Leukocyte-endothelium interactions in cutaneous inflammatory processes

It is over 100 years since an active role for vascular endothelium was first established in leukocyte localisation to sites of inflammation. A critical part of this process is now known to be mediated via adhesion interactions between receptors on circulating leukocytes and their ligands, particularly ELAM-1, VCAM-1 and ICAM-1 induced on activated endothelium, allowing leukocytes to “roll”, “arrest” and subsequently undergo “diapedesis” through the vessel wall towards the inflammatory focus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46934/1/281_2004_Article_BF00200534.pd

Adhesion Molecule Expression in Polymorphic Light Eruption

Endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) are cytokine-regulated cell-surface Ieukocyte adhesion molecules. We have investigated the in vivo kinetics and pattern of expression of these adhesion molecules in relation to tissue accumulation of leukocytes in the photodermatosis, polymorphic light eruption (PMLE), which is characterized by dense perivascular leukocytic infiltration. Immunohistology was performed on biopsies taken at varying time points from PMLE lesions induced in 11 subjects by suberythemal solar simulated irradiation. Vascular endothelial ELAM-1 expression was first observed at 5 h, maximal at 24 to 72 h, and remained elevated at 6 d. VCAM-1, minimally expressed in control skin, was induced above background levels on endothelium and some perivascular cells after 24h and maintained at 6 d. Endothelial cell ICAM-1 expression was increased above control levels at 72h and 6 d. Keratinocyte ICAM-1 expression, most marked overlying areas of dermal leukocytic infiltration, began at 5h and was strong at 72h and 6 d. In addition to lymphocytes, significant number of neutrophils of but not eosinophils were detected in the dermal leukocytic infiltrate that appeared at 5h and persisted at 6 d. The pattern of adhesion molecule expression that we have observed is similar to that seen in normal skin during a delayed hypersensitivity reaction: These observations support an immunologic basis for PMLE

A Replication of Failure, Not a Failure to Replicate

Purpose: The increasing role of systematic reviews in knowledge production demands greater rigor in the literature search process. The performance of the Social Work Abstracts (SWA) database has been examined multiple times over the past three decades. The current study is a replication within this line of research. Method: Issue level coverage was examined for the same 33 SWA core journals and the same time period as our 2009 study. Results: The mean percentage of issues missing in the current study was 20%. The mean percentage of issues missing in the current study was significantly greater than the mean percentage of issues missing in the 2009 study. Discussion: The research of other groups, and that of our own, has failed to prompt NASW Press to act. SWA was failing, it is failing and NASW Press has failed to correct those failures

Transmission of Salmonella between broiler chickens fed with fermented liquid feed

In the light of food safety and the control of Salmonella at chicken farms, fermented liquid feed (FLF) was studied. This moistened feed reduced the susceptibility of chickens for Salmonella. To assess the effect of the fermented feed on the transmission of Salmonella between chickens, a transmission experiment was performed. Salmonella shedding was followed within groups of two susceptible chickens together with two previously inoculated chickens. The between-chicken transmission was quantified by calculating a reproduction ratio (R0) and a transmission rate parameter ([beta]). R0 and [beta] in the FLF-treated groups were reduced, but a typical infectious chicken fed with FLF, could on average still infect more than one new infectious case. FLF can therefore reduce the transmission of Salmonella in chicken flocks, but it will not prevent the occurrence of major outbreaks

Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager

We present observations using the Small Array of the Arcminute Microkelvin Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning 0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of these without any attempt at source subtraction, although strong source contamination is present. With radio-source measurements from high-resolution observations, and under the assumptions of spherical $\beta$-model, isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in the visibility plane detects extended SZ decrements in all seven clusters over and above receiver noise, radio sources and primary CMB imprints. Bayesian evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and 3000:1 for one with substantially less data than the others. We present posterior probability distributions for, e.g., total mass and gas fraction averaged over radii internal to which the mean overdensity is 1000, 500 and 200, r_200 being the virial radius. Reaching r_200 involves some extrapolation for the nearer clusters but not for the more-distant ones. We find that our estimates of gas fraction are low (compared with most in the literature) and decrease with increasing radius. These results appear to be consistent with the notion that gas temperature in fact falls with distance (away from near the cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed Figure 1

Large scale meta-analysis characterizes genetic architecture for common psoriasis associated variants

Psoriasis is a complex disease of skin with a prevalence of about 2%. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for psoriasis to date, including data from eight different Caucasian cohorts, with a combined effective sample size amp;gt;39,000 individuals. We identified 16 additional psoriasis susceptibility loci achieving genome-wide significance, increasing the number of identified loci to 63 for European-origin individuals. Functional analysis highlighted the roles of interferon signalling and the NFkB cascade, and we showed that the psoriasis signals are enriched in regulatory elements from different T cells (CD8(+) T-cells and CD4(+) T-cells including T(H)0, T(H)1 and T(H)17). The identified loci explain similar to 28% of the genetic heritability and generate a discriminatory genetic risk score (AUC = 0.76 in our sample) that is significantly correlated with age at onset (p = 2 x 10(-89)). This study provides a comprehensive layout for the genetic architecture of common variants for psoriasis.Funding Agencies|National Institutes of Health [R01AR042742, R01AR050511, R01AR054966, R01AR063611, R01AR065183]; Foundation for the National Institutes of Health; Dermatology Foundation; National Psoriasis Foundation; Arthritis National Research Foundation; Ann Arbor Veterans Affairs Hospital; Dawn and Dudley Holmes Foundation; Babcock Memorial Trust; Medical Research Council [MR/L011808/1]; German Ministry of Education and Research (BMBF); Doris Duke Foundation [2013106]; National Institute of Health [K08AR060802, R01AR06907]; Taubman Medical Research Institute; Department of Health via the NIHR comprehensive Biomedical Research Center; Kings College London; KCH NHS Foundation Trust; Barbara and Neal Henschel Charitable Foundation; Heinz Nixdorf Foundation; Estonian Ministry of Education and Research [IUT20-46]; Centre of Translational Genomics of University of Tartu (SP1GVARENG); European Regional Development Fund (Centre of Translational Medicine, University of Tartu); German Federal Ministry of Education and Research (BMBF); National Human Genome Research Institute of the National Institutes of Health [R44HG006981]; International Psoriasis Council</p

Dark matter effective field theory scattering in direct detection experiments

We examine the consequences of the effective field theory (EFT) of dark matter–nucleon scattering for current and proposed direct detection experiments. Exclusion limits on EFT coupling constants computed using the optimum interval method are presented for SuperCDMS Soudan, CDMS II, and LUX, and the necessity of combining results from multiple experiments in order to determine dark matter parameters is discussed. We demonstrate that spectral differences between the standard dark matter model and a general EFT interaction can produce a bias when calculating exclusion limits and when developing signal models for likelihood and machine learning techniques. We also discuss the implications of the EFT for the next-generation (G2) direct detection experiments and point out regions of complementarity in the EFT parameter space.National Science Foundation (U.S.)United States. Dept. of EnergyNatural Sciences and Engineering Research Council of CanadaSpain. Ministerio de Economia y Competitividad (MultiDark

Improved WIMP-search reach of the CDMS II germanium data

CDMS II data from the five-tower runs at the Soudan Underground Laboratory were reprocessed with an improved charge-pulse fitting algorithm. Two new analysis techniques to reject surface-event backgrounds were applied to the 612 kg days germanium-detector weakly interacting massive particle (WIMP)-search exposure. An extended analysis was also completed by decreasing the 10 keV analysis threshold to ~5  keV, to increase sensitivity near a WIMP mass of 8  GeV/c[superscript 2]. After unblinding, there were zero candidate events above a deposited energy of 10 keV and six events in the lower-threshold analysis. This yielded minimum WIMP-nucleon spin-independent scattering cross-section limits of 1.8 × 10[superscript −44] and 1.18 × 10[superscript −41] at 90% confidence for 60 and 8.6  GeV/c[superscript 2] WIMPs, respectively. This improves the previous CDMS II result by a factor of 2.4 (2.7) for 60 (8.6)  GeV/c[superscript 2] WIMPs.National Science Foundation (U.S.)United States. Dept. of EnergyNatural Sciences and Engineering Research Council of CanadaSpain. Ministerio de Economia y Competitividad (MultiDark