Photodynamic and anti- VEGF therapy for polypoidal choroidal vasculopathy - 'real world' outcomes in a caucasian population

Background: The prevalence of polypoidal choroidal vasculopathy (PCV) is significantly higher amongst Asian populations compared to Caucasian, and evidence regarding the clinical outcomes of Caucasian patients is limited. Objective: This retrospective study sought to investigate real-world clinical outcomes of Caucasian PCV patients treated with polypoidal verteporfin photodynamic therapy (PDT) in combination with anti-VEGF therapy up to 36 months post-treatment. Methods: Consecutive PCV patients who received PDT between 2011 and 2017 were included. Mean change in visual acuity (VA) measured by ETDRS letter score and mean change in central subfield thickness (CST) were the main outcome measures. Data were collected at baseline, 3, 12, 24 and 36 months. Regression analyses were carried out on pre-treatment clinical features to determine if there were any factors associated with a good visual outcome (better than or equal to 70 ETDRS letters at 12 months). Results: Seventy six patients (96% Caucasian) and seventy eight eyes were included in the analysis. Mean change in VA was-1,-4, and 0 ETDRS letters at 12, 24, and 36 months, respectively. CST was reduced by a mean of-51,-54, and-55 microns at 12, 24, and 36 months, respectively. Better pre-treatment VA was the only pre-treatment clinical feature associated with a good visual outcome at 12 months (OR 1.16, p<0.001). Conclusion: PDT, in combination with anti-VEGF therapy, maintains VA and may reduce the anti-VEGF therapy burden in Caucasian patients with PCV. Better pre-treatment VA is associated with a good visual outcome

Obscured star formation in intermediate-density environments:A Spitzer study of the Abell 901/902 supercluster

We explore the amount of obscured star formation as a function of environment in the Abell 901/902 (A901/902) supercluster at z = 0.165 in conjunction with a field sample drawn from the A901 and CDFS fields, imaged with the Hubble Space Telescope as part of the Space Telescope A901/902 Galaxy Evolution Survey and Galaxy Evolution from Morphology and Spectral Energy Distributions (SEDs) Survey. We combine the combo-17 near-UV/optical SED with Spitzer 24 mu m photometry to estimate both the unobscured and obscured star formation in galaxies with M-* > 10(10) M-circle dot. We find that the star formation activity in massive galaxies is suppressed in dense environments, in agreement with previous studies. Yet, nearly 40% of the star-forming (SF) galaxies have red optical colors at intermediate and high densities. These red systems are not starbursting; they have star formation rates (SFRs) per unit stellar mass similar to or lower than blue SF galaxies. More than half of the red SF galaxies have low infrared-to-ultraviolet (IR-to-UV) luminosity ratios, relatively high Sersicindices, and they are equally abundant at all densities. They might be gradually quenching their star formation, possibly but not necessarily under the influence of gas-removing environmental processes. The other greater than or similar to 40% of the red SF galaxies have high IR-to-UV luminosity ratios, indicative of high dust obscuration. They have relatively high specific SFRs and are more abundant at intermediate densities. Our results indicate that while there is an overall suppression in the SF galaxy fraction with density, the small amount of star formation surviving the cluster environment is to a large extent obscured, suggesting that environmental interactions trigger a phase of obscured star formation, before complete quenching

STAGES: the Space Telescope A901/2 Galaxy Evolution Survey

We present an overview of the Space Telescope A901/2 Galaxy Evolution Survey (STAGES). STAGES is a multiwavelength project designed to probe physical drivers of galaxy evolution across a wide range of environments and luminosity. A complex multi-cluster system at z~0.165 has been the subject of an 80-orbit F606W HST/ACS mosaic covering the full 0.5x0.5 (~5x5 Mpc^2) span of the supercluster. Extensive multiwavelength observations with XMM-Newton, GALEX, Spitzer, 2dF, GMRT, and the 17-band COMBO-17 photometric redshift survey complement the HST imaging. Our survey goals include simultaneously linking galaxy morphology with other observables such as age, star-formation rate, nuclear activity, and stellar mass. In addition, with the multiwavelength dataset and new high resolution mass maps from gravitational lensing, we are able to disentangle the large-scale structure of the system. By examining all aspects of environment we will be able to evaluate the relative importance of the dark matter halos, the local galaxy density, and the hot X-ray gas in driving galaxy transformation. This paper describes the HST imaging, data reduction, and creation of a master catalogue. We perform Sersic fitting on the HST images and conduct associated simulations to quantify completeness. In addition, we present the COMBO-17 photometric redshift catalogue and estimates of stellar masses and star-formation rates for this field. We define galaxy and cluster sample selection criteria which will be the basis for forthcoming science analyses, and present a compilation of notable objects in the field. Finally, we describe the further multiwavelength observations and announce public access to the data and catalogues.Comment: 29 pages, 22 figures; accepted to MNRAS. Full data release available at http://www.nottingham.ac.uk/astronomy/stage

A comparative phase I study of combination, homologous subtype-C DNA, MVA, and Env gp140 protein/adjuvant HIV vaccines in two immunization regimes

There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) adjuvanted CN54gp140. They were randomised to receive them in combination at the same visit at 16 and 20 weeks (accelerated) or sequentially with MVA-C at 16, 20, and GLA-AF/gp140 at 24 and 28 weeks (standard). All vaccinations were intramuscular. Primary outcomes included ≥grade 3 safety events and the titer of CN54gp140-specific binding IgG. Other outcomes included neutralization, binding antibody specificity and T-cell responses. Two participants experienced asymptomatic ≥grade 3 transaminitis leading to discontinuation of vaccinations, and three had grade 3 solicited local or systemic reactions. A total of 100% made anti-CN54gp140 IgG and combining vaccines did not significantly alter the response; geometric mean titer 6424 (accelerated) and 6578 (standard); neutralization of MW965.2 Tier 1 pseudovirus was superior in the standard group (82 versus 45% responders,  = 0.04). T-cell ELISpot responses were CD4+ and Env-dominant; 85 and 82% responding in the accelerated and standard groups, respectively. Vaccine-induced IgG responses targeted multiple regions within gp120 with the V3 region most immunodominant and no differences between groups detected. Combining MVA and gp140 vaccines did not result in increased adverse events and did not significantly impact upon the titer of Env-specific binding antibodies, which were seen in 100% individuals. The approach did however affect other immune responses; neutralizing antibody responses, seen only to Tier 1 pseudoviruses, were poorer when the vaccines were combined and while T-cell responses were seen in >80% individuals in both groups and similarly CD4 and Env dominant, their breadth/polyfunctionality tended to be lower when the vaccines were combined, suggesting attenuation of immunogenicity and cautioning against this accelerated regimen

Molecular identification, cloning and characterization of transmitted/founder HIV-1 subtype A, D and A/D infectious molecular clones

AbstractWe report the molecular identification, cloning and initial biological characterization of 12 full-length HIV-1 subtype A, D and A/D recombinant transmitted/founder (T/F) genomes. T/F genomes contained intact canonical open reading frames and all T/F viruses were replication competent in primary human T-cells, although subtype D virus replication was more efficient (p<0.05). All 12 viruses utilized CCR5 but not CXCR4 as a co-receptor for entry and exhibited a neutralization profile typical of tier 2 primary virus strains, with significant differences observed between subtype A and D viruses with respect to sensitivity to monoclonal antibodies VRC01, PG9 and PG16 and polyclonal subtype C anti-HIV IgG (p<0.05 for each). The present report doubles the number of T/F HIV-1 clones available for pathogenesis and vaccine research and extends their representation to include subtypes A, B, C and D

STAGES: the Space Telescope A901/2 Galaxy Evolution Survey

We present an overview of the Space Telescope A901/2 Galaxy Evolution Survey (STAGES). STAGES is a multiwavelength project designed to probe physical drivers of galaxy evolution across a wide range of environments and luminosity. A complex multicluster system at z∼ 0.165 has been the subject of an 80-orbit F606W Hubble Space Telescope (HST)/Advanced Camera for Surveys (ACS) mosaic covering the full span of the supercluster. Extensive multiwavelength observations with XMM-Newton, GALEX, Spitzer, 2dF, Giant Metrewave Radio Telescope and the 17-band COMBO-17 photometric redshift survey complement the HST imaging. Our survey goals include simultaneously linking galaxy morphology with other observables such as age, star formation rate, nuclear activity and stellar mass. In addition, with the multiwavelength data set and new high-resolution mass maps from gravitational lensing, we are able to disentangle the large-scale structure of the system. By examining all aspects of an environment we will be able to evaluate the relative importance of the dark matter haloes, the local galaxy density and the hot X-ray gas in driving galaxy transformation. This paper describes the HST imaging, data reduction and creation of a master catalogue. We perform the Sérsic fitting on the HST images and conduct associated simulations to quantify completeness. In addition, we present the COMBO-17 photometric redshift catalogue and estimates of stellar masses and star formation rates for this field. We define galaxy and cluster sample selection criteria, which will be the basis for forthcoming science analyses, and present a compilation of notable objects in the field. Finally, we describe the further multiwavelength observations and announce public access to the data and catalogue

The STAGES view of red spirals and dusty red galaxies: Mass-dependent quenching of star-formation in cluster infall

We investigate the properties of optically passive spirals and dusty red galaxies in the A901/2 cluster complex at redshift ~0.17 using restframe near-UV-optical SEDs, 24 micron IR data and HST morphologies from the STAGES dataset. The cluster sample is based on COMBO-17 redshifts with an rms precision of sigma_cz~2000 km/sec. We find that 'dusty red galaxies' and 'optically passive spirals' in A901/2 are largely the same phenomenon, and that they form stars at a substantial rate, which is only 4x lower than that in blue spirals at fixed mass. This star formation is more obscured than in blue galaxies and its optical signatures are weak. They appear predominantly in the stellar mass range of log M*/Msol=[10,11] where they constitute over half of the star-forming galaxies in the cluster; they are thus a vital ingredient for understanding the overall picture of star formation quenching in clusters. We find that the mean specific SFR of star-forming galaxies in the cluster is clearly lower than in the field, in contrast to the specific SFR properties of blue galaxies alone, which appear similar in cluster and field. Such a rich red spiral population is best explained if quenching is a slow process and morphological transformation is delayed even more. At log M*/Msol<10, such galaxies are rare, suggesting that their quenching is fast and accompanied by morphological change. We note, that edge-on spirals play a minor role; despite being dust-reddened they form only a small fraction of spirals independent of environment.Comment: Accepted for publication in MNRA

Induction of Asthma and the Environment: What We Know and Need to Know

The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop “Environmental Influences on the Induction and Incidence of Asthma” to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment

Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine

in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers.. Two volunteers mounted antibodies that were able to neutralize clade-matched viruses.ADMVA was well-tolerated and elicited durable humoral and cellular immune responses