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

Antioxidant enzymes mediate survival of breast cancer cells deprived of extracellular matrix.

Metastasis by cancer cells relies upon the acquisition of the ability to evade anoikis, a cell death process elicited by detachment from extracellular matrix (ECM). The molecular mechanisms that ECM-detached cancer cells use to survive are not understood. Striking increases in reactive oxygen species (ROS) occur in ECM-detached mammary epithelial cells, threatening cell viability by inhibiting ATP production, suggesting that ROS must be neutralized if cells are to survive ECM-detachment. Here, we report the discovery of a prominent role for antioxidant enzymes, including catalase and superoxide dismutase, in facilitating the survival of breast cancer cells after ECM-detachment. Enhanced expression of antioxidant enzymes in nonmalignant mammary epithelial cells detached from ECM resulted in ATP elevation and survival in the luminal space of mammary acini. Conversely, silencing antioxidant enzyme expression in multiple breast cancer cell lines caused ATP reduction and compromised anchorage-independent growth. Notably, antioxidant enzyme-deficient cancer cells were compromised in their ability to form tumors in mice. In aggregate, our results reveal a vital role for antioxidant enzyme activity in maintaining metabolic activity and anchorage-independent growth in breast cancer cells. Furthermore, these findings imply that eliminating antioxidant enzyme activity may be an effective strategy to enhance susceptibility to cell death in cancer cells that may otherwise survive ECM-detachment

Efficacy of lymph node dissection during robotic-assisted lobectomy for non-small cell lung cancer: retrospective review of 159 consecutive cases.

BACKGROUND: We investigated whether robotic-assisted surgery improves mediastinal lymph node dissection (MLND). METHODS: We analyzed patients (pts) who underwent robotic-assisted video-assisted thoracoscopic surgery (R-VATS) lobectomy for non-small cell lung cancer (NSCLC) over 36 months. Perioperative outcomes, tumor histology, numbers, locations, and status of all lymph nodes (LNs), and TNM (tumor, nodal, and metastasis) stage changes were analyzed. RESULTS: One hundred fifty-nine pts had mean tumor size 3.3±0.2 cm, most commonly being adenocarcinoma. Assessment of ≥3 N2 stations occurred in 156 (98.1%) pts, with 141 (88.7%) pts having \u3e3 N2 stations reported. Mean total N1 + N2 stations assessed was 5.6±0.1 stations, including mean 4.1±0.1 N2 stations assessed. Mean N2 LNs reported was 7.2±0.3 LNs, and mean total N1 + N2 LNs reported was 13.4±0.4 LNs. There were 118 (74.2%) clinical stage-I pts versus 96 (60.4%) pathologic stage-I pts. Overall, 48 (30.2%) pts were upstaged, including 13 pts with cN0-pN1, 13 pts with cN0-pN2, 4 pts with cN1-pN2, and 18 pts with changes in T. CONCLUSIONS: R-VATS lobectomy is safe and results in perioperative outcomes comparable to those reported for conventional VATS. R-VATS MLND is effective at detecting occult metastatic disease during lobectomy for NSCLC

Surgical outcomes associated with postoperative atrial fibrillation after robotic-assisted pulmonary lobectomy: retrospective review of 208 consecutive cases.

BACKGROUND: In this study, we sought to investigate the effect of post-operative atrial fibrillation (POAF) after robotic-assisted video-thoracoscopic pulmonary lobectomy on comorbid postoperative complications, chest tube duration, and hospital length of stay (LOS). METHODS: We retrospectively analyzed prospectively collected data from 208 consecutive patients who underwent robotic-assisted pulmonary lobectomy by one surgeon for known or suspected lung cancer. Postoperatively, 39 (18.8%) of these patients experienced POAF during their hospital stay. The occurrence of postoperative complications other than POAF, chest tube duration, and hospital LOS were analyzed in patients with POAF and without POAF. Statistical significance (P≤0.05) was determined by unpaired Student\u27s t-test or by Chi-square test. RESULTS: Of patients with POAF, 46% also had other concurrent postoperative complications, while only 31% of patients without POAF experienced complications. The average number of postoperative complications experienced by patients with POAF was significantly higher than that experienced by those without POAF (0.9 vs. 0.4, P CONCLUSIONS: This study demonstrated the association between the incidence of POAF and a more complicated hospital course. Further studies are needed to determine whether confounders were involved in this association

Effect of small body habitus on peri-operative outcomes after robotic-assisted pulmonary lobectomy: retrospective analysis of 208 consecutive cases.

BACKGROUND: Patients with smaller body surface area (BSA) have smaller pleural cavities, which limit visualization and instrument mobility during video-assisted thoracoscopic surgery (VATS). We investigated the effects of BSA on outcomes with robotic-assisted VATS lobectomy. METHODS: We analyzed 208 consecutive patients who underwent robotic-assisted lobectomy over 34 months. Patients were separated into group A (BSA ≤1.65 m(2)) and group B (BSA \u3e1.65 m(2)). Operative times, estimated blood loss (EBL), conversions to thoracotomy, complications, hospital length of stay (LOS), and in-hospital mortality were compared. RESULTS: Group A had 40 patients (BSA 1.25-1.65 m(2)), and group B had 168 patients (BSA 1.66-2.86 m(2)). Median skin-to-skin operative times [± standard error of the mean (SEM)] were 169±16 min for group A and 176±6 min for group B (P=0.34). Group A had median EBL of 150±96 mL compared to 200±24 mL for group B (P=0.37). Overall conversion rate to thoracotomy was 8/40 (20.0%) in group A versus 12/168 (7.1%) in group B (P=0.03); while emergent conversion for bleeding was 2/40 (5.0%) in group A versus 5/168 (3.0%) in group B (P=0.62). Postoperative complications occurred in 12/40 (30.0%) in group A, compared to 66/168 (39.3%) in group B (P=0.28). Patients from both groups had median hospital LOS of 5 days (P=0.68) and had similar in-hospital mortality. CONCLUSIONS: Patients with BSA ≤1.65 m(2) have similar perioperative outcomes and complication risks as patients with larger BSA. Patients with BSA ≤1.65 m(2) have a higher overall conversion rate to thoracotomy, but similar conversion rate for bleeding as patients with larger BSA. Robotic-assisted pulmonary lobectomy is feasible and safe in patients with small body habitus