bluuebunny/crossref_metadata_2025 huggingface dataset:
Ideal MHD spectrum calculations for the ARIES-CS configuration
Authors: Turnbull A.D. , Cooper W.A. , Lao L.L. , Ku Long-Poe
Published: November 2011

Ideal MHD stability calculations for the ARIES compact stellarator (ARIES-CS) reactor design (Najmabadi et al 2008 Fusion Sci. Technol.
54 655) show a spectrum of instabilities. The ARIES design considered is a three field-period stellarator with engineering coil constraints optimized for magnetic well and alpha particle confinement. The reference design has high β ∼ 5%. The study is restricted to ideal modes and the calculations assume nested flux surfaces, with a limited plasma boundary surrounded by a vacuum. At β = 4%, with a conformal wall at twice the minor plasma radius, the equilibrium is slightly unstable to a periodicity-preserving, predominantly m/n = 9/6 mode peaked at the edge and a periodicity-breaking global m/n = 3/2 mode. At β ∼ 5%, these modes are destabilized but the growth rates are still moderate. At higher β, above the design value, several modes become unstable. Stabilization by a close fitting conducting wall is ineffective at β = 5% and below but becomes more effective at stabilizing external modes at higher β. The equilibrium at β ∼ 6% can be stabilized by a conformal wall at 1.1 times the minor plasma radius, although very weakly unstable internal modes remain at β > 6% with a wall on the plasma boundary. The sensitivity to the presence of the rational rotational transform ι = 2/3 surface at the edge of the plasma was also investigated. Generally, either the m/n = 3/2 mode is further destabilized or other modes are introduced. The stability calculations numerically impose a broadening of the singular perturbed current to eliminate spurious singularities. The effect of this is considered in detail and it is suggested that this numerical resonance detuning can model a physical broadening from non-ideal effects. Although the reference design with β ∼ 5% is above the strict ideal β limit, common experience in tokamaks indicates that weakly unstable internal modes and edge-localized modes result in relatively benign MHD activity. This is consistent with observations in large stellarator experiments that indicate some level of instability is tolerated and the results are discussed in this context and in relation to the numerical broadening of the singular perturbed currents.
Animal Welfare Economics
Authors: Lusk Jayson L. , Norwood F. Bailey
Published: November 2011

This article highlights some key areas where economics can contribute to the current debate about animal welfare. Production economics reveals that producers will not maximize animal welfare, even if animal well‐being is highly correlated with output. Welfare economics raises thorny issues about the double‐counting of benefits when humans exhibit altruism towards animals, while public economics uncovers potential market failures and possible solutions. Consumer economics provides a means of determining human and animal benefits from animal well‐being policies in dollar terms. Overall, economists have much to contribute to the animal welfare debate and the well‐being of humans and animals could be improved with more economic analysis on the effects of private and government actions related to animal welfare.
Bone Health in Children With Celiac Disease Assessed By Dual X‐ray Absorptiometry
Authors: Margoni Daphne , Chouliaras Giorgos , Duscas Grigoris , Voskaki Irene , Voutsas Nikolaos , Papadopoulou Anna , Panayiotou Joanna , Roma Eleftheria
Published: November 2011

Objectives:

In the present study, we aimed to assess bone status and the effect of gluten‐free diet (GFD) in children with celiac disease (CD), and to evaluate the predictive value of standard serum biochemical indices in the diagnosis of bone mineral density (BMD) disturbances.

Methods:

Forty‐five children at the time of diagnosis of CD (group A, 77.8% girls) and 36 children receiving GFD for >2 years (group B, 75% girls) were included. Sixteen children in group A were reexamined 12 months after initiation of GFD. Serum measurements of biochemical bone health indices and BMD, assessed by dual x‐ray absorptiometry, were obtained.

Results:

Patients after 1 year of receiving GFD had higher BMD z scores compared with baseline (−1.45 ± 0.28 vs −0.61 ± 0.25, respectively, P = 0.004). BMD z scores were significantly lower than expected for the normal population, after 1 (P = 0.03) or at least 2 (P < 0.001) years of receiving GFD. In group B, BMD z score was positively correlated with 25‐hydroxy vitamin D levels (P = 0.009). In the repeated measurements group, 25‐hydroxy vitamin D differed between pre‐ and post‐GFD (P = 0.018). No biochemical index was capable of predicting an abnormal BMD z score (receiver operating characteristic curve analysis, all of the areas under the curve <0.66).

Conclusions:

GFD has a beneficial effect on bone health. Two years receiving diet do not ensure normalization. Biochemical markers are not indicative of BMD disturbances. Dual x‐ray absorptiometry should be included in the standard management of children with CD.
Health‐related Quality of Life in Pediatric Patients With Long‐standing Pancreatitis
Authors: Pohl John F. , Limbers Christine A. , Kay Marie , Harman Annette , Rollins Michael , Varni James W.
Published: November 2011

Objectives:

There are limited data on health‐related quality of life (HRQOL) in pediatric patients with long‐standing pancreatitis (including acute relapsing and chronic pancreatitis) using age‐appropriate measurement instruments.

Methods:

We evaluated HRQOL in children with long‐standing pancreatitis using the PedsQL 4.0 Generic Core Scales by patient self‐report as well as parent proxy report. Additionally, patient self‐reports and parent proxy reports were completed for the PedsQL Multidimensional Fatigue Scale.

Results:

Across all of the dimensions, significantly impaired HRQOL and higher fatigue were noted for both pediatric patient self‐report and parent proxy report in comparison with the matched healthy children samples. Higher fatigue was associated with lower HRQOL. There was moderate to good agreement between patient self‐reports and parent proxy reports.

Conclusions:

Given the impaired HRQOL and fatigue documented in the present study, future studies are needed to determine whether specific factors can modify HRQOL and fatigue in this patient population.
Utility of the New ESPGHAN Criteria for the Diagnosis of Celiac Disease in At‐risk Groups
Authors: Kurppa Kalle , Salminiemi Jaakko , Ukkola Anniina , Saavalainen Päivi , Löytynoja Katja , Laurila Kaija , Collin Pekka , Mäki Markku , Kaukinen Katri
Published: November 2011

Objective:

Demonstration of small‐bowel mucosal damage has been the basis of celiac disease diagnosis, but the diagnostic approach is undergoing changes. The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recently stated that in a subgroup of children, high positive transglutaminase 2 antibody (TG2ab) values may be sufficient for the diagnosis. The utility of these new criteria was evaluated by applying the human red blood cell TG2 antibody test (RBC‐TG2ab) to a large cohort of children and adults belonging to at‐risk groups.

Methods:

RBC‐TG2ab and endomysial antibodies (EmA) were measured in 3031 family members or other relatives of patients with celiac disease. The RBC‐TG2ab values were classified as weak (20–29 U), moderate (30–99 U), and strong (≥100 U) positive. Seropositive subjects were further tested by human recombinant TG2ab (Hr‐TG2ab) and for the presence of celiac disease–associated human leukocyte antigen‐DQ alleles. Gastroscopy was recommended for all with positive RBC‐TG2ab, EmA, or Hr‐TG2ab, or weak positive RBC‐TG2ab and symptoms.

Results:

Strong positive RBC‐TG2ab has good correlation with EmA and Hr‐TG2ab and positivity of DQ2/8, and the diagnosis was established in 94% of both children and adults. In contrast, moderately positive (≥30 U) RBC‐TG2ab showed poor correlation with the other tests, and celiac disease was diagnosed in 69% of children and 86% of adults. Most participants with weak positive RBC‐TG2ab were negative for EmA and Hr‐TG2ab.

Conclusions:

In accordance with the new European Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria, strong positive RBC‐TG2ab showed good accuracy and excellent correlation with the other antibodies and celiac‐type human leukocyte antigen. In contrast, low or moderately positive RBC‐TG2ab values were of unsatisfactory prognostic value for a subsequent diagnosis.
Solitary Rectal Ulcer Syndrome in Children and Adolescents
Authors: Perito Emily R. , Mileti Elizabeth , Dalal Deepal H. , Cho Soo‐Jin , Ferrell Linda D. , McCracken Marjorie , Heyman Melvin B.
Published: November 2011

Objectives:

The aim of this study was to describe the presenting symptoms, endoscopic and histologic findings, and clinical courses of pediatric patients diagnosed with solitary rectal ulcer syndrome (SRUS).

Methods:

We describe 15 cases of SRUS diagnosed at our institution during a 13‐year period. Cases were identified by review of a pathology database and chart review and confirmed by review of biopsies. Data were collected by retrospective chart review.

Results:

Presenting symptoms were consistent but nonspecific, most commonly including blood in stools, diarrhea alternating with constipation, and abdominal/perianal pain. Fourteen of 15 patients had normal hemoglobin/hematocrit, erythrocyte sedimentation rate, and albumin at diagnosis. Endoscopic findings, all limited to the distal rectum, ranged from erythema to ulceration and polypoid lesions. Histology revealed characteristic findings. Stool softeners and mesalamine suppositories improved symptoms, but relapse was common.

Conclusions:

SRUS in children presents with nonspecific symptoms and endoscopic findings. Clinical suspicion is required, and diagnosis requires histologic confirmation. Response to present treatments is variable.
Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone‐ and buprenorphine‐maintained subjects
Authors: Gelston Eloise A. , Coller Janet K. , Lopatko Olga V. , James Heather M. , Schmidt Helmut , White Jason M. , Somogyi Andrew A.
Published: November 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Although not well recognized, methadone inhibits CYP2D6 in vivo and in vitro and UGT2B7 and 2B4 in vitro.

• We aimed to investigate the effect of methadone on the pathways of codeine metabolism, namely O‐demethylation (CYP2D6), 6‐glucuronidation (UGT2B4/7) and N‐demethylation (CYP3A4/2C8), in subjects maintained on methadone or buprenorphine as a control.

WHAT THIS STUDY ADDS

• Compared with subjects on buprenorphine, methadone reduced the clearance of codeine to morphine and to codeine‐6‐glucuronide but had no effect on norcodeine formation.

• Plasma morphine concentrations remained unchanged, as although its formation was reduced, its metabolism to M3G and M6G was also reduced.

• Metabolic drug interactions with methadone cannot assume substrate‐dependent inhibition.

AIMS

To compare the O‐demethylation (CYP2D6‐mediated), N‐demethylation (CYP3A4‐mediated) and 6‐glucuronidation (UGT2B4/7‐mediated) metabolism of codeine between methadone‐ and buprenorphine‐maintained CYP2D6 extensive metabolizer subjects.

METHODS

Ten methadone‐ and eight buprenorphine‐maintained subjects received a single 60 mg dose of codeine phosphate. Blood was collected at 3 h and urine over 6 h and assayed for codeine, norcodeine, morphine, morphine‐3‐ and ‐6‐glucuronides and codeine‐6‐glucuronide.

RESULTS

The urinary metabolic ratio for O‐demethylation was significantly higher (P= 0.0044) in the subjects taking methadone (mean ± SD, 2.8 ± 3.1) compared with those taking buprenorphine (0.60 ± 0.43), likewise for 6‐glucuronide formation (0.31 ± 0.24 vs. 0.053 ± 0.027; P < 0.0002), but there was no significant difference (P= 0.36) in N‐demethylation. Similar changes in plasma metabolic ratios were also found. In plasma, compared with those maintained on buprenorphine, the methadone‐maintained subjects had increased codeine and norcodeine concentrations (P < 0.004), similar morphine (P= 0.72) and lower morphine‐3‐ and ‐6‐ and codeine‐6‐glucuronide concentrations (P < 0.008).

CONCLUSION

Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine‐6‐glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6.
Synergistic effects of supplementation of dietary antioxidants during growth on adult phenotype in ring‐necked pheasants,Phasianus colchicus
Authors: Orledge Josephine M. , Blount Jonathan D. , Hoodless Andrew N. , Pike Thomas W. , Royle Nick J.
Published: November 2011

1. Oxidative stress may provide a proximate link between investment in growth and/or reproduction and investment in self‐maintenance. Dietary antioxidants, such as carotenoids and vitamin E, provide potentially important roles in regulating these trade‐offs. Recent work suggests that carotenoids may have synergistic effects in combination with non‐pigmentary antioxidants (e.g. vitamin E) on the expression of sexually selected traits in adulthood. However, these studies involved the supplementation of antioxidants to adults so did not take account of early life‐history effects.

2. Here, we test the independent and combined roles of supplementation of carotenoids and vitamin E during early growth in regulating the expression of traits in adulthood, in ring‐necked pheasants,Phasianus colchicus. Individuals supplemented with a combination of carotenoids and vitamin E were larger at adulthood than individuals receiving other treatment diets (including vitamin E or carotenoids alone), but there were no differences in ornament expression, immune function, the swelling response to phytohaemagglutinin or levels of oxidative damage.

3. This shows that there are synergistic early life‐history effects of these dietary antioxidants on body size at adulthood and suggest that the allocation of limited antioxidant resources are prioritized towards traits that increase competitive ability rather than sexual attractiveness in this strongly sexually selected species.
Consumption of tabular acroporid corals by reef fishes: a comparison with plant–herbivore interactions
Authors: Cole Andrew J. , Lawton Rebecca J. , Wilson Shaun K. , Pratchett Morgan S.
Published: November 2011

1. Interactions between primary producers and consumers (i.e. grazers) are of fundamental importance to the successful functioning of ecological communities. Plant–herbivore interactions have been extensively studied, and herbivory has been accepted as an important process contributing to the structure of terrestrial and aquatic ecosystems. In contrast, the functional importance of the ecologically equivalent interaction between scleractinian reef corals and polyp‐feeding fishes is largely untested, but has generally been dismissed as unimportant.

2. This study quantified the amount of tabular acroporid coral tissue biomass consumed at the population level by corallivorous butterflyfishes and determined the proportion of both the standing biomass and productivity that is consumed annually at three exposed reef crest sites at Lizard Island, Great Barrier Reef and Australia.

3. Total daily coral consumption ranged from 18·6 (±1·6) to 27·4 (±1·5) g 200 m−2 day−1 with 61–68% of this consumption directed towards tabular acroporid corals. This selective feeding resulted in an annual consumption of between 8·9–13·5% of the total available tissue biomass and between 52–79% of the annual productivity of these tabular acroporid corals.

4. The proportion of standing coral tissue biomass removed by corallivorous butterflyfishes is similar to that removed from terrestrial plants by herbivores. However, the proportion of primary productivity consumed is considerably greater on coral reefs for both corallivorous and herbivorous fishes compared with terrestrial systems.

5. In terrestrial systems, even relatively low levels of defoliation can have significant effects on plant growth rates, seed production and overall fitness. Considering the high proportion of productivity that is consumed by polyp‐feeding fishes, it would seem incongruous that these grazing fishes do not have similar effects on coral community structure and population dynamics. Our findings highlight the need to revisit previously held assumptions regarding the functional importance of corallivorous fishes to coral reef ecosystems.
Soil C erosion and burial in cropland
Authors: VandenBygaart A. J. , Kroetsch DAVID , Gregorich EDWARD G. , Lobb DAVID
Published: November 2011

Erosion influences the lateral and vertical distribution of soil in agricultural landscapes. A better understanding of the effects of erosion and redistribution on soil organic carbon (C) within croplands would improve our knowledge of how management practices may affect global C dynamics. In this study, the vertical and lateral distribution of soil organic C was characterized to evaluate the amounts and timescales of soil organic C movement, deposition and burial over the last 50 years in different agroecosystems across Canada. There was strong evidence that a substantial portion of eroded sediment and soil organic C was deposited as colluvium close to its source area, thereby burying the original topsoil. The deepest aggraded profile was in a potato field and contained over 70 cm of deposited soil indicating an accumulation rate of 152 Mg ha yr−1; aggraded profiles in other sites had soil deposition rates of 40–90 Mg ha−1 yr−1. The largest stock of soil organic C was 463 Mg ha−1 (to 60 cm depth) and soil C deposition ranged from about 2 to 4 Mg ha−1 yr−1 across all sites. A distinct feature observed in the aggraded profiles at every site was the presence of a large increase in soil organic C concentration near the bottom of the A horizon; the concentration of this C was greater than that at the soil surface. Compared to aggraded profiles, the SOC concentration in eroded profiles did not differ with depth, suggesting that dynamic replacement of soil organic C had occurred in eroded soils. A large amount of soil organic C is buried in depositional areas of Canadian croplands; mineralization of this stock of C appears to have been constrained since burial, but it may be vulnerable to future loss by management practices, land use change and a warming climate.
Projecting the effects of climate change on the distribution of maize races and their wild relatives in Mexico
Authors: Ureta Carolina , Martínez‐Meyer Enrique , Perales Hugo R. , Álvarez‐Buylla Elena R.
Published: November 2011

Climate change is expected to be a significant threat to biodiversity, including crop diversity at centers of origin and diversification. As a way to avoid food scarcity in the future, it is important to have a better understanding of the possible impacts of climate change on crops. We evaluated these impacts on maize, one of the most important crops worldwide, and its wild relatives Tripsacum and Teocintes. Maize is the staple crop in Mexico and Mesoamerica, and there are currently about 59 described races in Mexico, which is considered its center of origin . In this study, we modeled the distribution of maize races and its wild relatives in Mexico for the present and for two time periods in the future (2030 and 2050), to identify the potentially most vulnerable taxa and geographic regions in the face of climate change. Bioclimatic distribution of crops has seldom been modeled, probably because social and cultural factors play an important role on crop suitability. Nonetheless, rainfall and temperature still represent a major influence on crop distribution pattern, particularly in rainfed crop systems under traditional agrotechnology. Such is the case of Mexican maize races and consequently, climate change impacts can be expected. Our findings generally show significant reductions of potential distribution areas by 2030 and 2050 in most cases. However, future projections of each race show contrasting responses to climatic scenarios. Several evaluated races show new potential distribution areas in the future, suggesting that proper management may favor diversity conservation. Modeled distributions of Tripsacum species and Teocintes indicate more severe impacts compared with maize races. Our projections lead to in situ and ex situ conservation recommended actions to guarantee the preservation of the genetic diversity of Mexican maize.
Micro‐marsupialization as an alternative treatment for mucocele in pediatric dentistry
Authors: PIAZZETTA CLETO M. , TORRES‐PEREIRA CASSIUS , AMENÁBAR JOSÉ M.
Published: November 2011

International Journal of Paediatric Dentistry 2012; 22: 318–323

Background.  Mucocele is a common oral lesion in children and adolescents. Different techniques have been described for the treatment; however, all of them are invasive.

Aim.  This work studied the efficacy of micro‐marsupialization for the treatment for mucoceles in paediatric patients.

Design.  A retrospective review was performed using the clinical records of patients aged between 0 and 18 years with a clinical diagnosis of mucocele. The following data were obtained: age, gender, location and size of the lesion, duration of mucocele development, and type of treatment and its results.

Results.  The mean age of the patients was 11.1 ± 3.95 years. Mucoceles were found in the lower lip (83.7%), buccal mucosa (11.6%), and tongue (4.7%). From the overall cohort of 86 cases, 33 were treated by micro‐marsupialization, of which five developed a recurrence that required surgical excision. The other 53 cases were treated by surgical excision, and three of these had recurrent disease. No statistically significant difference was found between the treatment methods.

Conclusions.  Micro‐marsupialization can be used to treat mucoceles in paediatric dentistry. It is simpler to perform, minimally invasive, requires no local infiltration of anaesthesia, has a lower postoperative complications rate, and is well‐tolerated by patients.
Nine years of vegetation development in a postmining site: effects of spontaneous and assisted site recovery
Authors: Baasch Annett , Kirmer Anita , Tischew Sabine
Published: November 2011

1. Highly disturbed areas such as surface‐mined land provide a great challenge for ecological restoration. The goal is to identify appropriate restoration approaches in a continuum between technical reclamation and spontaneous succession. In particular, on slopes endangered by erosion, appropriate methods are needed that quickly establish vegetation cover but also take into account the natural potentials of the site.

2. In the mined area Roßbach (Saxony‐Anhalt, Germany), we evaluated the effects of spontaneous succession and assisted site recovery (species introduction through hay transfer and sowing) during a 9‐year experiment. We asked how rates and pathways of vegetation development differ between treatments and whether species composition converges over time owing to species exchange.

3. The application of green hay as well as the sowing of regional seed mixtures clearly accelerated vegetation development and led to the rapid establishment of species‐rich grasslands. Hay transfer was most successful owing to the high amount of transferable target species. Moreover, both treatments facilitated the establishment of cryptogams and provided effective erosion control. Also, hay transfer and sowing clearly affected the pathway of succession.Calamagrostis epigejosmigrated from nearby source populations and became increasingly dominant at sites with spontaneous succession. In contrast, the species‐rich grasslands established after hay transfer and sowing were highly resistant to invasion ofCalamagrostisand other ruderals.

4. Species exchange between treatments led to increasing similarity in vegetation composition over time. Nine years after implementation of the experiment, we did not find any significant differences between treatments in terms of total vegetation cover, species richness and the number of target species. However, the dominance ratio between target and nontarget species differed significantly. Species introduction through hay transfer and sowing led to a permanently higher abundance of grassland species and a lower coverage of ruderals compared with spontaneously developed sites. Hence, our results highlight the importance of initial floristic composition and the order of species arrivals for long‐term vegetation development.

5. Synthesis and applications. Hay transfer and sowing of regional seed mixtures are appropriate restoration tools to achieve rapid revegetation when no potential seed sources of target species are available nearby or there are undesirable species that need to be suppressed. Our results show that introduced grassland species are able to grow under postmining site conditions and can migrate into adjacent spontaneously developing sites. A combination of spontaneous and assisted site recovery can promote the development of species‐rich grasslands in postmining landscapes.
Eight (and a half) deadly sins of spatial analysis
Authors: Hawkins Bradford A.
Published: November 2011

Biogeography is spatial by nature. Over the past 20 years, the literature related to the analysis of spatially structured data has exploded, much of it focused on a perceived problem of spatial autocorrelation and ways to deal with it. However, there are a number of other issues that permeate the biogeographical and macroecological literature that have become entangled in the spatial autocorrelation web. In this piece I discuss some of the assumptions that are often made in the analysis of spatially structured data that can lead to misunderstandings about the nature of spatial data, the methods used to analyse them, and how results can be interpreted.
Time‐course effects of St John’s wort on the pharmacokinetics of cyclosporine in dogs
Authors: FUKUNAGA K. , ORITO K.
Published: November 2011

Fukunaga, K., Orito, K. Time‐course effects of St John’s wort on the pharmacokinetics of cyclosporine in dogs. J. vet. Pharmacol. Therap. 35, 446–451.

To clarify the interaction between St John’s wort (SJW) and cyclosporine (CsA) in dogs, the pharmacokinetics of CsA before and during the repeated administration of SJW were analyzed. In the SJW group, SJW (300 mg) was given orally to four dogs every 24 h for 14 days. A single dose of CsA (5 mg/kg) was given orally 7 days before and 7 and 14 days after the initiation of the repeated administration of SJW. In the Control group, a single dose of CsA (5 mg/kg) was given orally to four other dogs in accordance with that in the SJW group. Blood samples from both groups were collected, and whole‐blood concentrations of CsA were determined using high‐performance liquid chromatography with UV detection. The maximum whole‐blood concentration and AUC0–∞ of the SJW group were significantly lower and the CLtot/F and Vd/F were significantly higher than those in the Control group 7 and 14 days after the initiation of repeated SJW. Thus, repeated administrations of SJW affect the pharmacokinetic profiles of CsA in dogs. Further studies are necessary to elucidate the mechanisms of interaction between SJW and CsA in dogs.
Tumour necrosis factor‐α‐857T allele reduces the risk of hepatitis B virus infection in an Asian population
Authors: Shi K.‐Q. , Cai X.‐H. , Xiao D.‐D. , Wu S.‐J. , Peng M.‐M. , Lin X.‐F. , Liu W.‐Y. , Fan Y.‐C. , Chen Y.‐P. , Zheng M.‐H.
Published: November 2011

Summary.  Tumour necrosis factor‐α (TNF‐α) plays a pivotal role in hepatitis B virus (HBV) clearance and host immune response determining the chronicity of HBV infection. However, studies of the association between TNF‐α‐857 polymorphism and chronic HBV infection have reported conflicting results. So a meta‐analysis was carried out to draw a more precise conclusion. Pubmed (January, 1966–March, 2011) and the China Biological Medicine Database (January, 1978–March, 2011) were searched using the keywords TNF‐α gene polymorphism in combination with HBV infection without language restriction. Fourteen studies including 4929 chronic HBV infection cases and 2702 controls describing the C857T genotype were included in the meta‐analysis. All fourteen studies focussed on an Asian population. The overall meta‐analysis suggested that TNF‐α‐857T allele reduced the risk of chronic HBV infection in the Asian population (OR = 0.82, 95% CI: 0.71–0.95, P = 0.008) when compared with a spontaneously recovered population. In the sensitivity analyses of the groups obeying Hardy–Weinberg equilibrium (HWE), without the largest study population and without the smallest study population, a similar association was revealed (OR = 0.81, 95% CI: 0.68–0.98, P = 0.043; OR = 0.77, 95% CI: 0.68–0.87, P = 0.0001; OR = 0.81, 95% CI: 0.70–0.95, P = 0.009, respectively). However, when compared with a healthy population, no significant association was found in the Asian population in all groups. So, we draw the conclusion that the TNF‐α‐857T allele reduces the risk of chronic HBV infection in this Asian population.
Two decades of describing the unseen majority of aquatic microbial diversity
Authors: ZINGER LUCIE , GOBET ANGÉLIQUE , POMMIER THOMAS
Published: November 2011

Aquatic environments harbour large and diverse microbial populations that ensure their functioning and sustainability. In the current context of global change, characterizing microbial diversity has become crucial, and new tools have been developed to overcome the methodological challenges posed by working with microbes in nature. The advent of Sanger sequencing and now next‐generation sequencing technologies has enabled the resolution of microbial communities to an unprecedented degree of precision. However, to correctly interpret microbial diversity and its patterns this revolution must also consider conceptual and methodological matters. This review presents advances, gaps and caveats of these recent approaches when considering microorganisms in aquatic ecosystems. We also discuss potentials and limitations of the available methodologies, from water sampling to sequence analysis, and suggest alternative ways to incorporate results in a conceptual and methodological framework. Together, these methods will allow us to gain an unprecedented understanding of microbial diversity in aquatic ecosystems.
A genetic discontinuity in root‐nodulating bacteria of cultivated pea in the Indian trans‐Himalayas
Authors: RAHI PRAVEEN , KAPOOR RITI , YOUNG J. P. W. , GULATI ARVIND
Published: November 2011

Evolutionary relationships of 120 root‐nodulating bacteria isolated from the nodules of Pisum sativum cultivated at 22 different locations of the trans‐Himalayan valleys of Lahaul and Spiti in the state of Himachal Pradesh of India were studied using 16S rRNA gene PCR‐RFLP, ERIC‐PCR, sequencing of 16S rRNA, atpD, recA, nodC and nifH genes, carbon‐source utilization pattern (BIOLOG™), and whole‐cell fatty acid profiling. The results demonstrated that all isolates belonged to Rhizobium leguminosarum symbiovar viciae (Rlv). Isolates from the two valleys were clearly separated on the basis of ERIC fingerprints, carbon‐source utilization pattern, and whole‐cell fatty acid methyl esters. Phylogenetic analysis of atpD, recA, nodC and nifH genes revealed a common Rlv sublineage in Spiti valley. Lahaul valley isolates were represented by three sequence types of atpD and recA genes, and four sequence types of nodC and nifH genes. Genotypes from the two valleys were completely distinct, except for two Lahaul isolates that shared nodC and nifH sequences with Spiti isolates but were otherwise more similar to other Lahaul isolates. Isolates from the two highest Spiti valley sites (above 4000 m) had a distinctive whole‐cell fatty acid profile. Spiti valley isolates are closely related to Rlv sublineages from Xinjiang and Shanxi provinces in China, while Lahaul valley isolates resemble cosmopolitan strains of the western world. The high mountain pass between these valleys represents a boundary between two distinct microbial populations.
Reflections on a sticky situation: how surface contact pulls the trigger for bacterial adhesion
Authors: Kirkpatrick Clare L. , Viollier Patrick H.
Published: November 2011

Adhesion of bacterial cells to surfaces can be mediated by a wide variety of extracellular structures, which can either recognize specific molecular motifs or adhere in non‐specific ways to multiple types of surfaces. The attachment is thought to be highly regulated, but the underlying sensory mechanism(s) are poorly understood. In the α‐proteobacterium Caulobacter crescentus, the formation of adhesive organelles is ‘hardwired’ into the cell cycle regulatory circuitry. In this issue of Molecular Microbiology, Li et al. (2011) employed this model organism to examine the adhesion process and the transition from temporary to permanent attachment using total internal reflection fluorescence (TIRF) microscopy. Surprisingly, they observed that adhesin production was not only under developmental control, but was also stimulated by surface contact. Initial reversible contact of the pili with the surface was followed by flagellum rotation arrest and subsequent induction of the holdfast to allow irreversible surface adhesion. These findings demonstrate that Caulobacter produces its holdfast only at the appropriate time for surface attachment, preventing premature export of the adhesin, which could then be inactivated by ‘curing’ or be masked by occluding particles. Importantly, their results support the notion that the flagellum serves as a mechanosensor for adhesion.
Systematic knockdown of morphine pathway enzymes in opium poppy using virus‐induced gene silencing
Authors: Wijekoon Champa P. , Facchini Peter J.
Published: November 2011

Opium poppy (Papaver somniferum) remains the sole commercial source for several pharmaceutical alkaloids including the narcotic analgesics codeine and morphine, and the semi‐synthetic drugs oxycodone, buprenorphine and naltrexone. Although most of the biosynthetic genes have been identified, the post‐transcriptional regulation of the morphinan alkaloid pathway has not been determined. We have used virus‐induced gene silencing (VIGS) as a functional genomics tool to investigate the regulation of morphine biosynthesis via a systematic reduction in enzyme levels responsible for the final six steps in the pathway. Specific gene silencing was confirmed at the transcript level by real‐time quantitative PCR (polymerase chain reaction), and at the protein level by immunoblot analysis using antibodies raised against salutaridine synthase (SalSyn), salutaridine reductase (SalR), salutaridine 7‐O‐acetyltransferase (SalAT), thebaine 6‐O‐demethylase (T6ODM), codeinone reductase (COR), and codeine O‐demethylase (CODM). In some cases, silencing a specific biosynthetic gene resulted in a predictable accumulation of the substrate for the corresponding enzyme. Reduced SalSyn, SalR, T6ODM and CODM protein levels correlated with lower morphine levels and a substantial increase in the accumulation of reticuline, salutaridine, thebaine and codeine, respectively. In contrast, the silencing of genes encoding SalAT and COR resulted in the accumulation of salutaridine and reticuline, respectively, which are not the corresponding enzymatic substrates. The silencing of alkaloid biosynthetic genes using VIGS confirms the physiological function of enzymes previously characterized in vitro, provides insight into the biochemical regulation of morphine biosynthesis, and demonstrates the immense potential for metabolic engineering in opium poppy.
Critical review of the Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA): suggestions for harmonization, implementation and improvement
Authors: Datema Tjeerd A. M. , Oskam Linda , van Beers Stella M. , Klatser Paul R.
Published: November 2011

Objective  Clinical laboratories in low‐ and middle‐income countries (LMIC) need fundamental improvement because quality laboratory services are essential for the decision‐making capacity of clinicians, health workers and public health authorities. To this end, a tiered accreditation scheme Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA) was developed by WHO‐AFRO, CDC and others for clinical laboratories in LMIC. One to five stars are accredited to laboratories based on the level of compliance with a checklist. Our aim was to evaluate the quality and applicability of this accreditation scheme compared with international quality standards.

Methods  We performed a critical review of this scheme to formulate recommendations for implementation, harmonization and improvement. Two analyses were performed: one assessing its coverage of the ISO 15189:2007 standard and one to identify and evaluate priorities of the accreditation checklist.

Results  Although the content of the checklist covers all aspects of total quality management, it strongly prioritizes resource management activities. We recommend identifying critical requirements for each tier of accreditation to assure a certain level of quality for each tier or instead using a pass/fail approach towards accreditation. In addition, the checklist should include more questions for assessing proper management, ethics and continuous improvement to meet ISO 15189.

Conclusion  Launching accreditation schemes for laboratories in LMIC should be encouraged. After further optimization of SLIPTA, clinical laboratories may certainly benefit, leading to more correctly diagnosed patients and less waste of resources.
A multi‐allergen standard for the calibration of immunoassays: CREATE principles applied to eight purified allergens
Authors: Filep S. , Tsay A. , Vailes L. , Gadermaier G. , Ferreira F. , Matsui E. , King E. M. , Chapman M. D.
Published: November 2011

To cite this article: Filep S, Tsay A, Vailes L, Gadermaier G, Ferreira F, Matsui E, King EM, Chapman MD. A multi‐allergen standard for the calibration of immunoassays: CREATE principles applied to eight purified allergens. Allergy 2012; 67: 235–241.

Background:  Allergen measurements are widely used for environmental exposure assessments and for determining the potency of allergen vaccines, yet few purified allergen standards have been developed. The aim of the study was to develop a single standard containing multiple purified allergens that could be used in enzyme immunoassays and in multiplex arrays for the standardization of allergen measurements.

Methods:  Eight purified allergens were formulated into a single multi‐allergen, or ‘universal’, standard based on amino acid analysis. Dose–response curves were compared with previous individual ELISA standards and allergen measurements of house dust extracts to obtain correction factors. Measured allergen concentrations were also modeled using linear regression, and the predictive accuracy was determined.

Results:  Parallel dose–response curves were obtained between the universal allergen standard and the individual ELISA standards, with close agreement between curves for 5/8 allergens. Quantitative differences of greater than twofold were observed for Fel d 1, Can f 1, and Der f 1, which were confirmed by the analysis of house dust extracts. Correction factors were developed that allowed ELISA data to be expressed in terms of the universal standard. Linear regression data confirmed the predictive accuracy of the universal standard.

Conclusion:  This study shows that a single standard of eight purified allergens can be used to compare allergen measurements by immunoassay. This approach will improve the continuity of environmental exposure assessments and provide improved standardization of allergy diagnostics and vaccines used for immunotherapy.
Quantitation of human herpesvirus‐6 (HHV‐6) DNA in a cord blood transplant recipient with chromosomal integration of HHV‐6
Authors: Kobayashi D. , Kogawa K. , Imai K. , Tanaka T. , Hiroi S. , Satoh H. , Tanaka‐Taya K. , Nonoyama S.
Published: November 2011

Chromosomal integration of the human herpesvirus‐6 (HHV‐6) genome (CIHHV‐6) is an important consideration if HHV‐6 DNA is detected during the course of transplantation. A 4‐year‐old girl with refractory anemia with excess blasts type‐2 was diagnosed with CIHHV‐6 before a cord blood transplantation. HHV‐6 DNA was serially quantitated by polymerase chain reaction assay in the transplant period. The possibility of HHV‐6 reactivation in a transplant recipient with CIHHV‐6 was suspected in our case.
Evaluation of the hemostatic potential including thrombin generation of three different therapeutic pathogen‐reduced plasmas
Authors: Hacquard M. , Lecompte T. , Belcour B. , Geschier C. , Jacquot C. , Jacquot E. , Schneider T.
Published: November 2011

Background and Objectives  Several pathogen inactivation methods currently applied to therapeutic plasma may result in products with different hemostatic properties. This study aims at evaluating and comparing the hemostatic potential of different therapeutic plasma preparations currently available in France.

Materials and methods  We studied three types of pathogen‐reduced plasma for transfusion (MB/light, Amotosalen/UVA, industrial S/D plasma). Quarantine, non‐pathogen‐reduced plasma, was used as a control. This study compared more specifically the content in FVIII, fibrinogen (clottable and antigen assays) and ADAMTS‐13 and evaluated the intrinsic hemostatic properties using a thrombin generation test [Calibrated Automated Thrombogram (CAT)] at high and low concentrations of tissue factor to assess the maximum quantity of thrombin generated or the contribution of FVIII and FIX in the amplification phase of thrombin generation, respectively.

Results  The median FVIII concentration was >70 IU/dl for each preparation. Endogenous thrombin potential values were significantly different among the methods of plasma preparation (P < 0·001) but were all in the range of the values measured in donors’ plasma. Control by the thrombomodulin‐activated protein C system was preserved in all preparations (>50% inhibition of endogenous thrombin potential). Fibrinogen concentrations were all within normal range but fibrinogen levels were lower in the plasmas treated with photochemical methods. ADAMTS‐13 levels were preserved.

Conclusion  The hemostatic potential appears well preserved in all therapeutic plasmas tested but there are some differences between preparations, the clinical relevance of which remains to be elucidated.
High‐dose esomeprazole is required for intraesophageal acid control in gastroesophageal reflux disease patients with hiatus hernia
Authors: Peng Sui , Xiao Ying‐Lian , Cui Yi , Lin Jin‐Kun , Zhang Ning , Hu Pin‐Jin , Chen Min‐Hu
Published: November 2011

Background and Aim:  The aim of this study was to assess whether the efficacy of proton pump inhibitors (PPI) therapy at a standard dose in esophageal acid control is affected by the presence of hiatus hernia in Chinese gastroesophageal reflux disease patients, and whether a higher dose of PPI is required for acid control.

Methods:  Consecutive gastroesophageal reflux disease patients who had typical reflux symptoms and abnormal baseline 24‐h esophageal pH and underwent upper endoscopy were enrolled to receive esomeprazole at 40 mg once daily for 4 weeks. Patients underwent the dual‐channel 24‐h pH test at the end of 4‐week therapy. If the 24‐h esophageal pH was still abnormal at the end of 4‐week therapy, then esomeprazole at 40 mg twice daily was given for another 4 weeks after a washout interval of 1 week, and a 24‐h pH test was repeated at the end of the therapy.

Results:  Overall, 76 patients were included, 13 with hiatus hernia. Of the 76 patients treated with a 40 mg of esomeprazole daily, esophageal acid exposure was normalized in 64 (84.2%). Normalization of acid exposure was achieved by standard PPI therapy in 53.2% (7/13) of patients with hiatus hernia and 90.5% (57/63) of those without (P = 0.004). A double dose of esomeprazole was successful in normalizing the esophageal pH in all 12 non‐responders to the standard dose of esomeprazole, including the six patients with hiatus hernia and six patients without.

Conclusions:  The standard‐dose of esomeprazole fails to normalize the esophageal pH in almost 50% of patients with hiatus hernia, in whom the “double‐dose” esomeprazole therapy is required.
Expression profile of genes involved in pathogenesis of pediatric Crohn's disease
Authors: Sim Winnie H , Wagner Josef , Cameron Donald J , Catto‐Smith Anthony G , Bishop Ruth F , Kirkwood Carl D
Published: November 2011

Background and Aim:  Expression profiling of genes specific to pediatric Crohn's Disease (CD) patients was performed to elucidate the molecular mechanisms underlying disease cause and pathogenesis at disease onset.

Methods:  We used suppressive subtractive hybridization (SSH) and differential screening analysis to profile the mRNA expression patterns of children with CD and age‐ and sex‐matched controls without inflammatory bowel disease (IBD).

Results:  Sequence analysis of 1000 clones enriched by SSH identified 75 functionally annotated human genes, represented by 430 clones. The 75 genes have potential involvement in gene networks, such as antigen presentation, inflammation, infection mechanism, connective tissue development, cell cycle and cancer. Twenty‐eight genes were previously described in association with CD, while 47 were new genes not previously reported in the context of IBD. Additionally, 29 of the 75 genes have been previously implicated in bacterial and viral infections. Quantitative real‐time reverse transcription polymerase chain reaction performed on ileal‐derived RNA from 13 CD and nine non‐IBD patients confirmed the upregulation of extracellular matrix gene MMP2 (P = 0.001), and cell proliferation gene REG1A (P = 0.063) in our pediatric CD cohort.

Conclusion:  The retrieval of 28 genes previously reported in association with adult CD emphasizes the importance of these genes in the pediatric setting. The observed upregulation of REG1A and MMP2, and their known impact on cell proliferation and extracellular matrix remodeling, agrees with the clinical behavior of the disease. Moreover, the expressions of bacterial‐ and virus‐related genes in our CD‐patient tissues support the concept that microbial agents are important in the etiopathogenesis of CD.
Clinical impact of HFE mutations in Japanese patients with chronic hepatitis C
Authors: Ishizu Yoji , Katano Yoshiaki , Honda Takashi , Hayashi Kazuhiko , Ishigami Masatoshi , Itoh Akihiro , Hirooka Yoshiki , Nakano Isao , Goto Hidemi
Published: November 2011

Background and Aim:  HFE mutations, a common cause of hereditary hemochromatosis (HH), are reportedly associated with hepatic iron overload, severe liver fibrosis, and good response to interferon treatment in European patients with chronic hepatitis C (CHC). HH shows ethnicity‐based differences and little is known about the effects of HH mutations on CHC in the Japanese. Thus, the aim of this study was to clarify the clinical influence of HFE mutations in Japanese CHC patients.

Methods:  In a total of 251 patients with CHC, we analyzed the frequencies of H63D and S65C mutations in the HFE gene, and the influence of these mutations on clinical parameters and response to pegylated‐interferon‐alpha 2b (PEG‐IFN) plus ribavirin therapy.

Results:  Fourteen patients (5.6%) carried the H63D mutation; all were heterozygotes. No S65C mutations were found. Only hemoglobin levels in the H63D heterozygotes were higher than in wild‐type patients. Eleven of 14 H63D heterozygotes achieved sustained virological response (SVR). On univariate analysis, factors associated with SVR were interleukin 28B (IL28B) polymorphism, age, hepatitis C virus (HCV) genotype, HCV viral load, white blood cell count, stage of fibrosis and H63D mutation. All patients with both TT genotype in IL28B (rs8099917) and H63D mutation in HFE (n = 10) achieved SVR.

Conclusions:  The H63D mutation has little impact on the clinical characteristics of CHC, but is related to favorable response to PEG‐IFN plus ribavirin therapy, particularly in patients with the TT allele in IL28B.