bluuebunny/crossref_metadata_2025 huggingface dataset:
Hackers' Accounts
Authors: Turgeman-Goldschmidt Orly
Published: January 2005

Hacking is a widespread international phenomenon, and hackers'actions occasionally reach the media headlines. This study was designed to explore hackers' accounts. Understanding the concept of accounts is important in itself because it enables us to comprehend how people view themselves within their cultural context. The research was based on unstructured, in-depth, face-to-face interviews with 54 Israeli hackers who where asked to tell their life stories. The interviewees were located by a snowball or chain referral sampling strategy. This study found that hacking in general, and penetrating computer systems or software in particular, constitutes a newform of entertainment for hackers. Thus, as it is based on the play-like quality that characterizes the use of digital technology, hacking often constitutes a new form of social activity.
The Challenges of Regulating Warez Trading
Authors: Goldman Eric
Published: January 2005

This article analyzes the policy challenges of legally conforming the behavior of warez traders. The article discusses the motivations for warez trading, how criminalizing the behavior may counterproductively encourage it, and why legislators and prosecutors continue to targetwarez trading despite the counterproductive effects.
Challenging Online Behaviors of Youth
Authors: Berson Ilene R. , Berson Michael J.
Published: January 2005

Child-serving professionals have struggled to understand the often complex emotional and behavioral responses of children and youth who are immersed in interconnected environments and consumed by digital technologies. Acomparative analysis on challenging online behaviors of adolescent girls in the United States and New Zealand was completed. Survey results confirm that when online, a significant number of adolescent girls are engaging in risky activities including disclosing personal information, sending personal photos to online acquaintances, and arranging face-to-face meetings. Many respondents continue potentially problematic offline practices as a result of these online interactions. The data also suggest that there is a lapse in preventative intervention to create and maintain awareness and safety for young people. Implications of this research for preparing youth to successfully harness the potential of the Internet are explored.
Types of Deception and Underlying Motivation
Authors: Utz Sonja
Published: January 2005

In computer-mediated communication, there are various types of possible deception such as category deception (gender switching), attractiveness deception, or identity concealment. The present article argues that it is meaningful to differentiate among these types of deception. More specifically, it is assumed that people attribute the various types of deception to different motivations and that these assumed motivations determine the evaluation of the deception. To examine whether individuals indeed attribute different types of deception to different underlying motivations, a scenario study was conducted. The results were in line with the expectations. For example, identity concealment was mainly attributed to privacy concerns, whereas gender switchingwas mainly perceived as playing with newroles and unknownaspects of the self. The assumed malicious intention predicted the evaluation of the deception.
The Realness of Cybercheating
Authors: Whitty Monica T.
Published: January 2005

This article considers the deviant behavior of Internet infidelity. Although a plethora of research has been conducted on offline infidelity and jealousy, to date, there has been very little written about Internet infidelity and jealousy associated with cyber-relationships. Given the potential problems that online infidelity might bring to a relationship, this area of research warrants some attention. This study drew from Kitzinger and Powell's (1995) story completion method to explore men's and women's understandings of Internet infidelity. Two hundred thirty-four participants wrote a story to a cue relating to Internet infidelity. Although not all participants saw this as a real act of betrayal the majority did see this as not only real infidelity but as also having as serious an impact on the couple as a traditional offline affair. The most important finding here was that emotional infidelity was given as much attention as sexual infidelitywas. Moreover, similar gender differences found in studies on offline infidelity emerged in this research. These results present a way forward in our thinking about cyberaffairs.
Understanding Cyberhate
Authors: Douglas Karen M. , Mcgarty Craig , Bliuc Ana-Maria , Lala Girish
Published: January 2005

This study investigated the self-enhancement strategies used by online White supremacist groups. In accordance with social identity theory, we proposed that White supremacist groups, in perceiving themselves as members of a high-status, impermeable group under threat from out-groups, should advocate more social conflict than social creativity strategies. We also expected levels of advocated violence to be lower than levels of social conflict and social creativity due to legal constraints on content. As expected, an analysis of 43 White supremacist web sites revealed that levels of social creativity and social conflict were significantly greater than were levels of advocated violence. However, contrary to predictions, the web sites exhibited social creativity to a greater extent than they exhibited social conflict. The difference between social creativity and social competition strategieswas not moderated by identifiability. Results are discussed with reference to legal impediments to overt hostility in online groups and the purpose of socially creative communication.
Sexual Harassment on the Internet
Authors: Barak Azy
Published: January 2005

Sexual harassment offline is a well-known, highly prevalent, extensively investigated, and intensively treated social problem. An accepted model classifies sexual harassment behaviors into the categories of gender harassment, unwanted sexual attention, and sexual coercion. Theory and research show that sexual harassment behavior occurs as a product of person · situation characteristics and has substantial personal and organizational costs. This article reviews the available information on sexual harassment in cyberspace, equates this phenomenon with what has been learned about sexual harassment offline, points to specific characteristics of online culture and technology that reinforce the behavior, and proposes ways of promoting prevention.
Storming and Forming a Normative Response to a Deception Revealed Online
Authors: Birchmeier Zachary , Joinson Adam N. , Dietz-Uhler Beth
Published: January 2005

Reactions to an admitted charade of bogus self-presentation within an online community were examined over time for themes of support, condemnation, and interactivity. Evidence for the subjective group dynamics account of intragroup reactions to perceived deviance was observed in that support was modeled by a cubic function over time, whereas condemnation remained prominent. The community eventually expelled the deceptive member, supporting the black sheep effect. Natural groups, including those situated in cyberspace, may rely on inductive categorization when faced with ambiguous threats to group uniformity. The expected role of referent informational influence in determining normatively negative group reactions was challenged by evidence that support for the deception was initially more likely to be expressed by high-status members. In addition, low-status members expressed their condemnation with greater conviction, overall. Members may have been referring to different group prototypes in seeking validation for their feelings aboutambiguously deviant members.
The Social Processes of Learning to Use Computers
Authors: Selwyn Neil
Published: January 2005

The ability to use a computer is assumed to be a cornerstone of effective citizenship in the Information Age, with a range of initiatives and educational provisions being introduced to encourage people to become competent with information technology (IT). Despite such provision, levels of computer use and competence have been found to vary widely throughout the general population, and we knowlittle of how different ways of learning to use computers contribute to people's eventual use of IT. Based on data from in-depth interviews with 100 adults in the United Kingdom, this article examines the range and social stratification of formal and informal learning about computers that is taking place, suggesting that formal computer instruction orientated toward the general public may inadvertently widen the digital knowledge gap. In particular, the data highlight the importance of informal learning about IT and of encouraging such learning, especially in the home.
Public Priorities Concerning the Development of E-Government in Flanders
Authors: Kampen Jarl K. , Snijkers Kris , Bouckaert Geert
Published: January 2005

The authors analyze preference data of Flemish citizens regarding various aspects of e-government (e.g., front office, back office, e-democracy, e-administration). The results indicate that the common strategy of governments, to put more services online that is rewarded by benchmarking studies of most consultancy firms and the Organization for Economic Cooperation and Development (OECD), does not correspond to the demands of most citizens. Citizens, in short, demand better services, not more services online.
A comparison of biologically variable ventilation to recruitment manoeuvres in a porcine model of acute lung injury
Authors: Funk Duane J , Graham M Ruth , Girling Linda G , Thliveris James A , McManus Bruce M , Walker Elizabeth KY , Rector Edward S , Hillier Craig , Scott J Elliott , Mutch W Alan C
Published: January 2005

Background

Biologically variable ventilation (return of physiological variability in rate and tidal volume using a computer-controller) was compared to control mode ventilation with and without a recruitment manoeuvre – 40 cm H2O for 40 sec performed hourly; in a porcine oleic acid acute lung injury model.

Methods

We compared gas exchange, respiratory mechanics, and measured bronchoalveolar fluid for inflammatory cytokines, cell counts and surfactant function. Lung injury was scored by light microscopy. Pigs received mechanical ventilation (FIO2 = 0.3; PEEP 5 cm H2O) in control mode until PaO2 decreased to 60 mm Hg with oleic acid infusion (PaO2/FIO2 <200 mm Hg). Additional PEEP to 10 cm H2O was added after injury. Animals were randomized to one of the 3 modes of ventilation and followed for 5 hr after injury.

Results

PaO2 and respiratory system compliance was significantly greater with biologically variable ventilation compared to the other 2 groups. Mean and mean peak airway pressures were also lower. There were no differences in cell counts in bronchoalveolar fluid by flow cytometry, or interleukin-8 and -10 levels between groups. Lung injury scoring revealed no difference between groups in the regions examined. No differences in surfactant function were seen between groups by capillary surfactometry.

Conclusions

In this porcine model of acute lung injury, various indices to measure injury or inflammation did not differ between the 3 approaches to ventilation. However, when using a low tidal volume strategy with moderate levels of PEEP, sustained improvements in arterial oxygen tension and respiratory system compliance were only seen with BVV when compared to CMV or CMV with a recruitment manoeuvre.
Constraint Logic Programming approach to protein structure prediction
Authors: Dal Palù Alessandro , Dovier Agostino , Fogolari Federico
Published: January 2005

Background

The protein structure prediction problem is one of the most challenging problems in biological sciences. Many approaches have been proposed using database information and/or simplified protein models. The protein structure prediction problem can be cast in the form of an optimization problem. Notwithstanding its importance, the problem has very seldom been tackled by Constraint Logic Programming, a declarative programming paradigm suitable for solving combinatorial optimization problems.

Results

Constraint Logic Programming techniques have been applied to the protein structure prediction problem on the face-centered cube lattice model. Molecular dynamics techniques, endowed with the notion of constraint, have been also exploited. Even using a very simplified model, Constraint Logic Programming on the face-centered cube lattice model allowed us to obtain acceptable results for a few small proteins. As a test implementation their (known) secondary structure and the presence of disulfide bridges are used as constraints. Simplified structures obtained in this way have been converted to all atom models with plausible structure. Results have been compared with a similar approach using a well-established technique as molecular dynamics.

Conclusions

The results obtained on small proteins show that Constraint Logic Programming techniques can be employed for studying protein simplified models, which can be converted into realistic all atom models. The advantage of Constraint Logic Programming over other, much more explored, methodologies, resides in the rapid software prototyping, in the easy way of encoding heuristics, and in exploiting all the advances made in this research area, e.g. in constraint propagation and its use for pruning the huge search space.
prot4EST: Translating Expressed Sequence Tags from neglected genomes
Authors: Wasmuth James D , Blaxter Mark L
Published: January 2005

Background

The genomes of an increasing number of species are being investigated through generation of expressed sequence tags (ESTs). However, ESTs are prone to sequencing errors and typically define incomplete transcripts, making downstream annotation difficult. Annotation would be greatly improved with robust polypeptide translations. Many current solutions for EST translation require a large number of full-length gene sequences for training purposes, a resource that is not available for the majority of EST projects.

Results

As part of our ongoing EST programs investigating these "neglected" genomes, we have developed a polypeptide prediction pipeline, prot4EST. It incorporates freely available software to produce final translations that are more accurate than those derived from any single method. We show that this integrated approach goes a long way to overcoming the deficit in training data.

Conclusions

prot4EST provides a portable EST translation solution and can be usefully applied to >95% of EST projects to improve downstream annotation. It is freely available from http://www.nematodes.org/PartiGene.
A two-way interface between limited Systems Biology Markup Language and R
Authors: Radivoyevitch Tomas
Published: January 2005

Background

Systems Biology Markup Language (SBML) is gaining broad usage as a standard for representing dynamical systems as data structures. The open source statistical programming environment R is widely used by biostatisticians involved in microarray analyses. An interface between SBML and R does not exist, though one might be useful to R users interested in SBML, and SBML users interested in R.

Results

A model structure that parallels SBML to a limited degree is defined in R. An interface between this structure and SBML is provided through two function definitions: write.SBML() which maps this R model structure to SBML level 2, and read.SBML() which maps a limited range of SBML level 2 files back to R. A published model of purine metabolism is provided in this SBML-like format and used to test the interface. The model reproduces published time course responses before and after its mapping through SBML.

Conclusions

List infrastructure preexisting in R makes it well-suited for manipulating SBML models. Further developments of this SBML-R interface seem to be warranted.
ABC: software for interactive browsing of genomic multiple sequence alignment data
Authors: Cooper Gregory M , Singaravelu Senthil AG , Sidow Arend
Published: January 2005

Background

Alignment and comparison of related genome sequences is a powerful method to identify regions likely to contain functional elements. Such analyses are data intensive, requiring the inclusion of genomic multiple sequence alignments, sequence annotations, and scores describing regional attributes of columns in the alignment. Visualization and browsing of results can be difficult, and there are currently limited software options for performing this task.

Results

The Application for Browsing Constraints (ABC) is interactive Java software for intuitive and efficient exploration of multiple sequence alignments and data typically associated with alignments. It is used to move quickly from a summary view of the entire alignment via arbitrary levels of resolution to individual alignment columns. It allows for the simultaneous display of quantitative data, (e.g., sequence similarity or evolutionary rates) and annotation data (e.g. the locations of genes, repeats, and constrained elements). It can be used to facilitate basic comparative sequence tasks, such as export of data in plain-text formats, visualization of phylogenetic trees, and generation of alignment summary graphics.

Conclusions

The ABC is a lightweight, stand-alone, and flexible graphical user interface for browsing genomic multiple sequence alignments of specific loci, up to hundreds of kilobases or a few megabases in length. It is coded in Java for cross-platform use and the program and source code are freely available under the General Public License. Documentation and a sample data set are also available http://mendel.stanford.edu/sidowlab/downloads.html.
Analysis of superfamily specific profile-profile recognition accuracy
Authors: Casbon James A , Saqi Mansoor AS
Published: January 2005

Background

Annotation of sequences that share little similarity to sequences of known function remains a major obstacle in genome annotation. Some of the best methods of detecting remote relationships between protein sequences are based on matching sequence profiles. We analyse the superfamily specific performance of sequence profile-profile matching. Our benchmark consists of a set of 16 protein superfamilies that are highly diverse at the sequence level. We relate the performance to the number of sequences in the profiles, the profile diversity and the extent of structural conservation in the superfamily.

Results

The performance varies greatly between superfamilies with the truncated receiver operating characteristic, ROC10, varying from 0.95 down to 0.01. These large differences persist even when the profiles are trimmed to approximately the same level of diversity.

Conclusions

Although the number of sequences in the profile (profile width) and degree of sequence variation within positions in the profile (profile diversity) contribute to accurate detection there are other superfamily specific factors.
4-D single particle tracking of synthetic and proteinaceous microspheres reveals preferential movement of nuclear particles along chromatin – poor tracks
Authors: Bacher Christian P , Reichenzeller Michaela , Athale Chaitanya , Herrmann Harald , Eils Roland
Published: January 2005

Background

The dynamics of nuclear organization, nuclear bodies and RNPs in particular has been the focus of many studies. To understand their function, knowledge of their spatial nuclear position and temporal translocation is essential. Typically, such studies generate a wealth of data that require novel methods in image analysis and computational tools to quantitatively track particle movement on the background of moving cells and shape changing nuclei.

Results

We developed a novel 4-D image processing platform (TIKAL) for the work with laser scanning and wide field microscopes. TIKAL provides a registration software for correcting global movements and local deformations of cells as well as 2-D and 3-D tracking software. With this new tool, we studied the dynamics of two different types of nuclear particles, namely nuclear bodies made from GFP-NLS-vimentin and microinjected 0.1 μm – wide polystyrene beads, by live cell time-lapse microscopy combined with single particle tracking and mobility analysis. We now provide a tool for the automatic 3-D analysis of particle movement in parallel with the acquisition of chromatin density data.

Conclusions

Kinetic analysis revealed 4 modes of movement: confined obstructed, normal diffusion and directed motion. Particle tracking on the background of stained chromatin revealed that particle movement is directly related to local reorganization of chromatin. Further a direct comparison of particle movement in the nucleoplasm and the cytoplasm exhibited an entirely different kinetic behaviour of vimentin particles in both compartments.

The kinetics of nuclear particles were slightly affected by depletion of ATP and significantly disturbed by disruption of actin and microtubule networks. Moreover, the hydration state of the nucleus had a strong impact on the mobility of nuclear bodies since both normal diffusion and directed motion were entirely abolished when cells were challenged with 0.6 M sorbitol. This effect correlated with the compaction of chromatin. We conclude that alteration in chromatin density directly influences the mobility of protein assemblies within the nucleus.
Diversity and specificity in the interaction between Caenorhabditis elegans and the pathogen Serratia marcescens
Authors: Schulenburg Hinrich , Ewbank Jonathan J
Published: January 2005

Background

Co-evolutionary arms races between parasites and hosts are considered to be of immense importance in the evolution of living organisms, potentially leading to highly dynamic life-history changes. The outcome of such arms races is in many cases thought to be determined by frequency dependent selection, which relies on genetic variation in host susceptibility and parasite virulence, and also genotype-specific interactions between host and parasite. Empirical evidence for these two prerequisites is scarce, however, especially for invertebrate hosts. We addressed this topic by analysing the interaction between natural isolates of the soil nematode Caenorhabditis elegans and the pathogenic soil bacterium Serratia marcescens.

Results

Our analysis reveals the presence of i) significant variation in host susceptibility, ii) significant variation in pathogen virulence, and iii) significant strain- and genotype-specific interactions between the two species.

Conclusions

The results obtained support the previous notion that highly specific interactions between parasites and animal hosts are generally widespread. At least for C. elegans, the high specificity is observed among isolates from the same population, such that it may provide a basis for and/or represent the outcome of co-evolutionary adaptations under natural conditions. Since both C. elegans and S. marcescens permit comprehensive molecular analyses, these two species provide a promising model system for inference of the molecular basis of such highly specific interactions, which are as yet unexplored in invertebrate hosts.
Rooting a phylogenetic tree with nonreversible substitution models
Authors: Yap Von Bing , Speed Terry
Published: January 2005

Background

We compared two methods of rooting a phylogenetic tree: the stationary and the nonstationary substitution processes. These methods do not require an outgroup.

Methods

Given a multiple alignment and an unrooted tree, the maximum likelihood estimates of branch lengths and substitution parameters for each associated rooted tree are found; rooted trees are compared using their likelihood values. Site variation in substitution rates is handled by assigning sites into several classes before the analysis.

Results

In three test datasets where the trees are small and the roots are assumed known, the nonstationary process gets the correct estimate significantly more often, and fits data much better, than the stationary process. Both processes give biologically plausible root placements in a set of nine primate mitochondrial DNA sequences.

Conclusions

The nonstationary process is simple to use and is much better than the stationary process at inferring the root. It could be useful for situations where an outgroup is unavailable.
A simulation model of Escherichia coli osmoregulatory switch using E-CELL system
Authors: Srividhya KV , Krishnaswamy Sankaran
Published: January 2005

Background

Bacterial signal transduction mechanism referred to as a "two component regulatory systems" contributes to the overall adaptability of the bacteria by regulating the gene expression. Osmoregulation is one of the well-studied two component regulatory systems comprising of the sensor, EnvZ and the cognate response regulator, OmpR, which together control the expression of OmpC and OmpF porins in response to the osmolyte concentration.

Results

A quantitative model of the osmoregulatory switch operative in Escherichia coli was constructed by integrating the enzyme rate equations using E-CELL system. Using the substance reactor logic of the E-CELL system, a total of 28 reactions were defined from the injection of osmolyte till the regulated expression of porins by employing the experimental kinetic constants as reported in literature. In the case of low osmolarity, steady state production of OmpF and repression of OmpC was significant. In this model we show that the steady state – production of OmpF is dramatically reduced in the high osmolarity medium. The rate of OmpC production increased after sucrose addition, which is comparable with literature results. The relative porin production seems to be unaltered with changes in cell volume changes, ATP, EnvZ and OmpR at low and high osmolarity conditions. But the reach of saturation was rapid at high and low osmolarity with altered levels of the above components.

Conclusions

The E-CELL system allows us to perform virtual experiments on the bacterial osmoregulation model. This model does not take into account interaction with other networks in the cell. It suggests that the regulation of OmpF and OmpC is a direct consequence of the level of OmpRP in the cell and is dependent on the way in which OmpRP interacts with ompF and ompC regulatory regions. The preliminary simulation experiment indicates that both reaching steady state expression and saturation is delayed in the case of OmpC compared to OmpF. Experimental analysis will help improve the model. The model captures the basic features of the generally accepted view of EnvZ-OmpR signaling and is a reasonable starting point for building sophisticated models and explaining quantitative features of the system.
DNA-free RNA preparations from mycobacteria
Authors: Stephan Joachim , Bail Johannes G , Titgemeyer Fritz , Niederweis Michael
Published: January 2005

Background

To understand mycobacterial pathogenesis analysis of gene expression by quantification of RNA levels becomes increasingly important. However, current preparation methods yield mycobacterial RNA that is contaminated with chromosomal DNA.

Results

After sonication of RNA samples from Mycobacterium smegmatis genomic DNA is efficiently removed by DNaseI in contrast to untreated samples.

Conclusions

This procedure eliminates one of the most prevalent error sources in quantification of RNA levels in mycobacteria.
Allele specific synthetic lethality between priC and dnaA
ts alleles at the permissive temperature of 30°C in E. coli K-12
Authors: Hinds Tania , Sandler Steven J
Published: January 2005

Background

DnaA is an essential protein in the regulation and initiation of DNA replication in many bacteria. It forms a protein-DNA complex at oriC to which DnaC loads DnaB. DNA replication forks initiated at oriC by DnaA can collapse on route to the terminus for a variety of reasons. PriA, PriB, PriC, DnaT, Rep and DnaC form multiple pathways to restart repaired replication forks. DnaC809 and dnaC809,820 are suppressors of priA2::kan mutant phenotypes. The former requires PriC and Rep while the latter is independent of them. RnhA339::cat mutations allow DnaA-independent initiation of DNA replication.

Results

It is shown herein that a priC303::kan mutation is synthetically lethal with either a dnaA46 or dnaA508 temperature sensitive mutation at the permissive temperature of 30°C. The priC-dnaA lethality is specific for the dnaA allele. The priC303::kan mutant was viable when placed in combination with either dnaA5, dnaA167, dnaA204 or dnaA602. The priC-dnaA508 and priC-dnaA46 lethality could be suppressed by rnhA339::cat. The priC-dnaA508 lethality could be suppressed by a dnaC809,820 mutation, but not dnaC809. Neither of the dnaC mutations could suppress the priC-dnaA46 lethality.

Conclusions

A hitherto unknown function for either DnaA in replication restart or PriC in initiation of DNA replication that occurs in certain dnaA temperature sensitive mutant strains at the permissive temperature of 30°C has been documented. Models considering roles for PriC during initiation of DNA replication and roles for DnaA in replication restart were tested and found not to decisively explain the data. Other roles of dnaA in transcription and nucleoid structure are additionally considered.
Foxo3a induces motoneuron death through the Fas pathway in cooperation with JNK
Authors: Barthélémy Catherine , Henderson Christopher E , Pettmann Brigitte
Published: January 2005

Background

Programmed cell death of motoneurons in the developing spinal cord is thought to be regulated through the availability of target-derived neurotrophic factors. When deprived of trophic support, embryonic spinal motoneurons in vitro over-express FasL, a ligand activating a Fas-mediated death pathway. How trophic factors regulate the expression of FasL is presently unclear, but two regulators of FasL, FOXO3a (FKHRL1) and JNK have been described to play a role in other cell types. Thus, their potential function in motoneurons was investigated in this study.

Results

We show here that as a result of removal of neurotrophic factors and the consequent reduction in signalling through the PI3K/Akt pathway, Foxo3a translocates from the cytoplasm to the nucleus where it triggers cell death. Death is reduced in Fas and FasL mutant motoneurons and in the presence of JNK inhibitors indicating that a significant part of it requires activation of the Fas/FasL pathway through JNK.

Conclusions

Therefore, in motoneurons as in other cell types, FOXO transcriptional regulators provide an important link between other signalling pathways and the cell death machinery.
Management of acute renal colic in the UK: a questionnaire survey
Authors: Lasoye Tunji A , Sedgwick Philip M , Patel Nilay , Skinner Chas , Nayeem Nadeem
Published: January 2005

Background

There is great variation in the Accident and Emergency workload and location of Urology services in UK hospitals. This study investigated the relationship of the initial management of acute renal colic with the department workload plus local facilities including location of X-ray and urology services in UK Accident and Emergency (A&E) departments.

Methods

A&E departments in each of the 11 UK Deanery regions were stratified based on departmental workload, namely <30,000 (small); 30,000 to 50,000 (medium); 50,000 to 80,000 (large) and >80,000 (very large) patients per year. One third of departments were selected in each group leading to a sample size of 106. A questionnaire was administered. Associations between categorical variables were investigated using the chi-squared test and when not valid, Fisher's Exact test was employed. Differences between groups in ordinal variables were investigated using the Mann-Whitney test.

Results

All questionnaires were returned. Twenty-nine units (27.4%) did not perform any radiological investigation on renal colic patients. The number of radiological investigations that were available to departments was associated with workload (P = 0.003); with 57.1% of the small departments performing none and at least 82.8% of units in the other categories performing at least one. Of those departments with X-ray facilities in or adjacent to the department, 63% performed an intravenous urography (IVU) compared to 25% of those departments without (P = 0.026). Of those departments with on-site urology services, 86% performed at least one radiological investigation compared to 52% of units without such services (P = 0.001). Department workload was associated with the first choice analgesia (NSAIDs or parenteral opiates) (P = 0.011). Of the small departments, 64.3% used NSAIDs, 21.4% used parenteral opiates and 14.3% used neither. In comparison, NSAIDS were used by at least 87%, and opiates by at most 12.5% of units in each of the other three categories of department workload.

Conclusions

Over a quarter of UK A&E departments did not perform any radiological investigations and some departments do not even offer renal colic patients any analgesia. Patient management was associated with departmental workload, location of X-ray and Urology services. National guidelines are needed to ensure optimum care for all patients.
Dissemination of information to General Practitioners: a questionnaire survey
Authors: Moorjani Padma , Fortnum Heather
Published: January 2005

Background

Early identification of permanent hearing impairment in children enables appropriate intervention which reduces adverse developmental outcomes. The UK Government has introduced a universal hearing screening programme for neonates. All involved health professionals, including those in Primary Care, need to be aware of the service to enable them to offer appropriate support to their patients. A programme of information dissemination within Primary Care was therefore undertaken. The aim of the current study was to determine the extent to which the information had reached General Practitioners (GPs), the GPs' preferred mode of dissemination and the sources from which GPs accessed information

Methods

Postal questionnaire survey of a randomised sample of 1000 GPs in the Phase I pilot sites of the Neonatal Hearing Screening Programme (NHSP).

Results

Responses were received from 54.2% of the sample. Just under 50% of those responding had received information, 62.2% of respondents said they would like to receive more information and the preferred methods of dissemination were the written word and web-sites to allow access when needed. Few GPs perceive themselves to have a core role in the delivery of the NHSP and thence a need for knowledge in the subject. Many are keen to delegate detail to a third party, usually the health visitor, who has traditionally had responsibility for hearing screening.

Conclusions

Dissemination efforts for service developments of relevance to GPs should concentrate on advertising a website address via brief but memorable posted literature and/or articles in relevant journals and magazines. The website should be GP-friendly, and have a dedicated area for GPs including information of specific relevance and downloadable information sheets.
TGF β1 and PDGF AA override Collagen type I inhibition of proliferation in human liver connective tissue cells
Authors: Geremias Alvaro T , Carvalho Marcelo A , Borojevic Radovan , Monteiro Alvaro NA
Published: January 2005

Background

A marked expansion of the connective tissue population and an abnormal deposition of extracellular matrix proteins are hallmarks of chronic and acute injuries to liver tissue. Liver connective tissue cells, also called stellate cells, derived from fibrotic liver have been thoroughly characterized and correspond phenotypically to myofibroblasts. They are thought to derive from fat-storing Ito cells in the perisinusoidal space and acquire a contractile phenotype when activated by tissue injury. In the last few years it has become evident that several peptide growth factors such as PDGF AA and TGF-β are involved in the development of fibrosis by modulating myofibroblast proliferation and collagen secretion. The fact that during the development of chronic fibrosis there is concomitant deposition of collagen, a known inhibitory factor, and sustained cell proliferation, raises the possibility that stellate cells from chronic liver fibrosis patients fail to respond to normal physiologic controls.

Methods

In this study we address whether cells from fibrotic liver patients respond to normal controls of proliferation. We compared cell proliferation of primary human liver connective tissue cells (LCTC) from patients with liver fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV; TGF-β, PDGF AA and combinations of collagen type I and TGF-β or PDGF AA.

Results

Our results indicate that despite displaying normal contact and collagen-induced inhibition of proliferation LCTC respond more vigorously to lower concentrations of PDGF AA. In addition, we show that collagen type I synergizes with growth factors to promote mitogenesis of LCTC but not SF.

Conclusions

The synergistic interaction of growth factors and extracellular matrix proteins may underlie the development of chronic liver fibrosis.
Gastric emptying is slow in chronic fatigue syndrome
Authors: Burnet Richard B , Chatterton Barry E
Published: January 2005

Background

Gastrointestinal symptoms are common in patients with Chronic Fatigue Syndrome (CFS). The objective of this study was to determine the frequency of these symptoms and explore their relationship with objective (radionuclide) studies of upper GI function.

Methods

Thirty-two (32) patients with CFS and 45 control subjects completed a questionnaire on upper GI symptoms, and the 32 patients underwent oesophageal clearance, and simultaneous liquid and solid gastric emptying studies using radionuclide techniques compared with historical controls.

Results

The questionnaires showed a significant difference in gastric (p > 0.01) symptoms and swallowing difficulty. Nocturnal diarrhoea was a significant symptom not previously reported.

5/32 CFS subjects showed slightly delayed oesophageal clearance, but overall there was no significant difference from the control subjects, nor correlation of oesophageal clearance with symptoms. 23/32 patients showed a delay in liquid gastric emptying, and 12/32 a delay in solid gastric emptying with the delay significantly correlated with the mean symptom score (for each p ≪ 0.001).

Conclusions

GI symptoms in patients with chronic fatigue syndrome are associated with objective changes of upper GI motility.
Can mutations in ELA2, neutrophil elastase expression or differential cell toxicity explain sulphasalazine-induced agranulocytosis?
Authors: Jacobson Annica , Melhus Håkan , Wadelius Mia
Published: January 2005

Background

Drug-induced agranulocytosis, a severe side effect marked by a deficit or absolute lack of granulocytic white blood cells, is a rare side-effect of the anti-inflammatory drug sulphasalazine. Mutations in the human neutrophil elastase gene (ELA2), causing increased intracellular concentration of this serine protease, inhibits neutrophil differentiation in severe congenital neutropenia (SCN). Since the clinical symptoms of agranulocytosis and SCN are similar, we hypothesized that it may origin from a common genetic variation in ELA2 or that sulphasalazine may affect human neutrophil elastase activity and protein expression.

Methods

We screened for genetic differences in ELA2 in DNA from 36 patients who had suffered from sulphasalazine-induced agranulocytosis, and compared them with 72 patients treated with sulphasalazine without blood reactions. We also performed in vitro studies of the blood cell lines HL60 and U937 after sulphasalazine exposure with respect to cell survival index, neutrophil elastase protein expression and activity.

Results

None of the mutations in ELA2, which previously have been reported to be associated with SCN, was found in this material. Protein expression of human neutrophil elastase in lymphoma U937 cells was not affected by treatment with concentrations equivalent to therapeutic doses. Cell survival of lymphoma U937 and promyelocytic leukemia HL-60 cells was not affected in this concentration range, but exhibited a decreased proliferative capacity with higher sulphasalazine concentrations. Interestingly the promyelocytic cells were more sensitive to sulphasalazine than the lymphoma cell line.

Conclusion

Neutrophil elastase expression and ELA2 mutations do, however, not seem to be involved in the etilogy of sulphasalazine-induced agranulocytosis. Why sulphasalazine is more toxic to promyelocytes than to lymphocytes remains to be explained.
The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: case reports and literature review
Authors: Wu Alan KL , Cheng Vincent CC , Tang Bone SF , Hung Ivan FN , Lee Rodney A , Hui David S , Yuen Kwok Y
Published: January 2005

Background

Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently.

Case presentation

We aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/μL to 125/μL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature.

Conclusions

PCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis.
Streptococcal necrotising fasciitis from diverse strains of Streptococcus pyogenes in tropical northern Australia: case series and comparison with the literature
Authors: Hassell Marilyn , Fagan Peter , Carson Phillip , Currie Bart J
Published: January 2005

Background

Since the mid-1980's there has been a worldwide resurgence of severe disease from group A streptococcus (GAS), with clonal clusters implicated in Europe and the United States. However GAS associated sepsis and rheumatic fever have always remained at high levels in many less developed countries. In this context we aimed to study GAS necrotising fasciitis (NF) in a region where there are high background rates of GAS carriage and disease.

Methods

We describe the epidemiology, clinical and laboratory features of 14 consecutive cases of GAS NF treated over a seven year period from tropical northern Australia.

Results

Incidence rates of GAS NF in the Aboriginal population were up to five times those previously published from other countries. Clinical features were similar to those described elsewhere, with 7/14 (50%) bacteremic and 9/14 (64%) having associated streptococcal toxic shock syndrome. 11/14 (79%) had underlying chronic illnesses, including all four fatalities (29% mortality overall). Important laboratory differences from other series were that leukocytosis was absent in 9/14 (64%) but all had substantial lymphopenia. Sequence typing of the 14 NF-associated GAS isolates showed no clonality, with only one emm type 1 and two emm type 3 strains.

Conclusions

While NF clusters can occur from a single emergent GAS clone, this was not evident in our tropical region, where high rates of NF parallel high overall rates of GAS infection from a wide diversity of strains. The specific virulence factors of GAS strains which do cause NF and the basis of the inadequate host response in those patients who develop NF on infection with these GAS require further elucidation.
Reexamining the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality
Authors: Ananth Cande V , Platt Robert W
Published: January 2005

Background

Low birth weight (<2,500 g) is a strong predictor of infant mortality. Yet low birth weight, in isolation, is uninformative since it is comprised of two intertwined components: preterm delivery and reduced fetal growth. Through nonparametric logistic regression models, we examine the effects of gestational age, fetal growth, and maternal smoking on neonatal mortality.

Methods

We derived data on over 10 million singleton live births delivered at ≥ 24 weeks from the 1998–2000 U.S. natality data files. Nonparametric multivariable logistic regression based on generalized additive models was used to examine neonatal mortality (deaths within the first 28 days) in relation to fetal growth (gestational age-specific standardized birth weight), gestational age, and number of cigarettes smoked per day. All analyses were further adjusted for the confounding effects due to maternal age and gravidity.

Results

The relationship between standardized birth weight and neonatal mortality is nonlinear; mortality is high at low z-score birth weights, drops precipitously with increasing z-score birth weight, and begins to flatten for heavier infants. Gestational age is also strongly associated with mortality, with patterns similar to those of z-score birth weight. Although the direct effect of smoking on neonatal mortality is weak, its effects (on mortality) appear to be largely mediated through reduced fetal growth and, to a lesser extent, through shortened gestation. In fact, the association between smoking and reduced fetal growth gets stronger as pregnancies approach term.

Conclusions

Our study provides important insights regarding the combined effects of fetal growth, gestational age, and smoking on neonatal mortality. The findings suggest that the effect of maternal smoking on neonatal mortality is largely mediated through reduced fetal growth.