Sea Surface Salinity Measurements in the Historical Database

We have examined historical distributions of sea surface salinity (SSS) observations in a data set consisting of a combination of the World Ocean Database 1998 (WOD98) and a thermosalinograph and bucket salinity database collected from volunteer observing ships. It is well known that SSS in much of the world\u27s ocean is measured infrequently or not at all. We find that 27% of one-degree squares in the world ocean (open and coastal, excluding the Arctic Ocean) had no observations of SSS in the historical database, and 70% had 10 or fewer. Systematic sampling of SSS (more than 10,000 observations per year globally) did not start until after 1960. Most SSS observations in the WOD98 are concentrated in the North Sea and coast of northern Europe, the east and west coasts of North America, and around Japan. About 28% of SSS measurements are in coastal waters. We plotted frequency histograms of SSS for some selected well-sampled one-degree squares in the North Atlantic and tropical Pacific. We found most frequency histograms to be non-Gaussian. The main departure from normal distribution is due to anomalous low-salinity measurements creating a negative skewness. This conclusion is verified as a global phenomenon by examining statistics of mean-median SSS difference within one-degree squares. This quantity is found to be predominantly negative over the global ocean. These anomalous low-salinity values may be due to rainfall events, but there are other plausible physical mechanisms, like frontal movement and eddy activity. There were also areas where the distributions were bimodal due to the presence of meandering fronts with little cross-frontal mixing. Examples are shown where the non-Gaussian nature of the distributions in the areas examined is both a short-term and a long-term phenomenon. That is, the distributions are skewed on a nearly instantaneous (similar to1 month) basis and averaged over long time periods (1+years). This has important implications for climatologies because the differences between mean and modal SSS, for the analyzed one-degree squares, is of order 0.1. Furthermore, the implication for validation studies for remote sensing missions is that the studies must make enough measurements of SSS to determine the extent to which the probability density is not Gaussian

Differences Among Subtropical Surface Salinity Patterns

The subtropical ocean, exposed to evaporation excess over precipitation, is characterized by regional sea surface salinity maxima (SSS-max). Ocean circulation and mixing processes inject freshwater, establishing a quasi-steady state, though imbalances across the time spectrum result in periods of increasing and decreasing SSS-max. The integrated effect of the array of atmospheric and oceanic forces governing sea surface salinity is shaped by the specific regional ocean basin configuration as well as their coupling to the global ocean system, resulting in SSS-max patterns and locations that display marked differences between the subtropical regimes. We provide a brief description of the SSS-max characteristics of the five subtropical regimes and present aspects of their regional settings that may account for their dissimilarities

Intensification of the global water cycle and evidence from ocean salinity: a synthesis review

The ocean plays a dominant role in the global water cycle. It is the center of action for global evaporation and precipitation and supplies the moisture that falls as continental precipitation. It also acts to some extent as nature's rain gauge, as it tells us about the long‐term changes in the global water cycle through monitoring of the changes in ocean surface salinity. As climate warms, the global water cycle is expected to intensify as a result of the strong nonlinear dependence of water vapor pressure (moisture‐holding capacity) on temperature. Such change is of great concern, as it has profound socioeconomic impacts throughout the globe. Despite the evidence of an intensified global water cycle, two important questions remain: What is the pattern of the warming‐induced intensification of the water cycle? and What is the rate of intensification? Our article provides a synthesis review of recent progress in diagnosing and understanding the changes in both the global water cycle and ocean salinity in recent decades. Targeted numerical ocean model experiments are also reviewed to provide insights into the response of salinity to the changes in evaporation‐minus‐precipitation flux, meltwater runoff, and ocean warming

2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative

Objective The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct “rheumatoid arthritis.” Results In the new criteria set, classification as “definite RA” is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0–5), serologic abnormality (score range 0–3), elevated acute-phase response (score range 0–1), and symptom duration (2 levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct “rheumatoid arthritis.”Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78045/1/27584_ftp.pd

The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report

Objective The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. Methods Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of “developing RA,” complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. Results The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. Conclusion The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78048/1/27580_ftp.pd

Magna Carta, the Rule of Law and the Limits on Government

This paper surveys the legal tradition that links Magna Carta with the modern concepts of the rule of law and the limits on government. It documents that the original understanding of the rule of law included substantive commitments to individual freedom and limited government. Then, it attempts at explaining how and why such commitments were lost to a formalist interpretation of the rule of law from 1848 to 1939. The paper concludes by arguing how a revival of the substantive commitments of the rule of law is central in a project of reshaping modern states

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival