Fermat Potentials for Non-Perturbative Gravitational Lensing

The images of many distant galaxies are displaced, distorted and often multiplied by the presence of foreground massive galaxies near the line of sight; the foreground galaxies act as gravitational lenses. Commonly, the lens equation, which relates the placement and distortion of the images to the real source position in the thin-lens scenario, is obtained by extremizing the time of arrival among all the null paths from the source to the observer (Fermat's principle). We show that the construction of envelopes of certain families of null surfaces consitutes an alternative variational principle or version of Fermat's principle that leads naturally to a lens equation in a generic spacetime with any given metric. We illustrate the construction by deriving the lens equation for static asymptotically flat thin lens spacetimes. As an application of the approach, we find the bending angle for moving thin lenses in terms of the bending angle for the same deflector at rest. Finally we apply this construction to cosmological spacetimes (FRW) by using the fact they are all conformally related to Minkowski space.Comment: accepted for publication in Phys. Rev.

Iterative Approach to Gravitational Lensing Theory

We develop an iterative approach to gravitational lensing theory based on approximate solutions of the null geodesic equations. The approach can be employed in any space-time which is ``close'' to a space-time in which the null geodesic equations can be completely integrated, such as Minkowski space-time, Robertson-Walker cosmologies, or Schwarzschild-Kerr geometries. To illustrate the method, we construct the iterative gravitational lens equations and time of arrival equation for a single Schwarzschild lens. This example motivates a discussion of the relationship between the iterative approach, the standard thin lens formulation, and an exact formulation of gravitational lensing.Comment: 27 pages, 2 figures, submitted to Phys.Rev.D, minor revisions, new reference

Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes

BACKGROUND Probiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora. Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals. There is a paucity of data regarding the effectiveness of probiotics in this cohort. The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology, self-reported illness symptoms and immunity in healthy well trained individuals. METHODS Competitive cyclists (64 males and 35 females; age 35 ± 9 and 36 ± 9 y, VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1, mean ± SD) were randomised to either probiotic (minimum 1 × 109 Lactobacillus fermentum (PCC®) per day) or placebo treatment for 11 weeks in a double-blind, randomised, controlled trial. The outcome measures were faecal L. fermentum counts, self-reported symptoms of illness and serum cytokines. RESULTS Lactobacillus numbers increased 7.7-fold (90% confidence limits 2.1- to 28-fold) more in males on the probiotic, while there was an unclear 2.2-fold (0.2- to 18-fold) increase in females taking the probiotic. The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group. However, there was a substantial 0.7 (0.2 to 1.2) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males, which became more pronounced as training load increased. The load (duration×severity) of lower respiratory illness symptoms was less by a factor of 0.31 (99%CI; 0.07 to 0.96) in males taking the probiotic compared with placebo but increased by a factor of 2.2 (0.41 to 27) in females. Differences in use of cold and flu medication mirrored these symptoms. The observed effects on URTI had too much uncertainty for a decisive outcome. There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines. CONCLUSION L. fermentum may be a useful nutritional adjunct for healthy exercising males. However, uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved. TRIAL REGISTRATION The trial was registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12611000006943).The study was funded by Christian Hansen A/S, Probiomics and the Australian Institute of Sport

Structure-activity relationships and molecular modeling of sphingosine kinase inhibitors

The design, synthesis, and evaluation of the potency of new isoform-selective inhibitors of sphingosine kinases 1 and 2 (SK1 and SK2), the enzyme that catalyzes the phosphorylation of d-erythro-sphingosine to produce the key signaling lipid, sphingosine 1-phosphate, are described. Recently, we reported that 1-(4-octylphenethyl)piperidin-4-ol (RB-005) is a selective inhibitor of SK1. Here we report the synthesis of 43 new analogues of RB-005, in which the lipophilic tail, polar headgroup, and linker region were modified to extend the structure-activity relationship profile for this lead compound, which we explain using modeling studies with the recently published crystal structure of SK1. We provide a basis for the key residues targeted by our profiled series and provide further evidence for the ability to discriminate between the two isoforms using pharmacological intervention

The effect of exercise on innate mucosal immunity

METHODS The authors conducted a prospective observational study comparing salivary lactoferrin and lysozyme concentration over 5 months (chronic changes) in elite rowers (n=17, mean age 24.3+/-4.0 years) with sedentary individuals (controls) (n=18, mean age=27.2+/-7.1 years) and a graded exercise test to exhaustion (acute changes) with a cohort of elite rowers (n=11, mean age 24.7+/-4.1). RESULTS Magnitudes of differences and changes were interpreted as a standardised (Cohen's) effect size (ES). Lactoferrin concentration in the observational study was approximately 60% lower in rowers than control subjects at baseline (7.9+/-1.2 microg/ml mean+/-SEM, 19.4+/-5.6 microg/ml, p=0.05, ES=0.68, 'moderate') and at the midpoint of the season (6.4+/-1.4 microg/ml mean +/- SEM, 21.5+/-4.2 microg/ml, p=0.001, ES=0.89, 'moderate'). The concentration of lactoferrin at the end of the study was not statistically significant (p=0.1) between the groups. There was no significant difference between rowers and control subjects in lysozyme concentration during the study. There was a 50% increase in the concentration of lactoferrin (p=0.05, ES=1.04, 'moderate') and a 55% increase in lysozyme (p=0.01, ES=3.0, 'very large') from pre-exercise to exhaustion in the graded exercise session. CONCLUSION Lower concentrations of these proteins may be indicative of an impairment of innate protection of the upper respiratory tract. Increased salivary lactoferrin and lysozyme concentration following exhaustive exercise may be due to a transient activation response that increases protection in the immediate postexercise period

Cosmic Microwave Background anisotropies from second order gravitational perturbations

This paper presents a complete analysis of the effects of second order gravitational perturbations on Cosmic Microwave Background anisotropies, taking explicitly into account scalar, vector and tensor modes. We also consider the second order perturbations of the metric itself obtaining them, for a universe dominated by a collision-less fluid, in the Poisson gauge, by transforming the known results in the synchronous gauge. We discuss the resulting second order anisotropies in the Poisson gauge, and analyse the possible relevance of the different terms. We expect that, in the simplest scenarios for structure formation, the main effect comes from the gravitational lensing by scalar perturbations, that is known to give a few percent contribution to the anisotropies at small angular scales.Comment: 15 pages, revtex, no figures. Version to be published in Phys. Rev.

Was Sinn Féin dying? A quantitative post-mortem of the party's decline and the emergence of Fianna Fáil

This article calls for a reappraisal of the consensus surrounding the split within Sinn Féin in 1926 that led to the foundation of Fianna Fáil. It demonstrates that quantitative factors cited to demonstrate Sinn Féin’s “terminal” decline – finances, cumann numbers, and election results – and to explain de Valera’s decision to leave Sinn Féin and establish a rival republican organisation, Fianna Fáil, do not provide sufficient objective grounds to explain the republican leader’s actions. This article demonstrates that Sinn Féin’s election results during the period in question (1923-1926) were encouraging and the decline in finances and cumann numbers can be explained by the fact that the base year used to compare progress was 1923, an election year. Moreover, this article compares the performance of Sinn Féin to the first five years of Fianna Fáil (1926-1931) to show that what has been interpreted as terminal decline can also be attributed to normal inter-election lulls in party activity. Correspondingly, subjective factors – e.g. personal rivalries, differences in ideology, organisational style and levels of patience in terms of achieving political power – were most likely the determining factors rather than organisational decline

Immune and acute phase markers in exercising adults

Many reports have documented the anti-inflammatory effects of regular exercise in adults. However clinicians and researchers remain uncertain on selecting specific biomarkers that are useful for predicting or monitoring chronic inflammatory states and/or disease. Clearer identification of markers (or clusters of markers) in physically active individuals that vary from established references ranges will indicate the extent of the purported anti-inflammatory effect of regular exercise. Physically active adults were recruited from the community to participate in a prospective study comparing self-reported health outcomes and exercise activity across 150 days of dietary intervention. Of the 450 participants recruited, 64 males (mean age 37.4 y, mean BMI = 25.3) and 59 females (mean age 40.4y, mean BMI= 23.4) agreed to supply a baseline blood sample taken at rest. A total of 187 analytes were measured by standard techniques on these pre-intervention samples including 11 immune markers (cell-types and immunoglobulins) and 11 acute phase reactants (WCC, albumin, haptoglobin, CRP, C3, C4, IGF-1, transferrin, iron, ferritin & ceruloplasmin). We compared baseline values with relevent hospital reference range (RR) values where these are assumed to be more reflective of a much less physically-active community population. A total of 5 out of 11 of the acute phase reactants (Hapt, C3, Fer, Trf (for females), and ceruloplasmin (for males)) had \u3e10% of values below the low ‘cut-off end’ of the relevant RR. Three immune cell-types (CD19, CD8 & CD16/56) had \u3e10% of values below the ‘low-cut-off end’ of the relevant RR. In contrast 25% of subjects had an IgE value that exceeded the RR. Collectively our results support the notion that regular exercise or physical activity exerts an anti-inflammatory affect. The results suggest putative roles for a host of exercise associated adaptive mechanisms beyond the generally accepted role for IL-6 derived from skeletal muscle and\or visceral fat. We conclude that across a host of measures, exercising adults have values for immune and acute phase reactants largely within, but at the non-inflammatory ‘end’ of clinical reference ranges

Nonlinear Effects in the Cosmic Microwave Background

Major advances in the observation and theory of cosmic microwave background anisotropies have opened up a new era in cosmology. This has encouraged the hope that the fundamental parameters of cosmology will be determined to high accuracy in the near future. However, this optimism should not obscure the ongoing need for theoretical developments that go beyond the highly successful but simplified standard model. Such developments include improvements in observational modelling (e.g. foregrounds, non-Gaussian features), extensions and alternatives to the simplest inflationary paradigm (e.g. non-adiabatic effects, defects), and investigation of nonlinear effects. In addition to well known nonlinear effects such as the Rees-Sciama and Ostriker-Vishniac effects, further nonlinear effects have recently been identified. These include a Rees-Sciama-type tensor effect, time-delay effects of scalar and tensor lensing, nonlinear Thomson scattering effects and a nonlinear shear effect. Some of the nonlinear effects and their potential implications are discussed.Comment: Invited contribution to Relativistic Cosmology Symposium (celebrating the 60th year of GFR Ellis); to appear Gen. Rel. Gra

Angiogenic gene expression and vascular density are reflected in ultrasonographic features of synovitis in early Rheumatoid Arthritis: an observational study.

INTRODUCTION: Neovascularization contributes to the development of sustained synovial inflammation in the early stages of Rheumatoid Arthritis. Ultrasound (US) provides an indirect method of assessing synovial blood flow and has been shown to correlate with clinical disease activity in patients with Rheumatoid Arthritis. This study examines the relationship of US determined synovitis with synovial vascularity, angiogenic/lymphangiogenic factors and cellular mediators of inflammation in a cohort of patients with early Rheumatoid Arthritis (RA) patients prior to therapeutic intervention with disease modifying therapy or corticosteroids. METHODS: An ultrasound guided synovial biopsy of the supra-patella pouch was performed in 12 patients with early RA prior to treatment. Clinical, US and biochemical assessments were undertaken prior to the procedure. Ultrasound images and histological samples were obtained from the supra-patella pouch. Histological samples were stained for Factor VIII and a-SMA (a-smooth muscle actin). Using digital imaging analysis a vascular area score was recorded. QT-PCR (quantitative-PCR) of samples provided quantification of angiogenic and lymphangiogenic gene expression and immunohistochemistry stained tissue was scored for macrophage, T cell and B cell infiltration using an existing semi-quantitative score. RESULTS: Power Doppler showed a good correlation with histological vascular area (Spearman r--0.73) and angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), Angiopoietin 2 and Tie-2. In addition, lymphangiogenic factors such as VEGF-C and VEGF-R3 correlated well with US assessment of synovitis. A significant correlation was also found between power Doppler and synovial thickness, pro-inflammatory cytokines and sub-lining macrophage infiltrate. Within the supra-patella pouch there was no significant difference in US findings, gene expression or inflammatory cell infiltrate between any regions of synovium biopsied. CONCLUSION: Ultrasound assessment of synovial tissue faithfully reflects synovial vascularity. Both grey scale and power Doppler synovitis in early RA patients correlate with a pro-angiogenic and lymphangiogenic gene expression profile. In early RA both grey scale and power Doppler synovitis are associated with a pro-inflammatory cellular and cytokine profile providing considerable validity in its use as an objective assessment of synovial inflammation in clinical practice