Polysorbate identity and quantity dictate the extensional flow properties of protein-excipient solutions

While protein medications are promising for treatment of cancer and autoimmune diseases, challenges persist in terms of development and injection stability of high-concentration formulations. Here, the extensional flow properties of protein-excipient solutions are examined via dripping-onto-substrate extensional rheology, using a model ovalbumin (OVA) protein and biocompatible excipients polysorbate 20 (PS20) and 80 (PS80). Despite similar PS structures, differences in extensional flow are observed based on PS identity in two regimes: at moderate total concentrations where surface tension differences drive changes in extensional flow behavior, and at small PS:OVA ratios, which impact the onset of weakly elastic flow behavior. Undesirable elasticity is observed in ultra-concentrated formulations, independent of PS identity; higher PS contents are required to observe these effects than in analogous polymeric excipient solutions. These studies reveal novel extensional flow behaviors in protein-excipient solutions, and provide a straightforward methodology for assessing the extensional flow stability of new protein-excipient formulations.     

National survey of mammographic facilities in 1985, 1988, and 1992

PURPOSE: To determine trends in mammography in the United States. MATERIALS AND METHODS: A sample of mammographic facilities was selected for each year of the Nationwide Evaluation of X-ray Trends. The same protocol was followed for the 1985, 1988, and 1992 surveys. Data were collected with use of the same imaging phantom for all three surveys and also with a different phantom in the 1988 and 1992 surveys. RESULTS: Of the 356 facilities surveyed in 1992, 59% claimed to be in compliance with the Health Care Financing Administration (HCFA) mammography requirements, 42% were accredited by the American College of Radiology (ACR), and 23% did not hold credentials from either the HCFA or the ACR. Since 1985, there has been a 34% improvement in acceptable phantom image quality score and a 20% decrease in the mean glandular dose. CONCLUSION: Mammography as practiced today is essentially a screen-film technique. Mammographic phantom image quality has improved considerably. The overall mean glandular dose has decreased primarily because of the elimination of xeroradiography.     

The effect of systematic variation in retrospective conduct disorder reports on antisocial personality disorder diagnoses.

A diagnosis of antisocial personality disorder (ASPD) requires a conduct disorder (CD) diagnosis. A CD diagnosis is often obtained retrospectively. This study tested the influence of current behavior on CD recall and the association between recent behavior change and inconsistencies in contemporaneous and retrospective CD reports. Five hundred young adults reported ASPD; retrospective CD; current problem behavior; and, at ages 12 to 15 years, contemporaneous CD. True-positive, true-negative, false-positive, and false-negative CD and ASPD groups were identified. The results supported the hypotheses. Participants whose current behavior agreed with past behavior provided reliable retrospective CD reports. Inaccurate diagnoses occurred among participants whose current behavior was inconsistent with past behavior, either becoming more problematic (CD and ASPD false positives) or less problematic (CD and ASPD false negatives) over time. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Nationwide survey of fluoroscopy: radiation dose and image quality

PURPOSE: To determine the average abdominal entrance air kerma, low-contrast sensitivity, and spatial resolution in upper gastrointestinal tract fluoroscopy in the United States. MATERIALS AND METHODS: A random sample of fluoroscopic facilities was selected to be surveyed for the Nationwide Evaluation of X-ray Trends program. Measurements were performed by using a newly developed fluoroscopic phantom. The surveys were conducted by state radiation control personnel. RESULTS: Average air kerma rates 1 cm above the tabletop, free in air, were 43 mGy/min (n = 340). The rate increased to 64 mGy/min when a 1.6-mm-thick copper filter, which simulated the use of barium contrast medium, was added to increase attenuation. The average entrance air kerma, free in air, for radiographs was 3.4 mGy, and an average of 12 radiographs were obtained per examination. Of 352 facilities surveyed, 306 (87%) were able to resolve wire mesh with 20 or more lines per inch. Of 339 facilities for which percentage contrast could be calculated, 192 (57%) had minimum percentage contrast values of 4% or more. CONCLUSION: Spatial resolution for fluoroscopy is adequate for most of the facilities surveyed, but a substantial proportion of facilities could not visualize low-contrast test objects, which strongly suggests image quality problems.     

Creation and Design of Energy Center

Rural Alaskan communities have special challenges to supply dependable heat and electric power while preserving environmental quality. To help address these issues in a coherent fashion, we have established an energy center at the University of Alaska Fairbanks. Initially, we will evaluate fuel cells and reformers in a test chamber, looking at both performance and reliability. Later, we will study the integration of the electric and other utilities and focus on arctic engineering issues. In designing the test chamber, we were confronted with a number of conflicting heat balance issues related to (1) additional heat for freeze protection and (2) removal of heat generated by people and equipment. This paper discusses some of the details of how we addressed these issues.     

Reciprocal influences between parenting and adolescent problem-solving behavior

This investigation evaluated the hypothesis that the development of either effective or disruptive adolescent problem-solving behavior is reciprocally associated with the child-rearing strategies of parents. Longitudinal data collected over 3 time points from a large sample of families were analyzed at 1-year and 2-year measurement intervals by using structural equation modeling. Parent and adolescent behavior was assessed by independent observers. Reciprocal parent--adolescent interactions occurred primarily in the presence of disruptive adolescent behavior. Analyses involving positive adolescent behavior produced unidirectional effects from parent behavior to adolescent behavior. Also, reciprocal associations were most evident when the 2-year measurement interval was used.     

Family interactions in adoptive compared to nonadoptive families.

Despite the large and growing numbers of adoptive families, little research describes interactions in families with adopted adolescents. Yet, adopted adolescents' increased risk for adjustment problems, combined with the association between family interactions and adolescent adjustment in nonadoptive families, raises questions about differences in adoptive and nonadoptive family interactions. We compared observed and self-reported family interactions between 284 adoptive and 208 nonadoptive families and within 123 families with 1 adopted and 1 nonadopted adolescent. Adolescents averaged 14.9 years of age. Comparisons were made using analysis of variance incorporating hierarchical linear methods in SAS PROC MIXED to control family-related correlations in the data. Parents and children reported more conflict in adoptive families when compared with nonadoptive families. Families with 1 adopted and 1 nonadopted adolescent reported more conflict between parents and adopted adolescents. Observed parental behavior was similar across adoptive and nonadoptive children although adopted adolescents were less warm and, in families with 2 adopted children, more conflictual than nonadopted adolescents. These findings suggest a need for further investigation of the association between family interactions and adopted adolescent problem behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electrophysiological characterization of the effect of long-term duloxetine administration on the rat serotonergic and noradrenergic systems

3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferases (KdtA) are multifunctional glycosyltransferases with primary structures of low similarity. Totally degenerated primers were deduced from two stretches of identical amino acids between known KdtA sequences and used to amplify by PCR a kdtA-specific fragment from Acinetobacter baumannii ATCC 15308 DNA which was then applied as a probe for the cloning and sequencing of the complete Kdo transferase gene. With conserved PCR primers for this structural gene from A. baumannii ATCC 15308, also kdtA genes of A. baumannii ATCC 19606 and A. haemolyticus ATCC 17906 were obtained, cloned from the chromosome and sequenced. The genes coded for proteins with similarities to known Kdo transferases. Within the genus Acinetobacter, the identity and similarity of the deduced amino acid sequences were 71% and 84.5%, respectively. The kdtA sequences of both A. baumannii strains were identical and possessed a TTG start codon, whereas ATG was found in the case of A. haemolyticus. The genes from Acinetobacter and kdtA from Escherichia coli K-12 were expressed in the Gram-positive bacterium Corynebacterium glutamicum. In vitro tests confirmed the function of the gene products as Kdo transferases, which transferred mainly two Kdo residues to a synthetic lipid A precursor of E. coli. Also, no differences between the cloned kdtA genes from A. baumanniii, A. haemnolyticus and E. coli were observed when tetraacyl or hexaacyl lipid A were tested, since all transferases acted more efficiently on the former. With limiting amounts of acceptor, all Kdo transferases were able to transfer a third Kdo residue with varying efficiency.     

In vivo electrophysiological assessment of the agonistic properties of flibanserin at pre- and postsynaptic 5-HT1A receptors in the rat brain

Flibanserin (BIMT 17) has been described as a 5-HT1A agonist with preferential affinity for postsynaptic 5-HT1A receptors and as a 5-HT2A antagonist. Indeed, using the forskolin-stimulated cAMP accumulation technique, flibanserin but not the 5-HT1A agonists buspirone and 8-OH-DPAT had agonistic activity at postsynaptic 5-HT1A receptors in the cerebral cortex. The present in vivo electrophysiological study investigated the agonistic properties of this novel compound in pre- and postsynaptic areas of the anesthetized rat brain using local microiontophoretic application and systemic administration. The inhibition induced by either local or intravenous administration of flibanserin was current- and dose-dependent. Based on the ability of 5-HT1A antagonists to block or reverse the inhibitory action of the compound, the effect of flibanserin was shown to be mediated via 5-HT1A receptors. In addition, as determined by the concurrent microiontophoretic application of flibanserin and 5-HT, flibanserin behaved as a full agonist in the dorsal raphe nucleus (DRN) and the medial prefrontal cortex (mPFC), but as a partial agonist in the CA3 region of the hippocampus. Based on neuronal responsiveness observed with the local microiontophoretic application of flibanserin, it was found that the agonist was most potent on 5-HT1A receptors in the hippocampus, followed by the mPFC and DRN (I.T50 values: 260, 1,260, and 1,365 nanocoulombs, respectively). However, based on the ED50 values obtained from intravenous administration of the drug, flibanserin was most potent in the DRN followed by the hippocampus and mPFC (ED50 values: 239, 1,414, and 2,984 micrograms/kg, respectively). Therefore, flibanserin presented a marked selectivity for postsynaptic 5-HT1A receptors when applied locally, but not when administered intravenously. It remains to be determined if flibanserin preferentially activates postsynaptic 5-HT1A receptors upon sustained systemic administration.