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

Climigration? Population and climate change in Arctic Alaska

Residents of towns and villages in Arctic Alaska live on “the front line of climate change.” Some communities face immediate threats from erosion and flooding associated with thawing permafrost, increasing river flows, and reduced sea ice protection of shorelines. The term climigration, referring to migration caused by climate change, originally was coined for these places. Although initial applications emphasized the need for government relocation policies, it has elsewhere been applied more broadly to encompass unplanned migration as well. Some historical movements have been attributed to climate change, but closer study tends to find multiple causes, making it difficult to quantify the climate contribution. Clearer attribution might come from comparisons of migration rates among places that are similar in most respects, apart from known climatic impacts. We apply this approach using annual 1990–2014 time series on 43 Arctic Alaska towns and villages. Within-community time plots show no indication of enhanced out-migration from the most at-risk communities. More formally, there is no significant difference between net migration rates of at-risk and other places, testing several alternative classifications. Although climigration is not detectable to date, growing risks make either planned or unplanned movements unavoidable in the near future

Linear Redshift Distortions and Power in the PSCz Survey

We present a state-of-the-art linear redshift distortion analysis of the recently published IRAS Point Source Catalog Redshift Survey (PSCz). The procedure involves linear compression into 4096 Karhunen-Loeve modes culled from a potential pool of about 3 x 10^5 modes, followed by quadratic compression into three separate power spectra, the galaxy-galaxy, galaxy-velocity, and velocity-velocity power spectra. Least squares fitting to the decorrelated power spectra yields a linear redshift distortion parameter beta = Omega_m^0.6/b = 0.41(+0.13,-0.12).Comment: Minor changes to agree with accepted version. Slight changes to power spectrum, including one more point added at large scales, from binning points formerly discarded as too noisy. 5 pages, including 4 embedded PostScript figures. Accepted for publication in MNRAS Letters (pink pages). Power spectrum data available at http://casa.colorado.edu/~ajsh/pscz

Staying in place during times of change in Arctic Alaska: The implications of attachment,alternatives, and buffering

The relationship between stability and change in social-ecological systems has received considerable attention in recent years, including the expectation that significant environmental changes will drive observable consequences for individuals, communities, and populations. Migration, as one example of response to adverse economic or environmental changes, has been observed in many places, including parts of the Far North. In Arctic Alaska, a relative lack of demographic or migratory response to rapid environmental and other changes has been observed. To understand why Arctic Alaska appears different, we draw on the literature on environmentally driven migration, focusing on three mechanisms that could account for the lack of response: attachment, the desire to remain in place, or the inability to relocate successfully; alternatives, ways to achieve similar outcomes through different means; and buffering, the reliance on subsidies or use of reserves to delay impacts. Each explanation has different implications for research and policy, indicating a need to further explore the relative contribution that each makes to a given situation in order to develop more effective responses locally and regionally. Given that the Arctic is on the front lines of climate change, these explanations are likely relevant to the ways changes play out in other parts of the world. Our review also underscores the importance of further attention to the details of social dynamics in climate change impacts and responses

Forest management and wildfire risk in inland northwest

This brief reports the results of a mail survey of forest landowners in northeastern Oregon conducted in the fall of 2012 by the Communities and Forests in Oregon (CAFOR) Project at the University of Colorado and the University of New Hampshire in cooperation with Oregon State University College of Forestry Extension. The mail survey--a follow-up to a telephone survey conducted for the counties of Baker, Union, and Wallowa in the fall of 2011 -was administered to understand who constituted forest landowners in these three coun¬ties and their perceptions about forest management on both public and private land, as well as risks to forests in the area and the actions they have taken to reduce those risks. The respondents indicated that they perceive wildfire as the greatest threat to their lands, and they consider cooperation with neighbors as very or extremely important for land management. Forest landowners believe public lands are managed poorly and see a greater risk of wildfire occurring on neighboring public land than on their own land. Their opinions on land management are not strongly related to background factors or ideology (for example, gender, age, political party, wealth) but may be heavily influenced by personal experience with wildfire

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic (March 25 - 27, 2018 -- The University of New Hampshire) paired two of NSF\u27s 10 Big Ideas: Navigating the New Arctic and Growing Convergence Research at NSF. During this event, participants assessed economic, environmental, and social impacts of Arctic change on New England and established convergence research initiatives to prepare for, adapt to, and respond to these effects. Shipping routes through an ice-free Northwest Passage in combination with modifications to ocean circulation and regional climate patterns linked to Arctic ice melt will affect trade, fisheries, tourism, coastal ecology, air and water quality, animal migration, and demographics not only in the Arctic but also in lower latitude coastal regions such as New England. With profound changes on the horizon, this is a critical opportunity for New England to prepare for uncertain yet inevitable economic and environmental impacts of Arctic change

The DataHawk2 uncrewed aircraft system for atmospheric research

The DataHawk2 (DH2) is a small, fixed-wing, uncrewed aircraft system, or UAS, developed at the University of Colorado (CU) primarily for taking detailed thermodynamic measurements of the atmospheric boundary layer. The DH2 weighs 1.7&thinsp;kg and has a wingspan of 1.3&thinsp;m, with a flight endurance of approximately 60&thinsp;min, depending on configuration. In the DH2's most modern form, the aircraft carries a Vaisala RSS-421 sensor for pressure, temperature, and relative humidity measurements, two CU-developed infrared temperature sensors, and a CU-developed fine-wire array, in addition to sensors required to support autopilot function (pitot tube with pressure sensor, GPS receiver, inertial measurement unit), from which wind speed and direction can also be estimated. This paper presents a description of the DH2, including information on its design and development work, and puts the DH2 into context with respect to other contemporary UASs. Data from recent field work (MOSAiC, the Multidisciplinary drifting Observatory for the Study of Arctic Climate) is presented and compared with radiosondes deployed during that campaign to provide an overview of sensor and system performance. These data show good agreement across pressure, temperature, and relative humidity as well as across wind speed and direction. Additional examples of measurements provided by the DH2 are given from a variety of previous campaigns in locations ranging from the continental United States to Japan and northern Alaska. Finally, a look toward future system improvements and upcoming research campaign participation is given. &nbsp;</p