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Carbapenem-resistant Enterobacteriaceae (CRE) have spread globally and represent a serious and growing threat to public health. Rapid methods for tracking plasmids carrying carbapenemase genes could greatly benefit infection control efforts. Here, we demonstrate that real-time, direct tracking of a single plasmid in a bacterial strain responsible for an outbreak is possible using a commercial matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) system. In this case, we retrospectively tracked the bla KPC carbapenemase gene-bearing pKpQIL plasmid responsible for a CRE outbreak that occurred at the NIH Clinical Center in 2011. An ∼11,109-Da MS peak corresponding to a gene product of the bla KPC pKpQIL plasmid was identified and characterized using a combination of proteomics and molecular techniques. This plasmid peak was present in spectra from retrospectively analyzed K. pneumoniae outbreak isolates, concordant with results from whole-genome sequencing, and absent from a diverse control set of bla KPC -negative clinical Enterobacteriaceae isolates. Notably, the gene characterized here is located adjacent to the bla KPC Tn 4401 transposon on the pKpQIL plasmid. Sequence analysis demonstrates the presence of this gene in other bla KPC Tn 4401 -containing plasmids and suggests that this signature MS peak may be useful in tracking other plasmids conferring carbapenem resistance. Plasmid identification using this MALDI-TOF MS method was accomplished in as little as 10 min from isolated colonies and 30 min from positive (spiked) blood cultures, demonstrating the potential clinical utility for real-time plasmid tracking in an outbreak.

This chapter provides an introduction to phylogenetic cladograms – a systems biology evolutionary-based computational methodology that emphasizes the importance of considering multilevel heterogeneity in living systems when mining data related to these systems. We start by defining intelligence as the ability to predict, because prediction is a very important objective in mining data, especially biomedical data (Sect. 16.1). We then give a brief review of artificial intelligence (AI) and computational intelligence (CI) (Sects. 16.2, 16.3), provide a conciliatory overview of CI, and suggest that phylogenetic cladograms which provide hypotheses about speciation and inheritance relationships should be considered to be a CI methodology. We then discuss heterogeneity in biomedical data and talk about data types, how statistical methods blur heterogeneity, and the different results obtained between more traditional CI methodologies (phenetic) and phylogenetic techniques. Finally, we give an example of constructing and interpreting a phylogenetic cladogram tree.

This book explores what makes people unusually successful with regard to health, wealth, and social status. Author Malcolm Gladwell examines such “outliers” from novel and unexpected perspectives. He discusses the importance of persistence and the illusion of meritocracy, and he provides examples of how hidden and sometimes arbitrary advantages accrue to individuals who excel in their area of expertise. He discusses the limitations of IQ testing and informs us that beyond a certain IQ threshold higher values don’t seem to matter with regard to success. He provides an example of two highly intelligent subjects: one poor and unsuccessful, the other affluent and famous. Only the affluent subject’s family successfully cultivated assertiveness and intellectual ability in the child. Gladwell attributes the story of a successful Manhattan attorney to his Jewish ethnicity, early rejection by establishment law firms, a demographic shortage of smart college-age men in the 1940s, and a family heritage of skilled, meaningful work in the garment industry. He describes multigenerational family feuds in Kentucky as the legacy of animal-herding cultures that favor honor and courage, even over life. The ethnic theory that culture underlies observed risks such as plane crashes is plausibly supported by close descriptions of Korean and Colombia plane crashes. Higher culture-associated respect for authority seems reversible, because assertiveness training significantly improves global air safety. Innovative explanations of Asian success in mathematics and commerce are offered, based on centuries of cultures praising the steady, careful, hard work through the year that is necessary for rice farming; a more logical counting system; and a claim that such diligence and persistence is a key to success in mathematics. A South Bronx experimental public school, the KIPP Academy, …

We developed a methodology for constructing scoring systems to support bivalent decision making in clinical medicine. Such systems could be of great benefit in forced-choice decision-making situations as well as in triaging, screening, and diagnostic applications. Our methodology combines medical judgment with explicit computer-derived information to identify an optimum parsimonious set of variables for predicting bivalent (2-class) outcomes. It includes a process for using these variables to produce scores for each negative (d=0) and positive (d=1) class entity and for using these scores in decision making. We produced this methodology while attempting to devise a system that determines which African Americans are most likely to be glucose intolerant (i.e. pre-diabetic) and hence would benefit by taking an oral glucose tolerance test. We achieved excellent results as evidenced by ROC plot areas of .85 for men alone and .94 for women alone. We anticipate actual clinical use of the scoring systems that we constructed. We also anticipate constructing and deploying other similar useful clinical decision support systems with our methodology.

We thank Sally Partridge for contributing her [very insightful analysis and thoughts][1] ([1][2]). In our study ([2][3]), we found that it was possible to track a pKpQIL plasmid using a MALDI-TOF MS peak corresponding to a cleavage product of p019, a pKpQIL-encoded protein. Dr. Partridge points out

Background Different DNA aberrations processes can cause colorectal cancer (CRC). Herein, we conducted a comprehensive molecular characterization of 27 CRCs from Iranian patients. Materials and Methods Array CGH was performed. The MSI phenotype and the methylation status of 15 genes was established using MSP. The CGH data was compared to two established lists of 41 and 68 cancer genes, respectively, and to CGH data from African Americans. A maximum parsimony cladogram based on global aberrations was established. Results The number of aberrations seem to depend on the MSI status. MSI-H tumors displayed the lowest number of aberrations. MSP revealed that most markers were methylated, except RNF182 gene. P16 and MLH1 genes were primarily methylated in MSI-H tumors. Seven markers with moderate to high frequency of methylation (SYNE1, MMP2, CD109, EVL, RET, LGR and PTPRD) had very low levels of chromosomal aberrations. All chromosomes were targeted by aberrations with deletions more frequent than amplifications. The most amplified markers were CD248, ERCC6, ERGIC3, GNAS, MMP2, NF1, P2RX7, SFRS6, SLC29A1 and TBX22. Most deletions were noted for ADAM29, CHL1, CSMD3, FBXW7, GALNS, MMP2, NF1, PRKD1, SMAD4 and TP53. Aberrations targeting chromosome X were primarily amplifications in male patients and deletions in female patients. A finding similar to what we reported for African American CRC patients. Conclusion This first comprehensive analysis of CRC Iranian tumors reveals a high MSI rate. The MSI tumors displayed the lowest level of chromosomal aberrations but high frequency of methylation. The MSI-L were predominantly targeted with chromosomal instability in a way similar to the MSS tumors. The global chromosomal aberration profiles showed many similarities with other populations but also differences that might allow a better understanding of CRC's clinico-pathological specifics in this population.

This book explores how physicians make difficult diagnoses. Cognitive processes, not merely learning correlations between symptoms and diseases, must be an integral part of clinical medicine. We are introduced to a woman with abdominal complaints, undiagnosed for more than 15 years. Finally, a physician carefully listens to her entire story, and makes the correct diagnosis. A patient with sudden shortness of breath is rescued by a visiting cardiologist, who quickly makes the diagnosis using pattern recognition and heuristics. Most medical errors are mistakes in thinking. Patients may be misdiagnosed due to the physician’s positive or negative social stereotypes. Errors may result from availability errors (recent experience) and confirmation bias (disregarding data inconsistent with one’s first guess), according to economics Nobel laureates Tversky and Kahneman. Patients can assume active roles by asking questions and helping to shape physician thinking. The time that medical gatekeepers (general internists, general pediatricians, and family practitioners) spend talking with patients is undervalued. Cognitive bias (matching the patient to a familiar prototype), zebra retreat (avoiding a rare diagnosis), and diagnosis momentum (passing along a first-impression diagnosis to peers) point physicians to a misdiagnosis. Physicians should accept uncertainty as an intrinsic feature of medical practice. The author-as-patient consulted 6 surgeons for a long-standing hand ailment, received 4 different diagnoses, and chose the surgeon with the best cognitive assessment. Current medical knowledge cannot entirely rely on evidence-based medicine and clinical trials for individual diagnoses and treatment. The author discusses errors that radiologists make in their practice, although similar errors are also made in other specialties. One problem may be an increase in the complexity and number of images that are …

This clever and entertaining book provides a hundred philosophical puzzles that stimulate thought and dialogue on a variety of moral, social, and personal issues. Organized into brief chapters that each consist of a fictional scenario followed by discussion of the dilemma presented by the scenario, this book includes a wide range of thought-provoking topics. The instant reaction of many scientists to deem a philosophical book as beyond their field of interest would deprive them of considering some scenarios that are very much related to scientific interests. For example, the “Black and white and red all over” chapter discusses a color-blind scientist who is an expert in objective measures of the color red. The question of whether gaining color vision will alter the scientist’s impression of red is raised in the dialogue section, and the potential role of subjective impressions on the largely objective discipline of science is considered. Additional topics included in the book arise from science fiction scenarios, such as consideration of what traits will be most useful when populating a colony on Mars. The space colonization situation presented in “The veil of ignorance” chapter raises questions regarding societal organization, while “Bigger Brother” introduces a mind-reading computer that predicts a person’s actions, leading to a discussion of whether humans are nothing more than a machine-like mix of chemical reactions and electrical signals. Given the broad range of topics presented in the 100 “thought experiments” within this book, most readers will find at least one chapter captivates their interest, although it is more likely that a reader will have several favorite chapters. As revealed in the Commentaries section …