Intensive glycemic treatment during Type 1 diabetes pregnancy: A story of (mostly) sweet success!

Studies from Scotland and Canada confirm large increases in the incidence of pregnancies complicated by pregestational type 1 diabetes (T1D). With this increased antenatal workload comes more specialization and staff expertise, which may be important as diabetes technology use increases. While euglycemia remains elusive and obstetrical intervention (earlier delivery, increased operative deliveries) is increasing, there have been some notable successes in the past 5–10 years. These include a decline in the rates of congenital anomaly (Canada) and stillbirths (U.K.) and substantial reductions in both maternal hypoglycemia (both moderate and severe) across many countries. However, pregnant women with T1D still spend ∼30–45% of the time (8–11 h/day) hyperglycemic during the second and third trimesters. The duration of maternal hyperglycemia appears unchanged in routine clinical care over the past decade. This ongoing fetal exposure to maternal hyperglycemia likely explains the persistent rates of large for gestational age (LGA), neonatal hypoglycemia, and neonatal intensive care unit (NICU) admissions in T1D offspring. The Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) found that pregnant women using real-time continuous glucose monitoring (CGM) spent 5% less time (1.2 h/day) hyperglycemic during the third trimester, with clinically relevant reductions in LGA, neonatal hypoglycemia, and NICU admissions. This article will review the progress in our understanding of the intensive glycemic treatment of T1D pregnancy, focusing in particular on the recent technological advances in CGM and automated insulin delivery. It suggests that even with advanced diabetes technology, optimal maternal dietary intake is needed to minimize the neonatal complications attributed to postprandial hyperglycemia

On the parabolic equation method in internal wave propagation

A parabolic equation for the propagation of periodic internal waves over varying bottom topography is derived using the multiple-scale perturbation method. Some computational aspects of the numerical implementation are discussed. The results of numerical experiments on propagation of an incident plane wave over a circular-type shoal are presented in comparison with the analytical result, based on Born approximation.Comment: Submitted to Coastal Engineering. 16 pages, 5 figures. One figure was excluded from article because of size problem

Evolution of surface gravity waves over a submarine canyon

The effects of a submarine canyon on the propagation of ocean surface waves are examined with a three-dimensional coupled-mode model for wave propagation over steep topography. Whereas the classical geometrical optics approximation predicts an abrupt transition from complete transmission at small incidence angles to no transmission at large angles, the full model predicts a more gradual transition with partial reflection/transmission that is sensitive to the canyon geometry and controlled by evanescent modes for small incidence angles and relatively short waves. Model results for large incidence angles are compared with data from directional wave buoys deployed around the rim and over Scripps Canyon, near San Diego, California, during the Nearshore Canyon Experiment (NCEX). Wave heights are observed to decay across the canyon by about a factor 5 over a distance shorter than a wavelength. Yet, a spectral refraction model predicts an even larger reduction by about a factor 10, because low frequency components cannot cross the canyon in the geometrical optics approximation. The coupled-mode model yields accurate results over and behind the canyon. These results show that although most of the wave energy is refractively trapped on the offshore rim of the canyon, a small fraction of the wave energy 'tunnels' across the canyon. Simplifications of the model that reduce it to the standard and modified mild slope equations also yield good results, indicating that evanescent modes and high order bottom slope effects are of minor importance for the energy transformation of waves propagating across depth contours at large oblique angles

Whole body and hepatic insulin action in normal, starved, and diabetic rats

In normal (N), 3-days starved (S), and streptozotocin-treated (65 mg/kg) 3-days diabetic (D) rats we examined the in vivo dose-response relationship between plasma insulin levels vs. whole body glucose uptake (BGU) and inhibition of hepatic glucose production (HGP) in conscious rats, as determined with the four-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]glucose infusion. Twelve-hour fasting (basal) HGP was 3.0 +/- 0.2, 2.1 +/- 0.2, and 5.4 +/- 0.5 mg/min in N, S, and D rats, respectively. Next, all rats were clamped at matched glycemia (6 mM). Lowering plasma glucose in D rats from +/- 20 to 6.0 mM did not increase plasma norepinephrine, epinephrine, glucagon, and corticosterone levels. For BGU, insulin sensitivity was increased (70 +/- 11 microU/ml) in S and unchanged (113 +/- 21 microU/ml) in D compared with N rats (105 +/- 10 microU/ml). Insulin responsiveness was unchanged (12.4 +/- 0.8 mg/min) in S and decreased (8.5 +/- 0.8 mg/min) in D compared with N rats (12.3 +/- 0.7 mg/min). For HGP, insulin sensitivity was unchanged (68 +/- 10 microU/ml) in S and decreased (157 +/- 21 microU/ml) in D compared with N rats (71 +/- 5 microU/ml). Insulin responsiveness was identical among N, S, and D rats (complete suppression of HGP). In summary, 1) insulin resistance in D rats is caused by hepatic insensitivity and by a reduction in BGU responsiveness. 2) S rats show normal hepatic insulin action, but insulin sensitivity for BGU is increased. Therefore, S and D rats both suffering from a comparable catabolic state (10-15% body wt loss in 3 days) show opposite effects on in vivo insulin action. This indicates that in vivo insulin resistance in D rats is not caused by the catabolic state per se

Hard Real-Time Linux for Off-The-Shelf Multicore Architectures

This document describes the research results that were obtained from the development of a real-time extension for the Linux operating system. The paper describes a full extension of the kernel, which enables hard real-time performance on a 64-bit x86 architecture. In the first part of this study, real-time systems are categorized and concepts of real-time operating systems are introduced to the reader. In addition, numerous well-known real-time operating systems are considered. QNX Neutrino, RT_PREEMPT Linux Patch and HLRT Linux Patch are analyzed in detail. The core concepts of these systems are shown and discussed. Furthermore, a test suite is developed, which is used to obtain expressive benchmarks from the systems that were analyzed before. The systems are evaluated on the basis of these benchmarks and compared to the real-time extension which is developed in this work. A requirements catalogue is defined based on the analysis of the stated operating systems. The design of a real-time extension is developed based on the specification catalogue and the identified core concepts. Furthermore, the concrete implementation of the developed real-time extension is presented in detail. Finally, the benchmarks of all analyzed systems, including the developed real-time extension, are compared to each other and evaluated

The philosophy of scientific experimentation: a review

Practicing and studying automated experimentation may benefit from philosophical reflection on experimental science in general. This paper reviews the relevant literature and discusses central issues in the philosophy of scientific experimentation. The first two sections present brief accounts of the rise of experimental science and of its philosophical study. The next sections discuss three central issues of scientific experimentation: the scientific and philosophical significance of intervention and production, the relationship between experimental science and technology, and the interactions between experimental and theoretical work. The concluding section identifies three issues for further research: the role of computing and, more specifically, automating, in experimental research, the nature of experimentation in the social and human sciences, and the significance of normative, including ethical, problems in experimental science

Practical use of variational principles for modeling water waves

This paper describes a method for deriving approximate equations for irrotational water waves. The method is based on a 'relaxed' variational principle, i.e., on a Lagrangian involving as many variables as possible. This formulation is particularly suitable for the construction of approximate water wave models, since it allows more freedom while preserving the variational structure. The advantages of this relaxed formulation are illustrated with various examples in shallow and deep waters, as well as arbitrary depths. Using subordinate constraints (e.g., irrotationality or free surface impermeability) in various combinations, several model equations are derived, some being well-known, other being new. The models obtained are studied analytically and exact travelling wave solutions are constructed when possible.Comment: 30 pages, 1 figure, 62 references. Other author's papers can be downloaded at http://www.denys-dutykh.com

Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims<br/> Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.<br/> Methods<br/> Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). <br/>Results<br/> Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).<br/> Conclusions<br/> In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response