Accuracy and Longevity of an Implantable Continuous Glucose Sensor in the PRECISE Study: A 180-Day, Prospective, Multicenter, Pivotal Trial

It is known that continuous glucose monitoring (CGM) systems can lower mean glucose compared with episodic self-monitoring of blood glucose. Implantable CGM systems may provide additional benefits. We studied the Eversense (Senseonics Inc.) implantable CGM sensor in 71 participants aged 18 years and older with type 1 and type 2 diabetes in a 180-day multinational, multicenter pivotal trial. Participants used the CGM system at home and in the clinic. CGM accuracy was assessed during eight in-clinic visits with the mean absolute relative difference (MARD) for venous reference glucose values >4.2 mmol/L as the primary end point. Secondary end points included Clarke Error Grid Analysis and alarm performance. The primary safety outcome was device-related serious adverse events. This trial is registered with ClinicalTrials.gov, number NCT02154126. The MARD value against reference glucose values >4.2 mmol/L was 11.1% (95% CI 10.5, 11.7). Clarke Error Grid Analysis showed 99.2% of samples in the clinically acceptable error zones A and B. Eighty-one percent of hypoglycemic events were detected by the CGM system within 30 min. No device-related serious adverse events occurred during the study. Our results indicate the safety and accuracy of this new type of implantable CGM system and support it as an alternative for transcutaneous CG

Acceptability of Implantable Continuous Glucose Monitoring Sensor

Real-time continuous glucose monitoring is associated with significant benefits for diabetes management. Implantable sensors could overcome some challenges reportedly associated with device visibility, psychosocial functioning and sensor durability. A psychosocial assessment was conducted to determine acceptability and impact of an implantable continuous glucose monitoring (CGM) sensor as part of the PRECISE trial. Questionnaires were administered to participants comprising the Diabetes Distress Scale, the CGM impact scale, and bespoke device satisfaction. Fifty-one participants across the United Kingdom (n = 10) and Germany (n = 41) completed the questionnaires. Of these, 90% had T1D, 50% followed an insulin pump therapy regimen, and 45% of the participants were previous CGM users. CGM Impact Scale results show 86% (n = 44) of participants reported feeling better (14% neutral) about their diabetes control with 90% CGM naïve participants and 81% previous CGM users reporting increased confidence about their diabetes management. Furthermore, 73% (n = 37) felt more safe (27% neutral) while sleeping and 78% (n = 39) more confident (22% neutral) about avoiding serious hypoglycemia. Responses correspond with an average improvement in HbA1c from 7.51 to 7.05 ( P < .0001) over the 90 days use of the CGM. Overall, the system was rated highly on ease of use, convenience and comfort. 84% would choose to be inserted again with 93% of CGM naïve participants (86% previous CGM users) reporting minimized burden of diabetes. Implantable CGM devices are acceptable to users and are evaluated favorably. The considerable majority of participants (93% of first time users and 77% previous CGM users) would like to continue using the system to help manage their diabetes more effectivel

Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan-L trial

IGTPAims: To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose-lowering drugs. Materials and Methods: In this exploratory analysis of LixiLan-L (N = 736), efficacy outcomes were assessed within population subgroups derived from the following baseline characteristics: glycated haemoglobin [HbA1c; <8%, ≥8% (<64, ≥64 mmol/mol)]; duration of T2DM (<10, ≥10 years); body mass index (<30, ≥30 kg/m2). Furthermore, the incidence of symptomatic hypoglycaemia with plasma glucose ≤3.9 mmol/L (≤70 mg/dL) was also analysed according to the same subgroups. Results: Compared with the iGlar treatment group, patients treated with iGlarLixi showed consistently greater reductions in HbA1c during the treatment period, with higher percentages of patients achieving the HbA1c target level of <7% (<53 mmol/mol) in all of the subpopulations tested (P < .0001 for all), having consistent mitigation of body weight gain and with no major differences in the incidence of hypoglycaemia. Conclusions: iGlarLixi consistently improved glycaemic control compared with iGlar in all baseline characteristic subgroups of patients with T2DM inadequately controlled with insulin, including difficult-to-treat subgroups of patients with long duration of diabetes, obesity and high HbA1c. Clinical trial number: NCT02058160 (clinicaltrials.gov)

Using computer simulation to aid the research of drilling processes

Drilling wells is one of the primary methods used for mineral exploration. Scientific studies have aimed at improving the technical and economic aspects of drilling because of the current competitive economic conditions. Note that the primary topic of these studies has been developing new effective rock-cutting tools. To design a new rock-cutting tool, a thorough, reliable, and accurate study of the processes that occur during drilling is necessary. During drilling, mechanical, hydraulic, thermal, and chemical phenomena, which are interdependent and affect the performance of a drilling tool, simultaneously occur; therefore, a systematic, integrated approach is required for studying drilling processes. Field-based and laboratory experiments are quite tedious to perform and require high material costs, and it is often not possible to separately evaluate small elements of the drilling model. Therefore, computer simulation is an important research tool that enables accurate and reliable visualization of even small parts of the model. The aim. The aim of this study is to examine the potential for computer simulation of the processes that occur during drilling. Objective. In this study, we evaluated the simulation features of various software products, such as KOMPAS-3D, ANSYS, Delphi, and LabVIEW, for their utility in studying the processes that occur during drilling. The possibility of computer simulation for studying drilling processes, including its advantages and disadvantages, are demonstrated. The results are obtained from a model that simulates a rock cutting tool. The main uses of the rock cutting tool are outlined, and the drilling simulation development is planned. Choice of research method. The study of the capabilities of existing modern software products, for use in drilling process research, is carried out by an analytical review method

TU Dortmund Olaf Spinczyk TU Dortmund

Abstract—State-machine replication has received widespread attention for the provisioning of highly available services in data centers. However, current production systems focus on tolerating crash faults only and prominent service outages caused by state corruptions have indicated that this is a risky strategy. In the future, state corruptions due to transient faults (such as bit flips) become even more likely, caused by ongoing hardware trends regarding the shrinking of structure sizes and reduction of operating voltages. In this paper we present CROSSCHECK, an approach to tolerate arbitrary state corruption (ASC) in the context of faulttolerant replication of multithreaded services. CROSSCHECK is able to detect silent data corruptions ahead of execution, and by crosschecking state changes with co-executing replicas, even ASCs can be detected. Finally, fault tolerance is achieved by a finegrained recovery using fault-free replicas. Our implementation is transparent to the application by utilizing fine-grained softwarehardening mechanisms using aspect-oriented programming. To validate CROSSCHECK we present a replicated multithreaded key-value store that is resilient to state corruptions. I

Effects of sequential treatment with lixisenatide, insulin glargine, or their combination on meal-related glycaemic excursions, insulin and glucagon secretion, and gastric emptying in patients with type 2 diabetes

$\bf Aim:$ To examine the glucose-lowering mechanisms of the glucagon-like peptide-1 receptor agonist lixisenatide after two subsequent meals and in combination with basal insulin. $\textbf {Materials and Methods:}$ Twenty-eight metformin-treated patients with type 2 diabetes were randomly assigned to treatment sequences with either lixisenatide or insulin glargine alone for 4 weeks, and a combination of both treatments for 4 weeks. Metabolic examinations were performed before and after each treatment period following breakfast and a late lunch 8 hours later. $\bf Results:$ Lixisenatide mainly reduced postprandial glycaemia, while insulin glargine mainly reduced fasting glucose after breakfast ($\it P$ < 0.05). This was partially preserved after a late lunch ($\it P$ < 0.05). After breakfast, lixisenatide reduced insulin secretion and glucagon levels significantly. These effects were lost after a late lunch. Insulin glargine did not significantly reduce glucagon or insulin secretion. Gastric emptying was slowed by lixisenatide, but not by insulin glargine after breakfast. After the late lunch, lixisenatide slightly accelerated gastric emptying. $\bf Conclusions:$ Lixisenatide decelerates gastric emptying after breakfast, thereby reducing glycaemic excursions, insulin secretion and glucagon levels. The glycaemic reduction persists until after a late lunch, despite accelerated gastric emptying. The combination with insulin glargine enhances the glucose-lowering effect because of complementary modes of action