bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose‐response relationship and time‐course of the effect of inhaled magnesium sulphate on airflow in normal and asthmatic subjects.
Authors: Hill J. , Britton J.
Published: July 2012

1. Magnesium is a dietary cation with a wide range of actions of potential relevance to asthma. 2. To determine the dose‐response relationship and time‐course of the effect of inhaled magnesium sulphate on the airway, we have studied the effect of 0, 90, 135, 180 and 360 mg of magnesium sulphate given by nebulizer on specific airways conductance (sGaw) in 20 normal subjects, and forced expiratory volume in one second (FEV1), forced vital capacity (FVC), flow at 25% forced vital capacity (Vmax25) and peak expiratory flow (PEF) in 19 asthmatic subjects. 3. On five occasions after baseline measurements of airway calibre, one of the five doses of magnesium sulphate in 3 ml normal saline was administered by nebulizer in a randomized, double‐blind design. Measurements of sGaw or FEV1, FVC, Vmax25 and PEF were made at 5 and 10 min after nebulization and at 10 min intervals thereafter up to 90 min. 4. There was no significant difference in the mean area under the curve (AUC) for change from baseline in sGaw or maximum increase from baseline between doses in normal subjects. 5. In asthmatic subjects there was no significant difference in the mean AUC for change from baseline in FEV1, FVC or Vmax25 when compared between doses by analysis of variance. There was a difference in the mean AUC for change from baseline in PEF between doses (ANOVA P for all groups 0.052) but this can be explained by a detrimental effect of the maximum dose of magnesium sulphate. 6. It would appear that inhaled magnesium does not act as a bronchodilator in normal or asthmatic subjects.
Effect of multiple doses of losartan on the pharmacokinetics of single doses of digoxin in healthy volunteers.
Authors: De Smet M. , Schoors DF , De Meyer G. , Verbesselt R. , Goldberg MR , Fitzpatrick V. , Somers G.
Published: July 2012

1. Losartan (DuP 753, MK‐954) is a novel, potent and highly selective AT1 angiotensin II receptor antagonist. The effect of multiple oral doses of losartan on digoxin pharmacokinetics was evaluated in healthy male subjects. 2. In a double‐blind and randomized fashion, subjects received 50 mg losartan or placebo once daily for 15 days in each period. At least 7 days elapsed between the two treatment periods. On days 4 and 11 of each period, subjects also received a single 0.5 mg dose of digoxin intravenously and orally respectively. 3. Eleven of 13 subjects completed the study. Side effects were mild and transient (12 out of 13 subjects reported at least one adverse experience). During the study, no laboratory abnormalities were noted. 4. Multiple oral doses of losartan (50 mg daily) did not affect the pharmacokinetic parameters of 0.5 mg of digoxin i.v. AUC(0.48h) of immunoreactive digoxin during losartan 28.8 +/‐ 2.9 vs 28.5 +/‐ 3.9 ng ml‐1 h during placebo; not significant, and 96 h urinary excretion [% dose] during losartan 54.0 +/‐ 7.2 vs 51.9 +/‐ 6.5% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.03 (0.98, 1.08) and 1.09 (0.98, 1.21). 5. Multiple oral doses of losartan did not affect the pharmacokinetic parameters of oral digoxin AUC(0.48 h) during losartan 23.6 +/‐ 3.7 ng ml‐1 h vs 22.4 +/‐ 2.6 ng ml‐1 h during placebo; not significant, Cmax 3.5 +/‐ 0.7 ng ml‐1 with vs 3.1 +/‐ 0.5 ng ml‐1 without losartan; not significant and tmax 0.6 +/‐ 0.2 h with vs 0.9 +/‐ 0.7 h without losartan; not significant, and 96 h urinary excretion [% dose] during losartan 51.2 +/‐ 6.3 vs 46.3 +/‐ 2.4% during placebo; not significant). Geometric mean ratios (90% confidence interval) for AUC and urinary excretion were respectively, 1.06 (0.98, 1.14) and 1.12 (0.97, 1.28). 6. We conclude that multiple oral doses of losartan (50 mg daily) do not alter the pharmacokinetics of immunoreactive digoxin, following either intravenous or oral digoxin. Furthermore, the co‐ administration of digoxin with losartan is well tolerated by healthy male volunteers.
Acute effects of ANP and BNP on hypoxic pulmonary vasoconstriction in humans.
Authors: Cargill RI , Lipworth BJ
Published: July 2012

1. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have pulmonary vasorelaxant activity with plasma concentrations being elevated in patients with hypoxaemic pulmonary hypertension. However, their effects on acute hypoxic pulmonary vasoconstriction (HPV), the initiating stimulus for pulmonary hypertension have not to date been investigated. We have therefore studied the effects of ANP and BNP on acute HPV in humans. 2. Eight healthy volunteers were studied on three separate occasions. After reaching a resting haemodynamic state (t0), an infusion of either ANP (10 pmol kg‐1 min‐1), BNP (10 pmol kg‐1 min‐ 1) or placebo (5% dextrose) was commenced. This was given alone for 30 min (t30) before subjects were rendered hypoxaemic (SaO2 75‐80%) for a further 30 min (t60), with the initial infusion continuing to t60. Pulsed‐wave Doppler analysis of pulmonary artery flow was used to measure mean pulmonary arterial pressure (MPAP) and hence total pulmonary vascular resistance (PVR) was calculated. 3. MPAP and PVR both tended to decrease in response to ANP and BNP infusion, although compared with placebo, the difference at t30 was only statistically significant for PVR. Hypoxaemia increased MPAP and PVR, although values at t60 were significantly lower following both ANP and BNP compared with placebo. 4. In terms of the actual change in PVR (delta PVR) induced by hypoxaemia (from t30 to t60), BNP (146(16) dyn s cm‐5), but not ANP (183(21) dyn s cm‐5) significantly attenuated delta PVR compared with placebo (194(26) dyns s cm‐5): mean difference BNP versus placebo 48 dyn s cm‐5, 95% Cl 3‐93. An identical pattern was observed for delta MPAP where BNP (15.9(1.1) mmHg), but not ANP (18.0(1.2) mmHg) significantly attenuated delta MPAP compared with placebo (19.0(1.7) mmHg): mean difference BNP versus placebo 3.1 mmHg, 95% Cl 0.7‐5.5. 5. Thus, although both ANP and BNP exhibit pulmonary vasorelaxant activity, only BNP significantly attenuated the MPAP and PVR responses to acute hypoxaemia. This suggests that the natriuretic peptides may have a role in attenuating pulmonary hypertension secondary to hypoxaemia.
Lack of an effect of nefazodone on the pharmacokinetics and pharmacodynamics of theophylline during concurrent administration in patients with chronic obstructive pulmonary disease.
Authors: Dockens RC , Rapoport D. , Roberts D. , Greene DS , Barbhaiya RH
Published: July 2012

The effect of nefazodone on the pharmacokinetics and pharmacodynamics of theophylline was evaluated in a multiple‐dose, randomized placebo‐ controlled, double‐blind two‐period crossover study in 13 patients who were undergoing theophylline therapy for chronic obstructive pulmonary disease. Two treatments were administered, each for 7 days: theophylline + 200 mg nefazodone twice daily (every 12h) and theophylline+matching nefazodone placebo capsule twice daily (every 12h). Mean peak and trough plasma concentrations of theophylline ranged from 13.1 to 14.5 micrograms ml‐1 and 11.6 to 14.2 micrograms ml‐1, respectively, at steady‐state when theophylline was administered with or without concurrent dosing of nefazodone. Similarly, the mean area under the curve for theophylline ranged from 93.5 to 103 micrograms ml‐ 1 h. When nefazodone and theophylline were co‐administered, theophylline pharmacokinetic parameters did not significantly differ from those obtained when theophylline was administered with placebo. Forced expiratory volume in one second (FEV1) measurements taken when nefazodone or placebo were administered with theophylline did not differ from those obtained at baseline. The plasma concentration‐time profiles for nefazodone and its metabolites were similar to those in other studies where nefazodone was administered alone. Since nefazodone did not affect the pharmacokinetics or the pharmacodynamics of theophylline, no change in theophylline dose should be needed as a consequence of nefazodone co‐administration.
Meeting the challenges of haemophilia care and patient support in China and Brazil
Authors: OZELO MARGARETH C. , MATTA MÁRCIA A. P. , YANG RENCHI
Published: July 2012

Summary.  Projects are underway in many developing countries to try to improve the provision of treatment and access to care for people with haemophilia (PWH), as long‐term prophylactic treatment, which improves quality of life for PWH, is still restricted to developed countries. In most developing countries, therapy is limited to on‐demand treatment or even no replacement treatment at all. Combined with limited healthcare resources, this lack of treatment can lead to a vicious circle of lack of care, disability, unemployment and lack of access to health insurance for haemophilia patients. In China, the establishment of the Haemophilia Treatment Centre Collaborative Network of China (HTCCNC), in conjunction with the World Federation of Hemophilia, has improved haemophilia care and the identification of PWH. In Brazil, on‐demand treatment has improved the health of PWH but does not prevent musculoskeletal (MSK) complications, the major cause of deterioration in quality of life for PWH. The Novo Nordisk Haemophilia Foundation BR2 project was therefore designed to improve quality of life of PWH through improvements in their physical, mental and social wellbeing. This paper will briefly review these projects and describe the current status of haemophilia care in these countries. While there is still a long way to go before optimal care becomes a reality for all PWH in developing countries, significant progress has been made, and knowledge of the impact and outcomes of these projects can inform best practice worldwide.
Trehalose‐6‐phosphate synthase from the cat flea Ctenocephalides felis and Drosophila melanogaster: gene identification, cloning, heterologous functional expression and identification of inhibitors by high throughput screening
Authors: Kern C. , Wolf C. , Bender F. , Berger M. , Noack S. , Schmalz S. , Ilg T.
Published: July 2012

Trehalose phosphate synthase (EC 2.4.1.15; TPS) is the crucial enzyme for the biosynthesis of trehalose, the main haemolymph sugar of insects, and therefore a potential insecticidal molecular target. In this study, we report the functional heterologous expression of Drosophila melanogaster TPS, the gene identification, full length cDNA cloning and functional expression of cat flea (Ctenocephalides felis) TPS, and the Michaelis–Menten constants for their specific substrates glucose‐6‐phosphate and uridinediphosphate‐glucose. A novel high throughput screening‐compatible TPS assay and its use for the identification of the first potent insect TPS inhibitors from a large synthetic compound collection (>115 000 compounds) is described. One compound class that emerged in this screening, the 4‐substituted 2,6‐diamino‐3,5‐dicyano‐4H‐thiopyrans, was further investigated by analysing preliminary structure–activity relationships. Here, compounds were identified that show low µM to high nM half maximal inhibitory concentrations on insect TPS and that may serve as lead compounds for the development of insecticides with a novel mode of action.
New applications for Schizosaccharomyces pombe in the alcoholic fermentation of red wines
Authors: Benito Santiago , Palomero Felipe , Morata Antonio , Calderón Fernando , Suárez‐Lepe José A.
Published: July 2012

The fermentation of grape must using non‐Saccharomyces yeasts with particular metabolic and biochemical properties is of growing interest. In the present work, red grape must was fermented using four strains of Schizosaccharomyces pombe (935, 936, 938 and 2139), Saccharomyces cerevisiae 7VA and Saccharomyces uvarum S6U, and comparisons were made over the fermentation period in terms of must sugar (glucose + fructose), malic acid, acetic acid, ammonia, primary amino nitrogen, lactic acid, urea (a possible fermentation activator or precursor of other metabolites) and pyruvic acid (a molecule affecting vitisin formation and therefore colour stability) concentration. The colour intensity of the fermenting musts was also recorded. The Schizosaccharomyces strains consumed less primary amino nitrogen and produced less urea and more pyruvic acid than other Saccharomyces species. Further, three of the four Schizosaccharomyces strains completed the breakdown of malic acid by day 4 of fermentation. The main negative effect of the use of Schizosaccharomyces was strong acetic acid production. The Schizosaccharomyces strains that produced most pyruvic acid (938 and 936) were associated with better ‘wine’ colour than the remaining yeasts. The studied Schizosaccharomyces could therefore be of oenological interest.
Authentic leadership, performance, and job satisfaction: the mediating role of empowerment
Authors: Wong Carol A. , Laschinger Heather K.S.
Published: July 2012

Aim

To report a study conducted to test a model linking authentic leadership of managers with nurses' perceptions of structural empowerment, performance, and job satisfaction.

Background

Authentic leadership has been proposed as the root element of effective leadership needed to build healthier work environments because there is special attention to the development of empowering leader–follower relationships. Although the influence of leadership style and empowerment on job satisfaction is well documented, there are few studies examining the influence of authentic leadership on nurses' empowerment and work outcomes.

Design

A non‐experimental, predictive survey.

Method

In 2008, a random sample of 600 Registered Nurses working in acute care hospitals across Ontario in Canada was surveyed. The final sample consisted of 280 (48% response rate) nurses. Variables were measured using the Authentic Leadership Questionnaire, Conditions of Work Effectiveness Questionnaire, Global Job Satisfaction Survey, and General Performance scale. The theoretical model was tested using structural equation modelling.

Results/outcomes

The final model fit the data acceptably. Authentic leadership significantly and positively influenced staff nurses' structural empowerment, which in turn increased job satisfaction and self‐rated performance.

Conclusion

The results suggest that the more managers are seen as authentic, by emphasizing transparency, balanced processing, self‐awareness and high ethical standards, the more nurses perceive they have access to workplace empowerment structures, are satisfied with their work, and report higher performance.
Implementing video conferencing in mental health practice
Authors: DE WEGER E. , MACINNES D. , ENSER J. , FRANCIS S. J. , JONES F. W.
Published: July 2012

Accessible summary

In this paper we review past research that suggests video conferencing (VC) can be successfully used in a number of ways in mental health services. These ways include holding staff meetings remotely, conducting assessment and treatment when it is not easy for the clinician and service user to be at the same location, and running staff training remotely.

We also present some guidance regarding issues to be considered when introducing VC into mental health settings, such as the importance of staff and service user consultation, the necessity for training in VC and advice about how to conduct meetings by VC.

Beginning to use VC can represent a significant cultural change for staff and service users. We hope that this paper will provide a useful summary of things that may help support this change.

The aim of this paper is to provide an overview of the evidence base regarding the use of video conferencing (VC), implementation issues, policies, procedures, technical requirements and VC etiquette. The paper is based on a literature review of VC within the mental health sector and the authors' experience in implementing VC. Six themes emerged from the literature review: applications of VC, VC assessments, treatment, training and supervision, practitioner anxiety, and VC administrative processes. The results of the review support the use of VC in mental health services. Guidelines for the implementation of VC are discussed, including the importance of staff and service user consultations, training in the use of VC, clear guidance for staff with regards to usage, confidentiality and data protection policies, and VC etiquette. Challenges that can arise when implementing VC in a mental health context are also discussed. Arguably, it is not the technology, but the cultural change it represents to staff which seems to be the most important factor regarding successful implementation.
Carrion flies of forensic interest: a study of seasonal community composition and succession in Lisbon, Portugal
Authors: PRADO E CASTRO C. , SERRANO A. , MARTINS DA SILVA P. , GARCÍA M. D.
Published: July 2012

Information on Diptera community, seasonality and successional patterns in every geographical region is fundamental for the use of flies as forensic indicators of time of death. In order to obtain these data from the Lisbon area (Portugal), experiments were conducted during the four seasons of the year, using piglet carcasses as animal models. Five stages were recognized during the decomposition process. The stages, besides visually defined, could be separated taking into account the occurrence and abundance of the specific groups of Diptera collected. In general, the bloated stage recorded higher abundance and species‐richness values. Seventy‐one species were identified, belonging to 39 families, in a total of 20 144 adult Diptera collected. Autumn yielded the highest values of species richness, whereas winter had the lowest. In all seasons of the year, Calliphoridae was the dominant family; Muscidae and Fanniidae were very abundant as well. Calliphora vicina Robineau‐Desvoidy, Calliphora vomitoria (Linnaeus), Chrysomya albiceps (Wiedemann), Lucilia ampullacea Villeneuve, Lucilia caesar (Linnaeus), Lucilia sericata (Meigen) (Calliphoridae), Hydrotaea ignava (Harris), Muscina prolapsa (Harris), Synthesiomyia nudiseta (van der Wulp) (Muscidae), Piophila megastigmata McAlpine, Stearibia nigriceps (Meigen) (Piophilidae) and Nemopoda nitidula (Fallén) (Sepsidae) were revealed to be very important members of the Diptera community collected. The necrophagous behaviour, demonstrated by their immatures, using carrion as a food source makes them useful forensic indicator species. Also of relevance is the presence of Chrysomya megacephala (Fabricius), S. nudiseta and P. megastigmata, foreign species established in the local carrion communities. This study also marks the first record of S. nudiseta in Portugal.
The flickering genes of the last mammoths
Authors: THOMAS M. G.
Published: July 2012

Woolly mammoths, Mammuthus primigenius, are arguably the most iconic of the extinct Pleistocene megafauna, and an abundance of large permafrost‐embedded bone and ivory material (Fig. 1) means they were also among the first to yield credible DNA sequences (Hagelberg et al. 1994; Hoss et al. 1994). Despite mammoth remains being numerous throughout northern Eurasia and North America, both the earliest and most recent fossils are found in northeast Siberia, with the last known population being confined to Wrangel Island in the Arctic Ocean from around 10,000 years ago until their extinction around 4,000 years ago. The extent to which these Holocene mammoths were descended from the Pleistocene populations of Wrangel Island and the demographic nature of their terminal decline have, until now, remained something of a mystery. In this issue of Molecular Ecology, Nyström et al. (2012) report the first use of autosomal variation to track the decline of the last mammoths and, in doing so, take a significant step towards resolving these questions. The authors genotyped four microsatellite loci in 59 Pleistocene and Holocene mammoths from Wrangel Island and Chukotka in mainland northeastern Siberia and showed that while the Pleistocene‐to‐Holocene transition is associated with a significant reduction in genetic diversity, subsequent levels of variation remain constant until extinction. Such a pattern is somewhat surprising as it indicates that while the last mammoths were confined to only a few Arctic islands, their final extinction on Wrangel Island was not a gradual process resulting from loss of genetic diversity/inbreeding. Instead, it seems they maintained a viable effective population size of around 500 until near their presumably rapid extinction. While the ultimate agent of mammoth extinction remains unknown, the work of Nyström et al. (2012). suggests that we should be looking for something sudden, like a rapid change in climate/ecology or perhaps the arrival of humans.

 Sergey Vartanyan during field collection, holding a woolly mammoth tusk found along a river embankment in northeast Siberia (photographer: Diana Solovyeva).

image
Prognostic yield of esophageal manometry in chronic intestinal pseudo‐obstruction: a retrospective cohort of 116 adult patients
Authors: AMIOT A. , JOLY F. , CAZALS‐HATEM D. , MERROUCHE M. , JOUET P. , COFFIN B. , BOUHNIK Y.
Published: July 2012

Background  Chronic intestinal pseudo‐obstruction (CIPO) refers to a wide and heterogeneous group of neuromuscular disorders, which classically involve the small intestine. However, further investigation is required to determine if motility disturbances involve all parts of the gastrointestinal (GI) tract.

Methods  Medical records and follow‐up examinations of 116 adult CIPO patients [70F, median age 28 (0–79) years] were reviewed and performed at our institution since 1980. Manometry (esophageal, small bowel and anorectal) and gastric emptying scintigraphy reports were retrieved and analyzed. Survival, home parenteral nutrition requirement, and the inability to maintain sufficient oral feeding was analyzed using univariate and multivariate analysis.

Key Results  The median follow‐up time was 6 (0.1–30) years. In all, 90% of patients who underwent at least one motility test, with the exception of small bowel manometry, exhibited at least one abnormal pattern. Esophageal manometry was abnormal in 73% of the cases, including 51% with severe ineffective esophageal motility. Anorectal manometry was abnormal in 59% of the cases, including only 17% with severe abnormalities. Gastric emptying was abnormal in 61% of the cases. Only esophageal motor disorders had significant predicting values for survival, home parenteral nutrition requirement, and an inability to maintain sufficient oral feeding.

Conclusions & Inferences  Our study showed that CIPO was associated with a diffuse involvement of all parts of the GI tract and was not restricted to the small intestine in 90% of the cases studied. Esophageal manometry had a significant prognostic yield and should be systematically performed in CIPO patients.
Optimal stomatal conductance in relation to photosynthesis in climatically contrasting Eucalyptus species under drought
Authors: HÉROULT ARNAUD , LIN YAN‐SHIH , BOURNE AIMEE , MEDLYN BELINDA E. , ELLSWORTH DAVID S.
Published: July 2012

Models of stomatal conductance (gs) are based on coupling between gs and CO2 assimilation (Anet), and it is often assumed that the slope of this relationship (‘g1’) is constant across species. However, if different plant species have adapted to different access costs of water, then there will be differences in g1 among species. We hypothesized that g1 should vary among species adapted to different climates, and tested the theory and its linkage to plant hydraulics using four Eucalyptus species from different climatic origins in a common garden.

Optimal stomatal theory predicts that species from sub‐humid zones have a lower marginal water cost of C gain, hence lower g1 than humid‐zone species. In agreement with the theory that g1 is related to tissue carbon costs for water supply, we found a relationship between wood density and g1 across Eucalyptus species of contrasting climatic origins. There were significant reductions in the parameter g1 during drought in humid but not sub‐humid species, with the latter group maintaining g1 in drought. There are strong differences in stomatal behaviour among related tree species in agreement with optimal stomatal theory, and these differences are consistent with the economics involved in water uptake and transport for carbon gain.
Benzoylation and sinapoylation of glucosinolate R‐groups in Arabidopsis
Authors: Lee Shinyoung , Kaminaga Yasuhisa , Cooper Bruce , Pichersky Eran , Dudareva Natalia , Chapple Clint
Published: July 2012

Glucosinolates (GSLs) are nitrogen‐ and sulfur‐containing metabolites that contribute to human health and plant defense. The biological activities of these molecules are largely dependent on modification of the GSL R‐groups derived from their corresponding amino acid precursors. In Arabidopsis seeds, esterification of the R‐group of hydroxylated GSLs (OH‐GSLs) leads to the accumulation of benzoylated GSLs (BzGSLs) and sinapoylated GSLs (SnGSLs). BzGSLs were thought to be synthesized from OH‐GSLs and benzoyl CoA by a BAHD acyltransferase, but no BAHD gene is strongly co‐expressed with the two reference genes BZO1 and AOP3 that are required for BzGSL biosynthesis. In contrast, three genes encoding serine carboxypeptidase‐like (SCPL) acyltransferases [SCPL5, SCPL17 and SCPL19 (SNG2)] do exhibit strong co‐expression. Using a reverse genetic approach, we found that the GSL profile of the scpl5 mutant was identical to that of wild‐type, but both BzGSLs and SnGSLs were barely detectable in scpl17 mutants and their amounts were decreased in the sng2 mutant. In addition, both scpl17 and sng2 mutants accumulate the putative BzGSL precursors OH‐GSLs and benzoylglucose. The results of further GSL analyses in other phenylpropanoid mutants and benzoate feeding experiments suggested that SCPL17 mediates the acyltransferase reaction directly, while the mutation in sng2 causes a decrease in BzGSLs and SnGSLs via an unknown indirect mechanism. Finally, benzoate feeding experiments using bzo1 mutants and BZO1 biochemical characterization indicated that the in vivo role of BZO1 is to synthesize the benzoate precursor cinnamoyl CoA rather than to generate benzoyl CoA from benzoate and CoA as previously predicted.
The role of textures to improve the detection accuracy of Rumex obtusifolius in robotic systems
Authors: HIREMATH S , VAN DER HEIJDEN G , VAN EVERT F K , STEIN A
Published: July 2012

Hiremath S, Van Der Heijden G, Van Evert FK & Stein A (2012) The role of textures to improve the detection accuracy of Rumex obtusifolius in robotic systems. Weed Research.52, 430–440.

Rumex obtusifolius is a common weed that is difficult to control in organic farming systems. Among the proposed non‐chemical treatment methods, robotic systems to mechanically remove the weed have potential for its automatic detection and removal. This article considers a recently developed robot with a real‐time vision system capable of detecting R. obtusifolius in a pasture with the objective of improving its detection accuracy. We show that the texture measure used by the current system is equivalent to local variance and has limited value for detecting R. obtusifolius in a complex background like pasture. To improve the system, two different sets of visual texture features corresponding to Gray level Co‐occurence Matrix (GLCM) and Laws’ filter masks were investigated. Through feature selection, we determined that GLCM features of contrast, entropy and correlation were the best among the two sets of features and were 25% more accurate in estimating the taproot location than the current system. We incorporated these texture features in a new segmentation algorithm and demonstrated its robustness by testing it on a data set of 92 images with high complexity in terms of variation in illumination and weed size. The new segmentation algorithm had a detection accuracy of 90%, with an average error of 141 mm in the estimation of the location of the taproot of R. obtusifolius, compared with 308 mm with the former algorithm.
Thymic stromal lymphopoietin stimulates the formation of eosinophil extracellular traps
Authors: Morshed M. , Yousefi S. , Stöckle C. , Simon H.‐U. , Simon D.
Published: July 2012

Background

Thymic stromal lymphopoietin (TSLP) that is released by epithelial cells upon certain environmental triggers activates cells of the innate and adaptive immune system resulting in a preferential T helper 2 immune response. By releasing eosinophil extracellular traps (EETs), eosinophils achieve an efficient extracellular bacterial killing. Eosinophil extracellular traps release, however, has been observed in both infectious and noninfectious eosinophilic diseases. Here, we aim to investigate whether eosinophils generate functional EETs as a direct response to TSLP, and further to study the extra‐ and intracellular mechanisms involved in this process as well as TSLP receptor (TSLPR) expression by eosinophils in vitro and in vivo.

Methods

Thymic stromal lymphopoietin receptor expression on blood and tissue eosinophils was assessed by immunoblotting, flow cytometry, and immunofluorescence staining. Purified eosinophils were stimulated with recombinant human TSLP. The release of extracellular DNA in association with eosinophilic cationic protein (ECP) was detected by fluorescence staining techniques and confocal microscopy. In addition, cell survival, cell adhesion, production of reactive oxygen species (ROS), and the inhibition of bacterial growth by TSLP‐stimulated eosinophils were measured.

Results

Thymic stromal lymphopoietin receptor was observed on peripheral blood eosinophils as well as on tissue infiltrating eosinophils in skin diseases. TSLP did not affect eosinophil survival, but induced the formation of EETs consisting of mitochondrial DNA in association with ECP in a concentration‐ and time‐dependent manner. Eosinophil extracellular trap release could be inhibited by blocking either cell adhesion or ROS production. While eosinophils prevented the growth of both Staphylococcus aureus and Staphylococcus epidermidis, the latter were unable to elicit EET formation and eosinophils required additional TSLP stimulation to achieve this antibacterial activity.

Conclusions

thymic stromal lymphopoietin directly stimulates eosinophils to produce EETs. Our observations link epithelial TSLP expression triggered by environmental factors with pathogen defense mechanisms involving eosinophils.
TNF‐alpha is a key mediator in the development of Th2 cell response to inhaled allergens induced by a viral PAMP double‐stranded RNA
Authors: Choi J.‐P. , Kim Y.‐S. , Kim O. Y. , Kim Y.‐M. , Jeon S. G. , Roh T.‐Y. , Park J.‐S. , Gho Y. S. , Kim Y.‐K.
Published: July 2012

Background

Viral pathogen–associated molecular patterns, such as dsRNA, disrupt airway tolerance to inhaled allergens. Specifically, the Th2 and Th17 cell responses are induced by low‐dose dsRNA and the Th1‐dominant response by high‐dose dsRNA.

Objective

In this model, we evaluate the role of TNF‐α in the development of adaptive immune dysfunction to inhaled allergens induced by airway sensitization with dsRNA‐containing allergens.

Methods

A virus‐associated asthma mouse model was generated via simultaneous airway administration of ovalbumin (OVA) and low (0.1 μg) or high (10 μg) doses of polyinosine–polycytidylic acid (poly[I:C]). The effect of TNF‐α on Th2 airway inflammation was evaluated using TNF‐α‐deficient mice and recombinant TNF‐α.

Results

TNF‐α production was enhanced by airway exposure to low and high doses of poly[I:C]. After airway sensitization with OVA plus low‐dose poly[I:C], TNF‐α‐deficient mice exhibited less OVA‐induced airway inflammation than did wild‐type (WT) mice. However, this did not occur upon sensitization with high‐dose poly[I:C]. In terms of T‐cell response, the production of IL‐4 from lung T cells after OVA challenge was enhanced by airway sensitization with OVA plus low‐dose poly[I:C] in WT mice, and this phenotype was inhibited by the absence of TNF‐α. Moreover, the Th2 cell response induced by sensitization with OVA plus low‐dose poly[I:C], which was abolished in TNF‐α‐deficient mice, was restored in these mice upon addition of recombinant TNF‐α.

Conclusion

The results of this study suggest that TNF‐α produced by airway exposure to low‐dose dsRNA is a key mediator in the development of Th2 cell response to inhaled allergens.
Height matters: position above the substratum influences the growth of two demosponge species
Authors: McLean Elizabeth L. , Lasker Howard R.
Published: July 2012

In benthic communities sponges commonly outcompete other organisms in the race for suitable space. Superior competitive ability allows them to grow and overgrow other sessile organisms, some of these being octocorals. Acquiring substratum space, a resource often more limiting than food, is the obvious benefit of these competitive interactions. However, sponges that overgrow larger structures such as branching octocorals also change their position in the water column, and potentially their access to food and exposure to grazers. This study explored the potential benefit of sponge–octocoral associations by examining the effect of height off the bottom on growth of two species of ropelike demosponges under natural conditions. The growths of Amphimedon compressa and Iotrochota birotulata were monitored over 12 months at Cross Harbour, Great Abaco, The Bahamas, using small (5‐cm) sponge fragments that were established at three heights above the bottom (0–5, 30, 60 cm). Growth rates differed among the two species and among different heights. Over 12 months, the mean volumetric growth for A. compressa was 17.7 cm3 ± 1.4 compared with 8.9 cm3 ± 1.4 for I. birotulata. Both species had a higher growth rate at the 60‐cm level. These results suggest that these ropelike sponges benefit from their association and growth on octocorals, not only by using the octocoral skeletal axis as support, but also by acquiring exposure to higher water flow.
Sponge disease in the Adriatic Sea
Authors: Di Camillo Cristina G. , Bartolucci Igor , Cerrano Carlo , Bavestrello Giorgio
Published: July 2012

A mass mortality episode involving three marine dyctioceratid sponges, Ircina variabilis, Sarcotragus spinosulus and Spongia officinalis, was observed on ‘Scoglio del Trave’ (Conero Promontory, North Adriatic Sea) in late summer 2009. In this area, calm sea and high temperatures throughout summer created unfavorable environmental conditions, leading to the outbreak of the disease. Affected specimens showed evident necrotic areas and portions with bare skeleton, and many specimens of S. spinosulus were covered with a white mat of cyanobacteria. In September 2009, about 22% of these demosponges suffered from this disease. The mortality event ceased when sea temperature dropped below 20 °C. Small specimens turned out to be more sensitive to the diseases, whereas the damaged tissues of large specimens were able to recover. In October, the damaged specimens were detached by the rough sea and more than 900 beached sponges were found along the 1‐km‐long beach, showing the seriousness of the phenomenon, which probably involved not only the area studied but also areas adjacent to it.
Placebo controlled evaluation of Xilei San, a herbal preparation in patients with intractable ulcerative proctitis
Authors: Fukunaga Ken , Ohda Yoshio , Hida Nobuyuki , Iimuro Masaki , Yokoyama Yoko , Kamikozuru Koji , Nagase Kazuko , Nakamura Shiro , Miwa Hiroto , Matsumoto Takayuki
Published: July 2012

Background and Aim:  Topical mesalamine or corticosteroid has shown efficacy in patients with ulcerative proctitis, but patients often become refractory to these interventions. Xilei San is a herbal preparation with evidence of anti‐inflammatory effects. We evaluated the efficacy of topical Xilei San in ulcerative proctitis patients.

Methods:  In a double blind setting, 30 patients with intractable ulcerative proctitis despite ≥ 4 weeks of topical mesalamine or corticosteroid were randomly assigned to True (n = 15) and placebo (n = 15). Patients in True received suppository Xilei San (0.1 g/dose per day of Xilei San), the other 15 received placebo suppository. The initial efficacy was evaluated on day 14. Primary endpoint of the trial was avoiding relapse during 180 days, relapse meant recurrence of active disease. Riley's index was applied for endoscopic and histological evaluations, while patients' quality of life was evaluated by an inflammatory bowel disease questionnaire.

Results:  On day 14, the number of patients who achieved remission, clinical activity index ≤ 4 in True was significantly higher versus placebo (P < 0.04). Likewise, at day 180, an 81.8% of patients in True were without relapse versus 16.7% in placebo (P < 0.001). Further, significant endoscopic (P < 0.01), histological (P < 0.02) and inflammatory bowel disease questionnaire (P < 0.04) improvements were observed in True, but not in placebo.

Conclusions:  This is the first controlled investigation showing significant clinical and endoscopic efficacy for Xilei San in patients with intractable ulcerative proctitis. Topical Xilei San was well tolerated, and was without safety concerns.
Primary rhabdoid tumor with low grade glioma component of the central nervous system in a young adult
Authors: Endo Shogo , Terasaka Shunsuke , Yamaguchi Shigeru , Ikeda Hitoshi , Kato Tsutomu , Kobayashi Hiroyuki , Tanaka Shinya , Houkin Kiyohiro
Published: July 2012

In the CNS, primary tumors with rhabdoid components are classified as atypical teratoid/rhabdoid tumor, rhabdoid meningioma or rhabdoid glioblastoma. The authors present a young adult patient with supratentorial rhabdoid tumor incidentally found after head trauma as a small pre‐existing lesion in the parahippocampal gyrus. MRI demonstrated an area of hypointensity on T1‐weighted images and hyperintensity on T2‐weighted and fluid attenuated inversion recovery images. A serial MR scan revealed no change 3 months after the initial examination but drastic changes at 6 months. As the tumor and accompanying intratumoral hemorrhage enlarged rapidly, resection of the tumor was performed. Histopathology revealed that the main component of the tumor was typical rhabdoid cells with some necrotic areas. There were also pathological features consistent with oligoastrocytoma. The specimen had neither vascular proliferation usually seen in high‐grade glioma nor the meningothelial pattern that suggests meningioma. Immunohistochemical findings revealed that cells were strongly positive for vimentin, epithelial membrane antigen and INI‐1 antibody throughout the specimen. Further, monosomy 22 was detected by fluorescence in situ hybridization. The tumor was finally thought to be an unclassifiable primitive rhabdoid tumor with oligoastrocytoma that arose in the CNS. The patient died within 5 months of detection of the tumor, regardless of surgical resection, radiotherapy and chemotherapy.
Gaps in health care for the somatic health of outpatients with severe mental illness
Authors: van Hasselt Fenneke M. , Schorr Susanne G. , Mookhoek Evert J. , Brouwers Jacobus R. B. J. , Loonen Anton J. M. , Taxis Katja
Published: July 2012

The physical health of outpatients with severe mental illness (SMI) can be improved by changes in the health‐care system. Analysis of current practice is necessary to develop these strategies. We compared the number of somatic health problems of outpatients with SMI with the frequency of consulting a general practitioner (GP). This was a cross‐sectional study based on interviews, and records from the GP and the pharmacy. We checked whether Dutch community pharmacies had complete and correct information about the patients' medication. We observed that all patients (n = 118) had somatic problems in need of clinical attention. Patients who visited their GP less than once a year (35%, n = 42), had a mean of 2.8 somatic health problems. This was less than patients who consulted their GP more than once a year (P ≤ 0.01). In 37% of cases, the pharmacy did not have adequate information on the drug use. Many patients with SMI seemed to have insufficient contact with their GP for their somatic health problems. Insufficient information about the patients' medication suggested that the pharmacist and GP should increase exchange of information. Mental health nurses can take a lead in coordinating the care to improve somatic health for their patients.
Discordance in Pena–Shokeir phenotype/fetal akinesia deformation sequence in a monoamniotic twin
Authors: Mayumi Miyuki , Obata‐Yasuoka Mana , Ogura Tsuyoshi , Hamada Hiromi , Miyazono Yayoi , Yoshikawa Hiroyuki
Published: July 2012

We here report the first case of discordant Pena–Shokeir phenotype observed in monoamniotic twins. A 34‐year‐old woman, pregnant with twins, was referred at 10 weeks' gestation because one of the twins had increased nuchal translucency. Serial ultrasonographic examinations suggested that twin A may have had several other abnormalities, including pleural effusion at 21 weeks' gestation, decreased movement and contracted limbs at 24 weeks, and fetal growth restriction at 26 weeks. No abnormalities were observed in twin B. At 34 weeks of gestation, the twins were delivered by cesarean section. There were cord entanglements, and although the resuscitation of twin A was attempted, it proved difficult due to lockjaw. Twin A died during the second hour of life, and autopsy findings were consistent with the diagnosis of Pena–Shokeir phenotype. We suggest that cord entanglement during early gestation is a possible cause for the occurrence of Pena–Shokeir phenotype through an anoxic‐ischemic mechanism.
Metastatic adenocarcinoma of mammary‐like glands of the vulva successfully treated with surgery and hormonal therapy
Authors: Benito Virginia , Arribas Sara , Martínez David , Medina Norberto , Lubrano Amina , Arencibia Octavio
Published: July 2012

Vulvar cancer is a rare malignancy; most tumors are squamous cell type while adenocarcinomas are rare. Primary adenocarcinomas of the vulva predominantly include extramammary Paget's disease and sweat gland carcinomas. Greene first described a rare form of adenocarcinoma in 1936, which was called adenocarcinoma of mammary‐like glands of the vulva because of its morphologic and immunohistochemical resemblance to breast adenocarcinomas. In the management of this entity, varying combinations of surgery, radiation therapy, systemic chemotherapy and/or hormonal therapy may be used, as in patients with orthotopic breast carcinoma. However, hormonal therapy leads the way in patients with positive hormonal receptors, where other therapies cannot be used due to comorbidities or advanced age. We present the first reported case of an elderly patient with metastatic vulvar adenocarcinoma arising from mammary‐like glands, successfully treated with a combination of surgery and hormonal therapy.
Evidence for intersexual chemical mimicry in a dioecious plant
Authors: Soler Catherine C. L. , Proffit Magali , Bessière Jean‐Marie , Hossaert‐McKey Martine , Schatz Bertrand
Published: July 2012

The dioecious Mediterranean fig, Ficus carica, displays a unique phenology in which males sometimes bloom synchronously with females (in summer), and sometimes not (in spring). Ficus carica is engaged in an obligatory mutualism with a specific pollinating wasp, which reproduces only within figs, localising them by their specific scents. We show that scents emitted by male figs show seasonal variation within individual trees. Scents of summer male figs resemble those of the co‐flowering females, and are different from those of the same male trees in spring, when female figs are absent. These differences hold even if only compounds electrophysiologically active for pollinators are considered. The similar scents of summer males and females may explain why the rewardless females are still pollinated. These results offer a tractable model for future studies of intersexual chemical mimicry in mutualistic pollination interactions.
Safety, pharmacokinetics and pharmacodynamics of multiple‐ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus
Authors: Morrow L. A. , Leonsson‐Zachrisson M. , Ericsson H. , Wollbratt M. , Knutsson M. , Hompesch M. , Norjavaara E.
Published: July 2012

Aims

To assess the safety, pharmacokinetics and pharmacodynamics of multiple‐ascending doses of the novel glucokinase activator AZD1656 in patients with type 2 diabetes mellitus (T2DM).

Methods

This randomized, single‐blind, placebo‐controlled, monotherapy study was carried out in two parts. In part A, 32 patients received AZD1656 (7, 20, 40 or 80 mg) twice daily or placebo for 8 days in hospital. In part B, another 20 patients received, as outpatients, individually titrated AZD1656 15–45 mg twice daily or placebo for 28 days. Safety, pharmacokinetics and pharmacodynamic variables were evaluated.

Results

AZD1656 was generally well tolerated. Pharmacokinetics of AZD1656 were virtually dose‐ and time‐independent. AZD1656 was rapidly absorbed and eliminated. An active metabolite was formed which had a longer half‐life than AZD1656, but showed ∼15% of the area under the plasma concentration versus time curve from 0 to 24 h compared with that of AZD1656. Renal excretion of AZD1656 and the metabolite was low. In part A, fasting plasma glucose (FPG) was reduced by up to 21% and mean 24‐h plasma glucose was reduced by up to 24% with AZD1656 versus placebo, depending on dose. No dose‐related changes in serum insulin or C‐peptide were observed with AZD1656 at the end of treatment. Results in part B confirmed the glucose‐lowering effect of AZD1656 versus placebo.

Conclusions

AZD1656 was well tolerated with predictable pharmacokinetics in patients with T2DM. Dose‐dependent reductions in plasma glucose were observed.
A qualitative exploration of the effects of increasing the minimum purchase age of alcohol inThailand
Authors: Limaye Rupali J. , Srirojn Bangorn , Lilleston Pam , Aramrattana Apinun , Thomson Nicholas , Celentano David D. , Sherman Susan G.
Published: July 2012

Introduction and Aims

Although prevalence of alcohol consumption has been relatively stable amongThai youth, concerns over alcohol‐related harms affecting youth influenced the passage of new laws in early 2008, which made it illegal to sell alcohol to anyone under the age of 20. This qualitative study explored the effects of the law on the purchasing patterns of underageThai bar patrons, in order to understand the strategies employed by underage youth to circumvent the law.

Design and Methods

A total of 41 in‐depth interviews were conducted with 18‐ to 19‐year‐old bar patrons inChiangMai,Thailand.

Results

Underage Thai bar patrons frequented shops where enforcement was not strict and purchased alcohol from familiar shopkeepers in their neighbourhoods. Participants suggested that purchasing alcohol was relatively easy as long as shopkeepers were driven by the need to make a profit.

Discussion and Conclusions

To address alcohol‐related harms, the control law must be enforced in a meaningful way to deter youth from purchasing alcohol. Otherwise, the law will have minimal effectiveness in reducing the harms associated with alcohol.
ASSESSING THE EFFECT OF PUBLIC SUBSIDIES ON FIRM R&D INVESTMENT: A SURVEY
Authors: Zúñiga‐Vicente José Ángel , Alonso‐Borrego César , Forcadell Francisco J. , Galán José I.
Published: July 2012

This survey examines the empirical literature on the relationship between public R&D subsidies and private R&D investment over the past five decades. The survey reveals a considerable heterogeneity of empirical results that cannot be explained fully by methodological issues. We aim to provide further explanations of the possible causes of that heterogeneity. In particular, we emphasise a set of issues that, in our view, are critical to understanding the potential effect of public R&D subsidies on private R&D spending. Special attention is paid to the dynamic aspects and composition of firm R&D, the constraints faced by the firm (such as financial constraints), and the amount and source of public subsidies. None of these issues have been investigated in depth. We formulate a set of research assumptions to guide future empirical research in this field.