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The development of microwave power amplifiers (PAs) based on transistors with an AlGaN/GaN heterojunction are discussed in terms of the possible enhancement of their efficiency. The main focus is on the synthesis of the transforming circuits, which ensure the reactive load at the second- and third-harmonic frequencies and complex impedance at the fundamental frequency. This makes it possible to optimize the complex operation mode of a PA; i.e., to reduce the scattering power and enhance the efficiency. A microwave PA based on the Schottky-barrier-gate field-effect transistor with 80 electrodes based on the GaN pHEMT transistor with a gate length of 0.25 nm and a gate width of 125 nm is experimentally investigated. The amplifier has a pulse output power of 35 W and a power-added efficiency of at least 50% at a working frequency of 9 GHz. [ABSTRACT FROM AUTHOR]

Background: Climate change has adverse effects on youth mental health and wellbeing, but limited large-scale data exist globally or in the USA. Understanding the patterns and consequences of climate-related distress among US youth can inform necessary responses at the individual, community, and policy level., Methods: A cross-sectional descriptive online survey was done of US youth aged 16-25 years from all 50 states and Washington, DC, between July 20 and Nov 7, 2023, via the Cint digital survey marketplace. The survey assessed: climate-related emotions and thoughts, including indicators of mental health; relational aspects of climate-related emotions; beliefs about who or what has responsibility for causing and responding to climate change; desired and planned actions in response to climate change; and emotions and thoughts about the US Government response to climate change. Respondents were asked whether they had been affected by various severe weather events linked to climate change and for their political party identification. Sample percentages were weighted according to 2022 US census age, sex, and race estimates. To test the effects of political party identification and self-reported exposure to severe weather events on climate-related thoughts and beliefs we used linear and logistic regression models, which included terms for political party identification, the number of self-reported severe weather event types in respondents' area of residence in the past year, and demographic control variables., Findings: We evaluated survey responses from 15 793 individuals (weighted proportions: 80·5% aged 18-25 years and 19·5% aged 16-17 years; 48·8% female and 51·2% male). Overall, 85·0% of respondents endorsed being at least moderately worried, and 57·9% very or extremely worried, about climate change and its impacts on people and the planet. 42·8% indicated an impact of climate change on self-reported mental health, and 38·3% indicated that their feelings about climate change negatively affect their daily life. Respondents reported negative thoughts about the future due to climate change and actions planned in response, including being likely to vote for political candidates who support aggressive climate policy (72·8%). In regression models, self-reported exposure to more types of severe weather events was significantly associated with stronger endorsement of climate-related distress and desire and plans for action. Political party identification as Democrat or as Independent or Other (vs Republican) was also significantly associated with stronger endorsement of distress and desire and plans for action, although a majority of self-identified Republicans reported at least moderate distress. For all survey outcomes assessed in the models, the effect of experiencing more types of severe weather events did not significantly differ by political party identification., Interpretation: Climate change is causing widespread distress among US youth and affecting their beliefs and plans for the future. These effects may intensify, across the political spectrum, as exposure to climate-related severe weather events increases., Funding: Avaaz Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Policymaking is quickly gaining focus in the field of implementation science as a potential opportunity for aligning cross-sector systems and introducing incentives to promote population health, including substance use disorders (SUD) and their prevention in adolescents. Policymakers are seen as holding the necessary levers for realigning service infrastructure to more rapidly and effectively address adolescent behavioral health across the continuum of need (prevention through crisis care, mental health, and SUD) and in multiple locations (schools, primary care, community settings). The difficulty of aligning policy intent, policy design, and successful policy implementation is a well-known challenge in the broader public policy and public administration literature that also affects local behavioral health policymaking. This study will examine a blended approach of coproduction and codesign (i.e., Policy Codesign), iteratively developed over multiple years to address problems in policy formation that often lead to poor implementation outcomes. The current study evaluates this scalable approach using reproducible measures to grow the knowledge base in this field of study., Methods: This is a single-arm, longitudinal, staggered implementation study to examine the acceptability and short-term impacts of Policy Codesign in resolving critical challenges in behavioral health policy formation. The aims are to (1) examine the acceptability, feasibility, and reach of Policy Codesign within two geographically distinct counties in Washington state, USA; (2) examine the impact of Policy Codesign on multisector policy development within these counties using social network analysis; and (3) assess the perceived replicability of Policy Codesign among leaders and other staff of policy-oriented state behavioral health intermediary organizations across the USA., Discussion: This study will assess the feasibility of a specific approach to collaborative policy development, Policy Codesign, in two diverse regions. Results will inform a subsequent multi-state study measuring the impact and effectiveness of this approach for achieving multi-sector and evidence informed policy development in adolescent SUD prevention and treatment., (© 2024. The Author(s).)

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally. Here, we evaluated the impact on AMPAR function of one frameshift and 43 rare missense GRIA3 variants identified in patients with NDD by electrophysiological assays. Thirty-one variants alter receptor function and show loss-of-function or gain-of-function properties, whereas 13 appeared neutral. We collected detailed clinical data from 25 patients (from 23 families) harbouring 17 of these variants. All patients had global developmental impairment, mostly moderate (9/25) or severe (12/25). Twelve patients had seizures, including focal motor (6/12), unknown onset motor (4/12), focal impaired awareness (1/12), (atypical) absence (2/12), myoclonic (5/12) and generalized tonic-clonic (1/12) or atonic (1/12) seizures. The epilepsy syndrome was classified as developmental and epileptic encephalopathy in eight patients, developmental encephalopathy without seizures in 13 patients, and intellectual disability with epilepsy in four patients. Limb muscular hypotonia was reported in 13/25, and hypertonia in 10/25. Movement disorders were reported in 14/25, with hyperekplexia or non-epileptic erratic myoclonus being the most prevalent feature (8/25). Correlating receptor functional phenotype with clinical features revealed clinical features for GRIA3-associated NDDs and distinct NDD phenotypes for loss-of-function and gain-of-function variants. Gain-of-function variants were associated with more severe outcomes: patients were younger at the time of seizure onset (median age: 1 month), hypertonic and more often had movement disorders, including hyperekplexia. Patients with loss-of-function variants were older at the time of seizure onset (median age: 16 months), hypotonic and had sleeping disturbances. Loss-of-function and gain-of-function variants were disease-causing in both sexes but affected males often carried de novo or hemizygous loss-of-function variants inherited from healthy mothers, whereas affected females had mostly de novo heterozygous gain-of-function variants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Caenorhabditis elegans is a useful model organism to study the xenobiotic detoxification pathways of various natural and synthetic toxins, but the mechanisms of phase II detoxification are understudied. 1-Hydroxyphenazine (1-HP), a toxin produced by the bacterium Pseudomonas aeruginosa , kills C. elegans . We previously showed that C. elegans detoxifies 1-HP by adding one, two, or three glucose molecules in N2 worms. Our current study evaluates the roles that some UDP-glycosyltransferase ( ugt ) genes play in 1-HP detoxification. We show that ugt-23 and ugt-49 knockout mutants are more sensitive to 1-HP than reference strains N2 or PD1074. Our data also show that ugt-23 knockout mutants produce reduced amounts of the trisaccharide sugars, while the ugt-49 knockout mutants produce reduced amounts of all 1-HP derivatives except for the glucopyranosyl product compared to the reference strains. We characterized the structure of the trisaccharide sugar phenazines made by C. elegans and showed that one of the sugar modifications contains an N -acetylglucosamine (GlcNAc) in place of glucose. This implies broad specificity regarding UGT function and the role of genes other than ogt-1 in adding GlcNAc, at least in small-molecule detoxification.

Biallelic variants in the Golgi SNAP receptor complex member 2 gene ( GOSR2 ) have been reported in progressive myoclonus epilepsy with neurodegeneration. Typical clinical features include ataxia and areflexia during early childhood, followed by seizures, scoliosis, dysarthria, and myoclonus. Here, we report two novel patients from unrelated families with a GOSR2 -related disorder and novel genetic and clinical findings. The first patient, a male compound heterozygous for the GOSR2 splice site variant c.336+1G>A and the novel c.364G>A,p.Glu122Lys missense variant showed global developmental delay and seizures at the age of 2 years, followed by myoclonus at the age of 8 years with partial response to clonazepam. The second patient, a female homozygous for the GOSR2 founder variant p.Gly144Trp, showed only mild fine motor developmental delay and generalized tonic-clonic seizures triggered by infections during adolescence, with seizure remission on levetiracetam. The associated movement disorder progressed atypically slowly during adolescence compared to its usual speed, from initial intention tremor and myoclonus to ataxia, hyporeflexia, dysmetria, and dystonia. These findings expand the genotype-phenotype spectrum of GOSR2 -related disorders and suggest that GOSR2 should be included in the consideration of monogenetic causes of dystonia, global developmental delay, and seizures.

Background: Strategies for supporting evidence-informed health policy are a recognized but understudied area of policy dissemination and implementation science. Codesign describes a set of strategies potentially well suited to address the complexity presented by policy formation and implementation. We examine the health policy literature describing the use of codesign in initiatives intended to combine diverse sources of knowledge and evidence in policymaking., Methods: The search included PubMed, MEDLINE, PsychInfo, CINAHL, Web of Science, and Google Scholar in November 2022 and included papers published between 1996 and 2022. Terms included codesign, health, policy, and system terminology. Title and abstracts were reviewed in duplicate and included if efforts informed policy or system-level decision-making. Extracted data followed scoping review guidelines for location, evaluation method, health focus, codesign definition, description, level of health system user input, sectors involved, and reported benefits and challenges., Results: From 550 titles, 23 citations describing 32 policy codesign studies were included from multiple continents (Australia/New Zealand, 32%; UK/Europe, 32%; South America, 14%; Africa, 9%; USA/Canada 23%). Document type was primarily case study (77%). The area of health focus was widely distributed. Policy type was more commonly little p policy (47%), followed by big p policy (25%), and service innovations that included policy-enabled funding (25%). Models and frameworks originated from formal design (e.g., human-centered or participatory design (44%), political science (38%), or health service research (16%). Reported outcomes included community mobilization (50%), policy feasibility (41%), improved multisector alignment (31%), and introduction of novel ideas and critical thinking (47%). Studies engaging policy users in full decision-making roles self-reported higher levels of community mobilization and community needs than other types of engagement., Discussion: Policy codesign is theoretically promising and is gaining interest among diverse health sectors for addressing the complexity of policy formation and implementation. The maturity of the science is just emerging. We observed trends in the association of codesign strategies and outcomes that suggests a research agenda in this area could provide practical insights for tailoring policy codesign to respond to local contextual factors including values, needs, and resources., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Self-injurious behaviors are repetitive, persistent actions directed toward one's body that threaten or cause physical harm. These behaviors are seen within a broad spectrum of neurodevelopmental and neuropsychiatric conditions, often associated with intellectual disability. Injuries can be severe and distressing to patients and caregivers. Furthermore, injuries can be life-threatening. Often, these behaviors are challenging to treat and require a tiered, multimodal approach which may include mechanical/physical restraints, behavioral therapy, pharmacotherapy, or in some cases, surgical management, such as tooth extraction or deep brain stimulation. Here, we describe a series of 17 children who presented to our institution with self-injurious behaviors in whom botulinum neurotoxin injections were found helpful in preventing or lessening self-injury.

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family. To date, only 6 variants have been reported. In this study, we evaluated genotype-phenotype correlations in individuals with biallelic SLC18A2 variants., Methods: A total of 42 affected individuals with homozygous SLC18A2 variant alleles were identified. We evaluated genotype-phenotype correlations and the missense variants in the affected individuals based on the structural modeling of rat VMAT2 encoded by Slc18a2, with cytoplasm- and lumen-facing conformations. A Caenorhabditis elegans model was created for functional studies., Results: A total of 19 homozygous SLC18A2 variants, including 3 recurrent variants, were identified using exome sequencing. The affected individuals typically showed global developmental delay, hypotonia, dystonia, oculogyric crisis, and autonomic nervous system involvement (temperature dysregulation/sweating, hypersalivation, and gastrointestinal dysmotility). Among the 58 affected individuals described to date, 16 (28%) died before the age of 13 years. Of the 17 patients with p.Pro237His, 9 died, whereas all 14 patients with p.Pro387Leu survived. Although a dopamine agonist mildly improved the disease symptoms in 18 of 21 patients (86%), some affected individuals with p.Ile43Phe and p.Pro387Leu showed milder phenotypes and presented prolonged survival even without treatment. The C. elegans model showed behavioral abnormalities., Conclusion: These data expand the phenotypic and genotypic spectra of SLC18A2-related disorders., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: Most reported patients carrying GNAO1 mutations showed a severe phenotype characterized by early-onset epileptic encephalopathy and/or chorea., Objective: The aim was to characterize the clinical and genetic features of patients with mild GNAO1-related phenotype with prominent movement disorders., Methods: We included patients diagnosed with GNAO1-related movement disorders of delayed onset (>2 years). Patients experiencing either severe or profound intellectual disability or early-onset epileptic encephalopathy were excluded., Results: Twenty-four patients and 1 asymptomatic subject were included. All patients showed dystonia as prominent movement disorder. Dystonia was focal in 1, segmental in 6, multifocal in 4, and generalized in 13. Six patients showed adolescence or adulthood-onset dystonia. Seven patients presented with parkinsonism and 3 with myoclonus. Dysarthria was observed in 19 patients. Mild and moderate ID were present in 10 and 2 patients, respectively., Conclusion: We highlighted a mild GNAO1-related phenotype, including adolescent-onset dystonia, broadening the clinical spectrum of this condition. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Tyrosine hydroxylase (TH) deficiency is an autosomal recessive condition first described as a progressive, early-onset hypokinetic-rigid and dystonic syndrome that was responsive to levodopa. Here we present a child with developmental regression, proximal tremor, and encephalopathy found to have tyrosine hydroxylase deficiency in whom treatment resulted in acquisition of developmental milestones., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Objectives: Functional (psychogenic) movement disorders (FMDs) are conditions in which affected patients develop abnormal movements that are incongruous with known, organic, movement disorders, often associated with psychological stressors., Methods: In this case series, electronic medical records of all patients who presented to our adult and pediatric tertiary care movement disorders clinics between March 1 and October 30, 2020, and during the same period in 2019 were reviewed. All patients diagnosed with functional (psychogenic) movement disorder were included if they satisfied diagnostic criteria., Results: Among 550 new patients referred for evaluation at our tertiary care movement disorders centers, 45 (8.2%) received a diagnosis of FMD; 75.6% were female, in comparison to the prior year during which time 665 new patients were evaluated and 5.1% were diagnosed with FMD. This represents a 60.1% increase (90.1% in pediatric cohort, 50.9% in adult cohort) in new patients diagnosed with FMD during the COVID-19 pandemic., Conclusions: Within our patient population, there has been increased incidence of FMDs in the setting of the COVID-19 pandemic, possibly reflecting increased psychological and other stressors during this period., (© 2021 American Academy of Neurology.)

Abstract: The recent COVID-19 pandemic is having profound impacts on every sector of society, and New York City (NYC) emerged as an early epicenter of the disease. Given the novelty and scale of the disease, information surrounding COVID-19 has been marked by considerable uncertainty and confusion. Although various factors have been associated with COVID-19 distress, little is known about the relations between levels of intolerance of uncertainty (IU) and anxiety symptoms and behaviors. This cross-sectional study sought to examine potential correlates and pathways between anxiety and precautionary behaviors with the two levels of IU: prospective and inhibitory. Individuals from NYC (N = 99) completed an online survey through Amazon Mechanical Turk. Findings revealed that fear of COVID-19 accounts for associations between prospective IU and greater anxiety symptoms and behaviors, whereas precaution adherence accounts for associations between prospective IU and reduced anxiety symptoms and behaviors. In addition, precaution adherence accounts for associations between inhibitory IU and greater anxiety symptoms and behaviors. The results shed light on ways in which variations in IU may be associated with anxiety symptoms and behaviors in the context of COVID-19 and future pandemic scenarios., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Movement disorders presenting in childhood include tics, dystonia, chorea, tremor, stereotypy, myoclonus, and parkinsonism, each of which can be part of various clinical syndromes with distinct etiologies.  Some of these conditions are benign and require only reassurance; others are bothersome and require treatment, or may be clues that herald underlying pathology.  Answers lie in the inherent characteristics of the movements themselves, together with the clinical context provided in the history obtained by the examiner.  The aim of this review is to present an overview of the categories of involuntary movements, along with examples of common acquired and genetic causes, and an approach to history-taking, examination, and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Pathogenic variants in ATP1A2, a gene encoding the α subunit of the Na,K-ATPase, cause familial hemiplegic migraine type 2 (FHM2). In contrast, pathogenic variants in ATP1A3, an ATP1A2 paralog, cause alternating hemiplegia of childhood (AHC), a severe neurodevelopmental disorder with infantile onset hemiplegic attacks, seizures, dystonia, chorea and developmental delay. Despite high sequence homology with ATP1A3, ATP1A2 variants rarely associate with severe phenotypes resembling those linked to ATP1A3. Here we describe two unrelated patients with infantile onset hemiplegic attacks, refractory epilepsy, movement disorders, abnormal eye movements and truncal ataxia with a shared de novo variant in ATP1A2, c.2438T > A (p.Met813Lys). The variant is not found in population databases, is predicted to be damaging by in silico analysis, and affects a highly conserved residue. Both patients experienced severe attacks with unilateral cerebral edema followed by sustained, stepwise regression. This report highlights the need to sequence ATP1A2 in the workup of patients with features of AHC that do not fulfill AHC diagnostic criteria., Competing Interests: Declaration of competing interest Mered Parnes has served on an advisory committee or as a consultant for the Kadmon Corporation and Teva Pharmaceutical Industries Ltd. He has received payment for his contributions to Medlink. Lisa Emrick received a consulting fee from PTC Therapeutics and has also received payment for her contributions to Medlink. The other authors have no conflicts of interest to declare., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Opisthotonus refers to abnormal axial extension and arching of the trunk produced by excessive contractions of the paraspinal muscles. In childhood, the abnormal posture is most often related to dystonia in the setting of hypoxic injury or a number of other acquired and genetic etiologies. The condition is often painful, interferes with ambulation and quality of life, and is challenging to treat. Therapeutic options include oral benzodiazepines, oral and intrathecal baclofen, botulinum neurotoxin injections, and deep brain stimulation. Management of opisthotonus within the pediatric population has not been systematically reviewed. Here, we describe a series of seven children who presented to our institution with opisthotonus in whom symptom relief was achieved following administration of botulinum neurotoxin injections.

Voltage-gated sodium (Na V ) channels are transmembrane proteins that initiate and propagate neuronal and cardiac action potentials. Na V channel β subunits have been widely studied due to their modulatory role. Mice null for Scn1b , which encodes Na V β1 and β1b subunits, have defects in neuronal development and excitability, spontaneous generalized seizures, cardiac arrhythmias, and early mortality. A mutation in exon 3 of SCN1B , c.308A>T leading to β1_p.D103V and β1b_p.D103V, was previously found in a patient with a history of proarrhythmic conditions with progressive atrial standstill as well as cognitive and motor deficits accompanying structural brain abnormalities. We investigated whether β1 or β1b subunits carrying this mutation affect Na V 1.5 and/or Na V 1.1 currents using a whole cell patch-clamp technique in tsA201 cells. We observed a decrease in sodium current density in cells co-expressing Na V 1.5 or Na V 1.1 and β1 D103V compared to β1 WT . Interestingly, β1b D103V did not affect Na V 1.1 sodium current density but induced a positive shift in the voltage dependence of inactivation and a faster recovery from inactivation compared to β1b WT . The β1b D103V isoform did not affect Na V 1.5 current properties. Although the SCN1B _c.308A>T mutation may not be the sole cause of the patient's symptoms, we observed a clear loss of function in both cardiac and brain sodium channels. Our results suggest that the mutant β1 and β1b subunits play a fundamental role in the observed electrical dysfunction., (Copyright © 2020 Martinez-Moreno, Selga, Riuró, Carreras, Parnes, Srinivasan, Wangler, Pérez, Scornik and Brugada.)

Background: Geniospasm is a rare genetic disorder characterized by paroxysmal rhythmic or irregular movements of the chin and lower lip due to repetitive contractions of the mentalis muscle. Pathophysiology is poorly understood, and optimal treatment has not been established., Methods: Geniospasm was characterized in a series of patients after evaluation in our clinics, and a comprehensive review of all cases in the medical literature was performed., Results: We evaluated four patients (1 female) in four families with geniospasm, aged 4 months to 9 years. Bothersome symptoms were present in one patient, who was treated with regular injections of onabotulinumtoxinA, with complete resolution of symptoms and no adverse effects. 9 patients in the literature have had similar outcomes., Conclusions: Limited data exist with regard to the effective treatment of geniospasm. Several treatments have been used historically, with variable outcomes. Our results, together with those of prior reported cases, demonstrate benefit of the use of botulinum toxin injections for management of this condition., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2020 The Author(s).)

Interstitial deletions involving chromosome region 6p21.31p21.2 have not been previously reported in the literature. Here, we present a 2 year old girl with global developmental delay, severe speech delay, dysmorphic features, laryngeal cleft, anterior descending aorta that occluded the left main bronchus and a novel de novo deletion of chromosome 6: arr[hg19] 6p21.31p21.2 (35462950-36725083)x1. The deletion, which was diagnosed by array comparative genomic hybridization and further confirmed with fluorescence in situ hybridization, was approximately 1.26 Mb and contained 28 RefSeq genes. The deleted region includes 24 protein coding genes and 4 non-coding genes. This represents a novel microdeletion that has not been previously reported in the literature., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In the past decade, brief bursts of fast oscillations in the ripple range have been identified in the scalp EEG as a promising non-invasive biomarker for epilepsy. However, investigation and clinical application of this biomarker have been limited because standard approaches to identify these brief, low amplitude events are difficult, time consuming, and subjective. Recent studies have demonstrated that ripples co-occurring with epileptiform discharges ('spike ripple events') are easier to detect than ripples alone and have greater pathological significance. Here, we used objective techniques to quantify spike ripples and test whether this biomarker predicts seizure risk in childhood epilepsy. We evaluated spike ripples in scalp EEG recordings from a prospective cohort of children with a self-limited epilepsy syndrome, benign epilepsy with centrotemporal spikes, and healthy control children. We compared the rate of spike ripples between children with epilepsy and healthy controls, and between children with epilepsy during periods of active disease (active, within 1 year of seizure) and after a period of sustained seizure-freedom (seizure-free, >1 year without seizure), using semi-automated and automated detection techniques. Spike ripple rate was higher in subjects with active epilepsy compared to healthy controls (P = 0.0018) or subjects with epilepsy who were seizure-free ON or OFF medication (P = 0.0018). Among epilepsy subjects with spike ripples, each month seizure-free decreased the odds of a spike ripple by a factor of 0.66 [95% confidence interval (0.47, 0.91), P = 0.021]. Comparing the diagnostic accuracy of the presence of at least one spike ripple versus a classic spike event to identify group, we found comparable sensitivity and negative predictive value, but greater specificity and positive predictive value of spike ripples compared to spikes (P = 0.016 and P = 0.006, respectively). We found qualitatively consistent results using a fully automated spike ripple detector, including comparison with an automated spike detector. We conclude that scalp spike ripple events identify disease and track with seizure risk in this epilepsy population, using both semi-automated and fully automated detection methods, and that this biomarker outperforms analysis of spikes alone in categorizing seizure risk. These data provide evidence that spike ripples are a specific non-invasive biomarker for seizure risk in benign epilepsy with centrotemporal spikes and support future work to evaluate the utility of this biomarker to guide medication trials and tapers in these children and predict seizure risk in other at-risk populations., (© The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Over the past two decades, West Nile virus has become the most common arbovirus in North America, leading to several outbreaks and infecting thousands of people. Mosquitos help transmit the virus in the majority of cases, but transmission occurs via blood transfusions, organ transplantation, and possibly pregnancy and breastfeeding. While most infected patients experience mild to no symptoms, thousands of West Nile virus-associated neuroinvasive cases have been reported in the United States, with over 700 cases occurring in children from 2003 to 2016. Neuroinvasive disease presents as meningitis, encephalitis, or acute flaccid paralysis, and carries a high likelihood of poor outcome, including severe neurological disability or death. To date, no pharmacologic treatment has proven effective. Therapeutic clinical trials have not been successfully completed due to the sporadic nature of viral outbreaks and resultant poor study enrollment. Although older age and chronic disease are risk factors for neuroinvasive West Nile virus disease in adults, the specific factors that influence the risk in pediatric populations have not been fully elucidated. This review summarizes the most recent literature regarding West Nile virus-associated neuroinvasive disease, especially as it pertains to the pediatric population. Moreover, the review describes the epidemiology, clinical, laboratory, and radiographic findings, and outlines the various therapies that have been trialed and potential future research directions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Since its localization to the NKX2-1 gene in 2002, the phenotype of the disorder historically called "benign hereditary chorea" has been expanding beyond chorea., Methods: The phenomenology of movement disorders and other symptomatology associated with mutations in NKX2-1 were characterized after a detailed evaluation of consecutive patients evaluated in our clinic over the past 3 years., Results: We studied 5 patients (3 females), ages 2 to 31 years, with confirmed pathogenic variants in NKX2-1. All patients exhibited chorea, gross motor delay, and gait impairment. Other symptoms included neonatal respiratory failure (n = 4), cognitive deficits (n = 3), hypothyroidism (n = 4), joint laxity (n = 2), myoclonus (n = 1), hypotonia (n = 3), and seizures (n = 1). Chorea often proved refractory to medical therapies., Conclusions: The phenotype associated with pathogenic variants in NKX2-1 frequently includes disabling and often medically refractory neurological and non-neurological abnormalities. We therefore suggest that the term benign hereditary chorea be abandoned in favor of its genetic designation as NKX2-1 -related disorder.

Social capital plays a key role in college and career success, and research indicates that a dearth of on-campus connections contributes to challenges first-generation college students face in effectively navigating the college environment. This study investigates a novel intervention that focuses on the development of skills and attitudes to empower first-generation college students to cultivate social capital and on-campus connections during the transition to college. A mixed methods, explanatory design was used to evaluate impacts and processes of the intervention among first-generation college students (n = 164) in the context of an ethnically diverse, urban, public university in the Northeast. Results indicated that students who participated in the intervention demonstrated improved attitudes and behaviors around seeking support in college, closer relationships with instructors, and higher GPAs at the end of their first year in college. These results suggest the potential benefits of a relatively scalable approach to supporting the needs of first-generation college students., (© Society for Community Research and Action 2017.)

In clinical research, it is sometimes desirable to dichotomize a continuous variable so that the information expressed using a dichotomous variable is more straightforward for clinicians to interpret and communicate with patients. The distribution of the continuous variable can differ between two populations defined by a disease case status. Under such a scenario, the dichotomization process can be based on distributions of the continuous variable in two distinct populations. The resulting dichotomous variable can be used as an endpoint in future studies. Even though dichotomization has not been extensively studied, dichotomization has been commonly carried out in clinical trials. We developed a methodology for determining the optimal cutoff point based on maximizing the correlation between the two populations and the dichotomous variable. In some real-world scenarios where outcome status in samples from two populations is not completely identified, we recommend using EM method to first estimate the parameters associated with the two populations before applying the proposed method to find the optimal cutoff point. In addition, we have investigated the performance of the proposed method for several common distributions (e.g., normal, log-normal and exponential distribution) of the continuous variable. Finally, we applied the proposed methods to a varicella vaccine example.

Participants performed a physical comparison task of pairs of positive and pairs of negative one-digit numbers while their electrophysiological brain activity was measured. The numerical value of the presented digits was either congruent or incongruent with the physical size of the digits. Analysis has shown that the earliest event-related potential (ERP) difference between positive and negative numbers was found in the P300 ERP component peak, where there was an inverse effect of congruity in the negative pairs, compared with the positive ones. This pattern of results supports the idea that natural numbers serve as primitives of the human cognitive system, whereas negative numbers are apparently generated if needed., (2012 APA, all rights reserved)