Objectives: S. pneumoniae (SPN) continues to be recognized as a significant respiratory and bacteremic pathogen. Resistance to both oral and parenteral antibiotics used to treat SPN infection is evolving and newer antibiotics are needed with anti-SPN activity. This report documents the activity of tigecycline and comparators against 5501 SPN collected globally since 2004. Methods: Between 2004–2007, 387 hospital sites in 48 countries collected 5501 SPN deemed clinically significant from a variety of sources. MICs were determined at each site using supplied broth microdilution panels and MIC results interpreted by CLSI standards at each site. Results: The % SPN inhibited at each MIC are shown below: Conclusions: Tigecycline demonstrated excellent in vitro activity against SPN with 100% of isolates inhibited at ≤0.5 mcg/ml. Globally, only 61.5% of SPN were susceptible to penicillin, while 0.2% were resistant to levofloxacin. Continued surveillance of resistance in SPN to new and established antimicrobials is warranted.
Abstract While evolutionary approaches to medicine show promise, measuring evolution itself is difficult due to experimental constraints and the dynamic nature of body systems. In cancer evolution, continuous observation of clonal architecture is impossible, and longitudinal samples from multiple timepoints are rare. Increasingly available DNA sequencing datasets at single cell resolution enable the reconstruction of past evolution using mutational history, allowing for a better understanding of dynamics prior to detectable disease. We derive methods based on coalescent theory for estimating the net growth rate of clones from either reconstructed phylogenies or the number of shared mutations. Using single-cell datasets from blood, we apply and validate our analytical methods for estimating the net growth rate of hematopoietic clones, eliminating the need for complex simulations. We show that our estimates may have broad applications to improve mechanistic understanding and prognostic ability. Compared to clones with a single or unknown driver mutation, clones with multiple drivers have significantly increased growth rates (median 0.94 vs. 0.25 per year; p = 1.6 × 10 -6 ). Further, stratifying patients with a myeloproliferative neoplasm (MPN) by the growth rate of their fittest clone shows that higher growth rates are associated with shorter time from clone initiation to MPN diagnosis (median 13.9 vs. 26.4 months; p = 0.0026).
SummaryWe prove that every triangle in the hyperbolic plane can be circumscribed by an ellipse. The Intermediate Value Theorem is a key ingredient in the proof.
Intussusception is the most common cause of infant bowel obstruction. Because delays in diagnosis can lead to severe outcomes, differentiating milder cases from those with potentially serious outcomes is important.The objective of this study was to identify factors associated with bowel resection among intussusception cases using data from a large nationwide study, which investigated the association between intussusception and Rotashield.We examined characteristics of 376 intussusception cases not associated with Rotashield use. Cases were confirmed by a radiologic procedure, surgery, or autopsy. Clinical characteristics of infants with and without bowel resection were compared.During the week before hospitalization, 93% of the 376 infants with intussusception had vomiting, 72% reported bloody stool, 63% had hemoccult positive stool, 51% had diarrhea, 43% reported fever, and 14% had documented fever. Surgery was performed on 209 cases (56%). Of these 209 cases, 33% (67/209) required bowel resection. Documented fever on admission significantly increased the risk of bowel resection (odds ratio, adjusted for race and sex, 2.7; 95% confidence interval, 1.2-6.0). Among infants with intussusception, the presence of a reported symptom for at least 2 days before hospital admission was also an independent predictor of bowel resection (adjusted odds ratio, 2.7; 95% confidence interval, 1.5-4.8).Bowel resection appears to be more likely among intussusception patients with documented fever and symptoms for at least 2 days. However, because resection also occurred among those without fever or prolonged symptoms, severe disease must also be considered in absence of these symptoms.
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