Eigenfunctions and matrix elements for a class of eigenvalue problems with staggered ladder spectra

We present an alternate solution to an eigenvalue problem which arises in the study of the Fokker-Planck equation for generalized Ornstein-Uhlenbeck processes. We obtain the staggered ladder spectra found previously but in addition we obtain the normalized eigenfunctions in terms of associated Laguerre polynomials. The representation of the eigenfunctions in this form greatly simplifies the evaluation of matrix elements required in calculating ensemble averages and correlation coefficients for various observables. The solution to the eigenvalue problem is given in the generic and general cases

Semiclassical threshold law when the Wannier exponent diverges

Using semiclassical methods we investigate the threshold behavior for three-particle breakup of a system with one particle of charge Z and two other particles of charge -q. For the particular case where the ratio of the charges of the third particle to the wing particles is Z/g = 1/4, the Wannier exponent for breakup diverges and the threshold law changes from a power law to an exponential law of the form exp(-lambda/root E). The threshold behavior is tested above the region of divergence and it is found that for Z/q < 0.3 a power law does not hold. Ionizing trajectories show that the dynamics within the near zone can become crucial to the energy dependence of the cross section. Cases are found to arise where more than one trajectory contributes to the same final state giving rise to semiclassical interference effects

Toll-Like Receptor mRNA Expression Is Selectively Increased in the Colonic Mucosa of Two Animal Models Relevant to Irritable Bowel Syndrome

Background: Irritable bowel syndrome (IBS) is largely viewed as a stress-related disorder caused by aberrant brain-gut– immune communication and altered gastrointestinal (GI) homeostasis. Accumulating evidence demonstrates that stress modulates innate immune responses; however, very little is known on the immunological effects of stress on the GI tract. Toll-like receptors (TLRs) are critical pattern recognition molecules of the innate immune system. Activation of TLRs by bacterial and viral molecules leads to activation of NF-kB and an increase in inflammatory cytokine expression. It was our hypothesis that innate immune receptor expression may be changed in the gastrointestinal tract of animals with stressinduced IBS-like symptoms. Methodology/Principal Findings: In this study, our objective was to evaluate the TLR expression profile in the colonic mucosa of two rat strains that display colonic visceral hypersensivity; the stress-sensitive Wistar-Kyoto (WKY) rat and the maternally separated (MS) rat. Quantitative PCR of TLR2-10 mRNA in both the proximal and distal colonic mucosae was carried out in adulthood. Significant increases are seen in the mRNA levels of TLR3, 4 & 5 in both the distal and proximal colonic mucosa of MS rats compared with controls. No significant differences were noted for TLR 2, 7, 9 & 10 while TLR 6 could not be detected in any samples in both rat strains. The WKY strain have increased levels of mRNA expression of TLR3, 4, 5, 7, 8, 9 & 10 in both the distal and proximal colonic mucosa compared to the control Sprague-Dawley strain. No significant differences in expression were found for TLR2 while as before TLR6 could not be detected in all samples in both strains. Conclusions: These data suggest that both early life stress (MS) and a genetic predisposition (WKY) to stress affect the expression of key sentinels of the innate immune system which may have direct relevance for the molecular pathophysiology of IBS

Continuous stochastic Schrodinger equations and localization

The set of continuous norm-preserving stochastic Schrodinger equations associated with the Lindblad master equation is introduced. This set is used to describe the localization properties of the state vector toward eigenstates of the environment operator. Particular focus is placed on determining the stochastic equation which exhibits the highest rate of localization for wide open systems. An equation having such a property is proposed in the case of a single non-hermitian environment operator. This result is relevant to numerical simulations of quantum trajectories where localization properties are used to reduce the number of basis states needed to represent the system state, and thereby increase the speed of calculation.Comment: 18 pages in LaTeX + 6 figures (postscript), uses ioplppt.sty. To appear in J. Phys.

Reformulation of the strong-field approximation for light-matter interactions

We consider the interaction of hydrogen-like atoms with a strong laser field and show that the strong field approximation and all its variants may be grouped into a set of families of approximation schemes. This is done by introducing an ansatz describing the electron wave packet as the sum of the initial state wave function times a phase factor and a function which is the perturbative solution in the Coulomb potential of an inhomogeneous time-dependent Schr\"odinger equation. It is the phase factor that characterizes a given family. In each of these families, the velocity and length gauge version of the approximation scheme lead to the same results at each order in the Coulomb potential. By contrast, irrespective of the gauge, approximation schemes belonging to different families give different results. Furthermore, this new formulation of the strong field approximations allows us to gain deeper insight into the validity of the strong field approximation schemes. In particular, we address two important questions: the role of the Coulomb potential in the output channel and the convergence of the perturbative series in the Coulomb potential. In all the physical situations we consider here, our results are compared to those obtained by solving numerically the time-dependent Schr\"odinger equation.Comment: 19 pages, 9 figures, submitted for publicatio

Hydrodynamic gene delivery in human skin using a hollow microneedle device

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50 μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery

Predicting 1‐year mortality in older hospitalized patients: external validation of the HOMR Model

Objectives: Accurate prognostic information can enable patients and physicians to make better healthcare decisions. The Hospital‐patient One‐year Mortality Risk (HOMR) model accurately predicted mortality risk (concordance [C] statistic = .92) in adult hospitalized patients in a recent study in North America. We evaluated the performance of the HOMR model in a population of older inpatients in a large teaching hospital in Ireland. Design: Retrospective cohort study. Setting: Acute hospital. Participants: Patients aged 65 years or older cared for by inpatient geriatric medicine services from January 1, 2013, to March 6, 2015 (n = 1654). After excluding those who died during the index hospitalization (n = 206) and those with missing data (n = 39), the analytical sample included 1409 patients. Measurements: Administrative data and information abstracted from hospital discharge reports were used to determine covariate values for each patient. One‐year mortality was determined from the hospital information system, local registries, or by contacting the patient's general practitioner. The linear predictor for each patient was calculated, and performance of the model was evaluated in terms of its overall performance, discrimination, and calibration. Recalibrated and revised models were also estimated and evaluated. Results: One‐year mortality rate after hospital discharge in this patient cohort was 18.6%. The unadjusted HOMR model had good discrimination (C statistic = .78; 95% confidence interval = .76‐.81) but was poorly calibrated and consistently overestimated mortality prediction. The model's performance was modestly improved by recalibration and revision (optimism corrected C statistic = .8). Conclusion: The superior discriminative performance of the HOMR model reported previously was substantially attenuated in its application to our cohort of older hospitalized patients, who represent a specific subset of the original derivation cohort. Updating methods improved its performance in our cohort, but further validation, refinement, and clinical impact studies are required before use in routine clinical practice