Identifying prognostic structural features in tissue sections of colon cancer patients using point pattern analysis

Diagnosis and prognosis of cancer is informed by the architecture inherent in cancer patient tissue sections. This architecture is typically identified by pathologists, yet advances in computational image analysis facilitate quantitative assessment of this structure. In this article we develop a spatial point process approach in order to describe patterns in cell distribution within tissue samples taken from colorectal cancer (CRC) patients. In particular, our approach is centered on the Palm intensity function. This leads to taking an approximate-likelihood technique in fitting point processes models. We consider two Neyman-Scott point processes and a void process, fitting these point process models to the CRC patient data. We find that the parameter estimates of these models may be used to quantify the spatial arrangement of cells. Importantly, we observe characteristic differences in the spatial arrangement of cells between patients who died from CRC and those alive at follow-up

Ellipticity weakens chameleon screening

The chameleon mechanism enables a long-range fifth force to be screened in dense environments when nontrivial self-interactions of the field cause its mass to increase with the local density. To date, chameleon fifth forces have mainly been studied for spherically symmetric sources; however, the nonlinear self-interactions mean that the chameleon responds to changes in the shape of the source differently to gravity. In this work we focus on ellipsoidal departures from spherical symmetry and compute the full form of the chameleon force, comparing its shape dependence to that of gravity. Enhancement of the chameleon force by up to 40% is possible when deforming a sphere to an ellipsoid of the same mass, with an ellipticity ∼0.99

Carotenoid evolution during short-storage period of durum wheat (Triticum turgidum conv. durum) and tritordeum (×Tritordeum Ascherson et Graebner) whole-grain flours

38 páginas, 3 figuras, 3 tablasThis study investigates the effect of storage temperature on carotenoid composition in durum wheat and tritordeum whole-grain flours. For both cereal genotypes, total carotenoid content significantly decreased during storage, following a temperature dependent first-order kinetic model. Individual and total carotenoid content decay were similar for durum wheat, with a maximum at 50 °C at the end of the storage period (94%). In contrast, the evolution of lutein ester fractions in tritordeum showed lower losses than for free lutein (∼50%), and consequently the total carotenoid content was less affected (83%). A decrease in the lutein monoesters fraction was observed, coinciding with an increase in the diesterified forms, especially for lutein dilinoleate. These data suggest an esterifying activity in flours different from the enzyme systems operating in vivo (xanthophyll acyl transferase). The formation of lutein diesters, with greater stability, explains the slower carotenoid degradation in tritordeum whole-grain flours.We are grateful to Dr. Sergio G. Atienza for providing the plant material. This work was supported by funding from the Ministerio de Ciencia e Innovación (Spanish Government, Project AGL2010-14850/ALI) and the Consejería de Economía, Innovación, Ciencia y Empleo (Junta de Andalucía, Project P08-AGR-03477). EMO was the recipient of a JAE-Predoctoral grant (CSIC) cofinanced by the ESF. Authors are members of the IBERCAROT Network, funded by CYTED (Ref. 112RT0445).Peer reviewe

Model-Based Prediction of the Patient-Specific Response to Adrenaline

A model for the cardiovascular and circulatory systems has previously been validated in simulated cardiac and circulatory disease states. It has also been shown to accurately capture the main hemodynamic trends in porcine models of pulmonary embolism and PEEP (positive end-expiratory pressure) titrations at different volemic levels. In this research, the existing model and parameter identification process are used to study the effect of different adrenaline doses in healthy and critically ill patient populations, and to develop a means of predicting the hemodynamic response to adrenaline. The hemodynamic effects on arterial blood pressures and stroke volume (cardiac index) are simulated in the model and adrenaline-specific parameters are identified. The dose dependent changes in these parameters are then related to adrenaline dose using data from studies published in the literature. These relationships are then used to predict the future, patient-specific response to a change in dose or over time periods from 1-12 hours. The results are compared to data from 3 published adrenaline dosing studies comprising a total of 37 data sets. Absolute percentage errors for the identified model are within 10% when re-simulated and compared to clinical data for all cases. All identified parameter trends match clinically expected changes. Absolute percentage errors for the predicted hemodynamic responses (N=15) are also within 10% when re-simulated and compared to clinical data. Clinically accurate prediction of the effect of inotropic circulatory support drugs, such as adrenaline, offers significant potential for this type of model-based application. Overall, this work represents a further clinical, proof of concept, of the underlying fundamental mathematical model, methods and approach, as well as providing a template for using the model in clinical titration of adrenaline in a decision support role in critical care. They are thus a further justification in support of upcoming human clinical trials to validate this model

Clinical and Economic Effectiveness of an Inpatient Anticoagulation Service

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90256/1/phco.19.13.1064.31591.pd

A semiconductor source of triggered entangled photon pairs?

The realisation of a triggered entangled photon source will be of great importance in quantum information, including for quantum key distribution and quantum computation. We show here that: 1) the source reported in ``A semiconductor source of triggered entangled photon pairs''[1. Stevenson et al., Nature 439, 179 (2006)]} is not entangled; 2) the entanglement indicators used in Ref. 1 are inappropriate, relying on assumptions invalidated by their own data; and 3) even after simulating subtraction of the significant quantity of background noise, their source has insignificant entanglement.Comment: 5 pages in pre-print format, 1 tabl

Natural history of murine gamma-herpesvirus infection

Murine gamma-herpesvirus 68 (MHV-68) is a natural pathogen of small rodents and insectivores (mice, voles and shrews). The primary infection is characterized by virus replication in lung epithelial cells and the establishment of a latent infection in B lymphocytes. The virus is also observed to persist in lung epithelial cells, dendritic cells and macrophages. Splenomegaly is observed two weeks after infection, in which there is a CD4+ T-cell-mediated expansion of B and T cells in the spleen. At three weeks post-infection an infectious mononucleosis-like syndrome is observed involving a major expansion of Vbeta4+CD8+ T cells. Later in the course of persistent infection, ca. 10% of mice develop lymphoproliferative disease characterized as lymphomas of B-cell origin. The genome from MHV-68 strain g2.4 has been sequenced and contains ca. 73 genes, the majority of which are collinear and homologous to other gamma-herpesviruses. The genome includes cellular homologues for a complement-regulatory protein, Bcl-2, cyclin D and interleukin-8 receptor and a set of novel genes M1 to M4. The function of these genes in the context of latent infections, evasion of immune responses and virus-mediated pathologies is discussed. Both innate and adaptive immune responses play an active role in limiting virus infection. The absence of type I interferon (IFN) results in a lethal MHV-68 infection, emphasizing the central role of these cytokines at the initial stages of infection. In contrast, type II IFN is not essential for the recovery from infection in the lung, but a failure of type II IFN receptor signalling results in the atrophy of lymphoid tissue associated with virus persistence. Splenic atrophy appears to be the result of immunopathology, since in the absence of CD8+ T cells no pathology occurs. CD8+ T cells play a major role in recovery from the primary infection, and also in regulating latently infected cells expressing the M2 gene product. CD4+ T cells have a key role in surveillance against virus recurrences in the lung, in part mediated through 'help' in the genesis of neutralizing antibodies. In the absence of CD4+ T cells, virus-specific CD8+ T cells are able to control the primary infection in the respiratory tract, yet surprisingly the memory CD8+ T cells generated are unable to inhibit virus recurrences in the lung. This could be explained in part by the observations that this virus can downregulate major histocompatibility complex class I expression and also restrict inflammatory cell responses by producing a chemokine-binding protein (M3 gene product). MHV-68 provides an excellent model to explore methods for controlling gamma-herpesvirus infection through vaccination and chemotherapy. Vaccination with gp150 (a homologue of gp350 of Epstein-Barr virus) results in a reduction in splenomegaly and virus latency but does not block replication in the lung, nor the establishment of a latent infection. Even when lung virus infection is greatly reduced following the action of CD8+ T cells, induced via a prime-boost vaccination strategy, a latent infection is established. Potent antiviral compounds such as the nucleoside analogue 2'deoxy-5-ethyl-beta-4'-thiouridine, which disrupts virus replication in vivo, cannot inhibit the establishment of a latent infection. Clearly, devising strategies to interrupt the establishment of latent virus infections may well prove impossible with existing methods