Insulin analog preparations and their use in children and adolescents with type 1 diabetes mellitus.

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: a pilot study.

AIMS: To compare the performance of ultrasound elastography with conventional ultrasound in the assessment of axillary lymph nodes in suspected breast cancer and whether ultrasound elastography as an adjunct to conventional ultrasound can increase the sensitivity of conventional ultrasound used alone. MATERIALS AND METHODS: Fifty symptomatic women with a sonographic suspicion for breast cancer underwent ultrasound elastography of the ipsilateral axilla concurrent with conventional ultrasound being performed as part of triple assessment. Elastograms were visually scored, strain measurements calculated and node area and perimeter measurements taken. Theoretical biopsy cut points were selected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) analysis was performed and compared for elastograms and conventional ultrasound images with surgical histology as the reference standard. RESULTS: The mean age of the women was 57 years. Twenty-nine out of 50 of the nodes were histologically negative on surgical histology and 21 were positive. The sensitivity, specificity, PPV, and NPV for conventional ultrasound were 76, 78, 70, and 81%, respectively; 90, 86, 83, and 93%, respectively, for visual ultrasound elastography; and for strain scoring, 100, 48, 58 and 100%, respectively. There was no significant difference between any of the node measurements CONCLUSIONS: Initial experience with ultrasound elastography of axillary lymph nodes, showed that it is more sensitive than conventional ultrasound in detecting abnormal nodes in the axilla in cases of suspected breast cancer. The specificity remained acceptable and ultrasound elastography used as an adjunct to conventional ultrasound has the potential to improve the performance of conventional ultrasound alone.

Simple model of electronic density of states of graphite and its application to the investigation of superlattices

A model of graphite which is easy to comprehend and simple to implement for the simulation of scanning tunneling microscopy (STM) images is described. This model simulates the atomic density of graphite layers, which in turn correlates with the local density of states. The mechanism and construction of such a model is explained with all the necessary details which have not been explicitly reported before. This model is applied to the investigation of rippling fringes which have been experimentally observed on a superlattice, and it is found that the rippling fringes are not related to the superlattice itself. A superlattice with abnormal topmost layers interaction is simulated, and the result affirms the validity of the moiré rotation pattern assumption. The "odd-even" transition along the atomic rows of a superlattice is simulated, and the simulation result shows that when there is more than one rotated layer at the top, the "odd-even" transition will not be manifest. ©2005 The Japan Society of Applied Physics.

Integrated avalanche diode for 600 v Trench IGBT over-voltage protection

Avalanche multiplication has been one of the major destructive failure mechanisms in IGBTs; in order to avoid operating an IGBT under abnormal conditions, it is desirable to develop peripheral protecting circuits monolithically integrated without compromising the operation and performance of the IGBT. In this paper, a monolithically integrated avalanche diode (D av) for 600V Trench IGBT over-voltage protection is proposed. The mix-mode transient simulation proves the clamping capability of the D av when the IGBT is experiencing over-voltage stress in unclamped inductive switching (UIS) test. The spread of avalanche energy, which prevents hot-spot formation, through the help of the avalanche diode feeding back a large fraction of the avalanche current to a gate resistance (R G) is also explained. © 2011 IEEE.

700V smart trench IGBT with monolithic over-voltage and over-current protecting functions

An advanced 700V Smart Trench IGBT with monolithically integrated over-voltage and over-current protecting circuits is presented in this paper. The proposed Smart IGBT comprises a sense IGBT, a low voltage lateral n-channel MOSFET (M 1), an avalanche diode (D av), and poly-crystalline Zener diodes (ZD) and resistor (R poly). Mix-mode transient simulations with MEDICI have proven the functionalities of the protecting circuits when the device is operating under abnormal conditions, such as Unclamped Inductive Switching (UIS) and Short Circuit (SC) condition. A Trench IGBT process is used to fabricate this device with total 11 masks including one metal mask only. The characterizations of the fabricated device exhibit the clamping capability of the avalanche diode and voltage pull-down ability of the MOSFET. © 2012 IEEE.

Weighted least squares with expectation-maximization algorithm for burst detection in U.K. water distribution systems

Flow measurement data at the district meter area (DMA) level has the potential for burst detection in the water distribution systems. This work investigates using a polynomial function fitted to the historic flow measurements based on a weighted least-squares method for automatic burst detection in the U.K. water distribution networks. This approach, when used in conjunction with an expectationmaximization (EM) algorithm, can automatically select useful data from the historic flow measurements, which may contain normal and abnormal operating conditions in the distribution network, e.g., water burst. Thus, the model can estimate the normal water flow (nonburst condition), and hence the burst size on the water distribution system can be calculated from the difference between the measured flow and the estimated flow. The distinguishing feature of this method is that the burst detection is fully unsupervised, and the burst events that have occurred in the historic data do not affect the procedure and bias the burst detection algorithm. Experimental validation of the method has been carried out using a series of flushing events that simulate burst conditions to confirm that the simulated burst sizes are capable of being estimated correctly. This method was also applied to eight DMAs with known real burst events, and the results of burst detections are shown to relate to the water company's records of pipeline reparation work. © 2014 American Society of Civil Engineers.