bluuebunny/crossref_metadata_2025 huggingface dataset:
The Pomp of Superfluous Causes: The Interpretation of Evolutionary Theory
Authors: Walsh D. M.
Published: July 2008

There are two competing interpretations of the modern synthesis theory of evolution: the dynamical (also know as ‘traditional’) and the statistical. The dynamical interpretation maintains that explanations offered under the auspices of the modern synthesis theory articulate the causes of evolution. It interprets selection and drift as causes of population change. The statistical interpretation holds that modern synthesis explanations merely cite the statistical structure of populations. This paper offers a defense of statisticalism. It argues that a change in trait frequencies in a population can be attributed only to selection or drift against the background of a particular statistical description of the population. The traditionalist supposition that selection and drift are description-independent causes of population change leads the dynamical interpretation into a dilemma: it must face a contradiction or accept the loss of explanatory power.
Biorobotic Experiments for the Discovery of Biological Mechanisms
Authors: Datteri Edoardo , Tamburrini Guglielmo
Published: July 2008

Robots are being extensively used for the purpose of discovering and testing empirical hypotheses about biological sensorimotor mechanisms. We examine here methodological problems that have to be addressed in order to design and perform “good” experiments with these machine models. These problems notably concern the mapping of biological mechanism descriptions into robotic mechanism descriptions; the distinction between theoretically unconstrained “implementation details” and robotic features that carry a modeling weight; the role of preliminary calibration experiments; the monitoring of experimental environments for disturbing factors that affect both modeling features and theoretically unconstrained implementation details of robots. Various assumptions that are gradually introduced in the process of setting up and performing these robotic experiments become integral parts of the background hypotheses that are needed to bring experimental observations to bear on biological mechanism descriptions.
Cytoprophet: a Cytoscape plug-in for protein and domain interaction networks inference
Authors: Morcos Faruck , Lamanna Charles , Sikora Marcin , Izaguirre Jesús
Published: July 2008

Summary:  Cytoprophet is a software tool that allows prediction and visualization of protein and domain interaction networks. It is implemented as a plug-in of Cytoscape, an open source software framework for analysis and visualization of molecular networks. Cytoprophet implements three algorithms that predict new potential physical interactions using the domain composition of proteins and experimental assays. The algorithms for protein and domain interaction inference include maximum likelihood estimation (MLE) using expectation maximization (EM); the set cover approach maximum specificity set cover (MSSC) and the sum-product algorithm (SPA). After accepting an input set of proteins with Uniprot ID/Accession numbers and a selected prediction algorithm, Cytoprophet draws a network of potential interactions with probability scores and GO distances as edge attributes. A network of domain interactions between the domains of the initial protein list can also be generated. Cytoprophet was designed to take advantage of the visual capabilities of Cytoscape and be simple to use. An example of inference in a signaling network of myxobacterium Myxococcus xanthus is presented and available at Cytoprophet's website.

Availability:  http://cytoprophet.cse.nd.edu

Contact:  cytoprophet@cse.nd.edu

Supplementary information: Examples and supplementary data are accessible at http://cytoprophet.cse.nd.edu
Robust and efficient identification of biomarkers by classifying features on graphs
Authors: Hwang TaeHyun , Sicotte Hugues , Tian Ze , Wu Baolin , Kocher Jean-Pierre , Wigle Dennis A. , Kumar Vipin , Kuang Rui
Published: July 2008

Motivation: A central problem in biomarker discovery from large-scale gene expression or single nucleotide polymorphism (SNP) data is the computational challenge of taking into account the dependence among all the features. Methods that ignore the dependence usually identify non-reproducible biomarkers across independent datasets. We introduce a new graph-based semi-supervised feature classification algorithm to identify discriminative disease markers by learning on bipartite graphs. Our algorithm directly classifies the feature nodes in a bipartite graph as positive, negative or neutral with network propagation to capture the dependence among both samples and features (clinical and genetic variables) by exploring bi-cluster structures in a graph. Two features of our algorithm are: (1) our algorithm can find a global optimal labeling to capture the dependence among all the features and thus, generates highly reproducible results across independent microarray or other high-thoughput datasets, (2) our algorithm is capable of handling hundreds of thousands of features and thus, is particularly useful for biomarker identification from high-throughput gene expression and SNP data. In addition, although designed for classifying features, our algorithm can also simultaneously classify test samples for disease prognosis/diagnosis.

Results: We applied the network propagation algorithm to study three large-scale breast cancer datasets. Our algorithm achieved competitive classification performance compared with SVMs and other baseline methods, and identified several markers with clinical or biological relevance with the disease. More importantly, our algorithm also identified highly reproducible marker genes and enriched functions from the independent datasets.

Availability: Supplementary results and source code are available at http://compbio.cs.umn.edu/Feature_Class.

Contact:  kuang@cs.umn.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Is there an acceleration of the CpG transition rate during the mammalian radiation?
Authors: Peifer M. , Karro J. E. , von Grünberg H. H.
Published: July 2008

Motivation: In this article we build a model of the CpG dinucleotide substitution rate and use it to challenge the claim that, that rate underwent a sudden mammalian-specific increase approximately 90 million years ago. The evidence supporting this hypothesis comes from the application of a model of neutral substitution rates able to account for elevated CpG dinucleotide substitution rates. With the initial goal of improving that model's accuracy, we introduced a modification enabling us to account for boundary effects arising by the truncation of the Markov field, as well as improving the optimization procedure required for estimating the substitution rates.

Results: When using this modified method to reproduce the supporting analysis, the evidence of the rate shift vanished. Our analysis suggests that the CpG-specific rate has been constant over the relevant time period and that the asserted acceleration of the CpG rate is likely an artifact of the original model.

Contact:  peifer@uni-graz.at

Supplementary information:  Supplementary data are available at Bioinformatics online.
Mixture models for protein structure ensembles
Authors: Hirsch Michael , Habeck Michael
Published: July 2008

Motivation: Protein structure ensembles provide important insight into the dynamics and function of a protein and contain information that is not captured with a single static structure. However, it is not clear a priori to what extent the variability within an ensemble is caused by internal structural changes. Additional variability results from overall translations and rotations of the molecule. And most experimental data do not provide information to relate the structures to a common reference frame. To report meaningful values of intrinsic dynamics, structural precision, conformational entropy, etc., it is therefore important to disentangle local from global conformational heterogeneity.

Results: We consider the task of disentangling local from global heterogeneity as an inference problem. We use probabilistic methods to infer from the protein ensemble missing information on reference frames and stable conformational sub-states. To this end, we model a protein ensemble as a mixture of Gaussian probability distributions of either entire conformations or structural segments. We learn these models from a protein ensemble using the expectation–maximization algorithm. Our first model can be used to find multiple conformers in a structure ensemble. The second model partitions the protein chain into locally stable structural segments or core elements and less structured regions typically found in loops. Both models are simple to implement and contain only a single free parameter: the number of conformers or structural segments. Our models can be used to analyse experimental ensembles, molecular dynamics trajectories and conformational change in proteins.

Availability: The Python source code for protein ensemble analysis is available from the authors upon request.

Contact:  michael.habeck@tuebingen.mpg.de
Contaminants in marine ecosystems: developing an integrated indicator framework using biological-effect techniques
Authors: Thain John E. , Vethaak A. Dick , Hylland Ketil
Published: July 2008

Thain, J. E., Vethaak, A. D., and Hylland, K. 2008. Contaminants in marine ecosystems: developing an integrated indicator framework using biological-effect techniques. – ICES Journal of Marine Science, 65: 1508–1514. Input of contaminants is an important pressure in most urbanized coastal areas, but establishing appropriate indicators of their presence and effects has been challenging. Such indicators would, at the very least, have to integrate chemical and biological data. One difficulty has arisen because the measurements provide information on different levels of biological organization (gene level up to community), although it is not obvious how this information could be conceptually linked. In addition, there are complicating factors, such as the differing ecological relevance of measurements, natural variation, confounding factors, and knowledge of background level or responses for each method. The challenge of how to take these issues forwards is discussed in light of current scientific thinking and of meeting international obligations. First, an integrated approach must be developed to using biological-effect techniques with chemical measurements, and second, assessment tools are required. Proposals for both of these have been initiated by ICES and OSPAR working groups and workshops. Concomitantly, steps have been taken to develop integrated assessment tools on a national basis. These show promise but highlight the difficulties of using biological-effect measures as indicators of ecosystem health.
Use of oncolytic viruses for the eradication of drug-resistant cancer cells
Authors: Wodarz Dominik
Published: July 2008

Targeted therapy using small-molecule inhibitors is a promising new therapy approach against cancer, but drug-resistant mutants present an obstacle to success. Oncolytic virus therapy, where viruses replicate specifically in cancer cells and kill them, is another promising therapy approach against cancer. While encouraging results have been observed in clinical trials, consistent success has not been possible so far. Based on a computational framework, I report that even if oncolytic virus therapy fails to eradicate a cancer, it can have the potential to eradicate the sub-population of drug-resistant cancer cells. Once this has occurred, targeted drug therapy can be used to induce cancer remission. For this to work, a drug resistance mutation must confer a certain fitness cost to the cell, as has been documented in the literature. The reason for this finding is that in the presence of a shared virus, the faster growing (drug-sensitive) cell population produces an amount of virus that is too much for the slower growing (drug-resistant) cell population to survive. This is derived from a population dynamic principle known as apparent competition. Therefore, a sequential combination of oncolytic virus and targeted therapies can overcome major weaknesses of either approach alone.
Epidemic thresholds in dynamic contact networks
Authors: Volz Erik , Meyers Lauren Ancel
Published: July 2008

The reproductive ratio,R0, is a fundamental quantity in epidemiology, which determines the initial increase in an infectious disease in a susceptible host population. In most epidemic models, there is a specific value ofR0, the epidemic threshold, above which epidemics are possible, but below which epidemics cannot occur. As the complexity of an epidemic model increases, so too does the difficulty of calculating epidemic thresholds. Here we derive the reproductive ratio and epidemic thresholds for susceptible–infected–recovered (SIR) epidemics in a simple class of dynamic random networks. As in most epidemiological models,R0depends on two basic epidemic parameters, the transmission and recovery rates. We find thatR0also depends on social parameters, namely the degree distribution that describes heterogeneity in the numbers of concurrent contacts and the mixing parameter that gives the rate at which contacts are initiated and terminated. We show that social mixing fundamentally changes the epidemiological landscape and, consequently, that static network approximations of dynamic networks can be inadequate.
The fixation probability of beneficial mutations
Authors: Patwa Z , Wahl L.M
Published: July 2008

The fixation probability, the probability that the frequency of a particular allele in a population will ultimately reach unity, is one of the cornerstones of population genetics. In this review, we give a brief historical overview of mathematical approaches used to estimate the fixation probability of beneficial alleles. We then focus on more recent work that has relaxed some of the key assumptions in these early papers, providing estimates that have wider applicability to both natural and laboratory settings. In the final section, we address the possibility of future work that might bridge the gap between theoretical results to date and results that might realistically be applied to the experimental evolution of microbial populations. Our aim is to highlight the concrete, testable predictions that have arisen from the theoretical literature, with the intention of further motivating the invaluable interplay between theory and experiment.
Spatially selective sampling of single cells using optically trapped fusogenic emulsion droplets: a new single-cell proteomic tool
Authors: Lanigan Peter M.P , Chan Karen , Ninkovic Tanya , Templer Richard H , French P.M.W , de Mello A.J , Willison K.R , Parker P.J , Neil M.A.A , Ces Oscar , Klug D.R
Published: July 2008

We present a platform for the spatially selective sampling of the plasma membrane of single cells. Optically trapped lipid-coated oil droplets (
smart droplet microtools
, SDMs), typically 0.5–5 μm in size, composed of a hexadecane hydrocarbon core and fusogenic lipid outer coating (mixture of 1,2-dioleoyl-phosphatidylethanolamine and 1,2-dioleoyl-
sn
-glycero-3-phosphatidylcholine) were brought into controlled contact with target colon cancer cells leading to the formation of connecting membrane tethers. Material transfer from the cell to the SDM across the membrane tether was monitored by tracking membrane-localized enhanced green fluorescent protein.
Automatic imitation in budgerigars
Authors: Mui Rosetta , Haselgrove Mark , Pearce John , Heyes Cecilia
Published: July 2008

A fully automated procedure, involving computer-controlled stimulus presentation and computer-recorded response measurement, was used for the first time to study imitation in non-human animals. After preliminary training to peck and step on a manipulandum, budgerigars were given a discrimination task in which they were rewarded with food for pecking during observation of pecking and for stepping during observation of stepping (Compatible group), or for pecking while observing stepping and for stepping while observing pecking (Incompatible group). The Incompatible group, which had to counter-imitate for food reward, showed weaker discrimination performance than the Compatible group. This suggests that, like humans, budgerigars are subject to ‘automatic imitation’; they cannot inhibit online the tendency to imitate pecking and/or stepping, even when imitation of these behaviours interferes with the performance of an ongoing task. The difference between the two groups persisted over 10 test sessions, but the Incompatible group eventually acquired the discrimination, making more counter-imitative than imitative responses in the final sessions. These results are consistent with the associative sequence learning model, which suggests that, across species, the development of imitation and the mirror system depends on sensorimotor experience and phylogenetically ancient mechanisms of associative learning.
Single‐step affinity purification of recombinant proteins using a self‐excising module from Neisseria meningitidis FrpC
Authors: Sadilkova Lenka , Osicka Radim , Sulc Miroslav , Linhartova Irena , Novak Petr , Sebo Peter
Published: July 2008

Purification of recombinant proteins is often a challenging process involving several chromatographic steps that must be optimized for each target protein. Here, we developed a self‐excising module allowing single‐step affinity chromatography purification of untagged recombinant proteins. It consists of a 250‐residue‐long self‐processing module of the Neisseria meningitidis FrpC protein with a C‐terminal affinity tag. The N terminus of the module is fused to the C terminus of a target protein of interest. Upon binding of the fusion protein to an affinity matrix from cell lysate and washing out contaminating proteins, site‐specific cleavage of the Asp–Pro bond linking the target protein to the self‐excising module is induced by calcium ions. This results in the release of the target protein with only a single aspartic acid residue added at the C terminus, while the self‐excising affinity module remains trapped on the affinity matrix. The system was successfully tested with several target proteins, including glutathione‐S‐transferase, maltose‐binding protein, β‐galactosidase, chloramphenicol acetyltransferase, and adenylate cyclase, and two different affinity tags, chitin‐binding domain or poly‐His. Moreover, it was demonstrated that it can be applied as an alternative to two currently existing systems, based on the self‐splicing intein of Saccharomyces cerevisiae and sortase A of Staphylococcus aureus.
Modulation of kinase‐inhibitor interactions by auxiliary protein binding: Crystallography studies on Aurora A interactions with VX‐680 and with TPX2
Authors: Zhao Baoguang , Smallwood Angela , Yang Jingsong , Koretke Kristin , Nurse Kelvin , Calamari Amy , Kirkpatrick Robert B. , Lai Zhihong
Published: July 2008

VX‐680, also known as MK‐0457, is an ATP‐competitive small molecule inhibitor of the Aurora kinases that has entered phase II clinical trials for the treatment of cancer. We have solved the cocrystal structure of AurA/TPX2/VX‐680 at 2.3 Å resolution. In the crystal structure, VX‐680 binds to the active conformation of AurA. The glycine‐rich loop in AurA adopts a unique bent conformation, forming a π–π interaction with the phenyl group of VX‐680. In contrast, in the published AurA/VX‐680 structure, VX‐680 binds to AurA in the inactive conformation, interacting with a hydrophobic pocket only present in the inactive conformation. These data suggest that TPX2, a protein cofactor, can alter the binding mode of VX‐680 with AurA. More generally, the presence of physiologically relevant cofactor proteins can alter the kinetics, binding interactions, and inhibition of enzymes, and studies with these multiprotein complexes may be beneficial to the discovery and optimization of enzyme inhibitors as therapeutic agents.
Structure of AscE and induced burial regions in AscE and AscG upon formation of the chaperone needle‐subunit complex of type III secretion system in Aeromonas hydrophila
Authors: Tan Yih Wan , Yu Hong Bing , Leung Ka Yin , Sivaraman J. , Mok Yu‐Keung
Published: July 2008

In the type III secretion system (T3SS) of Aeromonas hydrophila, the putative needle complex subunit AscF requires both putative chaperones AscE and AscG for formation of a ternary complex to avoid premature assembly. Here we report the crystal structure of AscE at 2.7 Å resolution and the mapping of buried regions of AscE, AscG, and AscF in the AscEG and AscEFG complexes using limited protease digestion. The dimeric AscE is comprised of two helix–turn–helix monomers packed in an antiparallel fashion. The N‐terminal 13 residues of AscE are buried only upon binding with AscG, but this region is found to be nonessential for the interaction. AscE functions as a monomer and can be coexpressed with AscG or with both AscG and AscF to form soluble complexes. The AscE binding region of AscG in the AscEG complex is identified to be within the N‐terminal 61 residues of AscG. The exposed C‐terminal substrate‐binding region of AscG in the AscEG complex is induced to be buried only upon binding to AscF. However, the N‐terminal 52 residues of AscF remain exposed even in the ternary AscEFG complex. On the other hand, the 35‐residue C‐terminal region of AscF in the complex is resistant to protease digestion in the AscEFG complex. Site‐directed mutagenesis showed that two C‐terminal hydrophobic residues, Ile83 and Leu84, of AscF are essential for chaperone binding.
Microsatellite development and survey of genetic variation in skipjack tuna Katsuwonus pelamis
Authors: Menezes M. R. , Noguchi D. , Nakajima M. , Taniguchi N.
Published: July 2008

A survey of five newly developed microsatellite DNA markers in skipjack tuna Katsuwonus pelamis revealed high levels of polymorphism in two samples off the west coast of India (Minicoy Island and Kochi coast) and one sample off the Japan coast. Although significant differentiation (P < 0·01) in the number of specific alleles was observed between Minicoy and Kochi samples, the F‐statistics values among the samples were very low (average = 0·0014) and not significant (P = 0·284).
Recruitment variability of resident brown trout in peripheral populations from southern Europe
Authors: NICOLA GRACIELA G. , ALMODÓVAR ANA , JONSSON BROR , ELVIRA BENIGNO
Published: July 2008

1. Population regulation was studied for seven consecutive years (1992–98) in five rivers at the periphery of the distribution ofSalmo trutta, where the fish were living under environmental constraints quite different from those of the main distribution area.

2. Recruitment is naturally highly variable and the populations had been earlier classified as overexploited. Thus we expected that densities of young trout in most populations would be too low for density‐dependent mortality to operate. We tested this by fitting the abundance of recruits to egg densities over seven consecutive years (stock–recruitment relationship), and used the results to judge whether exploitation should be restricted in the interests of conserving the populations.

3. The density of 0+ trout in early September, as well as the initial density of eggs and parents, varied greatly among localities and years. The data for all populations fitted the Ricker stock–recruitment model. The proportion of variance explained by the population curves varied between 32% and 51%. However, in most cases the observations were in the density‐independent part of the stock–recruitment curve, where densities of the recruits increased proportionally with egg densities.

4. Our findings suggest that recruitment densities in most rivers and years were below the carrying capacity of the habitats. Although density‐dependent mechanisms seemed to regulate fish abundance in some cases, environmental factors and harvesting appeared generally to preclude populations from reaching densities high enough for negative feedbacks to operate. The findings thus lend support toHaldane’s (1956)second hypothesis that changes in population density are primarily due to density‐independent factors in unfavourable areas and areas with low density due to exploitation. Exploitation should be reduced to allow natural selection to operate more effectively.
Transcription factors involved in pancreas development are expressed in paediatric solid pseudopapillary tumours
Authors: Galmiche L , Sarnacki S , Verkarre V , Boizet B , Duvillie B , Fabre M , Jaubert F
Published: July 2008

Aims:  Solid pseudopapillary tumours (SPT) are rare pancreatic tumours, especially in children. The origin of this benign tumour remains unknown. Mutations of β‐catenin, a gene essential for pancreatic development, are constantly found, leading to delocalization of immunohistochemical signals from the cytoplasm to the nuclei of tumour cells. The aim was to report clinical and histological data of eight children with SPT and explore the immunohistochemical expression of pancreatic duodenal homeobox (PDX) 1 and Sox9, known to be crucial for pancreatic development and linked to the β‐catenin cascade.

Methods and results:  Eight children with features suggestive of SPT underwent surgical resection. Tumours displayed typical histological appearances. One was incompletely resected and recurred. Immunolabelling revealed nuclear location of β‐catenin in all cases and strong cytoplasmic but no nuclear expression of PDX1 or Sox9 in all but one case.

Conclusions:  The clinical behaviour of SPT in the paediatric population is similar to its adult counterpart. Complete surgical resection is essential. PDX1 and Sox9 proteins are exclusively expressed in the cytoplasmic compartment in SPT, suggesting overexpression of the corresponding genes linked to β‐catenin mutations. These findings favour the hypothesis that SPT originates from transformation of normally quiescent pancreatic stem cells.
The effect of par‐baking and frozen storage time on the quality of cup cake
Authors: Karaoğlu Mehmet Murat , Kotancilar Halis Gürbüz , Gerçekaslan Kamil Emre
Published: July 2008

The effects of frozen storage and initial baking time of par‐baked cake on baking loss, volume, moisture, colour and textural properties of cake obtained after thawing and rebaking were investigated. Cakes, par‐baked at 175 °C for 15, 20 and 25 min, were stored at −18 °C for 3, 6 and 9 months. After storage, par‐baked cakes were thawed and rebaked at 175 °C for 10, 15 and 20 min. Baking loss, moisture content, L and +b colour values, firmness, gumminess and chewiness of the resulting full‐baked cakes were significantly affected by both par‐baking and frozen storage time, while specific volume, cohesiveness, springiness and resilience values were significantly affected by frozen storage time. The increase in the time of frozen storage of the par‐baked cake leads to a decrease in the quality of the rebaked cake, namely an increase of baking loss and cake crumb firmness, and a loss in the moisture content and specific volume. Moisture of cake crumb, L and +b colour values, firmness, gumminess and chewiness significantly increased as the par‐baking time increased. However, regarding baking loss, specific volume, moisture content and textural properties, 3‐month intermediate storage at −18 °C and 20‐min initial baking time gave the best result among the cakes produced by using the two‐step baking procedure.
Comparison of rheological models for determining dark chocolate viscosity
Authors: Afoakwa Emmanuel Ohene , Paterson Alistair , Fowler Mark , Vieira Joselio
Published: July 2008

Parameters in chocolate rheology, namely shear viscosity and yield stress, are important in manufacture and directly influenced by product particle size distribution (PSD) and composition. The Casson model was the standard confectionery industry strategy to quantify rheological properties of molten chocolate until in 2000, the International Confectionery Association recommended the use of interpolation data to describe viscosity. The two strategies are compared and correlated in defining rheological properties of molten dark chocolates prepared using different PSD, fat and lecithin content. Rheological parameters were determined using a shear rate‐controlled rheometer and data examined using correlation, regression and principal component analyses to establish their inter‐relationships. Correlation and regression analyses showed high correlation (r = 0.89–1.00) and regression coefficients (R2 = 0.84–1.00). The newer International Confectionery Association technique gave higher correlation and regression coefficients than the Casson model, but multivariate principal component analysis showed that the two models were highly related and either could effectively quantify dark chocolate viscosity parameters.
Ethical dilemmas of a large national multi‐centre study in Australia: time for some consistency
Authors: Driscoll Andrea , Currey Judy , Worrall‐Carter Linda , Stewart Simon
Published: July 2008

Aims and objectives.  To examine the impact and obstacles that individual Institutional Research Ethics Committee (IRECs) had on a large‐scale national multi‐centre clinical audit called the National Benchmarks and Evidence‐based National Clinical guidelines for Heart failure management programmes Study.

Background.  Multi‐centre research is commonplace in the health care system. However, IRECs continue to fail to differentiate between research and quality audit projects.

Methods.  The National Benchmarks and Evidence‐based National Clinical guidelines for Heart failure management programmes study used an investigator‐developed questionnaire concerning a clinical audit for heart failure programmes throughout Australia. Ethical guidelines developed by the National governing body of health and medical research in Australia classified the National Benchmarks and Evidence‐based National Clinical guidelines for Heart failure management programmes Study as a low risk clinical audit not requiring ethical approval by IREC.

Results.  Fifteen of 27 IRECs stipulated that the research proposal undergo full ethical review. None of the IRECs acknowledged: national quality assurance guidelines and recommendations nor ethics approval from other IRECs. Twelve of the 15 IRECs used different ethics application forms. Variability in the type of amendments was prolific. Lack of uniformity in ethical review processes resulted in a six‐ to eight‐month delay in commencing the national study.

Conclusions.  Development of a national ethics application form with full ethical review by the first IREC and compulsory expedited review by subsequent IRECs would resolve issues raised in this paper. IRECs must change their ethics approval processes to one that enhances facilitation of multi‐centre research which is now normative process for health services.

Relevance to clinical practice.  The findings of this study highlight inconsistent ethical requirements between different IRECs. Also highlighted are the obstacles and delays that IRECs create when undertaking multi‐centre clinical audits. However, in our clinical practice it is vital that clinical audits are undertaken for evaluation purposes. The findings of this study raise awareness of inconsistent ethical processes and highlight the need for expedient ethical review for clinical audits.
Nurse supplementary prescribing for patients with diabetes: a national questionnaire survey
Authors: Carey Nicola , Courtenay Molly
Published: July 2008

Aims and objectives.  To examine the prescribing practices of nurse supplementary prescribing in diabetes.

Background.  Nurses in several roles are involved in the management of medicines for patients with diabetes. Nurse prescribing should help optimise these roles. Nurses in the UK have virtually the same independent prescribing rights as doctors. There is little or no evidence on the extent to which nurse supplementary prescribing is used, or the impact and activity of nurse supplementary prescribing for patients with diabetes.

Design.  Survey.

Method.  A random sample of 214 nurse supplementary prescribers self‐completed a written questionnaire.

Results.  The majority of nurses held an academic qualification at degree level or higher, had a wealth of clinical experience, worked full‐time, were based in primary care and worked in general practice. The majority of nurses prescribed between one and five items a week. Oral anti‐diabetic drugs, hypertension and lipid‐regulating drugs and insulins were the products most often prescribed. Over 85% had undertaken specialist training in diabetes prior to undertaking the prescribing programme.

Conclusion.  Supplementary prescribing provides a practical and useful framework within which to prescribe medicines for patients with diabetes and its associated complications. Specialist diabetes training is a necessary prerequisite for nurses prescribing in this area. It is evident that there is still a place for supplementary prescribing.

Implications for clinical practice.  • Recent legislative changes mean that nurses can now independently prescribe practically any drug.

• Nurses in general practice appear to prescribe most frequently as a nurse supplementary prescriber for patients with diabetes.

• Nurse supplementary prescribers are likely to use this mode of prescribing to deliver medicines to patients with diabetes.

• Over two‐thirds prescribe for common but serious complications of diabetes, e.g. hypertension, hyperlipidaemia and cardiovascular disease
Relapse prevention in serious and enduring mental illness: a pilot study
Authors: FOSTER J. H. , JUMNOODOO R.
Published: July 2008

The purpose of the research was to ascertain whether coping knowledge and relapse outcomes are enhanced after 12 months following a programme of community‐based relapse prevention (RP). Relapse to mental illness has high societal costs and this programme aims to lessen the likelihood of relapse by equipping service users with greater coping mechanisms by employing a quasi‐experimental design with some controls. Participants are recruited from a day hospital in London. There are two groups: (1) experimental group (n = 10) and (2) control group (n = 10). The experimental group is given an 8‐week RP programme, and the control group receives routine care. Both groups are then followed up at 1, 2 and 12 months. The research hypothesis was participants undergoing a programme of RP will have greater 12‐month knowledge and superior relapse outcomes. The 52‐week follow‐up rates are 80% for experimental group and 70% for control group. There are no differences in the two groups in terms of relapse outcomes. Knowledge between baseline and 52 weeks is improved in the experimental group though most of the changes are observed during the first 12 weeks. We conclude that an 8‐week RP programme resulted in improved knowledge but not relapse outcomes at 52 weeks. A randomized controlled trial should now be conducted to assess whether these results are replicated.
Alanine aminotransferase‐based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B
Authors: Chan H. L.‐Y. , Wong G. L.‐H. , Choi P. C.‐L. , Chan A. W.‐H. , Chim A. M.‐L. , Yiu K. K.‐L. , Chan F. K.‐L. , Sung J. J.‐Y. , Wong V. W.‐S.
Published: July 2008

Summary.  The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
Regulation of glucocorticoid receptor in nasal polyps by systemic and intranasal glucocorticoids
Authors: Pujols L. , Alobid I. , Benítez P. , Martínez‐Antón A. , Roca‐Ferrer J. , Fokkens W. J. , Mullol J. , Picado C.
Published: July 2008

Background:  Poor response of nasal polyps to glucocorticoids (GCs) may be because of abnormal expression of GC receptors (GR) α and β or to downregulation of GRα. We aimed to evaluate the in vivo regulation of GR isoforms in GC‐treated nasal polyps and to assess the relationship between clinical response to GCs and GR levels.

Methods:  Patients with nasal polyps were randomly (3:1) treated (n = 51) or not (n = 14) with oral prednisone and intranasal budesonide for 2 weeks, plus intranasal budesonide for 10 additional weeks. Nasal symptoms were evaluated. Biopsies were obtained before (w0) and after 2 (w2) and 12 (w12) weeks of treatment, and analysed for their inflammatory content and GR mRNA (102 cDNA copies/μg total RNA) and protein (% immunoreactive inflammatory cells) expression. Healthy nasal mucosa (n = 11) was also investigated. Data are presented as median and 25–75th percentile.

Results:  At w0, nasal polyps expressed less GRα mRNA (1343;683–2263; P < 0.05) and GR protein (41;29–54; P < 0.05) than nasal mucosa (2474;1346–2933; 60;51–72, respectively). GRβ immunoreactivity was higher in nasal polyps (11;4–19; P < 0.05) than in nasal mucosa (5;2–5). At w2, increased GRα mRNA (2010;1037–2732; P < 0.01) and GR protein (56;27–71; P = 0.056) were found compared with w0 (1177;759–2058; 37;29–55, respectively). At w12, GRα mRNA and GR protein were similar to w0. GRβ expression was unaltered by treatment. Neither GRα nor GRβ correlated with nasal symptoms. GR immunoreactivity negatively correlated with eosinophils (r = −0.478; P < 0.001).

Conclusions:  GRα is downregulated in nasal polyps and upregulated by GC treatment. Neither GRα nor GRβ appear to determine the sensitivity to GCs in nasal polyposis.
AllergoOncology: the role of IgE‐mediated allergy in cancer
Authors: Jensen‐Jarolim E. , Achatz G. , Turner M. C. , Karagiannis S. , Legrand F. , Capron M. , Penichet M. L. , Rodríguez J. A. , Siccardi A. G. , Vangelista L. , Riemer A. B. , Gould H.
Published: July 2008

Epidemiological studies have suggested inverse associations between allergic diseases and malignancies. As a proof of concept for the capability of immunoglobulin E (IgE) to destruct tumor cells, several experimental strategies have evolved to specifically target this antibody class towards relevant tumor antigens. It could be demonstrated that IgE antibodies specific to overexpressed tumor antigens have been superior to any other immunoglobulin class with respect to antibody‐dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) reactions. In an alternative approach, IgE nonspecifically attached to tumor cells proved to be a powerful adjuvant establishing tumor‐specific immune memory. Active Th2 immunity could also be achieved by applying an oral immunization regimen using mimotopes, i.e. epitope mimics of tumor antigens. The induced IgE antibodies could be cross‐linked by live tumor cells leading to tumoricidic mediator release. Thus, IgE antibodies may not only act in natural tumor surveillance, but could possibly also be exploited for tumor control in active and passive immunotherapy settings. Thereby, eosinophils, mast cells and macrophages can be armed with the cytophilic IgE and become potent anti‐tumor effectors, able to trace viable tumor cells in the tissues. It is strongly suggested that the evolving new field AllergoOncology will give new insights into the role of IgE‐mediated allergy in malignancies, possibly opening new avenues for tumor therapy.
Quantitative Trait Loci for Resistance to Powdery Mildew in Cucumber under Seedling Spray Inoculation and Leaf Disc Infection
Authors: Longzhou Liu , Xiaojun Yuan , Run Cai , Junsong Pan , Huanle He , Lihua Yuan , Yuan Guan , Lihuang Zhu
Published: July 2008

Powdery mildew (PM) is an economically important disease of cucumber (Cucumis sativus L.) caused by the obligate biotrophic pathogen, Podosphaera xanthii, in greenhouse and field. In this study, a resistant breeding line S06 (greenhouse European type) and a susceptible cucumber inbred line S94 (Northern China open‐field type) and their F2:3 populations were used to investigate PM resistance under seedling spray inoculation in two growing seasons and leaf disc infection in one season. Quantitative trait loci (QTL) analysis was undertaken based on a constructed molecular linkage map of the corresponding F2 population using composite interval mapping. Five QTL (PM1.1, PM1.2, PM2.1, PM2.2 and PM5.1) for PM resistance were identified and located on linkage groups (LG) 1, 2 and 5, explaining 3.4–45.0% of the phenotypic variation. Three consistent QTL (PM1.1, PM2.1 and PM5.1) were detected under the three test conditions. The present results of the QTL analysis for PM resistance have laid a basis for breeding PM‐resistant cucumber varieties by molecular marker‐assisted selection.
Sporulation, Inoculation Methods and Pathogenicity of Ustilaginoidea albicans, the Cause of White Rice False Smut in China
Authors: Wang Shu , Li Min , Dong Hai , Liu Xiao‐Zhou , Bai Yuan‐Jun , Yang Hao
Published: July 2008

Sporulation and inoculation methods were studied to determine the pathogenicity of Ustilaginoidea albicans S Wang and JK Bai, the cause of white rice false smut, isolated in China. High sporulation was obtained using solid culture, liquid fermentation and double layer incubation system. In liquid culture, the culture media composition contributed to observed differences in sporulation. Potato sucrose broth was the optimal media to promote conidia production, increasing the concentration to up to 4.8 × 108 spores/ml. Inoculation by injection and spraying resulted in disease development, demonstrating that conidia of white rice false smut are virulent to rice plants, despite apparent differences in disease incidence. Estimates of mean disease severity were higher for injection than for spraying as assessed by percent infected panicles. The two methods resulted in disease severity ranging from 12.0 to 28.7% and 8.2 to 20.7%, respectively. Low temperature exposure after inoculation had a strong stimulatory effect on disease development.
Differences in multidisciplinary team assessment and treatment between patients with stage IV colon and rectal cancer
Authors: Segelman J. , Singnomklao T. , Hellborg H. , Martling A.
Published: July 2008

Objective  At diagnosis, 14–27% of patients with colorectal cancer (CRC) have distant metastases (stage IV) and a poor prognosis. Today, treatment decisions for CRC patients are often made at multidisciplinary team (MDT) conferences. The aim of this study was to evaluate the effects of development and implementation of MDT assessment and treatment in patients with stage IV colon cancer (CC) and rectal cancer (RC) in a large population.

Method  All 1449 patients who had stage IV CRC at the time of diagnosis and were registered in the regional quality registry of Stockholm from 1995 to 2004 were included. Patients with CC and RC were grouped according to treatment and their characteristics were analysed separately.

Results  In total, 1000 patients with CC and 449 patients with RC had stage IV disease. Of these, 689 (68.9%) CC patients and 352 (78.4%) RC patients were assessed by a MDT and the proportion increased over the study period (P < 0.001). Surgery for metastases was undertaken on 39 (3.9%) CC patients and 38 (8.5%) RC patients (P < 0.001). CRC patients selected for metastasis surgery had 37% 5‐year survival when compared with 2% in patients who were not selected for metastasis surgery (P < 0.001).

Conclusion  Patients with CC were less often assessed by a MDT and less often had metastasis surgery than RC patients. The proportion of patients with CC and RC assessed by a MDT increased during the study period, as did the proportion who had surgery for metastases. MDT assessment opens up the opportunity for more aggressive treatment with better outcomes.
Adenocarcinoma complicating restorative proctocolectomy for ulcerative colitis with mucosectomy performed by Cavitron Ultrasonic Surgical Aspirator®
Authors: Branco B. C. , Sachar D. B. , Heimann T. , Sarpel U. , Harpaz N. , Greenstein A. J.
Published: July 2008

This is a report of adenocarcinoma arising in an ileal pouch after restorative proctocolectomy (RPC) with rectal mucosal stripping performed by Cavitron Ultrasonic Surgical Aspirator (CUSA®) for ulcerative colitis. The CUSA® was introduced to simplify and optimize ileal pouch–anal anastomosis with mucosectomy and has been shown to shorten the operative time and reduce blood loss. Its use however, may increase the number of pathology specimens made uninterpretable on account of tissue ablation. In the present case, even though preoperative colonoscopy had clearly shown dysplasia, the surgical pathology report could not detect any neoplasia in the specimen; hence, the patient was not surveyed for pouch cancer. Six years later, the patient presented with intestinal obstruction caused by cancer. While protocols for universal pouch surveillance remain somewhat controversial, we conclude on the basis of this case and a review of the literature that in RPC with mucosectomy performed by CUSA®, pouch cancer surveillance is particularly important because remnants of rectal epithelium may have been left behind and tissue ablation may have made the surgical pathology report uninterpretable.
Blow as well as pull: an innovative technique for dealing with a rectal foreign body.
Authors: Manimaran N. , Shorafa M. , Eccersley J.
Published: July 2008

Removal of a rectal foreign body (FB) has become increasingly common in the recent times. Nature of rectal FB is limited only by the imagination of the patient concerned. Many techniques have been described for removal and various theories have been put forward to explain the mechanics of the procedure. We report a case where a new technique had been employed.
Mechanisms of action of intravesical botulinum treatment in refractory detrusor overactivity
Authors: Drake Marcus J.
Published: July 2008

Urinary retention is one of a multitude of autonomic deficits resulting from acute botulism (oral botulinum intoxication). The powerful influence of botulinum‐A neurotoxin (BoNT‐A) on autonomic function has now been harnessed to the benefit of patients with detrusor overactivity (DO), by injecting the agent intramurally, with consequent improvement in urodynamic and clinical variables. Nonetheless, the complexity of bladder cellular physiology and putative mechanisms underlying the pathophysiological basis of DO even now render the precise mechanisms of clinical response to intravesical BoNT‐A uncertain. In this review, the processes by which BoNT‐A affects nerve function and the state‐of‐the‐art in the physiological understanding of bladder dysfunction are discussed together, conveying how much must be reckoned when attempting to understand the mechanisms by which this powerful agent can improve refractory and bothersome DO.