Erythropoietin therapy for acute stroke is both safe and beneficial

BACKGROUND: Erythropoietin (EPO) and its receptor play a major role in embryonic brain, are weakly expressed in normal postnatal/adult brain and up-regulated upon metabolic stress. EPO protects neurons from hypoxic/ ischemic injury. The objective of this trial is to study the safety and efficacy of recombinant human EPO (rhEPO) for treatment of ischemic stroke in man. MATERIALS AND METHODS: The trial consisted of a safety part and an efficacy part. In the safety study, 13 patients received rhEPO intravenously (3.3 X 10(4) IU/50 ml/30 min) once daily for the first 3 days after stroke. In the double-blind randomized proof-of-concept trial, 40 patients received either rhEPO or saline. Inclusion criteria were age <80 years, ischemic stroke within the middle cerebral artery territory confirmed by diffusion-weighted MRI, symptom onset <8 hr before drug administration, and deficits on stroke scales. The study endpoints were functional outcome at day 30 (Barthel Index, modified Rankin scale), NIH and Scandinavian stroke scales, evolution of infarct size (sequential MRI evaluation using diffusion-weighted [DWI] and fluid-attenuated inversion recovery sequences [FLAIR]) and the damage marker S100ss. RESULTS: No safety concerns were identified. Cerebrospinal fluid EPO increased to 60-100 times that of nontreated patients, proving that intravenously administered rhEPO reaches the brain. In the efficacy trial, patients received rhEPO within 5 hr of onset of symptoms (median, range 2:40-7:55). Admission neurologic scores and serum S100beta concentrations were strong predictors ofoutcome. Analysis of covariance controlled for these two variables indicated that rhEPO treatment was associated with an improvement in follow-up and outcome scales. A strong trend for reduction in infarct size in rhEPO patients as compared to controls was observed by MRI. CONCLUSION: Intravenous high-dose rhEPO is well tolerated in acute ischemic stroke and associated with an improvement in clinical outcome at 1 month. A larger scale clinical trial is warranted.     

Ungrateful predators: capture and the creation of Cofán violence

In this article, I explore the history, logic, and practice of capture among the Cofán people of Amazonian Ecuador. Rather than acting as the subjects of capture, Cofán people have primarily been its objects. Centuries of pre‐Conquest, colonial, and postcolonial violence have exposed Cofán communities to repeated seizures by indigenous and non‐indigenous aggressors. Although capture by enemy others is a feared prospect that typically brings disaster, it also serves as the Cofán nation's central means of acquiring violent powers, which are essential to its defence. By investigating the uncertainties of capture as a productive process, I question dominant representations of native Amazonians as wilful participants in a cosmos of generalized predation, and I issue a plea for openness when considering the diversity of the region's peoples.     

Bold jaguars and unsuspecting monkeys: the value of fearlessness in Cofán politics

In their encounters with a globalizing political landscape, indigenous peoples enact and transform long-standing social relations. This article explores the struggle of Amazonian Ecuador's Cofán people to relate their socio-existential values to the challenges of political mobilization. I argue that distinct conceptions of 'fearlessness' structure the complex relationship between the majority of Cofán people and those morally ambivalent individuals, including shamans and federation leaders, who mediate the threats posed by impinging sources of violent difference. By employing a value-based approach to analyse this relationship, I seek to connect studies of indigenous social movements to investigations of indigenous socio-cosmological orders.  

Résumé

Dans leur rencontre avec un paysage politique globalisé, les peuples autochtones pratiquent et transforment des relations sociales anciennes. L'auteur explore ici les efforts des Cofán d'Amazonie équatorienne pour lier leurs valeurs socio-existentielles aux défis de la mobilisation politique. Il avance que différentes conceptions de « l'intrépidité >> structurent les relations complexes entre la majorité des Cofán et les individus moralement ambivalents, notamment les chamans et les chefs de fédération, médiateurs des menaces exercées par les sources de différence violente. En utilisant une approche basée sur la valeur pour analyser cette relation, l'article cherche à faire le lien entre les études des mouvements sociaux autochtones et les investigations des ordres socio-cosmologiques indigènes.     

A Proteomic Approach for the Diagnosis of Bacterial Meningitis

Background

The discrimination of bacterial meningitis (BM) versus viral meningitis (VM) shapes up as a problem, when laboratory data are not equivocal, in particular, when Gram stain is negative.

Methodology/Principal Findings

With the aim to determine reliable marker for bacterial or viral meningitis, we subjected cerebrospinal fluid (CSF) to a quantitative proteomic screening. By using a recently established 2D-DIGE protocol which was adapted to the individual CSF flow, we compared a small set of patients with proven BM and VM. Thereby, we identified six potential biomarkers out of which Prostaglandin-H2 D-isomerase was already described in BM, showing proof of concept. In the subsequent validation phase on a more comprehensive collective of 80 patients, we could validate that in BM high levels of glial fibrillary acidic protein (GFAP) and low levels of soluble amyloid precursor protein alpha/beta (sAPPα/β) are present as possible binding partner of Fibulin-1.

Conclusions/Significance

We conclude that our CSF flow-adapted 2D-DIGE protocol is valid especially in comparing samples with high differences in total protein and suppose that GFAP and sAPPα/β have a high potential as additional diagnostic markers for differentiation of BM from VM. In the clinical setting, this might lead to an improved early diagnosis and to an individual therapy.     

Cerebrospinal fluid-optimized two-dimensional difference gel electrophoresis (2-D DIGE) facilitates the differential diagnosis of Creutzfeldt-Jakob disease

So far only the detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is included in the diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD). However, this assay cannot be used for screening because of the high rate of false positive results in sCJD, and often negative results in variant CJD. To facilitate the differential diagnosis of CJD, we applied 2-D differential gel-electrophoresis (2-D DIGE) as a quantitative proteomic screening system for CSF proteins. We compared 36 patients suffering from sCJD with 30 patients suffering from other neurodegenerative diseases. Sample preparation was optimized in consideration of the fact that CSF is composed of blood- and brain-derived proteins, and an improved 2-D DIGE protocol was established. Using this method in combination with protein identification by MALDI-TOF-MS, several known surrogate markers of sCJD like 14-3-3 protein, neuron-specific enolase, and lactate dehydrogenase were readily identified. Moreover, a not yet identified protein with an approximate molecular mass of 85 kDa was found as marker for sCJD with high diagnostic specificity and sensitivity. We conclude that our proteomic approach is useful to differentiate CJD from other neurodegenerative diseases and expect that CSF-optimized 2-D DIGE will find broad application in the search for other brain derived proteins in CSF.     

At what spatial scale(s) do mammals respond to urbanization?

Spatial scale is fundamental in understanding species–landscape relationships because species’ responses to landscape characteristics typically vary across scales. Nonetheless, such scales are often unidentified or unreliably predicted by theory. Many landscapes worldwide are urbanizing, yet the spatial scaling of species’ responses to urbanization is poorly understood. We investigated the spatial scaling of urbanization effects on a community of 15 mammal species using ~60 000 wildlife detections collected from a constellation of 207 camera traps across an extensive urban park system. We embedded a bivariate Gaussian kernel in hierarchical multi-species models to determine two scales of effect (a scale of maximal effect and a broader scale of cumulative landscape effect) for two biological responses (occupancy and site visit frequency) across two seasons (winter and summer) for each species. We then assessed whether scales of effect varied according to theoretical predictions associated with biological responses and species traits (body size and mobility). Scales of effect ranged from < 50 m to > 9000 m and varied among species, but not as predicted by theory. Species’ occupancy generally showed a weak response to urbanization and the scale of this effect was both highly uncertain and consistent across species. We did not detect any relationship between scales of effect and species’ body size or mobility, nor was there any evident pattern of scaling across biological response or seasons. These results imply that 1) urbanization effects on mammals manifest across a very broad spectrum of spatial scales, and 2) current theories that a priori predict the scale at which urbanization affects mammals may be of limited use within a given system. Overall, this study suggests that developing general theory regarding the scaling of species–landscape relationships requires additional empirical work conducted across multiple species, systems and timescales.     

Exposure time of oral rabies vaccine baits relative to baiting density and raccoon population density

Oral rabies vaccination (ORV) baiting programs for control of raccoon (Procyon lotor) rabies in the USA have been conducted or are in progress in eight states east of the Mississippi River. However, data specific to the relationship between raccoon population density and the minimum density of baits necessary to significantly elevate rabies immunity are few. We used the 22-km2 US National Aeronautics and Space Administration Plum Brook Station (PBS) in Erie County, Ohio, USA, to evaluate the period of exposure for placebo vaccine baits placed at a density of 75 baits/km2 relative to raccoon population density. Our objectives were to 1) estimate raccoon population density within the fragmented forest, old-field, and industrial landscape at PBS: and 2) quantify the time that placebo, Merial RABORAL V-RG vaccine baits were available to raccoons. From August through November 2002 we surveyed raccoon use of PBS along 19.3 km of paved-road transects by using a forward-looking infrared camera mounted inside a vehicle. We used Distance 3.5 software to calculate a probability of detection function by which we estimated raccoon population density from transect data. Estimated population density on PBS decreased from August (33.4 raccoons/km2) through November (13.6 raccoons/km2), yielding a monthly mean of 24.5 raccoons/km2. We also quantified exposure time for ORV baits placed by hand on five 1-km2 grids on PBS from September through October. An average 82.7% (SD = 4.6) of baits were removed within 1 wk of placement. Given raccoon population density, estimates of bait removal and sachet condition, and assuming 22.9% nontarget take, the baiting density of 75/ km2 yielded an average of 3.3 baits consumed per raccoon and the sachet perforated.