Vitamin D and Allergic Disease: Sunlight at the End of the Tunnel?

A role for vitamin D in the regulation of immune function was first proposed after the identification of Vitamin D Receptors in lymphocytes. It has since been recognized that the active form of vitamin D, 1α,25(OH)2D3, has direct affects on naïve and activated helper T cells, regulatory T cells, activated B cells and dendritic cells. There is a growing body of literature linking vitamin D (serum 25(OH)D, oral intake and surrogate indicators such as latitude) to various immune-related conditions, including allergy, although the nature of this relationship is still unclear. This review explores the findings of epidemiological, clinical and laboratory research, and the potential role of vitamin D in promoting the inappropriate immune responses which underpin the rise in a broad range of immune diseases

Penicillin allergy SHACK : Survey of hospital and community knowledge

Aim Penicillin allergy accounts for the majority of all reported adverse drug reactions in adults and children. Foregoing first-line antibiotic therapy due to penicillin allergy label is associated with an increased prevalence of infections by resistant organisms and longer hospitalisation. Clinician awareness of allergy assessment, referral indications, management of allergy and anaphylaxis is therefore vital but globally lacking. We aim to assess the knowledge of penicillin allergy, assessment and management in Western Australian health professionals. Methods An anonymous survey was distributed to pharmacists, nurses and physicians within Western Australian paediatric and adult Hospitals, Community and General Practice. Results In total, 487/611 were completed and included in the statistical analysis. Only 62% (301/487) of respondents routinely assessed for patient medication allergies. Of those who assessed allergy, 9% (28/301) of respondents met the Australian standards for allergy assessment. Only 22% (106/487) of participants correctly cited all indications for management with adrenaline in anaphylaxis to antibiotics and 67% (197/292) of physicians rarely or never referred to an allergy service. Paediatric clinicians had an increased understanding of allergy assessment and anaphylaxis management. Recent penicillin allergy education within a 5-year period led to significant improvements in allergy knowledge. Conclusion Overall, knowledge, assessment and management of penicillin allergies among practitioners in Western Australia are currently inadequate in adults and paediatric clinicians to provide safe and effective clinical care. The implementation of a targeted education program for WA health professionals is urgently required and is expected to improve clinician knowledge and aid standardised penicillin assessment (de-labelling) practices

Decomposition of the QCD String into Dipoles and Unintegrated Gluon Distributions

We present the perturbative and non-perturbative QCD structure of the dipole-dipole scattering amplitude in momentum space. The perturbative contribution is described by two-gluon exchange and the non-perturbative contribution by the stochastic vacuum model which leads to confinement of the quark and antiquark in the dipole via a string of color fields. This QCD string gives important non-perturbative contributions to high-energy reactions. A new structure different from the perturbative dipole factors is found in the string-string scattering amplitude. The string can be represented as an integral over stringless dipoles with a given dipole number density. This decomposition of the QCD string into dipoles allows us to calculate the unintegrated gluon distribution of hadrons and photons from the dipole-hadron and dipole-photon cross section via kT-factorization.Comment: 43 pages, 14 figure

Epistemic Beliefs: Relationship to Future Expectancies and Quality of Life in Cancer Patients.

CONTEXT: Expectations about the future (future expectancies) are important determinants of psychological well-being among cancer patients, but the strategies patients use to maintain positive and cope with negative expectancies are incompletely understood. OBJECTIVES: To obtain preliminary evidence on the potential role of one strategy for managing future expectancies: the adoption of epistemic beliefs in fundamental limits to medical knowledge. METHODS: A sample of 1307 primarily advanced-stage cancer patients participating in a genomic tumor testing study in community oncology practices completed measures of epistemic beliefs, positive future expectancies, and mental and physical health-related quality of life (HRQOL). Descriptive and linear regression analyses were conducted to assess the relationships between these factors and test two hypotheses: 1) epistemic beliefs affirming fundamental limits to medical knowledge ( fallibilistic epistemic beliefs ) are associated with positive future expectancies and mental HRQOL, and 2) positive future expectancies mediate this association. RESULTS: Participants reported relatively high beliefs in limits to medical knowledge (M = 2.94, s.d.=.67) and positive future expectancies (M = 3.01, s.d.=.62) (range 0-4), and relatively low mental and physical HRQOL. Consistent with hypotheses, fallibilistic epistemic beliefs were associated with positive future expectancies (b = 0.11, SE=.03, P\u3c 0.001) and greater mental HRQOL (b = 0.99, SE=.34, P = 0.004); positive expectancies also mediated the association between epistemic beliefs and mental HRQOL (Sobel Z=4.27, P\u3c0.001). CONCLUSIONS: Epistemic beliefs in limits to medical knowledge are associated with positive future expectancies and greater mental HRQOL; positive expectancies mediate the association between epistemic beliefs and HRQOL. More research is needed to confirm these relationships and elucidate their causal mechanisms

Gamma(*)Gamma(*) reaction at high energies

The energy available for gamma(*)gamma(*) physics at LEP2 is opening a new window on the study of diffractive phenomena, both non-perturbative and perturbative. We discuss some of the uncertainties and problems connected with the experimental measurements and their interpretation.Comment: 6 pages, 6 figures, submitted to proceedings of the Durham Collider Workshop, 22-26 September 199

Confining QCD Strings, Casimir Scaling, and a Euclidean Approach to High-Energy Scattering

We compute the chromo-field distributions of static color-dipoles in the fundamental and adjoint representation of SU(Nc) in the loop-loop correlation model and find Casimir scaling in agreement with recent lattice results. Our model combines perturbative gluon exchange with the non-perturbative stochastic vacuum model which leads to confinement of the color-charges in the dipole via a string of color-fields. We compute the energy stored in the confining string and use low-energy theorems to show consistency with the static quark-antiquark potential. We generalize Meggiolaro's analytic continuation from parton-parton to gauge-invariant dipole-dipole scattering and obtain a Euclidean approach to high-energy scattering that allows us in principle to calculate S-matrix elements directly in lattice simulations of QCD. We apply this approach and compute the S-matrix element for high-energy dipole-dipole scattering with the presented Euclidean loop-loop correlation model. The result confirms the analytic continuation of the gluon field strength correlator used in all earlier applications of the stochastic vacuum model to high-energy scattering.Comment: 65 pages, 13 figures, extended and revised version to be published in Phys. Rev. D (results unchanged, 2 new figures, 1 new table, additional discussions in Sec.2.3 and Sec.5, new appendix on the non-Abelian Stokes theorem, old Appendix A -> Sec.3, several references added

Local endothelial complement activation reverses endothelial quiescence, enabling t-cell homing, and tumor control during t-cell immunotherapy.

Cancer immunotherapy relies upon the ability of T cells to infiltrate tumors. The endothelium constitutes a barrier between the tumor and effector T cells, and the ability to manipulate local vascular permeability could be translated into effective immunotherapy. Here, we show that in the context of adoptive T cell therapy, antitumor T cells, delivered at high enough doses, can overcome the endothelial barrier and infiltrate tumors, a process that requires local production of C3, complement activation on tumor endothelium and release of C5a. C5a, in turn, acts on endothelial cells promoting the upregulation of adhesion molecules and T-cell homing. Genetic deletion of C3 or the C5a receptor 1 (C5aR1), and pharmacological blockade of C5aR1, impaired the ability of T cells to overcome the endothelial barrier, infiltrate tumors, and control tumor progression in vivo, while genetic chimera mice demonstrated that C3 and C5aR1 expression by tumor stroma, and not leukocytes, governs T cell homing, acting on the local endothelium. In vitro, endothelial C3 and C5a expressions were required for endothelial activation by type 1 cytokines. Our data indicate that effective immunotherapy is a consequence of successful homing of T cells in response to local complement activation, which disrupts the tumor endothelial barrier

Community oncologists\u27 perceptions and utilization of large-panel genomic tumor testing.

PURPOSE: Large-panel genomic tumor testing (GTT) is an emerging technology with great promise but uncertain clinical value. Previous research has documented variability in academic oncologists\u27 perceptions and use of GTT, but little is known about community oncologists\u27 perceptions of GTT and how perceptions relate to clinicians\u27 intentions to use GTT. METHODS: Community oncology physicians (N = 58) participating in a statewide initiative aimed at improving access to large-panel GTT completed surveys assessing their confidence in using GTT, attitudes regarding the value of GTT, perceptions of barriers to GTT implementation, and future intentions to use GTTs. Descriptive and multivariable regression analyses were conducted to characterize these perceptions and to explore the relationships between them. RESULTS: There was substantial variability in clinicians\u27 perceptions of GTT. Clinicians generally had moderate confidence in their ability to use GTT, but lower confidence in patients\u27 ability to understand test results and access targeted treatment. Clinicians had positive attitudes regarding the value of GTT. Clinicians\u27 future intentions to use GTT were associated with greater confidence in using GTT and greater perceived barriers to implementing GTT, but not with attitudes about the value of GTT. CONCLUSIONS: Community oncologists\u27 perceptions of large-panel genomic tumor testing are variable, and their future intentions to use GTT are associated with both their confidence in and perceived barriers to its use, but not with their attitudes towards GTT. More research is needed to understand other factors that determine how oncologists perceive and use GTT in clinical practice

[11C]CHIBA-1001 as a Novel PET Ligand for α7 Nicotinic Receptors in the Brain: A PET Study in Conscious Monkeys

BACKGROUND: The alpha7 nicotinic acetylcholine receptors (nAChRs) play an important role in the pathophysiology of neuropsychiatric diseases such as schizophrenia and Alzheimer's disease. However, there are currently no suitable positron emission tomography (PET) radioligands for imaging alpha7 nAChRs in the intact human brain. Here we report the novel PET radioligand [11C]CHIBA-1001 for in vivo imaging of alpha7 nAChRs in the non-human primate brain. METHODOLOGY/PRINCIPAL FINDINGS: A receptor binding assay showed that CHIBA-1001 was a highly selective ligand at alpha7 nAChRs. Using conscious monkeys, we found that the distribution of radioactivity in the monkey brain after intravenous administration of [11C]CHIBA-1001 was consistent with the regional distribution of alpha7 nAChRs in the monkey brain. The distribution of radioactivity in the brain regions after intravenous administration of [11C]CHIBA-1001 was blocked by pretreatment with the selective alpha7 nAChR agonist SSR180711 (5.0 mg/kg). However, the distribution of [11C]CHIBA-1001 was not altered by pretreatment with the selective alpha4beta2 nAChR agonist A85380 (1.0 mg/kg). Interestingly, the binding of [11C]CHIBA-1001 in the frontal cortex of the monkey brain was significantly decreased by subchronic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (0.3 mg/kg, twice a day for 13 days); which is a non-human primate model of schizophrenia. CONCLUSIONS/SIGNIFICANCE: The present findings suggest that [11C]CHIBA-1001 could be a novel useful PET ligand for in vivo study of the receptor occupancy and pathophysiology of alpha7 nAChRs in the intact brain of patients with neuropsychiatric diseases such as schizophrenia and Alzheimer's disease