Population pharmacokinetics of single-dose intravenous paracetamol in children

Background To determine the pharmacokinetics (PK) of a new i.v. formulation of paracetamol (Perfalgan) in children ≤15 yr of age. Methods After obtaining written informed consent, children under 16 yr of age were recruited to this study. Blood samples were obtained at 0, 15, 30 min, 1, 2, 4, 6, and 8 h after administration of a weight-dependent dose of i.v. paracetamol. Paracetamol concentration was measured using a validated high-performance liquid chromatographic assay with ultraviolet detection method, with a lower limit of quantification (LLOQ) of 900 pg on column and an intra-day coefficient of variation of 14.3% at the LLOQ. Population PK analysis was performed by non-linear mixed-effect modelling using NONMEM. Results One hundred and fifty-nine blood samples from 33 children aged 1.8–15 yr, weight 13.7–56 kg, were analysed. Data were best described by a two-compartment model. Only body weight as a covariate significantly improved the goodness of fit of the model. The final population models for paracetamol clearance (CL), V1 (central volume of distribution), Q (inter-compartmental clearance), and V2 (peripheral volume of distribution) were: 16.51×(WT/70)0.75, 28.4×(WT/70), 11.32×(WT/70)0.75, and 13.26×(WT/70), respectively (CL, Q in litres per hour, WT in kilograms, and V1 and V2 in litres). Conclusions In children aged 1.8–15 yr, the PK parameters for i.v. paracetamol were not influenced directly by age but were by total body weight and, using allometric size scaling, significantly affected the clearances (CL, Q) and volumes of distribution (V1, V2).

The enantioselective population pharmacokinetics of intravenous ketorolac in children using a stereoselective assay suitable for microanalysis

Objective: To describe the effect of age and body size on enantiomer selective pharmacokinetic (PK) of intravenous ketorolac in children using a microanalytical assay. Methods: Blood samples were obtained at 0, 15 and 30 min and at 1, 2, 4, 6, 8 and 12 h after a weight-dependent dose of ketorolac. Enantiomer concentration was measured using a liquid chromatography tandem mass spectrometry method. Non-linear mixed-effect modelling was used to assess PK parameters. Key findings: Data from 11 children (1.7–15.6 years, weight 10.7–67.4 kg) were best described by a two-compartment model for R(+), S(−) and racemic ketorolac. Only weight (WT) significantly improved the goodness of fit. The final population models were CL = 1.5 × (WT/46)0.75, V1 = 8.2 × (WT/46), Q = 3.4 × (WT/46)0.75, V2 = 7.9 × (WT/46), CL = 2.98 × (WT/46), V1 = 13.2 × (WT/46), Q = 2.8 × (WT/46)0.75, V2 = 51.5 × (WT/46), and CL = 1.1 × (WT/46)0.75, V1 = 4.9 × (WT/46), Q = 1.7 × (WT/46)0.75 and V2 = 6.3 × (WT/46)for R(+), S(−) and racemic ketorolac. Conclusions: Only body weight influenced the PK parameters for R(+) and S(−) ketorolac. Using allometric size scaling significantly affected the clearances (CL, Q) and volumes of distribution (V1, V2).

Health and population effects of rare gene knockouts in adult humans with related parents

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans.

Population dynamics of the Sycamore Lace Bug (Corythucha Ciliata, Say, Heteroptera: Tingidae) in Hungary

Based on the observation of more than 10 000 leaves of plane trees, four populations of Corythucha ciliata (Say, 1832) (Heteroptera: Tingidae) are investigated. After having introduced some parameters derived from the data, we draw spatial-temporal patterns and describe the seasonal population dynamics of Corythucha ciliata. Amongst others, the temporal change of the density of population, the state plane of larvae–adults, the inclination to accumulate, and the intraspecific competition are examined. Population and biomass dynamics is characterized for populations with and without limited nutrient source in case of different weather circumstances and effects.

Observing population changes of thrips (Thysanoptera) species damaging forced pepper and their natural enemies

By the strengthening of environmental protection and food safety efforts in Hungary, integrated and especially biological pest control methods should increasingly put forward, for which a solid knowledge on the life course and efficiency of natural enemies applied against certain pests is necessary. Pepper has distinguished significance in domestic vegetable forcing, and the profitability of production is determined primarily by the efficiency of the control of thrips pests. This is why we attached great importance to study what results may be expected by introducing arthropod predators (Amblyseius cucumeris, Orius laevigatus) to control thrips species under domestic conditions on rock wool in a long vegetation period pepper culture. We also liked to find out what kind of role the cultivars play in the change of phytophagous and zoophagous populations. The A. cucumeris predatory mite introduced in late January proved to be effective in controlling thrips pests until mid-April. Despite repeated introductions, the predatory bug O. laevigatus (Heteroptera: Anthocoridae) did not proliferate. Among the three pepper cultivars (Hó, Keceli, Titán) grown at Ráckeve, thrips species proliferated in the highest number on cultivar ‘Hó’, while the population of predatory mites was lowest on the cultivar ‘Titán’, compared to the other two cultivars.

Population structure of spotted sunfish (Lepomis punctatus) in the Florida Everglades as revealed by DNA microsatellite analysis

Genetic diversity can be used to describe patterns of gene flow within and between local and regional populations. The Florida Everglades experiences seasonal fluctuations in water level that can influence local population extinction and recolonization dynamics. In addition, this expansive wetland has been divided into water management regions by canals and levees. These combined factors can affect genetic diversity and population structure of aquatic organisms in the Everglades. We analyzed allelic variation at six DNA microsatellite loci to examine the population structure of spotted sunfish (Lepomis punctatus) from the Everglades. We tested the hypothesis that recurrent local extinction and recent regional divisions have had an effect on patterns of genetic diversity. No marked differences were observed in comparisons of the heterozygosity values of sites within and among water management units. No evidence of isolation by distance was detected in a gene flow and distance correlation between subpopulations. Confidence intervals for the estimated F-statistic values crossed zero, indicating that there was no significant genetic difference between subpopulations within a region or between regions. Notably, the genetic variation among subpopulations in a water conservation area was greater than variation among regions (Fsp>FPT). These data indicate that the spatial scale of recolonization following local extinction appears to be most important within water management units.

Monitoring of Tree Island Conditions in the Southern Everglades: The Effects of Hurricanes and Hydrology on the Status and Population Dynamics of Sixteen Tropical Hardwood Hammock Tree Islands

In 2005 we began a multi-year intensive monitoring and assessment study of tropical hardwood hammocks within two distinct hydrologic regions in Everglades National Park, under funding from the CERP Monitoring and Assessment Program. In serving as an Annual Report for 2010, this document, reports in detail on the population dynamics and status of tropical hardwood hammocks in Shark Slough and adjacent marl prairies during a 4-year period between 2005 and 2009. 2005-09 was a period that saw a marked drawdown in marsh water levels (July 2006 - July 2008), and an active hurricane season in 2005 with two hurricanes, Hurricane Katrina and Wilma, making landfall over south Florida. Thus much of our focus here is on the responses of these forests to annual variation in marsh water level, and on recovery from disturbance. Most of the data are from 16 rectangular permanent plots of 225-625 m2 , with all trees mapped and tagged, and bi-annual sampling of the tree, sapling, shrub, and herb layer in a nested design. At each visit, canopy photos were taken and later analyzed for determination of interannual variation in leaf area index and canopy openness. Three of the plots were sampled at 2-month intervals, in order to gain a better idea of seasonal dynamics in litterfall and litter turnover. Changes in canopy structure were monitored through a vertical line intercept method.

Statue of Liberty after Women's March to Battery Park

General note: Title and date provided by Bettye Lane.

Ms. Magazine boat party to Statue of Liberty

General note: Title and date provided by Bettye Lane.

NOW women place banner at base of Statue of Liberty prior to first Women's March

General note: Title and date provided by Bettye Lane.