Computer-controlled in-vitro simulation of multiple dosing regimens

The bactericidal effect of gentarrucin on Pseudomonas aeruginosa ATCC 27853 was investigated in a computer controlled dynamic in-vitro model, which allows the simultaneous simulation of three different dosing regimens for several days. The same total dose reduced cfu-counts of Pseudomonas aeruginosa most effectively, when administered with peak concentrations of 32 mg/l every 32 h, whereas the other dosing regimens with peak concentrations of 16 mg/l every 16 h and 8 mg/l every 8 h were distinctly less effective following the second and subsequent doses. It was shown that the use of a microcomputer facilitates the in-vitro investigation of multiple dosing regimens but counting of cfu cannot be substituted by automatic measurements of turbidity when rapid bactericidal effects occu

Impact of electronic reminders on venous thromboprophylaxis after admissions and transfers

Objective Clinical decision support has the potential to improve prevention of venous thromboembolism (VTE). The purpose of this prospective study was to analyze the effect of electronic reminders on thromboprophylaxis rates in wards to which patients were admitted and transferred. The latter was of particular interest since patient handoffs are considered to be critical safety issues. Methods The trial involved two study periods in the six departments of a university hospital, three of which were randomly assigned to the intervention group displaying reminders during the second period. At 6 h after admission or transfer, the algorithm checked for prophylaxis orders within 0-30 h of the patient's arrival, increasing the specificity of the displayed reminders. Results The significant impact of the reminders could be seen by prophylaxis orders placed 6-24 h after admission (increasing from 8.6% (223/2579) to 12% (307/2555); p<0.0001) and transfer (increasing from 2.4% (39/1616) to 3.7% (63/1682); p=0.034). In admission wards, the rate of thromboprophylaxis increased from 62.4% to 67.7% (p<0.0001), and in transfer wards it increased from 80.2% to 84.3% (p=0.0022). Overall, the rate of prophylaxis significantly increased in the intervention group from 69.2% to 74.3% (p<0.0001). No significant changes were observed in the control group. Postponing prophylaxis checks to 6 h after admissions and transfers reduced the number of reminders by 62% and thereby minimized the risk of alert fatigue. Conclusions The reminders improved awareness of VTE prevention in both admission and transfer wards. This approach may contribute to better quality of care and safer patient handoff

Changes of the Atlantic meridional overturning circulation of the past 30ka recorded in a depth transect at the Blake Outer Ridge

Oceans and climate are a tightly coupled system interacting with each other in various ways such as storage of carbon dioxide in the deep ocean. Within the global conveyor belt the Atlantic Meridional Overturning Circulation (AMOC) holds a key function, transporting warm salty surface waters from the tropical to the northern Atlantic where deep water formation takes place. Following the continental rise of North America this newly formed deep water propagates southward as Western Boundary Undercurrent (WBUC) ventilating the deep Atlantic. In the past (e.g. the last glacial cycle) strength and geometry of the AMOC have changed significantly. This study aims to provide a better understanding of the temporal and spatial (also depth depended) evolution of the AMOC in the western Atlantic sector since the last glacial (∼30 ka). We have investigated four sediment cores of the Blake Outer Ridge (30°N, 74°W; ODP 1059 to 1062) in a depth transect from 3000 to 4700 m water depth in the main flow path of the WBUC. We measured four down-core profiles of neodymium (εNd) and 231Pa/230Th isotopes for the reconstruction of water mass provenance and circulation strength of the last ∼30 ka. In contrast to published Nd isotope and 231Pa/230Th records from the Blake Ridge area our records are of unprecedented resolution, resolving climate key features of the North Atlantic region: Heinrich Stadials (HS) 1 and 2, the Last Glacial Maximum (LGM), the Bølling-Allerød and Younger Dryas (YD). Radiogenic Nd isotope signatures during the LGM reveal AABW to be the prevalent water mass in the deep western North Atlantic. The trend to more unradiogenic signatures during the deglaciation point to an increased formation of NADW which was again replaced by AABW during YD. The Holocene shows the most unradiogenic signatures and therefore established NADW. The circulation strength-proxy 231Pa/230Th indicates reduced LGM deep circulation, a pronounced slowdown during HS1 and a strong and deep circulation during the Holocene. Compared to isotopic records from the Bermuda Rise (ODP 1063) we found depth depended geometry changes of the WBUC which have occurred through the last glacial. Here, we focus on how deep northern sourced water has reached during phases of reduced circulation (indicated by increased 231Pa/230Th ratios) and the timing of this southward progradation of lower NADW

LARES/WEBER-SAT and the equivalence principle

It has often been claimed that the proposed Earth artificial satellite LARES/WEBER-SAT-whose primary goal is, in fact, the measurement of the general relativistic Lense-Thirring effect at a some percent level-would allow to greatly improve, among (many) other things, the present-day (10^-13) level of accuracy in testing the equivalence principle as well. Recent claims point towards even two orders of magnitude better, i.e. 10^-15. In this note we show that such a goal is, in fact, unattainable by many orders of magnitude being, instead, the achievable level of the order of 10^-9.Comment: LaTex, 4 pages, no figures, no tables, 26 references. Proofs corrections included. To appear in EPL (Europhysics Letters

GATA3-driven Th2 responses inhibit TGF-beta1-induced FOXP3 expression and the formation of regulatory T cells.

Transcription factors act in concert to induce lineage commitment towards Th1, Th2, or T regulatory (Treg) cells, and their counter-regulatory mechanisms were shown to be critical for polarization between Th1 and Th2 phenotypes. FOXP3 is an essential transcription factor for natural, thymus-derived (nTreg) and inducible Treg (iTreg) commitment; however, the mechanisms regulating its expression are as yet unknown. We describe a mechanism controlling iTreg polarization, which is overruled by the Th2 differentiation pathway. We demonstrated that interleukin 4 (IL-4) present at the time of T cell priming inhibits FOXP3. This inhibitory mechanism was also confirmed in Th2 cells and in T cells of transgenic mice overexpressing GATA-3 in T cells, which are shown to be deficient in transforming growth factor (TGF)-beta-mediated FOXP3 induction. This inhibition is mediated by direct binding of GATA3 to the FOXP3 promoter, which represses its transactivation process. Therefore, this study provides a new understanding of tolerance development, controlled by a type 2 immune response. IL-4 treatment in mice reduces iTreg cell frequency, highlighting that therapeutic approaches that target IL-4 or GATA3 might provide new preventive strategies facilitating tolerance induction particularly in Th2-mediated diseases, such as allergy

Anthropology and STS: Generative interfaces, multiple locations

In this multi-authored essay, nine anthropologists working in different parts of the world take part in a conversation about the interfaces between anthropology and STS (science and technology studies). Through this conversation, multiple interfaces emerge that are heterogeneously composed according to the languages, places, and arguments from where they emerge. The authors explore these multiple interfaces as sites where encounters are also sites of difference&mdash;where complex groupings, practices, topics, and analytical grammars overlap, and also exceed each other, composing irregular links in a conversation that produces connections without producing closure

Human Impacts on Forest Biodiversity in Protected Walnut-Fruit Forests in Kyrgyzstan

We used a spatially explicit model of forest dynamics, supported by empirical field data and socioeconomic data, to examine the impacts of human disturbances on a protected forest landscape in Kyrgyzstan. Local use of 27 fruit and nut species was recorded and modeled. Results indicated that in the presence of fuelwood cutting with or without grazing, species of high socioeconomic impor- tance such as Juglans regia, Malus spp., and Armeniaca vulgaris were largely eliminated from the landscape after 50–150 yr. In the absence of disturbance or in the presence of grazing only, decline of these species occurred at a much lower rate, owing to competi- tive interactions between tree species. This suggests that the current intensity of fuelwood harvesting is not sustainable. Conversely, cur- rent grazing intensities were found to have relatively little impact on forest structure and composition, and could potentially play a positive role in supporting regeneration of tree species. These results indicate that both positive and negative impacts on biodiversity can arise from human populations living within a protected area. Potentially, these could be reconciled through the development of participatory approaches to conservation management within this reserve, to ensure the maintenance of its high conservation value while meeting human needs

Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Acceleration disturbances and requirements for ASTROD I

ASTRODynamical Space Test of Relativity using Optical Devices I (ASTROD I) mainly aims at testing relativistic gravity and measuring the solar-system parameters with high precision, by carrying out laser ranging between a spacecraft in a solar orbit and ground stations. In order to achieve these goals, the magnitude of the total acceleration disturbance of the proof mass has to be less than 10&#8722;13 m s&#8722;2 Hz&#8722;1/2 at 0.1 m Hz. In this paper, we give a preliminary overview of the sources and magnitude of acceleration disturbances that could arise in the ASTROD I proof mass. Based on the estimates of the acceleration disturbances and by assuming a simple controlloop model, we infer requirements for ASTROD I. Our estimates show that most of the requirements for ASTROD I can be relaxed in comparison with Laser Interferometer Space Antenna (LISA).Comment: 19 pages, two figures, accepted for publication by Class. Quantum Grav. (at press