Money, Money, Money—Or Not! Budget Realities and Transparency in Collection Development Decision‐Making

Each library’s budget is unique; however, the importance of providing information about the budget is common across all libraries and is a critical factor in how the library is perceived by its constituents. The cost of e‐resources, balancing the collection, and optimizing a flat budget in an era of escalating costs are issues often misinterpreted by the campus community, leading to both misunderstandings and misinformation. Limited budgets, escalating prices, and new acquisitions strategies necessitate clear communication with librarians and faculty about the financial realities and complex decisions surrounding collection development. One academic library used a two‐day workshop format to inform librarians about budget realities in order to provide financial transparency and minimize concerns about budget decisions. Library administrators at a large public university met with librarians to review and clarify funding sources, allocations, expenditures, deficits, high‐cost e‐resources, collection decision factors, and strategies for acquiring content. With a fuller understanding of the complexities of budget guidelines and limitations, librarians brainstormed solutions to real life collection development scenarios. Both an information‐sharing forum and professional development event, the workshop served to update, educate, and generate discussions for both veteran and new librarians. Strategies described in this paper reflect a comprehensive public university perspective and are scalable and adaptable to other types of institutions

Does protein kinase R mediate TNF-α- and ceramide-induced increases in expression and activation of matrix metalloproteinases in articular cartilage by a novel mechanism?

We investigated the role of the proinflammatory cytokine TNF-α, the second messenger C(2)-ceramide, and protein kinase R (PKR) in bovine articular cartilage degradation. Bovine articular cartilage explants were stimulated with C(2)-ceramide or TNF-α for 24 hours. To inhibit the activation of PKR, 2-aminopurine was added to duplicate cultures. Matrix metalloproteinase (MMP) expression and activation in the medium were analysed by gelatin zymography, proteoglycan release by the dimethylmethylene blue assay, and cell viability by the Cytotox 96(® )assay. C(2)-ceramide treatment of cartilage explants resulted in a significant release of both pro- and active MMP-2 into the medium. Small increases were also seen with TNF-α treatment. Incubation of explants with 2-aminopurine before TNF-α or C(2)-ceramide treatment resulted in a marked reduction in expression and activation of both MMP-2 and MMP-9. TNF-α and C(2)-ceramide significantly increased proteoglycan release into the medium, which was also inhibited by cotreatment with 2-aminopurine. A loss of cell viability was observed when explants were treated with TNF-α and C(2)-ceramide, which was found to be regulated by PKR. We have shown that C(2)-ceramide and TNF-α treatment of articular cartilage result in the increased synthesis and activation of MMPs, increased release of proteoglycan, and increased cell death. These effects are abrogated by treatment with the PKR inhibitor 2-aminopurine. Collectively, these results suggest a novel role for PKR in the synthesis and activation of MMPs and support our hypothesis that PKR and its activator, PACT, are implicated in the cartilage degradation that occurs in arthritic disease

The Molluscan Fauna of the Florida Middle Grounds with Comments on its Zoogeographical Affinities

Recent studies have indicated that the Gulf of Mexico is bounded by a discontinual series of hard substrates which support faunal and floral assemblages of both temperate and tropical origins. This substrate distribution has had a significant impact on molluscan fauna in the Gulf of Mexico. An investigation of the molluscan fauna of the Florida Middle Grounds has produced 75 species associated with this high relief substrate which is also characterized by hermatypic corals. Although the molluscan fauna is comprised of forms which are predominantly Caribbean eurythermic and Caribbean Restricted (76%) which is similar in composition to the West Flower Garden Bank of Texas, their species composition is quite dissimilar (only 23% similarity). For these and other reasons, it is proposed that the zoogeographic status of the Gulf of Mexico should be seriously reconsidered by specialists in other faunal groups

Significance of Extravascular Protein Binding for Antimicrobial Pharmacodynamics in an In Vitro Capillary Model of Infection

The effect of protein binding in an extravascular space on antimicrobial pharmacodynamics was studied in an in vitro capillary model of infection. Simulated 500-mg oral doses of dicloxacillin (~ 96% bound) or cephalexin (\u3c 5% bound) were administered every 6 h for four doses. A 10-fold-higher dose of dicloxacillin was also studied to determine the effect of drug concentration on the reduction of bacterial killing in the presence of protein. Staphylococcus aureus ATCC 25923 was inoculated into peripheral chambers filled with either Mueller-Hinton broth or Mueller-Hinton broth plus 25% human serum. Serial samples for bacterial counts were collected over 24 h. The presence of serum in the chambers significantly reduced bacterial killing by dicloxacillin but not by cephalexin during the first 6 h (two-way analysis of variance, F = 6.04, P \u3c 0.05) but not at 24 h. Reduction of dicloxacillin activity in serum-containing chambers persisted with the higher dose. These data suggest that despite attaining higher total drug concentrations in protein-containing extravascular spaces with highly bound drugs, protein binding reduces bactericidal activity during the early stages of treatment in this model

In Vitro Postantibiotic Effect Following Repeated Exposure to Imipenem, Temafloxacin, and Tobramycin

The postantibiotic effect (PAE) following three consecutive 2-h exposures to imipenem, temafloxacin, and tobramycin was determined in Pseudomonas aeruginosa. A PAE and a bactericidal effect were consistently observed for imipenem following each cycle of drug exposure and regrowth. In contrast, the PAE increased with repeated exposure with temafloxacin (1.8 to \u3e 5 h), but disappeared with tobramycin by the third exposure (0.9 to 0 h). These data show that the in vitro PAE may change within a strain following multiple cycles of drug exposure and bacterial regrowth

Combination Therapy with Ciprofloxacin plus Azlocillin against Pseudomonas aeruginosa: Effect of Simultaneous versus Staggered Administration in an In Vitro Model of Infection

The effect of dose scheduling on the pharmacodynamics of simulated human doses of ciprofloxacin (200 mg intravenously [iv] every 12 h) and azlocillin (4 g iv every 12 h) alone or in combination against Pseudomonas aeruginosa was studied in a two-compartment in vitro kinetic model of infection. Studies with the two drugs in combination were compared using simultaneous or staggered (first doses of each drug were administered 6 h apart) dosing schedules. Bacterial regrowth and resistance were prevented by all combination dosing schedules; however, the simultaneous regimen consistently provided the greatest extent of killing for all strains, particularly in those initially resistant to ciprofloxacin. These enhanced effects of the combination were corroborated by an increase in the peak and duration of bactericidal activity in the analogous "serum” compartment of the model. These data show the potential usefulness of simultaneous dosing of an antipseudomonal µ-lactam with ciprofloxacin against P. aeruginos

The schwartz center rounds: supporting mental health workers with the emotional impact of their work.

In healthcare settings there is an emotional cost to caring which can result in compassion-fatigue, burnout, secondary trauma and compromised patient care. Innovative workplace interventions such as the Schwartz Rounds offer a group reflective practice forum for clinical and non-clinical professionals to reflect on the emotional aspects of working in healthcare. Whilst the Rounds are established in medical health practice, this study presents an evaluation of the Rounds offered to mental health services. The Rounds were piloted amongst 150 mental health professionals for 6 months and evaluated using a mixed-methods approach with standardised evaluation forms completed after each Round and a focus group (n=9) at one-month follow-up. This paper also offers a unique six-year follow-up of the evaluation of the Rounds. Rounds were rated as helpful, insightful, relevant and at six years follow-up Rounds were still rated as valuable and viewed as embedded. Focus groups indicated that Rounds were valued because of the opportunity to express emotions (in particular negative emotions towards patients that conflict with the professional care-role), share experiences, and feel validated and supported by colleagues. The findings indicate that Schwartz Rounds offer a positive application in mental healthcare settings. The study supports the use of interventions which provide an ongoing forum in which to discuss emotions, develop emotional literacy, provide peer-support and set an intention for becoming a more compassionate organisation in which to work.N/

Exogenous sphingomyelinase increases collagen and sulphated glycosaminoglycan production by primary articular chondrocytes: an in vitro study

We previously established a role for the second messenger ceramide in protein kinase R (PKR)-mediated articular cartilage degradation. Ceramide is known to play a dual role in collagen gene regulation, with the effect of ceramide on collagen promoter activity being dependent on its concentration. Treatment of cells with low doses of sphingomyelinase produces small increases in endogenous ceramide. We investigated whether ceramide influences articular chondrocyte matrix homeostasis and, if so, the role of PKR in this process. Bovine articular chondrocytes were stimulated for 7 days with sphingomyelinase to increase endogenous levels of ceramide. To inhibit PKR, 2-aminopurine was added to duplicate cultures. De novo sulphated glycosaminoglycan and collagen synthesis were measured by adding [(35)S]-sulphate and [(3)H]-proline to the media, respectively. Chondrocyte phenotype was investigated using RT-PCR and Western blot analysis. Over 7 days, sphingomyelinase increased the release of newly synthesized sulphated glycosaminoglycan and collagen into the media, whereas inhibition of PKR in sphingomyelinase-treated cells reduced the level of newly synthesized sulphated glycosaminoglycan and collagen. Sphingomyelinase treated chondrocytes expressed col2a1 mRNA, which is indicative of a normal chondrocyte phenotype; however, a significant reduction in type II collagen protein was detected. Therefore, small increments in endogenous ceramide in chondrocytes appear to push the homeostatic balance toward extracellular matrix synthesis but at the expense of the chondrocytic phenotype, which was, in part, mediated by PKR

AMPA/kainate glutamate receptor antagonists prevent posttraumatic osteoarthritis

Musculoskeletal disorders represent the 3rd greatest burden on health in the developed world. Osteoarthritis is the single greatest cause of chronic pain, has no cure, and affects 8.5 and 27 million in the UK and US respectively. Osteoarthritis commonly occurs after joint injury, particularly affecting younger patients. Painful joints are often treated with injections of steroid or hyaluronic acid (HA), but treatments to prevent subsequent joint degeneration remain elusive. In animals, joint injury increases glutamate release into the joint, acting on nerves to cause pain, and joint tissues to cause inflammation and degeneration. This study investigated synovial fluid glutamate concentrations and glutamate receptor (GluR) expression in injured human joints and compared efficacy of GluR antagonists with current treatments in a mouse model of injury-induced osteoarthritis (ACL rupture). GluRs were expressed in ligament and meniscus after knee injury and synovial fluid glutamate concentrations ranged from 19–129 µM. Intra-articular injection of NBQX (GluR antagonist), administered at the time of injury, substantially reduced swelling and degeneration in the mouse ACL rupture model. HA had no effect and depo-medrone reduced swelling for 1 day, but increased degeneration by 50%. Intra-articular administration of NBQX was both symptom and disease modifying to a greater extent than current treatments. There is an opportunity for repurposing related drugs, developed for CNS disorders, with proven safety in man, to prevent injury-induced osteoarthritis. This could quickly reduce the substantial burden associated with osteoarthritis

A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1

Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by fibrosclerosing obliteration of the extrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA remains unknown, although environmental, inflammatory, infectious, and genetic risk factors have been proposed. We performed a genome-wide association study (GWAS) in a European-American cohort of 343 isolated BA patients and 1716 controls to identify genetic loci associated with BA. A second GWAS was performed in an independent European-American cohort of 156 patients with BA and other extrahepatic anomalies and 212 controls to confirm the identified candidate BA-associated SNPs. Meta-analysis revealed three genome-wide significant BA-associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 ×10-8), located within the fifth intron of the EFEMP1 gene, which encodes a secreted extracellular protein implicated in extracellular matrix remodeling, cell proliferation, and organogenesis. RNA expression analysis showed an increase in EFEMP1 transcripts from human liver specimens isolated from patients with either BA or other cholestatic diseases when compared to normal control liver samples. Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and vascular smooth muscle cells in liver specimens from patients with BA and other cholestatic diseases, but it is absent from cholangiocytes in normal control liver samples. Efemp1 transcripts had higher expression in cholangiocytes and portal fibroblasts as compared with other cell types in normal rat liver. The identification of a novel BA-associated locus, and implication of EFEMP1 as a new BA candidate susceptibility gene, could provide new insights to understanding the mechanisms underlying this severe pediatric disorder