bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Endovascular and Open Treatment for Infected Pseudoaneurysm of the Thoracic Aortic Arch
Authors: Kwok Keung Ho  , Kwok Philip Chong-hei , Shiu Shek Chung  , Wong Kan Wong
Published: October 2007

Infected pseudoaneurysm of the aortic arch is a rare but life-threatening condition. The conventional treatment involves cardiopulmonary bypass, prolonged vascular clamping, and an extensive bypass procedure. We report a case of infected pseudoaneurysm involving the aortic arch. The patient underwent debranching of the supra-aortic arteries and bypass surgery, followed by stent grafting the next day. The patient had good recovery, and the 1-year follow-up computed tomography scan showed resolution of the infected pseudoaneurysm.
Successful Repair of a Giant Abdominal Aortoiliac Aneurysm in a Jehovah's Witness
Authors: Bayam Levent , Tait William F. , Macartney Ian D.
Published: October 2007

We report the case of a 76-year-old man of the Jehovah's Witness faith who had a giant abdominal aortoiliac aneurysm that was successfully operated on using an aortoiliac Y-graft bypass technique, without the use of stored allogenic blood. Cell saver technique and recombinant human erythropoietin (epoetin beta) were used during the perioperative period. The patient had good postoperative care with a multidisciplinary approach.
Single-Center Experience of Endovascular Abdominal Aortic Aneurysm Repair (EVAR) in Patients Not Participating in the U.K. EVAR Trials
Authors: Sajid Muhammad S. , Tai Nigel R. M. , Iftikhar Mawara , Platts Andrew , Baker Daryll M. , Hamilton George
Published: October 2007

The objective was to evaluate outcomes of a high-risk patient cohort following endovascular abdominal aortic aneurysm repair (EVAR) treatment not entered into the U.K. endovascular stent-graft aortic aneurysm repair trials (EVAR-1 or -2) because of equipoise absence but where EVAR was judged to be the most appropriate intervention option on compassionate grounds. A single-center retrospective analysis was performed involving all patients undergoing compassionate EVAR treatment during the EVAR-1 and -2 trial period. Over an 8-year period, 34 patients underwent compassionate EVAR procedure. The mean (SD) age was 76 (79) years. The mean (SD) preoperative physiology score (P-POSSUM) was 25 (8.3) with a mean (SD) predicted early mortality of 9.9% (16%). The actual early mortality in our study was 2.9% and morbidity was 35%. There were 8 cases of endoleak: type I (n = 2), type II (n = 5), and type IV (n = 1). Aneurysm-related mortality and all-cause mortality after 8 years were 5.8% and 23.5% respectively. Satisfactory outcome with low mortality (2.9%) and morbidity can be achieved in patients with compassionate indications, where clinicians judge EVAR to be an advantage over open abdominal aortic aneurysm repair. Based on our study, the early mortality (2.9%) in our compassionate EVAR group is comparable to EVAR-1 outcomes (1.7%) and better than EVAR-2 mortality results (9%). EVAR should therefore not be denied to a significant number of high-risk abdominal aortic aneurysm patients who fall between the EVAR-1 and EVAR-2 criteria.
Race Independently Impacts Outcome of Infrapopliteal Bypass for Symptomatic Arterial Insufficiency
Authors: Rowe Vincent L. , Ram Kumar S. , Glass Holly , Hood Douglas B. , Weaver Fred A.
Published: October 2007

The impact of racial background on the outcome of lower extremity revascularization is unknown because a majority of studies have a preponderance of white patients. The charts of patients between 1988 and 2004 requiring infrapopliteal lower extremity revascularization were reviewed. Life-table analyses, the Cox proportional hazards model, and log-rank test were used to calculate graft patency and limb salvage. Bypasses were performed on 236 limbs in 225 patients. Mean follow-up was 18 ± 1.5 months. Twenty-eight (12%) bypasses were performed on whites, 43 (18%) on African Americans, 148 (63%) on Hispanics, and 17 (7.2%) on patients of other races. African American race negatively correlated with primary-assisted patency (hazard ratio 2.9, P = .03), secondary patency (hazard ratio 3.64, P = .02), and limb salvage (hazard ratio 8, P = .006) compared with whites. African American race has a negative impact on the long-term outcome of infrapopliteal revascularization, regardless of disease stage or associated risk factors.
Metachronous Giant Brachial Artery Pseudoaneurysms: A Case Report and Review of the Literature
Authors: Wahlgren Carl-Magnus , Lohman Robert , Pearce Benjamin J. , Spiguel Lisa R.P. , Dorafshar Amir , Skelly Christopher L.
Published: October 2007

Brachial artery pseudoaneurysms secondary to intravenous drug abuse represent a limb-threatening problem to patients and a technical challenge to the vascular surgeon. Here information is reported about a patient with metachronous bilateral giant brachial artery pseudoaneurysms secondary to intravenous drug use that were successfully treated with excision of the aneurysm and ligation of the brachial artery. Furthermore, a review of the current literature on the treatment of brachial artery aneurysm is presented.
Meta-analysis of community-based cluster randomization trials with binary outcomes
Authors: Darlington Gerarda A. , Donner Allan
Published: October 2007

Background Cluster randomization trials are widely used to test the effect of an intervention when individuals are naturally found in groups such as communities. For several separate studies of a similar intervention, it may be of interest to combine their results using meta-analysis procedures. However, this task requires consideration of both the likely dependencies among cluster members (intracluster correlation) and stratification based on the studies considered.

Purpose In this article, several possible approaches for meta-analysis are considered for cluster randomization trials having a binary outcome.

Methods It is first noted that the standard Mantel—Haenszel test is invalid in this context since it ignores dependencies among cluster members. Two modifications are therefore considered as well as a general inverse variance approach and a procedure based on the Woolf statistic which does not require the availability of trial-specific design effects. Empirical Type I errors and powers for the different procedures considered are evaluated using Monte Carlo simulation. To illustrate the techniques, data are used from trials performed in four countries to compare two antenatal care programs with respect to their effects on the risk of hypertension during pregnancy.

Results For the simulation scenarios considered, an adjusted Mantel—Haenszel procedure provides a valid test with the greatest power slightly outperforming the general inverse variance approach.

Limitations The potential need to adjust for possible confounding was not considered. However, more detailed information on confounders would not likely be available for most meta-analyses.

Conclusion Two procedures performed well. However, the choice of analysis approach also inevitably depends on the nature and extent of the available data. Clinical Trials 2007; 4: 491—498. http://ctj.sagepub.com
Maintaining data integrity in a rural clinical trial
Authors: Van den Broeck Jan , Mackay Melanie , Mpontshane Nontobeko , Kany Kany Luabeya Angelique , Chhagan Meera , Bennish Michael L.
Published: October 2007

Background Clinical trials conducted in rural resource-poor settings face special challenges in ensuring quality of data collection and handling. The variable nature of these challenges, ways to overcome them, and the resulting data quality are rarely reported in the literature.

Purpose To provide a detailed example of establishing local data handling capacity for a clinical trial conducted in a rural area, highlight challenges and solutions in establishing such capacity, and to report the data quality obtained by the trial.

Methods We provide a descriptive case study of a data system for biological samples and questionnaire data, and the problems encountered during its implementation. To determine the quality of data we analyzed test—retest studies using Kappa statistics of inter- and intra-observer agreement on categorical data. We calculated Technical Errors of Measurement of anthropometric measurements, audit trail analysis was done to assess error correction rates, and residual error rates were calculated by database-to-source document comparison.

Results Initial difficulties included the unavailability of experienced research nurses, programmers and data managers in this rural area and the difficulty of designing new software tools and a complex database while making them error-free. National and international collaboration and external monitoring helped ensure good data handling and implementation of good clinical practice. Data collection, fieldwork supervision and query handling depended on streamlined transport over large distances. The involvement of a community advisory board was helpful in addressing cultural issues and establishing community acceptability of data collection methods. Data accessibility for safety monitoring required special attention. Kappa values and Technical Errors of Measurement showed acceptable values. Residual error rates in key variables were low.

Limitations The article describes the experience of a single-site trial and does not address challenges particular to multi-site trials.

Conclusions Obtaining and maintaining data integrity in rural clinical trials is feasible, can result in acceptable data quality and can be used to develop capacity in developing country sites. It does, however, involve special challenges and requirements. Clinical Trials 2007; 4: 572—582. http://ctj.sagepub.com
Policing marginal spaces
Authors: James Zoë
Published: October 2007

Community policing initiatives that aim to address diversity are increasingly required to engage with Gypsies and Travellers. In this article the policing of Gypsies and Travellers is outlined through analysis of empirical research in the south-west of England. The research shows that the police work with multiple public and private agencies to control the movement and settlement of Gypsies and Travellers, but the engagement of Gypsies and Travellers in community policing initiatives is limited. The police primarily engage with Gypsies and Travellers through enforcement practice. Gypsies and Travellers are shown here to respond to their experiences of policing in a number of ways that attempt to place them beyond the gaze of formal agencies. In conclusion the article questions the degree to which policing agencies can reach Gypsies and Travellers via community policing approaches.
Policing diversity in the digital age
Authors: Wall David S. , Williams Matthew
Published: October 2007

Members of `terrestrial' communities are migrating in ever-increasing numbers to a new `Third Space' that manifests outside traditional geographical physical boundaries. This online space consists of purely social relations where interaction and community are performed at-a-distance. The diversifying populations of these virtual villages, towns and cities now constitute very real communities. Online non-gaming spaces such as Ebay, Active Worlds and Secondlife, for example, deliberately utilize the discourse of community in an attempt to instil a sense of communal space and shared responsibility among their members. While the majority subscribe to the rhetoric of `netizenship' others find alternative means to participate online. The avocations of these few have resulted in the endemic deviance/crime problem that exists online. As a result, online communities have developed their own distinct history of control and regulation.

This article explores the ways that online social spaces maintain orderly `communities'. It contrasts `proximal' (online) forms of governing online behaviour, such as online reputation management systems, `virtual' police services and vigilante groups that employ `online shaming', with `distal' (offline) forms such as offline policing and criminal justice processes. The central theme of the article is a critical account of how these, often contradicting, nodes of governance interact.
The politics of police reform
Authors: Chan Janet , Dixon David
Published: October 2007

In 1997, the Wood Royal Commission into the New South Wales Police Service concluded that a state of `systemic and entrenched corruption' existed in the police organization. Major reforms were introduced in the wake of the Commission, including the appointment of a new Police Commissioner, organizational restructuring, a complete revamp of recruit education, as well as increased monitoring and accountability. The magnitude and scope of the Commission's reform programme was bold and ambitious by international standards. This article takes stock of the impact of the Commission 10 years after the publication of its Final Report. Drawing on interviews with key informants, official reports and other documentary sources, the article analyses the activities of the Commission, the intentions of its recommendations and the implementation and consequences of reform. The lessons of the NSW experience are salutary not only for understanding the vagaries of police reform, they also demonstrate the complex relationship between police organizations and the volatile political environments in which they increasingly need to operate.
Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience
Authors: Park Sophie , Grabar Sophie , Kelaidi Charikleia , Beyne-Rauzy Odile , Picard Françoise , Bardet Valérie , Coiteux Valérie , Leroux Geneviève , Lepelley Pascale , Daniel Marie-Thérèse , Cheze Stéphane , Mahé Béatrice , Ferrant Augustin , Ravoet Christophe , Escoffre-Barbe Martine , Adès Lionel , Vey Norbert , Aljassem Lina , Stamatoullas Aspasia , Mannone Lionel , Dombret Hervé , Bourgeois Keith , Greenberg Peter , Fenaux Pierre , Dreyfus François
Published: October 2007

We analyzed prognostic factors of response, response duration, and possible impact on survival of epoetin α, epoetin β, or darbepoetin α (DAR) with or without granulocyte colony-stimulating factor in 403 myelodysplastic syndrome (MDS) patients. Sixty-two percent (40% major and 22% minor) and 50% erythroid responses were seen, and median response duration was 20 and 24 months according to IWG 2000 and 2006 criteria, respectively. Significantly higher response rates were observed with less than 10% blasts, low and int-1 International Prognostic Scoring System (IPSS), red blood cell transfusion independence, serum EPO level less than 200 IU/L, and, with IWG 2006 criteria only, shorter interval between diagnosis and treatment. Significantly longer response duration was associated with major response (IWG 2000 criteria), IPSS low to INT-1, blasts less than 5%, and absence of multilineage dysplasia. Minor responses according to IWG 2000 were reclassified as “nonresponders” or “responders” according to IWG 2006 criteria. However, among those IWG 2000 minor responders, response duration did not differ between IWG 2006 responders and nonresponders. Multivariate adjusted comparisons of survival between our cohort and the untreated MDS cohort used to design IPSS showed similar rate of progression to acute myeloid leukemia in both cohorts, but significantly better overall survival in our cohort, suggesting that epoetin or DAR treatment may have a favorable survival impact in MDS.
TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts
Authors: Bossen Claudia , Cachero Teresa G. , Tardivel Aubry , Ingold Karine , Willen Laure , Dobles Max , Scott Martin L. , Maquelin Aris , Belnoue Elodie , Siegrist Claire-Anne , Chevrier Stéphane , Acha-Orbea Hans , Leung Helen , Mackay Fabienne , Tschopp Jürg , Schneider Pascal
Published: October 2007

The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R–dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons.
The subunit composition of human extracellular superoxide dismutase (EC-SOD) regulate enzymatic activity
Authors: Petersen Steen V , Valnickova Zuzana , Oury Tim D , Crapo James D , Chr Nielsen Niels , Enghild Jan J
Published: October 2007

Background

Human extracellular superoxide dismutase (EC-SOD) is a tetrameric metalloenzyme responsible for the removal of superoxide anions from the extracellular space. We have previously shown that the EC-SOD subunit exists in two distinct folding variants based on differences in the disulfide bridge pattern (Petersen SV, Oury TD, Valnickova Z, Thøgersen IB, Højrup P, Crapo JD, Enghild JJ. Proc Natl Acad Sci USA. 2003;100(24):13875–80). One variant is enzymatically active (aEC-SOD) while the other is inactive (iEC-SOD). The EC-SOD subunits are associated into covalently linked dimers through an inter-subunit disulfide bridge creating the theoretical possibility of 3 dimers (aa, ai or ii) with different antioxidant potentials. We have analyzed the quaternary structure of the endogenous EC-SOD disulfide-linked dimer to investigate if these dimers in fact exist.

Results

The analyses of EC-SOD purified from human tissue show that all three dimer combinations exist including two homo-dimers (aa and ii) and a hetero-dimer (ai). Because EC-SOD is a tetramer the dimers may combine to generate 5 different mature EC-SOD molecules where the specific activity of each molecule is determined by the ratio of aEC-SOD and iEC-SOD subunits.

Conclusion

This finding shows that the aEC-SOD and iEC-SOD subunits combine in all 3 possible ways supporting the presence of tetrameric enzymes with variable enzymatic activity. This variation in enzymatic potency may regulate the antioxidant level in the extracellular space and represent a novel way of modulating enzymatic activity.
Investigations into the relationship between feedback loops and functional importance of a signal transduction network based on Boolean network modeling
Authors: Kwon Yung-Keun , Choi Sun Shim , Cho Kwang-Hyun
Published: October 2007

Background

A number of studies on biological networks have been carried out to unravel the topological characteristics that can explain the functional importance of network nodes. For instance, connectivity, clustering coefficient, and shortest path length were previously proposed for this purpose. However, there is still a pressing need to investigate another topological measure that can better describe the functional importance of network nodes. In this respect, we considered a feedback loop which is ubiquitously found in various biological networks.

Results

We discovered that the number of feedback loops (NuFBL) is a crucial measure for evaluating the importance of a network node and verified this through a signal transduction network in the hippocampal CA1 neuron of mice as well as through generalized biological network models represented by Boolean networks. In particular, we observed that the proteins with a larger NuFBL are more likely to be essential and to evolve slowly in the hippocampal CA1 neuronal signal transduction network. Then, from extensive simulations based on the Boolean network models, we proved that a network node with the larger NuFBL is likely to be more important as the mutations of the initial state or the update rule of such a node made the network converge to a different attractor. These results led us to infer that such a strong positive correlation between the NuFBL and the importance of a network node might be an intrinsic principle of biological networks in view of network dynamics.

Conclusion

The presented analysis on topological characteristics of biological networks showed that the number of feedback loops is positively correlated with the functional importance of network nodes. This result also suggests the existence of unknown feedback loops around functionally important nodes in biological networks.
On the detection of functionally coherent groups of protein domains with an extension to protein annotation
Authors: McLaughlin William A , Chen Ken , Hou Tingjun , Wang Wei
Published: October 2007

Background

Protein domains coordinate to perform multifaceted cellular functions, and domain combinations serve as the functional building blocks of the cell. The available methods to identify functional domain combinations are limited in their scope, e.g. to the identification of combinations falling within individual proteins or within specific regions in a translated genome. Further effort is needed to identify groups of domains that span across two or more proteins and are linked by a cooperative function. Such functional domain combinations can be useful for protein annotation.

Results

Using a new computational method, we have identified 114 groups of domains, referred to as domain assembly units (DASSEM units), in the proteome of budding yeastSaccharomyces cerevisiae. The units participate in many important cellular processes such as transcription regulation, translation initiation, and mRNA splicing. Within the units the domains were found to function in a cooperative manner; and each domain contributed to a different aspect of the unit's overall function. The member domains of DASSEM units were found to be significantly enriched among proteins contained in transcription modules, defined as genes sharing similar expression profiles and presumably similar functions. The observation further confirmed the functional coherence of DASSEM units. The functional linkages of units were found in both functionally characterized and uncharacterized proteins, which enabled the assessment of protein function based on domain composition.

Conclusion

A new computational method was developed to identify groups of domains that are linked by a common function in the proteome ofSaccharomyces cerevisiae. These groups can either lie within individual proteins or span across different proteins. We propose that the functional linkages among the domains within the DASSEM units can be used as a non-homology based tool to annotate uncharacterized proteins.
Genetic determinants of hyaloid and retinal vasculature in zebrafish
Authors: Alvarez Yolanda , Cederlund Maria L , Cottell David C , Bill Brent R , Ekker Stephen C , Torres-Vazquez Jesus , Weinstein Brant M , Hyde David R , Vihtelic Thomas S , Kennedy Breandan N
Published: October 2007

Background

The retinal vasculature is a capillary network of blood vessels that nourishes the inner retina of most mammals. Developmental abnormalities or microvascular complications in the retinal vasculature result in severe human eye diseases that lead to blindness. To exploit the advantages of zebrafish for genetic, developmental and pharmacological studies of retinal vasculature, we characterised the intraocular vasculature in zebrafish.

Results

We show a detailed morphological and developmental analysis of the retinal blood supply in zebrafish. Similar to the transient hyaloid vasculature in mammalian embryos, vessels are first found attached to the zebrafish lens at 2.5 days post fertilisation. These vessels progressively lose contact with the lens and by 30 days post fertilisation adhere to the inner limiting membrane of the juvenile retina. Ultrastructure analysis shows these vessels to exhibit distinctive hallmarks of mammalian retinal vasculature. For example, smooth muscle actin-expressing pericytes are ensheathed by the basal lamina of the blood vessel, and vesicle vacuolar organelles (VVO), subcellular mediators of vessel-retinal nourishment, are present. Finally, we identify 9 genes with cell membrane, extracellular matrix and unknown identity that are necessary for zebrafish hyaloid and retinal vasculature development.

Conclusion

Zebrafish have a retinal blood supply with a characteristic developmental and adult morphology. Abnormalities of these intraocular vessels are easily observed, enabling application of genetic and chemical approaches in zebrafish to identify molecular regulators of hyaloid and retinal vasculature in development and disease.
Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research
Authors: Hirunsatit Rungnapa , Ilomäki Risto , Malison Robert , Räsänen Pirkko , Ilomäki Essi , Kranzler Henry R , Kosten Thomas , Sughondhabirom Atapol , Thavichachart Nuntika , Tangwongchai Sookjaroen , Listman Jennifer , Mutirangura Apiwat , Gelernter Joel , Lappalainen Jaakko
Published: October 2007

Background

GABA transporter-1 (GAT-1; genetic locus SLC6A1) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in SLC6A1 in five populations representing three continental groups.

Results

We resequenced 12.4 kb of SLC6A1, including the promoters, exons and flanking intronic regions in African-American, Thai, Hmong, Finnish, and European-American subjects (total n = 40). LD in SLC6A1 was examined by genotyping 16 SNPs in larger samples. Sixty-three variants were identified through resequencing. Common population-specific variants were found in African-Americans, including a novel 21-bp promoter region variable number tandem repeat (VNTR), but no such variants were found in any of the other populations studied. Low levels of LD and the absence of major LD blocks were characteristic of all five populations. African-Americans had the highest genetic diversity. European-Americans and Finns did not differ in genetic diversity or LD patterns. Although the Hmong had the highest level of LD, our results suggest that a strategy based on the use of tag SNPs would not translate to a major improvement in genotyping efficiency.

Conclusion

Owing to the low level of LD and presence of recombination hotspots, SLC6A1 may be an example of a problematic gene for association and haplotype tagging-based genetic studies. The 21-bp promoter region VNTR polymorphism is a putatively functional candidate allele for studies focusing on variation in GAT-1 function in the African-American population.
The functional genome of CA1 and CA3 neurons under native conditions and in response to ischemia
Authors: Newrzella Dieter , Pahlavan Payam S , Krüger Carola , Boehm Christine , Sorgenfrei Oliver , Schröck Helmut , Eisenhardt Gisela , Bischoff Nadine , Vogt Gerhard , Wafzig Oliver , Rossner Moritz , Maurer Martin H , Hiemisch Holger , Bach Alfred , Kuschinsky Wolfgang , Schneider Armin
Published: October 2007

Background

The different physiological repertoire of CA3 and CA1 neurons in the hippocampus, as well as their differing behaviour after noxious stimuli are ultimately based upon differences in the expressed genome. We have compared CA3 and CA1 gene expression in the uninjured brain, and after cerebral ischemia using laser microdissection (LMD), RNA amplification, and array hybridization.

Results

Profiling in CA1 vs. CA3 under normoxic conditions detected more than 1000 differentially expressed genes that belong to different, physiologically relevant gene ontology groups in both cell types. The comparison of each region under normoxic and ischemic conditions revealed more than 5000 ischemia-regulated genes for each individual cell type. Surprisingly, there was a high co-regulation in both regions. In the ischemic state, only about 100 genes were found to be differentially expressed in CA3 and CA1. The majority of these genes were also different in the native state. A minority of interesting genes (e.g. inhibinbetaA) displayed divergent expression preference under native and ischemic conditions with partially opposing directions of regulation in both cell types.

Conclusion

The differences found in two morphologically very similar cell types situated next to each other in the CNS are large providing a rational basis for physiological differences. Unexpectedly, the genomic response to ischemia is highly similar in these two neuron types, leading to a substantial attenuation of functional genomic differences in these two cell types. Also, the majority of changes that exist in the ischemic state are not generated de novo by the ischemic stimulus, but are preexistant from the genomic repertoire in the native situation. This unexpected influence of a strong noxious stimulus on cell-specific gene expression differences can be explained by the activation of a cell-type independent conserved gene-expression program. Our data generate both novel insights into the relation of the quiescent and stimulus-induced transcriptome in different cells, and provide a large dataset to the research community, both for mapping purposes, as well as for physiological and pathophysiological research.
A motif-based search in bacterial genomes identifies the ortholog of the small RNA Yfr1 in all lineages of cyanobacteria
Authors: Voß Björn , Gierga Gregor , Axmann Ilka M , Hess Wolfgang R
Published: October 2007

Background

Non-coding RNAs (ncRNA) are regulators of gene expression in all domains of life. They control growth and differentiation, virulence, motility and various stress responses. The identification of ncRNAs can be a tedious process due to the heterogeneous nature of this molecule class and the missing sequence similarity of orthologs, even among closely related species. The small ncRNA Yfr1 has previously been found in the Prochlorococcus/Synechococcus group of marine cyanobacteria.

Results

Here we show that screening available genome sequences based on an RNA motif and followed by experimental analysis works successfully in detecting this RNA in all lineages of cyanobacteria. Yfr1 is an abundant ncRNA between 54 and 69 nt in size that is ubiquitous for cyanobacteria except for two low light-adapted strains of Prochlorococcus, MIT 9211 and SS120, in which it must have been lost secondarily. Yfr1 consists of two predicted stem-loop elements separated by an unpaired sequence of 16–20 nucleotides containing the ultraconserved undecanucleotide 5'-ACUCCUCACAC-3'.

Conclusion

Starting with an ncRNA previously found in a narrow group of cyanobacteria only, we show here the highly specific and sensitive identification of its homologs within all lineages of cyanobacteria, whereas it was not detected within the genome sequences of E. coli and of 7 other eubacteria belonging to the alpha-proteobacteria, chlorobiaceae and spirochaete. The integration of RNA motif prediction into computational pipelines for the detection of ncRNAs in bacteria appears as a promising step to improve the quality of such predictions.
BACTIBASE: a new web-accessible database for bacteriocin characterization
Authors: Hammami Riadh , Zouhir Abdelmajid , Ben Hamida Jeannette , Fliss Ismail
Published: October 2007

Background

Bacteriocins are very diverse group of antimicrobial peptides produced by a wide range of bacteria and known for their inhibitory activity against various human and animal pathogens. Although many bacteriocins are now well characterized, much information is still missing or is unavailable to potential users. The assembly of such information in one central resource such as a database would therefore be of great benefit to the exploitation of these bioactive molecules in the present context of increasing antibiotic resistance and natural bio-preservation need.

Description

In the present paper, we present the development of a new and original database BACTIBASE that contains calculated or predicted physicochemical properties of 123 bacteriocins produced by both Gram-positive and Gram-negative bacteria. The information in this database is very easy to extract and allows rapid prediction of relationships structure/function and target organisms of these peptides and therefore better exploitation of their biological activity in both the medical and food sectors.

Conclusion

The BACTIBASE database is freely available at http://bactibase.pfba-lab.org, web-based platform enabling easy retrieval, via various filters, of sets of bacteriocins that will enable detailed analysis of a number of microbiological and physicochemical data.
Prevalence of heroin and methamphetamine male users in the northern Taiwan, 1999–2002: capture-recapture estimates
Authors: Chiang Shu-Chuan , Chen Chuan-Yu , Chang Yuan-Ying , Sun Hsiao-Ju , Chen Wei J
Published: October 2007

Background

Illegal drug use and related problems have been emerging as an important public health issue in Taiwan. Via the capture-recapture approach, the present study aimed to offer insights into the size of heroin and methamphetamine male user population in the northern Taiwan during the period from 1999 to 2002.

Methods

Annual lists of male subjects were collated from both judiciary and medical systems in Taoyuan County, Taiwan. A total of 2809, 2486, 1661, and 1440 local male illegal drug users aged 15 to 54 years were identified in Taoyuan County from 1999 to 2002, respectively.

Results

An estimated number of 16192, 14532, 16844, and 11783 local male methamphetamine or heroin users were found in each of the four consecutive years in the region. From 1999 to 2002, the annual prevalence rate for heroin use was 0.27% (95% CI = 0.20%, 0.38%), 0.33% (95% CI = 0.25%, 0.44%), 0.63% (95% CI = 0.44%, 0.92%), and 0.72% (95% CI = 0.54%, 0.97%), respectively, suggesting a trend of significant increase (chi-square for linear trend = 1677.76, d.f. = 3, p < 0.0001). In contrast, a decreasing trend was found for methamphetamine (2.38%, 1.91%, 2.47%, and 1.24%), with a modest rebound in 2001. The prevalence rates of illegal drug use for male residents in Taoyuan County were approximately 2–3% during this period, and the scale of problem shows no sign of diminution.

Conclusion

By taking advantage of existing datasets that were incomplete by each alone, the approach of capture-recapture model may be ultimately considered as a tool to estimate the scale of illegal drug use problems. The population of heroin-using males apparently is stably expanding in the northern part of Taiwan in the first years of 21st century.
Glutathione mediated regulation of oligomeric structure and functional activity of Plasmodium falciparum glutathione S-transferase
Authors: Tripathi Timir , Rahlfs Stefan , Becker Katja , Bhakuni Vinod
Published: October 2007

Background

In contrast to many other organisms, the malarial parasitePlasmodium falciparumpossesses only one typical glutathioneS-transferase. This enzyme,PfGST, cannot be assigned to any of the known GST classes and represents a most interesting target for antimalarial drug development. ThePfGST under native conditions forms non-covalently linked higher aggregates with major population (~98%) being tetramer. However, in the presence of 2 mM GSH, a dimer ofPfGST is observed. Recently reported study on binding and catalytic properties ofPfGST indicated a GSH dependent low-high affinity transition with simultaneous binding of two GSH molecules toPfGST dimer suggesting that GSH binds to low affinity inactive enzyme dimer converting it to high affinity functionally active dimer. In order to understand the role of GSH in tetramer-dimer transition ofPfGST as well as in modulation of functional activity of the enzyme, detailed structural, functional and stability studies on recombinantPfGST in the presence and absence of GSH were carried out.

Results

Our data indicate that the dimer – and not the tetramer – is the active form ofPfGST, and that substrate saturation is directly paralleled by dissociation of the tetramer. Furthermore, this dissociation is a reversible process indicating that the tetramer-dimer equilibrium ofPfGST is defined by the surrounding GSH concentration. Equilibrium denaturation studies show that thePfGST tetramer has significantly higher stability compared to the dimer. The enhanced stability of the tetramer is likely to be due to stronger ionic interactions existing in it.

Conclusion

This is the first report for any GST where an alteration in oligomeric structure and not just small conformational change is observed upon GSH binding to the enzyme. Furthermore we also demonstrate a reversible mechanism of regulation of functional activity ofPlasmodium falciparumglutathioneS-transferase via GSH induced dissociation of functionally inactive tetramer into active dimers.
Online detection and quantification of epidemics
Authors: Pelat Camille , Boëlle Pierre-Yves , Cowling Benjamin J , Carrat Fabrice , Flahault Antoine , Ansart Séverine , Valleron Alain-Jacques
Published: October 2007

Background

Time series data are increasingly available in health care, especially for the purpose of disease surveillance. The analysis of such data has long used periodic regression models to detect outbreaks and estimate epidemic burdens. However, implementation of the method may be difficult due to lack of statistical expertise. No dedicated tool is available to perform and guide analyses.

Results

We developed an online computer application allowing analysis of epidemiologic time series. The system is available online athttp://www.u707.jussieu.fr/periodic_regression/. The data is assumed to consist of a periodic baseline level and irregularly occurring epidemics. The program allows estimating the periodic baseline level and associated upper forecast limit. The latter defines a threshold for epidemic detection. The burden of an epidemic is defined as the cumulated signal in excess of the baseline estimate. The user is guided through the necessary choices for analysis. We illustrate the usage of the online epidemic analysis tool with two examples: the retrospective detection and quantification of excess pneumonia and influenza (P&I) mortality, and the prospective surveillance of gastrointestinal disease (diarrhoea).

Conclusion

The online application allows easy detection of special events in an epidemiologic time series and quantification of excess mortality/morbidity as a change from baseline. It should be a valuable tool for field and public health practitioners.
Evaluating compulsory minimum volume standards in Germany: how many hospitals were compliant in 2004?
Authors: de Cruppé Werner , Ohmann Christian , Blum Karl , Geraedts Max
Published: October 2007

Background

Minimum hospital procedure volumes are discussed as an instrument for quality assurance. In 2004 Germany introduced such annual minimum volumes nationwide on five surgical procedures: kidney, liver, stem cell transplantation, complex oesophageal, and pancreatic interventions. The present investigation is the first part of a study evaluating the effects of these minimum volumes on health care provision. Research questions address how many hospitals and cases were affected by minimum volume regulations in 2004, how affected hospitals were distributed according to minimum volumes, and how many hospitals within the 16 German states complied with the standards set for 2004.

Methods

The evaluation is based on the mandatory hospital quality reports for 2004. In the reports, all hospitals are statutorily obliged to state the number of procedures performed for each minimum volume. The data were analyzed descriptively.

Results

In 2004, 485 out of 1710 German hospitals providing acute care and approximately 0.14% of all hospital cases were affected by minimum volume regulations. Liver, kidney, and stem cell transplantation affected from 23 to hospitals; complex oesophageal and pancreatic interventions affected from 297 to 455 hospitals. The inter-state comparison of the average hospital care area demonstrates large differences between city states and large area states and the eastern and western German states ranging from a minimum 51 km2 up to a maximum 23.200 km2, varying according to each procedure. A range of 9% – 16% of the transplantation hospitals did not comply with the standards affecting 1% – 2% of the patients whereas 29% and 18% of the hospitals treating complex oesophageal and pancreatic interventions failed the standards affecting 2% – 5% of the prevailing cases.

Conclusion

In 2004, the newly introduced minimum volume regulations affected only up to a quarter of German acute care hospitals and few cases. However, excluding the hospitals not meeting the minimum volume standards from providing the respective procedures deserves considering two aspects: the hospital health care provision concepts by the German states as being responsible and from a patient perspective the geographically equal access to hospital care.
Do the UK government's new Quality and Outcomes Framework (QOF) scores adequately measure primary care performance? A cross-sectional survey of routine healthcare data
Authors: Downing Amy , Rudge Gavin , Cheng Yaping , Tu Yu-Kang , Keen Justin , Gilthorpe Mark S
Published: October 2007

Background

General practitioners' remuneration is now linked directly to the scores attained in the Quality and Outcomes Framework (QOF). The success of this approach depends in part on designing a robust and clinically meaningful set of indicators. The aim of this study was to assess the extent to which measures of health observed in practice populations are correlated with their QOF scores, after accounting for the established associations between health outcomes and socio-demographics.

Methods

QOF data for the period April 2004 to March 2005 were obtained for all general practices in two English Primary Care Trusts. These data were linked to data for emergency hospital admissions (for asthma, cancer, chronic obstructive pulmonary disease, coronary hear disease, diabetes, stroke and all other conditions) and all cause mortality for the period September 2004 to August 2005. Multilevel logistic regression models explored the association between health outcomes (hospital admission and death) and practice QOF scores (clinical, additional services and organisational domains), age, sex and socio-economic deprivation.

Results

Higher clinical domain scores were generally associated with lower admission rates and this was significant for cancer and other conditions in PCT 2. Higher scores in the additional services domain were associated with higher admission rates, significantly so for asthma, CHD, stroke and other conditions in PCT 1 and cancer in PCT 2. Little association was observed between the organisational domain scores and admissions. The relationship between the QOF variables and mortality was less clear. Being female was associated with fewer admissions for cancer and CHD and lower mortality rates. Increasing age was mainly associated with an increased number of events. Increasing deprivation was associated with higher admission rates for all conditions and with higher mortality rates.

Conclusion

The associations between QOF scores and emergency admissions and mortality were small and inconsistent, whilst the impact of socio-economic deprivation on the outcomes was much stronger. These results have implications for the use of target-based remuneration of general practitioners and emphasise the need to tackle inequalities and improve the health of disadvantaged groups and the population as a whole.
Molecular signatures define two main classes of meningiomas
Authors: Carvalho Lucia Helena , Smirnov Ivan , Baia Gilson S , Modrusan Zora , Smith Justin S , Jun Peter , Costello Joseph F , McDermott Michael W , VandenBerg Scott R , Lal Anita
Published: October 2007

Background

Meningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant) and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis.

Results

We have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH) to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs) compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups.

Conclusion

Collectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.
Variable expressivity of the tumour suppressor protein TRP53 in cryopreserved human blastocysts
Authors: Chandrakanthan Vashe , Chami Omar , Stojanov Tomas , O'Neill Chris
Published: October 2007

In a mouse model, in vitro fertilization or extended embryo culture leads to the increased expression of TRP53 in susceptible embryos. Ablation of the TRP53 gene improved embryo viability indicating that increased expression of TRP53 is a cause of the reduction of embryo viability resulting from in vitro fertilization or embryo culture. This study investigates the status of TRP53 expression in human embryos produced by intracytoplasmic sperm injection. Following fertilization, embryos were cultured for 96 h and then cryopreserved. Immediately upon thawing they were fixed in formaldehyde and subjected to immunostaining for TRP53. Staining was visualized by confocal microscopy. Negative controls were incubated with isotype control immunoglobulin and showed negligible staining. All embryos showed TRP53 staining above negative controls. TRP53 staining was heterogenous within and between embryos. An embryo that showed retarded development showed high levels of TRP53 expression. A blastocyst that had a collapsed blastocoel also showed high levels of TRP53 compared to morphologically normal blastocysts. Most TRP53 staining was in the region of the nucleus. Morphologically normal blastocysts tended to show little nuclear accumulation of stain. However, some cells within these embryos had high levels of nuclear TRP53 expression. The results show that embryos have varying sensitivity to the stresses of production and culture in vitro, and this resulted in variable expressivity of TRP53.