Clinical profile of vigabatrin as monotherapy for treatment of infantile spasms

Jason T Lerner1, Noriko Salamon2, Raman Sankar1,31Departments of Pediatrics, 2Radiological Sciences, 3Neurology, David Geffen School of Medicine, University of California Los Angeles and Mattel Children’s Hospital at UCLA, Los Angeles, CA, USAAbstract: Vigabatrin, the first therapeutic agent to be approved by the Food and Drug Administration for the treatment of infantile spasms, as well as for adjunctive use in the treatment of refractory complex partial epilepsy, represents an important advance for patients with difficult-to-manage epilepsy. This review summarizes the complex history, chemistry, and pharmacology, as well as the clinical data leading to the approval of vigabatrin for infantile spasms in the US. The long path to its approval reflects the visual system and white matter toxicity concerns with this agent. This review provides a brief description of these concerns, and the regulatory safety monitoring and mitigation systems that have been put in place to enhance benefit over risk.Keywords: vigabatrin, infantile spasms, monotherap

Sources and characteristics of summertime organic aerosol in the Colorado Front Range: perspective from measurements and WRF-Chem modeling

Abstract. The evolution of organic aerosols (OAs) and their precursors in the boundary layer (BL) of the Colorado Front Range during the Front Range Air Pollution and Photochemistry Éxperiment (FRAPPÉ, July–August 2014) was analyzed by in situ measurements and chemical transport modeling. Measurements indicated significant production of secondary OA (SOA), with enhancement ratio of OA with respect to carbon monoxide (CO) reaching 0.085±0.003 µg m−3 ppbv−1. At background mixing ratios of CO, up to  ∼  1.8 µg m−3 background OA was observed, suggesting significant non-combustion contribution to OA in the Front Range. The mean concentration of OA in plumes with a high influence of oil and natural gas (O&G) emissions was  ∼  40 % higher than in urban-influenced plumes. Positive matrix factorization (PMF) confirmed a dominant contribution of secondary, oxygenated OA (OOA) in the boundary layer instead of fresh, hydrocarbon-like OA (HOA). Combinations of primary OA (POA) volatility assumptions, aging of semi-volatile species, and different emission estimates from the O&G sector were used in the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem) simulation scenarios. The assumption of semi-volatile POA resulted in greater than a factor of 10 lower POA concentrations compared to PMF-resolved HOA. Including top-down modified O&G emissions resulted in substantially better agreements in modeled ethane, toluene, hydroxyl radical, and ozone compared to measurements in the high-O&G-influenced plumes. By including emissions from the O&G sector using the top-down approach, it was estimated that the O&G sector contributed to  <  5 % of total OA, but up to 38 % of anthropogenic SOA (aSOA) in the region. The best agreement between the measured and simulated median OA was achieved by limiting the extent of biogenic hydrocarbon aging and consequently biogenic SOA (bSOA) production. Despite a lower production of bSOA in this scenario, contribution of bSOA to total SOA remained high at 40–54 %. Future studies aiming at a better emissions characterization of POA and intermediate-volatility organic compounds (IVOCs) from the O&G sector are valuable

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

Characterizing Ham and Loin Quality as Hot Carcass Weight Increases to an Average of 119 Kilograms

The objective was to characterize ham and loin quality of carcasses ranging from 78 to 145 kg (average ∼119 kg). Hot carcass weight (HCW), back fat depth, and loin depth was measured on 666 carcasses. Loin pH, instrumental and visual color and iodine value of clear plate fat (all 3 layers) was measured on approximately 90% of the population. Quality measurements of the ham, 14 d aged loin and chop, and loin chop shear force (SSF) were evaluated on approximately 30% of the population. Myosin heavy chain fiber type determination was completed on 49 carcasses. Slopes of regression lines and coefficients of determination between HCW and quality traits were calculated using the REG procedure in SAS and considered significantly different from 0 at P ≤ 0.05. As HCW increased, loin depth (b1 = 0.2496, P 0.15) and did not explain more than 1% (R2 ≤ 0.01) of the variation in 1 d loin color or pH. Loins from heavier carcasses were more tender (decreased SSF; b1 = –0.0674, P 0.22) muscle fiber type percentage or area. These results suggest that increasing HCW to an average of 119 kg did not compromise pork quality

Effects of Increased Pork Hot Carcass Weights. II: Loin Quality Characteristics and Palatability Ratings

The objective of this study was to evaluate the effects of increased pork hot carcass weight on loin quality and palatability of top loin chops. Pork loins (N = 200) were collected from 4 different hot carcass weight groups: A light weight (LT; less than 111.8 kg), medium-light weight (MLT; 111.8 to 119.1 kg), medium-heavy weight (MHVY; 119.1 to 124.4), and a heavyweight group (HVY; 124.4 and greater). Following fabrication, chops were assigned to fat and moisture analysis, Warner-Bratzler shear force (WBSF), consumer sensory panels, or trained sensory panels. Chops from the HVY group were rated as more (P 0.05) consumer flavor liking ratings. Hot carcass weight treatment did not contribute (P > 0.05) to the percentage of chops rated acceptable for flavor and overall liking. The greatest (P 0.05), with greater (P < 0.05) overall tenderness ratings compared to chops from LT carcasses. These results indicate chops from heavier weight carcasses may have improved tenderness and juiciness compared to chops from lighter carcasses

Effects of Increased Pork Hot Carcass Weights. I: Chop Thickness Impact on Consumer Visual Ratings

The objective of this study was to evaluate the effect of increased pork hot carcass weights on consumer visual acceptability and purchase intent ratings of top loin chops cut to various thicknesses in a price labeled versus unlabeled retail display scenario. Pork loins (N = 200) were collected from 4 different hot carcass weight groups: light weight (LT; less than 111.8 kg), medium-light weight (MLT; 111.8 to 119. kg), medium-heavy weight (MHVY; 119.1 to 124.4 kg), and a heavy weight group (HVY; 124.4 kg and greater). Loins were fabricated into 4 pairs of chops of specified thicknesses (1.27, 1.91, 2.54, and 3.18 cm). One chop from each pair was assigned to be packaged with or without a label. Consumers assessed chops for appearance, desirability, and purchase intent. For both appearance and purchase intent ratings, chops from HVY carcasses were given more desirable (P < 0.05) ratings compared to LT chops. Consumers gave greater (P < 0.05) appearance ratings to thicker cut chops. There was a hot carcass weight × chop thickness interaction (P < 0.05) for the percentage of consumers that indicated the chop was desirable overall. Regardless of hot carcass weight group, chops with a thickness of 1.27 cm had the lowest (P < 0.05) percentage of consumers indicate they were desirable overall. A greater (P < 0.05) percentage of consumers indicated “yes” they would purchase chops cut to a thickness of 2.54 cm compared to all other thicknesses. Additionally, there was a greater (P < 0.05) percentage of consumers who indicated they would purchase unlabeled chops compared to labeled chops. These results, within the population sampled, indicate that carcass weight and chop thickness can affect consumer preference and thus should be considered by retailers when marketing fresh pork loin chops

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder