Outplayed: Regaining Strategic Initiative in the Gray Zone, A Report Sponsored by the Army Capabilities Integration Center in Coordination with Joint Staff J-39/Strategic Multi-Layer Assessment Branch

U.S. competitors pursuing meaningful revision or rejection of the current U.S.-led status quo are employing a host of hybrid methods to advance and secure interests contrary to those of the United States. These challengers employ unique combinations of influence, intimidation, coercion, and aggression to incrementally crowd out effective resistance, establish local or regional advantage, and manipulate risk perceptions in their favor. So far, the United States has not come up with a coherent countervailing approach. It is in this “gray zone”—the awkward and uncomfortable space between traditional conceptions of war and peace—where the United States and its defense enterprise face systemic challenges to U.S. position and authority. Gray zone competition and conflict present fundamental challenges to U.S. and partner security and, consequently, should be important pacers for U.S. defense strategy.https://press.armywarcollege.edu/monographs/1924/thumbnail.jp

Genome modeling system: A knowledge management platform for genomics

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms

CD11b+, Ly6G+ Cells Produce Type I Interferon and Exhibit Tissue Protective Properties Following Peripheral Virus Infection

The goal of the innate immune system is containment of a pathogen at the site of infection prior to the initiation of an effective adaptive immune response. However, effector mechanisms must be kept in check to combat the pathogen while simultaneously limiting undesirable destruction of tissue resulting from these actions. Here we demonstrate that innate immune effector cells contain a peripheral poxvirus infection, preventing systemic spread of the virus. These innate immune effector cells are comprised primarily of CD11b+Ly6C+Ly6G- monocytes that accumulate initially at the site of infection, and are then supplemented and eventually replaced by CD11b+Ly6C+Ly6G+ cells. The phenotype of the CD11b+Ly6C+Ly6G+ cells resembles neutrophils, but the infiltration of neutrophils typically occurs prior to, rather than following, accumulation of monocytes. Indeed, it appears that the CD11b+Ly6C+Ly6G+ cells that infiltrated the site of VACV infection in the ear are phenotypically distinct from the classical description of both neutrophils and monocyte/macrophages. We found that CD11b+Ly6C+Ly6G+ cells produce Type I interferons and large quantities of reactive oxygen species. We also observed that depletion of Ly6G+ cells results in a dramatic increase in tissue damage at the site of infection. Tissue damage is also increased in the absence of reactive oxygen species, although reactive oxygen species are typically thought to be damaging to tissue rather than protective. These data indicate the existence of a specialized population of CD11b+Ly6C+Ly6G+ cells that infiltrates a site of virus infection late and protects the infected tissue from immune-mediated damage via production of reactive oxygen species. Regulation of the action of this population of cells may provide an intervention to prevent innate immune-mediated tissue destruction

i ACKNOWLEDGMENTS

I would like to begin by thanking my advisers, Andrea and Remzi Arpaci-Dusseau. Had they not been at Wisconsin, I don't know who else I would have worked with. They have a unique combination of taking their research and their student's work very seriously, while not taking themselves too seriously. Among other things, they taught me how to ask the right questions when conducting research. Indeed it has been an honor and a privilege working with both of them. I thank Jeff Naughton, Marv Solomon and Tehshik Yoon for serving on my thesis committee. They provided valuable advice and feedback. I thank Tehshik in particular for making it to my defense despite his illness that day so I could avoid delaying my graduation

ACKNOWLEDGMENTS

I would like to begin by thanking my advisers, Andrea and Remzi Arpaci-Dusseau. Had they not been at Wisconsin, I don’t know who else I would have worked with. They have a unique combination of taking their research and their student’s work very seriously, while not taking themselves too seriously. Among other things, they taught me how to ask the right questions when conducting research. Indeed it has been an honor and a privilege working with both of them. I thank Jeff Naughton, Marv Solomon and Tehshik Yoon for serving on my thesis committee. They provided valuable advice and feedback. I thank Tehshik in particular for making it to my defense despite his illness that day so I could avoid delaying my graduation. During my stay at Wisconsin, I have had the opportunity to collaborate with a number o

Collaborative research to support urban agriculture in the face of change: The case of the Sumida watercress farm on O'ahu.

As urban areas expand around the world, there are growing efforts to restore and protect natural and agricultural systems for the multitude of ecosystem services they provide to urban communities. This study presents a researcher-farmer collaboration in a highly urbanized area of O'ahu focused on understanding the historical and current challenges and opportunities faced by a culturally and socially valued spring-dependent urban farm, Sumida Farm, which produces the majority of the state of Hawai'i's watercress. We conducted a long-term trend analysis (25 years) of factors identified by the farmers to be important historical drivers of crop yield, including groundwater pumping, pest outbreaks, temperature, Oceanic Niño Index, and precipitation. We combined this analysis with a year of intensive spring water sampling on the farm to evaluate nutrient and contaminant composition and flow to understand water-related stressors, as well as evaluate the potential of the farm to provide nutrient retention services. We found negative correlations between historical crop yields and increases in the Oceanic Niño Index, temperature thresholds, and pest outbreaks. Despite the surrounding urbanization, we found on-farm water quality to be very high, and microbial analyses revealed an abundance of denitrifiers (nirS gene) suggesting that the farm provides a nutrient retention service to downstream systems. Finally, we found that socio-cultural values including heritage value, aesthetic value, and educational value are increasingly important for the Sumida family and surrounding community. These socio-cultural benefits alongside highly valued local food production and nutrient retention services are essential for continued community and political support. Collectively, our study demonstrates that challenges facing urban agricultural systems shift through time, and that recognition of the beyond crop-yield benefits of these systems to urban communities is essential to their long-term survival

Early Convalescent Plasma for High-Risk Outpatients with Covid-19.

BackgroundEarly administration of convalescent plasma obtained from blood donors who have recovered from coronavirus disease 2019 (Covid-19) may prevent disease progression in acutely ill, high-risk patients with Covid-19.MethodsIn this randomized, multicenter, single-blind trial, we assigned patients who were being treated in an emergency department for Covid-19 symptoms to receive either one unit of convalescent plasma with a high titer of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or placebo. All the patients were either 50 years of age or older or had one or more risk factors for disease progression. In addition, all the patients presented to the emergency department within 7 days after symptom onset and were in stable condition for outpatient management. The primary outcome was disease progression within 15 days after randomization, which was a composite of hospital admission for any reason, seeking emergency or urgent care, or death without hospitalization. Secondary outcomes included the worst severity of illness on an 8-category ordinal scale, hospital-free days within 30 days after randomization, and death from any cause.ResultsA total of 511 patients were enrolled in the trial (257 in the convalescent-plasma group and 254 in the placebo group). The median age of the patients was 54 years; the median symptom duration was 4 days. In the donor plasma samples, the median titer of SARS-CoV-2 neutralizing antibodies was 1:641. Disease progression occurred in 77 patients (30.0%) in the convalescent-plasma group and in 81 patients (31.9%) in the placebo group (risk difference, 1.9 percentage points; 95% credible interval, -6.0 to 9.8; posterior probability of superiority of convalescent plasma, 0.68). Five patients in the plasma group and 1 patient in the placebo group died. Outcomes regarding worst illness severity and hospital-free days were similar in the two groups.ConclusionsThe administration of Covid-19 convalescent plasma to high-risk outpatients within 1 week after the onset of symptoms of Covid-19 did not prevent disease progression. (SIREN-C3PO ClinicalTrials.gov number, NCT04355767.)

Onset of Coagulation Function Recovery Is Delayed in Severely Injured Trauma Patients with Venous Thromboembolism

BackgroundAltered coagulation function after trauma can contribute to development of venous thromboembolism (VTE). Severe trauma impairs coagulation function, but the trajectory for recovery is not known. We hypothesized that enhanced, early recovery of coagulation function increases VTE risk in severely injured trauma patients.Study designSecondary analysis was performed on data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, excluding patients who died within 24 hours or were on pre-injury anticoagulants. Patient characteristics, adverse outcomes, and parameters of platelet function and coagulation (thromboelastography) were compared from admission to 72 hours between VTE (n = 83) and non-VTE (n = 475) patients. A p value < 0.05 indicates significance.ResultsDespite similar patient demographics, VTE patients exhibited hypercoagulable thromboelastography parameters and enhanced platelet function at admission (p < 0.05). Both groups exhibited hypocoagulable thromboelastography parameters, platelet dysfunction, and suppressed clot lysis (low clot lysis at 30 minutes) 2 hours after admission (p < 0.05). The VTE patients exhibited delayed coagulation recovery (a significant change compared with 2 hours) of K-value (48 vs 24 hours), α-angle (no recovery), maximum amplitude (24 vs 12 hours), and clot lysis at 30 minutes (48 vs 12 hours). Platelet function recovery mediated by arachidonic acid (72 vs 4 hours), ADP (72 vs 12 hours), and collagen (48 vs 12 hours) was delayed in VTE patients. The VTE patients had lower mortality (4% vs 13%; p < 0.05), but fewer hospital-free days (0 days [interquartile range 0 to 8 days] vs 10 days [interquartile range 0 to 20 days]; p < 0.05) and higher complication rates (p < 0.05).ConclusionsRecovery from platelet dysfunction and coagulopathy after severe trauma were delayed in VTE patients. Suppressed clot lysis and compensatory mechanisms associated with altered coagulation that can potentiate VTE formation require additional investigation