Adaptability of Closed-Loop during Labour, Delivery and Postpartum: A secondary analysis of data from two randomized crossover trials in type 1 diabetes pregnancy

Background: Tight glucose control during labour and delivery is recommended for pregnant women with type 1 diabetes. This can be challenging to achieve using the current treatment modalities. The automated nature of closed-loop and its ability to adapt to real-time glucose levels make it well suited for use during labour, delivery and the immediate postpartum period. Methods: We report observational data of participants from two randomized crossover trials who chose to continue using closed-loop during labour, delivery and postpartum. Labour was defined as the 24 hours prior to delivery and postpartum as the 48 hours after delivery. The glucose target range during pregnancy was 3.5-7.8mmol/L (63-140mg/dL) and 3.9-10mmol/L (70-180mg/dL) after delivery. Results: Twenty-seven (84.4%) of the potential 32 trial participants used closed-loop through labor, delivery, and postpartum. Use of closed-loop was associated with 82.0% (IQR 49.3,93.0) time-in-target range during labor and delivery and a mean glucose of 6.9±1.4mmol/L (124±25mg/dL). Closed-loop performed well throughout vaginal, elective and emergency caesarean section deliveries. Postpartum, women spent 83.3% (IQR 75.2,94.6) time-in-target range (3.9-10.0mmol/L [70-180mg/dL]), with a mean glucose of 7.2±1.4mmol/L (130±25mg/dL). There was no difference in maternal glucose concentration between mothers of infants with and without neonatal hypoglycemia (6.9±1.6 and 6.8±1.1 mmol/L [124±29 and 122±20mg/dL] respectively; p=0.84). Conclusions: Automated closed-loop insulin delivery is feasible during hospital admissions for labour, delivery and postpartum. Larger scale studies are needed to evaluate its efficacyThe trials were funded by the National Institute for Health Research (HRM Career Development Fellowship, CDF-2013-06-035), Diabetes UK (BDA 07/0003551), Gates Cambridge Trust PhD fellowship (ZAS), Jean Hailes for Women’s Health (ZAS); Allen-Carey Scholarship in Women’s Health (JMY) and a grant from the NIHR Cambridge Biomedical Research Centre (RH). Abbott Diabetes Care supplied discounted CGM devices, sensors, and details of communication protocol to facilitate real-time connectivity. HRM conducts independent research supported by the National Institute for Health Research

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

Indication for the disappearance of reactor electron antineutrinos in the Double Chooz experiment

The Double Chooz Experiment presents an indication of reactor electron antineutrino disappearance consistent with neutrino oscillations. A ratio of 0.944 $\pm$ 0.016 (stat) $\pm$ 0.040 (syst) observed to predicted events was obtained in 101 days of running at the Chooz Nuclear Power Plant in France, with two 4.25 GW$_{th}$ reactors. The results were obtained from a single 10 m$^3$ fiducial volume detector located 1050 m from the two reactor cores. The reactor antineutrino flux prediction used the Bugey4 measurement as an anchor point. The deficit can be interpreted as an indication of a non-zero value of the still unmeasured neutrino mixing parameter \sang. Analyzing both the rate of the prompt positrons and their energy spectrum we find \sang = 0.086 $\pm$ 0.041 (stat) $\pm$ 0.030 (syst), or, at 90% CL, 0.015 $<$ \sang $\ <$ 0.16.Comment: 7 pages, 4 figures, (new version after PRL referee's comments

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

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.

Behavioral Patterns and Associations with Glucose Control During 12-Week Randomized Free-Living Clinical Trial of Day and Night Hybrid Closed-Loop Insulin Delivery in Adults with Type 1 Diabetes

$\textbf{Objectives}$: We evaluated patterns of meal intake, insulin bolus delivery, and fingerstick glucose measurements during hybrid closed-loop and sensor-augmented pump (SAP) therapy, including associations with glucose control. $\textbf{Methods}$: Data were retrospectively analyzed from pump-treated adults with type 1 diabetes who underwent, in random order, 12 weeks free-living closed-loop (n = 32) and 12 weeks SAP (n = 33) periods. We quantified daily patterns of main meals, snacks, prandial insulin boluses, correction boluses, and fingerstick glucose measurements by analyzing data recorded on the study glucometer and on study insulin pump. $\textbf{Results}$: We analyzed 1942 closed-loop days and 2530 SAP days. The total number of insulin boluses was reduced during closed-loop versus SAP periods by mean 1.0 per day (95% confidence interval 0.6–1.4, P < 0.001) mainly because of a reduced number of correction boluses by mean 0.7 per day (0.4–1.0, P < 0.001). Other behavioral patterns were unchanged. The carbohydrate content of snacks but not the number of snacks was positively correlated with (1) glycemic variability as measured by standard deviation of sensor glucose (closed-loop P < 0.05; SAP P < 0.01), (2) mean sensor glucose (P < 0.05), and (3) postintervention HbA1c (P < 0.05). Behavioral patterns explained 47% of between-subject variance in glucose variability during SAP period and 30%–33% of variance of means sensor glucose and postintervention HbA1c. $\textbf{Conclusion}$: Fewer correction boluses are delivered during closed-loop period. The size of snacks appears to worsen glucose control possibly because of carbohydrate-rich content of snacks. Modifiable behavioral patterns may be important determinants of glucose control.We acknowledge support by the staff at the Addenbrooke's Wellcome Trust Clinical Research Facility. 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. Barbara Semlitsch and Markus Schauer (both from Medical University of Graz) supported the study as insulin pump experts. Funding was by Seventh Framework Programme of the European Union (ICT FP7-247138). Additional support for the Artificial Pancreas work was by JDRF, National Institute for Health Research Cambridge Biomedical Research Centre, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09), and Helmsley Trust (Nos. 2016PG-T1D045 and 2016PG-T1D046). Abbott Diabetes Care supplied discounted continuous glucose monitoring devices, sensors, and communication protocol to facilitate real-time connectivity

New constraints on muon-neutrino to electron-neutrino transitions in MINOS

This paper reports results from a search for ν_μ → ν_e transitions by the MINOS experiment based on a 7×10^(20) protons-on-target exposure. Our observation of 54 candidate ν_e events in the far detector with a background of 49.1±7.0(stat)±2.7(syst) events predicted by the measurements in the near detector requires 2sin^2(2θ_(13))sin^2θ_(23)<0.12(0.20) at the 90% C.L. for the normal (inverted) mass hierarchy at δ_(CP)=0. The experiment sets the tightest limits to date on the value of θ_(13) for nearly all values of δ_(CP) for the normal neutrino mass hierarchy and maximal sin^2(2θ_(23))

Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.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, Wellcome Strategic Award (100574/Z/12/Z), EC Horizon 2020 (H2020-SC1-731560), NIDDK (DP3DK112176 and 1UC4DK108520-01), Efficacy and Mechanism Evaluation Programme of National Institute for Health Research (14/23/09) and Helmsley Trust (2016PG-T1D045 and #2016PG-T1D046)

Measurement of the underground atmospheric muon charge ratio using the MINOS Near Detector

The magnetized MINOS Near Detector, at a depth of 225 mwe, is used to measure the atmospheric muon charge ratio. The ratio of observed positive to negative atmospheric muon rates, using 301 days of data, is measured to be 1.266±0.001(stat)_(-0.014)^(+0.015)(syst). This measurement is consistent with previous results from other shallow underground detectors and is 0.108±0.019(stat+syst) lower than the measurement at the functionally identical MINOS Far Detector at a depth of 2070 mwe. This increase in charge ratio as a function of depth is consistent with an increase in the fraction of muons arising from kaon decay for increasing muon surface energie