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The results are presented of an experiment designed to demonstrate anomalous dispersion in a modified Belousov-Zhabotinsky system.

Rationale and Objectives: Cardiac magnetic resonance (CMR) and gated 13N-ammonia positron emission tomography myocardial perfusion imaging (PET-MPI) offer accurate and highly comparable global left ventricular ejection fraction (LVEF) measurements. In addition to accuracy, however, reproducibility is crucial to avoid variations in LVEF assessment potentially negatively impacting treatment decisions. We performed a head-to-head comparison of the reproducibility of LVEF measurements derived from simultaneously acquired CMR and PET-MPI using different state-of-the-art commercially available software., Materials and Methods: 93 patients undergoing hybrid PET/MR were retrospectively included. LVEF was derived from CMR and PET-MPI at two separate core labs, using two state-of-the-art software packages for CMR (cvi42 and Medis Suite MR) and PET (QPET and CardIQ Physio). Intra- and inter-reader agreement was assessed using correlation and Bland-Altman (BA) analyses., Results: While intra- and inter-reader reproducibility of LVEF was high among both modalities and all software packages (r ≥ 0.87 and ICC≥0.91, all significant at p < 0.0001), LVEF derived from PET-MPI and analyzed with QPET outperformed all other analyses (intra-reader reproducibility: r = 0.99, ICC=0.99; inter-reader reproducibility: r = 0.98, ICC=1.00; Pearson correlations significantly higher than all others at p ≤ 0.0001). BA analyses showed smaller biases for LVEF derived from PET-MPI (-0.1% and +0.9% for intra-reader, -0.4% and -0.8% for inter-reader agreement) than those derived from CMR (+0.7% and +2.8% for intra-reader, -0.9% and -2.2% for inter-reader agreement) with similar results for BA limits of agreement., Conclusion: Gated 13N-ammonia PET-MPI provides equivalent reproducibility of LVEF compared to CMR. It may offer a valid alternative to CMR for patients requiring LV functional assessment., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships, which may be considered as potential competing interests: The University Hospital of Zurich holds a research agreement with GE Healthcare. RR Buechel has received funding from the Swiss National Science Foundation as well as speaker honoraria from Pfizer, Gilead, IBA, and GE Healthcare, outside of the submitted work. C Gräni received funding from the Swiss National Science Foundation, InnoSuisse, CAIM foundation and GAMBIT foundation, outside of the submitted work. The other authors have no relevant competing interests to declare., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

This historical review of the development of the Oregonator model of the Belousov-Zhabotinsky reaction is based on a lecture Dick Field presented during IrvFest2015-Celebrating a founding father of chaos!, a meeting in commemoration of Irving R. Epstein's 70 th birthday. For Dick's 80 th birthday festschrift, we focus here on the five papers in the series named "Oscillations in chemical systems," published in 1972 [Noyes et al., J. Am. Chem. Soc. 94, 1394-1395 (1972); Field et al., J. Am. Chem. Soc. 94, 8649-8664 (1972); Field and Noyes, Nature 237, 390-392 (1972)] and 1974 [Field and Noyes, J. Chem. Phys. 60, 1877-1884 (1974); Field and Noyes, J. Am. Chem. Soc. 96, 2001-2006 (1974)].

Background: multisystem inflammatory syndrome in children (MIS-C) is a new disease associated with a recent infection with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Affected children can present predominantly with abdominal symptoms, fever and high inflammatory parameters that might lead to a consult by the pediatric surgeon and an indication for surgery., Methods: clinical data of three patients with MIS-C that underwent surgery were collected. Histopathological analysis of the appendix was performed., Results: we present the clinical course of three children with fever, abdominal pain and vomiting for several days. Clinical examination and highly elevated inflammation markers led to indication for laparoscopy; appendectomy was performed in two patients. Because of intraoperative findings or due to lack of postoperative improvement, all patients were reevaluated and tested positive for MIS-C associated laboratory parameters and were subsequently treated with corticosteroids, intravenous immunoglobulins, acetyl salicylic acid and/or light molecular weight heparin., Conclusions: we discuss the implications of MIS-C as a new differential diagnosis and stress the importance of assessing the previous medical history, identifying patterns of symptoms and critically surveilling the clinical course. We implemented an algorithm for pediatric surgeons to consider MIS-C as a differential diagnosis for acute abdomen that can be integrated into the surgical workflow.

Geographic tongue or benign migratory glossitis is a condition of an unknown cause characterized by chronic lesions that slowly migrate across the surface of the tongue. The condition's characteristic wavefronts suggest that it can be modeled as a reaction-diffusion system. Here, we present a model for geographic tongue pattern evolution using reaction-diffusion equations applied to portions of spheroids and paraboloids that approximate a tongue shape. We demonstrate that the observed patterns of geographic tongue lesions can be explained by propagating reaction-diffusion waves on these variably curved surfaces.

Background: Acute hematogenous osteomyelitis (OM) and septic arthritis require immediate diagnosis and treatment by an interdisciplinary team of pediatric infectious disease specialists and pediatric orthopedic surgeons. Adverse outcomes such as growth disturbance, bone deformity, and chronic infections have been described in older studies. However, there is only little known about long-term follow-up of patients of the last two decades. Therefore, we aimed to evaluate subjective and objective long-term outcomes of these children with osteoarticular infections treated in the millennial years. Methods: Cross-sectional study performed in two pediatric centers including patients admitted for OM and/or SA between 2005 and 2014 and follow-up consultations in 2019. Patients with symptoms of ≤2 weeks duration at initial presentation were contacted. Subjective outcomes were assessed by standardized interview, objective outcomes by clinical examination. Medical charts were used to extract data from the initial presentations. Statistical analysis was performed by non-parametric tests and Fisher's exact test. Results: Of 147 eligible patients 77 (52%) agreed to participate, of which 68 (88%) had an interview and physical examination and 9 (12%) an interview only. Thirty-three (39%) had OM, 26 (34%) SA, and 21 (27%) combined OM/SA. Median (IQR) age at follow-up was 13.3 (10.5-18.0) years with a median (IQR) follow-up of 7.1 (6.1-8.6) years. Persistent complaints including pain, functional differences and scar paresthesia, reported by 21 (28%) patients, were generally mild and only 3 (5%) required ongoing medical care. Objective sequelae including pain, limited range of motion, unilateral axis deformity or asymmetric gait were found in 8 (12%) participants. Older age, female sex, joint involvement, surgical intervention, persistent fever, and C-reactive protein elevation were associated with adverse clinical outcome. Conclusions: Adverse outcomes were observed in a considerable number of patients, most of which were minor, and only few required ongoing medical care. Long-term follow up is advisable for patients with risk factors identified during the initial presentation. This study was registered on ClinicalTrials.gov (NCT03827980)., (Copyright © 2020 Manz, Krieg, Buettcher, Ritz and Heininger.)

Diagnostic tools for the management of acute osteomyelitis (OM) and septic arthritis (SA) have improved over the last decade. To investigate the influence and availability of magnetic resonance imaging (MRI) and nucleic acid testing (NAT), a retrospective cohort study was done. Patients admitted with acute OM or SA between 2005 and 2014 were identified using ICD-10 discharge codes. Ninety-six children were identified: OM, n = 45; SA, n = 42; and OM + SA, n = 9. Diagnostic imaging was performed in 100% of OM or OM + SA and 95% of SA patients. MRI was performed in 85% of OM patients, 26% of SA patients and 100% OM + SA patients. In patients with OM or SA, concomitant joint/bone involvement was detected in 24 and 36% of patients, respectively. In 58% of patients, a pathogen was detected (Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae being most common). Blood and tissue culture were positive in 41 and 86% for OM patients and in 14 and 41%, respectively, for SA patients. In 42% of patients, no pathogen was identified, of which 40% had no material for blood or tissue culture/NAT taken., Conclusion: Optimal use of imaging modalities including MRI and systematic pathogen detection including NAT should be advocated to limit use of broad spectrum antibiotics and treatment duration. What is Known: • Magnetic resonance imaging and sonography have the best sensitivity for detection of acute osteomyelitis and septic arthritis in children. • Systematic use of blood cultures, tissue cultures and nucleic acid testing improves pathogen detection in children with acute osteomyelitis and septic arthritis. What is New: • The added value of imaging modalities other than magnetic resonance and sonography for detection of osteomyelitis and septic arthritis is limited, and their routine use should be questioned. • Despite availability of optimal pathogen detection methods, missed opportunities to improve pathogen detection are frequent.

The developmental trajectories of theta band (4-7Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. Associations between the theta EROs and genotypic variants of 4 KCNJ6 single nucleotide polymorphisms (SNPs) were found to vary with age, sex, scalp location, and task modality. Three of the four KCNJ6 SNPs studied here were found to be significantly associated with the same theta EROs in adults in a previous family genome wide association study. Since measures of the P3 response have been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of genetic effects on its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Differences in fast beta (20-28Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2)., Method: In a sample of 1564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings., Results: Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5×10 -8 ). The most significant SNP was rs2252790 (p<2.6×10 -8 ; MAF=0.36; β=0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p=1.2×10 -6 ) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3×10 -4 ; β=0.29). Previous studies have indicated that DSE is involved in a network of genes integral to membrane organization; gene-based tests indicated that several variants within this network (i.e., DSE, ZEB2, RND3, MCTP1, and CTBP2) were also associated with beta EEG (empirical p<0.05), and of these genes, ZEB2 and CTBP2 were associated with DSM-V Alcohol Use Disorder (AUD; empirical p<0.05).', Discussion: In this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Event related oscillations (EROs) are heritable measures of neurocognitive function that have served as useful phenotype in genetic research. A recent family genome-wide association study (GWAS) by the Collaborative Study on the Genetics of Alcoholism (COGA) found that theta EROs during visual target detection were associated at genome-wide levels with several single nucleotide polymorphisms (SNPs), including a synonymous SNP, rs702859, in the KCNJ6 gene that encodes GIRK2, a G-protein inward rectifying potassium channel that regulates excitability of neuronal networks. The present study examined the effect of the KCNJ6 SNP (rs702859), previously associated with theta ERO to targets in a visual oddball task, on theta EROs during reward processing in a monetary gambling task. The participants were 1601 adolescent and young adult offspring within the age-range of 17-25years (800 males and 801 females) from high-dense alcoholism families as well as control families of the COGA prospective study. Theta ERO power (3.5-7.5Hz, 200-500ms post-stimulus) was compared across genotype groups. ERO theta power at central and parietal regions increased as a function of the minor allele (A) dose in the genotype (AA>AG>GG) in both loss and gain conditions. These findings indicate that variations in the KCNJ6 SNP influence magnitude of theta oscillations at posterior loci during the evaluation of loss and gain, reflecting a genetic influence on neuronal circuits involved in reward-processing. Increased theta power as a function of minor allele dose suggests more efficient cognitive processing in those carrying the minor allele of the KCNJ6 SNPs. Future studies are needed to determine the implications of these genetic effects on posterior theta EROs as possible "protective" factors, or as indices of delays in brain maturation (i.e., lack of frontalization)., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Higher impulsivity observed in alcoholics is thought to be due to neurocognitive functional deficits involving impaired inhibition in several brain regions and/or neuronal circuits. Event-related oscillations (EROs) offer time-frequency measure of brain rhythms during perceptual and cognitive processing, which provide a detailed view of neuroelectric oscillatory responses to external/internal events. The present study examines evoked power (temporally locked to events) of oscillatory brain signals in alcoholics during an equal probability Go/NoGo task, assessing their functional relevance in execution and inhibition of a motor response. The current study hypothesized that increases in the power of slow frequency bands and their topographical distribution is associated with tasks that have increased cognitive demands, such as the execution and inhibition of a motor response. Therefore, it is hypothesized that alcoholics would show lower spectral power in their topographical densities compared to controls. The sample consisted of 20 right-handed abstinent alcoholic males and 20 age and gender-matched healthy controls. Evoked delta (1.0-3.5Hz; 200-600ms), theta (4.0-7.5Hz; 200-400ms), slow alpha (8.0-9.5Hz; 200-300ms), and fast alpha (10.0-12.5Hz; 100-200ms) ERO power were compared across group and task conditions. Compared to controls, alcoholics had higher impulsiveness scores on the Barrett Impulsiveness Scale (BIS-11) and made more errors on Go trials. Alcoholics showed significantly lower evoked delta, theta, and slow alpha power compared to controls for both Go and NoGo task conditions, and lower evoked fast alpha power compared to controls for only the NoGo condition. The results confirm previous findings and are suggestive of neurocognitive deficits while executing and suppressing a motor response. Based on findings in the alpha frequency ranges, it is further suggested that the inhibitory processing impairments in alcoholics may arise from inadequate early attentional processing with respect to the stimulus related aspects/semantic memory processes, which may be reflected in lower posterio-temporal evoked fast alpha power. It can thus be concluded that alcoholics show neurocognitive deficits in both execution and suppression of a motor response and inadequate early attentional processing with respect to the semantic memory/stimulus related aspects while suppressing a motor response., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. Event-related oscillations (EROs) have been used to effectively measure brain (dys)function during cognitive tasks in individuals with alcoholism and related disorders and in those at risk to develop these disorders. The current study examines ERO theta power during reward processing as well as impulsivity in adolescent and young adult subjects at high risk for alcoholism., Methods: EROs were recorded during a monetary gambling task (MGT) in 12-25 years old participants (N = 1821; males = 48%) from high risk alcoholic families (HR, N = 1534) and comparison low risk community families (LR, N = 287) from the Collaborative Study on the Genetics of Alcoholism (COGA). Impulsivity scores and prevalence of externalizing diagnoses were also compared between LR and HR groups., Results: HR offspring showed lower theta power and decreased current source density (CSD) activity than LR offspring during loss and gain conditions. Younger males had higher theta power than younger females in both groups, while the older HR females showed more theta power than older HR males. Younger subjects showed higher theta power than older subjects in each comparison. Differences in topography (i.e., frontalization) between groups were also observed. Further, HR subjects across gender had higher impulsivity scores and increased prevalence of externalizing disorders compared to LR subjects., Conclusions: As theta power during reward processing is found to be lower not only in alcoholics, but also in HR subjects, it is proposed that reduced reward-related theta power, in addition to impulsivity and externalizing features, may be related in a predisposition to develop alcoholism and related disorders.

Background: Individuals at high risk to develop alcoholism often manifest neurocognitive deficits as well as increased impulsivity. The goal of the present study is to elucidate reward processing deficits, externalizing disorders, and impulsivity as elicited by electrophysiological, clinical and behavioral measures in subjects at high risk for alcoholism from families densely affected by alcoholism in the context of brain maturation across age groups and gender., Methods: Event-related potentials (ERPs) and current source density (CSD) during a monetary gambling task (MGT) were measured in 12-25 year old offspring (N=1864) of families in the Collaborative Study on the Genetics of Alcoholism (COGA) Prospective study; the high risk (HR, N=1569) subjects were from families densely affected with alcoholism and the low risk (LR, N=295) subjects were from community families. Externalizing disorders and impulsivity scores were also compared between LR and HR groups., Results: HR offspring from older (16-25 years) male and younger (12-15 years) female subgroups showed lower P3 amplitude than LR subjects. The amplitude decrement was most prominent in HR males during the loss condition. Overall, P3 amplitude increase at anterior sites and decrease at posterior areas were seen in older compared to younger subjects, suggesting frontalization during brain maturation. The HR subgroups also exhibited hypofrontality manifested as weaker CSD activity during both loss and gain conditions at frontal regions. Further, the HR subjects had higher impulsivity scores and increased prevalence of externalizing disorders. P3 amplitudes during the gain condition were negatively correlated with impulsivity scores., Conclusions: Older male and younger female HR offspring, compared to their LR counterparts, manifested reward processing deficits as indexed by lower P3 amplitude and weaker CSD activity, along with higher prevalence of externalizing disorders and higher impulsivity scores., Significance: Reward related P3 is a valuable measure reflecting neurocognitive dysfunction in subjects at risk for alcoholism, as well as to characterize reward processing and brain maturation across gender and age group., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The developmental trajectories of theta band (4-7 Hz) event-related oscillations (EROs), a key neurophysiological constituent of the P3 response, were assessed in 2170 adolescents and young adults ages 12 to 25. The theta EROs occurring in the P3 response, important indicators of neurocognitive function, were elicited during the evaluation of task-relevant target stimuli in visual and auditory oddball tasks. These tasks call upon attentional and working memory resources. Large differences in developmental rates between males and females were found; scalp location and task modality (visual or auditory) differences within males and females were small compared to gender differences. Trajectories of interregional and intermodal correlations between ERO power values exhibited increases with age in both genders, but showed a divergence in development between auditory and visual systems during ages 16 to 21. These results are consistent with previous electrophysiological and imaging studies and provide additional temporal detail about the development of neurophysiological indices of cognitive activity. Since measures of the P3 response has been found to be a useful endophenotypes for the study of a number of clinical and behavioral disorders, studies of its development in adolescents and young adults may illuminate neurophysiological factors contributing to the onset of these conditions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Migrant farm workers are exposed to job hazards in Tennessee, which is among the top five tomato-producing states., Objectives: This project sought to cultivate and evaluate a partnership to marshal greater resources to address migrants' concerns and to better prepare future health professionals to address occupational issues., Methods: In the spring of 2008, an interprofessional student-faculty team at a regional university catalyzed a partnership with a clinic for migrants and a national network caring for the itinerant underserved., Results: Several community-based participatory research (CBPR) activities are underway. The partnership has resulted in the following projects: Use of the Rapid Entire Body Assessment (REBA) method to identify job tasks likely to be injurious, development and use of a health screening questionnaire to capture more information about occupational health, and continuing education seminars for providers and a case-based curriculum module for third-year medical students., Conclusions: Interprofessional service learning about migrant occupational health issues may have its greatest impact as participating students enter the regional workforce, caring for patients employed in slow-to-change agricultural operations.

Discrete time survival analysis was used to assess the age-specific association of event-related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2,938 adolescents and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens.

Event-related oscillations (EROs) represent highly heritable neuroelectric correlates of cognitive processes that manifest deficits in alcoholics and in offspring at high risk to develop alcoholism. Theta ERO to targets in the visual oddball task has been shown to be an endophenotype for alcoholism. A family-based genome-wide association study was performed for the frontal theta ERO phenotype using 634 583 autosomal single nucleotide polymorphisms (SNPs) genotyped in 1560 family members from 117 families densely affected by alcohol use disorders, recruited in the Collaborative Study on the Genetics of Alcoholism. Genome-wide significant association was found with several SNPs on chromosome 21 in KCNJ6 (a potassium inward rectifier channel; KIR3.2/GIRK2), with the most significant SNP at P = 4.7 × 10(-10)). The same SNPs were also associated with EROs from central and parietal electrodes, but with less significance, suggesting that the association is frontally focused. One imputed synonymous SNP in exon four, highly correlated with our top three SNPs, was significantly associated with the frontal theta ERO phenotype. These results suggest KCNJ6 or its product GIRK2 account for some of the variations in frontal theta band oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks., (© 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.)

Recent studies have linked alcoholism with a dysfunctional neural reward system. Although several electrophysiological studies have explored reward processing in healthy individuals, such studies in alcohol-dependent individuals are quite rare. The present study examines theta oscillations during reward processing in abstinent alcoholics. The electroencephalogram (EEG) was recorded in 38 abstinent alcoholics and 38 healthy controls as they performed a single outcome gambling task, which involved outcomes of either loss or gain of an amount (10 or 50¢) that was bet. Event-related theta band (3.0-7.0 Hz) power following each outcome stimulus was computed using the S-transform method. Theta power at the time window of the outcome-related negativity (ORN) and positivity (ORP) (200-500 ms) was compared across groups and outcome conditions. Additionally, behavioral data of impulsivity and task performance were analyzed. The alcoholic group showed significantly decreased theta power during reward processing compared to controls. Current source density (CSD) maps of alcoholics revealed weaker and diffuse source activity for all conditions and weaker bilateral prefrontal sources during the Loss 50 condition when compared with controls who manifested stronger and focused midline sources. Furthermore, alcoholics exhibited increased impulsivity and risk-taking on the behavioral measures. A strong association between reduced anterior theta power and impulsive task-performance was observed. It is suggested that decreased power and weaker and diffuse CSD in alcoholics may be due to dysfunctional neural reward circuitry. The relationship among alcoholism, theta oscillations, reward processing, and impulsivity could offer clues to understand brain circuitries that mediate reward processing and inhibitory control., (Copyright © 2011 Wiley-Liss, Inc.)

Several genome-wide association and candidate gene studies have linked chromosome 15q24-q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28

A recent study in a sample of Plains Indians showed association between eight single nucleotide polymorphisms (SNPs) located in the SGIP1 gene and resting θ electroencephalogram (EEG) power. This association appeared to generalize to alcohol use disorders, for which EEG power is a potential endophenotype. We analyzed a large, diverse sample for replication of the association of these implicated SGIP1 SNPs (genotyped on the Illumina 1M platform) with alcohol dependence (N=3988) and θ EEG power (N=1066). We found no evidence of association of the earlier implicated SGIP1 SNPs with either alcohol dependence or θ EEG power (all P>0.15) in this sample. The earlier implicated SNPs located in SGIP1 gene showed no association with alcohol dependence or θ EEG power in this sample of individuals with European and/or African ancestry. This failure to replicate may be the result of differences in ancestry between this sample and the original sample.

Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype-frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1 M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher's combined P = 3.68 × 10⁻⁶). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10⁻⁴), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case-control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders., (Copyright © 2010 Wiley-Liss, Inc.)

Objective: A dysfunctional neural reward system has been shown to be associated with alcoholism. The current study aims to examine reward processing in male alcoholics by using event-related potentials (ERPs) as well as behavioral measures of impulsivity and risk-taking., Methods: Outcome-related negativity (ORN/N2) and positivity (ORP/P3) derived from a single outcome gambling task were analyzed using a mixed model procedure. Current density was compared across groups and outcomes using standardized low resolution electromagnetic tomography (sLORETA). Behavioral scores were also compared across groups. Correlations of ERP factors with behavioral and impulsivity factors were also analyzed., Results: Alcoholics showed significantly lower amplitude than controls during all outcome conditions for the ORP component and decreased amplitude during the loss conditions for the ORN component. Within conditions, gain produced higher amplitudes than loss conditions. Topographically, both groups had an anterior focus during loss conditions and posterior maxima during gain conditions, especially for the ORN component. Decreased ORP current density at cingulate gyrus and less negative ORN current density at sensory and motor areas characterized the alcoholics. Alcoholics had higher levels of impulsivity and risk-taking features than controls., Conclusions: Deficient outcome/reward processing and increased impulsivity and risk-taking observed in alcoholics may be at least partly due to reward deficiency and/or dysfunctional reward circuitry in the brain, suggesting that alcoholism can be considered as part of the cluster of the reward deficiency syndrome (RDS)., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Event-related oscillations (EROs) have proved to be very useful in the understanding of a variety of neurocognitive processes including reward/outcome processing. In the present study, theta power (4.0-7.0 Hz) following outcome stimuli in the time window of the N2-P3 complex (200-500 ms) was analyzed in healthy normals (20 males and 20 females) while performing a gambling task that involved monetary loss and gain. The main aim was to analyze outcome processing in terms of event-related theta power in the context of valence, amount, gender, and impulsivity. The S-transform was used for the signal processing of the ERO data in terms of time-frequency-power. Results from filtered waveforms showed a partially consistent phase-alignment of the increased theta activity corresponding to N2 and P3 components following the outcome stimuli. Gain conditions produced more theta power than loss conditions. While there was anterior involvement in both gain and loss, posterior activation was stronger during gain conditions than during loss conditions. Females exhibited posterior maxima during gain conditions while males had an anterior maxima during both loss and gain conditions. The current source density of theta activity in females involved larger areas with a bilateral frontal activity while males predominantly had a frontal midline activity. Theta power was significantly higher in females than males across all conditions. Low theta (4.0-5.5 Hz) predominantly contributed to the posterior activity during gain conditions. High theta (5.5-7.0 Hz) was more associated with impulsivity measures than low theta activity. These findings may offer valuable clues to understand outcome processing, impulsivity, and gender differences.

We report results from experiments with a pseudo-one-dimensional Belousov-Zhabotinsky reaction that employs 1,4-cyclohexanedione as its organic substrate. This excitable system shows traveling oxidation pulses and pulse trains that can undergo complex sequences of propagation failures. Moreover, we present examples for (i) breathing pulses that undergo periodic changes in speed and size and (ii) backfiring pulses that near their back repeatedly generate new pulses propagating in opposite direction.

We report experimental and numerical results on temporal patterns of propagation failures in reaction-diffusion systems. Experiments employ the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction. The propagation failures occur in the frontier region of the wave train and can profoundly affect its expansion speed. The specific rhythms observed vary from simple periodic to highly complex and possibly chaotic sequences. All but the period-1 sequences are found in the transition region between "merging" and "tracking" dynamics, which correspond to wave behavior caused by two qualitatively different types of anomalous dispersion relations.

We present a theoretical analysis of stacking and destacking wave trains in excitable reaction-diffusion systems with anomalous velocity-wavelength dependence. For linearized dispersion relations, kinematic analysis yields an analytical function that rigorously describes front trajectories. The corresponding accelerations have exactly one extremum that slowly decays with increasing pulse number. For subsequent pulses these maxima occur with a lag time equal to the inverse slope of the linearized dispersion curve. These findings are reproduced in experiments with chemical waves in the 1,4-cyclohexanedione Belousov-Zhabotinsky reaction but should be also applicable to step bunching on crystal surfaces and certain traffic phenomena.

We report experimental results obtained from a chemical reaction-diffusion system in which wave propagation is limited to a finite band of wavelengths and in which no solitary pulses exist. Wave patterns increase their size through repeated annihilation events of the frontier pulse that allow the succeeding pulses to advance farther. A related type of wave dynamics involves a stable but slow frontier pulse that annihilates subsequent waves in front-to-back collisions. These so-called merging dynamics give rise to an unexpected form of spiral wave nucleation. All of these phenomena are reproduced by a simple, three-species reaction-diffusion model that reveals the importance of the underlying anomalous dispersion relation.

We have analyzed the protein content of proximal tubular fluid (PTF) by ultramicro disc electrophoresis and measured total protein excretion rates both in control conditions and during angiotensin infusion to the rat. Under control conditions PTF albumin concentration was 1.49 +/- 1.12 (SD) mg/100 ml and did not increase with distance from the glomerulus. Immediate postcapsular samples (Munich-Wistar strain) yielded nearly identical values so that both probably represent filtered albumin concentration. During infusion of angiotensin (0.15 mug/mix x 100 g of body wt), PTF albumin concentration increased on the average 26-fold in re-collections from control tubules. Total protein excretion increased from a control of 7.91 to 24.37 mg/24 hr x 100 g of body wt. Glomerular filtration rate (FGR), single nephron GFR (SNGFR), proximal transit time and tubular fluid to plasma (tf/p) inulin values did not change significantly. Net afferent filtration pressure decreased from 24.7 to 15.6 mm Hg and renal plasma flow fell from 2.16 to 1.31 mo/min x g of kidney wt. Data describe a protein reabsorptive system normally operating near capacity. Angiotensin-induced proteinuria derives from an increase in filtered protein (mostly albumin) resulting from permeability changes in the glomerular membrane.