1,301 research outputs found

    Embolic strokes of undetermined source: prevalence and patient features in the ESUS Global Registry

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    Background: Recent evidence supports that most non-lacunar cryptogenic strokes are embolic. Accordingly, these strokes have been designated as embolic strokes of undetermined source (ESUS). Aims: We undertook an international survey to characterize the frequency and clinical features of ESUS patients across global regions. Methods: Consecutive patients hospitalized for ischemic stroke were retrospectively surveyed from 19 stroke research centers in 19 different countries to collect patients meeting criteria for ESUS. Results: Of 2144 patients with recent ischemic stroke, 351 (16%, 95% CI 15% to 18%) met ESUS criteria, similar across global regions (range 16% to 21%), and an additional 308 (14%) patients had incomplete evaluation required for ESUS diagnosis. The mean age of ESUS patients (62 years; SD = 15) was significantly lower than the 1793 non-ESUS ischemic stroke patients (68 years, p ≤ 0.001). Excluding patients with atrial fibrillation (n = 590, mean age = 75 years), the mean age of the remaining 1203 non-ESUS ischemic stroke patients was 64 years (p = 0.02 vs. ESUS patients). Among ESUS patients, hypertension, diabetes, and prior stroke were present in 64%, 25%, and 17%, respectively. Median NIHSS score was 4 (interquartile range 2–8). At discharge, 90% of ESUS patients received antiplatelet therapy and 7% received anticoagulation. Conclusions: This cross-sectional global sample of patients with recent ischemic stroke shows that one-sixth met criteria for ESUS, with additional ESUS patients likely among those with incomplete diagnostic investigation. ESUS patients were relatively young with mild strokes. Antiplatelet therapy was the standard antithrombotic therapy for secondary stroke prevention in all global regions

    Blockade of MMP14 Activity in Murine Breast Carcinomas: Implications for Macrophages, Vessels, and Radiotherapy

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    Background: Matrix metalloproteinase (MMP) 14 may mediate tumor progression through vascular and immune-modulatory effects. Methods: Orthotopic murine breast tumors (4T1 and E0771 with high and low MMP14 expression, respectively; n = 5-10 per group) were treated with an anti-MMP14 inhibitory antibody (DX-2400), IgG control, fractionated radiation therapy, or their combination. We assessed primary tumor growth, transforming growth factor β (TGFβ) and inducible nitric oxide synthase (iNOS) expression, macrophage phenotype, and vascular parameters. A linear mixed model with repeated observations, with Mann-Whitney or analysis of variance with Bonferroni post hoc adjustment, was used to determine statistical significance. All statistical tests were two-sided. Results: DX-2400 inhibited tumor growth compared with IgG control treatment, increased macrophage numbers, and shifted the macrophage phenotype towards antitumor M1-like. These effects were associated with a reduction in active TGFβ and SMAD2/3 signaling. DX-2400 also transiently increased iNOS expression and tumor perfusion, reduced tissue hypoxia (median % area: control, 20.2%, interquartile range (IQR) = 6.4%-38.9%; DX-2400: 1.2%, IQR = 0.2%-3.2%, P = .044), and synergistically enhanced radiation therapy (days to grow to 800mm3: control, 12 days, IQR = 9-13 days; DX-2400 plus radiation, 29 days, IQR = 26-30 days, P < .001) in the 4T1 model. The selective iNOS inhibitor, 1400W, abolished the effects of DX-2400 on vessel perfusion and radiotherapy. On the other hand, DX-2400 was not capable of inducing iNOS expression or synergizing with radiation in E0771 tumors. Conclusion: MMP14 blockade decreased immunosuppressive TGFβ, polarized macrophages to an antitumor phenotype, increased iNOS, and improved tumor perfusion, resulting in reduced primary tumor growth and enhanced response to radiation therapy, especially in high MMP14-expressing tumor

    Carrots and sticks fail to change behavior in cocaine addiction.

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    Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of addicted individuals mainly rely on psychosocial approaches. Here we report on impairments in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior. When patients were rewarded for their behavior, prolonged training improved their response rate toward the goal but simultaneously rendered them insensitive to the consequences of their actions. By contrast, overtraining of avoidance behavior had no effect on patient performance. Our findings illustrate the ineffectiveness of punitive approaches and highlight the potential for interventions that focus on improving goal-directed behavior and implementing more desirable habits to replace habitual drug-taking.Sir Henry Wellcome Postdoctoral Fellowship (Grant ID: 101521/Z/12/Z)This is the author accepted manuscript. The final version is available from AAAS via http://dx.doi.org/10.1126/science.aaf370

    The impact of polio eradication on routine immunization and primary health care: a mixed-methods study.

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    BACKGROUND: After 2 decades of focused efforts to eradicate polio, the impact of eradication activities on health systems continues to be controversial. This study evaluated the impact of polio eradication activities on routine immunization (RI) and primary healthcare (PHC). METHODS: Quantitative analysis assessed the effects of polio eradication campaigns on RI and maternal healthcare coverage. A systematic qualitative analysis in 7 countries in South Asia and sub-Saharan Africa assessed impacts of polio eradication activities on key health system functions, using data from interviews, participant observation, and document review. RESULTS: Our quantitative analysis did not find compelling evidence of widespread and significant effects of polio eradication campaigns, either positive or negative, on measures of RI and maternal healthcare. Our qualitative analysis revealed context-specific positive impacts of polio eradication activities in many of our case studies, particularly disease surveillance and cold chain strengthening. These impacts were dependent on the initiative of policy makers. Negative impacts, including service interruption and public dissatisfaction, were observed primarily in districts with many campaigns per year. CONCLUSIONS: Polio eradication activities can provide support for RI and PHC, but many opportunities to do so remain missed. Increased commitment to scaling up best practices could lead to significant positive impacts

    WASP-167b/KELT-13b: Joint discovery of a hot Jupiter transiting a rapidly-rotating F1V star

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    peer reviewedWe report the joint WASP/KELT discovery of WASP-167b/KELT-13b, a transiting hot Jupiter with a 2.02-d orbit around a VV = 10.5, F1V star with [Fe/H] = 0.1 ±\pm 0.1. The 1.5 RJup_{\rm Jup} planet was confirmed by Doppler tomography of the stellar line profiles during transit. We place a limit of << 8 MJup_{\rm Jup} on its mass. The planet is in a retrograde orbit with a sky-projected spin-orbit angle of λ=165±5\lambda = -165^{\circ} \pm 5^{\circ}. This is in agreement with the known tendency for orbits around hotter stars to be more likely to be misaligned. WASP-167/KELT-13 is one of the few systems where the stellar rotation period is less than the planetary orbital period. We find evidence of non-radial stellar pulsations in the host star, making it a δ\delta-Scuti or γ\gamma-Dor variable. The similarity to WASP-33, a previously known hot-Jupiter host with pulsations, adds to the suggestion that close-in planets might be able to excite stellar pulsations

    WASP-92b, WASP-93b and WASP-118b: three new transiting close-in giant planets

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    KH and ACC acknowledge support from STFC doctoral training grant ST/M503812/1 and grant ST/M001296/1 respectively. The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2013-2016) under grant agreement number 312430 (OPTICON).We present the discovery of three new transiting giant planets, first detected with the WASP telescopes, and establish their planetary nature with follow up spectroscopy and ground-based photometric lightcurves. WASP-92 is an F7 star, with a moderately inflated planet orbiting with a period of 2.17 days, which has Rp = 1.461 ± 0.077RJ and Mp = 0.805 ± 0.068MJ. WASP-93b orbits its F4 host star every 2.73 days and has Rp = 1.597 ± 0.077RJ and Mp = 1.47 ± 0.029MJ. WASP-118b also has a hot host star (F6) and is moderately inflated, where Rp = 1.440 ± 0.036RJ and Mp = 0.513 ± 0.041MJ and the planet has an orbital period of 4.05 days. They are bright targets (V = 13.18, 10.97 and 11.07 respectively) ideal for further characterisation work, particularly WASP-118b, which is being observed by K2 as part of campaign 8. WASP-93b is expected to be tidally migrating outwards, which is divergent from the tidal behaviour of the majority of hot Jupiters discovered.Peer reviewe

    Physical, chemical and microbiological changes during natural fermentation of \"gowé\", a sprouted or non sprouted sorghum beverage from West-Africa

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    Gowé is a traditional Beninese fermented beverage prepared from sprouted and non- prouted cereals. Due to urbanization, a new technique without any malting step has appeared in Southern Benin and is now widely used. The two techniques were compared using sorghum as the raw material. The physical, chemical and microbiological changes that occurred during a 72 h fermentation period were studied in both techniques. The dominant microflora was a mixed population of lactic acid bacteria and yeasts. The lactic acid bacteria population was higher in the traditional product at the start of fermentation (6.1 log cfu/g wet basis versus 4.5 in the modified process) because of the malting step. It then increased to 9.3 log cfu/g after 48 h fermentation. Enterobacteriaceae counts increased slightly during the first stage of fermentation but fell below the detectable level after 24 h in the traditional raw gowé and after 48 h in the modified raw gowé. The pH decreased from 6.3 to 3.4 in the traditional process and from 6.6 to 3.8 in the modified process, while the titratable acidity increased from 0.4 to 6.4% (w/w, lactic acid) and from 0.4 to 4.2%, respectively. Total soluble and reducing sugar content first increased, and then decreased with a concomitant increase in organic acids. The major organic acids were lactic acid and acetic acid. The fermentation process was thus more intense and faster in the traditional process, giving a significantly lower level of crude fat.African Journal of Biotechnology Vol. 4 (6), pp. 487-496, 200

    Comprehensive Thermodynamic Study of the Calcium Sulfate–Water Vapor System. Part 1: Experimental Measurements and Phase Equilibria

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    International audienceThe calcium sulfate–water vapor system is of great scientific and technological importance due to its applications in several fields such as the construction materials industry, geology, and planetary sciences. While much effort has been concentrated during the past decades on characterizing the crystallographic structure of the different calcium sulfate polymorphs, some questions concerning their thermodynamic aspects as phase equilibria and their capability to increase their overall water content continuously beyond structural water content seem to have been left aside. Nevertheless, the comprehension of these aspects is of the utmost importance if we want to understand this chemical system fully. The present two-part work investigates these phenomena experimentally and by a thermodynamic modeling approach. In this first part, we develop a rigorous experimental protocol by thermogravimetric analysis under controlled temperature and water vapor partial pressure. We use this protocol to obtain thermodynamic equilibrium values for the overall water content of calcium sulfate hydrates. To ensure that the equilibrium was reached, we verified that these values could be obtained by distinct thermodynamic paths. With the equilibrium data, we were able to propose an updated equilibrium curve between soluble anhydrite AIII-CaSO4 and CaSO4·0.5H2O and estimate the thermodynamic parameters ΔrH° = (35.5 ± 1.0) kJ·mol–1 and ΔrS° = (80.0 ± 2.8) J·mol–1·K–1. After that, we were able to quantify the extent of water adsorption as a function of (T, PH2O), and we observed that it could represent a significant part of the overall water content of calcium sulfates
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