Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures

Objective To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters. Design Prospective, open-label, long-term mechanism of action study. Setting University clinic. Methods MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation. Results Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=−0.63, p=0.007). Conclusions MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion

Mosquitoes: The Long-term Effects of Malaria Eradication in India

We examine the effects of malaria on educational attainment and income by exploiting geographic variation in malaria prevalence in India prior to a nationwide eradication program in the 1950s. We find that the program led to modest increases in income for prime age men. This finding is robust to using very localized sources of geographic variation and to instrumenting for pre-eradication prevalence with climate factors. We do not observe improvements in income for women, suggesting that observed effects are likely driven by increased labor market productivity. We find no evidence of increased educational attainment for men, and mixed evidence for women.

Polymers near Metal Surfaces: Selective Adsorption and Global Conformations

We study the properties of a polycarbonate melt near a nickel surface as a model system for the interaction of polymers with metal surfaces by employing a multiscale modeling approach. For bulk properties a suitably coarse grained bead spring model is simulated by molecular dynamics (MD) methods with model parameters directly derived from quantum chemical calculations. The surface interactions are parameterized and incorporated by extensive quantum mechanical density functional calculations using the Car-Parrinello method. We find strong chemisorption of chain ends, resulting in significant modifications of the melt composition when compared to an inert wall.Comment: 8 pages, 3 figures (2 color), 1 tabl

A central line care maintenance bundle for the prevention of central line–associated bloodstream infection in non–intensive care unit settings

OBJECTIVE: To evaluate a central line care maintenance bundle to reduce central line-associated bloodstream infection (CLABSI) in non-ICU settings. DESIGN: Before-after trial with 12 month follow-up period. SETTING: 1250-bed teaching hospital. PARTICIPANTS: Patients with central lines on eight general medicine wards. Four wards received the intervention and four served as controls. INTERVENTION: A multifaceted catheter care maintenance bundle consisting of educational programs for nurses, update of hospital policies, visual aids, a competency assessment, process monitoring, regular progress reports, and consolidation of supplies necessary for catheter maintenance. RESULTS: Data were collected for 25,542 catheter-days including 43 CLABSI (rate = 1.68 per 1,000 CL-days) and 4,012 catheter dressing observations. Following the intervention, a 2.5% monthly decrease in the CLABSI incidence density was observed on intervention floors, but this was not statistically significant (95% confidence interval (CI); −5.3 – 0.4). On control floors, there was a smaller, but marginally significant decrease in CLABSI incidence during the study (change in monthly rate = −1.1%; 95% CI, −2.1 - −0.1). Implementation of the bundle was associated with improvement in catheter dressing compliance on intervention wards (78.8% compliance pre-intervention vs. 87.9% during intervention/follow-up; p<0.001) but improvement was also observed on control wards (84.9% compliance pre-intervention vs. 90.9% during intervention/follow-up; P = .001). CONCLUSIONS: A multi-faceted program to improve catheter care was associated with improvement in catheter dressing care, but no change in CLABSI rates. Additional study is needed to determine strategies to prevent CLABSI in non-ICU patients

MASS TIMBER CONSTRUCTION IN AUSTRALIA AND NEW ZEALAND—STATUS, AND ECONOMIC AND ENVIRONMENTAL INFLUENCES ON ADOPTION

Mass timber construction in Australia and New Zealand uses three main materials—laminated veneer lumber, glue laminated timber and cross-laminated timber (CLT). This article focuses on the use of mass timber in nonresidential construction—the use in single-family homes and apartments is not considered. In Australia and New Zealand, mass timber building technology has moved from being technologically possible to being a feasible alternative to reinforced concrete and steel construction. It has not taken over a large market share in either market and, as such, has not been a disruptive technology. The major changes in this market in the past 5-10 yr in Australia and New Zealand have been the development of new industrial capacity in CLT and the acquisition of computer controlled machining equipment to facilitate prefabrication of wooden building components. The development of new codes and standards and design guides is underway. The drivers of future growth in market share are expected to include more clients putting a higher weight on the various environmental benefits of building in wood, reduction in the real and perceived professional risk for builders and architects specifying mass timber construction, and fuller participation in the supply chain for timber buildings (from design to construction) by timber building specialists. Government policies to encourage the use of timber may also be helpful. Engineers and architects will continue to learn—through experience—how to optimize building construction methods to take advantage of the specific features and qualities of timber as a construction method.