Study Protocol for the Initial Choice of DPP-4 Inhibitor in Japanese Patients with Type 2 diabetes Mellitus: Effect of Linagliptin on QOL (INTEL-QOL) Trial

<p></p><p><b>Article full text</b></p><p><br></p><p>The full text of this article can be found here<b>. </b><u>https://link.springer.com/article/10.1007/s13300-018-0437-x</u></p><p><u><br></u></p><p><b>Provide enhanced content for this article</b></p><p><br></p><p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p><p><br></p><p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p><p><br></p><p>Other enhanced features include, but are not limited to:</p><p><br></p><p>• Slide decks</p><p>• Videos and animations</p><p>• Audio abstracts</p><p> </p><p>• Audio slides</p><p></p

Schematic representation of the closed-loop control system and markers captured by a motion capture system.

<p>(A) Schematic of the closed-loop control system. Instantaneous marker positions are displayed and used as the feedback information for stimulation frequency adjustments. (B) Three 2-mm-diameter reflective markers placed on a beetle for motion capture purposes. <i>A</i>–<i>B</i> is the axis of rotation of the protraction/retraction motion of the coxa, <i>C</i>–<i>D</i> is the axis of rotation of the levation/depression motion of the femur, and <i>X</i>–<i>Y</i> is the axis of rotation of the extension/flexion motion of the tibia. (C) Markers placed on the beetle are recognized by the 3D motion capture system as point objects and displayed on a computer screen. Two markers placed on the beetle's front leg were recognized as a solid line segment that represented the femur–tibia section of a beetle's leg, and the third marker on a beetle's body indicated the beetle's body position. (D) Overview of the 3D motion capture system. This 3D motion capture system captures and stores the <i>X</i>, <i>Y</i>, and <i>Z</i> coordinates of all markers. The stored 3D marker positions were used for precise numerical analyses of a beetle's leg motion. The closed-loop control system calculated the instantaneous angular displacements of leg motion and used this information to adjust the output stimulation frequencies. (D1) The system comprised six T40s VICON cameras (with resolution of 4 megapixels (2336×1728)) operating at 100 frames per second. (D2) A VICON server was used to acquire the camera signals and construct the marker positions in real time. (D3) A computer was used to collect the marker-position data from the server and issue stimulation commands to the final control element.</p

A Biological Micro Actuator: Graded and Closed-Loop Control of Insect Leg Motion by Electrical Stimulation of Muscles

<div><p>In this study, a biological microactuator was demonstrated by closed-loop motion control of the front leg of an insect (<i>Mecynorrhina torquata</i>, beetle) via electrical stimulation of the leg muscles. The three antagonistic pairs of muscle groups in the front leg enabled the actuator to have three degrees of freedom: protraction/retraction, levation/depression, and extension/flexion. We observed that the threshold amplitude (voltage) required to elicit leg motions was approximately 1.0 V; thus, we fixed the stimulation amplitude at 1.5 V to ensure a muscle response. The leg motions were finely graded by alternation of the stimulation frequencies: higher stimulation frequencies elicited larger leg angular displacement. A closed-loop control system was then developed, where the stimulation frequency was the manipulated variable for leg-muscle stimulation (output from the final control element to the leg muscle) and the angular displacement of the leg motion was the system response. This closed-loop control system, with an optimized proportional gain and update time, regulated the leg to set at predetermined angular positions. The average electrical stimulation power consumption per muscle group was 148 µW. These findings related to and demonstrations of the leg motion control offer promise for the future development of a reliable, low-power, biological legged machine (i.e., an insect–machine hybrid legged robot).</p></div

Variation in leg motion responses to different closed-loop control settings.

<p>(A) The overshoot angle and (B) the reaching time of protraction/retraction motion with respect to different <i>K</i>_p values and update time intervals <i>t</i> during closed-loop control (number of beetles = 5, 35≤ number of data points at each experiment setting ≤49). In general, as the <i>K</i>_p value was increased from 0.5 to 1.5 and the update time interval <i>t</i> was decreased from 300 ms to 100 ms, (A) the leg response overshoot angle (absolute values used for all the motions) increased, whereas (B) the reaching-time decreased. Numbers at the bottom of each graph indicate the <i>K</i>_p value used for the corresponding column above.</p

Anatomical view of a beetle's front leg.

<p>Anatomical view of the three pairs of antagonistic muscle groups that control a beetle's front leg. Red crosses indicate the implantation sites for stimulation electrodes. (A) The protraction/retraction muscle groups are inside the prothorax, connect the coxa to the pronotum, and control the protraction/retraction motion of the coxa. (B) The levation/depression muscle groups are inside the coxa and control the levation/depression motion of the femur. The extension/flexion muscle groups are inside the femur and control the extension/flexion motion of the tibia.</p

Representative stimulation pulses and electrical current flow through the retraction muscle group.

<p>(A) A positive stimulation pulse train of 1.5 V, 100 Hz, and a 1 ms pulse width produced by the function generator was applied between the two electrodes inserted in the retraction muscle group of a beetle's front leg. (B) Typical current wave that passed through the beetle's muscle (depression muscle group of the front leg).</p

Demonstration of controlling a beetle's front leg motions by electrical stimulation of muscles.

<p>Protraction, retraction, flexion, and extension motions of a beetle's front leg elicited by electrical stimulation with a positive pulse train at 100 Hz and a 1 ms pulse width (as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0105389#pone.0105389.s004" target="_blank">Video S1</a>). Each locomotion type was first stimulated individually, as shown in the upper four images; two muscles were then stimulated simultaneously to produce combined leg motion, as shown in the lower four images. Each light-emitting diode (LED) near the beetle's head indicated the time when a particular stimulation site had been switched on.</p

A typical retraction muscle EMG signal vs. time synchronized with beetle's front leg protraction/retraction motion.

<p>(A) The EMG signal from the retraction muscle group synchronized with (B) the front leg's protraction/retraction motion. Decrease in the angular displacement represents retraction motion of the front leg. No obvious EMG signals were observed when the beetle was at rest or when it performed protraction motions.</p

Maximum angular displacement elicited by stimulation amplitudes varied from 0.25 V to 2.5 V.

<p>A 30 Hz and 1 ms pulse width monophasic pulse train with varying amplitudes was used to determine the threshold voltage. Leg angular displacement (absolute values used for all the motions) occurred at approximately 1 V and increased steadily until 1.5 V (number of beetles = 5, 17≤ number of data points at each stimulation voltage ≤22). The angular displacement remained maximal when the stimulation voltage ranged from 1.5 to 2.5 V.</p

Representative closed-loop control of protraction/retraction motion at different <i>K</i>_p values and update time intervals.

<p>Comparison of the actual leg angular position (blue path) with a predetermined angular position (red path) during closed-loop control of protraction/retraction of a beetle's front leg at <i>K</i>_p = 0.1, 0.5, 1.0, and 1.5 and for update time intervals of 100 ms, 200 ms, and 300 ms. Positive angular displacement represents the retraction motion while negative angular displacement represents the protraction motion.</p