Multidimensional Proteomics Analysis of Amniotic Fluid to Provide Insight into the Mechanisms of Idiopathic Preterm Birth

Though recent advancement in proteomics has provided a novel perspective on several distinct pathogenetic mechanisms leading to preterm birth (inflammation, bleeding), the etiology of most preterm births still remains elusive. We conducted a multidimensional proteomic analysis of the amniotic fluid to identify pathways related to preterm birth in the absence of inflammation or bleeding.A proteomic fingerprint was generated from fresh amniotic fluid using surface-enhanced laser desorbtion ionization time of flight (SELDI-TOF) mass spectrometry in a total of 286 consecutive samples retrieved from women who presented with signs or symptoms of preterm labor or preterm premature rupture of the membranes. Inflammation and/or bleeding proteomic patterns were detected in 32% (92/286) of the SELDI tracings. In the remaining tracings, a hierarchical algorithm was applied based on descriptors quantifying similarity/dissimilarity among proteomic fingerprints. This allowed identification of a novel profile (Q-profile) based on the presence of 5 SELDI peaks in the 10-12.5 kDa mass area. Women displaying the Q-profile (mean+/-SD, gestational age: 25+/-4 weeks, n = 40) were more likely to deliver preterm despite expectant management in the context of intact membranes and normal amniotic fluid clinical results. Utilizing identification-centered proteomics techniques (fluorescence two-dimensional differential gel electrophoresis, robotic tryptic digestion and mass spectrometry) coupled with Protein ANalysis THrough Evolutionary Relationships (PANTHER) ontological classifications, we determined that in amniotic fluids with Q-profile the differentially expressed proteins are primarily involved in non-inflammatory biological processes such as protein metabolism, signal transduction and transport.Proteomic profiling of amniotic fluid coupled with non-hierarchical bioinformatics algorithms identified a subgroup of patients at risk for preterm birth in the absence of intra-amniotic inflammation or bleeding, suggesting a novel pathogenetic pathway leading to preterm birth. The altered proteins may offer opportunities for therapeutical intervention and future drug development to prevent prematurity

Modelling GDPR-Compliant Explanations for Trustworthy AI

Through the General Data Protection Regulation (GDPR), the European Union has set out its vision for Automated Decision- Making (ADM) and AI, which must be reliable and human-centred. In particular we are interested on the Right to Explanation, that requires industry to produce explanations of ADM. The High-Level Expert Group on Artificial Intelligence (AI-HLEG), set up to support the implementation of this vision, has produced guidelines discussing the types of explanations that are appropriate for user-centred (interactive) Explanatory Tools. In this paper we propose our version of Explanatory Narratives (EN), based on user-centred concepts drawn from ISO 9241, as a model for user-centred explanations aligned with the GDPR and the AI-HLEG guidelines. Through the use of ENs we convert the problem of generating explanations for ADM into the identification of an appropriate path over an Explanatory Space, allowing explainees to interactively explore it and produce the explanation best suited to their needs. To this end we list suitable exploration heuristics, we study the properties and structure of explanations, and discuss the proposed model identifying its weaknesses and strengths

Effect of the Inpatient General Medicine Rotation on Student Pursuit of a Generalist Career

BACKGROUND: Entry into general internal medicine (GIM) has declined. The effect of the inpatient general medicine rotation on medical student career choices is uncertain. OBJECTIVE: To assess the effect of student satisfaction with the inpatient general medicine rotation on pursuit of a career in GIM. DESIGN: Multicenter cohort study. PARTICIPANTS: Third-year medical students between July 2001 and June 2003. MEASUREMENTS: End-of-internal medicine clerkship survey assessed satisfaction with the rotation using a 5-point Likert scale. Pursuit of a career in GIM defined as: (1) response of “Very Likely” or “Certain” to the question “How likely are you to pursue a career in GIM?”; and (2) entry into an internal medicine residency using institutional match data. RESULTS: Four hundred and two of 751 (54%) students responded. Of the student respondents, 307 (75%) matched in the 2 years following their rotations. Twenty-eight percent (87) of those that matched chose an internal medicine residency. Of these, 8% (25/307) were pursuing a career in GIM. Adjusting for site and preclerkship interest, overall satisfaction with the rotation predicted pursuit of a career in GIM (odds ratio [OR] 3.91, P<.001). Although satisfaction with individual items did not predict pursuit of a generalist career, factor analysis revealed 3 components of satisfaction (attending, resident, and teaching). Adjusting for preclerkship interest, 2 factors (attending and teaching) were associated with student pursuit of a career in GIM (P<.01). CONCLUSIONS: Increased satisfaction with the inpatient general medicine rotation promotes pursuit of a career in GIM