Comparison of KRAS Mutation Assessment in Tumor DNA and Circulating Free DNA in Plasma and Serum Samples

Testing for mutations in the KRAS oncogene for patients with metastatic colorectal cancer (mCRC) is generally performed using DNA from formalin-fixed paraffin-embedded tumor tissue; however, access to specimens can be limited and analysis challenging. This study assessed the identification of KRAS mutations in circulating free DNA (cfDNA) using a commercially available KRAS polymerase chain reaction (PCR) kit. Matched plasma, serum and tumor samples were available from 71 patients with mCRC who had received prior therapy but whose disease progressed following therapy. Yields of cfDNA from plasma and serum samples were comparable. Analyses were successful in 70/71 plasma-extracted samples (specificity: 97%, sensitivity: 31%) and 67/71 serum- extracted samples (specificity: 100%, sensitivity: 25%). This study demonstrates that KRAS mutations can be detected in cfDNA using a commercially available KRAS PCR kit, confirming cfDNA as a potential alternative source of tumor DNA in a diagnostic setting if access to archival tumor specimens is limited

Liquid Polymorphism and Double Criticality in a Lattice Gas Model

We analyze the possible phase diagrams of a simple model for an associating liquid proposed previously. Our two-dimensional lattice model combines oreintati onal ice-like interactions and \"{}Van der Waals\"{} interactions which may be repulsive, and in this case represent a penalty for distortion of hydrogen bonds in the presence of extra molecules. These interactions can be interpreted in terms of two competing distances, but not necessarily soft-core. We present mean -field calculations and an exhaustive simulation study for different parameters which represent relative strength of the bonding interaction to the energy penalty for its distortion. As this ratio decreases, a smooth disappearance of the doubl e criticality occurs. Possible connections to liquid-liquid transitions of molecul ar liquids are suggested

Ethnic identity development and acculturation preferences among minority and majority youth: norms and contact

This article tests a longitudinal model of the antecedents and consequences of changes in identification with indigenous (Mapuche) among indigenous and nonindigenous youth in Chilean school contexts over a 6-month period (633 nonindigenous and 270 Mapuche students, Mages = 12.47 and 12.80 years, respectively). Results revealed that in-group norms supporting contact and quality of intergroup contact at Time 1 predicted student’s changes in Mapuche identification at Time 2, which in turn predicted changes in support for adoption of Chilean culture and maintenance of Mapuche culture at Time 2; some of the relationships between these variables were found to be moderated by age and ethnicity. Conceptual and policy implications are addressed in the Discussion

A philosophical analysis of the evidence-based medicine debate

BACKGROUND: The term "evidence-based medicine" (or EBM) was introduced about ten years ago, and there has been considerable debate about the value of EBM. However, this debate has sometimes been obscured by a lack of conceptual clarity concerning the nature and status of EBM. DISCUSSION: First, we note that EBM proponents have obscured the current debate by defining EBM in an overly broad, indeed almost vacuous, manner; we offer a clearer account of EBM and its relation to the alternative approaches to medicine. Second, while EBM proponents commonly cite the philosophical work of Thomas Kuhn and claim that EBM is a Kuhnian 'paradigm shift,' we argue that such claims are seriously mistaken and unduly polarize the EBM debate. Third, we suggest that it is much more fruitful to understand the relationship between EBM and its alternatives in light of a different philosophical metaphor: W.V. Quine's metaphor of the web of belief. Seen in this way, we argue that EBM is an approach to medical practice that is indeed importantly different from the alternatives. SUMMARY: We can have a more productive debate about the value of EBM by being clearer about the nature of EBM and its relationship to alternative approaches to medicine

A Cross-National Study on the Relations Among Prosocial Moral Reasoning, Gender Role Orientations, and Prosocial Behaviors

This research examined the correlates of prosocial moral reasoning (PMR) in 2 studies. Study I investigated age, gender, and culture group differences in PMR in Brazilian children and adolescents (n = 265) and U.S. adolescents (n = 67). Relations between PMR and both prosocial behaviors and gender role orientations in Brazilian adolescents (n = 136) were explored in Study 2. Self-reflective, internalized reasoning was positively related, and hedonistic reasoning was negatively related, to peer ratings of prosocial behaviors. Femininity was associated with more self-reflective, internalized concerns and with less concerns regarding gaining others’ approval. In general, age and gender differences in PMR were similar for both Brazilian and U.S. adolescents. However, U.S. adolescents scored higher on internalized moral reasoning than Brazilian adolescents. Discussion focused on the correlates of PMR in Brazilian and U.S. children

Bacteriophage-Based Detection of <i>Staphylococcus aureus</i> in Human Serum

Bacteriophages have been investigated for clinical utility, both as diagnostic tools and as therapeutic interventions. In order to be applied successfully, a detailed understanding of the influence of the human matrix on the interaction between bacteriophage and the host bacterium is required. In this study, a cocktail of luciferase bacteriophage reporters was assessed for functionality in a matrix containing human serum and spiked with Staphylococcus aureus. The inhibition of signal and loss of sensitivity was evident with minimal amounts of serum. This phenotype was independent of bacterial growth and bacteriophage viability. Serum-mediated loss of signal was common, albeit not universal, among S. aureus strains. Immunoglobulin G was identified as an inhibitory component and partial inhibition was observed with both the f(ab’)2 and Fc region. A modified bacteriophage cocktail containing recombinant protein A was developed, which substantially improved signal without the need for additional sample purification. This study highlights the importance of assessing bacteriophage activity in relevant host matrices. Furthermore, it identifies an effective solution, recombinant protein A, for promoting bacteriophage-based detection of S. aureus in matrices containing human serum