Spectrally combined four-diode-pumped femtosecond Ti:sapphire laser with 16.3 nJ pulse and its application to video-rate coherent anti-Stokes Raman scattering spectro-microscopy.

We demonstrate the generation of high-energy femtosecond pulses by a spectrally combined four-diode-pumped Ti:sapphire laser with semi-conductor saturable absorber mirror mode locking. To achieve energy scaling, the laser cavity was extended using a design based on the Herriott multipass cell. The laser operates at a 17.5 MHz repetition rate and generates pulses with energies as high as 16.3 nJ and 80 fs in duration. The signal-to-noise ratio at the fundamental frequency showed an extinction ratio of >50 dB relative to the carrier. This compact single laser was applied to video-rate forward and backward coherent anti-Stokes Raman scattering spectro-microscopy with a pixel dwell time of 122 ns, which is the lowest dwell time ever achieved, to the best of our knowledge.

High-resolution and a wide field-of-view eye-safe LiDAR based on a static unitary detector for low-SWaP applications.

High three-dimensional (3D) resolution for a wide field-of-view (FoV) is difficult in LiDARs because of the restrictions concerning size, weight, and power consumption (SWaP). Using a static unitary detector (STUD) approach, we developed a photodetector and a laser module for a LiDAR. Utilizing the fabricated photodetector and laser module, a LaserEye2 LiDAR prototype for low-SWaP applications was built using the STUD approach, which efficiently enables short-pulse detection with the increased FoV or large photosensitive area. The obtained 3D images demonstrated a diagonal FoV of > 31°, a frame rate of up to 15 Hz, and a spatial resolution of 320 × 240 pixels within a detection range of > 55 m. This prototype can be applied to drones to rapidly detect small or thin hazardous objects such as power lines.

Spectrally combined three-diode-pumped compact femtosecond Ti:sapphire laser exceeding 1 W mode-locked power.

The achievement of a high average power exceeding 1 W remains a major challenge for direct-diode pumped and mode-locked femtosecond Ti:sapphire lasers. Herein, we demonstrate high-power soliton-like pulses from a direct spectrally combined three-diode-pumped and semiconductor saturable absorber mirror (SESAM)-based mode-locked Ti:sapphire laser. Its mode-locked output power of up to 1 W was obtained in correspondence with a 68.8 MHz repetition rate and 55 fs pulse duration; thus, the pulse energy and peak power are 14.5 nJ and 264 kW, respectively. To the best of our knowledge, this is the highest reported output power and pulse energy from a Ti:sapphire laser with three spectrally combined pump diodes (471 nm, 491 nm, and 525 nm) and a simple beam expander. For efficient pumping, the combined pump beam, directed into the lens (f = 60 mm), which comprised three aspheric lenses along the fast axis and a shared cylindrical beam telescope (8× magnification) along the slow axis, resulting in a circular-focused beam in the Ti:sapphire crystal. The beam waist was measured to be 39 µm ×38 µm along the slow and fast axes.

Fabrication of 4 × 1 signal combiner for high-power lasers using hydrofluoric acid.

We report a new method to fabricate a 4 × 1 signal combiner that comprises an output fiber port and a tapered fused bundle (TFB) with four input fiber ports. The TFB is etched in a solution of hydrofluoric acid and spliced with an output fiber of core diameter 105 µm and cladding diameter 125 µm. Each cladding of the four input optical fiber is etched to approximately 72.5 µm. The etched TFB was fabricated by tapering after forming a bundle of four etched optical fibers. Subsequently, the 4 × 1 signal combiner is fabricated by fusion splicing between the fabricated TFB and output optical fiber with a numerical aperture of 0.15. The efficiency of each port of the fabricated 4 × 1 signal combiner is in the range of 93.3-98.3%. When an optical power of approximately 624.5 W was input to the signal combiner, the maximum output was ~612 W and the efficiency was ~98%. The beam quality factor, M 2is measured to be approximately 14.6, which is calculated as the beam parameter product (BPP) of 5.02 mm·mrad.

Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial.

BACKGROUND: Flexibility in the recommended dosing time for a statin may improve patient compliance. OBJECTIVE: This study was designed to compare the efficacy and tolerability of morning and evening doses of controlled-release simvastatin in Korean adults with dyslipidemia. It was carried out as a requirement to obtain authorization from the Korean regulatory agency to market the product. METHODS: In this prospective, randomized, double-blind, multicenter, placebo-controlled Phase III study, we randomly assigned 132 patients with hypercholesterolemia to a morning-dose group or an evening-dose group. Patients in the morning-dose group received 20 mg controlled-release simvastatin in the morning and a placebo in the evening, and those in the evening-dose group received a placebo in the morning and 20 mg controlled-release simvastatin in the evening. RESULTS: After 8 weeks of the treatment, the difference in the mean change of LDL-C between the morning-dose and evening-dose groups was -2.78% (95% confidence interval, -7.65 to 2.10). The changes in total cholesterol, triglycerides, HDL-C, apolipoprotein A1, apolipoprotein B, and lipoprotein (a) after treatment did not differ between groups. Also, the achievement rates of the target LDL-C goal suggested by the dyslipidemia treatment guideline of the Korean Society of Lipidology and Atherosclerosis were not different. No serious adverse event was observed in either group. Mild and moderate adverse events were observed similarly in both groups. CONCLUSIONS: Although controlled-release simvastatin significantly reduces LDL-C levels with good tolerability in Korean adults with dyslipidemia, the time of administration does not affect its efficacy.

Elevated free fatty acid is associated with cardioembolic stroke subtype.

BACKGROUND AND OBJECTIVES: Free fatty acids (FFAs), an important energy substrate, have an association with cardiovascular diseases, such as atherosclerosis, myocardial dysfunction and abnormal cardiac rhythm. However, limited reports are available on the association between FFAs and ischemic stroke. We hypothesized that plasma FFA concentration could be associated with an ischemic stroke, emphasizing the relationship between FFA and subtypes of ischemic stroke. METHODS: A cross-sectional study examined the association between FFA concentration and subtypes of stroke and cerebral atherosclerosis from a hospital-based acute stroke registry. RESULTS: Data of 715 stroke patients were analyzed. The concentration of FFA was highest in the cardioembolic stroke subtype compared with the other stroke subtypes. Logistic regression analysis revealed that an increase in FFA concentration was significantly associated with the cardioembolic subtype after the adjustment of covariates. FFA concentration was also higher in patients with atrial fibrillation (AF) than those without AF. According to the presence of atherosclerotic stenosis, no significantly difference of FFA concentration was found for intracranial and extracranial cerebral arterial atherosclerosis. CONCLUSION: Here we report a significant association between fasting FFA concentration and the cardioembolic stroke subtype. AF is suggested as the mediating factor between FFA and the cardioembolic stroke subtype.

Results of a phase III, 8-week, multicenter, prospective, randomized, double-blind, parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension.

BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension. OBJECTIVE: This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not. RESULTS: A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively). CONCLUSION: The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.

Effects of cilostazol on platelet activation in coronary stenting patients who already treated with aspirin and clopidogrel.

BACKGROUND: A recent study has shown that triple anti-platelet therapy (cilostazol+clopidogrel+aspirin) resulted in a significantly lower restenosis rate after coronary stenting than did conventional therapy (clopidogrel+aspirin). However, the anti-platelet effects of cilostazol, when combined with clopidogrel and aspirin, have not been evaluated. METHODS: Low dose cilostazol (50 mg/BID) was given to 47 patients who had already been taking clopidogrel (75 mg/day) and aspirin (100 mg/day) for more than 1 month subsequent to coronary stenting due to AMI and unstable angina. Markers of platelet activation, P-selectin and activated GPIIb/IIIa on platelets, were measured at baseline and 2 weeks after cilostazol treatment. We empirically divided patients into tertiles (low, n =16; moderate, n = 14; high group, n = 17), according to the baseline P-selectin expression. We then performed a comparative assessment of the anti-platelet effects of cilostazol at baseline and after 2 weeks of cilosatzol administration. RESULTS: P-selectin was significantly decreased after 2 weeks of cilostazol treatment in total patients (n = 47, 3.2 +/- 2.4% to 2.0 +/- 1.9%, p = 0.03). This inhibition of P-selectin expression was mainly achieved in the moderate and high P-selectin groups (low group; 1.4 +/- 0.5 to 1.9 +/- 1.3%, p > 0.05, moderate group; 2.5 +/- 0.3 to 1.3 +/- 0.3%, p < 0.05, high group; 5.4 +/- 2.7 to 2.7 +/- 2.8%, p < 0.05). Activated GPIIb/IIIa was not significantly changed (13.5% to 17.6%, p > 0.05). Underying disease, cardiovascular risk factors, concomitant medication including statin, and hsCRP were not related to the degree of P-selectin expression. CONCLUSION: Our data demonstrated that cilostazol treatment in addition to conventional anti-platelet therapy provides more effective suppression of platelet P-selectin expression in patients with relatively high platelet activity.