Variability of Insulin Requirements Over 12 Weeks of Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes.

OBJECTIVE: To quantify variability of insulin requirements during closed-loop insulin delivery. RESEARCH DESIGN AND METHODS: We retrospectively analyzed overnight, daytime, and total daily insulin amounts delivered during a multicenter closed-loop trial involving 32 adults with type 1 diabetes. Participants applied hybrid day-and-night closed-loop insulin delivery under free-living home conditions over 12 weeks. The coefficient of variation was adopted to measure variability of insulin requirements in individual subjects. RESULTS: Data were analyzed from 1,918 nights, 1,883 daytime periods and 1,564 total days characterized by closed-loop use over 85% of time. Variability of overnight insulin requirements (mean [SD] coefficient of variation 31% [4]) was nearly twice as high as variability of total daily requirements (17% [3], P < 0.001) and was also higher than variability of daytime insulin requirements (22% [4], P < 0.001). CONCLUSIONS: Overnight insulin requirements were significantly more variable than daytime and total daily amounts. This may explain why some people with type 1 diabetes report frustrating variability in morning glycemia.Seventh Framework Programme of the European Union (ICT FP7- 247138). Additional support for the Artificial Pancreas work by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre and Wellcome Strategic Award (100574/Z/12/Z). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity. We acknowledge support by the staff at the Addenbrooke’s Wellcome Trust Clinical Research Facility. Jasdip Mangat and John Lum (Jaeb Center) supported development and validation of the closed-loop system. Josephine Hayes (University of Cambridge) provided administrative support. Karen Whitehead (University of Cambridge) provided laboratory support. We acknowledge support by the staff at Profil Institut; Krisztina Schmitz-Grozs provided support as a research physician, Martina Haase supported the study as an insulin pump expert, and Maren Luebkert, Kirstin Kuschma and Elke Przetak provided administrative, coordinating and documentation support.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/dc15-262

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

An improved measurement of muon antineutrino disappearance in MINOS

We report an improved measurement of muon anti-neutrino disappearance over a distance of 735km using the MINOS detectors and the Fermilab Main Injector neutrino beam in a muon anti-neutrino enhanced configuration. From a total exposure of 2.95e20 protons on target, of which 42% have not been previously analyzed, we make the most precise measurement of the anti-neutrino "atmospheric" delta-m squared = 2.62 +0.31/-0.28 (stat.) +/- 0.09 (syst.) and constrain the anti-neutrino atmospheric mixing angle >0.75 (90%CL). These values are in agreement with those measured for muon neutrinos, removing the tension reported previously.Comment: 5 pages, 4 figures. In submission to Phys.Rev.Let

Active to Sterile Neutrino Mixing Limits from Neutral-Current Interactions in MINOS

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07×10^(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754±28(stat)±37(syst) for oscillations among three active flavors. The fraction f_s of disappearing ν_μ that may transition to ν_s is found to be less than 22% at the 90% C.L

A Study of Muon Neutrino Disappearance Using the Fermilab Main Injector Neutrino Beam

We report the results of a search for muon-neutrino disappearance by the Main Injector Neutrino Oscillation Search. The experiment uses two detectors separated by 734 km to observe a beam of neutrinos created by the Neutrinos at the Main Injector facility at Fermi National Accelerator Laboratory. The data were collected in the first 282 days of beam operations and correspond to an exposure of 1.27e20 protons on target. Based on measurements in the Near Detector, in the absence of neutrino oscillations we expected 336 +/- 14 muon-neutrino charged-current interactions at the Far Detector but observed 215. This deficit of events corresponds to a significance of 5.2 standard deviations. The deficit is energy dependent and is consistent with two-flavor neutrino oscillations according to delta m-squared = 2.74e-3 +0.44/-0.26e-3 eV^2 and sin^2(2 theta) > 0.87 at 68% confidence level.Comment: In submission to Phys. Rev.

Search for the disappearance of muon antineutrinos in the NuMI neutrino beam

We report constraints on antineutrino oscillation parameters that were obtained by using the two MINOS detectors to measure the 7% muon antineutrino component of the NuMI neutrino beam. In the Far Detector, we select 130 events in the charged-current muon antineutrino sample, compared to a prediction of 136.4 ± 11.7(stat)^(+10.2)_(-8.9)(syst) events under the assumption │Δm^2│ = 2.32 X 10^(-3) eV^2, sin^2(2θ) = 1.0

Measurement of the Atmospheric Muon Charge Ratio at TeV Energies with MINOS

The 5.4 kton MINOS far detector has been taking charge-separated cosmic ray muon data since the beginning of August, 2003 at a depth of 2070 meters-water-equivalent in the Soudan Underground Laboratory, Minnesota, USA. The data with both forward and reversed magnetic field running configurations were combined to minimize systematic errors in the determination of the underground muon charge ratio. When averaged, two independent analyses find the charge ratio underground to be 1.374 +/- 0.004 (stat.) +0.012 -0.010(sys.). Using the map of the Soudan rock overburden, the muon momenta as measured underground were projected to the corresponding values at the surface in the energy range 1-7 TeV. Within this range of energies at the surface, the MINOS data are consistent with the charge ratio being energy independent at the two standard deviation level. When the MINOS results are compared with measurements at lower energies, a clear rise in the charge ratio in the energy range 0.3 -- 1.0 TeV is apparent. A qualitative model shows that the rise is consistent with an increasing contribution of kaon decays to the muon charge ratio.Comment: 16 pages, 17 figure

Measurement of the Neutrino Mass Splitting and Flavor Mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10^(20) protons on target. A fit to neutrino oscillations yields values of |Δm^2|=(2.32_(-0.08)^(+0.12))×10^(-3)  eV^2 for the atmospheric mass splitting and sin^2(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively

Measurement of the neutrino mass splitting and flavor mixing by MINOS

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of $7.25 imes 10^{20}$ protons on target. A fit to neutrino oscillations yields values of $|Delta m^2| = (2.32^{+0.12}_{-0.08}) imes10^{-3}$,eV$^2$ for the atmospheric mass splitting and m sin^2!(2 heta) > 0.90 (90%,C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively

Improved Search for Muon-Neutrino to Electron-Neutrino Oscillations in MINOS

We report the results of a search for ν_e appearance in a ν_μ beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2×10^(20) protons on the NuMI target at Fermilab, we find 2sin^2(θ_(23))sin^2(2θ_(13))<0.12(0.20) at 90% confidence level for δ=0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin^2(θ_(23))sin^2(2θ_(13))=0.041^(+0.047)_(-0.031)(0.079^(+0.071)_(-0.053). The θ_(13)= 0 hypothesis is disfavored by the MINOS data at the 89% confidence level