A³: An Extensible Platform for Application-Aware Anonymity

This paper presents the design and implementation of Application-Aware Anonymity (A³), an extensible platform for deploying anonymity-based services on the Internet. A³ allows applications to tailor their anonymity properties and performance characteristics according to specific communication requirements. To support flexible path construction, A³ exposes a declarative language (A³LOG) that enables applications to compactly specify path selection and instantiation policies executed by a declarative networking engine. We demonstrate that our declarative language is sufficiently expressive to encode novel multi-metric performance constraints as well as existing relay selection algorithms employed by Tor and other anonymity systems, using only a few lines of concise code. We experimentally evaluate the A³ system using a combination of trace-driven simulations and deployment on Planet- Lab. Our experimental results demonstrate that A3 can flexibly support a wide range of path selection and instantiation strategies at low performance overhead

Radiographic Findings and Association With Clinical Severity and Outcomes in Critically Ill Patients With COVID-19

PURPOSE: To describe evolution and severity of radiographic findings and assess association with disease severity and outcomes in critically ill COVID-19 patients. MATERIALS AND METHODS: This retrospective study included 62 COVID-19 patients admitted to the intensive care unit (ICU). Clinical data was obtained from electronic medical records. A total of 270 chest radiographs were reviewed and qualitatively scored (CXR score) using a severity scale of 0-30. Radiographic findings were correlated with clinical severity and outcome. RESULTS: The CXR score increases from a median initial score of 10 at hospital presentation to the median peak CXR score of 18 within a median time of 4 days after hospitalization, and then slowly decreases to a median last CXR score of 15 in a median time of 12 days after hospitalization. The initial and peak CXR score was independently associated with invasive MV after adjusting for age, gender, body mass index, smoking, and comorbidities (Initial, odds ratio [OR]: 2.11 per 5-point increase, confidence interval [CI] 1.35-3.32, P= 0.001; Peak, OR: 2.50 per 5-point increase, CI 1.48-4.22, P= 0.001). Peak CXR scores were also independently associated with vasopressor usage (OR: 2.28 per 5-point increase, CI 1.30-3.98, P= 0.004). Peak CXR scores strongly correlated with the duration of invasive MV (Rho = 0.62, P\u3c 0.001), while the initial CXR score (Rho = 0.26) and the peak CXR score (Rho = 0.27) correlated weakly with the sequential organ failure assessment score. No statistically significant associations were found between radiographic findings and mortality. CONCLUSIONS: Evolution of radiographic features indicates rapid disease progression and correlate with requirement for invasive MV or vasopressors but not mortality, which suggests potential nonpulmonary pathways to death in COVID-19

Association of Trauma Molecular Endotypes With Differential Response to Transfusion Resuscitation Strategies

IMPORTANCE: It is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies. OBJECTIVE: To derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies. DESIGN, SETTING, AND PARTICIPANTS: This was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe injury from 12 North American trauma centers. The cohort was taken from the participants in the PROPPR trial who had complete plasma biomarker data available. Study data were analyzed on August 2, 2021, to October 25, 2022. EXPOSURES: TEs identified by K-means clustering of plasma biomarkers collected at hospital arrival. MAIN OUTCOMES AND MEASURES: An association between TEs and 30-day mortality was tested using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). Differential treatment response to transfusion strategy was assessed using an RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS. RESULTS: A total of 478 participants (median [IQR] age, 34.5 [25-51] years; 384 male [80%]) of the 680 participants in the PROPPR trial were included in this study analysis. A 2-class model that had optimal performance in K-means clustering was found. TE-1 (n = 270) was characterized by higher plasma concentrations of inflammatory biomarkers (eg, interleukin 8 and tumor necrosis factor α) and significantly higher 30-day mortality compared with TE-2 (n = 208). There was a significant interaction between treatment arm and TE for 30-day mortality. Mortality in TE-1 was 28.6% with 1:1:2 treatment vs 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs 7.3% with 1:1:1 treatment (P for interaction = .001). CONCLUSIONS AND RELEVANCE: Results of this secondary analysis suggest that endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs 1:1:2 resuscitation strategies in trauma patients with severe injury. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes

A Brief Overview of the NEBULA Future Internet Architecture

NEBULA is a proposal for a Future Internet Architecture. It is based on the assumptions that: (1) cloud computing will comprise an increasing fraction of the application workload offered to an Internet, and (2) that access to cloud computing resources will demand new architectural features from a network. Features that we have identified include dependability, security, flexibility and extensibility, the entirety of which constitute resilience.NEBULA provides resilient networking services using ultrareliable routers, an extensible control plane and use of multiple paths upon which arbitrary policies may be enforced. We report on a prototype system, Zodiac, that incorporates these latter two features

Trauma Sub-Endotypes Identified Using Latent Class Analysis Have a Differential Response to Blood Product Transfusion Ratios. A secondary analysis of the PROPPR Randomized Trial

Thesis (Master's)--University of Washington, 2022Background: The American Red Cross declared the first ever national blood shortage crisis amid the COVID epidemic in 2022. In severe traumatic injury, large volumes of blood products are often required to resuscitate patients with hemorrhagic shock. A 1:1:1 transfusion ratio (plasma:platelets:red blood cells) compared to a 1:1:2 ratio improves time to bleeding cessation in severely injured patients with hemorrhagic shock, but has not been associated with reduced mortality in randomized trials. It remains unclear whether certain patients within the trauma population benefit from a 1:1:1 or 1:1:2 resuscitation strategy. My objective was to derive trauma sub-endotypes using latent class analysis (LCA) of molecular data and determine whether these subgroups were associated with mortality and differential treatment response to 1:1:1 vs. 1:1:2 resuscitation strategies. Methods: A secondary analysis of the PROPPR trial, a randomized trial published in JAMA in 2015 that demonstrated no difference in 30-day mortality between the two blood transfusion resuscitation groups. LCA was performed on a panel of twelve plasma biomarkers in 478 severely injured patients (out of a total of 680 patients in the original PROPPR Trial) who had a complete panel of biomarkers drawn at the time of presentation and before blood product resuscitation. I tested for an association between trauma endotypes and 30-day mortality using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). I tested for a differential treatment response to transfusion strategy using a RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype group and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS. Results: LCA identified two endotype groups as the optimal model within the population. Trauma endotype-1 (TE-1, n = 248) was associated with significantly higher risk for 30-day mortality compared with trauma endotype-2 (TE-2, n = 230). Mortality in TE-1 was 28.6% with 1:1:2 treatment vs. 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs. 7.3% with 1:1:1 treatment. There was a significant interaction between treatment arm and TE for 30-day mortality (p-value for interaction = 0.02). Conclusions: Endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs. 1:1:2 resuscitation strategies in severely injured trauma patients. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes