Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo.

Experiments were designed to study the effect of systemically administered IL-5 on local eosinophil accumulation induced by the intradermal injection of the chemokine eotaxin in the guinea pig. Intravenous interleukin-5 (IL-5) stimulated a rapid and dramatic increase in the numbers of accumulating eosinophils induced by i.d.-injected eotaxin and, for comparison, leukotriene B4. The numbers of locally accumulating eosinophils correlated directly with a rapid increase in circulating eosinophils: circulating eosinophil numbers were 13-fold higher 1 h after intravenous IL-5 (18.3 pmol/kg). This increase in circulating cells corresponded with a reduction in the number of displaceable eosinophils recovered after flushing out the femur bone marrow cavity. Intradermal IL-5, at the doses tested, did not induce significant eosinophil accumulation. We propose that these experiments simulate important early features of the tissue response to local allergen exposure in a sensitized individual, with eosinophil chemoattractant chemokines having an important local role in eosinophil recruitment from blood microvessels, and IL-5 facilitating this process by acting remotely as a hormone to stimulate the release into the circulation of a rapidly mobilizable pool of bone marrow eosinophils. This action of IL-5 would be complementary to the other established activities of IL-5 that operate over a longer time course

Is communications a strategic activity in UK Education?

This qualitative exploratory paper investigates whether communications/public relations is regarded by opinion formers in UK education as a strategic business activity or a tactical marketing tool. It is based upon depth interviews with 16 senior managers with strategic roles in UK higher or further education, or Government bodies, conducted between June and September 2004. The findings seem to suggest that communications/PR is ideally seen by leaders as a strategic function, but that there are limitations to this vision becoming a reality. The research goes on to offer initial conclusions on some of the issues surrounding perception, resource, and implementation of strategic communications/PR in UK education, with implications for practitioners considered

Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.

Eosinophil accumulation is a prominent feature of allergic inflammatory reactions, such as those occurring in the lung of the allergic asthmatic, but the endogenous chemoattractants involved have not been identified. We have investigated this in an established model of allergic inflammation, using in vivo systems both to generate and assay relevant activity. Bronchoalveolar lavage (BAL) fluid was taken from sensitized guinea pigs at intervals after aerosol challenge with ovalbumin. BAL fluid was injected intradermally in unsensitized assay guinea pigs and the accumulation of intravenously injected 111In-eosinophils was measured. Activity was detected at 30 min after allergen challenge, peaking from 3 to 6 h and declining to low levels by 24 h. 3-h BAL fluid was purified using high performance liquid chromatography techniques in conjunction with the skin assay. Microsequencing revealed a novel protein from the C-C branch of the platelet factor 4 superfamily of chemotactic cytokines. The protein, eotaxin, exhibits homology of 53% with human MCP-1, 44% with guinea pig MCP-1, 31% with human MIP-1α, and 26% with human RANTES. Laser desorption time of flight mass analysis gave four different signals (8.15, 8.38, 8.81, and 9.03 kD), probably reflecting differential O-glycosylation. Eotaxin was highly potent, inducing substantial 111In-eosinophil accumulation at a 1-2-pmol dose in the skin, but did not induce significant 111In-neutrophil accumulation. Eotaxin was a potent stimulator of both guinea pig and human eosinophils in vitro. Human recombinant RANTES, MIP-1α, and MCP-1 were all inactive in inducing 111In-eosinophil accumulation in guinea pig skin; however, evidence was obtained that eotaxin shares a binding site with RANTES on guinea pig eosinophils. This is the first description of a potent eosinophil chemoattractant cytokine generated in vivo and suggests the possibility that similar molecules may be important in the human asthmatic lung

Norovirus Infection and Disease in an Ecuadorian Birth Cohort: Association of Certain Norovirus Genotypes With Host FUT2 Secretor Status.

BACKGROUND: Although norovirus is the most common cause of gastroenteritis, there are few data on the community incidence of infection/disease or the patterns of acquired immunity or innate resistance to norovirus. METHODS: We followed a community-based birth cohort of 194 children in Ecuador with the aim to estimate (1) the incidence of norovirus gastroenteritis from birth to age 3 years, (2) the protective effect of norovirus infection against subsequent infection/disease, and (3) the association of infection and disease with FUT2 secretor status. RESULTS: Over the 3-year period, we detected a mean of 2.26 diarrheal episodes per child (range, 0-12 episodes). Norovirus was detected in 260 samples (18%) but was not found more frequently in diarrheal samples (79 of 438 [18%]), compared with diarrhea-free samples (181 of 1016 [18%]; P = .919). A total of 66% of children had at least 1 norovirus infection during the first 3 years of life, and 40% of children had 2 infections. Previous norovirus infections were not associated with the risk of subsequent infection. All genogroup II, genotype 4 (GII.4) infections were among secretor-positive children (P < .001), but higher rates of non-GII.4 infections were found in secretor-negative children (relative risk, 0.56; P = .029). CONCLUSIONS: GII.4 infections were uniquely detected in secretor-positive children, while non-GII.4 infections were more often found in secretor-negative children

Inter-comparison of relative stopping power estimation models for proton therapy

Theoretical stopping power values were inter-compared for the Bichsel, Janni, ICRU and Schneider relative stopping power (RSP) estimation models, for a variety of tissues and tissue substitute materials taken from the literature. The RSPs of eleven plastic tissue substitutes were measured using Bragg peak shift measurements in water in order to establish a gold standard of RSP values specific to our centre's proton beam characteristics. The theoretical tissue substitute RSP values were computed based on literature compositions to assess the four different computation approaches. The Bichsel/Janni/ICRU approaches led to mean errors in the RSP of  −0.1/+0.7/−0.8%, respectively. Errors when using the Schneider approach, with I-values from the Bichsel, Janni and ICRU sources, followed the same pattern but were generally larger. Following this, the mean elemental ionisation energies were optimized until the differences between theoretical RSP values matched measurements. Failing to use optimized I-values when applying the Schneider technique to 72 human tissues could introduce errors in the RSP of up to  −1.7/+1.1/−0.4% when using Bichsel/Janni/ICRU I-values, respectively. As such, it may be necessary to introduce an additional step in the current stoichiometric calibration procedure in which tissue insert RSPs are measured in a proton beam. Elemental I-values can then optimized to match these measurements, reducing the uncertainty when calculating human tissue RSPs

Oxidation of Iron under Physiologically Relevant Conditions in Biological Fluids from Healthy and Alzheimer's Disease Subjects

Ferroxidase activity has been reported to be altered in various biological fluids in neurodegenerative disease, but the sources contributing to the altered activity are uncertain. Here we assay fractions of serum and cerebrospinal fluid with a newly validated triplex ferroxidase assay. Our data indicate that while ceruloplasmin, a multicopper ferroxidase, is the predominant source of serum activity, activity in CSF predominantly derives from a <10 kDa component, specifically from polyanions such as citrate and phosphate. We confirm that in human biological samples, ceruloplasmin activity in serum is decreased in Alzheimer's disease, but in CSF a reduction of activity in Alzheimer's disease originates from the polyanion component

Western Australian public opinions of a minimum pricing policy for alcohol: study protocol

Background: Excessive alcohol consumption has significant adverse economic, social, and health outcomes. Recent estimates suggest that the annual economic costs of alcohol in Australia are up to AUD $36 billion. Policies influencing price have been demonstrated to be very effective in reducing alcohol consumption and alcohol-related harms. Interest in minimum pricing has gained traction in recent years. However, there has been little research investigating the level of support for the public interest case of minimum pricing in Australia. Objective: This article describes protocol for a study exploring Western Australian (WA) public knowledge, understanding, and reaction to a proposed minimum price policy per standard drink. Methods: The study will employ a qualitative methodological design. Participants will be recruited from a wide variety of backgrounds, including ethnic minorities, blue and white collar workers, unemployed, students, and elderly/retired populations to participate in focus groups. Focus group participants will be asked about their knowledge of, and initial reactions to, the proposed policy and encouraged to discuss how such a proposal may affect their own alcohol use and alcohol consumption at the population level. Participants will also be asked to discuss potential avenues for increasing acceptability of the policy. The focus groups will adopt a semi-structured, open-ended approach guided by a question schedule. The schedule will be based on feedback from pilot samples, previous research, and a steering group comprising experts in alcohol policy and pricing. Results: The study is expected to take approximately 14 months to complete. Conclusions: The findings will be of considerable interest and relevance to government officials, policy makers, researchers, advocacy groups, alcohol retail and licensed establishments and organizations, city and town planners, police, and other stakeholder organizations

Gauge links for transverse momentum dependent correlators at tree-level

In this paper we discuss the incorporation of gauge links in hadronic matrix elements that describe the soft hadronic physics in high energy scattering processes. In this description the matrix elements appear in soft correlators and they contain non-local combinations of quark and gluon fields. In our description we go beyond the collinear approach in which case also the dependence on transverse momenta of partons is taken into consideration. The non-locality in the transverse direction leads to a complex gauge link structure for the full process, in which color is entangled, even at tree-level. We show that at tree-level in a 1-parton unintegrated (1PU) situation, in which only the transverse momentum of one of the initial state hadrons is relevant, one can get a factorized expression involving transverse momentum dependent (TMD) distribution functions. We point out problems at the level of two initial state hadrons, even for relatively simple processes such as Drell-Yan scattering.Comment: 25 pages, corrected typos and updated reference

Reproducible kk-means clustering in galaxy feature data from the GAMA survey

A fundamental bimodality of galaxies in the local Universe is apparent in many of the features used to describe them. Multiple sub-populations exist within this framework, each representing galaxies following distinct evolutionary pathways. Accurately identifying and characterising these sub-populations requires that a large number of galaxy features be analysed simultaneously. Future galaxy surveys such as LSST and Euclid will yield data volumes for which traditional approaches to galaxy classification will become unfeasible. To address this, we apply a robust $k$-means unsupervised clustering method to feature data derived from a sample of 7338 local-Universe galaxies selected from the Galaxy And Mass Assembly (GAMA) survey. This allows us to partition our sample into $k$ clusters without the need for training on pre-labelled data, facilitating a full census of our high dimensionality feature space and guarding against stochastic effects. We find that the local galaxy population natively splits into $2$, $3$, $5$ and a maximum of $6$ sub-populations, with each corresponding to a distinct ongoing evolutionary mechanism. Notably, the impact of the local environment appears strongly linked with the evolution of low-mass ($M_{*} < 10^{10}$ M$_{\odot}$) galaxies, with more massive systems appearing to evolve more passively from the blue cloud onto the red sequence. With a typical run time of $\sim3$ minutes per value of $k$ for our galaxy sample, we show how $k$-means unsupervised clustering is an ideal tool for future analysis of large extragalactic datasets, being scalable, adaptable, and providing crucial insight into the fundamental properties of the local galaxy population