Risk factors for failure of outpatient parenteral antibiotic therapy (OPAT) in infective endocarditis

Objectives: To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). Patients and methods: We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. ‘OPAT failure’ was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan–Meier survival analysis up to 36 months following OPAT. Results: We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84–29.66), P = 0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01–37.47), P = 0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P = 0.016 log-rank test). Conclusions: These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated

Polyploidy, infraspecific cytotype variation, and speciation in Goldenrods: The cytogeography of Solidago subsect. Humiles (Asteraceae) in North America

Polyploidy is an important evolutionary mechanism in plants, and in some genera (e.g., Solidago in Asteraceae) it is particularly widespread and is hypothesized to have played a major role in diversification. Goldenrods are notorious for their ploidy variation, with roughly 14% and 32% of recognized North American species being polyploid or including multiple cytotypes, respectively. We used traditional chromosome counts and flow cytometry to examine cytogeographic patterns, biogeographic and evolutionary hypotheses, and species boundaries in S. subsect. Humiles. Chromosome numbers and DNA ploidy determinations are reported for 337 individuals, including 148 new reports. Cytotypes show significant geographic structuring. Solidago simplex and S. spathulata were uniformly diploid (2n = 18) in western North America, while cytogeographic patterns in eastern North America were regionally complex and included 2n, 4n, and 6n cytotypes. Cytotypes within S. simplex were ecogeographically segregated and mixed‐ploidy populations were rare. Data from this study and additional biosystematic data indicate that cytotypes in S. simplex fulfill the requirements of multiple species concepts and should best be treated as distinct species. Polyploid cytotypes possibly formed recurrently, however, and evolution and species boundaries within poly ploid S. simplex will require additional study. Results from this study and accumulated data from other studies suggest that biological species diversity in Solidago is considerably higher than currently recognized taxonomically.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147108/1/tax611014-sup-001-PDF.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147108/2/tax611014.pd

Location Coding by Opponent Neural Populations in the Auditory Cortex

Although the auditory cortex plays a necessary role in sound localization, physiological investigations in the cortex reveal inhomogeneous sampling of auditory space that is difficult to reconcile with localization behavior under the assumption of local spatial coding. Most neurons respond maximally to sounds located far to the left or right side, with few neurons tuned to the frontal midline. Paradoxically, psychophysical studies show optimal spatial acuity across the frontal midline. In this paper, we revisit the problem of inhomogeneous spatial sampling in three fields of cat auditory cortex. In each field, we confirm that neural responses tend to be greatest for lateral positions, but show the greatest modulation for near-midline source locations. Moreover, identification of source locations based on cortical responses shows sharp discrimination of left from right but relatively inaccurate discrimination of locations within each half of space. Motivated by these findings, we explore an opponent-process theory in which sound-source locations are represented by differences in the activity of two broadly tuned channels formed by contra- and ipsilaterally preferring neurons. Finally, we demonstrate a simple model, based on spike-count differences across cortical populations, that provides bias-free, level-invariant localization—and thus also a solution to the “binding problem” of associating spatial information with other nonspatial attributes of sounds

New characterisations of tree-based networks and proximity measures

Phylogenetic networks are a type of directed acyclic graph that represent how a set X of present-day species are descended from a common ancestor by processes of speciation and reticulate evolution. In the absence of reticulate evolution, such networks are simply phylogenetic (evolutionary) trees. Moreover, phylogenetic networks that are not trees can sometimes be represented as phylogenetic trees with additional directed edges placed between their edges. Such networks are called tree-based, and the class of phylogenetic networks that are tree-based has recently been characterised. In this paper, we establish a number of new characterisations of tree-based networks in terms of path partitions and antichains (in the spirit of Dilworth’s theorem), as well as via matchings in a bipartite graph. We also show that a temporal network is treebased if and only if it satisfies an antichain-to-leaf condition. In the second part of the paper, we define three indices that measure the extent to which an arbitrary phylogenetic network deviates from being tree-based. We describe how these three indices can be computed efficiently using classical results concerning maximum-sized matchings in bipartite graphs

Tree-Based Unrooted Phylogenetic Networks

Phylogenetic networks are a generalization of phylogenetic trees that are used to represent non-tree-like evolutionary histories that arise in organisms such as plants and bacteria, or uncertainty in evolutionary histories. An unrooted phylogenetic network on a non-empty, finite set X of taxa, or network, is a connected, simple graph in which every vertex has degree 1 or 3 and whose leaf set is X. It is called a phylogenetic tree if the underlying graph is a tree. In this paper we consider properties of tree-based networks, that is, networks that can be constructed by adding edges into a phylogenetic tree. We show that although they have some properties in common with their rooted analogues which have recently drawn much attention in the literature, they have some striking differences in terms of both their structural and computational properties. We expect that our results could eventually have applications to, for example, detecting horizontal gene transfer or hybridization which are important factors in the evolution of many organisms. Correction available at dx.doi.org/10.1007/s11538-018-0530-

A Note on Encodings of Phylogenetic Networks of Bounded Level

Driven by the need for better models that allow one to shed light into the question how life's diversity has evolved, phylogenetic networks have now joined phylogenetic trees in the center of phylogenetics research. Like phylogenetic trees, such networks canonically induce collections of phylogenetic trees, clusters, and triplets, respectively. Thus it is not surprising that many network approaches aim to reconstruct a phylogenetic network from such collections. Related to the well-studied perfect phylogeny problem, the following question is of fundamental importance in this context: When does one of the above collections encode (i.e. uniquely describe) the network that induces it? In this note, we present a complete answer to this question for the special case of a level-1 (phylogenetic) network by characterizing those level-1 networks for which an encoding in terms of one (or equivalently all) of the above collections exists. Given that this type of network forms the first layer of the rich hierarchy of level-k networks, k a non-negative integer, it is natural to wonder whether our arguments could be extended to members of that hierarchy for higher values for k. By giving examples, we show that this is not the case

Antibiotic Resistance (ABR) in Neonates with Suspected Sepsis admitted to a Medecins Sans Frontieres (MSF) supported Medium Care Unit in Quetta, Pakistan

BACKGROUND: Neonatal Sepsis is a major cause of infant death, especially if associated with ABR. Choice of empirical antibiotics is particularly challenging without access to culture/DST, as in most resource limited settings. MSF care included blood cultures (BCs) since 2015. Here we describe the characteristics of babies, etiologies, ABR, treatment and outcomes

Positive correlation between transcriptomic stemness and PI3K/AKT/mTOR signaling scores in breast cancer, and a counterintuitive relationship with PIK3CA genotype

A PI3Kα-selective inhibitor has recently been approved for use in breast tumors harboring mutations in PIK3CA, the gene encoding p110α. Preclinical studies have suggested that the PI3K/AKT/mTOR signaling pathway influences stemness, a dedifferentiation-related cellular phenotype associated with aggressive cancer. However, to date, no direct evidence for such a correlation has been demonstrated in human tumors. In two independent human breast cancer cohorts, encompassing nearly 3,000 tumor samples, transcriptional footprint-based analysis uncovered a positive linear association between transcriptionally-inferred PI3K/AKT/mTOR signaling scores and stemness scores. Unexpectedly, stratification of tumors according to PIK3CA genotype revealed a “biphasic” relationship of mutant PIK3CA allele dosage with these scores. Relative to tumor samples without PIK3CA mutations, the presence of a single copy of a hotspot PIK3CA variant was associated with lower PI3K/AKT/mTOR signaling and stemness scores, whereas the presence of multiple copies of PIK3CA hotspot mutations correlated with higher PI3K/AKT/mTOR signaling and stemness scores. This observation was recapitulated in a human cell model of heterozygous and homozygous PIK3CAH1047R expression. Collectively, our analysis (1) provides evidence for a signaling strength-dependent PI3K-stemness relationship in human breast cancer; (2) supports evaluation of the potential benefit of patient stratification based on a combination of conventional PI3K pathway genetic information with transcriptomic indices of PI3K signaling activation