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The dopamine transporter gene (DAT1) and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether a DAT1 haplotype affected functional and structural brain alterations in children with ADHD and whether those alterations were associated with visual memory.
We recruited a total of 37 drug-naïve children with ADHD (17 with the DAT1 rs27048 (C)/rs429699 (T) haplotype and 20 without the CT haplotype) and 37 typically developing children (17 with the CT haplotype and 20 without the CT haplotype). Visual memory was assessed by the pattern recognition memory (PRM) and spatial recognition memory (SRM) tasks. We analyzed functional and structural brain architecture with regional homogeneity (ReHo) and gray matter volume (GMV).
The CT haplotype was associated with decreased ReHo in the left superior occipital gyrus, cuneus, and precuneus; and decreased GMV in the left superior occipital gyrus, cuneus, and precuneus, and in the right angular gyrus. Significant interactions of ADHD and the CT haplotype were found in the right postcentral gyrus for ReHo and in the right supplementary motor area for GMV. For the ADHD-CT group, we found negative correlations of total correct responses in PRM and SRM and positive correlations of mean latency of correct responses in PRM with the GMV in the left superior occipital gyrus, cuneus, and precuneus.
Our findings suggest that the DAT1-related GMV alterations in the posterior cortical regions may contribute to visual memory performance in children with ADHD.
Understanding the organic chemistry of molecular clouds, particularly the formation of biologically important molecules, is fundamental to the study of the processes which lead to the origin, evolution and distribution of life in the Galaxy. Determining the level of molecular complexity attainable in the clouds, and the nature of the complex organic material available to protostellar disks and the planetary systems that form from them, requires an understanding of the possible chemical pathways and is therefore a central question in astrochemistry. We have thus searched for prebiologically important molecules in the hot molecular cloud cores: Sgr B2(N-LMH), W51 e1/e2 and Orion-KL. Among the molecules searched: Pyrimidine is the unsubstituted ring analogue for three of the DNA and RNA bases. 2H-Azirine and Aziridine are azaheterocyclic compounds. And Glycine is the simplest amino acid. Detections of these interstellar organic molecular species will thus have important implications for Astrobiology. Our preliminary results indicate a tentative detection of interstellar glycine. If confirmed, this will be the first detection of an amino acid in interstellar space and will greatly strengthen the thesis that interstellar organic molecules could have played a pivotal role in the prebiotic chemistry of the early Earth.
The CMP challenges for advanced technology nodes are discussed. Global and local uniformity challenges and their cumulative effects are presented. Uniformity improvements for advanced node integration were achieved through slurry, pad and platen optimization, innovative integration schemes, the reduction of incoming variation and the reduction of cumulative effects. We discuss reduction of typical CMP defect types. Defects resulting from simple mechanisms (foreign material, polish residues) and those resulting from chemical and physical interactions (corrosion, chemical attack, scratches, physical migration) and strategies for control are studied. Defectivity reduction measures include new post-CMP clean chemicals, new slurries and pads and reduction of incoming defectivity. Finally we discuss an observed tradeoff between good defectivity and good uniformity.
There are two marine species in the genus Ozobranchus. Ozobranchus branchiatus mainly parasitizes green turtles and O. margoi parasitizes most turtle species. We used sequences for the mitochondrial cytochrome c oxidase subunit I gene (COI sequence analysis), along with morphological diagnosis, to compare the population genetic structures of O. branchiatus and O. margoi collected near Taiwan to those of their populations in the Atlantic. The results provide estimates of the genetic divergence between these leeches in the two regions. Ozobranchus branchiatus had a greater pairwise distance within Taiwan (0.0031–0.0141) than O. margoi (no differences). Phylogenetic tree analysis identified one O. branchiatus clade and one O. margoi clade in Taiwan. The better environmental adaptability and lower host specificity of O. margoi might result in lower genetic divergence among populations.
Repeat aerial photography is used to obtain closely spaced measurements of velocity and elevation over a complete transect of Ice Stream tributary B2, including the shear margins, the fast ice of the ice stream and several unusual features, as well as the UpB camp. Persistent features, mainly crevasses, are tracked to provide 1541 values of velocity and 1933 values of elevation. These are used to describe ice flow in the ice stream. Within the ice stream, the dominant velocity gradient is lateral shear. Crevasse patterns are studied in relation to measured velocity gradients. Crevasses intersect one another at acute angles, indicating that their origin is deeper than the depth to which crevasses penetrate. One feature within the ice stream seems to be a raft of stiff ice. Others are crevasse trains. Also, there are spreading ridges, perhaps due to upwelling ice. There is no evidence of large sticky spots within the studied transect, i.e. no steep surface slopes with associated surface stretching just up-glacier and surface compression down-glacier.
Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental disorder, yet the search for definite genetic etiologies remains elusive. Delineating ASD endophenotypes can boost the statistical power to identify the genetic etiologies and pathophysiology of ASD. We aimed to test for endophenotypes of neuroanatomy and associated intrinsic functional connectivity (iFC) via contrasting male youth with ASD, their unaffected brothers and typically developing (TD) males.
The 94 participants (aged 9–19 years) – 20 male youth with ASD, 20 unaffected brothers and 54 TD males – received clinical assessments, and undertook structural and resting-state functional magnetic resonance imaging scans. Voxel-based morphometry was performed to obtain regional gray and white matter volumes. A seed-based approach, with seeds defined by the regions demonstrating atypical neuroanatomy shared by youth with ASD and unaffected brothers, was implemented to derive iFC. General linear models were used to compare brain structures and iFC among the three groups. Assessment of familiality was investigated by permutation tests for variance of the within-family pair difference.
We found that atypical gray matter volume in the mid-cingulate cortex was shared between male youth with ASD and their unaffected brothers as compared with TD males. Moreover, reduced iFC between the mid-cingulate cortex and the right inferior frontal gyrus, and increased iFC between the mid-cingulate cortex and bilateral middle occipital gyrus were the shared features of male ASD youth and unaffected brothers.
Atypical neuroanatomy and iFC surrounding the mid-cingulate cortex may be a potential endophenotypic marker for ASD in males.
Methylphenidate and atomoxetine are commonly prescribed for treating attention deficit hyperactivity disorder (ADHD). However, their therapeutic neural mechanisms remain unclear.
After baseline evaluation including cognitive testing of the Cambridge Neuropsychological Test Automated Battery (CANTAB), drug-naive children with ADHD (n = 46), aged 7–17 years, were randomly assigned to a 12-week treatment with methylphenidate (n = 22) or atomoxetine (n = 24). Intrinsic brain activity, including the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), was quantified via resting-state functional magnetic resonance imaging at baseline and week 12.
Reductions in inattentive symptoms were related to increased fALFF in the left superior temporal gyrus and left inferior parietal lobule for ADHD children treated with methylphenidate, and in the left lingual gyrus and left inferior occipital gyrus for ADHD children treated with atomoxetine. Hyperactivity/impulsivity symptom reductions were differentially related to increased fALFF in the methylphenidate group and to decreased fALFF in the atomoxetine group in bilateral precentral and postcentral gyri. Prediction analyses in the atomoxetine group revealed negative correlations between pre-treatment CANTAB simple reaction time and fALFF change in the left lingual gyrus and left inferior occipital gyrus, and positive correlations between pre-treatment CANTAB simple movement time and fALFF change in bilateral precentral and postcentral gyri and left precuneus, with a negative correlation between movement time and the fALFF change in the left lingual gyrus and the inferior occipital gyrus.
Our findings suggest differential neurophysiological mechanisms for the treatment effects of methylphenidate and atomoxetine in children with ADHD.
The collision between aqueous drops in air typically leads to coalescence after impact. Rebounding of the droplets with similar sizes at atmospheric conditions is not generated, unless with significantly large pressure or high impact parameters exhibiting near-grazing collision. Here we demonstrate experimentally the creation of a non-coalescent regime through addition of a small amount of water-soluble surfactant. We perform a direct simulation to account for the continuum and short-range flow dynamics of the approaching interfaces, as affected by the soluble surfactant. Based on the immersed-boundary formulation, a conservative scheme is developed for solving the coupled surface-bulk convection–diffusion concentration equations, which presents excellent mass preservation in the solvent as well as conservation of total surfactant mass. We show that the Marangoni effect, caused by non-uniform distributions of surfactant on the droplet surface and surface tension, induces stresses that oppose the draining of gas in the interstitial gap, and hence prohibits merging of the interfaces. In such gas–liquid systems, the repulsion caused by the addition of surfactant, as frequently observed in liquid–liquid systems such as emulsions in the form of an electric double-layer force, was found to be too weak to dominate in the attainable range of interfacial separation distances. These results thus identify the key mechanisms governing the impact dynamics of surfactant-coated droplets in air and imply the potential of using a small amount of surfactant to manipulate impact outcomes, for example, to prevent coalescence between droplets or interfaces in gases.
The relationship between white-matter tracts and executive functions (EF) in attention deficit hyperactivity disorder (ADHD) has not been well studied and previous studies mainly focused on frontostriatal (FS) tracts. The authors explored the microstructural property of several fibre tracts hypothesized to be involved in EF, to correlate their microstructural property with EF, and to explore whether such associations differ between ADHD and typically developing (TD) youths.
We assessed 45 youths with ADHD and 45 individually matched TD youths with a computerized test battery for multiple dimensions of EF. From magnetic resonance imaging, FS tract, superior longitudinal fasciculus (SLF), arcuate fasciculus (AF) and cingulum bundle (CB) were reconstructed by diffusion spectrum imaging tractography. The generalized fractional anisotropy (GFA) values of white-matter tracts were computed to present microstructural property of each tract.
We found lower GFA in the left FS tract, left SLF, left AF and right CB, and poorer performance in set-shifting, sustained attention, cognitive inhibition and visuospatial planning in ADHD than TD. The ADHD and TD groups demonstrated different association patterns between EF and fibre tract microstructural property. Most of the EF were associated with microstructural integrity of the FS tract and CB in TD youths, while with that of the FS tract, SLF and AF in youths with ADHD.
Our findings support that the SLF, AF and CB also involve in a wide range of EF and that the main fibre tracts involved in EF are different in youths with ADHD.
Vancomycin-resistant enterococci (VRE) infections are a public health threat associated with increased patient mortality and healthcare costs. Antibiotic usage, particularly cephalosporins, has been associated with VRE colonization and VRE bloodstream infections (VRE BSI). We examined the relationship between antimicrobial usage and incident VRE colonization at the individual patient level. Prospective, weekly surveillance was undertaken for incident VRE colonization defined by negative admission but positive surveillance swab in a medical intensive care unit over a 17-month period. Antimicrobial exposure was quantified as days of therapy (DOT)/1000 patient-days. Multiple logistic regression was used to analyse incident VRE colonization and antibiotic DOT, controlling for demographic and clinical covariates. Ninety-six percent (1398/1454) of admissions were swabbed within 24 h of intensive care unit (ICU) arrival and of the 380 patients in the ICU long enough for weekly surveillance, 83 (22%) developed incident VRE colonization. Incident colonization was associated in bivariate analysis with male gender, more previous hospital admissions, longer previous hospital stay, and use of cefepime/ceftazidime, fluconazole, azithromycin, and metronidazole (P < 0·05). After controlling for demographic and clinical covariates, metronidazole was the only antibiotic independently associated with incident VRE colonization (odds ratio 2·0, 95% confidence interval 1·2–3·3, P < 0·009). Our findings suggest that risk of incident VRE colonization differs between individual antibiotic agents and support the possibility that antimicrobial stewardship may impact VRE colonization and infection.
Desorption of gold ions from liver tissue sections, in which intravenously injected gold nanorods were accumulated, were studied to evaluate properties of gold nanorods as a "mass-tag". Gold ions were sensitively detected by using a conventional MALDI-MS machine. When 50-µm-thick blank sections without gold nanorods were placed on or beneath a sample section, desorption of gold ions was almost suppressed. It was found that the escape depth of gold ions from liver tissue sections was less than 50 µm. It was found that we do not have to take account of the escape depth of gold ions if a section were sliced into 10-20 µm thickness.
The synthesis of biocompatible noble metal nanoparticles dispersible in a wide range of biological media with control of polycrystalinity and nanogeometry, pH sensitivity and salt tolerance has been a challenging requirements. The role of 3-aminopropyltrimethoxysilane (3-APTMS) and organic reducing reagents for real time synthesis of amphilic noble metal nanoparticles meeting these requirements are demonstrated justifying the following; (1) 3-APTMS capped noble metal ions are converted into respective metal nanoparticles in the presence of one of organic reducing agents i.e., cyclohexanone, tetrahydrofuran hydroperoxide (THF-HPO), formaldehyde, acetaldehyde, acetone, t-buty dimethyl keotone, 3-Glycidoxy-propyltrimethoxysilane (3-GPTMS); (2) 3-APTMS acts as micelle, promotes the interaction of metal ions with organic reducing agent, precisely controls the size of metal nanoparticles, pH sensititvity and salt tolerance and also provides a suitable medium for nanoparticles suspension, (3) the use of suitable organic reagent precisely controls the polarity of as made noble metal nanoparticles allowing specific biological interactions, and (4) 3-APTMS significantly increases the stability and controls the pH sensitivity and salt tolerance of metal nanoparticles. The as synthesized nanomaterials show potential viability in biomedical applications from many angles i.e. (a) as potential bioelectrocatalyst, (b) selective interaction with active proteins and cellular components, and (c) peroxidase mimetic.
Computed tomography (CT) is an important tool in clinical diagnostic imaging enabling three-dimensional anatomic imaging at high spatial resolution with short scan times. However, X-ray attenuation differences in physiological fluids and soft tissues are relatively small, requiring the use of contrast agents to achieve sufficient imaging contrast. Recent advances in energy-sensitive X-ray detectors have made spectral (color) CT commercially feasible by unmixing the energy-dependent attenuation profile of different materials and will potentially enable molecular imaging in CT. In order to leverage these capabilities for diagnostic imaging, we are developing a spectral library of nanoparticle contrast agents with K-shell absorption edges spaced at least 10 keV apart. The objective of this study was to demonstrate the ability of spectral CT to simultaneously detect up to three different contrast agents and unmixed their signals to create color images. Gadolinium oxide (Gd), hafnium oxide (Hf) and gold (Au) were chosen due to exhibiting K-edges spaced 10-20 keV apart. Core-shell nanoparticles of each composition were synthesized by various methods to have a core diameter of 15-20 nm and were coated with a silica shell at least 2-4 nm in thickness to create a common platform for surface functionalization. The contrast agents were imaged in a soft tissue equivalent phantom using source-side method for spectral CT imaging. The source-side approach utilized monochromatic synchrotron radiation at the Argonne National Laboratory which, while not clinically applicable, served as a gold standard due to providing the highest spectral resolution. The nanoparticles designed for this study have broad applications in biomedical imaging due to their modular assembly, potential for enabling multi-modal detection, and surface functionalization with biomolecules (e.g., antibodies, peptides or enzymes) for active targeting.
Deficits in executive function (EF), impaired school functioning and altered white matter integrity in frontostriatal networks have been associated with attention-deficit/hyperactivity disorder (ADHD). However, relationships between impairments in these areas are unclear. Using a sample of youths with and without ADHD, this study examined the association between microstructural integrity of frontostriatal tracts and school dysfunction and the mediating roles of EF and ADHD symptoms in this association.
The sample included 32 Taiwanese youths with ADHD and 32 age-, sex-, handedness- and IQ-matched typically-developing (TD) youths. Participants were assessed using psychiatric interviews, parent reports on ADHD symptoms and school functioning, and EF measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The frontostriatal tracts were reconstructed by diffusion spectrum imaging (DSI) tractography and were subdivided into four functionally distinct segments: caudate–dorsolateral, caudate–medial prefrontal, caudate–orbitofrontal and caudate–ventrolateral tracts.
Youths with ADHD, relative to TD youths, showed altered white matter integrity in all four bilateral pairs of frontostriatal tracts (decreased general fractional anisotropy, GFA), had poor attention, vigilance and response inhibition, and showed impaired school functioning. Altered microstructural integrity in frontostriatal tracts was significantly associated with school dysfunction, which was mediated by EF measures of attention/vigilance and response inhibition in addition to inattention and hyperactivity symptoms.
Our findings demonstrate an association between white matter integrity in the frontostriatal networks and school functioning and suggest that EF deficits and ADHD symptoms may be the mediating mechanisms for this association. Future research is needed to test the directionality and specificity of this finding.
An exact analysis of deformation and stress field in a laminated elastic tube under extension and uniform pressuring is presented. The problem of finite laminated tube is considered with emphasis on the end effect. The problem is formulated on the basis of the state space formalism for axisymmetric deformation of transversely isotropic layer. The transfer matrix transmits the state vector in radial direction from inner surface to outer surface and takes into account the interfacial continuity and lateral boundary conditions in a rigorous manner. Upon delineating the symplectic orthogonality relations of the eigenvectors and by using eigenfunction expansion, an exact solution which satisfies the end conditions is determined. The results show that the end effect is significant but confined to a local region near the base where the displacement and stress distributions are remarkably different from those according to the simplified solutions that only satisfy lateral BC.
In this paper, a novel set of macros with line/space width from 128nm/128nm, 64nm/64nm to 32nm/32nm was designed and installed on 20nm technology-node hardware. The pitch-dependent pad erosion post Cu CMP was studied by atomic-force microscopy (AFM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) quantitatively on these macros. Two methods were investigated to reduce the difference between pitch- and density-induced CMP non-uniformity. The first is using new scheme of partial Cu plating process followed by SiCNH insulator deposition and then CMP. The second is through the selection of slurries and pads. Both results are discussed in this paper.
Increased intra-individual variability (IIV) in reaction time (RT) across various tasks is one ubiquitous neuropsychological finding in attention deficit hyperactivity disorder (ADHD). However, neurobiological underpinnings of IIV in individuals with ADHD have not yet been fully delineated. The ex-Gaussian distribution has been proved to capture IIV in RT. The authors explored the three parameters [μ (mu), σ (sigma), τ (tau)] of an ex-Gaussian RT distribution derived from the Conners' continuous performance test (CCPT) and their correlations with the microstructural integrity of the frontostriatal–caudate tracts and the cingulum bundles.
We assessed 28 youths with ADHD (8–17 years; 25 males) and 28 age-, sex-, IQ- and handedness-matched typically developing (TD) youths using the CCPT, Wechsler Intelligence Scale for Children, 3rd edition and magnetic resonance imaging (MRI). Microstructural integrity, indexed by generalized fractional anisotropy (GFA), was measured by diffusion spectrum imaging tractrography on a 3-T MRI system.
Youths with ADHD had larger σ (s.d. of Gaussian distribution) and τ (mean of exponential distribution) and reduced GFA in four bilateral frontostriatal tracts. With increased inter-stimulus intervals of CCPT, the magnitude of greater τ in ADHD than TD increased. In ADHD youths, the cingulum bundles and frontostriatal integrity were associated with three ex-Gaussian parameters and with μ (mean of Gaussian distribution) and τ, respectively; while only frontostriatal GFA was associated with μ and τ in TD youths.
Our findings suggest the crucial role of the integrity of the cingulum bundles in accounting for IIV in ADHD. Involvement of different brain systems in mediating IIV may relate to a distinctive pathophysiological processing and/or adaptive compensatory mechanism.
It is difficult to obtain the derivative values from most mesh dependent numerical procedures in general. This study proposes an efficient computational tool to accurately evaluate the multi-order derivatives by the radial basis functions and local differential quadrature (LRBF-DQ) algorithm. Most of the traditional derivative calculations can be only adopted to evaluate the differential values with the regular meshes. Moreover, the traditional numerical schemes are very restricted by the order of the shape functions. The present technique can be applied to both the structured and unstructured meshes as well as meshless numerical algorithms – such as RBFs and LDQ method. In addition, the proposed model can be also used to estimate multi-order or mixed partial derivative values because its test function using RBFs is a multi-order differentiable function. All of the evaluation of derivative results will be compared with the exact solutions and other numerical techniques. Consequently, this study provides an effective algorithm of post process to accurately calculate the multi-order derivative values for any numerical schemes.
Attention deficit hyperactivity disorder (ADHD) is recognized as an early-onset neuropsychiatric disorder with executive dysfunctions and neurobiological deficits. The authors compared executive functions and microstructural integrity of the frontostriatal circuit in children with ADHD and typically developing children.
We assessed 25 children with ADHD and 25 age-, sex-, handedness- and intelligence-matched typically developing children by using psychiatric interviews, the Wechsler Intelligence Scale for Children – third edition, and the tasks involving executive functions in the Cambridge Neuropsychological Test Automated Battery. The frontostriatal tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into four functionally distinct segments, including dorsolateral, medial prefrontal, orbitofrontal and ventrolateral tracts. Tract-specific and matched case-control analyses were used and generalized fractional anisotropy values were computed.
Children with ADHD had lower generalized fractional anisotropy of all the bilateral frontostriatal fiber tracts and poorer performance in verbal and spatial working memory, set-shifting, sustained attention, cognitive inhibition and visuospatial planning. The symptom severity of ADHD and the executive functioning performance significantly correlated with integrity of the frontostriatal tracts, particularly the left orbitofrontal and ventrolateral tracts. Children with ADHD also demonstrated loss of the leftward asymmetry in the dorsolateral and medial prefrontal tracts that was present in typically developing children.
Our findings demonstrate disturbed structural connectivity of the frontostriatal circuitry in children with ADHD and add new evidence of associations between integrity of the frontostriatal tracts and measures of core symptoms of ADHD and a wide range of executive dysfunctions in both groups.