Opening the black box of selection

Peer reviewedPublisher PD

Selection into medicine : the predictive validity of an outcome-based procedure

Acknowledgements: The authors would like to thank Dr. Kelly Dore for valuable advice and sharing Computer-based Assessment for Sampling Personal characteristics (CASPer) assignments in order to develop our Situational Judgement Test and Angela Verheyen and Guus Smeets for their essential support in gathering data.Peer reviewedPublisher PD

Stabilizing role of platelet P2Y(12) receptors in shear-dependent thrombus formation on ruptured plaques

Background: In most models of experimental thrombosis, healthy blood vessels are damaged. This results in the formation of a platelet thrombus that is stabilized by ADP signaling via P2Y(12) receptors. However, such models do not predict involvement of P2Y(12) in the clinically relevant situation of thrombosis upon rupture of atherosclerotic plaques. We investigated the role of P2Y(12) in thrombus formation on (collagen-containing) atherosclerotic plaques in vitro and in vivo, by using a novel mouse model of atherothrombosis. Methodology: Plaques in the carotid arteries from Apoe(-/-) mice were acutely ruptured by ultrasound treatment, and the thrombotic process was monitored via intravital fluorescence microscopy. Thrombus formation in vitro was assessed in mouse and human blood perfused over collagen or plaque material under variable conditions of shear rate and coagulation. Effects of two reversible P2Y(12) blockers, ticagrelor (AZD6140) and cangrelor (AR-C69931MX), were investigated. Principal Findings: Acute plaque rupture by ultrasound treatment provoked rapid formation of non-occlusive thrombi, which were smaller in size and unstable in the presence of P2Y(12) blockers. In vitro, when mouse or human blood was perfused over collagen or atherosclerotic plaque material, blockage or deficiency of P2Y(12) reduced the thrombi and increased embolization events. These P2Y(12) effects were present at shear rates >500 s(-1), and they persisted in the presence of coagulation. P2Y(12)-dependent thrombus stabilization was accompanied by increased fibrin(ogen) binding. Conclusions/Significance: Platelet P2Y(12) receptors play a crucial role in the stabilization of thrombi formed on atherosclerotic plaques. This P2Y(12) function is restricted to high shear flow conditions, and is preserved in the presence of coagulation

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Increasing value in research:cost evaluations in health professions education

The authors use foo et al.'s discussion of the value of economic evaluations to consider how such techniques might advance the practice of selection for medical school

Identifying costs in health professions education:a scoping review protocol

INTRODUCTION: Profound changes in the healthcare sector and the growing, global shortage of healthcare workers are driving the demand to update and scale-up health professions education (HPE). At the same time, educational institutions are faced with increasing resource scarcity and decisions of where and how to allocate resources must be made conscious of costs. However, costs are known to be inaccurately and incompletely identified in HPE research. Therefore, to improve rigour in cost evidence and enable its use in decision-making, it is necessary to have a better understanding of the costs, stakeholders and cost identification methods being used in HPE research. This protocol has been developed to outline the rationale and methods for a scoping review of the literature intended to map the current state of cost and cost identification evidence in HPE. METHODS AND ANALYSIS: This protocol is developed in accordance with the Joanna Briggs Institute Manual for Evidence Synthesis. PubMed, ERIC, CINAHL and PsycInfo will be scoped for all types of English language publications from 2012 to 2022 that investigate costs associated with the education of health professionals. Two independent reviewers will assess publications for eligibility. Data will be extracted on the educational topic and context, the costs, cost types, perspectives and methods of cost identification as represented in the literature. ETHICS AND DISSEMINATION: No human participants are involved in this scoping review. All evidence for this study are sourced from public databases; therefore, ethical approval was not required. Final results will be disseminated through peer-reviewed publications and presented at conferences. TRIAL REGISTRATION NUMBER: https://doi.org/10.17605/OSF.IO/ET4XB

Platelets as messengers of early-stage cancer

Platelets have an important role in tumor angiogenesis, growth, and metastasis. The reciprocal interaction between cancer and platelets results in changes of several platelet characteristics. It is becoming clear that analysis of these platelet features could offer a new strategy in the search for biomarkers of cancer. Here, we review the human studies in which platelet characteristics (e.g., count, volume, protein, and mRNA content) are investigated in early-stage cancer. The main focus of this paper is to evaluate which platelet features are suitable for the development of a blood test that could detect cancer in its early stages