A Delta-f Monte Carlo method to calculate parameters in plasmas

A Monte Carlo code has been developed which very efficiently calculates plasma parameters, such as currents, potentials and transport coefficients for a fully three dimensional magnetic field configuration. The code computes the deviation, f, of the exact distribution function, f, from the Maxwellian, {dollar}F\sb{lcub}M{rcub},{dollar} with {dollar}\psi{dollar} the toroidal magnetic flux enclosed by a pressure surface and H the Hamiltonian. The particles in the simulation are followed with a traditional Monte Carlo scheme consisting of an orbit step in which new values for the positions and momenta are obtained and a collision step in which a Monte Carlo equivalent of the Lorentz operator is applied to change the pitch of each particle. Since the {dollar}\delta f{dollar} code calculates only the deviations from the Maxwellian rather than the full distribution function, it is about 10{dollar}\sp4{dollar} times as efficient as other Monte Carlo techniques used to calculate currents in plasmas.;The {dollar}\delta f{dollar} code was used to study the aspect ratio and collisionality dependence of the bootstrap current and two Fourier components of the Pfirsch-Schluter current. It was also used to calculate electric potentials within magnetic surfaces due to the explicit enforcement of the quasi-neutrality condition. The code also calculated transport coefficients for the ions and electrons under various conditions. The agreement between the values predicted by the code for the plasma currents and analytic theory is excellent. The transport parameters calculated for the ions and electrons are in qualitative agreement with values predicted from neoclassical transport theory, including transport induced by a toroidal ripple. The in-surface electric potentials induced by explicitly enforcing the quasi-neutrality condition are too small to significantly enhance transport across the magnetic surfaces

A Swedish Population-based Study of Adverse Birth Outcomes among Pregnant Women Treated with Buprenorphine or Methadone: Preliminary Findings

Background Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy. Objective The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden. Methods Pregnant women and their corresponding births during 2005–2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population. Results A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine ( N = 176) or methadone ( N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father. Conclusions An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders

Proteotranscriptomic Analysis Reveals Stage Specific Changes in the Molecular Landscape of Clear-Cell Renal Cell Carcinoma

<div><p>Renal cell carcinoma comprises 2 to 3% of malignancies in adults with the most prevalent subtype being clear-cell RCC (ccRCC). This type of cancer is well characterized at the genomic and transcriptomic level and is associated with a loss of <i>VHL</i> that results in stabilization of HIF1. The current study focused on evaluating ccRCC stage dependent changes at the proteome level to provide insight into the molecular pathogenesis of ccRCC progression. To accomplish this, label-free proteomics was used to characterize matched tumor and normal-adjacent tissues from 84 patients with stage I to IV ccRCC. Using pooled samples 1551 proteins were identified, of which 290 were differentially abundant, while 783 proteins were identified using individual samples, with 344 being differentially abundant. These 344 differentially abundant proteins were enriched in metabolic pathways and further examination revealed metabolic dysfunction consistent with the Warburg effect. Additionally, the protein data indicated activation of ESRRA and ESRRG, and HIF1A, as well as inhibition of FOXA1, MAPK1 and WISP2. A subset analysis of complementary gene expression array data on 47 pairs of these same tissues indicated similar upstream changes, such as increased HIF1A activation with stage, though ESRRA and ESRRG activation and FOXA1 inhibition were not predicted from the transcriptomic data. The activation of ESRRA and ESRRG implied that HIF2A may also be activated during later stages of ccRCC, which was confirmed in the transcriptional analysis. This combined analysis highlights the importance of HIF1A and HIF2A in developing the ccRCC molecular phenotype as well as the potential involvement of ESRRA and ESRRG in driving these changes. In addition, cofilin-1, profilin-1, nicotinamide N-methyltransferase, and fructose-bisphosphate aldolase A were identified as candidate markers of late stage ccRCC. Utilization of data collected from heterogeneous biological domains strengthened the findings from each domain, demonstrating the complementary nature of such an analysis. Together these results highlight the importance of the VHL/HIF1A/HIF2A axis and provide a foundation and therapeutic targets for future studies. (Data are available via ProteomeXchange with identifier PXD003271 and MassIVE with identifier MSV000079511.)</p></div

Differential protein abundance and gene expression between tumor and normal-adjacent ccRCC tissues.

<p>(A) Heatmap of 344 proteins with differential abundance between tumor and normal-adjacent samples (moderated <i>t</i>-test, Benjamini-Hockberg adjusted <i>p</i>-value < 0.05). (B) Heatmap of 1003 genes with differential expression between 94 tumor and normal-adjacent samples (moderated <i>t</i>-test BH adjusted <i>p</i> < 0.001 and absolute fold-change ≥ 4). Scale bar is standard deviation units around the mean of each protein abundance or gene expression level.</p

Correlation of differentially abundant proteins and respective gene expression levels in matched samples.

<p>(A) There were 725 proteins identified which had 1764 corresponding probes in the corresponding transcriptomic data. Pearson's linear correlation coefficient was used to correlate normalized spectral count levels and RMA normalized microarray data in matched samples (94 samples). The average Pearson's linear correlation coefficient (<i>r</i>) was 0.157 (dotted line). (B) Distribution of <i>r</i> for just the 344 differentially abundant proteins, of which 318 were also measured in the corresponding transcriptomic study. The average <i>r</i> was 0.347 (dotted line).</p

Candidate markers of advanced stage ccRCC.

<p>Heatmap of log₂ fold-change in protein abundance of four candidate markers of late stage ccRCC, cofilin-1 (CFL1), profilin-1 (PFN1), nicotinamide N-methyltransferase (NNMT), and fructose-bisphosphate aldolase A (ALDOA), in paired tumor and normal-adjacent tissues from 84 individuals, as well as 9 pairs that also included metastasis tissue.</p

Upstream regulation with stage.

<p>(A) Heatmap of six upstream targets predicted to be activated/inhibited in tumor versus normal at each ccRCC stage and using all stage data together. Scale is activation z-score, with ≥ 2 being likely activation and ≤ -2 being likely inhibition. Using all stage data together, activated or inhibited upstream targets (ESRRA, ESRRG, HIF1A, FOXA1, MAPK1, and WISP2) are shown. (B) Heatmap of six upstream targets predicted to be activated/inhibited in tumor versus normal-adjacent tissues using the proteomic data set. Corresponding activation z-scores from transcriptomic data analysis are included to demonstrate conserved trends at each ccRCC stage and using all stage data together.</p