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Insulin, the oldest U.S. Food and Drug Administration (FDA)-approved recombinant protein and a World Health Organization (WHO) essential medicine for treating diabetes globally, faces challenges due to its storage instability. One approach to stabilize insulin is the addition of poly(trehalose methacrylate) (pTrMA) as an excipient. The polymer increases the stability of the peptide to heat and mechanical agitation and has a low viscosity suitable for injection and pumps. However, the safety and stabilizing mechanism of pTrMA is not yet known and is required to understand the potential suitability of pTrMA as an insulin excipient. Herein is reported the immune response, biodistribution, and insulin plasma lifetime in mice, as well as investigation into insulin stabilization. pTrMA alone or formulated with ovalbumin did not elicit an antibody response over 3 weeks in mice, and there was no observable cytokine production in response to pTrMA. Micropositron emission tomography/microcomputer tomography of 64Cu-labeled pTrMA showed excretion of 78–79% ID/cc within 24 h and minimal liver accumulation at 6–8% ID/cc when studied out to 120 h. Further, the plasma lifetime of insulin in mice was not altered by added pTrMA. Formulating insulin with 2 mol equiv of pTrMA improved the stability of insulin to standard storage conditions: 46 weeks at 4 °C yielded 87.0% intact insulin with pTrMA present as compared to 7.8% intact insulin without the polymer. The mechanism by which pTrMA-stabilized insulin was revealed to be a combination of inhibiting deamidation of amino acid residues and preventing fibrillation, followed by aggregation of inactive and immunogenic amyloids all without complexing insulin into its hexameric state, which could delay the onset of insulin activity. Based on the data reported here, we suggest that pTrMA stabilizes insulin as an excipient without adverse effects in vivo and is promising to investigate further for the safe formulation of insulin.

Air cavity drag reduction is one promising method for reducing power consumption of ships. Its current practical applications are rather limited, owing largely to the fact that air cavity size and shape change drastically in response to variations in ship attitude, motions and speed, as well as sea conditions. This study explores how deployment of moveable hydrodynamic actuators near the air cavity on a small-scale simplified hull form can effectively increase the air cavity size in adverse hull positions. Experimentally investigated actuators included an adjustable plate in the front part of an air cavity, a stern spoiler, and a hydrofoil with regulated attack angle and streamwise position beneath the hull. In the cases of significant hull trims that are challenging for maintenance of long air cavities, optimal actuator placement increased cavity length by nearly 110% from its degraded state at negative trim and by 24% at positive trim. Actuator effects were more pronounced at higher water speeds.

While glucose-responsive insulin delivery systems are in widespread clinical use to treat insulin insufficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains understudied. A self-regulated glucagon release material is highly desired to mitigate the potential risks of severe insulin-induced hypoglycemia. Here, we describe a glucose-responsive polymeric nanosystem with glucagon covalently grafted to the end-group. Under normoglycemic conditions, phenylboronic acid units in the polymer chain reversibly bind glucose, triggering self-assembly of the conjugate into micelles. During hypoglycemia, however, the micelle disassembles into its original, unimeric state, revealing the active glucagon conjugate. The formulation showed a 5-fold increase in activity compared to native glucagon when tested in vitro. Glucagon-loaded micelles injected into mice prevented or reversed deep hypoglycemia when administered prior to or during an insulin challenge. Glucagon release was only observed at or below the counterregulatory threshold and not during normoglycemia or moderate hypoglycemia. The in vivoacute and chronic toxicity analysis, along with μPET/μCT imaging, established the biosafety profile of this formulation and demonstrated no organ accumulation. This proof-of-concept work is the first step toward development of a translational, stimuli-responsive glucagon delivery platform to control glycemia.

Near the start of her fascinating new book The Lost History of Liberalism, Helena Rosenblatt dryly observes that “available histories of liberalism are seldom helpful” (2). The point is well taken: the historiography of liberalism—largely written as intellectual history—is not particularly coherent, and has only sporadically adopted sound historical methodology. The genre emerged relatively late. The proliferation of the language of liberalism in the nineteenth century, not least in party politics, did not produce theoretically informed historical accounts of particular note. A historiography of liberalism really only developed in response to the perceived “crisis of liberalism” of the early twentieth century. Guido de Ruggiero's 1925 The History of European Liberalismwas written in a Hegelian idealist tradition, according to which liberalism was an “organic development of freedom coinciding with the organization of human society and its progressively higher and more spiritual forms.” Coming from a different direction was Harold Laski's The Rise of European Liberalism: An Essay in Interpretation,published in 1936. Laski's liberalism was as much a “habit of mind” as a set of doctrines, with a complex history making both “clarity difficult” and “precision unattainable.” An essentialized understanding of liberalism was nevertheless still at work. Laski's liberalism was that the individualist, utilitarian mode of thought necessary to an emerging capitalist society. “The liberal creed, in a word,” he wrote, “is a doctrine woven from the texture of bourgeois need.”

Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.Infect Control Hosp Epidemiol2018;39:750–752

The article discusses the potential of Australian-Canadian strategic alignment moving to a bipartisan framework, driven by weak commodity prices, deterioration of federal budgets and increasing costs of defense procurement. Topics discussed include areas where both can work closer such as security issues, defense procurement like submarine capacity, and energy policy, Sea1000 project of the Royal Australian Navy, and benefits of Candian-Australian joint procurement of submarines.

OBJECTIVE: This article aims to explore the future of translational research and its physical design implications for community hospitals and hospitals not attached to large centralized research platforms.BACKGROUND: With a shift in medical services delivery focus to community wellness, continuum of care, and comparative effectiveness research, healthcare research will witness increasing pressure to include community-based practitioners.METHODS: The roundtable discussion group, comprising 14 invited experts from 10 institutions representing the fields of biomedical research, research administration, facility planning and design, facility management, finance, and environmental design research, examined the issue in a structured manner. The discussion was conducted at the Washington Hospital Center, MedStar Health, Washington, D.C.CONCLUSIONS: Institutions outside the AMCs will be increasingly targeted for future research. Three factors are crucial for successful research in non-AMC hospitals: operational culture, financial culture, and information culture. An operating culture geared towards creation, preservation, and protection of spaces needed for research; creative management of spaces for financial accountability; and a flexible information infrastructure at the system level that enables complete link of key programmatic areas to academic IT research infrastructure are critical to success of research endeavors.

The renin‐angiotensin system regulates blood pressure via activation of the angiotensin II type 1 receptor (AT1R). The AT1R is involved in the pathology of cardiac and renal diseases such as heart failure and diabetic nephropathy. The aim of this study was to synthesize and characterize the O‐[11C]methylated derivative of the clinically used AT1receptor blocker losartan as a novel AT1R PET imaging radioligand. [11C]Methyl‐losartan was reliably synthesized (n≥ 40) via methylation of tetrazole‐protected losartan followed by deprotection using HCl in an overall yield of 30%–60% (decay‐corrected from [11C]MeI). Radiochemical purity was >99% and specific activity 700–3600 mCi/µmol. Copyright © 2011 John Wiley & Sons, Ltd.

Focuses on the training of the 82nd regiment of the U.S. Field Artillery in preparation for their mission in Iraq. Speed and mobility of the regiment's response during the 1919 Rio Grande conflict; Overview of the stability or support operations training development process; Training of the division's firing battery for the Iraq mission.

ABSTRACTThis article describes the design of the software framework and the vision system used by the UC Davis MIcro-RObot SOccer Tournament (MIROSOT) team. A fault tolerant and highly modular software framework is described. A software-based vision system capable of extracting location, orientation, and identity of objects is presented and justified. Our robot color scheme is illustrated and compared with another common system.

At present, there is no sensitive and specific test to confirm the clinical impression that a respiratory disorder is due to aspiration of gastric contents. Since intravenous technetium pertechnetate (99mTcO4−) has been shown to be safe, actively concentrated in the gastrointestinal tract, and secreted into gastric juice, we sought to determine whether 99mTcO4−, when given intravenously, is suitable to detect pulmonary aspiration of small amounts of gastric contents in rabbits. Biodistribution studies over 24 h revealed that 99mTcO4−persistently appeared in the stomach, thyroid, and salivary glands and did not appear in the lungs. Pharmacokinetic studies showed that 99mTcO4−was rapidly picked up by the stomach wall and secreted promptly into the stomach lumen and that the stomach wall persistently secreted 99mTcO4−into stomach contents for 24 h. By injecting 99mTcO4−through an intratracheal catheter in order to simulate aspiration, the radioactive threshold for imaging intrapulmonary 99mTcO4−was determined to range between <0.5 μCi and 2 μCi, depending on the amount of background activity in the blood pool. By measuring the radioactivity in stomach contents (μCi/g), over 24 h after intravenous injection of 2 mCi of 99mTcO4−, we were able to calculate the amount of aspirated stomach contents that our technique should reveal at various time points. We concluded from this preliminary feasibility study that 99mTcO4−, when given intravenously, is suitable to detect pulmonary aspiration of small amounts (≤4 ml for 8 h after an intravenous dose of 2 mCi) of gastric contents in human patients. Since our biodistribution studies show that saliva as well as stomach contents are potential sources for any aspirated 99mTcO4−, how to distinguish aspiration of oropharyngeal from stomach contents remains to be determined. It also remains to be determined how long 99mTcO4−remains in the lungs after it has been instilled; clearance that is too rapid significantly decreases the ability of this agent to reveal aspiration.

In recent years there has been considerable interest in reducing the duration of antibiotic treatment regimens in patients with common bacterial infections. We conducted two independent, investigator-blinded, multicenter, randomized clinical trials, one of which included microbiologic evaluation of middle ear fluid obtained by tympanocentesis, comparing the efficacy and safety of 5 or 10 days of treatment with cefuroxime axetil suspension (CAE) with that of 10 days of treatment with amoxicillin/clavulanate suspension (AMX/CL) in children with acute otitis media.

Antimicrobial agents play an important role in the treatment of patients with acute otitis media and otitis media with effusion (OME). The study was undertaken to determine the concentrations of cefuroxime in the blood and middle ear effusions (MEE) of children between 6 and 12 years of age with acute otitis media and chronic OME after a single oral dose administration of cefuroxime axetil, the ester prodrug of cefuroxime. Cefuroxime axetil (250 mg) was administered 2 to 6 hours before either myrin-gotomy for acute otitis media or myringotomy and tube insertion for chronic OME. Blood samples and middle ear aspirates were obtained from 31 children and the samples were analyzed by high performance liquid chromatography. Cefuroxime was recovered in measurable concentrations in ail serum samples and in 15 (79) of the 19 MEE specimens analyzed. No correlation was seen between cefuroxime MEE concentrations and effusion type, bacteriology or serum concentrations. This study shows that cefuroxime does penetrate into MEE when OME is present and that therapeutic concentrations can be achieved in some patients.

Across medicine, vocal, educated patients are collaborating with researchers to generate clinical trial outcome measures that matter to the patient yet remain scientifically sound. Medical literature refers to these people as “patient research partners,” “patient experts,” “patient representatives,” or “patient stakeholders.” Spearheaded by the rheumatology-based Outcome Measures in Rheumatology group, the medical community has learned the value of allowing patients to be involved actively in outcome measure creation. This paper discusses the history, education, utilization, recruitment, and expanding role of patient experts in dermatology. This information was collected through literature searches and the meetings of outcome measure groups such as Harmonizing Outcome Measures for Eczema, Acne Core Research Network, and International Dermatology Outcome Measures. It was found that over the past several years, patient experts have been helping develop dermatology outcome measures through these groups, leading to major trial design changes.

2-Mercaptobenzimidazole (2-MBI) is a member of the thioureylene compound family known for their potent antithyroid activity. Male Fischer-344 rats were exposed to 0.0, 3.13, 12.5, and 50.0 mg/m3 of 2-MBI via inhalation for 13 wk. Follicular cell hyperplasia occurred in the thyroid glands of rats from the 3 2-MBI treatment groups. Thyrotrophs in the pituitary glands from rats in these 3 groups were hyperplastic, and they had varying numbers of hypertrophic cells with either eosinophilic stippled cytoplasm or with eosinophilic globules within 1 or more large vacuoles that displaced the nucleus. These cells were compared by immunohistochemistry and ultrastructural examination to "thyroidectomy cells" within the anterior pituitary glands of thyroparathyroidectomized rats and were determined to be identical to them. Immunohistochemical staining for the ß-chain of thyroid-stimulating hormone confirmed that the hyperplastic and hypertrophic cells were thyrotrophs. Ultrastructurally, hypertrophic cells in 2-MBI-treated rats and thyroidectomy cells in thyroparathyroidectomized rats had expanded cytoplasm containing either increased profiles of rough endoplasmic reticulum (RER) or one or more widely dilated cisternae of RER, which displaced other cellular organelles. 2-MBI appears to act comparably to other thioureylene compounds that have been shown to produce low serum concentrations of triiodothyronine and thyroxine, which results in thyrotroph hypertrophy and hyperplasia, resultant thyroid hyperplasia, and subsequent goiter.

The pharmacokinetics of 111In-labeled 260F9, a murine monoclonal antibody directed against a breast-cancer-associated antigen, was determined in seven patients with advanced breast cancer. Six patients were administered 1 mg antibody containing 1 mCi 111In. The seventh patient was administered 20 mg unlabeled antibody followed by 1 mg 111In-labeled antibody all via a peripheral vein. Immunoprecipitation, HPLC and SDS-PAGE gels demonstrated the stability of radiolabel on the antibody. The serum clearance of the radiolabel closely fits (r2>0.95) a two-compartment model for the first six patients. The apparent volume of distribution of the radiolabel approximated to the plasma volume (3 1) and its mean residence time was 23.7 h. The radiolabel had an average t1/2ß of 22.9±12.21 h at the 1-mg dose. At the 20-mg dose one-compartment elimination kinetics were observed with the radiolabel and antibody showing similar mean residence times (36–41 h) and a t1/2ß of 26–28 h. Whole-body imaging showed that the blood-pool:liver ratio of radioactivity increased fourfold (at 48 h postinfusion) at the higher dose and the percentage of the injected dose of radioactivity in the liver decreased from 25% to 8% (24 h postinfusion).

The visual performances of eight low myopic subjects (-2 D to -7 D) and eight high myopic subjects (> -7 D) with normal visual acuities were analyzed by contrast sensitivity testing with both spectacle and contact lens corrections to determine if any differences in function exist between those groups. Statistically significant (p=0.0382) contrast sensitivity losses, particularly at the higher spatial frequencies, were found for the high myopic subjects when corrected with spectacles. However, with contact lens correction, no statistically significant overall difference between the two groups was evident (p=0.5083). We believe that these results confirm for highly myopic subjects the lack of any consistently present loss of resolution. The differences with spectacle correction are attributable to the nature of the optical correction.

4-Vinylcyclohexene (VCH), a dimer of 1,3-butadiene present in the gases discharged during tire curing, was examined for its toxic and carcinogenic effects in Fischer 344 (F344) rats and 66C3F1 mice by 2-yr chronic testing. VCH was administered orally by gavage in corn oil at doses of 0 (vehicle control), 200, or 400 mg/kg body weight to groups of 50 F344 rats and B6C3F1 mice of each sex for 103 wk (5 d/wk). Because the studies of VCH in male and female rats and in male mice were considered to be inadequate studies of carcinogenicity due to the extensive and early mortality at the high dose or both doses tested, as well as the lack of conclusive evidence of a carcinogenic effect, the present article focuses on the results of the 2-yr study of VCH in female B6C3F1 mice. Survival of high-dose female mice was lower (p < 0.001) than that of the vehicle controls, whereas survival of low-dose and survival of vehicle control female mice were comparable. Mean body weights of high-dose female mice were generally slightly lower than those of the vehicle controls, whereas the mean body weights of low-dose female mice were generally greater than or comparable to those of the vehicle controls. Oral administration of VCH by gavage to female B6C3F1 mice was associated with an increased incidence of a number of nonneoplastic lesions, including mild acute inflammatory lesions and epithelial hyperplasia of the forestomach, congestion of the lungs and adrenal glands at the high dose, and cytologie alteration of the adrenal cortex at both doses. However, the most striking finding was the markedly increased (p < 0.01) incidences of uncommon ovarian neoplasms, including mixed benign tumors, granulosa-cell tumors, and granulosa-cell tumors or carcinomas (combined), in both groups of dosed female mice. In addition, the increased incidence of adrenal-gland capsular adenomas in high-dose female mice may have been compound-related.

4-Vinylcyclohexene (VCH), a dimer of 1,3-butadiene present in the gases discharged during tire curing, was examined for its toxic effects in Fischer 344 (F344) rats and B6C3F1 mice by 14-d prechronic and 13-wk subchronic testing. In the 14-d studies, VCH was administered orally by gavage in corn oil at doses of 0 (vehicle control), 300, 600, 1250, 2500, or 5000 mg/kg body weight to groups of five F344 rats and B6C3F1 mice of each sex, while the doses for the 13-wk studies (10 animals/group; 5 d/wk) were 0 (vehicle control), 50, 100, 200, 400, or 800 mg/kg body weight for rats and 0 (vehicle control), 75, 150, 300, 600, or 1200 mg/kg body weight for mice. All rats and most mice in the 14-d studies died when administered doses ≥ 1250 mg/kg, although no compound-related gross or histopathologic effects were observed. In the 13-wk studies, extensive mortality was observed only in mice dosed at 1200 mg/kg. Final body weights were reduced in the 13-wk studies in male rats receiving doses ≥400 mg VCH/kg, in female rats receiving 800 mg/kg, and in female mice receiving 600 mg/kg. Compound-related histopathologic effects in the 13-wk studies included hyaline droplet degeneration of the proximal convoluted tubules of the kidney in dosed male rats, the severity of which was dose-related, and a reduction in the number of primary follicles and mature graafian follicles in the ovaries of female mice receiving 1200 mg VCH/kg. No compound-related gross or histopathologic effects were evident in dosed female rats or male mice in the 13-wk studies.

The article presents information on the South Carolina women's basketball, which plays the underdog in the National Collegiate Athletic Association tournaments (NCAA), highlighting the matches against other teams where the South California team lost. Topics include the teams competing in the NCAA tournaments, presents the opinions of the coaches including Lindsay Gottlieb and Joanne Boyle.