Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies

Some autoimmune conditions are associated with increased risk of lymphoid malignancies, but information on specific malignancy subtypes is limited. From the U.S. Surveillance Epidemiology and End Results-Medicare database, we selected 44,350 lymphoid malignancy cases (≥67 years) and 122,531 population-based controls. Logistic regression was used to derive odds ratios (ORs) comparing the prevalence of autoimmune conditions in cases and controls, by lymphoid malignancy subtype, adjusted for gender, age at malignancy/selection, year of malignancy/selection, race and number of physician claims. The strongest associations observed by Non-Hodgkin lymphoma (NHL) subtypes were diffuse large B-cell lymphoma with rheumatoid arthritis (OR 1.4, 95%CI 1.2-1.5) and Sjögren syndrome (2.0, 1.5-2.8); T-cell lymphoma with hemolytic anemia (9.7, 4.3-22), psoriasis (3.1, 2.5-4.0), discoid lupus erythematosus (4.4, 2.3-8.4), and celiac disease (5.0, 2.4-14.); and marginal zone lymphoma with Sjögren syndrome (6.6, 4.6-9.5), systemic lupus erythematosus (2.8, 1.7-4.7), and hemolytic anemia (7.4, 3.1-18). Hodgkin lymphoma was associated with several autoimmune conditions. Multiple myeloma was associated only with pernicious anemia (1.5, 1.3-1.7). Several autoimmune conditions were associated with increased risk of lymphoid neoplasms, especially NHLs of diffuse large B-cell, marginal zone and T-cell subtypes. These results support a mechanism whereby chronic antigenic stimulation leads to lymphoid malignancy

Dynamics of Dark-Bright Solitons in Cigar-Shaped Bose-Einstein Condensates

We explore the stability and dynamics of dark-bright solitons in two-component elongated Bose-Einstein condensates by developing effective 1D vector equations as well as solving the corresponding 3D Gross-Pitaevskii equations. A strong dependence of the oscillation frequency and of the stability of the dark-bright (DB) soliton on the atom number of its components is found. Spontaneous symmetry breaking leads to oscillatory dynamics in the transverse degrees of freedom for a large occupation of the component supporting the dark soliton. Moreover, the interactions of two DB solitons are investigated with special emphasis on the importance of their relative phases. Experimental results showcasing dark-bright soliton dynamics and collisions in a BEC consisting of two hyperfine states of $^{87}$Rb confined in an elongated optical dipole trap are presented.Comment: 4 pages, 5 figure

Identification of Small Molecule and Genetic Modulators of AON-Induced Dystrophin Exon Skipping by High-Throughput Screening

One therapeutic approach to Duchenne Muscular Dystrophy (DMD) recently entering clinical trials aims to convert DMD phenotypes to that of a milder disease variant, Becker Muscular Dystrophy (BMD), by employing antisense oligonucleotides (AONs) targeting splice sites, to induce exon skipping and restore partial dystrophin function. In order to search for small molecule and genetic modulators of AON-dependent and independent exon skipping, we screened ∼10,000 known small molecule drugs, >17,000 cDNA clones, and >2,000 kinase- targeted siRNAs against a 5.6 kb luciferase minigene construct, encompassing exon 71 to exon 73 of human dystrophin. As a result, we identified several enhancers of exon skipping, acting on both the reporter construct as well as endogenous dystrophin in mdx cells. Multiple mechanisms of action were identified, including histone deacetylase inhibition, tubulin modulation and pre-mRNA processing. Among others, the nucleolar protein NOL8 and staufen RNA binding protein homolog 2 (Stau2) were found to induce endogenous exon skipping in mdx cells in an AON-dependent fashion. An unexpected but recurrent theme observed in our screening efforts was the apparent link between the inhibition of cell cycle progression and the induction of exon skipping

Multi-parallel qPCR provides increased sensitivity and diagnostic breadth for gastrointestinal parasites of humans: field-based inferences on the impact of mass deworming

BACKGROUND: Although chronic morbidity in humans from soil transmitted helminth (STH) infections can be reduced by anthelmintic treatment, inconsistent diagnostic tools make it difficult to reliably measure the impact of deworming programs and often miss light helminth infections. METHODS: Cryopreserved stool samples from 796 people (aged 2-81 years) in four villages in Bungoma County, western Kenya, were assessed using multi-parallel qPCR for 8 parasites and compared to point-of-contact assessments of the same stools by the 2-stool 2-slide Kato-Katz (KK) method. All subjects were treated with albendazole and all Ascaris lumbricoides expelled post-treatment were collected. Three months later, samples from 633 of these people were re-assessed by both qPCR and KK, re-treated with albendazole and the expelled worms collected. RESULTS: Baseline prevalence by qPCR (n = 796) was 17 % for A. lumbricoides, 18 % for Necator americanus, 41 % for Giardia lamblia and 15% for Entamoeba histolytica. The prevalence was <1% for Trichuris trichiura, Ancylostoma duodenale, Strongyloides stercoralis and Cryptosporidium parvum. The sensitivity of qPCR was 98% for A. lumbricoides and N. americanus, whereas KK sensitivity was 70% and 32%, respectively. Furthermore, qPCR detected infections with T. trichiura and S. stercoralis that were missed by KK, and infections with G. lamblia and E. histolytica that cannot be detected by KK. Infection intensities measured by qPCR and by KK were correlated for A. lumbricoides (r = 0.83, p < 0.0001) and N. americanus (r = 0.55, p < 0.0001). The number of A. lumbricoides worms expelled was correlated (p < 0.0001) with both the KK (r = 0.63) and qPCR intensity measurements (r = 0.60). CONCLUSIONS: KK may be an inadequate tool for stool-based surveillance in areas where hookworm or Strongyloides are common or where intensity of helminth infection is low after repeated rounds of chemotherapy. Because deworming programs need to distinguish between populations where parasitic infection is controlled and those where further treatment is required, multi-parallel qPCR (or similar high throughput molecular diagnostics) may provide new and important diagnostic information

Excitation functions of hadronic observables from SIS to RHIC energies

We calculate excitation functions for various dynamical quantities as well as experimental observables from SIS to RHIC energies within the HSD transport approach which is based on string, quark, diquark ($q, \bar{q}, qq, \bar{q}\bar{q}$) and hadronic degrees of freedom without including any explicit phase transition to a quark-gluon plasma (QGP). It is argued that the failure of this more 'conventional' approach in comparison to experimental data should indicate the presence of a different phase which might be either attributed to space-time regions of vanishing scalar quark condensate ($$ = 0) or to the presence of a QGP phase with strongly interacting partons. We study the $K/\pi$ ratio, the low mass dilepton enhancement in the invariant mass regime from 0.2 -- 1.2 GeV as well as charmonium suppression for central Au + Au collisions as a function of the bombarding energy and present predictions for these observables as well as hadron rapiditiy distributions at RHIC energies. Whereas all observables studied within HSD show smooth increasing/decreasing excitation functions, the experimental $K^+/\pi^+$ ratio indicates a maximum at 11 A$\cdot$GeV (or above) which is interpreted as a signature for a chirally restored phase in the course of the reaction.Comment: 34 pages, LaTeX, including 14 postscript figures (high quality color versions of figs. 3,4 are available from http://theorie.physik.uni-giessen.de/~brat/own.html), Nucl. Phys.

Antibiotic use and risk of non-Hodgkin's lymphoma: a population-based case–control study

Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was compared. Neither total antibiotic use (odds ratio=0.7, 95% confidence interval=0.5–1.2), nor antibiotic use by site, was associated with total NHL, or NHL subtypes. There were no trends with frequency or age at first use (P trend=0.23 and 0.26, respectively)

Vortices and dynamics in trapped Bose-Einstein condensates

I review the basic physics of ultracold dilute trapped atomic gases, with emphasis on Bose-Einstein condensation and quantized vortices. The hydrodynamic form of the Gross-Pitaevskii equation (a nonlinear Schr{\"o}dinger equation) illuminates the role of the density and the quantum-mechanical phase. One unique feature of these experimental systems is the opportunity to study the dynamics of vortices in real time, in contrast to typical experiments on superfluid $^4$He. I discuss three specific examples (precession of single vortices, motion of vortex dipoles, and Tkachenko oscillations of a vortex array). Other unusual features include the study of quantum turbulence and the behavior for rapid rotation, when the vortices form dense regular arrays. Ultimately, the system is predicted to make a quantum phase transition to various highly correlated many-body states (analogous to bosonic quantum Hall states) that are not superfluid and do not have condensate wave functions. At present, this transition remains elusive. Conceivably, laser-induced synthetic vector potentials can serve to reach this intriguing phase transition.Comment: Accepted for publication in Journal of Low Temperature Physics, conference proceedings: Symposia on Superfluids under Rotation (Lammi, Finland, April 2010