Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine.

OBJECTIVE: An observational safety study of the quadrivalent human papillomavirus vaccine (HPV4) in women was conducted. This report presents findings from autoimmune surveillance. Design. Subjects were followed for 180days after each HPV4 dose for new diagnoses of 16 prespecified autoimmune conditions. SETTING: Two managed care organizations in California. Subjects. Number of 189,629 women who received ≥1 dose of HPV4 between 08/2006 and 03/2008. OUTCOME: Potential new-onset autoimmune condition cases amongst HPV4 recipients were identified by electronic medical records. Medical records of those with ≥12-month health plan membership prior to vaccination were reviewed by clinicians to confirm the diagnosis and determine the date of disease onset. The incidence of each autoimmune condition was estimated for unvaccinated women at one study site using multiple imputations and compared with that observed in vaccinated women. Incidence rate ratios (IRR) were calculated. Findings were reviewed by an independent Safety Review Committee (SRC). RESULTS: Overall, 1014 potential new-onset cases were electronically identified; 719 were eligible for case review; 31-40% were confirmed as new onset. Of these, no cluster of disease onset in relation to vaccination timing, dose sequence or age was found for any autoimmune condition. None of the estimated IRR was significantly elevated except Hashimoto's disease [IRR=1.29, 95% confidence interval: 1.08-1.56]. Further investigation of temporal relationship and biological plausibility revealed no consistent evidence for a safety signal for autoimmune thyroid conditions. The SRC and the investigators identified no autoimmune safety concerns in this study. CONCLUSIONS: No autoimmune safety signal was found in women vaccinated with HPV4.

Dynamic heterogeneity and non-Gaussian statistics for acetylcholine receptors on live cell membrane.

The Brownian motion of molecules at thermal equilibrium usually has a finite correlation time and will eventually be randomized after a long delay time, so that their displacement follows the Gaussian statistics. This is true even when the molecules have experienced a complex environment with a finite correlation time. Here, we report that the lateral motion of the acetylcholine receptors on live muscle cell membranes does not follow the Gaussian statistics for normal Brownian diffusion. From a careful analysis of a large volume of the protein trajectories obtained over a wide range of sampling rates and long durations, we find that the normalized histogram of the protein displacements shows an exponential tail, which is robust and universal for cells under different conditions. The experiment indicates that the observed non-Gaussian statistics and dynamic heterogeneity are inherently linked to the slow-active remodelling of the underlying cortical actin network.

Concentration and velocity patterns in a horizontal rotating suspension of non-Brownian settling particles.

We report a systematic experimental study of concentration and velocity patterns formed in a horizontal rotating cylinder filled completely with a monodisperse suspension of non-Brownian settling particles. The system shows a series of concentration and velocity patterns, or phases, with varying rotation rate and solvent viscosity. Individual phases are studied using both side and cross-sectional imaging to examine the detailed flow structures. The overall phase diagram of the system is mapped out as a function of the rotation rate and solvent viscosity. Attempts are made to analyze the functional form of the phase boundaries in order to understand the transition mechanism between different phases.

Pattern formation in a rotating suspension of non-Brownian settling particles.

We report band formation and other pattern formation for a settling suspension of uniform non-Brownian particles in a completely filled horizontal rotating cylinder. The system shows a series of sharp pattern changes that are mapped out as a function of the rotation period and suspension viscosity. The experiment suggests that a large number of patterns and rich dynamics result from the interplay among the viscous drag, and gravitational and centrifugal forces.

Radiofrequency heating pathways for gold nanoparticles.

This feature article reviews the thermal dissipation of nanoscopic gold under radiofrequency (RF) irradiation. It also presents previously unpublished data addressing obscure aspects of this phenomenon. While applications in biology motivated initial investigation of RF heating of gold nanoparticles, recent controversy concerning whether thermal effects can be attributed to nanoscopic gold highlight the need to understand the involved mechanism or mechanisms of heating. Both the nature of the particle and the nature of the RF field influence heating. Aspects of nanoparticle chemistry which may affect thermal dissipation include the hydrodynamic diameter of the particle, the oxidation state and related magnetism of the core, and the chemical nature of the ligand shell. Aspects of RF which may affect thermal dissipation include power, frequency and antenna designs that emphasize relative strength of magnetic or electric fields. These nanoparticle and RF properties are analysed in the context of three heating mechanisms proposed to explain gold nanoparticle heating in an RF field. This article also makes a critical analysis of the existing literature in the context of the nanoparticle preparations, RF structure, and suggested mechanisms in previously reported experiments.

Heme proteins: effect of an intermediate on photochemical behavior.

This paper analyzes, in terms of a triangular kinetic scheme, the possible effects of an intermediate in the photochemical behavior of simple heme proteins. Both steady-state and transient phenomena are analyzed. The magnitude of the quantum yield for a given system is determined by a competition between quenching and ligand detachment, measured by the two rate constants, kappa(-1) and kappa(2), respectively; as a first approximation, it can be described by a single parameter, namely the ratio kappa(-1)/kappa(2). The individual values of kappa(-1) and kappa(2) can only be determined at light intensities so high that the measured quantum yield becomes itself a function of light intensity. Under these conditions the relaxation time for transient approach to the steady-state can be complex, corresponding to heavily damped chemical oscillations. It is pointed out that when the model is extended to include more than one intermediate, multiple oscillations are possible. In this more general case the system in the steady-state may also show pseudocooperativity or anticooperativity.

Velocity difference measurement with a fiber-optic coupler.

Two single-mode fibers collect light with the same scattered wave vector from two spatially separated regions in a sample. These regions are illuminated by a single coherent laser beam, so that the collected signals interfere when combined by means of a fiber-optic coupler, before they are directed to a photomultiplier tube. The fibers and the coupler are polarization preserving to guarantee a high signal-to-noise ratio. The measured intensity fluctuations are used to determine the velocity difference omega v(L) for spatial separations L in the sample. Specifically, an intensity autocorrelation function is calculated theoretically for rigid body rotation and is tested experimentally. Experimental results span two orders of magnitude in L and agree with theoretical predictions with an error of less than 5%. This new technique will be very useful in the study of turbulent flow and particle settling dynamics.

Multiple-scattering suppression: cross correlation with tilted single-mode fibers.

Multiple light scattering can be suppressed by slightly tilting two single-mode fibers viewing the same sample volume. The cross-correlation function of the two signals shows more or less contributions from single scattering, depending on the tilt angle. We show experimental results for polystyrene spheres at a scattering angle of 90 degrees . The measured size, intercept, and second cumulant for different tilt angles demonstrate the practicality of this technique. Both polarization components show multiple-scattering contributions, but only the parallel component contains single scattering.

Settling statistics of hard sphere particles.

Direct imaging of settling, non-Brownian, hard sphere, particles allows measurement of particle occupancy statistics as a function of time and sampling volume dimension. Initially random relative particle number fluctuations, (2)>/ = 1, become suppressed, anisotropic, and dependent. Fitting to a simple Gaussian pair correlation model suggests a minute long ranged correlation leads to strong if not complete suppression of number fluctuations. Calflisch and Luke predict a divergence in velocity fluctuations with increasing sample volume size based on random (Poisson) statistics. Our results suggest this is not a valid assumption for settling particles.

Effects of treatment of whole fat soybeans or soy flour with formaldehyde to protect the polyunsaturated fatty acids from biohydrogenation in the rumen.

Full-fat, ground soy flour (GSF) was treated with 37% formaldehyde (HCHO) and evaluated by in vitro and in vivo criteria to determine the protection afforded linoleic acid against ruminal biohydrogenation when the materials described above were fed as a protein supplement to rations for growing lambs. The supplements compared were soybean meal (SBM), uked for 2 hours. Organoleptic evaluations were conducted to determine if any flavor differences in meat from lambs fed these supplements could be detected. Excellent protection of linoleic acid, the major polyunsaturated fatty acid in soybeans, was noted both in vitro and in vivo. Rump, shoulder, kidney knob and omental fat depots of lambs fed the HCHO treated GSF ration had significantly more linoleic acid than lambs fed untreated GSF while lambs fed untreated GSF had significantly, more linoleic acid in their fat depots than lambs fed SBM. Linoleic acid content of intramuscular (loin) fat from lambs fed HCHO treated GSF was not significantly different from lambs fed untreated GSF, but lambs fed untreated GSF had significantly more loin linoleic acid than lambs fed SBM. No significant differences were noted in daily feed intake, feed efficiency or average daily gain for lambs fed growing-finishing rations containing any of the products tested as the protein supplement. A taste panel could not detect any differences in flavor of ground loin among any of the treatments.

Proposal and testing for a fiber-optic-based measurement of flow vorticity.

A fiber-optic arrangement is devised to measure the velocity difference, deltav(l), down to small separation l. With two sets of optical fibers and couplers the new technique becomes capable of measuring one component of the time- and space-resolved vorticity vector omega(r, t). The technique is tested in a steady laminar flow, in which the velocity gradient (or flow vorticity) is known. The experiment verifies the working principle of the technique and demonstrates its applications. It is found that the new technique measures the velocity difference (and hence the velocity gradient when l is known) with the same high accuracy and high sampling rate as laser Doppler velocimetry does for the local velocity measurement. It is nonintrusive and capable of measuring the velocity gradient with a spatial resolution as low as ~50 mum. The successful test of the fiber-optic technique in the laminar flow with one optical channel is an important first step for the development of a two-channel fiber-optic vorticity probe, which has wide use in the general area of fluid dynamics, especially in the study of turbulent flows.

Cells with high cyclophilin A content support replication of human immunodeficiency virus type 1 Gag mutants with decreased ability to incorporate cyclophilin A.

Gag polyprotein-mediated incorporation of cellular cyclophilin A (CyPA) into virions is essential for the formation of infectious human immunodeficiency virus type 1 (HIV-1) virions. Either a point mutation in Gag (P222A) or drugs which bind CyPA decrease virion incorporation of CyPA and interfere with HIV-1 replication. We have found that lymphoid cells varied greatly in their CyPA content and that cells with high CyPA content supported the replication of P222A HIV-1 Gag mutants. These experiments demonstrated that a higher cellular CyPA content of some cells was able to compensate for the decreased binding affinity of P222A mutant Gag for CyPA, allowing virus replication to occur.

The case for integration of social work psychosocial services into rural primary care practice.

This article argues for health and mental health collaboration between social workers and rural primary care physicians and describes a study of physicians' attitudes toward integrated services. The physicians who expressed interest in a collaborative arrangement differed in practice characteristics, attitudes toward social workers, and endorsement of social work roles. Also, interested physicians treated significantly more patients, had the lowest proportion of patients over age 65, and endorsed as useful a significantly larger number of social work activities. If social workers aspire to collaborative arrangements in rural primary care, they must provide excellent services now, continue to work toward a better understanding of their broad mental health competencies, and be willing to provide services that conform to the expectations and limitations of primary care.

Crystallization by settling in suspensions of hard spheres.

We examine crystallization by settling for two different model hard-sphere suspensions. Sedimentation velocities, internal shock velocities, and crystal growth velocities are measured. Dynamic light scattering experiments measure volume fraction profiles in fluid phases, while Bragg scattering experiments determine volume fraction profiles in crystal phases. Centrifugation experiments determine the particle Péclet number above which samples will not crystallize. The sedimentation velocities, as a function of volume fraction, agree with other "hard-sphere" data. Remarkably, the value of the reduced crystal growth velocity (approximately 0.075) obtains for two orders of magnitude of the particle Péclet number. Kynch theory provides an adequate description of the data in the fluid phase, but is less adequate for volume fraction profiles in the crystal phase. The crystals in the dense sediment are compressed more along a vertical axis relative to the horizontal axis. Predicted Wilson-Frenkel crystal growth velocities, calculated using known hard-sphere equations of state and a short-time self-diffusion constant, rationalize the measured crystal growth velocities.

The E7 oncoprotein of human papillomavirus type 16 interacts with F-actin in vitro and in vivo.

We report here that E7 oncoprotein of human papillomavirus type 16 (HPV-16) forms a complex in vivo and in vitro with actin, one of the components of the cellular cytoskeleton. The in vivo interaction was detected by immunofluorescent staining and confocal microscopic examination of normal human oral keratinocytes (NHOK) and CV-1 cells after transient expression of E7 employing the vaccinia virus-T7 RNA polymerase system and by coimmunoprecipitation from an immortalized, nontumorigenic cell line obtained after transfecting NHOK with the cloned HPV-16 DNA genome. The in vitro interaction was detected by cosedimentation of bacterially expressed E7 phosphorylated with rabbit reticulocyte lysate or purified casein kinase II (CKII) prior to incubation with F-actin. This interaction was inhibited if E7 phosphorylation by the rabbit reticulocyte lysate was prevented with heparin, a CKII inhibitor, or if the amino acids Ser-31 and Ser-32 in E7, which are phosphorylated by CKII, were replaced with amino acids that cannot be phosphorylated. Interestingly, a decrease in the amount of polymerized actin occurred in cells expressing E7.

Polyethylene glycol-induced heteroassociation of malate dehydrogenase and citrate synthase.

Studies by dynamic and total intensity light scattering, ultracentrifugation, electron microscopy, and chemical crosslinking on solutions of the pig heart mitochondrial enzymes, malate dehydrogenase and citrate synthase (separately and together) demonstrate that polyethylene glycol induces very large homoassociations of each enzyme, and still larger heteroenzyme complexes between these two enzymes in the solution phase. Specificity of this heteroassociation is indicated by the facts that heteroassociations with bovine serum albumin were not observed for either the mitochondrial dehydrogenase or the synthase or between cytosolic malate dehydrogenase and citrate synthase. The weight fraction of the enzymes in the mitochondrial dehydrogenase-synthase associated particles in the solution phase was less than 0.03% with the dilute conditions used in the dynamic light scattering measurements. Neither palmitoyl-CoA nor other solution conditions tested significantly increased this weight fraction of associated enzymes in the solution phase. Because of the extremely low solubility of the associated species, however, the majority of the enzymes can be precipitated as the heteroenzyme complex. This precipitation is a classical first-order transition in spite of the large particle sizes and broad size distribution. Ionic effects on the solubility of the heteroenzyme complex appear to be of general electrostatic nature. Polyethylene glycol was found to be more potent in precipitating this complex than dextrans, polyvinylpyrrolidones, ficoll, and beta-lactoglobulin.

Cryoelectron microscopic examination of human immunodeficiency virus type 1 virions with mutations in the cyclophilin A binding loop.

The human immunodeficiency virus type 1 capsid protein contains a conserved P217X4PX2PX5P231 motif. Mutation at Pro-222 decreases virion incorporation of cyclophilin A, while mutation at Pro-231 abolishes infectivity. Although viral RNA incorporation and protease cleavage of the Gag precursor were not affected by these mutations, cryoelectron microscopy revealed a loss of virion maturation in P231A particles.