Exploring the Relationship Between Morphine Concentration and Oversedation in Children After Cardiac Surgery

Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration-effect relationship for morphine-associated oversedation after cardiac surgery in children aged 3 months to 3 years. Data on morphine dosing, as well as morphine plasma concentrations, were available from a previous study on the pharmacokinetics of morphine after cardiac surgery in children. Oversedation was defined as scores below 11 on the validated COMFORT-behavioral scale. Population pharmacokinetic-pharmacodynamic modeling was performed in NONMEM 7.3. The probability of oversedation as a function of morphine concentration was best described using a step function in which the EC50 was 46.3 ng/mL. At morphine concentrations below the EC50, the probability of oversedation was 2.9% (0.4& to 18%), whereas above the EC50 percentages were 13% (1.9% to 52%) (median value [95% prediction interval from interindividual variability]). Additionally, the risk of oversedation was found to be increased during the first hours after surgery (

Resequencing and Analysis of Variation in the TCF7L2 Gene in African Americans Suggests That SNP rs7903146 Is the Causal Diabetes Susceptibility Variant

OBJECTIVE—Variation in the transcription factor 7-like 2 (TCF7L2) locus is associated with type 2 diabetes across multiple ethnicities. The aim of this study was to elucidate which variant in TCF7L2 confers diabetes susceptibility in African Americans. RESEARCH DESIGN AND METHODS—Through the evalua-tion of tagging single nucleotide polymorphisms (SNPs), type 2 diabetes susceptibility was limited to a 4.3-kb interval, which contains the YRI (African) linkage disequilibrium (LD) block containing rs7903146. To better define the relationship between type 2 diabetes risk and genetic variation we resequenced this 4.3-kb region in 96 African American DNAs. Thirty-three novel and 13 known SNPs were identified: 20 with minor allele frequencies (MAF).0.05 and 12 with MAF.0.10. These poly-morphisms and the previously identified DG10S478 microsatellite were evaluated in African American type 2 diabetic cases (n

Exploring the Relationship Between Morphine Concentration and Oversedation in Children After Cardiac Surgery

Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration-effect relationship for morphine-associated oversedation after c

Exploring the relationship between morphine concentration and oversedation in children after cardiac surgery

Titrating analgesic and sedative drugs in pediatric intensive care remains a challenge for caregivers due to the lack of pharmacodynamic knowledge in this population. The aim of the current study is to explore the concentration-effect relationship for morphine-associated oversedation after cardiac surgery in children aged 3 months to 3 years. Data on morphine dosing, as well as morphine plasma concentrations, were available from a previous study on the pharmacokinetics of morphine after cardiac surgery in children. Oversedation was defined as scores below 11 on the validated COMFORT-behavioral scale. Population pharmacokinetic-pharmacodynamic modeling was performed in NONMEM 7.3. The probability of oversedation as a function of morphine concentration was best described using a step function in which the EC50 was 46.3 ng/mL. At morphine concentrations below the EC50, the probability of oversedation was 2.9% (0.4& to 18%), whereas above the EC50 percentages were 13% (1.9% to 52%) (median value [95% prediction interval from interindividual variability]). Additionally, the risk of oversedation was found to be increased during the first hours after surgery (P < .001) and was significantly lower during mechanical ventilation (P < .005). We conclude that morphine concentrations above approximately 45 ng/mL may increase the probability of oversedation in children after cardiac surgery. The clinician must evaluate, on a case-by-case basis, whether the analgesic benefits arising from dosing regimen associated with such concentrations outweigh the risks.Pharmacolog

Aldose Reductase Genotypes and Cardiorenal Complications: An 8-year prospective analysis of 1,074 type 2 diabetic patients

OBJECTIVE—We report the independent risk association of type 2 diabetic nephropathy with the z−2 allele of the 5′-(CA)n microsatellite and C-106T promoter polymorphisms of the aldose reductase gene (ALR2) using a case-control design. In this expanded cohort, we examined their predictive roles on new onset of cardiorenal complications using a prospective design

Facet dependent carrier dynamics of cuprous oxide regulating the photocatalytic hydrogen generation

The intrinsic carrier dynamics of cuprous oxide Cu2O are known to have a crucial influence on photocatalytic performances. The photoactivity of rhombic dodecahedral Cu2O with dominant 110 facets RD Cu2O is demonstrated to surpass that of cubic Cu2O with 100 surfaces CB Cu2O . Time resolved microwave conductivity TRMC measurements reveal the higher carrier mobility of RD Cu2O when compared to CB Cu2O. Additionally, modulated surface photovoltage SPV measurements further supported the better charge separation efficiency of RD Cu2O. Although CB Cu2O exhibited more pronounce SPV signals, the homogeneous distribution of electrical fields drives the majority charge inward and led to detrimental charge recombination. In contrast, the weak SPV signals for RD Cu2O were attributed to a modulated distribution of charges towards the facets and facet boundaries, demonstrating a better charge separation. This study shows that carrier dynamics and defect density should also be regarded as facet dependent properties that can have deciding influence on the photocatalytic activit

ALMA observations of molecules in Supernova 1987A

Supernova (SN) 1987A has provided a unique opportunity to study how SN ejecta evolve in 30 years time scale. We report our ALMA spectral observations of SN 1987A, taken in 2014, 2015 and 2016, with detections of CO, 28SiO, HCO+ and SO, with weaker lines of 29SiO. We find a dip in the SiO line profiles, suggesting that the ejecta morphology is likely elongated. The difference of the CO and SiO line profiles is consistent with hydrodynamic simulations, which show that Rayleigh-Taylor instabilities causes mixing of gas, with heavier elements much more disturbed, making more elongated structure. Using 28SiO and its isotopologues, Si isotope ratios were estimated for the first time in SN 1987A. The estimated ratios appear to be consistent with theoretical predictions of inefficient formation of neutron rich atoms at lower metallicity, such as observed in the Large Magellanic Cloud (about half a solar metallicity). The deduced large HCO+ mass and small SiS mass, which are inconsistent to the predictions of chemical model, might be explained by some mixing of elements immediately after the explosion. The mixing might have made some hydrogen from the envelope to sink into carbon and oxygen-rich zone during early days after the explosion, enabling the formation of a substantial mass of HCO+. Oxygen atoms may penetrate into silicon and sulphur zone, suppressing formation of SiS. Our ALMA observations open up a new window to investigate chemistry, dynamics and explosive-nucleosynthesis in supernovae

Lorentz breaking Effective Field Theory and observational tests

Analogue models of gravity have provided an experimentally realizable test field for our ideas on quantum field theory in curved spacetimes but they have also inspired the investigation of possible departures from exact Lorentz invariance at microscopic scales. In this role they have joined, and sometime anticipated, several quantum gravity models characterized by Lorentz breaking phenomenology. A crucial difference between these speculations and other ones associated to quantum gravity scenarios, is the possibility to carry out observational and experimental tests which have nowadays led to a broad range of constraints on departures from Lorentz invariance. We shall review here the effective field theory approach to Lorentz breaking in the matter sector, present the constraints provided by the available observations and finally discuss the implications of the persisting uncertainty on the composition of the ultra high energy cosmic rays for the constraints on the higher order, analogue gravity inspired, Lorentz violations.Comment: 47 pages, 4 figures. Lecture Notes for the IX SIGRAV School on "Analogue Gravity", Como (Italy), May 2011. V.3. Typo corrected, references adde

A computed tomography-based spatial reference for pedicle screw placement in adolescent idiopathic scoliosis

Study design: Cross-sectional. Objectives: To determine semiautomatically the 3D position of the pedicle axis in operative adolescent idiopathic scoliosis (AIS) patients relative to the operating table and the lamina, as orientation for pedicle screw placement for better understanding and reference of spine surgeons. Summary of background data: Pedicle morphology is well described as the angle between the convex and concave pedicle. However, the pedicle angle as relative to the neutral anterior–posterior axis or to an easy-to-use intravertebral landmark, remained unknown. Methods: The pedicles of the apex and two adjacent vertebrae cranial and caudal to the apex of 86 right-sided primary thoracic AIS curves were evaluated using semiautomatic 3D software on high-resolution CT scans, in the same prone position as during surgery. Pedicle vectors were obtained and calculated as transverse and sagittal angles, as relative to the neutral axis (corresponding with an axis perpendicular to the operating table) and to an axis perpendicular to the lamina. Results: At the apex, the mean convex and concave transverse pedicle angles were 14.3º (95% confidence interval [95% CI]: 12.0–16.6) and 30.4º (95% CI: 28.1–32.8) to the right. The angles decreased toward the adjacent levels cranial and caudal to the apex (p < 0.001) and linearly increased with a higher Cobb angle (r ≥ 0.472; p < 0.001). The mean transverse pedicle–lamina angles, sagittal pedicle angles and the sagittal pedicle–lamina angles differed along the curve as well (p < 0.001). Conclusions: Pedicle angulation differs between convex and concave and depends on the position of the vertebra relative to the apex, as well as the curve severity. The transverse and sagittal pedicle angles, as relative to the operating table and laminae, could provide useful reference for better understanding of the distorted 3D morphology, and the angles, as given in this study, could serve as an approximate guideline for the expected direction of the pedicle screw. Level of evidence: Level IV