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Concept: Limit superior and limit inferior

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Barbecuing or charcoal grilling has become part of the popular outdoor recreational activities nowadays; however, potential human health hazards through outdoor exposure to BBQ fume have yet to be adequately quantified. To fill this knowledge gap, atmospheric size-fractioned particle and gaseous samples were collected near an outdoor-barbecuing vendor stall (along with charcoal-grilled food items) in Xinjiang of Northwest China with a 10-stage Micro-Orifice Uniform Deposit Impactor and a PUF sampler and were analyzed for particulate matter and polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs through inhalation and dermal contact by adult consumers who spent one hour per day near a charcoal-grilled vendor for a normal meal (lunch or dinner) amounted to a BaP equivalent (BaPeq) dosage of 3.0-77 ng d-1 (inhalation: 2.8-27 ng d-1 of BaPeq; dermal contact: 0.2-50 ng d-1 of BaPeq), comparable to those (22-220 ng d-1 of BaPeq) through the consumption of charcoal-grilled meat assumed to be at the upper limit of 50-150 g. In addition, the potential health risk was in the range of 3.1×10-10-1.4×10-4 for people of different age groups with inhalation and dermal contact exposure to PAHs once a day, with the 95% confidence interval (7.2×10-9-1.2×10-5) comparable to the lower limit of the potential cancer risk range (1×10-6-1×10-4). Sensitivity analyses indicated that the area of dermal contact with gaseous contaminants is a critical parameter for risk assessment. These results indicated that outdoor exposure (particularly dermal contact) to BBQ fume may have become a significant but largely neglected source of health hazards to the general population and should be well recognized.

Concepts: Polycyclic aromatic hydrocarbon, Barbecue, Limit superior and limit inferior

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Soft, solvent-free poly(dimethylsiloxane) elastomers are fabricated by a one-step process via crosslinking bottlebrush polymers. The bottlebrush architecture prevents the formation of entanglements, resulting in elastomers with precisely controllable low moduli from 1 to 100 kPa, below the lower limit of traditional elastomers; moreover, the solvent-free nature enables their negligible adhesiveness compared to commercially available silicone products of similar stiffness.

Concepts: Polymer, Elastomer, Polydimethylsiloxane, Limit superior and limit inferior

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Objectives To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days' hormone free), on several coagulation factors and thrombin formation markers. Methods Randomised, open-label, parallel-group comparative study involving healthy women (18-40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months. Results A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [- 18.3 pmol/L] > - 130 pmol/L). Conclusions The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE.

Concepts: Birth control, Hormonal contraception, Combined oral contraceptive pill, Coagulation, Platelet, Menstrual cycle, Thrombin, Limit superior and limit inferior

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: The purpose of this study was to examine the effects of hot (37°C) and cool (10°C) environments on cycling time-to-exhaustion (TTE), pH, lactate, and core temperature (Tc). Eleven endurance-trained subjects completed four TTE trials: Hot, 80% VO2max (H80); Cool 80% (C80); Hot 100% (H100); and Cool 100% VO2max (C100). Esophageal temperature and blood was sampled before, every 5 min, at exhaustion, and 3 min post-exercise and analyzed for lactate, pH, and HCO3. Multifactorial ANOVA with repeated measures was used to determine differences between means (±SD). TTE was shorter in H100 and C100 vs. H80 and C80 (5.64±1.49, 5.83±1.03, 12.82±2.0, and 24.85±6.0 min, respectively), and shorter in H80 vs. C80 (p < 0.01). pH at exhaustion was different among all conditions (7.17±0.06, 7.15±0.07, 7.21±0.04, and 7.24±0.06 units for H100, C100, H80, and C80, respectively, p = 0.02). Tc at exhaustion was lower in H100 and C100 (37.93±0.67 and 37.62±0.58o C) vs. H80 and C80 (38.54±0.51 and 38.53±0.38o C) (p < 0.01). In H80 and C80 the higher Tc likely played a greater role in the termination of exercise; whereas, in H100 and C100, pH and metabolic changes may have been more important. Despite these differences, neither an upper limit for Tc, nor a lower limit for pH was identified; thus, fatigue based entirely on peripheral factors was not supported, and a combination of peripheral and central processes must be considered. The practical implications of these findings are that aerobic exercise at or near VO2max may be impacted more by metabolic factors, while lower intensities (approx. 80% Vo2max) may be affected more by heat stress; these differences should be considered when training for events of this type.

Concepts: Exercise physiology, Limit superior and limit inferior

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Carbon emissions resulting from deforestation and forest degradation are poorly known at local, national and global scales. In part, this lack of knowledge results from uncertain above-ground biomass estimates. It is generally assumed that using more sophisticated methods of estimating above-ground biomass, which make use of remote sensing, will improve accuracy. We examine this assumption by calculating, and then comparing, above-ground biomass area density (AGBD) estimates from studies with differing levels of methodological sophistication. We consider estimates based on information from nine different studies at the scale of Africa, Mozambique and a 1160 km(2) study area within Mozambique. The true AGBD is not known for these scales and so accuracy cannot be determined. Instead we consider the overall precision of estimates by grouping different studies. Since an the accuracy of an estimate cannot exceed its precision, this approach provides an upper limit on the overall accuracy of the group. This reveals poor precision at all scales, even between studies that are based on conceptually similar approaches. Mean AGBD estimates for Africa vary from 19.9 to 44.3 Mg ha(-1), for Mozambique from 12.7 to 68.3 Mg ha(-1), and for the 1160 km(2) study area estimates range from 35.6 to 102.4 Mg ha(-1). The original uncertainty estimates for each study, when available, are generally small in comparison with the differences between mean biomass estimates of different studies. We find that increasing methodological sophistication does not appear to result in improved precision of AGBD estimates, and moreover, inadequate estimates of uncertainty obscure any improvements in accuracy. Therefore, despite the clear advantages of remote sensing, there is a need to improve remotely sensed AGBD estimates if they are to provide accurate information on above-ground biomass. In particular, more robust and comprehensive uncertainty estimates are needed.

Concepts: Better, Improve, Africa, Measurement, Accuracy and precision, Uncertainty, Remote sensing, Limit superior and limit inferior

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BACKGROUND/AIM: To evaluate efficacy and safety of bimatoprost 0.03% preservative-free (PF) ophthalmic solution versus bimatoprost 0.03% (Lumigan) ophthalmic solution for glaucoma or ocular hypertension. METHODS: In this double-masked, parallel-group study, patients were randomised to bimatoprost PF or bimatoprost for 12 weeks. The primary analysis for non-inferiority was change from baseline in worse eye intraocular pressure (IOP) in the per-protocol population at week 12. For equivalence, it was average eye IOP in the intent-to-treat population at each time point at weeks 2, 6 and 12. RESULTS: 597 patients were randomised (bimatoprost PF, n=302 and bimatoprost, n=295). The 95% CI upper limit for worse eye IOP change from baseline was <1.5 mm Hg at each week 12 time point, meeting prespecified non-inferiority criteria. The 95% CI upper limit for the treatment difference for average IOP was 0.69 mm Hg and the lower limit was -0.50 mm Hg at all follow-up time points (hours 0, 2 and 8 at weeks 2, 6 and 12), meeting equivalence criteria. Both treatments showed decreases in mean average eye IOP at all follow-up time points (p<0.001), were safe and well tolerated. CONCLUSIONS: Bimatoprost PF is non-inferior and equivalent to bimatoprost in its ability to reduce IOP-lowering with a safety profile similar to bimatoprost.

Concepts: Intraocular pressure, Glaucoma, Ophthalmology, Limit superior and limit inferior

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Copper (Cu) is an important enzyme co-factor that is also extremely toxic at high intracellular concentrations, making active efflux mechanisms essential for preventing Cu accumulation. Here, we have investigated the mechanistic role of metallochaperones in regulating Cu efflux. We have constructed a computational model of Cu trafficking and efflux based on systems analysis of the Cu stress response of Halobacterium salinarum. We have validated several model predictions via assays of transcriptional dynamics and intracellular Cu levels, discovering a completely novel function for metallochaperones. We demonstrate that in addition to trafficking Cu ions, metallochaperones also function as buffers to modulate the transcriptional responsiveness and efficacy of Cu efflux. This buffering function of metallochaperones ultimately sets the upper limit for intracellular Cu levels and provides a mechanistic explanation for previously observed Cu metallochaperone mutation phenotypes.

Concepts: Scientific method, Molecular biology, Enzyme, Copper, Buffer, Limit of a sequence, Limit superior and limit inferior, Limit of a function

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Sepsis, the life-threatening organ dysfunction caused by a dysregulated host response to infection, is difficult to identify and to prognosticate for. In people with sepsis, procalcitonin (PCT) measurement aids diagnosis, enables therapeutic monitoring and improves prognostic accuracy. This study used a commercial canine PCT assay to measure plasma PCT concentrations in dogs with gastric dilatation volvulus (GDV) syndrome and in dogs with sepsis. It was hypothesised that dogs with GDV syndrome and with sepsis have greater plasma PCT concentrations than healthy dogs and that dogs with sepsis have greater PCT concentrations than dogs with GDV syndrome. Before analysing canine plasma samples, the ability of the assay to identify canine PCT, in addition to assay imprecision and the lower limit of detection were established. The assay had low imprecision with coefficients of variation ≤4.5 per cent. The lower limit of detection was 3.4 pg/ml. Plasma PCT concentrations were measured in 20 dogs with sepsis, in 32 dogs with GDV syndrome and in 52 healthy dogs. Median (IQR) PCT concentration in dogs with sepsis 78.7 pg/ml (39.1-164.7) was significantly greater than in healthy dogs 49.8 pg/ml (36.2-63.7) (P=0.019), but there were no significant differences between PCT concentrations in dogs with GDV syndrome and controls (P=0.072) or between dogs with sepsis and GDV syndrome (P=1.000). Dogs with sepsis have significantly increased plasma PCT concentrations compared with healthy dogs, although considerable overlap between these populations was identified. Future investigations should confirm this finding in other populations and evaluate the diagnostic and prognostic value of PCT in dogs with sepsis.

Concepts: AIDS, Measurement, Concentration, Prognosis, Limit superior and limit inferior

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In this study, a ratiometric strategy-based electrochemical sensor was developed by electropolymerization of thionine (THI) and β-cyclodextrin (β-CD) composite films on a glassy carbon electrode surface for imidacloprid (IMI) detection. THI played the role of an inner reference element to provide a built-in correction. In addition, the modified β-CD showed good selective enrichment for IMI to improve the sensitivity and anti-interference ability of the sensor. The current ratio between IMI and THI was calculated as the detected signal for IMI sensing. Compared with common single-signal sensing, the proposed ratiometric strategy showed a higher linear range and a lower limit of detection of 4.0 × 10-8-1.0 × 10-5 mol L-1 and 1.7 × 10-8 mol L-1, respectively, for IMI detection. On the other hand, the ratiometric strategy endowed the sensor with good accuracy, reproducibility, and stability. The sensor was also used for IMI determination in real samples with satisfactory results. The simple, effective, and reliable way reported in this study can be further used to prepare ratiometric strategy-based electrochemical sensors for the selective and sensitive detection of other compounds with good accuracy and stability.

Concepts: Electrochemistry, Sensitivity and specificity, Carbon, Real number, Sensor, Limit of a sequence, Limit superior and limit inferior, Glassy carbon

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The analysis of organic impurities plays an important role in impurity profiling of methamphetamine, which in turn provides valuable information about methamphetamine manufacturing, particular its synthetic route, chemicals and precursors used. Ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its excellent sensitivity, selectivity, and wide linear range in multiple reactions monitoring (MRM) mode. In this study, a dilute and shoot UHPLC-MS/MS method was developed for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine. The developed method was validated in terms of stability, limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared methamphetamine samples were analyzed. Due to its ability to detect ephedrine/pseudoephedrine and high sensitivity for critical target markers (e.g., chloro-pseudoephedrine, N-cyclohexylamphetamine, compounds B and P, etc.), more impurities and precursor/pre-precursors were identified and quantified versus the current procedure by gas chromatography-mass spectrometry (GC-MS). Consequently, more samples could be classified by their synthetic routes. However, the UHCPL-MS/MS method has difficulty in detecting neutral and untargeted emerging manufacturing impurities, and can therefore only serve as a complement to the current method. Despite this deficiency, the quantitative information acquired by the presented UHPLC-MS/MS methodology increased the sample discrimination power, thereby enhancing the capacity of methamphetamine profiling program (MPP) to conduct sample-sample comparisons.

Concepts: Mass spectrometry, Measurement, Analytical chemistry, Detection limit, Methodology, Liquid chromatography-mass spectrometry, Limit superior and limit inferior, Impurity