bluuebunny/crossref_metadata_2025 huggingface dataset:
Allergen Atlas: a comprehensive knowledge center and analysis resource for allergen information
Authors: Tong Joo Chuan , Lim Shen Jean , Muh Hon Cheng , Chew Fook Tim , Tammi Martti T.
Published: February 2009

Summary: A variety of specialist databases have been developed to facilitate the study of allergens. However, these databases either contain different subsets of allergen data or are deficient in tools for assessing potential allergenicity of proteins. Here, we describe Allergen Atlas, a comprehensive repository of experimentally validated allergen sequences collected from in-house laboratory, online data submission, literature reports and all existing general-purpose and specialist databases. Each entry was manually verified, classified and hyperlinked to major databases including Swiss-Prot, Protein Data Bank (PDB), Gene Ontology (GO), Pfam and PubMed. The database is integrated with analysis tools that include: (i) keyword search, (ii) BLAST, (iii) position-specific iterative BLAST (PSI-BLAST), (iv) FAO/WHO criteria search, (v) graphical representation of allergen information network and (vi) online data submission. The latest version contains information of 1593 allergen sequences (496 IUIS allergens, 978 experimentally verified allergens and 119 new sequences), 56 IgE epitope sequences, 679 links to PDB structures and 155 links to Pfam domains.

Availability: Allergen Atlas is freely available at http://tiger.dbs.nus.edu.sg/ATLAS/.

Contact:  martti@nus.edu.sg.
A Bayesian approach to estimating target strength
Authors: Fässler Sascha M. M. , Brierley Andrew S. , Fernandes Paul G.
Published: February 2009

Fässler, S. M. M., Brierley, A. S., and Fernandes, P. G. 2009. A Bayesian approach to estimating target strength. – ICES Journal of Marine Science, 66: 1197–1204. Currently, conventional models of target strength (TS) vs. fish length, based on empirical measurements, are used to estimate fish density from integrated acoustic data. These models estimate a mean TS, averaged over variables that modulate fish TS (tilt angle, physiology, and morphology); they do not include information about the uncertainty of the mean TS, which could be propagated through to estimates of fish abundance. We use Bayesian methods, together with theoretical TS models and in situ TS data, to determine the uncertainty in TS estimates of Atlantic herring (Clupea harengus). Priors for model parameters (surface swimbladder volume, tilt angle, and s.d. of the mean TS) were used to estimate posterior parameter distributions and subsequently build a probabilistic TS model. The sensitivity of herring abundance estimates to variation in the Bayesian TS model was also evaluated. The abundance of North Sea herring from the area covered by the Scottish acoustic survey component was estimated using both the conventional TS–length formula (5.34×109 fish) and the Bayesian TS model (mean = 3.17×109 fish): this difference was probably because of the particular scattering model employed and the data used in the Bayesian model. The study demonstrates the relative importance of potential bias and precision of TS estimation and how the latter can be so much less important than the former.
Acoustic estimates of mesopelagic fish: as clear as day and night?
Authors: O'Driscoll Richard L. , Gauthier Stéphane , Devine Jennifer A.
Published: February 2009

O'Driscoll, R. L., Gauthier, S., and Devine, J. A. 2009. Acoustic estimates of mesopelagic fish: as clear as day and night? – ICES Journal of Marine Science, 66: 1310–1317. The pelagic ecosystem on the Chatham Rise east of New Zealand has been monitored annually using acoustic surveys since 2001. Most of the acoustic backscatter comes from diurnally migrating mesopelagic fish, which are the major prey of hoki (Macruronus novaezelandiae) and other valuable commercial species. Mesopelagic schools and layers typically occur at 100–400 m depth during the day and migrate above 200 m depth at night. Previous acoustic estimates of the biomass of mesopelagic fish on the Chatham Rise were based only on night-time estimates from the upper 200 m and may significantly underestimate actual biomass. Paired day–night comparisons found that an estimated 20% of the total daytime backscatter migrates to depths of 0–14 m at night, where it is too shallow to be detected by hull-mounted acoustic instruments. In contrast, there is a positive bias associated with acoustic estimates of mesopelagic organisms during the day because they can occur close to the bottom mixed with demersal fish. Two alternative approaches for estimating biomass of diurnally migrating mesopelagic species are suggested. The first applies a correction based on the estimated proportion of backscatter migrating into the surface deadzone to night-time estimates of backscatter in the upper 200 m. The second uses night-time estimates of demersal backscatter, which remains deeper than 200 m at night, to correct daytime estimates of total backscatter. Both methods gave similar estimates of abundance and demonstrated that there was no statistically significant trend in mesopelagic fish biomass on the Chatham Rise over the past seven years.
Role of the zinc-finger and basic motifs of chrysanthemum virus B p12 protein in nucleic acid binding, protein localization and induction of a hypersensitive response upon expression from a viral vector
Authors: Lukhovitskaya N. I. , Ignatovich I. V. , Savenkov E. I. , Schiemann J. , Morozov S. Yu. , Solovyev A. G.
Published: February 2009

The genomes of carlaviruses encode cysteine-rich proteins (CRPs) of unknown function. The 12 kDa CRP of chrysanthemum virus B (CVB), p12, has been shown previously to induce a hypersensitive response (HR) when expressed from potato virus X (PVX). This study demonstrated that a p12-induced HR was preceded by induction of a number of genes related to pathogenesis, stress and systemic acquired resistance. p12 localized predominantly to the nucleus. Interestingly, it was found that p12 bound both RNA and DNAin vitro, but notably exhibited a preference for DNA in the presence of Zn2+ions. Mutational analysis of the p12 conserved sequence motifs demonstrated that the basic motif is required for p12 translocation to the nucleus, thus representing part of the protein nuclear localization signal, whereas the predicted zinc finger motif is needed for both Zn2+-dependent DNA binding and eliciting an HR in PVX-infected leaves. Collectively, these results link, for the first time, nuclear localization of the protein encoded by a cytoplasmically replicating virus and its DNA-binding capacity with HR induction. Furthermore, these data suggest that p12 may mediate induction of the host genes by binding to the plant genomic DNA, and emphasize that CVB p12 is functionally distinct from other known nuclear-localized proteins encoded by the plant positive-stranded RNA viruses.
Genetic characterization of dengue virus type 1 isolated in Brunei in 2005–2006
Authors: Osman Osmali , Fong Mun Yik , Sekaran Shamala Devi
Published: February 2009

The full-length genomes of two DENV-1 viruses isolated during the 2005–2006 dengue incidents in Brunei were sequenced. Twenty five primer sets were designed to amplify contiguous overlapping fragments of approximately 500–600 base pairs spanning the entire sequence of the genome. The amplified PCR products were sent to a commercial laboratory for sequencing and the nucleotides and the deduced amino acids were determined. Sequence analysis of the envelope gene at the nucleotide and amino acid levels between the two isolates showed 92 and 96 % identity, respectively. Comparison of the envelope gene sequences with 68 other DENV-1 viruses of known genotypes placed the two isolates into two different genotypic groups. Isolate DS06/210505 belongs to genotype V together with some of the recent isolates from India (2003) and older isolates from Singapore (1990) and Burma (1976), while isolate DS212/110306 was clustered in genotype IV with the prototype Nauru strain (1974) and with some of the recent isolates from Indonesia (2004) and the Philippines (2002, 2001). In the full-length genome analysis at the nucleotide level, isolate DS06/210505 showed 94 % identity to the French Guyana strain (1989) in genotype V while isolate DS212/110306 had 96 % identity to the Nauru Island strain (1974) in genotype IV. This work constitutes the first complete genetic characterization of not only Brunei DENV-1 virus isolates, but also the first strain from Borneo Island. This study was the first to report the isolation of dengue virus in the country.
Investigation of orf virus structure and morphogenesis using recombinants expressing FLAG-tagged envelope structural proteins: evidence for wrapped virus particles and egress from infected cells
Authors: Tan Joanne L. , Ueda Norihito , Mercer Andrew A. , Fleming Stephen B.
Published: February 2009

Orf virus (ORFV) is the type species of the genus Parapoxvirus, but little is known about the structure or morphogenesis of the virus. In contrast, the structure and morphogenesis of vaccinia virus (VACV) has been extensively studied. VACV has two main infectious forms, mature virion (MV) and extracellular virion (EV). The MV is wrapped by two additional membranes derived from the trans-Golgi to produce a wrapped virion (WV), the outermost of which is lost by cellular membrane fusion during viral egress to form the EV. Genome sequencing of ORFV has revealed that it has homologues of almost all of the VACV structural genes. Notable exceptions are A36R, K2L, A56R and B5R, which are associated with WV and EV envelopes. This study investigated the morphogenesis and structure of ORFV by fusing FLAG peptide to the structural proteins 10 kDa, F1L and ORF-110 to form recombinant viruses. 10 kDa and F1L are homologues of VACV A27L and H3L MV membrane proteins, whilst ORF-110 is homologous to VACV A34R, an EV membrane protein. Immunogold labelling of FLAG proteins on virus particles isolated from lysed cells showed that FLAG–F1L and FLAG–10 kDa were displayed on the surface of infectious particles, whereas ORF-110–FLAG could not be detected. Western blot analysis of solubilized recombinant ORF-110–FLAG particles revealed that ORF-110–FLAG was abundant and undergoes post-translational modification indicative of endoplasmic reticulum trafficking. Fluorescent microscopy confirmed the prediction that ORF-110–FLAG localized to the Golgi in virus-infected cells. Finally, immunogold labelling of EVs showed that ORF-110–FLAG became exposed on the surface of EV-like particles as a result of egress from the cell.
Caspase inhibitor P35 is required for the production of robust baculovirus virions in Trichoplusia ni TN-368 cells
Authors: Bryant Bart , Clem Rollie J.
Published: February 2009

Apoptosis can protect lepidopteran insects against baculovirus infection by limiting viral replication. Baculoviruses counter this response by expressing anti-apoptotic proteins such as the caspase inhibitor P35, which is expressed by several baculoviruses including Autographa californica mutiple nucleopolyhedrovirus (AcMNPV). Mutants of AcMNPV that lack the p35 gene induce apoptosis in Spodoptera frugiperda cells, and replication of these mutants is severely curtailed in S. frugiperda cell lines and larvae. However, cells from another lepidopteran species, Trichoplusia ni, do not undergo apoptosis when infected with AcMNPV mutants lacking p35, and p35 mutant and wild-type viruses replicate to equivalent levels in the T. ni cell line TN-368 and have equivalent infectivity in T. ni larvae by either oral or intrahaemocoelic injection. This has led to the conclusion that p35 is not required for AcMNPV replication in T. ni. However, in this study it was found that stocks of p35 mutant virus produced in TN-368 cells had defects in virion stability and infectivity. TN-368 cells infected with p35 mutant AcMNPV exhibited caspase activity, despite a lack of apoptosis, and propagation of the mutant virus in the presence of a chemical caspase inhibitor restored the normal infection phenotype to the progeny virus. These results suggest that caspases can directly or indirectly damage baculovirus virions, and reveal a novel aspect of the role of apoptosis in antiviral defence.
Genomic characterization of the first insectivoran papillomavirus reveals an unusually long, second non-coding region and indicates a close relationship to Betapapillomavirus
Authors: Schulz Eric , Gottschling Marc , Bravo Ignacio G. , Wittstatt Ullrich , Stockfleth Eggert , Nindl Ingo
Published: February 2009

Knowledge about biological diversity is the prerequisite to reliably reconstruct the evolution of pathogens such as papillomaviruses (PV). However, complete genomes of non-human PV have only been cloned and sequenced from 8 out of 18 orders within the Placentalia, although the host-specific variety of PV is considered much larger. We isolated and sequenced the complete genome of the first insectivoran PV type from hair follicle cells of the European hedgehog (Erinaceus europaeus), designated EHPV. We conducted phylogenetic analyses (maximum-likelihood criterion and Bayesian inference) with the genomic information of a systematically representative set of 67 PV types including EHPV. As inferred from amino acid sequence data of the separate genes E1, E2 and L1 as well as of the gene combination E6–E7–E1–E2–L1, EHPV clustered within the β-γ-π-Ξ-PV supertaxon and constituted the closest relative of genus Betapapillomavirus infecting primates. Beside the typical organization of the PV genome, EHPV exhibited a 1172 bp, non-coding region between the E2 and the L2 open reading frames. This trait has been previously described for the only distantly related Lambdapapillomavirus, but a common evolutionary origin of both non-coding regions is unlikely. Our results underscore the modular organization of the PV genome and the complex natural history of PV.
Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis – results from the EXPO study
Authors: LABENZ J. , ARMSTRONG D. , ZETTERSTRAND S. , EKLUND S. , LEODOLTER A.
Published: February 2009

Background  The ability to predict symptom response to reflux oesophagitis‐healing therapy may optimize treatment decisions.

Aim  To identify factors associated with heartburn resolution in patients receiving acid‐suppressive therapy for reflux oesophagitis.

Methods  In this multicentre, randomized, double‐blind trial (EXPO; AstraZeneca study code: SH‐NEG‐0008), patients with endoscopically confirmed reflux oesophagitis and reflux symptoms received once‐daily proton pump inhibitor therapy [esomeprazole 40 mg (n = 1562) or pantoprazole 40 mg (n = 1589)] for ≥4 weeks. Factors associated with heartburn resolution after 4 weeks were identified by multiple logistic regression analysis.

Results  Esomeprazole therapy, positive Helicobacter pylori status and greater age were associated with an increased likelihood of heartburn resolution [odds ratio (95% confidence interval): 1.31 (1.12, 1.54), 1.44 (1.19, 1.74) and 1.013 (1.007, 1.019) per year, respectively; all P < 0.001]. Men and patients with no acid regurgitation or epigastric pain pre‐treatment were also more likely to achieve heartburn resolution (all P < 0.05).

Conclusions  The use of esomeprazole rather than pantoprazole increases the probability of achieving resolution of heartburn during reflux oesophagitis‐healing therapy. Other factors, including H. pylori status, age, gender and symptom profile may be helpful in determining the likelihood of heartburn resolution in such patients.
Insights into syndepositional fault movement in a foreland basin; trends in seismites of the Upper Cretaceous, Wahweap Formation, Kaiparowits Basin, Utah, USA
Authors: Hilbert‐Wolf Hannah L. , Simpson Edward L. , Simpson Wendy S. , Tindall Sarah E. , Wizevich Michael C.
Published: February 2009

The Upper Cretaceous Wahweap Formation accumulated in the active Cordilleran foreland basin of Utah. Soft‐sediment deformation structures are abundant in the capping sandstone member of the Wahweap Formation. By comparing with well‐established criteria, a seismogenic origin was determined for the majority of structures, which places these soft‐sediment deformation features in a class of sedimentary features referred to as seismites. A systematic study of the seismite trends included their vertical and horizontal distribution and a semi‐quantitative intensity analysis using a scale from 1 to 5 that is based on magnitude, sedimentary structure type, and the predominance of inferred process of hydroplastic deformation, liquefaction or fluidization. In addition, orientations of soft‐sediment fold axes were recorded. Construction of a northwest‐to‐southeast stratigraphic and seismite intensity cross‐section demonstrates: (1) reduction in stratigraphic thickness and percentage of conglomerates to the southeast, (2) the presence of lower seismite, middle nonseismite, and upper seismite zones within the capping sandstone (permitting subdivision of the capping sandstone member), and (3) elimination of the nonseismite zone and amalgamation of the lower and upper seismite zones to the southeast. Regional isoseismal contour maps generated from the semi‐quantitative analysis indicate a decrease in overall intensity from northwest to southeast in the upper and lower seismic zones and in sandstone within 5 m stratigraphically of the contact between the upper and capping sandstone members. In addition, cumulative seismite fold orientations support a west–northwest direction towards regional epicentres. Isoseismal maps are used to distinguish the effects of intrabasinal normal faulting from those of regional orogenic thrusting. Thus, this study demonstrates the utility of mapping seismites to separate the importance of regional vs. local tectonic activity influencing foreland basin sedimentation by identifying patterns that delineate palaeoepicentres associated with specific local intrabasinal normal faults vs. regional trends in soft‐sediment deformation related to Sevier belt earthquakes.
The production of JAK2 wild‐type platelets is not downregulated in patients with JAK2 V617F mutant‐positive essential thrombocythaemia
Authors: Lambert Jonathan R. , Gale Rosemary E. , Linch David C.
Published: February 2009

To clarify the relationship between the levels of JAK2 wild‐type (WT) and V617F mutant‐positive platelets in patients with essential thrombocythaemia (ET), we quantified mutant levels in purified cells from 10 V617F‐positive patients prior to receiving cytoreductive therapy. Mutant levels were significantly higher in platelet than neutrophil RNA (P = 0·002), but the mutation was still only present in a sub‐population of platelets (median 54%). When the absolute number of WT platelets was calculated, it was always within or above the normal platelet range, indicating that there is an aberration in the negative feedback to JAK2 WT platelets in ET.
Effect of educational intervention on adoption of new endodontic technology by general dental practitioners: a questionnaire survey
Authors: Koch M. , Eriksson H. G. , Axelsson S. , Tegelberg Å.
Published: February 2009

Objectives  To survey the clinical endodontic protocols of general dental practitioners (GDPs) in public dental clinics and to assess the effect of an educational intervention on the adoption of a nickel–titanium (Ni–Ti) rotary system.

Methods  General dental practitioners in a Swedish Intervention County (IC), underwent an educational programme in endodontics. A follow‐up questionnaire was posted to 98 GDPs in the IC and to 97 GDPs in a Control County (CC), where no specific training had been provided. The questionnaire concerned demographics, clinical endodontic protocols and instrumentation techniques.

Results  The response rate to the questionnaire was 87%. More than 90% of all GDPs reported they always or generally used rubber dam, determined working length, used the canal irrigant 0.5% buffered NaOCl and calcium hydroxide as an interappointment dressing. Two of three GDPs reported, they generally or always informed the patient of the prognosis. Every second GDP reported routines for postoperative recall and follow‐up.

The Ni–Ti rotary technique was reported to be completely adopted by 77% of the GDPs in the IC, significantly higher than in the CC (6%), P < 0.001. In the IC 79% of the GDPs reported they completed instrumentation in one treatment session, compared with only 32% in the CC, P < 0.001. The ‘single‐cone’ mode of canal filling was reported to be significantly more frequent amongst GDPs in the IC, P < 0.001.

Conclusions  General dental practitioners in both counties reported using contemporary clinical endodontic protocols. GDPs who had undergone an educational programme in Ni–Ti rotary instrumentation reported they had successfully integrated the technique into daily clinical practice.
Quality of life after microscopic periradicular surgery using two different incision techniques: a randomized clinical study
Authors: Del Fabbro M. , Taschieri S. , Weinstein R.
Published: February 2009

Aim  To monitor the quality of life of patients after periradicular surgery when two different flap designs were used.

Methodology  Forty patients with teeth having a periradicular lesion of endodontic origin were included according to specific selection criteria. Patients were randomly assigned to two groups. In one group a sulcular incision (SI) with complete papilla mobilization was made, and in the other group a papilla‐base incision (PBI) was used. Periradicular surgery was performed using a surgical microscope. Parameters related to life quality were recorded daily in the first week post‐surgery using a questionnaire. Pain was evaluated with a 0–100 visual analog scale (VAS). Other symptoms (swelling, bleeding and nausea), plus functions (chewing, speaking, sleeping, daily routine and work) were assessed using a five‐point scale. Analgesic intake was recorded. Fisher’s test and unpaired t‐test were used to assess the difference between groups.

Results  The VAS score for pain, and the scores for swelling, chewing and phonetic impairment, peaked on days 1 and 2 postoperatively. A significant difference in favour of the PBI group was found for chewing and swelling in the first 4 days. Starting from day 3 post‐surgery, the PBI group reported a significantly more rapid decrease in pain levels and analgesics use than the SI group (P < 0.05). The other parameters were similar in the two groups.

Conclusions  The papilla‐base incision technique may be preferred as reduction of pain levels, swelling and drug intake were more rapid in the first week postoperatively compared with cases in which a sulcular incision was used.
The properties and applications of chlorhexidine in endodontics
Authors: Mohammadi Z. , Abbott P. V.
Published: February 2009

Microorganisms and their by‐products are considered to be the major cause of pulp and periradicular pathosis. Hence, a major objective in root canal treatment is to disinfect the entire root canal system, which requires that all contents of the root canal system be eliminated as possible sources of infection. This goal may be accomplished using mechanical instrumentation and chemical irrigation, in conjunction with medication of the root canal system between treatment sessions. To reduce or eliminate bacteria, various irrigation solutions have been advocated. Chlorhexidine is a cationic molecule, which can be used during treatment. It has a wide range of antimicrobial activity. Its cationic structure provides a unique property named substantivity. The purpose of this paper is to review the structure and mechanism of action of CHX, its antibacterial and antifungal activity, its effect on biofilm, its substantivity (residual antibacterial activity), its tissue solvent ability, its interaction with calcium hydroxide and sodium hypochlorite, its anticollagenolytic activity, its effect on coronal and apical leakage of bacteria, its toxicity and allergenicity and the modulating effect of dentine and root canal components on its antimicrobial activity. A Medline search was performed from 1981 to the end of March 2008 and was limited to English‐language papers. The keywords searched on Medline were ‘chlorhexidine AND endodontics’, ‘chlorhexidine AND root canal therapy’, ‘chlorhexidine AND substantivity’ and ‘chlorhexidine AND toxicity’. The reference lists of each article were manually checked for additional articles of relevance.
The development of dentist practice profiles and management
Authors: Lin Chinho , Lin Chun‐Mei , Hong Chienwen
Published: February 2009

Rationale and objectives  With the current large computerized payment systems and increase in the number of claims, unusual dental practice patterns to cover up fraud are becoming widespread and sophisticated. Clustering the characteristic of dental practice patterns is an essential task for improving the quality of care and cost containment. This study aims at providing an easy, efficient and practical alternative approach to developing patterns of dental practice profiles. This will help the third‐party payer to recognize and describe novel or unusual patterns of dental practice and thus adopt various strategies in order to prevent fraudulent claims and overcharges.

Methodology  Knowledge discovery (or data mining) was used to cluster the dentists' profiles by carrying out clustering techniques based on the features of service rates. It is a hybrid of the knowledge discovery, statistical and artificial neural network methodologies that extracts knowledge from the dental claim database.

Results  The results of clustering highlight characteristics related to dentists' practice patterns, and the detailed managerial guidance is illustrated to support the third‐party payer in the management of various patterns of dentist practice.

Conclusion  This study integrates the development of dentists' practice patterns with the knowledge discovery process. These findings will help the third‐party payer to discriminate the patterns of practice, and also shed more light on the suspicious claims and practice patterns among dentists.
Explaining the national differences in pressure ulcer prevalence between the Netherlands and Germany – adjusted for personal risk factors and institutional quality indicators
Authors: Tannen Antje , Dietz Ekkehart , Dassen Theo , Halfens Ruud
Published: February 2009

Background  Pressure ulcers have a known impact on quality of life as well as on morbidity and mortality of the persons affected. Remarkable differences in pressure ulcer prevalence between the Netherlands and Germany have been found during the last 6 years. This study explores to what extent the individual risk of the population and quality indicators of the institutions can explain the variation in national prevalence.

Methods  Data of a binational multi‐centred cross‐sectional study in 103 hospitals (n = 21 378 patients) and 129 nursing homes (n = 15 579 residents) were analysed using random effects regression models to calculate the differences in national prevalences within the nursing homes and hospitals, adjusted for personal risk for pressure ulcer and quality indicators.

Results  The prevalence of pressure ulcers among the at‐risk group (Bradenscore ≤20) in nursing homes was 30.8% in the Netherlands and 8.3% in Germany [OR: 4.9 (CI 95%: 4.2–5.7)]. In hospitals, the prevalence among the at‐risk group was 26.1% in the Netherlands and 21.2% in Germany [OR: 1.3 (CI 95%: 1.2–1.5)]. After adjusting for individual risk factors (age, gender, Bradenscore) as well as for quality structures (use of prevention and treatment protocols, experts groups, information leaflets, nurses training, central pressure ulcer statistics and regular updating of protocols), the chance of developing a pressure ulcer was 6.05 times higher (CI 95%: 4.0–9.2) in a Dutch nursing home than in a German nursing home. Within the hospitals, the OR for Dutch patients was 2.03 (CI 95%: 1.4–3.0).

Conclusion  A remarkable national variation exists in pressure ulcer prevalence and nursing practice. Neither the populations vulnerability for pressure ulcers nor pressure ulcer management as measured in this study could explain this national variation. Therefore, other risk factors should be taken into consideration. Additionally, it is possible that quality indicators are implemented in differing ways with varying levels of effectiveness. Therefore, further research is needed to examine prospectively and in more detail the reality of care within facilities in both countries.
Secondary care doctors' perception of appropriate prescribing
Authors: Ljungberg Christina , Lindblad Åsa Kettis , Tully Mary
Published: February 2009

Rationale, aim and objective  As the prescribing of drugs in secondary care is known to influence prescribing in primary care and because an understanding of prescribers' reasoning is essential for evaluating prescribing appropriateness, the aim of this study was to investigate secondary care doctors' views of appropriate prescribing, using qualitative individual interviews.

Method  Qualitative, semi‐structured individual interviews were conducted with 15 hospital doctors working in different medical specialities. The interviews, covering the doctors' views of the meaning of ‘appropriate’ prescribing, were audiotaped and analysed from an interpretivist perspective.

Results  Three different main themes were identified in the analysis of how the doctors perceived appropriate prescribing: ‘individualization of treatment’, ‘cost’ and ‘time’. Most importantly, treatment should be adjusted to the individual patient, although cost should also be justified. Ongoing medication reviews should be carried out, to adjust to changes in patient‐related factors over time.

Conclusions  The hospital doctors brought up continuous review as a necessary part of appropriate prescribing. Thus, from the prescribers' point of view, this time perspective should be explicitly incorporated in definitions of appropriate prescribing, in addition to individualization of treatment and cost considerations.
Can the Hospital Anxiety and Depression Scale be used in patients with schizophrenia?
Authors: Allan Richard , Martin Colin R.
Published: February 2009

Rationale, aims, objectives  The Hospital Anxiety and Depression Scale (HADS) was developed explicitly for use in non‐psychotic populations, yet is routinely used for screening patients with psychotic illness. The utility of the HADS as a screening instrument for use in patients with schizophrenia was investigated.

Method  Exploratory factor analysis and confirmatory factor analysis were conducted on the HADS to determine its psychometric properties in 100 patients with a primary ICD‐10 diagnosis of schizophrenia.

Results  Three distinct factors were identified within the HADS. Support was found for the clinical use of the HADS anxiety subscale to assess anxiety in patients with schizophrenia; however, evidence was also found that the HADS depression subscale may not be a unidimensional measure of depression in this clinical group.

Conclusions  Caution should be used when using the HADS depression subscale in this clinical group. The direction of future research in this area is indicated, in particular comparison of HADS anxiety and depression measures to determine further the validity or otherwise of these subscale domains.
Extreme regression models for characterizing high‐cost patients
Authors: Gregori Dario , Petrinco Michele , Barbati Giulia , Bo Simona , Desideri Alessandro , Zanetti Roberto , Merletti Franco , Pagano Eva
Published: February 2009

Objective  Healthcare cost distribution generally presents a high level of skewness, with a relatively small number of subjects accounting for a large portion of healthcare expenditures. Information on factors that predict high expenditures is of interest in healthcare planning. The aim of this paper was to inspect the behaviour of extreme regression (ER) models.

Methods  We performed a simple simulation study, based on the LogNormal distribution, to assess the performance of ER in the special cases of heterogeneity and strong asymmetry of the cost variable. We then discussed the application of ER models to the analysis of three data sets of diabetes, lung cancer and myocardial infarction patients.

Results  The ER showed to be able to cope fairly well with skewed distribution but under the condition that all observations have strictly positive costs.

Conclusion  The main advantage of the ER model is to unify these approaches in a unique framework, where the estimation of the cut‐offs and the production of the prediction rules are performed simultaneously for a continuous response variable. The final model can thus be analysed at any desiderate quantile of the cost distribution, avoiding the need of pre‐specifying any cut‐off.
Limited value of physical examinations in upper respiratory illness: account of personal experience and survey of doctors’ views
Authors: Kiderman A. , Dratva D. , Ever‐Hadani P. , Cohen R. , Brezis M.
Published: February 2009

Medical tradition considers a physical examination (PE) an essential part of the clinical encounter. In real medical practice, however, a full PE may not be necessary when the diagnosis is clear after anamnesis and general impression. We assessed the value of PEs in 500 diagnoses of upper respiratory infection (URI) and the attitudes of 123 doctors regarding the utility of PEs in virtual cases.

Methods  Computerized files of consecutive cases with a diagnosis of URI over 8 months in two practices were reviewed and correlation studies between the extent of PE and clinical outcomes were performed. In addition, doctors’ attitudes and declarations about PEs were compared.

Results  Five hundred paediatric and adult patients were included. Less than one‐fifth underwent a full PE. More patients who underwent a full PE returned because they still felt unwell or their parents felt they were unwell. Fewer doctors declared actually having performed PEs than supported giving one in two virtual cases of URI. Specialized doctors were less inclined to perform PEs than doctors without a specialization.

Conclusions  Our study suggests that in many cases presenting as URI, doctors may conduct limited PEs or even omit them entirely.
A new core promoter mutation and premature stop codon in the S gene in HBV strains from Iranian patients with cirrhosis
Authors: Veazjalali M. , Norder H. , Magnius L. , Jazayeri S. M. , Alavian S. M. , Mokhtari‐Azad T.
Published: February 2009

Summary.  In order to define hepatitis B virus (HBV) mutational patterns in Iran, nucleotide sequences obtained from 91 patients and encompassing the precore, basal core promoter (BCP) and surface (S) regions, were compared. The patients were grouped as asymptomatic carriers, chronic active hepatitis or cirrhotic patients. Genotypes and mutations were determined by sequencing and phylogenetic analysis. All strains belonged to genotype D, and most of them to subgenotype D1. All but two strains specified ayw2, one ayw3 and one adw2 determinants. Two deletions of 8‐ or 20‐bp were found in the X region in eight strains, six from patients with chronic active hepatitis. Eight of 21 strains from patients with cirrhosis harboured unusual mutations such as a stop codon at position 69 in the S region or a previously not described mutation in the BCP region (1761TC/ATTTG1766). All patients infected by strains with the stop codon mutation had detectable HBsAg and high viral load. The accumulation of mutations found in the BCP and S regions in HBV strains from patients with chronic active hepatitis and cirrhosis may predict disease progression in Iranian HBsAg carriers.
Molecular evidence for tick‐borne encephalitis virus in ticks in South Korea
Authors: KIM S. Y. , JEONG Y. E. , YUN S.‐M. , LEE I. Y. , HAN M. G. , JU Y. R.
Published: February 2009

Abstract To investigate whether tick‐borne encephalitis viruses (TBEVs) are present in South Korea, Korean ixodid ticks were tested for TBEV RNA. Ticks (n = 2460) were collected from wild and domestic animals or by flagging at forest and grassland in 12 regions of five provinces in 2005–06. Four species in two genera were identified, yielding 197 sample pools (1–20 ticks per pool); from these, 12 envelope protein gene fragments of TBEV were amplified by reverse transcriptase‐nested polymerase chain reaction (RT‐nested PCR). Ten of the 2104 adult ticks (0.4%) and two of the 356 nymph ticks (0.2%) were positive for the envelope (E) gene of TBEV. Twelve TBEV RNA‐positive samples were detected in Gyeonggi and Gangwon provinces. Phylogenetic analysis showed that the E genes of the TBEV isolates were clustered with the Western European subtype (98% identity). This study suggests that TBEVs may exist in Korea.
Models of development for blowfly sister species Chrysomya chloropyga and Chrysomya putoria
Authors: RICHARDS C. S. , CROUS K. L. , VILLET M. H.
Published: February 2009

Abstract Developmental curves for the sister species Chrysomya chloropyga (Wiedemann, 1818) and Chrysomya putoria (Wiedemann, 1830) (Diptera: Calliphoridae) were established at eight and 10 different constant temperatures, respectively, using developmental landmarks and body length as measures of age. The thermal summation constants (K) and developmental threshold (D0) were calculated for five developmental landmarks using a previously described method. Isomorphen and isomegalen diagrams were also constructed for the purpose of estimating postmortem intervals (PMIs). Chrysomya chloropyga had an average developmental threshold value (D0) of 10.91 °C (standard error [SE] = 0.94 °C, n = 5), significantly lower than that of C. putoria (13.42 °C, SE = 0.45 °C, n = 5) (paired t‐test: t = − 4.63, d.f. = 8, P < 0.00). Similarly, K values for C. chloropyga were larger than those for C. putoria for all developmental events except onset of the wandering phase. These are the first data that can be used to calculate minimum PMIs and predict population growth of C. chloropyga and C. putoria in Africa; the data indicate that developmental data for one of these species cannot be used as surrogate data for the sister species.
Population structure and geographical subdivision of theLeishmania majorvectorPhlebotomus papatasias revealed by microsatellite variation
Authors: HAMARSHEH O. , PRESBER W. , YAGHOOBI‐ERSHADI M.‐R. , AMRO A. , AL‐JAWABREH A. , SAWALHA S. , AL‐LAHEM A. , DAS M. L. , GUERNAOUI S. , SERIDI N. , DHIMAN R. C. , HASHIGUCHI Y. , GHRAB J. , HASSAN M. , SCHÖNIAN G.
Published: February 2009

AbstractMulti‐locus microsatellite typing (MLMT) has been employed to infer the population structure ofPhlebotomus papatasi(Scopoli) (Diptera: Psychodidae) sandflies and assign individuals to populations.Phlebotomus papatasisandflies were collected from 35 sites in 15 countries. A total of 188P. papatasiindividuals were typed using five microsatellite loci, resulting in 113 different genotypes. Unique microsatellite signatures were observed for some of the populations analysed. Comparable results were obtained when the data were analysed with Bayesian model and distance‐based methods. Bayesian statistic‐based analyses split the dataset into two distinct genetic clusters, A and B, with further substructuring within each. Population A consisted of five subpopulations representing large numbers of alleles that were correlated with the geographical origins of the sandflies. Cluster B comprised individuals collected in the Middle East and the northern Mediterranean area. The subpopulations B1 and B2 did not, however, show any further correlation to geographical origin. The genetic differentiation between subpopulations was supported byFstatistics showing statistically significant (Bonferroni‐correctedP < 0.005) values of 0.221 between B2 and B1 and 0.816 between A5 and A4. Identification of the genetic structure ofP. papatasipopulations is important for understanding the patterns of dispersal of this species and to developing strategies for sandfly control.
Herbicidal effect of a combination of oxygenic terpenoids on Echinochloa crus‐galli
Authors: HE H B , WANG H B , FANG C X , LIN Y Y , ZENG C M , WU L Z , GUO W C , LIN W X
Published: February 2009

He HB, Wang HB, Fang CX, Lin YY, Zeng CM, Wu LZ, Guo WC & Lin WX (2009). Herbicidal effect of a combination of oxygenic terpenoids on Echinochloa crus‐galli. Weed Research49, 183–192.

One objective of allelopathy research is to identify new allelochemicals that can serve as potential reduced‐risk herbicides, thereby reducing the use of synthetic herbicides for weed control. Five oxygenic terpenoids, namely (−)‐carveol, (+)‐carvone, (−)‐menthone, (−)‐carvyl acetate and (+)‐cedrol, were previously identified compounds or their analogues. The optimum combination of the five terpenoids was determined by orthogonal rotatable central composite design for five variables and five concentration levels in the glasshouse. In hydroponic experiments, the optimum combination significantly inhibited root length, plant height and plant dry weight of Echinochloa crus‐galli, causing a considerable decline in the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities in the root and leaves of E. crus‐galli. In paddy soil experiments, the mixture was highly effective in suppressing E. crus‐galli development in monoculture and grown with rice. However, the mixture was not harmful to the two rice accessions. Oxygenic terpenoids that show high inhibitory effects at low concentrations may be promising herbicidal candidates.
High levels of grass pollen inside European dairy farms: a role for the allergy‐protective effects of environment?
Authors: Sudre B. , Vacheyrou M. , Braun‐Fahrländer C. , Normand A.‐C. , Waser M. , Reboux G. , Ruffaldi P. , Von Mutius E. , Piarroux R. ,   the PASTURE study group
Published: February 2009

Background:  There is evidence of an allergy protective effect in children raised on farm. It has been assumed that microbial exposure may confer this protection. However in farm, little attention has been given to the pollen level and to concomitant microbiological exposure, and indoor pollen concentrations have never been precisely quantified.

Methods:  The kinetics of pollen in dairy farms have been studied in a pilot study (n = 9), and exposure in a sub‐sample of the ongoing European birth cohort PASTURE (n = 106). Measurements of viable microorganisms and pollen were performed in air samples. To identify factors that modulate the pollen concentration multivariate regression analyses were run.

Results:  Indoor pollen (95% of Poaceae fragments and grains) were significantly higher in winter than in summer (P = 0.001) and ranged between 858 to 11 265 counts/m3 during feeding in winter, thus exceeding typical outdoor levels during the pollen season. Geometric mean in French farms was significantly higher than in German and Swiss farms (7 534, 992 and 1 079 count/m3, respectively). The presence of a ventilation system and loose housing systems significantly reduced indoor pollen levels. This pollen concentration rise after feeding was accompanied by an increase in fungal and actinomycetal levels, whereas the concentration of bacteria was not associated with feeding.

Conclusions:  Farmers and their children who attend cowsheds during the feeding sessions are exposed perennially to high pollen concentrations. It might be speculated that the combined permanent exposure to microbes from livestock and grass pollen may initiate tolerance in children living on a farm.
Regulatory T cells in bronchial asthma
Authors: Ryanna K. , Stratigou V. , Safinia N. , Hawrylowicz C.
Published: February 2009

The main focus of this review was the role of a specific subset of T cells with immunomodulatory or immunosuppressive activities, termed regulatory T cells (Tregs), in the pathogenesis and treatment of bronchial asthma. Evidence that these cells are important in maintaining immune homeostasis in health and exhibit impaired activity in active disease will be discussed. Their therapeutic potential is perhaps best highlighted by evidence that therapies with demonstrated efficacy in allergic and asthmatic disease are associated with the induction or restoration of regulatory T‐cell function, e.g. glucocorticoids, allergen immunotherapy. Strategies to improve the safety and efficacy of these treatments and that induce or boost Tregs in bronchial asthma are discussed.
Recombinant factor VIIa and fibrinogen display additive effect during in vitro haemodilution with crystalloids
Authors: FENGER‐ERIKSEN C. , TØNNESEN E. , INGERSLEV J. , SØRENSEN B.
Published: February 2009

Background: Major blood loss requires fluid resuscitation for maintaining hemodynamic stability. Excessive volume infusions predispose to dilutional coagulopathy through loss, consumption and dilution of cells and proteins involved in haemostasis. Further treatment with fibrinogen concentrate and/or recombinant activated factor VII (rFVIIa) may be initiated, although the haemostatic effects in a situation with haemodilution are not fully detailed. The present study evaluates haemostatic effect of fibrinogen and rFVIIa and their combination in an in vitro model of haemodiluted whole blood with two commonly used crystalloids.

Methods: Eight healthy, male volunteers were enrolled. Outcome variables were clot initiation, propagation and strength assessed by thrombelastographic parameters: clotting time, clot formation time, maximum velocity, time until maximum velocity, maximum clot firmness evaluated at dilution levels of 0% (control), 10%, 30% and 50% with isotonic saline and Ringer's lactate in a model of tissue factor‐activated whole blood. Fibrinogen and rFVIIa were additional final reaction concentrations, reflecting commonly used clinically therapeutic dosages.

Results: Dose‐dependent coagulopathy developed following haemodilution with isotonic saline and Ringer's lactate, characterised by a prolonged clot initiation, reduced clot propagation and reduced clot strength. Fibrinogen improved clot strength and propagation phase while rFVIIa shortened clot initiation, both with a positive dose dependency.

Conclusions: The combination of fibrinogen and rFVIIa displays an additive effect and improves overall in vitro whole blood clot formation in a model of in vitro crystalloid‐induced haemodilution.
Comparison of closed loop vs. manual administration of propofol using the Bispectral index in cardiac surgery
Authors: AGARWAL J. , PURI G. D. , MATHEW P. J
Published: February 2009

Background: In recent years, electroencephalographic indices of anaesthetic depth have facilitated automated anaesthesia delivery systems. Such closed‐loop control of anaesthesia has been described in various surgical settings in ASA I–II patients (1–4), but not in open heart surgery characterized by haemodynamic instability and higher risk of intra‐operative awareness. Therefore, a newly developed closed‐loop anaesthesia delivery system (CLADS) to regulate propofol infusion by the Bispectral index (BIS) was compared with manual control during open heart surgery.

Methods: Forty‐four adult ASA II–III patients undergoing elective cardiac surgery under cardiopulmonary bypass were enrolled. The study participants were randomized to two groups: the CLADS group received propofol delivered by the CLADS, while in the manual group, propofol delivery was adjusted manually. The depth of anaesthesia was titrated to a target BIS of 50 in both the groups.

Results: During induction, the CLADS group required lower doses of propofol (P<0.001), resulting in lesser overshoots of BIS (P<0.001) and mean arterial blood pressure (P=0.004). Subsequently, BIS was maintained within ± 10 of the target for a significantly longer time in the CLADS group (P=0.01). The parameters of performance assessment, median absolute performance error (P=0.01), wobble (P=0.04) and divergence (P<0.001), were all significantly better in the CLADS group. Haemodynamic stability was better in the CLADS group and the requirement of phenylephrine in the pre‐cardiopulmonary bypass period as well as the cumulative dose of phenylephrine used were significantly higher in the manual group.

Conclusion: The automated delivery of propofol using CLADS was safe, efficient and performed better than manual administration in open heart surgery.