Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.

Stavudine (d4T) was, until recently, one of the most widely prescribed antiretroviral drugs worldwide. While there has been a major shift away from d4T use in resource-limited countries, a large number of patients have previously received (or continue to receive) d4T, and many have developed peripheral neuropathy. The identification of genetic predictors of increased risk might suggest novel therapeutic targets for such patients. In AIDS Clinical Trials Group protocol 384, antiretroviral-naïve patients were randomized to d4T/didanosine (ddI)- or zidovudine/lamivudine-containing regimens. Data from d4T/ddI recipients were analyzed for genome-wide associations (approximately 1 million genetic loci) with new onset distal sensory peripheral neuropathy. Analyses involved 254 patients (49 % White, 34 % Black, 17 % Hispanic), comprising 90 peripheral neuropathy cases (32 grade 1, 35 grade 2, 23 grade 3) and 164 controls. After correcting for multiple comparisons, no polymorphism was consistently associated with neuropathy among all patients, among White, Black, and Hispanic patients analyzed separately, both in genome-wide analyses (threshold, P < 5.0 × 10(-8)) and focused on 46 neuropathy-associated genes (threshold, P < 3.5 × 10(-5)). In the latter analyses, the lowest P values were in KIF1A among Whites (rs10199388, P = 8.4 × 10(-4)), in LITAF among Blacks (rs13333308, P = 6.0 × 10(-6)), and in NEFL among Hispanics (rs17763685, P = 5.6 × 10(-6)). Susceptibility to d4T/ddI-associated neuropathy is not explained by a single genetic variant with a marked effect

Exact scaling in the expansion-modification system

This work is devoted to the study of the scaling, and the consequent power-law behavior, of the correlation function in a mutation-replication model known as the expansion-modification system. The latter is a biology inspired random substitution model for the genome evolution, which is defined on a binary alphabet and depends on a parameter interpreted as a \emph{mutation probability}. We prove that the time-evolution of this system is such that any initial measure converges towards a unique stationary one exhibiting decay of correlations not slower than a power-law. We then prove, for a significant range of mutation probabilities, that the decay of correlations indeed follows a power-law with scaling exponent smoothly depending on the mutation probability. Finally we put forward an argument which allows us to give a closed expression for the corresponding scaling exponent for all the values of the mutation probability. Such a scaling exponent turns out to be a piecewise smooth function of the parameter.Comment: 22 pages, 2 figure

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Shock compression of polyurethane foams

Several shock studies have been made on polyurethane materials, both fully dense and distended in the form of foams. However, there is a lack of shock data between the densities of 0.321 and 1.264g/cm3 (fully dense). We present here data obtained from two different types of shock experiments at densities of 0.35, 0.5, 0.68, 0.78, and 0.9g/cm3 in order to fill in the density deficiencies and make it easier to develop an unreacted equation of state (EOS) for polyurethane as a function of density. A thermodynamically consistent EOS was developed, based on the Helmholtz free energy, and was used to predict the shock properties of polyurethane materials at densities from 1.264 to 0.348g/cm3. These estimates are compared to the available data. The data match quite close to the predictions and provide a basis for calculating polyurethane foam shock processes. Chemical reaction has been observed at relatively high pressure (21.7 GPa) in fully dense polyurethane in an earlier study, and the equation of state presented here is representative of the unreacted polyurethane foam. Lowering the density is expected to drop the shock pressure for chemical reaction, yet there is not enough data to address the low density shock reaction thresholds in this study

Shock compression of polyurethane foams

Several shock studies have been made on polyurethane materials, both fully dense and distended in the form of foams. However, there is a lack of shock data between the densities of 0.321 and 1.264g/cm3 (fully dense). We present here data obtained from two different types of shock experiments at densities of 0.35, 0.5, 0.68, 0.78, and 0.9g/cm3 in order to fill in the density deficiencies and make it easier to develop an unreacted equation of state (EOS) for polyurethane as a function of density. A thermodynamically consistent EOS was developed, based on the Helmholtz free energy, and was used to predict the shock properties of polyurethane materials at densities from 1.264 to 0.348g/cm3. These estimates are compared to the available data. The data match quite close to the predictions and provide a basis for calculating polyurethane foam shock processes. Chemical reaction has been observed at relatively high pressure (21.7 GPa) in fully dense polyurethane in an earlier study, and the equation of state presented here is representative of the unreacted polyurethane foam. Lowering the density is expected to drop the shock pressure for chemical reaction, yet there is not enough data to address the low density shock reaction thresholds in this study

Flyer Velocity Characteristics of the Laser-Driven Miniflyer System

The laser-driven MiniFlyer system is used to launch a small, thin flyer plate for impact on a target. Consequently, it is an indirect drive technique that de-couples the shock from the laser beam profile. The flyer velocity can be controlled by adjustment of the laser energy. The upper limits on the flyer velocity involve the ability of the substrate window to transmit the laser light without absorbing, reflecting, etc.; i.e., a maximum amount of laser energy is directly converted into kinetic energy of the flyer plate. We have investigated the use of sapphire, quartz, and BK-7 glass as substrate windows. In the past, a particular type of sapphire has been used for nearly all MiniFlyer experiments. Results of this study in terms of the performance of these window materials, based on flyer velocity, are discussed