Perception and reaction of Nanyang Technological University (NTU) researchers to different forms of research integrity education modality.

BACKGROUND: Research and academic institutions use various delivery channels to deliver Research Integrity (RI) education in their communities. Yet there is no consensus on the best delivery method and the effectiveness of these channels in inculcating a positive RI culture varies across institutions. Hence, this study aimed to understand the preferences of the research community in Nanyang Technological University (NTU), Singapore. METHODS: An online survey was conducted on NTU research community to understand their experience with, and preference for each RI education mode offered in NTU. The RI education modes surveyed in the general ranking question are Data Management Plan (DMP) workshops, Epigeum e-Learning, Compass e-newsletter (email), and NTU policy on Research Integrity and Responsible Conduct of Research. There were 242 responses, comprising 50% research students, 32.2% research staff and 17.8% faculty members. Non-parametric statistical techniques were used to analyse preferences across different RI education modes and within sub-groups (i.e., fields, age, native language, roles in research community). RESULTS: More than 92% of respondents subscribed to the importance of RI education, but with different preferences for education modes. With respect to RI education in NTU, Compass e-newsletters were ranked the lowest (p < 0.05). Most felt that they were too wordy and unengaging, making it difficult to absorb information. Similarly, Epigeum e-Learning (p < 0.05) and 'policy' (p < 0.05) were found to be too lengthy in presentation. The compulsory NTU RI education modes (Epigeum e-learning and 'policy') enjoyed higher participation rates of 70-80% compared with 32-37% for the self-regulated modes (DMP workshop and e-newsletter). This suggests that regulatory mechanisms are still necessary to promote participation in RI education, and thus, core RI education content should be made compulsory in research/academic institutions. Although Epigeum is a compulsory course, some may not have participated in the programme due to technical issues or they might have forgotten to participate in the programme within the permissible timeframe. For all four RI education modes in NTU, the lack of awareness was among the top cited reasons for not participating. CONCLUSIONS: Most NTU researchers perceived RI education positively although they may have reservations for some approaches. Conversely, e-Learning is favored over all the other modes except for the mode of Policy. Findings from this study are useful for improving the design of RI education strategies to be more appealing to the research community by enhancing user experience in terms of user-friendliness, relevance to specialisation, providing concise information and better presentation of materials For institutions with similar modes of RI education as NTU, these results may be relevant in improving participation rates and presentation of RI education modes, such as the use of infographics and more concise information.

Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects.

BACKGROUND: An 8-mm needle length is commonly used for insulin injections; however, recent recommendations suggest shorter needles may help patients avoid intramuscular injections and reduce pain, while maintaining adequate glucose control. The goal of these analyses was to compare the pharmacokinetics (PK) and glucodynamics (GD) of insulin lispro after a 5-mm or an 8-mm injection depth administration in 2 populations: normal weight (study 1) or obese (study 2). METHODS: In both open-label, randomized, 2-period crossover euglycemic clamp studies, subjects received single 0.25 U/kg insulin lispro doses on 2 occasions (at 5-mm and 8-mm injection depths); samples for PK and GD analyses were collected up to 6 hours postdose. Noncompartmental PK parameters AUC0-tlast, AUC0-∞, Cmax and GD parameters Gtot, Rmax, tRmax were log-transformed prior to analysis using a mixed effects model. RESULTS: There were no apparent differences between PK profiles at the 5-mm or 8-mm injection depth in either study, demonstrated by the ratios of geometric means of AUC0-tlast, AUC0-∞, and Cmax being close to 1, with 90% confidence intervals (CI) within (0.80, 1.25). There were no apparent differences between GD profiles at either injection depth with the ratios of Gtot and Rmax near unity and 90% CIs that included 1. In both studies, the tRmax values were similar between injection depths, with a small median of pairwise differences and a 90% CI that included zero. CONCLUSIONS: Injection depths in the 5-8 mm range did not affect the PK or GD of insulin lispro in normal weight or obese subjects.

Loss in long-storage-time optical cavities.

Long-storage-time Fabry-Perot cavities are a core component of many precision measurement experiments. Optical loss in such cavities is a critical parameter in determining their performance; however, it is very difficult to determine a priori from independent characterisation of the individual cavity mirrors. Here, we summarise three techniques for directly measuring this loss in situ and apply them to a high-finesse, near-concentric, 2 m system. Through small modifications of the cavity's length, we explore optical loss as a function of beam spot size over the 1-3 mm range. In this regime we find that optical loss is relatively constant at around 5 ppm per mirror and shows greater dependence on the positions of the beam spots on the cavity optics than on their size. These results have immediate consequences for the application of squeezed light to advanced gravitational-wave interferometers.

Stabilized high-power laser system for the gravitational wave detector advanced LIGO.

An ultra-stable, high-power cw Nd:YAG laser system, developed for the ground-based gravitational wave detector Advanced LIGO (Laser Interferometer Gravitational-Wave Observatory), was comprehensively characterized. Laser power, frequency, beam pointing and beam quality were simultaneously stabilized using different active and passive schemes. The output beam, the performance of the stabilization, and the cross-coupling between different stabilization feedback control loops were characterized and found to fulfill most design requirements. The employed stabilization schemes and the achieved performance are of relevance to many high-precision optical experiments.

Effects of smoking cessation, acute re-exposure and nicotine replacement in smokers on AIR inhaled insulin pharmacokinetics and glucodynamics.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Only one other study (Becker et al.) has reported on the influence of smoking cessation and smoking resumption on inhaled insulin pharmacokinetics and glucodynamics, concluding that the rapid changes associated with smoking resumption carry the risk for hypoglycaemia and thus should not be used by active smokers. WHAT THIS STUDY ADDS: * This is the first euglycaemic clamp study on the impact of smoking cessation, acute smoking re-exposure and nicotine replacement on AIR((R)) inhaled insulin pharmacokinetics and glucodynamics. * We demonstrate clinically and statistically significant shifts in glucodynamic response to acute re-exposure to a single cigarette, leading us to conclude that active smokers should be advised against inhaled insulin therapy until smoking abstinence is stable. * Additionally, these results are also the first to demonstrate an apparent independent effect of nicotine replacement therapy on insulin exposure and glucodynamic response. AIMS: To explore the effects of smoking cessation and acute smoking re-exposure on the pharmacokinetic (PK) and glucodynamic (GD) profiles of AIR inhaled insulin (AIR Insulin) with or without nicotine replacement therapy (NRT). METHODS: Nondiabetic smokers (n = 24) with normal pulmonary function completed a two-phase (four-period), open-label, randomized euglycaemic clamp study. During the initial study phase, subjects underwent glucose clamps following AIR Insulin dosing, shortly after smoking, 8-12 h after smoking, or following subcutaneous insulin lispro shortly after smoking. AIR Insulin PK and GD were again assessed during and after a 4-week smoking-cessation period with or without NRT. In the last study period, subjects smoked one cigarette shortly before final AIR Insulin dosing and glucose clamp, to study the effect of acute smoking re-exposure on inhaled insulin PK and GD. RESULTS: Compared with the preceding active smoking phase, the administration of AIR Insulin in nondiabetic subjects undergoing a 4-week period of smoking abstinence resulted in a decrease in PK and GD of approximately 25% (P = 0.008 for both), an effect which was greater in subjects using NRT. Following rechallenge with a single cigarette (without NRT), GD response to AIR Insulin increased significantly (P = 0.006) towards precessation levels, relative to smoking abstinence. In subjects using NRT, however, the increase in GD was less pronounced. CONCLUSION: Smoking, smoking cessation and acute re-exposure with a single cigarette are associated with clinically significant alterations in AIR Insulin pharmacokinetics and glucodynamics. AIR Insulin should not be used by smokers or those at risk for recidivism.

Atomoxetine pharmacokinetics in healthy Chinese subjects and effect of the CYP2D6*10 allele.

AIMS: To characterize atomoxetine pharmacokinetics, explore the effect of the homozygous CYP2D6*10 genotype on atomoxetine pharmacokinetics and evaluate the tolerability of atomoxetine, in healthy Chinese subjects. METHODS: Twenty-four subjects, all CYP2D6 extensive metabolizers (EM), were randomized to receive atomoxetine (40 mg qd for 3 days, then 80 mg qd for 7 days) or matching placebo (2 : 1 ratio) in a double-blind fashion. Atomoxetine serum concentrations were measured following single (40 mg) and multiple (80 mg) doses. Adverse events, clinical safety laboratory data and vital signs were assessed during the study. RESULTS: Atomoxetine was rapidly absorbed with median time to maximum serum concentrations of approximately 1.5 h after single and multiple doses. Atomoxetine concentrations appeared to decrease monoexponentially with a mean apparent terminal half-life (t(1/2)) of approximately 4 h. The apparent clearance, apparent volume of distribution and t(1/2) following single and multiple doses were similar, suggesting linear pharmacokinetics with respect to time. Homozygous CYP2D6*10 subjects had 50% lower clearances compared with other EM subjects, resulting in twofold higher mean exposures. No clinically significant changes or abnormalities were noted in laboratory data and vital signs. CONCLUSIONS: The pharmacokinetics of atomoxetine in healthy Chinese subjects appears comparable to other ethnic populations. Multiple dosing of 80 mg qd atomoxetine was well tolerated in this study.

Duloxetine pharmacokinetics are similar in Japanese and Caucasian subjects.

AIMS: To compare single- and multiple-dose duloxetine pharmacokinetics between healthy Japanese and Caucasians. METHODS: Twenty-four subjects of each race were given single oral doses of duloxetine (20, 40 and 60 mg) in a randomized, double-blind study. Another 20 subjects of each race received 20, 40 mg or placebo (2 : 2 : 1) twice-daily for 5 days. RESULTS: Following single doses, the mean duloxetine C(max) and AUC were approximately 20% greater in Japanese. This difference could be explained by the 15% lower average body weight in Japanese. Similar results were observed following multiple dosing. CONCLUSION: Duloxetine pharmacokinetics are not meaningfully different between Japanese and Caucasians.

Insulin-like growth factor binding protein-1 is independently affected by ethnicity, insulin sensitivity, and leptin in healthy, glucose-tolerant young men.

We examined the relationships among IGF binding protein (IGFBP)-1, insulin sensitivity, and leptin in different ethnic groups (Asian Indians, Chinese, and Caucasians) using the euglycemic hyperinsulinemic clamp. Ten healthy, young and nondiabetic subjects of each ethnic group, matched for body mass index, age, and physical activity were studied. A euglycemic clamp was performed on all subjects. IGFBP-1, insulin, and leptin were measured after fasting and during the clamp. Fasting IGFBP-1 concentration was highest in Chinese (P = 0.027). Asian Indians had the lowest insulin sensitivity index (P = 0.006). The ratio of insulin to IGFBP-1 at fasting and throughout the euglycemic clamp was higher in Asian Indians. Fasting IGFBP-1 had a strong negative correlation with fasting leptin levels (r = -0.715, P = 0.001). Multiple linear regression demonstrated that fasting insulin, leptin, ethnicity, and insulin sensitivity were significant predictors for fasting IGFBP-1. IGFBP-1 is independently determined by ethnicity, insulin sensitivity, and leptin in glucose-tolerant men. The presence of relative insulin resistance and low fasting IGFBP-1 levels in Asian Indians may contribute to their higher risk of developing diabetes and cardiovascular disease.

Evaluation of long-term triazolam use in an ambulatory Veterans Administration Medical Center population.

Triazolam is indicated for the short-term treatment of insomnia. To determine how it was being prescribed and used, we examined triazolam use in patients who had received the drug for greater than six weeks. We reviewed medical charts of 72 adult male patients from an ambulatory Veterans Administration population who had received a 30-day triazolam prescription with at least one refill. Results showed that although prescribed daily doses of triazolam were generally appropriate for the age of the patient being treated, the average length of therapy was 6.2 months. Seventy-five percent of the prescriptions had been written for a one-month supply with five refills. Neither prescriber specialty nor level of training was significantly related to length of therapy. Thirty-nine of the patients (54 percent) were available for a telephone interview to determine how the drug was actually being used and the adverse effects profile. Over 60 percent claimed to be taking the drug every night, 95 percent at the dose prescribed. Sixty-seven percent of the patients taking triazolam nightly reportedly did not sleep as well if they tried a night without the drug. Apart from effects on sleep, dizziness and confusion were the most commonly reported adverse effects. As a result of this study, automatic stop orders on discharge were implemented to limit triazolam therapy to inpatient stays. Physicians must evaluate the need for continued hypnotic therapy so that a longer-acting agent like flurazepam may be used if chronic medication is necessary.

Cyclic EEG and motility patterns during sleep in restrained infant rats.

When restrained in a quasi-fetal position, infant rats (2--3 weeks old) remain for an extended period in a sleep-like state as judged by polygraphic criteria. Moreover, they become very difficult to arouse by sensory stimuli, and show a level of spontaneous motility considerably higher than is normally found at this age during sleep. Phasic generalized body movements, which are often quite stereotyped, occur in trains at regular intervals, against a low background level of neck muscle tonus. The amplitude of the cortical EEG, especially in the delta band, is negatively correlated with the frequency of spontaneous motor burst activity. It is suggested that these REM-like "rapid body movements" in immature mammals may well represent a transitional stage between fetal behavior patterns and sleep motility in the adult organism.