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Background Selective amygdalohippocampectomy (SelAH) is designed to treat medically refractory mesial temporal lobe epilepsy with reduced morbidity compared to standard anterior temporal lobectomy. At our institution, we perform SelAH via a transcortical approach via small corticectomy in the middle temporal gyrus. Objective To discuss the surgical anatomy and nuances of SelAH, share our institutional experience, and perform a review of literature. Methods Institutional experience was recorded by collecting demographic and outcome data from 1999 to 2017 under an Institutional Review Board protocol in a prospective manner using a REDCap database. Results A total of 211 SelAH procedures were performed at our institution between 1999 and 2017. Of these patients, 54% (113/211) were females. The average age at surgery was 39.4 yr. Two-year Engel outcome data were available for 168 patients, of which 73% (123/168) had Engel I outcomes. Engel II outcomes were reported in 16.6% (28/168), III in 4.7% (8/168), and IV in 5.3% (9/168). Our review of literature showed that this is comparable to the seizure freedom rates reported by other groups. We then reviewed our surgical methodology based on operative reports and created illustrations of the surgical anatomy of temporal lobe approach. These illustrations were compared with postoperative magnetic resonance imaging to provide a better 3D understanding of the complex architecture of mesial temporal structures. Conclusion SelAH is a minimally invasive, safe, and effective approach for the treatment of medically refractory epilepsy with good surgical outcomes and low morbidity. We feel that mastering the complex anatomy of this approach helps achieve successful outcomes.

17 USC 105 interim-entered record; under review. The article of record as published may be found at http://dx.doi.org/10.1175/BAMS-D-19-0281.1 The inner shelf, the transition zone between the surfzone and the midshelf, is a dynamically complex region with the evolution of circulation and stratification driven by multiple physical processes. Cross-shelf exchange through the inner shelf has important implications for coastal water quality, ecological connectivity, and lateral movement of sediment and heat. The Inner-Shelf Dynamics Experiment (ISDE) was an intensive, coordinated, multi-institution field experiment from September–October 2017, conducted from the midshelf, through the inner shelf, and into the surfzone near Point Sal, California. Satellite, airborne, shore- and ship-based remote sensing, in-water moorings and ship-based sampling, and numerical ocean circulation models forced by winds, waves, and tides were used to investigate the dynamics governing the circulation and transport in the inner shelf and the role of coastline variability on regional circulation dynamics. Here, the following physical processes are highlighted: internal wave dynamics from the midshelf to the inner shelf; flow separation and eddy shedding off Point Sal; offshore ejection of surfzone waters from rip currents; and wind-driven subtidal circulation dynamics. The extensive dataset from ISDE allows for unprecedented investigations into the role of physical processes in creating spatial heterogeneity, and nonlinear interactions between various inner-shelf physical processes. Overall, the highly spatially and temporally resolved oceanographic measurements and numerical simulations of ISDE provide a central framework for studies exploring this complex and fascinating region of the ocean. U.S. Office of Naval Research (ONR) ONR Departmental Research Initiative (DRI) Inner-Shelf Dynamics Experiment (ISDE)

Purpose The percentage of a maternal cell-free DNA (cfDNA) sample that is fetal-derived (the fetal fraction; FF) is a key driver of the sensitivity and specificity of noninvasive prenatal screening (NIPS). On certain NIPS platforms, >20% of women with high body mass index (and >5% overall) receive a test failure due to low FF (

Objective In patients with medically refractory focal epilepsy, stereotactic-electroencephalography (SEEG) can aid in localizing epileptogenic regions for surgical treatment. SEEG, however, requires long hospitalizations to record seizures, and ictal interpretation can be incomplete or inaccurate. Our recent work showed that non-directed resting-state analyses may identify brain regions as epileptogenic or uninvolved. Our present objective is to map epileptogenic networks in greater detail and more accurately identify seizure-onset regions using directed resting-state SEEG connectivity. Methods In 25 patients with focal epilepsy who underwent SEEG, 2 minutes of resting-state, artifact-free, SEEG data were selected and functional connectivity was estimated. Using standard clinical interpretation, brain regions were classified into four categories: ictogenic, early propagation, irritative, or uninvolved. Three non-directed connectivity measures (mutual information [MI] strength, and imaginary coherence between and within regions) and four directed measures (partial directed coherence [PDC] and directed transfer function [DTF], inward and outward strength) were calculated. Logistic regression was used to generate a predictive model of ictogenicity. Results Ictogenic regions had the highest and uninvolved regions had the lowest MI strength. Although both PDC and DTF inward strengths were highest in ictogenic regions, outward strengths did not differ among categories. A model incorporating directed and nondirected connectivity measures demonstrated an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.88 in predicting ictogenicity of individual regions. The AUC of this model was 0.93 when restricted to patients with favorable postsurgical seizure outcomes. Significance Directed connectivity measures may help identify epileptogenic networks without requiring ictal recordings. Greater inward but not outward connectivity in ictogenic regions at rest may represent broad inhibitory input to prevent seizure generation.

Visualizing eigenmodes is crucial in understanding the behavior of state-of-the-art micromechanical devices. We demonstrate a method to optically map multiple modes of mechanical structures simultaneously. The fast and robust method, based on a modified phase-lock loop, is demonstrated on a silicon nitride membrane and shown to outperform three alternative approaches. Line traces and two-dimensional maps of different modes are acquired. The high quality data enables us to determine the weights of individual contributions in superpositions of degenerate modes.

Objective Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. Method The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48 h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. Results A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (p Conclusions We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.

OBJECTIVE: Classification of epilepsy into types and subtypes is important for both clinical care and research into underlying disease mechanisms. A quantitative, data-driven approach may augment traditional electroclinical classification and shed new light on existing classification frameworks. METHODS: We used latent class analysis, a statistical method that assigns subjects into groups called latent classes based on phenotypic elements, to classify individuals with common familial epilepsies from the Epi4K Multiplex Families study. Phenotypic elements included seizure types, seizure symptoms, and other elements of the medical history. We compared class assignments to traditional electroclinical classifications and assessed familial aggregation of latent classes. RESULTS: A total of 1120 subjects with epilepsy were assigned to five latent classes. Classes 1 and 2 contained subjects with generalized epilepsy, largely reflecting the distinction between absence epilepsies and younger onset (class 1) versus myoclonic epilepsies and older onset (class 2). Classes 3 and 4 contained subjects with focal epilepsies, and in contrast to classes 1 and 2, these did not adhere as closely to clinically defined focal epilepsy subtypes. Class 5 contained nearly all subjects with febrile seizures plus or unknown epilepsy type, as well as a few subjects with generalized epilepsy and a few with focal epilepsy. Family concordance of latent classes was similar to or greater than concordance of clinically defined epilepsy types. SIGNIFICANCE: Quantitative classification of epilepsy has the potential to augment traditional electroclinical classification by (1) combining some syndromes into a single class, (2) splitting some syndromes into different classes, (3) helping to classify subjects who could not be classified clinically, and (4) defining the boundaries of clinically defined classifications. This approach can guide future research, including molecular genetic studies, by identifying homogeneous sets of individuals that may share underlying disease mechanisms.

BACKGROUND: Focal seizures in temporal lobe epilepsy (TLE) are associated with widespread brain network perturbations and neurocognitive problems. OBJECTIVE: To determine whether brainstem connectivity disturbances improve with successful epilepsy surgery, as recent work has demonstrated decreased brainstem connectivity in TLE that is related to disease severity and neurocognitive profile. METHODS: We evaluated 15 adult TLE patients before and after (>1 yr; mean, 3.4 yr) surgery, and 15 matched control subjects using magnetic resonance imaging to measure functional and structural connectivity of ascending reticular activating system (ARAS) structures, including cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus (PPN), and ventral tegmental area (VTA). RESULTS: TLE patients who achieved long-term postoperative seizure freedom (10 of 15) demonstrated increases in functional connectivity between ARAS structures and fronto-parietal-insular neocortex compared to preoperative baseline (P = .01, Kruskal–Wallis), with postoperative connectivity patterns resembling controls’ connectivity. No functional connectivity changes were detected in 5 patients with persistent seizures after surgery (P = .9, Kruskal–Wallis). Among seizure-free postoperative patients, larger increases in CSC, PPN, and VTA functional connectivity were observed in individuals with more frequent seizures before surgery (P

Energy resource classification systems are useful assessment tools that support energy planning and project development, e.g., siting and feasibility studies. They typically establish standard classes of power, a measure of the opportunity for energy resource capture. In this study, we develop wave energy resource classification systems for the US based on wave power (J, kW/m) and its distribution with peak period ( T p , s ). These metrics are calculated for 70,386 sites from partitioned bulk wave parameters generated from a validated 30-year WaveWatch III model hindcast. As the operating resonant period bandwidth of a wave energy converter (WEC) technology is an important design characteristic, the dominant period band containing the largest energy content is identified among three peak period band classes. These classification systems, comprised of four power classes and three peak period band classes, are based on the total wave power or the partitioned wave power in the dominant peak period band. They discriminate distinct trends in wave energy resource among five regions within the US, and provide useful information for energy planners, project developers, and technology designers. They also establish a framework for investigating the feasibility of a compatible wave climate (design load) conditions and WEC technology classification system to reduce design and manufacturing costs.

Clinical genomic tests increasingly use a next-generation sequencing (NGS) platform due in part to the high fidelity of variant calls, yet rare errors are still possible. In germline DNA screening, failure to correct such errors could have serious consequences for patients, who may follow an unwarranted screening or surgical management path. It has been suggested that routine orthogonal confirmation by Sanger sequencing is required to verify NGS results, especially low-confidence positives with depressed allele fraction ( 15,000 samples. Licensed reviewers manually inspected both raw and processed data at the batch, sample, and variant levels, including raw NGS read pileups. Of ambiguous variant calls with 99% (n = 1701) as true positives (enriched for long insertions or deletions and homopolymers) or true negatives (often conspicuous NGS artifacts), with the remaining

Classification systems for wave energy resources and wave energy converter (WEC) technologies could provide similar benefits to those for the wind energy industry: resource classification facilitating reconnaissance studies and project planning at both regional and national scales; and WEC classification streamlining and reducing costs of WEC device design and manufacturing. In the present study, a classification system for U.S. wave resources is used to investigate the feasibility of WEC classification. Wave spectra inputs from three wave energy resource classes delineated in this system are used to derive distributions of optimized WEC design scaling factors, as well as WEC design responses. Preliminary results indicate that a single standard WEC design class could serve within a given resource class, and corresponding regional wave climate, due to distinct wave energy distributions and concentrations of energy within partitioned period bands for each resource class. The WEC response to extreme loads was found to vary considerably within the most energetic of the resource classes examined, suggesting the need for these standard design classes to meet structural design requirements based on the upper limits of load response within a given resource class. However, the observed load metric variation is lower than the inter-region resource variations.

Key Points Question What is the period prevalence and comorbidity of patients with functional seizures? Findings This case-control study including 3341 patients with functional seizures (period prevalence, 0.14%) identified from all patients at a university medical center found that posttraumatic stress disorder and sexual assault trauma were associated with functional seizures. Novel associations were identified, including cerebrovascular disease. Meaning The findings of this study suggest that patients who present with seizures and additional psychiatric comorbidities, sexual assault trauma history, or cerebrovascular disease should be referred for video electroencephalogram diagnostic assessment., This case-control study of patients at a large university medical center provides an epidemiological assessment of functional seizures and their association with comorbidities (eg, cerebrovascular disease) and risk factors (eg, sexual assault trauma)., Importance Functional seizures (formerly psychogenic nonepileptic seizures), paroxysmal episodes that are often similar to epileptic seizures in their clinical presentation and display no aberrant brain electrical patterns, are understudied. Patients experience a long diagnostic delay, few treatment modalities, a high rate of comorbidities, and significant stigma due to the lack of knowledge about functional seizures. Objective To characterize the clinical epidemiology of a population of patients with functional seizures observed at Vanderbilt University Medical Center (VUMC). Design, Setting, and Participants This case-control study included patients with functional seizures identified in the VUMC electronic health record (VUMC-EHR) system from October 1989 to October 2018. Patients with epilepsy were excluded from the study and all remaining patients in the VUMC medical center system were used as controls. In total, the study included 1431 patients diagnosed with functional seizures, 2251 with epilepsy and functional seizures, 4715 with epilepsy without functional seizures, and 502 200 control patients who received treatment at VUMC for a minimum of a 3 years. Data were analyzed from November 2018 to March 2020. Exposure Diagnosis of functional seizures, as identified from the VUMC-EHR system by an automated phenotyping algorithm that incorporated International Classification of Diseases, Ninth Revision (ICD-9) codes, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes, Current Procedural Terminology codes, and natural language processing. Main Outcomes and Measures Associations of functional seizures with comorbidities and risk factors, measured in odds ratios (ORs). Results Of 2 346 808 total patients in the VUMC-EHR aged 18 years or older, 3341 patients with functional seizures were identified (period prevalence, 0.14%), 1062 (74.2%) of whom were women and for which the median (interquartile range) age was 49.3 (39.4-59.9) years. This assessment replicated previously reported associations with psychiatric disorders including posttraumatic stress disorder (PTSD) (OR, 1.22; 95% CI, 1.21-1.24; P

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins. ispartof: NEUROBIOLOGY OF AGING vol:92 ispartof: location:United States status: published

PurposeThe percentage of a maternal cell-free DNA (cfDNA) sample that is fetal-derived (the fetal fraction; FF) is a key driver of the sensitivity and specificity of noninvasive prenatal screening (NIPS). On certain NIPS platforms, >20% of women with high body-mass index (and >5% overall) receive a test failure due to low FF (MethodsA scalable fetal-fraction amplification (FFA) technology was analytically validated on 1,264 samples undergoing whole-genome sequencing (WGS)-based NIPS. All samples were tested with and without FFA.ResultsZero samples had FFConclusionsFFA transforms low-FF samples into high-FF samples. By combining FFA with WGS-based NIPS, a single round of NIPS can provide nearly all women with confident results about the broad range of potential fetal chromosomal abnormalities across the genome.

Numerical models have been widely used for the resource characterization and assessment of tidal instream energy. The accurate assessment of tidal stream energy resources at a feasibility or project-design scale requires detailed hydrodynamic model simulations or high-quality field measurements. This study applied a three-dimensional finite-volume community ocean model (FVCOM) to simulate the tidal hydrodynamics in the Passamaquoddy&ndash, Cobscook Bay archipelago, with a focus on the Western Passage, to assist tidal energy resource assessment. IEC Technical specifications were considered in the model configurations and simulations. The model was calibrated and validated with field measurements. Energy fluxes and power densities along selected cross sections were calculated to evaluate the feasibility of the tidal energy development at several hotspots that feature strong currents. When taking both the high current speed and water depth into account, the model results showed that the Western Passage has great potential for the deployment of tidal energy farms. The maximum extractable power in the Western Passage was estimated using the Garrett and Cummins method. Different criteria and methods recommended by the IEC for resource characterization were evaluated and discussed using a sensitivity analysis of energy extraction for a hypothetical tidal turbine farm in the Western Passage.

Opportunities and constraints for wave energy conversion technologies and projects are evaluated by identifying and characterizing the dominant wave energy systems for United States (US) coastal waters using marginal and joint distributions of the wave energy in terms of the peak period, wave direction, and month. These distributions are computed using partitioned wave parameters generated from a 30 year WaveWatch III model hindcast, and regionally averaged to identify the dominant wave systems contributing to the total annual available energy ( A A E ) for eleven distinct US wave energy climate regions. These dominant wave systems are linked to the wind systems driving their generation and propagation. In addition, conditional resource parameters characterizing peak period spread, directional spread, and seasonal variability, which consider dependencies of the peak period, direction, and month, are introduced to augment characterization methods recommended by international standards. These conditional resource parameters reveal information that supports project planning, conceptual design, and operation and maintenance. The present study shows that wave energy resources for the United States are dominated by long-period North Pacific swells (Alaska, West Coast, Hawaii), short-period trade winds and nor’easter swells (East Coast, Puerto Rico), and wind seas (Gulf of Mexico). Seasonality, peak period spread, and directional spread of these dominant wave systems are characterized to assess regional opportunities and constraints for wave energy conversion technologies targeting the dominant wave systems.

Internal waves are ubiquitous features in coastal marine environments and have been observed to mediate vertical distributions of zooplankton. Internal waves possess fine-scale hydrodynamic cues that copepods and other zooplankton are known to sense, such as fluid density gradients and velocity gradients (quantified as shear strain rate). The role of copepod behavior in response to cues associated with internal waves is largely unknown. The objective is to provide insight to the bio-physical interaction and the role of biological versus physical forcing in mediating organism distributions. A laboratory-scale internal wave apparatus is designed to facilitate fine scale observations of copepod behavior in flows that replicate in situ conditions of internal waves in two-layer stratification. An experimental configuration is presented with a density jump of 1 sigma_t. Theoretical analysis of the two-layer system provided guidance to the target forcing frequency needed to generate a standing internal wave with a single dominate frequency of oscillation. Flow visualization and signal processing of the interface location were used to quantify the wave characteristics. The results show a close match to the target wave parameters. Marine copepod (mixed population of Acartia tonsa, Temora longicornis, and Eurytemora affinis) behavior assays were conducted for three different physical arrangements: (1) no density stratification (i.e. control), (2) stagnant two-layer density stratification, and (3) two-layer density stratification with internal wave motion. Digitized trajectories of copepod swimming behavior indicate that in the control (case 1) the animals showed no preferential aggregation. In the stagnant density jump treatment (case 2) copepods preferentially moved horizontally, parallel to the density interface. In the internal wave treatment (case 3) copepods demonstrated loopy, orbital trajectories near the density interface. Analysis of advected trajectories in the internal wave, with and without superimposed copepod swimming, reveal distinct differences with the observed copepod trajectories in the internal wave treatment. These differences and a consideration of the potential hydrodynamic cues indicate that copepod behavior response has a substantial influence on the swimming trajectories in the internal wave region.

ObjectiveTo determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses.MethodsWe acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach. We compared patients to controls and examined associations of network properties with disease metrics and neurocognitive testing.ResultsWe observed marked decreases in connectivity between NBM and the rest of the brain in patients with TLE (0.91 ± 0.88, mean ± SD) vs controls (1.96 ± 1.13, p < 0.001, t test). Larger decreases in connectivity between NBM and fronto-parietal-insular regions were associated with higher frequency of consciousness-impairing seizures (r = −0.41, p = 0.008, Pearson). A core network of altered nodes in TLE included NBM ipsilateral to the epileptogenic side and bilateral limbic structures. Furthermore, normal community affiliation of ipsilateral NBM was lost in patients, and this structure displayed the most altered clustering coefficient of any node examined (3.46 ± 1.17 in controls vs 2.23 ± 0.93 in patients). Abnormal connectivity between NBM and subcortical arousal community was associated with modest neurocognitive deficits. Finally, a logistic regression model incorporating connectivity properties of ipsilateral NBM successfully distinguished patients from control datasets with moderately high accuracy (78%).ConclusionsThese results suggest that while NBM is rarely studied in epilepsy, it may be one of the most perturbed network nodes in TLE, contributing to widespread neural effects in this disabling disorder.

Objectives Post marketing analysis of anti-epileptic drug (AED) efficacy and tolerability is of great value to the clinician since it is more representative of clinical practice than clinical trial data. We analyzed our experience with lacosamide (LCM) in patients treated after marketing. Patients and methods We identified all patients who were treated with LCM during the four year period after marketing, excluding patients who were in clinical trials. We recorded demographic data and analyzed efficacy and tolerability in patients who had at least one follow up visit or telephone call 3 months after the initiation of LCM. Results A total of 165 patients met our inclusion criteria. The mean age was 41 years. The majority of the cohort had focal epilepsy (146 patients) (88.4%). The mean duration of treatment was 31.2 months. Eighty one patients (49.1%) were continuing LCM at last follow up. Adverse effects (AEs) and discontinuation were significantly more common when LCM was added to one or more Na-channel blocking agents (NCB) (p = 0.0003 and 0.17). The 50% responder rate was 26% at 3 months and increased to 49% at 36 months. Patients were more likely to continue the drug and less likely to have AEs with slower titration over > 4 weeks (p = 0.02 for each). Four or more previously failed AEDs predicted poorer response rate compared to three or less AEDs (p = 0.001). Conclusion LCM use in clinical practice was associated with greater rate of seizure freedom than in clinical trials. Discontinuation and occurrence of AEs were significantly more likely with faster titration and adding LCM to NCB agents.

The ocean contains a variety of renewable energy resources, little of which has been exploited. Here, we review both tidal range and tidal stream energy, with a focus on the resource, feedbacks, and environmental interactions. The review covers a wide range of timescales of relevance to tidal energy, from fortnightly (spring-neap) and semi-diurnal variability, down to array, and device-scale turbulence. When simulating the regional tidal energy resource, and to assess environmental impacts, it is necessary to account for feedbacks between the tidal array and the resource itself. We critically review various methods for simulating energy extraction, from insights gained through theoretical studies of “tidal fences” in idealized channels, to realistic three-dimensional model studies with complex geometry and arrays of turbines represented by momentum sinks and additional turbulence due to the presence of rotors and support structures. We discuss how variability can be reduced by developing multiple (aggregated) sites with a consideration of the enhanced phase diversity offered by exploiting less energetic tidal currents. This leads to future research questions that have not yet been explored in depth at first-generation tidal sites in relatively sheltered channels (e.g., the interaction of waves with currents). Such enhanced understanding of real sea conditions, including the effects of wind and waves, leads to our other identified primary future research direction—reduced uncertainties in turbulence predictions, including the development of realistic models that simulate the interaction between ambient turbulence and the turbulence resulting from multiple wakes, and changes to system-wide hydrodynamics, water quality, and sedimentation.

Purpose of review Hepatic hydrothorax is a complication of end-stage liver disease that may have significant associated morbidity. Sodium restriction and diuretic therapy are the mainstays of treatment, though up to a quarter of patients will become refractory to this and will require a pleural drainage procedure. Thoracentesis, transjugular intrahepatic portosystemic shunt, and chemical pleurodesis all have variable success rates and associated complications in the management of hepatic hydrothorax. Indwelling tunneled pleural catheters (ITPC) have been successfully used to manage recurrent symptomatic malignant pleural effusions, and there is growing interest regarding their use in the management of hepatic hydrothorax. Recent findings Evidence regarding the use of ITPC for nonmalignant pleural effusions has been limited to retrospective studies and small feasibility trials. A recent meta-analysis regarding the use of IPTC for nonmalignant pleural effusions demonstrated a rate of spontaneous pleurodesis of 51%, whereas a small, prospective study demonstrated spontaneous pleurodesis rates of 33% and an infection rate of 16.7% in 24 patients with ITPC placed for hepatic hydrothorax in patients suitable for liver transplant evaluation. Summary ITPC may be an acceptable treatment option for the management of hepatic hydrothorax which are refractory to conventional medical management. Larger, randomized controlled trials are needed to further evaluate the safety and efficacy of these catheters for the management of nonmalignant pleural effusions.

Background Automatisms are frequently encountered during video-monitoring of patients with focal epilepsy in the EMU and generally thought to have a low lateralizing value in isolation. Rhythmic ictal nonclonic hand (RINCH) motions have been described in small series as a potentially lateralizing semiologic sign. We aimed to expand on prior work and determine the prevalence, characteristics, and lateralizing value of RINCH motions in general epilepsy monitoring unit (EMU) population with focal epilepsy. Methods All patients with recorded seizures in the EMU were included in our database search. Search was performed to identify seizures with reported RINCH motions. Both electroencephalography (EEG) and video of identified seizures were reviewed. Results We identified RINCH motions in 131 seizures in 71 patients. Overall seizure localization was temporal in 57 patients, frontotemporal in 3 patients, and extratemporal in 7 patients. We estimated RINCH motions to occur in 8.5% of EMU patients with recorded seizures. The most common RINCH motions in descending order were as follows: hand opening and closing, finger rubbing, milking motions, finger flexion/extension, and pill rolling. The mean RINCH motion latency from seizure onset was 34.48 s in temporal lobe epilepsy and 10.31 s in frontal lobe epilepsy. The RINCH motions were contralateral to seizure onset in 61 of 65 (93.8%) with lateralized seizure onset. Dystonic posturing was present in 43% of seizures with RINCH motions. Conclusion The RINCH motions are a common sign in focal seizures and should be distinguished from other types of manual automatism as they carry a strong lateralizing value.

While temporal lobe epilepsy (TLE) is a focal epilepsy, previous work demonstrates that TLE causes widespread brain-network disruptions. Impaired visuospatial attention and learning in TLE may be related to thalamic arousal nuclei connectivity. Our prior preliminary work in a smaller patient cohort suggests that patients with TLE demonstrate abnormal functional connectivity between central lateral (CL) thalamic nucleus and medial occipital lobe. Others have shown pulvinar connectivity disturbances in TLE, but it is incompletely understood how TLE affects pulvinar subnuclei. Also, the effects of epilepsy surgery on thalamic functional connectivity remains poorly understood. In this study, we examine the effects of TLE on functional connectivity of two key thalamic arousal-nuclei: lateral pulvinar (PuL) and CL. We evaluate resting-state functional connectivity of the PuL and CL in 40 patients with TLE and 40 controls using fMRI. In 25 patients, postoperative images (1 year) were also compared with preoperative images. Compared to controls, patients with TLE exhibit loss of normal positive connectivity between PuL and lateral occipital lobe (p 0.05), and a loss of normal negative connectivity between CL and medial occipital lobe (p 0.01, paired t-tests). FMRI amplitude of low-frequency fluctuation (ALFF) in TLE trended higher in ipsilateral PuL (p = 0.06), but was lower in the lateral occipital (p 0.01) and medial occipital lobe in patients versus controls (p 0.05, paired t-tests). More abnormal ALFF in the ipsilateral lateral occipital lobe is associated with worse preoperative performance on Rey Complex Figure Test Immediate (p 0.05, r = 0.381) and Delayed scores (p 0.05, r = 0.413, Pearson's Correlations). After surgery, connectivity between PuL and lateral occipital lobe remains abnormal in patients (p 0.01), but connectivity between CL and medial occipital lobe improves and is no longer different from control values (p 0.05, ANOVA, post hoc Fischer's LSD). In conclusion, thalamic arousal nuclei exhibit abnormal connectivity with occipital lobe in TLE, and some connections may improve after surgery. Studying thalamic arousal centers may help explain distal network disturbances in TLE.

The standard for monitoring sedation levels in critically ill patients is intermittent bedside evaluation, and is prone to anchoring bias. Quantitative electroencephalography (qEEG) allows automated processing of recorded brain electrical activity and could be used to continuously monitor level of consciousness in critically ill patients. The majority of qEEG studies have included persons 80 years of age or less, and the qEEG profiles of nonagenarians have been incompletely characterized. Knowledge of the qEEG patterns of patients 90 years and older is essential for appropriate interpretation of such metrics in this population. This retrospective cohort study characterized qEEG profiles of acutely ill nonagenarians. We investigated whether the relationship between qEEG and level of consciousness differed between patients with and without a history of dementia. We included patients 90-100 years old admitted to Vanderbilt University Medical Center who underwent EEG and as part of their clinical care. We compared qEEG features to nursing-defined level of arousal as measured by the Richmond Agitation-Sedation Scale (RASS) in patients with and without history of dementia. Between January and December 2019, 26 nonagenarians underwent EEG for clinical purposes. One study was excluded due to excessive artifact. Of the remaining, 6 (24%) were male and 18 (72%) were Caucasian. Among all patients, RASS decreased with increases in EEG theta variability (coefficient -7.7, 95%CI -10.6 to -4.8). This relationship was not significantly modified by history of dementia (coefficient of interaction term -0.36, 95%CI -3.7 to 2.9). Dementia does not impact qEEG features of level of consciousness in nonagenarians.

In upwelling regions, wind relaxations lead to poleward propagating warm water plumes that are important to coastal ecosystems. The coastal ocean response to wind relaxation around Pt. Conception, CA is simulated with a Regional Ocean Model (ROMS) forced by realistic surface and lateral boundary conditions including tidal processes. The model reproduces well the statistics of observed subtidal water column temperature and velocity at both outer and inner-shelf mooring locations throughout the study. A poleward-propagating plume of Southern California Bight water that increases shelf water temperatures by ≈ 5°C is also reproduced. Modeled plume propagation speed, spatial scales, and flow structure are consistent with a theoretical scaling for coastal buoyant plumes with both surface-trapped and slope-controlled dynamics. Plume momentum balances are distinct between the offshore (>30 m depth) region where the plume is surface-trapped, and onshore of the 30 m isobath (within 5 km from shore) where the plume water mass extends to the bottom and is slope controlled. In the onshore region, bottom stress is important in the alongshore momentum equation and generates vertical vorticity that is an order of magnitude larger than the vorticity in the plume core. Numerical experiments without tidal forcing show that modeled surface temperatures are biased 0.5°C high, potentially affecting plume propagation distance and persistence.

The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use.Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports.A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days.The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.

Modeling studies of estuary circulation show great sensitivity to the water exchange into and out of adjacent marshes, yet there is significant uncertainty in resolving the processes governing marsh surface flow. The objective of this study is to measure the estuary channel-to-saltmarsh pressure gradient and to guide parameterization for how it affects the surface flow in the high marsh. Current meters and high-resolution pressure transducers were deployed along a transect perpendicular to the nearby Little Ogeechee River in a saltmarsh adjacent to Rose Dhu Island near Savannah, Georgia, USA. The vertical elevations of the transducers were surveyed with static GPS to yield high accuracy water surface elevation data. It is found that water level differences between the Little Ogeechee River and neighboring saltmarsh are up to 15 cm and pressure gradients are up to 0.0017 m of water surface elevation change per m of linear distance during rising and falling tides. The resulting Little-Ogeechee-River-to-saltmarsh pressure gradient substantially affects tidal velocities at all current meter locations. At the velocity measurement station located closest to the Little Ogeechee River bank, the tidal velocity is nearly perpendicular to the bank. At this location, surface flow is effectively modeled as a balance between the pressure gradient force and the drag force due to marsh vegetation and bottom stress using the Darcy–Weisbach/Lindner's equations developed for flow-through-vegetation analysis in open channel flow. The study thus provides a direct connection between the pressure gradient and surface flow velocity in the high marsh, thereby overcoming a long-standing barrier in directly relating flow-through-saltmarsh studies to flow-through-vegetation studies in the open channel flow literature.

Historically, the Oregon Department of Transportation (DOT) has spent the Highway Safety Improvement Program (HSIP) funding only on state highways. However, half of the fatalities and serious injuries occur on nonstate roadways. To address this concern and to comply with the federal requirement that the HSIP funding be spent on all public roads, the Oregon DOT developed a jurisdictionally blind safety program, known as the All Roads Transportation Safety (ARTS) Program, to address safety problems on all public roads in Oregon. The objective of the ARTS Program is the same as that of the HSIP: to reduce fatalities and serious injuries on all public roads using a data-driven approach. The ARTS Program has two components: hot spot and systemic. For the first round of the ARTS Program, safety projects were selected by using a combination of a selection approach and an application-based approach. For the hot spot component, potential safety projects were identified by using crash history, and the projects were prioritized on the basis of benefit–cost ratios. The systemic component—with three emphasis areas: roadway departure, intersection, and pedestrian and bicycle—was an application-based process in which the Oregon DOT and local agencies competed for available safety funding. Systemic projects were prioritized on the basis either of benefit–cost ratios (roadway departure and intersection projects) or cost-effectiveness index (pedestrian and bicycle projects). Through collaboration with various stakeholders, the Oregon DOT was able to select safety projects on all public roads with a data-driven approach. It is expected that these projects will significantly improve safety on all Oregon roads by reducing fatal and serious injury crashes.

The wave energy resource is characterized and assessed for coastal waters of the United States to evaluate regional opportunities and constraints for wave energy converter (WEC) projects. Partitioned wave parameters generated from a 30-year WaveWatch III model hindcast are used to estimate the total wave energy potential as an annual available energy ( AAE ), which is a theoretical annual energy production per unit energy capture length without considering energy conversion losses. The distribution of AAE by peak period, wave direction, month, and year is quantified using summary statistics, including peak period spread, AAE -weighted period, AAE -directionality coefficient, and inter-annual and seasonal temporal variability. Geographical distributions of the AAE and these five resource attributes delineate distinct wave energy resource regions within United States coastal waters, where different opportunities and constraints may influence regional energy planning, WEC project development, and WEC conceptual design.

Clinical genomic tests increasingly use a next-generation sequencing (NGS) platform due in part to the high fidelity of variant calls, yet rare errors are still possible. In germline DNA screening, failure to correct such errors could have serious consequences for patients, who may follow an unwarranted screening or surgical management path. It has been suggested that routine orthogonal confirmation by Sanger sequencing is required to verify NGS results, especially low-confidence positives with depressed allele fraction (30% of alternate allele). We evaluated whether an alternative method of confirmation-software-assisted manual call review-performed comparably with Sanger confirmation in15,000 samples. Licensed reviewers manually inspected both raw and processed data at the batch, sample, and variant levels, including raw NGS read pileups. Of ambiguous variant calls with30% allele fraction (1707 total calls at 38 unique sites), manual call review classified99% (n = 1701) as true positives (enriched for long insertions or deletions and homopolymers) or true negatives (often conspicuous NGS artifacts), with the remaining1% (n = 6) being mosaic. Critically, results from software-assisted manual review and retrospective Sanger sequencing were concordant for samples selected from all ambiguous sites. We conclude that the confirmation required for high confidence in NGS-based germline testing can manifest in different ways; a trained NGS expert operating platform-tailored review software achieves quality comparable with routine Sanger confirmation.

Clinical genomic tests increasingly utilize a next generation sequencing (NGS) platform due in part to the high fidelity of variant calls, yet rare errors are still possible. In hereditary cancer screening, failure to correct such errors could have serious consequences for patients, who may follow an unwarranted screening or surgical-management path. It has been suggested that routine orthogonal confirmation via Sanger sequencing is required to verify NGS results, especially low-confidence positives with depressed allele fraction (15,000 samples. Licensed reviewers manually inspected both raw and processed data at the batch-, sample-, and variant-level, including raw NGS read pileups. Of ambiguous variant calls with 99% (1,701) as true positives (enriched for long insertions or deletions (“indels”) and homopolymers) or true negatives (often conspicuous NGS artifacts), with the remaining

BACKGROUND By identifying pathogenic variants across hundreds of genes, expanded carrier screening (ECS) enables prospective parents to assess the risk of transmitting an autosomal recessive or X-linked condition. Detection of at-risk couples depends on the number of conditions tested, the prevalence of the respective diseases, and the screen's analytical sensitivity for identifying disease-causing variants. Disease-level analytical sensitivity is often METHODS We present an analytical validation and preliminary clinical characterization of a 235-gene sequencing-based ECS with full coverage across coding regions, targeted assessment of pathogenic noncoding variants, panel-wide CNV calling, and specialized assays for technically challenging genes. Next-generation sequencing, customized bioinformatics, and expert manual call review were used to identify single-nucleotide variants, short insertions and deletions, and CNVs for all genes except FMR1 and those whose low disease incidence or high technical complexity precluded novel variant identification or interpretation. RESULTS Screening of 36859 patients' blood or saliva samples revealed the substantial impact on fetal disease-risk detection attributable to novel CNVs (9.19% of risk) and technically challenging conditions (20.2% of risk), such as congenital adrenal hyperplasia. Of the 7498 couples screened, 335 were identified as at risk for an affected pregnancy, underscoring the clinical importance of the test. Validation of our ECS demonstrated >99% analytical sensitivity and >99% analytical specificity. CONCLUSIONS Validated high-fidelity identification of different variant types—especially for diseases with complicated molecular genetics—maximizes at-risk couple detection.

Ocean currents represent an alternative source of clean energy given their inherent reliability, persistence and sustainability. The general ocean circulation is characterized by large rotating ocean gyres resulting in rapid ocean currents along the western boundaries because of the Coriolis Effect. The Gulf Stream system is formed by the western boundary current of the North Atlantic Ocean flowing along the east coast of the United States, and is of particular interest as a potential energy resource for the United States. This study presents a national database of ocean current kinetic energy resource derived from seven years of numerical model simulations to help advance awareness and market penetration for ocean current energy. A web based GIS interface is provided for dissemination of the national energy resource data: http://www.oceancurrentpower.gatech.edu/ . The website includes GIS layers of computed monthly and yearly mean ocean current speed and associated power density along the coastlines of the United States, as well as joint and marginal probability histograms for current velocities at a variable horizontal resolution of 4–7 km. Various tools are provided for viewing, identifying, filtering and downloading the data from this website. The Gulf Stream system, especially the Florida Current, concentrates the highest kinetic power density ( > 2000 W / m 2 ). The majority of the kinetic power and its variability are only present in relatively shallow water given the strong correlation with the surface wind stress. The kinetic energy flux in the Florida Current is estimated over 30 years to provide temporal variability of the undisturbed kinetic energy with high statistical significance. Available power of approximately 5 GW associated with the undisturbed natural flow condition from the Gulf Stream system is predicted based on hypothetical turbine parameters. Successful development of renewable energy generation requires further studies to account for more precise technical, economic and environmental constraints.

Increasing energy consumption and decreasing reserves of fossil fuels have led to growing interest in renewable energy from the ocean. Ocean currents are an alternative source of clean energy due to their inherent reliability, persistence and sustainability. General ocean circulations exist in the form of large rotating ocean gyres, and feature extremely rapid current flow in the western boundaries due to the Coriolis effect. The Gulf Stream system is formed by the western boundary current of the North Atlantic Ocean that flows along the east coastline of the United States, and therefore is of particular interest as a potential energy resource for the United States. The theoretical energy balance in the Gulf Stream system is examined using the two-dimensional ocean circulation equations based on the assumptions of the Stommel model for subtropical gyres with the quasi-geostrophic balance between pressure gradient, Coriolis force, wind stress and friction driving the circulation. To represent flow dissipation due to turbines a spatially varying turbine drag coefficient is formulated and a finite difference numerical approach is utilized to obtain an implicit solution of the model. The results show that considering extraction over a region representing the entire Florida Current portion of the Gulf Stream system, the average power dissipated ranges between 4 and 6 GW with a mean around 5.1 GW. This corresponds to an average of approximately 45 TWh/yr. However, if the extraction area approximates the entire portion of the Gulf Stream within 200 miles of the US coastline, the average power dissipated becomes 18.6 GW or 163 TWh/yr. The impact of the localized turbine drag on the hydrodynamics is primarily within the turbine region. The extra drag force from turbines slows down the current velocity and leads to redirection of the Gulf Stream flow. It also results in a sea surface drop in the turbine region. Localized turbine drag significantly reduces residual kinetic energy flux in the circulation. However, its influence on the residual volume flux depends on the area of the turbine region.

PurposeBy identifying pathogenic variants across hundreds of genes, expanded carrier screening (ECS) enables prospective parents to assess risk of transmitting an autosomal recessive or X-linked condition. Detection of at-risk couples depends on the number of conditions tested, the diseases’ respective prevalences, and the screen’s sensitivity for identifying disease-causing variants. Here we present an analytical validation of a 235-gene sequencing-based ECS with full coverage across coding regions, targeted assessment of pathogenic noncoding variants, panel-wide copy-number-variant (CNV) calling, and customized assays for technically challenging genes.MethodsNext-generation sequencing, a customized bioinformatics pipeline, and expert manual call review were used to identify single-nucleotide variants, short insertions and deletions, and CNVs for all genes except FMR1 and those whose low disease incidence or high technical complexity precludes novel variant identification or interpretation. Variant calls were compared to reference and orthogonal data.ResultsValidation of our ECS data demonstrated >99% analytical sensitivity and >99% specificity. A preliminary assessment of 15,177 patient samples reveals the substantial impact on fetal disease-risk detection attributable to novel CNV calling (13.9% of risk) and technically challenging conditions (15.5% of risk), such as congenital adrenal hyperplasia.ConclusionValidated, high-fidelity identification of different variant types—especially in diseases with complicated molecular genetics—maximizes at-risk couple detection.

Ocean basin scale wind-driven currents provide a possible source of renewable energy using ocean turbine technology to convert kinetic energy of the flow to electricity. The Gulf Stream System in the North Atlantic Ocean is part of one of the largest subtropical gyres in the world. Within these gyres, the western intensification due to the Coriolis force produces some of the largest and most persistent ocean currents. This chapter discusses the potential for generating energy from the Gulf Stream System with a particular focus on the Florida Current portion. The overall characteristics related to the energy potential of the Gulf Stream are described based on 7 years of model simulations and 30 years of volume flux observations across the Florida Straits. Within the Florida Current portion of the Gulf Stream System, the mean kinetic power is found to be over 22 GW with a standard deviation near 6 GW. However, this variability was found to be contained within the top 100 m of the water column. Assessments based on the undisturbed flow indicate that deployment on the order of 5000 turbines could average over 5 GW of power. To quantify the effects of the energy extraction on the circulation to obtain a better estimate of the available power, idealized and realistic modeling of the ocean circulation are presented. The idealized model indicates that a mean of 5 GW of power could be dissipated within the Florida Straits, with much more power dissipated if broader regions are considered for energy extraction. However, the practical constraints on ocean current energy extraction, such as the acceptable range of impacts on the flow as seen in a realistic 3D ocean model simulation, lead to a reduction in the assessment of the power available.

Hyrdokinetic tidal energy is the conversion of tidal current kinetic energy to another more useful form, frequently electricity. As with any other form of renewable energy, resource assessments are essential for the tidal energy project planning and design process. While tidal currents have significant spatial and temporal variability, the predictability of tidal flows makes deterministic modeling a suitable methodology for hydrokinetic tidal energy resource assessments. The scope (theoretical, technical, or practical resource) and scale (turbine, region, or project) of the assessment determine the basic concepts and methodology to be utilized and are described in this chapter. At the turbine scale, the technical resource is frequently quantified as the annual energy production (AEP) computed based on the velocity probability distribution for the specific location as well as the turbine properties. The uncertainty associated with the estimates of the AEP is highly dependent on the accuracy of the tidal constituent amplitudes and phases. Regional resource assessments are frequently used to determine the feasibility of tidal power at the scale of an estuary, using numerical models to predict the spatial distribution of the power density. In addition, simplified models or even analytical analysis can be done to produce an upper bound on the regional theoretical power, although with a high level of uncertainty due to the simplifications and assumptions. Resource assessments at the project scale provide both the theoretical and the technical energy as well as the practical energy accounting for many additional constraints, including social, economic, and environmental restrictions. The International Electrotechnical Commission technical specification for tidal energy resource assessments (IEC 2015) provides the essential guidelines for performing project-scale resource assessments. These guidelines include minimum grid resolution requirements as well as model calibration and validation procedures. In addition, larger projects will need to include the effect of energy extraction on the flow field to produce more accurate estimates of velocity probability distributions for computing the technical resource. An example case study demonstrating a regional feasibility and project-scale resource assessment is presented in this chapter.

A 3D numerical model is used to simulate the distortion of tidal hydrodynamics in the Ogeechee Estuary, GA. The Ogeechee, like many estuaries found in the Southeastern US, consists of shallow channel networks and extensive intertidal storage in the form of wetlands. Such features are known to induce non-linear overtide generation and significant tidal distortion, otherwise known as tidal stage asymmetry. Simulations are run with varying parameters to assess their effects on modeling tidal distortion for the Ogeechee Estuary: bottom friction coefficients, enhanced wetland friction coefficients, and tidal flat elevations. To succinctly quantify the degree of distortion across the domain, the statistical parameters of skewness and asymmetry are calculated for time series of water surface heights and channel volume fluxes. The intertidal storage causes the peak flood flux to occur later and the peak ebb flux to occur earlier, thereby resulting in positive asymmetry for the volume flux for the full estuary. However, ebb dominance is a localized feature and varies throughout the estuary. Increasing the intertidal storage by lowering wetland elevation enhances the effects on high tide and volume flux magnitudes, decreasing the ebb-dominance and volume flux asymmetry typically associated with intertidal storage thereby indicating the importance of the wetland elevation over the total storage volume. Increased channel bottom friction reduces ebb-dominance by extending the duration of the falling tide. More interestingly, increased wetland friction reduces the influence of wetland intertidal storage on tidal distortion. The model suggests an increase in wetland friction does little to dampen wave propagation at high tide but rather impedes the lateral flooding of wetlands, reducing ebb dominance. Tidal flat elevation has the largest impact on distortion for the Ogeechee Estuary whereas enhanced wetland and bottom frictional influences on distortion are small, albeit not insignificant.

The past two decades have brought many important advances in our understanding of the hereditary susceptibility to cancer. Numerous studies have provided convincing evidence that identification of germline mutations associated with hereditary cancer syndromes can lead to reductions in morbidity and mortality through targeted risk management options. Additionally, advances in gene sequencing technology now permit the development of multigene hereditary cancer testing panels. Here, we describe the 2016 revision of the Counsyl Inherited Cancer Screen for detecting single-nucleotide variants (SNVs), short insertions and deletions (indels), and copy number variants (CNVs) in 36 genes associated with an elevated risk for breast, ovarian, colorectal, gastric, endometrial, pancreatic, thyroid, prostate, melanoma, and neuroendocrine cancers. To determine test accuracy and reproducibility, we performed a rigorous analytical validation across 341 samples, including 118 cell lines and 223 patient samples. The screen achieved 100% test sensitivity across different mutation types, with high specificity and 100% concordance with conventional Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA). We also demonstrated the screen’s high intra-run and inter-run reproducibility and robust performance on blood and saliva specimens. Furthermore, we showed that pathogenic Alu element insertions can be accurately detected by our test. Overall, the validation in our clinical laboratory demonstrated the analytical performance required for collecting and reporting genetic information related to risk of developing hereditary cancers.