Predicting opportunities to increase utilization of laparoscopy for rectal cancer

Background: Despite proven safety and efficacy, rates of laparoscopy for rectal cancer in the US are low. With reports of inferiority with laparoscopy compared to open surgery, and movements to develop accredited centers, investigating utilization and predictors of laparoscopy are warranted. Our goal was to evaluate current utilization and identify factors impacting use of laparoscopic surgery for rectal cancer. Methods: The Premier™ Hospital Database was reviewed for elective inpatient rectal cancer resections (1/1/2010–6/30/2015). Patients were identified by ICD-9-CM diagnosis codes, and then stratified into open or laparoscopic approaches by ICD-9-CM procedure codes or billing charge. Logistic multivariable regression identified variables predictive of laparoscopy. The Cochran–Armitage test assessed trend analysis. The main outcome measures were trends in utilization and factors independently associated with use of laparoscopy. Results: 3336 patients were included—43.8% laparoscopic (n = 1464) and 56.2% open (n = 1872). Use of laparoscopy increased from 37.6 to 55.3% during the study period (p < 0.0001). General surgeons performed the majority of all resections, but colorectal surgeons were more likely to approach rectal cancer laparoscopically (41.31 vs. 36.65%, OR 1.082, 95% CI [0.92, 1.27], p < 0.3363). Higher volume surgeons were more likely to use laparoscopy than low-volume surgeons (OR 3.72, 95% CI [2.64, 5.25], p < 0.0001). Younger patients (OR 1.49, 95% CI [1.03, 2.17], p = 0.036) with minor (OR 2.13, 95% CI [1.45, 3.12], p < 0.0001) or moderate illness severity (OR 1.582, 95% CI [1.08, 2.31], p < 0.0174) were more likely to receive a laparoscopic resection. Teaching hospitals (OR 0.842, 95% CI [0.710, 0.997], p = 0.0463) and hospitals in the Midwest (OR 0.69, 95% CI [0.54, 0.89], p = 0.0044) were less likely to use laparoscopy. Insurance status and hospital size did not impact use. Conclusions: Laparoscopy for rectal cancer steadily increased over the years examined. Patient, provider, and regional variables exist, with hospital status, geographic location, and colorectal specialization impacting the likelihood. However, surgeon volume had the greatest influence. These results emphasize training and surgeon-specific outcomes to increase utilization and quality in appropriate cases

Resistive switching and threshold switching behaviors in La 0.1Bi 0.9Fe 1-xCo xO 3 ceramics

The effects of cobalt doping on the electrical conductivity of La 0.1Bi 0.9Fe 1-xCo xO 3 (LBFCO, x=0, 0.01, 0.03) ceramics were investigated. It is found that the leakage current increases with cobalt dopant concentration in LBFCO. On the application of bias voltage LBFCO ceramics with cobalt doping exhibits resistive switching effects at room temperature and threshold switching effects at elevated temperatures (50°C and 80°C). X-ray photoelectron spectroscopy of LBFCO ceramics show that cobalt dopant is bivalent as an acceptor, which induces an enhancement of oxygen vacancy concentration in LBFCO ceramics. Possible mechanisms for both resistive switching and threshold switching effects are discussed on the basis of the interplay of bound ferroelectric charges and mobile charged defects. © 2012 American Institute of Physics.published_or_final_versio

Electrical reliability and leakage mechanisms in highly resistive multiferroic La0.1Bi0.9FeO3 ceramics

Multiferroic La0.1 Bi0.9 FeO3 (LBFO) ceramics with high resistivity were synthesized by using a modified rapid thermal process. The LBFO ceramics show very low leakage and low dielectric loss. Well saturated ferroelectric hysteresis loops and polarization switching currents have been observed. For a maximum applied electric field of 145 kV/cm, the remanent polarization is 17.8 μC/ cm2 and the coercive filed is 75 kV/cm. The dominant conduction mechanism in the LBFO ceramics has been found to be the space-charge-limited current mechanism rather than the thermal excitation mechanism. Electrical reliability related to the fatigue and polarization retention of the LBFO ceramics has also been discussed with the leakage mechanisms. © 2011 American Institute of Physics.published_or_final_versio

Anti-epileptic effect of Ganoderma lucidum polysaccharides by inhibition of intracellular calcium accumulation and stimulation of expression of CaMKII a in epileptic hippocampal neurons

Purpose: To investigate the mechanism of the anti-epileptic effect of Ganoderma lucidum polysaccharides (GLP), the changes of intracellular calcium and CaMK II a expression in a model of epileptic neurons were investigated. Method: Primary hippocampal neurons were divided into: 1) Control group, neurons were cultured with Neurobasal medium, for 3 hours; 2) Model group I: neurons were incubated with Mg2+ free medium for 3 hours; 3) Model group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with the normal medium for a further 3 hours; 4) GLP group I: neurons were incubated with Mg2+ free medium containing GLP (0.375 mg/ml) for 3 hours; 5) GLP group II: neurons were incubated with Mg2+ free medium for 3 hours then cultured with a normal culture medium containing GLP for a further 3 hours. The CaMK II a protein expression was assessed by Western-blot. Ca2+ turnover in neurons was assessed using Fluo-3/AM which was added into the replacement medium and Ca2+ turnover was observed under a laser scanning confocal microscope. Results: The CaMK II a expression in the model groups was less than in the control groups, however, in the GLP groups, it was higher than that observed in the model group. Ca2+ fluorescence intensity in GLP group I was significantly lower than that in model group I after 30 seconds, while in GLP group II, it was reduced significantly compared to model group II after 5 minutes. Conclusion: GLP may inhibit calcium overload and promote CaMK II a expression to protect epileptic neuron

A Mechanistic Basis for the Coordinated Regulation of Pharyngeal Morphogenesis in Caenorhabditis elegans by LIN-35/Rb and UBC-18–ARI-1

Genetic redundancy, whereby two genes carry out seemingly overlapping functions, may in large part be attributable to the intricacy and robustness of genetic networks that control many developmental processes. We have previously described a complex set of genetic interactions underlying foregut development in the nematode Caenorhabditis elegans. Specifically, LIN-35/Rb, a tumor suppressor ortholog, in conjunction with UBC-18–ARI-1, a conserved E2/E3 complex, and PHA-1, a novel protein, coordinately regulates an early step of pharyngeal morphogenesis involving cellular re-orientation. Functional redundancy is indicated by the observation that lin-35; ubc-18 double mutants, as well as certain allelic combinations of pha-1 with either lin-35 or ubc-18, display defects in pharyngeal development, whereas single mutants do not. Using a combination of genetic and molecular analyses, we show that sup-35, a strong recessive suppressor of pha-1–associated lethality, also reverts the synthetic lethality of lin-35; ubc-18, lin-35; pha-1, and ubc-18 pha-1 double mutants. SUP-35, which contains C2H2-type Zn-finger domains as well as a conserved RMD-like motif, showed a dynamic pattern of subcellular localization during embryogenesis. We find that mutations in sup-35 specifically suppress hypomorphic alleles of pha-1 and that SUP-35, acting genetically upstream of SUP-36 and SUP-37, negatively regulates pha-1 transcription. We further demonstrate that LIN-35, a transcriptional repressor, and UBC-18–ARI-1, a complex involved in ubiquitin-mediated proteolysis, negatively regulate SUP-35 abundance through distinct mechanisms. We also show that HCF-1, a C. elegans homolog of host cell factor 1, functionally antagonizes LIN-35 in the regulation of sup-35. Our cumulative findings piece together the components of a novel regulatory network that includes LIN-35/Rb, which functions to control organ morphogenesis. Our results also shed light on general mechanisms that may underlie developmental genetic redundancies as well as principles that may govern complex disease traits

Fabrication of Uniform Au–Carbon Nanofiber by Two-Step Low Temperature Decomposition

This paper presents a facile and efficient way to prepare carbon nanofibers ornamented with Au nanoparticles (Au/CNFs). Gold nanoparticles were first deposited in the channels of an anodized aluminum oxide (AAO) membrane by thermal decomposition of HAuCl4and then carbon nanofibers were produced in the same channels loaded with the Au nanoparticles by decomposition of sucrose at 230 °C. An electron microscopy study revealed that the carbon nanofibers, ~10 nm thick and 6 μm long, were decorated with Au nanoparticles with a diameter of 10 nm. This synthetic route can produce uniform Au nanoparticles on CNF surfaces without using any additional chemicals to modify the AAO channels or the CNF surfaces

Magnetism and its microscopic origin in iron-based high-temperature superconductors

High-temperature superconductivity in the iron-based materials emerges from, or sometimes coexists with, their metallic or insulating parent compound states. This is surprising since these undoped states display dramatically different antiferromagnetic (AF) spin arrangements and N$\rm \acute{e}$el temperatures. Although there is general consensus that magnetic interactions are important for superconductivity, much is still unknown concerning the microscopic origin of the magnetic states. In this review, progress in this area is summarized, focusing on recent experimental and theoretical results and discussing their microscopic implications. It is concluded that the parent compounds are in a state that is more complex than implied by a simple Fermi surface nesting scenario, and a dual description including both itinerant and localized degrees of freedom is needed to properly describe these fascinating materials.Comment: 14 pages, 4 figures, Review article, accepted for publication in Nature Physic

Regionally Specific White Matter Disruptions of Fornix and Cingulum in Schizophrenia

Limbic circuitry disruptions have been implicated in the psychopathology and cognitive deficits of schizophrenia, which may involve white matter disruptions of the major tracts of the limbic system, including the fornix and the cingulum. Our study aimed to investigate regionally specific abnormalities of the fornix and cingulum in schizophrenia using diffusion tensor imaging (DTI). We determined the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) profiles along the fornix and cingulum tracts using a fibertracking technique and a brain mapping algorithm, the large deformation diffeomorphic metric mapping (LDDMM), in the DTI scans of 33 patients with schizophrenia and 31 age-, gender-, and handedness-matched healthy controls. We found that patients with schizophrenia showed reduction in FA and increase in RD in bilateral fornix, and increase in RD in left anterior cingulum when compared to healthy controls. In addition, tract-based analysis revealed specific loci of these white matter differences in schizophrenia, that is, FA reductions and AD and RD increases occur in the region of the left fornix further from the hippocampus, FA reductions and RD increases occur in the rostral portion of the left anterior cingulum, and RD and AD increases occur in the anterior segment of the left middle cingulum. In patients with schizophrenia, decreased FA in the specific loci of the left fornix and increased AD in the right cingulum adjoining the hippocampus correlated with greater severity of psychotic symptoms. These findings support precise disruptions of limbic-cortical integrity in schizophrenia and disruption of these structural networks may contribute towards the neural basis underlying the syndrome of schizophrenia and clinical symptomatology

Pregnane X Receptor and Yin Yang 1 Contribute to the Differential Tissue Expression and Induction of CYP3A5 and CYP3A4

The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 site is conserved in CYP3A4, but its inhibitory effect can be offset by PXR acting on response elements such as XREM. Taken together, the loss of YY1 binding site from promoters of the CYP3A5 gene lineage during primate evolution may have enabled the utilization of CYP3A5 both in the adaptive hepato-intestinal response to xenobiotics and as a constitutively expressed gene in other organs. Our results thus constitute a first description of uncoupling induction from constitutive expression for a major detoxifying enzyme. They also suggest an explanation for the considerable tissue expression differences between CYP3A5 and CYP3A4