria in a rural setting. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64793756

Recording Earthen Architecture at the Peruvian Andes: the Case of KUÑO Tambo CHURCH'S Historic Wall Paintings

According to UNESCO “Earthen architecture is one of the most original and powerful expressions of our ability to create a built environment with readily available resources. It includes a great variety of structures, ranging from mosques, palaces and granaries, to historic city centres, cultural landscapes and archaeological sites” (WHEAP, 2007). This contribution looks at developing effective methods for recording earthen his

Documentation for Emergency Stabilization and the Integrated Conservation Planning of Earthen Architecture Settlements: the Kasbah of Taourirt (Ouarzazate, Morocco)

Heritage recording serves as a basis for methodologies regarding diagnosis, treatment and preservation of historic places and contributes to make posterity records of our built cultural heritage. This work is not a stand-alone practice, but a part of the overall conservation of cultural heritage. Reco

Light Curves and Period Changes of Type II Cepheids in the Globular Clusters M3 and M5

Light curves in the B, V, and I_c passbands have been obtained for the type II Cepheids V154 in M3 and V42 and V84 in M5. Alternating cycle behavior, similar to that seen among RV Tauri variables, is confirmed for V84. Old and new observations, spanning more than a century, show that V154 has increased in period while V42 has decreased in period. V84, on the other hand, has shown large, erratic changes in period that do not appear to reflect the long term evolution of V84 through the HR diagram.Comment: 28 pages, 12 figure

Microfoundations

The paper argues that the microfoundations programme can be understood as an implementation of an underlying methodological principle, methodological individualism, and that it therefore shares a fundamental ambiguity with that principle, viz, whether the macro must be derived from and therefore reducible to, or rather consistent with micro-level behaviours. The pluralist conclusion of the paper is not that research guided by the principle of microfoundations is necessarily wrong, but that the exclusion of approaches not guided by that principle is indeed necessarily wrong. The argument is made via an examination of the advantages claimed for dynamic stochastic general equilibrium models, the relationship between parts and wholes in social science, and the concepts of reduction, substrate neutrality, the intentional stance, and hypostatisation

Microfoundations

This paper argues that the microfoundations programme can be understood as an implementation of an underlying methodological principle—methodological individualism—and that it therefore shares a fundamental ambiguity with that principle, viz, whether the macro must be derived from and therefore reducible to, or rather consistent with, micro-level behaviours. The pluralist conclusion of the paper is not that research guided by the principle of microfoundations is necessarily wrong, but that the exclusion of approaches not guided by that principle is indeed necessarily wrong. The argument is made via an examination of the advantages claimed for dynamic stochastic general equilibrium models, the relationship between parts and wholes in social science, and the concepts of reduction, substrate neutrality, the intentional stance, and hypostatisation

Bioactive Endophytes Warrant Intensified Exploration and Conservation

A key argument in favor of conserving biodiversity is that as yet undiscovered biodiversity will yield products of great use to humans. However, the link between undiscovered biodiversity and useful products is largely conjectural. Here we provide direct evidence from bioassays of endophytes isolated from tropical plants and bioinformatic analyses that novel biology will indeed yield novel chemistry of potential value.We isolated and cultured 135 endophytic fungi and bacteria from plants collected in Peru. nrDNAs were compared to samples deposited in GenBank to ascertain the genetic novelty of cultured specimens. Ten endophytes were found to be as much as 15–30% different than any sequence in GenBank. Phylogenetic trees, using the most similar sequences in GenBank, were constructed for each endophyte to measure phylogenetic distance. Assays were also conducted on each cultured endophyte to record bioactivity, of which 65 were found to be bioactive.The novelty of our contribution is that we have combined bioinformatic analyses that document the diversity found in environmental samples with culturing and bioassays. These results highlight the hidden hyperdiversity of endophytic fungi and the urgent need to explore and conserve hidden microbial diversity. This study also showcases how undergraduate students can obtain data of great scientific significance

The Impact of Advocacy Organizations on Low-Income Housing Policy in U.S. Cities

Financial support for affordable housing competes with many other municipal priorities. This work seeks to explain the variation in support for affordable housing among U.S. cities with populations of 100,000 or more. Using multivariate statistical analysis, this research investigates political explanations for the level of city expenditures on housing and community with a particular interest in the influence of housing advocacy organizations (AOs). Data for the model were gathered from secondary sources, including the U.S. Census and the National Center for Charitable Statistics. Among other results, the analysis indicates that, on average, the political maturity of AOs has a statistically significant, positive effect on local housing and community development expenditures

A survey for variable young stars with small telescopes: IX - Evolution of spot properties on YSOs in IC 5070

We present spot properties on 32 periodic young stellar objects in IC 5070. Long term, ∼5 yr, light curves in the V, R, and I-bands are obtained through the HOYS (Hunting Outbursting Young Stars) citizen science project. These are dissected into six months long slices, with 3 months oversampling, to measure 234 sets of amplitudes in all filters. We fit 180 of these with reliable spot solutions. Two thirds of spot solutions are cold spots, the lowest is 2150 K below the stellar temperature. One third are warm spots that are above the stellar temperature by less than ∼2000 K. Cold and warm spots have maximum surface coverage values of 40 per cent, although only 16 per cent of warm spots are above 20 per cent surface coverage as opposed to 60 per cent of the cold spots. Warm spots are most likely caused by a combination of plages and low density accretion columns, most common on objects without inner disc excess emission in K − W2. Five small hot spot solutions have &amp;lt;3 percent coverage and are 3000 – 5000 K above the stellar temperature. These are attributed to accretion, and four of them occur on the same object. The majority of our objects are likely to be accreting. However, we observe very few accretion hot spots as either the accretion is not stable on our timescale or the photometry is dominated by other features. We do not identify cyclical spot behaviour on the targets. We additionally identify and discuss a number of objects that have interesting amplitudes, phase changes, or spot properties