bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Entero‐Test, a simple approach for non‐invasive clinical evaluation of the biliary disposition of drugs
Authors: Guiney William J. , Beaumont Claire , Thomas Steve R. , Robertson Darren C. , McHugh Simon M. , Koch Annelize , Richards Duncan
Published: March 2011

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT

• Biliary secretion is often a major route of elimination of drugs and metabolites. Knowledge of the biliary disposition of a drug in man is important in understanding the contribution of this route to overall clearance and the potential for drug–drug interactions which may have clinical consequences.

• Current methods for collecting human bile as part of drug disposition studies are invasive and complex, requiring intubation of the duodenum. As a result, limited data exist regarding the biliary elimination of many drugs and their metabolites.

WHAT THIS STUDY ADDS

• This proof of utility study clearly demonstrates that bile samples for drug and metabolite analysis can be collected simply, safely and cost‐effectively from subjects using non‐invasive technology.

• Using such technology, the biliary disposition of simvastatin was evaluated successfully in healthy subjects. Qualitative metabolite data compared favourably with reported biliary data derived from intubated patients dosed with radiolabelled simvastatin.

• This technique has substantial utility for early clinical evaluation of biliary disposition of drugs.

AIM To evaluate the non‐invasive collection of bile from healthy human subjects for the qualitative characterization of the biliary disposition of a drug, using spectrometric techniques.

METHODS Twenty subjects underwent non‐invasive bile capture using a peroral string test (Entero‐Test) device prior to and following a single oral dose of simvastatin (80 mg). The device, consisting of a weighted gelatin capsule containing a highly absorbent nylon string, was swallowed by each subject with the proximal end of the string taped to the face. Once the weighted string was judged to have reached the duodenum, gallbladder contraction was stimulated in order to release bile. The string was then retrieved via the mouth, and bile samples were analysed for drug‐related material using spectrometric and spectroscopic techniques following solvent extraction.

RESULTS Numerous metabolites of simvastatin were detected, and the major metabolites were consistent with those reported from studies where bile was collected using invasive techniques from patients dosed with [14C]‐simvastatin.

CONCLUSIONS The results from this study demonstrate the utility of deploying the Entero‐Test in human studies to provide structural information on biliary metabolites. This can be readily applied in drug development studies, including those in the target patient population and may eliminate the need for more invasive sampling techniques.
Paracetamol in pregnancy and the risk of wheezing in offspring: a systematic review and meta‐analysis
Authors: Eyers S. , Weatherall M. , Jefferies S. , Beasley R.
Published: March 2011

Cite this as: S. Eyers, M. Weatherall, S. Jefferies and R. Beasley, Clinical & Experimental Allergy, 2011 (41) 482–489.

Background
There is evidence to suggest that the risk of asthma might be increased with exposure to paracetamol in the intrauterine environment, infancy, later childhood and adult life.

Objective
To review the evidence from studies investigating the association between paracetamol use in pregnancy and childhood asthma.

Methods
A systematic review and meta‐analysis was undertaken of studies reporting the association between paracetamol use in pregnancy and subsequent asthma in childhood. The primary outcome variable was wheeze in the last 12 months. For tabulated raw data, not adjusted for confounders, random effects odds ratios (OR) were pooled by the inverse variance weighted method.

Results
There were six studies identified that were included in the meta‐analysis. The age of children studied ranged from 30 to 84 months. The pooled random effects OR for the risk of current wheeze in the children of women who were exposed to any paracetamol during any stage of pregnancy was 1.21 (95% confidence interval 1.02–1.44). Features of the studies variably included an association with paracetamol use during all trimesters of pregnancy and an association with persistent asthma, severe asthma, and with atopy.

Conclusion and clinical relevance
The use of paracetamol during pregnancy is associated with an increased risk of childhood asthma. More research is urgently required to determine the impact of paracetamol during pregnancy on the risk of wheezing in offspring so that appropriate public health recommendations can be made.
The role of atorvastatin in regulating the immune response leading to vascular damage in a model of Kawasaki disease
Authors: Blankier S , McCrindle B W , Ito S , Yeung R S M
Published: March 2011

Superantigens have been implicated in a number of diseases including Kawasaki disease (KD), a multi-system vasculitis resulting in coronary artery aneurysms. We have characterized a murine disease model in which coronary arteritis is induced by a novel superantigen found in Lactobacillus casei cell wall extract (LCWE). Using this animal model of KD, we have identified three pathogenic steps leading to coronary artery aneurysm formation. These steps include T cell activation and proliferation, production of the proinflammatory cytokine tumour necrosis factor (TNF)-α and up-regulation of matrix metalloproteinase 9 (MMP-9), an elastolytic protease. In addition to their cholesterol-lowering effects, 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors (statins) have pleotropic immunomodulatory properties. Thus, we examined the effect of atorvastatin in modulating each of these three critical pathogenic processes leading to aneurysm formation in the disease model. Atorvastatin inhibited lymphocyte proliferation in response to superantigen stimulation in a dose-dependent manner. This inhibition was also observed for production of soluble mediators of inflammation including interleukin (IL)-2 and TNF-α. The inhibitory effect on proliferation was rescued completely by mevalonic acid, confirming that the mechanism responsible for this inhibitory activity on immune activation was inhibition of HMG-CoA reductase. Similarly, TNF-α-induced MMP-9 production was reduced in a dose-dependent manner in response to atorvastatin. Inhibition of extracellular-regulated kinase (ERK) phosphorylation appears to be the mechanism responsible for inhibition of MMP-9 production. In conclusion, atorvastatin is able to inhibit critical steps known to be important in the development of coronary aneurysms, suggesting that statins may have therapeutic benefit in patients with KD.
Saving the largest makes a difference: exploring effects of harvest regulations by model simulations for noble crayfish, Astacus astacus
Authors: SADYKOVA D. , SKURDAL J. , HESSEN Dag O. , SCHWEDER T.
Published: March 2011

Abstract  Harvesting regulations for crustacean decapods generally focus on total catch and minimum legal size of individuals. However, there are trade‐offs between total catch and minimum size, and possibly also for maximum size. The outcome of various harvesting restrictions was assessed by model iterations for one lake based on a long time series (29 years) of crayfish population size and annual harvesting. The paper explores how this decline might have been avoided by alternative harvest regulations based on a strong decline in the surveyed population and use of a deterministic model with two stable equilibria. The results of the model simulations suggested that the decline may have been avoided by reducing the annual catches by 15% without changing the minimum size regulation of 95 mm. The decline may also have been avoided by protecting the largest (and most fecund) individuals, e.g. by allowing harvesting of crayfish between 50 and 98 mm without reducing the total catches. The latter strategy might also have counteracted a long‐term evolution towards smaller crayfish caused by selective harvesting of the largest individuals.
Artificial neural network forward modelling and inversion of electrokinetic logging data
Authors: Ardjmandpour N. , Pain C. , Singer J. , Saunders J. , Aristodemou E. , Carter J.
Published: March 2011

An artificial neural network method is proposed as a computationally economic alternative to numerical simulation by the Biot theory for predicting borehole seismoelectric measurements given a set of formation properties. Borehole seismoelectric measurements are simulated using a finite element forward model, which solves the Biot equations together with an equation for the streaming potential. The results show that the neural network method successfully predicts the streaming potentials at each detector, even when the input pressures are contaminated with 10% Gaussian noise. A fast inversion methodology is subsequently developed in order to predict subsurface material properties such as porosity and permeability from streaming potential measurements. The predicted permeability and porosity results indicate that the method predictions are more accurate for the permeability predictions, with the inverted permeabilities being in excellent agreement with the actual permeabilities. This approach was finally verified by using data from a field experiment. The predicted permeability results seem to predict the basic trends in permeabilities from a packer test. As expected from synthetic results, the predicted porosity is less accurate. Investigations are also carried out to predict the zeta potential. The predicted zeta potentials are in agreement with values obtained through experimental self potential measurements.
Nurses’ wishes, knowledge, attitudes and perceived barriers on implementing research findings into practice among graduate nurses in Austria
Authors: Breimaier Helga E , Halfens Ruud JG , Lohrmann Christa
Published: March 2011

Aims.  To identify and describe nurses’ wishes, needs, knowledge and attitudes to nursing research, as well as perceived barriers to and facilitators of research utilisation in nursing practice in Austria.

Background.  Research results are not always used in daily nursing practice, despite their potential to improve nursing care quality. A variety of factors impede their implementation and use. Nurses’ wishes about research utilisation have scarcely been reported. No data are available yet from an Austrian perspective.

Design.  Descriptive and exploratory cross‐sectional survey.

Methods.  The study was conducted in an Austrian university hospital in May 2007, including all graduate nurses (n = 1825). One thousand and twenty‐three nurses returned the self‐reported questionnaire. Descriptive analysis was performed initially, then group comparisons (diploma <2001, ≥2001) were computed inferentially using the chi‐square test.

Results.  Nurses’ most frequently indicated wishes regarding research implementation were adequate information, structural availability and professional support. Special points of interest were topics concerning nursing phenomena and interventions. Nurses’ needs related to education in nursing science/research and its implementations were indicated as being predominantly of an introductory manner. Overall, nurses’ attitudes tended to the negative. The top three named barriers to research utilisation were lack of time (69·9%), lack of information/knowledge (45·4%) and lack of interest (25·9%). Ten statistically significant differences were found between nurses of the two compared diploma groups.

Conclusions.  Participating nurses perceived a lack in sufficient education/information and adequate organisational support, impeding them to use research results in daily practice.

Relevance to clinical practice.  The results provide important insights into the matter of nurses’ needs regarding the use and/or implementation of research results in practice, as well as about the promotion of positive attitudes towards research and its utilisation. These findings are of special interest to nurse educators, employers and countries introducing nursing science to improve the clinical outcomes for patients.
Living with life insurance: a qualitative analysis of the experience of male implantable defibrillator recipients in Spain
Authors: Palacios‐Ceña Domingo , Losa Marta E , Fernández‐de‐las‐Peñas César , Salvadores‐Fuentes Paloma
Published: March 2011

Background and objectives.  The implantation of defibrillators should not be studied simply on the basis of clinical improvement or quality of life: it is also important to understand the significance, which the recipients attach to the defibrillator and their experiences with it. The aim of this work was, therefore, to determine the experience of Spanish implantable defibrillator recipients.

Design.  A qualitative phenomenological study.

Methods.  Purposeful sampling of male implantable defibrillator recipients older than 18 years of age attended at the defibrillator consultancy at the Hospital Fuenlabrada or belonging to the Heart Patients’ Association (Asociación de Pacientes Coronarios, APACOR). A secondary, theoretical sampling was also carried out to gain a more in‐depth understanding of certain aspects identified in the first sampling, such as living with the discharges and difficulties during sexual activity. Data were collected using unstructured and semi‐structured questionnaires and applying a question guide, field notes and the recipients’ personal diaries/letters. Data collection was terminated once theoretical saturation was reached. Data were analysed using the Giorgi method. Finally, the seven themes, which showed what it means to be an implantable cardioverter‐defibrillator recipient, were described.

Results.  The defibrillator is perceived positively and is considered to be a form of life insurance, whereas the discharges are a limiting factor. The recipient’s outlook on life changes. Acceptance of the changes resulting from the implant leads to the development of strategies to facilitate everyday life.

Conclusions.  An understanding of the significance attached by recipients to their disease, diagnosis and treatment allows their behaviour and expectations to be understood.

Relevance to clinical practice.  Provide the basis for nursing assessment after discharge, understand the effects of the device in the recipient and track the process of adapting the recipient to daily life.
Dementia and loneliness: an Australian perspective
Authors: Moyle Wendy , Kellett Ursula , Ballantyne Alison , Gracia Natalie
Published: March 2011

Aim.  To explore the perceptions of loneliness according to people with early‐stage dementia, living in community and long‐term care and also the views of their family carers.

Background.  Research that specifically explores the influence of loneliness on dementia is limited and indicates the prevalence of loneliness and the negative relationship between loneliness and cognitive decline. There is a paucity of research that explores loneliness from the perspective of the person with dementia.

Design.  A descriptive exploratory qualitative approach was used.

Methods.  Data were collected through semi‐structured audio‐taped interviews. A purposive sample of 70 people with a diagnosis or probable dementia and 73 family carers were recruited from community and long‐term care from South East Queensland, Australia.

Results.  Four themes were identified: staying connected to others; losing the ability to socially engage; experiencing loneliness; and overcoming loneliness. The results emphasise the importance of familiar human relationships in reducing the feelings of loneliness in people experiencing dementia.

Conclusions.  People with dementia are at risk of loneliness, but placing them with unfamiliar people and environments may not improve their situation.

Relevance to clinical practice.  Better refinement of care that takes into account the potential for loneliness and an understanding of premorbid social tendency may assist in the implementation of individualised and evidence‐based strategies to assist people with dementia to lead a better quality of life. To maintain well‐being, the social needs of the person with dementia as well as the family need to be considered.
Not too loose, not too tight – just right. Biphasic control of the Tsr HAMP domain
Authors: Manson Michael D.
Published: March 2011

HAMP domains communicate between input and output signalling modules in a wide variety of bacterial sensor proteins. In the Tsr chemoreceptor, they convert a signal initiated by binding of serine to the periplasmic domain of the protein into regulation of receptor control of the CheA kinase, and ultimately of the direction of flagellar rotation. In this issue, Zhou et al. report an extensive mutational analysis of the Tsr HAMP domain that shows that it can assume a number of different signalling states, which presumably correspond to a variety of different conformations. The two conformational extremes of a tightly packed and a loosely packed HAMP four‐helix bundle support only low levels of CheA activity. Thus, Tsr HAMP does not function as a simple on‐off, two‐state device but rather as a dynamic structure with biphasic control. The normal physiological operating range of Tsr is proposed to be at intermediate degrees of packing of the HAMP four‐helix bundle, but HAMP domains in other proteins could occupy different portions of the conformational spectrum.
In vivo phosphorylation patterns of key stressosome proteins define a second feedback loop that limits activation of Bacillus subtilis	σB
Authors: Eymann Christine , Schulz Stephan , Gronau Katrin , Becher Dörte , Hecker Michael , Price Chester W.
Published: March 2011

The Bacillus subtilis stressosome is a 1.8 MDa complex that orchestrates activation of the σB transcription factor by environmental stress. The complex comprises members of the RsbR co‐antagonist family and the RsbS antagonist, which together form an icosahedral core that sequesters the RsbT serine‐threonine kinase. Phosphorylation of this core by RsbT is associated with RsbT release, which activates downstream signalling. RsbRA, the prototype co‐antagonist, is phosphorylated on T171 and T205 in vitro. In unstressed cells T171 is already phosphorylated; this is a prerequisite but not the trigger for activation, which correlates with stress‐induced phosphorylation of RsbS on S59. In contrast, phosphorylation of RsbRA T205 has not been detected in vivo. Here we find (i) RsbRA is additionally phosphorylated on T205 following strong stresses, (ii) this modification requires RsbT, and (iii) the phosphorylation‐deficient T205A substitution greatly increases post‐stress activation of σB. We infer that T205 phosphorylation constitutes a second feedback mechanism to limit σB activation, operating in addition to the RsbX feedback phosphatase. Loss of RsbX function increases the fraction of phosphorylated RsbS and doubly phosphorylated RsbRA in unstressed cells. We propose that RsbX both maintains the ready state of the stressosome prior to stress and restores it post‐stress.
Effects of crop canopy structure on herbicide deposition and performance
Authors: KIM D S , MARSHALL E J P , BRAIN P , CASELEY J C
Published: March 2011

Kim DS, Marshall EJP, Brain P & Caseley JC (2011). Effects of crop canopy structure on herbicide deposition and performance. Weed Research51, 310–320.

To explore the relationship between canopy structure of winter wheat and herbicide performance, new indices representing canopy structural characteristics have been devised. Canopy structures of six different wheat cultivars grown in trays were determined and herbicide deposition and performance measured in a split‐plot experiment. A canopy index (Cp) was devised as the ratio of growing canopy height to manually extended maximum plant height, as a representation of structure and stem and leaf inclination. Canopy volume was taken as the volume within the canopy consisting of one main stem and two tillers. Canopy index and volume were closely correlated with individual crop growth characteristics. These indices were also closely correlated with each other (r = 0.80; P < 0.001) and showed relatively consistent correlation with other characteristics, such as leaf area, plant height, canopy area, and light penetration as the wheat grew. Canopy index and volume were closely but negatively correlated with light penetration (r = −0.87; P < 0.001 and −0.71; P < 0.001 respectively), which in turn showed close correlation with herbicide deposition. The amount of herbicide deposition on the soil surface was positively correlated with weed biomass. Surprisingly, the amount on target weeds was uncorrelated with final weed biomass, indicating that herbicide performance was not dependent upon deposition on the target in different crop cultivars with different canopy structures. Our findings thus demonstrate the importance of crop canopy structure, represented by canopy index and volume, in herbicide performance. These new indices should be useful for investigating crop canopy structure in relation to crop competitivity and herbicide performance.
Potential immunosuppressive function of plasma indoleamine 2,3‐dioxygenase in patients with aGVHD after allo‐HSCT
Authors: Zhao Xiao‐Su , Liu Kai‐Yan , Liu Dai‐Hong , Xu Lan‐Ping , Chen Huan , Huang Xiao‐Jun
Published: March 2011

Zhao X‐S, Liu K‐Y, Liu D‐H, Xu L‐P, Chen H, Huang X‐J. Potential immunosuppressive function of plasma indoleamine 2,3‐dioxygenase in patients with aGVHD after allo‐HSCT. Clin Transplant 2011: 25: E304–E311. © 2011 John Wiley & Sons A/S.

Abstract:  Given the function of indoleamine 2,3‐dioxygenase (IDO) in the induction of immune tolerance as a T‐cell inhibitor, we investigated whether plasma IDO levels correlate with the biological activity of acute graft‐versus‐host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Plasma levels of IDO were monitored by ELISA in 147 samples from 65 patients who fulfilled the diagnostic histopathological and/or clinical criteria of aGVHD and 16 episodes of infection after allo‐HSCT. Elevated plasma IDO levels were associated with occurrence of infection or mild aGVHD (grade I–II). Most patients with grade III–IV aGVHD had relatively low levels of IDO compared to those with mild aGVHD or infection. Responses of aGVHD to immunosuppressive therapy were associated with a decrease in IDO levels in the majority of patients with mild aGVHD, whereas secondary infection was characterized by persistent or increased IDO levels after treatment. Although plasma IDO levels may indicate the severity and outcome of aGVHD and point to appropriate therapies through its function in immune tolerance, it is not aGVHD specific and may not be a distinguishing biomarker of aGVHD.
KCNQ1 gene variants and risk of new‐onset diabetes in tacrolimus‐treated renal‐transplanted patients
Authors: Tavira Beatriz , Coto Eliecer , Díaz‐Corte Carmen , Ortega Francisco , Arias Manuel , Torres Armando , Díaz Juan M. , Selgas Rafael , López‐Larrea Carlos , Campistol Jose M. , Ruiz‐Ortega Marta , Alvarez Victoria ,   The Pharmacogenetics of Tacrolimus REDINREN Study Group
Published: March 2011

Tavira B, Coto E, Díaz‐Corte C, Ortega F, Arias M, Torres A, Díaz JM, Selgas R, López‐Larrea C, Campistol JM, Ruiz‐Ortega M, Alvarez V, The Pharmacogenetics of Tacrolimus REDINREN Study Group. KCNQ1 gene variants and risk of new‐onset diabetes in tacrolimus‐treated renal‐transplanted patients. Clin Transplant 2011: 25: E284–E291. © 2011 John Wiley & Sons A/S.

Abstract:  Recent genome‐wide association studies identified single‐nucleotide polymorphisms (SNPs) in the gene encoding the pore‐forming subunit of the voltage‐gated K+ channel (KCNQ1) as a risk factor for type 2 diabetes. Tacrolimus (Tac) increased the risk of new‐onset diabetes after transplantation (NODAT). The aim of this study was to analyze the association between KCNQ1 variants and the risk for NODAT in kidney‐transplanted patients who received Tac as primary immunosuppressor. We genotyped three common KCNQ1 SNPs in 145 Spanish patients who received a cadaveric kidney graft and developed NODAT in the first‐year post‐transplant (the NODAT group), and 260 patients who remained non‐diabetics (non‐NODAT). In addition, we searched for DNA variants in the whole KCNQ1 coding exons in these patients.

SNP rs2237895 (genotype CC) was associated with an increased risk for NODAT in our population (p = 0.008; OR = 1.83, 95% CI = 1.14–2.93), independently of other risk factors as body mass index, recipient age, or tacrolimus dosage. Other KCNQ1 variants were not associated with NODAT in our patients. Our work supported a role for KCNQ1 gene variants as determinants of the risk of developing NODAT among Tac‐treated patients.
Molecular epidemiology of Escherichia coli bacteremia in liver transplant recipients
Authors: Bert F. , Huynh B. , Dondero F. , Johnson J.R. , Paugam‐Burtz C. , Durand F. , Belghiti J. , Valla D. , Moreau R. , Nicolas‐Chanoine M.‐H.
Published: March 2011

F. Bert, B. Huynh, F. Dondero, J.R. Johnson, C. Paugam‐Burtz, F. Durand, J. Belghiti, D. Valla, R. Moreau, M.‐H. Nicolas‐Chanoine. Molecular epidemiology of Escherichia coli bacteremia in liver transplant recipients. Transpl Infect Dis 2011: 13: 359–365. All rights reserved

Abstract: The characteristics of Escherichia coli strains causing bacteremia in profoundly immunosuppressed patients such as transplant recipients are undefined. The phylogenetic group and the virulence genotype of 57 distinct E. coli strains that caused bacteremia in 53 liver transplant recipients were investigated, and the association of these characteristics with host factors and in‐hospital mortality was examined. Phylogenetic groups A, B1, B2, and D accounted for 39%, 10%, 25%, and 26% of the isolates, respectively. The most prevalent virulence genes were fyuA (yersiniabactin system: 70%) and iutA (aerobactin system: 63%), whereas hlyA (alpha‐hemolysin) and cnf1 (cytotoxic necrotizing factor 1) occurred in only 14% and 12% of isolates, respectively. Most virulence genes were significantly more prevalent among group B2 and D isolates, vs. group A and B1 isolates. The overall rate of in‐hospital mortality after E. coli bacteremia was 20%. Predictors of mortality included onset of bacteremia within 30 days of transplantation or during the intensive care unit stay, and non‐urinary source and cutaneous source, but not E. coli phylogenetic group or virulence profile. Compared with historical E. coli bloodstream isolates from non‐transplant patients, those from liver transplant recipients are characterized by a higher prevalence of groups A and B1 isolates and reduced virulence gene content. This finding can be explained by the severely immunocompromised status of the patients and the predominance of abdominal‐source bacteremic episodes. Time of onset and source of bacteremia, not bacterial characteristics, predict mortality.
(3Z,6Z,9Z,12Z,15Z)‐pentacosapentaene and (9Z,11E)‐tetradecadienyl acetate: sex pheromone of the spruce coneworm Dioryctria abietella (Lepidoptera: Pyralidae)
Authors: Löfstedt C. , Svensson G. P. , Jirle E. V. , Rosenberg O. , Roques A. , Millar J. G.
Published: March 2011

The spruce coneworm, Dioryctria abietella Denis & Schiffermüller (Lepidoptera: Pyralidae), is a major pest in spruce seed orchards in Europe. Initial work on its pheromone ecology reported significant attraction of males to (9Z,11E)‐tetradecadienyl acetate (9Z,11E‐14:OAc), but this compound appeared to be a very weak attractant in field trials. In this study, we show that a second female‐produced compound, the polyunsaturated long‐chain hydrocarbon (3Z,6Z,9Z,12Z,15Z)‐pentacosapentaene (C25 pentaene), is a strong synergist to 9Z,11E‐14:OAc, and that both compounds are needed for significant attraction of males. In field‐trapping experiments, the highest catches were obtained with high amounts of pentaene added to the acetate (acetate:pentaene ratio from 1 : 10 to 1 : 30) and the highest doses (1–3 mg per rubber septum dispenser) were the most attractive. Two potential behavioural synergists, (Z)‐9‐tetradecenyl acetate and (9Z,12E)‐tetradecadienyl acetate, turned out to be behavioural antagonists and both reduced trap catch of D. abietella in a dose‐dependent way when added individually to the binary blend. The recent discovery of the C25 pentaene as a pheromone component of D. abietella, as well as of three North American congeners, suggests that the use of a mixture of so‐called type I and type II pheromone compounds is a widespread motif of sexual communication within the genus. The identification of a highly attractive sex pheromone will help in developing efficient strategies for monitoring and control of D. abietella populations in European spruce seed orchards.
Tumour necrosis factor‐α and its receptors in the beneficial effects of vagal stimulation after myocardial infarction in rats
Authors: Kong Shan‐Shan , Liu Jin‐Jun , Hwang Tyzh‐Chang , Yu Xiao‐Jiang , Lu Yi , Zang Wei‐Jin
Published: March 2011

1. Acute myocardial infarction (AMI) often activates the sympathetic system and inhibits the vagal system. Long‐term vagal nerve stimulation (VNS) exerts several beneficial effects on the ischaemic heart, including an anti‐inflammatory effect. The aim of the present study was to investigate whether short‐term VNS during AMI could inhibit tumour necrosis factor (TNF)‐α expression and the effect of TNF receptor (TNFR), key components in inflammatory responses to AMI, in a rodent model.

2. Adult male Sprague‐Dawley rats were divided into four groups, namely a control (C), VNS (S), AMI (M) and an AMI group subjected to prior VNS (MS). In the S and MS groups, the right vagus nerve was stimulated electrically for 4 h; in the M and MS groups, AMI was induced by occlusion of the left anterior descending coronary artery. Haemodynamic data were monitored continuously using a multichannel physiological recorder. Lactate dehydrogenase (LDH) leakage, creatine kinase (CK) leakage and infarct size were determined. The expression of TNF‐α and its receptors were analysed by reverse transcription–polymerase chain reaction, western blotting and ELISA.

3. Compared with the control group, rats in the M group had low blood pressure, high left ventricular (LV) end‐diastolic pressure, a depressed maximum dP/dt of LV pressure, higher LDH and CK leakage, a larger infarct size, increased TNF‐α levels and an increased TNFR1/TNFR2 ratio. However, these presumably harmful effects of AMI were all significantly ameliorated by VNS during AMI (MS group).

4. In conclusion, VNS can rectify ischaemia‐induced cardiac dysfunction partly via inhibition of a TNF‐α‐mediated signalling pathway.
Prospective evaluation of a new stool antigen test for the detection of Helicobacter pylori, in comparison with histology, rapid urease test, 13C‐urea breath test, and serology
Authors: Choi Jeongmin , Kim Chung Hyeon , Kim Donghee , Chung Su Jin , Song Ji Hyun , Kang Jung Mook , Yang Jong In , Park Min Jung , Kim Young Sun , Yim Jeong Yoon , Lim Seon Hee , Kim Joo Sung , Jung Hyun Chae , Song In Sung
Published: March 2011

Background and Aims:  This study aimed to evaluate the efficacy of a new polyclonal enzyme immunoassay for the detection of Helicobacter pylori (H. pylori) antigen in stool by determination of the optimal cut‐off value in the screening population.

Methods:  A consecutive 515 patients undergoing a routine health check‐up were prospectively enrolled. H. pylori infection was defined if at least two of four tests (histology, rapid urease test, 13C‐urea breath test, and serology) were positive. A stool antigen test (EZ‐STEP H. pylori) was performed for the detection of H. pylori. The optimal cut‐off value was determined by the receiver–operator characteristic curve. The diagnostic performance of each test was evaluated with regard to the histological diagnosis of atrophic gastritis (AG)/intestinal metaplasia (IM), degree of AG/IM, and old age.

Results:  Sensitivity, specificity, positive and negative predictive values, and accuracy of the stool antigen test were 93.1%, 94.6%, 95.1%, 92.3%, and 93.8%, respectively. The sensitivity of histology, rapid urease test, and the 13C‐urea breath test ranged from 89.1% to 97.6%, and their specificity was > 98%, while serology had high sensitivity, but low specificity. The accuracy of the stool antigen test was comparable to that of other methods (93.6–95.9%), whereas it was higher than that of serology. The stool antigen test still showed good diagnostic performance in the setting of progression of AG/IM and in patients over 40 years.

Conclusions:  The performance of a new stool antigen test was comparable to that of other methods in the diagnosis of H. pylori infection for the screening population, even with the presence of AG/IM.
Assessment and learning curve evaluation of endobronchial ultrasound skills following simulation and clinical training
Authors: STATHER DAVID R. , MACEACHERN PAUL , RIMMER KAREN , HERGOTT CHRISTOPHER A. , TREMBLAY ALAIN
Published: March 2011

Background and objective:  Endobronchial ultrasound is a revolutionary diagnostic pulmonary procedure. The use of a computer endobronchial ultrasound simulator could improve trainee procedural skills before attempting to perform procedures on patients. This study aims to compare endobronchial ultrasound performance following training with simulation versus conventional training using patients.

Methods:  A prospective study of pulmonary medicine and thoracic surgery trainees. Two cohorts of trainees were evaluated using simulated cases with performance metrics measured by the simulator. Group 1 received endobronchial ultrasound training by performing 15 cases on an endobronchial ultrasound simulator (n = 4). Group 2 received endobronchial ultrasound training by doing 15–25 cases on patients (n = 9).

Results:  Total procedure time was significantly shorter in group 1 than group 2 (15.15 (±1.34) vs 20.00 (±3.25) min, P < 0.05). The percentage of lymph nodes successfully identified was significantly better in group 1 than group 2 (89.8 (±5.4) vs 68.1 (±5.2), P < 0.05). There was no difference between group 1 and group 2 in the percentage of successful biopsies (100.0 (±0.0) vs 90.4 (±11.5), P = 0.13). The learning curves for simulation trained fellows did not show an obvious plateau after 19 simulated cases.

Conclusions:  Using an endobronchial ultrasound simulator leads to more rapid acquisition of skill in endobronchial ultrasound compared with conventional training methods, as assessed by an endobronchial ultrasound simulator. Endobronchial ultrasound simulators show promise for training with the advantage of minimizing the burden of procedural learning on patients.
Efficacy and comfort of volume‐guaranteed pressure support in patients with chronic ventilatory failure of neuromuscular origin
Authors: CRESCIMANNO GRAZIA , MARRONE ORESTE , VIANELLO ANDREAW
Published: March 2011

Background and objective:  Although non‐invasive ventilation is widely used for the management of patients with neuromuscular disease, it remains unclear which ventilatory mode is associated with optimal patient–ventilator interaction and provides more effective gas exchange. The effects of volume‐guaranteed pressure support (PSV‐VTG) as compared with pressure support ventilation (PSV) and assisted pressure controlled ventilation (APCV) on breathing pattern and patient–ventilator synchrony during sleep, blood gases and subjective comfort were evaluated in a group of stable patients with neuromuscular disease.

Methods:  PSV‐VTG, PSV and APCV were applied in random order on three consecutive nights, during which cardio‐respiratory monitoring was performed. Arterial blood gases were measured at the end of each ventilatory session. Evaluation of subjective sleep quality, comfort and perception of patient–ventilator synchrony was performed using a 10‐item visual analogue questionnaire.

Results:  Twenty‐eight patients were included in the study. The different ventilatory modes showed similar effects on breathing pattern during sleep, arterial blood gases and degree of subjective comfort. Ineffective efforts were only observed during PSV‐VTG and were inversely correlated with the variability of leaks (r = −0.61, P = 0.015). A greater number of prolonged inspirations was observed with PSV‐VTG and PSV compared with APCV (P = 0.048 and 0.029, respectively). There were no correlations between patient comfort and physiological variables or ventilator setting.

Conclusions:  PSV‐VTG did not outperform older modes of ventilation in terms of efficacy on breathing pattern and blood gases. In addition, application of PSV‐VTG was associated with a higher rate of patient–ventilator dyssynchrony.
Exploring the pharmacokinetics of oral ketamine in children undergoing burns procedures
Authors: Brunette Katharine E.J. , Anderson Brian J. , Thomas Jennifer , Wiesner Lubbe , Herd David W. , Schulein Simone
Published: March 2011

Aims:  The aim of this study was to describe ketamine pharmacokinetics when administered orally to children suffering from burn injury in >10% body surface area.

Methods:  Children (n = 20) were given ketamine 5 or 10 mg·kg−1 orally 20 min prior to presentation for surgical procedures. Anesthesia during procedures was maintained with a volatile anesthetic agent. Additional intravenous ketamine was given as a bolus (0.5–1 mg·kg−1) to nine children during the procedure while a further nine children were given an infusion (0.1 mg·kg−1·h−1) continued for 4–19 h after the procedure. Blood was assayed for ketamine and norketamine on six occasions over the study duration of 8–24 h. Data were pooled with those from an earlier analysis (621 observations from 70 subjects). An additional time–concentration profile from an adult given oral ketamine was gleaned from the literature (17 observations). A population analysis was undertaken using nonlinear mixed‐effects models.

Results:  The pooled analysis comprised 852 observations from 91 subjects. There were 20 children who presented for procedures related to burns management (age 3.5 sd 2.1 years, range 1–8 years; weight 14.7 sd 4.9 kg, range 7.9–25 kg), and these children contributed 214 ketamine and norketamine observations. A two‐compartment (central, peripheral) linear disposition model fitted data better than a one‐compartment model. Bioavailability of the oral formulation was 0.45 (90% CI 0.33, 0.58). Absorption half‐time was 59 (90% CI 29.4, 109.2) min and had high between‐subject variability (BSV 148%). Population parameter estimates, standardized to a 70‐kg person, were central volume 21.1 (BSV 47.1%) l·70 kg−1, peripheral volume of distribution 109 (27.5%) l·70 kg−1, clearance 81.3 (46.1%) l·h−1·70 kg−1, and inter‐compartment clearance 259 (50.1%) l·h−1·70 kg−1. Under the assumption that all ketamine was converted to norketamine, the volume of the metabolite was 151.9 (BSV 39.1%) l·70 kg−1 with an elimination clearance of 64.4 (BSV 63.4%) l·h−1·70 kg−1 and a rate constant for intermediate compartments of 26.2 (BSV 52.1%) h−1·70 kg−1.

Conclusions:  The ketamine pharmacokinetics in children with minor burns are similar to those without burns. The peak ratio of norketamine/ketamine at 1 h is 2.8 after oral administration allowing an analgesic contribution from the metabolite at this time. There is low relative bioavailability (<0.5) and slow variable absorption. Dose simulation in a child (3.5 years, 15 kg) suggests a dose regimen of oral ketamine 10 mg·kg−1 followed by intravenous ketamine 1 mg·kg−1 i.v. with the advent of short‐duration surgical dressing change at 45 min.
Mathematical Modeling of Powder‐Snow Avalanche Flows
Authors: Dutykh Denys , Acary‐Robert Céline , Bresch Didier
Published: March 2011

Powder‐snow avalanches are violent natural disasters which represent a major risk for infrastructures and populations in mountain regions. In this study we present a novel model for the simulation of avalanches in the aerosol regime. The second scope of this study is to get more insight into the interaction process between an avalanche and a rigid obstacle. An incompressible model of two miscible fluids can be successfully employed in this type of problems. We allow for mass diffusion between two phases according to the Fick's law. The governing equations are discretized with a contemporary fully implicit finite volume scheme. The solver is able to deal with arbitrary density ratios. Several numerical results are presented. Volume fraction, velocity, and pressure fields are presented and discussed. Finally, we point out how this methodology can be used for practical problems.
Quasi‐Periodic Solutions of Nonlinear Evolution Equations Associated with a 3 × 3 Matrix Spectral Problem
Authors: Geng Xianguo , Wu Lihua , He Guoliang
Published: March 2011

A hierarchy of new nonlinear evolution equations associated with a 3 × 3 matrix spectral problem with three potentials is proposed. With the aid of the characteristic polynomial of Lax matrix for the hierarchy, we introduce an algebraic curve  of arithmetic genus m − 1, and discuss in detail the properties of the associated Baker–Akhiezer function and meromorphic function. On the basis of the theory of algebraic curves, we obtain the explicit theta function representations of the Baker–Akhiezer function, the meromorphic function, and, in particular, that of solutions for the entire hierarchy of nonlinear evolution equations.
MONOPOLISTIC COMPETITION, MULTIPRODUCT FIRMS AND PRODUCT DIVERSITY*
Authors: OTTAVIANO GIANMARCO I. P. , THISSE JACQUES‐FRANÇOIS
Published: March 2011

This paper has two objectives. First, it presents a linear model of monopolistic competition in which weak strategic interactions among single‐product firms are allowed for. Second, it extends this model to the case of multiproduct firms, thus showing how product diversity is affected by strong strategic interactions among oligopolists. In our setting, monopolistic competition with single‐product firms is a good approximation of oligopolistic competition with multiproduct firms either when varieties are sufficiently differentiated or when scope economies are low.
Someday They’ll Have a War and Nobody Will Come
Authors: Lynd Staughton
Published: March 2011

There is a contradiction in U.S. law concerning conscientious objection. The Nuremburg Tribunal was premised on the concept that an individual must refuse to commit war crimes in a particular war. High‐ranking German and Japanese personnel who were found to have violated this mandate were executed. The Nuremburg concept has been incorporated in the United States Army’s manual. Yet, the law of conscientious objection still requires a member of the military to object to service in all wars, that is, to be a pacifist, in order to qualify for conscientious objection. This must be changed.
World War II Resisters: Creating Communities of Resistance in Prison
Authors: Rhoton Nicole
Published: March 2011

World War II war resisters—those men who actively refused to register for the draft because it violated their principles, whether political, moral, religious, or otherwise—aggressively challenged the limits of freedom in American society by rejecting military service because they believed that killing, under any pretense, was always wrong. As a maximum protest against war, resisters refused conscription, thus violating the draft law, which resulted in their imprisonment. Paradoxically, resisters found the prison to be a site of virtue as they rejected mandatory enlistment as a citizen’s duty. Resisters turned the prison into a forum for the development of political thought and action regarding radical pacifism and nonviolence. Through direct action, prisoners realized the potential of nonviolent resistance, a method and technique they cultivated before the war, mastered in prison, and carried with them after the war to champion civil rights, racial equality, and peace in subsequent conflicts.
De Gaulle’s Peace Program for Vietnam: The Kennedy Years
Authors: McLaughlin Sean J.
Published: March 2011

This article examines the Kennedy administration’s rejection of French President Charles de Gaulle’s critique of American intervention in Vietnam. In discussions with their American counterparts, de Gaulle and his officials consistently touched on four major themes from his first meeting with Kennedy in May 1961 until Kennedy’s assassination in November 1963: recognition of the principle of Vietnamese self‐determination, the withdrawal of American troops from South Vietnam, acceptance of controlled neutrality for Southeast Asia, and the necessity of dealing with mainland China directly. Kennedy rejected all elements of this platform. He was highly sceptical of neutrality, which he viewed as a stalking horse for communism, and believed that the United States needed to show resolve in Southeast Asia or risk jeopardizing its prestige with allies across the globe. The manner in which Kennedy’s New Frontiersmen framed their rejection of de Gaulle’s position on Vietnam reflected long‐standing American cultural antipathy toward Europe, France, in particular. At no point did the Kennedy administration recognize the Gaullist position on Vietnam as a legitimate expression of relevant French experience nor did it believe that France was capable of acting as an honest broker and negotiating a real truce between North and South. As a result, the Kennedy administration missed out on a perfect opportunity to disengage from a grim and distant conflict late in the summer of 1963, when de Gaulle had the resources and the will to broker peace.
The Mutation of the Vietnam Syndrome: Underreported Resistance during the 1991 Persian Gulf War
Authors: Mirra Carl
Published: March 2011

This paper challenges the prevailing narrative of the 1991 Persian Gulf War as a popular war. While support for war against Iraq after its invasion of Kuwait on August 2, 1990, was evident, it was not universally shared by U.S. citizens. Substantial antiwar rallies occurred during the build‐up to war. In addition, soldiers who refused orders grew rapidly during the short conflict. This paper documents the considerable tide of antiwar dissent, with special attention given to GI resisters. A related focus is the underreporting and mismanagement of conscientious objector claims during the war, which is inseparable from the general tendency to discourage and reduce dissent. Scholarly studies have all but ignored this GI resistance, and the very suggestion that there was a viable GI antiwar movement during the Persian Gulf War is likely to arouse doubt and suspicion. By foregrounding GI opposition, and how the military systematically attempted to expunge it, this essay helps to illustrate that the so‐called popular war was met with significant resistance.
The rise of agrarian capitalism and the decline of family farming in England1
Authors: SHAW‐TAYLOR LEIGH
Published: March 2011

Historians have documented rising farm sizes throughout the period 1450–1850. Existing studies have revealed much about the mechanisms underlying the development of agrarian capitalism. However, we currently lack any consensus as to when the critical developments occurred. This is largely due to the absence of sufficiently large and geographically wide‐ranging datasets but is also attributable to conceptual weaknesses in much of the literature. This article develops a new approach to the problem and argues that agrarian capitalism was dominant in southern and eastern England by 1700 but that in northern England the critical developments came later.