Bioresorbable Polylactide Interbody Implants in an Ovine Anterior Cervical Discectomy and Fusion Model: Three-Year Results

Study Design. In vivo study of anterior discectomy and fusion using a bioresorbable 70:30 poly(l-lactide-co-d,l-lactide) interbody implant in an ovine model. Objective. To evaluate the efficacy of the polylactide implant to function as an interbody fusion device, and to assess the tissue reaction to the material during the resorption process. Summary of Background Data. The use of polylactide as a cervical interbody implant has several potential advantages when compared with traditional materials. Having an elastic modulus very similar to bone minimizes the potential for stress shielding, and as the material resorbs additional loading is transferred to the developing fusion mass. Although preclinical and clinical studies have demonstrated the suitability of polylactide implants for lumbar interbody fusion, detailed information on cervical anterior cervical discectomy and fusion (ACDF) with polylactide devices is desirable. Methods. Single level ACDF was performed in 8 skeletally mature ewes. Bioresorbable 70:30 poly (l-lactide-co-d,l-lactide) interbody implants packed with autograft were used with single-level metallic plates. Radiographs were made every 3 months up to 1 year, and yearly thereafter. The animals were killed at 6 months (3 animals), 12 months (3 animals), and 36 months (2 animals). In addition to the serial plain radiographs, the specimens were evaluated by nondestructive biomechanical testing and undecalcified histologic analysis. Results. The bioresorbable polylactide implants were effective in achieving interbody fusion. The 6-month animals appeared fused radiographically and biomechanically, whereas histologic sections demonstrated partial fusion (in 3 of 3 animals). Radiographic fusion was confirmed histologically and biomechanically at 12 months (3 of 3 animals) and 36 months (2 of 2 animals). A mild chronic inflammatory response to the resorbing polylactide implant was observed at both 6 months and 12 months. At 36 months, the operative levels were solidly fused and the implants were completely resorbed. No adverse tissue response was observed in any animal at any time period. Conclusion. Interbody fusion was achieved using bioresorbable polylactide implants, with no evidence of implant collapse, extrusion, or adverse tissue response to the material. The use of polylactide as a cervical interbody device appears both safe and effective based on these ACDF animal model results

Loss of the Heparan Sulfate Sulfotransferase, Ndst1, in Mammary Epithelial Cells Selectively Blocks Lobuloalveolar Development in Mice

Considerable evidence indicates that heparan sulfate is essential for the development of tissues consisting of branching ducts and tubules. However, there are few examples where specific sulfate residues regulate a specific stage in the formation of such tissues.We examined the role of heparan sulfation in mammary gland branching morphogenesis, lactation and lobuloalveolar development by inactivation of heparan sulfate GlcNAc N-deacetylase/N-sulfotransferase genes (Ndst) in mammary epithelial cells using the Cre-loxP system. Ndst1 deficiency resulted in an overall reduction in glucosamine N-sulfation and decreased binding of FGF to mammary epithelial cells in vitro and in vivo. Mammary epithelia lacking Ndst1 underwent branching morphogenesis, filling the gland with ductal tissue by sexual maturity to the same extent as wildtype epithelia. However, lobuloalveolar expansion did not occur in Ndst1-deficient animals, resulting in insufficient milk production to nurture newly born pups. Lactational differentiation of isolated mammary epithelial cells occurred appropriately via stat5 activation, further supporting the notion that the lack of milk production was due to lack of expansion of the lobuloalveoli.These findings demonstrate a selective, highly penetrant, cell autonomous effect of Ndst1-mediated sulfation on lobuloalveolar development

SWOG S1400B (NCT02785913), a Phase II Study of GDC-0032 (Taselisib) for Previously Treated PI3K-Positive Patients with Stage IV Squamous Cell Lung Cancer (Lung-MAP Sub-Study).

BackgroundS1400B is a biomarker-driven Lung-MAP substudy evaluating the phosphatidylinositol 3-kinase (PI3K) inhibitor taselisib (GDC-0032) in patients with PI3K pathway-activated squamous NSCLC (sqNSCLC).MethodsEligible patients had tumoral phosphatidylinositol-4,5-biphosphate 3 kinase catalytic subunit alpha (PIK3CA) alterations by next-generation sequencing and disease progression after at least one line of platinum-based therapy. Patients received 4-mg taselisib orally daily. The primary analysis population (PAP) was a subset of patients having substitution mutations believed to be associated with clinical benefit of PI3K inhibitors. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival and duration of response.ResultsTwenty-six patients treated with taselisib comprised the full evaluable population (FEP); 21 patients comprised the PAP. Median age for patients in the FEP was 68 years (range: 53-83 years), 19 were male (73%). The study was closed for futility at interim analysis with one responder in the PAP (5% response rate, 95% confidence interval [CI]: 0%-24%). Two possibly treatment-related deaths (one respiratory failure, one cardiac arrest) were observed; one patient had grades 4 and 11 had grade 3 adverse events. Median progression-free survival and overall survival in the PAP group were 2.9 months (95% CI: 1.8-4.0 mo) and 5.9 months (95% CI: 4.2-7.8 mo), respectively. These numbers were nearly the same in the FEP.ConclusionsStudy S1400B evaluating taselisib in PIK3CA-altered sqNSCLC failed to meet its primary endpoint and was closed after an interim futility analysis. The trial is unique in cataloguing the diversity of PIK3CA mutations in sqNSCLC

Evaluating Connectivity between Marine Protected Areas Using CODAR High-Frequency Radar

To investigate the connectivity between central California marine protected areas (MPAs), back-projections were calculated using the network of high-frequency (HF) radar ocean surface current mapping stations operated along the California coast by the member institutions of the Coastal Ocean Currents Monitoring Program with funding provided by California voters through Propositions 40 & 50 and administered by the State Coastal Conservancy. Trajectories of 1 km resolution grids of water particles were back-projected from ten MPAs each hour, out through 40 days in the past, from each day in 2008, producing a map of where surface waters travel over a 40-day period to reach the MPAs - and visualizations of the length of time the waters travel along these paths. By comparing the travel times of those back-projected track-points that crossed between MPA regions, the connection time between MPAs along the State\u27s central coast was assessed. Repeating these calculations resulted in a connectivity matrix between the MPAs in the region, and may be useful for assessing connectivity for the important invertebrate and fish larvae that are restricted to the surface ocean during a fraction of their lifecycle

Author Correction: A population-specific reference panel empowers genetic studies of Anabaptist populations.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

The Structure of the Local Interstellar Medium V: Electron Densities

We present a comprehensive survey of CII* absorption detections toward stars within 100 pc in order to measure the distribution of electron densities present in the local interstellar medium (LISM). Using high spectral resolution observations of nearby stars obtained by GHRS and STIS onboard the Hubble Space Telescope, we identify 13 sight lines with 23 individual CII* absorption components, which provide electron density measurements, the vast majority of which are new. We employ several strategies to determine more accurate CII column densities from the saturated CII resonance line, including, constraints of the line width from the optically thin CII* line, constraints from independent temperature measurements of the LISM gas based on line widths of other ions, and third, using measured SII column densities as a proxy for CII column densities. The sample of electron densities appears consistent with a log-normal distribution and an unweighted mean value of n_e(CII_SII) = 0.11^+0.10_-0.05 cm^-3. Seven individual sight lines probe the Local Interstellar Cloud (LIC), and all present a similar value for the electron density, with a weighted mean of n_e(LIC) = 0.12 +/- 0.04 cm^-3. The Hyades Cloud, a decelerated cloud at the leading edge of the platoon of LISM clouds, has a significantly higher electron density than the LIC. Observed toward G191-B2B, the high electron density may be caused by the lack of shielding from such a strong radiation source. Given some simple assumptions, the range of observed electron densities translates into a range of thermal pressures, P/k = 3300^+5500_-1900 K cm^-3. This work greatly expands the number of electron density measurements and provides important constraints on the ionization, abundance, and evolutionary models of the local interstellar medium. (abridged)Comment: 41 pages, 9 figures; Accepted for publication in Ap

Associations of HDL metrics with coronary artery calcium score and density among women traversing menopause

The cardioprotective association of high-density lipoprotein cholesterol (HDL-C) may vary by menopause stage or estradiol level. We tested whether associations of comprehensive HDL metrics (HDL subclasses, phospholipid and triglyceride content, and HDL cholesterol efflux capacity [HDL-CEC]) with coronary artery calcium (CAC) score and density vary by menopause stage or estradiol level in women transitioning through menopause. Participants (N = 294; mean age [SD]: 51.3 [2.9]) had data on HDL metrics and CAC measures at one or two time points during the menopause transition. Generalized estimating equations were used for analyses. Effect modifications by menopause stage or estradiol level were tested in multivariable models. In adjusted models, menopause stage modified the associations of specific HDL metrics with CAC measures. Higher small HDL particles (HDL-P) concentrations (p-interaction = 0.008) and smaller HDL size (p-interaction = 0.02) were associated with greater odds of CAC presence in late perimenopause than in pre/early perimenopause stage. Women in the highest estradiol tertile, but not the lower tertiles, showed a protective association of small HDL-P with CAC presence (p-interaction = 0.007). Lower large HDL-P concentrations (p-interaction = 0.03) and smaller HDL size (p-interaction = 0.03) were associated with lower CAC density in late perimenopause than in postmenopause stage. Associations of HDL phospholipid and triglyceride content and HDL-CEC with CAC measures did not vary by menopause stage or estradiol level. We concluded that HDL subclasses may impact the likelihood of CAC presence and the stability of coronary plaque differently over the menopause transition. Endogenous estradiol levels may contribute to this observation

Phase-ordering dynamics of the Gay-Berne nematic liquid crystal

Phase-ordering dynamics in nematic liquid crystals has been the subject of much active investigation in recent years in theory, experiments and simulations. With a rapid quench from the isotropic to nematic phase a large number of topological defects are formed and dominate the subsequent equilibration process. We present here the results of a molecular dynamics simulation of the Gay-Berne model of liquid crystals after such a quench in a system with 65536 molecules. Twist disclination lines as well as type-1 lines and monopoles were observed. Evidence of dynamical scaling was found in the behavior of the spatial correlation function and the density of disclination lines. However, the behavior of the structure factor provides a more sensitive measure of scaling, and we observed a crossover from a defect dominated regime at small values of the wavevector to a thermal fluctuation dominated regime at large wavevector.Comment: 18 pages, 16 figures, animations available at http://www.physics.brown.edu/Users/faculty/pelcovits/lc/coarsening.htm

Metalorganic Vapor-Phase Epitaxial Growth and Characterization of Quaternary AlGaInN

In this letter we report the growth (by MOVPE) and characterization of quaternary AlGaInN. A combination of PL, high-resolution XRD, and RBS characterizations enables us to explore and delineate the contours of equil-emission energy and lattice parameters as functions of the quaternary compositions. The observation of room temperature PL emission as short as 351nm (with 20% Al and 5% In) renders initial evidence that the quaternary could be used to provide confinement for GaInN (and possibly GaN). AlGaInN/GdnN MQW heterostructures have also been grown; both x-ray diffraction and PL measurement suggest the possibility of incorporating this quaternary into optoelectronic devices

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap