bluuebunny/crossref_metadata_2025 huggingface dataset:
Failure Resilient Heterogeneous Parallel Computing Across Multidomain Clusters
Authors: Kurzyniec Dawid , Sunderam Vaidy
Published: May 2005

We propose lightweight middleware solutions that facilitate and simplify the execution of failure-resilient Message Passing Interface (MPI) programs across multidomain clusters. The system described in this paper leverages H2O, a distributed metacomputing framework, to route MPI message passing across heterogeneous aggregates located in different administrative or network domains. MPI communication is aided by a specially written H2O pluglet; messages that are destined for remote sites are intercepted and transparently forwarded to their final destinations. We demonstrate that the proposed technique is indeed effective in enabling communication by MPI programs across distinct clusters and across firewalls. Only marginally lowered performance was observed in our tests, and we believe the substantially increased functionality would compensate for this overhead in most situations. In addition to enabling multicluster communications, we note that with the increasing size and distribution of metacomputing environments, fault tolerance aspects become critically important. We argue that the fault tolerance model proposed by FT-MPI fits well in geographically distributed environments, even though its current implementation is confined to a single administrative domain. We describe extensions to overcome these limitations by combining FT-MPI with the H2O framework. Our holistic approach allows users to run fault-tolerant MPI programs on heterogeneous, geographically distributed shared machines, without sacrificing performance and with minimal involvement of resource providers.
From Initiator to Consumer
Authors: Karsten Luchien , van Veen Kees
Published: May 2005

The Dutch government has played a significant role in the dissemination of management knowledge to the Dutch business community and as such in the professionalization of management since the mid-1940s. After the Second World War, the Dutch government initiated and stimulated the development of an institutionalized network to transfer management knowledge. In the 1980s, however, the government’s position changed dramatically. Its directive role as stimulator and distributor of knowledge diminished and was taken over by actors such as consulting agencies, gurus and commercial publishers. As well as decreasing its role as distributor, the government also changed its own position. Governmental bodies themselves increasingly began to use management knowledge and in doing so became one of the largest consumers in the Netherlands.
Indoor Air Quality Certification Scheme for Hong Kong Buildings
Authors: Burnett John
Published: May 2005

The Hong Kong SAR Government has taken initiatives to improve indoor air quality (IAQ) in various facilities. The most recent is the development of an IAQ Certification Scheme for Offices and Public Places. Following criticism of an earlier draft some of the IAQ criteria were relaxed, yet remain comparatively tight specifications for air-conditioned buildings. Launched as a voluntary scheme it could become a significant driving force to improve building performance. However, pilot studies have shown the complexity and cost of undertaking an assessment will be a significant deterrent. Here, the key elements of the scheme are outlined, the suitability of the IAQ criteria discussed, and the difficulties in meeting the prescribed measurement protocols identified. Suggestions are made for improvements to the scheme that would encourage take-up by building owners.
Volatile Organic Compounds in the Indoor Air of Warsaw Office Buildings
Authors: Pośniak Malgorzata , Makhniashvili Ivan , Koziel Ewa
Published: May 2005

The aim of this study was to assess exposure to volatile organic compounds (VOCs) in office buildings. Five large office buildings in different areas of Warsaw were selected for the investigation. The identification and the determination of VOCs in the working environment were carried out twice during the year - in the spring-summer time and in the autumn-winter time in 50 offices. The most abundant compounds found were aliphatic and aromatic hydrocarbons. The carcinogenic compounds, benzene and formaldehyde were among the VOCs found in the offices.

Because of the absence of health based indoor air quality standards for the office working environment in Poland and in the world, the exposure assessment for 50 workers employed in 5 office buildings was carried out with reference to ambient air quality standards and standards established for rooms in public utility buildings under Polish law. Notice was also taken of the recommended standard for total VOCs proposed by Seifert and Mølhave.

The analysis of the results of the exposure assessment of VOCs in offices in the buildings investigated shows what these compounds occur in at levels which could contribute to the “sick building syndrome” (SBS), particularly in those buildings that were not air-conditioned.
Studies on Occupational Asbestos in Lithuania: Achievements and Problems
Authors: Smolianskienė Gražina , Adamonienė Danute , Šeškauskas Viktoras
Published: May 2005

One of the most dangerous chemical factors throughout industry in the developed countries is asbestos. An adequate legislative basis has been created in Lithuania and there are in force legislation documents that set forth the requirements for work with asbestos as well as the measurements that need to be made in the work environment. In Lithuania the technique used for determination of the concentration of asbestos fibres (as f·cm 3) is by the method of phase-contrast optical microscopy. Mostly, measurements of asbestos exposures in the work environment have been made in the chemical industry, industry concerned with the production of machinery, the construction industry, transport and the energy sector. The average concentration of asbestos fibres in workplace atmospheres was found to be highest in the chemical industry, namely, 0.07f·cm 3. It is now necessary to harmonise the legislative base according to the requirements of the EU Directive 2003/18/EC and put them in practice.
Augmenting GEM-encoded clinical practice guidelines with relevant best evidence autonomously retrieved from MEDLINE
Authors: Abidi Syed Sibte Raza , Kershaw Michael , Milios Evangelos
Published: May 2005

Clinical practice guidelines (CPG) are instrumental in standardizing the quality and delivery of care across different practitioners, departments and institutions. Health practitioners will use current best evidence to validate or supplement their understanding of CPG. This study investigates the potential of supplementing computerized CPG with relevant best evidence sourced from reliable medical literature repositories. A web-enabled Best-evidence Retrieval and Delivery (BiRD) system facilitates autonomous retrieval of pertinent medical literature with respect to user-specified content from a GEM-encoded CPG. A multilevel literature search strategy categorizes the search towards predefined clinical query intentions, and subsequently filters insignificant medical terms. The resultant is a highly focused medical literature search query that is objectively derived from CPG content. The technical architecture comprises existing medical language processing tools and vocabularies, together with newly developed tools to automatically generate optimum search queries, retrieve medical articles from MEDLINE, and embed the articles within XML-based CPG.
Stakeholders’ experience of teledermatology in a nurse-led community clinic: a case study
Authors: Lawton Sandra , Timmons Stephen
Published: May 2005

Dermatology is regarded as especially suitable for the application of telemedicine because it relies to a large extent on visual information for diagnosis and holds promise as an alternative means of delivering healthcare. Interest in teledermatology has come at a time when there is an increased demand for dermatological services and has been advocated as a mode of delivery that may diminish inequalities in the provision of an overstretched service and improve access to dermatological care. A qualitative case study based on interviews and observations was undertaken to explore the perceptions of stakeholders (nurses, patients, GPs, consultants) when interacting with a nurse-led teledermatology service in primary care. The study found that the delineation of roles and changing professional boundaries were important issues for stakeholders. It has provided further evidence that teledermatology is more than images and diagnostics.
What’s so different about mobile information communication technologies (MICTs) for clinical work practices? A review of selected pilot studies
Authors: Martins Henrique M. G. , Jones Matthew R.
Published: May 2005

This article seeks to highlight some distinctive issues involved in the use of mobile information and communication technologies (MICTs) in the healthcare context. A three-layered framework for analysing cases of MICT-in-use is developed from the literature and employed to analyse evidence from a number of healthcare MICT pilot studies. These indicate that MICTs create new implementation challenges, and that developers and implementers appear to pay little attention to the particular workflow modalities of mobility and their relationship with the type of MICT. In terms of effects on clinical work practices, MICTs seemed to make access to information easier but not necessarily faster. Better integration of MICTs with other hospital systems and use of wireless networks were seen as necessary to achieve greater uptake. Areas for further research that might support the implementation of MICTs in healthcare are identified.
Performance of surgical services within a diagnostic and treatment centre: an analysis of Trust X
Authors: Page Steve , Howard Christopher
Published: May 2005

The need for change within the National Health Service (NHS) to improve performance and increase value for money has been discussed for many years by academics, practitioners and political parties. Change initiatives have come and gone and yet the problems still exist. This research explores possible changes in practice that may be required to improve the performance of operating theatres within a diagnostic and treatment centre in England - Trust X. The research investigates the difficulties of implementing such changes within Trust X, gives some insight into why these difficulties arise, and suggests possible future options as to how the aforementioned difficulties may be addressed.
Knowledge support for interdisciplinary models of healthcare delivery: a study of knowledge needs and roles in managed clinical networks
Authors: Burnett Simon M. , Williams Dorothy A. , Webster Linda
Published: May 2005

Managed clinical networks (MCNs), a relatively new phenomenon in the health service, aim to ensure equitable provision of high-quality, evidence-based care using an innovative interdisciplinary work model. This article describes a study that aimed to highlight themes which could be explored in a fuller information needs analysis of individuals working in MCNs. Comparison with an earlier study of staff in more traditional roles shows that staff working in MCNs have a greater appreciation of: the value of information and knowledge in the organizational context; the tools and skills required to use information and knowledge to improve service delivery; the value of personal or tacit knowledge and the role of individuals in coordinating networks of knowledge; and the importance of developing a culture which includes the patient in the knowledge network. These findings indicate that MCNs may support a more ‘knowledge-based’ work model than traditional structures within the health service.
Lifestyles, reliance on traditional news media and online news adoption
Authors: Chan Joey Ka-Ching , Leung Louis
Published: May 2005

This exploratory study examines the predictive power of lifestyle orientations, reliance on traditional news media, attributes of online news, traditional mass media use and demographics on online news adoption. Data was gathered from 453 internet users. The study found that experiencers, a lifestyle savouring the new, read more online international/China news. In contrast, survivors, who live narrowly focused lives, seldom do. Although lifestyles were not predictive as to whether internet users would adopt online news, they were the strongest predictors for the enjoyment of interactive capability of online news for adopters. Specifically, interactivity can satisfy the need for seeking fun among strivers, a desire for self-expression among makers and aspiration for new ideas on the part of innovators. Furthermore, as practical people, makers enjoy multimedia features for their functional purpose. In conclusion, some of the implications for news publishers in offering personalized editions of online news are discussed.
Power, reason, closure: critical perspectives on new media theory
Authors: Röhle Theo
Published: May 2005

This article addresses the question of new media studies’ meta-theoretical premises. It is argued that the field’s exceptional openness towards theory and method is a valuable asset, which needs to be cultivated by means of a more explicit meta-theoretical debate. Drawing on critical theory, three meta-theoretical criteria concerning power, reason and closure are suggested and applied in a review of common theoretical perspectives at use in the field. A discussion of political economy and postmodern perspectives prepares the ground for an analysis of approaches inspired by Habermas and Foucault. The article concludes by advocating the theoretical concept of the dispositif or social apparatus, developed by Foucault and Deleuze. It is argued that the concept provides an effective tool to map the intricate relations of power and knowledge around the internet, as well as a possibility to analyse how processes of subjectification are fostered or circumscribed in specific settings.
House society and practice theories illuminate American campsteads
Authors: Brereton Derek P.
Published: May 2005

House society theory’s experientially grounded flexibility founds an understanding of century-old American campsteads at Squam Lake, New Hampshire. These conjoin five to seven familial generations with place, property, architecture, and memory; foster a sort of experience with conceptual and structural implications for both people and the local landscape. The morphogenic relations between experience, intelligibilia, and structuring conditions, in turn, find a clear theoretical model in Margaret Archer’s practice theory. This article describes such campsteads, locating their emergence and continuing structural importance in cycles of American nature religion. The campstead thus assumes a spiritual mantle, and fosters in campsteaders a self intimately shaped by close experience having heightened personal significance.
From flows to violence
Authors: Kalb Don
Published: May 2005

Recent globalization theory reflected a chain of world historical events since the end of the Cold War. Globalization theories were tools for the making of political alliances between market liberals and political liberals. From the mid-1990s a broad range of institutionalist social science programs showed that globalization outcomes were often better explained by institutional logics (including cultural ones) than by global flows per se. This is, among others, illustrated by the debate on global inequality data. The emerging debate on empire and imperalism is discussed as a logical offshoot of the globalization discussion just as the phenomenon itself is seen as a likely outcome of an epoch of market-driven globalization. Globalization was predicated on the emergence of a US-led transnational western state structure on behalf of the transnational capitalist class based in finance and the large corporations. Territory and space have become more important rather than less, but the explanation of regional trajectories must now be located more firmly in the interaction between local and global structures. This leads to a new agenda in the social sciences: one oriented toward common interdisciplinary programs with a limited range of core questions - about state formations, class formations, mobilizations, claim making, and associated cultural processes. Programs should be more theory driven, comparative, and in search of explanations of divergent spatial and temporal outcomes of universal process.
Mouse Polycomb M33 is required for splenic vascular and adrenal gland formation through regulating Ad4BP/SF1 expression
Authors: Katoh-Fukui Yuko , Owaki Akiko , Toyama Yoshiro , Kusaka Masatomo , Shinohara Yuko , Maekawa Mamiko , Toshimori Kiyotaka , Morohashi Ken-ichirou
Published: May 2005

Mice with disrupted mammalian PcG (Polycomb group) genes commonly show skeletal transformation of anterior-posterior identities. Disruption of the murine M33 gene, a PcG member, displayed posterior transformation of the vertebral columns and sternal ribs. In addition, failure of T-cell expansion and hypoplasia and sex-reversal of the gonads, have been observed. In the present study, we identified defects in the splenic and adrenal formation of M33–knock-out (KO) mice on a C57BL/6 genetic background. The spleen in these animals was smaller than in the wild-type mice and was spotted red because of nonuniform distribution of blood cells. Histologic examination revealed disorganization of the vascular endothelium and its surrounding structures, and immunohistochemistry demonstrated disturbances in vascular formation and colonization of immature hematopoietic cells. These splenic phenotypes observed in the M33-KO mice were quite similar to those seen in Ad4BP/SF1 (Nr5a1) knock-outs. Moreover, the adrenal glands of M33-KO and Ad4BP/SF1 heterozygous KO mice were smaller than those of the wild-type mice. Western blot, immunohistochemistry, and reverse transcriptase–polymerase chain reaction (RT-PCR) analyses of the M33 knock-outs all indicated significantly low expression of adrenal 4 binding protein/steroidogenic factor-1 (Ad4BP/SF-1), indicating that M33 is an essential upstream regulator of Ad4BP/SF1. In agreement with these observations, chromatin immunoprecipitation assays with adrenocortical Y-1 cells revealed direct binding of the M33-containing PcG to the Ad4BP/SF1 gene locus.
Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia
Authors: Holleman Amy , Boer Monique L. den , Kazemier Karin M. , Beverloo H. Berna , von Bergh Anne R. M. , Janka-Schaub Gritta E. , Pieters Rob
Published: May 2005

Drug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7, -8, -10, and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) in cells from children with acute lymphoblastic leukemia (ALL; n = 43) and acute myeloid leukemia (AML; n = 10). PARP expression was present in all B-lineage samples, but absent in 4 of 15 T-lineage ALL samples and 3 of 10 AML cases, which was not caused by genomic deletions. PARP expression was a median 7-fold lower in T-lineage ALL (P < .001) and 10-fold lower in AML (P < .001) compared with B-lineage ALL. PARP expression was 4-fold lower in prednisolone, vincristine and L-asparaginase (PVA)-resistant compared with PVA-sensitive ALL patients (P < .001). Procaspase-2 expression was 3-fold lower in T-lineage ALL (P = .022) and AML (P = .014) compared with B-lineage ALL. In addition, procaspase-2 expression was 2-fold lower in PVA-resistant compared to PVA-sensitive ALL patients (P = .042). No relation between apoptotic protease-activating factor 1 (Apaf-1), procaspases-3, -6, -7, -8, -10, and drug resistance was found. In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia. (Blood. 2005;106:1817-1823)
Rapid immunosuppressive effects of glucocorticoids mediated through Lck and Fyn
Authors: Löwenberg Mark , Tuynman Jurriaan , Bilderbeek Joyce , Gaber Timo , Buttgereit Frank , van Deventer Sander , Peppelenbosch Maikel , Hommes Daniel
Published: May 2005

Glucocorticoids (GCs) are effective immunosuppressive agents and mediate well-defined transcriptional effects via GC receptors. There is increasing evidence that GCs also initiate rapid nongenomic signaling events. Using activated human CD4+ lymphocytes and a peptide array containing 1176 different kinase consensus substrates, we generated a comprehensive profile of GC-induced rapid effects on signal transduction. The results show marked early differences in phosphorylation between GC-pretreated cells and control cells, including impaired phosphorylation of p56lck/p59fyn (Lck/Fyn) consensus substrates. Immunoprecipitation and in vitro kinase assays reveal rapid GC-induced down-modulation of Lck and Fyn kinases using SAM68 (Src [pp60c-src]-associated in mitosis 68 kDa) as a substrate. Additionally, immunoprecipitation experiments revealed reduced Lck-CD4 and Fyn-CD3 associations, suggesting GC inhibited recruitment of these kinases to the T-cell receptor complex. Western blot analysis revealed reduced phosphorylation of a series of downstream signaling intermediates following GC treatment, including protein kinase B (PKB), protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). Experiments with GC receptor-negative Jurkat cells and a pharmacologic GC receptor ligand (RU486) indicated that rapid inhibition of Lck and Fyn kinases is GC receptor dependent. Parallel experiments conducted following the application of GCs in healthy individuals confirmed suppression of Lck/Fyn in T cells within 1 hour in vivo. These results identify the inhibition of Lck and Fyn kinases as rapid targets of GCs, mediated via a GC receptor-dependent pathway. (Blood. 2005; 106:1703-1710)
The effect of refurbishing a UK steel plant on PM10 metal composition and ability to induce inflammation
Authors: Hutchison Gary R , Brown David M , Hibbs Leon R , Heal Mathew R , Donaldson Ken , Maynard Robert L , Monaghan Michelle , Nicholl Andy , Stone Vicki
Published: May 2005

Background

In the year 2000 Corus closed its steel plant operations in Redcar, NE of England temporarily for refurbishment of its blast furnace. This study investigates the impact of the closure on the chemical composition and biological activity of PM10 collected in the vicinity of the steel plant.

Methods

The metal content of PM10 samples collected before during and after the closure was measured by ICP-MS in order to ascertain whether there was any significant alteration in PM10 composition during the steel plant closure. Biological activity was assessed by instillation of 24 hr PM10 samples into male Wistar rats for 18 hr (n = 6). Inflammation was identified by the cellular and biochemical profile of the bronchoalveolar lavage fluid. Metal chelation of PM10 samples was conducted using Chelex beads prior to treatment of macrophage cell line, J774, in vitro and assessment of pro-inflammatory cytokine expression.

Results

The total metal content of PM10 collected before and during the closure period were similar, but on reopening of the steel plant there was a significant 3-fold increase (p < 0.05) compared with the closure and pre-closure samples. Wind direction prior to the closure was predominantly from the north, compared to south westerly during the closure and re-opened periods. Of metals analysed, iron was most abundant in the total and acid extract, while zinc was the most prevalent metal in the water-soluble fraction. Elevated markers of inflammation included a significant increase (p < 0.01) in neutrophil cell numbers in the bronchoalveolar lavage of rats instilled with PM10 collected during the reopened period, as well as significant increases in albumin (p < 0.05). Extracts of PM10 from the pre-closure and closure periods did not induce any significant alterations in inflammation or lung damage. The soluble and insoluble extractable PM10 components washed from the reopened period both induced a significant increase in neutrophil cell number (p < 0.05) when compared to the control, and these increases when added together approximately equalled the inflammation induced by the whole sample. PM10 from the re-opened period stimulated J774 macrophages to generate TNF-α protein and this was significantly prevented by chelating the metal content of the PM10 prior to addition to the cells.

Conclusion

PM10-induced inflammation in the rat lung was related to the concentration of metals in the PM10 samples tested, and activity was found in both the soluble and insoluble fractions of the particulate pollutant.
Pattern similarity study of functional sites in protein sequences: lysozymes and cystatins
Authors: Nakai Shuryo , Li-Chan Eunice CY , Dou Jinglie
Published: May 2005

Background

Although it is generally agreed that topography is more conserved than sequences, proteins sharing the same fold can have different functions, while there are protein families with low sequence similarity. An alternative method for profile analysis of characteristic conserved positions of the motifs within the 3D structures may be needed for functional annotation of protein sequences. Using the approach of quantitative structure-activity relationships (QSAR), we have proposed a new algorithm for postulating functional mechanisms on the basis of pattern similarity and average of property values of side-chains in segments within sequences. This approach was used to search for functional sites of proteins belonging to the lysozyme and cystatin families.

Results

Hydrophobicity and β-turn propensity of reference segments with 3–7 residues were used for the homology similarity search (HSS) for active sites. Hydrogen bonding was used as the side-chain property for searching the binding sites of lysozymes. The profiles of similarity constants and average values of these parameters as functions of their positions in the sequences could identify both active and substrate binding sites of the lysozyme of Streptomyces coelicolor, which has been reported as a new fold enzyme (Cellosyl). The same approach was successfully applied to cystatins, especially for postulating the mechanisms of amyloidosis of human cystatin C as well as human lysozyme.

Conclusion

Pattern similarity and average index values of structure-related properties of side chains in short segments of three residues or longer were, for the first time, successfully applied for predicting functional sites in sequences. This new approach may be applicable to studying functional sites in un-annotated proteins, for which complete 3D structures are not yet available.
A multistep bioinformatic approach detects putative regulatory elements in gene promoters
Authors: Bortoluzzi Stefania , Coppe Alessandro , Bisognin Andrea , Pizzi Cinzia , Danieli Gian Antonio
Published: May 2005

Background

Searching for approximate patterns in large promoter sequences frequently produces an exceedingly high numbers of results. Our aim was to exploit biological knowledge for definition of a sheltered search space and of appropriate search parameters, in order to develop a method for identification of a tractable number of sequence motifs.

Results

Novel software (COOP) was developed for extraction of sequence motifs, based on clustering of exact or approximate patterns according to the frequency of their overlapping occurrences. Genomic sequences of 1 Kb upstream of 91 genes differentially expressed and/or encoding proteins with relevant function in adult human retina were analyzed. Methodology and results were tested by analysing 1,000 groups of putatively unrelated sequences, randomly selected among 17,156 human gene promoters. When applied to a sample of human promoters, the method identified 279 putative motifs frequently occurring in retina promoters sequences. Most of them are localized in the proximal portion of promoters, less variable in central region than in lateral regions and similar to known regulatory sequences. COOP software and reference manual are freely available upon request to the Authors.

Conclusion

The approach described in this paper seems effective for identifying a tractable number of sequence motifs with putative regulatory role.
HinT proteins and their putative interaction partners in Mollicutes and Chlamydiaceae
Authors: Hopfe Miriam , Hegemann Johannes H , Henrich Birgit
Published: May 2005

Background

Background

HinT proteins are found in prokaryotes and eukaryotes and belong to the superfamily of HIT proteins, which are characterized by an histidine-triad sequence motif. While the eukaryotic variants hydrolyze AMP derivates and modulate transcription, the function of prokaryotic HinT proteins is less clearly defined. In Mycoplasma hominis, HinT is concomitantly expressed with the proteins P60 and P80, two domains of a surface exposed membrane complex, and in addition interacts with the P80 moiety.

Results

An cluster of hit ABL genes, similar to that of M. hominis was found in M. pulmonis, M. mycoides subspecies mycoides SC, M. mobile and Mesoplasma florum. RT-PCR analyses provided evidence that the P80, P60 and HinT homologues of M. pulmonis were polycistronically organized, suggesting a genetic and physical interaction between the proteins encoded by these genes in these species. While the hit loci of M. pneumoniae and M. genitalium encoded, in addition to HinT, a protein with several transmembrane segments, the hit locus of Ureaplasma parvum encoded a pore-forming protein, UU270, a P60 homologue, UU271, HinT, UU272, and a membrane protein of unknown function, UU273. Although a full-length mRNA spanning the four genes was not detected, amplification of all intergenic regions from the center of UU270 to the end of UU273 by RT-PCR may be indicative of a common, but unstable mRNA.

In Chlamydiaceae the hit gene is flanked upstream by a gene predicted to encode a metal dependent hydrolase and downstream by a gene putatively encoding a protein with ARM-repeats, which are known to be involved in protein-protein interactions. In RT-PCR analyses of C. pneumoniae, regions comprising only two genes, Cp265/Cp266 and Cp266/Cp267 were able to be amplified. In contrast to this in vivo interaction analysis using the yeast two-hybrid system and in vitro immune co-precipitation revealed an interaction between Cp267, which contains the ARM repeats, Cp265, the predicted hydrolase, and Cp266, the HinT protein.

Conclusion

In the Mollicutes HinT proteins were shown to be linked with membrane proteins while in the Chlamydiaceae they were genetically and physically associated with cytoplasmic proteins, one of which is predicted to be a metal-dependent phosphoesterase. Future work will elucidate whether these differing associations indicate that HinT proteins have evolved independently or are indeed two hotspots of a common sphere of action of bacterial HinT proteins.
Clinical outcomes in typhoid fever: adverse impact of infection with nalidixic acid-resistant Salmonella typhi
Authors: Kadhiravan Tamilarasu , Wig Naveet , Kapil Arti , Kabra SK , Renuka K , Misra Anoop
Published: May 2005

Background

Widespread use of fluoroquinolones has resulted in emergence of Salmonella typhi strains with decreased susceptibility to fluoroquinolones. These strains are identifiable by their nalidixic acid-resistance. We studied the impact of infection with nalidixic acid-resistant S. typhi (NARST) on clinical outcomes in patients with bacteriologically-confirmed typhoid fever.

Methods

Clinical and laboratory features, fever clearance time and complications were prospectively studied in patients with blood culture-proven typhoid fever, treated at a tertiary care hospital in north India, during the period from November 2001 to October 2003. Susceptibility to amoxycillin, co-trimoxazole, chloramphenicol, ciprofloxacin and ceftriaxone were tested by disc diffusion method. Minimum inhibitory concentrations (MIC) of ciprofloxacin and ceftriaxone were determined by E-test method.

Results

During a two-year period, 60 patients (age [mean ± SD]: 15 ± 9 years; males: 40 [67%]) were studied. All isolates were sensitive to ciprofloxacin and ceftriaxone by disc diffusion and MIC breakpoints. However, 11 patients had clinical failure of fluoroquinolone therapy. Infections with NARST isolates (47 [78%]) were significantly associated with longer duration of fever at presentation (median [IQR] 10 [7-15] vs. 4 [3-6] days; P = 0.000), higher frequency of hepatomegaly (57% vs. 15%; P = 0.021), higher levels of aspartate aminotransferase (121 [66–235] vs. 73 [44–119] IU/L; P = 0.033), and increased MIC of ciprofloxacin (0.37 ± 0.21 vs. 0.17 ± 0.14 μg/mL; P = 0.005), as compared to infections with nalidixic acid-susceptible isolates. All 11 patients with complications were infected with NARST isolates. Total duration of illness was significantly longer in patients who developed complications than in patients who did not (22 [14.8–32] vs. 12 [9.3–20.3] days; P = 0.011). Duration of prior antibiotic intake had a strong positive correlation with the duration of fever at presentation (r = 0.61; P = 0.000) as well as the total duration of illness (r = 0.53; P = 0.000).

Conclusion

Typhoid fever caused by NARST infection is associated with poor clinical outcomes, probably due to delay in initiating appropriate antibiotic therapy. Fluoroquinolone breakpoints for S. typhi need to be redefined and fluoroquinolones should no longer be used as first-line therapy, if the prevalence of NARST is high.
Minimum follow-up time required for the estimation of statistical cure of cancer patients: verification using data from 42 cancer sites in the SEER database
Authors: Tai Patricia , Yu Edward , Cserni Gábor , Vlastos Georges , Royce Melanie , Kunkler Ian , Vinh-Hung Vincent
Published: May 2005

Background

The present commonly used five-year survival rates are not adequate to represent the statistical cure. In the present study, we established the minimum number of years required for follow-up to estimate statistical cure rate, by using a lognormal distribution of the survival time of those who died of their cancer. We introduced the term, threshold year, the follow-up time for patients dying from the specific cancer covers most of the survival data, leaving less than 2.25% uncovered. This is close enough to cure from that specific cancer.

Methods

Data from the Surveillance, Epidemiology and End Results (SEER) database were tested if the survival times of cancer patients who died of their disease followed the lognormal distribution using a minimum chi-square method. Patients diagnosed from 1973–1992 in the registries of Connecticut and Detroit were chosen so that a maximum of 27 years was allowed for follow-up to 1999. A total of 49 specific organ sites were tested. The parameters of those lognormal distributions were found for each cancer site. The cancer-specific survival rates at the threshold years were compared with the longest available Kaplan-Meier survival estimates.

Results

The characteristics of the cancer-specific survival times of cancer patients who died of their disease from 42 cancer sites out of 49 sites were verified to follow different lognormal distributions. The threshold years validated for statistical cure varied for different cancer sites, from 2.6 years for pancreas cancer to 25.2 years for cancer of salivary gland. At the threshold year, the statistical cure rates estimated for 40 cancer sites were found to match the actuarial long-term survival rates estimated by the Kaplan-Meier method within six percentage points. For two cancer sites: breast and thyroid, the threshold years were so long that the cancer-specific survival rates could yet not be obtained because the SEER data do not provide sufficiently long follow-up.

Conclusion

The present study suggests a certain threshold year is required to wait before the statistical cure rate can be estimated for each cancer site. For some cancers, such as breast and thyroid, the 5- or 10-year survival rates inadequately reflect statistical cure rates, and highlight the need for long-term follow-up of these patients.
Female breast cancer incidence and survival in Utah according to religious preference, 1985–1999
Authors: Merrill Ray M , Folsom Jeffrey A
Published: May 2005

Background

Female breast cancer incidence rates in Utah are among the lowest in the U.S. The influence of the Church of Jesus Christ of Latter-day Saint (LDS or Mormon) religion on these rates, as well as on disease-specific survival, will be explored for individuals diagnosed with breast cancer in Utah from 1985 through 1999.

Methods

Population-based records for incident female breast cancer patients were linked with membership records from the LDS Church to determine religious affiliation and, for LDS Church members, level of religiosity. Incidence rates were age-adjusted to the 2000 U.S. standard population using the direct method. Cox proportional hazards model was used to compare survival among religiously active LDS, less religiously active LDS, and non-LDS with simultaneous adjustment for prognostic factors.

Results

Age-adjusted breast cancer incidence rates were consistently lower for LDS than non-LDS in Utah from 1985 through 1999. Rates were lower among LDS compared with non-LDS across the age span. In 1995–99, the age-adjusted incidence rates were 107.6 (95% CI: 103.9 – 111.3) for LDS women and 130.5 (123.2 – 137.9) for non-LDS women. If non-LDS women in Utah had the same breast cancer risk profile as LDS women, an estimated 214 (4.8%) fewer malignant breast cancer cases would have occurred during 1995–99. With religiously active LDS serving as the reference group, the adjusted death hazard ratio for religiously less active LDS was 1.09 (0.94 – 1.27) and for non-LDS was 0.86 (0.75 – 0.98).

Conclusion

In Utah, LDS lifestyle is associated with lower incidence rates of female breast cancer. However, LDS experience poorer survivability from breast cancer than their non-LDS counterparts. Parity and breastfeeding, while protective factors against breast cancer, may contribute to poorer prognosis of female breast cancer in LDS women.
Early discontinuation of intravenous antimicrobial therapy in pediatric oncology patients with febrile neutropenia
Authors: Hodgson-Viden Heather , Grundy Paul E , Robinson Joan L
Published: May 2005

Background

There are no standard criteria for when to discontinue intravenous antimicrobial therapy (IVAMT) in children with febrile neutropenia (FN), but it is now common to discontinue IVAMT and discharge patients with an absolute neutrophil count (ANC) ≤ 500 /mm3. The purpose of this study was to evaluate the outcome of a large cohort of children with FN who had IVAMT discontinued with an ANC ≤ 500 /mm3

Methods

A retrospective chart review was completed of patients in the Northern Alberta Children's Cancer Program with FN and no apparent clinical source of fever from June 1, 1997 to July 1, 2002.

Results

Out of a total of 275 patients, 127 (46%) had at least one episode of FN, with FN occurring in patients with sarcomas more commonly than in those with leukemia/ lymphoma and least in those with other solid tumors. In 59 of 276 episodes of FN (21%) patients had a microbiologically defined infection at admission. Of the 217 remaining episodes, 112 of 199 patients (56%) with known neutrophil counts had IVAMT discontinued before their absolute neutrophil count (ANC) reached 500 /mm3 at the discretion of the clinician. Fever recurred in only two of these patients after discharge, and there were no bacterial infections diagnosed after parenteral antibiotics were discontinued.

Conclusion

Even without use of standard criteria for early discharge, clinicians appear to be skilled at selecting children with FN who can safely have IVAMT discontinued with an ANC ≤ 500 /mm3.
Intrarectal quinine for treating Plasmodium falciparum malaria: a systematic review
Authors: Eisenhut Michael , Omari Aika , MacLehose Harriet G
Published: May 2005

Background

In children with malaria caused by Plasmodium falciparum, quinine administered rectally may be easier to use and less painful than intramuscular or intravenous administration. The objective of this review was to compare the effectiveness of intrarectal with intravenous or intramuscular quinine for treating falciparum malaria.

Methods

All randomized and quasi-randomized controlled trials comparing intrarectal with intramuscular or intravenous quinine for treating people with falciparum malaria located through the following sources were included: Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS and CINAHL. Trial quality was assessed and data, including adverse event data, were extracted. Dichotomous data were analysed using odds ratios and continuous data using weighted mean difference.

Results

Eight randomized controlled trials (1,247 children) fulfilled the inclusion criteria. The same principal investigator led seven of the trials. Five compared intrarectal with intravenous quinine, and six compared intrarectal with intramuscular treatment. No statistically significant difference was detected for death, parasite clearance by 48 hours and seven days, parasite and fever clearance time, coma recovery time, duration of hospitalization and time before drinking began. One trial (898 children) reported that intrarectal was less painful than intramuscular administration.

Conclusion

No difference in the effect on parasites and clinical illness was detected for the use of intrarectal quinine compared with other routes, but most trials were small. Pain during application may be less with intrarectal quinine. Further larger trials, in patients with severe malaria and in adults, are required before the intrarectal route could be recommended.
Effects of a self-care program on quality of life of cirrhotic patients referring to Tehran Hepatitis Center
Authors: Zandi Mitra , Adib-Hajbagheri Mohsen , Memarian Robabeh , Nejhad Anooshiravan Kazem , Alavian Seyed Moayed
Published: May 2005

Background

Chronic liver disease especially liver cirrhosis is one of the medical problems that substantially reduces the quality of life of its victims. Because of the chronic and irreversible nature of the disease, it needs self-care programs to be developed according to client's needs and to maintain their independence and sense of well-being. The purpose of this study was to determine the effects of a self-care educational program on Quality of Life (QoL) of a sample of Iranian cirrhotic patients.

Methods

A quasi-experimental study was conducted on 44 cirrhotic patients in Tehran Hepatitis Center. Longitudinal case registry and random allocation technique were used to divide the sample into experimental (n = 21) and control (n = 23) groups. Chronic liver disease questionnaire (CLDQ) was used for measuring the quality of life. The experimental group was given a questionnaire to assess their educational needs. A self-care educational program was conducted and the patients were followed for 3 months. Then the quality of life of both groups was compared using descriptive and analytical statistics.

Results

The experimental and control groups were the same concerning the effective factors on the quality of life, such as age, sex, etc (P > 0.05). There was no significant difference between QOL mean score of both groups before the intervention, however the QoL significantly improved in the experimental group after the intervention (P= 0.001), while the QoL decreased in control group.

Conclusion

The result of the present study confirmed the positive effects of the educational and self care programs on the QoL of cirrhotic patients. Extensive educational and self-care programs along with long-term follow up such as the program conducted in this study are suggested.
PCI proteins eIF3e and eIF3m define distinct translation initiation factor 3 complexes
Authors: Zhou Chunshui , Arslan Fatih , Wee Susan , Krishnan Srinivasan , Ivanov Alexander R , Oliva Anna , Leatherwood Janet , Wolf Dieter A
Published: May 2005

Background

PCI/MPN domain protein complexes comprise the 19S proteasome lid, the COP9 signalosome (CSN), and eukaryotic translation initiation factor 3 (eIF3). The eIF3 complex is thought to be composed of essential core subunits required for global protein synthesis and non-essential subunits that may modulate mRNA specificity. Interactions of unclear significance were reported between eIF3 subunits and PCI proteins contained in the CSN.

Results

Here, we report the unexpected finding that fission yeast has two distinct eIF3 complexes sharing common core subunits, but distinguished by the PCI proteins eIF3e and the novel eIF3m, which was previously annotated as a putative CSN subunit. Whereas neither eIF3e nor eIF3m contribute to the non-essential activities of CSN in cullin-RING ubiquitin ligase control, eif3m, unlike eif3e, is an essential gene required for global cellular protein synthesis and polysome formation. Using a ribonomic approach, this phenotypic distinction was correlated with a different set of mRNAs associated with the eIF3e and eIF3m complexes. Whereas the eIF3m complex appears to associate with the bulk of cellular mRNAs, the eIF3e complex associates with a far more restricted set. The microarray findings were independently corroborated for a random set of 14 mRNAs by RT-PCR analysis.

Conclusion

We propose that the PCI proteins eIF3e and eIF3m define distinct eIF3 complexes that may assist in the translation of different sets of mRNAs.
Innate immunity and inflammation in ageing: a key for understanding age-related diseases
Authors: Licastro Federico , Candore Giuseppina , Lio Domenico , Porcellini Elisa , Colonna-Romano Giuseppina , Franceschi Claudio , Caruso Calogero
Published: May 2005

The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased chance of long life survival in a "permissive" environment with reduced pathogen load, medical care and increased quality of life.