bluuebunny/crossref_metadata_2025_split huggingface dataset:
IDH1 mutation is associated with seizures and protoplasmic subtype in patients with low‐grade gliomas
Authors: Liubinas Simon V. , D'Abaco Giovanna M. , Moffat Bradford M. , Gonzales Michael , Feleppa Frank , Nowell Cameron J. , Gorelik Alexandra , Drummond Katharine J. , O'Brien Terence J. , Kaye Andrew H. , Morokoff Andrew P. 
Published: June 2014

SummaryObjectiveThe isocitrate dehydrogenase 1 (IDH1) R132H mutation is the most common mutation in World Health Organization (WHO) grade II gliomas, reported to be expressed in 70–80%, but only 5–10% of high grade gliomas. Low grade tumors, especially the protoplasmic subtype, have the highest incidence of tumor associated epilepsy (TAE). The IDH1 mutation leads to the accumulation of 2‐hydroxyglutarate (2HG), a metabolite that bears a close structural similarity to glutamate, an excitatory neurotransmitter that has been implicated in the pathogenesis of TAE. We hypothesized that expression of mutated IDH1 may play a role in the pathogenesis of TAE in low grade gliomas.MethodsThirty consecutive patients with WHO grade II gliomas were analyzed for the presence of the IDH1‐R132H mutation using immunohistochemistry. The expression of IDH1 mutation was semiquantified using open‐source biologic‐imaging analysis software.ResultsThe percentage of cells positive for the IDH1‐R132H mutation was found to be higher in patients with TAE compared to those without TAE (median and interquartile range (IQR) 25.3% [8.6–53.5] vs. 5.2% [0.6–13.4], p = 0.03). In addition, we found a significantly higher median IDH1 mutation expression level in the protoplasmic subtype of low grade glioma (52.2% [IQR 19.9–58.6] vs. 13.8% [IQR 3.9–29.4], p = 0.04).SignificanceIncreased expression of the IDH1‐R132H mutation is associated with seizures in low grade gliomas and also with the protoplasmic subtype. This supports the hypothesis that this mutation may play a role in the pathogenesis of both TAE and low grade gliomas.
Sudden unexpected death in epilepsy: Assessing the public health burden
Authors: Thurman David J. , Hesdorffer Dale C. , French Jacqueline A. 
Published: June 2014

SummaryObjectiveThere is not yet a clear consensus on the incidence of sudden unexpected death in epilepsy (SUDEP) or the extent of its burden on public health. In this systematic review, we seek to summarize the incidence of SUDEP and its age distribution, as well as the years of potential life lost and cumulative risks of SUDEP for persons with epilepsy.MethodsWe conducted a systematic search for epidemiologic studies of sudden death in epilepsy and rated their quality of evidence. We pooled data from comparable higher quality population‐based studies of SUDEP incidence across all age groups, calculating the overall incidence of SUDEP per 100,000 population, and per 1,000 people with epilepsy. Using standard formulas, we also calculated the years of potential life lost and cumulative risks associated with SUDEP.ResultsSUDEP has an estimated overall crude annual incidence rate of 0.81 cases per 100,000 population, or 1.16 cases per 1,000 patients with epilepsy. Comparing years of potential life lost from SUDEP with selected other neurologic diseases, SUDEP ranks second only to stroke.SignificanceDespite limitations to the data on which our analysis is based, we conclude that the public health burden of SUDEP, which has previously been underappreciated, is substantial and deserves much more attention from clinicians, researchers, and the public health community.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Distinct functional and structural MRI abnormalities in mesial temporal lobe epilepsy with and without hippocampal sclerosis
Authors: Coan Ana C. , Campos Brunno M. , Beltramini Guilherme C. , Yasuda Clarissa L. , Covolan Roberto J. M. , Cendes Fernando 
Published: June 2014

SummaryObjectiveWe aimed to investigate patterns of electroencephalography‐correlated functional MRI (EEG‐fMRI) and subtle structural abnormalities in patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE‐HS) or normal MRI (MTLE‐NL).MethodsWe evaluated EEG‐fMRI acquisition of the 25 patients with diagnosis of MTLE who had interictal epileptiform discharges (IEDs) in the intra‐MRI EEG: 13 MTLE‐HS and 12 MTLE‐NL. fMRI was performed using echo‐planar images in a 3T MRI coupled with EEG acquired with 64 MRI‐compatible electrodes. In the first level analyses, the time of the IEDs ipsilateral to the epileptogenic zone was used as the paradigm, and four contrasts maps were built according to the variation of the hemodynamic response function (HRF) peaks (0, +3, +5, and +7 s). Second level group analyses were performed combining the contrast maps of MTLE‐HS or MTLE‐NL patients with each different HRF obtained at the first level. Areas of gray matter atrophy were evaluated with voxel‐based morphometry (VBM) in both groups.ResultsMTLE‐HS and MTLE‐NL had IED‐related positive BOLD (posBOLD) detected in the ipsilateral anterior temporal lobe and insula. However, only MTLE‐HS had significant posBOLD on contralateral hippocampus and anterior cingulate, whereas MTLE‐NL had areas of posBOLD on ipsilateral frontal lobe. Both groups had significant IED‐related negBOLD responses in areas of the default mode network (DMN), such as posterior cingulate and precuneus. There was no overlap of both posBOLD and negBOLD and areas of atrophy detected by VBM.SignificanceSimilar IEDs have different patterns of hemodynamic responses in sub‐groups of MTLE. In both MTLE‐HS and MTLE‐NL, there is a possible suppression of the DMN related to IEDs, as demonstrated by the negBOLD in these areas. The brain areas involved in the interictal related hemodynamic network are not the regions with the most significant gray matter atrophy in MTLE with or without MRI signs of HS.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Antiseizure effects of TrkB kinase inhibition
Authors: Liu Gumei , Kotloski Robert J , McNamara James O. 
Published: June 2014

SummaryObjectiveThe principal molecular targets of conventional antiseizure drugs consist of ligand‐gated and voltage‐gated ion channels and proteins subserving synaptic function. Inhibition of the receptor tyrosine kinase TrkB limits epileptogenesis, but its effect on individual seizures is unknown. We sought to determine whether inhibition of TrkB kinase exerts an antiseizure effect.MethodsWe utilized the kindling model in combination with an inducible conditional knockout of the TrkB gene (Act‐CreER TrkBflox/flox mice treated with tamoxifen), and also with a chemical‐genetic approach in which mice carry a TrkB kinase with a phenylalanine to alanine substitution of residue 616 (TrkBF616A), which allows inhibition of the kinase by a blood–brain barrier permeable small molecule, 1′‐naphthylmethyl‐4‐amino‐1‐tert‐butyl‐3‐(p‐methylphenyl)pyrazolo[3,4‐d]pyrimidine (1NMPP1).ResultsFollowing induction of kindling, reduction of TrkB protein levels in Act‐CreER TrkBflox/flox mice treated with tamoxifen was associated with reduced severity of behavioral seizures evoked by stimulation. Treatment with 1NMPP1 for 2 weeks following induction of kindling reversibly elevated both focal electrographic and generalized seizure thresholds in TrkBF616A, but not wild‐type (WT), mice. In contrast to kindled animals, treatment of naive TrkBF616A mice for 2 weeks had no detectable effect on electrographic seizure threshold (EST).SignificanceThis study provides proof of concept of a novel molecular target for antiseizure drugs, namely the receptor tyrosine kinase TrkB.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Efficacy and safety of pregabalin versus levetiracetam as adjunctive therapy in patients with partial seizures: A randomized, double‐blind, noninferiority trial
Authors: Zaccara Gaetano , Almas Mary , Pitman Verne , Knapp Lloyd , Posner Holly 
Published: June 2014

SummaryObjectivesTo assess the comparative efficacy and safety of pregabalin and levetiracetam for the reduction of seizure frequency in patients with partial seizures.MethodsThis was a randomized, double‐blind, flexible‐dose, parallel‐group noninferiority study of pregabalin and levetiracetam (randomized 1:1) as adjunctive treatment in adult patients with refractory partial seizures. The study included a 6‐week baseline phase, 4‐week dose‐escalation phase, and 12‐week maintenance phase. The primary endpoint was the proportion of patients with a ≥50% reduction in 28‐day seizure rate during the 12‐week maintenance phase, as compared with baseline. Noninferiority of pregabalin was declared if the lower limit of the 95% confidence interval (CI) for the difference in responder rates was greater than the prespecified noninferiority margin of −12%. A key secondary endpoint was the percent change from baseline in 28‐day seizure rate during the dose‐escalation and maintenance phases.ResultsFive hundred nine patients were randomized to pregabalin (n = 254) or levetiracetam (n = 255) and 418 (208 pregabalin, 210 levetiracetam) completed the maintenance phase. With both pregabalin and levetiracetam, the proportion of patients with a ≥50% reduction in 28‐day seizure rate was 0.59 (difference between groups [95% CI], 0.00 [−0.08 to 0.09]). Because the lower bound of the 95% CI was greater than the prespecified noninferiority margin of −12%, pregabalin was not inferior to levetiracetam. There was no significant difference between pregabalin and levetiracetam in the percent change in 28‐day seizure rate (median difference [95% CI], 4.1 [−2.6 to 10.9], p = 0.3571). In a post hoc analysis, the proportion of patients who were seizure‐free for the maintenance phase was lower with pregabalin (8.4%) than with levetiracetam (16.2%), p = 0.0155. Safety profiles were similar and consistent with prior trials.SignificanceThese results indicate that pregabalin is noninferior, and has a similar tolerability, to levetiracetam as adjunctive therapy in reducing seizure frequency in patients with partial seizures.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Lennox‐Gastaut syndrome and phenotype: Secondary network epilepsies
Authors: Archer John S. , Warren Aaron E. L. , Stagnitti Monique R. , Masterton Richard A. J. , Abbott David F. , Jackson Graeme D. 
Published: June 2014

SummaryObjectiveLennox‐Gastaut syndrome (LGS) is a severe epilepsy phenotype with characteristic electroclinical features despite diverse etiologies. We previously found common cerebral networks involved during slow spike‐and‐wave (SSW) and generalized paroxysmal fast activity (PFA), characteristic interictal discharges. Some patients have a Lennox‐Gastaut–like phenotype and cortical lesions. We wished to explore the interaction between cerebral networks and lesions in this group.Methods3 Tesla electroencephalography–functional magnetic resonance imaging (EEG‐fMRI) on six subjects with Lennox‐Gastaut phenotype and a structural lesion. Timings of SSW and PFA events were used in an event‐related fMRI analysis, and to estimate the time course of the hemodynamic response from key regions.Results(1) PFA‐robust fMRI signal increases were observed in frontal and parietal association cortical areas, thalamus, and pons, with simultaneous increases in both “attention” and resting‐state (default mode) networks, a highly unusual pattern. (2) SSW showed mixed increased and decreased fMRI activity, with preevent increases in association cortex and thalamus, and then prominent postevent reduction. There was decreased fMRI activity in primary cortical areas. (3) Lesion‐variable fMRI increases were observed during PFA and SSW discharges. Three subjects who proceeded to lesionectomy are >1 year seizure‐free.SignificanceWe conceptualize Lennox‐Gastaut phenotype as a being a network epilepsy, where key cerebral networks become autonomously unstable. Epileptiform activity in Lennox‐Gastaut phenotype, and by implication in LGS, appears to be amplified and expressed through association cortical areas, possibly because the attention and default‐mode networks are widely interconnected, fundamental brain networks. Seizure freedom in the subjects who proceeded to lesionectomy suggests that cortical lesions are able to establish and maintain this abnormal unstable network behavior. LGS may be considered a secondary network epilepsy because the unifying epileptic manifestations of the disorder, including PFA and SSW, reflect network dysfunction, rather than the specific initiating process.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Fate of Nutrients in Shallow Groundwater Receiving Treated Septage, Malibu, CA
Authors: Izbicki John A. 
Published: June 2014

AbstractTreated wastewater discharged from more than 400 onsite wastewater treatment systems (OWTS) near the Civic Center area of Malibu, California, 40 km west of downtown Los Angeles, composes 28% of the recharge to a 3.4 km2 alluvial aquifer. On the basis of δ18O and δD data, the fraction of wastewater in some samples was >70%. Ammonium and nitrate concentrations in water from 15 water‐table wells sampled in July 2009 and April 2010 ranged from <0.01 to 12 milligrams per liter as nitrogen (mg/L as N), and from <0.01 to 11 mg/L as N, respectively. Chemical and isotopic data (δ15N of ammonium and nitrate, and δ18O of nitrate) show two processes remove nitrogen discharged from OWTS. Where groundwater was reducing, sorption of ammonium resulted in 30 to 50% nitrogen removal. Where groundwater was initially oxic, nitrification with subsequent denitrification as reducing conditions developed, resulted in up to 60% nitrogen removal. Nitrogen removal through sorption dominated during the cooler April sample period, and denitrification dominated during the warmer July sample period. The combination of mixing and nitrogen removal due to denitrification, sorption, and volatilization produces a δ15N apparent fractionation factor (εapp = −5), that can be explained using laboratory‐derived fractionation factors (ε) for the individual processes. Phosphate concentrations ranged from < 0.04 to 2 mg/L as phosphorous. Sorption to iron oxides on the surfaces of mineral grains at near‐neutral pH's removed some phosphate; however, little removal occurred at more alkaline pH's (>7.3).
An Analytical Approach for Flow Analysis in Aquifers with Spatially Varying Top Boundary
Authors: Zlotnik Vitaly A. , Toundykov Daniel , Cardenas M. Bayani 
Published: June 2014

AbstractAnalytical models of groundwater flow with a spatially varying elevation of a top boundary are widely used. However, a vast majority of previous analytical studies truncated the irregularly shaped top section with little to no analyses of the shortcomings of the approximate solutions for the resulting rectangles or parallelepipeds. We present an analytical approach based on a perturbation technique that treats complete domains. It is especially accurate near the top boundary, where fluid circulation is most pronounced and higher accuracy is typically needed, such as in regional or hyporheic systems flow. The approach is illustrated by analyzing flow for a Tóthian unit basin.
MODFLOW‐Based Coupled Surface Water Routing and Groundwater‐Flow Simulation
Authors: Hughes J.D. , Langevin C.D. , White J.T. 
Published: June 2014

AbstractIn this paper, we present a flexible approach for simulating one‐ and two‐dimensional routing of surface water using a numerical surface water routing (SWR) code implicitly coupled to the groundwater‐flow process in MODFLOW. Surface water routing in SWR can be simulated using a diffusive‐wave approximation of the Saint‐Venant equations and/or a simplified level‐pool approach. SWR can account for surface water flow controlled by backwater conditions caused by small water‐surface gradients or surface water control structures. A number of typical surface water control structures, such as culverts, weirs, and gates, can be represented, and it is possible to implement operational rules to manage surface water stages and streamflow. The nonlinear system of surface water flow equations formulated in SWR is solved by using Newton methods and direct or iterative solvers. SWR was tested by simulating the (1) Lal axisymmetric overland flow, (2) V‐catchment, and (3) modified Pinder‐Sauer problems. Simulated results for these problems compare well with other published results and indicate that SWR provides accurate results for surface water‐only and coupled surface water/groundwater problems. Results for an application of SWR and MODFLOW to the Snapper Creek area of Miami‐Dade County, Florida, USA are also presented and demonstrate the value of coupled surface water and groundwater simulation in managed, low‐relief coastal settings.
Regional Frequency Analysis of Extreme Groundwater Levels
Authors: Fürst Josef , Bichler Andrea , Konecny Franz 
Published: June 2014

AbstractFlood risk is generally perceived as being a consequence of surface water inundation. However, large damage is also caused by high groundwater levels. In surface hydrology, statistical frequency analysis is a standard tool to estimate discharge with a given return period or exceedance probability. First, a suitable probability distribution is fit to a series of annual maximum peaks. Second, this distribution is used to determine the discharge corresponding to the desired return period. Where only short series of recorded data are available, the estimates can often be improved by regional frequency analysis (RFA). Unfortunately, there is little information in the literature on analogous approaches for the estimation of extreme groundwater levels. In this contribution, the applicability of l‐moments‐based RFA for the estimation of extreme groundwater levels is investigated. The main issues specific to groundwater levels are (1) appropriate transformation of the data, (2) criteria for identification of statistically homogeneous regions, (3) consideration of correlation between sites, and (4) choice of distribution function. This study is based on data from more than 1100 observation sites in four shallow Austrian Aquifers with a record length of 10 to 50 years. Results show that homogeneous regions for l‐moments‐based RFA can be identified covering about one half of the total area of the aquifers. The confidence intervals for the 30‐ and 100‐year return levels can be significantly reduced by RFA. Out of the four investigated distribution functions, none is to be preferred generally.
Empire, Industry, and Globalization: Rethinking the Emergence of the Gold Standard in the 19th‐century World
Authors: Taylor Vurpillat J. 
Published: June 2014

AbstractThis state of the field essay surveys recent scholarship on the history of the international gold standard. Taken together, recent studies have re‐situated the emergence of the classical gold standard in historical context, emphasizing the rapidly changing world of 19th‐century globalization, industrialization, and imperialism. This work has significant implications for our understanding of the gold standard in world history. In particular, recent studies have placed new emphasis on non‐economic factors that led to the establishment of a truly international gold standard. Among these factors, the ambitions for empire and modernization among leaders in the non‐European world played a key role in the decline of regional monetary regimes based on silver or bimetallism and the emergence of the international gold standard in the late‐19th century.
The History of Mum and Dad: Recent Historical Research on Parenting in England from the 16th to 20th centuries
Authors: Bailey Joanne 
Published: June 2014

AbstractParenting has a complex but only recently examined history. This article surveys this scholarship, which is driven by the histories of gender, emotions, medicine, bodies, material culture, class and deviance to uncover how parenting is socially and culturally constructed and therefore changes over time. It traces several significant arguments. First, shifting gender constructions have reshaped expectations about mothers' and fathers' roles. Thus, while paternal breadwinning and maternal care is always important, at times fathers have been commended for caring for infants and mothers for economic provision of offspring. Secondly, the material aspects of life have powerfully affected parenting. Until relatively recently, parents struggled against implacably high rates of infant and child mortality: nursing children, preparing them for death and the afterlife, and coping with grief. Therefore, although the depth of feeling over this remained consistent, varying emotional regimes have influenced forms of parental expression and practice. Parents' responsibilities for their children's health at times of inadequate medical treatment often left them physically and mentally exhausted and woefully disempowered. Other limitations or freedoms were imposed on mothering and fathering by the objects and spaces associated with bringing up children. Thirdly, levels of wealth and social class affect parenting, with working‐class, poor and lone parents especially vulnerable to family disruption due to poverty, ill‐health and under‐ or unemployment. Fourthly, the parameters of bad parenting shift over time, and even those mothers and fathers who killed their children were viewed differently over time and place as cultural sensibilities shifted. Finally, the article concludes with some suggestions for the further development of this exciting new field.
Repositioning History for the Future ‐ Recent Academic Debates in China
Authors: Eben v.Racknitz Ines 
Published: June 2014

AbstractChanges in the politics and society in post‐Deng China are reflected in the research priorities of mainland Chinese university history departments, while questions of political legitimation in China and contact with colleagues abroad in the United States and Europe continue to generate new research topics. This article intends to show how several factors contribute to the shaping of historical research in China today. Ongoing developments in China will be demonstrated through two examples, namely the field of world history and the discussion surrounding New Qing history in China.
Effect of dutasteride 0.5 mg/d in men with androgenetic alopecia recalcitrant to finasteride
Authors: Jung Jae Yoon , Yeon Je Ho , Choi Jee Woong , Kwon Soon Hyo , Kim Beom Joon , Youn Sang Woong , Park Kyoung Chan , Huh Chang Hun 
Published: June 2014

AbstractBackgroundFinasteride at a dose of 1 mg/d has been reported to show no significant improvement in 30–50% of patients with androgenetic alopecia (AGA). Dutasteride, a dual inhibitor of both type I and type II 5 alpha‐reductase, inhibits the conversion of testosterone to dihydrotestosterone, which is the key contributor of AGA.Materials and methodsOur aim is to evaluate clinical efficacy and tolerability of dutasteride in men with AGA who do not show clinical improvement to the conventional finasteride treatment. A total of 35 Korean men with AGA who had not shown significant clinical improvement when treated with finasteride 1 mg/d for at least six months received dutasteride at a dose of 0.5 mg/d for six months. Efficacy was evaluated by global photograph assessment and phototrichogram. Safety assessment was performed through physical examination and adverse event report.ResultsOf the 31 patients who completed the treatment, 24 patients (77.4%) were improved by the global photography (17 were slightly, six moderately, and one markedly improved) compared with the post‐finasteride treatment. There was no significant change in seven patients (22.6%), and aggravation was not reported. Hair density and thickness significantly increased by 10.3% (87 ± 12–96 ± 12/cm2) and 18.9% (0.053 ± 0.012–0.063 ± 0.011 mm), respectively, in phototrichogram assessment. Side effects included transient sexual dysfunction in six patients (17.1%).ConclusionsDutasteride is suggestive to be an alternative treatment option to patients with AGA who do not clinically respond to finasteride in six months.