Patient-level meta-analysis of the EDITION 1, 2 and 3 studies : glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes

AimsTo conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively. MethodsThe EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249). ResultsNo significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with 1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low ( ConclusionGla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.Peer reviewe

Computational Investigation of Novel Tip Leakage Mitigation Methods for High Pressure Turbine Blades

This paper presents preliminary findings on a possible approach to reducing tip leakage losses. In this paper a computational study was conducted on the EEE (Energy Efficient Engine) HPT (High Pressure Turbine) rotor tip geometry using the commercial numerical solver ANSYS FLUENT. The flow solver was validated against aerodynamic data acquired in the NASA Transonic Turbine Blade Cascade facility. The scope of the ongoing study is to computationally investigate how the tip leakage and overall blade losses are affected by 1. injection from the tip near the pressure side, 2. injection from the tip surface at the camber line, and 3. injection from the tip surface into the tip separation bubble. The objective is to identify the locations on the tip surface at which to place appropriately configured blowing keeping in mind the film cooling application of tip blowing holes. The validation was conducted at Reynolds numbers of 85,000, 343,000 and 685,000 and at engine realistic flow conditions. The coolant injection simulations were conducted at a Reynolds number of 343,000 based on blade chord and inlet velocity and utilized the SST turbulence model in FLUENT. The key parameters examined are the number of jets, jet angle and jet location. A coolant to inlet pressure ratio of 1.0 was studied for angles of +30 deg., -30 deg. and 90 deg. to the local free stream on the tip. For the 3 hole configuration, 3 holes spaced 3 hole diameters apart with length to diameter ratio of 1.5 were used. A simulation including 11 holes along the entire mean camber line is also presented (30 degrees toward suction side). In addition, the effect of a single hole is also compared to a flat tip with no injection. The results provide insight into tip flow control methods and can be used to guide further investigation into tip flow control. As noted in past research it is concluded that reducing leakage flow is not necessarily synonymous with reducing losses due to leakage

The Sunyaev-Zel'dovich Infrared Experiment: A Millimeter-wave Receiver for Cluster Cosmology

Measurements of the Sunyaev-Zel'dovich (S-Z) effect towards distant clusters of galaxies can be used to determine the Hubble constant and the radial component of cluster peculiar velocities. Determination of the cluster peculiar velocity requires the separation of the two components of the S-Z effect, which are due to the thermal and bulk velocities of the intracluster plasma. The two components can be separated practically only at millimeter (mm) wavelengths. Measurements of the S-Z effect at mm wavelengths are subject to minimal astrophysical confusion and, therefore, provide an important test of results obtained at longer wavelengths. We describe the instrument used to make the first significant detections of the S-Z effect at millimeter wavelengths. This instrument employs new filter, detector, and readout technologies to produce sensitive measurements of differential sky brightness stable on long time scales. These advances allow drift scan observations which achieve high sensitivity while minimizing common sources of systematic error.Comment: 19 pages, 15 postscript figures, LaTeX(aaspptwo.sty), ApJ(in press

Genes Involved in the Balance between Neuronal Survival and Death during Inflammation

Glucocorticoids are potent regulators of the innate immune response, and alteration in this inhibitory feedback has detrimental consequences for the neural tissue. This study profiled and investigated functionally candidate genes mediating this switch between cell survival and death during an acute inflammatory reaction subsequent to the absence of glucocorticoid signaling. Oligonucleotide microarray analysis revealed that following lipopolysaccharide (LPS) intracerebral administration at striatum level, more modulated genes presented transcription impairment than exacerbation upon glucocorticoid receptor blockage. Among impaired genes we identified ceruloplasmin (Cp), which plays a key role in iron metabolism and is implicated in a neurodegenative disease. Microglial and endothelial induction of Cp is a natural neuroprotective mechanism during inflammation, because Cp-deficient mice exhibited increased iron accumulation and demyelination when exposed to LPS and neurovascular reactivity to pneumococcal meningitis. This study has identified genes that can play a critical role in programming the innate immune response, helping to clarify the mechanisms leading to protection or damage during inflammatory conditions in the CNS

Optical 3D-storage in sol-gel materials with a reading by Optical Coherence Tomography-technique

We report on the recording of 3D optical memories in sol-gel materials by using a non-linear absorption effect. This effect induces a local change of the optical properties of the material which is read and quantified with a high resolution full-field Optical Coherence Tomography setup. It is the first time that this technique is used for this purpose. Data recording was performed by focused picosecond (ps) single-pulse irradiation at 1064 nm with energy densities of 10 and 33 J/cm2 per pulse.Comment: 19 pages, 7 figure

Measurement of the Hubble Constant from X-ray and 2.1 mm Observations of Abell 2163

We report 2.1 mm observations of the Sunyaev-Zel'dovich (S-Z) effect; these observations confirm our previous detection of a decrement in the Cosmic Microwave Background intensity towards the cluster Abell 2163. The S-Z data are analyzed using the relativistically correct expression for the Comptonization. We begin by assuming the intracluster (IC) gas to be isothermal at the emission weighted average temperature determined by a combined analysis of the ASCA and GINGA X-ray satellite observations. Combining the X-ray and S-Z measurements, we determine the Hubble constant to be H_0(q_0=0.5)= 60 +40/-23 km/s/Mpc, where the uncertainty is dominated by the systematic difference in the ASCA and GINGA determined IC gas temperatures. ASCA observations suggest the presence of a significant thermal gradient in the IC gas. We determine $H_0$ as a function of the assumed IC gas thermal structure. Using the ASCA determined thermal structure and keeping the emission weighted average temperature the same as in the isothermal case, we find H_0(q_0=0.5)= 78 +54/-28 km/s/Mpc. Including additional uncertainties due to cluster asphericity, peculiar velocity, IC gas clumping, and astrophysical confusion, we find H_0(q_0=0.5)= 78 +60/-40 km/s/Mpc.Comment: 24 pages, 10 postscript figures, LaTeX(aaspptwo.sty), ApJ(in press

Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection

<p>Abstract</p> <p>Background</p> <p>Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards <it>in vitro </it>studies. To detail the local <it>in vivo </it>genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic <it>Escherichia coli </it>(UPEC) infection within the kidney of a live rat.</p> <p>Results</p> <p>Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-γ (IFN-γ) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-γ in rats with an ongoing local kidney infection, correlating to splenic, rather than renal <it>Ifng </it>induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections.</p> <p>Conclusion</p> <p>Our hypothesis-free approach identified components of infection-associated multi-cellular tissue responses and demonstrated how a comparative analysis allows retrieval of relevant information from lower-quality data sets. The data further define marked representation of IFN-γ responsive genes and a prompt inter-organ communication as a hallmark of an early local tissue response to infection.</p

Cetaceans have complex brains for complex cognition

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