In Vivo Efficacy of Artemether-Lumefantrine and Chloroquine against Plasmodium vivax: A Randomized Open Label Trial in Central Ethiopia

Background In vivo efficacy assessments of antimalarials are essential for ensuring effective case management. In Ethiopia, chloroquine (CQ) without primaquine is the first-line treatment for Plasmodium vivax in malarious areas, but artemether-lumefantrine (AL) is also commonly used. Methods and Findings In 2009, we conducted a 42-day efficacy study of AL or CQ for P. vivax in Oromia Regional State, Ethiopia. Individuals with P. vivax monoinfection were enrolled. Primary endpoint was day 28 cure rate. In patients with recurrent parasitemia, drug level and genotyping using microsatellite markers were assessed. Using survival analysis, uncorrected patient cure rates at day 28 were 75.7% (95% confidence interval (CI) 66.8–82.5) for AL and 90.8% (95% CI 83.6–94.9) for CQ. During the 42 days of follow-up, 41.6% (47/113) of patients in the AL arm and 31.8% (34/107) in the CQ arm presented with recurrent P. vivax infection, with the median number of days to recurrence of 28 compared to 35 days in the AL and CQ arm, respectively. Using microsatellite markers to reclassify recurrent parasitemias with a different genotype as non-treatment failures, day 28 cure rates were genotype adjusted to 91.1% (95% CI 84.1–95.1) for AL and to 97.2% (91.6–99.1) for CQ. Three patients (2.8%) with recurrent parasitemia by day 28 in the CQ arm were noted to have drug levels above 100 ng/ml. Conclusions In the short term, both AL and CQ were effective and well-tolerated for P. vivax malaria, but high rates of recurrent parasitemia were noted with both drugs. CQ provided longer post-treatment prophylaxis than AL, resulting in delayed recurrence of parasitemia. Although the current policy of species-specific treatment can be maintained for Ethiopia, the co-administration of primaquine for treatment of P. vivax malaria needs to be urgently considered to prevent relapse infections. Trial Registration ClinicalTrials.gov NCT0105258

Nautical Research Platform for Water-Bound Experiments

Conducting research in lakes and rivers requires large crews and heavy-duty equipment, making even simple tests more costly and time consuming. Newer research methods are evolving constantly as new technology enables more precise and accessible experiments to be conducted. The need for simple execution of water-bound experiments exists and must be addressed to aid our understanding of these environments. We at the Microgravity Undergraduate Research Team have taken our previous research in autonomous Unmanned Surface Vehicles (USVs) and applied our efforts to relieving this problem. Our current research aims to provide a universal platform for research and experiments to be conducted in lakes and rivers, where we can then expand our efforts to more broad applications. The design allows for remote-control navigation by one user and easy portability. To address precision in experimentation, we have integrated autonomous GPS waypoint navigation which removes user error in sensitive measurements. The most important factor in its design is modularity; the ability to accommodate a wide range of equipment for research. Our platform succeeds in making water-bound experiments more accessible and more precise for a multitude of potential applications

Simposio Internacional “Mundos Conectados: Saberes, imágenes y sonidos del Caribe y Centroamérica en el mundo atlántico"

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Amanda Denham\u27s Promo

Promo for Amanda Denham\u27s art exhibit. Designed by Emmaline Poehttps://jagworks.southalabama.edu/flyers/1017/thumbnail.jp

New Classification of Caprock Associated with Salt Diapirs

Caprock assemblages associated with salt bodies typically consist of a vertically zoned sequence in ascending order: anhydrite directly above the salt body, a transitional gypsum zone, and occasionally a complex zone of limestone and/or dolomite. Caprock forms when the upper part of a rising diapir is exposed to a crossflow of NaCl-undersaturated water, causing halite to dissolve and the less soluble components, largely anhydrite and to a lesser extent gypsum, to accrete via underplating to the base of the previously formed caprock. If hydrocarbons are present, the CaSO4 minerals are replaced by carbonate minerals in a process mediated by sulfate-reducing bacteria. Utilizing new facies mapping and petrographic analysis of outcropping caprock from three different salt basins, Paradox Basin and Gulf Coast Region, USA and Flinders Ranges, South Australia, we recognize a wider variety of fabrics and mineralogies. We propose a new classification based on fabric types in order to facilitate a discussion and interpretation of caprock lithologies in an organized and effective manner. The development of a comprehensive classification is the first step toward deciphering the complex diagenetic processes involved in caprock formation. Understanding the genetic history of caprock fabrics will allow for better identification and prediction of the distribution of caprock mineralogies and fabrics. We introduce the term “capstone” to be used when discussing a particular caprock lithology, as disambiguation for the term “caprock” that is used for discussing the entire rock body. Capstone classification is based on the recognition of four distinct megascopic fabric types: 1) massive: consisting of a homogeneous mineralogy and texture; 2) porphyritic: comprising two distinct crystal sizes; 3) layered, with microlaminated, laminated, and banded as subdivisions based on layer size; and 4) brecciated, which is subdivided based on the degree of separation between capstone clasts, which may be closely, loosely, or spatially independent and subdivided into crackle breccia, mosaic breccia and disorganized breccia, respectively. The classification scheme presented here is chiefly descriptive and directs attention to specific diagenetic fabric properties that may be significant to deciphering a paragenetic history, thereby unlocking an archive of the fluid history at salt diapirs

A monkey's tale: The origin of Plasmodium vivax as a human malaria parasite

The high prevalence of Duffy negativity (lack of the Duffy blood group antigen) among human populations in sub-Saharan Africa has been used to argue that Plasmodium vivax originated on that continent. Here, we investigate the phylogenetic relationships among 10 species of Plasmodium that infect primates by using three genes, two nuclear (β-tubulin and cell division cycle 2) and a gene from the plastid genome (the elongation factor Tu). We find compelling evidence that P. vivax is derived from a species that inhabited macaques in Southeast Asia. Specifically, those phylogenies that include P. vivax as an ancient lineage from which all of the macaque parasites could originate are significantly less likely to explain the data. We estimate the time to the most recent common ancestor at four neutral gene loci from Asian and South American isolates (a minimum sample of seven isolates per locus). Our analysis estimates that the extant populations of P. vivax originated between 45,680 and 81,607 years ago. The phylogeny and the estimated time frame for the origination of current P. vivax populations are consistent with an “out of Asia” origin for P. vivax as hominoid parasite. The current debate regarding how the Duffy negative trait became fixed in Africa needs to be revisited, taking into account not only human genetic data but also the genetic diversity observed in the extant P. vivax populations and the phylogeny of the genus Plasmodium

A Structure-Activity Relationship Comparison of Imidazodiazepines Binding at Kappa, Mu, and Delta Opioid Receptors and the GABAA Receptor

Analgesic and anti-inflammatory properties mediated by the κ opioid receptor (KOR) have been reported for oxadiazole imidazodiazepines. Affinities determined by radioligand competition assays of more than seventy imidazodiazepines using cell homogenates from HEK293 cells that overexpress KOR, µ opioid receptor (MOR), and δ opioid receptor (DOR) are presented. Affinities to synaptic, benzodiazepine-sensitive receptors (BZR) were determined with rat brain extract. The highest affinity for KOR was recorded for GL-I-30 (Ki of 27 nM) and G-protein recruitment was observed with an EC50 of 32 nM. Affinities for MOR and DOR were weak for all compounds. Ester and amide imidazodiazepines were among the most active KOR ligands but also competed with 3H-flunitrazepam for brain extract binding, which is mediated predominately by gamma aminobutyric acid type A receptors (GABAAR) of the α1-3β2-3γ1-2 subtypes. Imidazodiazepines with carboxylic acid and primary amide groups did not bind KOR but interacted strongly with GABAARs. Pyridine substitution reduced KOR affinity. Oxadiazole imidazodiazepines exhibited good KOR binding and interacted weakly with BZR, whereas oxazole imidazodiazepines were more selective towards BZR. Compounds that lack the imidazole moiety, the pendent phenyl, or pyridine substitutions exhibited insignificant KOR affinities. It can be concluded that a subset of imidazodiazepines represents novel KOR ligands with high selectivity among opioid receptors

The controllers used to make responses in each condition.

(A) Image of the Logitech F310 controller used in the 2D and 3D conditions (B) Image of the HTC Vive hand controllers used in the VR condition.</p

The participants’ view in the VR, 3D, and 2D conditions.

(A) An example screenshot of the view for participants in the VR condition. Specifically, this showcases the participant’s view at the beginning of each trial. No stimulus features are visible. (B) An example screenshot from the 3D condition showing the participant’s point of view during the feedback phase. Participant’s choice shown in red, correct answer shown in green. Participant’s choice lights up in green if they answered correctly. (C) The 2D stimulus as presented to the 2D group. Symbols and category structure are the same across all three conditions.</p