An analysis of the dependence of saccadic latency on target position and target characteristics in human subjects

BACKGROUND: Predictions from conduction velocity data for primate retinal ganglion cell axons indicate that the conduction time to the lateral geniculate nucleus for stimulation of peripheral retina should be no longer than for stimulation of central retina. On this basis, the latency of saccadic eye movements should not increase for more peripherally located targets. However, previous studies have reported relatively very large increases, which has the implication of a very considerable increase in central processing time for the saccade-generating system. RESULTS: In order to resolve this paradox, we have undertaken an extended series of experiments in which saccadic eye movements were recorded by electro-oculography in response to targets presented in the horizontal meridian in normal young subjects. For stationary or moving targets of either normal beam intensity or reduced red intensity, with the direction of gaze either straight ahead with respect to the head or directed eccentrically, the saccadic latency was shown to remain invariant with respect to a wide range of target angular displacements. CONCLUSIONS: These results indicate that, irrespective of the angular displacement of the target, the direction of gaze or the target intensity, the saccade-generating system operates with a constant generation time

The ACS Survey of Galactic Globular Clusters: M54 and Young Populations in the Sagittarius Dwarf Spheroidal Galaxy

We present new Hubble Space Telescope photometry of the massive globular cluster M54 (NGC 6715) and the superposed core of the tidally disrupted Sagittarius (Sgr) dSph galaxy as part of the ACS Survey of Galactic Globular Clusters. Our deep (F606W~26.5), high-precision photometry yields an unprecedentedly detailed color-magnitude diagram showing the extended blue horizontal branch and multiple main sequences of the M54+Sgr system. The distance and reddening to M54 are revised usingboth isochrone and main-sequence fitting to (m-M)_0=17.27 and E(B-V)=0.15. Preliminary assessment finds the M54+Sgr field to be dominated by the old metal-poor populations of Sgr and the globular cluster. Multiple turnoffs indicate the presence of at least two intermediate-aged star formation epochs with 4 and 6 Gyr ages and [Fe/H]=-0.4 to -0.6. We also clearly show, for the first time, a prominent, 2.3 Gyr old Sgr population of near-solar abundance. A trace population of even younger (0.1-0.8 Gyr old), more metal-rich ([Fe/H]\sim0.6) stars is also indicated. The Sgr age-metallicity relation is consistent with a closed-box model and multiple (4-5) star formation bursts over the entire life of the satellite, including the time since Sgr began disrupting.Comment: Accepted to ApJ Letter; 11 pages, 2 figures; figure 1 uploaded as jpg; paper in ApJ format with full-resolution figures available at: http://www.astro.ufl.edu/~ata/public_hstgc/paperIV/paperIV.p

Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

Bone marrow mononuclear cell (BM-MNC) therapy in ST-elevation acute myocardial infarction (STEMI) has no biological inclusion criteria. Here, we analyzed 63 biomarkers and cytokines in baseline plasma samples from 77 STEMI patients treated with BM-MNCs in the TIME and Late-TIME trials as well as 61 STEMI patients treated with placebo. Response to cell therapy was defined by changes in left ventricular ejection fraction, systolic/diastolic volumes, and wall motion indexes. We investigated the clinical value of circulating proteins in outcome prediction using significance testing, partial least squares discriminant analysis, and receiver operating characteristic (ROC) analysis. Responders had higher biomarker levels (76-94% elevated) than non-responders. Several biomarkers had values that differed significantly (P < 0.05) between responders and non-responders including stem cell factor, platelet-derived growth factor, and interleukin-15. We then used these lead candidates for ROC analysis and found multiple biomarkers with values areas under the curve >0.70 including interleukin 15. These biomarkers were not involved in the placebo-treated subjects suggesting that they may have predictive power. We conclude that plasma profiling after STEMI may help identify patients with a greater likelihood of response to cell-based treatment. Prospective trials are needed to assess the predictive value of the circulating biomarkers

The ACS Survey of Galactic Globular Clusters. I. Overview and Clusters without PreviousHubble Space Telescope Photometry

We present the first results of a large Advanced Camera for Surveys (ACS) survey of Galactic globular clusters. This Hubble Space Telescope (HST) Treasury project is designed to obtain photometry with S/N (signal-to-noise ratio) 10 for main-sequence stars with masses 0.2 M⊙ in a sample of globulars using the ACS Wide Field Channel. Here we focus on clusters without previous HST imaging data. These include NGC 5466, NGC 6779, NGC 5053, NGC 6144, Palomar 2, E3, Lyngå 7, Palomar 1, and NGC 6366. Our color-magnitude diagrams (CMDs) extend reliably from the horizontal branch to as much as 7 mag fainter than the main-sequence turnoff and represent the deepest CMDs published to date for these clusters. Using fiducial sequences for three standard clusters (M92, NGC 6752, and 47 Tuc) with well-known metallicities and distances, we perform main-sequence fitting on the target clusters in order to obtain estimates of their distances and reddenings. These comparisons, along with fitting the cluster main sequences to theoretical isochrones, yield ages for the target clusters. We find that the majority of the clusters have ages that are consistent with the standard clusters at their metallicities. The exceptions are E3, which appears ~2 Gyr younger than 47 Tuc, and Pal 1, which could be as much as 8 Gyr younger than 47 Tuc

Author Correction: Circulating Biomarkers to Identify Responders in Cardiac Cell therapy.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

The ACS Survey of Galactic Globular Clusters XI: The Three-Dimensional Orientation of the Sagittarius Dwarf Spheroidal Galaxy and its Globular Clusters

We use observations from the ACS study of Galactic globular clusters to investigate the spatial distribution of the inner regions of the disrupting Sagittarius dwarf spheroidal galaxy (Sgr). We combine previously published analyses of four Sgr member clusters located near or in the Sgr core (M54, Arp 2, Terzan 7 and Terzan 8) with a new analysis of diffuse Sgr material identified in the background of five low-latitude Galactic bulge clusters (NGC 6624, 6637, 6652, 6681 and 6809) observed as part of the ACS survey. By comparing the bulge cluster CMDs to our previous analysis of the M54/Sgr core, we estimate distances to these background features. The combined data from four Sgr member clusters and five Sgr background features provides nine independent measures of the Sgr distance and, as a group, provide uniformly measured and calibrated probes of different parts of the inner regions of Sgr spanning twenty degrees over the face of the disrupting dwarf. This allows us, for the first time, to constrain the three dimensional orientation of Sgr's disrupting core and globular cluster system and compare that orientation to the predictions of an N-body model of tidal disruption. The density and distance of Sgr debris is consistent with models that favor a relatively high Sgr core mass and a slightly greater distance (28-30 kpc, with a mean of 29.4 kpc). Our analysis also suggests that M54 is in the foreground of Sgr by ~2 kpc, projected on the center of the Sgr dSph. While this would imply a remarkable alignment of the cluster and the Sgr nucleus along the line of sight, we can not identify any systematic effect in our analysis that would falsely create the measured 2 kpc separation. Finally, we find that the cluster Terzan 7 has the most discrepant distance (25 kpc) among the four Sgr core clusters, which may suggest a different dynamical history than the other Sgr core clusters.Comment: 41 pages, 16 figures, accepted to Ap

Cellular Immune Responses and Viral Diversity in Individuals Treated during Acute and Early HIV-1 Infection

Immune responses induced during the early stages of chronic viral infections are thought to influence disease outcome. Using HIV as a model, we examined virus-specific cytotoxic T lymphocytes (CTLs), T helper cells, and viral genetic diversity in relation to duration of infection and subsequent response to antiviral therapy. Individuals with acute HIV-1 infection treated before seroconversion had weaker CTL responses directed at fewer epitopes than persons who were treated after seroconversion. However, treatment-induced control of viremia was associated with the development of strong T helper cell responses in both groups. After 1 yr of antiviral treatment initiated in acute or early infection, all epitope-specific CTL responses persisted despite undetectable viral loads. The breadth and magnitude of CTL responses remained significantly less in treated acute infection than in treated chronic infection, but viral diversity was also significantly less with immediate therapy. We conclude that early treatment of acute HIV infection leads to a more narrowly directed CTL response, stronger T helper cell responses, and a less diverse virus population. Given the need for T helper cells to maintain effective CTL responses and the ability of virus diversification to accommodate immune escape, we hypothesize that early therapy of primary infection may be beneficial despite induction of less robust CTL responses. These data also provide rationale for therapeutic immunization aimed at broadening CTL responses in treated primary HIV infection

Regulatory T Cells in γ Irradiation-Induced Immune Suppression

Sublethal total body γ irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naïve mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg) phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Reassessing Britain’s ‘post-war consensus’: the politics of reason 1945–1979

Since the late-1970s, scholars have been engaged in a vibrant debate about the nature of post-war British politics. While some writers have suggested that the three decades that succeeded the Second World War witnessed a bi-partisan consensus on key policy questions, others have argued that it was conflict, not agreement, that marked the period. This article offers a novel contribution to this controversy by drawing attention to the epistemological beliefs of the Labour and Conservative parties. It argues that once these beliefs are considered, it becomes possible to reconcile some of the competing claims made by proponents and critics of the ‘post-war consensus’ thesis. Labour and Conservative leaders may have been wedded to different beliefs, but they also shared a common enthusiasm for empiricist reasoning and were both reluctant to identify fixed political ‘ends’ that they sought to realise. Consequently, they were both committed to evolutionary forms of change, and they eschewed the notion that any social or political arrangement was of universal value