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Objective: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. Methods: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow‐up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. Results: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow‐up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10‐year follow‐up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal‐appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty‐four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten‐year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. Significance: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status. [ABSTRACT FROM AUTHOR]

A critical step in photocatalytic water dissociation is the hole‐mediated oxidation reaction. Molecular‐level insights into the mechanism of this complex reaction under realistic conditions with high temporal resolution are highly desirable. Here, we use femtosecond time‐resolved, surface‐specific vibrational sum frequency generation spectroscopy to study the photo‐induced reaction directly at the interface of the photocatalyst TiO2 in contact with liquid water at room temperature. Thanks to the inherent surface specificity of the spectroscopic method, we can follow the reaction of solely the interfacial water molecules directly at the interface at timescales on which the reaction takes place. Following the generation of holes at the surface immediately after photoexcitation of the catalyst with UV light, water dissociation occurs on a sub‐20 ps timescale. The reaction mechanism is similar at pH 3 and 11. In both cases, we observe the conversion of H2O into Ti−OH groups and the deprotonation of pre‐existing Ti−OH groups. This study provides unique experimental insights into the early steps of the photo‐induced dissociation processes at the photocatalyst‐water interface, relevant to the design of improved photocatalysts. [ABSTRACT FROM AUTHOR]

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We analyze adolescent BMI and middle‐age systolic blood pressure (SBP) repeatedly measured on women enrolled in the Fels Longitudinal Study (FLS) between 1929 and 2010 to address three questions: Do adolescent‐specific growth rates in body mass index (BMI) and menarche affect middle‐age SBP? Do they moderate the aging effect on middle‐age SBP? Have the effects changed over historical time? To address the questions, we propose analyzing a growth curve model (GCM) that controls for age, birth‐year cohort, and historical time. However, several complications in the data make the GCM analysis nonstandard. First, the person‐specific adolescent BMI and middle‐age SBP trajectories are unobservable. Second, missing data are substantial on BMI, SBP, and menarche. Finally, modeling the latent trajectories for BMI and SBP, repeatedly measured on two distinct sets of unbalanced time points, are computationally intensive. We adopt a bivariate GCM for BMI and SBP with correlated random coefficients. To efficiently handle missing values of BMI, SBP, and menarche assumed missing at random, we estimate their joint distribution by maximum likelihood via the EM algorithm where the correlated random coefficients and menarche are multivariate normal. The estimated distribution will be transformed to the desired GCM for SBP that includes the random coefficients of BMI and menarche as covariates. We demonstrate unbiased estimation by simulation. We find that adolescent growth rates in BMI and menarche are positively associated with, and moderate, the aging effect on SBP in middle age, controlling for age, cohort, and historical time, but the effect sizes are at most modest. The aging effect is significant on SBP, controlling for cohort and historical time, but not vice versa. [ABSTRACT FROM AUTHOR]

Summary: Body composition estimates are widely used in clinical research and field studies as measures of energy‐nutrient balance, functionality and health. Despite their broad relevance and multiple applications, important gaps remain in techniques available for accurately and precisely quantifying body composition in infants and children from birth through 5 years. Identifying these gaps and highlighting research needs in this age group were the topics of a National Institutes of Health workshop held in Bethesda, MD, USA, 30–31 May 2019. Experts reviewed available methods (multicompartment models, air‐displacement plethysmography, dual‐energy X‐ray absorptiometry, weight‐length and height indices, bioimpedance analysis, anthropometry‐skinfold techniques, quantitative magnetic resonance, optical imaging, omics and D3‐creatine dilution), their limitations in this age range and high priority research needs. A summary of their individual and collective workshop deliberations is provided in this report. [ABSTRACT FROM AUTHOR]

Objective Our aim was to explore the association between plasma cytokines and febrile status epilepticus ( FSE) in children, as well as their potential as biomarkers of acute hippocampal injury. Methods Analysis was performed on residual samples of children with FSE (n = 33) as part of the Consequences of Prolonged Febrile Seizures in Childhood study (FEBSTAT) and compared to children with fever (n = 17). Magnetic resonance imaging (MRI) was obtained as part of FEBSTAT within 72 h of FSE. Cytokine levels and ratios of antiinflammatory versus proinflammatory cytokines in children with and without hippocampal T2 hyperintensity were assessed as biomarkers of acute hippocampal injury after FSE. Results Levels of interleukin (IL)-8 and epidermal growth factor ( EGF) were significantly elevated after FSE in comparison to controls. IL-1β levels trended higher and IL-1 RA trended lower following FSE, but did not reach statistical significance. Children with FSE were found to have significantly lower ratios of IL-1 RA/ IL-1β and IL-1 RA/ IL-8. Specific levels of any one individual cytokine were not associated with FSE. However, lower ratios of IL-1 RA/ IL-1β, IL-1 RA/1L-6, and IL-1 RA/ IL-8 were all associated with FSE. IL-6 and IL-8 levels were significantly higher and ratios of IL-1 RA/ IL-6 and IL-1 RA/ IL-8 were significantly lower in children with T2 hippocampal hyperintensity on MRI after FSE in comparison to those without hippocampal signal abnormalities. Neither individual cytokine levels nor ratios of IL-1 RA/ IL-1β or IL-1 RA/ IL-8 were predictive of MRI changes. However, a lower ratio of IL-1 RA/ IL-6 was strongly predictive (odds ratio [OR] 21.5, 95% confidence interval [CI] 1.17-393) of hippocampal T2 hyperintensity after FSE. Significance Our data support involvement of the IL-1 cytokine system, IL-6, and IL-8 in FSE in children. The identification of the IL-1 RA/ IL-6 ratio as a potential biomarker of acute hippocampal injury following FSE is the most significant finding. If replicated in another study, the IL-1 RA/ IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy ( MTLE). [ABSTRACT FROM AUTHOR]

Few articles have been written on analyzing three-way interactions between drugs. It may seem to be quite straightforward to extend a statistical method from two-drugs to three-drugs. However, there may exist more complex nonlinear response surface of the interaction index ( [ABSTRACT FROM AUTHOR]

Objectives: To identify risk and risk factors for developing a subsequent febrile seizure (FS) in children with a first febrile status epilepticus (FSE) compared to a first simple febrile seizure (SFS). To identify home use of rescue medications for subsequent FS. Methods: Cases included a first FS that was FSE drawn from FEBSTAT and Columbia cohorts. Controls were a first SFS. Cases and controls were classified according to established FEBSTAT protocols. Cumulative risk for subsequent FS over a 5-year period was compared in FSE versus SFS, and Cox proportional hazards regression was conducted. Separate analysis examined subsequent FS within FSE. The use of rescue medications at home was assessed for subsequent FS. Results: Risk for a subsequent FSE was significantly increased in FSE versus SFS. Any magnetic resonance imaging (MRI) abnormality increased the risk 3.4-fold (p < 0.05), adjusting for age at first FS and FSE and in analyses restricted to children whose first FS was FSE (any MRI abnormality hazard ratio [HR] 2.9, p < 0.05). The risk for a second FS of any type or of subsequent FS lasting >10 min over the 5-year follow-up did not differ in FSE versus SFS. Rectal diazepam was administered at home to 5 (23.8%) of 21 children with subsequent FS lasting =10 min. Significance: Compared to controls, FSE was associated with an increased risk for subsequent FSE, suggesting the propensity of children with an initial prolonged seizure to experience a prolonged recurrence. Any baseline MRI abnormality increased the recurrence risk when FSE was compared to SFS and when FSE was studied alone. A minority of children with a subsequent FS lasting 10 min or longer were treated with rectal diazepam at home, despite receiving prescriptions after the first FSE. This indicates the need to further improve the education of clinicians and parents in order to prevent subsequent FSE. [ABSTRACT FROM AUTHOR]

Objective Treatment of seizures varies by region, with no standard emergency treatment protocol. Febrile status epilepticus ( FSE) is often a child's first seizure; therefore, families are rarely educated about emergency treatment. Methods From 2002 to 2010, 199 subjects, age 1 month to 6 years, were recruited as part of a prospective, multicenter study of consequences of FSE, which was defined as a febrile seizure or series of seizures lasting >30 min. The patients' charts were reviewed. No standardized treatment protocol was implemented for this observational study. Results One hundred seventy-nine children received at least one antiepileptic drug ( AED) to terminate FSE, and more than one AED was required in 140 patients (70%). Median time from the seizure onset to first AED by emergency medical services (EMS) or emergency department (ED) was 30 min. Mean seizure duration was 81 min for subjects given medication prior to ED and 95 min for those who did not (p = 0.1). Median time from the first dose of AED to end of seizure was 38 min. Initial dose of lorazepam or diazepam was suboptimal in 32 (19%) of 166 patients. Ninety-five subjects (48%) received respiratory support by EMS or ED. Median seizure duration for the respiratory support group was 83 min; for the nonrespiratory support group the duration was 58 min (p-value < 0.001). Reducing the time from seizure onset to AED initiation was significantly related to shorter seizure duration. Significance FSE rarely stops spontaneously, is fairly resistant to medications, and even with treatment persists for a significant period of time. The total seizure duration is composed of two separate factors, the time from seizure onset to AED initiation and the time from first AED to seizure termination. Earlier onset of treatment results in shorter total seizure duration. A standard prehospital treatment protocol should be used nationwide and education of EMS responders is necessary. [ABSTRACT FROM AUTHOR]

Objective Whether febrile status epilepticus (FSE) produces hippocampal sclerosis (HS) and temporal lobe epilepsy (TLE) has long been debated. Our objective is to determine whether FSE produces acute hippocampal injury that evolves to HS. Methods FEBSTAT and 2 affiliated studies prospectively recruited 226 children aged 1 month to 6 years with FSE and controls with simple febrile seizures. All had acute magnetic resonance imaging (MRI), and follow-up MRI was obtained approximately 1 year later in the majority. Visual interpretation by 2 neuroradiologists informed only of subject age was augmented by hippocampal volumetrics, analysis of the intrahippocampal distribution of T2 signal, and apparent diffusion coefficients. Results Hippocampal T2 hyperintensity, maximum in Sommer's sector, occurred acutely after FSE in 22 of 226 children in association with increased volume. Follow-up MRI obtained on 14 of the 22 with acute T2 hyperintensity showed HS in 10 and reduced hippocampal volume in 12. In contrast, follow-up of 116 children without acute hyperintensity showed abnormal T2 signal in only 1 (following another episode of FSE). Furthermore, compared to controls with simple febrile seizures, FSE subjects with normal acute MRI had abnormally low right to left hippocampal volume ratios, smaller hippocampi initially, and reduced hippocampal growth. Interpretation Hippocampal T2 hyperintensity after FSE represents acute injury often evolving to a radiological appearance of HS after 1 year. Furthermore, impaired growth of normal-appearing hippocampi after FSE suggests subtle injury even in the absence of T2 hyperintensity. Longer follow-up is needed to determine the relationship of these findings to TLE. ANN NEUROL 2014;75:178-185 [ABSTRACT FROM AUTHOR]

Purpose: In a prospective study, Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT), we determined the frequency of human herpesvirus (HHV)-6 and HHV-7 infection as a cause of febrile status epilepticus (FSE). Methods: Children ages 1 month to 5 years presenting with FSE were enrolled within 72 h and received a comprehensive assessment including specimens for HHV-6 and HHV-7. The presence of HHV-6A, HHV-6B, or HHV-7 DNA and RNA (amplified across a spliced junction) determined using quantitative polymerase chain reaction (qPCR) at baseline indicated viremia. Antibody titers to HHV-6 and HHV-7 were used in conjunction with the PCR results to distinguish primary infection from reactivated or prior infection Key Findings: Of 199 children evaluated, HHV-6 or HHV-7 status could be determined in 169 (84.9%). HHV-6B viremia at baseline was found in 54 children (32.0%), including 38 with primary infection and 16 with reactivated infection. No HHV-6A infections were identified. HHV-7 viremia at baseline was observed in 12 children (7.1%), including eight with primary infection and four with reactivated infection. Two subjects had HHV-6/HHV-7 primary coinfection at baseline. There were no differences in age, characteristics of illness or fever, seizure phenomenology or the proportion of acute EEG or imaging abnormalities in children presenting with FSE with or without HHV infection. Significance: HHV-6B infection is commonly associated with FSE. HHV-7 infection is less frequently associated with FSE. Together, they account for one third of FSE, a condition associated with an increased risk of both hippocampal injury and subsequent temporal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Purpose: Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hippocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology. Methods: The 'Consequences of Prolonged Febrile Seizures in Childhood' (FEBSTAT) study is a prospective, multicenter study. Enrolled are children, aged 1 month to 6 years of age, presenting with a febrile seizure lasting 30 min or longer based on ambulance, emergency department, and hospital records, and parental interview. At baseline, procedures included a magnetic resonance imaging (MRI) study and electroencephalography (EEG) recording done within 72 h of FSE, and a detailed history and neurologic examination. Baseline development and behavior are assessed at 1 month. The baseline assessment is repeated, with age-appropriate developmental testing at 1 and 5 years after enrollment as well as at the development of epilepsy and 1 year after that. Telephone calls every 3 months document additional seizures. Two other groups of children are included: a 'control' group consisting of children with a first febrile seizure ascertained at Columbia University and with almost identical baseline and 1-year follow-up examinations and a pilot cohort of FSE from Duke University. Key Findings: The FEBSTAT cohort consists of 199 children with a median age at baseline of 16.0 months (interquartile range [IQR] 12.0-24.0) and a median duration of FSE of 70.0 min (IQR 47.0-110.0). Seizures were continuous in 57.3% and behaviorally intermittent (without recovery in between) in 31.2%; most were partial (2.0%) or secondary generalized (65.8%), and almost all (98.0%) culminated in a generalized tonic-clonic seizure. Of the 199 children, 86.4% had normal development and 20% had prior febrile seizures. In one third of cases, FSE was unrecognized in the emergency department. The Duke existing cohort consists of 23 children with a median age of FSE onset of 18.0 months (IQR 14.0-28.0) and median duration of FSE of 90.0 min (IQR 50.0-170.0). The Columbia control cohort consists of 159 children with a first febrile seizure who received almost the same workup as the FEBSTAT cohort at baseline and at 1 year. They were followed by telephone every 4 months for a median of 42 months. Among the control cohort, 64.2% had a first simple FS, 26.4% had a first complex FS that was not FSE, and 9.4% had FSE. Among the 15 with FSE, the median age at onset was 14.0 months (IQR 12.0-20.0) and the median duration of FSE was 43.0 min (IQR 35.0-75.0). Significance: The FEBSTAT study presents an opportunity to prospectively study the relationship between FSE and acute hippocampal damage, the development of mesial temporal sclerosis, epilepsy (particularly temporal lobe epilepsy), and impaired hippocampal function in a large cohort. It is hoped that this study may illuminate a major mystery in clinical epilepsy today, and permit the development of interventions designed to prevent the sequelae of FSE. [ABSTRACT FROM AUTHOR]

Objectives: To determine secular trends by birth decade in body mass index (BMI), waist circumference/height (W/Ht), percent body fat (PBF), and fat-free mass adjusted for height squared (FFM/Ht2) in children and adolescents aged 8-18 years. Methods: Serial data were analyzed from 628 boys and 591 girls aged 8-18 years who participated in the Fels Longitudinal Study. Subjects were stratified by birth decade from 1960 to 1999. Means and standard deviations were computed for all measurements by birth decade, age, and sex. A repeated-measures analysis of variance was used data to ascertain secular trends separately for boys and girls. Results: Boys and girls born in the 1990s had significantly higher mean BMI, W/Ht, and PBF than did children born in previous decades. Mean FFM/Ht2 was significantly smaller in boys born in the 1990s than boys of the same age born in earlier decades. No secular trend was noted in FFM/Ht2 in girls by decade of birth. Conclusion: Our analysis of serial data collected over 4 decades confirms the secular trend in childhood BMI previously observed in successive cross-sectional studies. Our analysis discloses significant positive secular trends in W/Ht and PBF in both boys and girls and a significant negative secular trend in FFM/Ht2 in boys over the last 4 decades of the 20th century. The secular changes presage increases in the prevalence of conditions associated with childhood and adolescent obesity-such as hypertension, glucose intolerance, and dyslipidemia-that may appear as early as the second decade of life. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the relationship between childhood obesity and hypertension. The study is based on the Fels Longitudinal Study (FLS), which analyzed systolic blood pressure (SBP) and diastolic blood pressure (DBP) of Caucasian males and females. The role of lifestyle in determining body composition and hypertension is also considered.

Objective: We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue.Research Methods and Procedures: Contiguous 1-cm-thick magnetic resonance (MR) images of the abdomen were collected from 820 African-American and white adults. Repeated-measures ANOVA was used to examine the effects of image location, sex, race, and age (>or=50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data.Results: Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4-L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4-L5 (p < 0.0001). African-American men had greater total VAT volume than African-American women (p < 0.01), but this sex difference was only significant using single images cranial to L4-L5 + 2 cm. Age-related increases in VAT tended to be greatest 5 to 10 cm above L4-L5 in men and near L4-L5 in women.Discussion: A single MR image 5 to 10 cm above L4-L5 may allow more accurate conclusions than the L4-L5 image regarding group differences in visceral adiposity. [ABSTRACT FROM AUTHOR]

Previous studies estimated critical periods of childhood BMI growth and linked these events to adult adiposity and cardiovascular health. We expand upon both results to link childhood BMI growth patterns with adult blood pressure (BP). Data from male and female participants in the Fels Longitudinal Study (FLS) were used to estimate childhood BMI growth curves, from which we isolate ages of childhood BMI divergence based upon adult BMI and BP measurements. Repeated measure analysis of variances models were used to estimate BMI growth curves from age 2 to age 17.5 based on both adult BMI (< 25 kg/m2 or ≥ 25 kg/m2) and adult BP (< 120 mm Hg or ≥ 120 mm Hg for systolic BP (SBP); < 80 mm Hg or ≥ 80 mm Hg for diastolic BP (DBP)). Participants with lower body weight throughout childhood had lower SBP and DBP in early adulthood. Any relationships between childhood adiposity and adult body weight and BP disappeared by age 60. These results were independent of adult BMI and were observed in both men and women. Increased adult BP has its genesis in part from increased childhood BMI. [ABSTRACT FROM AUTHOR]

Background: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels., Methods: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts., Results: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information., Conclusions: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off., (© 2023 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

A number of recent reports suggest that the average age at menarche of US girls has declined over the past 20 years. Because the putative declines in the age at menarche are concurrent with increases in childhood body mass index (BMI), it has been suggested that these two trends may be causally linked. We examined differences in mean age of menarche in Fels Longitudinal Study girls who were born in six 10-year birth cohorts (1930s, 1940s, 1950s, 1960s, 1970s, and 1980s) and simultaneous cohort changes in mean BMI measured cross-sectionally at selected ages from 3-35 years (n = 371). Girls born in the 1980s had a mean age at menarche of 12.34 years, which was approximately 3-6 months earlier than that of girls born previously (P < 0.001). While the mean BMI values at ages 25 and 35 generally increased from the 1930s to the 1970s, the mean BMI during childhood and adolescence remained constant across the six birth cohorts. In summary, we found no evidence that the recent decline in the age at menarche in the Fels Longitudinal Study girls was reflected in concurrent increases in BMI at any point in childhood or adolescence. Conversely, girls born in the 1960s and 1970s have subsequently become heavier in young and mid-adulthood than were girls from earlier birth cohorts, without any concurrent change in the mean age at menarche over that time period. These two findings suggest that population-level shifts in BMI and the timing of menarche are largely independent, although sometimes coincident, processes., (Copyright 2004 Wiley-Liss, Inc.)