Practical whole-system provenance capture

Data provenance describes how data came to be in its present form. It includes data sources and the transformations that have been applied to them. Data provenance has many uses, from forensics and security to aiding the reproducibility of scientific experiments. We present CamFlow, a whole-system provenance capture mechanism that integrates easily into a PaaS offering. While there have been several prior whole-system provenance systems that captured a comprehensive, systemic and ubiquitous record of a system’s behavior, none have been widely adopted. They either A) impose too much overhead, B) are designed for long-outdated kernel releases and are hard to port to current systems, C) generate too much data, or D) are designed for a single system. CamFlow addresses these shortcoming by: 1) leveraging the latest kernel design advances to achieve efficiency; 2) using a self-contained, easily maintainable implementation relying on a Linux Security Module, NetFilter, and other existing kernel facilities; 3) providing a mechanism to tailor the captured provenance data to the needs of the application; and 4) making it easy to integrate provenance across distributed systems. The provenance we capture is streamed and consumed by tenant-built auditor applications. We illustrate the usability of our implementation by describing three such applications: demonstrating compliance with data regulations; performing fault/intrusion detection; and implementing data loss prevention. We also show how CamFlow can be leveraged to capture meaningful provenance without modifying existing applications.Engineering and Applied Science

A Frugal Approach to Reduce RCU Grace Period Overhead

Grace period computation is a core part of the Read-Copy-Update (RCU) synchronization technique that determines the safe time to reclaim the deferred objects' memory. We first show that the eager grace period computation employed in the Linux kernel is appropriate only for enterprise workloads such as web and database servers where a large amount of reclaimable memory awaits the completion of a grace period. However, such memory is negligible in High-Performance Computing (HPC) and mostly idling environments due to limited OS kernel activity. Hence an eager approach is not only futile but also detrimental as the CPU cycles consumed to compute a grace period leads to jitter in HPC and frequent CPU wake-ups in idle environments. We design frugal grace periods, an economical grace period computation for non-enterprise environments that consume fewer CPU cycles. In addition, we reduce the number of grace periods either by using heuristics or by letting the memory allocator to explicitly request for a grace period only when it is running out of free objects. Our implementation in the Linux kernel reduces the number of grace periods by 68% to 99%, reduces the CPU time consumed by grace periods by 39% to 99%, improves the throughput by up to 28% for NAS parallel benchmarks and increases the CPU time spent in low power states by 2.4x when the system is idle

What If I Don't Treat My PSA-Detected Prostate Cancer? Answers from Three Natural History Models

Background: Making an informed decision about treating a prostate cancer detected after a routine prostate-specific antigen (PSA) test requires knowledge about disease natural history, such as the chances that it would have been clinically diagnosed in the absence of screening and that it would metastasize or lead to death in the absence of treatment. Methods: We use three independently developed models of prostate cancer natural history to project risks of clinical progression events and disease-specific deaths for PSA-detected cases assuming they receive no primary treatment. Results: The three models project that 20%-33% of men have preclinical onset; of these 38%-50% would be clinically diagnosed and 12%-25% would die of the disease in the absence of screening and primary treatment. The risk that men age less than 60 at PSA detection with Gleason score 2-7 would be clinically diagnosed in the absence of screening is 67%-93% and would die of the disease in the absence of primary treatment is 23%-34%. For Gleason score 8 to 10 these risks are 90%-96% and 63%-83%. Conclusions: Risks of disease progression among untreated PSA-detected cases can be nontrivial, particularly for younger men and men with high Gleason scores. Model projections can be useful for informing decisions about treatment. Impact: This is the first study to project population-based natural history summaries in the absence of screening or primary treatment and risks of clinical progression events following PSA detection in the absence of primary treatment. Cancer Epidemiol Biomarkers Prev; 20(5); 740-50. (C)2011 AACR

Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS).

BACKGROUND Endpoints used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. OBJECTIVE To develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. METHODS Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. RESULTS The COS consists of four outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life (QoL). A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a two-round Delphi process and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, EoE Histology Scoring System, EoE Endoscopic Reference Score, and patient-reported measures of dysphagia and QoL. CONCLUSIONS This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE, which will facilitate meaningful treatment comparisons and improve the quality of data synthesis

Survivor: A Fine-Grained Intrusion Response and Recovery Approach for Commodity Operating Systems

International audienceDespite the deployment of preventive security mechanisms to protect the assets and computing platforms of users, intrusions eventually occur. We propose a novel intrusion survivability approach to withstand ongoing intrusions. Our approach relies on an orchestration of fine-grained recovery and per-service responses (e.g., privileges removal). Such an approach may put the system into a degraded mode. This degraded mode prevents attackers to reinfect the system or to achieve their goals if they managed to reinfect it. It maintains the availability of core functions while waiting forpatches to be deployed. We devised a cost-sensitive response selection process to ensure that while the service is in a degraded mode, its core functions are still operating. We built a Linux-based prototype and evaluated the effectiveness of our approach against different types of intrusions. The results show that our solution removes the effects of the intrusions, that it can select appropriate responses, and that it allows services to survive when reinfected. In terms of performance overhead, in most cases, we observed a small overhead, except in the rare case of services that write many small files asynchronously in a burst, where we observed a higher but acceptable overhead

Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study.

BACKGROUND: Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical-pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states. METHODS: We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis. FINDINGS: The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36-0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32-0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1-3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04-10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09-0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11-6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84-34·64; p=0·0013) and adult onset (2·22, 1·19-4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm. INTERPRETATION: Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis. FUNDING: National Institutes of Health

Alignment of parent- and child-reported outcomes and histology in eosinophilic esophagitis across multiple CEGIR sites.

BACKGROUND: Patient-reported outcome metrics for eosinophilic esophagitis (EoE) have been developed and validated but not used in a multicenter pediatric population or systematically aligned with histology. OBJECTIVE: We sought to understand (1) the potential of caregiver report to predict patient self-reported symptoms and (2) the correlation of patient-reported outcome domains with histology. METHODS: Patients with EoE (n = 310) and their parents participating in the Consortium of Gastrointestinal Eosinophilic Disease Researchers (CEGIR) observational clinical trial were queried for baseline patient symptoms and quality of life (QOL) by using the Pediatric Eosinophilic Esophagitis Symptom Score, version 2 (PEESSv2.0), and the Pediatric QOL EoE module (PedsQL-EoE), and biopsy specimens were analyzed by using the EoE Histology Scoring System. RESULTS: PEESSv2.0 parental and child reports aligned across all domains (r = 0.68-0.73, P < .001). PedsQL-EoE reports correlated between parents and children across ages and multiple domains (r = 0.48-0.79, P < .001). There was a tight correlation between symptoms on PEESSv2.0 and their effects on QOL both on self-report and parental report (P < .001). Self-reported symptoms on PEESSv2.0 (positively) and PedsQL-EoE (inversely) showed a weak correlation with proximal, but not distal, peak eosinophil counts and features and architectural tissue changes on the EoE Histology Scoring System (P < .05). CONCLUSIONS: Parents of children with EoE aged 3 to 18 years accurately reflected their childrens disease symptoms and QOL. Self- and parent-reported symptoms correlate with proximal esophageal histology. Our data suggest that parental report in young children can function as an adequate marker for self-reported symptoms and that self-reported symptoms can reflect changes in tissue histology in the proximal esophagus. These findings should be considered during clinical trials for drug development