C-labeled YH4808, a novel potassium-competitive acid blocker, was intravenously administered as a microtracer at 80 μg (11.8 kBq or 320 nCi) concomitantly with the nonradiolabeled oral drug at 200 mg to determine the absolute bioavailability and to assess the effect of pharmacogenomics on the oral absorption of YH4808. The absolute bioavailability was low and highly variable (mean, 10.1%; range, 2.3-19.3%), and M3 and M8, active metabolites of YH4808, were formed 22.6- and 38.5-fold higher after oral administration than intravenous administration, respectively. The product of the fraction of an oral YH4808 dose entering the gut wall and the fraction of YH4808 passing on to the portal circulation was larger in subjects carrying the variants of the CHST3, SLC15A1, and SULT1B1 genes. A combined LC+AMS is a useful tool to construct a rich and highly informative pharmacokinetic knowledge core in early clinical drug development at a reasonable cost.

This study examined the effects of lighting colour on emotional states and the effects of ethnicity on the impact of lighting colours on emotional states, based on the Mehrabian and Russell’s emotional state model measuring pleasure, arousal and dominance. It was hypothesised that there are significant differences in pleasure and arousal among six lighting colours: red, green, blue, yellow, orange and purple and that different ethnicities (i.e. Asian and Caucasian) can influence the effects of the six lighting colours on pleasure and arousal. To test the hypotheses, an experiment was conducted in a controlled lab using a colour-changing LED lighting fixture with 82 participants. The results revealed that there were significant differences in pleasure and arousal among the six lighting colours. Ethnicity had significant effects on the impact of lighting colour on pleasure but not on arousal. Blue was the most pleasant lighting colour and showed significantly higher pleasure than red and purple. Red was the least pleasant lighting colour and showed significantly lower pleasure than all other lighting colours. Asians found red and purple lighting significantly less pleasant than all other colours and tended to feel more unpleasant when exposed to red, orange and purple lighting than Caucasians.

Background The development of myocardial fibrosis is a key mechanism in the transition from compensated hypertrophy to heart failure in aortic stenosis (AS). Focal and diffuse fibrosis can be quantified using cardiac magnetic resonance (CMR) imaging late gadolinium-enhanced (LGE) and T1 mapping techniques. Purpose To assess T1 mapping measures of fibrosis in patients with severe AS referred for aortic valve intervention, and determine their associations with clinical characteristics, disease severity and long-term clinical outcome. Methods In this international prospective cohort study, patients with severe AS underwent contrast enhanced CMR with T1 mapping and LGE prior to aortic valve intervention. Image analysis was performed by a single core laboratory and the extracellular volume fraction [ECV%] calculated from T1 mapping images. The presence of LGE was determined visually and quantified using the full-width-at-half-maximum technique. Results Four-hundred and forty patients (70±10 years, 59% male) from ten international centres were enrolled. Aortic valve intervention was performed 15 [4 to 58] days following CMR. Within a follow-up of 3.8 [2.8 to 4.6] years, 52 patients died. ECV% (mean 27.7±3.6%) correlated with increasing age, Society of Thoracic Surgeons Predicted Risk of Mortality score, known coronary artery disease, lower peak aortic-jet velocity, larger left ventricular (LV) mass, lower LV ejection fraction, and presence of LGE (P<0.05 for all). Following adjustment for all demographic and clinical variables, ECV% remained associated with age (P=0.028), LV ejection fraction (P<0.001) and presence of LGE (P=0.035). Univariable predictors of all-cause mortality included age, male sex, impaired LV ejection fraction and presence of LGE (all P<0.05). A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6 and 52.7 deaths per 1000 patient-years; log-rank test, P=0.009). ECV% was independently associated with all-cause mortality following adjustment for age, sex, impaired LV ejection fraction and presence of LGE (HR per unit increase in ECV: 1.10, 95%, (1.02–1.19), P=0.013). ECV440 abstract iamge Conclusion In patients with severe aortic stenosis scheduled for aortic valve intervention, extracellular volume-based T1 mapping correlates with LV decompensation. ECV% is a strong independent predictor of late all-cause mortality and is a potential therapeutic target.

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Purpose To introduce and characterize a new “reverse‐Fricke” radiation reporting system utilizing the reduction of ferric ions (Fe3+) to ferrous ions (Fe2+). Methods Two formulations of the radiochromic reporting system, referred to as A and B, were prepared for investigation. Formulation‐A consisted of 14 mM 1,10‐phenanthroline, 42 mM ethanol, and 57 mM ammonium ferric oxalate in water. Formulation‐B consisted of 27 mM 1,10‐phenanthroline, 42 mM ethanol, and 28 mM ammonium ferric oxalate in water. Solutions were prepared immediately prior to irradiation with a Cobalt‐60 unit with radiation doses of 0, 1, 5, 10, 15, 20, and 25 Gy. The change in optical density over the visible range of 450–650 nm was measured using a spectrophotometer immediately after irradiation. The effective atomic numbers of the formulations were calculated using Mayneord's formula. Results Ionizing radiation energy absorbed in the solutions causes the reduction of ferric ions (Fe3+) into ferrous ions (Fe2+), which then forms a 1:3 red colored complex with 1,10‐phenanthroline ([(C1 2H8N2)3Fe]2+) that can be measured spectrophotometrically. The absorbance spectra of the resulting complex displayed a peak maximum at 512 nm with a greater change in absorbance for Formulation‐B after receiving comparable radiation doses. The change in absorbance relative to dose exhibited a linear response up to 25 Gy for both Formulation‐A (R2 = 0.98) and Formulation‐B (R2 = 0.97). The novel formulations were also nearly water equivalent (Zeff = 7.42) with effective atomic numbers of 7.65 and 7.52 and mass densities within 0.2% of water. Conclusion Both formulations displayed visible Fe2+ complex formation with 1,10‐phenanthroline after irradiation using a Cobalt‐60 source. The higher sensitivity measured for Formulation‐B is attributed to the increase in 1,10‐phenanthroline concentration and the increase in the 1,10‐phenanthroline to ammonium ferric oxalate ratio. Further investigation of this radiation reporting system in a 3D matrix material is encouraged. NSF GRFP Grant Award #LH‐102SPS