Zebrafish models of the immune response: taking it on the ChIn

The zebrafish is proving to be an extremely versatile new experimental model for unraveling the mysteries of innate immunity and has considerable promise as a system for the identification of novel modulators of this crucial biological process. A rate-limiting factor, however, is the mechanical stimulus required to induce the inflammatory response. A new chemically induced inflammation assay ('ChIn' assay) published in BMC Biology obviates this requirement and seems set to accelerate progress in the field

A Closed-Form Solution of the Multi-Period Portfolio Choice Problem for a Quadratic Utility Function

In the present paper, we derive a closed-form solution of the multi-period portfolio choice problem for a quadratic utility function with and without a riskless asset. All results are derived under weak conditions on the asset returns. No assumption on the correlation structure between different time points is needed and no assumption on the distribution is imposed. All expressions are presented in terms of the conditional mean vectors and the conditional covariance matrices. If the multivariate process of the asset returns is independent it is shown that in the case without a riskless asset the solution is presented as a sequence of optimal portfolio weights obtained by solving the single-period Markowitz optimization problem. The process dynamics are included only in the shape parameter of the utility function. If a riskless asset is present then the multi-period optimal portfolio weights are proportional to the single-period solutions multiplied by time-varying constants which are depending on the process dynamics. Remarkably, in the case of a portfolio selection with the tangency portfolio the multi-period solution coincides with the sequence of the simple-period solutions. Finally, we compare the suggested strategies with existing multi-period portfolio allocation methods for real data.Comment: 38 pages, 9 figures, 3 tables, changes: VAR(1)-CCC-GARCH(1,1) process dynamics and the analysis of increasing horizon are included in the simulation study, under revision in Annals of Operations Researc

Evolution of H3N2 Influenza Virus in a Guinea Pig Model

Studies of influenza virus evolution under controlled experimental conditions can provide a better understanding of the consequences of evolutionary processes with and without immunological pressure. Characterization of evolved strains assists in the development of predictive algorithms for both the selection of subtypes represented in the seasonal influenza vaccine and the design of novel immune refocused vaccines. To obtain data on the evolution of influenza in a controlled setting, naïve and immunized Guinea pigs were infected with influenza A/Wyoming/2003 (H3N2). Virus progeny from nasal wash samples were assessed for variation in the dominant and other epitopes by sequencing the hemagglutinin (HA) gene to quantify evolutionary changes. Viral RNA from the nasal washes from infection of naïve and immune animals contained 6% and 24.5% HA variant sequences, respectively. Analysis of mutations relative to antigenic epitopes indicated that adaptive immunity played a key role in virus evolution. HA mutations in immunized animals were associated with loss of glycosylation and changes in charge and hydrophobicity in and near residues within known epitopes. Four regions of HA-1 (75–85, 125–135, 165–170, 225–230) contained residues of highest variability. These sites are adjacent to or within known epitopes and appear to play an important role in antigenic variation. Recognition of the role of these sites during evolution will lead to a better understanding of the nature of evolution which help in the prediction of future strains for selection of seasonal vaccines and the design of novel vaccines intended to stimulated broadened cross-reactive protection to conserved sites outside of dominant epitopes

Clinicians’ response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2

Hyperoxia may induce pulmonary injury and may increase oxidative stress. In this retrospective database study we aimed to evaluate the response to hyperoxia by intensivists in a Dutch academic intensive care unit. All arterial blood gas (ABG) data from mechanically ventilated patients from 2005 until 2009 were extracted from an electronic storage database of a mixed 32-bed intensive care unit in a university hospital in Amsterdam. Mechanical ventilation settings at the time of the ABG tests were retrieved. The results of 126,778 ABG tests from 5,498 mechanically ventilated patients were retrieved including corresponding ventilator settings. In 28,222 (22%) of the ABG tests the arterial oxygen tension (PaO2) was > 16 kPa (120 mmHg). In only 25% of the tests with PaO2 > 16 kPa (120 mmHg) was the fraction of inspired oxygen (FiO(2)) decreased. Hyperoxia was accepted without adjustment in ventilator settings if FiO(2) was 0.4 or lower. Hyperoxia is frequently seen but in most cases does not lead to adjustment of ventilator settings if FiO(2) <0.41. Implementation of guidelines concerning oxygen therapy should be improved and further research is needed concerning the effects of frequently encountered hyperoxi

Comparative effectiveness of asthma interventions within a practice based research network

<p>Abstract</p> <p>Background</p> <p>Asthma is a chronic lung disease that affects more than 23 million people in the United States, including 7 million children. Asthma is a difficult to manage chronic condition associated with disparities in health outcomes, poor medical compliance, and high healthcare costs. The research network coordinating this project includes hospitals, urgent care centers, and outpatient clinics within Carolinas Healthcare System that share a common electronic medical record and billing system allowing for rapid collection of clinical and demographic data. This study investigates the impact of three interventions on clinical outcomes for patients with asthma. Interventions are: an integrated approach to care that incorporates asthma management based on the chronic care model; a shared decision making intervention for asthma patients in underserved or disadvantaged populations; and a school based care approach that examines the efficacy of school-based programs to impact asthma outcomes including effectiveness of linkages between schools and the healthcare providers.</p> <p>Methods/Design</p> <p>This study will include 95 Practices, 171 schools, and over 30,000 asthmatic patients. Five groups (A-E) will be evaluated to determine the effectiveness of three interventions. Group A is the usual care control group without electronic medical record (EMR). Group B practices are a second control group that has an EMR with decision support, asthma action plans, and population reports at baseline. A time delay design during year one converts practices in Group B to group C after receiving the integrated approach to care intervention. Four practices within Group C will receive the shared decision making intervention (and become group D). Group E will receive a school based care intervention through case management within the schools. A centralized database will be created with the goal of facilitating comparative effectiveness research on asthma outcomes specifically for this study. Patient and community level analysis will include results from patient surveys, focus groups, and asthma patient density mapping. Community variables such as income and housing density will be mapped for comparison. Outcomes to be measured are reduced hospitalizations and emergency department visits; improved adherence to medication; improved quality of life; reduced school absenteeism; improved self-efficacy and improved school performance.</p> <p>Discussion</p> <p>Identifying new mechanisms that improve the delivery of asthma care is an important step towards advancing patient outcomes, avoiding preventable Emergency Department visits and hospitalizations, while simultaneously reducing overall healthcare costs.</p

CCR2 Acts as Scavenger for CCL2 during Monocyte Chemotaxis

<div><h3>Background</h3><p>Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces or on matrices along the attracting gradient towards increasing concentrations of agonist. On the other hand agonist-induced desensitization and internalization is a general paradigm for chemokine receptors which is inconsistent with the prolonged migratory capacity.</p> <h3>Methodology/Principal Findings</h3><p>Chemotaxis of monocytes was monitored in response to fluorescent CCL2-mCherry by time-lapse video microscopy. Uptake of the fluorescent agonist was used as indirect measure to follow the endogenous receptor CCR2 expressed on primary human monocytes. During chemotaxis CCL2-mCherry becomes endocytosed as cargo of CCR2, however, the internalization of CCR2 is not accompanied by reduced responsiveness of the cells due to desensitization.</p> <h3>Conclusions/Significance</h3><p>During chemotaxis CCR2 expressed on monocytes internalizes with the bound chemoattractant, but cycles rapidly back to the plasma membrane to maintain high responsiveness. Moreover, following relocation of the source of attractant, monocytes can rapidly reverse their polarization axis organizing a new leading edge along the newly formed gradient, suggesting a uniform distribution of highly receptive CCR2 on the plasma membrane. The present observations further indicate that during chemotaxis CCR2 acts as scavenger consuming the chemokine forming the attracting cue.</p> </div

Measurement and Interpretation of Fermion-Pair Production at LEP energies above the Z Resonance

This paper presents DELPHI measurements and interpretations of cross-sections, forward-backward asymmetries, and angular distributions, for the e+e- -> ffbar process for centre-of-mass energies above the Z resonance, from sqrt(s) ~ 130 - 207 GeV at the LEP collider. The measurements are consistent with the predictions of the Standard Model and are used to study a variety of models including the S-Matrix ansatz for e+e- -> ffbar scattering and several models which include physics beyond the Standard Model: the exchange of Z' bosons, contact interactions between fermions, the exchange of gravitons in large extra dimensions and the exchange of sneutrino in R-parity violating supersymmetry.Comment: 79 pages, 16 figures, Accepted by Eur. Phys. J.

Search for Dark Matter Annihilation in the Galactic Center with IceCube-79

The Milky Way is expected to be embedded in a halo of dark matter particles, with the highest density in the central region, and decreasing density with the halo-centric radius. Dark matter might be indirectly detectable at Earth through a flux of stable particles generated in dark matter annihilations and peaked in the direction of the Galactic Center. We present a search for an excess flux of muon (anti-) neutrinos from dark matter annihilation in the Galactic Center using the cubic-kilometer-sized IceCube neutrino detector at the South Pole. There, the Galactic Center is always seen above the horizon. Thus, new and dedicated veto techniques against atmospheric muons are required to make the southern hemisphere accessible for IceCube. We used 319.7 live-days of data from IceCube operating in its 79-string configuration during 2010 and 2011. No neutrino excess was found and the final result is compatible with the background. We present upper limits on the self-annihilation cross-section, \left, for WIMP masses ranging from 30 GeV up to 10 TeV, assuming cuspy (NFW) and flat-cored (Burkert) dark matter halo profiles, reaching down to $\simeq 4 \cdot 10^{-24}$ cm$^3$ s$^{-1}$, and $\simeq 2.6 \cdot 10^{-23}$ cm$^3$ s$^{-1}$ for the $\nu\overline{\nu}$ channel, respectively.Comment: 14 pages, 9 figures, Submitted to EPJ-C, added references, extended limit overvie

A Determination of the Centre-of-Mass Energy at LEP2 using Radiative 2-fermion Events

Using e+e- -> mu+mu-(gamma) and e+e- -> qqbar(gamma) events radiative to the Z pole, DELPHI has determined the centre-of-mass energy, sqrt{s}, using energy and momentum constraint methods. The results are expressed as deviations from the nominal LEP centre-of-mass energy, measured using other techniques. The results are found to be compatible with the LEP Energy Working Group estimates for a combination of the 1997 to 2000 data sets.Comment: 20 pages, 6 figures, Accepted by Eur. Phys. J.