Thermal conductivity of hexagonal BC2P – a first-principles study

In this work, we report a high thermal conductivity (k) of 162 W m⁻¹ K⁻¹ and 52 W m⁻¹ K⁻¹ at room temperature, along the directions perpendicular and parallel to the c-axis, respectively, of bulk hexagonal BC₂P (h-BC₂P), using first-principles calculations. We systematically investigate elastic constants, phonon group velocities, phonon linewidths and mode thermal conductivity contributions of transverse acoustic (TA), longitudinal acoustic (LA) and optical phonons. Interestingly, optical phonons are found to make a large contribution of 30.1% to the overall k along a direction perpendicular to the c-axis at 300 K. BC₂P is also found to exhibit high thermal conductivity at nanometer length scales. At 300 K, a high k value of ∼47 W m⁻¹ K⁻¹ is computed for h-BC₂P at a nanometer length scale of 50 nm, providing avenues for achieving efficient nanoscale heat transfer.

In this work, we report a high thermal conductivity (k) of 162 W m⁻¹ K⁻¹ and 52 W m⁻¹ K⁻¹ at room temperature, along the directions perpendicular and parallel to the c-axis, respectively, of bulk hexagonal BC₂P (h-BC₂P), using first-principles calculations.     

A proinvasive role for the Ca2+‐activated K+ channel KCa3.1 in malignant glioma

Glioblastoma multiforme are highly motile primary brain tumors. Diffuse tissue invasion hampers surgical resection leading to poor patient prognosis. Recent studies suggest that intracellular Ca²⁺ acts as a master regulator for cell motility and engages a number of downstream signals including Ca²⁺‐activated ion channels. Querying the REepository of Molecular BRAin Neoplasia DaTa (REMBRANDT), an annotated patient gene database maintained by the National Cancer Institute, we identified the intermediate conductance Ca²⁺‐activated K⁺ channels, KCa3.1, being overexpressed in 32% of glioma patients where protein expression significantly correlated with poor patient survival. To mechanistically link KCa3.1 expression to glioma invasion, we selected patient gliomas that, when propagated as xenolines in vivo, present with either high or low KCa3.1 expression. In addition, we generated U251 glioma cells that stably express an inducible knockdown shRNA to experimentally eliminate KCa3.1 expression. Subjecting these cells to a combination of in vitro and in situ invasion assays, we demonstrate that KCa3.1 expression significantly enhances glioma invasion and that either specific pharmacological inhibition with TRAM‐34 or elimination of the channel impairs invasion. Importantly, after intracranial implantation into SCID mice, ablation of KCa3.1 with inducible shRNA resulted in a significant reduction in tumor invasion into surrounding brain in vivo. These results show that KCa3.1 confers an invasive phenotype that significantly worsens a patient's outlook, and suggests that KCa3.1 represents a viable therapeutic target to reduce glioma invasion. GLIA 2014;62:971–981     

Plasmapheresis Eliminates the Negative Impact of AAV Antibodies on Microdystrophin Gene Expression Following Vascular Delivery

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.     

Gallbladder Lesions Identified on Ultrasound. Lessons from the Last 10?Years

Background

Possible mass lesions identified on ultrasound (US) of the gallbladder may prompt an aggressive surgical intervention due to the possibility of a malignant neoplasm.

Aim

This study aims to utilize a large modern series of patients with gallbladder lesions identified on US to evaluate imaging characteristics consistent with malignancy.

Methods

A retrospective review was conducted of gallbladder ultrasound reports and clinicopathologic data of patients with a mass identified on US.

Results

Approximately 59,271 abdominal ultrasounds and 9,117 cholecystectomies were performed between February 2000 and February 2010. We identified 213 patients with a questionable gallbladder neoplasm on ultrasonography who underwent surgical exploration. Median age was 52?years (range?=?11?C87?years) and 147 (69%) were females. Final pathology demonstrated no neoplasm in 130 patients (61%), while 32 patients (15%) had a wall adenomyoma, 36 (17%) had a polyp (five of which were malignant), 14 (7%) had an adenocarcinoma not arising from a polyp, and one patient had a cystic papillary neoplasm. The smaller the lesion, the more likely it was to be a pseudo-mass. For lesions measuring <5?mm on US, 83% had no lesion found on final pathology. Significant predictors of malignancy were age >52?years (p?p?=?0.004), size >9?mm (p?p?5?mm (p?Conclusions Despite improvements in imaging, most apparent lesions measuring <5?mm on US are not identified in the surgical specimen. US size >9?mm, age >52?years, US suggestion of invasion at the liver interface, and wall thickening >5?mm, especially in the presence of gallstones, should raise the suspicion of malignancy.     

Biomechanical investigation of a novel integrated device for intra-articular stabilization of the C1-C2 (atlantoaxial) joint

Background contextThe anatomy of the atlantoaxial joint makes stabilization at this level challenging. Current techniques that use transarticular screw fixation (Magerl) or segmental screw fixation (Harms) give dramatically improved stability but risk damage to the vertebral artery. A novel integrated device was designed and developed to obtain intra-articular stabilization via primary interference fixation within the C1–C2 lateral mass articulation.PurposeTo assess the atlantoaxial stability achieved with a novel integrated device when compared with the intact, destabilized, and stabilized state using the Harms technique.Study designA biomechanical study of implants in human cadaveric cervical spines.MethodsSix human cadaveric specimens were used. Biomechanical testing was performed with moment control in flexion-extension, lateral bending, and axial rotation. Range of motion (ROM) was measured in the intact state, after both destabilization by creation of a Type II odontoid peg fracture and sequential stabilization using the integrated device and the Harms technique.ResultsMean flexion-extension ROM of the intact specimens at C1–C2 was 14.1°±2.9°. Destabilization increased the ROM to 31.6°±4.6°. Instrumentation with the Harms technique reduced flexion-extension motion to 4.0°±1.4° (p<.01). The integrated device reduced flexion-extension motion to 3.6°±1.8° (p<.01). In lateral bending, the respective mean angular motions were 1.8°±1.1°, 14.1°±5.8°, 1.4°±0.7°, and 0.4°±0.3° for the intact destabilized Harms technique and integrated device. For axial rotation, the respective mean values were 67.3°±13.8°, 74.2°±16.1°, 1.4°±0.7° and 0.9°±0.7°. Both the Harms technique and integrated device significantly reduced motion compared with the destabilized spine in flexion-extension, lateral bending, and axial rotation (p<.05). Direct comparison of the Harms technique and the integrated device revealed no significant difference (p>.10).ConclusionsThe integrated device resulted in interference fixation at the C1–C2 lateral mass joints with comparable stability to the Harms technique. Perceived advantages with the integrated device include avoidance of fixation below the C2 lateral mass where the vertebral artery is susceptible to injury, and access to the C1 screw entry point through the blade of the integrated device avoiding extended dissection superior to the C2 nerve root and its surrounding venous plexus.