SYSTEMS AND METHODS FOR CONTROLLING IN-APP PROMOTIONAL CAMPAIGNS IN CONTENT PLATFORMS BASED ON CONTENT CONSUMPTION

Third-party content can be provided to users as in-app popups, push notifications, or email. A data processing system can identify a first group of client devices and a second group of client devices. The first and second groups include client devices installing a given application or accessing a given content platform (e.g., YouTube). The data processing system can set (or adjust) one or more settings parameters of an ad campaign such that content items (or a specific content item) of the ad campaign are provided for display to the second group of client devices but not to the first group of client devices. The data processing system can monitor one or more user experience metrics for both the first and second groups of client devices. By comparing user experience metrics associated with both groups, the data processing system can detect any negative effect on user experience due to display of third-party content to users of the second group, and take proper actions to alleviate or eliminate the cause of any degradation on user experience

Dynamic Throttling of In-App Promotions to Reduce Marketing Spend Based on Machine-Learning

This document describes a technique of dynamically throttling a promotion or content item placement to reduce marketing spending using machine-learning. A data processing system can determine a click score or an auction score based on various factors. The data processing system can further determine a threshold, for example, by predicting an annoyance effect of showing the promotion or the content item to a user. If the click score or the auction score is below the threshold, the data processing system can throttle the promotion or the content item placement such that the promotion or the content item is not shown to the user

Hijacking of the Pleiotropic Cytokine Interferon-γ by the Type III Secretion System of Yersinia pestis

Yersinia pestis, the causative agent of bubonic plague, employs its type III secretion system to inject toxins into target cells, a crucial step in infection establishment. LcrV is an essential component of the T3SS of Yersinia spp, and is able to associate at the tip of the secretion needle and take part in the translocation of anti-host effector proteins into the eukaryotic cell cytoplasm. Upon cell contact, LcrV is also released into the surrounding medium where it has been shown to block the normal inflammatory response, although details of this mechanism have remained elusive. In this work, we reveal a key aspect of the immunomodulatory function of LcrV by showing that it interacts directly and with nanomolar affinity with the inflammatory cytokine IFNγ. In addition, we generate specific IFNγ mutants that show decreased interaction capabilities towards LcrV, enabling us to map the interaction region to two basic C-terminal clusters of IFNγ. Lastly, we show that the LcrV-IFNγ interaction can be disrupted by a number of inhibitors, some of which display nanomolar affinity. This study thus not only identifies novel potential inhibitors that could be developed for the control of Yersinia-induced infection, but also highlights the diversity of the strategies used by Y. pestis to evade the immune system, with the hijacking of pleiotropic cytokines being a long-range mechanism that potentially plays a key role in the severity of plague

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Coerced Cache Eviction and Discreet Mode Journaling: Dealing with Misbehaving Disks

a new method to force writes to disk in the presence of a disk cache that does not properly obey write-cache configuration or flush requests. We demonstrate the utility of CCE by building a new journaling mode within the Linux ext3 file system. When mounted in this discreet mode, ext3 uses CCEs to ensure that writes are properly ordered and thus maintains file system integrity despite the presence of an improperly behaving disk. We show that discreet mode journaling operates with acceptable overheads for most workloads. Keywords-file systems; disks; journaling; reliability. I