Purchasing Power: The Corporate-White House Alliance to Pass the China Trade Bill Over the Will of the American People

The passage of China Permanent Normal Trade Relations (PNTR) by the U.S. House of Representatives in late May 2000 over the overwhelming will of the American people was the result of the most forceful and aggressive corporate legislative campaign in history. Despite four-to-one public opposition, the bill was passed by the use of unprecedented amounts of corporate money in political contributions, advertising, lobbying and rented "experts," as well as the application of the White House s full resources. To fulfill their own overlapping goals, the corporate coalition and the White House worked in such tight coordination that the General Accounting Office has reported that federal law on Executive branch lobbying practices was violated. Deaf to pleas from even pro-PNTR House Democrats, the administration launched the China PNTR crusade to build a legacy for the President knowing it would damage Democrats chances to regain a House majority. To celebrate the House PNTR vote, President Clinton went out that night to a corporate political fund-raiser boycotted by many Democratic House Leaders. The corporate interest was in eliminating the annual Congressional review of China trade and to obtain unconditional, unlimited access to the U.S. market for goods produced in China. The day after the House vote, the Wall Street Journal and other papers finally reported that the corporations were not so much interested in access to the Chinese market to sell goods there, but rather sought guaranteed U.S. access for goods they could produce in China with its remarkably high-quality, cheap, government-controlled labor and lax environmental controls. Passing China PNTR was an important priority for both players for another important and symbolic reason: the proponents of corporate globalization and corporate managed trade had been defeated for five years by a determined citizen s movement that recognized that the corporate and White House globalization agenda was benefitting narrow corporate interests at the expense of working families and the environment. The Clinton administration and the corporate lobbies had pushed the North American Free Trade Agreement (NAFTA) and the Uruguay Round of the General Agreement on Tariffs and Trade (GATT) which established the World Trade Organization (WTO) through the Congress during the administration s first term. While the NAFTA and WTO fights required concerted corporate lobbying and public relations efforts, obtaining political support for expanding existing globalization policies had become much more difficult. Polling showed that people had become aware of the all-too-real down sides of what its proponents dubbed "free trade," but was increasingly revealed to be corporate managed trade. Several years after NAFTA's passage when its negative impacts became apparent, public opinion, never supportive of the corporate-White House trade agenda, turned frosty. Significant relocation of high-wage manufacturing jobs to Mexico, increased border pollution and health problems, and the declining safety of America s increasingly imported food supply made the public increasingly skeptical of the promises and projections made by the "free trade" proponents. The complete executive summary and access to the full report available via the link below

Bacteria-Specific Neutrophil Dysfunction Associated with Interferon-Stimulated Gene Expression in the Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a poorly understood condition with greater than 30% mortality. Massive recruitment of neutrophils to the lung occurs in the initial stages of the ARDS. Significant variability in the severity and duration of ARDS-associated pulmonary inflammation could be linked to heterogeneity in the inflammatory capacity of neutrophils. Interferon-stimulated genes (ISGs) are a broad gene family induced by Type I interferons. While ISGs are central to anti-viral immunity, the potential exists for these genes to evoke extensive modification in cellular response in other clinical settings. In this prospective study, we sought to determine if ISG expression in circulating neutrophils from ARDS patients is associated with changes in neutrophil function. Circulating neutrophil RNA was isolated, and hierarchical clustering ranked patients' expression of three ISGs. Neutrophil response to pathogenic bacteria was compared between normal and high ISG-expressing neutrophils. High neutrophil ISG expression was found in 25 of 95 (26%) of ARDS patients and was associated with reduced migration toward interleukin-8, and altered responses to Staphylococcus aureus, but not Pseudomonas aeruginosa, which included decreased p38 MAP kinase phosphorylation, superoxide anion release, interleukin-8 release, and a shift from necrotic to apoptotic cell death. These alterations in response were reflected in a decreased capacity to kill S. aureus, but not P. aeruginosa. Therefore, the ISG expression signature is associated with an altered circulating neutrophil response phenotype in ARDS that may predispose a large subgroup of patients to increased risk of specific bacterial infections

Transcriptomic Signatures in Sepsis and a Differential Response to Steroids. From the VANISH Randomized Trial.

Non-commercial use onlyRATIONALE: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration, but conflicting survival effects. Two transcriptomic sepsis response signatures (SRSs) have been identified. SRS1 is relatively immunosuppressed, whereas SRS2 is relatively immunocompetent. OBJECTIVES: We aimed to categorize patients based on SRS endotypes to determine if these profiles influenced response to either norepinephrine or vasopressin, or to corticosteroids in septic shock. METHODS: A post hoc analysis was performed of a double-blind, randomized clinical trial in septic shock (VANISH [Vasopressin vs. Norepinephrine as Initial Therapy in Septic Shock]). Patients were included within 6 hours of onset of shock and were randomized to receive norepinephrine or vasopressin followed by hydrocortisone or placebo. Genome-wide gene expression profiling was performed and SRS endotype was determined by a previously established model using seven discriminant genes. MEASUREMENTS AND MAIN RESULTS: Samples were available from 176 patients: 83 SRS1 and 93 SRS2. There was no significant interaction between SRS group and vasopressor assignment (P = 0.50). However, there was an interaction between assignment to hydrocortisone or placebo, and SRS endotype (P = 0.02). Hydrocortisone use was associated with increased mortality in those with an SRS2 phenotype (odds ratio = 7.9; 95% confidence interval = 1.6-39.9). CONCLUSIONS: Transcriptomic profile at onset of septic shock was associated with response to corticosteroids. Those with the immunocompetent SRS2 endotype had significantly higher mortality when given corticosteroids compared with placebo. Clinical trial registered with www.clinicaltrials.gov (ISRCTN 20769191).Supported by the UK National Institute for Health Research (NIHR) under Research for Patient Benefit program grant PB-PG-0610-22350, NIHR Clinician Scientist Award NIHR/CS/009/007, and NIHR Research Professor award RP-2015-06-018 (A.C.G.); also supported by the NIHR Imperial Biomedical Research Centre, the UK Intensive Care Foundation, Wellcome Trust grant 090532/Z/09/Z to core facilities at the Wellcome Centre for Human Genetics, Wellcome Trust Investigator Award 204969/Z/16/Z (J.C.K.), and by the NIHR Oxford Biomedical Research Centre

Range-wide sources of variation in reproductive rates of northern spotted owls

We conducted a range-wide investigation of the dynamics of site-level reproductive rate of northern spotted owls using survey data from 11 study areas across the subspecies geographic range collected during 1993–2018. Our analytical approach accounted for imperfect detection of owl pairs and misclassification of successful reproduction (i.e., at least one young fledged) and contributed further insights into northern spotted owl population ecology and dynamics. Both nondetection and state misclassification were important, especially because factors affecting these sources of error also affected focal ecological parameters. Annual probabilities of site occupancy were greatest at sites with successful reproduction in the previous year and lowest for sites not occupied by a pair in the previous year. Site-specific occupancy transition probabilities declined over time and were negatively affected by barred owl presence. Overall, the site-specific probability of successful reproduction showed substantial year-to-year fluctuations and was similar for occupied sites that did or did not experience successful reproduction the previous year. Site-specific probabilities for successful reproduction were very small for sites that were unoccupied the previous year. Barred owl presence negatively affected the probability of successful reproduction by northern spotted owls in Washington and California, as predicted, but the effect in Oregon was mixed. The proportions of sites occupied by northern spotted owl pairs showed steep, near-monotonic declines over the study period, with all study areas showing the lowest observed levels of occupancy to date. If trends continue it is likely that northern spotted owls will become extirpated throughout large portions of their range in the coming decades

An immune dysfunction score for stratification of patients with acute infection based on whole-blood gene expression

Dysregulated host responses to infection can lead to organ dysfunction and sepsis, causing millions of global deaths each year. To alleviate this burden, improved prognostication and biomarkers of response are urgently needed. We investigated the use of whole-blood transcriptomics for stratification of patients with severe infection by integrating data from 3149 samples from patients with sepsis due to community-acquired pneumonia or fecal peritonitis admitted to intensive care and healthy individuals into a gene expression reference map. We used this map to derive a quantitative sepsis response signature (SRSq) score reflective of immune dysfunction and predictive of clinical outcomes, which can be estimated using a 7- or 12-gene signature. Last, we built a machine learning framework, SepstratifieR, to deploy SRSq in adult and pediatric bacterial and viral sepsis, H1N1 influenza, and COVID-19, demonstrating clinically relevant stratification across diseases and revealing some of the physiological alterations linking immune dysregulation to mortality. Our method enables early identification of individuals with dysfunctional immune profiles, bringing us closer to precision medicine in infection.peer-reviewe

The effects of habitat, climate, and Barred Owls on long-term demography of Northern Spotted Owls

Estimates of species' vital rates and an understanding of the factors affecting those parameters over time and space can provide crucial information for management and conservation. We used mark–recapture, reproductive output, and territory occupancy data collected during 1985–2013 to evaluate population processes of Northern Spotted Owls (Strix occidentalis caurina) in 11 study areas in Washington, Oregon, and northern California, USA. We estimated apparent survival, fecundity, recruitment, rate of population change, and local extinction and colonization rates, and investigated relationships between these parameters and the amount of suitable habitat, local and regional variation in meteorological conditions, and competition with Barred Owls (Strix varia). Data were analyzed for each area separately and in a meta-analysis of all areas combined, following a strict protocol for data collection, preparation, and analysis. We used mixed effects linear models for analyses of fecundity, Cormack-Jolly-Seber open population models for analyses of apparent annual survival (ϕ), and a reparameterization of the Jolly-Seber capture–recapture model (i.e. reverse Jolly-Seber; RJS) to estimate annual rates of population change (λ[subscript]RJS) and recruitment. We also modeled territory occupancy dynamics of Northern Spotted Owls and Barred Owls in each study area using 2-species occupancy models. Estimated mean annual rates of population change (λ) suggested that Spotted Owl populations declined from 1.2% to 8.4% per year depending on the study area. The weighted mean estimate of λ for all study areas was 0.962 (± 0.019 SE; 95% CI: 0.925–0.999), indicating an estimated range-wide decline of 3.8% per year from 1985 to 2013. Variation in recruitment rates across the range of the Spotted Owl was best explained by an interaction between total winter precipitation and mean minimum winter temperature. Thus, recruitment rates were highest when both total precipitation (29 cm) and minimum winter temperature (−9.5°C) were lowest. Barred Owl presence was associated with increased local extinction rates of Spotted Owl pairs for all 11 study areas. Habitat covariates were related to extinction rates for Spotted Owl pairs in 8 of 11 study areas, and a greater amount of suitable owl habitat was generally associated with decreased extinction rates. We observed negative effects of Barred Owl presence on colonization rates of Spotted Owl pairs in 5 of 11 study areas. The total amount of suitable Spotted Owl habitat was positively associated with colonization rates in 5 areas, and more habitat disturbance was associated with lower colonization rates in 2 areas. We observed strong declines in derived estimates of occupancy in all study areas. Mean fecundity of females was highest for adults (0.309 ± 0.027 SE), intermediate for 2-yr-olds (0.179 ± 0.040 SE), and lowest for 1-yr-olds (0.065 ± 0.022 SE). The presence of Barred Owls and habitat covariates explained little of the temporal variation in fecundity in most study areas. Climate covariates occurred in competitive fecundity models in 8 of 11 study areas, but support for these relationships was generally weak. The fecundity meta-analysis resulted in 6 competitive models, all of which included the additive effects of geographic region and annual time variation. The 2 top-ranked models also weakly supported the additive negative effects of the amount of suitable core area habitat, Barred Owl presence, and the amount of edge habitat on fecundity. We found strong support for a negative effect of Barred Owl presence on apparent survival of Spotted Owls in 10 of 11 study areas, but found few strong effects of habitat on survival at the study area scale. Climate covariates occurred in top or competitive survival models for 10 of 11 study areas, and in most cases the relationships were as predicted; however, there was little consistency among areas regarding the relative importance of specific climate covariates. In contrast, meta-analysis results suggested that Spotted Owl survival was higher across all study areas when the Pacific Decadal Oscillation (PDO) was in a warming phase and the Southern Oscillation Index (SOI) was negative, with a strongly negative SOI indicative of El Niño events. The best model that included the Barred Owl covariate (BO) was ranked 4th and also included the PDO covariate, but the BO effect was strongly negative. Our results indicated that Northern Spotted Owl populations were declining throughout the range of the subspecies and that annual rates of decline were accelerating in many areas. We observed strong evidence that Barred Owls negatively affected Spotted Owl populations, primarily by decreasing apparent survival and increasing local territory extinction rates. However, the amount of suitable owl habitat, local weather, and regional climatic patterns also were related to survival, occupancy (via colonization rate), recruitment, and, to a lesser extent, fecundity, although there was inconsistency in regard to which covariates were important for particular demographic parameters or across study areas. In the study areas where habitat was an important source of variation for Spotted Owl demographics, vital rates were generally positively associated with a greater amount of suitable owl habitat. However, Barred Owl densities may now be high enough across the range of the Northern Spotted Owl that, despite the continued management and conservation of suitable owl habitat on federal lands, the long-term prognosis for the persistence of Northern Spotted Owls may be in question without additional management intervention. Based on our study, the removal of Barred Owls from the Green Diamond Resources (GDR) study area had rapid, positive effects on Northern Spotted Owl survival and the rate of population change, supporting the hypothesis that, along with habitat conservation and management, Barred Owl removal may be able to slow or reverse Northern Spotted Owl population declines on at least a localized scale.Keywords: Northern Spotted Owl, occupancy, population change, Strix varia, Strix occidentalis caurina, fecundity, Barred Owl, surviva

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19

Functional genomics of the sepsis response

Sepsis is defined as a dysregulated immune response to infection causing organ dysfunction, and is a major area of unmet clinical need. Although conventionally considered a unified disease with a common pathway to organ failure and death, substantial clinical and molecular heterogeneity is seen, which has limited efforts to understand pathophysiology and improve therapeutic strategies. Sepsis is associated with global changes in gene expression, and genetic variants are known to affect the response to infection. This thesis therefore uses an integrated functional genomics approach to investigate disease mechanisms and variation in the sepsis response. Data are presented for 551 patients admitted to intensive care with sepsis due to community acquired pneumonia (CAP) or faecal peritonitis (FP). The sepsis response is explored using genome-wide gene expression and proteomics data, and molecular quantitative trait loci (QTL) are mapped in the context of disease. Comparisons with cardiac surgery patients are performed to identify shared and specific aspects of the host response. The host transcriptomic response was largely shared across sources of sepsis, although some specificity relating to viral infection and interferon signalling was observed and validated in prospectively recruited patients. Expression-based sepsis response signature (SRS) subgroups previously described in CAP were validated, and were additionally observed in FP. SRS1 is associated with higher early mortality, and shows enrichment of pathways relating to T cell exhaustion, cell death, and endotoxin tolerance. Differences between SRS groups were also observed in the FP plasma proteome. Serial sampling enabled the investigation of temporal changes in gene expression and protein abundance within patients. Lastly, disease-relevant expression QTL were identified, and interactions with source of sepsis and SRS determined, highlighting the potential impact of regulatory variation on the sepsis response. This thesis demonstrates the benefit of an integrative functional genomics approach to explore heterogeneity in sepsis, and highlights opportunities for patient stratification and personalised medicine.</p

Functional genomics of the sepsis response

Sepsis is defined as a dysregulated immune response to infection causing organ dysfunction, and is a major area of unmet clinical need. Although conventionally considered a unified disease with a common pathway to organ failure and death, substantial clinical and molecular heterogeneity is seen, which has limited efforts to understand pathophysiology and improve therapeutic strategies. Sepsis is associated with global changes in gene expression, and genetic variants are known to affect the response to infection. This thesis therefore uses an integrated functional genomics approach to investigate disease mechanisms and variation in the sepsis response. Data are presented for 551 patients admitted to intensive care with sepsis due to community acquired pneumonia (CAP) or faecal peritonitis (FP). The sepsis response is explored using genome-wide gene expression and proteomics data, and molecular quantitative trait loci (QTL) are mapped in the context of disease. Comparisons with cardiac surgery patients are performed to identify shared and specific aspects of the host response. The host transcriptomic response was largely shared across sources of sepsis, although some specificity relating to viral infection and interferon signalling was observed and validated in prospectively recruited patients. Expression-based sepsis response signature (SRS) subgroups previously described in CAP were validated, and were additionally observed in FP. SRS1 is associated with higher early mortality, and shows enrichment of pathways relating to T cell exhaustion, cell death, and endotoxin tolerance. Differences between SRS groups were also observed in the FP plasma proteome. Serial sampling enabled the investigation of temporal changes in gene expression and protein abundance within patients. Lastly, disease-relevant expression QTL were identified, and interactions with source of sepsis and SRS determined, highlighting the potential impact of regulatory variation on the sepsis response. This thesis demonstrates the benefit of an integrative functional genomics approach to explore heterogeneity in sepsis, and highlights opportunities for patient stratification and personalised medicine.</p

The NAA Challenge: Serving Millennials Through Subscription Boxes

As an older generation of University of Nebraska-Lincoln graduates phases out, capturing the attention of millennials becomes more and more important. Unfortunately for the Nebraska Alumni Association (NAA), many soon to be and recent UNL graduates do not see the value in spending hundreds of dollars to become a lifetime member. Although some people we interviewed saw an NAA membership as just a donation and are not expecting much in return. We believe that the Nebraska Alumni Association can take advantage of its connections with the University of Nebraska-Lincoln to offer experiences through subscription boxes that will engage millennials and increase membership interest. Our survey has shown us that interest is high in UNL themed subscription boxes with our millennial targets. We have laid out the basic expenses and revenues associated with the subscription boxes and have estimated that the NAA could make additional money while greatly growing millennial\u27s interest in the association. Approximately seventy-five percent of our survey respondents noted that Nebraska Alumni Association subscription boxes would have a higher value than other benefits such as coupons or university news. This shows that the value in a subscription box service would increase millennial\u27s interest in joining the NAA