bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethyl 7′-(6-benzyloxy-2,2-dimethyltetrahydrofuro[3,2-d][1,3]dioxol-5-yl)-2-oxo-5′,6′,7′,7a'-tetrahydro-1′H,2H-spiro[acenaphthylene-1,5′-pyrrolo[1,2-c][1,3]thiazole]-6′-carboxylate
Authors: Jagadeesan G. , Sethusankar K. , Prasanna R. , Raghunathan R.
Published: July 2012

In the title compound, C34H35NO7S, the acenaphthylene unit is essentially planar (r.m.s. deviation = 0.0335 Å). The pyrrolothiazole ring system is folded about the bridging N—C bond; the thiazolidine and pyrrolidine rings adopt S- and C-envelope conformations, respectively, with a `butterfly' angle between the mean planes of 51.38 (10)°. The dioxolane and tetrahydrofuran rings adopt O- and a C-envelope conformations, respectively, with a `butterfly' angle between the mean planes of 57.12 (10)°. Two C atoms are each disordered over two positions with site-occupancy factors of 0.450 (7) and 0.550 (7). The crystal packing is stabilized by C—H...O interactions, generating anR22(14) graph-set ring motif.
(3,5-Di-tert-butyl-2-ethoxybenzylidene)[2-(3,5-di-tert-butyl-1H-pyrazol-1-yl)ethyl]amine
Authors: Spencer Lara C. , Guzei Ilia A. , Ainooson Michael K. , Darkwa James
Published: July 2012

The angles within the benzene ring in the title compound, C30H49N3O, ranging from 116.34 (16) to 124.18 (16)°, reflect the presence of electron-donating and electron-withdrawing substituents. The angles at the two electron-donatingtert-butyl substituents are smaller than 120°, at the electron-withdrawing ethoxy substituent larger than 120°, and at the imine substituent equal to 119.59 (16)°. The latter does not reflect the electron-donating nature of the imine group due to the presence of other substituents.
Ethyl 1-(2-bromoethyl)-3-(4-methoxyphenyl)-1H-pyrazole-5-carboxylate
Authors: Yin Ling , Wang Yi , Wang Ying-Ying , Wang Jian-Wu
Published: July 2012

In the title compound, C15H17BrN2O3, the dihedral angle between the benzene and pyrazole rings is 5.63 (2)°. The crystal packing is stabilized by weak π–π stacking interactions [centroid–centroid distance = 3.927 (5) Å] and intermolecular C—H...O and C—H...Br hydrogen bonds.
10-(1,2,2-Trichlorovinyl)-10H-phenothiazine 5,5-dioxide
Authors: Tabata Hideyuki , Okuno Tsunehisa
Published: July 2012

The title compound, C14H8Cl3NO2S, forms a dimeric structure by intermolecular Cl...O=S interactions. The dimers make a two-dimensional array parallel to (101) by other Cl...O=S interactions. The two-dimensional network is found to be kept unchanged, although the trichlorovinyl group is disordered (relative occupancies 0.65:0.35).
Diaquabis[2,6-bis(4H-1,2,4-triazol-4-yl)pyridine-κN2]bis(selenocyanato-κN)cobalt(II)
Authors: Liu Yuan-Yuan , Yang Pan
Published: July 2012

In the title compound, [Co(NCSe)2(C9H7N7)2(H2O)2], the Co2+cation is coordinated by two selenocyanate anions, two 2,6-bis(4H-1,2,4-triazol-4-yl)pyridine ligands and two water molecules within a slightly distorted N4O2octahedron. The asymmetric unit consists of one Co2+cation, which is located on a center of inversion, as well as one selenocyanate anion, one 2,6-bis(4H-1,2,4-triazol-4-yl)pyridine ligand and one water molecule in general positions. Intermolecular O—H...N hydrogen bonds join the complex molecules into layers parallel to thebcplane. The layers are linked by C—H...N and C—H...Se hydrogen bonds into a three-dimensional supramolecular architecture.
Diaquabis(thiocyanato-κN)bis[6-(4H-1,2,4-triazol-4-yl-κN1)pyridin-2-amine]cadmium
Authors: Liu Yuan-Yuan , Yang Pan , Ding Bin
Published: July 2012

In the title compound, [Cd(NCS)2(C7H7N5)2(H2O)2], the CdIIcation lies on an inversion center and is coordinated by the N atoms of two thiocyanate anions, by N atoms of two 6-(4H-1,2,4-triazol-4-yl)pyridin-2-amine ligands and by the O atoms of two water molecules in a distorted N4O2octahedral geometry. The dihedral angle between the triazole and pyridine rings is 23.15 (12)°. In the crystal, molecules are linked by N—H...N and O—H...S hydrogen bonds. Offset π–π stacking between parallel pyridine rings of adjacent molecules is also observed, the centroid–centroid distance being 3.6319 (14) Å.
1,3-Dibenzylimidazolidine-2-thione
Authors: Mietlarek-Kropidłowska Anna , Chojnacki Jaroslaw , Becker Barbara
Published: July 2012

In the title compound, C17H18N2S, the imidazolidine ring adopts a twisted conformation. In the crystal, molecules are linked by slipped π–π interactions between the benzene rings of neighbouring molecules [centroid-to-centroid distance = 3.903 (2) Å].
Serotype‐dependent expression patterns of stabilized lipopolysaccharide aggregates in Aggregatibacter actinomycetemcomitans strains
Authors: Kikuchi Haruko , Fujise Osamu , Miura Mayumi , Tanaka Ayako , Hisano Kyoko , Haraguchi Akira , Hamachi Takafumi , Maeda Katsumasa
Published: July 2012

Above a critical concentration, amphiphilic lipopolysaccharide (LPS) molecules in an aqueous environment form aggregate structures, probably because of interactions involving hydrophobic bonds. Ionic bonds involving divalent cations stabilize these aggregate structures, making them resistant to breakdown by detergents. The aim of this study was to examine expression patterns of stabilized LPS aggregates in Aggregatibacter actinomycetemcomitans, a microorganism that causes periodontitis. A. actinomycetemcomitans strains of various serotypes and truncated LPS mutants were prepared for this study. Following treatment with a two‐phase separation system using the detergent Triton X‐114, crude LPS extracts of the study strains were separated into detergent‐phase LPS (DP‐LPS) and aqueous‐phase LPS (AP‐LPS). Repeated treatment of the aqueous phase with the two‐phase separation system produced only a slight decrease in AP‐LPS, suggesting that AP‐LPS was resistant to the detergent and thus distinguishable from DP‐LPS. The presence of divalent cations increased the yield of AP‐LPS. AP‐LPS expression patterns were serotype‐dependent; serotypes b and f showing early expression, and serotypes a and c late expression. In addition, highly truncated LPS from a waaD (rfaD) mutant were unable to generate AP‐LPS, suggesting involvement of the LPS structure in the generation of AP‐LPS. The two‐phase separation was able to distinguish two types of LPS with different physical states at the supramolecular structure level. Hence, AP‐LPS likely represents stabilized LPS aggregates, whereas DP‐LPS might be derived from non‐stabilized aggregates. Furthermore, time‐dependent expression of stabilized LPS aggregates was found to be serotype‐dependent in A. actinomycetemcomitans.
Neuropsychiatric events in varenicline and nicotine replacement patch users in the Military Health System
Authors: Meyer Tamra E. , Taylor Lockwood G. , Xie Suji , Graham David J. , Mosholder Andrew D. , Williams James R. , Moeny David , Ouellet‐Hellstrom Rita P. , Coster Trinka S.
Published: July 2012

Aim

To determine the rate ratio of neuropsychiatric hospitalizations in new users of varenicline compared to new users of nicotine replacement therapy (NRT) patch in the Military Health System (MHS).

Design, setting and participants

Varenicline (n = 19 933) and NRT patch (n = 15 867) users who initiated therapy from 1 August 2006 to 31 August 2007 within the MHS were included in this retrospective cohort study. After matching according to propensity scores, 10 814 users remained in each cohort. The study population included those with and without a history of neuropsychiatric disease.

Measurements

Patients were followed for neuropsychiatric hospitalizations defined by primary neuropsychiatric discharge diagnosis using ICD‐9 codes from in‐patient administrative claims. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated after propensity score matching on exposure for socio‐demographic factors, health‐care utilization, comorbidities, medication history and neuropsychiatric history.

Findings

There was no increase in the rate of neuropsychiatric hospitalizations in patients treated with varenicline compared to NRT patch when followed for 30 days (propensity‐score matched HR = 1.14, 95% CI: 0.56–2.34). Results were similar after 60 days of follow‐up.

Conclusions

There does not appear to be an increase in neuropsychiatric hospitalizations with varenicline compared with nicotine replacement therapy patch over 30 or 60 days after drug initiation.
Polymorphism identification in goat GNRH1 and GDF9 genes and their association analysis with litter size
Authors: An X. P. , Hou J. X. , Zhao H. B. , Li G. , Bai L. , Peng J. Y. , M Yan Q. , Song Y. X. , Wang J. G. , Cao B. Y.
Published: July 2012

This study investigated the polymorphisms of
GNRH1 and GDF9 genes in 641 goats of three breeds: Xinong Saanen, Guanzhong and Boer. Two allelic variants were identified in the GNRH1 gene (JN645280:g.3548A>G and JN645281:g.3699G>A) and one allelic variant was found in the GDF9 gene (JN655693:g.4093G>A). Furthermore, g.4093G>A was a missense mutation (p.Val397Ile of GDF9). Results of an association analysis indicated that SNPs g.3548A>G and g.4093G>A had significant effects on litter size (P < 0.05). The combination genotypes of SNPs g.3548A>G, g.3699G>A and g.4093G>A also affected litter size with the C5 genotype having the highest litter size in the first, third, fourth and average parity. Hence, the biochemical and physiological functions, together with the results obtained in our investigation, suggest that the GNRH1 and
GDF9 genes could serve as genetic markers for litter size in goat breeding.
Intrinsic factors affecting adequacy of thyroid nodule fine‐needle aspiration cytology
Authors: Grani Giorgio , Calvanese Anna , Carbotta Giovanni , D'Alessandri Mimma , Nesca Angela , Bianchini Marta , Sordo Marianna Del , Fumarola Angela
Published: July 2012

Objective

To evaluate intrinsic nodule features predictive of an inadequate report in fine‐needle aspiration cytology (FNAC).

Design

Single‐centre cross‐sectional study.

Methods

Between May 2005 and April 2011, 3279 ultrasonography‐assisted FNACs were carried out and features of nodules recorded prospectively. Univariate logistic regression analyses were performed to estimate the association between nondiagnostic cytology and variables such as age, gender, single nodule, maximum nodule diameter and estimated volume.

Results

Inadequate or nondiagnostic samples were reported in 1195 FNACs. All diameters were found to be predictors of nondiagnostic cytology; estimated nodule volume, on the other hand, was not. Nodules with a diameter <10 mm were more frequently nondiagnostic (OR 1·65, 95% CI 1·40–1·94, P < 0·001). Neither micro‐ nor macrocalcification increased the risk of inadequacy. On the contrary, mixed lesions were more frequently diagnostic (OR 0·68, 95% CI 0·85–0·80, P < 0·001). Solid nodule aspiration was performed more easily on isoechogenic nodules (OR 0·64, 95% CI 0·54–0·77, P < 0·001); the same procedure was more cumbersome on hypoechogenic lesions (OR 1·87, 95% CI 1·62–2·16, P < 0·001). Increased vascularization did not cause a significant increase in the nondiagnostic results. Blurred margins increased the inadequacy rate (OR 1·45, 95% CI 1·24–1·69, P < 0·001), while presence of a hypoechogenic halo decreased it (OR 0·67, 95% CI 0·54–0·82, P < 0·001).

Conclusions

Some ultrasonographic features suggestive of malignancy may be predictive of inadequate cytology. Patients must be notified that the FNA report may be nondiagnostic and that this represents a limitation of the technique related to the structure of lesions.
Coherent and random noise attenuation via multichannel singular spectrum analysis in the randomized domain
Authors: Chiu Stephen K.
Published: July 2012

The attenuation of coherent and random noise still poses technical challenges in seismic data processing, especially in onshore environments. Multichannel Singular Spectrum Analysis (MSSA) is an existing and effective technique for random‐noise reduction. By incorporating a randomizing operator into MSSA, this modification creates a new and powerful filtering method that can attenuate both coherent and random noise simultaneously. The key of the randomizing operator exploits the fact that primary events after NMO are relatively horizontal. The randomizing operator randomly rearranges the order of input data and reorganizes coherent noise into incoherent noise but has a minimal effect on nearly horizontal primary reflections. The randomizing process enables MSSA to suppress both coherent and random noise simultaneously. This new filter, MSSARD (MSSA in the randomized domain) also resembles a combination of eigenimage and Cadzow filters. I start with a synthetic data set to illustrate the basic concept and apply MSSARD filtering on a 3D cross‐spread data set that was severely contaminated with ground roll and scattered noise. MSSARD filtering gives superior results when compared with a conventional 3D f‐k filter. For a random‐noise example, the application of MSSARD filtering on time‐migrated offset‐vector‐tile (OVT) gathers also produces images with higher signal‐to‐noise ratios than a conventional f‐xy deconvolution filter.
A qualitative inquiry into consumer beliefs about the causes of mental illness
Authors: BAKER A. E. Z. , PROCTER N. G.
Published: July 2012

Accessible summary

People with a mental illness hold a range of beliefs about factors or situations which may cause mental illness.

Several losses are suggested as possible causes of mental illness, particularly social losses such as the death of a loved one or loss of a nurturing relationship in childhood because of abuse.

Mental health professionals should be aware of, and willing to engage in discussions about the diverse range of explanatory models for mental illness.

This paper examines consumer or service user beliefs about the causes of mental illness. It presents a qualitative, participatory action research study involving semi‐structured in‐depth interviews with 16 people who had been diagnosed with a mental illness and attended a community mental health centre in metropolitan South Australia. Inductive thematic analysis was undertaken, with a range of beliefs about the possible cause of mental illness identified. Findings are organized within two key areas: social or environmental factors and physical or biological factors. The social or environmental category included varied situations, clustered under the subcategories of: stress during childhood, events in adulthood and religious beliefs. Physical or biological factors included beliefs that mental illness was inherited, caused by brain malfunction or chemical imbalance. Of note, one‐third of consumer participants who discussed possible causes of mental illness identified multiple potential causes. Implications for service delivery, specifically related to therapeutic trust and engagement, are also considered.
Comparison of calculations to estimate gastric emptying half‐time of solids in humans
Authors: Zinsmeister A. R. , Bharucha A. E. , Camilleri M.
Published: July 2012

Background  Measuring solid gastric emptying (GE) at 4 h is used to identify gastroparesis. GE half‐time (GE T1/2) is useful to assess overall and early GE.

Aim  To examine the validity of hourly imaging as a measurement of GE T1/2 compared with estimates from more detailed imaging.

Methods  155 human subjects (99 female, 56 male) underwent scintigraphic GE of a solid–liquid meal. We calculated the GE T1/2 using linear interpolation based on a full set of abdominal images obtained over 4 h, and the GE T1/2 based on images at 1, 2, 3, and 4 h after the meal with interpolation of data.

Key Results  Differences in GE T1/2 values (entire set of scan times compared with just the hourly scans) were small [overall median (5th, 95th percentiles) = −0.2[−7.5, 4.6] min] with slightly greater differences in males compared with females. The agreement between the two methods was very high [concordance correlation coefficient (CCC) (95% CI) = 0.993 (0.990, 0.995)] and a Bland–Altman plot indicated the variation in the results between the two methods did not change appreciably across the range of GE studied (within ±10 min for all but four subjects). Calculated GE T1/2 values, omitting the 3‐h data from the hourly measurements, were associated with similar high accuracy overall and for fast GE, but were less accurate with slow GE.

Conclusions & Inferences  Results of GE T1/2 solids, using hourly imaging over 4 h, are accurate in the range 75–235 min which reflects the typical range of GE of solids in health and disease.
Across breed multi‐trait random regression genomic predictions in the Nordic Red dairy cattle
Authors: Makgahlela M.L. , Mäntysaari E.A. , Strandén I. , Koivula M. , Nielsen U.S. , Sillanpää M.J. , Juga J.
Published: July 2012

The current study evaluates reliability of genomic predictions in selection candidates using multi‐trait random regression model, which accounts for interactions between marker effects and breed of origin in the Nordic Red dairy cattle (RDC). The population structure of the RDC is admixed. Data consisted of individual animal breed proportions calculated from the full pedigree, deregressed proofs (DRP) of published estimated breeding values (EBV) for yield traits and genotypic data for 37 595 single nucleotide polymorphic markers. The analysed data included 3330 bulls in the reference population and 812 bulls that were used for validation. Direct genomic breeding values (DGV) were estimated using the model under study, which accounts for breed effects and also with GBLUP, which assume uniform population. Validation reliability was calculated as a coefficient of determination from weighted regression of DRP on DGV (), scaled by the mean reliability of DRP. Using the breed‐specific model increased the reliability of DGV by 2 and 3% for milk and protein, respectively, when compared to homogeneous population GBLUP. The exception was for fat, where there was no gain in reliability. Estimated validation reliabilities were low for milk (0.32) and protein (0.32) and slightly higher (0.42) for fat.
A retrospective survey of the ocular histopathology of the pinniped eye with emphasis on corneal disease
Authors: Miller Sarah , Colitz Carmen M. H. , St. Leger Judy , Dubielzig Richard
Published: July 2012

Objective  A retrospective review of globes from 70 pinnipeds submitted to the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) describing the type and frequency of ocular disease.

Animals studied  The study included 50 California sea lions, four animals listed only as ‘sea lion’, nine Northern elephant seals, five harbor seals, 1 Northern fur seal, and 1 Hooded seal.

Procedures  Globes were classified by microscopic findings. Categories were not mutually exclusive.

Results  The largest category was corneal disease (63 globes from 40 pinnipeds). The second largest was cataractous changes (35 globes from 23 pinnipeds). Additional ocular diseases included traumatic ocular injuries (nine globes from eight animals), phthisis bulbi (nine globes from eight pinnipeds), neoplasia (nine globes from six adult California sea lions), amyloid deposition in the corneal stroma, ciliary body, or both locations (five globes from four pinnipeds), and fungal disease (three globes from two pinnipeds). Pinnipeds with corneal disease were further categorized: stromal pathology (39 globes from 27 pinnipeds); epithelial pathology (37 globes from 27 pinnipeds); Descemet’s pathology (11 globes from eight pinnipeds); endothelial attenuation or absence (33 globes from 22 pinnipeds); presence of retrocorneal membranes (15 globes from 10 pinnipeds); anterior synechia (eight globes from six animals), and keratitis (seven globes from five pinnipeds).

Conclusions  This is the first report of ocular amyloid in pinniped eyes. All cases of neoplasia were in a pattern suggesting metastatic disease. In this study, there was a higher prevalence of ocular disease in captive pinnipeds, particularly in the posterior cornea.
Long‐term effects of the Diabetes Prevention Program interventions on cardiovascular risk factors: a report from the DPP Outcomes Study
Authors:   The Diabetes Prevention Program Outcomes Study Research Group; prepared on behalf of the DPPOS Research Group, Orchard T. J. , Temprosa M. , Barrett‐Connor E. , Fowler S. E. , Goldberg R. B. , Mather K. J. , Marcovina S. M. , Montez M. , Ratner R. E. , Saudek C. D. , Sherif H. , Watson K. E.
Published: July 2012

Diabet. Med. 30, 46–55 (2013)

Aims  Whether long‐term cardiovascular risk is reduced by the Diabetes Prevention Program interventions is unknown. The aim of this study was to determine the long‐term differences in cardiovascular disease risk factors and the use of lipid and blood pressure medications by the original Diabetes Prevention Program intervention group.

Methods  This long‐term follow‐up (median 10 years, interquartile range 9.0–10.5) of the three‐arm Diabetes Prevention Program randomized controlled clinical trial (metformin, intensive lifestyle and placebo), performed on 2766 (88%) of the Diabetes Prevention Program participants (who originally had impaired glucose tolerance), comprised a mean of 3.2 years of randomized treatment, approximately 1‐year transition (during which all participants were offered intensive lifestyle intervention) and 5 years follow‐up (Diabetes Prevention Program Outcomes Study). During the study, participants were followed in their original groups with their clinical care being provided by practitioners outside the research setting. The study determined lipoprotein profiles and blood pressure and medication use annually.

Results  After 10 years’ follow‐up from Diabetes Prevention Program baseline, major reductions were seen for systolic (−2 to −3) and diastolic (−6 to −6.5 mmHg) blood pressure, and for LDL cholesterol (−0.51 to −0.6 mmol/l) and triglycerides (−0.23 to −0.25 mmol/l) in all groups, with no between‐group differences. HDL cholesterol also rose significantly (0.14 to 0.15 mmol/l) in all groups. Lipid (P = 0.01) and blood pressure (P = 0.09) medication use, however, were lower for the lifestyle group during the Diabetes Prevention Program Outcomes Study.

Conclusion  Overall, intensive lifestyle intervention achieved, with less medication, a comparable long‐term effect on cardiovascular disease risk factors, to that seen in the metformin and placebo groups.
The benefits from public agricultural research in Uruguay
Authors: Bervejillo José E. , Alston Julian M. , Tumber Kabir P.
Published: July 2012

We use newly constructed data to model and measure agricultural productivity growth and the returns to public agricultural research conducted in Uruguay over the period 1961–2010. We pay attention specifically to the role of levy‐based funding under INIA, which was established in 1990. Our results indicate that the creation of INIA was associated with a revitalization of funding for agricultural R&D in Uruguay, which spurred sustained growth in agricultural productivity during the past two decades when productivity growth was stagnating in many other countries. The econometric results were somewhat sensitive to specification choices. The preferred model includes two other variables with common trends, a time‐trend variable and a proxy for private research impacts, as well as a variable representing the stock of public agricultural knowledge that entailed a lag distribution with a peak impact at year 24 of the 25‐year lag. It implies a marginal benefit‐cost ratio of 48.2, using a real discount rate of 5 per cent per annum and a modified internal rate of return of 24 per cent per annum. The benefit‐cost ratio varied significantly across models with different lag structures or that omitted the trend or the private research variable, but across the same models, the modified internal rate of return was very stable, ranging from 23 per cent per annum to 27 per cent per annum. These results suggest that the revitalized investment in research spending under INIA has been very profitable for Uruguay and that a greater rate of investment would have been justified.
Production economics in the presence of risk*
Authors: Shankar Sriram
Published: July 2012

This paper provides an overview of the literature on production under the influence of risk. Various specifications of stochastic production function such as models with additive and multiplicative uncertainty, Just and Pope model, output‐cubical, state‐allocable and state‐general models are discussed. Further, criteria determining optimal producer behaviour are derived for deterministic production technology and for various kinds of state‐contingent technologies such as output‐cubical, state‐specific, state‐allocable and state‐general technologies. Finally, a brief discussion is presented about the drawbacks of each of these specifications of technology.
Optimal convergence rates in non‐parametric regression with fractional time series errors
Authors: Feng Yuanhua , Beran Jan
Published: July 2012

Consider the estimation of g(ν), the νth derivative of the mean function, in a fixed‐design non‐parametric regression model with stationary time series errors ξi. We assume that , ξi are obtained by applying an invertible linear filter to iid innovations, and the spectral density of ξi has the form as λ → 0 with constants cf > 0 and α  ∈  (−1,1). Under regularity conditions, the optimal convergence rate of is shown to be with r = (1 − α)(k − ν)/(2k+1 − α). This rate is achieved by local polynomial fitting. Moreover, in spite of including long memory and antipersistence, the required conditions on the innovation distribution turn out to be the same as in non‐parametric regression with iid errors.
Does headCTscan pathology predict outcome after mild traumatic brain injury?
Authors: Lannsjö M. , Backheden M. , Johansson U. , af Geijerstam J. L. , Borg J.
Published: July 2012

Background and purpose

More evidence is needed to forward our understanding of the key determinants of poor outcome after mild traumatic brain injury (MTBI). A large, prospective, national cohort of patients was studied to analyse the effect of headCTscan pathology on the outcome.

Methods

One‐thousand two‐hundred and sixty‐two patients withMTBI(GlasgowComaScale score 15) at 39 emergency departments completed a study protocol including acute headCTscan examination and follow‐up by theRivermeadPostConcussionSymptomsQuestionnaire and theGlasgowOutcomeScaleExtended (GOSE) at 3 months afterMTBI. Binary logistic regression was used for the assessment of prediction ability.

Results

In 751 men (60%) and 511 women (40%), with a mean age of 30 years (median 21, range 6–94), we observed relevant or suspect relevant pathologic findings on acuteCTscan in 52 patients (4%). Patients aged below 30 years reported better outcome both with respect to symptoms andGOSEas compared to patients in older age groups. Men reported better outcome than women as regards symptoms (OR0.64,CI0.49–0.85 for ≥3 symptoms) and global function (OR0.60,CI0.39–0.92 forGOSE1–6).

Conclusions

Pathology on acuteCTscan examination had no effect on self‐reported symptoms or global function at 3 months afterMTBI. Female gender and older age predicted a less favourable outcome. The findings support the view that other factors than brain injury deserve attention to minimize long‐term complaints afterMTBI.
Auto‐amplification of cortisol actions in human carotid atheroma is linked to arterial remodeling and stroke
Authors: Ayari Hanène , Legedz Liliana , Lantelme Pierre , Feugier Patrick , Randon Jacques , Cerutti Catherine , Lohez Olivier , Scoazec Jean‐Yves , Li Jacques Yuan , Gharbi‐Chihi Jouda , Bricca Giampiero
Published: July 2012

High cortisol and aldosterone levels increase cardiovascular risk, but the respective roles of each hormone within the arterial wall remain controversial. We tested the hypothesis that cortisol production within the arterial wall may contribute to atherosclerotic remodeling and act through illicit activation of the mineralocorticoid receptor (MR). Gene expression studies of the corticoid system components and marker genes of the atherosclerotic process in human carotid atheroma plaque and nearby macroscopically intact tissue (MIT) were considered together with clinical data and compared with pharmacological stimulations of human vascular smooth muscle cells (VSMCs) in contractile or lipid‐storing phenotypes. The components of corticoid production and action were present and active within the human carotid wall and VSMCs. Atheroma plaque and lipid‐storing VSMCs expressed 11β‐hydroxysteroid deshydrogenase‐1 (11β‐HSD1) at two‐ to tenfold higher levels than MIT or contractile VSMCs. The 11β‐HSD1 expression was stimulated by cortisol and cortisone, especially in lipid‐storing VSMCs. MR mRNA level was lower in atheroma and lipid‐storing VSMCs and downregulated via MR by fludrocortisone and cortisol. Cortisol upregulated collagen1 and MCP‐1 mRNAs via the glucocorticoid receptor (GRα), in both VSMC phenotypes, whereas fludrocortisone stimulated the collagen1 expression only in lipid‐storing VSMCs. The GRα mRNA level in MIT was higher in patients with previous stroke and correlated positively with the collagen1 mRNA but negatively with diastolic blood pressure. Local cortisol production by 11β‐HSD1, and its action via high parietal GRα could be relevant from the first step of atherosclerotic remodeling and auto‐amplify with transdifferentiation of VSMCs during atheroma progression.
ISOTOPES ON THE BEACH, PART 1: STRONTIUM ISOTOPE RATIOS AS A PROVENANCE INDICATOR FOR LIME RAW MATERIALS USED IN ROMAN GLASS‐MAKING
Authors: BREMS D. , GANIO M. , LATRUWE K. , BALCAEN L. , CARREMANS M. , GIMENO D. , SILVESTRI A. , VANHAECKE F. , MUCHEZ P. , DEGRYSE P.
Published: July 2012

The provenancing of Roman natron glass is one of the most challenging problems in the field of archaeometry. Although the use of Sr and Nd isotope ratios and trace element signatures as an indication of provenance has proven promising, there are still many unknowns. In this study, the influence of the different raw materials on the final Sr isotopic composition of Roman natron glass is examined. It is shown that the 87Sr/86Sr ratio in natron glass is significantly influenced by the silicate fraction of the sand used and does not always provide a clear indication of the lime source used.
ANTICONVULSANT COMPOUNDS AND 5‐HYDROXY‐TRYPTAMINE IN RAT BRAIN
Authors: BONNYCASTLE D. D. , GIARMAN N. J. , PAASONEN M. K.
Published: July 2012

In rats, a series of anticonvulsant compounds have been shown to cause a significant elevation of brain 5‐hydroxytryptamine (5‐HT) levels in comparison with control values. This increase in 5‐HT only occurred in brain tissue and was not observed in spleen, upper small intestine or blood. Elevation of brain levels of 5‐HT by iproniazid (Marsilid) or 5‐hydroxytryptophan failed to give protection against the convulsant or lethal action of lept zol (75 mg./kg.).
THE INTERACTION BETWEEN EDROPHONIUM (TENSILON) AND ACETYLCHOLINE AT THE MOTOR END‐PLATE
Authors: KATZ B. , THESLEFF S.
Published: July 2012

The effect of edrophonium (3‐hydroxy‐phenyl‐dimethylethylammonium chloride) on the motor end‐plate and its interaction with acetylcholine and carbachol has been investigated. Use was made of intracellular recording of membrane potential and of ionophoretic micro‐application of drugs from single and twin‐pipettes.

Small doses of edrophonium potentiate the depolarizing effect of acetylcholine, but not that of carbachol. This action can be observed with doses of edrophonium which have no depolarizing effect by themselves. Large doses of edrophonium have some depolarizing action and, at the same time, inhibit depolarizations produced by carbachol. After treatment with neostigmine, edrophonium fails to potentiate the acetylcholine response. The observations are in agreement with the view that the principal action of edrophonium on the neuromuscular junction is that of a potent and rapidly acting anticholinesterase.
THE ENZYMATIC HYDROLYSIS OF IMIDAZOLEACRYLOYLCHOLINE (MUREXINE) AND IMIDAZOLEPROPIONYLCHOLINE (DIHYDROMUREXINE) BY VARIOUS CHOLINESTERASES
Authors: GRELIS M. E. , TABACHNICK I. I. A.
Published: July 2012

Several choline esters, including the imidazoleacryloyl and imidazolepropionyl compounds, have been hydrolysed by cholinesterases from various sources. The imidazolepropionyl ester was metabolized by cholinesterases obtained from human plasma, ox spleen, ox serum, and guinea‐pig liver, but not by rat liver or bovine red cell cholinesterase. It is suggested the imidazolepropionylcholine or a closely related ester might be the natural substrate for “nonspecific” cholinesterase.
THE MECHANISM OF ACTION OF MUREXINE ON NEUROMUSCULAR TRANSMISSION IN THE FROG
Authors: QUILLIAM J. P.
Published: July 2012

Murexine (urocanoylcholine, [2‐β‐imidazol‐4(5)‐ylacryloyloxyethyl]trimethylammonium chloride hydrochloride) produced a contracture like acetylcholine in the frog rectus and a neuromuscular block in the rat diaphragm which was not relieved by neostigmine but was antagonized by hexamethonium. Using the foot muscle of the frog, electrical recordings showed that murexine produced a neuromuscular block and depolarized the end‐plate region. These effects were similar to those seen with suxamethonium, decamethonium and acetylcholine. While murexine had the same depolarizing potency as decamethonium, it was only one‐tenth as active as suxamethonium and acetylcholine. It was concluded that murexine could be classified as a “depolarizing type” of neuromuscular blocking agent but was less potent than suxamethonium.
INHIBITION BY MORPHINE OF THE RELEASE OF ACETYLCHOLINE FROM THE INTESTINE OF THE GUINEA‐PIG
Authors: SCHAUMANN W.
Published: July 2012

In experiments on the isolated small intestine of the guinea‐pig, morphine inhibited the release of acetylcholine (ACh) into the bath fluid. Experimental evidence is presented which suggests that the reduced release of ACh could not be explained by an inhibition of the synthesis of ACh, nor by stabilization of the bound form of ACh in the tissue. Apparently morphine reduces the excitability of postganglionic structures and thereby the liberation of ACh from nerve endings during the process of excitation.
THE BIOLOGICAL ACTION OF CHLOROPHENOLS
Authors: FARQUHARSON MURIEL E. , GAGE J. C. , NORTHOVER JEAN
Published: July 2012

The biological action of a series of chlorinated phenols has been investigated. With increasing chlorination there is an increase in toxicity in which the convulsant action of phenol is replaced by the signs characteristic of poisoning by dinitrophenol; the higher chlorinated phenols produce a contracture of the isolated rat phrenic nerve diaphragm and a stimulation of in vitro oxygen uptake of rat brain homogenate. These actions of the chlorinated phenols have been correlated with their dissociation constants; it is suggested that the higher chlorinated phenols interfere with oxidative phosphorylation, and that this property may be attributed to the chlorophenate ion. The convulsant action of the lower chlorinated phenols is probably associated with the undissociated molecule.
THE RENAL REMOVAL OF INJECTED [14C]HISTAMINE FROM THE BLOOD IN DOGS
Authors: LINDELL S.‐E. , SCHAYER R. W.
Published: July 2012

The amounts of [14C]histamine in arterial blood, in renal venous blood and in urine during a steady intravenous infusion of [14C]histamine were measured in five anaesthetized dogs. The extraction ratio for [14C]histamine was 0.7 to 0.8, indicating that the histamine was efficiently taken up from the blood by the kidney. Only a small part (14 to 18%) of the [14C]histamine removed from the blood by the kidney appeared in the urine as histamine. Evidence was obtained that [14C]histamine was metabolized in the kidney not only by histaminase (diamine oxidase) but also by the histamine methylating enzyme.
SOME EFFECTS OF HISTAMINE IN THE NORMAL AND HAEMOPHILUS PERTUSSIS VACCINATED RAT
Authors: BOVET D. , KOHN R. , MAROTTA M. , SILVESTRINI B.
Published: July 2012

The effects of histamine in the normal and H. pertussis vaccinated rat have been investigated. In the normal animal small doses of histamine (from 1 to 30 mg./kg., i.v.) produced significant, reversible alterations in the blood pressure, electrocardiogram and electroencephalogram. Doses of 100 mg./kg. or more caused bronchoconstriction and doses of 200 mg./kg. or more an effect on the muscular contractions after electrical stimulation of the nerve. Acute histamine intoxication resulted on rapid injection of 500 mg./kg. intravenously; death was probably due to cardiovascular collapse. In the vaccinated rat, a distinction could be made between the immediate and delayed effects of histamine. With a sublethal dose of histamine (5 mg./kg.) alterations in the blood pressure, electrocardiogram and electroencephalogram were noted. The neuromuscular system, which in the normal animal was the least reactive to histamine, showed the most marked increase in sensitivity in the vaccinated rat. The delayed effects of histamine observed after an interval of 5 to 30 min. were characteristic and irreversible, leading to death of the animal. The mechanism of death in the vaccinated rat after histamine appears to differ from that of the normal animal and has been discussed in the light of present knowledge.
A QUANTITATIVE METHOD FOR THE ASSAY OF INHIBITORS OF ACID GASTRIC SECRETION IN THE RAT
Authors: GHOSH M. N.
Published: July 2012

Assays of inhibitors of gastric secretion are described by a method of recording continuously acid gastric secretion in the rat. A number of doses of inhibitor comprising several assay blocks can be administered in one preparation and complete assays with known fiducial limits performed with only two rats. Assays were carried out with vasopressin against secretion induced by histamine, and with atropine, methanthelinium and atropine methylnitrate against secretion induced by methacholine.
STUDIES OF THE ACTION OF HYPOGLYCIN‐A, AN HYPOGLYCAEMIC SUBSTANCE
Authors: FENG P. C. , PATRICK S. J.
Published: July 2012

Some biological effects of hypoglycin‐A, a compound isolated from the fruit of Blighia sapida, have been investigated. Administration of this compound to animals caused drowsiness progressing to coma, and when large doses were given the animals died. For the rat, the oral and intraperitoneal LD50 values were 98 and 97 mg./kg. respectively. Fasting increased the toxicity considerably. The most outstanding biochemical change produced by hypoglycin‐A was a delayed hypoglycemia, the depth of which was related to the dose. The hypoglycaemia was preceded by exhaustion of liver glycogen. There were also smaller decreases in the glycogen stores of the heart, skeletal muscle and kidney, without any increase in blood pyruvate or lactate. Hypoglycin‐A lessened the effect of adrenaline on blood glucose and decreased both glucose tolerance and insulin sensitivity. Hypoglycin‐A also decreased the oxygen consumption and carbon dioxide production of the intact rat. All these effects are consistent with the hypothesis that the primary action of hypoglycin‐A is the interference with glycogen production by the liver.
THE RÔLE OF QUININE IN HAEMOLYSIS
Authors: GREWAL R. S.
Published: July 2012

Quinine produces haemolysis of rabbit and human red blood cells in concentrations up to 1 in 700. In a concentration of 1 in 10,000 it increases the degree of haemolysis produced by various haemolytic agents like saponin, bile salts and digitonin in vitro. Quinine when injected intravenously in 35 mg./kg. dose in rabbits increases the susceptibility of red blood cells to the haemolytic action of saponin. Intravascular haemolysis following the administration of quinine is seen in cases of blackwater fever, and on the basis of experimental work described in the paper it is suggested that quinine precipitates these haemolytic episodes by rendering the red blood cells more susceptible to the action of tissue lytic factors.
THE DISTRIBUTION OF METHYLPENTYNOL AND OF METHYLPENTYNOL CARBAMATE IN TISSUES AND BODY FLUIDS OF CATS
Authors: MARLEY E. , VANE J. R.
Published: July 2012

A method is described for the estimation of methylpentynol and methylpentynol carbamate in body fluids and tissues. After intravenous administration, the distribution of these drugs throughout the body was found to be similar to that of ethanol. They entered cells, and crossed the blood‐brain barrier and the placenta. They were excreted or secreted into the saliva, milk, gastric secretion, aqueous and vitreous humour, amniotic liquor, bile and urine. Methylpentynol was found in the expired air. Calculation of the volume of distribution and measurement of concentration in the tissues showed that both drugs were only slowly metabolized or excreted, suggesting the possibility that blood concentrations might rise cumulatively over a period of days.
DERIVATIVES OF 3: 4‐XYLIDINE AND RELATED COMPOUNDS AS INHIBITORS OF INFLUENZA VIRUS: RELATIONSHIPS BETWEEN CHEMICAL STRUCTURE AND BIOLOGICAL ACTIVITY
Authors: CLARK R. J. , ISAACS A. , WALKER J.
Published: July 2012

A series of compounds, based primarily on 3:4‐xylidine, was examined for inhibitory activity towards the growth of influenza virus in tissue culture. Marked dependence of inhibitory activity upon chemical structure was observed particularly when the 3:4‐xylyl group was replaced by other simple aryl radicals. N‐(2‐Piperidinoethyl)‐3:4‐xylidine dihydrochloride, a typical compound combining high intrinsic inhibitory activity with no obvious toxicity towards the host tissues, did not inactivate the virus directly before its adsorption, did not interfere with adsorption of virus by the tissues, and did not inhibit the release of freshly synthesized virus by the tissues, but specifically depressed the synthesis of viral haemagglutinin to a greater extent than it depressed the synthesis of complement‐fixing soluble antigen. The inhibition of growth of influenza virus caused by this compound in tissue culture was reversed by appropriate addition of 4:5‐dimethyl‐o‐phenylenediamine, but not apparently by riboflavin or by vitamin B12. The action of this substance, and, by inference, of related compounds, in inhibiting viral synthesis may be the result of depressed cytoplasmic protein synthesis.
EFFECT OF INHIBITORS OF CHOLINE ACETYLATION ON ACETYLCHOLINE OUTPUT AND MOTILITY IN RESPONSE TO ANTICHOLINESTERASES AND TO DISTENSION OF THE LUMEN OF ISOLATED GUINEA‐PIG ILEUM
Authors: GIOIA A. , MORPURGO C.
Published: July 2012

Some pharmacological effects of acyl‐aryl compounds, which inhibit the enzymatic acetylation of choline, have been studied on the isolated guinea‐pig ileum. Diphenylylbutylacetic acid (M.G. 1763) greatly reduced the output of acetylcholine from intestine. The intestinal contractions produced by anticholinesterase drugs were inhibited, while the response to acetylcholine itself was little affected. The contraction of longitudinal muscle elicited by raising intra‐luminal pressure was also decreased, while the emptying phase of the peristaltic reflex was scarcely affected. There was a correlation between inhibitory activity and chemical structure.
SLOW‐CONTRACTING SUBSTANCES IN HUMAN URINE
Authors: JENSEN K. B.
Published: July 2012

A method has been developed for purifying the principle in human urine causing contraction of the rat uterus. The method, based on adsorption on the cation exchange resin Amberlite IRC‐50, is better suited for dealing with large quantities of urine than the method of Gomes (1955). The presence of the two active fractions described by Walaszek (1957) has been confirmed by a different method.
PHARMACOLOGICAL PROPERTIES OF ββ‐DIMETHYL‐ACRYLOYLCHOLINE AND SOME OTHER β‐SUBSTITUTED ACRYLOYLCHOLINES
Authors: HOLMSTEDT B. , WHITTAKER V. P.
Published: July 2012

The mammalian pharmacology of a new naturally occurring ester of choline, ββ‐dimethyl‐acryloylcholine (DMAC), has been studied, mainly in the cat, together with that of two synthetic β‐substituted acryloylcholines, crotonoylcholine and pent‐2‐enoylcholine. Comparisons have been made with the reduced form of DMAC, isovalerylcholine, with another naturally occurring β‐substituted acryloylcholine, murexine (urocanoylcholine), and with suxamethonium. DMAC has been shown to be a ganglion stimulating and neuromuscular blocking agent generally similar, in potency and properties, to murexine. It is also a powerful respiratory stimulant. The other unsaturated esters behaved similarly but were less potent.
COMPARATIVE EFFECTS OF ANALGESICS ON PAIN THRESHOLD, RESPIRATORY FREQUENCY AND GASTROINTESTINAL PROPULSION
Authors: GREEN A. F.
Published: July 2012

In the rat, the ratio of the analgesic to the respiratory depressant potency was the same for morphine, codeine, diamorphine, methadone, dipipanone, piperidylisomethadone, phenadoxone, dextromoramide, and propoxyphene. The relative respiratory depressant activity of pethidine tended to be less, but the difference was not significant. The ratio of the analgesic dose to the dose preventing transport of a charcoal meal in the rat was about the same for morphine, codeine, pethidine, methadone, phenadoxone, dimethylthiambutene, and propoxyphene; the relative activities of these compounds in inhibiting the peristaltic reflex of the isolated guinea‐pig ileum were also similar. However, because of differences in the slopes of regression lines in the charcoal meal test, some compounds (for example, morphine) had a greater effect on gastrointestinal propulsion than others (for example, pethidine) when given at moderate analgesic dose levels.

In studies of the effects of intracisternal morphine in the rat, effects on the spinal reflex of the tail were to some extent dissociated from effects on the threshold for a squeak response. Further, the delaying of transport of a charcoal meal paralleled depression of respiratory rate, and this is evidence for the participation of a central as well as a peripheral action in the effect of morphine on the gastrointestinal tract. The delay in propulsion was reduced by nalorphine and increased by atropine and two general anaesthetic substances, but was unaffected by a number of other pharmacological agents.
ACTIONS OF SOME ANALOGUES OF TRYPTAMINE ON THE ISOLATED RAT UTERUS AND ON THE ISOLATED RAT FUNDUS STRIP PREPARATIONS
Authors: BARLOW R. B. , KHAN I.
Published: July 2012

Some 3‐(2‐dialkylaminoethyl)‐, 3‐(2‐alkylaminoethyl)‐, and 3‐(2‐dialkylaminoethyl)‐2‐methylindoles have been synthesized and tested, along with 5‐benzyloxygramine, 5‐benzyloxy‐3‐(2‐dimethylaminoethyl)‐, 3‐(2‐aminopropyl)‐ and 3‐(2‐aminobutyl)‐indoles, on the rat uterus and rat fundus strip. 5‐Benzyloxy‐3‐(2‐dimethylaminoethyl)indole, even though it contains an ethylene side‐chain, was a less potent antagonist of 5‐hydroxytryptamine than was 5‐benzyloxygramine. The remaining compounds were still less active. There are differences between the ability of some of them to antagonize 5‐hydroxytryptamine and to antagonize tryptamine. 3‐(2‐Dimethylaminoethyl)‐2‐methylindole, in particular, shows a considerable degree of specific antagonism of 5‐hydroxytryptamine on both tissues.

Nearly all the compounds stimulate the preparations, some combining antagonism of 5‐hydroxytryptamine at low concentrations with stimulant activity at higher concentrations. The most active compound is 3‐(2‐dipropylaminoethyl)indole. On the rat fundus strip this has, on a molar basis, 1/40th of the stimulant activity of 5‐hydroxytryptamine, and is 20 times as active as tryptamine: on the rat uterus it is only 1/200th as active as 5‐hydroxytryptamine, and equal in activity to tryptamine.
HUMAN URINARY KININ EXCRETION
Authors: HORTON E. W.
Published: July 2012

It has been shown that the isolated rat duodenum relaxes in the presence of low concentrations of plasma and urinary kinin. The tissue is at least as sensitive as the rat uterus. Vasopressin and oxytocin, in large doses, also caused relaxation of the duodenum whereas acetylcholine, substance P and 5‐hydroxytryptamine caused contraction. It was concluded that if an extract is assayed on the rat uterus and the rat duodenum in parallel using plasma kinin as a standard, and the results agree, this is good evidence that the active principle being estimated is a kinin. This method is therefore both sensitive and specific for kinin estimations, but it will not distinguish between kinins of different origin. The urinary excretion of kinin in 14 healthy adults was found to be fairly constant. The minute output was unaffected by the rate of urine formation, urinary pH, or time of day. There was no increase during sweating or salivation.