Developmental divergence: motor trajectories in children with fragile X syndrome with and without co-occurring autism.

BackgroundAutism spectrum disorder (ASD) is highly prevalent in fragile X syndrome (FXS), affecting 50-70% of males. Motor impairments are a shared feature across autism and FXS that may help to better characterize autism in FXS. As motor skills provide a critical foundation for various language, cognitive, and social outcomes, they may serve an important mechanistic role for autism in FXS. As such, this study aimed to identify differences in motor trajectories across direct assessment and parent-report measures of fine and gross motor development between FXS with and without autism, and typical development, while controlling for cognitive functioning.MethodsThis prospective longitudinal study included 42 children with FXS, 24 of whom also had ASD (FXS + ASD), as well as 40 typically developing children. The Mullen Scales of Early Learning provided a direct measure of fine and gross motor skills, and the Vineland Adaptive Behavior Scales provided a measure of parent-reported fine and gross motor skills. Random slopes and random intercepts multilevel models were tested to determine divergence in developmental motor trajectories between groups when controlling for cognitive level.ResultsModel results indicated the children with FXS + ASD diverged from TD children by 9-months on all measures of gross and fine motor skills, even when controlling for cognitive level. Results also indicated an early divergence in motor trajectories of fine and gross motor skills between the FXS + ASD and FXS groups when controlling for cognitive level. This divergence was statistically significant by 18 months, with the FXS + ASD showing decelerated growth in motor skills across direct observation and parent-report measures.ConclusionsThis study is the first to examine longitudinal trends in motor development in children with FXS with and without comorbid ASD using both direct assessment and parent-report measures of fine and gross motor. Furthermore, it is among the first to account for nonverbal cognitive delays, a step towards elucidating the isolated role of motor impairments in FXS with and without ASD. Findings underscore the role of motor impairments as a possible signal representing greater underlying genetic liability, or as a potential catalyst or consequence, of co-occurring autism in FXS

Defect-unbinding transitions and inherent structures in two dimensions

We present a large-scale (36000-particle) computational study of the "inherent structures" (IS) associated with equilibrium, two-dimensional, one-component Lennard-Jones systems. Our results provide strong support both for the inherent-structures theory of classical fluids, and for the KTHNY theory of two-stage melting in two dimensions. This support comes from the observation of three qualitatively distinct "phases" of inherent structures: a crystal, a "hexatic glass", and a "liquid glass". We also directly observe, in the IS, analogs of the two defect-unbinding transitions (respectively, of dislocations, and disclinations) believed to mediate the two equilibrium phase transitions. Each transition shows up in the inherent structures---although the free disclinations in the "liquid glass" are embedded in a percolating network of grain boundaries. The bond-orientational correlation functions of the inherent structures show the same progressive loss of order as do the three equilibrium phases: long-range to quasi-long-range to short-range.Comment: RevTeX, 8 pages, 15 figure

Cama de frango como substrato para a produção de biogás após diferentes períodos de estocagem.

RESUMO: Na avicultura a cama de frango é produzida sazonalmente, em função do modo de produção. Para obter energia do biogás por meio da biodigestão da cama de frango, de forma contínua, o armazenamento do resíduo pode ser uma solução. Ensaios de Potencial Bioquímico de Metano (BMP) foram utilizados neste trabalho para estimar a capacidade de produção de biogás e metano da cama de frango removida após o sexto lote de reutilização e a diferentes tempos de armazenamento após a coleta, assim, verificar a viabilidade de utilização da cama de frango como um substrato em unidade produtora de biogás. A produção de biogás e metano, nas amostras em diferentes períodos de armazenamento, foi comparada: antes de armazenar 245 LN biogas.kgSV adic-1 e 159 LN CH4.kgSV adic-11, seis meses com 252 LN biogas.kgSV adic-1 e 160 LN CH4.kgSV adic-1 e um ano 209 LN biogas.kgSV adic-1 e 117 LNCH4.kgSV adic-1, demonstrando que o período de armazenamento é caracterizado por uma relativa perda do conteúdo de matéria orgânica após um ano, contudo, não há diferença significativa entre a produção de biogás e metano após seis meses armazenada e antes de armazenar. Verificou-se a viabilidade da estocagem de cama de frango do sexto lote de reutilização, no período de seis meses, sem perda significativa de matéria orgânica para a conversão em biogás e metano. ABSTRACT: In poultry litter is produced seasonally due to production mode. To get energy from biogas through the bio digestion of poultry litter, continuously, the storage of the residue can be a solution. Biochemical Methane Potential (BMP) assays were used in this study to estimate the production of biogas and methane poultry litter removed after the sixth lot of reuse and in different storage times after collect, so check the feasibility of use poultry litter as a feedstock in biogas producer unit. The production of biogas and methane in the samples in different periods of storage was compared: before storage 245 LN biogas.kgVS add-1 E 159 LN C H4 kg SV add-1, six months with 252 LN biogas.kgVS add-1 e 160 LN C H4 kg SV add-1 and a year 209 LN biogas.kgVS add-1 and one year 117 LN C H4 kg SV add-1, demonstrating that the storage period is characterized by a relative loss of content of organic matter after a year, however there's no significant difference between the production of biogas and methane in six months storaged and before storage . It was verified the viability of storage of poultry litter of the sixth lot of reuse, in the six-month period, without significant loss of organic matter for conversion to biogas and methane

Esmethadone (REL-1017) and Other Uncompetitive NMDAR Channel Blockers May Improve Mood Disorders via Modulation of Synaptic Kinase-Mediated Signaling

This article presents a mechanism of action hypothesis to explain the rapid antidepressant effects of esmethadone (REL-1017) and other uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonists and presents a corresponding mechanism of disease hypothesis for major depressive disorder (MDD). Esmethadone and other uncompetitive NMDAR antagonists may restore physiological neural plasticity in animal models of depressive-like behavior and in patients with MDD via preferential tonic block of pathologically hyperactive GluN2D subtypes. Tonic Ca2+ currents via GluN2D subtypes regulate the homeostatic availability of synaptic proteins. MDD and depressive behaviors may be determined by reduced homeostatic availability of synaptic proteins, due to upregulated tonic Ca2+ currents through GluN2D subtypes. The preferential activity of low-potency NMDAR antagonists for GluN2D subtypes may explain their rapid antidepressant effects in the absence of dissociative side effects

RXTE Absolute Timing Results for the Pulsars B1821-24 and B1509-58

Observations with the Rossi X-ray Timing Explorer and the Jodrell Bank, Parkes, and Green Bank telescopes have enabled us to determine the time delay between radio and X-ray pulses in the two isolated pulsars B1821-24 and B1509-58. For the former we find that the narrow X-ray and radio pulse components are close to being coincident in time, with the radio peak leading by 0.02 period (60 +/- 20 microsec), while the wide X-ray pulse component lags the last of the two wider radio components by about 0.08 period. For the latter pulsar we find, using the standard value for the dispersion measure, that the X-ray pulse lags the radio by about 0.27 period, with no evidence for any energy-dependence in the range 2-100 keV. However, uncertainties in the history of the dispersion measure for this pulsar make a comparison with previous results difficult. It is clear that there are no perceptable variations in either the lag or the dispersion measure at time scales of a year or less.Comment: 20 pages including 6 figures, accepted by Astrophysical Journa

Measurement Bias in Caregiver-Report of Early Childhood Behavior Problems across Demographic Factors in an Echo-Wide Diverse Sample

BACKGROUND: Research and clinical practice rely heavily on caregiver-report measures, such as the Child Behavior Checklist 1.5-5 (CBCL/1.5-5), to gather information about early childhood behavior problems and to screen for child psychopathology. While studies have shown that demographic variables influence caregiver ratings of behavior problems, the extent to which the CBCL/1.5-5 functions equivalently at the item level across diverse samples is unknown. METHODS: Item-level data of CBCL/1.5-5 from a large sample of young children ( RESULTS: Items with the most impactful DIF across child and caregiver groupings were identified for Internalizing, Externalizing, and total Problems. The robust item sets, excluding the high DIF items, showed good reliability and high correlation with the original Internalizing and total Problems scales, with lower reliability for Externalizing. Language version of CBCL administration, education level and sex of the caregiver respondent showed the most significant impact on MI, followed by child age. Sensitivity analyses revealed that child race has a unique impact on DIF over and above socioeconomic status. CONCLUSIONS: The CBCL/1.5-5, a caregiver-report measure of early childhood behavior problems, showed bias across demographic groups. Robust item sets with less DIF can measure Internalizing and total Problems equally as well as the full item sets, with slightly lower reliability for Externalizing, and can be crosswalked to the metric of the full item set, enabling calculation of normed T scores based on more robust item sets

Identification of developmental and behavioral markers associated with genetic abnormalities in Autism Spectrum Disorder

ObjectiveAside from features associated with risk of neurogenetic syndromes in general (e.g., cognitive impairment), limited progress has been made in identifying phenotype-genotype relationships in autism spectrum disorder (ASD). The objective of this study was to extend work in the Simons Simplex Collection by comparing the phenotypic profiles of ASD probands with or without identified de novo loss of function mutations or copy number variants in high-confidence ASD-associated genes or loci.MethodAnalyses preemptively accounted for documented differences in sex and IQ in affected individuals with de novo mutations by matching probands with and without these genetic events on sex, IQ, and age before comparing them on multiple behavioral domains.ResultsChildren with de novo mutations (N=112) had a greater likelihood of motor delay during early development (later age at walking), but they were less impaired on certain measures of ASD core symptoms (parent-rated social communication abnormalities and clinician-rated diagnostic certainty about ASD) in later childhood. These children also showed relative strengths in verbal and language abilities, including a smaller discrepancy between nonverbal and verbal IQ and a greater likelihood of having achieved fluent language (i.e., regular use of complex sentences).ConclusionsChildren with ASD with de novo mutations may exhibit a "muted" symptom profile with respect to social communication and language deficits relative to those with ASD with no identified genetic abnormalities. Such findings suggest that examining early milestone differences and standardized testing results may be helpful in etiologic efforts, and potentially in clinical differentiation of various subtypes of ASD, but only if developmental and demographic variables are properly accounted for first

Association of Atopobium vaginae, a recently described metronidazole resistant anaerobe, with bacterial vaginosis

BACKGROUND: Bacterial vaginosis (BV) is a polymicrobial syndrome characterized by a change in vaginal flora away from predominantly Lactobacillus species. The cause of BV is unknown, but the condition has been implicated in diverse medical outcomes. The bacterium Atopobium vaginae has been recognized only recently. It is not readily identified by commercial diagnostic kits. Its clinical significance is unknown but it has recently been isolated from a tuboovarian abcess. METHODS: Nucleotide sequencing of PCR amplified 16S rRNA gene segments, that were separated into bands within lanes on polyacrylamide gels by denaturing gradient gel electrophoresis (DGGE), was used to examine bacterial vaginal flora in 46 patients clinically described as having normal (Lactobacillus spp. predominant; Nugent score ≤ 3) and abnormal flora (Nugent score ≥ 4). These women ranged in age from 14 to 48 and 82% were African American. RESULTS: The DGGE banding patterns of normal and BV-positive patients were recognizably distinct. Those of normal patients contained 1 to 4 bands that were focused in the centre region of the gel lane, while those of BV positive patients contained bands that were not all focused in the center region of the gel lane. More detailed analysis of patterns revealed that bands identified as Atopobium vaginae were present in a majority (12/22) of BV positive patients, while corresponding bands were rare (2/24) in normal patients. (P < 0.001) Two A. vaginae isolates were cultivated from two patients whose DGGE analyses indicated the presence of this organism. Two A. vaginae 16S rRNA gene sequences were identified among the clinical isolates. The same two sequences were obtained from DGGE bands of the corresponding vaginal flora. The sequences differed by one nucleotide over the short (~300 bp) segment used for DGGE analysis and migrated to slightly different points in denaturing gradient gels. Both isolates were strict anaerobes and highly metronidazole resistant. CONCLUSION: The results suggest that A. vaginae may be an important component of the complex bacterial ecology that constitutes abnormal vaginal flora. This organism could play a role in treatment failure if further studies confirm it is consistently metronidozole resistant