A Comprehensive Study of Leptoquark Bounds

We make a comprehensive study of indirect bounds on scalar leptoquarks that couple chirally and diagonally to the first generation by examining available data from low energy experiments as well as from high energy e+ e- and p pbar accelerators. The strongest bounds turn out to arise from low energy data: For leptoquarks that couple to right--handed quarks, the most stringent bound comes from atomic parity violation. For leptoquarks that couple to left--handed quarks, there are two mass regions: At low masses the bounds arise from atomic parity violation or from universality in leptonic pi decays. At masses above a few hundred GeV's, the dominant bounds come from the FCNC processes that are unavoidable in these leptoquarks: The FCNC bound of the up sector, that arises from D-Dbar mixing, combines with the FCNC bounds from the down sector, that arise from rare K decays and K-Kbar mixing, to a bound on the flavour CONSERVING coupling to the first generation. The bounds restrict leptoquarks that couple with electromagnetic strength to lie above 600 GeV or 630 GeV for leptoquarks that couple to RH quarks, and above 1040 GeV, 440 GeV, and 750 GeV for the SU(2)_W scalar, doublet and triplet leptoquarks that couple to LH quarks. These bounds are considerably stronger than the first results from the direct searches at HERA. Our bounds also already exclude large regions in the parameter space that could be examined by various methods proposed for indirect leptoquark searches.Comment: 23 Pages (LaTeX), including 3 uufiled postscript figures. WIS--93/90/Sept--PH. To appear in PRD. Changes: updated numbers ---> stronger bound

Does treatment of subsyndromal depression improve depression and diabetes related outcomes: protocol for a randomised controlled comparison of psycho-education, physical exercise and treatment as usual

<p>Abstract</p> <p>Background</p> <p>The prevalence of mood difficulties in persons with diabetes is approximately twice that in the general population, affecting the health outcomes and patients' quality of life in an undesirable way. Although subsyndromal depression is an important predictor of a more serious clinical depression, it is often overlooked. This study aims to compare the effects of two non-pharmacological interventions for subsyndromal depression, psychoeducation and physical exercise, with diabetes treatment as usual on mood- and diabetes-related outcomes.</p> <p>Methods and Design</p> <p>Type 2 diabetic patients aged 18-65 yrs. who report mood difficulties and the related need for help in a mail survey will be potential participants. After giving informed consent, they will be randomly assigned to one of the three groups (psychoeducation, physical activity, treatment as usual). Depressive symptoms, diabetes distress, health-related quality of life and diabetes self-care activities will be assessed at baseline, at 6 weeks, 6 months and 12 months. A structured clinical interview for DSM-IV Axis I Disorders (SCID-I) will be performed at baseline and at one-year follow-up in order to determine the clinical significance of the patients' depressive symptoms. Disease-related data will be collected from patients' files and from additional physical examinations and laboratory tests.</p> <p>The two interventions will be comparable in terms of format (small group work), duration (six sessions) and approach (interactive learning; supporting the participants' active roles). The group treated as usual will be informed about their screening results and about the importance of treating depression. They will be provided with brief re-education on diabetes and written self-help instructions to cope with mood difficulties.</p> <p>Primary outcomes will be depressive symptoms. Secondary outcomes will be glycaemic control, diabetes-related distress, self-management of diabetes and health-related quality of life. Tertiary outcomes will be biochemical markers reflecting common pathophysiological processes of insulin resistance, inflammation and oxidative damage that are assumed to be intertwined in both diabetes and depression. The mixed-effect linear model will be used to compare the outcome variables.</p> <p>Power analysis has indicated that the two intervention groups and the control group should comprise 59 patients to enable detection of clinically meaningful differences in depressive symptoms with a power of 80% and alpha = 0.05. Outcomes will be analysed on an intention-to-treat basis.</p> <p>Trial Registration</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN05673017">ISRCTN05673017</a></p

Modulation of ROS production in human leukocytes by ganglioside micelles

Recent studies have reported that exogenous gangliosides, the sialic acid-containing glycosphingolipids, are able to modulate many cellular functions. We examined the effect of micelles of mono- and trisialoganglioside GM1 and GT1b on the production of reactive oxygen species by stimulated human polymorphonuclear neutrophils using different spectroscopic methods. The results indicated that exogenous gangliosides did not influence extracellular superoxide anion (O2.-) generation by polymorphonuclear neutrophils activated by receptor-dependent formyl-methionyl-leucyl-phenylalanine. However, when neutrophils were stimulated by receptor-bypassing phorbol 12-myristate 13-acetate (PMA), gangliosides above their critical micellar concentrations prolonged the lag time preceding the production in a concentration-dependent way, without affecting total extracellular O2.- generation detected by superoxide dismutase-inhibitable cytochrome c reduction. The effect of ganglioside GT1b (100 µM) on the increase in lag time was shown to be significant by means of both superoxide dismutase-inhibitable cytochrome c reduction assay and electron paramagnetic resonance spectroscopy (P < 0.0001 and P < 0.005, respectively). The observed phenomena can be attributed to the ability of ganglioside micelles attached to the cell surface to slow down PMA uptake, thus increasing the diffusion barrier and consequently delaying membrane events responsible for PMA-stimulated O2.- production