fMRI biomarkers of social cognitive skills training in psychosis: Extrinsic and intrinsic functional connectivity.

Social cognitive skills training interventions for psychotic disorders have shown improvement in social cognitive performance tasks, but little was known about brain-based biomarkers linked to treatment effects. In this pilot study, we examined whether social cognitive skills training could modulate extrinsic and intrinsic functional connectivity in psychosis using functional magnetic resonance imaging (fMRI). Twenty-six chronic outpatients with psychotic disorders were recruited from either a Social Cognitive Skills Training (SCST) or an activity- and time-matched control intervention. At baseline and the end of intervention (12 weeks), participants completed two social cognitive tasks: a Facial Affect Matching task and a Mental State Attribution Task, as well as resting-state fMRI (rs-fMRI). Extrinsic functional connectivity was assessed using psychophysiological interaction (PPI) with amygdala and temporo-parietal junction as a seed region for the Facial Affect Matching Task and the Mental State Attribution task, respectively. Intrinsic functional connectivity was assessed with independent component analysis on rs-fMRI, with a focus on the default mode network (DMN). During the Facial Affect Matching task, we observed stronger PPI connectivity in the SCST group after intervention (compared to baseline), but no treatment-related change in the Control group. Neither group showed treatment-related changes in PPI connectivity during the Mental State Attribution task. During rs-fMRI, we found treatment-related changes in the DMN in the SCST group, but not in Control group. This study found that social cognitive skills training modulated both extrinsic and intrinsic functional connectivity in individuals with psychotic disorders after a 12-week intervention. These findings suggest treatment-related changes in functional connectivity as a potential brain-based biomarker of social cognitive skills training

Multiply Folded Graphene

The folding of paper, hide, and woven fabric has been used for millennia to achieve enhanced articulation, curvature, and visual appeal for intrinsically flat, two-dimensional materials. For graphene, an ideal two-dimensional material, folding may transform it to complex shapes with new and distinct properties. Here, we present experimental results that folded structures in graphene, termed grafold, exist, and their formations can be controlled by introducing anisotropic surface curvature during graphene synthesis or transfer processes. Using pseudopotential-density functional theory calculations, we also show that double folding modifies the electronic band structure of graphene. Furthermore, we demonstrate the intercalation of C60 into the grafolds. Intercalation or functionalization of the chemically reactive folds further expands grafold's mechanical, chemical, optical, and electronic diversity.Comment: 29 pages, 10 figures (accepted in Phys. Rev. B

Mandated Marketing Programs For California Commodities

Agricultural and Food Policy, Marketing,

Prevalence and clinical features of patients with concurrent HBsAg and anti‐HBs: Evaluation of the hepatitis B research network cohort

The prevalence of concurrent HBsAg and anti‐HBs in plasma of persons with chronic hepatitis B virus (HBV) infection is variable and its clinical significance enigmatic. We examined the prevalence and clinical and virological features of concurrent HBsAg and anti‐HBs in children and adults with chronic HBV infection living in North America. A total of 1462 HBsAg positive participants in the Hepatitis B Research Network paediatric and adult cohorts were included (median age 41 (range 4‐80) years, 48% female, 11% white, 13% black, 73% Asians). Only 18 (1.2%) were found to be anti‐HBs positive (≥10 mIU/mL) at initial study evaluation. Distributions of sex, race, HBV genotype and ALT were similar between participants with and without concurrent anti‐HBs. Those who were anti‐HBs positive appeared to be older (median age 50 vs 41 years, P = .06), have lower platelet counts (median 197 vs 222 × 103/mm3, P = .07) and have higher prevalence of HBeAg (44% vs 26%, P = .10). They also had lower HBsAg levels (median 2.0 vs 3.5 log10 IU/mL, P = .02). Testing of follow‐up samples after a median of 4 years (range 1‐6) in 12 of the 18 participants with initial concurrent anti‐HBs showed anti‐HBs became undetectable in 6, decreased to <10 mIU/mL in 1 and remained positive in 5 participants. Two patients lost HBsAg during follow‐up. In conclusion, prevalence of concurrent HBsAg and anti‐HBs was low at 1.2%, with anti‐HBs disappearing in some during follow‐up, in this large cohort of racially diverse children and adults with chronic HBV infection living in North America. Presence of concurrent HBsAg and anti‐HBs did not identify a specific phenotype of chronic hepatitis B, nor did it appear to affect clinical outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156489/3/jvh13312.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156489/2/jvh13312-sup-0001-FigS1-S3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156489/1/jvh13312_am.pd

Blood and tissue biomarker analysis in dogs with osteosarcoma treated with palliative radiation and intra-tumoral autologous natural killer cell transfer.

We have previously reported radiation-induced sensitization of canine osteosarcoma (OSA) to natural killer (NK) therapy, including results from a first-in-dog clinical trial. Here, we report correlative analyses of blood and tissue specimens for signals of immune activation in trial subjects. Among 10 dogs treated with palliative radiotherapy (RT) and intra-tumoral adoptive NK transfer, we performed ELISA on serum cytokines, flow cytometry for immune phenotype of PBMCs, and PCR on tumor tissue for immune-related gene expression. We then queried The Cancer Genome Atlas (TCGA) to evaluate the association of cytotoxic/immune-related gene expression with human sarcoma survival. Updated survival analysis revealed five 6-month survivors, including one dog who lived 17.9 months. Using feeder line co-culture for NK expansion, we observed maximal activation of dog NK cells on day 17-19 post isolation with near 100% expression of granzyme B and NKp46 and high cytotoxic function in the injected NK product. Among dogs on trial, we observed a trend for higher baseline serum IL-6 to predict worse lung metastasis-free and overall survival (P = 0.08). PCR analysis revealed low absolute gene expression of CD3, CD8, and NKG2D in untreated OSA. Among treated dogs, there was marked heterogeneity in the expression of immune-related genes pre- and post-treatment, but increases in CD3 and CD8 gene expression were higher among dogs that lived &gt; 6 months compared to those who did not. Analysis of the TCGA confirmed significant differences in survival among human sarcoma patients with high and low expression of genes associated with greater immune activation and cytotoxicity (CD3e, CD8a, IFN-γ, perforin, and CD122/IL-2 receptor beta). Updated results from a first-in-dog clinical trial of palliative RT and autologous NK cell immunotherapy for OSA illustrate the translational relevance of companion dogs for novel cancer therapies. Similar to human studies, analyses of immune markers from canine serum, PBMCs, and tumor tissue are feasible and provide insight into potential biomarkers of response and resistance

Newtonian Hydrodynamics of the Coalescence of Black Holes with Neutron Stars I: Tidally locked binaries with a stiff equation of state

We present a detailed study of the hydrodynamical interactions in a Newtonian black hole-neutron star binary during the last stages of inspiral. We consider close binaries which are tidally locked, use a stiff equation of state (with an adiabatic index Gamma=3) throughout, and explore the effect of different initial mass ratios on the evolution of the system. We calculate the gravitational radiation signal in the quadrupole approximation. Our calculations are carried out using a Smooth Particle Hydrodynamics (SPH) code.Comment: Replaces previous version which had figures separate from the text of the paper. Now 47 pages long with 19 embedded figures (the figures are the same, they were renumbered) Uses aaspp4.st

Adhesion of MC3T3-E1 cells to RGD peptides of different flanking residues: Detachment strength and correlation with long-term cellular function

We synthesized a series of RGD peptides and immobilized them to an amine-functional self-assembled monolayer using a modified maleimide-based conjugate technique that minimizes nonspecific interactions. Using a spinning disc apparatus, a trend in the detachment strength (τ50) of RGD peptides of different flanking residues was found: RGDSPK ≻ RGDSVVYGLR ≈ RGDS ≻ RGES. Using blocking monoclonal antibodies, cellular adhesion to the peptides was shown to be primarily α√-integrin-mediated. In contrast, the τ50 value of the cells on fibronectin (Fn)-coated substrates of similar surface density was 6-7 times higher and involved both α5β1 and ανβ3 integrins. Cellular spreading was enhanced on RGD peptides after 1 h when compared to RGE and unmodified substrates. However, no significant differences were observed between the different RGD peptides. Long-term function of MC3T3-E1 cells was also evaluated by measuring alkaline phosphatase (ALP) activity and mineral deposition. Among the four peptides, RGDSPK exhibited the highest level of ALP activity after 11 days and mineralization after 15 days and reached comparable levels as Fn substrates after 15 and 24 days, respectively. These findings collectively illustrate both the advantages and limitations of enhancing cellular adhesion and function by the design of RGD peptides