Abstract:
Random Forest is an excellent classification tool, especially in the –omics sciences such as metabolomics, where the number of variables is much greater than the number of subjects, i.e., “n << p.” However, the choices for the arguments for the random forest implementation are very important. Simulation studies are performed to compare the effect of the input parameters on the predictive ability of the random forest. The number of variables sampled, m-try, has the largest impact on the true prediction error. It is often claimed that the out-of-bag error (OOB) is an unbiased estimate of the true prediction error. However, for the case where n << p, with the default arguments, the out-of-bag (OOB) error overestimates the true error, i.e., the random forest actually performs better than indicated by the OOB error. This bias is greatly reduced by subsampling without replacement and choosing the same number of observations from each group. However, even after these adjustments, there is a low amount of bias. The remaining bias occurs because when there are trees with equal predictive ability, the one that performs better on the in-bag samples will perform worse on the out-of-bag samples. Cross-validation can be performed to reduce the remaining bias.

Abstract:
In metabolomics data, like other -omics data,
normalization is an important part of the data processing. The goal of
normalization is to reduce the variation from non-biological sources (such as
instrument batch effects), while maintaining the biological variation. Many
normalization techniques make adjustments to each sample. One common method is
to adjust each sample by its Total Ion Current (TIC), i.e. for each feature in the sample, divide its intensity value by
the total for the sample. Because many of the assumptions of these methods are
dubious in metabolomics data sets, we compare these methods to two methods that
make adjustments separately for each metabolite, rather than for each sample.
These two methods are the following: 1) for each metabolite, divide its value
by the median level in bridge samples (BRDG); 2) for each metabolite divide its
value by the median across the experimental samples (MED). These methods were
assessed by comparing the correlation of the normalized values to the values
from targeted assays for a subset of metabolites in a large human plasma data
set. The BRDG and MED normalization techniques greatly outperformed the other
methods, which often performed worse than performing no normalization at all.

Abstract:
Aim: To review recent literature on the diagnosis and management options for globus pharyngeus. Recent Findings: Strong evidence for the cause of globus pharyngeus is lacking however there is some research to suggest a possible link between laryngopharyngeal reflux (LPR) and globus pharyngeus. Radiological investigations used to find the cause of globus pharyngeus are often normal with little evidence to support their routine use. There are no long term controlled studies investigating the effectiveness of proton pump inhibitors (PPI’s) for the treatment of globus pharyngeus however, these are commonly used. A recent nonplacebo-controlled study has shown promising results using liquid alginate suspension to treat laryngopharyngeal reflux symptoms. Other treatment modalities used, such as speech and language therapy, have shown some improvement in symptoms but these are often small trials. Summary: Globus pharyngeus is a clinical diagnosis. Investigations should be reserved for those with atypical symptoms. Thorough clinical evaluation and examination, including fibreoptic laryngoscopy, are key points in management.

Abstract:
Breast cancer cell lines were sorted into CD44posCD24pos and CD44posCD24neg populations to evaluate their progeny for the expression of CD44, CD24, and markers of a mesenchymal phenotype. The populations, separated by fluorescence activated cell sorting (FACS) were injected into immunocompromised mice to evaluate their tumorigenicity and invasiveness of the resulting xenografts.CD24 expression was dynamically regulated in vitro in all evaluated breast cancer cell lines. Furthermore, a single noninvasive, epithelial-like CD44posCD24pos cell had the ability to give rise to invasive, mesenchymal CD44posCD24neg progeny. Importantly, this interconversion occurred in vivo as CD44posCD24pos cells gave rise to xenografts with locally invasive borders as seen in xenografts initiated with CD44posCD24neg cells. Lastly, the ability of CD44posCD24pos cells to give rise to mesenchymal progeny, and vice versa, was blocked upon ablation of Activin/Nodal signaling.Our data demonstrate that the invasive, mesenchymal CD44posCD24neg phenotype is under dynamic control in breast cancer cell lines both in vitro and in vivo. Furthermore, our observations suggest that therapies targeting CD44posCD24neg tumor cells may have limited success in preventing primary tumor metastasis unless Activin/Nodal signaling is arrested.The CD24 gene encodes a highly glycosylated, glycosylphosphatidylinositol anchored cell surface protein [1]. Thought to function as an adhesion molecule, it is known to bind Platelet Activation-Dependent Granule to External Membrane Protein (aka P-Selectin) [2] and facilitate intracellular signaling despite lacking a transmembrane domain [3]. In both normal and cancerous mammary tissue, CD24 positivity is frequently associated with a terminally differentiated, luminal phenotype [4-6]. In spite of this classification, the influence of CD24 expression on tumorigenicity and invasiveness is inconsistent, ranging from a positive [7-10] to a negative one [11-14].Al-Hajj et al. [14]

Abstract:
Adult humans’ recognition of self and others in diverse media (e.g., mirrors, videos) provides evidence for their skills at kinesthetic-visual and visual-visual matching, respectively. In this study, we examine self- and other-recognition in point-light displays (PLDs). Participants (7 men, 4 women) were filmed while walking in the dark with lighted joints to create two PLDs each, one showing a frontal view and one showing a half-profile view. Ten of the participants then observed 22 PLDs, two of themselves and two each of 10 familiar persons, and named whom they perceived in each PLD. Participants achieved greater than chance levels of accuracy in identifying themselves (55% of the time) and others (29.5%). Comparisons using three measures showed that participants were better at detecting themselves than others; however, variability in self- and other-detection within and across studies suggests caution prior to generalizing. Participants were equally successful in detecting walkers in frontal and half-profile PLDs, on average detecting about 3 walkers out of 11 in each perspective. Thus, participants showed some skill in using kinesthetic-visual and visual-visual matching in recognizing self and other, respectively, from the limited information present in PLDs.

Abstract:
The title of a 1697 pamphlet about London’s stock-jobbers referred to the “extravagant humour of stock-jobbing,” using the imagery of contemporary medical knowledge to suggest that stock-jobbers represented a potentially unbalancing element within the English body-politic. Members of different social orders, however, perceived differently the threat stock-jobbers allegedly posed. Landowners, merchants, craftworkers, bureaucrats, and the officers of joint-stock companies all saw the stock-jobbers perils specific to their own social statuses and ambitions. The few defenders of the stock-jobbers therefore also sought to demonstrate the benefits that dealings joint-stock companies could offer to the body-politic as a whole as well as to all its members in particular.

Abstract:
We give an analysis of a continuation algorithm for the numerical solution of the force-based quasicontinuum equations. The approximate solution of the force-based quasicontinuum equations is computed by an iterative method using an energy-based quasicontinuum approximation as the preconditioner. The analysis presented in this paper is used to determine an efficient strategy for the parameter step size and number of iterations at each parameter value to achieve a solution to a required tolerance. We present computational results for the deformation of a Lennard-Jones chain under tension to demonstrate the necessity of carefully applying continuation to ensure that the computed solution remains in the domain of convergence of the iterative method as the parameter is increased. These results exhibit fracture before the actual load limit if the parameter step size is too large.

Abstract:
We derive a model problem for quasicontinuum approximations that allows a simple, yet insightful, analysis of the optimal-order convergence rate in the continuum limit for both the energy-based quasicontinuum approximation and the quasi-nonlocal quasicontinuum approximation. The optimal-order error estimates for the quasi-nonlocal quasicontinuum approximation are given for all strains up to the continuum limit strain for fracture. The analysis is based on an explicit treatment of the coupling error at the atomistic to continuum interface, combined with an analysis of the error due to atomistic and continuum schemes using the stability of the quasicontinuum approximation.

Abstract:
The atomistic to continuum interface for quasicontinuum energies exhibits nonzero forces under uniform strain that have been called ghost forces. In this paper, we prove for a linearization of a one-dimensional quasicontinuum energy around a uniform strain that the effect of the ghost forces on the displacement nearly cancels and has a small effect on the error away from the interface. We give optimal order error estimates that show that the quasicontinuum displacement converges to the atomistic displacement at the optimal rate O($h$) in the discrete $\ell^\infty$ norm and O($h^{1/p}$) in the $w^{1,p}$ norm for $1 \leq p < \infty.$ where $h$ is the interatomic spacing. We also give a proof that the error in the displacement gradient decays away from the interface to O($h$) at distance O($h|\log h|$) in the atomistic region and distance O($h$) in the continuum region. E, Ming, and Yang previously gave a counterexample to convergence in the $w^{1,\infty}$ norm for a harmonic interatomic potential. Our work gives an explicit and simplified form for the decay of the effect of the atomistic to continuum coupling error in terms of a general underlying interatomic potential and gives the estimates described above in the discrete $\ell^\infty$ and $w^{1,p}$ norms.

Abstract:
We analyze a force-based quasicontinuum approximation to a one-dimensional system of atoms that interact by a classical atomistic potential. This force-based quasicontinuum approximation is derived as the modification of an energy-based quasicontinuum approximation by the addition of nonconservative forces to correct nonphysical ``ghost'' forces that occur in the atomistic to continuum interface. We prove that the force-based quasicontinuum equations have a unique solution under suitable restrictions on the loads. For Lennard-Jones next-nearest-neighbor interactions, we show that unique solutions exist for loads in a symmetric region extending nearly to the tensile limit. We give an analysis of the convergence of the ghost force iteration method to solve the equilibrium equations for the force-based quasicontinuum approximation. We show that the ghost force iteration is a contraction and give an analysis for its convergence rate.