Glucagon-like peptide-1 (GLP-1) and the regulation of human invariant natural killer T cells: lessons from obesity, diabetes and psoriasis

Aims/hypothesis The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKTcells. Methods We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells. Results The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro. Conclusions/interpretation The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis

Cooling-time determination of spent fuel

Two methods to determine the cooling time using data from high-resolution gamma-ray measurements are discussed; one is useful when the irradiation history information is available, the other when the irradiation history is not available. We have applied both methods and found that the cooling time can be determined to within an average of 3% and 4.1%, respectively

Clinical and genetic analyses in a patient with PAPA syndrome complicated with inflammatory bowel disease

POSTER PRESENTATIO

Nondestructive verification of relative burnup values and cooling times of irradiated MTR fuel elements

Sixteen irradiated MTR fuel elements have been examined using nondestructive gamma-ray and neutron techniques. The consistency of declared burnup values and cooling times has been measured. Measured parameters have been identified that best predict the burnup and cooling time values of individual elements and their relative importances have been quantified using established statistical methods of analysis. Various detector systems, including germanium, cadmium telluride, and Be(..gamma..,n) detector, and fission chamber have been used to measure the axial activity profiles

Multicore Scheduling for Lightweight Communicating Processes

Process-oriented programming is a design methodology in which software applications are constructed from communicating concurrent processes. A process-oriented design is typically composed of a large number of small isolated concurrent components. These components allow for the scalable parallel execution of the resulting application on both shared-memory and distributed-memory architectures. In this paper we present a runtime designed to support process-oriented programming by providing lightweight processes and communication primitives. Our run-time scheduler, implemented using lock-free algorithms, automatically executes concurrent components in parallel on multicore systems. Run-time heuristics dynamically group processes into cache-affine work units based on communication patterns. Work units are then distributed via wait-free work-stealing. Initial performance analysis shows that, using the algorithms presented in this paper, process-oriented software can execute with an efficiency approaching that of optimised sequential and coarse-grain threaded designs

The Inadequacy Of The Y-axis Of Growth (sngn) For The Vertical Pattern Assessment In Patients With Sagittal Discrepancies.

The aim of this cephalometric study was to evaluate the influence of the sagittal skeletal pattern on the 'Y-axis of growth' measurement in patients with different malocclusions. Lateral head films from 59 patients (mean age 16y 7m, ranging from 11 to 25 years) were selected after a subjective analysis of 1630 cases. Sample was grouped as follows: Group 1 - class I facial pattern; group 2 - class II facial pattern; and Group 3 - class III facial pattern. Two angular measurements, SNGoGn and SNGn, were taken in order to determine skeletal vertical facial pattern. A logistic regression with errors distributed according to a binomial distribution was used to test the influence of the sagittal relationship (Class I, II, III facial patterns) on vertical diagnostic measurement congruence (SNGoGn and SNGn). RESULTS show that the probability of congruence between the patterns SNGn and SNGoGn was relatively high (70%) for group 1, but for groups II (46%) and III (37%) this congruence was relatively low. The use of SNGn appears to be inappropriate to determine the vertical facial skeletal pattern of patients, due to Gn point shifting throughout sagittal discrepancies. Clinical Significance: Facial pattern determined by SNGn must be considered carefully, especially when severe sagittal discrepancies are present.15169-7