BackgroundTo evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE).MethodsOur systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence.ResultsWe included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence.ConclusionsThis study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke.Trial registrationPROSPERO; CRD42017073904.

Network vulnerability can be analyzed automatically by attack graph. Attack graph tools can generate attack paths in network and show users the network vulnerabilities analyzing process for network security risk analysis. There are some problems such as state space explosion, the high complexity of algorithms, being difficult to demonstrate graphically, and so on, for attack graph generation and visualization techniques. Therefore, we surveyed and analyzed the attack graph generation and visualization technology. We summarized the open source tools like MulVAL, TVA, Attack Graph Toolkit, NetSPA and so on, and the commercial tools, for example, Cauldron, FireMon, Skybox View. We compared and analyzed these tools from the aspects of the attack graph types, scalability, or complexity of attack graph generation algorithm, the degree of attack graph visualization. Their common denominator was summarized, and their different points were analyzed. The future and applications for attack graph were forecasted, for example its applications in industrial control systems, and in the network security defense and risk assessment.

This paper begins with a discussion of the role and value of industrial control system (ICS) testbed which apply a universal, controllable, realistic, and repeatable experimental platform to SCADA control system cybersecurity research. According to ICS layered architecture, ICS testbed based on emulation, physical, and simulation (EPS-ICS Testbed) is designed and implemented. EPS-ICS Testbed enables experimenters to create experiments with varying levels of fidelity and is widely used in vulnerability digging, comprehensive security training, facilitate development of security standards, develop advanced control system architectures and technologies that are more secure and robust.

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Part 1: Control Systems SecurityInternational audienceThis paper demonstrates the utility of an industrial control system testbed that incorporates a universal, realistic, measurable, controllable and reusable experimental platform for cyber security research and testing. The testbed has a layered architecture that leverages physical devices and emulation and simulation technologies. The testbed enables researchers to create experiments of varying levels of fidelity for vulnerability discovery, product evaluation and system certification. The utility of the testbed is demonstrated via a case study involving an industrial boiler control system

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The complex etiopathology of retained placenta (RP) and hazards associated with it has made it crucial for researchers and clinical veterinarians to study pathogenesis, early-warning diagnosis, and treatment. This study aimed to screen the potential prognostic markers of RP in dairy cows using plasma metabolomics coupled with clinical laboratory indicators. Blood samples were collected from 260 dairy cows at 21, 14, 7, and 0 days before parturition and 7, 14, and 21 days after parturition. Consequently, 10 healthy cows and 10 cows with RP with similar parity, body condition score, and age were included in the study. The changes in clinical laboratory indicators of the enrolled cows from 21 before parturition to 21 days after parturition were assessed. After initial overview of the multivariate statistical data using PCA analysis, the data were subjected to orthogonal partial least-squares discriminant analysis. Compared with cows with RP at 7 days before parturition, the levels of endothelin and 6-keto-prostaglandin F1α were increased in healthy cows, while the level of estradiol and progesterone decreased. Adenine dinucleotide phosphate, hypoxanthine, guanine dinucleotide phosphate, inosine monophosphate, and L-arginine were revealed as potential prognostic markers of cows with RP at 7 days before parturition involved in the regulation of taste transduction, purine and glutathione metabolism, and autophagy. The best period for the early-warning diagnosis of RP in dairy cows is 7 days before parturition, and purine metabolism and autophagy may play a vital role in the occurrence and development of RP in dairy cows.