Fetal fraction amplification within prenatal cfDNA screening enables detection of genome-wide copy-number variants at enhanced resolution.

Purpose: Clinically significant copy-number variants (CNVs) occur in 1% to 2% of pregnancies and are difficult to detect via prenatal cell-free DNA (cfDNA) screening because of the low fraction of fetal-derived cfDNA in maternal plasma. Here, we use fetal fraction amplification (FFA) and improved computational algorithms to enhance the resolution and sensitivity of CNV detection.

Methods: We implemented and characterized the performance of a hidden Markov model that identifies fetal CNVs.

The probabilistic dependence of ship-induced waves is preserved spatially and temporally in the Savannah River (USA).

The rapid changes in the shipping fleet during the last decades has increased the ship-induced loads and, thus, their impact on infrastructures, margin protections and ecosystems. Primary waves have been pointed out as the cause of those impacts, with heights that can exceed 2 m and periods around 2 minutes. Consequently, extensive literature can be found on their estimation mainly from a deterministic perspective with methods based on datasets limited to one location, making difficult their generalization.

Network signatures define consciousness state during focal seizures.

Objective: Epilepsy is a common neurological disorder affecting 1% of the global population. Loss of consciousness in focal impaired awareness seizures (FIASs) and focal-to-bilateral tonic-clonic seizures (FBTCSs) can be devastating, but the mechanisms are not well understood. Although ictal activity and interictal connectivity changes have been noted, the network states of focal aware seizures (FASs), FIASs, and FBTCSs have not been thoroughly evaluated with network measures ictally.

Inter- and intra-observer variability of radial-endobronchial ultrasound image interpretation for peripheral pulmonary lesions.

Background: Radial probe endobronchial ultrasound (R-EBUS) is often utilized in guided bronchoscopy for the diagnosis of peripheral pulmonary lesions. R-EBUS probe positioning has been shown to correlate with diagnostic yield, but overall diagnostic yield with this technology has been inconsistent across the published literature. Currently there is no standardization for R-EBUS image interpretation, which may result in variability in grading concentricity of lesions and subsequently procedure performance.

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Epilepsy with anterior temporal encephaloceles: Baseline characteristics, post-surgical outcomes, and comparison to mesial temporal sclerosis.

Objective: To review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy.

Methods: Patients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS.

Functional seizures are associated with cerebrovascular disease and functional stroke is more common in patients with functional seizures than epileptic seizures.

Purpose: To characterize the relationship between functional seizures (FSe), cerebrovascular disease (CVD), and functional stroke.

Method: A retrospective case-control study of 189 patients at a single large tertiary medical center. We performed a manual chart review of medical records of patients with FSe or epileptic seizures (ES), who also had ICD code evidence of CVD.

Enhanced rates of detection and treatment of depression and anxiety disorders among adult patients with epilepsy using automated EMR-based screening.

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.

Experience From 211 Transcortical Selective Amygdalohippocampectomy Procedures: Relevant Surgical Anatomy and Review of the Literature.

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.

Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy.

Objective: To 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.

Methods: We 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.

Epidemiology of Functional Seizures Among Adults Treated at a University Hospital.

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).

People with mesial temporal lobe epilepsy have altered thalamo-occipital brain networks.

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.

High-throughput fetal fraction amplification increases analytical performance of noninvasive prenatal screening.

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 (<4%).

Methods: A scalable fetal fraction amplification (FFA) technology was analytically validated on 1264 samples undergoing whole-genome sequencing (WGS)-based NIPS.

Seizure-onset regions demonstrate high inward directed connectivity during resting-state: An SEEG study in focal epilepsy.

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.

Antiplatelet Agents in Sepsis-Putting it all together: A Call to Action.

Tiwari NR, Chaudhari KS, Sharma R, Haas KP, Sharma VR. Antiplatelet Agents in Sepsis-Putting it all together: A Call to Action. Indian J Crit Care Med 2020;24(6):483-484.

Rhythmic ictal nonclonic hand (RINCH) motions in general EMU patients with focal epilepsy.

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.

Brainstem Functional Connectivity Disturbances in Epilepsy may Recover After Successful Surgery.

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.

Lung cancer screening: assessment of health literacy and readability of online educational resources.

Background: Lung cancer screening can reduce mortality but can be a complex, multi-step process. Poor health literacy is associated with unfavorable outcomes and decreased use of preventative services, so it is important to address barriers to care through efficient and practical education. The readability of lung cancer screening materials for patients is unknown and may not be at the recommended 6th grade reading level set by the American Medical Association.

Indwelling Tunneled Pleural Catheters for Refractory Hepatic Hydrothorax in Patients With Cirrhosis: A Multicenter Study.

Background: The outcome of indwelling pleural catheter (IPC) use in hepatic hydrothorax (HH) is unclear. This study aimed to review the safety and feasibility of the IPC in patients with refractory HH.

Methods: A retrospective multicenter study of patients with HH from January 2010 to December 2016 was performed.

Lacosamide efficacy and tolerability in clinical practice - Post marketing analysis from a single dedicated epilepsy center.

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.

Validation of an Expanded Carrier Screen that Optimizes Sensitivity via Full-Exon Sequencing and Panel-wide Copy Number Variant Identification.

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 <100% in ECS tests because copy number variants (CNVs) are typically not interrogated because of their technical complexity.

A randomized controlled trial of levodopa in patients with Angelman syndrome.

Treatment for Angelman syndrome (AS) is currently limited to symptomatic interventions. A mouse model of AS has reduced calcium/calmodulin-dependent kinase II activity due to excessive phosphorylation of specific threonine residues, leading to diminished long-term potentiation. In a rat model of Parkinson disease, levodopa reduced phosphorylation of various proteins, including calcium/calmodulin-dependent kinase II.