Genome-wide association analysis in primary sclerosing cholangitis identifies two non-HLA susceptibility loci.

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease affecting 2.4-7.5% of individuals with inflammatory bowel disease. We performed a genome-wide association analysis of 2,466,182 SNPs in 715 individuals with PSC and 2,962 controls, followed by replication in 1,025 PSC cases and 2,174 controls. We detected non-HLA associations at rs3197999 in MST1 and rs6720394 near BCL2L11 (combined P = 1.1 × 10⁻¹⁶ and P = 4.1 × 10⁻⁸, respectively)

Fluctuating Interfaces in Microemulsion and Sponge Phases

A simple Ginzburg-Landau theory with a single, scalar order parameter is used to study the microscopic structure of microemulsions and sponge phases. The scattering intensity in both film and bulk contrast, as well as averages of the internal area $S$, the Euler characteristic $\chi_E$, and the mean curvature squared $$, are calculated by Monte Carlo methods. The results are compared with results obtained from a variational approach in combination with the theory of Gaussian random fields and level surfaces. The results for the location of the transition from the microemulsion to oil/water coexistence, for the scattering intensity in bulk contrast, and for the dimensionless ratio $\chi_E V^2/S^3$ (where $V$ is the volume) are found to be in good quantitative agreement. However, the variational approach fails to give a peak in the scattering intensity in film contrast at finite wavevector, a peak which is observed both in the Monte Carlo simulations and in experiment. Also, the variational approach fails to produce a transition from the microemulsion to the lamellar phase.Comment: 23 pages (LaTeX) + 15 figures appended, figures 10-13 upon request, LMU-WAG-94053

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log <sub>10</sub> increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence