The effect of meninges on the electric fields in TES and TMS: Numerical modeling with adaptive mesh refinement

Background When modeling transcranial electrical stimulation (TES) and transcranial magnetic stimulation (TMS) in the brain, the meninges – dura, arachnoid, and pia mater – are often neglected due to high computational costs. Objective We investigate the impact of the meningeal layers on the cortical electric field in TES and TMS while considering the headreco segmentation as the base model. Method We use T1/T2 MRI data from 16 subjects and apply the boundary element fast multipole method with adaptive mesh refinement, which enables us to accurately solve this problem and establish method convergence at reasonable computational cost. We compare electric fields in the presence and absence of various meninges for two brain areas ( and ) and for several distinct TES and TMS setups. Results Maximum electric fields in the cortex for focal TES consistently increase by approximately 30% on average when the meninges are present in the CSF volume. Their effect on the maximum field can be emulated by reducing the CSF conductivity from 1.65 S/m to approximately 0.85 S/m. In stark contrast to that, the TMS electric fields in the cortex are only weakly affected by the meningeal layers and slightly (∼6%) decrease on average when the meninges are included. Conclusion Our results quantify the influence of the meninges on the cortical TES and TMS electric fields. Both focal TES and TMS results are very consistent. The focal TES results are also in a good agreement with a prior relevant study. The solver and the mesh generator for the meningeal layers (compatible with SimNIBS) are available online

miR-221 Mediates Chemoresistance of Esophageal Adenocarcinoma by Direct Targeting of DKK2 Expression

Background:Chemoresistance is a main obstacle to effective esophageal cancer (EC) therapy. We hypothesize that altered expression of microRNAs (miRNAs) play a role in EC cancer progression and resistance to 5-fluorouracil (5-FU) based chemotherapeutic strategies.Methods:Four pairs of esophageal adenocarcinoma (EAC) cell lines and corresponding 5-FU resistant variants were established. The expression levels of miRNAs previously shown to be involved in the general regulation of stem cell pathways were analyzed by qRT-PCR. The effects of selected miRNAs on proliferation, apoptosis, and chemosensitivity were evaluated both in vitro and in vivo. We identified a particular miRNA and analyzed its putative target genes in 14 pairs of human EC tumor specimens with surrounding normal tissue by qRT-PCR as well as Wnt pathway associated genes by immunohistochemistry in another 45 EAC tumor samples.Results:MiR-221 was overexpressed in 5-FU resistant EC cell lines as well as in human EAC tissue. DKK2 was identified as a target gene for miR-221. Knockdown of miR-221 in 5-FU resistant cells resulted in reduced cell proliferation, increased apoptosis, restored chemosensitivity, and led to inactivation of the Wnt/-catenin pathway mediated by alteration in DKK2 expression. Moreover, miR-221 reduction resulted in alteration of EMT-associated genes such as E-cadherin and vimentin as well as significantly slower xenograft tumor growth in nude mice. RT2 profiler analysis identified a substantial dysregulation of 4 Wnt/-catenin signaling and chemoresistance target genes as a result of miR-221 modulation: CDH1, CD44, MYC, and ABCG2.Conclusion:MiR-221 controls 5-FU resistance of EC partly via modulation of Wnt/-catenin-EMT pathways by direct targeting of DKK2 expression. MiR-221 may serve as a prognostic marker and therapeutic target for patients with 5-FU resistant EAC

Investigation of the Performance of the New Orleans Flood Protection System in Hurricane Katrina on August 29, 2005: Volume 1

This report presents the results of an investigation of the performance of the New Orleans regional flood protection system during and after Hurricane Katrina, which struck the New Orleans region on August 29, 2005. This event resulted in the single most costly catastrophic failure of an engineered system in history. Current damage estimates at the time of this writing are on the order of $100 to$200 billion in the greater New Orleans area, and the official death count in New Orleans and southern Louisiana at the time of this writing stands at 1,293, with an additional 306 deaths in nearby southern Mississippi. An additional approximately 300 people are currently still listed as “missing”; it is expected that some of these missing were temporarily lost in the shuffle of the regional evacuation, but some of these are expected to have been carried out into the swamps and the Gulf of Mexico by the storm’s floodwaters, and some are expected to be recovered in the ongoing sifting through the debris of wrecked homes and businesses, so the current overall regional death count of 1,599 is expected to continue to rise a bit further. More than 450,000 people were initially displaced by this catastrophe, and at the time of this writing more than 200,000 residents of the greater New Orleans metropolitan area continue to be displaced from their homes by the floodwater damages from this storm event. This investigation has targeted three main questions as follow: (1) What happened?, (2) Why?, and (3) What types of changes are necessary to prevent recurrence of a disaster of this scale again in the future? To address these questions, this investigation has involved: (1) an initial field reconnaissance, forensic study and data gathering effort performed quickly after the arrival of Hurricanes Katrina (August 29, 2005) and Rita (September 24, 2005), (2) a review of the history of the regional flood protection system and its development, (3) a review of the challenging regional geology, (4) detailed studies of the events during Hurricanes Katrina and Rita, as well as the causes and mechanisms of the principal failures, (4) studies of the organizational and institutional issues affecting the performance of the flood protection system, (5) observations regarding the emergency repair and ongoing interim levee reconstruction efforts, and (6) development of findings and preliminary recommendations regarding changes that appear warranted in order to prevent recurrence of this type of catastrophe in the future. In the end, it is concluded that many things went wrong with the New Orleans flood protection system during Hurricane Katrina, and that the resulting catastrophe had it roots in three main causes: (1) a major natural disaster (the Hurricane itself), (2) the poor performance of the flood protection system, due to localized engineering failures, questionable judgments, errors, etc. involved in the detailed design, construction, operation and maintenance of the system, and (3) more global “organizational” and institutional problems associated with the governmental and local organizations responsible for the design, construction, operation, maintenance and funding of the overall flood protection system

Landslides Triggered by the MW 7.8 14 November 2016 Kaikoura Earthquake, New Zealand

The MW 7.8 14 November 2016 Kaikoura earthquake generated more than 10000 landslides over a total area of about 10000 km2, with the majority concentrated in a smaller area of about 3600 km2. The largest landslide triggered by the earthquake had an approximate volume of 20 (±2) M m3, with a runout distance of about 2.7 km, forming a dam on the Hapuku River. In this paper, we present version 1.0 of the landslide inventory we have created for this event. We use the inventory presented in this paper to identify and discuss some of the controls on the spatial distribution of landslides triggered by the Kaikoura earthquake. Our main findings are (1) the number of medium to large landslides (source area ≥10000 m2) triggered by the Kaikoura earthquake is smaller than for similar sized landslides triggered by similar magnitude earthquakes in New Zealand; (2) seven of the largest eight landslides (from 5 to 20 x 106 m3) occurred on faults that ruptured to the surface during the earthquake; (3) the average landslide density within 200 m of a mapped surface fault rupture is three times that at a distance of 2500 m or more from a mapped surface fault rupture ; (4) the “distance to fault” predictor variable, when used as a proxy for ground-motion intensity, and when combined with slope angle, geology and elevation variables, has more power in predicting landslide probability than the modelled peak ground acceleration or peak ground velocity; and (5) for the same slope angles, the coastal slopes have landslide point densities that are an order of magnitude greater than those in similar materials on the inland slopes, but their source areas are significantly smaller