A functional polymorphism of toll-like receptor 4 is not associated with likelihood or severity of meningococcal disease.

Human Toll-like receptor 4 (TLR4) transduces proinflammatory cytokine release by human cells in response to lipopolysaccharide (LPS). This study tested the hypothesis that, if TLR4 is rate limiting for a successful response to bacterial LPS in humans, a human gene polymorphism that results in the amino acid substitution Asp299Gly and causes reduced expression and function of TLR4 should influence susceptibility to or severity of natural gram-negative infection. The allele frequency of the Asp299Gly polymorphism was 5.9% among 879 blood donors, 6.5% among 1047 patients with microbiologically proven meningococcal disease, and 4.1% among 86 patients who died of meningococcal disease. No significant differences were observed, including those analyzed after stratification of the infected population by age and by meningococcal serogroup. Therefore, this functional TLR4 polymorphism does not influence susceptibility to or severity of meningococcal disease.

Consistent canonical quantization of general relativity in the space of vassiliev invariants

We present a quantization of the Hamiltonian and diffeomorphism constraint of canonical quantum gravity in the spin network representation. The novelty consists in considering a space of wave functions based on the Vassiliev invariants. The constraints are finite, well defined, and reproduce at the level of quantum commutators the Poisson algebra of constraints of the classical theory. A similar construction can be carried out in 2+1 dimensions leading to the correct quantum theory.

Making classical and quantum canonical general relativity computable through a power series expansion in the inverse cosmological constant.

We consider general relativity with a cosmological constant as a perturbative expansion around a completely solvable diffeomorphism invariant field theory. This theory is the lambda --> infinity limit of general relativity. This allows an explicit perturbative computational setup in which the quantum states of the theory and the classical observables can be explicitly computed. An unexpected relationship arises at a quantum level between the discrete spectrum of the volume operator and the allowed values of the cosmological constant.

Grazing collisions of black holes via the excision of singularities.

We present the first simulations of non-head-on (grazing) collisions of binary black holes in which the singularities are excised from the simulation. Initially equal mass m black holes (spinning or not) are separated by approximately 10m and with impact parameter approximately 2m. Evolutions to t approximately 35m are obtained where two separate horizons are present for t approximately 3.8m; then a single enveloping horizon forms indicating that the holes merged. Apparent horizon area estimates suggest gravitational radiation of about 2%-3% of the total mass. The evolutions end after a moderate amount of time because of instabilities.

Holmium:YAG laser-assisted capsular shift in a canine model: intraarticular pressure and histologic observations.

The purpose of this study was to determine the initial effects of Holmium:YAG laser energy on the shoulder joint capsule. A new surgical procedure to correct shoulder joint instability uses Holmium:YAG laser energy to cause "shrinkage" of joint capsular tissues. To date there has been no information concerning an intraoperative measurable end point for the application of laser energy at surgery or the resultant depth and degree of tissue alteration. Seven greyhound dogs were used in this study. Preoperative intraarticular pressures (IAP) were measured on entry and after injection of 10 ml of solution. Laser energy was applied to the cranial medial glenohumeral ligament and joint capsule of all right shoulders with arthroscopic visualization. The unoperated left shoulders served as the control group. Six weeks after surgery pressure measurements were performed on both shoulders. A "second look" arthroscopy was performed on the shoulders. After euthanasia was performed, the anterior capsular tissues were harvested from both shoulders for histologic examination. The specimens were inspected by three blinded examiners. After 6 weeks the postoperative laser-treated IAP were higher than the same joint preoperative IAP in four of six dogs for both static nondistension and 10 ml distension measurements. At this same interval the marked tissue damage of the treated capsule was easily discerned by blinded observers. On histologic evaluation the laser-treated capsule showed synovitis and pericapsular tissue reactivity. The depth of the injury was beyond the joint capsule into the pericapsular tissue. It was not possible to determine the end point of the capsular "shrinkage" operation by combined pressure/volume intraoperative measurements. There was no uniform joint capsule compliance at 6 weeks. The histologic changes were extensive in both magnitude and depth. Future studies in this animal should include decreased laser energy plus other means of monitoring the intraoperative effects of laser use.

Effects of holmium: YAG laser energy on cartilage metabolism, healing, and biochemical properties of lesional and perilesional tissue in a weight-bearing model.

Comparison of perilesional cartilage, lesional repair tissue, and subchondral bone activity 6 months after application of holmium-yttrium-aluminum-garnet (Ho:YAG) laser energy to chronic (10 week) induced 10-mm full-thickness (FT) circular articular cartilage craters followed by 6 months' intermittent active motion (IAM) in a free exercise environment was investigated. The 2.1-microns wavelength was delivered in hand-controlled near-contact mode by arthroscopic surgery in a saline medium. Bilateral arthroscopy was performed on normal antebrachiocarpal, intercarpal, and metacarpophalangeal joints of six adult horses. Full-thickness craters were created in nine sites per limb on weight-bearing articular surfaces with a motorized bur. Right limb craters served as sham operated controls. Animals were killed at 10 weeks after FT crater creation (n = 2), and at 24 weeks (6 months) after laser energy application (n = 4). Histological analysis using hematoxylineosin (HE) and Safranin-O staining consisted of a modified Mankin grading of perilesional cartilage and lesional repair tissue scoring. Biochemical analysis was performed for cellularity and glycosaminoglycan (GAG) synthesis. Histological analysis showed clustering of chondrocytes or perilesional zonal cloning (PZC) in 83% of laser-treated lesions and in no control lesions. No differences were observed between treated and control lesional repair activity. Laser-treated perilesional cartilage showed a significant (P < .02) decrease in GAG synthesis. No adverse effects to distant cartilage were observed after application of laser energy regarding cell proliferation or GAG synthesis. Significance of decreased GAG synthesis in treated perilesional cartilage and perilesional zonal cloning of chondrocytes in treated cartilage is unknown. Additional study of Ho:YAG laser energy application to cartilage and subchondral bone is needed before its application in the surgical management and repair of cartilage damage.

The use of a structured assessment interview as an intervention to reduce dropout rates in outpatient relapse prevention groups for "problem" drinkers.

The problem of dropout rates in outpatient relapse prevention groups for "problem" drinkers is addressed. To test the hypothesis that the dropout rates were due to anxiety and lack of clarity among the participants about the purpose and expectations of the group, a structured induction was developed. The results obtained show that the induction made a significant difference in reducing the dropout rate. These findings can also be applied to other outpatient groups.