3D Printing of a Polymer Bioactive Glass Composite for Bone Repair

A major limitation of synthetic bone repair is insufficient vascularization of the interior region of the scaffold. In this study, we investigated the 3D printing of adipose derived mesenchymal stem cells (AD-MSCs) with polycaprolactone (PCL)/bioactive glass composite in a single process. This offered a three-dimensional environment for complex and dynamic interactions that govern the cell’s behavior in vivo. Borate based bioactive (13-93B3) glass of different concentrations (10 to 50 weight %) was added to a mixture of PCL and organic solvent to make an extrudable paste. AD-MSCs suspended in Matrigel was extruded as droplets using a second syringe. Scaffolds measuring 10x10x1 mm3 in overall dimensions with a filament width of ~500 μm and pore sizes ranging from 100 to 200 μm were fabricated. Strut formability dependence on paste viscosity, scaffold integrity, and printing parameters for droplets of ADMSCs suspended in Matrigel were investigated

Enhanced magnetocaloric effect in frustrated magnets

The magnetothermodynamics of strongly frustrated classical Heisenberg antiferromagnets on kagome, garnet, and pyrochlore lattices is examined. The field induced adiabatic temperature change (dT/dH)_S is significantly larger for such systems compared to ordinary non-frustrated magnets and also exceeds the cooling rate of an ideal paramagnet in a wide range of fields. An enhancement of the magnetocaloric effect is related to presence of a macroscopic number of soft modes in frustrated magnets below the saturation field. Theoretical predictions are confirmed with extensive Monte Carlo simulations.Comment: 7 page

The genomic landscape across 474 surgically accessible epileptogenic human brain lesions

Understanding the exact molecular mechanisms involved in the etiology of epileptogenic pathologies with or without tumor activity is essential for improving treatment of drug-resistant focal epilepsy. Here, we characterize the landscape of somatic genetic variants in resected brain specimens from 474 individuals with drug-resistant focal epilepsy using deep whole-exome sequencing (>350×) and whole-genome genotyping. Across the exome, we observe a greater number of somatic single-nucleotide variants (SNV) in low-grade epilepsy-associated tumors (LEAT; 7.92 ± 5.65 SNV) than in brain tissue from malformations of cortical development (MCD; 6.11 ± 4 SNV) or hippocampal sclerosis (HS; 5.1 ± 3.04 SNV). Tumor tissues also had the largest number of likely pathogenic variant carrying cells. LEAT had the highest proportion of samples with one or more somatic copy number variants (CNV; 24.7%), followed by MCD (5.4%) and HS (4.1%). Recurring somatic whole chromosome duplications affecting Chromosome 7 (16.8%), chromosome 5 (10.9%), and chromosome 20 (9.9%) were observed among LEAT. For germline variant-associated MCD genes such as TSC2, DEPDC5, and PTEN, germline SNV were frequently identified within large loss of heterozygosity regions, supporting the recently proposed 'second hit' disease mechanism in these genes. We detect somatic variants in twelve established lesional epilepsy genes and demonstrate exome-wide statistical support for three of these in the etiology of LEAT (e.g., BRAF) and MCD (e.g., SLC35A2 and MTOR). We also identify novel significant associations for PTPN11 with LEAT and NRAS Q61 mutated protein with a complex MCD characterized by polymicrogyria and nodular heterotopia. The variants identified in NRAS are known from cancer studies to lead to hyperactivation of NRAS, which can be targeted pharmacologically. We identify large recurrent 1q21-q44 duplication including AKT3 in association with focal cortical dysplasia type 2a with hyaline astrocytic inclusions, another rare and possibly under-recognized brain lesion. The clinical genetic analyses showed that the numbers of somatic SNV across the exome and the fraction of affected cells were positively correlated with the age at seizure onset and surgery in individuals with LEAT. In summary, our comprehensive genetic screen sheds light on the genome-scale landscape of genetic variants in epileptic brain lesions, informs the design of gene panels for clinical diagnostic screening, and guides future directions for clinical implementation of epilepsy surgery genetics

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09, Qapzola) Intravesical Instillation Post Transurethral Resection of Bladder Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer

Contains fulltext : 195581.pdf (Publisher’s version ) (Open Access)Background: Guidelines recommend a single postoperative instillation of intravesical chemotherapy within 24 hours of transurethral resection of bladder tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC) to reduce recurrence risk. Objective: To evaluate the 2-year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1-G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo. Methods: Two nearly identical Phase 3, multinational, randomized, double-blind, placebo-controlled trials were conducted in patients with histologically confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of a single instillation of apaziquone post-TURBT. A single intravesical instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6 hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and time to recurrence (TTR) respectively. Results: Overall, 1614 patients were enrolled, including 1146 patients in the Target Population. Individually, the two studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7% vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc subgroup analysis was performed by time window of drug instillation post-TURBT. Patients who had drug instilled in the time window 60+/-30 minutes post-TURBT demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR = 0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was well tolerated with minimal toxicity. Conclusions: Two identical Phase 3 studies supported the safety of apaziquone (4 mg/40 mL) administered as a single intravesical instillation post-TURBT and identified efficacy when instilled within 60+/-30-minutes time interval which requires further study

Social barriers in ecological landscapes: the social resistance hypothesis

Across animal societies, individuals invest time and energy in social interactions. The social landscape that emerges from these interactions can then generate barriers that limit the ability of individuals to disperse to, and reproduce in, groups or populations. Therefore, social barriers can contribute to the difference between the physical capacity for movement through the habitat and subsequent gene flow. We call this contributing effect ‘social resistance’. We propose that social resistance can act as an agent of selection on key life-history strategies and promote the evolution of social strategies that facilitate effective dispersal. By linking landscape genetics and social behaviour, the social resistance hypothesis generates predictions integrating dispersal, connectivity, and life-history evolution.Nicolette C.Armansin, Adam J.Stow, Mauricio Cantor, Stephan T.Leu, James A.Klarevas-Irb