R-matrix Floquet theory for laser-assisted electron-atom scattering

A new version of the R-matrix Floquet theory for laser-assisted electron-atom scattering is presented. The theory is non-perturbative and applicable to a non-relativistic many-electron atom or ion in a homogeneous linearly polarized field. It is based on the use of channel functions built from field-dressed target states, which greatly simplifies the general formalism.Comment: 18 pages, LaTeX2e, submitted to J.Phys.

Detecting autoreactive B cells in the peripheral blood of people with type 1 diabetes using ELISpot

Type 1 diabetes mellitus (T1D) is an autoimmune disorder where T lymphocytes damage the islet beta cells but B lymphocytes also play an important role. Although changes in peripheral B cell phenotype have been observed, little is known about the B cells that secrete the autoantibodies. We developed a sensitive B cell enzyme-linked immunospot assay (ELISpot assay) to detect individual B cell antibody responses to glutamic acid decarboxylase (GAD) and islet antigen-2 (IA-2). We found that even healthy donors have B cells that secrete antibodies in response to GAD and IA-2 in the ELISpot. There was increased B cell reactivity to autoantigens in the peripheral blood of individuals with newly-diagnosed, but not long-standing, type 1 diabetes. However, no correlation with serum autoantibody levels was found, indicating that additional factors such as antigen affinity or exposure to antigens in vivo are required for antibody secretion, and that even healthy donors have potentially autoreactive B cells

Comparison of IFCC-calibrated HbA1c from laboratory and point of care testing systems

Objective: WHO, IDF and ADA recommend HbA1c ≥6.5% (48 mmol/mol) for diagnosis of diabetes with pre-diabetes 6.0% (42 mmol/mol) [WHO] or 5.7% (39 mmol/mol) [ADA] to 6.4% (47 mmol/mol). We have compared HbA1c from several methods for research relating glycaemic markers.Research design and methods: HbA1c was measured in EDTA blood from 128 patients with diabetes on IE HPLC analysers (Bio-Rad Variant II NU, Menarini HA8160 and Tosoh G8), point of care systems, POCT, (A1cNow+ disposable cartridges and DCA 2000®+ analyser), affinity chromatography (Primus Ultra2) and the IFCC secondary reference method (Menarini HA8160 calibrated using IFCC SRM protocol).Results: median (IQ range) on IFCC SRM was 7.5% (6.8–8.4) (58(51–68) mmol/mol) HbA1c with minimum 5.3%(34 mmol/mol)/maximum 11.9%(107 mmol/mol). There were positive offsets between IFCC SRM and Bio-Rad Variant II NU, mean difference (1SD), +0.33%(0.17) (+3.6(1.9) mmol/mol), r2 = 0.984, p &lt; 0.001 and Tosoh G8, +0.22%(0.20) (2.4(2.2) mmol/mol), r2 = 0.976, p &lt; 0.001 with a very small negative difference −0.04%(0.11) (−0.4(1.2) mmol/mol), r2 = 0.992, p &lt; 0.001 for Menarini HA8160. POCT methods were less precise with negative offsets for DCA 2000®+ analyser −0.13%(0.28) (−1.4(3.1) mmol/mol), r2 = 0.955, p &lt; 0.001 and A1cNow+ cartridges −0.70%(0.67) (−7.7(7.3) mmol/mol), r2 = 0.699, p &lt; 0.001 (n = 113). Positive biases for Tosoh and Bio-Rad (compared with IFCC SRM) have been eliminated by subsequent revision of calibration.Conclusions: small differences observed between IFCC-calibrated and NGSP certified methods across a wide HbA1c range were confirmed by quality control and external quality assurance. As these offsets affect estimates of diabetes prevalence, the analyser (and calibrator) employed should be considered when evaluating diagnostic data.</p

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in Type 1 diabetes

Antigen-specific immunotherapy is immunomodulatory strategy for autoimmune diseases, such as Type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune beta-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNP), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well-tolerated in participants with Type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies

Loss of CXCR3 expression on memory B cells in individuals with long-standing type 1 diabetes

Aims/hypothesis Islet-specific autoantibodies can predict the development of type 1 diabetes. However, it remains unclear if B cells, per se, contribute to the causal pancreatic immunopathology. We aimed to identify phenotypic signatures of disease progression among naive and memory B cell subsets in the peripheral blood of individuals with type 1 diabetes. Methods A total of 69 participants were recruited across two separate cohorts, one for discovery purposes and the other for validation purposes. Each cohort comprised two groups of individuals with type 1 diabetes (one with newly diagnosed type 1 diabetes and the other with long-standing type 1 diabetes) and one group of age- and sex-matched healthy donors. The phenotypic characteristics of circulating naive and memory B cells were investigated using polychromatic flow cytometry, and serum concentrations of various chemokines and cytokines were measured using immunoassays. Results A disease-linked phenotype was detected in individuals with long-standing type 1 diabetes, characterised by reduced C-X-C motif chemokine receptor 3 (CXCR3) expression on switched (CD27+IgD−) and unswitched (CD27intermediateIgD+) memory B cells. These changes were associated with raised serum concentrations of B cell activating factor and of the CXCR3 ligands, chemokine (C-X-C motif) ligand (CXCL)10 and CXCL11. A concomitant reduction in CXCR3 expression was also identified on T cells. Conclusions/interpretation Our data reveal a statistically robust set of abnormalities that indicate an association between type 1 diabetes and long-term dysregulation of a chemokine ligand/receptor system that controls B cell migration

Administering a small rapid-acting insulin bolus 3 hours after eating a mixed macronutrient meal improves postpandial glucose control, without hypoglycaemia, in people with Type 1 diabetes [conference abstract]

Conference abstrac