The Surface Area to Volume Ratio Changes the Pharmacokinetic and Pharmacodynamic Parameters in the Subcutaneous Tissue Cage Model:As Illustrated by Carprofen in Sheep

Introduction: Pharmacokinetic and pharmacodynamic models can be powerful tools for predicting outcomes. Many models are based on repetitive sampling of the vascular space, due to the simplicity of obtaining samples. As many drugs do not exert their effect in the vasculature, models have been developed to sample tissues outside the bloodstream. Tissue cages are hollow devices implanted subcutaneously, or elsewhere, that are filled with fluid allowing repetitive sampling to occur. The physical dimensions of the cage, namely, the diffusible surface area to volume ratio, would be expected to change the rate of drug movement into and out of tissue cages. Methods: Seven sheep were implanted with five pairs of tissue cages, subcutaneously. Each pair of cages had a different length but a fixed diffusible surface area, so the surface area to volume ratio differed. Carrageenan was injected into half of the cages in each animal during one sampling period in a cross-over design. Samples from each cage and the bloodstream were obtained at 14-time points during two sampling periods. The concentration of carprofen was measured using LC–MS/MS and the results were modeled using nonlinear mixed-effects techniques. Prostaglandin metabolites were also measured and the change over time was analyzed using linear mixed effect modeling. Results: The presence of carrageenan within an animal changed the systemic pharmacokinetics of carprofen. The rate of drug movement into and out of the tissue cages varied with the surface area to volume ratio. The concentration time curve for prostaglandin metabolites changed with cage size. Conclusion: The surface area volume ratio of tissue cages will influence the calculated pharmacokinetic parameters and may affect calculated pharmacodynamics, thus, it is an important factor to consider when using tissue cage data for dosing regimes

The Luminosity Function for L>L* Galaxies at z > 3

Through use of multiband (U, B, R, I) photometry we have isolated high redshift (3.0<z<3.5) galaxy candidates in a survey of 1.27 deg^2 to R = 21.25 and a survey of 0.02 deg^2 to R = 23.5. Our pool of candidates constrains the nature of the 3.0 < z < 3.5 luminosity function over the range L* < L < 100 L*, if we grant a similar level of completeness to these data as for very faint samples (to R = 25.5) selected in a similar fashion. Our constraints agree with the high redshift sky density at R = 20.5 estimated from Yee et al.'s (1996) serendipitous discovery of a bright, z = 2.7 galaxy, as well as the density at R ~ 23 by Steidel et al. (1996b). We strongly rule out -- by more than two orders of magnitude at M(R) = -25 -- the L > L* luminosity function for z = 3-5 galaxies obtained by a photometric redshift analysis of the Hubble Deep Field (HDF) by Gwyn & Hartwick (1996). Our results at R ~ 23 are more consistent with the photometric redshift analysis of the faint HDF galaxies by Sawicki & Yee (1996), but our present upper limits at the brightest magnitudes (R < 21.5, M(R) < -24) allow more generous volume densities of these super-L* galaxies.Comment: Accepted for publication in ApJ Letters; 14 pages Latex, including 3 figure

Survey incompleteness and the evolution of the QSO luminosity function

We concentrate on a type of QSO survey which depends on selecting QSO candidates based on combinations of colors. Since QSO's have emission lines and power-law continua, they are expected to yield broadband colors unlike those of stellar photospheres. Previously, the fraction of QSO's expected to be hiding (unselected) within the locus of stellar (U-J, J-F) colors was estimated at about 15 percent. We have now verified that the KK88 survey is at least 11 percent incomplete, but have determined that it may be as much as 34 percent incomplete. The 'missing' QSO's are expected to be predominantly at z less than or = 2.2. We have studied the proper motion and variability properties of all stellar objects with J less than or = 22.5 or F less than or = 21.5 in the SA 57 field which has previously been surveyed with a multicolor QSO search by KK88

The flexibility of modified-linker MIL-53 materials

The flexibility of eight aluminium hydroxo terephthalates [Al(OH)(BDC–X)]·n(guest) (BDC = 1,4-benzene-dicarboxylate; X = –H, –CH3, –Cl, –Br, –NH2, –NO2, –(OH)2, –CO2H) crystallising in the MIL-53-type structure was investigated upon thermal dehydration of as-made samples, superhydration and methanol adsorption/desorption using in situ powder X-ray diffraction (PXRD). Profile fitting was used to determine lattice parameters as a function of time and/or temperature to describe their structural evolution. It has thus been shown that while methanol vapour adsorption induces an opening of all the modified frameworks, except the –NH2 material, superhydration only leads to open structures for Al-MIL-53–NO2, –Br and –(OH)2. All the MIL-53 solids, except Al-MIL-53–(OH)2 are present in the open structures upon thermal dehydration. In addition to the exploration of the breathing behavior of this MIL-53 series, the issue of disorder in the distribution of the functional groups between the organic linkers was explored. As a typical illustration, density functional theory calculations were carried out on different structures of Al-MIL-53–Cl, in which the distribution of –Cl within two adjacent BDC linkers is varied. The results show that the most energetically stable configuration leads to the best agreement with the experimental PXRD pattern. This observation supports that the distribution of the selected linker substituent in the functionalised solid is governed by energetics and that there is a preference for an ordering of this arrangement

Intravenous acetaminophen does not provide adequate postoperative analgesia in dogs following ovariohysterectomy

(1) Objective: To investigate the analgesic effects of intravenous acetaminophen after intravenous administration in dogs presenting for ovariohysterectomy. (2) Methods: 14 ASA I client-owned female entire dogs. In this randomized, blinded, clinical study, dogs were given meperidine and acepromazine intramuscularly before induction of anesthesia with intravenous propofol. Anesthesia was maintained with isoflurane in oxygen. Intravenous acetaminophen 20 mg/kg or 0.9% NaCl was administered postoperatively. Pain assessments were conducted using the Glasgow Pain Scale short form before premedication and at 10, 20, 60, 120, and 180 min post-extubation or until rescue analgesia was given. The pain scores, times, and incidences of rescue analgesia between the groups was compared. Blood was collected before and 2, 5, 10, 20, 40, and 80 min after acetaminophen administration. Acetaminophen plasma concentration was quantified by liquid chromatography-mass spectrometry. The acetaminophen plasma concentration at the time of each pain score evaluation was subsequently calculated. (3) Results: There was no significant difference in pain scores at 10 min, highest pain scores, or time of rescue analgesia between groups. In each group, 3 dogs (43%) received rescue analgesia within 20 min. (4) Conclusions: Following ovariohysterectomy in dogs, there was no detectable analgesic effect of a 20 mg/kg dosage of intravenous acetaminophen administered at the end of surgery

Predictors of placement from a juvenile detention facility

The purpose of this project was to determine whether certain personal, socioeconomic, and court-related factors are significantly related to the differential placement of delinquent and dependent children from the detention facility at the Donald E. Long Home. A stratified random sample was composed of 173 placements of children who were held in detention after a preliminary hearing. The review of literature revealed that little systematic. Information is known regarding the placement process as it is related to differential placement of children from a detention facility. A code sheet was developed for recording the information in the children’s records maintained by the court. Fourteen variables were ultimately selected for analysis of their relationship to differential placement. These variables were subjected to three statistical approaches; a descriptive analysis of the random sample, testing of the significance of each variable to the alternatives in placement by either Chi square or analyses of variance, and testing of several variables in combination by discriminant function. This study was limited by the fact that only demographic variables were tested. Although three individual variables were found to have a high degree of significance in relation to placement, the data as produced within the scope of this research project does not provide an effective placement profile. The need for additional research in the area of the differential placement process is clearly indicated. Suggestions are made for future research

Managed moves: schools collaborating for collective gain

Government guidance in the United Kingdom encourages groups of schools to take collective responsibility for supporting and making provision for excluded pupils and those at risk of exclusion. Managed-moves are one way that some schools and authorities are enacting such guidance. This paper presents the results of an evaluation of one such scheme. The scheme, involving seven neighbouring secondary schools, was nearing its first year of completion. The paper draws primarily on interview data with pupils, parents and school staff to describe a number of positive outcomes associated with the scheme and to explore how these were achieved. We found that while some of these could be attributed directly to the managed-move, others arose from the more inclusive ethos and practices of particular schools. The concepts of tailored support, care and commitment emerged as strong themes that underpinned the various practical ways in which some schools in the cluster were able to re-engage 'at-risk' pupils. As managed moves become more widely practiced it will be important to remember that it is how the move proceeds and develops rather than the move itself that will ultimately make the difference for troubled and troublesome pupils