Assessment of dynamic susceptibility contrast cerebral blood flow response to amphetamine challenge: A human pharmacological magnetic resonance imaging study at 1.5 and 4 T

Pharmacological MRI (phMRI) techniques can be used to monitor the neurophysiological effects of central nervous system (CNS) active drugs. In this study, we investigated whether dynamic susceptibility contrast (DSC) perfusion imaging employing the use of superparamagnetic iron oxide nanoparticles (Resovist) could be used to measure hemodynamic response to d-amphetamine challenge in human subjects at both 1.5 and 4 T. Significant changes in cerebral blood flow (CBF) were found in focal regions associated with the nigrostriatal circuit and mesolimbic and mesocortical dopaminergic pathways. More significant CBF responses were found at higher field strength, mainly within striatal structures. The results from this study indicate that DSC perfusion imaging using Resovist can be used to assess the efficacy of CNS-active drugs and may play a role in the development of novel psychiatric therapies at the preclinical level. �� 2005 Wiley-Liss, Inc.

VFT performance of a 180/110 mm co-axial gap in SF6 up to 4 bar absolute

Disconnector switch operation in GIS generates VFT voltages in the system. It is important, for insulation co-ordination purposes, to obtain accurate VFT V-t data for typical gap geometries found in GIS. This paper presents experimentally obtained VFT V-t data for a 180/1 lOmm co-axial gap. The VFT has a time to first peak of 35 ns and a oscillation frequency of 13,6 MHz. Due to the location of the voltage divider in a compartment adjacent to the gap, a correction factor of 1.1 is used to relate the measured breakdown voltage to that in the gap. Positive polarity VFT V-t data is presented for 1, 2, 3 and 4 bar absolute and negative polarity VFT data for 3 and 4 bar absolute. Two methods of generating the VFT's are used. The first is to power up the test transformer at power frequency. The second is to generate a switching impulse by discharging a capacitor into the primary of the test transformer.

On the growth process of Cu2ZnSn(S,Se)4 absorber layer formed by selenizing Cu���ZnS���SnS precursors and its photovoltaic performance

Sputtering and subsequent sulfurization(orselenization)is one of the methods that have been extensively employed to fabricate Cu2ZnSn(S,Se)4 (CZTSSe) thin films. However, there are limited reports on the effect of precursor stacking order of the sputtered source materials on the properties of the synthesized CZTSSe films. In this work,the morphology and crystallization process of the CZTSSe films which were prepared by selenizing Cu���ZnS���SnS precursor layers with different stacking sequences and the adhesion property between the as-synthesized CZTSSe layer and Mosubstrate have been thoroughly investigated. It has been found that the growth of CZTSSe material and the morphology of the film strongly depend on the location of Culayer in the precursor film. The formation of CZTSSe starts from the diffusion of Cu���Se to Sn(S,Se)layert o form Cu���Sn���(S,Se) compound,followed by the reaction with Zn(S,Se). The investigation of themorphology of the CZTSSe films has shown that large grains are formed in the film with the precursor stacking order of Mo/SnS/ZnS/Cu,which is attributed to a bottom-to-top growth mechanism. In contrast, the film made from a precursor with a stacking sequence of Mo/ZnS/ SnS/Cu is mainly consisted of small grains due to a top-to-bottom growth mechanism. The best CZTSSe solar cell with energy conversion efficiency of3.35%has been achieved with the selenized Mo/ZnS/ SnS/Cu film, which is attributed to a good contact between the absorber layer and the Mosubstrate.

Crystal structure of poly[[di-mu2-aqua-aquasodium] 4-amino-3,5,6-trichloropyridine-2-carboxylate trihydrate], the sodium salt of the herbicide picloram

In the structure of the title complex [[Na(H2O)3]+ (C6H2Cl3N2O2)-^ . 3(H2O)]n, the Na salt of the herbicide picloram, the cation is a polymeric chain structure, based on doubly water-bridged NaO5 trigonal bipyramidal complex units which have in addition, a singly-bonded monodentate water molecule. Each of the bridges within the chain which lies along the a cell direction is centrosymmetric with Na...Na separations of 3.4807(16) and 3.5109(16)Ang. In the crystal, there are three water molecules of solvation and these, as well as the coordinated water molecules and the amino group of the 4-amino-3,5,6-trichloropicolinate anion are involved in extensive inter-species hydrogen-bonding interactions with carboxyl and water O-atoms as well as the pyridine N-atom. Among these association is a centrosymmetric cyclic tetra-water R4/4(8) ring , resulting in an overall three-dimensional structure.

Association of sporadic chondrocalcinosis with a -4-basepair G-to-A transition in the 5���-untranslated region of ANKH that promotes enhanced expression of ANKH protein and excess generation of extracellular inorganic pyrophosphate

Objective Certain mutations in ANKH, which encodes a multiple-pass transmembrane protein that regulates inorganic pyrophosphate (PPi) transport, are linked to autosomal-dominant familial chondrocalcinosis. This study investigated the potential for ANKH sequence variants to promote sporadic chondrocalcinosis. Methods ANKH variants identified by genomic sequencing were screened for association with chondrocalcinosis in 128 patients with severe sporadic chondrocalcinosis or pseudogout and in ethnically matched healthy controls. The effects of specific variants on expression of common markers were evaluated by in vitro transcription/translation. The function of these variants was studied in transfected human immortalized CH-8 articular chondrocytes. Results Sporadic chondrocalcinosis was associated with a G-to-A transition in the ANKH 5���-untranslated region (5���-UTR) at 4 bp upstream of the start codon (in homozygotes of the minor allele, genotype relative risk 6.0, P = 0.0006; overall genotype association P = 0.02). This -4-bp transition, as well as 2 mutations previously linked with familial and sporadic chondrocalcinosis (+14 bp C-to-T and C-terminal GAG deletion, respectively), but not the French familial chondrocalcinosis kindred 143-bp T-to-C mutation, increased reticulocyte ANKH transcription/ANKH translation in vitro. Transfection of complementary DNA for both the wild-type ANKH and the -4-bp ANKH protein variant promoted increased extracellular PPi in CH-8 cells, but unexpectedly, these ANKH mutants had divergent effects on the expression of extracellular PPi and the chondrocyte hypertrophy marker, type X collagen. Conclusion A subset of sporadic chondrocalcinosis appears to be heritable via a -4-bp G-to-A ANKH 5���-UTR transition that up-regulates expression of ANKH and extracellular PPi in chondrocyte cells. Distinct ANKH mutations associated with heritable chondrocalcinosis may promote disease by divergent effects on extracellular PPi and chondrocyte hypertrophy, which is likely to mediate differences in the clinical phenotypes and severity of the disease.

Confronting expectation in grade 4: Tossing two coins

This study focuses on the experiences of 91 Grade 4 students who had been introduced to expectation and variation through trials of tossing a single coin many times. They were then given two coins to toss simultaneously and asked to state their expectation of the chances for the possible outcomes, in a similar manner expressed for a single coin. This paper documents the journey of the students in discovering that generally their initial expectation for two coins was incorrect and that despite variation, a large number of tosses could confirm a new expectation.

The three-dimensional hydrogen-bonded structures in the ammonium and sodium salt hydrates of 4-aminophenylarsonic acid

The structures of two hydrated salts of 4-aminophenylarsonic acid (p-arsanilic acid), namely ammonium 4-aminophenylarsonate monohydrate, NH4(+)��C6H7AsNO3(-)��H2O, (I), and the one-dimensional coordination polymer catena-poly[[(4-aminophenylarsonato-��O)diaquasodium]-��-aqua], [Na(C6H7AsNO3)(H2O)3]n, (II), have been determined. In the structure of the ammonium salt, (I), the ammonium cations, arsonate anions and water molecules interact through inter-species N-H...O and arsonate and water O-H...O hydrogen bonds, giving the common two-dimensional layers lying parallel to (010). These layers are extended into three dimensions through bridging hydrogen-bonding interactions involving the para-amine group acting both as a donor and an acceptor. In the structure of the sodium salt, (II), the Na(+) cation is coordinated by five O-atom donors, one from a single monodentate arsonate ligand, two from monodentate water molecules and two from bridging water molecules, giving a very distorted square-pyramidal coordination environment. The water bridges generate one-dimensional chains extending along c and extensive interchain O-H...O and N-H...O hydrogen-bonding interactions link these chains, giving an overall three-dimensional structure. The two structures reported here are the first reported examples of salts of p-arsanilic acid.

Clinical pathways for chronic cough in children

Background Chronic cough (a cough lasting longer than four weeks) is a common problem internationally. Chronic cough has associated economic costs and is distressing to the child and to parents; ignoring cough may lead to delayed diagnosis and progression of serious underlying respiratory disease. Clinical guidelines have been shown to lead to ef���cient and effective patient care and can facilitate clinical decision making. Cough guidelines have been designed to facilitate the management of chronic cough. However, treatment recommendations vary, and speci���c clinical pathways for the treatment of chronic cough in children are important, as causes of and treatments for cough vary signi���cantly from those in adults. Therefore, systematic evaluation of the use of evidence-based clinical pathways for the management of chronic cough in children would be bene���cial for clinical practice and for patient care. Use of a management algorithm can improve clinical outcomes; such management guidelines can be found in the guidelines for cough provided by the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS). Objectives To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. Search methods The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of re levant articles were searched. The latest search was conducted in January 2014. Selection criteria All randomised controlled trials of parallel-group design comparing use versus non-use of a clinical pathway for treatment of chronic cough in children (< 18 years of age). Data collection and analysis Results of searches were reviewed against predetermined cr iteria for inclusion. Two review authors independently selected studies and performed data extraction in duplicate. Main results One study was included in the review. This multi-centre trial was based in ���ve Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six wee ks post randomisation (de���ned as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was signi���cantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% con���dence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for e very ���ve children treated via th e cough pathway (number needed to treat for an additional bene���cial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-speci���c parent-reported quality of life scores were signi���cantly better in th e early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was signi���cantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Authors��� conclusions. Current evidence suggests that using a clinical algorithm for the management of children with ch r onic cough in h ospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

Association of a disintegrin and metalloprotease 33 (ADAM33) gene polymorphisms with the risk of COPD: An updated meta-analysis of 2,644 cases and 4,804 controls

A series of observational studies have been made to investigate the association of the ADAM33 gene polymorphisms with the risk of COPD, but their results were conflicting. Therefore, we performed an updated meta-analysis to quantitatively summarize the associations of ADAM33 gene polymorphisms with the risk of COPD. Thirteen case���control studies referring to nine SNPs were identified: V4 (rs2787094), T+1 (rs2280089), T2 (rs2280090), T1 (rs2280091), S2 (rs528557), S1 (rs3918396), Q���1 (rs612709), F+1 (rs511898) and ST+5 (rs597980). A dominant model (AA+Aa vs. aa), recessive model (AA vs. Aa+aa), additive model (AA vs. aa) and allelic model (A vs. a) were used to evaluate the association of ADAM33 polymorphism with the risk of COPD. The results indicated that significant associations were found for ADAM33 T1, T2, S1, Q���1, F+1 and ST+5 polymorphisms associated with the risk of COPD in different populations. However, no significant associations were found for V4, T+1 and S2 polymorphisms with the risk of COPD in all genetic models, even in the subgroup analysis by ethnicity. This meta-analysis provided evidence that the ADAM33 T1, T2, S1, Q���1, F+1 and ST+5 six locus polymorphisms association with the risk of COPD. Furthermore, T2, Q���1 and ST+5 indicated an association with the risk of COPD in the European populations, whereas T1, T2, S1, F+1 and Q���1 indicated an association with the risk of COPD in the Asian populations.

Toll-like receptor 4 and CD14 polymorphisms in ankylosing spondylitis: Evidence of a weak association in finns

Objective To investigate the association of CD14 and Toll-like receptor (TLR4) with ankylosing spondylitis (AS). Methods A promoter variant in CD14 and 2 coding polymorphisms in TLR4 were investigated in UK and Finnish families with AS and in a UK case-control study. A metaanalysis of published TLR4 and CD14 studies was performed. Results In the Finnish study the CD74-260bp T variant showed an association (p = 0.006), and the common 2-marker TLR4 haplotype showed a weak association (global p = 0.03), with AS. No associations were seen in the UK based studies or in the metaanalyses. Conclusion CD14 and TLR4 showed an association with AS in the Finns only.

Effect of an estrogen receptor-�� intron 4 polymorphism on fat mass in 11-year-old children

Context: in the ESR1 gene encoding estrogen receptor (ER)-�� may be associated with fat mass in adults. Objectives: The objective of the study was to establish whether ESR1 polymorphisms influence fat mass in childhood. Design: This was a cross-sectional analysis after genotyping of rs9340799, rs2234693, and rs7757956 ESR1 polymorphisms. Setting: The Avon Longitudinal Study of Parents and Children (ALSPAC) was a population-based prospective study. Participants: Participants included 3097 11-yr-old children with results for ESR1 genotyping, puberty measures, and dual-energy x-ray absorptiometry results. Outcomes: Relationships between ESR1 polymorphisms and indices of body composition were measured. Results: The rs7757956 polymorphism was associated with fat mass (P = 0.002). Total body fat mass (adjusted for height) was reduced by 6% in children with TA/AA genotypes, and risk of being overweight (���85th centile of fat mass) was decreased by 20%. This genetic effect appeared to interact with puberty in girls (P = 0.05 for interaction): in those with the TT genotype, total body fat mass (adjusted for height) was 18% higher in Tanner stages 3-5 vs. stages 1-2; the equivalent difference was 7% in those with TA/AA genotypes. Furthermore, the risk of being overweight was 36% lower in girls with TA/AA genotypes in Tanner stages 3-5, but no reduction was seen in those in stages 1-2. Neither rs9340799 nor rs2234693 polymorphisms were associated with body composition measures. Conclusions: Fat mass in 11-yr-old children was related to the rs7757956 ESR1 polymorphism. This association was strongest in girls in more advanced puberty, in whom the risk of being overweight was reduced by 36% in those with the TA/AA genotype.

Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with susceptibility to rheumatoid arthritis in British Caucasians

The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.

Crystal structure of morpholin-4-ium cinnamate

In the anhydrous salt formed from the reaction of morpholine with cinnamic acid, C4H10NO+ C9H7O2-, the acid side chain in the trans-cinnamate anion is significantly rotated out of the benzene plane [C-C-C-C torsion angle = 158.54(17)deg. In the crystal, one of the the aminium H atoms is involved in a asymmetric three-centre cation-anion N-H...(O,O') R2/1(4) hydrogen-bonding interaction with the two carboxyl O-atom acceptors of the anion. The second aminium H atom forms an inter-species N-H...O(carboxyl) hydrogen bond, generating a one-dimensional chain structure extending along [100]. Chains are linked by C-H...O interactions forming a supramolecular layer parallel to (01-1).

Determination of refractive and volatile elements in sediment using laser ablation inductively coupled plasma mass spectrometry

Wet-milling protocol was employed to produce pressed powder tablets with excellent cohesion and homogeneity suitable for laser ablation (LA) analysis of volatile and refractive elements in sediment. The influence of sample preparation on analytical performance was also investigated, including sample homogeneity, accuracy and limit of detection. Milling in volatile solvent for 40 min ensured sample is well mixed and could reasonably recover both volatile (Hg) and refractive (Zr) elements. With the exception of Cr (���52%) and Nb (+26%) major, minor and trace elements in STSD-1 and MESS-3 could be analysed within ��20% of the certified values. Comparison of the method with total digestion method using HF was tested by analysing 10 different sediment samples. The laser method recovers significantly higher amounts of analytes such as Ag, Cd, Sn and Sn than the total digestion method making it a more robust method for elements across the periodic table. LA-ICP-MS also eliminates the interferences from chemical reagents as well as the health and safety risks associated with digestion processes. Therefore, it can be considered as an enhanced method for the analysis of heterogeneous matrices such as river sediments.