Protease activated receptors (PARs) are G-protein coupled receptors (GPCRs) that have a unique activation mechanism. Unlike other GPCRs that can be activated by free ligands, under physiological conditions, PARs are activated by the tethered ligand, which is a part of their N-terminus that is unmasked by proteolysis. It has been 30 years since the first member of the family, PAR1, was identified. In this review, we will discuss this unique tethered ligand mediate receptor activation of PARs in detail how they interact with the proteases, the complex structural rearrangement of the receptors upon activation, and the termination of the signaling. We also summarize the structural studies of the PARs and how single nucleotide polymorphisms impact the receptor reactivity. Finally, we review the current strategies for inhibiting PAR function with therapeutic targets for anti-thrombosis. The focus of this review is PAR1 and PAR4 as they are the thrombin signal mediators on human platelets and therapeutics targets. We also include the structural studies of PAR2 as it informs the mechanism of action for PARs in general. Patients with type 1 diabetes have high risk of developing microvascular complications, and microangiopathy contributes to premature cardiovascular disease in this population. The role that microvesicles (MVs) may play in the development of microangiopathy in type 1 diabetes remains unclear. Plasma levels of endothelial MVs (EMVs) and platelet MVs (PMVs) in 130 patients with type 1 diabetes without microangiopathy, 106 patients with microangiopathy and 100 matched healthy controls were analyzed using flow cytometry. MV expression of procoagulant phosphatidylserine (PS) and proinflammatory high mobility group box-1 protein (HMGB1) was also assessed. Patients with type 1 diabetes had markedly elevated levels of EMVs and PS+ EMVs as well as PMVs and PS+ PMVs compared to healthy controls (p<.001 for all). Furthermore, HMGB1+ EMVs and HMGB1+ PMVs were significantly increased in patients (p<.001 for all). After adjusting for potential confounders, there were no clear differences between patients with ortory effects that drive endothelial dysfunction, and it would therefore be of interest to further study the role of HMGB1+ MVs in the development of macrovascular complications in type 1 diabetes. Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19). To evaluate the incidence of VTE in patients with COVID-19. MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19. Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis. 3487 patients from 30 studies were included. Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%-66%). PE with or without DVT occurred in 12% of patients (95% PI, 2%-46%) and DVT alone in 14% (95% PI, 1%-75%). Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%-57%) and DVT in 6% (95% PI, 0%-60%), compared to 11% (95% PI, 2%-46%) and 24% (95% PI, 2%-85%) in studies using other diagnostic strategies or patient sampling. In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%-66%), PE in 19% (95% PI, 6%-47%), and DVT alone in 7% (95% PI, 0%-69%). Corresponding values in general wards were respectively 9% (95% PI, 0%-94%), 4% (95% PI, 0%-100%), and 7% (95% CI, 1%-49%). VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE. The threshold for clinical suspicion should be low to trigger prompt diagnostic testing.VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE. The threshold for clinical suspicion should be low to trigger prompt diagnostic testing. Multi-drug resistant (MDR) bacteria are a major health concern. In this retrospective study, a rule-based classification algorithm, MOCA-I (Multi-Objective Classification Algorithm for Imbalanced data) is used to identify hospitalized patients at risk of testing positive for multidrug-resistant (MDR) bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA), before or during their stay. Applied to a data set of 48,945 hospital stays (including known cases of carriage) with up to 16,325 attributes per stay, MOCA-I generated alert rules for risk of carriage or infection. A risk score was then computed from each stay according to the triggered rules.Recall and precision curves were plotted. The classification can be focused on specifically detecting high risk of having a positive test, or identifying large numbers of at-risk patients by modulating the risk score cut-off level. For a risk score above 0.85,recall (sensitivity) is 62 % with 69 % precision (confidence) for MDR bacteria, recall is r identification of large numbers of patients at risk. MOCA-I can thus contribute to more adapted treatments and preventive measures from admission, depending on the clinical setting or management strategy. Health information systems (HIS) are expected to be effective and efficient in improving healthcare services, but empirical observation of HIS reveals that most perform poorly in terms of these metrics. Theoretical factors of HIS performance are widely studied, and solutions to mitigate poor performance have been proposed. In this paper we implement effective methods to eliminate some common drawbacks of HIS design and demonstrate the synergy between the methods. CI-1040 MEK inhibitor JointCalc, the first comprehensive patient-facing web-based decision support tool for joint replacement, is used as a case study for this purpose. User-centred design and thorough end-user involvement are employed throughout the design and development of JointCalc. This is supported by modern software production paradigms, including continuous integration/continuous development, agile and service-oriented architecture. The adopted methods result in a user-approved application delivered well within the scope of project. This work supports the claims of high potential efficiency of HIS.