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ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

Objective: Despite widespread monotherapy use of lamotrigine or levetiracetam during pregnancy, prospectively collected, blinded child development data are still limited. The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study prospectively recruited a new cohort of women with epilepsy and their offspring for longitudinal follow‐up. Methods: Pregnant women of <21 weeks gestation (n = 401) were recruited from 21 hospitals in the UK. Data collection occurred during pregnancy (recruitment, trimester 3) and at 12 and 24 months of age. The primary outcome was blinded assessment of infant cognitive, language, and motor development on the Bayley Scales of Infant and Toddler Development (3rd edition) at 24 months of age with supplementary parent reporting on the Vinelands Adaptive Behavior Scales (2nd edition). Results: There were 394 live births, with 277 children (70%) completing the Bayley assessment at 24 months. There was no evidence of an association of prenatal exposure to monotherapy lamotrigine (−.74, SE = 2.9, 95% confidence interval [CI] = −6.5 to 5.0, p =.80) or levetiracetam (−1.57, SE = 3.1, 95% CI = −4.6 to 7.7, p =.62) with poorer infant cognition, following adjustment for other maternal and child factors in comparison to nonexposed children. Similar results were observed for language and motor scores. There was no evidence of an association between increasing doses of either lamotrigine or levetiracetam. Nor was there evidence that higher dose folic acid supplementation (≥5 mg/day) or convulsive seizure exposure was associated with child development scores. Continued infant exposure to antiseizure medications through breast milk was not associated with poorer outcomes, but the number of women breastfeeding beyond 3 months was low. Significance: These data are reassuring for infant development following in utero exposure to monotherapy lamotrigine or levetiracetam, but child development is dynamic, and future follow‐up is required to rule out later emerging effects. [ABSTRACT FROM AUTHOR]

Discusses how to use movement to reinforce literacy in children with hearing impairments, describing: characteristics of children with hearing impairments; methods of including them in physical education; the problem of phonetic awareness among pre-literate children; integration of abstract symbols and sign language; and integration of reading process theories with movement analysis activities within the organizational levels of literacy. (SM)

The construction and characterization of a nitrate reductase-based amperometric electrode for determination of nitrate ion is described. The electrode consisted of nitrate reductase held by dialysis membrane onto a Nation-coated glassy carbon electrode. Methyl viologen was allowed to absorb into the Nation layer, which acted as a reservoir for the electron mediator. The utility of the electrode to assay fertilizer and water sample for nitrate was demonstrated. The assays conducted with this electrode compared well with colorimetric and potentiometric assays of the same samples.

Most of what we known about the population generating uncompensated care is inferred from data on the uninsured population. The use of insurance status as an indicator for potential charity patients is justifiable considering the lack of alternative information. This study directly examines uncompensated hospital care using a unique data set generated from a special survey conducted in Florida. A selection model estimated using these data explains who is likely to default on their bill and what amount will be left unpaid. The results provide a clearer picture of the uncompensated hospital care problem.

Objective: The mechanisms by which antiepileptic drugs (AEDs) cause birth defects (BDs) are unknown. Data suggest that AED-induced BDs may result from a genome-wide increase of de novo variants in the embryo, a mechanism that we investigated.Methods: Whole exome sequencing data from child-parent trios were interrogated for de novo single-nucleotide variants/indels (dnSNVs/indels) and de novo copy number variants (dnCNVs). Generalized linear models were applied to assess de novo variant burdens in children exposed prenatally to AEDs (AED-exposed children) versus children without BDs not exposed prenatally to AEDs (AED-unexposed unaffected children), and AED-exposed children with BDs versus those without BDs, adjusting for confounders. Fisher exact test was used to compare categorical data.Results: Sixty-seven child-parent trios were included: 10 with AED-exposed children with BDs, 46 with AED-exposed unaffected children, and 11 with AED-unexposed unaffected children. The dnSNV/indel burden did not differ between AED-exposed children and AED-unexposed unaffected children (median dnSNV/indel number/child [range] = 3 [0-7] vs 3 [1-5], p = 0.50). Among AED-exposed children, there were no significant differences between those with BDs and those unaffected. Likely deleterious dnSNVs/indels were detected in 9 of 67 (13%) children, none of whom had BDs. The proportion of cases harboring likely deleterious dnSNVs/indels did not differ significantly between AED-unexposed and AED-exposed children. The dnCNV burden was not associated with AED exposure or birth outcome.Interpretation: Our study indicates that prenatal AED exposure does not increase the burden of de novo variants, and that this mechanism is not a major contributor to AED-induced BDs. These results can be incorporated in routine patient counseling. ANN NEUROL 2020;87:897-906. [ABSTRACT FROM AUTHOR]

Objective: To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME). Methods: People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12‐month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females. Results: We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08‐1.13], P < 0.001) and female sex (1.41 [1.07‐1.85], P = 0.02) were associated with shorter trial duration. Valproate was associated with the longest treatment duration; trials with carbamazepine and topiramate were significantly shorter (HR [CI]: 3.29 [2.15‐5.02], P < 0.001 and 1.93 [1.31‐2.86], P < 0.001). The relative frequency of valproate trials shows a decreasing trend since 2003 while there is an increasing trend for levetiracetam. Fewer females than males received valproate (76.2% vs 92.6%, P = 0.001). Significance: In people with JME, valproate is an effective AED; levetiracetam emerged as an alternative. Valproate is now contraindicated in women of childbearing potential without special precautions. With appropriate selection and safeguards in place, valproate should remain available as a therapy, including as an alternative for women of childbearing potential whose seizures are resistant to other treatments. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy is the recommended treatment after breast‐conserving surgery (BCS) for early‐stage breast cancer (BC). However, there is no clear evidence whether radiotherapy after BCS improves the survival of elderly women diagnosed with early‐stage hormone receptor‐positive (HR+) BC. The aim of this study was to investigate the survival benefit associated with radiotherapy plus hormonal therapy vs hormonal therapy alone after BCS for early‐stage HR+ BC patients. Methods: Using the Surveillance, Epidemiology, and End Results linked with Medicare data, we identified elderly (65 years and older) women diagnosed with early‐stage HR+ BC (2006‐2011) who received hormonal therapy with or without radiotherapy after BCS. A log‐rank test, Cox proportional hazards models, and propensity score matching were used to estimate the overall survival (OS) benefit associated with radiotherapy after BCS. Results: Of the 5688 patients, there were 303 deaths from any cause. One hundred and eighty‐five (61%) of these deaths occurred in the hormonal therapy group, and 118 (39%) deaths occurred in the radiotherapy plus hormonal therapy group. The mean survival time in the radiotherapy plus hormonal therapy group was 5.32 ± 1.86 years compared with 4.92 ± 1.86 years in the hormonal therapy group. Based on the adjusted and propensity score matching analysis, patients in the adjuvant radiotherapy group had a lower risk of death compared with those who did not receive radiotherapy. Radiotherapy plus hormonal therapy decreased the risk of death by 32%. The effect estimates were similar in the adjusted and matched cohorts. Conclusions: Radiotherapy plus hormonal therapy resulted in a significant improvement in the OS of elderly women diagnosed with HR+ BC. Due to limited number of elderly patients' participation in randomized controlled trials, the treatment decision in elderly patients often depends on the result of RCTs on younger patients, which makes the treatment decision challenging for clinicians and patients. Thus, the result of this study may help inform clinical decision‐making.. [ABSTRACT FROM AUTHOR]

Invasions occurring in natural environments provide the opportunity to study how vital rates change and life histories evolve in the presence of a competing species. In this work, we estimate differences in reproductive traits, individual growth trajectories, survival, life histories and population dynamics between a native species living in allopatry and in sympatry with an invasive species of the same taxonomic Family. We used as a model system marble trout Salmo marmoratus (native species) and rainbow trout Oncorhynchus mykiss (non‐native) living in the Idrijca River (Slovenia). An impassable waterfall separates the stream into two sectors only a few 100 meters apart: a downstream sector in which marble trout live in sympatry with rainbow trout and an upstream sector in which marble trout live in allopatry. We used an overarching modelling approach that uses tag‐recapture and genetic data (>2,500 unique marble and rainbow trout were sampled and genotyped) to reconstruct pedigrees, test for synchrony of population dynamics and model survival and growth, while accounting for individual heterogeneity. The population dynamics of the two marble trout populations and of rainbow trout were synchronous. We found higher prevalence of younger parents, higher mortality and lower population density in marble trout living in sympatry with rainbow trout than in marble trout living in allopatry. There were no differences in the average individual growth trajectories between the two marble trout populations. Faster life histories of marble trout living in sympatry with rainbow trout are consistent with predictions of life history theory. Invasions occurring in natural environments provide the opportunity to study how vital rates change and life histories evolve in the presence of a competing species. We tested whether the life histories of a freshwater fish (marble trout) were faster when living in sympatry with a species of the same Family (rainbow trout) than when living alone, as predicted by life‐history theory. We found faster life histories (higher prevalence of younger parents and higher mortality) of marble trout when living in sympatry with rainbow trout. [ABSTRACT FROM AUTHOR]