Extent of stacking disorder in diamond

Hexagonal diamond has been predicted computationally to display extraordinary physical properties including a hardness that exceeds cubic diamond. However, a recent electron microscopy study has shown that so-called hexagonal diamond samples are in fact not discrete materials but faulted and twinned cubic diamond. We now provide a quantitative analysis of cubic and hexagonal stacking in diamond samples by analysing X-ray diffraction data with the DIFFaX software package. The highest fractions of hexagonal stacking we find in materials which were previously referred to as hexagonal diamond are below 60%. The remainder of the stacking sequences are cubic. We show that the cubic and hexagonal sequences are interlaced in a complex way and that naturally occurring Lonsdaleite is not a simple phase mixture of cubic and hexagonal diamond. Instead, it is structurally best described as stacking disordered diamond. The future experimental challenge will be to prepare diamond samples beyond 60% hexagonality and towards the so far elusive 'perfect' hexagonal diamond

Return to Sport and Athletic Function in an Active Population After Primary Arthroscopic Labral Reconstruction of the Hip

Background: Labral reconstruction has been advocated as an alternative to debridement for the treatment of irreparable labral tears, showing favorable short-term results. However, literature is scarce regarding outcomes and return to sport in the nonelite athletic population. Purpose: To report minimum 1-year clinical outcomes and the rate of return to sport in athletic patients who underwent primary hip arthroscopy with labral reconstruction in the setting of femoroacetabular impingement syndrome and irreparable labral tears. Study Design: Case series; Level of evidence, 4. Methods: Data were prospectively collected and retrospectively analyzed for patients who underwent an arthroscopic labral reconstruction between August 2012 and December 2017. Patients were included if they identified as an athlete (high school, college, recreational, or amateur); had follow-up on the following patient-reported outcomes (PROs): modified Harris Hip Score (mHHS), Nonarthritic Hip Score (NAHS), Hip Outcome Score–Sport Specific Subscale (HOS-SSS), and visual analog scale (VAS); and completed a return-to-sport survey at 1 year postoperatively. Patients were excluded if they underwent any previous ipsilateral hip surgery, had dysplasia, or had prior hip conditions. The proportions of patients who achieved the minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) for mHHS and HOS-SSS were calculated. Statistical significance was set at P =.05. Results: There were 32 (14 females) athletes who underwent primary arthroscopic labral reconstruction during the study period. The mean age and body mass index of the group were 40.3 years (range, 15.5-58.7 years) and 27.9 kg/m2 (range, 19.6-40.1 kg/m2), respectively. The mean follow-up was 26.4 months (range, 12-64.2 months). All patients demonstrated significant improvement in mHHS, NAHS, HOS-SSS, and VAS (P \u3c.001) at latest follow-up. Additionally, 84.4% achieved MCID and 81.3% achieved PASS for mHHS, and 87.5% achieved MCID and 75% achieved PASS for HOS-SSS. VAS pain scores decreased from 4.4 to 1.8, and the satisfaction with surgery was 7.9 out of 10. The rate of return to sport was 78%. Conclusion: At minimum 1-year follow-up, primary arthroscopic labral reconstruction, in the setting of femoroacetabular impingement syndrome and irreparable labral tears, was associated with significant improvement in PROs in athletic populations. Return to sport within 1 year of surgery was 78%

Accounting for autocorrelation in multi-drug resistant tuberculosis predictors using a set of parsimonious orthogonal eigenvectors aggregated in geographic space

Spatial autocorrelation is problematic for classical hierarchical cluster detection tests commonly used in multidrug resistant tuberculosis (MDR-TB) analyses as considerable random error can occur. Therefore, when MDR-TB clusters are spatially autocorrelated the assumption that the clusters are independently random is invalid. In this research, a product moment correlation coefficient (i.e. the Moran’s coefficient) was used to quantify local spatial variation in multiple clinical and environmental predictor variables sampled in San Juan de Lurigancho, Lima, Peru. Initially, QuickBird (spatial resolution = 0.61 m) data, encompassing visible bands and the near infra-red bands, were selected to synthesize images of land cover attributes of the study site. Data of residential addresses of individual patients with smear-positive MDR-TB were geocoded, prevalence rates calculated and then digitally overlaid onto the satellite data within a 2 km buffer of 31 georeferenced health centres, using a 10 m2 grid-based algorithm. Geographical information system (GIS)- gridded measurements of each health centre were generated based on preliminary base maps of the georeferenced data aggregated to block groups and census tracts within each buffered area. A three-dimensional model of the study site was constructed based on a digital elevation model (DEM) to determine terrain covariates associated with the sampled MDRTB covariates. Pearson’s correlation was used to evaluate the linear relationship between the DEM and the sampled MDR-TB data. A SAS/GIS® module was then used to calculate univariate statistics and to perform linear and non-linear regression analyses using the sampled predictor variables. The estimates generated from a global autocorrelation analyses were then spatially decomposed into empirical orthogonal bases, using a negative binomial regression with a non-homogeneous mean. Results of the DEM analyses indicated a statistically non-significant, linear relationship between georeferenced health centres and the sampled covariate elevation. The data exhibited positive spatial autocorrelation and the decomposition of Moran’s coefficient into uncorrelated, orthogonal map pattern components which revealed global spatial heterogeneities necessary to capture latent autocorrelation in the MDR-TB model. It was thus shown that Poisson regression analyses and spatial eigenvector mapping can elucidate the mechanics of MDR-TB transmission by prioritizing clinical and environmental-sampled predictor variables for identifying high risk populations

SLC19A1 transports immunoreactive cyclic dinucleotides.

The accumulation of DNA in the cytosol serves as a key immunostimulatory signal associated with infections, cancer and genomic damage1,2. Cytosolic DNA triggers immune responses by activating the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway3. The binding of DNA to cGAS activates its enzymatic activity, leading to the synthesis of a second messenger, cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP)4-7. This cyclic dinucleotide (CDN) activates STING8, which in turn activates the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), promoting the transcription of genes encoding type I interferons and other cytokines and mediators that stimulate a broader immune response. Exogenous 2'3'-cGAMP produced by malignant cells9 and other CDNs, including those produced by bacteria10-12 and synthetic CDNs used in cancer immunotherapy13,14, must traverse the cell membrane to activate STING in target cells. How these charged CDNs pass through the lipid bilayer is unknown. Here we used a genome-wide CRISPR-interference screen to identify the reduced folate carrier SLC19A1, a folate-organic phosphate antiporter, as the major transporter of CDNs. Depleting SLC19A1 in human cells inhibits CDN uptake and functional responses, and overexpressing SLC19A1 increases both uptake and functional responses. In human cell lines and primary cells ex vivo, CDN uptake is inhibited by folates as well as two medications approved for treatment of inflammatory diseases, sulfasalazine and the antifolate methotrexate. The identification of SLC19A1 as the major transporter of CDNs into cells has implications for the immunotherapeutic treatment of cancer13, host responsiveness to CDN-producing pathogenic microorganisms11 and-potentially-for some inflammatory diseases

Non-uniform central airways ventilation model based on vascular segmentation

Improvements in the understanding of the physiology of the central airways require an appropriate representation of the non-uniform ventilation at its terminal branches. This paper proposes a new technique for estimating the non-uniform ventilation at the terminal branches by modelling the volume change of their distal peripheral airways, based on vascular segmentation. The vascular tree is used for sectioning the dynamic CT-based 3D volume of the lung at 11 time points over the breathing cycle of a research animal. Based on the mechanical coupling between the vascular tree and the remaining lung tissues, the volume change of each individual lung segment over the breathing cycle was used to estimate the non-uniform ventilation of its associated terminal branch. The 3D lung sectioning technique was validated on an airway cast model of the same animal pruned to represent the truncated dynamic CT based airway geometry. The results showed that the 3D lung sectioning technique was able to estimate the volume of the missing peripheral airways within a tolerance of 2%. In addition, the time-varying non-uniform ventilation distribution predicted by the proposed sectioning technique was validated against CT measurements of lobar ventilation and showed good agreement. This significant modelling advance can be used to estimate subject-specific non-uniform boundary conditions to obtain subject-specific numerical models of the central airway flow

Resonance Broadening and Heating of Charged Particles in Magnetohydrodynamic Turbulence

The heating, acceleration, and pitch-angle scattering of charged particles by MHD turbulence are important in a wide range of astrophysical environments, including the solar wind, accreting black holes, and galaxy clusters. We simulate the interaction of high-gyrofrequency test particles with fully dynamical simulations of subsonic MHD turbulence, focusing on the parameter regime with beta ~ 1, where beta is the ratio of gas to magnetic pressure. We use the simulation results to calibrate analytical expressions for test particle velocity-space diffusion coefficients and provide simple fits that can be used in other work. The test particle velocity diffusion in our simulations is due to a combination of two processes: interactions between particles and magnetic compressions in the turbulence (as in linear transit-time damping; TTD) and what we refer to as Fermi Type-B (FTB) interactions, in which charged particles moving on field lines may be thought of as beads spiralling around moving wires. We show that test particle heating rates are consistent with a TTD resonance which is broadened according to a decorrelation prescription that is Gaussian in time. TTD dominates the heating for v_s >> v_A (e.g. electrons), where v_s is the thermal speed of species s and v_A is the Alfven speed, while FTB dominates for v_s << v_A (e.g. minor ions). Proton heating rates for beta ~ 1 are comparable to the turbulent cascade rate. Finally, we show that velocity diffusion of collisionless, large gyrofrequency particles due to large-scale MHD turbulence does not produce a power-law distribution function.Comment: 20 pages, 15 figures; accepted by The Astrophysical Journal; added clarifying appendices, but no major changes to result

Replication-incompetent influenza A viruses armed with IFN-γ effectively mediate immune modulation and tumor destruction in mice harboring lung cancer

Low pathogenic influenza A viruses (IAVs) have shown promising oncolytic potential in lung cancer-bearing mice. However, as replication-competent pathogens, they may cause side effects in immunocompromised cancer patients. To circumvent this problem, we genetically engineered nonreplicating IAVs lacking the hemagglutinin (HA) gene (ΔHA IAVs), but reconstituted the viral envelope with recombinant HA proteins to allow a single infection cycle. To optimize the therapeutic potential and improve immunomodulatory properties, these replication-incompetent IAVs were complemented with a murine interferon-gamma (mIFN-γ) gene. After intratracheal administration to transgenic mice that develop non-small cell lung cancer (NSCLC), the ΔHA IAVs induced potent tumor destruction. However, ΔHA IAVs armed with mIFN-γ exhibited an even stronger and more sustained effect, achieving 85% tumor reduction at day 12 postinfection. In addition, ΔHA-mIFN-γ viruses were proven to be efficient in recruiting and activating natural killer cells and macrophages from the periphery and in inducing cytotoxic T lymphocytes. Most important, both viruses, and particularly IFN-γ-encoding viruses, activated tumor-associated alveolar macrophages toward a proinflammatory M1-like phenotype. Therefore, replication-incompetent ΔHA-mIFN-γ-IAVs are safe and efficient oncolytic viruses that additionally exhibit immune cell activating properties and thus represent a promising innovative therapeutic option in the fight against NSCLC